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Acute pain management: scientific evidence
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Endorsed November 1998
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Commonwealth of Australia 1999 ISBN 1864960426 This work is copyright. Apart from any use as permitted under the Copyright Act 1968, no part may be reproduced by any process without permission from AusInfo. Requests and enquiries concerning reproduction and rights should be addressed to the Manager, Legislative Services, AusInfo, GPO Box 1920, Canberra, ACT 2601. The strategic intent of the National Health and Medical Research Council (NHMRC) is to work with others for the health of all Australians, by promoting informed debate on ethics and policy, providing knowledge-based advice, fostering a high quality and internationally recognised research base, and applying research rigour to health issues.
This document is sold through AusInfo at a price which covers the cost of printing and distribution only. For publication purchases, please contact AusInfo on their toll-free number 13 24 47 or through their internet address: http://www.ausinfo.gov.au. NHMRC documents are prepared by panels of experts drawn from appropriate Australian academic, professional, community and government organisations. NHMRC is grateful to these people for the excellent work they do on an honorary basis and in addition to their usual work commitments. Produced by ampersand editorial & design, Canberra
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Contents
Preface ..................................................................................................................... 7 Executive summary ................................................................................................. 9 Summary of scientific evidence and key management points ........................... 11 Introduction ............................................................................................................ 21 1 The clinical picture ........................................................................................... 25 1.1 Acute pain: mechanisms and clinical applications .................................... 25 1.2 Adverse physiological and psychological effects of pain ............................ 29 2 Acute pain services .......................................................................................... 31 3 Principles of acute pain assessment and management ................................ 35 3.1 Assessment of pain and pain history ......................................................... 35 3.2 Diagnosing neuropathic pain ..................................................................... 39 3.3 Agents used to manage acute pain............................................................. 40 3.4 Education about pain management ........................................................... 42 4 Acute postoperative pain management in adults ......................................... 45 4.1 Agents used in postoperative analgesia..................................................... 45 4.2 Pain management plans ............................................................................ 81 4.3 Special postoperative patients optimising pain relief ............................ 83 5 Obstetric analgesia .......................................................................................... 87 6 Pain in children ................................................................................................. 93 6.1 Assessment of pain in children .................................................................. 94 6.2 Procedures and pain................................................................................... 95 6.3 Management of pain associated with paediatric surgery .......................... 98 6.4 Managing postoperative pain in neonates and infants............................ 106 6.5 Pain in children with cancer .................................................................... 107 7 Burns and trauma pain ................................................................................... 109 7.1 Emergency phase ..................................................................................... 109 7.2 The healing phase .................................................................................... 110 7.3 The rehabilitation phase .......................................................................... 111 8 Acute pain associated with medical conditions .......................................... 115 8.1 Cardiac pain............................................................................................. 115 8.2 Acute herpes zoster infection (shingles)................................................... 116 8.3 Acute abdominal pain .............................................................................. 117 8.4 Acute headache ........................................................................................ 120 8.5 Acute pain in haemophilia/haemarthrosis............................................... 125 8.6 Acute dental and orofacial pain ............................................................... 126 8.7 Acute musculoskeletal pain ..................................................................... 126 8.8 Sporting injuries ...................................................................................... 137
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9 Acute pain in patients with cancer or HIV/AIDS ........................................... 139 9.1 Acute pain in patients with cancer .......................................................... 139 9.2 Acute pain in patients with HIV and AIDS ............................................. 148 10 Adjuvant agents and the treatment of acute neuropathic pain ................ 151 10.1 Adjuvant agents in the treatment of acute pain ..................................... 151 10.2 Treatment of acute neuropathic pain....................................................... 152 11 Patients with special needs ............................................................................ 157 11.1 Non-Englishspeaking patients............................................................... 157 11.2 Aboriginal and Torres Strait Island peoples............................................ 157 11.3 Other ethnic groups ................................................................................. 158 11.4 Patients with psychiatric illnesses........................................................... 158 11.5 Elderly patients........................................................................................ 159 11.6 Management of acute pain in opioid-dependent patients ........................ 163 12 Emergency department and intensive care guidelines ............................... 167 12.1 Acute pain in the emergency department................................................ 167 12.2 Issues in intensive care and other critical care settings.......................... 169 Appendixes A: Membership and terms of reference of the Working Party...................... 175 B: Process report........................................................................................... 177 Acronyms and abbreviations ............................................................................. 181 Glossary ................................................................................................................ 183 Bibliography ......................................................................................................... 187 Index..................................................................................................................... 221 This document is a general guide to appropriate practice, to be followed only subject to the clinicians judgement in each individual case. The report is designed to provide information to assist decision making and is based on the best information available at the date of publication.
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List of tables
Table 1.1 Table 2.1 Table 3.1 Table 3.2 Table 4.1 Table 4.2 Table 4.3 Table 4.4 Table 4.5 Table 4.6 Table 4.7 Table 4.8 Table 7.1 Metabolic and endocrine responses to surgery ................................... 30 Organisational aspects of a postoperative pain program ................... 32 Taking a pain history.......................................................................... 37 Features that suggest neuropathic pain............................................. 39 Summary of pharmacological interventions ....................................... 45 Suggested starting doses for IM/SC morphine and IM pethidine in adults .............................................................................................. 47 Equi-analgesic doses of opioid............................................................. 48 Sedation score ..................................................................................... 51 Comparison of representative agents from anti-emetic drug classes . 54 Important elements of intravenous PCA preprinted orders ............... 61 Commonly prescribed initial values for intravenous PCA variables.. 62 NSAID dosages and pharmacokinetic data ........................................ 75 Opioid doses in children.................................................................... 101 Causes of abdominal pain ................................................................. 118
Table 6.1
Table 8.1 Table 8.2 Table 8.3 Table 8.4
Table 9.1 Table 9.2 Table 9.3
Table 10.1 Table of adjuvant agents................................................................... 151 Table 10.2 Proposed mechanisms of action of certain adjuvant agents ............. 152 Table 10.3 Efficacy of anticonvulsants for neuropathic pain ............................. 153 Table 12.1 Red flags against the use of nitrous oxide....................................... 168
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Management of burn and trauma pain............................................. 112 Causes of headache ........................................................................... 120
Red flags for potentially serious spinal conditions ........................... 127 Pointers to serious sporting injury ................................................... 138 Acute pain associated with direct tumor involvement...................... 143 Acute pain associated with cancer therapy ...................................... 144 Common painful syndromes in HIV/AIDS........................................ 149
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Preface
One of the acknowledged tasks of medicine and other healing sciences through the ages has been to seek to relieve pain. While acknowledging with sensitivity the differing philosophical approaches to pain, and the genuine pursuit by some of deep and spiritual meaning in suffering and pain, medicine has sought out ways whereby effective relief can be given to patients when desired. This report is concerned with the scientific basis of pain relief how relief can be best achieved for pain that occurs suddenly and which may be attributable to different causes. It enunciates principles for the relief of acute pain based on the best scientific evidence currently available. It does not concern pain that is chronic or long lasting and which requires management of a different style and order. The disabling impact of acute pain as experienced by individuals can also be located within a social context. In Australian society, rough estimates suggest that the financial costs associated with severe unrelieved pain may be as high as $10 billion a year. Acute pain thus must rank with the more serious causes of contemporary morbidity in our society, and be one of the most expensive. The intention of the National Health and Medical Research Council in publishing this report is to make accessible to health care professionals, patients and their carers and friends, scientific evidence which might be used in finding the best pathway to relief. I thank the authors for their diligence and attention to critically important detail, and all those who contributed through consultation to its final form. On behalf of the National Health and Medical Research Council, I commend this document to its wide, intended audience.
Richard Larkins Chairman National Health and Medical Research Council
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Executive summary
Despite numerous advances in the field of medicine, the management of acute pain fails to be given appropriate priority and acute pain is not properly treated in a variety of clinical situations. One survey found that 77 per cent of adults believed that postoperative pain is to be expected, with almost 60 per cent regarding this as their primary fear before surgery (level III; Warfield & Kahn1995). Unfortunately, these fears are justified, given that the traditional and common practice of administering as needed intramuscular opioids in the past has led to unrelieved pain in more than half of postoperative patients (level III; Austin et al 1980, Oden 1989). A National Health and Medical Research Council (NHMRC) report on the management of severe pain (1988, p vii) found that changes are called for in training, knowledge, attitudes and practice of medical, nursing and allied professionals, along with greater public awareness and expectations in the treatment of pain.
Reasons for ineffective analgesia
The common idea that pain is merely a symptom and not harmful in itself. The mistaken impression that analgesia makes accurate diagnosis difficult or impossible (level II; Attard et al 1992). Fear of the potential for addiction to opioids. Concerns about respiratory depression and other opioid-related side effects such as nausea and vomiting. Lack of understanding of the pharmacokinetics of various agents. Lack of appreciation of variability in analgesic response to opioids. Prescriptions for opioids which include the use of inappropriate doses and/or dose intervals. Misinterpretation of doctors orders by nursing staff, including use of lower ranges of opioid doses and delaying opioid administration. The mistaken belief that patient weight is the best predictor of opioid requirement. The mistaken belief that opioids must not be given more often than four hourly. Patients difficulties in communicating their need for analgesia. (level IV; Cousins & Phillips 1986, Macintyre & Ready 1996)
In the literature, there are a number of references on the topic of ethics in the management of pain. In this material there is a clear directive that clinicians have a moral obligation to treat pain effectively as one of a patients basic rights. A survey over time of nursing attitudes to ethical issues frequently encountered in clinical practice found that pain relief and its management rated the highest (level III; Omery et al 1995). Most evidence for inadequate relief of pain concerns postoperative pain. Postoperative pain should not be thought inevitable, harmless or merely a discomfort to be tolerated. Although the evidence is less well documented, it appears that the treatment of pain is also inadequate for acute trauma, burns, childbirth and in children and the elderly. 9
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The American Pain Society has identified a number of key strategies to improve acute pain management including: recognition and prompt treatment of pain; making information about analgesics readily available; defining policies for use of advanced analgesic technologies; and examining the process and outcomes of pain management with the goal of continuous improvement (American Pain Society 1995). The widespread inadequacy of acute pain management has prompted recent efforts by multiple health care disciplines, including surgery (Royal College of Surgeons & College of Anaesthetists 1990), anaesthesia (Phillips & Cousins 1986, Ready et al 1988, Macintyre & Ready 1996); nursing (American Nurses Association 1991), and national and international bodies (NHMRC 1988, American Pain Society 1990, Ready & Edwards 1992). This NHMRC report attempts to update earlier reports and present statements for management based on recent evidence, in an Australian context.
Principles of pain management

Principles of postoperative pain management (applicable in all areas of acute pain management).
Adverse physiological and psychological effects result from unrelieved severe pain. Proper assessment and control of pain require patient involvement, frequent assessment and re-assessment of pain intensity and charting of analgesia. Effective pain relief requires flexibility and tailoring of treatment to an individual rather than rigid application of formulae and prescriptions. Pain is best treated early because established, severe pain is more difficult to treat (Bach et al 1988, Katz et al 1996). While it is not possible or always desirable to completely alleviate all pain in the postoperative period, it should be possible to reduce pain to a tolerable or comfortable level. Postoperative analgesia should be planned pre-operatively, with consideration given to the type of surgery, medical condition of the patient, peri-operative use of analgesics and regional anaesthetic techniques. Postoperative physical therapy requirements for early mobilisation should be discussed with the patient and the timing of appropriate and adequate analgesia and early physical therapy requirements considered. Ultimate responsibility for pain management should be assigned to those most experienced in its administration and not to the most junior staff members. Safe and effective analgesia depends on: adequate education of all involved in pain management, including the patient; formal programs, protocols and guidelines covering acute pain management relevant to the institution; and formal quality assurance programs to regularly evaluate the effectiveness of pain management. (adapted from AHCPR 1992)
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Executive summary
Summary of scientific evidence and key management points

Statements of evidence (for which there is level I, II or III evidence as defined on page 23) are presented in each section of the report. They are also presented in this summary section, for quick reference. Readers should turn to the appropriate sections to understand the context of this evidence (relevant page numbers are indicated for each statement of evidence). The key points are observations about management which are rated level IV (the opinions of respected authorities based on clinical experience, descriptive studies or reports of expert committees).
Acute pain services

Key points
A multidisciplinary approach to the management of acute pain, particularly in a formal acute pain service, leads to improved pain relief and better patient outcomes. Effective pain management is fundamental to the quality of care. The key to successful pain management is education and training of all staff.
Assessment of pain
Key points
Careful assessment of pain should occur initially and then regularly throughout treatment, using self-reporting techniques. As pain varies so markedly between individuals, patient involvement in the initial and continuing assessment of their pain is essential. Pain should be assessed both at rest and during activity and pain relief assessed as to its adequacy to allow appropriate function. Unexpected levels of pain or pain that suddenly increases, especially when associated with changes in other vital signs, may signal the development of a new surgical or medical diagnosis (eg postoperative complication, neuropathic pain). Although not specific, an important indicator of neuropathic pain is the inability to relieve pain with opioids, or no apparent relief of pain with a rapidly increasing opioid dose. Other indicators can be obtained from the history and physical examination, as shown in Table 3.2 on page 39.
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Acute postoperative pain management in adults

General Statements of evidence 1 p 52 As significant background and/or intermittent hypoxaemia may occur for a number of days postoperatively, supplemental oxygen is recommended for at least the first 48 to 72 hours following major surgery and in elderly or high-risk patients, regardless of the analgesic method used. Multimodal analgesia (ie the combined use of different classes of analgesics) improves the effectiveness of pain relief after surgery. There may also be an associated reduction of the dose of each analgesic drug and the intensity of any side effects. Studies to date suggest that more aggressive, and possibly pre-emptive, approaches to the management of early postoperative pain may reduce the transition to chronic postoperative pain. Level of evidence
III Reeder et al 1992a
2 p 76
II Kehlet & Dahl 1993a, 1993b, Power et al 1994, Schulze et al 1988, Brodner et al 1998 II Katz et al 1996; Bach et al 1988
3 p 77
Opioid analgesia Statements of evidence 4 p 60
Patient-controlled analgesia (PCA) managed by an acute pain service (APS) or by non-pain specialist health professionals is associated with similar pain scores; however the incidence of side effects is lower in patients whose PCA is managed by an APS. Further well designed studies are needed to evaluate how supervision of PCA by an APS affects cost, quality of care and patient satisfaction.
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Level of evidence
III Stacey et al 1997
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PCA has been shown to provide greater patient satisfaction and improved ventilation compared to conventional routes of administration.
II McArdle 1987
Key points
Respiratory depression and hypoxia are often feared consequences of opioid administration but can generally be avoided with careful titration and individualisation of dose. A decrease in respiratory rate has been found to be a late and unreliable clinical indicator of respiratory depression. Sedation is a better indicator and all patients on opioids should be monitored using a sedation score. To attain therapeutic effects with minimal adverse effects, it is necessary to individualise and titrate doses of opioids. This relies on using age as the initial guide for dosage range (in adults), and the use of dose intervals appropriate to the route of administration, monitoring of pain and sedation scores, respiratory rate and other side effects.
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Executive summary Key points (cont)
The aim of analgesia should be patient comfort with minimal sedation and impairment of respiratory function (eg sedation score of less than 2 and respiratory rate greater than 8/minute). A true allergy to opioids is very uncommon. As with any drug, the term allergy is often mistakenly applied to an intolerance to the drug, a common side effect, or a dose-related effect. There is no evidence that the use of opioids for treatment of severe pain leads to opioid dependence or addiction. Traditional methods of opioid administration include oral, intramuscular, subcutaneous, intravenous and continuous intravenous routes. These methods each have advantages and disadvantages in different groups of patients, but are more likely to be effective when the dosage regimen is tailored to the individual. The patients need for pain relief should be seen as more important than strict adherence to a dose interval. Patient-controlled analgesia (PCA) allows patients to adjust the degree of pain relief to their own desired level of comfort and tolerance of side effects. Adequate knowledge of patient-controlled analgesia (PCA) is essential to avoid documented serious outcomes. Regional techniques
Key point
Regional methods of pain relief using local anaesthetic, either alone or in combination with systemic analgesia, can be effective after a number of localised procedures. Epidural analgesia Statements of evidence
6 Postoperative epidural analgesia can significantly p 65 reduce the incidence of pulmonary morbidity.
7 Large audits of closely supervised epidural analgesia p 65 show the safety of the technique to be equivalent to that of traditional analgesic methods when coordinated by an acute pain service with appropriate patient observations and monitoring. 8 Epidural opioids are more effective when used in p 65 combination with local anaesthetic to produce a synergistic analgesic action and reduce the required dose and side effects associated with either the local anaesthetic or opioid alone.
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Level of evidence
I Ballantyne et al 1998 III Ready et al 1991, Schug & Torrie 1993, Scott et al 1995, Tanaka et al 1993, Breivik 1996; Rawal & Allvin 1996 I Wiebalck et al 1997
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Non steroidal anti-inflammatory drugs (NSAIDs) Statements of evidence 9 While the currently available NSAIDs do not relieve p 72 severe pain when used alone, their efficacy as components of multimodal analgesia has been confirmed by clinical trials.
Level of evidence
I McQuay & Moore 1998, Royal College of Anaesthetists 1998 II Power et al 1990, 1994, Cepeda et al 1995, Pavy 1995, Liu et al 1995a II, III Power et al 1992, Strom et al 1996; Gillis & Brogden 1997; Feldman et al 1997; Merry & Power 1995: Jaquenod et al 1998
10 The adverse effects of NSAIDs are potentially p 72 serious and it is imperative that contraindications are respected.
Non-pharmacological methods Statement of evidence
11 In 15 of 17 randomised controlled trials of transcutp 80 aneous electrical nerve stimulation (TENS) in postoperative pain, there was no benefit compared with placebo. In excluded non-randomised studies there was an overestimation of treatment effects of TENS.
Key point
Although evidence for the efficacy of non-pharmacological modalities such as physical therapeutic agents and modalities such as spinal manual therapy, mobilisation, application of superficial heat or cold, massage, exercise, transcutaneous electrical nerve stimulation (TENS) therapy and acupuncture in acute pain management is largely at the expert opinion level, certain patients derive benefit from these techniques.
Special postoperative patients

Day surgical patients Statements of evidence
12 A recent meta-analysis confirmed that paracetamol is p 76 an effective postoperative analgesic, and that codeine 60 mg added to paracetamol produces worthwhile additional pain relief even in single oral doses.
13 Pain following discharge from day surgery influences the p 81 time taken to return to normal activity and may lead to further, unplanned hospitalisation. It is recommended that adequate plans are made for post-discharge analgesia.
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Level of evidence
I Carroll et al 1996
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Level of evidence
I Moore & Collins 1997
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III Fancourt-Smith et al 1990, Gold et al 1989
Executive summary Key points
The ability to perform increasingly complex surgery on a day-case basis highlights the need for appropriate screening, selection, pre-operative preparation, treatment and discharge planning for these patients. Pharmacological options for day-case postoperative analgesia include oral opioids, non-steroidal anti-inflammatory drugs (NSAIDs) and local anaesthetics, or combinations of these treatments. Simple oral analgesics such as aspirin and paracetamol are more effective than placebo and should not be overlooked, particularly in cases of mild to moderate pain. Neurosurgical patients
Key point
Pain management in neurosurgical patients employs conventional analgesic agents plus adjuvant agents where appropriate. Extremely careful monitoring is required, including assessment for abnormal neurological signs and symptoms during the postoperative period. Pain and sedation scoring systems should be an integral part of this monitoring.
Obstetric analgesia
14 p 88
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Statements of evidence
Level of evidence
I Howell & Chalmers 1992
Lumbar epidural analgesia is the most effective form of pain relief during childbirth. Using low-dose local anaesthetic/opioid mixtures can significantly reduce the severity of side effects.
15 p 89
Recent studies appear to indicate that there is no increase in caesarean delivery rate associated with epidural analgesia.
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II Sharma et al 1997, Bofill et al 1997
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Key points
All options for pain relief, and their efficacy, should be discussed with the parturient so that she can make an informed decision. Pain relief planned during the antenatal period and implemented during labour should be monitored and appropriately modified during the course of the labour. The wishes of the woman and the well-being of the baby are paramount. Maternal-foetal factors and obstetric management, not epidural analgesia, are the main determinants of caesarean section rates.
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Pain in children
Key points
Regular assessment of pain and monitoring of treatment in children present particular challenges to health carers. Close observation of non-verbal cues and behaviour is important. The use of pain rating scales suitable for the age and developmental stage of the child is essential for the accurate treatment of pain. The child should be respected as an authority on their own pain. Procedural pain in children should be managed systematically, using a combination of analgesia and non-drug strategies and avoiding painful routes of administration where possible. General anaesthesia may be required, especially for frequent painful interventions where other strategies have failed. Drug therapy is the mainstay of postoperative analgesia in children, but non-drug modalities may also be useful. Analgesia should be given by the least painful route where possible. Regular re-evaluation of analgesic efficacy is required. There is no evidence that the use of opioids for treatment of severe pain in children leads to opioid dependence or addiction. PCA provides safe and effective analgesia in children as young as five to six years and offers superior analgesia to intermittent intramuscular injections in children. Regular assessment of vital signs and level of consciousness is necessary when parenteral opioids are used for managing postoperative pain. Regional techniques are almost always employed as an adjunct to general anaesthesia in children, while in adults they are frequently used as a primary technique.
Burns and trauma pain

Key points
Patients with burn or trauma pain need a range of strategies which may differ during the emergency, healing and rehabilitation phases. A combination of nociceptive and neuropathic pain is common and psychological/ environmental factors usually play an important role (eg anxiety, fear of permanent disability or death). Severe pain may persist in the healing and rehabilitation phases; pain treatment is an essential ingredient of an active rehabilitation plan. The use of long-acting oral opioids is appropriate while there is obvious evidence of trauma-associated persisting nociception. Treatment of neuropathy may need to continue well after the healing phase. Unexpectedly prolonged requirement for opioids should prompt referral for multidisciplinary pain unit assessment.
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Executive summary
Acute herpes zoster infection

Statements of evidence 16 p 116 17 p 116 Antiviral agents used early for the treatment of acute herpes zoster infection have been shown to accelerate lesion healing and result in faster resolution of pain. Antidepressants and anticonvulsants are effective in the treatment of neuropathic pain such as postherpetic neuralgia. Level of evidence
I Kost & Straus 1996
I McQuay et al 1996, 1995a
Acute headache
Statements of evidence 18 p 121 A stepwise approach to the use of pharmacological agents in the treatment of migraine is effective. Moderate to severe migraine may require the use of specific antimigraine medications such as ergotamine or sumatriptan, unless contraindicated. The combination of aspirin (900 mg) and metaclopramide is as effective as sumatriptan in the treatment of migraine, is better tolerated and is also considerably cheaper. Pethidine has been found to be no more effective than dihydroergotamine, chlorpromazine or NSAIDs in the treatment of migraine. Level of evidence
III Raskin 1986, Callahan & Raskin 1986
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19 p 121 20 p 121
II Tfelt-Hansen et al 1995
II Lane et al 1989, Stiell et al 1991, Davis 1995, Scherl 1995, Nicolodi 1996
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Key point
There are very few situations in which pethidine is useful in acute migraine, although it may be considered during pregnancy when the use of ergotamine preparations, triptans and dihydroergotamine is contraindicated.
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Acute musculoskeletal pain

Statements of evidence 21 p 131 22 p 131 Treatment for acute lower back pain based on bed rest and immobilisation is ineffective. A return to a normal range of activities as soon as possible leads to more rapid recovery from acute lower back pain than do either bed rest or backmobilising exercises. Spinal manual therapy is used for the treatment of acute lower back pain in the first six weeks following onset of pain. The scientific evidence for its efficacy has yet to be established. The little evidence available about the use of spinal manual therapy for acute neck pain suggests some benefit in mechanical neck pain, although subgroups of patients need to be better identified. Although rare, serious complications have been associated with neck manipulation and such procedures should therefore be performed only by appropriately trained personnel. Level of evidence
I Koes & van den Hoogen 1994 II Malmivaara et al 1995, Hadler et al 1987 I Koes et al 1996
23 p 132
24 p 132
I Gross et al 1998, Shekelle & Coulter 1997, Aker et al 1996. III Hurwitz et al 1996, Rivett & Reid 1998, Rivett & Milburn 1997, Rivett & Milburn 1996 III Wrenn et al 1964, Kapetanos 1982, Wesley et al 1991
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25 p 132
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Corticosteroids are effective anti-inflammatory agents, but are not suitable treatment for acute sporting injuries for up to six weeks after the incident. Experimental studies have shown that corticosteroids may adversely affect normal tissue healing and repair.
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Key points
The key to managing acute lower back pain is to clearly distinguish serious pathology from benign musculoskeletal causes. The treatment of serious spinal pathology requires urgent referral to specialist services. Non-specific backache is best managed using a simple multimodal approach aimed at pain relief, active rehabilitation and return to normal activity. While they do have a role in the treatment of myositis ossificans following intramuscular haematoma, and in the management of chronic sporting injuries, non-steroidal anti-inflammatory drugs (NSAIDs) have not been shown to be effective in the treatment of ligament sprains.
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Executive summary
Acute pain in patients with cancer

Statements of evidence 27 p 144 28 p 146 29 p 147 30 p 147 Oral analgesics are the mainstay of pain relief in patients with cancer. Strong opioids are safe and effective for moderate to severe pain. Radiotherapy plays a major role in the management of acute pain due to cancer. Bisphosphonates have a general role in the treatment of bone pain related to breast cancer and myeloma (and possibly prostate cancer). Epidural, intrathecal and intracerebroventricular opioids are often effective in treating acute pain in patients with cancer that is not controlled with conventional treatment. Level of evidence
I AHPCR 1994b I McQuay 1997 II Purohit et al 1994 III Coleman et al 1997 I Ballantyne et al 1996
Key points
Not all acute pain in patients with cancer is due to the cancer progressing. Optimal communication between oncological, surgical, anaesthetic, and palliative care teams is essential. Even when the cancer is progressing, it is important to consider the anatomic aetiology, as this may be amenable to disease-specific therapy (radiotherapy, chemotherapy, surgery etc). While waiting for specific anti-cancer therapy to work, adequate analgesia must be provided. Invasive procedures (spinal opioids, nerve blocks etc) are occasionally required. Acute pain in cancer patients often takes place against a background of chronic pain and therefore existing analgesic use. An integral part of management is the recognition and treatment of procedural pain and breakthrough pain. The barriers to management of pain in cancer patients must be recognised and overcome if possible.
Acute pain in patients with HIV/AIDS

Key points
Acute pain in HIV/AIDS patients often has more than one cause and location and tends to increase in severity with disease progression. Intervention requires a multidisciplinary approach. A careful history and physical examination commonly identifies treatable pain syndromes seen in HIV/AIDS. Determination of the level of immunosuppression in patients presenting with pain is a critical diagnostic manoeuvre, as immunocompetent patients are more likely to have benign conditions than infections or malignancies.
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Adjuvant agents and the treatment of neuropathic pain

Statement of evidence 31 p 152 Anticonvulsants and antidepressants have been shown by meta-analysis to be effective in the treatment of neuropathic pain. Level of evidence
Key point
The effectiveness of anticonvulsants and antidepressants in the treatment of pain needs to be balanced against their potential adverse effects.
Pain in the elderly

Statement of evidence 32 p 161 Non-steroidal anti-inflammatory drugs (NSAIDs) should only be used with extreme caution in elderly people. For non-inflammatory complaints, paracetamol and/or low-dose opioids are recommended. Low-dose corticosteroids may be appropriate in inflammatory conditions. Level of evidence
III Roth 1989
Key point
Effective pain management in elderly people needs to consider a number of factors which may complicate management, including co-existent pathologies, multiple medications, altered pain response and cognitive impairment.
Emergency department and critical care

Statements of evidence 33 p 168 34 p 169 Level of evidence
II Attard et al 1992, Zoltie & Cust 1986 II Hetherington & Philp 1986 Walden et al 1993
Key points
In most acute care situations in the emergency department, the intravenous route of opioid delivery is by far the most efficacious and is therefore preferable. All of the techniques and drugs used to treat acute postoperative pain, including non-drug techniques, are potentially applicable in intensive care units.
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Early administration of opioids in patients with an acute abdomen does not reduce the detection rate of serious pathology, but may actually facilitate it. Non-steroidals have been shown to be more effective than opioids in relieving the pain of renal colic. A comparative study of an intramuscular NSAID and intramuscular opioid has verified the efficacy of NSAIDs in this indication. Comparison of two NSAIDs, diclofenac and ketoprofen, in another study found them to be equally effective in relieving the pain of acute ureteral colic.
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Introduction
Background
The National Health and Medical Research Council (NHMRC), through its Quality of Care and Health Outcomes Committee (QCHOC), established a working party in 1996 to review the scientific evidence for the management of acute pain. The initiative is part of a national program to promote the development of evidencebased clinical practice guidelines aimed at improving both the quality of health care and health outcomes. Acute pain was identified by health professionals and consumers as an area where a review of the scientific evidence would be valuable. This is because there has been no coordinated multidisciplinary approach to the treatment of acute pain, and it is undertreated in a variety of clinical situations. This report aims to assist health professionals in the management of acute pain of various types, including: postoperative and post-trauma pain; diverse acute medical conditions such as cardiac pain, acute herpes zoster infection (shingles), acute abdominal pain and acute headache; acute exacerbations of pain in patients with cancer and in chronic illnesses or degenerative diseases; and specialised forms of acute pain such as that during childbirth, pain from burns and pain from sporting injuries. The approach taken in these categories is to emphasise strategies that are common to the treatment of all patients with acute pain, and to highlight approaches used in the specialised setting which may sometimes be valuable in other settings of acute pain management. The report was prepared by a working party and consultant group, which used as their framework the document Guidelines for the Development and Implementation of Clinical Practice Guidelines (NHMRC 1995). Care was taken to include representatives from the disciplines and professional organisations that have a significant role in the treatment of acute pain, as well as a consumer representative. An evidence-based approach was fundamental to the preparation of the report (see levels of clinical evidence on page 23). The report was developed within the context of a number of reviews of the literature and guidelines on acute pain management. The following were major sources of information. The Oxford Pain Research Group headed by Dr H McQuay and Dr RA Moore. The group provided a database of several thousand randomised prospective controlled trials which have been carefully scrutinised and culled. It also gave information about all of the currently published meta-analyses in the field of pain management and generously provided in press manuscripts of meta-analyses. An important evidence-based resource for pain relief has recently been published by the Oxford Group with a broad range of critical analyses of pain relief treatments which include acute pain management (McQuay & Moore 1998).
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Clinical practice guidelines on acute pain management published by the Agency for Health Care Policy and Research (AHCPR) of the United States Department of Health and Human Services. The same agency has prepared guidelines on cancer pain management (AHCPR 1994a) and on acute lower back pain (AHCPR 1994b), and these also served as helpful source documents in the preparation of this report. The assistance of Dr D Carr is acknowledged. In addition, a number of professional organisations and official bodies provided material which is acknowledged at appropriate places in the report.
Scope
This report presents statements to assist clinical decision making, based on the synthesis of available evidence. It is not intended to replace clinical judgement but provides a consensus from a wide body of documented knowledge. The report is intended for health care practitioners engaged in the care of patients experiencing acute pain. It is likely that all medical and allied health professionals will be involved in the management of patients with acute pain at some point in their practice. This report cannot provide complete coverage of all recent developments in the treatment of acute pain. Nor can it cover in detail all of the treatment modalities used in the many specialised situations in which acute pain is managed. However, an attempt has been made to highlight the major aspects of new knowledge and to provide key references that will allow a deeper perusal of this material. A deliberate effort has been made to identify the main treatment options that may be applicable across the broad range of acute pain problems. It is hoped that this will stimulate a re-evaluation of methods and approaches that are currently not utilised in some patients and in some situations of acute pain management. It has now become clear that the provision of appropriate pain relief does not impair the diagnosis of acute conditions, nor does it mask the appearance of complications. Health care professionals and patients should be aware that patients have a right to effective treatment of acute pain, limited only by availability of methods that can be safely applied in their particular situation. There is substantial, and quite deliberate, overlap in the report concerning the treatment of pain in cancer patients and chronic non-cancer pain, mainly with respect to acute exacerbations of pain. However, reference is also made to the potential preventative role of early intervention in persistent acute pain, as a method of preventing chronic pain. The Working Party has taken care not to encroach otherwise on the important subjects of cancer pain and chronic non-cancer pain; it is strongly recommended that separate reports be written on both these areas of pain management. This is a high priority in view of the enormous individual, family and community suffering and the financial costs of severe unrelieved pain, currently amounting to more than $10 billion annually in Australia.
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Introduction
Levels of clinical evidence

This report has been written in a way that enables readers to judge the strength of the evidence on which statements of evidence are based. In relation to issues of effectiveness of health care, the report uses the four-point rating system given below to identify the evidence base for key decision points. The rating system has been adapted from the system developed by the United States Preventive Services Task Force and is recommended by the NHMRC (1995).
Levels of evidence ratings Level I Level II Level III
Evidence obtained from systematic review of relevant randomised controlled trials (with meta-analysis where possible). Evidence obtained from one or more well-designed randomised controlled trials. Evidence obtained from well-designed non-randomised controlled trials; OR from well-designed cohort or case-control analytical studies, preferably multicentre or conducted at different times. The opinions of respected authorities based on clinical experience, descriptive studies or reports of expert committees.
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Level IV
While level I evidence represents the desired standard on which to base clinical decision making, treatment based on other levels of evidence can be used in appropriate circumstances. Level I evidence was not available for many areas in the report. It is hoped that, in a future revision of the report, it will be possible to commission further meta-analyses for major areas in the document that currently lack such evidence. In discussion with the Oxford group, many such areas have been identified, however major metaanalysis can take up to 12 months, at significant cost. It is hoped that their work will act as a focus to stimulate the formation of subgroups in a number of countries, to carry out meta-analyses in a cooperative manner. This will ensure that the field of acute pain management is based upon a comprehensive evidence-based approach.
Information for consumers
In addition to this report, the NHMRC will also publish a consumers guide on acute pain management which is intended to inform patients, their families and carers, and members of the general community about the current status of acute pain management, the options available to consumers, and the best ways for them to communicate with health care professionals in order to obtain effective and safe pain relief.
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Implications for general practice

The general practitioner (GP) is in the front line for a wide range of the presentations of acute pain described in this report. It is estimated that back pain accounts for about one third of the total costs of chronic pain and associated disability. This emphasises the total size of the problem of back pain, which mostly falls into the area of general practice. Early and appropriate interventions by the GP can have a major impact in improving assessment and treatment of acute back pain. Other opportunities exist for improved assessment and treatment strategies that can be implemented in general practice. Examples include acute herpes zoster infection, acute abdominal pain, acute headache, acute exacerbations of pain in cancer patients, acute pain in haemophilia/haemarthrosis, acute pain in HIV/AIDS, acute orofacial pain, acute musculoskeletal pain and severe dysmenorrhoea. The GP is also commonly called upon to deal with patients with special needs and some who need emergency care. In some settings, particularly rural and remote areas, GPs may be involved in acute pain management in association with adult post-surgical patients, obstetric patients, paediatric patients and burns and trauma. In these more demanding areas of acute pain management, GPs will need to make an assessment of their own expertise and the local facilities and support staff, in deciding which treatments are appropriate in the particular setting of their own practice. Obviously, some of the highly specialised methods of pain relief may not be feasible or safe in some general practice environments. A particular challenge for GPs in managing forms of acute pain such as back pain and headache, is to practice a coordinated care approach, strongly anchored in evidencebased medicine. Thus GPs should use the evidence presented in this report to consider the options for their patients, choosing only those options where there is sound evidence, and continue to play a role in coordinating each aspect of the patients care and the duration of such care. An excellent example of this approach is the management of acute musculoskeletal pain (see Section 8.7 on page 126 and associated figures/tables). A Quick Reference Guide for GPs will be derived from this report, to provide quick access to the major management points of relevance to GPs.
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1.1
The clinical picture

Acute pain: mechanisms and clinical applications
Definition of acute pain

According to the International Association for the Study of Pain (IASP), pain is a sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage (level IV; Merskey 1979). This definition applies to acute pain, cancer pain and chronic non-cancer pain. The IASP defines acute pain as: pain of recent onset and probable limited duration. It usually has an identifiable temporal and causal relationship to injury or disease. This is in distinction to chronic pain which is defined as pain lasting for long periods of time. Chronic pain commonly persists beyond the time of healing of an injury and frequently there may not be any clearly identifiable cause. (Ready & Edwards 1992) While there is no absolute distinction between acute pain and chronic pain, this definition is still useful because there are many areas of difference in their management. Evidence from experimental models is revising concepts of pain mechanisms. This has implications for clinical practice, as it enables treatments to be based on scientific principles rather than on traditions. In areas in which pain mechanisms are still poorly understood (eg neuropathic pain) there is a lack of effective treatment options (Siddall & Cousins 1995a).
Pain perception and pain pathways
Pain perception involves multiple interacting central and peripheral mechanisms. In addition, pain is multifactorial and involves physical, psychological and environmental aspects in every individual. Acute pain begins when algogens (pain-causing substances) are released at the site of injury. They stimulate the nerve endings of small fibres (nociceptors) which transmit the signal into the dorsal horn of the spinal cord (nociception). The signal is then projected into specific areas of the brain. At all points of this pain pathway, there are responses which can increase or decrease the duration and nature of the pain perceived. For example, nociceptors may be activated by simple direct pressure, chemical or heat stimuli. These may be exaggerated by sensitisation from multiple inflammatory mediators including substance P, serotonin, bradykinin and the products of arachidonic acid metabolism (Campbell et al 1989). These mediators create a sensitising soup which is responsible for primary hyperalgesia (increased pain in response to painful stimuli in the injured area) and which contains components modifiable by non-steroidal anti-inflammatory drugs (NSAIDs) (Vane 1971). While opioids have been considered to exert their action in central pathways, receptors for opioids at peripheral sites may exist following tissue damage (Bentley et al 1981, Stein 1995). Unmyelinated primary afferent neurons that respond actively only in the presence of chemical sensitisation have been identified (Schaible & 25
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Acute pain management: scientific evidence Schmidt 1988). These silent nociceptors require further study to determine their exact role in pain transmission but highlight the important role that peripheral mechanisms have in pain perception.
In practice, pain is characterised by both peripheral sensitisation as described above (see Figure 1.2) and central sensitisation, which occurs by means of a change in the excitability of neurons in the spinal cord. This brings about a number of changes including an increased area of the periphery provoking a response in dorsal horn neurons, an increased duration of response and a decrease in the threshold to activation (see Figure 1.1). These progressive changes in the response of spinal cord neurons have been termed wind-up. The results of this combined sensitisation are allodynia (pain in response to stimuli not normally associated with pain) and secondary hyperalgesia (increased pain in response to painful stimuli in areas away from the injured area).
Primary afferent fibres, the dorsal horn and descending modulation

Following activation of primary afferent neurons, release of substances from these fibres at their termination in the dorsal horn activates spinothalamic, spinoreticular and other ascending pain pathways (see Figure 1.1). Section of these primary afferent fibres (eg during an operation) can result in a variety of anatomical, physiological and biochemical changes arising from aberrant activity at the periphery, at dorsal root ganglia and at dorsal horn neurons. Changes in the dorsal horn mediate central sensitisation, resulting in secondary hyperalgesia in areas remote from the site of initial injury, and allodynia as described above. Descending modulation from higher centres provides a powerful inhibitory system to modify these enhanced neuronal responses (see Figure 1.3).
Figure 1.1 Under physiological conditions, low intensity stimuli activate low threshold receptors to generate non-painful sensations and high intensity stimuli activate high threshold nociceptors which may lead to pain transmission. In clinical practice, central and peripheral changes lead to abnormal excitability in the nervous system. This means that low intensity stimuli are able to produce pain (figure adapted from Woolf & Chong 1993).
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Peripheral Sensitisation
Tissue damage Inflammation Sympathetic terminals
Sensitising soup
Hydrogen ions Noradrenaline Bradykinin Histamine Potassium ions Prostaglandins Purines Cytokines 5-HT Leucotrienes Nerve growth factor Neuropeptides High threshold nociceptor Transduction sensitivity Low threshold nociceptor
*5-HT = 5-hydroxytryptamine
Figure 1.2 The sensitivity of high threshold nociceptors can be modified in the periphery by a combination of chemicals that act as a sensitising soup. These chemicals are produced by damaged tissue, as part of the inflammatory reaction, and by sympathetic terminals (from Woolf & Chong 1993).
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Figure 1.3 Simplified schema of afferent sensory pathways (left) and descending modulatory pathways (right). Stimulation of nociceptors in the skin surface leads to impulse generation in the primary afferent. Concomitant with this impulse generation, increased levels of various endogenous algesic agents (substance P, prostaglandins, histamine, serotonin, bradykinin) are detected near the area of stimulation in the periphery. Primary afferent nociceptors relay to projection neurons in the dorsal horn, which ascend in the anterolateral funiculus to terminate in the thalamus. En route, collaterals of the projecttion neurons activate multiple higher centers, including in the nucleus reticularis gigantocellularis (NRG). Neurons from the NRG project to the thalamus and also activate the nucleus raphe magnus (NRM) and peri-aqueductal grey (PAG) of the midbrain. Descending fibres from the PAG project to the NRM and reticular formation adjacent to the NRM. These neurons activate descending inhibitory neurons which are located in these regions and travel via the dorsolateral funiculus to terminate in the dorsal horn of the spinal cord. Descending projections also arise from a number of brainstem sites including the locus ceruleus. A number of neurotransmitters are released by afferent fibres, descending terminations, or local inter neurons in the dorsal horn and modulate peripheral nociceptive input. These include substance P, gamma-aminobutyric acid (GABA), serotonin, noradrenaline, enkephalin, neurotensin, acetylcholine, dynorphin, cholecystokinin, vasoactive intestinal peptide, calcitonin-gene-related peptide, somatostatin, adenosine, neuropeptide Y, glutamate, nitric oxide, bombesin and prostaglandins. Inhibitors of enzymes such as enkephalinase, acetylcholinesterase and nitric oxide synthase may act to modify the action of these neurotransmitters (from Cousins & Bridenbaugh 1998).
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1.2
Adverse physiological and psychological effects of pain
Acute pain is a symptom which signals tissue damage or impending tissue damage (Ready & Edwards 1992). While there are clear ethical reasons for reducing pain, the requirement for analgesia in order to modify the injury response is less apparent. Generally, the intensity of the injury response is proportional to the degree of tissue trauma (Chernow 1987), but is influenced by a variety of other factors (see Figure 1.4). Substances released from injured tissue evoke stress hormone responses in addition to activation of cytokines, adhesion molecules and coagulation factors (Fong et al 1994). The end result of these responses consists of numerous physiological changes promoting catabolism, sympathetic activation, hypercoagulability, immunosuppression and other adverse states. Adverse cardiovascular effects including hypertension, tachycardia and increased cardiac work may result from unrelieved pain and may compromise at-risk cardiac patients. Respiratory effects of unrelieved pain can also result in substantial reductions in respiratory parameters and the ability to cough. The psychological effects of pain may be less readily observed but are no less harmful and interact with physical alterations, often as part of a vicious cycle (see Figure 1.5) (Cousins & Phillips 1986, Dinarello 1984).
Postoperative pain Surgical trauma
Psychological, environmental factors Other factors (eg drugs)
Figure 1.4 Note that pain is only one of the factors, including psychological and environmental factors, that trigger complex intermediates (neural, humoral etc) leading to the injury response. Thus, acute pain and the injury response are inevitably inter-related. The end result is physical and mental deactivation. It is therefore appropriate to regard an acute pain service as one of pain management and acute rehabilitation (see Cousins 1989).
Physiological changes brought about by pain are produced by activation of both the peripheral and central nervous systems (Woolf 1989, Kehlet 1997). Changes that reflect the stress response include alterations in all major organ systems with a predominant input from the neuroendocrine system (see Table 1.1). It should be noted that effective analgesia is capable of modifying many of these responses, thereby assisting recovery. Patients at great risk of adverse outcomes from unrelieved pain include those with concomitant medical illness, those undergoing major surgery (eg repair of abdominal aortic aneurysm) and the very young or very old.
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INJURY RESPONSE including: Inflammation Hyperalgesia Catabolism Other systemic adaptations Physical, mental deactivation
Acute phase cytokines (eg Interleukin 1,6) Neural
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Humoral Metabolic Immune
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Anxiety
Pain
Sleeplessness
Figure 1.5 Vicious cycle of pain, anxiety and sleeplessness.
Psychological factors have been closely linked to the exacerbation or, when favourable, the diminution of pain. Psychological determinants that may positively or negatively influence the experience of pain include: fear and anxiety; depression; the degree of control felt by the patient over their pain and disease; learned responses to pain; the meaning of pain to the patient; and the personal consequences of both the pain and its cause. The endocrine and metabolic responses to surgery are summarised in Table 1.1.
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Anabolic hormones
Table 1.1
Metabolic and endocrine responses to surgery Catabolic hormones ACTH, cortisol, ADH, growth hormone, catecholamines angiotensin II, aldosterone, glucagon, IL-1, TNF, IL-6 insulin, testosterone hepatic glycogenolysis, gluconeogenesis (cortisol, glucagon, growth hormone, adrenaline, free fatty acids) insulin secretion/action cortisol, adrenaline, glucagon, IL-1, IL-6, TNF
Endocrine
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Metabolic Carbohydrate
Hyperglycaemia, glucose intolerance, insulin resistance
Protein Fat Water and electrolyte flux
Muscle protein catabolism, synthesis of acute phase proteins Increased lipolysis and oxidation Retention of water and sodium, excretion of potassium and functional ECF with shifts to ICF
ACTH=adrenocorticotropic hormone; ADH=antidiuretic hormone; IL=interleukin; TNF=tumour necrosis factor; ECF=extracellular fluid; ICF=intracellular fluid
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Acute pain services
Sophisticated methods of pain relief, such as epidural analgesia and patientcontrolled analgesia (PCA), have been used for the management of postoperative pain since the early 1980s. However, their widespread use, particularly in general wards, was not common until the introduction of a more organised approach to acute pain management and the establishment of acute pain services. Acute pain services generally include at least members of the medical and nursing staff. In institutions where such teams cannot be recruited, responsibility is usually given to particular members of staff. Anaesthetists have been identified as being particularly qualified to develop and manage acute pain teams because the knowledge and techniques employed are extensions of those used in anaesthesia (level IV; Ready et al 1988). The first acute pain service (APS) was established in 1986 at the University of Washington, Seattle (Ready et al 1988). Services began to develop worldwide in the late 1980s (Macintyre et al 1990, Wheatley et al 1991). Around that time, a report of the Royal College of Surgeons of England and College of Anaesthetists (Royal College of Surgeons of England & College of Anaesthetists 1990) recommended that acute pain teams be established in all major hospitals. Similarly, the US Department of Health and Human Services recommended a formal, team approach to the management of acute pain with clear lines of responsibility (AHCPR 1992). A formal acute pain service can offer: education about acute pain management in general as well as more specialised analgesic techniques; the introduction of newer and more specialised methods of pain relief and guidance to improve more traditional methods; the provision and standardisation of orders, procedures and methods of pain assessment for all methods of pain relief, as well as ongoing improvement to these based on the results of audit activity; daily supervision and 24-hour cover for patients under the care of the acute pain service, as well as for patients with any other acute pain management problems; and audit and clinical research activity. Details of these aspects are given in Chapter 4. In order to fulfil these roles effectively, a coordinated team approach is essential. The American Society of Anesthesiologists (ASA) guidelines summarise suggested organisational aspects of an acute pain service (see Table 2.1).
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Acute pain management: scientific evidence Table 2.1 Organisational aspects of a postoperative pain program
1 Education (initial, updates): Anaesthetists Surgeons Nurses Pharmacists Patients and families Hospital administrators Health insurance carriers 2 Areas of regular administrative activity: Maintenance of clear lines of communication Workforce24-hour availability of pain service personnel Evaluation (including safety) of equipment (eg pumps) Secretarial support Economic issues Continuous quality improvement
Resident medical teaching (if applicable) Pain management-related research 3 Collaboration with nursing services: Nursing policies and procedures
Job description of pain service nurse (if applicable) Nurses in-service and continuing education Definition of roles in patient care Institutional administrative activities Continuous quality improvement Research activities (if applicable) 4 Elements of documentation Preprinted orders Procedures Protocols Daily consultation notes Educational packages Modified from Ready et al 1995.
Bedside pain management flow sheets
As part of this multidisciplinary approach, all medical and paramedical staff have a role to play in pain management, whether there is a formalised team such as an acute pain service or in routine practice.
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Acute pain services
Where an anaesthesia-based service is not possible, the desired improvement in acute pain management may be achieved by: institutional commitment to the relief of pain and suffering; multidisciplinary, regular education programs on pain management; responsibility of care to be assigned to those most knowledgeable, experienced and available to deal with patients needs in a timely fashion; and regular quality review of outcome. Effective pain management by all members of the multidisciplinary team can only be achieved by sound educational strategies instigated at an institutional level (see Section 3.3 on page 40).
Sample case: early pain service intervention and acute rehabilitation
A 23-year-old male suffers multiple injuries, requiring laparotomy for intra-abdominal trauma, and internal fixation of left lower limb fractures. By seven days postoperatively he is making a good general recovery, except that he is now requiring escalating doses of opioid via PCA and complaining of severe burning pain in the left leg and foot below his limb fracture site. As a result he cannot tolerate the continuous passive movement treatment for his left lower limb and has been unable to even sit out of bed. The patient, his family, the orthopaedic surgeon and nursing staff are frustrated and a view is forming that he is a difficult patient who is not cooperating with rehabilitation. Surgical assessment reveals no surgically treatable complications. The pain service in this hospital is an integrated acute, chronic and cancer pain service. When consulted, immediate diagnosis of neuropathic pain, secondary to left lateral popliteal nerve trauma, is made and a subcutaneous lignocaine infusion relieves the pain, permitting withdrawal of opioids. The patient is able to cooperate fully with rehabilitation and is subsequently followed by the pain service and treated with a low dose of sodium valproate (200 mg bd) and amitriptyline (25 mg) at night. (The treatment of neuropathic pain is discussed in Section 10.2 on page 152.)
Key points
A multidisciplinary approach to the management of acute pain, particularly in a formal acute pain service, leads to improved pain relief and better patient outcomes. Effective pain management is fundamental to the quality of care. The key to successful pain management is education and training of all staff.
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3.1
Principles of acute pain assessment and management

Assessment of pain and pain history
Pain rating methods

Because pain is an individual experience influenced by many factors including previous experiences, culture, prognosis, coping strategies and fear and anxiety, there is a poor correlation between patient and staff assessments of pain severity. Self reports are among the most reliable indicators of pain severity, with a number of simple self-reporting tools commonly used for adults. The approach commonly used for postoperative patients is to use verbal pain scoring methods such as the categorical rating scale. Different descriptors can be used to rate the patients pain, eg no pain, mild pain, moderate pain, severe pain, worst possible pain. The visual analogue scale (VAS) employs a 10 cm line rated from no pain at the left to worst pain possible on the right and requires the patient to mark their pain on this continuum. The VAS score is the distance from the no pain point to the patients estimate.
no pain
The verbal numerical rating scale (VNRS) also asks the patient to rate their pain from no pain (0) to worst pain possible (10). Numbers are avoided on this scale in order to prevent the patient receiving cues. There is good correlation from pooled data between the VAS and the VNRS of pain scoring (level III; Murphy et al 1988). However, for an individual, once an appropriate scale has been selected it should continue to be used for monitoring pain. While it is not always possible to relieve pain entirely, the aim should be to achieve comfort. Patients should be assessed during movement and activity as well as at rest, and incident pain (pain during movement) reduced as much as possible.
Patients with special needs
Patients who have difficulty communicating their pain (eg children, hearing and cognitively impaired patients) require special attention. There are a number of pain rating scales designed for use in children (see page 94). The needs of patients whose educational or cultural background differs significantly from that of their health care team should be taken into account, with scales modified to suit the individual needs of patients. Patients who do not speak English should be given the opportunity to communicate in their chosen language through an interpreter.
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worst possible pain
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Continuing assessment
A patients pain and response to treatment should be assessed regularly, at least every two hours for the first 24 to 48 hours following major surgery. It is important to monitor pain and response to therapy, and to tailor the frequency of monitoring to the individual patients needs. If pain is poorly controlled or therapy is being altered, assessment may need to be more frequent. Pain assessment should be recorded in a readily available and visible form, such as on the bedside chart with other vital observations. It should be remembered that an unexpected increase in pain, especially when associated with changes in other vital signs, may signal the development of a new diagnosis or postoperative complication (eg peritonitis, compartment syndrome or neuropathic pain) (level IV; AHCPR 1992). Patients should be actively involved in the continuing assessment of their pain. Any factors which reduce the efficacy of the treatment will alter their confidence in the pain management plan. Patients may also experience a change in the character and severity of pain in association with a complication. A careful history and examination of the patient is essential when pain severity increases unexpectedly.
Key points
Careful assessment of pain should occur initially and then regularly throughout treatment, using self-reporting techniques. As pain varies so markedly between individuals, patient involvement in the initial and continuing assessment of their pain is essential. Pain should be assessed both at rest and during activity and pain relief assessed as to its adequacy, to allow appropriate function. Unexpected levels of pain or pain that suddenly increases, especially when associated with changes in other vital signs, may signal the development of a new surgical or medical diagnosis (eg postoperative complication, neuropathic pain).
Pain history
In addition to a thorough general medical history and physical examination, patients with any form of pain should be evaluated with a specific pain history as follows in Table 3.1. A useful method for assessing the extent of pain is for patients to chart the primary area of pain and areas of radiation on a pain diagram (a sample chart is given in Figure 3.1).
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Principles of acute pain assessment and management Table 3.1 Taking a pain history
Circumstances associated with pain onset Primary site of pain (see Figure 3.1) Radiation of pain (see Figure 3.1) Character of pain (using McGill Melzack multidimensional pain inventory eg is pain throbbing, sharp, aching etc) Intensity of pain (eg on visual analogue scale) at rest on movement at present during last week highest level
Factors altering pain what makes it worse? what makes it better?
Associated symptoms (eg nausea) Temporal factors
is pain present continuously or otherwise? Effect of pain on activities Effect of pain on sleep
Medications taken for pain
Other treatments used for pain
Health professionals consulted for pain treatment Expectations of outcome of pain treatment
Pain history information of significance for symptomatic treatment of pain Patients belief concerning the causes of pain
Reduction in pain required to resume reasonable activities Patients typical coping response for stress or pain, including presence of anxiety or psychiatric disorders (eg depression or psychosis) Family expectations and beliefs about pain, stress and postoperative course Ways the patient describes or shows pain Patients knowledge, expectations and preferences for pain management
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Figure 3.1 Pain diagram
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3.2
Diagnosing neuropathic pain
Neuropathic pain is underdiagnosed in patients with acute pain in many different settings eg postoperative, post-trauma and acute pain in patients with cancer. A useful definition is pain associated with injury, disease or surgical section of the peripheral or central nervous system. A wide range of neuropathic pain syndromes is described in the IASP taxonomy of chronic pain syndromes (IASP Task Force on Taxonomy 1994). As described in Section 1.1 on pain mechanisms (see page 25), neuropathic pain frequently involves both peripheral and central sensitisation. The treatment of neuropathic pain is discussed in Section 10.2 on page 152. Diagnosis of neuropathic pain can usually be made on the basis of history and physical examination. There is often a history of an event which may have resulted in nerve damage associated with the onset of neuralgia, or complex regional pain syndrome after surgery. There may be considerable delay between the event and the onset of pain. Pain is often described as paroxysmal, burning, stabbing, pulsing, electric shock-like or dysaesthesic. Hyperalgesia may be present in the area of injury (primary) or in the surrounding area (secondary) which is indicative of central sensitisation. Allodynia (pain in response to a non-painful stimulus such as a light touch) also indicates central sensitisation. Hyperpathia may be present, where there is an increased pain threshold and repetitive stimulation results in summation of pain. Early diagnosis and treatment of neuropathic pain are preferable as chronic neuropathic pain is extremely difficult to treat. Complex regional pain syndromes (CRPS) are discussed on page 154.
Key point
Although not specific, an important indicator of neuropathic pain is the inability to relieve pain with opioids, or no apparent relief of pain with a rapidly increasing opioid dose. Other indicators can be obtained from the history and physical examination, as shown in Table 3.2.
Table 3.2
Pain in the absence of ongoing tissue damage Pain in an area of sensory loss Paroxysmal or spontaneous pain Allodynia (pain in response to non-painful stimuli) Hyperalgesia (increased pain in response to painful stimuli) Dysaesthesias (unpleasant abnormal sensations; ants crawling on the skin etc) Characteristic of pain different from nociception: burning, pulsing, stabbing pain Sometimes a delay in onset of pain after nerve injury (NB some neuropathic pain has immediate onset) Hyperpathia: increasing pain with repetitive stimulation; after response (continued exacerbation of pain after stimulation); radiation of pain to adjacent areas after stimulation Tapping of neuromas (spontaneously firing growth buds from damaged peripheral nerves) produces a radiating electric shock sensation in the distribution of the nerve (Tinels sign) Poor response (not unresponsiveness) to opioids Presence of a major neurological deficit (eg brachial plexus avulsion, spinal cord injury etc)
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Features that suggest neuropathic pain
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3.3
Agents used to manage acute pain
In this section there is a brief description of the major agents used in the management of acute pain. More detail about dosing, routes of administration, optimal usage and side effects can be found in the chapters on managing specific types of pain, especially in the chapter on postoperative pain.
Pharmacological interventions
Opioids Opioid analgesics are the cornerstone of the management of moderate to severe pain. They produce analgesia by binding to opioid receptors both within and outside the central nervous system. Opioid analgesics are classified as full agonists, partial agonists or mixed agonist-antagonists, depending on the way in which they interact with opioid receptors. Full agonists produce a maximal response within the cells to which they bind; partial agonists produce a lesser response, regardless of their concentration; and mixed agonist-antagonists activate one type of opioid receptor while simultaneously blocking another type. The most important receptor type for clinical analgesia is named mu because of its affinity for morphine. Examples of other commonly used mu opioid agonists include codeine, pethidine, oxycodone, methadone and fentanyl. Tramadol, a recently introduced mu opioid agonist, also has important non-opioid spinal and central nervous system effects. These opioids all have the potential to cause important side effects, which are discussed on page 50. Titration The key to effective titration of opioids is the use of incremental doses and careful observation of side effects and relief of pain. Routes of administration Traditional methods of opioid administration are via oral, rectal, intravenous, subcutaneous, or intramuscular routes. Newer methods, using the epidural or intrathecal routes and PCA, have been shown to be effective and safe but need to be administered by highly skilled staff. Non-steroidal anti-inflammatory drugs NSAIDs can be very useful for managing mild to moderate pain. They act by decreasing levels of inflammatory mediators generated at the site of tissue injury. When NSAIDs alone cannot control pain, they have a significant opioid dose-sparing effect and can be useful in reducing opioid side effects. The concurrent use of opioids and NSAIDs often provides more effective analgesia than either of the drug classes alone. Most NSAIDs are available in both oral and rectal forms. Certain NSAIDs can also be given intravenously or intramuscularly. NSAIDs have important side effects and cannot be used in all patients. Potential risks are discussed on page 73. Paracetamol Paracetamol is an important option in the treatment of mild to moderate pain and an adjunct to opioids in more severe pain. It has analgesic and antipyretic effects, but is not considered to be anti-inflammatory. There is controversy about the mechanism of action, but paracetamol seems to have a significant central action. It is available in both oral and rectal forms. Proparacetamol, an intravenous preparation, is available in some European countries and appears to be more effective than paracetamol. 40
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Local anaesthetics Local anaesthetics interrupt pain pathways by blocking axonal conduction. Local anaesthetics for acute pain relief have various indications, including infiltration and nerve and plexus block, and are often used with opioids in continuous epidural administration. Adjuvant agents A number of adjuvant agents have been shown to be effective in the treatment of certain pain syndromes. These include antidepressants, anticonvulsants and corticosteroids (see Section 10.1 on page 151). Multimodal analgesia There is evidence that patients benefit from the use of multimodal analgesia (ie use of different classes of analgesics) after surgery. NSAIDs, local anaesthetics, paracetamol, other non-opioid analgesics and opioids are used in combination to improve pain relief and to reduce the dose of each analgesic drug and the intensity of side effects. Future agents Recently, the roles of the N-methyl-D-aspartate (NMDA) receptor and nitric oxide in the production of wind-up and morphine tolerance have been investigated (Ren 1994, level III; Mao et al 1995). Ketamine, an NMDA antagonist, has been shown to markedly reduce opioid requirements when given pre-operatively (level III; Royblat et al 1993). When combined with morphine, ketamine has been shown to provide superior postoperative pain relief at a lower dosage and with fewer side effects than morphine alone (level II; Javery et al 1996). Ketamine may be used by low-dose infusion where pain relief by opioids proves to be difficult, such as for acute neuropathic pain, although it may cause unpleasant psychomimetic side effects. S-Ketamine has been reported to have a lower incidence of side effects in clinical studies but is not yet approved for use in Australia. It appears that the pain mechanisms involving nitric oxide work through the NMDA receptor. Further therapeutic manoeuvres based on the manipulation of nitric oxide are anticipated, probably initially by investigation of the long-used component of cough mixtures, dextromethorphan. This has an excellent safety record and is a proven NMDA receptor blocker. Current clinical trials of dextromethorphan plus morphine in postoperative pain are evaluating whether dextromethorphan reduces the doses of morphine required for pain relief. At present, dextromethorphan or other novel analgesics acting on NMDA or nitric oxide mechanisms are not approved for postoperative pain management. Non-pharmacological interventions These interventions are appropriate for patients who wish to use them, who may benefit from reducing drug therapy, or who are likely to experience a prolonged interval of pain. Cognitive-behavioural approaches include preparatory information, simple relaxation, imagery, hypnosis and biofeedback. Physical therapeutic agents and modalities include spinal manual therapy, mobilisation, application of superficial heat or cold, massage, exercise, electro-analgesia such as transcutaneous electrical nerve stimulation (TENS) therapy and acupuncture. These techniques are discussed further on pages 78, 87, 95 and 131.
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3.4
Education about pain management
Given the importance of good pain management and the changes in clinical practice in this field, continuing education of GPs, medical specialists, junior medical staff, nurses and allied health professionals is essential.
Medical and allied health workers

Professional colleges now recognise the importance of appropriate training for pain management. The Australian and New Zealand College of Anaesthetists (ANZCA) includes pain management as a major area of experience for all specialty trainees. In 1996, the ANZCA initiated a Certificate in Pain Management, based upon a postqualification year of experience in an ANZCA approved multidisciplinary pain centre which manages acute, chronic and cancer pain. Pain management is a significant component of examinations of the Royal Australasian College of Surgeons (RACS). Education programs for allied health professionals are equally important because of the key role they play in the management of acute pain. Nursing staff have a major responsibility for continuing assessment and management of patients in pain. In acute care settings, they assess and document patients pain, administer prescribed medication, monitor delivery of medication via infusion pumps (including PCA, intravenous and epidural infusions), and take responsibility for detection, monitoring and appropriate reporting of side effects and adverse reactions. They also contribute to patients education and support. Accreditation and educational programs in individual institutions would enable nurses to identify their learning needs, to acquire appropriate knowledge and skills and to ensure that they are adequately prepared for the responsibilities involved in pain management. Ward nursing staff are directly involved in the implementation of all analgesic techniques and regimens and nursing education programs are therefore essential for providing safe and effective analgesia. These programs should cover the following (level IV; Macintyre & Ready 1996): drugs and techniques used (including simple techniques); early recognition and treatment of side effects; physiological and psychological benefits of better acute pain management; and patient education. The effectiveness of these programs should be evaluated regularly. Nurses also need to adapt their approaches to patients with special needs and therefore require education in: appropriate use of comfort measures and other non-pharmacological techniques; cultural issues in pain management; assessment strategies in cognitively impaired patients; and ethical issues in pain management. All allied health workers who are involved in physical activities with patients in acute pain need to be informed of the importance of adequate pain management.
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Patients and their carers

Patient and family education, which follows a careful eliciting of patient expectations and fears, can positively influence the outcome of pain management, since patient attitudes have been shown to modify pain perception and analgesic requirements (level III; Egbert et al 1964; level I/II; Johnston & Vogele 1993, Suls & Wan 1989). Too much information, however, may have an adverse effect on patients with high anxiety levels and poor coping skills. Patients should be informed that effective methods of acute pain relief are now available, that they should be aware of their analgesic options, and that they have a right to effective and safe pain relief. This approach should help to identify patients with persistent acute pain who require early and vigorous intervention to prevent chronic pain. There is a variety of methods for delivering information to patients and using a combination of methods probably gives the best results. Verbal explanations should be reinforced with written information, diagrams and demonstrations (see also pages 7879). Broadly speaking, information given to patients should include: treatment goals and benefits (including the benefits of physiotherapy and early mobilisation); options for acute pain management; how pain and the management of pain (including possible side effects) will be monitored (emphasising the need for patient involvement); and availability of the NHMRC booklet, A Consumers Guide: Acute Pain Management, and other relevant material for consumers. The needs of patients whose educational or cultural background differs significantly from that of their health care team should be taken into account. Patients who do not speak English should be given the opportunity to communicate in their chosen language through an interpreter.
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Studies over the last three decades have suggested that up to 75 per cent of patients experience moderate to severe pain following surgery, and that in many cases this pain is not relieved adequately (level III; Oden 1989, Donovan 1983). This issue is currently being addressed by health care groups involved in postoperative and acute pain management, in improving methods of analgesic delivery (eg intrathecal, epidural and PCA) and in developing an improved understanding and application of traditional delivery methods. A recent evidence-based resource for pain relief includes analyses of acute pain management (McQuay & Moore 1998).
4.1
Table 4.1
Agents used in postoperative analgesia

Summary of pharmacological interventions
Intervention1 Comments (level of evidence2) NSAIDs Oral (alone) (I) Effective for mild to moderate pain. Relatively contraindicated in patients with renal disease and risk of or actual coagulopathy. Risk of coagulopathy, gastro-intestinal bleeding and other risk factors should be carefully sought. Oral (adjunct to Potentiating effect resulting in opioid sparing. Cautions as above. opioid) (I) Parenteral Effective for moderate to severe pain. Useful where opioids are (ketorolac) (I) contraindicated or to produce opioid sparing, and to minimise respiratory depression, sedation and gastro-intestinal stasis associated with opioid administration. Best used as part of a multimodal analgesia regimen. Rectal (IV) Similar efficacy to oral preparations. Paracetamol Oral (II) Effective for mild to moderate pain, and as an adjunct to opioids in Rectal (IV) more severe pain. Opioids Oral (IV) As effective as parenteral in appropriate doses. Use as soon as oral medication tolerated. Route of choice.* Intramuscular (I) Has been the standard parenteral route, but injections painful and absorption unreliable. Hence, avoid this route when possible.* Subcutaneous (via Preferable to intramuscular because of patient comfort and a reduced indwelling risk of needlestick injury.* subcutaneous needle/cannula) (I) Intravenous (I) Parenteral route of choice after major surgery. Suitable for titrated bolus or continuous administration. Significant risk of respiratory depression with inappropriate dosing.* PCA (systemic) (I) Intravenous or subcutaneous routes recommended. Good steady level of analgesia. Popular with patients but requires special infusion pumps and staff education. See cautions about opioids above.* 1 Selected references are included in report; 2 See levels of evidence key on page 23; * Administration of opioids by any route requires monitoring.
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Acute pain management: scientific evidence Table 4.1 Summary of pharmacological interventions (cont)
Intervention1 Comments (level of evidence2) Opioids (cont) Epidural & When suitable, provides good analgesia. Risk of respiratory depression intrathecal (I) (as with opioids by other routes), but sometimes delayed in onset. Requires careful monitoring. Use of infusion pumps requires additional equipment and staff education. Expensive if infusion pumps are employed.* Sublingual (IV) Effective for mild to moderate pain. Local anaesthetics Epidural & Indications in particular settings. Effective regional analgesia. May intrathecal (I) blunt stress response and aid recovery. Opioid sparing. Addition of opioid to local anaesthetic may improve analgesia. Risks of hypotension, weakness, numbness. Requires careful monitoring. Use of infusion pump requires additional equipment and staff education. Peripheral nerve Plexus block, peripheral nerve block and infiltration. Effective block (I) regional analgesia. Opioid sparing. 1 Selected references are included in report; 2 See levels of evidence key on page 23; * Administration of opioids by any route requires monitoring. Source: AHCPR 1994
Opioids
Sites of action There are three main sites of action of opioids. Supraspinal. Opioid actions are associated with areas in the medial brain stem around the nucleus raphe magnus and extending rostrally to the peri-aqueductal and periventricular grey areas. Spinal cord. The greatest density of opioid receptors are found around the C-fibre terminals in lamina I and the substantia gelatinosa (lamina II). Receptors of the mu subtype predominate (70 per cent mu, 24 per cent delta, 6 per cent kappa). Presynaptic receptors are more prevalent and respond to lower doses of opioids than do postsynaptic receptors. Peripheral tissue. Opioid receptors are synthesised in the dorsal root ganglion and are transported centrally in C-fibre afferents to become presynaptic receptors. In the presence of inflammation, peripheral axonal transport of opioid receptors also occurs. In addition, the number of peripheral sensory-nerve terminals increases (sprouting) and access to neuronal opioid receptors is increased as inflammation disrupts the perineurium. Arrival of endogenous opioids in injury sites has been shown to be related to immune cell proliferation. Opioid peptides are expressed by the resident immune cells, and released in response to endogenous substances such as corticotrophin-releasing hormone and cytokines (Stein 1995). Thus, local application of opioids may have an analgesic action in damaged tissue (eg intraarticular opioids following arthroscopy). Opioid doses The dosage schedule for opioids needs to be individualised. The patients response to opioid agents must be determined in relation to both efficacy of analgesia and the occurrence of side effects. As individual opioid requirements vary greatly, an appropriate opioid agent, dose and dosing interval, and route of administration must be determined for each patient. Titration of opioid by giving small increments intravenously is often the best method for estimating the optimal starting dose. 46
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All opioids are capable of producing the same degree of analgesia providing equianalgesic doses are administered. Dose schedules will vary according to the age of the patient, concomitant disease states, use of other medications and route of administration. Suggested starting doses for intramuscular/subcutaneous morphine and pethidine are given in Table 4.2, and approximate equi-analgesic doses of a number of opioids are given in Table 4.3. Subsequent doses may need to be altered according to the patients response and level of ongoing pain or side effects. In adults, patient age rather than weight has been shown to be a better predictor of opioid requirement (level III; Macintyre & Jarvis 1995). In opioid-naive patients prescribed PCA morphine for postoperative pain relief after major surgery, the first 24hour morphine requirements were shown to approximate the following relationship: Average first 24-hour maintenance PCA morphine requirements in patients after major surgery aged between 20 and 70 years of age = 100 age. (level III; Macintyre & Jarvis 1995). That is, there was a progressive decrease in morphine requirement as patient age increased. There is large interpatient variability, with differences in morphine requirements of up to 10-fold in each age group. However, this relationship can be used as a guide to initial opioid dose for any parenteral or oral route of administration. Elderly patients require lower doses of opioids to achieve an equivalent analgesic effect and the duration of analgesic effect is often longer due to an age-related increase in the terminal elimination half-life of the opioids. Thus elderly patients require lower doses than do younger patients (see page 159). In children, weight is currently employed as the most important determinant of opioid requirements. However, as with adults, clinicians must review and monitor the response to analgesic agents to allow adjustment of doses and dose intervals according to individual requirements (see Table 6.1 on page 101).
Table 4.2 Opioid
Morphine5 Pethidine6
1
Smaller doses will be required if intermittent intravenous bolus doses of an opioid are given (see Figure 4.3). For starting doses of an oral opioid, use equi-analgesic doses. 2 Suggested doses do not apply to patients with renal or hepatic insufficiency or other conditions affecting drug metabolism and kinetics. 3 The age of the patient should be used as a guide to initial starting dose; subsequent doses must be titrated to effect. 4 These doses have been derived from the table of morphine doses in Macintyre & Jarvis 1995 and are suggestions only. 5 Morphine can also be administered by intermittent subcutaneous injection. 6 Pethidine is irritant and is not recommended for subcutaneous administration. IM=intramuscular; SC=subcutaneous
A systematic review of the efficacy of a single IM dose of morphine 10 mg for moderate to severe postoperative pain reported numbers needed to treat (NNT) of 2.9. This means that one out of every three patients achieved more than 50 per cent pain relief 47
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Suggested starting doses for IM/SC morphine and IM pethidine in adults1,2 Doses will vary according to the age of the patient3 4059 years 6069 years 2.57.5 mg 2575 mg 7085 years 2.55.0 mg 2550 mg >85 years4 2.03.0 mg 2030 mg
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with morphine, which they would not have achieved with placebo. This NNT for a single dose of morphine 10 mg compares to: NNT 4.6 for oral paracetamol 1000 mg; NNT 1.9 for paracetamol 1000 mg with codeine 60 mg; NNT 2.7 for ibuprofen 400 mg; NNT 2.3 for diclofenac 50 mg (level I; McQuay & Moore 1998). In this comparative light, morphine seems surprisingly impotent, however increasing the dose lowers the NNT. Also, the key to the use of morphine is to titrate the dose to analgesic effect in individual patients.
Table 4.3 Equi-analgesic doses of opioid Opioid Agonist Morphine Pethidine2 Oxycodone Fentanyl3 Hydromorphone Methadone4 Codeine5 10 mg 100 mg 15 mg 100 g 1.5 mg 10 mg 130 mg 100 mg 0.4 mg 0.40.8 mg (sublingual) 30 mg 300 mg 2030 mg NA 7.5 mg 20 mg 200 mg 130 mg Approximate equi-analgesic dose1 Parenteral Oral
Dextropropoxyphene6 Tramadol7 Partial agonist Buprenorphine

1
Published tables vary in the suggested doses that are equi-analgesic to morphine. Clinical response is the criterion that must be applied to each patient; titration to clinical response is necessary. Because there is not complete cross tolerance among these drugs it is usually necessary to use a lower than equi-analgesic dose when changing drugs and to retitrate to response. 2 High doses and/or prolonged use of pethidine can lead to an accumulation of norpethidine and associated norpethidine toxicity. The use of oral pethidine is not recommended. 3 Fentanyl is not recommended for intermittent IM administration. 4 Duration of action of methadone may vary from 6 to 80 hours with a risk of accumulation with repeat dosing. It should only be used if special indications exist and if close monitoring of effects and side effects can be assured. 5 In general, single oral doses above 60 mg are not recommended. 6 These drugs are commonly used for mild to moderate pain. Suggested starting doses are those which are commonly used and are not equivalent to the stated doses of morphine. Dextropropoxyphene 65 mg has an NNT of 7.7, dextropropoxyphene 130 mg has an NNT of 2.8 (McQuay & Moore 1998). 7 Tramadol 100 mg has an NNT of 4.8 and for 150 mg doses the NNT is 2.4 (McQuay & Moore 1998). Caution: some drug preparations may include paracetamol or aspirin and recommended doses for these drugs should not be exceeded. NA=not available
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Opioids administered by the intra-articular route have been employed for pain relief following orthopaedic surgery. Systematic review of the literature has so far failed to reveal evidence of efficacy for this route of administration (McQuay & Moore 1998). The following cases illustrate some important issues about opioid dosing.
Sample Case 1
A 28-year-old male undergoes a colectomy for colitis and is ordered morphine 7.5 mg every four hours, as needed, intramuscularly. He is requesting these injections every four hours, and sometimes more frequently, 18 hours after the operation. The nursing staff report that his wife is concerned he may become addicted to his pain killers.
Management points
There is wide interindividual variation in effective doses of opioids. Patient weight is traditionally used to determine dosage despite there being no evidence for the efficacy of this in adults, with age being a better guide to dosage requirements. Commonly employed time intervals between injections do not necessarily reflect the pharmacokinetics of opioids. Addiction to opioids is rare when these agents are used for acute pain relief. Patients and relatives are frequently concerned about the possibility of addiction and these fears should be pre-empted prior to operations and other procedures. Orders for opioids on an as needed basis intramuscularly are frequently inadequate after major surgery with epidural and PCA being more effective in these situations. All analgesic prescribing (particularly of opioids) requires regular assessment and adjustment of dosage. Analgesic requirements may vary according to site and extent of surgical incision. This patient was given intravenous bolus doses of morphine and was found to require a total of 15 mg to obtain pain relief. Subsequently he obtained good continuing pain relief on PCA with boluses of morphine 2 mg required.
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Acute pain management: scientific evidence Sample Case 2
Three days after a gastrectomy, a 62-year-old woman reports severe abdominal pain that is increasing in intensity. This is noted to be associated with a rapid rise in her temperature. She states that the analgesia currently ordered for her (pethidine 75 mg every four hours intramuscularly), which had previously been effective, is now useless.
Management points
The onset of unexpected pain, especially later in the postoperative course, may indicate a surgical or medical complication which must be excluded as part of the pain management process. Effective analgesia does not interfere with the ability to diagnose surgical conditions either before or after surgery. Clinical signs of peretonism and gas under the diaphragm on abdominal radiological studies with contrast media are followed by laparotomy and suturing of leaking bowel anastomonies. Titration of analgesic requirements revealed that pain relief required six morphine 1.5 mg boli over a 30 minute period. Analgesia was maintained postoperatively with an intravenous morphine infusion of 3 mg/hr. Opioid requirements decreased to 2 mg/hr 24 hours postoperatively. Adverse effects of opioids The most common side effects of opioids are sedation, pruritus, nausea, vomiting, slowing of gastro-intestinal function and urinary retention. Others include respiratory depression, hypoxia and various effects on the central nervous system, such as dysphoria (including unpleasant dreams). As most (but not all) side effects are dose dependent, one option for management of any particular side effect is to reduce dosage, provided satisfactory analgesia is maintained. Another option is pharmacological treatment of side effects by specific agents (eg anti-emetics for vomiting). Opinions vary as to the efficacy of changing to another opioid. However, some patients may be more susceptible to side effects from one opioid than from another. Equi-analgesic doses of various opioids generally have similar adverse effects profiles, apart from a higher incidence of pruritus that has been noted with morphine (level II; Woodhouse et al 1996). Respiratory depression Fear of respiratory depression and hypoxia often leads to inadequate dosing with opioids. Respiratory depression can generally be avoided with careful titration and individualisation of dose. Clinically, unrelieved pain tends to antagonise the respiratory depression associated with opioids (level IV; Cousins & Phillips 1986). In human volunteers, pain stimulates respiration and attenuates morphine-induced respiratory depression (level III; Borgbjerg et al 1996). Respiratory depression may occur in the following situations: overdose due to administration of an incorrect dose by any route, accumulation during an inadequately monitored continuous infusion, or inappropriate use of long-acting drugs (eg methadone, sustained release morphine); co-administration of other sedative agents including benzodiazepines, antihistamines and certain anti-emetics;
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intercurrent disease states such as electrolyte abnormalities, hypovolaemia, uraemia, hepatic dysfunction, respiratory disease or raised intracranial pressure; and obstructive sleep apnoea or intermittent airways obstruction. Overnight pulse oximetry may play a role in identifying patients at risk of postoperative airway obstruction (level III; Reeder et al 1992b). Such patients may benefit from use of nasal continuous positive airway pressure (CPAP) to reduce the degree of hypoxia and resultant haemodynamic changes which can lead to cardiovascular morbidity. A decrease in respiratory rate has been found to be a late and unreliable clinical indicator of respiratory depression. Sedation is a better indicator and should be monitored using a sedation score (Table 4.4). However, this method has limitations if a patient who is deeply sedated is assessed as being in normal sleep. Normal sleep means that the patient is asleep but is rousable; for example, the patient responds while the pulse rate is being taken. It is important that all nursing staff receive adequate education about assessing sedation level.
Table 4.4 Sedation score 0 = none
1 = mild, occasionally drowsy, easy to rouse 2 = moderate, constantly or frequently drowsy, easy to rouse 3 = severe, somnolent, difficult to rouse S = normal sleep Source: Ready et al 1988.
Opioids given in excessive doses can lead to respiratory depression and hypoxaemia. However, episodic hypoxaemia without respiratory depression has also been noted in patients receiving opioids, regardless of route and not necessarily associated with high doses. This is often due to intermittent upper airway obstruction and is very similar to sleep apnoea syndrome. As patients after major operations may already have a background hypoxaemia due to the lung function changes that may accompany surgery and anaesthesia, intermittent upper airway obstruction may lead to profound decreases in oxygen saturation (level III; Jones et al 1990). Pulse oximetry is not a reliable method for measuring the interaction between pain, opioids and respiration (Catley et al 1985, Bulow et al 1995). In some studies hypoxaemic episodes were frequent in patients with high pain scores, possibly due to restriction of adequate ventilation by pain, or residual effects of anaesthesia and surgery (Miller et al 1976). Oxygen saturation as measured by pulse oximetry may also be a poor indicator of respiratory function if the patient is receiving supplemental oxygen. As significant background and/or intermittent hypoxaemia may occur for a number of days postoperatively, particularly during sleep (Beydon et al 1992), supplemental oxygen is recommended for at least the first 48 to 72 hours following major surgery and in elderly or high-risk patients (level III; Reeder et al 1992a). This may be of vital importance to high-risk patients because of the link between postoperative hypoxaemia and myocardial infarction (level III; Mangano et al 1992).
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Acute pain management: scientific evidence Key points
Respiratory depression and hypoxia are often feared consequences of opioid administration but can generally be avoided with careful titration and individualisation of dose. A decrease in respiratory rate has been found to be a late and unreliable clinical indicator of respiratory depression. Sedation is a better indicator and all patients receiving opioids should be monitored using a sedation score. Statement of evidenceopioids As significant background and/or intermittent hypoxaemia may occur for a number of days postoperatively, supplemental oxygen is recommended for at least the first 48 to 72 hours following major surgery and in elderly or high-risk patients, regardless of the analgesic method used. Level of evidence
III Reeder et al 1992a
Central nervous system effects In addition to respiratory depression and sedation, opioids may result in euphoria, hallucinations, miosis and muscle rigidity. In patients on monoamine oxidase inhibitors, there is a risk of coma if pethidine is given. Metabolite toxicity Pethidine is N-demethylated to an active metabolite norpethidine, which in turn is hydrolysed to norpethidinic acid. Accumulation of norpethidine is associated with excitatory effects ranging from nervousness to tremors, twitches, multifocal myoclonus and seizures. Pethidine should probably not be used for more than 72 hours for the management of postoperative pain, because of the risk of norpethidine accumulation. However, the evidence for this risk is not strongly documented. In one study, symptomatic patients with cancer-related pain had higher norpethidine levels (>400 ng/ml) and a higher ratio of norpethidine to pethidine (>1.3 compared with 0.2 in asymptomatic patients) (Kaiko et al 1983). However, some patients with relatively low levels of norpethidine had significant problems. Norpethidine toxicity has also been seen in patients receiving patient-controlled pethidine (Stone et al 1993). Impaired renal function increases the half-life of norpethidine (15 to 30 hours) and increases the risk of norpethidine accumulation. Naloxone does not reverse, and may aggravate, norpethidine toxicity. Morphine is metabolised in the liver to morphine-3-glucuronide (M3G) and morphine6-glucuronide (M6G). M6G has similar affinity for mu receptors as morphine but is ten times as potent an analgesic (Abbott & Palmour 1988, Mather & Smith 1997). In the presence of impaired renal function, accumulation of M6G may contribute to analgesia and prolonged sedation. M3G has no affinity for the mu receptor, may antagonise the action of morphine at supraspinal sites, and has been postulated to cause myoclonic jerks and hyperalgesia in patients receiving very high doses of morphine (Bartlett et al 1994a, Bartlett et al 1994b, Davies et al 1996). Chronic morphine administration, impaired renal function, and age greater than 70 years have all been associated with higher ratios of morphine metabolites to morphine (Osborne et al 1993, Davies et al 1996, Mather & Smith 1997).
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Cardiovascular effects Cardiovascular effects of opioids vary with the agent, dose and route of administration. Generally, the effects of opioids on blood pressure will depend on the co-existing intravascular volume status and level of sympathetic activation. Opioids may diminish a previously raised sympathetic tone and result in decreased blood pressure, if intravascular volume is decreased. Morphine may result in vasodilatation. Pethidine may be associated with an increased heart rate. Nausea and vomiting Nausea and vomiting are common and distressing symptoms in many patients following surgery, and may be contributed to by the type of surgery performed, gastrointestinal disorders (inflammation, gastric stasis or bowel obstruction), chemical factors (drugs or metabolic disorder), raised intracranial pressure, vestibular imbalance, and psychological factors (Andrews 1992, Watcha & White 1992). This mechanism is illustrated in Figure 4.1. The vomiting centre, which is situated in the reticular formation, is supplied by muscarinic cholinergic and histamine (H1) receptors, and can be excited directly by visceral afferent impulses from the gastrointestinal tract, input from the vestibular system, hypoxia and hypotension. The chemoreceptor trigger zone, located in the medullary area postrema, has specific receptors for dopamine (D2) and serotonin (5HT3), and may be stimulated by circulating drugs such as opioids or anaesthetic agents. Anti-emetics acting at the vomiting centre include central acting anticholinergic agents (atropine and scopolamine), and antihistamines (cyclizine and promethazine). Neuroleptic drugs such as haloperidol, droperidol and prochlorperazine block the chemoreceptor trigger zone D2 receptor. Metoclopramide acts peripherally to enhance gastric emptying, and centrally at D2 receptors to reduce vomiting. Drugs acting on specific 5HT3 receptors, such as ondansetron, have been shown to be very effective for control of postoperative and cytotoxic drug-induced nausea and vomiting (Leeser & Lip 1991, Andrews 1992, Watcha & White 1992, Watcha & Smith 1994, Paxton et al 1995). A number of general measures may be employed in the treatment of postoperative nausea and vomiting, including: hydration and maintenance of adequate blood pressure; avoiding excessive movement in the immediate postoperative phase; and reducing the patients anxiety. A number of agents suitable for treating nausea and vomiting are listed in Table 4.5.
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Acute pain management: scientific evidence Opioid analgesics Chemoreceptor trigger zone Anaesthetic agents eg N2O Hypoxia
Vestibular
Vomiting centre
Oropharynx
Pain (especially visceral or pelvic)
Gut Psychological
Hypotension
Figure 4.1 Postoperative nausea and vomitingmechanisms of causative factors and their
management. Table 4.5
Agent Class
Comparison of representative agents from anti-emetic drug classes

Metoclopramide D2 antagonist 4 Droperidol Butyrophenone 46 (low dose) 24 (high dose) ++ + + 0.250.5 46 hourly IV, IM Ondansetron 5-HT3 antagonist 824 Prochlorpera Phenothiazin 6
Duration of action (h) Adverse effects EPSE Sedation
Anticholinergic Dose (mg)
Frequency
Formulations
EPSE=extra pyramidal side effects; NA=not applicable; PO=by mouth; IV=intravenous; IM=intramuscular
Allergy A true allergy to opioids is very uncommon. As with any drug, the term allergy is often mistakenly applied to an intolerance to the drug, a common side effect, or a dose-related effect. Tolerance to opioids Tolerance is a phenomenon in which an organism becomes less susceptible to the effect of a drug as a result of its prior administration. However, the development of tolerance is only one factor involved in declining analgesic effects or requirements for increased opioid dose, with chronic use. Increased activity in nociceptive pathways from disease progression, evolution of neuropathic pain, psychological processes, changes in pharmacokinetic factors, as well as plasticity of opioid mechanisms, will all influence opioid responsiveness. Surgical review is needed if opioid requirements increase rapidly in the postoperative phase as the increase in pain may be due to a surgical complication which requires intervention (eg development of lower limb ischaemia and compartment syndrome) rather than being due to tolerance at this early stage. If no other cause requires treatment, a decrease in analgesic effect should be managed by increasing the dose of opioid; this only becomes a problem if limiting side effects occur before analgesic doses are achieved.
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There is no evidence that the use of opioids for treatment of severe pain leads to opioid addiction in the opioid na ve patient (Chapman & Hill 1989, Foley 1989, Porter & Jick 1980).
Key points
To attain therapeutic effects with minimal adverse effects, it is necessary to individualise and titrate doses of opioids. This relies on using age as the initial guide for dosage range (in adults), and the use of dose intervals appropriate to the route of administration, monitoring of pain and sedation scores, respiratory rate and other side effects. The aim of analgesia should be patient comfort with minimal sedation and impairment of respiratory function (eg sedation score of less than 2 and respiratory rate greater than 8/minute) (Macintyre & Ready 1996). A true allergy to opioids is very uncommon. As with any drug, the term allergy is often mistakenly applied to an intolerance to the drug, a common side effect, or a dose-related effect. There is no evidence that the use of opioids for treatment of severe pain leads to opioid dependence or addiction (Chapman & Hill 1989, Foley 1989, Porter & Jick 1980). Routes of opioid administration Opioids should be administered by the safest and most effective route available. This will vary throughout the peri-operative period and consideration must be given to the patients overall condition and the availability of specialised equipment and trained staff, which may vary from one institution to the next. Oral therapy is simple and non-invasive but obviously has limited application in the early peri-operative phase when patients may be fasting or unable to absorb oral medications due to gastric stasis or vomiting. Absorption from intramuscular and subcutaneous injections will be reduced if peripheral perfusion is poor (ie in hypovolaemia and hypothermia) leading to inadequate analgesia, and the formation of a depot of analgesic that may be absorbed at a later time when perfusion improves. The same principles of individualisation of dose and dosing intervals apply to the administration of opioids by any route. A lack of flexibility in dose schedules has often meant that intermittent and prn (as needed) methods of pain relief have been ineffective whether administered by the oral, intramuscular, subcutaneous or intravenous route. Intermittent administration is associated with marked variations in plasma concentration. As a result, patients may swing between pain with subtherapeutic concentrations and side effects following a bolus dose, with little time spent within the therapeutic range. Frequent assessment of the patients pain severity and response to treatment rather than strict adherence to a dose regimen is required to ensure adequate analgesia.
Traditional methods of opioid administration
Oral Oral opioids are generally reserved for the postoperative period after the return of gastric motility, when the patient is able to tolerate fluids freely. If equi-analgesic doses are administered and absorbed, opioids are as effective orally as when given by other more invasive routes. Codeine is frequently utilised for pain of moderate severity, while oxycodone may be used for pain of moderate to severe severity. Oral 55
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morphine can be given as short-acting morphine sulphate solution. In patients with ongoing severe pain whose morphine requirements have been determined by previous intravenous or oral morphine solution administration, it may be beneficial to use a long-acting preparation (see page 62).
Sample case
A 25-year-old female suffered a mutilating compound fracture to the left tibia and fibula, involving vascular injury and extensive tissue necrosis. The limb has been salvaged; however pain has been severe and associated with anxiety and sleeplessness, with intravenous PCA requirements of 100120 mg morphine per day for the five days following surgery. This stable intravenous dose is equivalent to 200240 mg oral morphine/day (50 per cent bioavailability with repetitive oral dosing). This patient was completely relieved of pain on sustained release morphine 100 mg twice daily, with breakthrough doses of oral morphine solution (10 mg/ml) 2.53 ml). She required only two breakthrough doses of oral morphine 25 mg on the first two days and none thereafter. She became much less anxious, slept regularly for 8 hours per night and began to mobilise. Two weeks later the sustained release morphine dose was gradually weaned and replaced by intermittent paracetamol and oxycodone. Intramuscular Intramuscular injections have been the traditional mainstay of postoperative pain management. The actual dose administered should be based on the patients age and medical condition and should be titrated according to response (see page 46 and Table 4.2 on page 47). Dose intervals should be long enough to ensure that a dose has had its maximum effect before another dose is given, but short enough to ensure that the patient receives further analgesia if required (see Figure 4.2). If properly titrated, intramuscular opioids are unlikely to be required as often as every two hours but an order of two-hourly prn will allow added flexibility should additional doses be required (Macintyre & Ready 1996). Alternatively, a longer dosing interval may be considered using a larger opioid dose, provided the patient has not experienced significant side effects at the lower dose. Subcutaneous Subcutaneous injections can be administered intermittently or by infusion. Small gauge infusion devices (eg 27-gauge butterfly or plastic cannula) can be placed subcutaneously to avoid frequent skin punctures, can remain in place for two to three days, and reduce the likelihood of needle stick injury associated with repeated subcutaneous or intramuscular injections (Macintyre & Ready 1996). Absorption of morphine from the subcutaneous route has been found to be comparable to, and just as variable as, absorption of intramuscular morphine (level III; Semple et al 1996). In addition, a recent paper comparing the intramuscular and subcutaneous routes for intermittent morphine injections found that while the side effect profiles and level of analgesia attained were no different, patients expressed a strong preference for the subcutaneous route (level II; Cooper 1996). Continuous infusions provide more stable plasma levels and avoid bolus effects (toxicity at peak concentration and/or pain breakthrough at the trough concentration), provided cardiovascular stability has been achieved and cutaneous perfusion is adequate. This route is widely used in the treatment of severe cancer pain and may have applications in some postoperative patients, particularly if intravenous access is unavailable. Morphine and hydromorphone are suitable for subcutaneous infusion as 56
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both are low irritant. As dose requirements increase, more concentrated solutions are required to maintain a low hourly volume infusion (12 ml/hour). Intravenous (intermittent dose) Intermittent intravenous bolus doses require a reduction in dose and dosage interval compared with intermittent intramuscular injections. The smaller and more frequent intravenous doses permit a more rapid, predictable and readily observable response and allow titration of dose to response (see Figure 4.3). Indeed, this is the rationale behind PCA and explains the success of this technique. For practical reasons, it is not possible to use intermittent intravenous bolus doses of opioid routinely on general wards but they do have applications in: obtaining initial and rapid pain relief (eg immediately after an operation or following acute trauma); providing analgesia for patients who are hypovolaemic or hypotensive, when there is poor uptake of drug from muscle or subcutaneous tissue; and covering episodes of incident pain (eg dressing changes, physiotherapy) or inadequate analgesia. Rapid control of severe acute pain may be obtained by giving small intravenous bolus doses of opioid (eg morphine 0.5 to 4 mg every 3 to 5 minutes) (see Figure 4.3 on page 59) until pain relief is achieved. The total dose needed for this titration is a guide to the subsequent dose requirements. Patients must be continuously monitored during the titration.
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Initial morphine orders (2-hourly prn)
Age (yrs) 2029 3039 4049 5059 6069 7079 8085 >85
Dose range (mg) 7.512.5 7.512.5 5.010.0 5.010.0 2.57.5 2.55.0 2.55.0 2.03.0
Patient is uncomfortable and requests pain relief. Record pain score.
Is an opioid ordered?(a valid order is 2 hrly prn; dose range as per table). Yes Is sedation score < 2 and resp. rate > 8/min? Yes Give injection. 1 hour later record sedation score and resp. rate and pain score.
No Get order.
No Seek advice.
Figure 4.2 Intermittent subcutaneous/intramuscular opioid administration Note: Pain scores provide the guide to effective analgesia and should be assessed regularly and recorded on the bedside chart with other observations. Pethidine should not be given subcutaneously. IV=intravenous; prn=as needed. Reproduced with the permission of the Acute Pain Service, Royal Adelaide Hospital.
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Is sedation score < 2 and resp. rate > 8/min? Yes
No Re-assess later. No
Seek advice. Hold further doses until sedation score < 2 and resp. rate > 8/min. Consider naloxone (100 g increments IV).
Is patient uncomfortable (in pain) and/ or requesting another injection? Record pain score. Yes
Is sedation score < 2 and resp. rate > 8/min? Yes
Is it more than 2 hours since patient had last dose?
Yes Repeat same dose unless Increase size of subsequent clinical situation is doses. altered.
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Seek advice. Hold further doses until sedation score < 2 and resp. rate > 8/min. Consider naloxone (100 g increments IV).
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No
Seek advice about giving injection before 2 hours.
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Decrease size of subsequent doses.
PAIN? Yes Pain protocol and opioid ordered?
No
Routine observations.
No
Get order.
Routine observations. No Yes
Yes Prepare in saline morphine 1 mg/ml, pethidine 10 mg/ml or fentanyl 20 g/ml.
10 ml syringedraw up to 10 mg morphine,100 mg pethidine or 200 g fentanyl and make up to 10 ml with saline.
PAIN?
Sedation score < 2?
No
Seek advice.
Resp. rate > 8? Yes BP OK? Yes
No
Hold further doses until sedation score is <2 and resp. rate is >8/min. Consider naloxone (100 g increments IV).
WAIT 5 min.
Figure 4.3 Intermittent intravenous opioid administration Note: Pain scores provide the guide to effective analgesia and should be assessed regularly and recorded on the bedside chart with other observations. IV=intravenous. Reproduced with the permission of the Acute Pain Service, Royal Adelaide Hospital.
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No Give 1 ml IV. No Give 4 ml IV.
Seek advice.
No
Seek advice.
Aged under 70?
No
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Yes SEVERE pain? Some relief with last 2 doses? Yes Give 2 ml IV.
No
SEVERE pain? Yes
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Give 0.5 ml. No
Give 2 ml IV.
Some relief with last 2 doses? Yes Give 1 ml IV.
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Continuous intravenous infusion Continuous intravenous opioid infusions are used to avoid the peaks and troughs in blood concentrations associated with intermittent administration. However, it is difficult to predict the required blood level for a particular patient and opioid requirements may vary with time. Safe and effective administration of intravenous infusions requires reliable infusion devices and frequent assessment and monitoring of patients by trained staff, with appropriate adjustment of infusion rates and administration of bolus doses. To reach 95 per cent of the final steady state concentration for drugs given by infusion requires five half-lives (up to 20 hours for morphine). Increasing the infusion rate alone in response to inadequate analgesia will result in considerable delays in achieving analgesia, and the potential danger of further rising opioid concentrations once analgesia has been attained. If analgesia is inadequate, an increase in opioid concentration is best achieved by administration of a small bolus dose before increasing the infusion rate. The response to any change in dose must be carefully and frequently assessed as opioid administration continues with infusions regardless of the conscious state of the patient.
Key point
Traditional methods of opioid administration include oral, intramuscular, subcutaneous, intravenous and continuous intravenous routes. These methods each have advantages and disadvantages in different groups of patients, but are more likely to be effective when the dosage regimen is tailored to the individual. The patients need for pain relief should be seen as more important than strict adherence to a dose interval. Patient-controlled analgesia While patient control should be an aspect of all analgesic delivery, the term patientcontrolled analgesia commonly refers to the use of sophisticated infusion devices that can be activated by the patient to self-administer small doses of intravenous opioids. This overcomes the wide variation in patients analgesic requirements and allows patients to adjust the level of analgesia to their own level of comfort and tolerance of side effects. PCA has been shown to provide better patient satisfaction and improved ventilation than do conventional routes of administration (level II; McArdle 1987). When used in PCA mode only (ie without a background infusion), the possibility of sedated patients receiving further opioids is minimised. In adults, background infusions increase the amount of opioid delivered and increase the risk of side effects without significantly improving analgesia (Owen & Plummer 1997). In contrast, in patients already receiving opioids with a degree of opioid tolerance, background infusions are reasonable and the infusion rate should be derived from the patients current daily opioid requirement (Macintyre & Ready 1996). Patients must be given adequate instruction pre-operatively about the use of PCA and their suitability for the technique confirmed (ie they must understand the principles of the technique and be able to activate the device). Given the financial and resource constraints in many institutions, there may be insufficient PCA machines or adequately trained staff to operate them. In this situation, it is important to select patients most likely to derive maximum benefit from PCA.
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This includes patients who: have had major operations and are fasting; have marked incident pain (eg pain associated with physiotherapy or dressing changes); have a contraindication to intramuscular injections even for a short time (eg coagulopathy such as haemophilia); or are strongly motivated and appropriately educated in the use of PCA. While PCA is usually associated with intravenous administration, it may be used to deliver opioids subcutaneously or epidurally. There is evidence that PCA is more effective when it is overseen by an acute pain service, which at a minimum includes an anaesthetist and a clinical nurse specialist who are experienced in specific pain management modalities (level III; Stacey et al 1997). Adequate knowledge of PCA is essential to avoid documented serious outcomes (level IV; Kreitzer et al 1989). Effective use of PCA also requires adequate maintenance of equipment, appropriate protocols and standard monitoring of treatment records. The use of PCA in the absence of these requirements is less likely to be associated with effective and safe pain relief. Safe and appropriate use of PCA by patients requires frequent and informed monitoring by registered nurses who have undergone relevant inservice education and accreditation in the management of these devices. Standard orders and drug dilutions are suggested to maximise the effectiveness of PCA and minimise complications, although, as with all methods of analgesic delivery, flexibility in prescribing is required in order to assess patients needs for analgesia and their response to required therapy, and to make changes if necessary (ie adjusting the size of bolus dose). Important elements of PCA standard or preprinted orders are listed in Table 4.6. Commonly used settings for intravenous PCA are listed in Table 4.7.
Table 4.6
1 Drug(s), concentrations 2 Pump settings
3 Mode of use 4 5 6 7 8 9
Initial drug loading instructions Instructions for treating breakthrough pain A statement to eliminate the ordering of CNS depressants by others Monitoring instructions Availability of drugs to treat side effects Instructions for the treatment of side effects Respiratory depression Nausea and/or vomiting Pruritus Urinary retention 10 Instructions about concurrent use of other CNS depressants, if ordered by pain service 11 Instructions about whom to contact if problems occur 12 Date, time, signature
CNS=central nervous system. Source: Ready et al 1995.
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Important elements of intravenous PCA preprinted orders Incremental dose Lock-out interval Other limits (eg 4-hr, 1-hr) PCA only Continuous infusion
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Acute pain management: scientific evidence Table 4.7 Commonly prescribed initial values for intravenous PCA variables Value 0 mg (ie zero) Morphine 1 mg Pethidine 10 mg Fentanyl 20 g Hydromorphone 0.2 mg Variable Comments Best to titrate for each patient before starting PCA Consider starting with doses half these amounts in patients over 70 years of age Best if standardised for each drug
Variable Loading dose Incremental dose (bolus dose)
Concentration Dose duration Lock-out period Background infusion
Cannot be adjusted in most PCA machines, but where this can be done stat is the shortest dose duration 58 minutes 0 mg/hour (ie zero) Exceptions: opioid tolerant patients, those with severe pain at night, and those needing PCA for long periods Consider varying according to patient age and prior opioid use
1-hour or 4-hour limits
30 mg morphine (or equivalent) in 4 hours
Source: Macintyre & Ready 1996.
Statement of evidence patient-controlled analgesia
PCA has been shown to provide greater patient satisfaction and improved ventilation compared to conventional routes of administration. Patient-controlled analgesia (PCA) managed by an acute pain service (APS) or by non-pain specialist health professionals is associated with similar pain scores; however the incidence of side effects is lower in patients whose PCA is managed by an APS. Further well designed studies are needed to evaluate how supervision of PCA by an APS affects cost, quality of care and patient satisfaction.
Key points
Patient-controlled analgesia (PCA) allows patients to adjust the degree of pain relief to their own desired level of comfort and tolerance of side effects. Adequate knowledge of patient-controlled analgesia (PCA) is essential to avoid documented serious outcomes. Novel routes and methods of opioid administration
Controlled release oral opioid preparations Oral long-acting opioids can be used to relieve acute pain after surgery, but certain measures must be taken to ensure the safe use of these preparations (level IV; Smith & Power 1998). Many patients suffer an analgesic gap after surgery, between good analgesia in hospital provided by parenteral opioids or regional analgesic techniques and the time when they are at home only requiring a simple analgesic (such as 62
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Level of evidence
II McArdle 1987 III Stacey et al 1997
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paracetamol) for their pain (level IV; Audit Commission 1997). Oral controlled-release opioids given in low dosage, with a short-acting opioid prescribed as rescue medication (with NSAID or paracetamol) may be used to bridge this gap. For example, Kapanol 20 to 40 mg twice daily given for 48 hours with rescue oxycodone 10 mg three hourly (if required) has been used with some success recently (Smith & Power 1998). The safety of this regimen depends on the normal resumption of gastro-intestinal function before the oral opioid is given (level III; Pinnock et al 1986); at least 24 hours should have elapsed after resumption of normal gastric emptying before using controlled-release oral opioids. Another safety factor is the use of the long-acting opioid in a low dose which only provides pain relief at rest; the patient must be given oxycodone to satisfy analgesia during activity (Smith & Power 1998). Sublingual The sublingual route has potential advantages if oral treatment is not possible due to severe vomiting or malabsorption. Hepatic first pass metabolism is avoided, and higher serum concentrations may be obtained. Sublingual absorption of lipophilic drugs is relatively high (buprenorphine 55 per cent, fentanyl 51 per cent, methadone 34 per cent), but hydrophilic drugs are less well absorbed (morphine 18 per cent). The potential for more rapid onset following sublingual rather than oral administration would benefit patients with intermittent, breakthrough or incident pain. However, the lack of available formulations and the inability to deliver high doses limits the role of sublingual administration for constant severe pain. Buprenorphine is available in a sublingual dosage form, and may be effective for moderate pain but, as it is a partial agonist, it has a ceiling effect for analgesia and could precipitate withdrawal if high doses are administered in conjunction with high doses of full agonists. Transmucosal Oral transmucosal fentanyl citrate (OTFC; fentanyl incorporated into a palatable, flavoured solid matrix) has been evaluated as a pre-anaesthetic medication in children, and found to be effective. The average onset of pain relief is within 9.5 minutes, but in addition to transmucosal absorption, gastric absorption (which is slower) also contributes to plasma levels. Side effects of nausea and vomiting and preoperative reductions in oxygen saturation limit the clinical usefulness of this preparation. It is not currently available in Australia. Transdermal Transdermal therapeutic systems (TTS) allow continuous parenteral administration of drug without requiring needles or infusion devices. Lipid soluble drugs are suitable (eg fentanyl citrateTTS-fentanyl). Transdermal fentanyl patches are available with different delivery rates ranging between 25 and 100 g/hour. Current patches have a slow onset, with a large and variable delay time (16.7 10 hours) being recorded for blood fentanyl concentrations to reach therapeutic concentrations, and absorption continues for up to 72 hours while the patch is in place. After removal of the patch, significant blood concentrations may persist for a similar period of time to that observed during onset of analgesia (approximately 16 hours). The slow onset and offset of action and relative inflexibility of dosing limit the usefulness of topical preparations in routine postoperative pain management. High-dose transdermal fentanyl given in combination with rescue analgesic may increase the risk of respiratory depression (level III; Bulow et al 1995, level II; Sandler 1994). Caution should be taken with disposal as significant amounts of residual drug remain in the patch. Iontophoresis is being investigated in drug delivery systems, with the aim of improving transdermal absorption.
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Rectal The rectal route may be used when patients have nausea or vomiting, but is contraindicated in patients with painful peri-anal lesions, diarrhoea or immune suppression. Doses similar to oral doses should be commenced, and then titrated according to response. Suppositories of oxycodone (30 mg), NSAIDs (diclofenac 100 mg, indomethacin 100 mg or ketoprofen 100 mg) or paracetamol (125 mg or 250 mg) are available, but the lack of dose flexibility in commercial preparations may limit their use (part suppositories should not be used due to uneven distribution in the preparation). Inhaled/intranasal Inhaled/intranasal opioid preparations, delivered by metered inhalers with a lock-out period, are being trialed. Such preparations may allow for non-invasive patientcontrolled analgesia in the future. Nasal spray formulations of fentanyl are also becoming available. Tramadola new opioid Tramadol is a synthetic analgesic which was used in Germany for a number of years before being introduced into other countries only relatively recently (level IV; Eggers & Power 1995). The advantage of tramadol is that it is analgesic with minimal sedation, respiratory depression, gastro-intestinal stasis, or abuse potential. Tramadol is a weak mu opioid agonist but also has important non-opioid spinal and central nervous system effects via noradrenergic and serotoninergic pathways (level II; Aronson 1997). Tramadol is therefore both an opioid and a non-opioid analgesic. The main disadvantages of tramadol include cost (level II; Lewis & Han 1997), and side effects including dizziness, nausea, sedation, dry mouth and sweating (Lee et al 1993). When given parenterally, tramadol produces equivalent analgesia to morphine except in severe postoperative pain (level II; Lewis & Han 1997, James et al 1996), being approximately equipotent to pethidine (Lee et al 1993). Epidural tramadol is less effective than epidural morphine (level II; Lewis & Han 1997). Tramadol is presented in oral and parenteral preparations and the recommended dose for postoperative pain relief is 100 mg, with a daily total of 600 mg.
Regional techniques
There are a number of ways in which nerve blocks with local anaesthetics can be used to treat acute pain regionally. These vary from simple wound infiltration to continuous neural blockade using catheters. The performance of single shot nerve blockade can give many hours of analgesia. However, this may only delay the onset of pain and requirement for a continuing form of pain relief. Greater benefit is obtained by the use of continuous catheter techniques that allow analgesia to be maintained for prolonged periods. Examples of this include interpleural, brachial plexus and femoral nerve analgesia. Pain relief is maintained either by repeated boluses or a continuous infusion of local anaesthetic. Interpleural analgesia has been used for relief of unilateral pain following chest trauma, thoracotomy, breast surgery, renal surgery and open cholecystectomy (Murphy 1993). Compared with systemic opioid analgesia alone, interpleural analgesia can improve postoperative respiratory function (level II; Frenette et al 1991), although the presence of a chest drainage tube, haemothorax or pleural collection will diminish its effectiveness (Ferrante et al 1991). It may need to be supplemented with other analgesics. Some forms of acute on chronic pain (thoracic herpetic neuralgia, complex regional pain syndrome of the upper limb and pancreatitis) also respond to interpleural analgesia. 64
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Continuous brachial plexus analgesia is produced by the placement of a catheter near the brachial plexus by one of the usual approaches (see Cousins & Bridenbaugh 1998). The analgesia produced covers nearly all the upper limb and also produces sympathetic blockade which can be beneficial following certain types of surgery (eg plastic surgery skin flaps). Continuous femoral nerve analgesia is useful for relief of pain and muscle spasm following knee surgery and can facilitate recovery from knee arthroplasty (see Cousins & Bridenbaugh 1998). Wound infiltration after minor surgery or trauma and after paediatric surgery is a well established analgesic method. However, the benefit of wound infiltration after major surgery is less certain. A review of randomised, placebo-controlled, double-blind trials found, in general, only a small reduction in opioid requirements and/or pain intensity with this method (level III; Dahl et al 1994a). However, a subset of these trials did show benefit where large doses or volumes of local anaesthetic were infiltrated into deeper wound structures (fascia, peritoneum or muscle) rather than just subcutaneously (level III; Dahl et al 1994a).
Key point
Regional methods of pain relief using local anaesthetic, either alone or in combination with systemic analgesia, can be effective after a number of localised procedures.
Epidural and intrathecal analgesia1

Epidural and intrathecal analgesic techniques have the potential to improve postoperative analgesia and modify physiological changes associated with surgery. Postoperative epidural analgesia can significantly reduce the incidence of pulmonary morbidity (level I; Ballantyne et al 1998, see Figure 4.4). When combined with active convalescent protocols and acute postoperative rehabilitation, epidural analgesia may improve overall outcome. However, these techniques also have rare but important risks related to catheter insertion (eg neurological injury), and the potential for life-threatening complications (eg intravascular injection of large doses of local anaesthetic). Therefore, the risk-benefit ratio for each patient must be determined, and the availability of adequate specialised postoperative care of epidural infusions at different institutions must be considered before choosing peri-operative epidural or intrathecal analgesic techniques. Detailed information about indications, contraindications and management are available in standard texts (eg Cousins & Bridenbaugh 1998). Epidural and intrathecal techniques should be administered and managed by an anaesthetist. Selection of an appropriate route of administration (intrathecal versus epidural) and site of catheter insertion (lumbar versus thoracic epidural) should be based on individual patient factors, the intra-operative surgical requirements, and the planned postoperative analgesic regimen. If local anaesthetics and a lipid soluble opioid are to be administered postoperatively, an epidural catheter should be placed as close as possible to the level of the dermatomes affected by the surgical incision. In adults, most epidural catheters are placed before the operation and the response to a test dose of local anaesthetic noted before induction of general anaesthesia. If this
1 Epidural administration refers to drug delivery outside the dura into the epidural space. Intrathecal administration refers to drug delivery directly into the cerebrospinal fluid.
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procedure is not followed, the response to surgical stimulation may be used as a guide to inadequate epidural blockade. Epidural analgesia may be administered by either a continuous infusion or a patientcontrolled method. Recent data shows the patient-controlled technique to be safe and effective even in the general ward environment (level III; Liu et al 1998).
Figure 4.4 Risk ratios and confidence intervals (CI) for postoperative pulmonary dysfunction in randomised controlled trials of epidural opioid versus intramuscular as-needed opioid, intravenous opioid by continuous infusion, or patient-controlled intravenous opioid bolus doses. Left: results from individual trials. Right: Estimates obtained by stepwise accumulation of results from successive trials. Source: Ballantyne et al 1998 (level I).
Epidural and intrathecal analgesic techniques can be safely managed on general wards if:
patients are carefully selected;
patients are regularly reviewed by an anaesthetist, and an anaesthetist is available for consultation or management of complications at all times; nursing staff have received specific teaching and accreditation about the management of these methods and potential adverse effects (see page 69); there are appropriate standard orders, nursing policies and procedures; pain score, sedation score, respiratory rate and motor and sensory block signs are monitored at frequent intervals; the epidural site is checked regularly for signs of inflammation/infection leakage and catheter dislodgement; when local anaesthetics are used, blood pressure and heart rate are monitored and documented and reportable values determined for each individual patient; and other medical staff caring for the patient are aware of the analgesic technique used, potential complications, and consult specialised pain management staff as required. 66
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Statements of evidenceepidural analgesia Postoperative epidural analgesia can significantly reduce the incidence of pulmonary morbidity Large audits of closely supervised epidural analgesia show the safety of the technique to be equivalent to traditional analgesic methods when coordinated by an acute pain service with appropriate patient observations and monitoring.
Level of evidence
I Ballantyne et al 1998 III Ready et al 1991, Schug & Torrie 1993, Scott et al 1995, Tanaka et al 1993, Breivik 1996, Rawal & Allvin 1996
Agents used in epidural/intrathecal analgesia Local anaesthetic The effect of spinally administered local anaesthetics is not limited to blockade of nociceptive afferent pathways alone. Sympathetic efferent activity is blocked, systemically absorbed local anaesthetic has additional effects, and the ability to modify physiological responses to surgery is improved. Opioids Epidural and intrathecal opioids produce selective analgesia by blocking opioid receptors in the dorsal horn (see Cousins & Mather 1984, Carr & Cousins 1998). Epidurally and intrathecally administered opioids have analgesic actions and a duration of effect which parallels cerebrospinal fluid (CSF) concentrations rather than plasma concentrations. Lower doses of opioids are required when given by the epidural/intrathecal route and thus systemic side effects may be reduced. However, plasma concentrations of opioid may be significant and contribute to early analgesia, particularly following epidural administration of lipophilic agents. Epidural opioids have been shown to be more effective when used in combination with local anaesthetic to produce a synergistic analgesic action and reduce the required dose and side effects associated with either the local anaesthetic or opioid alone (level II; Wiebalck et al 1997). Opioid uptake after epidural injection may follow at least four routes: diffusion through the dural membrane of the spinal root cuff into the CSF and to the dorsal horn of the spinal cord and to the brain (via cephalad migration in CSF); possible direct transfer from the epidural space to the spinal cord via spinal radicular arteries (level III; Bernards 1993); vascular uptake into the bloodstream; and diffusion into surrounding lipophilic tissues that lack opioid receptors. The physicochemical properties of different opioids result in differences in distribution, duration of effect and side-effect profile when these agents are administered spinally: Hydrophilic agents such as morphine have a longer residence time in the CSF with associated cephalad migration. This has the advantage of allowing prolonged duration of analgesia following a single dose (12 to 24 hours) and the epidural catheter tip does not need to be close to the source of nociceptive impulses (eg lumbar epidural injection may provide analgesia for thoracic level pain). Because of its long residence in neural tissue, morphine has the potential for delayed respiratory depression 12 to 24 hours after the last dose. 67
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Lipophilic agents, such as fentanyl, exhibit less migration and more segmental analgesia. The duration of action is also shorter and administration by an infusion with attention to the spinal level of the epidural catheter tip is required. A lipophilic agent not yet available in Australia, sufentanil, has a segmental spread in the CSF and has been used safely on the ward when guidelines were followed (level II/III; Hansdottir et al 1995, 1996a, 1996b) In some studies, no clear advantage has been shown with opioids administered spinally (not combined with local anaesthetics) when compared with systemic opioids. High incidences of episodic postoperative hypoxaemia have been shown with parenteral or epidural opioid, and the stress response is only partially attenuated by opioids alone (level I; Liu et al 1995b). Statement of evidence Epidural opioids are more effective when used in combination with local anaesthetic to produce a synergistic analgesic action and reduce the required dose and side effects associated with either the local anaesthetic or opioid alone. Level of evidence
II Wiebalck et al 1997
Non-opioid spinal analgesics Knowledge of the physiology and pharmacology of spinal sensory processing is increasing. Non-opioid receptor systems are targets for spinal modulation of nociception, with the aims of improving analgesia (particularly in patients with neuropathic pain) and of reducing side effects. Analgesic efficacy, as well as systemic and local toxicity, of potential spinal analgesics must be carefully evaluated before clinical use. At this time, the following agents under investigation are not approved for routine spinal administration for analgesia in Australia. Clonidine (alpha2 receptor agonist), which shifts the opioid dose-response curve to the left and has a synergistic analgesic action when co-administered spinally with opioids. Addition of clonidine to epidural local anaesthetic prolongs the duration of analgesia. Side effects include hypotension, bradycardia and sedation. The hypotensive action of clonidine is countered at larger doses by a direct peripheral vasoconstrictive effect. Clonidine does not produce respiratory depression or nausea. GABA (gamma-aminobutyric acid) agonists. Benzodiazepines are agonists at the GABA-A receptor. Intrathecal and epidural midazolam has been shown to have analgesic properties but this agent is currently not approved for spinal use. Baclofen, a GABA-B receptor agonist, is administered intrathecally to treat spasticity following central nervous system damage, but its analgesic effects have not been extensively studied. Neostigmine (cholinesterase inhibitor) produces analgesia when administered spinally, but dose-response data and side-effect profiles are not fully elucidated. Neostigmine has a synergistic analgesic action with clonidine and offsets the cardiovascular side effects of this agent. The spinal analgesic action, side effects and toxicology of many agents are currently being investigated, including aspirin, NSAIDs, amitriptyline and specific neuronal calcium channel antagonists (SNX-111). The role of these agents in acute postoperative pain management has not yet been determined. 68
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Complications and side effects of epidural and intrathecal techniques Catheter-related complications Dural puncture. The rate of inadvertent dural puncture during epidural insertion is 0.6 to 1.3 per cent. The likelihood of developing a post-dural puncture headache varies between 16 to 86 per cent as multiple factors are involved (eg needle size, patient age). Serious neurological injury occurs very rarely in association with lumbar epidural analgesia. This is also true for insertion at the thoracic level (level III; Giebler et al 1997). When compared with general anaesthesia, the incidence is probably not different (level IV; Kroll et al 1990). Epidural haematoma. Clinically significant epidural haematoma occurs rarely in association with epidural analgesia. The risk is increased by impaired haemostasis at the time of epidural catheter insertion or removal. The risk may also be increased by the concurrent use of prophylactic low-dose heparin or low molecular weight heparin (US FDA 1997). Published safety guidelines specify the use of minimal effective doses of anticoagulant at appropriate intervals, with insertion and removal of epidural catheters separated by at least an entire half life of the anticoagulant used, timed from the last dose of anticoagulant given. These guidelines show the importance of safety precautions for significantly minimising this risk (level IV; Tryba & Wedel 1997, Horlocker & Wedel 1998, Vandermeulen et al 1994). Epidural abscess or meningitis. As with epidural haematoma, this complication is rare but requires early detection and urgent surgical intervention to minimise the risk of long-standing neurological sequelae secondary to spinal cord compression. Local anaesthetic effects Local anaesthetic cardiovascular and central nervous system toxicity due to inadvertent local anaesthetic overdose or intravascular injection. Urinary retention. Total spinal analgesia if excessive local anaesthetic doses are administered intrathecally rather than epidurally. Variable haemodynamic effects of sympathetic blockade, postural hypotension and increased intravenous fluid requirement. Motor block (with high concentrations of local anaesthetic) which impairs mobilisation, in combination with sensory block, may contribute to the development of pressure areas. Opioid-related side effects Respiratory depression can occur with all spinally administered opioids if these are given in excessive doses. The risk of delayed respiratory depression is greatest with morphine as its hydrophilic structure results in long-term transit time in the CSF with cephalad migration to the brainstem and prolonged residence in neural tissue. Respiratory depression with appropriate doses of spinally administered opioids is not likely in patients already on long-term opioids. Pruritus, nausea and urinary retention are most frequent with morphine and less likely following fentanyl, but the incidence varies in different studies.
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Potential advantages of epidural analgesia Cardiovascular system Epidural local anaesthetic has the potential to reduce myocardial oxygen demand (reduction in sympathetic activation and stress response) and also to increase myocardial oxygen supply (decrease in hypoxaemic episodes, reduction in postoperative hypercoagulable state, and reduction in coronary vasoconstriction) (level III; Meissner et al 1997). These effects require blockade of cardiac sympathetic fibres (T1 to T5) and will be offset unless intravascular volume is adequate and circulatory stability is maintained. The effects of epidural analgesia on outcome related to myocardial ischaemia remain controversial, although reduced morbidity and mortality have been suggested in studies of high-risk patients (level II; Yeager et al 1987, Tuman et al 1991). Unfortunately, the study of Yeager et al (1987) suffers from design defects and the most compelling evidence of beneficial effects of thoracic epidural analgesia comes from studies of patients with unstable angina. In such patients, segmental (T1 to T5) thoracic epidural block is associated with improved indices of myocardial function (level III; Blomberg et al 1989a,1989b, Koch et al 1990, Olausson et al 1997). Respiratory system Epidural local anaesthetics have the potential to improve pulmonary function by reducing diaphragmatic dysfunction due to reflex inhibition of phrenic nerve activity, in addition to relief of pain. Current data are insufficient to conclude that the improvement in pulmonary function by neural blockade reduces the incidence of pulmonary infective complications. Larger studies are required that include standardised epidural protocols in combination with active rehabilitation, physiotherapy and mobilisation in the postoperative period (Kehlet 1997). A meta-analysis of randomised controlled trials showed that when compared with conventional analgesic delivery, epidural opioid analgesia produced clinically significant beneficial effects on arterial oxygen saturation and on the incidence of atelectasis (level I; Ballantyne et al 1998). Stress response Surgery and local trauma lead to the release of neuroendocrine mediators and cytokines, resulting in a variety of physiological changes collectively termed the stress response. Catabolic active hormones are elevated while anabolic hormones are lowered, with resultant increases in circulating catecholamines, metabolic rate and cardiac output. Fluid and electrolyte balance shifts towards water and sodium retention and coagulation is activated and fibrinolysis inhibited (level II; Kehlet 1997). Stress response mediators also inhibit the immune system and may contribute to positive immunosuppression and infection. In high-risk surgical patients, modifying the stress response may reduce the hypermetabolism and increased demands on body mass and physiological reserve, and may reduce morbidity. General anaesthesia, with the exception of high-dose opiate anaesthesia (24 mg/kg morphine or 50200 g/kg fentanyl), has no modifying influence on the stress response. Epidural anaesthesia is effective in abolishing the stress response after lower abdominal and lower limb surgery, but results in minimal or varying degrees of modulation following upper abdominal or thoracic surgery. Differences in the extent, density and duration of neural blockade, choice of local anaesthetic and epidural technique, and magnitude of local release of stress mediators associated with different surgical procedures may explain the variable effects seen in different studies (level I/II; Kehlet 1997).
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Coagulation A hypercoagulable state occurs following major surgery due to increased concentration of coagulation factors, decreased concentration of coagulation inhibitors, enhanced platelet activity and impaired fibrinolysis. Epidural local anaesthesia can modify the risk of peri-operative thrombotic complications by reducing the stress response which initiates the above changes, and by attenuating the excessive coagulability. In addition, blockade of sympathetic efferents improves blood flow, and systemic levels of local anaesthetics may have a direct effect on platelet aggregation. Reductions in lower limb vascular graft occlusion (level II; Tuman et al 1991, Christopherson et al 1993) and in the incidence of deep venous thrombosis and pulmonary embolism following hip surgery (level III; Modig et al 1983) have been shown with the use of peri-operative epidural local anaesthesia and analgesia. Gut function Postoperative ileus delays hospital discharge and may contribute to postoperative morbidity. Early enteral feeding has been shown to reduce the surgical stress response, reduce postoperative septic complications, and improve wound healing (Liu et al 1995a). Epidural local anaesthetics have been shown to reduce the duration of postoperative ileus (level II; Liu et al 1995a). Bowel motility is improved by blockade of both the afferent nociceptive and efferent sympathetic components of the spinal reflex arc by which abdominal pain inhibits intestinal motility. In order to gain maximum benefit, epidural local anaesthetic should be continued for several days postoperatively and opioid dose should be minimised by use of a multimodal analgesic regimen. Surgical protocols need to be updated to ensure early removal of nasogastric tubes and resumption of enteral feeding. Blood loss Intra-operative blood loss is reduced by an average of 30 per cent during operations in the lower part of the body. No such advantage has been demonstrated during major upper abdominal or thoracic procedures (level II; Kehlet 1997). Outcomes following epidural anaesthesia and analgesia The greatest benefit associated with epidural techniques have been shown in highrisk patients undergoing major surgery in whom epidural anaesthesia (with or without general anaesthesia) was followed by adequate epidural analgesia for two to five days postoperatively (level II; Liu et al 1995b). Currently, insufficient numbers of patients have been studied, with adequate standardisation of patient groups, types of surgery, site of catheter insertion, type and duration of analgesic agent delivered, to clearly determine the risk-benefit analysis of epidural or intrathecal analgesia in lowrisk patients who have a low incidence of complications. Improved pain relief with epidural analgesia, as a sole peri-operative strategy, is unlikely to improve outcome and reduce hospital stay. However, in addition to providing pain relief, epidural analgesia alters sympathetic efferent activity and the pathophysiological changes which follow surgical stress. Modification of surgical and nursing protocols to ensure early enteral feeding, improved nutrition and active mobilisation is required to maximise the effects of neural blockade on pain, perioperative stress responses and organ dysfunction. A combined approach which incorporates all aspects of peri-operative rehabilitation is likely to offer the best chances of improving outcome, reducing hospital stay and ensuring cost-benefit advantages (Kehlet 1997).
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Non-steroidal anti-inflammatory drugs

Early investigation of the use of NSAIDs for relieving postoperative pain demonstrated the benefits of improved analgesia without sedation or respiratory depression, using either an intravenous form of acetylsalicylate (level II; Kweekel-De Vries 1974), or indomethacin (level II; Reasbeck et al 1982). Such early reports also predicted the possibility of side effects including impaired platelet function. More recent studies have confirmed the efficacy of NSAIDs as analgesics in the postoperative period, although currently available agents are not powerful enough to be used alone for severe pain (level II; Power et al 1990a, Cepeda et al 1995). Many NSAIDs have now been studied and found to be useful analgesics after surgery. These include: indomethacin (level II; Turner & Gorringe 1994); tenoxicam (level II; Elkahim & Nafie 1995, Vandermeulen et al 1997); ketorolac (level I; Gillis and Brogden 1997; level II; Power et al 1990b, Brown et al 1990, Kostamovaara et al 1998, Etches et al 1995); diclofenac (level I; McQuay & Moore 1998, level II; Kostamovaara et al 1998, Gillberg et al 1993); and ibuprofen (level I; McQuay & Moore 1998). For the management of moderate to severe pain after surgery, a single dose of diclofenac 50 mg alone has an NNT of 2.3. This means that one out of every two to three patients experiences at least 50 per cent pain relief compared to placebo. The NNT for ibuprofen 400 mg is 2.7 (McQuay & Moore 1998). NSAIDs may be of particular use for pain relief after outpatient, ambulatory surgery (level II; Jakobsson et al 1996). At present, ketorolac is the only NSAID available in an injectable form in Australia, and is only recommended for short-term use postoperatively (limit five days). It is currently not clear whether the oral, rectal or injection method of administration of NSAIDs is more effective (McQuay & Moore 1998). The pre-emptive use of NSAIDs as sole analgesics has not been justified by welldesigned clinical studies (level II; Espinet et al 1996, Buggy et al 1994), although this is an area of active research. The efficacy of NSAIDs as components of multimodal analgesia has been confirmed by clinical trials (level II; Kehlet 1997, Power et al 1994, Pavy et al 1995). For example, the incorporation of two different NSAIDs (parenteral ketorolac and oral ibuprofen) into a multimodal analgesic program has been shown to improve the rate of recovery of bowel function after major colonic surgery (level II; Liu et al 1995a). In situations where there are no contraindications, NSAIDs are the drug of choice after many day-case procedures. If the oral route is unavailable, NSAIDs may be given rectally or by injection. In some situations topical NSAID may be useful and has been reported to have an NNT of 3 to 5 (McQuay & Moore 1998). Royal College of Anaesthetists Guidelines for the use of NSAIDs in the peri-operative period A working party of the Royal College of Anaesthetists (United Kingdom) has recently undertaken a comprehensive structured review of the published literature concerning the use of NSAIDs in the perioperative period. This has led to the publication by the Royal College of Anaesthetists of authoritative and evidence-based guidelines for the use of NSAIDs in the perioperative period (level I; Royal College of Anaesthetists 1998).
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In the guideline summary, the working party made the following Grade A conclusions (based on the strongest evidence available, including at least one randomised trial as part of the body of literature of overall good quality). NSAIDs are not sufficiently effective as the sole agent after major surgery in most patients. NSAIDs are often effective after minor or moderate surgery. NSAIDs often decrease opioid requirement. Significant reduction in opioid sideeffects has been noted in a few studies only. The quality of opioid-based analgesia is often enhanced by NSAIDs. NSAIDs increase bleeding time and some studies have shown increased blood loss. The Working Party also made the following Grade B conclusion (based on availability of well-conducted studies but not randomised trials). The clinician should be aware that many important drug interactions have been reported. Important pharmacokinetic interactions between NSAIDs and warfarin, lithium, oral hypoglycaemics, phenytoin, methotrexate, digoxin, aminoglycosides, cyclosporin, tacrolimus and probenicid are examined in the report. Pharmacodynamic interactions between NSAIDs and antihypertensives, anticardiac failure therapy and anticoagulants are also examined (Royal College of Anaesthetists 1998). Adverse effects of aspirin and NSAIDs The major adverse effects fall into the following groups: gastro-intestinal; renal; platelet; and aspirin-induced asthma. The adverse effects of NSAIDs are potentially serious and it is imperative that contraindications are respected (level II; Merry & Power 1995). The most important adverse effects for surgical patients are those of the gastro-intestinal system (level III; Strom et al 1996), renal and platelet function and the possibility of aspirin-induced asthma in susceptible individuals (level IV; Power 1993). Patients who have known risk factors for NSAID-related adverse effects should not be given these drugs in the peri-operative period. In general, the incidence and severity of adverse effects related to NSAIDs are greater in elderly patients. The route of administration of NSAIDs does not influence the potential for serious side effects. Renal effects It is known that renal prostaglandins are important for the maintenance of renal function in the peri-operative period and that NSAIDs can have demonstrable effects when given at the time of surgery (level II; Power et al 1992). There have been case reports of sudden and unexplained renal dysfunction in association with the use of ketorolac (level IV; Smith et al 1993), emphasising the need for vigilance when using this drug. Risk factors include concomitant use of nephrotoxic antibiotics (such as gentamicin) (level II; Jaquenod et al 1998), raised intra-abdominal pressure (such as at laparoscopy), hypovolaemia and age greater than 65 years. Ketorolac given for less than five days may not increase the rate of acute renal failure, but the risk increases with longer duration of therapy (level III; Feldman et al 1997). Nevertheless, use of appropriate doses peri-operatively, in several million patients without complications
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Acute pain management: scientific evidence Feldman et al 1997).
administered NSAIDs worldwide, has not resulted in renal complications (level III;
Effects on platelet function NSAIDs may reduce the incidence of myocardial ischaemia after surgery, but it is not clear whether this is via inhibition of thromboxane production and platelet function, improved analgesia, or an intrinsic effect on the heart (level II; Beattie et al 1997). NSAIDs inhibit platelet function by preventing the production of thromboxanes. Various studies have found that this does not produce any clinical problems, although skin bleeding time is increased (level II; Power et al 1990b). In certain clinical circumstances, the antiplatelet effect of the NSAID may lead to increased potential for surgical bleeding, as reported after outpatient tonsillectomy in children (level II; Gunter et al 1995). The antiplatelet effect of aspirin does not increase the risk of performing central regional nerve blocks, including epidurals (level II; Beroyz et al 1994, Horlocker et al 1995, level IV; Smith et al 1996). Interestingly, the antiplatelet effect of aspirin may be of some benefit and aspirin has been proposed as adjunctive therapy to reduce the incidence of venous thrombo-embolism and arterial thrombotic events after surgery (level I; Antiplatelet Trialists Collaboration 1994). Statements of evidenceNSAIDs
While the currently available NSAIDs do not relieve severe pain when used alone, their efficacy as components of multimodal analgesia has been confirmed by clinical trials.
The adverse effects of NSAIDs are potentially serious and it is imperative that contraindications are respected.
NSAID doses NSAIDs and their doses are listed in Table 4.8. It is wisest to choose an NSAID with a short or intermediate duration of action, so that if side effects do occur they will abate quickly with cessation of the drug. Ketorolac is a reasonable choice in this respect. However, it is vital to observe dosage recommendations for ketorolac closely since increasing the dose will not increase analgesia but will increase side effects (level II; Gillis & Brogden 1997).
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I McQuay & Moore 1998, Royal College of Anaesthetists 1998 II Power et al 1990a, 1994; Cepeda et al 1995; Pavy 1995; Liu et al 1995a II, III Power et al 1992, Strom et al 1996; Gillis & Brogden 1997, Feldman et al 1997, Merry & Power 1995, Jaquenod et al 1998
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Acute postoperative pain management in adults Table 4.8 Drug NSAID dosages and pharmacokinetic data Usual dose (mg) Dosing interval (h) Maximum daily dose (mg) Time to peak plasma conc. (h) Elimination half-life (h)
Oral Formulations Salicylates Aspirin Diflunisal Acetic acids Indomethacin Diclofenac Sulindac Ketorolac (<65 yrs) (65 yrs) Propionic acids Ibuprofen Ketoprofen Naproxen Tiaprofenic acid Oxicams Piroxicam Tenoxicam Pyrazolones Phenylbutazone
300600 250500 50100 2550 100200 10 10 200400 100 250500 300 1020 1020
4 12 612 812 12 46 68 68 1224 12 1224 24 24
3,600 1,000 200 150 400 40 30 1,600 200 1,000 600 20 20 600
12 24 12 24 1
0.25 812 6 7 46
0.51.5 0.52 12 1 24 12.6 2
22.5 1.5 15 2 53 72 50 100
Anthranilic acids Mefanamic acid 500 8 1,500 24 34 Parenteral formulations Acetic acids Ketorolac (< 65 yrs) 1030 46 90 1 46 Ketorolac ( 65 yrs) 1015 46 60 Rectal preparations of some NSAIDs are available eg (adult doses): indomethacin suppository 100 mg; diclofenac suppository 100 mg.
New NSAIDs: selective cyclo-oxygenase-2 inhibitors The mechanism of action of aspirin and other NSAIDs, of prevention of prostaglandin production by inhibition of the cyclo-oxygenase enzyme, has been recognised for over three decades, but significant advance was made with the description of an inducible form of cyclo-oxygenase (Cox-2) (level I; Vane et al 1998). Cox-2 is induced by a number of factors including surgical trauma and other forms of tissue damage, endotoxin, IL-1 and hypoxia (level I; Fosslien 1998). In contrast, Cox-1 is constitutively expressed and is thought to be responsible for normal physiological prostaglandin production in many tissues (eg cytoprotection in the gastric mucosa and aspects of renal tubular function) (Fosslien 1998). Most NSAIDs presently available for clinical use inhibit both Cox-1 and Cox-2. NSAIDs have now been developed that may have fewer side effects because they inhibit only the inducible form of cyclo-oxygenase (Cox-2) while sparing the constitutive (Cox-1) enzyme (level II; Laneuville et al 1994, Hawkey 1995). One new selective Cox-2 inhibitor, meloxicam, is as effective an analgesic as diclofenac in patients with osteo-arthritis of the knee (level II; Lund et al 1998), and the incidence of gastro-intestinal symptoms is halved in patients receiving meloxicam 75
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compared with diclofenac (level II; The et al 1997). A meta-analysis involving 1,100 patient years of treatment with meloxicam showed an improved gastro-intestinal safety, but similar renal and liver toxicity compared with conventional NSAID (level I; Furst 1997). Nimesulide is another selective inhibitor of Cox-2 with equivalent analgesic activity to conventional NSAID but with reduced gastro-intestinal side effects (level I; Rabasseda 1996, Famaey 1997). At present, much of the clinical information on the use of selective Cox-2 antagonists is from the rheumatology literature. More research is needed on the efficacy and safety of the use of these agents for acute pain relief.
Paracetamol
Paracetamol is effective for mild to moderate pain, and as an adjunct to opioids in more severe pain (level II; Schug et al 1998). It is available in both oral (various doses) and rectal forms (500 mg suppository). Paracetamol 1000 mg alone has an NNT of 4.6. Paracetamol 1000 mg with codeine 60 mg has an NNT of 1.9 (McQuay & Moore 1998; Moore et al 1997). Paracetamol has analgesic and antipyretic effects but is not considered to be antiinflammatory. Although there remains controversy about its mechanism of action, it may act by inhibiting the cyclo-oxygenase enzyme in the central nervous system, while sparing peripheral prostaglandin production. Recent research confirms a significant central action (level III; Bannwarth et al 1995). In adult patients with normal renal and hepatic function, the recommended dose is 500 to 1,000 mg oral or rectal, every three to six hours when necessary, with a maximum daily dose of 6 g a day in divided doses for acute use and 4 g a day for chronic use. Paracetamol is rapidly absorbed from the gut and peak plasma concentrations are reached 30 to 60 minutes after oral ingestion. Paracetamol is metabolised in the liver and excreted by the kidneys. Plasma protein binding is low and the elimination halflife is two to three hours. Single doses of more than 100 mg/kg may result in severe liver damage, hypoglycaemia and acute tubular necrosis. Contraindications include active liver disease, alcohol-induced liver disease and glucose-6-phosphate dehydrogenase deficiency. In general, paracetamol has fewer side effects than NSAIDs, and can be used when the latter are contraindicated (eg asthma, peptic ulcers). There is evidence that paracetamol may protect against malignancies, in a manner similar to that in which long-term low-dose aspirin protects against gastro-intestinal malignancies (level II; Cramer et al 1998). The most recent development in the use of paracetamol has been the introduction in some European countries of an intravenous preparation in the form of the precursor propacetamol (2 g of the precursor is converted to 1 g of paracetamol). Studies have not only shown propacetamol to be effective for postoperative analgesia (level II; Granry et al 1997) but also more effective than paracetamol (level II; Jarde & Boccard 1997). A recent investigation demonstrated a 46 per cent reduction in opioid requirements in orthopaedic patients given regular propacetamol (level II; Peduto et al 1998).
Multimodal analgesia
There is evidence that patients benefit from the use of multimodal, or balanced, analgesia after surgery. NSAID, paracetamol, local anaesthetics, other non-opioid analgesics, and opioids are employed in combination to improve pain relief (level II; Kehlet & Dahl 1993a, 1993b). Multimodal analgesia employs a variety of drugs, given perhaps by different routes, to achieve analgesia with a reduction in the incidence and severity of side effects (level II; Kehlet 1989, Kehlet 1997). One good example is that the 76
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addition of regular injections of ketorolac to a regime previously based on intercostal nerve blocks and patient-controlled morphine significantly improved analgesia after thoracotomy (level II; Power et al 1994). Non-opioid analgesics contribute significantly to multimodal analgesia and postoperative recovery of the patient by minimising opioid side effects including the inevitable opioid induced gastro-intestinal stasis which delays the resumption of normal enteral nutrition after surgery. After bowel surgery, multimodal analgesia comprising epidural analgesia using a mixture of local anaesthetics and low-dose opioid provides excellent analgesia and hastens the rate of recovery of gastrointestinal function after surgery of the colon, especially if systemic NSAIDs are used to avoid the need for opioid administration after the epidural has been ceased (level II; Liu et al 1995a). It is possible to eliminate pain after surgery using multimodal analgesia with a significant reduction in total opioid consumption (level II; Schulze et al 1988, Dahl et al 1990). However the effect on morbidity and mortality has been disappointing in some studies (level II; Moiniche et al 1994a), demonstrating that very good pain control is not automatically associated with an improvement in outcome after surgery. Recent research has suggested, however, that the use of multimodal analgesia after major surgery may improve recovery and thus reduce costs (level II; Brodner et al 1998). Kehlet has proposed that the pain free state should be employed as a fundamental component of an aggressive regime of postoperative mobilisation and early oral feeding in a process of acute rehabilitation after surgery (Kehlet & Dahl 1993a). Clearly, multimodal analgesia employing non-opioids to minimise opioid requirements has the particular advantage over unimodal systemic opioid administration of providing excellent pain relief upon movement allowing early mobilisation. In addition, by using non-opioids as part of a balanced analgesic plan, the patient can return to normal enteral nutrition much more quickly by avoiding the undesirable opioid problems of gastro-intestinal stasis and nausea and vomiting (level II; Moiniche et al 1994a, Moiniche 1994b, Bardram et al 1995). Statement of evidencemultimodal analgesia
Multimodal analgesia (ie the combined use of different classes of analgesics) improves the effectiveness of pain relief after surgery. There may also be an associated reduction of the dose of each analgesic drug and the intensity of any side effects.
Pre-emptive analgesia
The importance of peripheral and central sensitisation in continuing and exaggerating pain perception has prompted attempts to develop agents to interrupt this mechanism. One concept that has attracted interest among researchers and clinicians is that of pre-emptive analgesia, in which pain perception is reduced by an intervention before a noxious stimulus (level III; McQuay 1992, Woolf & Chong 1993). By blocking sensitisation, pre-emptive analgesia may reduce opioid requirements and the severity of pain in the entire postoperative period. Extrapolation from basic studies appears to validate its usefulness in clinical practice (but see McQuay & Moore 1998).
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II Kehlet & Dahl 1993a, 1993b, Power et al 1994, Schulze et al 1988, Brodner et al 1998
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The basis of pre-emptive analgesia is the hypothesis that it is possible to prevent some of the pathophysiological changes of peripheral and central sensitisation by the administration of analgesics before tissue damage occurs. Evidence of the efficacy of pre-emptive analgesia in animals has been convincing, but evidence in humans after surgery has been equivocal or has failed to support the concept (level II; Tverskoy et al 1990, Rice 1995, Dahl et al 1992, Dierking et al 1992, Dahl et al 1994b, Aguilar 1996). However, a recent well designed study in human volunteers did demonstrate an effective pre-emptive effect which prevented central sensitisation (level II; Pedersen 1996). It is now clear that simple, once only, pre-emptive therapy before surgery is likely to fail, as the afferent neuronal activity in the spinal cord present during surgery continues for some time afterwards because of the inflammatory response at the site of tissue injury. If pre-emptive therapy is to be successful, the prevention of central sensitisation by pre-emptive analgesia must include a strategy for modulating the prolonged neuronal input into the spinal cord in the post-operative period produced by the inflammatory process at the site of tissue damage (level III; Woolf & Chong 1993). Statement of evidencepre-emptive analgesia Studies to date suggest that more aggressive, and possibly pre-emptive, approaches to the management of early postoperative pain may reduce the transition to chronic postoperative pain. Level of evidence
II Katz et al 1996; Bach et al 1988
Non-pharmacological methods
The following modalities may prove to be beneficial in the management of acute pain: cognitive-behavioural therapies; heat or cold applications; TENS.
massage, exercise and immobilisation;
Although evidence for the efficacy of these modalities in acute pain management is largely at the expert opinion level, certain patients may derive benefit from them. Cognitive-behavioural therapies are a broad group of interventions involving the application of principles derived from the study of learning (or behaviour change) and experimentally derived methods to change the ways in which pain sufferers perceive and react to their pain (and other stressors) (Bradley 1996). More correctly, these may be considered as applications of experimental clinical psychology rather than cognitive-behavioural therapies (which are perhaps the best-known of these approaches). Typically, these methods focus on both overt behaviours and cognitions (thought processes) in the patient, but they can also involve interactions with others, such as medical and nursing staff, as well as families. They may entail the provision of information, training in skills (eg relaxation and other coping strategies), and other behavioural techniques (eg modelling and systematic desensitisation). They may be aimed at reducing the perceived severity or distressing nature of pain and at enhancing a patients sense of their ability to cope with their pain. In some areas, especially preparation for surgery, painful medical procedures, postsurgical pain and distress, there is high level evidence supporting the use of some of these methods (levels I/II; Johnston & Vogele 1993, Suls & Wan 1989). 78
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In the meta-analysis by Johnston and Vogele (1993) four psychological interventions were found to be effective in achieving improvements on pain measures and reduced use of analgesics in the postoperative period. These were relaxation training, procedural information, cognitive coping methods, and behavioural instructions. The authors also found these interventions were effective in achieving improvements on measures of negative effect, length of stay (not cognitive methods in this case), and recovery. Relaxation training usually involves training a patient in ways of calming him/ herself, either by listening to a recorded audio tape or following written (or spoken) instructions. Regardless of the approach used, repeated practice of the technique by the patient is regarded as critical. Relaxation techniques are closely related to, and often indistinguishable from, forms of meditation and self hypnosis. While hypnosis shares many features of relaxation and imagery, it has a long history of use in acute pain conditions. Although much of the literature on the use of hypnosis in acute pain has often been at the levels of evidence of III and IV, recent papers have displayed more experimental rigour. Syrjala et al (1992), for example, described a study involving cancer patients undergoing bone marrow transplantation and found that those subjects which received hypnosis training reported reduced oral pain compared to those who received cognitive behavioural coping skills training, treatment as usual and therapist contact (level II; Syrjala et al 1992). Procedural information involves advising a patient on what is going to happen during the planned treatment, while sensory information entails advising a patient on expected sensations during the procedure (see Suls & Wan 1989, for a meta-analysis of research studies). It should be noted, however, that in some patients, especially those with avoidant coping styles, giving too much information or asking them to make too many decisions can exacerbate anxiety and pain (Wilson 1981). Accordingly, assessment of a patients normal approach to managing stress could help to identify the best option for that patient. Cognitive coping methods can involve various distraction techniques, such as imagery, dissociation, and re-interpretation of painful stimuli (see Fernandez & Turk 1989, for a meta-analysis of research studies). However, cognitive methods can also involve methods aimed at altering the processing of unhelpful pain-related thoughts that can heighten anxiety and distress. For example, a number of studies have found that patients who engage in catastrophic thoughts when in pain tend to be more distressed than those who do not respond to their pain in this way (eg Kiecolt-Glaser & Williams 1987). Behavioural instruction involves a range of strategies, including modelling (where the patient may be shown a video tape of another person undergoing the medical procedure so that the patient can both familiarise themselves with the procedure and copy the responses of the model). Behavioural instructions can also involve specific anxiety reduction methods, such as systematic desensitisation, whereby the patient utilises relaxation techniques and cognitive strategies to overcome anxiety associated with aspects of the intended medical procedure. Typically, the procedure would be divided into components associated with ascending levels of anxiety and the patient would be helped to deal successfully with each one (using imagery), starting with the scene provoking least anxiety, until they feel able to manage the scene provoking most anxiety (eg the actual insertion of a cannula). The involvement of clinical psychologists in pre-operative patient preparation, where their specialised techniques have been shown to provide clinically useful outcomes, has been underemphasised. The same could be said for acute pain settings in general. The result, almost inevitably, is that some useful treatments are not made available and new treatments derived from psychological research are slow to be implemented. 79
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Physical agents or modalities may provide comfort, correct physical dysfunction, alter physiological responses, and reduce fears associated with pain-related immobility or activity restriction. Patients should receive instruction on the importance of coughing, deep breathing, turning and walking, along with suggestions on how to decrease the physical discomfort of such activities. This instruction should start pre-operatively and supportive and reassuring reminders should continue postoperatively. Applications of heat or cold are used with the aim of decreasing pain, reducing muscle spasm and decreasing congestion in an injured area. Applications of cold are used initially to decrease tissue injury response. Later, heat is used to facilitate perfusion of injured tissue and clearance of accumulated fluids. Massage and exercise are used to stretch and regain muscle and tendon length. Immobilisation may maintain the alignment necessary fore techniques are designed to supplement pharmacological modalities. TENS therapy has been effective in reducing pain and analgesic use in a variety of situations such as after major abdominal or orthopaedic surgery (level IV; Hargreaves & Lander 1989, Jensen et al 1985). Both TENS therapy and application of electrodes without transmission of electric current (sham-TENS) significantly reduced analgesic use and subjective reports of pain; no significant differences were found between TENS therapy and sham-TENS (Hargreaves & Lander 1989). Even though these findings suggest a placebo effect underlying the analgesic effects of TENS therapy, beneficial effects may occur in some patients (AHCPR 1992). However, in a recent systematic review of studies of TENS in postoperative pain relief, 15 of 17 randomised controlled trials found no benefit compared with placebo. In non-randomised studies which were excluded from the review, there was an overestimation of treatment effects (level I; Carroll et al 1996). Acupuncture has been clinically evaluated in postoperative patients. Although there is some variability in the way in which acupuncture is administered, there are a number of randomised, controlled studies which suggest that the use of acupuncture results in a reduction in pain and analgesic consumption following dental and abdominal surgery (level II; Christensen et al 1989, Sung et al 1977). Placebo One field that has been studied extensively is the area of placebo response (the response to a known inert or sham intervention) and placebo effect (the non-specific response to any therapy). Placebo effect rates vary across the entire population, but everyone has the potential to have a placebo effect. Contrary to traditional teaching, placebo effects are not always responsible for 50 per cent of the response of the potent drug under comparison. The amount of relief obtained with a placebo varies considerably among patients. In an analysis of controlled trials, 38 per cent obtained more than 10 per cent of maximum possible pain relief after placebo, while 16 per cent obtained greater than 50 per cent relief (level I; McQuay et al 1995b). In general, the time-effect profile of the placebo effect follows that of the potent drug, but is usually of briefer duration and tends to diminish or disappear with repetitive dosing. A placebo effect should never be used to imply that the patient does not have real painplacebos are capable of relieving severe pain in some patients, under appropriate circumstances. There is no justification for giving an intramuscular injection of saline, to see if this patient is faking pain. There is probably a placebo component in the analgesic response to potent drugs, which will vary according to the circumstances of administration. The mechanism of placebo effect may be through classical conditioning (or association), expectancy (with a stronger effect if patients believe they are receiving a stronger analgesic), and the production of endogenous opioids. It
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may be that maximising the placebo effect in the way analgesics are administered might increase pain relief without the need for the administration of an actual placebo agent. Statement of evidence non-pharmacological modalities In 15 of 17 randomised controlled trials of TENS in postoperative pain, there was no benefit compared with placebo. In excluded non-randomised studies there was an overestimation of treatment effects of TENS.
Key point
Level of evidence
I Carroll et al 1996
Although evidence for the efficacy of non-pharmacological modalities such as physical therapeutic agents and modalities such as spinal manual therapy, mobilisation, application of superficial heat or cold, massage, exercise, transcutaneous electrical nerve stimulation (TENS) therapy and acupuncture in acute pain management is largely at the expert opinion level, certain patients derive benefit from these techniques.
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Pain management plans
Postoperative pain management plans should include alternative analgesic strategies to help focus discussion of options with patients. Plans should reflect co-existing and/or chronic problems such as cancer-related pain or opioid tolerance. They should also be consistent with the overall surgical and anaesthetic plans. Staff should note their plans for pre-operative, intra-operative and postoperative pain management in the patients chart so that other staff members can respond to patient questions and coordinate plans for rehabilitation and discharge. The sample case (see page 83) highlights the importance of pre-operative discussion of analgesic strategies with patients. Figures 4.4 and 4.5 illustrate the continuing nature of pre-operative, intra-operative and postoperative pain management. Following intra-operative anaesthesia and analgesia, postoperative pain assessment and management begin. Based on the preoperative plan, postoperative drug and non-drug interventions are initiated. Patients should be re-assessed at frequent intervals (not less than every two to four hours for the first 24 hours) to determine the efficacy of the intervention in reducing pain. If the intervention is ineffective, additional causes of pain should be considered, the plan reevaluated and appropriate modifications made. Pharmacological interventions should be titrated to achieve optimal pain control with minimal adverse effects. Continuing re-assessment ensures satisfactory pain relief with the most appropriate balance of drug and non-drug strategies.
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Discharge planning
Inpatients, as well as ambulatory surgical patients, should be given a written pain management plan at discharge. Pertinent instructions related to pain management include: specific drugs to be taken; frequency of drug administration; potential side effects of the medication; potential drug interactions; specific precautions to follow when taking the medication (eg physical activity limitations, dietary restrictions); and name of the person to notify about pain problems and other postoperative concerns.

Assess resources for pain management Pre-operative patient assessment Develop collaborative plan (RN, MD, pain team) Patient (and family) preparation and pre-operative interventions Pre-operative pain Analgesia Intra-operative anaesthesia and analgesia Initial preemptive measures for postoperative pain control Postoperative management
No pre-operative pain
Figure 4.5 Pre and postoperative treatment. RN=registered nurse; MD=Medical Doctor. Reproduced from AHCPR 1992.
Termination of operative anaesthesia/analgesia
No pain or pain not requiring intervention Re-assess Unacceptable side effects or inadequate analgesia Change drug, interval, dose, route, modality; add adjuvant; or treat side effects
No
Figure 4.6 Postoperative treatment. Reproduced from AHCPR 1992.
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Significant pain consistent with surgical trauma Initiate postoperative analgesia or adjust dose/interval of pre-operative analgesia Assess: did intervention produce satisfactory pain relief?
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Significant pain not explained by surgical trauma Surgical evaluation Treat
Optimise dose interval Satisfactory response Discharge planning
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Sample casemultimodal pain relief A 58-year-old man with carcinoma of the colon is scheduled for open colectomy. He had surgery at a younger age for a benign gastric ulcer; this was associated with severe unrelieved postoperative pain, prolonged ileus, basal pneumonia, very prolonged hospitalisation and slow recovery. The patients fears resulting from his prior experience are discussed with him and his family. Treatment options for pain relief and acute rehabilitation are outlined, together with the advantages and disadvantages of each option individually and as part of a multimodal approach. The patient says that he feels less anxious after this discussion, and is strongly motivated to have multimodal analgesia. Arrangements are made to insert a lowthoracic epidural catheter and a combination of 2 per cent lignocaine with adrenaline and fentanyl is used, during surgery, supplemented by a light general anaesthetic; the epidural catheter is tested before surgery to ensure that the appropriate segments are blocked. Upon the patients recovery from anaesthesia, intramuscular ketorolac is started at a dose of 15 mg every eight hours for 48 hours. The epidural block is continued with 0.125 per cent bupivacaine combined with a small dose of fentanyl. Since the colonic resection was straightforward, a gastric tube is not used. No supplementary systemic opioids are used. The day after surgery, the patient is out of bed and walking, with minimal pain. Bowel sounds are present at about 36 hours and he begins oral feeding at 48 hours. He leaves hospital at 72 hours on oral diclofenac.
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Special postoperative patients optimising pain relief
Neurosurgical patients
Despite advances in neurosurgical anaesthesia and the understanding of pain mechanisms, pain relief in neurosurgical patients has mainly focused on safety issues. Unrelieved pain in these patients may provoke a state of post-injury hyper-responsiveness which can aggravate the stress response and make effective pain management difficult. Neurosurgical patients require careful monitoring, including assessment for abnormal neurological signs and symptoms during the postoperative period. Pain and sedation scoring systems should be an integral part of this monitoring. Opioids remain a key modality in postneurosurgical analgesia. Intensive monitoring should allow application of potent shorter acting agents and new methods of delivery. However, the administration of opioids requires consideration as they may contribute to effects such as raised intracranial pressure and the obscuring of clinical signs like pupillary dilatation. Cerebral blood flow and cerebral metabolic rate appear to be little affected by opioids (level IV; Albanese et al 1993). Administration methods that avoid large doses (such as intermittent boluses) are available in critical care settings and reduce the theoretical likelihood of a number of adverse effects. Target controlled infusions such as those involving computer programs may provide greater effectiveness and improved safety (level IV; Davies et al 1992). A postcraniotomy patient without complications and with typical mild to moderate pain can be managed initially by parenteral medications, of which intravenous administration by PCA or infusion offers a number of advantages in selected patients (AHCPR 1992). Non-craniotomy patients, including those having undergone laminectomy and 83
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other spinal procedures, potentially have a greater indication for techniques such as PCA. Such patients may also benefit from use of an NSAID such as ketorolac (level IV; Souter et al 1994). The use of non-steroidal analgesics, however, may be contraindicated when: the risk of coagulopathy or haemorrhage is high; the need to assess fever is important; or the degree of pain is higher than the analgesic ceiling of these agents. Patients with spinal cord injury are at risk of developing acute neuropathic pain, among other forms of pain. The use of agents specific for this (eg tricyclic antidepressants and anticonvulsants) has been helpful (Siddall & Cousins 1995b). Severe burning dysaesthesia, hyperalgesia and allodynia occurring acutely after surgery for spinal injury may be effectively managed by intravenous or subcutaneous lignocaine infusion, using a similar regimen (11.5 mg/kg/hour) to that described by Brose and Cousins (1991) for cancer-related neuropathic pain. Lignocaine blood levels must be monitored. More interventional techniques such as the intrathecal administration of morphine, clonidine and the GABA agonist baclofen have been shown to be of some use in certain patients (level IV; Siddall et al 1994). Epidural opioids and/or local anaesthetics can minimise the need for systemic opioids and allow more accurate monitoring of brainstem and cerebral function. However, a single dose of epidural morphine may produce significant blood concentrations (level III; Max et al 1985) and these in turn have effects within the central nervous system. One study could not demonstrate a difference in neuropsychiatric functioning between patients receiving oral morphine and those receiving it epidurally (level III; Sjgren & Banning 1989). Motor and sensory dysfunction associated with epidural local anaesthetics (which are often co-administered with opioids) may obscure important neurologic signs; however, low doses of opioid combined with local anaesthetic usually do not impair motor function, and monitoring for motor and sensory impairment permits cessation of infusion if needed. Regional analgesic techniques are effective in neurosurgical patients. Wound infiltration has the potential to reduce recovery time (level III; Dahl et al 1994a) and postoperative opioid requirements. Operative intervention in patients with failed spinal decompression surgery and acute on chronic lower back pain should be considered cautiously. These patients may be suffering from arachnoiditis or other non-surgical problems which may be best evaluated in a multidisciplinary pain management centre.
Key point
Pain management in neurosurgical patients employs conventional analgesic agents plus adjuvant agents where appropriate. Extremely careful monitoring is required, including assessment for abnormal neurological signs and symptoms during the postoperative period. Pain and sedation scoring systems should be an integral part of this monitoring.
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Day surgical patients

The advent and increasing use of laparoscopic surgery has had a marked impact on the length of hospital stay of surgical patients and on their postoperative management, including pain management. The rise in the number of patients having surgery as day cases has been pronounced and, given the comparative cost savings, this number is likely to rise. While there is some evidence that minimally invasive surgery results in less pain and lower intake of analgesic medication than do traditional surgical techniques (level IV; Whitwam 1993), there has been little research in this area as yet. A recent telephone survey of day surgery patients in the United Kingdom reported that most patients were satisfied with pain relief obtained from analgesics prescribed on discharge or available in the home, although 21 per cent reported moderate pain and a further 11 per cent reported severe pain following their return home (level IV; Hawkshaw 1994). The ability to perform increasingly complex surgery on a day-case basis highlights the need for appropriate screening, selection, pre-operative preparation, treatment and discharge of these patients. The brevity of the patients hospitalisation and contact with health care professionals, make adequate pain management a particular challenge. Assessment of risks for complications of analgesic medication needs to be made and the patient and family need to be prepared to deal with inadequate pain relief and/or other symptoms. Pain following discharge from day surgery influences the time taken to return to normal activity (level II; Fraser 1989) and may lead to further, unplanned hospitalisation (level III; Fancourt-Smith et al 1990, Gold et al 1989). Pharmacological options for postoperative analgesia include oral opioids, NSAIDs and local anaesthetics. Simple oral analgesics such as aspirin and paracetamol are more effective than placebo and should not be overlooked, particularly in cases of mild to moderate pain. A recent meta-analysis confirmed that paracetamol is an effective postoperative analgesic, and that codeine 60 mg added to paracetamol produces worthwhile additional pain relief even in single oral doses (level I; Moore & Collins 1997). NSAIDs are effective after ambulatory surgery (Himendra et al 1985, van Ee et al 1993). They may be more effective than certain opioids and offer better tolerability profiles (level II; McLoughlin et al 1990, Wong et al 1993, Lysack et al 1994). Opioid selection should give preference to agents with shorter half-lives, to avoid side effects that may delay discharge from hospital (White & Schafer 1986). When used intra-operatively, however, short-acting opioids such as fentanyl may not be effective for postoperative pain relief (level III; Cade & Ross 1992). The use of NSAIDs may provide improved tolerability (Anonymous 1991 [Lancet editorial]) and a reduction in postoperative opioid requirements (level II; McLoughlin et al 1990). The use of local anaesthetics in laparoscopic surgery, by wound infiltration or intraperitoneally at the time of operation, is effective in the treatment of postoperative pain unless catheter techniques are used (level II; Alexander et al 1987, Wheatley et al 1994) and can produce a prolonged analgesic effect (level II; Benhamou et al 1994). Drug combinations, such as the addition of an NSAID or opioid to local anaesthetic infiltration, can offer more effective analgesia than any of these agents administered alone (level II; Smith et al 1992, Nehra et al 1995).
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Statements of evidenceday surgical patients A recent meta-analysis confirmed that paracetamol is an effective postoperative analgesic, and that codeine 60 mg added to paracetamol produces worthwhile additional pain relief even in single oral doses. Pain following discharge from day surgery influences the time taken to return to normal activity and may lead to further, unplanned hospitalisation. It is recommended that adequate plans are made for post-discharge analgesia.
Level of evidence
I Moore & Collins 1997
III Fancourt-Smith 1990; Gold et al 1989
Key points
The ability to perform increasingly complex surgery on a day-case basis highlights the need for appropriate screening, selection, pre-operative preparation, treatment and discharge planning for these patients. Pharmacological options for day-case postoperative analgesia include oral opioids, NSAIDs and local anaesthetics, or combinations of these treatments. Simple oral analgesics such as aspirin and paracetamol are more effective than placebo and should not be overlooked, particularly in cases of mild to moderate pain.
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Obstetric analgesia
Pain in childbirth is highly specialised and it is beyond the scope of this report to discuss it in detail. There are many guidelines and reports dedicated to the subject, including a recent World Health Organisation document entitled Care in Normal Birth: a Practical Guide (WHO 1997). This chapter outlines the current evidence on the efficacy of pharmacological and non-pharmacological options for pain relief during childbirth. Pain in childbirth is frequently severe, being rated by many women as the most painful experience of their lives. Options for effective analgesia should be made available to all women in labour. However, women vary widely in their desire and need for pain relief during labour, and for many women the best possible birth experience will not necessarily be pain free. All options for pain relief, and their efficacy, should be discussed with the parturient so that she can make an informed decision. Pain relief planned during the antenatal period and implemented during labour should be monitored and appropriately modified during the course of the labour. The wishes of the woman and the well-being of the baby are paramount. Severe, acute pain in childbirth can have adverse physiological effects. Uterine contractions in the first stage of labour are associated with visceral pain that can cause delayed gastric emptying (increasing the risk of pulmonary aspiration), hyperventilation (with adverse sequelae including respiratory alkalosis and metabolic acidaemia), increased cardiac output and blood pressure, and in some circumstances, discoordinate uterine contractions and reduced placental perfusion. This is particularly so with prolonged painful childbirth when foetal acidosis can have detrimental effects on the infant (level III; Schnider et al 1979). These effects on the mother and infant may be almost completely reversed by effective analgesia (level III; Pearson & Davies 1974). Pain experienced during delivery involves somatic neural pathways and is thus different in character to the visceral pain associated with uterine contractions. Ascribing dysphoric effects to analgesic side effects, when pain is the actual cause, may lead to the withholding of pain relief and worsening of the physiological and psychological state of the mother.
Acute pain during pregnancy
Some women require medication for pain during pregnancy. The stage of the pregnancy and the side effects of the drug in relation to foetal development have to be respected when considering appropriate pain management for these women (level IV; Rathmell et al 1997).
Non-pharmacological methods
There are several non-drug options available to women in labour, such as prepared childbirth training, TENS therapy and physical therapy. There is a lack of clear evidence supporting their efficacy but they may have benefits in individual situations and may reduce the need for pharmacological pain relief. In a systematic review, TENS was ineffective (Carroll et al 1997). Women should be given a realistic assessment of the severity of labour pain and the relative efficacy of non-pharmacological
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methods; for example, prepared childbirth training reduces labour pain by only about 10 per cent (level III; Melzack et al 1981).
Pharmacological methods
Most women request pharmacological analgesia and there is a variety of agents and methods of administration. These include: inhalation of nitrous oxide and oxygen; pethidine and other opioids administered by injection; and epidural administration of opioid and local anaesthetic. Women should be informed of the potential adverse effects of analgesia. Inhalational analgesia The inhalation of nitrous oxide combined with oxygen, via face mask or mouthpiece, has several benefits. It is safe (if entirely self administered), has a short onset and duration of action allowing it to be timed with contractions, and may be initiated by midwives. However, its analgesic effect is limited, with at least one study of its use in early labour showing no real reduction in pain scores during contractions (level III; Carstoniu et al 1994). While nitrous oxide combined with oxygen alone has no effects on neonatal neuro-adaptive capacity or Apgar scores (level III; Stefani et al 1982), a combination of opioids such as pethidine and nitrous oxide combined with oxygen can produce maternal (and thereby foetal) hypoxaemia. Such episodes appear to be of doubtful clinical importance as they are transient and are followed immediately by periods of hyperoxaemia. Parenteral opioids Pethidine (and other opioids) administered via the intramuscular route are very commonly used but their analgesic effect varies widely among patients (level II; Olofsson et al 1996; level IV; Reynolds & Crowhurst 1997). For women who do find this route adequate, the ease of administration confers some benefit. Intermittent intravenous bolus doses of opioids or PCA reduce the time to maximal effect and allow more accurate titration of dose, with lower pain scores compared with equal amounts of intramuscularly administered opioid (level III; Isenor & Penny-MacGillivray 1993). Fentanyl, morphine and pethidine are suitable, with fentanyl producing less nausea and sedation and a faster effect (level II; Rayburn et al 1989). Neonatal depression in infants by opioids is reversed by naloxone (0.1 mg/kg intramuscularly, or 0.04 mg increments intravenously), with intramuscular absorption prolonging this agents relatively short-lived effect compared with opioid agonists (level II; Wiener et al 1977). The infant should be monitored and the dose repeated as required.
Regional analgesia
Regional techniques to alleviate labour pain have undergone several revisions recently. The use of caudal epidurals has fallen out of common usage due to the risk of local anaesthetic toxicity and other risks to the neonate. Lumbar epidural analgesia Epidural analgesia is a highly effective method of relieving labour pain, which has gained acceptance in Australia and throughout much of the developed world. Most epidural techniques today use a combination of low doses of opioid and local 88
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anaesthetic (eg lignocaine with or without adrenaline as a test dose followed by bupivacaine or ropivacaine). Epidural techniques are able to blunt the stress response (see page 70), and this applies also in labour. An epidural catheter technique allows titration and individualisation of dose to pain intensity, usually avoiding motor block. The dose may be increased to allow instrumental vaginal delivery and other procedures to be carried out. Pain relief with epidural analgesia has been shown to be greatly superior to that achieved by other analgesic methods. Intravenous fluids are given as required during epidural analgesia, after routine pre-loading. Some centres have also found it safe and practical to allow women to mobilise after a low-dose epidural. Adverse effects The adverse effects that may arise as a result of the epidural include: motor blockade leading to diminished mobility and ability to push during the second stage; bladder distension; diminished awareness of uterine contractions; postural hypotension; side effects related to epidural opioids (eg respiratory depression, pruritus, nausea); dural tap and subsequent postpartum headache (Brownridge 1996); and superficial infections at the site of epidural placement. Many of the unwanted side effects associated with traditional lumbar epidural analgesia are dose related and can be overcome by using low-dose local anaesthetic/opioid combinations. Rare, but potentially serious, complications include systemic local anaesthetic toxicity (eg convulsions), development of a high block, meningitis, epidural haematoma or abscess possibly causing spinal cord or cauda equina lesions, anterior spinal artery syndrome, and neurotoxicity due to injection of the wrong drug. Epidural analgesia and rates of intervention Controversy continues concerning the relationship between epidural analgesia for labour and caesarean delivery rates. However, more recent studies appear to indicate that there is no increase in caesarean delivery rate associated with epidural analgesia. Two recent investigations (level II; Sharma et al 1997, Bofill et al 1997) found no increase in caesarean delivery rate in the epidural groups compared to the intravenous opioid analgesia groups. Moreover, parturients who received epidurals had significantly more effective analgesia. A study (level III; Lyon et al 1997) comparing outcome of labour on an obstetric service before and after availability of epidural analgesia indicated that, when patients were stratified according to parity and indications for caesarean delivery, there were no differences in primary caesarean rates. A review of randomised prospective controlled trials comparing epidural with non-epidural forms of pain relief concluded that there is a need to conduct larger, better designed randomised controlled trials of this method of analgesia (level I; Howell & Chalmers 1992). It is important in the interpretation of study results to identify study design deficiencies such as patient selection bias and to recognise that the results apply only to the conditions under which the investigation was conducted. Patients requesting epidural analgesia often have more severe pain, which in itself is an omen for 89
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prolonged labour and risk of caesarean delivery. Thus, an increased caesarean rate may be selection bias rather than an epidural-related phenomenon. Moreover, epidural analgesia management varies markedly between practice locations, with the use of more dilute analgesic solutions less likely to lead to more caesarean deliveries. Epidural analgesia may actually reduce the caesarean rate by increasing the likelihood of vaginal delivery, as in women with previous caesarean sections or with breech presentation (level IV; Chestnut 1997). Overall, the use of epidural analgesia does not appear to increase the incidence of caesarean delivery, especially if administered in a fashion tailored toward more dilute solutions of local anaesthetics with supplementation by epidural opioids. Based on current evidence, it would appear that maternal-foetal factors and obstetric management, not epidural analgesia, are the main determinants of caesarean section rates (level IV; Chestnut 1997). Bias in terms of patient selection (eg favouring primiparae, patients with prolonged labour) and obstetric management may be responsible for the purported association of epidural analgesia with higher rates of instrumental vaginal delivery. Many centres have demonstrated that the need for instrumental delivery can be significantly reduced by the use of low-dose local anaesthetic-opioid epidural solutions and by allowing time for spontaneous foetal descent to occur. One investigation has shown that, despite the introduction of an epidural service, the operative vaginal delivery rate did not rise (level III; Lyon et al 1997).
New epidural techniques
New methods of epidural drug administration are being developed in an attempt to minimise side effects and increase patient satisfaction with the technique, by introducing a degree of flexibility to dosage regimens that allows the epidural analgesia to be tailored to the individual (level IV; Brownridge 1990, 1991a). These methods include: midwife-managed intermittent doses, in which midwives can adjust the degree of analgesia depending on patient preference and clinical circumstances; continuous infusions, in which a more constant level of analgesia can be maintained and side effects reduced; patient-controlled epidural analgesia, which allows the parturient to exercise control over the desired level of analgesia; and combined spinal epidural analgesia (ambulatory epidural analgesia), which produces rapid onset of intense analgesia with minimal motor block, potentially allowing ambulation during labour. These and other methods are likely to grow in popularity as evidence of their efficacy emerges. However, at present, they are not feasible in many settings and their use requires highly trained staff and regular retraining. Combined spinal epidural (CSE) analgesia uses a combination of epidural and spinal techniques. After identification of the epidural space, a long, atraumatic, 26- or 27gauge spinal needle is inserted intrathecally through the epidural needle, and a small dose of opioid and/or local anaesthetic is injected. The spinal needle is removed and an epidural catheter is threaded into the epidural space; doses of opioid and/or local anaesthetic are then used epidurally to maintain analgesia. This method produces analgesia of rapid onset associated with minimal motor weakness or opioid exposure to the neonate. It is, however, associated with a greater incidence of pruritus (level IV; Paech 1996). Incidence of postdural puncture headache after uncomplicated CSE is low 90
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and comparable to epidural analgesia alone, and therapeutic blood patches are not required more frequently following CSE analgesia (level III; Norris et al 1994). A new local anaesthetic, ropivacaine, has been shown to exhibit less intense motor blockade than does bupivacaine and to be less cardiotoxic following inadvertent intravenous administration (level IV; Feldman et al 1989, 1991). In a multicentre investigation (level II; Muir et al 1997) ropivacaine 0.25 per cent, when administered epidurally by intermittent top-ups for labour analgesia, was found to be as efficacious as bupivacaine 0.25 per cent. Some results (level II; Stienstra et al 1995) suggest that ropivacaine may be advantageous over bupivacaine with respect to neonatal neurobehavioural performance. More clinical experience with ropivacaine is needed to demonstrate conclusively advantages of ropivacaine over bupivacaine. Over recent years there has been an increasing trend towards the use of single shot intrathecal, rather than epidural, anaesthesia for caesarean delivery, because of the availability of small, specially designed, atraumatic needles that minimise the risk of postdural puncture headache. This has greatly reduced the dose of local anaesthetic given and therefore lowered the risk of local anaesthetic toxicity. A small amount of opioid (eg 0.25 mg of morphine) added to the local anaesthetic may provide up to 24 hours of post-operative analgesia. In opioid naive patients, monitoring for signs of respiratory depression should continue for the duration of analgesic effect. Statements of evidence obstetric epidural analgesia
Lumbar epidural analgesia is the most effective form of pain relief during childbirth. Using low-dose local anaesthetic/opioid mixtures can significantly reduce the severity of side effects. Recent studies appear to indicate that there is no increase in caesarean delivery rate associated with epidural analgesia.
Key points
All options for pain relief, and their efficacy, should be discussed with the parturient so that she can make an informed decision. Pain relief planned during the antenatal period and implemented during labour should be monitored and appropriately modified during the course of the labour. The wishes of the woman and the well-being of the baby are paramount. Maternal-foetal factors and obstetric management, not epidural analgesia, are the main determinants of caesarean section rates.
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Pain in children
The expression and assessment of pain in children is a complex issue that is dependent on individual factors for each child. These include age, developmental level, previous pain experiences, medical, social and racial factors. Treatment should consider these factors and include combined pharmacological and non-pharmacological approaches. Despite significant improvements in paediatric pain management over the last five years, children often undergo invasive, painful procedures without adequate attention to analgesia (Southall et al 1993). Many children do not receive any opioid analgesics after surgical procedures, despite the fact that the postoperative courses are known to be painful (Foster & Hester 1990a, 1990b). In addition, children in hospital receive proportionally less analgesia than do adults with the same pathology (Schechter et al 1986) and opioid doses and intervals are often inadequate (Foster & Hester 1989, 1990a). One of the problems in providing effective pain relief to children is that numerous myths abound, including: children experience less pain than adults; pain is character building for children; respiratory depression occurs frequently in children after opioid administration (this may lead to inadequate doses and dosage intervals); neonates dont experience or remember pain; children cannot localise or describe their pain; opioids are addictive or otherwise too dangerous to use in children; and there is little variation in pain intensity following the same procedure in different children or even in the same child on different occasions. In addition to these misconceptions, pain relief in children poses particular challenges because: childrens pain can be masked and they often do not report pain, although prn ordering persists despite this (level IV; Bush et al 1989); there are difficulties in assessing pain character and intensity in infants and very young children; there are complicating additional factors eg developmental delay; children prefer continuing pain to having an intramuscular injection (level IV; Mather & Mackie 1983); there can be greater technical problems eg with intravenous access, epidural insertion; and the pharmacokinetics of local anaesthetics and opioids are altered in neonates.
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6.1
Assessment of pain in children
Assessment should always involve a careful history and examination. Self reporting of pain is reliable in children over four years of age (level IV; Maunuksela et al 1987;
readers are referred to Finley & McGrath 1998 for a definitive review of pain measurement in infants and children).
Other useful tools for assessing acute pain in children include the following: observation of non-verbal cues, remembering that a quiet, withdrawn child may be in severe pain; observation of other behaviour over time which may suggest an increase in pain intensity (Hester & Foster 1990); use of pain rating scales suitable to the age and development of the child by one of the following methods: physiological, behavioural/observational and self reporting. Many pain rating scales have been devised for specific areas eg postoperative pain. Some examples are CRIES (Krechel & Bildner 1995) for neonates and modified visual analogue scales eg the Poker Chip Tool (Hester 1979, Hester & Foster 1990). Faces scales for younger children include the Oucher scale (Beyer 1984), WongBaker Faces scale (Whaley & Wong 1991) and other faces scales (Bieri et al 1990, McGrath et al 1985);
(Wong-Baker Faces Scale, adapted from Whaley & Wong 1991)
physiological signs, such as tachycardia, may play a key role in very young children but need to be interpreted in the clinical context; pain ratings provided by parents or regular carers can be accurate (level III; Wilson & Doyle 1996); and the ability to console children may help to distinguish pain from other causes of distress such as parental separation, an unfamiliar environment, and hunger and thirst with fasting.
Key point
Regular assessment of pain and monitoring of treatment in children present particular challenges to health carers. Close observation of non-verbal cues and behaviour is important. The use of pain rating scales suitable for the age and developmental stage of the child is essential for the accurate treatment of pain. The child should be respected as an authority on their own pain.
Paediatric pain service
Establishing a paediatric acute pain service is an essential exercise in a childrens hospital. In adult or general hospitals where children are cared for, the acute pain team should consider the safe administration of particular analgesic techniques in children. This service should formulate dosage guidelines and protocols, ensure clinical supervision of inpatients, coordinate education of the child and family as well as medical and nursing staff, and audit results (level IV; Lloyd-Thomas & Howard 1994). 94
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6.2
Procedures and pain
A major advance in pain management in children has been recognising the importance of reducing the pain and distress associated with commonly performed procedures. This is of greatest relevance in those children who need long-term treatment with frequent procedures eg children with leukaemia. Hospitalised children may undergo a range of painful procedures including: insertion of intravenous and arterial cannulae; lumbar punctures; chest tube insertions; bone marrow aspirations; biopsy procedures; cardiac catheterisation; burn dressing changes; blood collection; and suturing, splinting or plastering fractures. Children find invasive procedures distressing and often cite this as the most unpleasant part of illness or treatment (Fowler-Kerry & Lander 1987, Weekes & Savedra 1988). To optimise compliance, preparation of children for painful procedures must be approached systematically and properly handled by health care professionals (level IV; Schechter 1989). General principles for the management of procedural pain and distress can be applied to all painful procedures. Most hospitalised children undergo minor invasive procedures, and careful consideration should be given to either spreading procedures over time, or alternatively, deliberately clustering them and covering with an appropriate general anaesthetic. Painful routes of administration should be avoided where possible. During any procedure, parents and caregivers (other than the person undertaking the procedure) have a vital role in comforting the child. Non-pharmacological methods Non-pharmacological strategies can be effective for pain and anxiety associated with minor procedures, especially if repeated on a regular basis. They are less useful in the acute situation. Non-pharmacological interventions include psychological, cognitivebehavioural and complementary techniques such as relaxation, guided imagery, visualisation, and massage. Examples are using a pacifier, or using verbal or tactile strategies (Campos 1989, Field & Goldson 1984, Triplett & Arneson 1979). The child and the family can be prepared in several ways, through provision of preparatory sensory information (Siegel & Peterson 1980), empathetic preparation (Fernald & Corry 1981), or a multimodality approach using stories, art and play (Fassler 1985). Other potentially effective cognitive-behavioural strategies include: distraction techniques such as music (Fowler-Kerry & Lander 1987, Ryan 1989); improving coping skills; hypnosis (Zeltzer & LeBaron 1982); play therapy (Ellerton et al 1985); and thought-stopping (Ross 1984). Cognitive-behavioural treatment can be useful in children with cancer who experience procedure-related pain (Jay et al 1995). Physical agents include TENS therapy (Eland 1990) and counterirritants such as ice (Zeltzer et al 1990). 95
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Pharmacological strategies for procedural pain

Treatment of anxiety complements analgesia and decreases overall distress but can blunt the childs behavioural responses and thereby mask pain. Infants under six months of age need to be approached differently (see page 106). Agents that can be given to children include the following. Simple analgesics such as paracetamol (dose 20 mg/kg orally or 30 mg/kg rectally). Local anaesthetics whether administered by local infiltration or topically (eutectic mixture of local anaesthetic [EMLA] or equivalents). Intravenous opioids, given in increments (eg morphine at 0.030.05 mg/kg every five minutes) and titrated to analgesic effect. Oral opioids can be used when close and rapid titration to effect is not required. Benzodiazepines, given either orally (midazolam 0.5 mg/kg), intranasally (midazolam 0.3 mg/kg) or intravenously (midazolam 0.1 mg/kg). Like opioids, intravenous benzodiazepines are given in increments and titrated to sedative effect (Zeltzer et al 1990). Unlike diazepam, midazolam does not cause pain and local sclerosis when given intravenously and titrated to sedative effect (level IV; Zeltzer et al 1990) and anxiolysis. Benzodiazepines provide sedation and amnesia, not analgesia, and hence they are often used with opioids for painful procedures. If the combination of an opioid plus a benzodiazepine is used, the risk of respiratory depression is increased. Pulse oximetry monitoring is essential in this situation. Nitrous oxide is a potent gaseous analgesic with very rapid onset and offset of action, making it very useful for procedural pain in children (level IV; Griffin et al 1981). It is used in varying concentrations of 30 to 70 per cent with oxygen by trained personnel. It can also provide significant anxiolysis for procedures (level III; Vetter 1995) and, when given at 50 per cent concentration without adjuvant agents, has minimal effect on protective laryngeal reflexes (level III; Roberts & Wignall 1982). Ketamine should only be given by trained personnel (eg anaesthetists) as it is a general anaesthetic and its use requires close monitoring in areas with appropriate resuscitation equipment (Zeltzer et al 1989). General anaesthesia may be appropriate in certain situations (Zeltzer et al 1990). Supplementation with opioids is helpful in some cases, especially when there may be difficulty in performing the procedure. Children over five years of age who can effectively use cognitive and behavioural coping skills may prefer not to use sedatives or opioids (Zeltzer et al 1990). Management strategies for bone marrow aspirations and biopsies include either general anaesthesia or conscious sedation using benzodiazepines and opioids, along with local anaesthesia. Adequate time is necessary for the local anaesthetic agent to have full effect. Nitrous oxide is also useful in this setting (level IV; Miser et al 1988) and is commonly used as such in a number of large Australian centres. Bone marrow aspirations and lumbar punctures are performed as part of the diagnostic work-up for children with acute lymphatic leukemia, T cell lymphoma or Hodgkins disease. It should be remembered that a proportion of these children have anterior mediastinal masses and thus are at risk of life-threatening complications during deep sedation or general anaesthesia, due to airway obstruction or compression of pulmonary arteries.
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Monitoring conscious sedation for procedural pain Skilled supervision is necessary whenever systemic pharmacological agents are used for conscious sedation, as verbal contact with the patient is essential for safety. A health care provider not involved in performing the procedure or holding the child should monitor conscious sedation, including frequent assessment of heart rate, respiratory rate and effort, blood pressure and level of consciousness. Continuous pulse oximetry is strongly encouraged. Immediate access to resuscitative drugs and equipment and the presence of at least one health professional trained in advanced life support are necessary. After completion of the procedure, monitoring should continue until the child is fully awake and has resumed the former level of function. Deep sedation Deep sedation in which the patient is not responsive to verbal or physical stimuli is equivalent to general anaesthesia and should only be performed under controlled circumstances by a professional trained in its use and skilled in paediatric airway management and basic paediatric life support. Reference to specific published guidelines on this is recommended (American Academy of Pediatrics 1992). To quote from the American guidelines, The caveat that loss of consciousness should be unlikely is a particularly important aspect of the definition of conscious sedation, and the drugs and techniques used should carry a margin of safety wide enough to render unintended loss of consciousness highly unlikely. Since the patient who receives conscious sedation may progress into a state of deep sedation and obtundation, the practitioner should be prepared to increase the level of vigilance corresponding to that necessary for deep sedation. Systemic drugs that alter level of consciousness are generally not used in acute medical illnesses, such as the acute phase of meningitis, where observation of the level of consciousness is crucial to treatment.
Pain related to burn dressing changes
Changing burn dressings in hospitalised children requires both drug and non-drug strategies. Oral sustained release morphine preparations may provide basal analgesia. Depending on the child and the level of anxiety, an opioid may be administered alone or combined with a benzodiazepine, although nitrous oxide given by trained personnel has been extensively used for this purpose with good effect (level IV; Keneally 1997). Unrelieved pain can escalate anxiety and therefore optimal pain control is necessary. Tolerance to opioids and benzodiazepines can develop, necessitating higher doses with repeated dressing changes. Initially, pain management may involve a continuous infusion or regular intermittent opioid dosing with additional bolus doses of an opioid and a benzodiazepine before dressing changes. Extensive debridement procedures may require general anaesthesia. Children as young as 18 months deal better with burn dressing changes if their participation and control are maximised (Kavanagh 1983a, 1983b).
Key point
Procedural pain in children should be managed systematically, using a combination of analgesia and non-drug strategies and avoiding painful routes of administration where possible. General anaesthesia may be required, especially for frequent painful interventions where other strategies have failed. 97
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6.3
Management of pain associated with paediatric surgery
Pre-operative management
Preparation that starts at home with psychological support may decrease fear and anxiety of surgical procedures (Ferguson 1979, McGrath 1979, Visintainer & Wolfer 1975, Wolfer & Visintainer 1979). Familiarisation with equipment and procedures preoperatively facilitates the use of PCA after the operation. The presence of parents or care givers during the anaesthetic induction decreases postoperative pain and reduces adverse psychological sequelae (Hannallah & Rosales 1983, Johnston et al 1988, Schofield & White 1989). Where possible, pre-operative medication should be given by the least painful route. EMLA patches are now available across the counter from pharmacies. Parents can be instructed to apply a patch over a venous access site before leaving home to go to the hospital for their childs procedure.
Intra-operative management
Commencement of analgesic techniques intra-operatively serves to decrease intraoperative anaesthetic requirements, minimise the stress response to surgery, reduce untoward intra-operative reflexes such as laryngospasm, and allow for smooth emergence with minimal discomfort. These techniques consist of: local anaesthetic infiltration of the wound or specific peripheral nerve blocks; intra-operative parenteral loading of opioid to achieve adequate blood levels for postoperative analgesia. This allows for immediate commencement of other techniques such as opioid infusion in the immediate postoperative period; and use of adjunctive analgesics such as rectal paracetamol. Rectal administration of paracetamol at the time of anaesthetic induction is a useful adjunct, but if it is being used as the sole analgesic, higher doses are required and adequate analgesic levels may not be achieved in the initial postoperative phase after short surgical procedures (level III; Anderson et al 1996).
Postoperative management
While drug therapy is the mainstay of postoperative analgesia, non-drug modalities may be used as described previously (see page 95). Good analgesia should be attained in the recovery room before discharge to the ward. In the case of day surgery, this may be achieved by relatively simple means, such as the use of paracetamol. Wherever possible, oral analgesia is preferable. Drug therapy for postoperative pain depends on the childs age, medical condition, type of surgery, and expected postoperative course. Pain after minor surgery, such as orchiopexy or herniorrhaphy, can usually be managed orally with paracetamol with or without codeine. Children are often sent home on the day of surgery after such procedures and require sufficient information on analgesia to be given on discharge (Gedaly-Duff & Ziebarth 1991). For major surgery, such as abdominal, thoracic, urological or orthopaedic procedures, parenteral opioids are the mainstay of pain management. These drugs can be administered systemically or spinally, depending on individual needs. Local anaesthetic blocks also have a definite role to play following major surgery and may be initiated intra-operatively (see page 102). 98
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Pain in children Key points
Drug therapy is the mainstay of postoperative analgesia in children, but non-drug modalities may also be useful. Analgesia should be given by the least painful route where possible. Regular re-evaluation of analgesic efficacy is required.
Opioid analgesia
There is often inappropriate concern about the potential for psychological dependence and addiction when opioids are used to control pain in children. In adults, the risk of addiction after use of opioids for pain relief is small. With the exception of rare, anecdotal cases in older children and adolescents with personality and psychological disorders, there is no evidence that the use of opioids for treatment of severe pain in children leads to opioid dependence or addiction. Oral Codeine is a commonly used opioid with good oral bioavailability. It is useful for transitional pain ie mild to moderate pain when a child is changing from parenteral opioids postoperatively to oral analgesia. The conversion of codeine to morphine is under polymorphic (genetic) control and 10 per cent of adults (and probably a similar proportion of children) cannot perform this conversion at an acceptable rate as they lack the appropriate enzyme. The dose is 0.51.0 mg/kg every four to six hours. Regular dosing may cause constipation which should be anticipated and treated prophylactically. Codeine can be used in conjunction with non-opioid analgesics such as paracetamol and other NSAIDs. In general, slow-release morphine preparations (eg MS Contin, Kapanol) do not have a role in the management of acute pain states in children. They may be of use in longer term severe pain such as that arising from burns. Oral morphine sulphate may be required for breakthrough pain in this setting. Conversion from the intravenous route to the oral route based on 24-hour consumption may be required. Intramuscular injection In the immediate postoperative period after major surgery, systemic opioids are required by parenteral routes. Intermittent intramuscular injections provide poor analgesia and are painful and frightening to children (Eland & Anderson 1977). Since an intravenous cannula is required for fluid replacement postoperatively, this route is freely available. Intramuscular injection may be of use as a single dose in the emergency room setting if there is no other route of administration. Subcutaneous opioids Subcutaneous analgesia has similar absorption characteristics to the intramuscular route. Morphine is the agent of choice. Dosages of 0.10.15 mg/kg of morphine can be used. It can be administered intermittently postoperatively via an indwelling cannula inserted when the child is anaesthetised (level IV; Lamacraft et al 1997). Nursing staff prefer to give analgesia via this route than administer an intramuscular injection. Continuous subcutaneous infusion of morphine can also provide good analgesia in children (level IV; McNicol 1993). This route requires normothermia, adequate hydration and normal peripheral perfusion. Its use is not recommended in a shocked child who may accumulate the opioid subcutaneously and have a sudden systemic reabsorption of the drug after resuscitation, fluid replacement and warming. 99
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Intravenous infusion Intermittent boluses of opioids can be provided in recovery after intra-operative loading using a dose of 0.030.05 mg/kg morphine or its analgesic equivalent, until the child is comfortable. An appropriate infusion may then be started. Continuous infusions of morphine (0.010.04 mg/kg/h) for children over six months of age have been well studied (Bray 1983, Hendrickson et al 1990, Lynn et al 1984). Continuous infusions avoid the extreme variations that may occur with intermittent dosing. Small doses of 0.010.04 mg/kg morphine can be offered for breakthrough pain. This is the equivalent of one hours dose. Nurse-controlled morphine infusions can be used safely with appropriate observation and monitoring in children from six months to five to six years and older if PCA is not an option (Lloyd & McLauchlan 1994). The use of intravenous infusion of opioids in children less than six months of age is discussed in Section 6.4 on page 106. Patient-controlled analgesia PCA provides safe, effective analgesia in children as young as five to six years (level IV; Gaukroger et al 1991) and offers superior analgesia to intermittent intramuscular injections in older children (Berde et al 1991). PCA may be used for postoperative pain control in oncology, and for intermittent painful procedures and burns (level IV; Gaukroger et al 1991). It may be used like adult PCA with a bolus of 0.010.02 mg/kg and a five minute lock-out period. A small basal rate of morphine (5 g/kg/h) may improve analgesia for major surgery in children without increasing side effects (Doyle et al 1993) or the total dose of opioid (Berde 1991). Note that this contrasts with the situation in adults. The dose is important; in the study by Doyle et al (1993), there was an increased incidence of nausea and vomiting and a greater number of episodes of oxygen desaturation with a background infusion of 10 g/kg/hour. Children and young adolescents benefit from regular reminders on how to use PCA in the immediate postoperative period. The child itself rather than family members should activate the PCA machine. Regular assessment of pain and its side effects is necessary, and supervision by professionals trained in its use is essential. Education of the patient and family is important to the success of this technique. There are several groups of children for whom PCA is unsuitable including those: less than five years of age; with developmental delay;
with altered level of consciousness;
unable to understand the concept of PCA after suitable explanation; with suspected intra-abdominal or intracranial pathology; and who have had severe side effects to opioids. Caution should be exercised in children who have renal failure, with bolus administration only. Since the effects of the first bolus dose of opiate will be difficult to predict and may be unexpectedly pronounced, small bolus doses should be titrated with careful observation of effects. Management of side effects such as vomiting, pruritus, constipation and respiratory depression should employ similar agents to those used in adults. Young children may have difficulty expressing subjective symptoms like nausea and dysphoria. If a child becomes increasingly restless despite adequate analgesia, other causes such as hypoxia or metabolic disturbances should be considered. Guidelines for opioid dosage for children are provided in Table 6.1. 100
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Pain in children Table 6.1 Oral Opioid doses in children
Morphine Pethidine Fentanyl Codeine 0.3 mg/kg 0.51.0mg/kg NA NA q34hr** q46hr IV bolus 0.1 mg/kg (half this 0.51.0 mg/kg 0.51.0g/kg NA (single)* for <3 months) Intramuscular 0.10.15 mg/kg 11.5 mg/kg NA 0.51.0mg/kg (intermittent) q23hrs q34hr q3h Subcutaneous 0.10.15 mg/kg 0.51.0mg/kg NA NA (intermittent) q23hrs q3h Intravenous 1040 g/kg/hr 0.52.0 g/kg/hr NA 100400 g/kg/hr@ (infusion) (< 3 months up to 10 g/kg/hr) PCA# 20 g/kg bolus +/ 200 g/kg bolus@ 0.40.5 g/kg bolus NA No background 0.20.5 g/kg/hr 45 g/kg/hr backinfusion. Hourly background Hourly ground infusion. Hourly limit: limit: 1.3 mg/kg limit: 3.0 g/kg 130 g/kg NA not applicable; IV= intravenous * Subsequent intravenous bolus doses should be halved. ** Dosages for sustained release preparations need to be worked out on 24-hr usage. # lock-out interval is usually five minutes, background infusions may be helpful for severe postoperative pain or if opioid tolerant. @ Not commonly used. These doses are for infants older than three months, some guidelines for morphine in infants of less than three months are included. Adapted from Cooper 1995 and McKenzie et al 1997.
Monitoring
Opioid administration in children requires close monitoring of heart and respiratory rates, respiratory effort, blood pressure and responsiveness to stimuli. Practical protocols are available (level IV; Morton 1993). Regular assessment of the level of sedation is important as increasing sedation is often the first sign of opioid toxicity. A decrease in tidal volume will occur before a decrease in respiratory rate which may be a late sign of opioid induced respiratory depression. Frequent or continuous assessment of arterial oxygen saturation using pulse oximetry is a valuable adjunct to close clinical observation. Acute decreases in ventilatory frequency and saturation are greater with pethidine than with morphine at equi-analgesic doses (level III; Hamunen 1993). Pain scores appropriate to age and development should be monitored. Several additional issues are pertinent to opioid administration in children. As in adults, morphine is the drug of first choice. Fentanyl is a useful alternative, especially in patients with renal failure, with side effects related to histamine release or where cardiovascular stability is an issue. Pethidine is now uncommonly used because of neurotoxicity related to norpethidine accumulation. Side effects should be managed with similar agents to those used in adults, remembering that young children may have difficulty expressing subjective symptoms, like pruritus, nausea and dysphoria. Presumptive treatment of side effects may be required if a child becomes increasingly restless despite apparently adequate analgesia. Vomiting and respiratory depression need special mention as more serious effects of opioids. Regular assessment of vital signs and level of consciousness is necessary when parenteral opioids are used for managing postoperative pain.
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There is no evidence that the use of opioids for treatment of severe pain in children leads to opioid dependence or addiction. PCA provides safe and effective analgesia in children as young as five to six years and offers superior analgesia to intermittent intramuscular injections in children. Regular assessment of vital signs and level of consciousness is necessary when parenteral opioids are used for managing postoperative pain.
Non-opioid analgesia
Paracetamol is an effective agent in children, can be given orally or rectally, and can be used to augment other forms of systemic analgesia. Safe doses allow up to 100 mg/kg/24 hours in children and up to 60 mg/kg/24 hours in neonates. NSAIDs such as naproxen (57.5 mg/kg orally q12h) or ibuprofen (410 mg/kg orally q68h) may be used in children. There are a number of contraindications to their use including renal dysfunction, peptic ulcer disease, bleeding diatheses and aspirinsensitive asthma. Aspirin should be used with caution because of the risk of Reyes syndrome. The role of intravenous NSAIDs in children has yet to be established. The contraindications for NSAIDs in children include: gastro-intestinal ulceration, ulcerative colitis or Crohns disease; liver dysfunction; coagulopathy; asthma; and renal disease, hypovolaemia, diuretic therapy. A non-opioid analgesic has potential advantages following tonsillectomy as this procedure is associated with a high incidence of vomiting, and children with a history of obstructive sleep apnoea may be at greater risk of respiratory depression. However, any reduction in opioid-related side effects must be weighed against the potential for increased bleeding due to NSAID effects on platelet function. Two recent studies using ketorolac for post-tonsillectomy analgesia were terminated as the authors felt the incidence of haemorrhagic complications was excessive (Gunter et al 1995, Splinter et al 1996). Withholding keterolac until the end of surgery did not protect against later increased bleeding (Gunter et al 1995).
Regional analgesia
Regional analgesia is widely used in children and young infants, including the newborn. The haemodynamic and respiratory effects appear minimal (level IV; Murat et al 1987). Neural blockade in children should only be instituted by practitioners familiar with the individual techniques and their complications, taking into account the age of the child. Familiarity with the anatomical basis of the block and the volume/concentration of local anaesthetic required to provide effective analgesia without toxicity is important. Paediatric regional techniques are almost always employed as an adjunct to general anaesthesia, as opposed to the situation in adults where they are frequently used as a primary technique.
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The advantages conferred by their use include: a reduction in the amount of volatile anaesthetic agent required, contributing to earlier awakening; a reduction in the response to surgical stimulation; and the ability to provide analgesia without administration of opioids, favouring early return to oral intake. These factors are particularly significant in day-case surgery where time to discharge is important. Specific situations A wide variety of neural blocking techniques has been developed for paediatric use. Some are adaptations of existing adult blocks which recognise that anatomy may differ in subtle ways in children. Infiltration of surgical wounds with local anaesthetic agent is a worthwhile adjunct to other modes of postoperative analgesia, and for many minor day-case procedures (eg herniotomy) may suffice as the sole analgesic technique. Surgeons frequently perform wound infiltration, so it is important that they are aware of the maximum volume that can be injected and the existence of other blocks already performed. In general, adequate analgesia will be attained using 0.25 per cent bupivacaine as this is approximately equipotent to lignocaine 1 per cent, the usual anaesthetic agent used for skin infiltrative analgesia. There is no evidence that higher concentrations achieve better analgesia or prolong the duration of analgesia. Lower concentrations, eg 0.125 per cent, are suitable in the newborn infant. Due to its lower potential for cardiotoxicity, ropivacaine may become an important alternative to bupivacaine. Caudal analgesia is a versatile technique for providing both operative and postoperative analgesia for a wide variety of procedures. The major risks associated with this technique (intravascular injection and dural puncture) can be minimised by using short-bevel needles (level III; Dalens & Hasnaoui 1989, level IV; Brown & Fisk 1992) as these have been shown to reduce the incidence of incorrect placement. Adrenaline-containing local anaesthetic solutions are unreliable as indicators of intravascular injection in anaesthetised children. Intravenous atropine 10 g/kg five minutes before a test dose of lignocaine with adrenaline 1:200,000 results in an earlier and greater increase in heart rate (level III: Desparmet et al 1990). Electrocardiogram (ECG) monitoring showing changes in rate and increases in T-wave amplitude may reflect intravascular injection with adrenaline containing local anaesthetic solutions in children (level IV; Fisher et al 1997). Isoprenaline has been suggested as an additive to local anaesthetic to provide a marker of intravascular injection, and has been shown in intravenous injection studies to result in a greater increase in heart rate than adrenaline-containing solutions (level III; Perillo et al 1993). Further studies of neural toxicity and dose-response evaluation are required before these results can be extrapolated to epidural injection. Prolonged sacral analgesia in inpatients can be achieved by supplementation with caudal morphine 2030 g/kg, provided that appropriate facilities are available for respiratory monitoring. Recent experience supports the safety of supplemental clonidine 12 g/kg via the caudal route (level II; Jamali et al 1994; level III Constant et al 1998). Alternatively, blockade can be extended by placement of a caudal epidural catheter and the use of an infusion, as for lumbar epidural analgesia. Neonatal circumcision is discussed on page 107.
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Inguinal herniotomy can be performed with good postoperative analgesia using ilioinguinal/iliohypogastric block or local infiltration alone with equal success (level II; Trotter et al 1995). Caudal analgesia, though widely practised, is sometimes inadequate in this situation unless large doses are used. Caudal analgesia may result in leg weakness or urinary retention, delaying discharge from hospital; if smaller doses are used, the block may fail to reach lower thoracic and upper lumbar segments and will require supplementation by surgical infiltration. Intravenous regional anaesthesia using lignocaine 0.5 per cent has been successful for treatment of upper limb fractures in children as young as three years (level IV; Turner et al 1986). Prilocaine 0.5 per cent is the recommended drug for this technique because of its wide margin of safety. This technique is ideally suited because of its technical ease and the short duration of blockade compared to other methods of brachial plexus blockade. Appropriate equipment and personnel should be available. Femoral nerve block can provide good analgesia for fractured shaft of femur to allow traction or splitting using 0.5 ml/kg of bupivacaine 0.25 per cent. The use of EMLA cream can do much to reduce the pain and fear of injections for painful procedures such as lumbar puncture, combined if necessary with sedation, eg nitrous oxide. EMLA should be applied generously under an occlusive dressing at least an hour before the procedure. EMLA patches are also available. Toxicity The volume of local anaesthetic solution required to achieve a satisfactory block in children is relatively large (on a per kilogram basis) compared with adults, and doses cannot be scaled down from adult practice. There are several reasons for this: most blocks are performed under general anaesthesia so it is not possible to use paraesthesia as an aid to localisation; many blocks utilise loss of resistance or fascial pop techniques to identify tissue planes and hence accurate localisation is not requiredhowever, larger volumes may be required; and the neuraxis develops early in life and is relatively large in infants and younger children. Fat and connective tissue in the epidural space is less densely packed, so relatively large volumes may be required. Despite the need for large volumes, the concentration required is usually lower as individual nerves are smaller, internodal distance is shorter and there is less myelin in the very young, and there is less need for profound motor block under general anaesthesia. Recommendations about maximum dose depend on the age of the child and whether or not an infusion of local anaesthetic is to be used, in which case the initial dose may need to be reduced. For single-shot techniques such as caudals (level IV; Eyres et al 1983), bupivacaine 3 mg/kg results in acceptable blood levels, but should be reduced to a maximum of 2.5 mg/kg in the neonate. The addition of adrenaline to bupivacaine does not appear to reduce absorption (as for lignocaine) and therefore does not permit a larger dose to be used; however, adrenaline has been shown to significantly prolong caudal blockade in infants and younger children (level III; Warner et al 1987). Other agents such as ketamine and clonidine may provide an even greater duration of caudal block and are still being evaluated (level III; Cook et al 1995). In clinical practice, it is usual to calculate the maximum dose that can be used and then derive the final concentration from the volume required to achieve a block, taking into account any supplemental analgesia (such as local infiltration) that may be required. 104
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In general, there are no special requirements for the postoperative care of patients receiving routine regional (single-shot) analgesia, although parents need to be made aware of the likely duration of blockade and any precautions that may be required. The use of regional analgesia may cause concern about conventional discharge criteria (eg the use of caudal analgesia and the need to void postoperatively) and guidelines may need to be reviewed on an institutional basis if they are impractical. Postoperative care of local anaesthetic infusions Continuous epidural analgesia is effective for providing pain relief following thoracic, abdominal, urological and orthopaedic procedures, but requires close postoperative monitoring by experienced personnel. With increasing use of continuous infusion techniques (including intra-pleural, brachial plexus, lumbar plexus as well as epidural), it is important to define maximum rates of infusion and guidelines for postoperative care. There is currently limited information on the pharmacokinetics of such infusions. However the following recommendations (level IV; Berde 1992) should not be exceeded: Bupivacaine 0.125 per cent (with fentanyl 12 g/ml) at 0.4 ml/kg/h in infants and children; Bupivacaine 0.1 per cent (with fentanyl 1 g/ml) in newborn infants at 0.25 ml/kg/h. The use of such infusions must take into account the childs age and general condition, in particular co-existing disease. In the newborn period, reduced levels of albumin and alpha-1 acid glycoprotein, the principal plasma proteins responsible for binding and slowing metabolism of bupivacaine, may result in greater risk of toxicity (level IV; Eyres 1995). It is essential that children with local anaesthetic or neuraxial opioid infusions are cared for in a suitable ward setting with appropriate cardiorespiratory monitoring available and staff trained and accredited in the care of such patients. Infants under one year of age should have continuous cardiorespiratory monitoring. Regular observation should include pain score, sedation, extent of motor blockade and cardiorespiratory parameters, as well as checking of the infusion rate. All infusions should be delivered with an appropriate volumetric pump, and ideally solutions for epidural infusion should be prepared within a central sterile suite under the supervision of a pharmacist. An anaesthetist should be available onsite to deal with any problems, in particular inadequate analgesia due to block regression. The overall management should remain under the care of the anaesthetist initiating the block, with appropriate on-call anaesthetic cover after hours, preferably within the context of an acute pain service.
Key point
Regional techniques are almost always employed as an adjunct to general anaesthesia in children while in adults they are frequently used as a primary technique.
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6.4
Managing postoperative pain in neonates and infants
There is now overwhelming evidence that all of the neurophysiological components required for pain perception are present by mid gestation in the human foetus, and that these components are active by the time viable pre-term birth occurs (level IV; Fitzgerald 1994). Appropriate neonatal pain scoring systems are now available (level IV; Johnson et al 1993, Krechel & Bildner 1995).
Opioids
Previously, minimal intra-operative opioid analgesia was provided for infants due to concerns about respiratory and haemodynamic side effects. However, optimal opioid analgesia appears to be well tolerated, even in critically ill infants, provided it is used in a carefully monitored setting by skilled anaesthetists (Collins et al 1985, Yaster 1987). Adequate intra-operative analgesia in pre-term and full-term infants significantly reduces surgical stress and postoperative morbidity (level II; Anand & Hickey 1992). The pharmacokinetics of opioids are widely variable among pre-term and full-term neonates and infants. This relates to liver enzyme immaturity and different pathways of metabolism. The elimination half-life of opioids is prolonged and the blood-brain barrier is more permeable (level III; Lynn & Slattery 1987, Choonara et al 1990, Barrett et al 1991). The cytochrome P450 enzyme system in the liver does not reach maturity until several months after birth. Morphine dosage guidelines for infants less than three months for intravenous bolus and infusion are included in Table 6.1 (page 101). Young infants, especially premature neonates or those with neurologic abnormalities or pulmonary disease, are susceptible to apnoea and respiratory depression. The available data are based on small numbers of infants. Most practitioners reduce the initial and infusion dose for infants up to six months of age (level III; McRorie et al 1992). Institutions in which major surgery on neonates and infants is performed should provide training for personnel in the effective and safe administration of opioids for children in this age group, as well as technological monitoring and respiratory support. The long-term effects of opioids on neonates and infants in terms of pain pathway development is unknown (level IV; Aynsley-Green 1996).
Non-opioid analgesics
Paracetamol is a valuable analgesic that can also be given rectally. It can be safely administered to neonates and infants for short courses at recommended doses (Berde 1989, 1991) and can be used to augment other forms of systemic analgesia. Aspirin should be used with caution as there is a risk of Reyes Syndrome with this agent.
Regional techniques
Regional analgesia is widely used in young infants, including the newborn. As with older children, neural blockade in the very young should only be instituted by practitioners familiar with the individual techniques and their complications, taking into account the age of the child. Familiarity with the anatomical basis of the block and the volume/ concentration of local anaesthetic required to provide effective analgesia without toxicity is important. In the newborn, provision of analgesia using local anaesthetic techniques may have added benefit by reducing the need for postoperative ventilation, even in those undergoing major surgery (level IV; Murrell et al 1993).
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Pain in children
Spinal anaesthesia is of particular use in pre-term infants, where there is greater risk of apnoea following general anaesthesia (level II; Krane et al 1995). It is still necessary to monitor the infant postoperatively, even though this risk is reduced. EMLA cream should be used with care in the newborn infant, and application restricted to one site per day as there is potential for toxicity, eg methaemoglobinaemia secondary to prilocaine absorption. Its use in the first week of life in premature neonates of less than 32 weeks gestation is not recommended (level IV; Gourrier et al 1996). Neonatal circumcision This procedure raises several important issues. Compared with past practice, relatively few circumcisions are now performed in the newborn period. General anaesthesia is not regarded as an option for this procedure in terms of resources and risks and difficulties in this age group. It is usually recommended that circumcision be deferred until the child reaches six to twelve months of age, when the operation can be safely performed as a day-case procedure under general anaesthesia with dorsal penile nerve block (or caudal block) as a supplement. This should be performed by an anaesthetist skilled in the technique. Despite these recommendations, there are many parental requests for circumcision in the neonatal period, for social or religious reasons. Neurobehavioural changes can persist for several days in neonates who have circumcision without local anaesthesia (level IV; Dixon et al 1984). The provision of analgesia is difficult as dorsal penile nerve block in this age group is associated with a higher incidence of complications, particularly haematoma formation (level III; Shellman & Stang 1995, level IV; Servour et al 1995). Local infiltration of plain bupivacaine (maximum 2.5 mg/kg) as a ring block at the shaft of the penis is one option, perhaps combined with application of EMLA cream an hour before the procedure, and regular paracetamol postoperatively. Adrenaline-containing solutions should not be used for penile block as there is a risk of vasoconstricting end arteries. There is recent evidence of the safety and efficacy of EMLA alone for the procedure (level III; Taddio et al 1997). However, as mentioned above, there is a risk of methaemoglobinaemia if too much EMLA is used on very small babies. The practice of performing infant circumcision without any form of analgesia is considered by most authorities to be unacceptable.
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Pain in children with cancer
The spectrum of pain in children with cancer is different to that of adults. This is related to the differing aetiologies of childhood cancer. It can be equally divided into cancer-related and procedure-related pain. Most cancer-related pain in children can be treated with appropriate opioid therapy and other analgesics (level IV; Miser 1993). Acute procedural pain for procedures such as lumbar puncture and bone marrow aspiration requires intravenous analgesia and sometimes general anaesthesia. Non-pharmacological measures and other coping mechanisms can be very helpful in promoting optimal pain relief. There is level II evidence for the use of some cognitivebehavioural treatments in children with cancer who experience procedure-related pain. A recent study by Jay et al (1995) compared the effectiveness of cognitivebehavioural therapy with short-acting mask anaesthesia in paediatric cancer patients undergoing bone marrow aspirations. The authors found that in the first minute of lying on the treatment table the cognitive-behavioural therapy group exhibited more behavioural distress, but 24 hours following the bone marrow aspiration, the parents rated behavioural adjustment symptoms higher in the anaesthesia group. The
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authors also drew attention to the recommendations made by Zeltzer et al (1990) in their report of the Subcommittee on the Management of Pain Associated with Procedures in Children with Cancer, which indicated that both psychological intervention and general anaesthesia should be offered as viable alternatives, or in combination, to patients and their parents (level II; Jay et al 1995, 1991, 1987). Once an illness has reached the palliative phase, severe acute pain may require a multidisciplinary approach (level IV; Stevens et al 1994) including regional anaesthetic techniques (level IV; Collins et al 1996) and palliative radiotherapy.
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There has been little research in the area of managing burns and trauma pain. This section has been adapted from the IASP guide to management of acute pain (Ready & Edwards 1992). More detail can be found in this text and in current reviews of burn pain (eg Silbert et al 1997). Relieving pain is only one component of managing an individual suffering burns or trauma-related injury. A team approach to managing the injury itself, other medical conditions, pain and the emotional response of the patient, family and carers is important. Pain secondary to either burns or trauma presents in three distinct phases: the emergency phase, the healing phase and the rehabilitation phase. Pain may be poorly localised, as it is when there are extensive burns or trauma to multiple organ systems in many anatomical locations, or it may be regionalised in one extremity, body cavity or system. Temporal characteristics of the pain need to be considered in each phase, and treatment directed at both background pain which is present at rest or during normal activities, and procedure-associated or incident pain. A combination of nociceptive and neuropathic pain is common and psychological/environmental factors play an important role. Multiple pain generating mechanisms may be involved with varying contributions at different stages. Pain during the emergency phase is caused by direct, massive and prolonged nociceptive stimulation which originates in damaged tissue. The resultant inflammatory response contributes to the development of primary hyperalgesia, and ongoing primary afferent input results in secondary hyperalgesia. Trauma to some part of the nervous system may also result in neuropathic pain. Occasionally it presents immediately after injury but often develops days or weeks later, and may persist as a chronic pain state. It must be distinguished from nociceptive pain and treated differently (see page 39 and pages 152154). Burn pain has often been underestimated and inadequately treated in the past (Perry & Heidrich 1982, Latarjet & Choiniere 1995). Beliefs that third degree burns are not painful are inaccurate, as damaged nerve endings may result in neuropathic pain. Inadequate pain management may lead to detrimental effects due to further exacerbation of the hypermetabolic state, and may increase the likelihood of psychological disturbances (depression and post-traumatic stress disorder) in the recovery phase (level III; Latarjet & Choiniere 1995). Establishment of treatment protocols for both background and incident pain are required, with continuing assessment of pain severity and response to analgesic treatment. A summary of agents used in the management of burn and trauma pain can be found in Table 7.1 on page 112.
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7.1
Emergency phase
During the emergency phase, the goal of treatment is stabilisation of the injured patient and preservation of life and function. The modalities used for pain control are influenced by many variables including the condition of the patient. The provision of analgesia is not contraindicated once the life-saving surgical and neurological evaluation of the trauma patient are performed; in fact, the improved cooperation of the injured patient once appropriate analgesia is provided may facilitate completion of the evaluations. The role of anxiety and fear must be carefully assessed. Reassurance
and information may help considerably in managing agitation, often assumed to be a pain response during this phase. Following severe burn injuries, treatment must be directed at airway management, fluid replacement, prevention of sepsis, and management of pain. Inhalational injuries during burns may result in upper airway obstruction and respiratory compromise due to: thermal injury with progressive upper airway oedema in the first 24 to 48 hours; chemical burns due to the presence of corrosive gases and chemical irritants in carbonaceous particles; or inhalation of toxins such as carbon monoxide which impair oxygenation. Careful titration of analgesics is required in this setting with ongoing evaluation and monitoring of the respiratory status of the patient. Associated injuries such as neck injuries may require urgent intervention. Compartment syndromes due to circumferential limb burns can result in ischaemia and require urgent escharotomy. Systemic pharmacological techniques are the mainstay of therapy during the emergency phase. Intravenous titration of small doses of opioid allows adjustment for individual variation. Intramuscular or subcutaneous injection of opioids will generally not be as effective, and absorption will be delayed and inadequate in the presence of hypovolaemia. Once established, analgesia can be maintained with a continuous infusion of opioid and/or PCA. PCA has been shown to be effective in both adult and paediatric burn patients (level II; Choiniere et al 1992, level III; Gaukroger 1991). Longacting opioids such as MS Contin and Kapanol usually have no place in this phase.
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The healing phase
This phase may continue for weeks or months depending on the nature of injury, and continues until all the wounds are closed. The hallmark of the healing phase is continuous background pain punctuated by incident or procedure-related pain. Pain may also increase as traumatised patients begin to mobilise during this phase.
Pain patterns and treatment options
The goal of therapy during the healing phase becomes the provision of adequate baseline analgesia with intense analgesia provided for incident pain related to procedures, mobilisation and physical therapy. The challenge is in providing this intense analgesia without leaving the patient over-sedated for long periods afterwards. Rapid recovery and the avoidance of prolonged fasting are necessary to allow for adequate nutrition. During the healing phase, the patient must also deal with the emotional impact of the injury. Careful pharmacological management combined with cognitive-behavioural pain control and coping skills training are likely to be useful during this phase. Background pain Background pain is most often managed with opioids by continuous intravenous infusion or PCA. As background analgesic requirements become more stable and the patient is tolerating oral fluids and diet, orally administered longer acting opioids may be useful. Regular paracetamol (orally or rectally) can be used in conjunction with opioids or alone to control less severe background pain (level III; Meyer et al 1997). NSAIDs may be relatively contraindicated in the early phases due to the risk of gastro-intestinal complications and increased bleeding during extensive debridement; but can be used in appropriate doses as supplemental analgesics in the recovery phase (see page 45). 110
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Opioid doses require ongoing revision as individual requirements vary, and the development of tolerance and neuropathic pain may result in increased opioid requirements. The pharmacokinetics of opioids are also altered in burn patients. A hypermetabolic state develops following burn injuries with increased blood flow to the liver and kidneys; and plasma albumin levels may be decreased. Changes in the volume of distribution, clearance, and elimination half-life of opioids result; and may vary at different stages of recovery. These pharmacokinetic changes further emphasise the need to review and individualise opioid doses (Herman et al 1994, Martyn 1986). Incident pain During the healing phase of burn injuries, ongoing debridement, skin grafting and dressing changes are a frequent source of procedure-related pain. Initially, general anaesthesia is required, particularly in children. Due to the often widespread distribution of burn and graft sites, haemodynamic instability in the emergency phase, and the ongoing risk of sepsis in the recovery phase, the role of epidural and intrathecal regional anaesthesia and analgesia is limited (level IV; Latarjet & Choiniere 1995, Ashburn 1995). However, peripheral nerve blocks are useful peri-operatively to provide analgesia for donor skin graft sites (eg lateral cutaneous nerve of thigh and femoral nerve blocks to cover donor sites on the anterolateral thigh). As healing progresses, titration of systemic analgesics such as opioids or ketamine, or inhalation of nitrous oxide can be used to manage procedure-related pain in the ward setting, if adequate monitoring and supervision by trained staff are available. Explanation and preparation of the patient before the procedure, with supplemental anxiolytics and/or non-pharmacological techniques, are useful in conjunction with analgesics to minimise the pain and anxiety associated with repeated procedures (see also page 97). Ketamine is a potent analgesic at subanaesthetic doses, but may be associated with prolonged sedation and psychomimetic side effects. Benzodiazepines reduce the central side effects of ketamine, and may also have a role in conjunction with opioids to reduce the anxiety associated with procedures. Inhalation of nitrous oxide can provide effective analgesia for burn dressing changes. Administration via a mouthpiece rather than a mask is useful in small children and patients with facial burns. Prolonged repeated administration of nitrous oxide reduces activity of methionine synthetase (which has vitamin B12 as a co-enzyme), and may result in megaloblastic anaemia and neuropathy (Amess et al 1978). It is not known what duration of exposure to nitrous oxide in individual patients poses a risk of neuropathy or immune impairment. Scavenging of excess nitrous oxide is required to reduce staff exposure.
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7.3
The rehabilitation phase
The length of this phase is indeterminate. In burns patients, it is characterised by the completion of wound closure and the continuation of physical and occupational therapy. Traumatised patients will have been fully mobilised, and in almost all cases are out of an acute care hospital setting. The character of pain experienced during this phase is usually described as deep and aching. Longer term pain problems such as neuropathic pain or sympathetically maintained pain syndromes may develop during this phase (see pages 39 and 152). Other problems such as post-traumatic stress disorder may arise in this stage and it is important that such patients are identified and referred to a psychiatrist or clinical psychologist for further management. Opioid therapy is rarely required during this time except in those patients whose prolonged use of opioids in the healing phase has made them pharmacologically
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dependent. A weaning schedule from potent opioids is usually developed for such patients, using regular administration of a long-acting agent on a gradually declining dosage. Pain management is best accomplished with NSAIDs, paracetamol, or if necessary an opioid. Pain associated with procedures during this phase can be treated as it would be during the healing phase.
Table 7.1 Management of burn and trauma pain
Pharmacologic
Systemic opioids, for burn pain
continuous IV intermittent IVprovider administered intermittent IVPCA combination of continuous IV and intermittent IV (provider administered or PCA) oral opioidssustained release paracetamol, NSAIDs (aspirin may be used alone or in conjunction with opioids) Ketamine Nitrous oxide Anxiolytic
Non-opioids
General anaesthesia (for extensive procedures)
Regional anaesthesia
peripheral nerve block
epidural analgesia (selected patients) Distraction / guided imagery Hypnosis TENS Relaxation
Non-pharmacologic
Sample casetrauma pain A 23-year-old woman is injured in an automobile accident sustaining a compound fracture of tibia and fibula, with extensive soft tissue trauma, vascular injury requiring surgery and a neuropraxia of the common peroneal nerve. On admission, she complains of excruciating pain on the lateral aspect of the leg which is burning and stabbing, accompanied by extreme sensitivity of the skin. There is also a very deep aching pain in the leg and foot. She is extremely anxious and tearful and is convinced that she will lose the leg. Pre-operatively, substantial time is spent explaining the proposed surgical treatment and discussing analgesic options. It is agreed that under cover of intravenous analgesia and sedation (to a light level) an epidural catheter will be placed and an infusion of local anaesthetic and opioid commenced to relieve pain and improve limb perfusion. Intra-operatively, the epidural is supplemented by light general anaesthesia. Surgical management includes vascular surgery to repair the popliteal artery, internal fixation of the fractures and extensive debridement of necrotic skin and muscle.
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Sample casetrauma pain (cont) Postoperatively, the burning pain is well controlled but several bolus doses of local anaesthetic/opioid epidurally are required to control the deep aching pain which has become more severe. The pain relief is continued with an epidural infusion of 0.125 per cent bupivacaine plus low-dose fentanyl. The patient is maintained on low-dose heparin, so frequent observation is made of neurological status in the lower limbs, and any new occurrence of back pain is reported immediately. The epidural block does not impair sensation and motor function, which are monitored closely. Seven days after surgery the epidural is discontinued. However, the patient requires mexilitine 200 mg tds to control the burning pain. The deep aching pain persists and requires a combination of regular paracetamol and oral morphine sulphate. After three days, the morphine sulphate 100 mg/day is converted to slow-release morphine at a dose of 50 mg bd. This regimen is continued for the next two months while the open wound is gradually healing. At this time the slow-release morphine is tapered over the next four weeks and then discontinued. The mexitiline is still required at the same dose. From day one after surgery the patient is mobilised. She is also taught techniques of relaxation and imagery, which she continues to use during the rehabilitation phase.
Key points
Patients with burn or trauma pain need a range of strategies which may differ during the emergency, healing and rehabilitation phases. A combination of nociceptive and neuropathic pain is common and psychological/ environmental factors play an important role (eg anxiety, fear of permanent disability or death). Severe pain may persist in the healing and rehabilitation phasespain treatment is an essential ingredient of an active rehabilitation plan. The use of long-acting oral opioids is appropriate while there is obvious evidence of trauma-associated persisting nociception. Treatment of neuropathy may need to continue well after the healing phase. Unexpectedly prolonged requirement for opioids should prompt referral for multidisciplinary pain unit assessment.
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Acute pain associated with medical conditions
Much of the preceding information in this report has referred to the treatment of pain after surgical procedures or trauma. There is also a variety of painful conditions that are classified as resulting from medical causes, for which the same principles of effective analgesia apply. In this category, the most effective way to relieve pain is to diagnose and treat the underlying cause whenever possible. However, pain should be treated even while the condition is being diagnosedin many instances, delaying treatment may be detrimental to outcome This chapter discusses examples of commonly occurring medical conditions which illustrate important principles of acute pain management. It is important to note that in these medical conditions there is often no dichotomy between acute and chronic pain, especially in those that are recurrent or incurable.
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8.1
The aim of treating pain due to ischaemic heart disease is to reduce or abolish myocardial ischaemia which is the cause of pain. This is accomplished by interventions which restore coronary blood flow (either mechanically or pharmacologically) and/or limit the extent of ischaemia and myocardial tissue damage (by restoring coronary blood flow or by reducing myocardial oxygen demand through the use of pharmacological agents including nitrates, beta blockers and calcium antagonists). Patients suffering from acute cardiac ischaemic pain are at risk of cardiac arrest. Should the pain last for longer than 10 minutes they should go directly to the emergency department of the nearest hospital, where an early ECG will be performed to determine whether there is evidence of an acute myocardial infarction. This assists in determining the subsequent management of the patient. In the setting of acute myocardial infarction, measures to increase coronary blood flow include aspirin and thrombolytic therapy, or balloon angioplasty with or without stenting (level I; Michels & Yusuf 1995). The first line pharmacological agent in relieving ischaemic cardiac pain is sublingual nitroglycerin in the form of a tablet of spray. This drug improves myocardial perfusion and reduces myocardial oxygen demand. Other agents that reduce myocardial oxygen demand include intravenous beta blockade, which is of value particularly if the heart rate and systolic blood pressure are elevated. Measures which have a direct effect on pain may also be useful. Opioids, particularly morphine, have a role in treating pain as well as in reducing central autonomic and neuro-endocrine responses. This is important as morphine may be associated with amelioration of increased cardiac work and oxygen consumption, which may minimise the size of infarction (level IV; Sethna et al 1982). Other short-acting drugs with special benefits such as fentanyl and midazolam are widely used during acute coronary intervention. Although not applicable to acute presentations of unstable angina, the use of thoracic epidural analgesia may be valuable in acute on chronic episodes of angina. Patients likely to be considered for this form of pain relief are those in whom operative intervention is not possible or for which there is likely to be a long waiting 115
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period. The favourable effects of thoracic epidural analgesia on indices of cardiac function recommends it as an option in this situation (Blomberg et al 1989a,1989b, Koch et al 1990, Olausson et al 1997; see also page 70). Further detail about treatment of unstable angina and the use of coronary revascularisation procedures can be found in the relevant NHMRC clinical practice guidelines (NHMRC 1996a, 1996b). The American College of Cardiology/American Heart Association has published guidelines for coronary artery bypass surgery (ACC/AHA 1991) and balloon angioplasty (ACC/AHA 1993).
8.2
Acute herpes zoster infection (shingles)
Acute herpes zoster infection is common. It leads to severe acute pain in dermatomes supplied by varicella zoster-infected spinal or cranial dorsal root ganglia. Postherpetic neuralgia, as a complication of herpes zoster infection, is a chronic condition, particularly in elderly and immunocompromised patients. It is resistant to therapy and is a prime example of neuropathic pain.
Treatment of acute pain
Antiviral agents Antiviral agents are useful in shortening the period of viral shedding and hastening the healing of the vesicular rash. Debate continues about the usefulness of antiviral agents in reducing the degree and duration of post-herpetic neuralgia. A number of randomised controlled trials have found that antiviral agents significantly reduce the duration of post-herpetic neuralgia in older patients (level I; Kost & Straus 1996). Corticosteroids Corticosteroids are sometimes given for acute herpes zoster infection. The risk of dissemination is minimised by concurrent antiviral treatment. Corticosteroids have little analgesic effect and evidence for the reduction in the incidence and severity of post-herpetic neuralgia is conflicting. Likewise, sympathetic blockade with local anaesthetic and corticosteroids is widely used despite there being little evidence for its efficacy. Antidepressants and anticonvulsants There is evidence from a meta-analysis of studies on the treatment of neuropathic pain that antidepressants and anticonvulsants are effective for this general category of pain (level I; McQuay 1995a; see also page 152). The role of amitriptyline in the management of post-herpetic neuralgia has been demonstrated in placebo-controlled trials by Watson et al (1982) and Max et al (1988). It has been suggested that the earlier amitriptyline is commenced, the better the long-term outcome (Bowsher 1994). There is little evidence that anticonvulsants have any benefit over antidepressants, although the practice of combining these two classes of agent is quite common. Various authors claim that anticonvulsants tend to be of more benefit when the pain has a shooting component, while antidepressants are more helpful for continuous, burning pains. However, a recent systematic review does not support a difference between anticonvulsants and antidepressants in the treatment of neuropathic pain (level I; McQuay et al 1996).
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Statements of evidenceacute herpes zoster infection Antiviral agents used early for the treatment of acute herpes zoster infection have been shown to accelerate lesion healing and result in faster resolution of pain. Antidepressants and anticonvulsants are effective in the treatment of neuropathic pain such as post-herpetic neuralgia.
Level of evidence
I Kost & Straus 1996 I McQuay et al 1995a
8.3
Acute abdominal pain
Acute abdominal pain has many causes, not all of which are treated by surgery. Prompt recognition of the cause of abdominal pain is most important. Visceral pain is typically poorly localised, midline and associated with autonomic features such as sweating, restlessness, nausea, vomiting and pallor. On the other hand, somatic or parietal pain is generally sharp and well localised. Inflammation of the peritoneum can usually be accurately localised. Referred pain, neuropathic pain and psychological/environmental factors should also be considered. In terms of pain relief, treating the primary cause is often a priority, particularly with surgical conditions such as appendicitis. A common belief is that analgesia masks the symptoms and signs of such illnesses and should therefore be withheld until a diagnosis and management plan is established. However, this can be a time-consuming process. There is evidence that analgesia does not interfere with the diagnostic process but may actually facilitate it (level II; Attard et al 1992).
Treatment
Treatment of acute abdominal pain is critically dependent on diagnosis of a potential underlying physical cause, as outlined in Table 8.1. An accurate pain history is very important (see page 37). In patients in whom a physical cause is difficult to define, further exploration of psychological/environmental factors may be necessary, possibly in a multidisciplinary pain unit setting. An example of this is the management of patients with chronic pancreatitis, who have a background of chronic opioid use and who may present with acute episodes of abdominal pain. Patients presenting with recurrent attacks of acute abdominal pain may be better considered as chronic pain sufferers, and treated with an approach that includes a cognitivebehavioural pain program. Diagnostic local anaesthetic (coeliac plexus block) may sometimes be helpful in distinguishing a visceral from a somatic, or other cause, of pain. However, neurolytic coeliac plexus block is rarely if ever appropriate for treatment of recurrent acute episodes of chronic non-cancer abdominal pain (level IV; Patt & Cousins 1998).
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Sample caseabdominal pain A 68-year-old woman presents with a prior history of ill-defined episodes of abdominal pain and now complains of acute severe generalised abdominal pain. She lives alone, is sleeping very poorly, fears she has cancer and is a poor historian. Thorough evaluation reveals no acute surgical cause for the pain. However, on more detailed questioning, it is found that diabetes was diagnosed many years ago and the patient has been poorly compliant with treatment. Arrangements are made to improve and regularly monitor treatment of her diabetes. The pain history has features of neuropathic pain (see Table 3.1 on page 37), in particular it has burning and paroxysm features. Treatment is commenced with the membrane stabiliser mexilitine at a starting dose of 50 mg bd slowly increasing to 150 mg tds. A small night-time dose of doxepin 10 mg, increasing slowly to 30 mg is also commenced. The pain decreases after only 24 hours and after five days has almost subsided. The patient is now sleeping well. Management point The acute presentation of abdominal pain may occur on a background of lowgrade abdominal pain associated with an underlying medical diagnosisin this case diabetes. Diabetic neuropathy in the thoracolumbar region can be associated with acute and/or chronic abdominal pain, which is poorly responsive to opioids. Psychological/ environmental factors were also playing a part in this lonely woman, who had become despondent about her future and thus poorly compliant with treatment of her diabetes. Further problems with treatment compliance and thus further acute abdominal pain presentations are likely.
Table 8.1 I
Intra-abdominal
A Parietal peritoneal inflammation 1 Generalised peritonitis a Perforated viscus: peptic ulcer, gall bladder, colonic diverticulum b Primary bacterial peritonitis: pneumococcal, streptococcal, enteric bacillus, tuberculosis c Non-bacterial peritonitis; ruptured ovarian cyst d Familial Mediterranean fever (familial periodic peritonitis) e Spontaneous bacterial peritonitis 2 Localised peritonitis: (many types may proceed to generalised peritonitis) a Appendicitis b Cholecystitis c Peptic ulcer d Meckels diverticulitis e Regional enteritis f Acute colonic diverticulitis g Colitis: ulcerative, amoebic, bacterial h Gastro-enteritis I Pancreatitis j Hepatitis: viral, toxic k Pelvic inflammatory disease l Endometriosis m Lymphadenitis
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Acute pain associated with medical conditions Table 8.1 Causes of abdominal pain (cont)
B Acute increased tension of hollow viscera 1 Intestinal obstruction: adhesions, hernia, tumour, volvulus, faecal impaction, intussusception 2 Intestinal hypermotility: irritable colon, gastro-enteritis 3 Biliary obstruction: gallstone, stricture tumour, parasites, haemobilia 4 Ureteral obstruction: calculi, tumour C Increased tension of visceral surfaces 1 Hepatic capsule distension: acute hepatitis (toxic, viral, Rickettsial), common duct obstruction, Budd-Chiari syndrome, haematoma 2 Renal capsule distension: pyelonephritis, ureteral obstruction, haematoma 3 Uterine obstruction: neoplasm, childbirth 4 Ruptured ectopic pregnancy D Vascular disturbances 1 Intestinal angina or infarction: embolism, polyarteritis, arterial stenosis 2 Splenic infarction 3 Torsion: gall bladder, spleen, ovarian cyst, testicle, omentum, appendix epiploica 4 Hepatic infarction: toxaemia 5 Tumour necrosis: hepatoma, uterine fibroid 6 Intestinal migraine 7 Sickle cell anaemia E Abdominal wall 1 Distortion or traction of the mesentery 2 Trauma or infection of muscles II Extra-abdominal A Thoracic 1 Pneumonitis 2 Pulmonary embolism 3 Pneumothorax 4 Empyema 5 Myocardial ischaemia 6 Myocarditis, endocarditis 7 Oesophagitis 8 Oesophageal rupture B Neuropathic 1 Radiculitis: spinal cord or peripheral nerve tumours, arthritis of spine, herpes zoster infection 2 Tabes dorsalis 3 Abdominal epilepsy 4 Diabetic thoraco-abdominal neuropathy 5 Causalgia C Metabolic 1 Uraemia 2 Diabetic keto-acidosis 3 Porphyria 4 Acute adrenal insufficiency 5 Osteoporosis D Toxins 1 Hypersensitivity reactions: insect bites, reptile venoms 2 Drugs: lead poisoning etc E Psychogenic Source: Ready & Edwards 1992.
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8.4
Acute headache
There are many causes of acute headache, some of which involve structures other than the head (eg the neck). Before initiating a course of analgesic treatment, it is vital to rule out serious intracranial or other pathology.
Table 8.2
1 a b c d e f g 2 a b c 3 a b c 4 a b c d e f 5 a b 6 a b c d e f g h i 7 a b c d e f g
Causes of headache
8 Headache associated with substances or their withdrawal a Headache induced by acute substance use or exposure b Headache induced by chronic substance use or exposure (eg opioid rebound) c Headache from substance withdrawal (acute use) d Headache from substance withdrawal (chronic use) e Headache associated with substances but with uncertain mechanism 9 Headache associated with non-cephalic infection a Viral infection b Bacterial infection c Headache related to other infection 10 Headache associated with metabolic disorder a Hypoxia b Hypercapnia c Mixed hypoxia and hypercapnia d Hypoglycaemia e Dialysis f Headache related to other metabolic abnormality 11 Headache or facial pain associated with disorder of facial or cranial [or neck] structures a Cranial bone b Neck [cervicogenic headache] c Eyes d Ears e Nose and sinuses f Teeth, jaws and related structures g Temporomandibular joint disease 12 Cranial neuralgias, nerve trunk pain, and differentiation pain a Persistent (in contrast to tic-like) pain of cranial nerve origin b Trigeminal neuralgia c Glossopharyngeal neuralgia d Nervus intermedius neuralgia e Superior laryngeal neuralgia f Central causes of head and facial pain other than tic douloureux g Facial pain not fulfilling criteria in groups 11 or 12 13 Headache not classifiable
Migraine Migraine without aura Migraine with aura Ophthalmoplegic migraine Retinal migraine Precursor childhood periodic syndromes Complications of migraine Migrainous disorder not fulfilling above criteria Tension-type headache Episodic tension-type headache Chronic tension-type headache Tension-type headache not fulfilling above criteria Cluster headache and chronic paroxysmal hemicrania Cluster headache Chronic paroxysmal hemicrania Cluster-like disorder not fulfilling above criteria Miscellaneous headaches not associated with structural lesion Idiopathic stabbing headache External compression headache Cold stimulus headache Benign cough headache Benign exertional headache Headache associated with sexual activity Headache associated with head trauma Acute post-traumatic headache Chronic post-traumatic headache Headache associated with vascular disorders Acute ischaemic cerebrovascular disorder Intracranial haematoma Subarachnoid haemorrhage Unruptured vascular formation Arteritis Carotid or vertebral artery pain Venous thrombosis Arterial hypertension Other vascular disorder Headache associated with non-vascular cranial disorder High CSF pressure Low CSF pressure (eg post-lumbar puncture headache) Intracranial infection Intracranial sarcoidosis and other non-infectious inflammatory diseases Headache related to intrathecal injections Intracranial neoplasm Other cranial disorder
Source: Headache Classification Committee of the International Headache Society 1988. (Minor amendements are given in square parentheses.)
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Acute migraine
Despite the fact that acute migraine is a well known and common pain condition that affects about 20 per cent of the population, there are no clear guidelines for its management. While a number of agents have been recognised as being effective in treating migraine, their success in individual patients is difficult to predict. Patients who experience only mild or occasional attacks may be treated with simple analgesics, either alone or in combination. For more severe or frequent migraine, a stepwise approach to the use of pharmacological agents is recommended. Specific treatments for migraine Moderate to severe migraine requires the use of specific antimigraine medications such as ergotamine (level II; Belgrade et al 1989, Klapper & Stanton 1993, level III; Raskin 1986) or sumatriptan (level II; Comparative Study Group 1992, level III; Callahan & Raskin 1986). Ergotamine derivatives are most appropriate in patients with frequent, moderately severe or severe infrequent migraine headaches. Wide variations in the effectiveness of ergotamine results from its erratic gastro-intestinal absorption. Caffeine has been reported to increase the absorption of ergots, which is why it is included in migraine combinations. The use of intravenous dihydroergotamine 0.5 mg is recommended when nausea is prominent. Triptans, notably sumatriptan, naritriptan and zolmitriptan, have been major advances in the management of migraine headaches, although a recent randomised controlled trial has found that the combination of soluble aspirin (900 mg) and metoclopramide is as effective as sumatriptan in the treatment of migraine, is better tolerated and is also considerably cheaper (level II; Tfelt-Hansen et al 1995). Cardiac adverse effects are the major concern with triptans and intravenous administration should be avoided due to the risk of coronary artery spasm. Likewise, subcutaneous administration is contraindicated in patients with a history of ischaemic heart disease, Prinzmetal angina or hypertension. Sumatriptan has been attributed with a causal role in myocardial infarction (level IV; Ottervanger et al 1993). Anti-emetics and benzodiazepines have value in symptom control and relief of distress particularly when more specific agents are precluded. Non-steroidal anti-inflammatory drugs Short-acting NSAID therapy for acute migraine has been examined by a number of studies. There is little to differentiate one NSAID from another in this application, but studies of naproxen and ketoprofen demonstrated a significantly better response with these agents than that demonstrated with ergotamine (level III; Treves et al 1992, Lange & Lentz 1995, Kangasniemi & Kaaja 1992). Opioids Opioids are commonly used to treat migraine, although this practice is not based on opioid receptors having a specific mechanism in migraine. Randomised controlled trials have shown that pethidine is no more effective than dihydroergotamine, chlorpromazine or NSAIDs (level II; Lane et al 1989, Stiell et al 1991, Davis 1995, Scherl & Wilson 1995). Most studies note that the dosage of opioid required for clinical effect in acute migraine may be higher than for other types of pain. A study in the emergency department setting concluded that ketorolac in large doses was as effective as the combination of pethidine and hydroxyzine (level II; Duarte et al 1992). In one study of limited power, the use of morphine without antinauseants for migraine was shown to
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Acute pain management: scientific evidence Nicolodi 1996).
be no more effective than placebo and to provoke unacceptable side effects (level II; The Australian Association of Neurologists ad hoc committee on the use of opioids in the management of migraine recommends that pethidine should not be used for migraine treatment unless the patient is unresponsive to all other measures or during pregnancy when the use of ergotamine tartrate preparations, triptans and dihydroergotamine is contraindicated. The frequency of use should be monitored as administration of short-acting opioids may reinforce drug-seeking behaviours and physiological dependence. Recognition of an apparent increase in dose or frequency of pethidine in this context should prompt specialist referral (Lance et al 1997). Other treatments for acute migraine Corticosteroid therapy can be effective in reducing pain in refractory migraine (status migrainosus). Anti-emetic treatment used in the absence of other medicationtwo randomised controlled trials have concluded that intravenous prochlorperazine is more effective than metoclopramide, and both were significantly more effective in relieving pain and nausea than was placebo. Intravenous prochlorperazine was more effective than was rectal prochlorperazine (level II; Coppola et al 1995, Thomas et al 1994).
Acupuncturethree randomised controlled studies support the effectiveness of acupuncture in the treatment of migraine (level II; Loh et al 1984, Hesse et al 1994, Vincent 1989). However, these studies examine the effects in the long term or for prophylaxis and do not examine effectiveness during acute migraine. While acupuncture may be useful as a preventative treatment, thereby reducing the incidence or severity of acute migraine, the analgesic effect during an acute episode appears to be unknown. Cervical manual therapy has been reported to help some patients in acute migraine attacks. However, no significant difference has been identified in comparing cervical manipulation and gentle mobilisation with gentle movement within the normal range of the neck and joints (level II; Parker et al 1978). Analgesic rebound headache This is a condition of intractable daily or near daily headaches sustained by analgesic use required to abort each episode (level IV; Headache Classification Committee 1988, Soloman & Lipton 1992, Mathew 1993). A severe, throbbing character is one feature among others that make these attacks resemble migraine. Symptomatic treatment may be offered for each attack but long-term management requires the cautious reduction of analgesic medication and the addition of prophylactic antimigraine treatment. This has been shown to improve headache control in nearly 80 per cent of individuals (level IV; Welch 1993a, Welch 1993b). In order to cope without opioids, such patients may benefit from early entry to a cognitivebehavioural program.
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Statement of evidencemigraine A stepwise approach to the use of pharmacological agents in the treatment of migraine is effective. Moderate to severe migraine may require the use of specific antimigraine medications such as ergotamine or sumatriptan, unless contraindicated. The combination of soluble aspirin (900 mg) and metoclopramide is as effective as sumatriptan in the treatment of migraine, is better tolerated and is also considerably cheaper. Pethidine has been found to be no more effective than dihydroergotamine, chlorpromazine or NSAIDs in the treatment of migraine.
Level of evidence
III Raskin 1986, Callahan & Raskin 1986
II Tfelt-Hansen et al 1995
II Lane et al 1989, Stiell et al 1991, Davis 1995, Scherl 1995, Nicolodi 1996
Key point
There are very few situations in which pethidine is useful in acute migraine, although it may be considered during pregnancy when the use of ergotamine preparations, triptans and dihydroergotamine is contraindicated.
Tension headaches
Tension headaches can be extremely debilitating, with acute episodes varying in intensity from mild to very severe. There is considerable overlap with migraine and cervicogenic headache. Chronic rebound headache from many proprietary analgesics and anti-migraine preparations is a significant contributing factor. Additional contributing factors including psychological, physical and environmental issues may be best considered in a broad assessment setting where nonpharmacological strategies may be undertaken to greatly reduce the number of severe attacks and to provide a more rational contingency plan for management of severe attacks. Similar approaches may be beneficial in other types of recurrent acute headache. Musculoskeletal problems in the neck may provoke severe headache. An appropriate program of active physical therapy (including stretching), relaxation and biofeedback techniques and cognitive-behavioural techniques (eg pacing) may be helpful (level III; Arena et al 1995). Acupuncture and hypnotherapy may be considered in tension headache management, although disappointing reductions in headache scores have been noted (level III; Melis et al 1991, Carlsson et al 1990). Low-dose tricyclic or sodium valproate is advocated for prophylaxis but there may be no advantage over placebo (level II; Pfaffenrath et al 1994) and apart from occasional use of simple analgesia for acute episodic tension headache, regular analgesia is not advised. The following clinical example highlights some relevant management issues in the area of headache.
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Sample case A 36-year-old woman, divorced and working in a responsible position, attends the emergency department with a severe, pounding, generalised headache. She has a history of intermittent migraine occurring once or twice each month and she takes paracetamol with codeine 30 mg several times a week for milder headache. Her current headache is of similar character to her usual migraine and was heralded by visual blurring, photophobia and nausea with vomiting. She reports that an injection generally settles her headache quickly. Management points This patient presents with two headache problemsmigraine, which occurs intermittently, and mild headache occurring frequently. The patients previous migraine headaches have not occurred with sufficient frequency to warrant regular prophylactic medication. Management of the current acute migraine should comprise adequate hydration and anti-emetic therapy with prochlorperazine or metoclopramide. Injected ergotamine may be suitable if the duration of the acute headache is short but injected sumatriptan may be effective throughout the acute phase of headache and is preferable to opioid analgesia. The patients regular consumption of paracetamol with codeine 30 mg for the frequent mild headache is inappropriate and the likelihood of opioid tolerance must be considered. It is also possible that she is suffering from analgesic rebound headache which is interpreted as migraine. Management includes control of the acute headache and consideration of the longer term condition which requires a broad-based assessment and good communication between health carers. The patient requires a broad review of physical, pharmacological, psychological and environmental factors to determine whether non-pharmacological measures may be helpful for the mild headache and perhaps to decrease the frequency of migraine episodes.
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Cervicogenic headache
This type of headache usually involves recurrent, acute attacks of moderate to moderately severe unilateral head pain, (without change of side), generally involving the whole hemicranium. As indicated by its name, cervicogenic headache usually starts in the neck or occipital area, eventually involving the forehead and temporal areas, where the maximal pain is frequently located. The headache often appears in acute episodes of varying duration in the early phase but with time may become more continuous, with exacerbations and remissions. Symptoms and signs such as mechanical precipitation of attacks imply involvement of the neck. There may be: a reduced range of motion in the neck, in one or more directions; headache may be elicited by neck movements or neck position during sleep; and external pressure over the greater occipital protuberance on the symptomatic side may precipitate headache. Treatment Treatment should focus on the neck in the first instance, with investigation of neck posture at work, during sleep and other activities. There is some evidence that exercises for cervical muscles and local spinal mobilisation may be helpful (level IV; Bovim et al 1992); such treatment is currently under investigation. There is also 124
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evidence that structures in the posterior scalp (including periosteum of occipital area) may be involved in the pathogenesis of this type of headache, but at present the precise aetiology is uncertain. However, the contribution of regular analgesic and proprietary anti-headache medication must be carefully evaluated in each case. Local anaesthetic blockade of the greater occipital nerve (GON) may provide temporary relief of the headache (level III; Sjaastad 1992, Sjaastad et al 1995). Cryoprobe blockade or operative section of the GON may provide relief for months or years, but rarely provides permanent relief; such procedures may themselves produce neuropathic pain.
Post-lumbar puncture headache

Headaches of this type often improve spontaneously with simple measures such as bed rest, hydration and analgesics. In some cases the headache may persist for many days or even weeks. Such headaches are often severe and associated with meningism, auditory and visual symptoms, and nausea and vomiting. There is evidence for the use of epidural blood patches for persisting severe postural headache (level II; Heide & Diener 1990).
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Acute pain in haemophilia/haemarthrosis
Resulting from a sex-linked recessive inherited deficiency of factor VIII, haemophilia is characterised by a coagulopathy of variable severity in affected boys and young men. The degree of coagulopathy depends on the severity of the factor VIII deficiency (often < 1 per cent of normal in severe cases). Acute pain usually results when uncontrolled bleeding occurs into confined spaces such as joints or muscles (Tyler 1990). Bleeding also occurs into soft tissues and the central nervous system but this is less often associated with pain. Bleeding follows minor surgery or trauma, but in the case of severely affected individuals may occur spontaneously. Diagnosis is confirmed by demonstration of the coagulopathy on clotting studies but is usually already known to the patient and family because of the family history, and because haemarthrosis normally requires substantial trauma in non-haemophiliacs. Many haemophiliac patients became human immunodeficiency virus (HIV) or hepatitis C positive in the 1980s due to transfusion with infected blood products, but this is now rare in newly diagnosed cases. This is relevant because a haemarthrosis with an unusual pain pattern, fever and HIV seropositivity raises the diagnosis of a pyoarthrosis (Gilbert 1993).
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Treatment
There is no cure for haemophilia. The mainstay of treatment is prompt replacement of factor VIII with intravenous fresh frozen plasma or factor VIII concentrates such as cryoprecipitate for acute bleeding episodes, as well as prophylactic management of bleeding associated with anticipated trauma or surgery. Many haemophiliacs self treat in this way. Pain management is a major problem. Analgesics are the cornerstone, but aspirin and NSAIDs are ordinarily avoided because of their inhibitory effects on platelet function. Opioids may be required but should not be given intramuscularly because of the risk of producing a haematoma. Joint aspiration can be considered after factor VIII replacement and arthroscopy is being used for this purpose (level III; Baker 1992). Physical therapies such as cold packs may also have a role (Tyler 1990). Prolonged rest should be avoided as patients with haemophilia are at risk of chronic
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pain due to haemophiliac arthropathy. Steroids may help acute synovitis pain associated with acute haemophiliac arthropathy (level III; Gilbert 1993).
8.6
Acute dental and orofacial pain
Orofacial pain of predominantly physical origin is generally acute and usually caused by dental and periodontal disease. Management aimed at correcting the underlying disease (eg root canal treatment and extractions) and application of simple physical and pharmacological therapies (including local anaesthesia and NSAIDs) generally control these acute pain episodes well. Recurrent acute and persisting acute/chronic dental and orofacial pain syndromes require a different therapeutic approach. Analgesic interventions used in routine acute pain management are destined to fail and may result in mutilation, drug toxicity and neuropathic pain syndromes that are difficult to treat. Common orofacial pain syndromes include: neuropathic pain (trigeminal and glossopharyngeal neuralgia, post-herpetic neuralgia, deafferentation pain); temporomandibular disorders (including pain from soft tissues and anatomical disorders of the temporomandibular joint); vascular type pain (cluster headache, migraine, carotidynia); and oral dysaesthesia and atypical facial pain which includes the burning mouth syndrome, atypical odontalgia, phantom pain.
Atypical odontalgia
Atypical odontalgia and atypical facial pain may present as a variety of pain patterns over time, including acute and recurrent acute. There may also be a number of associated reports of swelling, ulceration and discharge which are often unsubstantiated. The term atypical facial pain is poorly defined (level IV; Millard & Mason 1993) and may include atypical odontalgia, glossodynia and burning mouth syndrome. Patients given this label are commonly middle-aged women with a history of long-standing orofacial pain, pain elsewhere and psychologic issues (Vickers et al 1998). Dental practitioners may respond to this clinical picture with surgical interventions such as extraction of teeth, removal of bone or sectioning of nerves. These procedures are unnecessary in this setting and may produce severe, intractable neuropathic pain syndromes that are difficult and costly to treat (Vickers & Cousins 1994). The new IASP Dental Pain Curriculum synthesises the treatment of operative dental pain and common orofacial pain syndromes (level IV; Gerschman et al 1993).
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8.7
Acute musculoskeletal pain
Acute spinal pain
The management of acute spinal pain is an extensive field, involving a wide variety of health practitioners. It is beyond the scope of this report to provide a comprehensive evaluation of the range of treatments available. More detailed evaluations of current management can be found in existing guidelines devoted
solely to the management of acute spinal pain, produced by organisations such as the AHCPR (1994a), ACC New Zealand (ACC & National Health Committee 1997), and the Royal College of General Practitioners UK (Waddell et al 1996). In acute spinal conditions it is important to make a broad assessment of physical, psychological and environmental factors.
Acute lower back pain

Although acute lower back pain may be attributable to trauma (especially in an osteoporotic spine), infection, neoplasm or metabolic bone disease, the most common presentation is non-specific pain associated with decreased spinal movement, which is labelled mechanical. This can occur in any age group and is usually self limiting. The cost of lower back pain is considerable, in terms of financial burden and morbidity (CSAG 1994). Treatment based on bed rest and immobilisation is ineffective (level I, Koes & van den Hoogen 1994); promoting effective rehabilitation is more likely to reduce the burden of this disorder. Accurate assessment The key to managing acute lower back pain is to distinguish serious pathology from the benign musculoskeletal causes that constitute about 90 per cent of cases (CSAG 1994). Some examples of pathology considered serious are acute disc prolapse with neurological deficit, spinal fracture, spinal tumour or infection and the cauda equina syndrome. Certain features suggest serious pathology (see Table 8.3 and Figure 8.1), and should be sought by careful history and examination.
Table 8.3 Possible fracture
From medical history Major trauma, such as vehicle accident or fall from height. Minor trauma or even strenuous lifting (in older or potentially osteoporotic patient).
From physical examination
Source: AHCPR 1992.
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Red flags for potentially serious spinal conditions Possible tumour or infection Possible cauda equina syndrome Saddle anaesthesia. Recent onset of bladder dysfunction, such as urinary retention, increased frequency, or overflow incontinence. Severe or progressive neurological deficit in the lower extremity.
Age over 50 or under 20. History of cancer. Constitutional symptoms, such as recent fever or chills or unexplained weight loss. Risk factors for spinal infection: recent bacterial infection (eg urinary tract infection); IV drug abuse; or immune suppression (from steroids, transplant or HIV); diabetes. Pain that worsens when supine, severe night-time pain.
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Unexpected laxity of anal sphincter. Peri-anal/perineal sensory loss. Major motor weakness: quadriceps (knee extension weakness); ankle plantar flexors, evertors and dorsiflexors (foot drop).
Investigation is indicated only on high clinical suspicion of serious spinal pathology. The most common causes of acute back pain cannot be diagnosed radiologically; in most cases of uncomplicated spinal pain, no relevant pathology will be revealed. Not only does pain correspond poorly with the usual age-related changes demonstrable on routine radiology but also the radiation used in standard radiographs of the lumbosacral spine is two orders of magnitude greater than that for a chest radiograph. Radiological investigation of the lumbar spine may be indicated where there is suspicion of serious pathology (see Table 8.3 and Figure 8.1). In this case computed tomography, magnetic resonance imaging or radionuclide scans are more appropriate than plain films but should be obtained after specialist consultation. Nerve root (radicular) pain, often referred to by the obsolete term sciatica in the case of the lower limb, is accompanied by signs of nerve root dysfunction (radiculopathy), myotomal weakness and associated reflex changes and/or dermatomal hyperaesthesia or hypo-aesthesia (see Figure 8.1). Signs of nerve root irritation include reduced straight leg raising which often provokes leg pain and motor, sensory or reflex changes, that are limited to one nerve root. Pathology in one nerve root may produce secondary hyperalgesia in adjacent segments as a result of central sensitisation.
Figure 8.1 Testing for lumbar nerve root compromise. Note: Quadriceps femoris has innervation by L3 and L4. Tibialis anterior and tibialis posterior may have some L4 as well as L5 innervation. L4 motor weakness may produce some weakness of dorsiflexion of the foot as well as weakness of knee extension. It should be borne in mind that there is a variation in the lumbosacral plexus so that there may be variation in the pattern of neurological deficit associated with an individual nerve root lesion. Source: AHCPR 1994a.
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The process of assessment can be summarised in the following algorithms from the AHCPR guidelines on acute lower back pain (AHCPR 1994a).
Adults with < 3 months of activity intolerance due to lower back pain and/or back related leg symptoms. Perform focused medical history and physical examination. Search for RED FLAGS (see Table 8.8). Examination includes neurological screening and straight leg raising test (SLR). Any RED FLAGS?
Yes
No
RED FLAGS for cancer infection.
RED FLAGS for spine fracture.
RED FLAGS for cauda equina syndrome or rapidly progressing neurological deficit. Immediate consultation for emergency studies and definitive care.
CBC, ESR, UA, EPG, IEPG If still suspicious, consider consultation or seek further evidence with bone scan, X-ray or other lab. Negative Xray alone does not rule out disease. If positive, define anatomy with MRI.
Plain X-ray of lumbosacral spine. If after 10 days, fracture still suspected or multiple sites of pain, consider bone scan and consultation before defining anatomy with CT.
In the absence of RED FLAGS, diagnostic testing is not clinically helpful in first 4 weeks of symptoms.
Figure 8.2 Initial evaluation of acute lower back problem. CBC=complete blood count; ESR=erythrocyte sedimentation rate; UA=urine analysis; CT=computed tomography; MRI=magnetic resonance imaging Source: AHCPR 1994b.
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Evidence of serious disease? No Yes Arrange appropriate treatment or consultation. Exit Yes
Evidence of non-spinal medical problems causing referred back complaints?
No
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Go to Figure 8.3.
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Initial visit Adults with lower back pain and no underlying serious condition (see Figure 8.2). Provide assurance; education about back problems. Recommend/prescribe comfort options based on risk/benefits.
Does patient require help relieving symptoms?
Yes
No Recommend activity alterations to avoid back irritation. Review activity limitations (if any) due to back problem; encourage to continue or return to normal activities (including work, with or without restrictions) as soon as possible. Encourage low stress aerobic exercise. Symptoms improving?
Yes
Return to normal activities.
Follow-up visits
Figure 8.3 Treatment of acute lower back pain problem on initial and follow-up visits. * AHCPR clinical practice guidelines: Acute Low Back Pain in Adults. Quick reference guide no 14, December 1994 (AHCPR 1994a). Note: There is level II evidence that a graded activity program with a behavioural approach is more effective than is traditional care for subacute back pain (see page 131) (Lindstrom et al 1992a, 1992b). Source: AHCPR 1994a.
Key point
The key to managing acute lower back pain is to clearly distinguish serious pathology from benign musculoskeletal causes.
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No Yes Review history and physical findings.
Change in symptoms?
No Provide assurance that recovery is expected. Recommend activities to avoid debilitation and No reduce risk of recurrence. Support return to work or required daily activities. Can begin muscle conditioning exercises after a few weeks.
Any RED FLAGS? Yes Symptom recurrence?
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No Evaluate further as in AHCPR* algorithms 3 to 5
Has reasonable activity tolerance returned within 4 weeks?
Yes No
Yes Return to Figure 8.2.
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Return to normal activities.
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Acute neck pain

The most common presentation of acute neck pain is, as with lower back pain, nonspecific mechanical pain. Patients with neck pain also commonly complain of headache, visual disturbances, dizziness, weakness and paraesthesiae. This presentation may occur in any age group; the cause is usually obscure and the condition self limiting. Simple analgesia and physical therapy are usually satisfactory treatment.
Treatment of acute spinal pain

Appropriate education and advice is important in managing acute lower back and neck pain in the absence of red flags (Indahl et al 1995). Stressing the non-serious nature of the condition and advising patients not to be afraid of their back has been found to promote a better overall outcome. Having excluded serious spinal pathology, the treatment of which requires urgent referral to specialist services, non-specific backache is best managed using a simple multimodal approach aimed at pain relief, active rehabilitation and return to activity. Non-pharmacological treatment Rehabilitation Clinicians should ensure that patients with simple acute back pain are aware of strategies to assist in their rehabilitation, including the need to: avoid prolonged bed rest; avoid hospitalisation; avoid the use of prolonged spinal traction; resume activity as soon as possible; and limit lifting. Patients should be informed that discomfort during activity is not necessarily a sign of additional damage to the spine. There is evidence that a return to normal activities as soon as possible leads to more rapid recovery than do either bed rest or some back-mobilising exercises (level II; Malmivaara et al 1995, Hadler et al 1987). Studies of chronic lower back pain have found that recommended exercise quotas that are gradually increased result in better outcomes than telling patients to stop if pain occurs (Fordyce et al 1986, Lindstrom et al 1992a). A program of active physical therapy combined with cognitive-behavioural approaches has been shown to be effective in a number of controlled studies of subacute back pain (level II; Lindstrom et al 1992a, 1992b). With respect to neck pain, initial immobilisation of the neck is less effective than allowing a return to normal cervical movements, provided serious pathology is excluded (Mealy et al 1986). Structured exercise programs and acute back pain In acute back pain (less than six weeks duration), there is no evidence that a structured exercise program provides any benefit in terms of reduced pain, decreased time off work or other relevant measures (level I; Koes et al 1991a, 1991b, Faas 1996, Scheer et al 1995). Advising patients to return to normal activity is more effective than a structured exercise program and does improve outcome (level II; Malmivaara et al 1995). There is some evidence that specific exercises for the lower spine are ineffective in acute lower back pain (ACC & National Health Committee 1997, Waddell et al 1996), apart from McKenzies protocol of exercises and advice, which has been
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shown to decrease sick leave, recurrence of pain and pain intensity more than back school (Stankovic & Johnell 1991, 1995). In subacute spinal pain (duration longer than six weeks but less than three months), a program of individualised graded exercises has been shown to be effective. Measures to discourage fear of activity and to decrease illness behaviour are also effective (level II; Lindstrom et al 1992a, 1992b). Spinal manual therapy and acute spinal pain Spinal manual therapy describes a range of manual treatments applied to the spine. It includes gentle oscillatory pressures or mobilisations applied to the vertebrae, the high velocity thrust known as a manipulation, and spinal movements passively applied by the health professional, such as rotation of the spine. Spinal manual therapy is widely used in the treatment of spinal pain, by a range of health professionals. It has been difficult to obtain definitive evidence of the benefits and risks (AHCPR 1994a, Gonzalez & Materson 1997, Frank 1998, Ernst & Assenfeldt 1998). Research in this area is inherently difficult. While there are systematic reviews and meta-analyses of randomised clinical studies of spinal manual therapy, there are problems in taking their results at face value. Many studies are of poor design and do not compare the technique with a standard treatment, and it is also difficult to define homogenous subgroups of lower back pain patients. Manipulation is not appropriate for patients with abnormalities in the straight leg raising (SLR) test with acute neurological deficit. Any form of spinal manual therapy is inappropriate in patients with the red flag conditions described in Table 8.3. Spinal manual therapy of the neck and lower back under general anesthesia has no proven efficacy and carries at least the same significant risks of cerebral vascular, spinal cord and nerve root injury as manipulation without anaesthesia (Caplan 1986, Schmidley & Koch 1984). This procedure is not recommended. In acute neck pain (less than six weeks duration), the little evidence available suggests some benefit for the use of spinal manual therapy in mechanical neck pain, although subgroups of patients need to be better identified (level I; Gross et al 1998, Shekelle & Coulter 1997, Aker et al 1996). Although rare, serious complications have been associated with neck manipulation (level III; Hurwitz et al 1996, Rivett & Reid 1998, Rivett & Milburn 1997, Rivett & Milburn 1996), and such procedures should therefore be performed only by appropriately trained personnel. It is generally recommended that tests of cerebrovascular sufficiency (vertebral artery tests) are performed before each manipulation of the neck to enhance safety (APA protocol 1988, Refshauge 1994, Weingart & Bischoff 1992). In acute lower back pain (less than six weeks duration), Koes et al (1991a, 1991b, 1992a, 1992b) initially reported that spinal manual therapy was more effective than standard physiotherapy, which in turn was more effective than GP management alone. A recent comparison of physiotherapy exercises, spinal manipulation therapy and provision of an educational booklet for treatment of patients with low back pain showed no significant differences among patients receiving these treatments. Patients receiving physiotherapy or spinal manipulation therapy had only brief, non-sustained marginally better outcomes than those receiving the minimal intervention of an educational booklet (level II; Cherkin et al 1998). However, a recent systematic review suggests that further work should be completed before definitive conclusions can be drawn (level I; Koes et al 1996).
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Koes et al (1996) concluded: the efficacy of spinal manual therapy for patients with acute or chronic low back pain has not been demonstrated with sound randomised controlled trials. There certainly are indications that spinal manual therapy might be effective in some subgroups of patients with low back pain. These impressions justify additional research efforts on the topic. Methodological quality remains a critical aspect that should be dealt with in future studies. The US Association of Academic Physiatrists (health professionals using physical therapy) recently published a text (Gonzales & Materson 1997) which is a critique and rebuttal of the AHCPR guidelines on acute lower back pain (AHCPR 1994a). The text provides a useful compendium of information but a critical evaluation recently published in New England Journal of Medicine (Frank 1998) concluded that: The state of the evidence is not the key issue for the practising experts in spinal medicine who wrote this book. The issue for them is rather what the appropriate conclusion should be when, as so often was the case for the literature the AHCPR panel reviewed, there is simply no good evidence one way or the other. Pharmacological therapy Drug therapy consists of adequate simple analgesia, such as paracetamol 1 g qid regularly. In situations where paracetamol provides insufficient pain relief, use of an NSAID may be considered (level I; Koes et al 1997), taking into consideration contraindications and side effects. Opioids (oral) may be required in the acute stage, with regular rather than pain-contingent dosing with a short-acting agent such as oxycodone or codeine. Some prior studies have raised concerns about the use of opioids in this situation (level III; Brown et al 1986, Muncie et al 1986, Weisel et al 1980). However, there is no strong evidence currently available to allow either proscription or endorsement of the use of opioids for acute lower back pain. As in other situations, opioids are appropriate when the clinical diagnosis points to a physical cause for the pain (level IV; Molloy et al 1997, Graziotti & Goucke 1997). An apparent requirement for prolonged use of opioids in acute spinal pain should prompt re-assessment, including consideration of referral to a multidisciplinary pain unit. Oral corticosteroids may be considered for acute episodes of neuropathic pain associated with nerve root irritation; such use should be restricted to the short term. Epidural steroid injections The efficacy of epidural steroid injections in the treatment of acute lower back pain and leg pain has been evaluated in recent meta-analyses. One of these metaanalyses indicated that this treatment had an overall benefit compared with placebo treatment; patients were two-thirds more likely to achieve pain control with epidural steroids (level I; Merry et al 1996). Another meta-analysis was unable to determine if this modality had any benefit and suggested that further research is required, paying close attention to the methodology of the trials (level I; Koes et al 1995). In 1994, an NHMRC working party on epidural use of steroids in the management of back pain stated that NHMRC can neither endorse nor proscribe the epidural use of steroids in the management of back pain and leg pain of spinal origins. Further, it advised that if epidural steroid was employed that it be used only for radicular pain (NHMRC 1994a).
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Zygapophyseal joint blocks The zygapophyseal joints (ZJ) or facet joints are possible sources of pain in patients presenting with lower back pain (Schwarzer et al 1995), neck pain (Bogduk & Marsland 1988) and possibly thoracic back pain. It is not possible to make a diagnosis of pain due to ZJs with clinical examination or by imaging (Bogduk 1997). Controlled diagnostic nerve blocks are the only means available to identify this source of pain (Bogduk 1997). The application of ZJ blocks has been mainly documented for the diagnosis and treatment of chronic back pain (Bogduk 1997); however in some situations of acute back pain, local anaesthetic ZJ blocks may be considered as an option to assist in mobilising patients who fail to respond to measures recommended above. Statements of evidence acute musculoskeletal pain Treatment for acute lower back pain based on bed rest and immobilisation is ineffective. A return to a normal range of activities as soon as possible leads to more rapid recovery from acute lower back pain than do either bed rest or back-mobilising exercises. Spinal manual therapy is used for the treatment of acute lower back pain in the first six weeks following onset of pain. The scientific evidence for its efficacy remains to be established. The little evidence available about the use of spinal manual therapy for acute neck pain suggests some benefit in mechanical neck pain, although subgroups of patients need to be better identified. Although rare, serious complications have been associated with neck manipulation and such procedures should therefore be performed only by appropriately trained personnel. Level of evidence
I Koes & van den Hoogen 1994 II Malmivaara et al 1995, Hadler 1987
Key points
The treatment of serious spinal pathology requires urgent referral to specialist services. Non-specific backache is best managed using a simple multimodal approach aimed at pain relief, active rehabilitation and return to normal activity.
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I Koes et al 1996 I Gross et al 1998, Shekelle & Coulter 1997, Aker et al 1996. III Hurwitz et al 1996, Rivett & Reid 1998, Rivett & Milburn 1997, Rivett & Milburn 1996
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Factors associated with the progression from acute to chronic spinal pain
Despite the generally benign nature of back complaints, a percentage of cases do proceed to a chronic course. Psychosocial predictors (yellow flags) of the development of chronic pain have been identified and are important to document before choosing a method of treatment (ACC & National Health Committee 1997). It is anticipated that this area will be covered in more detail in a subsequent NHMRC report on chronic non-cancer pain. Studies in motor vehicle accident-related neck pain (whiplash) fail to clearly identify psychosocial factors but do show that somatic factors are not definitely linked (level III; Barnsley et al 1994, Radanov et al 1991). There appear to be three strong predictors of the likelihood that a patient will progress from an acute episode of lower back pain to a chronic pain syndrome: high self report of functional impairment; inappropriate beliefs about lower back pain, including high fear of re-injury; and low job satisfaction (level III; Weiser & Cedraschi 1992). In both acute and subacute lower back pain, multiple regression analysis showed that the level of persisting disability depended principally on measures in the psychosocial domain. For acute presentations, outcome is also dependent on the presence or absence of a prior history of back problems (Burton et al 1995). Functional impairment and fear behaviour are measured from a questionnaire. The questionnaires that have a demonstrated high reliability and validity include the Oswestry and Roland-Morris questionnaires identifying perceived functional impairment, and the Fear Avoidance Behaviour Questionnaire identifying beliefs about lower back pain (Waddell et al 1993). High scores in any of these are strong predictors of developing chronic pain syndromes. Reduced back extensor muscle endurance, measured isometrically using the Biering-Sorensen test, is also a strong predictor of the development of chronic or recurrent lower back pain. There have been three randomised controlled trials of behavioural therapy for acute lower back pain. Fordyce et al (level II; 1986) reported modest improvement at 12 months of time-contingent over pain-contingent prescription of analgesics and of exercise. Linton et al (level II; 1989) found significant improvements in a range of measures, including pain, after intervention with physical and behavioural therapy, with the improvements largely maintained at six months. Phillips et al (level II; 1991) found no difference at six months between groups with gradual programmed reactivation or pain-contingent reactivation, with or without explanatory or control counselling.
Peripheral musculoskeletal presentations
Certain musculoskeletal conditions present as emergencies (eg septic arthritis, osteomyelitis, and the peripheral features of infective endocarditis). Three main mechanisms which may be responsible for musculoskeletal pain are inflammation, altered biomechanics and somatic referred phenomena. The hallmark of joint disease is swelling. Aspiration of joint effusions allows instant diagnostic distinction between inflammation (including infection) and other mechanisms, but should only be performed with full sterile technique including gown and gloves by a health professional familiar with the technique of joint aspiration.
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The history should address the character of the pain, with a particular search for symptoms that suggest conditions requiring urgent evaluation and treatment. A diagnosis is usually possible in the periphery and is highly desirable, because in the periphery, unlike in the spine, management is frequently contingent upon diagnosis. Symptoms suggesting the need for urgent evaluation and management Symptoms suggesting the need for urgent evaluation and management include:2 history of significant trauma; hot, swollen joints; features of systemic illness; weakness that is not pain related; pain of neuropathic origin; and claudication paingradually increasing lower limb pain on walking, relieved by resting. History and examination will determine which investigations to pursue. Once inflammation (especially that due to local or systemic infection ) has been excluded, management of acute musculoskeletal pain should address symptom control and functional problems with painful parts. Local physical therapy of painful musculoskeletal structures with either heat (for stiff joints) or cold (for swollen parts) is common and may have a useful placebo effect. Other forms of physical therapy play a substantial role in the management of peripheral musculoskeletal conditions. Anti-inflammatory therapy is indicated where inflammation has been demonstrated to be the relevant mechanism but not where the pain is due to biomechanical or neuropathic mechanisms. No advantage of NSAIDs over paracetamol has been shown in symptomatic osteoarthritis (level II; Bradley et al 1991, Williams et al 1993). Nonetheless, there are individual patients with symptomatic osteoarthritis whose symptoms respond better to NSAIDs than to paracetamol alone. This can be ascertained in a simple N-of-1 trial design (level III; March et al 1994).
Acute exacerbations of chronic musculoskeletal pain

Acute exacerbations of chronic conditions such as arthritis (both inflammatory and degenerative), spinal pain and regional musculoskeletal pain syndromes (including diagnoses such as chronic fatigue syndrome and fibromyalgia) are common. In many instances, such patients will be on maintenance analgesic and/or antiinflammatory therapy. As with all chronic conditions, it is important to consider existing pain and treatments when utilising acute pain management techniques. Management of the chronic phase of these conditions will be discussed in detail in a subsequent NHMRC guideline on the management of chronic pain.
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Adapted from American College of Rheumatology guidelines for the initial evaluation of the adult patient with acute musculoskeletal symptoms, 1996. Diagnosis of the underlying condition is of extreme importance in peripheral musculoskeletal presentations. The reader is referred to this guideline for detailed presentation of this important area.
Assessment of these situations includes looking for evidence of any changes in: the underlying somatic condition (eg acutely swollen joint or development of neurological signs); usage of the painful part; and the patients mood. There should then be identification of other psychosocial factors which may influence the distress with which the patient presents. In the absence of clinical features suggesting potentially serious spinal conditions (see Table 8.3), the principles of management include reassurance about the absence of change in the underlying condition and attention to factors which may be reinforcing disability. These measures can be supported with temporary increase in analgesic dosage, temporary institution of analgesics or consideration of adjuvant analgesic medication, as outlined elsewhere in this report.
8.8
Sporting injuries
Prompt assessment and treatment of acute musculoskeletal conditions is important in the prevention of continuing trauma. Delaying treatment, or treating only with rest and immobilisation, can precipitate the transition of acute injury to chronic injury and subsequent chronic pain. The acute treatment of sporting injuries generally follows the principles of: Rest/Ice/Compression/Elevation (RICE) which needs to be applied for sufficient time (approximately 48 hours); simple analgesics; and early rehabilitation and mobilisation. There are few injuries that require the level of immobilisation provided by a plaster cast and when this is required, limited range of motion braces are preferable. Rest has a spectrum of meanings including simply avoiding aggravating activities, performing graded exercise regimens, not bearing weight and, occasionally, complete rest. Chronic injuries may present as bone pain (non-union of fractures), muscle pain (myositis ossificans), ligamentous pain (dystrophic calcification) and soft tissue pain which may result from poorly organised fibrotic tissue. Pharmacological treatment The benefits of NSAIDs relate mainly to their analgesic effects and the way in which they decrease resistance to movement caused by damaged muscles, and thereby facilitate rehabilitation. While they do have a role in the treatment of myositis ossificans following intramuscular haematoma, and in the management of chronic sporting injuries, NSAIDs have not been shown to be effective in the treatment of ligament sprains (level IV; Almekinders 1995). An awareness of the list of banned and restricted substances is important when treating athletes involved in high-level competition. Opioids other than codeine are banned while simple analgesics (aspirin and paracetamol) and all NSAIDs are permissible. Corticosteroid use is restricted, although injections are possible with notification to the drug-testing or sporting body. Corticosteroids are effective anti-inflammatory agents but are not suitable for treatment of acute sporting injuries for up to six weeks after the incident due to the tendency for these agents to be associated with re-injury, tendon rupture and the 137
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masking of more significant injury. Experimental studies have shown that corticosteroids may adversely affect normal tissue healing and repair (level III; Wrenn et al 1964, Kapetanos 1982, Wesley et al 1991). While athletes are highly motivated to return to training early, emphasis needs to be placed on maximising rehabilitation. Early mobilisation is required once serious injury is excluded.
Table 8.4 Pointers to serious sporting injury Joint swelling (rapid joint swelling following injury usually indicates bone or ligament trauma) Neurological symptoms Bony tenderness Loss of joint motion Inability to bear weight
A number of complications can arise from soft tissue injuries due to sporting trauma and these include complex regional pain syndrome (CRPS) type I (see page 154), muscle wasting, joint stiffness and adhesions. The incidence and severity of these conditions may be reduced by early rehabilitation, mobilisation and effective pain relief. Statement of evidenceacute sporting injuries Corticosteroids are effective anti-inflammatory agents, but are not suitable treatment for acute sporting injuries for up to six weeks after the incident. Experimental studies have shown that corticosteroids may adversely affect normal tissue healing and repair.
Key point
While they do have a role in treatment of myositis ossificans following intramuscular haematoma, and in management of chronic sporting injuries, NSAIDs have not been shown to be effective in the treatment of ligament sprains.
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9.1
Acute pain in patients with cancer or HIV/AIDS

Acute pain in patients with cancer
Classification of pain in patients with cancer

In patients with cancer, pain is typically a progressive problem that frequently becomes chronic. It is clearly not within the scope of this report to address all cancerrelated pain in detail, but it is important to recognise the need for appropriate assessment and treatment of episodes of acute pain in patients with cancer, and to overcome the barriers to adequate pain relief. Many of the classic chronic pain syndromes occurring in cancer patients have acute manifestations. Acute pain in patients with cancer can be monophasic or recurrent. The latter may be associated with pain-free intervals or superimposed on chronic pain. Consequently, two main types of acute pain in patients with cancer can be identified: acute pain in the classic sense (short lived, self limiting) and acute exacerbations of chronic cancer pain (pain on activity or breakthrough pain). The onset of either type of acute pain in patients with cancer can be paroxysmal or gradual, and it can be predictable or unpredictable. Acute pain in cancer patients, like chronic pain, can be due to: direct infiltration of anatomical structures by tumour (see Table 9.1); a side effect of diagnosis or treatment (see Table 9.2); debility, in patients with far advanced cancer (eg constipation, pressure sores); and a cause unrelated to the cancer or its treatment (eg acute musculoskeletal pain). Common syndromes of acute pain in patients with cancer are becoming better recognised and are shown in Tables 9.1 and 9.2. This section will discuss pain management in the major categories of cancer pain, where acute presentations may occur. As with most causes of acute pain, the specific aetiology of acute pain in patients with cancer is usually obvious, such as: cancer per se diagnostic procedures; surgery; other therapeutic interventions; delivery of pain relief; anticancer therapy; infection (eg acute herpetic neuralgia); and pain on activity (eg on moving, dressing etc).
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The most common barriers to adequate pain relief in patients with cancer include (Grossman 1993, Ward et al 1993): Failure of the health professional to appreciate the severity of pain and to assess/re-assess it. This can be improved by the use of pain measurement tools. Failure to administer adequate doses of opioid analgesics due to concerns about tolerance addiction and side effects. Failure to identify the aetiology of the pain and consider the most appropriate therapeutic options.
Assessing acute pain in patients with cancer

When assessing acute pain in patients with cancer, it is important to establish what has triggered the acute painful episode, as acute pain syndromes often signal disease progression (Ready & Edwards 1992). The aetiology is frequently obvious (eg incisional pain after an operation) but when it is not, a more thorough assessment is required. Full assessment involves history taking, physical examination and investigations, if necessary, to determine the exact nature of the acute pain episode. Because cancer patients with recurrent disease are often chronically ill, evaluation of the psychosocial status may be an appropriate part of the acute pain assessment. In view of its many causes, acute pain in patients with cancer can be generalised, focal or referred, which includes radicular pain arising from damage to a nerve root. Treatable conditions (eg muscle spasm in patients with bone metastases ) need to be kept prominently in mind. Sample case A 48-year-old male with pancreatic cancer is admitted for laparotomy. He has been taking slow-release morphine 100 mg bd for abdominal pain for the past two months. PCA is ordered for postoperative pain control on the basis of a pre-operative daily dose of morphine of 200 mg orally (equivalent to 100 mg IV). Thus daily maintenance requirements can be provided by a background IV infusion of morphine 96 mg/day (4mg/hour).* Increased pain due to surgery will require PCA bolus doses of approximately 4mg, to be adjusted on the basis of analgesic response and side effects.
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This patient has previously been administered morphine and is thus an exception to the general rule in adults that background infusions are not used.
Types of acute pain syndromes in cancer patients

Pain from diagnostic tests Diagnostic studies in cancer patients include venipuncture, insertion of intravenous cannulae, invasive radiological investigations (eg myelogram), lumbar punctures, biopsies and endoscopy. These procedures can all be associated with predictable, selflimited episodes of acute pain. Interventions for managing procedural pain need to take into account the type of procedure, the anticipated level of pain, the positioning required and patient variables. Local anaesthetics may be of benefit in preventing procedural pain; when penetration of the skin is to occur, topical cream (EMLA) applied 60 to 90 minutes before the procedure may be useful (level III; Kapelushnik et al 1990).
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Postoperative pain In many respects, postoperative pain in cancer patients needs to be managed in the same way as in non-cancer patients. PCA is effective for pain in cancer patients and is well accepted although its use requires special pumps and education of staff on oncology wards (level III; Swanson et al 1989, Portenoy et al 1986). Cancer patients are often elderly and hence there is a greater incidence of cognitive impairment which makes PCA difficult (level IV; Ferrell 1991). In addition, cancer patients are rarely opioid naive and require appropriate doses of opioids to achieve satisfactory effects (see sample case). Pain relief for major surgery in cancer, such as oesophagectomy via the trans-thoracic route, is best managed using an intra- and postoperative thoracic epidural. This not only provides superior analgesia but probably improves outcome (level II; Katz et al 1996). Communication between various services including surgery, acute pain service, oncology and palliative care is required to avoid confusion and errors. Prolonged postoperative pain may occur because cancer patients may be in poor general condition and will take longer to recover. However, continuing pain should always be fully assessed and not dismissed, as it may signal the development of a postoperative complication or a new cancer pain syndrome. Psychological issues may also play a large role in the aetiology of pain, particularly if a patient requires an operation because of progression of their cancer. Other therapeutic interventions Chemical pleurodesis and tumour embolisation are examples of other procedures that can be associated with significant pain. The possibility of pain, even with relatively minor procedures, should be anticipated and preparations made for effective analgesia. Pain from cancer treatments Anti-neoplastic therapies are a key component of the comprehensive, multimodal management of cancer pain. Despite this, a number of acute pain syndromes have been identified as being caused by the administration of anti-cancer therapy. Some are relatively common (eg mucositis due to certain chemotherapy regimens) while others are extremely rare (eg spinal cord and nerve plexus injuries following radiotherapy). Chemotherapy may be associated with mucositis, which is less common with standard therapy but almost always seen with intensive regimens. Treatment should involve a combination of effective analgesia (including PCA) and antimicrobials (level II; Hill et al 1991). The intravenous infusion of cytotoxics may be associated with pain due to venous spasm, phlebitis or the extravasation of vesicants (level IV; Schneider & Distelhorst 1989). Other pain syndromes are related to the particular cytotoxic being used and these include: headache with methotrexate due to an acute meningeal syndrome; diffuse abdominal pain with hepatic artery infusion; chest pain with 5fluorouracil; a number of agents can cause a transient painful peripheral neuropathy. Hormonal therapy and immunotherapy have been shown to result in a number of painful conditions, such as the transient flare of bone pain seen with tamoxifen, and various myalgias and interferon-associated arthralgias, which are preventable with paracetamol (level III; Jones & Itri 1986).
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Radiotherapy has a major role in controlling pain and other symptoms from tumours at specific sites (level I, McQuay 1997). Nevertheless, it is capable of producing acute pain in some situations. Relatively common examples include: pain on activity (acute exacerbation of chronic pain) associated with positioning for therapy; and mucosal inflammation post-radiotherapy, especially when it effects the mouth, pharynx, the anorectal region or the urethra. Rarer examples are: acute presentations of plexopathy (Salner et al 1981); and subacute radiation myelopathy (Earnist & Trier 1989). In these two conditions, the pain is of a neuropathic type, sometimes presents acutely and may require treatment with anticonvulsant and/or antidepressant drugs. Postradiation plexopathy usually results in severe persistent neuropathic pain, which may require intraspinal opioid and/or other drug treatment. Subacute radiation myelopathy develops in weeks to months and lasts for three to six months. It may also give rise to neuropathic pain. Intravenous or subcutaneous infusion of lignocaine may be effective for severe neuropathic pain (level III; Brose & Cousins 1991). Pain caused by the delivery of analgesia in cancer patients When treating pain in cancer patients, it is important to consider the method of administration and attempt to give pain relief by the least painful route (orally, rectally or transdermally). Repeated intramuscular injections should therefore be avoided; repeated subcutaneous injections via an indwelling butterfly needle are usually preferable. A painful spinal opioid hyperalgesia syndrome has been reported with the use of high doses of spinal opioids but tends to remit after discontinuation of opioids (level IV; de Conno et al 1991). Low-dose subcutaneous or intravenous infusion of ketamine (1030 mg/h) may be helpful in neuropathic pain relief and in modification of opioid tolerance (in this and other situations). Pain caused by infection Acute pain may also be associated with infection. The typical example cited is acute episodes of herpes zoster infection, given that this condition is common in patients with immunosuppression. Antidepressants and anticonvulsants have been shown to be effective (see also Section 8.2 on page 116 and Section 10.1 on page 151). In situations of severe pain unresponsive to other measures, sympathetic block may be used to attempt to reduce the intensity and duration of acute episodes of herpes zoster infection (level IV; Raj 1993). Acute pain due to direct tumour involvement Acute pain may occur with tumour involvement of bone, viscera or nerve (Table 9.1). Frequently, these episodes occur as exacerbations of chronic cancer pain syndromes but they can arise de novo. Phenomena exacerbating chronic cancer pain include movement in patients with bony metastases, liver capsule pain when lying on the right (with hepatic distension or tumour infiltration), pelvic pain on defaecation (from constipation or tenesmus), and oesophageal pain on swallowing. Acute episodes may also be paroxysms of neuropathic pain; acute radiculopathy due to tumour invasion of the brachial plexus is an example of this.
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Acute pain in patients with cancer or HIV/AIDS Table 9.1 Acute pain associated with direct tumor involvement
1 Tumor infiltration of bone a Pathologic fracture b Muscle spasm c Abrupt shift of damaged structures with movement 2 Tumor infiltration of viscera a Obstruction of hollow viscus (eg colon, biliary tract) b Stretch, compression or torsion of organ capsules of related fascia (eg hepatic capsule bleed, acute hydronephrosis) 3 Tumor infiltration of nerve, plexus and meninges a Headache associated with infiltration of brain 1 Multiple cerebral metastases 2 Single posterior fossa lesion 3 Leptomeningeal disease 4 Cavernous sinus thrombosis 5 Middle cranial fossa lesion 7 Jugular foramen lesion c 6 Glossopharyngeal neuralgia
b Pain associated with infiltration of nerve roots Pain associated with plexopathies, brachial or lumbosacral d Pain associated with epidural spinal cord compression Adapted from Ready & Edwards 1992.
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Acute pain management: scientific evidence Table 9.2 Acute pain associated with cancer therapy
1 Postoperative Pain 2 Post-radiotherapy pain a Acute exacerbation of chronic pain 1 Associated with positioning for therapy b Post-radiotherapy pain 1 Mucositis 2 Low-grade abdominal obstruction 3 Skin reactions 4 Bowel stenosis and acute pain on defaecation 5 LHermittes sign (transient demyelination of cervical/thoracic cord; rare) 6 Infarction and ischaemia of the bowel (rare) 3 Post-chemotherapy pain a Acute meningeal syndrome 1 Associated with intrathecal methotrexate 2 Associated with L asparaginase therapy b Mucositis 1 Due to chemotherapy alone 2 Due to chemotherapy and other factors (e.g., infection, neutropenic stomatitis) c Painful peripheral neuropathies (associated with Vinca alkaloids and cis-platinum) d Muscle cramps e Extravasation f Perineal pain (with intravenous administration of high doses of dexamthasone) g Aseptic necrosis of femoral or humoral head 4 Tumor embolisation 5 Chemical pleurodesis 6 Pain associated with diagnostic procedures a Bone marrow aspiration b Repeated venipuncture c Acute exacerbation of chronic pain associated with positioning (eg for myelogram or magnetic resonance imagery) d Lymphangiography 7 Pain associated with analgesic therapy a Chemical neurolysis b Neuroablative procedures c Intraspinal opioid therapy Adapted from Ready & Edwards 1992.
Treatment of acute pain in cancer patients
Management of acute episodes of pain in cancer patients requires an organised approach similar to that used in the management of chronic cancer pain. It is based on identifying the cause, removing or modifying it and utilising multimodal analgesic techniques including pharmacotherapy, anti-neoplastic therapies, physical and psychosocial modalities, and the interruption of pain pathways.
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In managing acute pain in patients with cancer the following principles need to be kept in mind: Not all acute pain in patients with cancer is due to the cancer getting worse. Other possibilities to be kept in mind include osteoporotic fracture, pressure sores, constipation, side effects of treatment (eg mucositis), procedural pain, deep venous thrombosis and pulmonary emboli, infections (eg herpes zoster). Even when the pain is due to the cancer progressing, it is important to consider the anatomic aetiology, as this may be amenable to specific therapy (eg spinal cord compression, bony fractures, obstruction of a viscus, brain metastases etc). Review of the patient by an oncological specialist is recommended. If the pain is due to progression of cancer, the best therapy is often one which treats the underlying malignant process. Anti-cancer therapy options include radiotherapy (including radiopharmaceuticals), chemotherapy, hormonal therapy, surgery, interventional radiology and pharmacological agents. The selection of an appropriate treatment for a particular patient depends upon the underlying type of malignancy, the site and extent of disease and the condition of the patient. An oncological opinion is recommended. While waiting for definitive therapy to work, analgesic medications will be required, including opioid analgesics, simple analgesics and adjuvant analgesic drugs. Physical therapies and psychosocial therapy will be important in some cases. As analgesic needs will change when definitive measures begin to work, frequent re-assessment and gradual weaning off medication may be appropriate. Invasive procedures (spinal opioids, nerve blocks, neurosurgical techniques) will be required in cases that are difficult to manage. Involvement of a comprehensive pain service is recommended. Treating procedural pain Specific issues in the management of pain associated with invasive diagnostic techniques, surgery and other therapeutic interventions have already been discussed. General points influencing the management which need to be considered include: patients already taking regular oral analgesics need to be transferred to a parenteral route if fasting before the procedure; analgesia provided after the procedure in opioid-tolerant patients needs to take into account the previous daily requirements; physiological, metabolic and psychological effects of the procedure need to be considered (eg patient age, renal impairment, nausea and vomiting, bone marrow failure, anxiety and depression); and optimal communication between oncological, surgical, anaesthetic, and palliative care teams is essential.
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Treating incident or breakthrough pain Systemic analgesics form the mainstay of the management of incident pain especially on the background of chronic pain and regular analgesic use. A number of points need to be considered when managing these episodes: a supply of immediate-release opioid (ie oral morphine) solution must be available; a recent consensus statement from the European Association for Palliative Care recommends that the breakthrough dose of morphine should be the same as the four-hourly immediate-release morphine dose for chronic pain, given as frequently as necessary (level IV; Hanks et al 1996); if repeated doses of breakthrough morphine are required, an adjustment to the regular baseline opioid requirement should be made; alternative routes, such as subcutaneous injection, are useful in establishing control over pain when dosages need to be rapidly titrated to response; and there may even be a place for PCA in extreme situations. Sample case A 45-year-old man had extensive metastatic melanoma in the pre-auricular region that was progressively eroding the base of skull. He had increasing pain in the head and neck region that previously responded to escalating doses of morphine (up to 600 mg/day). Lately, the patient had begun to experience intermittent exacerbations of very severe pain. He presented to the emergency department with three days of excruciating pain that he rated 25 out of 10. Five bolus injections of subcutaneous morphine 25 mg over an eight hour period had no effect and he became very distressed (suicidal). IV morphine via PCA was commenced immediately at 5 mg/hr baseline infusion with 5 mg PCA boluses (no lock-out period). By 12 hours, the baseline infusion had been increased to 30 mg/hr (with the same bolus) and the pain score had fallen to 5/10. By 36 hours the patient was pain free on 20 mg/hr IV morphine and he was no longer needing to use the PCA function. He was changed back to oral morphine, and was discharged home a few days later, pain free, on 1600 mg/day of sustained release oral morphine. He died of disseminated melanoma three months later, with adequate pain control on 2 gm oral morphine/day. NSAIDs have a place in the treatment of acute episodes of pain given their potential opioid-sparing effects, thus reducing side effects such as excessive sedation. They have been shown to be effective in the treatment of symptomatic bone secondaries (level II; Levick et al 1988). Tricyclic antidepressants are useful in the treatment of particular episodes of acute pain in patients with cancer. These agents modify the neuropathic response to nerve injury and alter pain perception through mood-elevating effects. Neuropathic pain is also sometimes effectively treated by use of anticonvulsant medication (particularly carbamazepine, sodium valproate and more recent GABA-ergic and NMDA active agents such as vigabatrin and gabapentin) (see page 152). Radiotherapy is of particular use for incident pain due to bone metastases, with good response rates being achieved (Neilsen et al 1991). Recent randomised trials have shown a lack of correlation between pain relief and site, tumour type, radio-
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sensitivity or radiotherapy dose and it appears that a single low-dose fraction is as effective as fractionated, higher dose schedules (level II; Price et al 1986, Cole 1989). There is a lack of data on whether single fractionated doses are effective in patients with radicular or neuropathic pain. Radiotherapy is useful for many other types of acute pain in cancer patients, including: headache from brain metastases; neuropathic pain from tumour-induced plexopathies and spinal cord compression; and pain from inoperable lung, pancreatic and rectal cancer. Orthopaedic procedures may be of benefit to some patients with painful bone metasases. Examples include fixation of a pathological fracture and spinal orthopaedic surgery for painful vertebral tumours with spinal cord or nerve root compression. For patients who have painful metastases in a weight-bearing bone where there is a high risk of consequent pathological fracture, prophylactic fixation of the bone may be appropriate prior to radiotherapy. An orthopaedic surgical opinion should be obtained on patients who have a painful bone metastases, particularly if the tumour involves a weight-bearing bone or if there is a solitary spinal lesion. Bone pain from metastatic prostate or breast cancer may also be treated with radiopharmaceuticals such as strontium-89. Hypercalcaemia can be associated with increased pain in patients with bone metastases (although the hypercalcaemia may not be due to the bone metastases per se). There will often be an associated drowsiness, confusion, nausea and constipation. If the serum calcium is elevated, treatment options include saline diuresis and intravenous administration of the bisphosphonate calcium-lowering drugs such as pamidronate. Such measures frequently result in a rapid decrease in pain and confusion. Bisphosphonates have a general role (quite apart from treating hypercalcaemia) in the treatment of bone pain related to breast cancer and myeloma (and possibly prostate cancer) (level II; Purohit et al 1994, level III; Coleman et al 1997). Corticosteroids may be useful for short-term treatment of neuropathic pain. In the acute management of pain associated with spinal cord compression, corticosteroids are usually combined with radiotherapy (level III; Boojerd & van der Sande 1993). New routes of opioid administration A recent comparative review of epidural, intrathecal and intracerebroventricular opioids in the treatment of cancer pain concluded that these forms of treatment are often effective in severe acute and/or chronic pain that is not controlled with conventional treatment. Intracerebroventricular administration is effective for pain in all locations as it is able to activate descending inhibitory pain pathways. It has marginally greater efficacy than epidural and intrathecal administration of opioids. Failure rates are significantly higher with epidural administration, although the epidural route is simple and versatile (level I; Ballantyne et al 1996).
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Statements of evidence acute pain in patients with cancer Oral analgesics are the mainstay of pain relief in patients with cancer. Strong opioids are safe and effective for moderate to severe pain. Radiotherapy plays a major role in the management of acute pain due to cancer. Bisphosphonates have a general role in the treatment of bone pain related to breast cancer and myeloma (and possibly prostate cancer). Epidural, intrathecal and intracerebroventricular opioids are often effective in treating acute pain in patients with cancer that is not controlled with conventional treatment.
Key points
Level of evidence
I AHPCR 1994b I McQuay 1997 II Purohit et al 1994 III Coleman et al 1997 I Ballantyne et al 1996
Not all acute pain in patients with cancer is due to the cancer progressing. Optimal communication between oncological, surgical, anaesthetic, and palliative care teams is essential. Even when the cancer is progressing, it is important to consider the anatomic aetiology, as this may be amenable to disease-specific therapy (radiotherapy, chemotherapy, surgery etc). While waiting for specific anti-cancer therapy to work, adequate analgesia must be provided. Invasive procedures (spinal opioids, nerve blocks etc) are occasionally required. Acute pain in cancer patients often takes place against a background of chronic pain and therefore existing analgesic use. An integral part of management is the recognition and treatment of procedural pain and breakthrough pain. The barriers to management of pain in cancer patients must be recognised and overcome if possible.
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9.2
Acute pain in patients with HIV and AIDS
Acute episodes of pain are common in patients with HIV and AIDS, occurring with a frequency similar to that seen in cancer patients (level III; Singer 1993). The common painful syndromes seen in HIV/AIDS are summarised in Table 9.3. As with pain in cancer patients, pain in HIV/AIDS patients often has more than one cause and location and tends to increase in severity with disease progression. Intervention requires a similar multidisciplinary approach (level IV; Carr et al 1994). While there are similarities in acute pain episodes between cancer patients and HIV/AIDS patients, there are also a number of fundamental differences. Acute pain episodes in patients with HIV/AIDS are often more readily treatable than those in cancer patients. Other differences in certain patients include a heightened sensitivity to drug side effects, chemical dependence, psychiatric comorbidity and polypharmacy (Glare & Cooney 1996).
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A careful history and physical examination commonly identifies treatable pain syndromes seen in HIV/AIDS. Determination of the level of immunosuppression in patients presenting with pain is a critical diagnostic manoeuvre, as the most likely causes vary with different levels of immunosuppression. Immunocompetent HIVpositive patients are unlikely to develop opportunistic infections and malignancies and are more likely to be experiencing a range of benign conditions (eg vascular or tension headache is more probable in this group than is toxoplasmosis).
Table 9.3 Common painful syndromes in HIV/AIDS 26% 25% 20% 17% 63% 12% 10% 5% 16% 5% 5% 5% Abdominal pain Peripheral neuropathy Throat pain HIV-related headaches HIV-unrelated headaches Tension Migraine with aura Unclassifiable Migraine without aura AZT-induced headache Arthralgia Herpes zoster infection Back pain
Headache should alert practitioners and nursing staff to the possibility of conditions such as HIV encephalitis and toxoplasmosis in patients with significant immunocompromise (T4 count < 200). AZT (azidothymidine, now known as zidovudine) therapy is a relatively common cause of headache. Various arthropathies are seen in HIV/AIDS patients including Reiters syndrome (often associated with diarrhoea), septic arthritis, vasculitis and polymyositis. Neuropathic pain is common in HIV and AIDS and relates, in a large number of cases, to the development of peripheral neuropathy or myelopathy. The acute abdomen in a patient with HIV/AIDS suggests a number of conditions not routinely considered in patients of the ages that tend to be afflicted with this illness. Malignancies and lymphoma can present as a bowel obstruction or perforation. The analgesic requirements of these complications are obvious. Unusual infections may also present with abdominal pain, while hepatic and pancreatic disease due to cytotoxic drug effects are also possible. AZT and paracetamol have the potential for interaction and this combination should be employed cautiously. The integration of opioids and other adjuvants is important in treating conditions such as neuropathic pain where antidepressant and anticonvulsant agents have an important role to play, although the data are only level IIIIV at this stage (level IIIIV; Anand et al 1994, Kimball & McCormick 1996, Lebovits et al 1994). Preventing or promptly treating opioid side effects (eg with antiemetics and laxative agents) improves the patients tolerance of stronger opioids when they do become necessary, but polypharmacy is a problem.
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Acute pain in HIV/AIDS patients often has more than one cause and location and tends to increase in severity with disease progression. Intervention requires a multidisciplinary approach. A careful history and physical examination commonly identifies treatable pain syndromes seen in HIV/AIDS. Determination of the level of immunosuppression in patients presenting with pain is a critical diagnostic manoeuvre, as immunocompetent patients are more likely to have benign conditions than infections or malignancies.
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10
Adjuvant agents and the treatment of acute neuropathic pain
10.1 Adjuvant agents in the treatment of acute pain

There is evidence from systematic meta-analysis of randomised controlled trials for the effectiveness of commonly used adjuvant agents in the treatment of various pain syndromes, including neuropathic pain. The following table outlines a number of adjuvant agents according to drug class and the level of evidence from trials that supports their effectiveness in clinical use. The proposed mechanisms of action of some of these drugs are given in Table 10.2.
Table 10.1 Table of adjuvant agents Drug class
Tricyclic antidepressants
Anticonvulsants
New anticonvulsants Corticosteroids
Membrane stabilisers
CNS stimulants Anxiolytics
Alpha2 agonists NMDA blockers
CNS=central nervous system; GABA=gamma-aminobutyric acid; NMDA=N-methyl-D-aspartate (See also McQuay & Moore 1998.)
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Level of evidence I I III/IV II II II II III
Amitryptiline, doxepin, nortryptiline, dothiepin
Carbamazepine, sodium valproate, phenytoin Gabapentin, lamotrigine, vigabatrin Lignocaine, mexilitine, flecainide
Dexamethasone (for spinal cord decompression or raised intracranial pressure)
Dexamphetamine (one study shows analgesic efficacy), cocaine Hydroxyzine (analgesic/anxiolytic) Propofol (? for neuropathic pain), midazolam (GABA-ergic ? analgesic); diazepam (relief of muscle spasm and secondary effects of pain) Clonidine (analgesic, also modifies opioid withdrawal) Ketamine, dextromethorphan (both also modify opioid withdrawal)
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Acute pain management: scientific evidence Table 10.2 Proposed mechanisms of action of certain adjuvant agents Drug class (drug) Tricyclic antidepressants (eg amitryptiline, doxepin, nortryptiline, dothiepin) Anticonvulsants (eg phenytoin, carbamazepine, sodium valproate) New anticonvulsants Lamotrigine Frequency-dependent block of neuronal sodium channels. Also sodium valproate may block neuronal calcium channels (T-type) Blocks sodium channels (as above). Diminishes evoked release of glutamate (and thus decreased NMDA activation) Lang et al 1993 Mechanism of analgesia Spinal and brain 2-adrenoceptors (inhibit nociception) References McQuay et al 1996
Davadi & Hamann 1998, Yarmitsky et al 1998, Zakrzewska et al 1997, Webb & Kamali 1998
Vigabatrin
Gabapentin
Membrane stabilisers
(Lignocaine, mexilitine, flecainide)
GABA=gamma-aminobutyric acid; MRI=magnetic resonance imaging; NMDA=N-methyl-D-aspartate
10.2 Treatment of acute neuropathic pain

The diagnosis of neuropathic pain was discussed in Chapter 3 (see page 39). A realistic goal in the treatment of acute neuropathic pain is to reduce the level of pain to an acceptable level for the patient, as total pain eradication is rarely possible. Opioid drugs have a limited role for this type of pain. Available data indicate that neuropathic pain may be at least partially relieved by opioids, despite the fact that this pain is relatively opioid resistant. Studies of chronic neuropathic pain can be extrapolated to the use of a number of agents in severe acute neuropathic pain, particularly the antidepressants and anticonvulsants described in Section 10.1. Anticonvulsants The effectiveness of these agents in the treatment of a variety of neuropathic pain states, including trigeminal neuralgia and diabetic neuropathy, and as migraine prophylaxis, has recently been evaluated (level I; McQuay 1995a). Numbers needed to treat calculations for efficacy and the occurrence of minor adverse effects showed that these agents are frequently effective, while adverse effects also occur frequently. For 152
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Decreases catabolism of GABA via inhibition of GABA transaminase (thus increased GABA inhibitionimportant in neuropathic pain) ?decreased glutamate (catabolism); ?GABA transport, re-uptake; ?increased GABA release Binding to calcium channel subunit (brain MRIs show GABA content) Block sodium channels (as above) and modify axonal action potential generation. Higher doses also have pre- and post-synaptic inhibitory actions in dorsal horn of spinal cord Goldlust et al 1995, Honmou et al 1995, Gee et al 1996
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example, for cabamazepine, it is necessary to treat 2.6 patients to demonstrate analgesic efficacy, while adverse effects will be observed in association with the treatment of 3.4 patients (for further discussion see McQuay & Moore 1998). The numbers needed to treat particular conditions and agents employed are summarised in Table 10.3.
Table 10.3 Efficacy of anticonvulsants for neuropathic pain Condition Agents studied Level of evidence I I I I I 1.6 2.4 Numbers needed to treat Analgesia Trigeminal neuralgia Diabetic neuropathy Migraine prophylaxis Carbamazepine Carbamazepine Phenytoin Sodium valproate Carbamazepine 2.6 2.5 Adverse effects 3.4 3.1
The minimum effective dose of the anticonvulsants in the management of neuropathic pain is often less than the dose required for seizure control. The most commonly used anticonvulsant is carbamazepine. Some patients, especially the elderly, are particularly sensitive to this drug, developing sedation, ataxia, dizziness, confusion, nausea and vomiting at low doses. Effective doses can often be achieved if carbamazepine is started at a low dose, such as 50 or 100 mg daily in elderly patients, and titrated upwards. The effectiveness of anticonvulsant agents needs to be balanced against their adverse effects. In the case of trigeminal neuralgia, it is acceptable to allow temporary side effects in view of the severity of the pain, while in the case of migraine prophylaxis, adverse effects are more significant. A number of studies indicating the effectiveness of sodium valproate in migraine prophylaxis have been published (level II; Welch 1993a, Welch 1993b, Mathew et al 1995). In terms of their mechanism in migraine prophylaxis, anticonvulsants may be better considered as a form of chronic pain control. Antidepressants The tricyclic antidepressants of use for neuropathic pain have noradrenergic activity. A number of studies have evaluated the use of antidepressants in the treatment of neuropathic pain and other pain states that are difficult to treat (level I; McQuay et al 1996). In patients with diabetic neuropathy, six of thirteen studies in a meta-analysis revealed significant benefits of these agents over placebo. Post-herpetic neuralgia also tends to respond to these agents, as does atypical facial pain. Comparisons amongst specific tricyclic antidepressants failed to show that any particular agent is more efficacious; however, paroxetine and mianserin in this review were less effective than was imipramine. Other sources suggest that tertiary amine compounds (amitriptyline, imipramine and doxepin) have the greatest effect in chronic neuropathic pain via their increased effect on the nor-adrenergic system. In animal models, these agents provide greater efficacy than do the modern tricyclic agents. Many of the side effects of tricyclic antidepressants, such as dry mouth and sedation, are transitory or irritating. Sedation may be used to advantage in pain sufferers who have insomnia. Other adverse effects are potentially serious, particularly in the elderly; for instance, postural hypotension, urinary retention, paralytic ileus, narrow angle glaucoma and cardiac arrythmias. Many of the side effects are related to the 153
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anticholinergic effects of the tricyclic antidepressants, and therefore special precaution is required when combining them with other medications with anticholinergic effects, such as antiparkinsonian and neuroleptic drugs. Tricyclic antidepressants potentiate the central nervous system depressant effects of alcohol, narcotics, neuroleptics and anxiolytics; they may cause delirium and seizures in those at risk, those with pre-existing brain injury or the elderly. Newer agents such as the selective serotonergic re-uptake inhibitors (SSRI) have more favourable sideeffect profiles but have not been shown to be as efficacious as tricyclic antidepressants in the relief of neuropathic pain. The simultaneous use of tricyclic antidepressants and SSRIs may precipitate a serotenergic crisis. Corticosteroids Corticosteroids are effective for short-term relief of neuropathic pain. A particular application is for pain associated with spinal cord compression, usually in combination with radiotherapy (level III; Boogerd & van der Sande 1993). Statement of evidence anticonvulsants and antidepressants Anticonvulsants and antidepressants have been shown by meta-analysis to be effective in the treatment of neuropathic pain.
Key point
The effectiveness of anticonvulsants and antidepressants in the treatment of pain needs to be balanced against their potential adverse effects.
Complex regional pain syndromes
Complex regional pain syndromes (CRPS) are particularly important to diagnose and treat in the early postoperative or post-trauma period. CRPS type I used to be known as reflex sympathetic dystrophy (RSD) and CRPS type II used to be known as causalgia (see IASP Task Force on Taxonomy 1994). These syndromes are associated with minor (CRPS type I) or major (eg plexus) neural damage and are characterised by pain in an extremity (eg a limb, breast, penis or nose). The pain tends to be a burning sensation and there are usually hyperalgesia, allodynia, excessive sweating and vasomotor changes ranging from a red appearance to a blue blotchy appearance. The extremity may be either abnormally hot or cold. Oedema may be present and trophic changes may occur later (Walker & Cousins 1997). These features associated with sympathetic hyperactivity have led to the term sympathetically maintained pain (SMP). However, SMP is not a feature of all CRPS and thus the term sympathetically independent pain (SIP) has also been coined. This is not pure semantics because some patients with CRPS respond to sympathetic blocking drugs with immediate relief of pain and associated symptoms (SMP) while others do not (SIP). Sympathetic blockade can be used to diagnose SMP and SIP. It should be noted that a systematic review of sympathetic blockade by intravenous guanethidine found no evidence that it was superior to placebo (level I; McQuay et al 1996). Some surgeons prefer to carry out hand surgery, with anaesthesia provided by a continuous catheter brachial plexus block technique. This provides a pre-operative 154
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pre-emptive neural blockade, with a local anaesthetic infusion then carried into the postoperative period. Analgesia must be adequate to permit diagnostic procedures and effective physical therapy, which plays a key role in the rehabilitation of patients with CPRS and involves the early establishment of weight bearing. It is not known if the afferent sensory block prevents central sensitisation and/or if the accompanying sympathetic blockade plays a role. In any case, early diagnosis and treatment of CRPS are preferable as chronic neuropathic pain is extremely difficult to treat.
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This chapter discusses several groups of patients with special needs who sometimes challenge the skills of pain management providers. Though diverse in many ways, these patients are commonly at risk of receiving suboptimal health care. In culture, language or life experience, such patients may share little with their health carers and therefore require more time to be spent in assessment and patient education. Good communications and a cross-cultural perspective on pain experience and reporting are necessary on the part of the clinician to ensure than an accurate diagnosis is made and cooperation achieved in a treatment plan. Where doubt exists as to the adequacy of the clinicians information base, the assistance of an interpreter, community member or other liaison person may be required.
11.1 Non-Englishspeaking patients

Patients who are unable to communicate because of language difficulties are at a particular disadvantage when it comes to obtaining adequate pain relief. In order to overcome problems with treating patients who do not speak English it is necessary to be aware of: interpreter services; the different language of pain;
different meanings of pain to different cultural groups; and differing attitudes to pain relief and analgesics.
11.2 Aboriginal and Torres Strait Island peoples

Despite interest from various health care groups on the nature of acute pain and its management in Aboriginal People and Torres Strait Islanders, the literature shows a lack of systematic study of these groups. Anecdotal evidence suggests that indigenous people who live a traditional cultural lifestyle have a different pain response from those who are urbanised. For example, pain responses may be stoic in more traditional groups with consequent undertreatment of pain. Urbanised groups are more likely to use pain as a means of communication and entry into the health care system. This can lead to the overprescription of simple, over-the-counter analgesics, sometimes with a failure to address underlying pathology. The difficulties of obtaining a reliable assessment of pain in these groups are often compounded by the presence of comorbidity which can interact with the pain stimulus and also with the pain response itself. Furthermore, in some communities, when a patient presents with an injury, he or she may be intoxicated and not experiencing pain. Nonetheless, a pain management plan is required as part of the injury treatment, to avoid unnecessary discomfort. Where possible, an indigenous health worker or liaison officer who is known to the patient should be included in the consultation to enhance communication. The overall principle in treating a person of Aboriginal or Torres Strait Islander descent is to remember that the pain response may differ from that usually exhibited by people of European descent and that accurate pain assessment requires an empathetic and accurate evaluation of their presenting problem. Health carers 157
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working in indigenous communities, or who frequently provide health care to indigenous people, should consider producing pain scoring scales (see page 35) in the language of the local people.
11.3 Other ethnic groups

Cultural and ethnic diversity has influenced Australian society in a number of ways. Recent studies have suggested that the perception of pain varies significantly among different ethnic groups. For example, one study demonstrated that postoperative requirements for pethidine were significantly lower in adult Asians than in Europeans experiencing pain of a similar intensity (Houghton et al 1992). Another study found that, despite a degree of assimilation of an ethnic group into the United States community, the cultural expectations of the various ethnic groups continue to affect the expression of pain (Greenwald 1991). While findings such as these need to be cautiously translated in individual circumstances, clinicians should be aware of potentially different pain responses. These differences may affect the individuals analgesic requirements and their capacity/desire to utilise the various modalities of pain relief which are available. These differences may extend to subsequent generations.
11.4 Patients with psychiatric illnesses

Patients with a primary psychiatric disorder may experience difficulties with the assessment, diagnosis and management of their pain for a number of reasons. An individual with a primary psychiatric disorder may develop an exacerbation of their pain problem. This may be seen, for example, in patients who suffer from migraine. In some cases there may be an exacerbation of the migraine if the individual experiences an episode of depression. Patients with a primary psychiatric disorder may present with pain as the principle complaint. The symptom in these cases relates specifically to the psychiatric illness rather than to the presence of organic disease. The presence of a psychiatric illness does not, however, exclude the development of organic disease (Slater 1965). For the patient with a psychiatric diagnosis there is a risk that the organic pathology will be misdiagnosed and, even when correctly diagnosed, the management of their disorder may be affected by the presence of a psychiatric illness. Patients taking mono-amine oxidase inhibitors may have important drug interactions, which may include coma with pethidine, and hypertension with the administration of vasopressors. The following sample cases highlight the difficulties in managing acute episodes of pain in patients with continuing background pain and psychiatric illness. Sample case 1 A 39-year-old woman presented initially to her GP complaining of facial pain. After a number of referrals to various specialists and dentists and having undergone multiple investigations, she was being treated with multiple agents, including oral opioids and intermittent opioid injections. She was then referred to the pain clinic; subsequently she was diagnosed as having depression. Antidepressant medication was administered and effectively resolved both her pain and the primary mood disturbance. 158
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Sample case 2 A 45-year-old man with chronic schizophrenia had a history of auditory hallucinations and prominent somatic delusions. He complained to various GPs and specialists of upper abdominal pain, a situation not unfamiliar to the clinicians who had treated him in the past. Six months after initially complaining of this pain, he was diagnosed with a gastric carcinoma. During his postoperative period and the eventual terminal phase of his illness his pain management proved difficult due to the continued presence of somatic delusions, the nature of his organic pathology and the difficulties some treating staff experienced in managing a man with a severe chronic psychotic disorder. Pain secondary to organic pathology may be associated with a number of psychiatric disorders. A common situation which arises in the postoperative period or following injury is the development of an organic brain syndrome (delirium), which may not be recognised. Patients with pain may develop a psychiatric disorder as a consequence of the organic pathology and/or its treatment, the treatment of the pain or as a stress response to the presence of an illness. Disorders which may arise include anxiety, depression or occasionally a psychotic illness. The presence of these various problems may result in the inappropriate management of the patients pain, with the treatment process at times further complicated by the patients personality.
11.5 Elderly patients
Attitudes to pain relief in the elderly among health care professionals, the lay public and patients themselves may impede appropriate care. Many members of all three groups consider acute and chronic pain a part of normal ageing (level III; Ferrell et al 1990, Ferrell 1991). This attitude may deny many elderly people not only appropriate pain relief but also maintenance of a reasonable level of activity. The principles of acute pain management in the elderly are similar to those in a younger population. Several factors make pain management in the elderly problematic. Elderly people often have multiple co-existing pathologies (level IV; NIH 1979) any one of which potentially accounts for the symptoms. Atypical presentation of disease is common. Cognitive and other impairments may create a barrier to assessment, selection of therapy and compliance. Elderly people are more likely to be on multiple medications contributing to an increased frequency of adverse drug reactions and drug interactions (level III; Kane et al 1989). Treatment of the painful condition may potentially aggravate an unrelated problem. Advancing age is associated with an increasing prevalence of pathology, with 48 per cent) of elderly people having a handicap and 71 per cent of persons aged over 80 having a handicap (ABS 1993). As pain is a cardinal symptom of many diseases, one would expect an increasing prevalence of pain in older adults. Some acutely painful conditions that are more prevalent in the elderly include acute exacerbations of arthritis, osteoporotic fractures of the spine and pain associated with peripheral vascular disease (level IV; Foley 1985, NIH 1979). Epidemiological surveys report an increase in prevalence of chronic pain up until the age of 6570 years beyond which the levels remain static (level III, Gibson & Helme 1995). In contrast, the only agespecific study of temporary or acute pain reported a constant rate of approximately 5 per cent across all age groups (level IV, Crook 1984). One limitation of this study was the small number of individuals aged over 80 years.
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Community prevalence studies may not report diseases with higher incidence in the elderly if the prevalence rates are relatively low or survival brief. For instance, the incidence of neuropathic pain states such as acute herpes zoster infection and postherpetic neuralgia have a strong age correlation which is not detected in community surveys (level IV; De Moragas 1957). Other neuropathic pains also more common in the elderly include peripheral neuropathies, trigeminal neuralgia and central post-stroke pain syndrome. The frequency of pain report does not appear to increase at the same rate as the increase in pathology in the elderly. Elderly patients often demonstrate altered pain responses to painful conditions, for example silent myocardial infarction and painless intra-abdominal emergencies (Bayer et al 1986, Bender 1989). The majority of psychophysical studies report a modest increase in pain threshold intensity with advancing age, particularly for thermal stimulation (level III; Gibson & Helme 1995), but the significance of these findings in the clinical setting remains uncertain. There is limited evidence that, once a stimulus is perceived as painful, response is not any different in older patients. Alteration in pain report may be related to psychological and cultural patterns that arise in older people. Clinically, elderly adults may be more accepting of mild pain because it is perceived to be a normal consequence of ageing (Leventhal & Prohaska 1986) and may rate this level of pain less adversely than do younger individuals (Ebrahim et al 1991).
Institutional care
Ferrell (level IV; 1995) reported 45 to 80 per cent of nursing home residents have pain which often contributes to functional impairment and decreased quality of life. Substantial barriers to assessment of pain in this setting include a high prevalence of dementia, communication disorders and multiple concurrent illnesses. Sengstaken and King (level IV; 1993) reported that pain was not documented by physicians in 34 per cent of nursing home residents who reported pain on interview. Logistic problems in carrying out diagnostic procedures and interventions make nursing home residents vulnerable to less than optimal management of acute pain. These difficulties should not be insurmountable barriers to adequate pain relief.
Cognitive impairment
Delirium (common during acute illness in the elderly) and dementia are serious obstacles to pain assessment. The prevalence of dementia doubles every five years, reaching about 25 per cent by the age of 85 years. Among residents of nursing homes and residential care facilities the prevalence of dementia is more than 50 per cent (Jorm et al 1993). In a study of 758 nursing home residents, Parmelee et al (level III; 1993) found no evidence of masking of pain complaints by the presence of dementia. Elderly people with mild to moderate cognitive impairment often require more time to assimilate and respond to questions regarding pain. Immediate reports of acute pain may be reasonably accurate, while long-term recall is more likely to be impaired. A reliable history from an informant should be sought. Ferrell et al (level III; 1995) reported that 83 per cent of cognitively impaired nursing home patients could complete at least one unidimensional pain scale, with the highest completion rate for the Present Pain Intensity Scale of the McGill Pain Questionnaire. Visual and hearing impairments are frequent obstacles to the completion of pain scales. Whether behavioural observations (eg agitation, groaning) are sensitive and specific for pain among the cognitively impaired remains to be shown.
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Management
Elderly people, especially frail people aged over 85, are at particular risk of both under and overtreatment. Unfortunately, few studies of analgesic dosage requirements are performed in the elderly, and most have systematically excluded potential subjects over 65. Age-related observations are extremely variable among elderly people. Indeed, variance in measurements of most physiological and pharmacological parameters increases with age in cross-sectional studies (level III; Kane et al 1989). There has been a much needed increase in knowledge about opioid and non-opioid drug use in this population, as reviewed by Ferrell (1995), who concludes that pain relief can be effectively and safely given. This requires a thorough assessment of the patient by a medical practitioner with knowledge and training in the care of the elderly, particularly in the problems of use of analgesics in this population (Ferrell 1995). In general, medication doses are lower and increased at a slower pace. All medications should be regularly reviewed, and discontinued if ineffective or no longer indicated. When practical, physical and psychological strategies should be employed in conjunction with pharmacological approaches, potentially allowing smaller doses of medications to achieve adequate analgesia and hence minimising the risk of adverse drug reactions. NSAIDs The NHMRC report on musculo-skeletal problems in the elderly advises extreme caution with the use of NSAIDs (NHMRC 1994b). The risk of gastric and renal toxicity from NSAIDs is increased among the elderly. Unusual drug reactions including cognitive impairment, constipation and headaches are also more common (level III; Roth 1989). There are many important drug interactions between NSAIDs and medications commonly prescribed in the elderly, such as diuretics, anticoagulants, hypoglycemic agents and anticonvulsants. NSAIDs have been frequently used in the elderly for a wide range of conditions, but should be restricted to patients with inflammatory arthritis, such as rheumatoid arthritis, when alternative therapies such as intra-articular steroids, low-dose oral corticosteroids or disease modifying therapy is not adequate. If gastric ulceration is of particular concern, coadministration of misoprostol, famotidine or omeprazole with the NSAID should be considered. For noninflammatory complaints such as osteoarthritis, paracetamol and/or low-dose opioids are appropriate (level II, Bradley et al 1991). Rubefacients and topically applied NSAIDs are widely used for acute musculoskeletal disorders. They have very few systemic side effects and may be of benefit in reducing requirements for systemic administration of analgesics, however evidence of efficacy is lacking. Opioids Opioid analgesic drugs are effective for the management of postoperative pain and other severe acute pains in elderly patients. Cheyne-Stokes breathing patterns are often seen during sleep in the elderly and do not need prompt discontinuation of opioid analgesia unless such analgesia is clearly associated with unacceptable degrees of arterial oxygen desaturation (saturation < 85 per cent). PCA has been shown in at least one study to be safe and effective for postoperative pain relief among selected patients (Egbert et al 1990). If PCA is used, careful titration of the initial dosage is necessary to avoid undesirable effects due to drug accumulation, or to a decrease in the arousal effect as painful stimuli subside later in the patients course. Elderly people are more sensitive to the analgesic effects of opioid drugs as they experience a higher peak and longer duration of pain relief (level III; Kaiko et al 1982). They are also more sensitive to sedation and respiratory depression, probably as a result of altered
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distribution and excretion of the drugs. This is especially true in opioid-naive patients. For this reason, caution is required in using longer acting drugs such as methadone (level III; Ferrell 1991). Opioids produce cognitive and neuropsychiatric dysfunction, through poorly defined mechanisms that in part include the accumulation of biologically active metabolites such as M6G or norpethidine (level III/IV; Wood & Cousins 1989). Opioid dosage titration should take account not only of analgesic effects but also of side effects that extend beyond cognitive impairment. These side effects may include: urinary retention which poses a greater threat in elderly males with prostatic hypertrophy; constipation and intestinal obstruction; respiratory depression; or exacerbation of Parkinsons disease. The management of nausea using phenothiazines or antihistamines is fraught with problems, because elderly people are sensitive to anticholinergic side effects including delirium, bladder and bowel dysfunction, and movement disorders (level III; Ferrell 1991). Dextropropoxyphene poses hazards of accumulation of parent drug or long half-life metabolites that may be cardiotoxic. Regional techniques Local anaesthetic epidural or brachial plexus infusions may result in cognitive impairment if significant blood levels are reached. Yet before that point, orthostatic hypotension may result from sympathetic blockade, and clumsiness may ensue from partial motor or sensory anaesthesia. Appropriate precautions should be taken, such as help with ambulation. Treating neuropathic pain The prevalence of neuropathic pain states increases with age. These pain states are often resistant to conventional analgesia. Early intervention in the treatment of acute herpes zoster infection with antiviral agents reduces the time to healing, duration of acute pain and postherpetic neuralgia (level II, Kost & Straus 1996), as discussed in Section 8.2. The early introduction of amitriptyline may improve long-term outcome (Bowsher 1994). Regardless of the cause of the neuropathic pain, adjuvant agents such as the tricyclic antidepressants and anticonvulsants are often indicated, either individually or in combination. As the elderly are particularly sensitive to these agents, and are more likely to develop adverse responses, these medications should be started at very low doses and titrated slowly. Common side effects of tricyclic antidepressants in the elderly include orthostatic hypotension, which increases the risk of falls, sedation and anticholinergic side effects such as constipation, urinary retention and dry mouth. The initial dose should be small, and the individual monitored frequently as the dose is increased to therapeutic levels. Statement of evidenceelderly patients
NSAIDs should only be used with extreme caution in elderly people. For non-inflammatory complaints, paracetamol and/or low-dose opioids are recommended. Low-dose corticosteroids may be appropriate in inflammatory conditions.
Key point
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11.6 Management of acute pain in opioiddependent patients

An understanding of the terms dependence and addiction is necessary when assessing patients believed to exhibit these phenomena. Physical dependence refers to the development of withdrawal phenomena after cessation or antagonism of a drug. This may be avoided by careful tapering of agents and the avoidance of antagonists (including agonist-antagonist agents such as pentazocine) as these agents may precipitate withdrawal in these patients (level III; Cherny 1996). Addiction, on the other hand, describes a psychological syndrome that translates into drug-seeking behaviours. It is marked by compulsion, loss of control over use, and ongoing use, despite physical or social harm. These two terms are disparate and cannot be used interchangeably as is often done, albeit unwittingly. Pseudo-addiction is a term that has been coined to describe patients who exhibit drug-seeking behaviour, resembling addiction, in response to unrelieved pain. This is frequent in cancer patients who may end up stigmatised as having a problem with addiction (level IV; Weissman & Haddox 1989). Unrelieved pain requires careful assessment and therapeutic manoeuvres which aim to treat the pain. Addiction is a surprisingly uncommon consequence of medically administered opioids (level III; Schuster 1989, Chapman & Hill 1989, Foley 1989). Survey data show that the risk of substance abuse behaviours developing in opioid-naive patients given opioids postoperatively appears to be small (level III; Porter & Jick 1980). Certain features indicate the possibility that a patient is seeking opioids as part of a pattern of psychological dependence. These include: seeking injectable rather than oral opioids; seeking repeated supplies of opioids; attempting to negotiate opioid treatment; denying having a regular medical practitioner; attending multiple practitioners; requesting supplies of opioids in more than one form eg oral and injectable; requesting opioids by name (particularly pethidine); and requesting specific agents of other drug classes commonly used by substance abusers. In practice, management depends on whether patients are: a) known opioid-dependent or addicted patients stable on a methadone program; b) known opioid-dependent or addicted patients not stable on a methadone program and still self-abusing opioids (usually intravenous heroin); c) known drug-dependent patients on high or regular doses of prescribed opioids or other drugs; or d) patients with a history of opioid dependence and/or addiction.
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The general principles in managing acute pain in patients with opioid dependence or addiction are to: identify the group to which the patient belongs and the extent of the problem; understand that pain scoring systems are not likely to be as reliable; design a management plan with other staff and the patient involved; transfer back to oral dose regimen as soon as practical using a long-acting opioid; and set expected goals of dosage regimen, time frame and change with the patient. In the case of patients falling into category (a) the goal will be to discharge on methadone (possibly at a higher rate) into the care of a drug and alcohol service. Patients in group (a) will need slow reduction of their opioid doses but may need continuing assistance for total withdrawal after resolution of the acute episode. Patients in group (b) may be the most difficult in terms of drug and behavioural management. While punitive and judgmental approaches should be avoided, it is important to set behavioural guidelines with the patient. It is also, however, important to reassure them that the staff will be trying to make them as comfortable as possible as safely as possible, as they do with all patients. The use of PCA in this group was initially thought to be contraindicated but, while it may not be suitable for all, it is now recognised as a potentially useful method of providing pain relief for these patients. This is partly because of their often high opioid requirements and partly because it helps to avoid staff/patient confrontations about analgesia. In patients already receiving opioids, who will have a degree of opioid tolerance, background infusions are reasonable. It may be possible to derive the infusion rate from the patients current daily opioid requirement. Appropriate staff allocation and interstaff communication are important. It is important to: set a planned analgesic regimen and be firm; be prepared to titrate the opioid dose up to avoid withdrawal symptoms; attempt to encourage patients to accept drug and alcohol referral but recognise that this may fail; consider the risk of transmittable diseases; and consider the possibility of dependence on other drugs and the risks of withdrawal from these. Further important points when dealing with patients with possible addiction or dependence follow. Every effort should be made to define the mechanism of the pain and to treat the primary problem. Possibilities include infection, tissue ischaemia or a postoperative complication that may require surgical or other intervention. It should not be assumed that requests for further analgesia are merely part of drug-seeking behaviour. Clinicians should attempt to ascertain the current status of drug usage and how recent the drug addiction has been eg by contacting the appropriate state authority, drug and alcohol service or GP. It is important to follow relevant pharmacological principles in treating patients with known or suspected opioid dependence, including the avoidance of antagonists and agonist-antagonists as these may promote withdrawal phenomena in these patients. Loading doses of opioids will be required in normal patients, as 164
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well as in substance abusers, to reduce the intensity of postoperative pain to acceptable levels. PCA is being used with increasing frequency for many patients, including patients with known opioid dependence. PCA doses must be increased when used in patients with tolerance to opioids to achieve the same analgesic effect as for opioid-naive patients. Non-opioid therapies, either as alternatives or as adjunctive medication, are also effective in patients with opioid tolerance. Agents such as NSAIDs, local anaesthetic solutions given via catheter into the epidural space or surrounding peripheral nerves, cryo-analgesia, TENS and non-drug therapies are included in this group. Appropriate use of non-opioid therapies will frequently reduce the dosage requirement for opioid analgesia. While it is important not to develop punitive or pejorative attitudes towards patients who exhibit drug-seeking behaviour, firmness and the setting of clear limits of which the patient is aware are useful. Discussion that also considers the medical, ethical and legal consequences to the patient and physician if drug abuse behaviours continue needs to take place and demands on staff need to be considered. Security measures that are generally in place (locked cabinets, drug checks each nursing shift and antitamper features on PCA machines) will frustrate most attempts to bypass the usual means to obtain opioids. Care givers should set limits to avoid excessive negotiation about drug selections or choices, including the pressure to prescribe a particular agent (eg pethidine) when requested. The treatment plan should include clear criteria by which opioid doses will be tapered and eventually ceased. Careful and objective assessment of the postoperative patient with an active or previous substance abuse history will provide the patient with the opportunity to obtain pain relief with opioids, where necessary, while being less able to dupe the clinician into continuing opioids when they are no longer necessary. A survey of nurses knowledge of pain control indicated that while nurses had a sound knowledge of issues of pain assessment and patient advocacy, they lacked knowledge of opioid dependence and addiction (level III; Hamilton & Edgar 1992). In the outpatient setting, clear instructions (preferably written out and copied into the patients record) should be made regarding doses and frequency of medication and the number of days the prescription is expected to last. The addition of a random urine testing procedure to outpatient medication contracts should be considered in all outpatients with a known history of substance abuse who are given opioid analgesics for pain. The following example provides management points in relation to opioid tolerance and physical dependence:
Sample case
A 39-year-old man with a history of chronic abdominal pain is admitted for resection of a pancreatic pseudocyst diagnosed on abdominal computed tomography (CT). He has a history of alcohol abuse and regularly takes Panadeine Forte for recurrent bouts of acute abdominal pain. He sometimes requests pethidine injections when Panadeine Forte is ineffective. Pre-operatively he states that he has terrible pain and repeatedly requests injections of pethidine.
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Management points This man certainly has opioid tolerance and physical dependence and may possibly have opioid addiction. He will require close monitoring and opioid requirements will be greater than usual on the basis of determinants such as his age. Pain assessment using the patients self report may be unreliable and other methods of assessment (eg observation of vital signs and of daily activities) should be used as a supplement to self report. Upper abdominal surgery such as required in this setting produces severe pain and thoracic splinting. When associated with co-existing respiratory disease, this may result in significant postoperative respiratory morbidity; thus adequate pain relief must be achieved by some appropriate method. It is important to establish close liaison with a drug and alcohol or drugdependence service during the postoperative period, encouraging the patient to accept continuing assistance from drug and alcohol service staff. The service should be advised of the patients status on discharge. Pain and opioid dependence may continue to be a problem after recovery from surgery, requiring skilled intervention using a multidisciplinary approach.
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Emergency department and intensive care guidelines
12.1 Acute pain in the emergency department

Patients presenting to emergency departments are often in a state of physical and psychological extremes. Poor analgesia may turn apprehension to fear, anxiety, resentment and loss of control. Various studies have shown that analgesia in emergency departments is often inadequate in terms of the route, dosage and frequency of administration. Assessment of pain should involve careful consideration of the patient being treated, and treatment should aim to provide the most appropriate method of pain relief for that patient. Detailed information about analgesic agents and possible adverse effects is given in Chapter 4. Various groups have special needs which must be addressed when treating acute pain in the emergency department. Special attention is required to reduce the distress associated with analgesic administration in children. The management of acute pain in children is discussed in Chapter 6. In the elderly, an increased propensity for adverse drug interactions warrants cautious treatment. In addition, atypical presentation of disease is common in the elderly, and pain may even be absent in conditions where it is typically a cardinal symptom, such as myocardial infarction. The management of acute pain in the elderly and other patients with special needs is discussed in Chapter 11.
Pain relief techniques in the emergency department

Techniques and agents that are commonly employed and are useful in the emergency department include: local anaesthetics which can be effectively employed in regional techniques, from wound infiltration to nerve blocks (eg the femoral nerve block for the fractured shaft of femur); inhaled agentsnitrous oxide in combination with oxygen as a 50:50 mixture is safe and rapid in onset and offset and is extremely effective in the prehospital setting for mild to moderate pain states although it is not appropriate in a number of circumstances (see Table 12.1); opioid analgesicspure agonists are the most sensible choice and these include morphine, pethidine and fentanyl; non-opioid analgesics including NSAIDs, which are generally inadequate in severe pain but have specific beneficial effects in ureteric and possibly biliary colic; and other therapiesplacebo effects need to be understood (see page 80) but emergency staff should never attempt to trick patients thought to be opioid dependent or feigning pain for secondary gain.
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Morphine and fentanyl are the standard pure agonists used in many emergency departments. Pethidine has approximately one-eighth of the potency of morphine and causes the same degree of bronchospasm and increased biliary pressure as morphine. It is metabolised via hydrolysis and demethylation to norpethidine which has potential toxic effects as outlined elsewhere in this report. There are also potential interactions with other agents, particularly the mono-amine oxidase class of antidepressants. Pethidine is the most commonly requested agent by patients seeking opioids. There are several routes of administration available for opioid agonists in the emergency department setting including: oral; intravenous; intramuscular which has shown to lead to fluctuating concentrations and a slower rate of onset; sublingual; rectal; and epidural when handled by staff trained in its administration.
Key point
In most acute care situations in the emergency department, the intravenous route of opioid delivery is by far the most efficacious and is therefore preferable.
Table 12.1 Red flags against the use of nitrous oxide
impairment of consciousness inebriation
inability to understand instructions
dyspnoea, cyanosis, suspicion of pneumothorax decompression sickness, air embolism severe airflow limitation
abdominal pain with distension or suspicion of obstruction presence in the patient of any acute air-containing space
Methoxyflurane is used widely in some ambulance services. It has the advantage of being more portable (the Penthrane whistle) and produces far less environmental hazard. However, prolonged use causes renal toxicity.
Time of administration
While it has traditionally been held that pain relief masks the clinical signs of pathology, there is evidence from at least two randomised controlled trials that early administration of opioids in patients with an acute abdomen does not reduce the detection rate of serious pathology, but may actually facilitate it (level II; Attard et al 1992, Zoltie & Cust 1986). In these trials, patients who received analgesia had a change in their physical signs (as did the patients that received placebo), but this was not related to the presence of genuine pathology. Clearly, the effect of analgesia on physical signs cannot be used as a diagnostic test. 168
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Common pain conditions

A number of common pain conditions present in the emergency department, including cardiac pain, acute herpes zoster infection, severe headache, abdominal pain and acute musculoskeletal pain. The assessment and treatment of these conditions are discussed in Chapter 8. Renal colic Parenteral non-steroidals have been shown to be more effective than opioids in relieving the pain of renal colic. Rectal NSAIDs are as effective as parenteral NSAIDs in the treatment of renal colic. Indomethacin suppositories in conjunction with intravenous opioids are also effective in treating renal colic. Prostaglandins play a major role in producing the pain of renal colic, giving a rational basis for the use of NSAIDs in this condition. A comparative study of an intramuscular NSAID and intramuscular opioid has verified the efficacy of NSAIDs in this indication (level II; Hetherington & Philp 1986). Two NSAIDs, diclofenac and ketoprofen, were compared and found to be equally effective in relieving the pain of acute ureteral colic (level II; Walden et al 1993). (Note: Ketorolac is the only NSAID available in an injectable form in Australia.) Statements of evidence acute pain in the emergency department Early administration of opioids in patients with an acute abdomen does not reduce the detection rate of serious pathology, but may actually facilitate it. Non-steroidals have been shown to be more effective than opioids in relieving the pain of renal colic. A comparative study of an intramuscular NSAID and intramuscular opioid has verified the efficacy of NSAIDs in this indication. Comparison of two NSAIDs, diclofenac and ketoprofen, in another study found them to be equally effective in relieving the pain of acute ureteral colic.
12.2 Issues in intensive care and other critical care settings

Despite the importance of adequate pain relief in intensive care units (ICUs), there is a paucity of data on which to base rational treatment. Much that has been learnt in the postoperative setting can be applied in the ICU. However, there is an urgent need for application of specific data obtained in this setting. Available data indicate that pain continues to be a problem in ICUs (level III; Dracup & Bryan-Brown 1995). Patients in intensive care environments are often at greater risk of unrelieved pain due to acute pain arising from their disease and the need to perform invasive diagnostic interventions such as arterial cannulation and the insertion of nasogastric and tracheostomy tubes. Pain in these settings has the ability to exacerbate the stress response that already exists as a result of injury or disease. It is common for patients in the ICU setting to undergo psychological and physiological adverse effects from the interaction of pain, anxiety and sleeplessness (level IV; Cousins & Phillips 1986). 169
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Level of evidence
II Attard et al 1992, Zoltie & Cust 1986 II Hetherington & Philp 1986 Walden et al 1993
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Assessment of pain
Patients in this environment are often unable to communicate, due to the severe nature of their illnesses (eg coma) and to the limitations set by various interventions (eg insertion of endotracheal tube). Other forms of non-verbal communication that can normally be used to relay pain to staff (such as facial expressions, hand movements, crying or wincing) are also often inhibited because of underlying disease or the use of sedatives and opioids in combination (level III; Lunse & Price 1992).
Treatment of pain
All of the techniques and drugs described in the discussion of postoperative pain management (see Chapter 4) are potentially applicable in ICUs, including non-drug techniques. It is also important to recognise that a critically ill patient who remains in the ICU for weeks or months, and has continuing pain, has chronic rather than acute pain. Such patients require multidisciplinary assessment and treatment. This should be instituted early to prevent harmful physical and psychological sequelae. It may be helpful to use an algorithm for management of pain in the ICU. One such approach is given in Figure 12.1 (level IV; Molloy & Cousins 1997). A second algorithm, given in Figure 12.2 and an accompanying case study, illustrate the importance of accurately assessing and treating pain, anxiety, dyspnoea and delirium in the ICU. In intubated ventilated patients, a controlled intravenous infusion of morphine and a benzodiazepine (eg midazolam) is often used. However drug cumulations and delayed recovery may pose problems. A new drug that recently became available, remifentanil, may prove a major advance as it is inactivated by blood and tissue esterases and has a context-sensitive half-life of three to four minutes, which is constant over a 15-fold variation in effect rate concentration and is independent of duration of infusion. Epidural analgesia may be valuable in the treatment of thoracic trauma or post-thoracotomy pain. There is evidence that this form of analgesia may shorten the time required for artificial ventilation (level II; Yeager et al 1987). Spontaneously breathing patients pose a range of different pain relief challenges, depending upon their underlying pathology. For example, a patient with a crushed chest may be best managed with a thoracic epidural rather than running the risk of respiratory depression with systemic opioid treatment. Patients with multiple limb fractures may respond well to patient-controlled administration of opioid. Neuropathic pain (see Section 3.2 on page 39 and Section 10.2 on page 152) is frequently associated with trauma, surgery and disease states (eg neuropathy in severe diabetes) that are commonly the reason for patients being in ICUs. Early recognition and treatment of neuropathic pain are very important. Important new concepts have emerged for the use of opioid drugs by infusion over long periods of time, such as in the ICU. Old concepts of short and long elimination half-lives are no longer appropriate since all opioid pharmacokinetics are described by multicompartment analysis. In future, rational choice of opioids for intensive care should be based upon concepts such as biophase (ie effect site) and context-sensitive half-life (the time taken for the central compartment drug concentration to decrease by 50 per cent) (level III; Shafer & Varvel 1991).
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These concepts are of great practical significance, since they permit more rational adjustment of opioid infusion rate for each opioid. This is critical to maintain pain relief and/or sedation while patients are intubated and then rapidly regain adequate ventilatory drive at the time of extubation. It is now known that an 80 to 90 per cent fall in opioid concentration is required after opioid and sedative states to permit patients to regain adequate control of ventilation (Shafer & Varvel 1991). Prolonged infusion of morphine at inappropriate infusion rates may be associated with high concentrations of parent drug and sedative/analgesic metabolites, thus potentially delaying recovery. A similar situation exists for fentanyl which accumulates during prolonged infusion. At present, alfentanil provides the best option for rapid decline in plasma concentration. The place of the rapidly cleared remifentanil in intensive care awaits further evaluation.
Key point
All of the techniques and drugs used to treat acute postoperative pain, including non-drug techniques, are potentially applicable in intensive care units.
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Conscious and cooperative No
Pain assessment
Unconscious
Re-assess
Pain? Autonomic response consistent with nociception/ neuropathy
Yes Opioid adjuvant non-drug approaches Assess pain at rest (VAS) and on activity (eg cough; eg incentive spirometer) Yes Pain relief?
Monitor pain
No
Treat change drug adjuvant regional technique
Pain Medical/ No consistent with surgical history? evaluation Yes Treat Treat
Figure 12.1 Pain assessment in the intensive care environment. VAS=visual analogue scale; IV=intravenous. Source: adapted from Molloy & Cousins 1997.
Figure 12.2 (facing page) Sedation algorithm. Source: Jensen & Justic 1995.
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Re-assess Consider regional technique Suitable no contraindications Re-assess
Unacceptable side effects?
Treat Re-assess
Consider other causes eg neuropathic pain Consider IV ketamine Consider IV lignocaine infusion
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If oral route available, membrane stabilisors, anticonvulsants, antidepressants
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Cause of anxiety?
1
Pain? no Dyspnoea? no Delirium1? no Knowledge deficit? no Another cause of anxiety3? no
yes
Treat pain.
2 3
yes
Treat dyspnoea.
Symptoms of delirium include: disordered or incoherent speech; irritibility; hallucinations, delusions or misperceptions; fluctuating periods of restlessness, agitation and lethargy; paranoia; disorientation; worsening of symptoms at night. Possible underlying causes include: ICU psychosis, alcohol/ chemical withdrawal, infection; toxins; medications etc. Other causes of anxiety may include: finances; fears; relationship problems.
yes
Identify and treat cause.2 Treat deficit.
Treat symptoms with neuroleptic alone or in combination with anxiolytic.
Assess patient and document response.
yes
yes
Can anxiety be treated without medication?
yes Treat causes and document (causes, treatment and response).
History of anxiety? no
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yes Drugs and/or therapy successful in past? no Is patient ventilated no mild to moderate yes no no yes Effective? Increase drip before bolus. no yes
yes
Can this be continued? no Severity of anxiety?
yes
Continue successful treatment.
yes Still anxious? no
Assess patient and document response.
yes
moderate to severe
Does patient have nasogastric, feeding, or gastrostomy tube? Can they take PO? no
Give oral anxiolytic and allow time for effect.
Effective? no
yes
Repeat or increase dose, allow adequate time for effect, or change drug.
yes Assess patient, document response, keep on lowest effective dose, consider patient condition, wean when appropriate as per weaning guidelines. yes Use intermittent sedation for 24h. Effective? Check frequency and duration. no
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Start infusion AFTER bolus. yes Effective? Will patient be on drip for more than 5 days? no
Consider intramuscular/intravenous drugs.
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Effective? Would patient benefit from continuous infusion? yes
Give enough bolus to reduce anxiety and allow time for effect. yes Still anxious? no Keep at present drip rate.
no
For episodic anxiety, continue intermittent use.
ED
Assess patient, document response, keep on lowest effective dose, consider patient condition, wean when appropriate as per weaning guidelines.
Consider intermittent doses of longer acting drugs (ie lorazepam, diazepam) or consider combination of drugs (ie buspirone) to manage long-term anxiety.
Assess patient every 24 hours and document progress, keep on lowest effective dose, consider patient condition, wean when appropriate as per weaning guidelines.
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Acute pain management: scientific evidence Sample case
The patient is a 45-year-old woman who was admitted to the ICU with a new onset of unstable angina. She has multiple risk factors: a 25-year history of cigarette use, a cholesterol level of 6.5 mmol/l, and her mothers death at age 50 from an acute myocardial infarction. Other medical factors include adult onset diabetes and asthma. Psychosocial factors include a divorce within the past nine months and being laid off from her factory job six months ago. When informed that she is scheduled for an angiogram, the patient is anxious and weeps periodically. Her vital signs are as follows: blood pressure (BP) 164/92, heart rate (HR) 100, respiratory rate (RR) 32.
Management points (using the algorithm in Figure 12.2 as a guide)
The first step is to assess for dyspnoea. The patient indicates that she uses an inhaler occasionally as needed. Upon auscultation of the chest, it is noted that the patient has wheezes. A bronchodilator is administered, the wheezing stops, and the RR decreases to 24/min. When questioned about pain, the patient quantifies her pain as a 3 on a VNRS of 110, and describes it as mid-sternal heaviness with no radiation. Two nitroglycerin tablets sublingually give complete relief within 10 minutes. The patient is oriented and responds to questions appropriately, and exhibits no signs of cognitive impairment or delirium at this time. However, signs of anxiety persist, and after referring to the algorithm, the treatment team considers administering a small dose of an anxiolytic at this time. According to information from the admission database, the patient has a low level of education, and all information given to her is adjusted to her level of understanding. Non-medical language and diagrams are used whenever possible. A real angiogram catheter is shown to the patient. She says that she feels less scared about the procedure, but is still worried about her medical bills and about dying like her mother. A plan is developed to help her verbalise concerns about death and dying issues. It is determined that she does not need a psychiatric evaluation at this time but she does need to talk about her fears. Visits from the chaplain on call and the social worker are arranged. Due to the severity of her disease, the patient undergoes the coronary angiogram with a percutaneous transluminal coronary angioplasty. Her course after the procedure is routine, except for some confusion and agitation noted during the night. Before sheath removal, midazolam and morphine sulphate are administered. Subsequently, she becomes agitated and screams that she is in pain when pressure is held on her groin. She begins to thrash in the bed, strike out at staff and attempt to bend her cannulated leg, risking haemorrhage. She is given additional midazolam and morphine sulphate; however, neither sedation nor pain relief results. Instead she becomes more agitated. She is diagnosed as having delirium because she is quite fearful, her speech is incoherent and she seems disoriented. After receiving a 2 mg bolus dose of haloperidol intravenously, the patient is calm and sedated within 30 minutes. Serious outcomes were avoided because the delirium was diagnosed and promptly treated. The patient is discharged two days later without further complications.
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Appendix A:
Membership
Membership and terms of reference of the Working Party
Professor Michael Cousins AM (Chair) Expert in pain medicine and pain research Mr John Bell Community pharmacist Dr Michael Bollen Expert in general practice Dr Milton Cohen Expert in rheumatology Mr Brian Collopy Expert in surgery and in clinical indicators Mrs Anne Evans Registered nurse
Dr Roger Goucke Expert in pain management Dr David Gronow Expert in pain management Dr Richard Halliwell Acute pain specialist
Professor Irena Madjar Nurse educator
Associate Professor Ian Power Acute pain specialist Ms Meryl Fullerton Consumer Representative
Dr Ron Tomlins was invited to join the working party during the second stage consultation process.
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Terms of reference
Undertake the development of clinical practice guidelines and implementation strategies for the management of acute pain in specific settings, following the procedures recommended by the Quality of Care and Health Outcomes Committees draft first edition of Guidelines for the Development and Implementation of Clinical Practice Guidelines. Specifically: examine and identify: the scope of the problem and the current status of acute pain management; the questions to be addressed by the guidelines; and the target groups and settings to be addressed by the guidelines assess any existing guidelines; review and evaluate: the literature on patients experience and the efficacy and outcomes of pain management in various clinical settings; and the extent and strength of scientific evidence for the effectiveness and appropriateness of relevant interventions, including:
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the appropriateness of recommending preventative approaches in the various settings of acute pain management;
the risk/benefit ratio of invasive and non-invasive methods of acute pain management; and - pharmacologic and non-pharmacologic interventions; identify: cost issues involved in the effective management of acute pain; short and long-term health outcomes and measures; recommendations for best practice; and areas for future research; write evidence-based guideline documents for the identified target groups. As a minimum it is expected that two documents will be written: one aimed at clinicians and one aimed at consumers. A short summary for day-to-day use by health care professionals may also be developed; prepare appropriate appendices to the clinician and consumer guideline documents; undertake wider consultation; report on the guideline development process, including: a strategy for dissemination and implementation; and
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a short and long-term plan for evaluating and updating the guideline documents; and
provide advice and present clinical practice guidelines to the Quality of Care and Health Outcomes Committee.
Appendix B: Process report

As part of the national program to promote the development of evidence-based clinical practice aimed at improving both the quality or health care and health outcomes, the then National Health Advisory Committee (NHAC) discussed the development of clinical practice guidelines for the management of acute pain in February 1995. There had been emerging evidence of the adverse physiological and psychological effects of unrelieved severe acute pain impacting heavily on the health care system in Australia and it was felt that the implementation of the guidelines could significantly reduce the overall cost of health care. A multidisciplinary working party and consultative group that was established in late 1995 through the NHACs Quality of Care and Health Outcomes Committee (QCHOC) to consider the submissions met for the first time on 20 October 1995 in Sydney. Membership of the Working Party is outlined at Appendix A Consultative Group A consultative group was also established to assist with the review of submissions and consisted of: Dr Pam Macintyre Acute pain specialist Ms Judith Atkinson Nurse educator and acute pain specialist Dr David Crompton Psychiatrist
As the Working Party had not completed its task by the end of the NHMRC triennium at the close of 1996, it was disbanded and re-established with the addition of the following members to the consultative group:
Dr Chris Baggoley Emergency medicine Dr Fran Boyle Oncology
Associate Professor Peter Brownridge Obstetrics anaesthesia/analgesia Dr Geoff M Clark Intensive care
Dr Michael Cooper Paediatric anaesthesia/pain management Dr Seamus Dalton Rehabilitation medicine Professor Ben Freedman Cardiac-related pain Dr Ray Garrick Neurology and pain management Dr Jack Gersham Dental and orofacial pain Dr Paul Glare Palliative care
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Professor Ross Harris Clinical psychology/pain management Dr Geoff Gourlay Clinical pharmacology/pain management Dr Benny Katz Geriatrics/pain management Dr Henry Kilham Paediatrics/pain management Professor John Levi Oncology Dr David Murrell Paediatric anaesthesia/pain management Dr Michael Nicholas Clinical psychology/pain management Dr Michael Paech Obstetrics anaesthesia
Dr Kathryn Refshauge Physiotherapy
Dr Stephen Ruff Orthopaedic and trauma surgery
Dr Phillip Siddall Anaesthesia/pain management and research Professor Dennis Smith Rehabilitation medicine
Dr Suellen Walker Anaesthesia/pain management (adult and paediatric) Dr Elizabeth Ward Obstetrics anaesthesia/analgesia
The aim of the report is to outline practitioner principles for the treatment and management of acute pain based on a systematic evaluation of current evidence. The report is not intended to be prescriptive or to replace clinical knowledge or judgement. Target group The target group for the report is health care practitioners engaged in the care of patients experiencing acute pain.
Process
First stage consultation In accordance with Section 12 of the National Health and Medical Research Council Act 1992, as part of the required public consultation process, advertisements appeared in the government gazette and the media Australia wide (August 1995) notifying of the intent to issue clinical guidelines in the management of acute pain (including cancer pain). The public was invited to make submissions and the 11 submissions received were considered by the working party in its task of compiling the report. Although the Working Party met regularly to identify future directions, a considerable proportion of its work was conducted out of session. The Working Party 178
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Process report
considered current available evidence and submissions received, a technical writer was contracted to make revisions and finalise the editing of the document. The draft report was submitted to the 1516 September 1997 meeting of NHAC where approval was given to proceed to the second stage consultation process. Second stage consultation A notice appeared in the government gazette of 23 October 1997 calling for submissions from the public for the second stage consultation process with a submission deadline of 24 November. A media release was issued on 7 November, and an article appeared in the Australian Doctor on 21 November. A wide range of government and non-government organisations, professional associations, colleges, academics and research staff, health professionals, consumers and consumer groups were also invited to submit comments on the draft document some 300 in all. Of the 80 submissions received, some dealt with chronic pain rather than acute pain which had not been the focus of the report. The Working Party commenced its task of consideration of submissions and adjustment to the report where evidence was presented for such a change. Concern had been expressed by groups representing chiropractors, acupuncturists, radiation oncologists and obstetricians regarding the reports content under their particular discipline. Considerable effort was made to address the issues raised. There had been two teleconferences and one face-to-face meeting of the Working Party during the second stage consultation process, there having been considerable work conducted out of session to complete the report. A clinicians quick reference guide for the management of acute pain, summarising the major components of the report and a consumer guide on acute pain management are to be published in addition to the report. Dissemination The document will be available for: clinical colleges; academic departments; allied health organisations; State and Territory health departments; public policy makers; hospitals; consumer and patient groups; health economists; and professional journals. The document will also be published electronically.
In addition individual members of the Working Party would make themselves available to discuss the quick reference guide, by phone or in person, with whoever is nominated by various divisions of general practice to become a reference/promotion person. Evaluation and updating The report and guides reflect existing knowledge and practices at the time of publication. However, this is a rapidly changing area and as new evidence becomes available revision of the report and guides will be required. 179
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List of acronyms and abbreviations

5HT3 ABS ACC ACTH ADH AHA AHCPR ANZCA APS ASA AZT bd BP CBC CI CNS CPAP CRPS CSE CSF CT D2 ECF ECG EMLA EPSE ESR GABA GON GP H1 serotonin Australian Bureau of Statistics American College of Cardiology adrenocorticotropic hormone antidiuretic hormone American Heart Association Agency for Health Care Policy and Research Australian and New Zealand College of Anaesthetists acute pain service American Society of Anesthiologists azidothymidine (zidovudine) twice daily blood pressure complete blood count confidence interval central nervous system continuous positive airway pressure complex regional pain syndromes combined spinal epidural cerebrospinal fluid computed tomography dopamine extracellular fluid electrocardiogram eutectic mixture of local anaesthetic extra pyramidal side effects erythrocyte sedimentation rate gamma-aminobutyric acid greater occipital nerve general practitioner histamine
HIV/AIDS HR IASP ICF ICU IL IM
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interleukin intramuscular
human immunodeficiency virus/acquired immune deficiency syndrome heart rate International Association for the Study of Pain intracellular fluid intensive care unit
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IV M3G M6G MD MRI NHAC NHMRC NMDA NNT NO NRG NRM NSAIDs OTFC PAG PAR PCA PO prn QCHOC qid RACS RCTs RICE RN RR RSD SC SIP SLR SMP SSRI TENS TNF TTS UA VAS VNRS WHO ZJ
intravenous morphine-3-glucuronide morphine-6-glucuronide Doctor of Medicine magnetic resonance imaging National Health Advisory Committee National Health and Medical Research Council N-methyl-D-aspartate numbers needed to treat nitrous oxide nucleus reticularis gigantocellularis nucleus raphe magnus non-steroidal anti-inflammatory drugs oral transmucosal fentanyl citrate peri-aqueductal grey
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patient-activated reservoir patient-controlled analgesia by mouth as needed Quality of Care Health Outcomes Committee four times a day Royal Australian College of Surgeons randomised controlled trials Rest/Ice/Compression/Elevation registered nurse respiratory rate reflex sympathetic dystrophy (now CRPS type I) subcutaneous sympathetically independent pain straight leg raising sympathetically maintained pain selective serotinergic re-uptake inhibitors transcutaneous electrical nerve stimulation tumour necrosis factor transdermal therapeutic systems urine analysis visual analogue scale verbal numerical rating scale World Health Organization zygapophyseal joints
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Glossary
Methodology
Best evidence synthesis: Evidence based on the best evidence principle as used in law, in which the same evidence that would be essential in one case might be disregarded in a second case because better evidence becomes available. Case study design: A non-experimental study that extensively explores a single unit (a unit may be a person, family, or group) or a very small number of units. Descriptive study: A non-experimental study in which variables or subject characteristics are examined as they naturally occur for the purpose of describing or comparing samples or examining relationships among a set of variables. Experimental study: (Randomised controlled trial or randomised clinical trial) An experiment that uses random assignment to create treatment and control groups so that changes can be inferred or attributed to the experimental treatment. Meta-analysis: The process of combining the results of several related studies to obtain more reliable conclusions. Numbers needed to treat: Indication of the number of patients required to undergo a modality in order to gain outcome. Peer review: Evaluation of the present document by an interdisciplinary panel of experts using the Institute of Medicine attributes of clinical practice guidelines (Field & Lohr 1990) as evaluation criteria. Pilot review: Review and testing of the present report by clinicians to evaluate aspects of the report such as clarity, clinical applicability, flexibility, resource utilisation, training needs, and cost of implementation. Review of a consumer version of the present report by consumers and clinicians to evaluate its clarity, usefulness, flexibility, and accuracy. Quasi-experimental study: (Includes non-randomised controlled trial or nonrandomised clinical trial) A design that does not use random assignment to create treatment and control groups but uses other methods to control validity threats so that changes can be inferred or attributed to the experimental treatment. Scientific review: An exhaustive literature search to define and critically evaluate the knowledge base for pain assessment and interventions.
Pain terms
Allodynia: Pain due to a stimulus which does not normally provoke pain. Central pain: Pain initiated or caused by a primary lesion or dysfunction in the central nervous system. Complex regional pain syndrome type I (reflex sympathetic dystrophy): Syndrome incorporating pain, hyperalgesia, allodynia, swelling, vasomotor and sudomotor changes in the region of pain following an noxious event but not limited to a single peripheral nerve and out of proportion to the initial trauma. Complex regional pain syndrome type II (causalgia): A syndrome of sustained burning pain, allodynia and hyperpathia after a traumatic nerve lesion, often combined with vasomotor and sudomotor dysfunction and leter trophic changes. Dysaesthesia: An unpleasant abnormal sensation, whether spontaneous or provoked. Hyperaesthesia: Increased sensitivity to stimulation, excluding the special senses. Hyperalgesia: Increased pain in response to a painful stimulus.
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Hyperpathia: A painful syndrome characterised by an abnormal pain reaction to a stimulus, especially a repetitive stimulus, as well as an increased threshold. Hypo-aesthesia: Decreased sensitivity to stimulation, excluding the special senses. Hypo-algesia: Diminished pain in response to a normally painful stimulus. Neuralgia: Pain in the distribution of a nerve or nerves. Neuritis: Inflammation of a nerve or nerves. Neuropathic pain: Pain initiated or caused by a primary lesion, dysfunction, or transitory perturbation in the peripheral or central nervous system. Neuropathy: A disturbance of function or pathological change in a nerve or nerves. Nociception: The signalling of tissue damage, usually but not always associated with pain. Nociceptor: A receptor preferentially sensitive to a noxious stimulus or a stimulus which would become noxious if prolonged. Noxious stimulus: A stimulus which is damaging to normal tissues. Pain threshold: The level of stimulus at which a sensation is described as painful. Pain tolerance level: The greatest level of pain which a subject is prepared to tolerate. Pain: An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage. Paraesthesia: An abnormal sensation, whether spontaneous or evoked. Peripheral neuropathic pain: Pain initiated or caused by a primary lesion or dysfunction in the peripheral nervous system. Phantom pain: Pain referred to a surgically removed limb or portion thereof. Radicular pain: Well localised, dysaesthetic pain in the distribution of a spinal nerve root, accompanied by signs of nerve root dysfunction (radiculopathy). Referred pain: Pain appreciated remote from but neuro-anatomically related to its origin. Sciatica: Old term referring to pain arising in the lower limb as a result of nerve compression. Should be abandoned in preference of describing pain as referred, radicular or as pain in the lower limb. Spinal pain: Pain perceived as arising from the vertebral column or its associated structures. Stump pain: Pain at the extremity of an amputation.
Pharmacological management
Analgesia: Absence of pain in response to stimulation which would normally be painful. Anaesthesia dolorosa: Pain in an area or region which is anaesthetised. EMLA (eutectic mixture of local anaesthetic): An ointment that contains local anaesthetics so that topical application causes local anaesthesia without the need for injection. Epidural: Situated within the spinal canal, on or outside the dura mater (tough membrane surrounding the spinal cord); synonyms are extradural and peridural. Equi-analgesic: Having equal pain-relieving effect; for example, morphine sulfate 10 mg intramuscular is generally used for opioid analgesic comparisons. Interpleural: Situated between the membrane surrounding the lungs and the membrane lining the thoracic cavity.
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Glossary
Intrathecal: Within a sheath (eg cerebrospinal fluid that is contained within the dura mater). Local nerve block: Infiltration of a local anaesthetic around a peripheral nerve so as to produce anaesthesia in the area supplied by the nerve. Mixed opioid agonist-antagonist: A compound that has an affinity for two or more types of opioid receptors and blocks opioid effects on one receptor type while producing opioid effects on a second receptor type. NSAID (non-steroidal anti-inflammatory drug): Aspirin-like drug that reduces pain and inflammation arising from injured tissue. Opioid agonist: Any morphine-like compound that produces bodily effects including pain relief, sedation, constipation, and respiratory depression. Opioid partial agonist: A compound that has an affinity for and stimulates physiological activity at the same cell receptors as opioid agonists but that produces only a partial (ie submaximal) bodily response. PCA (patient-controlled analgesia): Self administration of an analgesic by a patient instructed in doing so; usually refers to self dosing with intravenous opioid (eg morphine) administered by means of a programmable pump. Perineural: Surrounding a nerve.
Non-pharmacological management
Acupuncture: The piercing of specific body sites with needles to produce pain relief. Counterirritant: An agent that is applied to produce irritation at one site so as to decrease perception of pain at the same or a distant site. Cryo-analgesia: The damage of peripheral nerves by extreme cold to achieve prolonged pain relief. Cryotherapy: The therapeutic use of cold to reduce discomfort, limit progression of tissue oedema, or break a cycle of muscle spasm. Patient education: Providing the patient with an explanation of peri-operative procedures, expected postoperative sensations, and instruction to help decrease mobility-related discomfort. Relaxation methods: A variety of techniques to help decrease anxiety and muscle tension; these may include imagery, distraction, and progressive muscle relaxation. Tactile strategies: Strategies that provide comfort through the sense of touch, such as stroking or massage. TENS (transcutaneous electrical nerve stimulation): A method of producing electroanalgesia through electrodes applied to the skin.
Miscellaneous termspatient management and monitoring

Conscious sedation: Light sedation during which the patient retains airway reflexes and responses to verbal stimuli. Oximetry: Determination of the oxygen saturation of arterial blood, typically by means of an external probe applied around a finger or toe. Paradoxical reaction: A response (eg to a drug) that is the opposite of the usual response, such as agitation produced in a individual patient by a drug normally considered to be a sedative.
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Index
abdominal pain ......................... 11719 in HIV/AIDS patients ................ 149 Aboriginal and Torres Strait Island peoples.......................... 15758 acupuncture ...................................... 41 for migraine ............................... 122 for postoperative pain ............ 80, 81 for tension headache.................. 123 acute pain service ...... 29, 3133, 61, 67 adjuvant agents ........................ 15152 allied health workers, role in pain management......................... 42 anaesthesia, general ................. 70, 112 anaesthesia, local.................................. 41, 65, 6465, 70, 76, 77, 84, 85, 112, 113 for children ............................ 1025 for orofacial pain........................ 126 in elderly patients...................... 162 in neonates and infants ............. 106 analgesia, inadequate......................... 9 analgesia, multimodal ...........41, 7677 anticonvulsants .................41, 151, 152 for herpes zoster infection ... 11617 for neuropathic pain .....15253, 154 in HIV/AIDS patients ................ 149 postoperative pain ....................... 84 antidepressants .................41, 151, 152 for herpes zoster infection ... 11617 for neuropathic pain ............ 11617 in HIV/AIDS patients ................ 149 postoperative pain ....................... 84 anxiety ..30, 35, 37, 43, 53, 56, 109, 111 APS ...............See acute pain service aspirin adverse effects ........................ 7374 for burn pain ..............................112 for children.................................102 for trauma pain ..........................112 in postoperative patients..............68 assessment of pain .............. 3538, 109 in intensive care settings ...........170 pain history ............................ 3637 patient history..............................36 patient involvement .....................36 physical examination ...................36 back pain...................... See spinal pain burn pain................................... 10913 background pain................... 11011 emergency care......10910, 111, 113 incident pain ..............................111 rehabilitation ....................... 11112 caesarean delivery ................ 89, 90, 91 cancer patients, pain in....... 56, 13948 children .................................. 1078
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cardiac pain............................... 11516 children aspirin ........................................102 assessment of pain .......................94 intra-operative management .......98 local anaesthesia .................... 1025 nitrous oxide...............................111 non-pharmacological strategies ....... ......................................... 95, 107 NSAIDs ................................ 74, 102 opioids ............................ 63, 99102 pain from surgical procedures.......... ......................................... 98105
childbirth.............................. See labour
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children (cont) pain in cancer patients .......... 1078 pain management ................ 93108 paracetamol ............................... 102 patient-controlled analgesia ............ .......................................100101 postoperative management.......... 98 pre-operative management.......... 98 procedural pain...................... 9597 communication difficulties.................. 9 complex regional pain syndromes......... ...................................... 15455 consumers ................................... 23, 43 corticosteroids................................... 41 for herpes zoster infection ......... 116 for migraine ............................... 122 in elderly patients.............. 161, 162 neuropathic pain ................ 147, 154 spinal pain ................................. 133 day surgery ................................. 8586 dental pain...................................... 126 education ..... 10, 31, 33, 4243, 61, 110 elderly patients cognitive impairment in..... 160, 162 neuropathic pain........................ 162 NSAIDs ...................................... 161 opioids ........................................ 161 pain in................. 47, 52, 73, 15962 emergency department ............. 16769 environmental factors 29, 109, 113, 118
ethnic groups...................................158 general practice.................................24 haemarthrosis, pain in.............. 12526 haemophilia, pain in ........... 61, 12526 headache acupuncture ...............................123 analgesic rebound ......................122 cervicogenic .......................... 12425 post-dural puncture......................69 post-lumbar puncture.................125 tension........................................123 herpes zoster infection antiviral agents ..........................116 pain in .................................. 11617 HIV/AIDS, pain in..................... 14850 hyperalgesia .............25, 26, 52, 84, 109 hypoxia.................................. 51, 53, 75 intensive care ............................ 16974 interventions cognitive-behavioural....................... .. 41, 7879, 87, 95, 107, 112, 113 pharmacological .................... 4041. See also anaesthesia, NSAIDs, aspirin, corticosteroids, nitrous oxide, opioids, paracetamol physical ...................... 41, 80, 81, 87
epidural analgesia ...........31, 6571, 77 advantages............................. 7071 for burn pain.............................. 112 in labour................................. 8891 local anaesthetic .......................... 67 non-opioid analgesics................... 68 opioids .................................... 6768 outcomes ...................................... 71 side effects and complications...... 69 epidural steroids for spinal pain............................ 133
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intrathecal analgesia .................. 6571 side effects and complications ......69
labour, pain in............................. 8791 migraine .................................... 12123 acupuncture ...............................122 anti-emetic agents......................122 cervical manual therapy ............122 corticosteroids ............................122 ergotamine .................................121 NSAIDs ......................................121 opioids ........................................121 triptans.......................................121 musculoskeletal pain ................ 12638 neck pain................................... 13134
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neonatal circumcision ..................... 107 neonates and infants postoperative pain ................. 1067 neuropathic pain..............109, 111, 113 corticosteroids .................... 147, 154 diagnosis ...................................... 39 in elderly patients...................... 162 in HIV/AIDS patients ................ 149 in postoperative patients ............. 54 treatment of ......................... 15255 nitrous oxide for incident pain......................... 111 in labour....................................... 88 nociceptive pain ..... 54, 67, 71, 109, 113 non-Englishspeaking patients ............ .................................35, 43, 157 NSAIDs..........................25, 7276, 185 adverse effects........................ 7374 dosage .................................... 7475 for burn pain...................... 110, 112 for haemophilia.......................... 125 for migraine ............................... 121 for orofacial pain........................ 126 for trauma pain.......................... 112 guidelines for use of ............... 7273 in children.................................. 102 in elderly patients...................... 161 in postoperative patients ....... 64, 68
opioids (cont) for burn pain .............. 110, 111, 112 for cardiac pain ..........................115 for haemophilia ..........................125 for incident pain .........................111 for migraine................................121 for neuropathic pain...................152 for spinal pain ............................133 for trauma pain ..........................112 in children ............................ 99102 in elderly patients ................ 16162 in epidural analgesia.............. 6768 in HIV/AIDS patients.................149 in intensive care settings ...........170 in labour .......................................88 in postoperative patients.. 33, 4564 ineffective in neuropathic pain ....39 neonates and infants..................106 routes of administration......... 5564 sites of action................................46 tolerance.......................................54 orofacial pain...................................126 paediatrics......................... See children pain history ............................... 36, 117 pain management plans.............. 8183 pain pathways............................. 2528 pain perception............................ 2526 pain rating scales ........................ 35, 84 paracetamol................................. 40, 76 for background pain ...................110 for burn pain ..............................112 for HIV/AIDS..............................149 for spinal pain ............................133 for trauma pain ..........................112 in children ..................................102 in neonates and infants..............106 in postoperative patients........ 63, 64 patient comfort............................ 45, 55 patient involvement ..........................43
nursing staff, role in pain management .............................................. 42 obstetric analgesia ...................... 8791 opioids 25, 40, 83 addiction ................................ 49, 55 adverse effects........................ 5055 allergy to ................................ 54, 55 dependence .......................... 16366 dosage .................................... 4650 epidural........................................ 84 for background pain................... 110
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patient-controlled analgesia ................. 33, 47, 49, 56, 57, 6062, 83, 110, 112, 185 in children...........................100101 placebo effect .................................... 80 post-discharge analgesia................... 86 postoperative pain37, 41, 80, 83, 4586 chronic ......................................... 78 in neonates and infants ......... 1067 neurosurgical patients ........... 8384 NSAIDs ........................................ 72 pregnancy, pain in ............................ 87 psychiatric illness ..................... 15859 psychological effects of pain........ 29, 30 psychological factors ....................... 118 rehabilitation ...................33, 65, 70, 83 peri-operative............................... 71 renal colic........................................ 169 respiratory depression ................ 5052 respiratory rate................55, 61, 66, 69 return to normal activity ............ 85, 86
sedation ................................................. 50, 51, 52, 55, 64, 66, 68, 72, 83, 111, 112 sedation score.................. 51, 52, 55, 84 spinal manual therapy.......................... ...................41, 81, 122, 13233 spinal pain......................... 12635, 184 bed rest.......................................127 chronic........................................135 corticosteroids ............................133 epidural steroids ........................133 lower back pain .................... 12730 neck pain ....................................131 non-pharmacological strategies ....... ......................................... 13133 NSAIDs ......................................133 opioids ........................................133 paracetamol................................133 sporting injuries........................ 13738 TENS .....................41, 78, 80, 81, 112 training .............................................33 trauma pain ........................ 57, 10913 emergency care............. 10910, 113 rehabilitation ....................... 11112
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Acute pain management: scientific evidence

Endorsed November 1998

Table 8.1 Table 8.2 Table 8.3 Table 8.4

Table 9.1 Table 9.2 Table 9.3

Richard Larkins Chairman National Health and Medical Research Council

Acute pain management: scientific evidence

Principles of pain management

Summary of scientific evidence and key management points

Acute pain services

Acute pain management: scientific evidence

Acute postoperative pain management in adults

Opioid analgesia Statements of evidence 4 p 60

Executive summary Key points (cont)

Acute pain management: scientific evidence

Non-pharmacological methods Statement of evidence

Special postoperative patients

III Fancourt-Smith et al 1990, Gold et al 1989

Executive summary Key points

II Sharma et al 1997, Bofill et al 1997

Acute pain management: scientific evidence

Burns and trauma pain

Acute herpes zoster infection

I McQuay et al 1996, 1995a

Acute pain management: scientific evidence

Acute musculoskeletal pain

Acute pain in patients with cancer

Acute pain in patients with HIV/AIDS

Acute pain management: scientific evidence

Adjuvant agents and the treatment of neuropathic pain

Pain in the elderly

Emergency department and critical care

Acute pain management: scientific evidence

Levels of clinical evidence

Information for consumers

Acute pain management: scientific evidence

Implications for general practice

The clinical picture

Definition of acute pain

Pain perception and pain pathways

Primary afferent fibres, the dorsal horn and descending modulation

The clinical picture

Acute pain management: scientific evidence

The clinical picture

Adverse physiological and psychological effects of pain

Postoperative pain Surgical trauma

Psychological, environmental factors Other factors (eg drugs)

Acute phase cytokines (eg Interleukin 1,6) Neural

Acute pain management: scientific evidence

Figure 1.5 Vicious cycle of pain, anxiety and sleeplessness.

Hyperglycaemia, glucose intolerance, insulin resistance

Protein Fat Water and electrolyte flux

Acute pain services

Bedside pain management flow sheets

Acute pain services

Principles of acute pain assessment and management

Pain rating methods

Patients with special needs

worst possible pain

Acute pain management: scientific evidence

Factors altering pain what makes it worse? what makes it better?

Associated symptoms (eg nausea) Temporal factors