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Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e >

Chapter 35: Acute Pain Management

James Ducharme

INTRODUCTION
Pain is the most common presenting symptom for patients coming to the ED, with 75% to 80% of all
patients having pain as their primary complaint.1 Despite increasing research and information about pain
management, oligoanalgesia, or the under treatment of pain, persists.2,3,4,5 While all patients are
susceptible to oligoanalgesia, certain subgroups, such as ethnic minorities, the aged, the very young, and
those with diminished cognitive function, are more at risk (Table 35-1).6,7,8,9 Pain management is further
influenced by concerns of prescription opioid misuse, a rising concern in all age groups but most notably in
adolescents and young adults. Pain and addiction are not mutually exclusive,10 and appropriate treatment
of acute pain should not be withheld for fear of facilitating drug misuse.

TABLE 35-1
Barriers to Adequate ED Pain Control

Patient Related Provider Related System Related

Ethnicity, gender, age (very Inadequate education Lack of clearly articulated

young, very old)
Diminished cognitive function
Fear of medications:
addiction, side e ects
Acceptance of pain as being
inevitable
Unwillingness to bother
healthcare providers
No objective measuring tool for pain standards
Accepting only pain reports that conform Paucity of treatment
to our expectations guidelines
Perception of addiction and drug-seeking Fear of regulatory sanctions
behavior Lack of healthcare provider
accountability

Specific measures to treat pain should occur in addition to, and at the same time as, treatment of the
underlying illness or injury. It is not possible to generalize the extent and quality of pain control needed for
a specific patient. For example, pain is an indicator of ongoing cardiac ischemia, and the goal should be to
eliminate all pain. On the other hand, a patient with a traumatic injury may choose to endure more pain
out of personal or cultural beliefs. Physicians may limit analgesics in those with head injuries to perform
serial neurologic examinations. Whenever possible, medications that act on specific sites that initiate the
pain signal—a mechanistic approach—are preferred to agents such as opioids that mask pain, which is a

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symptomatic approach. Current migraine treatment is an excellent example of the mechanistic approach;
preferred treatment includes a serotonin agonist (triptan)11 or a dopamine antagonist (phenothiazine),12
rather than opiates.13,14

PATHOPHYSIOLOGY
Pain is the physiologic response to a noxious stimulus, whereas su ering—the expression of pain—is
modified by the complex interaction of cognitive, behavioral, and sociocultural dimensions. Individual pain
experience is therefore not static, but varies depending on current and past medical history, physical and
emotional maturity, cognitive state, meaning of pain, family attitudes, culture, and environment. Emotions
can modify pain either negatively or positively: fear and anxiety may accentuate pain, or pain can be
suppressed completely if an essential task must be performed or if there is acute concern about a loved
one.

The peripheral nervous system (e.g., nociceptors, C fibers, A-δ fibers, and free nerve endings) initiates the
sensation of somatic pain by responding to a noxious stimulus and sending a neuronal discharge to the
dorsal horn of the spinal cord.15 Neurons in the dorsal horn of the spinal cord integrate and modulate input
from multiple peripheral nerves and other sensory stimuli. Transmission then proceeds up the spinal cord
to the CNS (e.g., hypothalamus, thalamic nuclei, limbic system, and reticular activating system) where
further integration and processing generate the perception of pain. Identification and localization of pain,
cognitive interpretation, and triggering of emotional and physiologic reactions also occur at these central
sites. Unlike somatic pain, which is easily localized, visceral pain pathways are more complex and di er in
structure from somatic pain pathways, which may explain the poor localization of visceral pain.

Opioid analgesics work by binding to receptors in the spinal cord and brain. There are four types of opioid
receptors: three classic families (delta, kappa, and mu, each with identified subtypes) and nociceptin, a
receptor with significant structural homology. These receptors are found in the brain, spinal cord, and GI
tract where their physiologic function is to interact with endogenous dynorphins, enkephalins,
endomorphins, endorphins, and nociceptin. Opioid analgesics interact with these receptors in varying
degrees, accounting for the di erence in desired and adverse e ects among the drugs in this class.
Stimulation of the mu-1 (μ1) receptor produces supraspinal analgesia. Stimulation of the mu-2 (μ2)
receptor results in euphoria, miosis, respiratory depression, and depressed GI motility. Stimulation of the
delta (δ) receptor produces analgesia, but less than the μ1 receptor, and also exerts an antidepressant
e ect. Stimulation of the kappa (κ) receptor produces dysphoria, along with dissociation, delirium, and
diuresis by inhibiting antidiuretic hormone release.

EVALUATION
Document the degree of pain on initial assessment. This process serves to identify patients with severe
pain, facilitates treatment, and meets the mandates of regulatory agencies that promote assessing and
treating pain. ED pain assessment should determine duration, location, quality, severity, and exacerbating
and relieving factors. The patient's subjective reporting of pain, not the physician's impression, is the basis
for pain assessment and treatment. There is at best a weak correlation between nonverbal signs, such as
tachycardia, tachypnea, and changes in patient expression and movements, and the patient's report of
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pain, so do not rely on these to determine the severity of a patient's pain16,17 or response to treatment.18
Because pain is dynamic and changes with time, periodic pain reassessment is needed.

Although standardized scales for measuring reported pain are commonly used, their impact on e ective
pain control is uncertain.19,20 The primary value of pain scales is their essential role in research enabling
reproducible comparisons of interventions. Some studies have suggested that the use of pain scales may
actually decrease the provision of analgesics. Given the subjectivity both of pain reporting and the
provider's interpretation of such reporting, the use of simple descriptors such as "a little" or "an awful lot"
is equally valid in the clinical setting. What is important is that the patient's subjective reporting should be
the basis for assessment and management. For most, but not all, painful conditions, the goal is to control
pain to the level the patient desires. Asking if the patient requires more analgesic may even be simpler and
accomplish more than using any standardized pain evaluation tool.21,22

PAIN SCALES

The purpose of pain scales is to quantitate pain severity, guide the selection and administration of an
analgesic agent, and reassess the pain response to determine the need for repeated doses or more
e ective analgesics. Several self-report instruments are valid in patients with acute pain, and some require
only a verbal response (Table 35-2). Each tool has advantages and specific limitations. ED personnel in any
one location should use the same tool so information collected is standardized. A value assigned by a
patient is not an absolute value but rather a reference point based on past personal experience.23

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TABLE 35-2
Pain Scales29A

Scale Method Comments

Adjective Patient rates pain by choosing from an Easy to administer.

rating scale ordered list of pain descriptors, ranging
(Figure 35- from no pain to worst possible pain, with
1) allowance for marks between discrete
labels.

Visual Patient places a mark that best describes Pain intensity measured in millimeters from
analog pain intensity along a 10-cm linear scale the no-pain end.
scale (VAS) marked at one end with a term such as no A di erence of 13 mm is the minimum
(Figure 35- pain and at the other end with worst clinically significant change noticeable by
2) imaginable pain. patients, whereas an average decrease of 30
mm appears to be the minimum acceptable
change for pain control.*

Numeric The patient is asked to self-report pain on Can be used in patients with visual, speech, or
rating scale a scale of 0 to 10 with descriptors. manual dexterity di iculties by using upheld
(Figure 35- fingers.
3) Not as discriminating as the VAS.

5-Point Patient rates pain as: A decrease of 1 point is a large change; scales
global scale 0 = none with more choices allow monitoring of small
1 = a little changes in pain and may be more sensitive to
2 = some changes.
3 = a lot
4 = worst possible

Verbal The patient is asked to self-report pain on Most commonly used scale; easy to
quantitative a scale of 0 to 10 without descriptors. administer.
scale

FIGURE 35-1.
Pain scale: Adjective rating scale.

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FIGURE 35-2.
Pain scale: Visual analog scale (VAS).

FIGURE 35-3.
Pain scale: Numeric rating scale.

PAIN SCALE PERFORMANCE IN SPECIAL PATIENT POPULATIONS

The elderly o en report pain di erently from younger patients because of physiologic, psychological, and
cultural changes associated with aging. Visual, hearing, motor, and cognitive impairments can be barriers
to e ective pain assessment. Using a numerical pain scale, the elderly may also experience a decrease in
the minimum clinically significant noticeable di erence in acute pain over time.24,25 Family members and
caregivers are o en able to judge nonverbal actions of the patient as representing pain or distress, so they
should be used if available to help with pain assessment in the noncommunicating elderly patient.

Trauma patients and those with acute intoxication do not perform as well on pain scales.26 Women are
more likely to express pain and to actively seek treatment for pain,27,28 yet there is a tendency to
underestimate and undertreat pain in women. Ethnicity of both the patient and the physician has a bearing
on di erent cultural concepts of pain and on the characteristics of culturally appropriate pain-related
behaviors.7 Translators and family members should be asked to provide assistance. There is also interplay
between the ethnicity of the patient and that of the physician.7 When there are language di iculties or
cross-cultural di erences, the visual analog scale is the preferred pain assessment tool because it is the
least a ected by these factors.

PHARMACOLOGIC PAIN TREATMENT

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The administration of pharmacologic agents is the mainstay of acute pain management. The key to
e ective pharmacologic pain management in the ED is selection of an agent appropriate for the intensity of
pain and it's time to onset of analgesic activity, ease of administration, safety, and e icacy.29 Acute pain is
usually accompanied by anxiety and feelings of loss of control. If verbal reassurance combined with an
analgesic does not su ice, an anxiolytic may be useful.

The "tiered approach" to pain management starts with an agent of low potency regardless of pain intensity,
assesses the response a er a clinically relevant period, and sequentially changes to agents of higher
potency if pain persists. The tiered approach for acute pain management unnecessarily subjects the patient
to more prolonged su ering. It is preferable to select initial analgesics that are appropriate to treat the
intensity (mild, moderate, or severe) of the patient's pain. Agents such as nonsteroidal anti-inflammatory
drugs should be considered for mild to moderate pain, and systemic opioids for moderate to severe pain
(Table 35-3). In specific instances such as renal and biliary colic, a parenteral nonsteroidal anti-
inflammatory drug may control severe pain, although combination therapy with an opioid is usually
superior.

TABLE 35-3
Pain Severity with VAS or NRS

Pain Severity VAS (0 to 100 mm) or NRS (0 to 10)

Mild VAS: 0 to 30–40 mm or NRS: 0 to 3–4

Moderate VAS: 40 to 60–70 mm or NRS: 4 to 6–7

Severe VAS: >60–70 mm or NRS: >6–7

Abbreviations: NRS = numeric rating scale; VAS = visual analog scale.

When possible, local anesthesia is a useful adjunct (Table 35-4). Peripheral nerve blockade for pain control
and for procedures is a useful option, especially if guided by US (see chapter 36, Local and Regional
Anesthesia).30,31

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TABLE 35-4
Pain Treatment: Comparison of Pharmacologic Classes

Class Route Advantages Disadvantages

Nonsteroidal anti- PO Mild/moderate somatic Use caution in the elderly and in those
inflammatory pain plus severe colicky with renal, GI, and hematologic
drugs pain disorders

Parenteral Does not require GI No more e ective than PO

absorption More costly

Opioids PO Can be e ective if Variable absorption, somewhat slower

adequately dosed onset

IM No IV access required Painful injections

Unreliable absorption

IV Ideal for titrated dosing Need for IV access

Local anesthetics Infiltration Technical ease Limited duration of action

Peripheral Opioid sparing Technically di icult at some sites

nerve Facilitated with use of US guidance
block

OPIOID ANALGESICS

Opioid analgesics are the cornerstone of pharmacologic management of moderate to severe acute pain
(Table 35-5). The term opiate refers to agents that are structurally related to natural alkaloids found in
opium, the dried resin of the opium poppy. The term opioid describes any compound with pharmacologic
activity similar to an opiate, regardless of chemical structure. Opioid use in the ED is o en a ected by
concern for the precipitation of adverse events, such as respiratory depression or hypotension, or for
facilitating drug-seeking behavior. As noted, a greater concern is oligoanalgesia and inadequate dosing of
opioids when used. Considerations for use of opioids include (1) desired onset of action, (2) available
routes of administration, (3) achievable frequency of administration, (4) concurrent use of nonopioid
analgesics and adjunctive agents, (5) possible incidence and severity of side e ects, and (6) continuation of
the agent in an inpatient or ambulatory setting

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TABLE 35-5
Pain Treatment: Initial Opioid Dosing

Typical Initial
Drug [Class] Pharmacokinetics Comments
Adult Dose

Morphine 0.1 Onset: 1–2 min Histamine release may produce transient
[natural milligram/kg (IV) and 10–15 hypotension or nausea and emesis; neither
alkaloid] IV min (IM/SC) require routine adjunctive treatment.

10 milligrams Peak e ect: 3–5  

IM/SC min (IV) and 15–
30 min (IM)

0.3 Duration: 1–2 h  

milligram/kg (IV) and 3–4 h
PO (IM/SC)

Hydromorphone 0.015 Onset: 3–5 min More euphoria inducing than morphine.
[semi-synthetic milligram/kg (IV)
alkaloid] IV

1–2 Peak e ect: 7–10

milligrams IM min (IV)

Duration: 2–4 h
(IV)

Fentanyl 1.0 Onset: <1 min (IV) Less cardiovascular depression than morphine.
[synthetic microgram/kg High doses can cause chest wall rigidity (>5
piperidine] IV Peak e ect: 2–5 micrograms/kg IV).
min (IV)

Duration: 30–60
min (IV)

100-   Used for breakthrough pain in opioid-tolerant

microgram cancer patients.
nasal spray in Wait >2 h before treating another episode.
1 nostril May increase dose by 100 micrograms per
episode.

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Typical Initial
Drug [Class] Pharmacokinetics Comments
Adult Dose

100-   Used for breakthrough pain in opioid-tolerant

microgram cancer patients.
buccal May repeat a er 30 min.
mucosa tablet

Wait >4 h before treating another episode.

May increase dose by 100 micrograms per
episode.
Available transmucosal forms not
bioequivalent.

Meperidine 1.0–1.5 Onset: 5 min (IV) Contraindicated when patient is taking a

(pethidine) milligrams/kg monoamine oxidase inhibitor.
[synthetic IV/IM Peak e ect: 5–10 Neurotoxicity may occur when multiple doses
piperidine] min (IV) are given in the presence of renal failure.

Duration: 2–3 h
(IV)

Oxycodone 5–10 Onset: 10–15 min Lower incidence of nausea.

[semi-synthetic milligrams PO (PO) Possible inadvertent acetaminophen overdose
alkaloid] OR with combination agents.
0.125
milligram/kg
PO

30 milligrams Duration: 3–6 h

PR (PO)

Hydrocodone 5–10 Onset: 30–60 min Lower incidence of nausea.

[semi-synthetic milligrams PO (PO) Possible inadvertent acetaminophen overdose
alkaloid] with combination agents.
Duration: 4–6 h
(PO)

Codeine [natural 30–60 Onset: 30–60 min High incidence of GI side e ects.
alkaloid] milligrams PO (PO) Some patients cannot convert to codeine-6-
glucuronide and morphine.
30–100 Duration: 4–6 h Possible inadvertent acetaminophen overdose
milligrams IM (PO) with combination agents.

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Typical Initial
Drug [Class] Pharmacokinetics Comments
Adult Dose

Tramadol 50–100 Onset: 10–15 min CNS side e ects common.

[other] milligrams PO (PO)

Duration: 4–6 h
(PO)

Opioids need to be titrated to e ect; patients di er greatly in their response to opioid analgesics.32,33,34
Variation in pain reduction is related to age, initial pain severity, and previous or chronic exposure to
opioids, but not body mass35,36 or gender.37 Relative potency estimates provide a rational basis for
selecting the appropriate starting dose to initiate analgesic therapy,38 changing the route of administration
(e.g., from parenteral to PO), or switching to another opioid (Table 35-6), but undue reliance on these ratios
is an oversimplification with potential for over- or underdosing.39

TABLE 35-6
Equipotent Opioid Doses

Equipotent IV Dose Equipotent PO Dose Equipotent IM Dose

Drug
(milligrams) (milligrams) (milligrams)

Morphine 10 60 (acute) and 30 10

(chronic)

Hydromorphone 1.5 7.5 1.5

Fentanyl 0.1 0.2 (transmucosal) 0.1

Meperidine 75 300 75
(pethidine)

Oxycodone 15 30 15

Hydrocodone — 30 —

Codeine 130 200 130

Tramadol — 350 —

Opioid hypersensitivity is uncommon, and true allergic reactions are extremely rare. There is minimal
evidence of clinical cross-sensitivity within opioid classes, with the possible exception that cross-sensitivity

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has been suggested among the piperidines (fentanyl, alfentanil, sufentanil, and meperidine). Until more is
known, it would be prudent to switch to a drug from a di erent opioid class if a patient develops a
hypersensitivity reaction. When used in equianalgesic doses, there is no compelling evidence to
recommend one opioid over another. As much as possible, avoid using multiple agents, and titrate a single
drug to the desired e ect.

The use of meperidine is discouraged for several reasons: it is o en underdosed; meperidine can interact
with many drugs to precipitate a serotonin syndrome; and the parent drug is metabolized to
normeperidine, which has neuroexcitatory properties and a long elimination half-life (24 to 48 hours).40
Normeperidine can accumulate and produce toxicity in the elderly and those with renal failure, although
this is a rare event.

Codeine is not a reliable analgesic, and it produces more nausea, vomiting, and dysphoria than other
opioids. The analgesic e ect of codeine is highly dependent on the metabolic conversion to the active
metabolites codeine-6-glucuronide and morphine. Up to 10% of the U.S. population is deficient in the
relevant enzymes for this conversion and, therefore, has an inadequate analgesic response to codeine.
Conversely, there are case reports of neonatal deaths as a result of breastfeeding from mothers who were
hypermetabolizers of codeine. In addition, the standard PO dose of 30 to 60 milligrams produces little
analgesic e ect above that of acetaminophen or nonsteroidal anti-inflammatory drugs.41

Tramadol binds to mu-receptors and weakly inhibits the reuptake of norepinephrine and serotonin
producing a central opioid analgesic e ect. Common side e ects include dizziness, nausea, constipation
and headache. Tramadol can induce the serotonin syndrome. Severe toxicity can include agitation and
seizures. It is one of the many substances that can produce a false-positive result on the urine
phencyclidine screen.42

Adverse e ects of opioids include nausea, vomiting, constipation, pruritus, urinary retention, confusion,
and respiratory depression. Pruritus, urinary retention, confusion, and respiratory depression are more
common with IV, transmucosal, and epidural administrations as opposed to PO administration.

Adjuncts are sometimes used to enhance the analgesic e ect, reduce the amount of opioid required, and
prevent side e ects (Table 35-7). Depending on the agent, amount, route, and setting, a beneficial e ect
can be seen. However, appropriate titration with opioids in the ED is highly e ective, and there are few data
to support the routine use of adjuncts with opioids in the ED.43 Pretreatment with antiemetics is not
necessary given the low risk of emesis,44 but symptom-targeted therapy is sometimes necessary.

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TABLE 35-7
Pain Management: Adjunctive Medications

Drug Initial Dosing Pharmacokinetics Comments

Prochlorperazine 5–10 milligrams IV/IM Duration: 4–6 h Can cause extrapyramidal reactions

Promethazine 25–50 milligrams IV/IM Duration: 4–6 h Can cause extrapyramidal reactions

Metoclopramide 5–10 milligrams IV/IM Duration: 4–6 h Can cause extrapyramidal reactions

Transdermal formulations are not useful for acute pain treatment because of delayed onset and prolonged
duration of action. Transdermal fentanyl and transdermal buprenorphine preparations are used for chronic
pain, particularly in cancer patients. When such patients are treated for acute pain in the ED, it is best to
remove the delayed-release transdermal opioid patches to better titrate the acute opioid dose and to
minimize adverse reactions from the combination of agents.

OPIOID AGONISTS-ANTAGONISTS

Opioid agonists-antagonists are used to minimize some of the adverse e ects of pure opioid agonists
(Table 35-8). The major benefit claimed is a ceiling on respiratory depression (no further reduction in
respiration with increasing doses past a set amount). It is not clear if there is a ceiling e ect for analgesia.
The variability in e icacy relates to each particular agent's a inity for the various central opioid receptors.
Because of the antagonistic e ects, these agents should be used with extreme caution in patients with
opioid addiction as they may precipitate withdrawal symptoms.

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TABLE 35-8
Pain Management: Initial Opioid Agonist-Antagonist Dosing

Drug [Class] Initial Dosing Pharmacokinetics Comments

Buprenorphine 0.3 milligram IV/IM every Onset: rapid Sedation, dizziness,

[synthetic oripavine] 6h Duration: 4–10 h nausea

0.4 milligram
sublingually every 6-8 h

Butorphanol [synthetic 0.5–2.0 milligrams IV Onset: <1 min Sedation, dizziness,

morphinan] every 3–4 h Duration: 2–4 h nausea

1–4 milligrams IM every

3–4 h

Dezocine [synthetic 2.5–10.0 milligrams IV Onset: 15 min (IV) and 30 Dizziness, respiratory
benzomorphan] every 4 h min (IM) depression
Duration: 4–6 h
5–20 milligrams IM every
6h

Nalbuphine [synthetic 10–20 milligrams Onset: 2–3 min (IV) and Sedation, headache,
morphinan] IV/IM/SC every 3–6 h 30 min (IM) dizziness
Duration: 3–6 h

Pentazocine [synthetic 30 milligrams IV/IM/SC Onset: 2–3 min (IV) and CNS side e ects
benzomorphan] every 3–6 h 15–20 min (IM)
Duration: 2–3 h

NONOPIOID AGENTS

Acetaminophen (paracetamol) is an e ective analgesic for mild to moderate pain (Table 35-9).45
Acetaminophen does not a ect platelet aggregation and does not have anti-inflammatory properties. No
change is required for renal or mild hepatic impairment (see chapter 190, Acetaminophen).

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TABLE 35-9
Pain Management: Nonopioid Analgesics
Drug Adult Dosage
Acetaminophen 325–1000 milligrams PO every 4–6 h
(paracetamol)
325–650 milligrams PR every 4–6 h
If >50 kg: 1 gram IV every 6 h
If <50 kg: 15 milligrams/kg IV every 6
h
Aspirin 325–650 milligrams PO every 4 h
300–600 milligrams PR every 4–6 h
Ibuprofen 400–800 milligrams PO every 4–6 h
400–800 milligrams IV every 6 h
Naproxen 250–500 milligrams PO every 8–12 h
Indomethacin 25–50 milligrams PO every 8 h
50 milligrams PR every 6 h
Ketorolac Multiple dose therapy: 30 milligrams
IV/IM every 6 h, 15 milligrams IV/IM
every 6 h if age >65 y or weight <50
kg
Single dose therapy: 60 milligrams
IM or 30 milligrams IV, 30 milligrams
IM or 15 milligrams IV if age >65 y or
weight <50 kg
10 milligrams PO every 4-6 h
Comments
Liver dysfunction and necrosis.
Maximum oral dose is 3.9 grams per day when
using the 325-milligram oral preparation and 3
grams per day when using the 500-milligram
oral preparation.
Maximum IV dose is 4 g per day.
GI irritation and mucosal bleeding.
Platelet dysfunction.
Tinnitus, CNS toxicity, metabolic acidosis.
Maximum dose is 4 g per day.
GI upset, platelet dysfunction, renal
dysfunction, bronchospasm.
Maximum dose is 2400 milligrams per day.
GI upset, platelet dysfunction, renal
dysfunction, bronchospasm.
Maximum dose is 1250 milligrams per day for
acute therapy.
GI upset, platelet dysfunction, renal
dysfunction, bronchospasm.
Maximum dose is 200 milligrams per day.
GI upset, platelet dysfunction, renal
dysfunction, bronchospasm.
Greater risk of GI bleeding than ibuprofen.
Use limited to 3 d IV and 5 d PO.
Maximum IV/IM dose is 120 milligrams per day,
but if age >65 y or weight <50 kg, then
maximum dose is 60 milligrams per day.
Maximum PO dose is 40 milligrams per day.
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Drug Adult Dosage Comments

Ketamine 0.15–0.4 milligrams/kg IV over 10 No renal or hepatic adjustment; adverse e ects

min; can follow by IV infusion 0.1– uncommon with single doses; dizziness,
0.2 milligrams/kg/h agitation, hallucinations possible with higher
doses.

Aspirin and the nonsteroidal anti-inflammatory drugs are both anti-inflammatory agents and analgesics.
As anti-inflammatory agents, aspirin and nonsteroidal anti-inflammatory drugs decrease the production of
prostanoids and arachidonic acid–mediated inflammatory peptides generated at the site of tissue injury,
diminishing the inflammatory response seen with some noxious stimuli. As analgesics, inhibition of the
cyclooxygenase-2 enzyme in the spinal cord decreases the excitability of dorsal horn neurons that produce
hyperalgesia and allodynia. These agents do not cause sedation or respiratory depression or interfere with
bowel or bladder function. Nonsteroidal anti-inflammatory drugs have significant opioid dose-sparing
e ects.

Adverse e ects of nonsteroidal anti-inflammatory drugs include platelet dysfunction, GI irritation and
mucosal bleeding, nephropathy, headaches, and dizziness. All nonsteroidal anti-inflammatory drugs
increase the risk of cardiac death in patients with ischemic heart disease,46,47 although the
cyclooxygenase-2–specific agents appear to carry higher risk than the nonselective agents.48,49
Nonsteroidal anti-inflammatory drug–induced acute renal failure is more common in elderly patients and
in those who are volume depleted, have preexisting renal or cardiac disease, or are taking loop diuretics.

OTHER PHARMACOLOGIC AGENTS

Ketamine

A phencyclidine derivative, ketamine produces analgesia and/or dissociative anesthesia with the
advantage of causing minimal respiratory depression with usual doses (see chapter 37, Procedural
Sedation). Low-dose (subdissociative) infusions of ketamine are e ective in combination with opioids for
patients in severe pain.50,51,52 Ketamine dosing for analgesia is typically a loading dose of 0.15 to 0.4
milligrams/kg IV over 10 minutes followed by an infusion if desired. Ketamine can be used in trauma
patients, resulting in a lower opioid requirement for pain control, and is also e ective in controlling acute
flare-ups of neuropathic pain. Ketamine is also useful as an SC infusion in palliative care patients. Adverse
e ects include hypersalivation and reemergence phenomena (disagreeable dreams or hallucinations upon
awakening), especially when larger induction doses are used (1.5 milligrams/kg IV).

Nitrous Oxide

Nitrous oxide is a fast-onset, short-acting analgesic and sedative inhalational agent useful for brief, minor
procedures (see chapter 37) and for prehospital analgesia.53 The primary adverse e ects are nausea and
vomiting. Nitrous oxide is usually supplied as a preblended 50% mixture with oxygen and administered to
the patient by face mask, but if available, the 70/30 nitrous oxide/oxygen mixture is more e ective. Barriers

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to ED use of nitrous oxide include the need for patient cooperation and an e ective scavenging system. In
addition, nitrous oxide is contraindicated in patients with altered mental status, head injury, suspected
pneumothorax, or perforated abdominal viscus. Severe pulmonary disease also may alter the respiratory
elimination of nitrous oxide.

Cyclic Antidepressants and Anticonvulsants

Patients with acute-onset neuropathic pain, such as postherpetic or trigeminal neuralgia, are di icult to
treat with short-acting opioid analgesics. It may be di icult to identify neuropathic causes of pain in ED
patients, but if suspected, more specific therapy and follow-up instructions are needed. Long-acting
opioids, cyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and anticonvulsants are
e ective for neuropathic pain (Table 35-10). When initiating an agent for patients with new-onset
neuropathic pain, close follow-up with the primary care physician is important so that titration to e ect
may continue.54,55 Patients already taking one of these agents for chronic neuropathic pain may require
either titration upward of their medication or addition of a second agent; this should be discussed with the
patient's regular physician.

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TABLE 35-10
Pain Management: Neuropathic Pain Syndromes

Initial Typical E ective Dosage (Maximum

Drug Use Titrate
Dosage Daily Dose)

Amitriptyline or Chronic pain 0.1 Increase over 0.5–2.0 milligrams/kg per day PO
nortriptyline milligram/kg 2–3 wk (maximum 150 milligrams per day)
PO once in
the evening

Carbamazepine Trigeminal 100 Increase 100– 200–400 milligrams PO twice per

neuralgia milligrams 200 milligrams day (1200 milligrams per day)
PO twice per per day
day

Oxcarbazepine Trigeminal 300 Increase 300– 450–1200 milligrams PO twice per

neuralgia milligrams 600 milligrams day
PO twice per per day every
day week

Duloxetine Diabetic 30 Increase a er 60 milligrams PO once per day

neuropathic milligrams 1 wk on initial (maximum 120 milligrams per day)
pain PO once per dose
day

Gabapentin Neuropathic 300 Increase up to 300–1200 milligrams PO three times

pain, milligrams 300 milligrams per day (maximum 3600 milligrams
postherpetic PO per day per day per day)
neuralgia

Pregabalin Neuropathic 50 Increase over 150 milligrams PO twice per day to

pain, milligrams 1 wk 100 milligrams PO three times per
postherpetic PO three day (maximum 600 milligrams per
neuralgia times per day)
day

Topical Medications

Topical administration of medications at the site of injury or inflammation can provide pain relief with
reduced systemic drug absorption and a lower risk of adverse drug reactions (Table 35-11).56 This approach
di ers from the transdermal drug administration to achieve systemic e ects, typically with opioids (see

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Route of Administration). Topical nonsteroidal anti-inflammatory drugs are e ective for treating acute so
tissue injuries such as sprains and strains and also for chronic joint pain from osteoarthritis. Topical
lidocaine therapy is e ective for patients with postherpetic neuralgia and diabetic neuropathy. Topical
capsaicin has produced variable results depending on the treatment population and dose applied; regular
use appears necessary for prolonged pain relief. A single 60-minute application of a high-dose preparation
(8% capsaicin topical patch) is e ective for postherpetic neuralgia but requires professional application
and removal to minimize side e ects.

TABLE 35-11
Pain Management: Topical Analgesic Agents

Agent Preparation Comments

Diclofenac 1% gel Gel: apply using dosing card—4 grams for knees, ankles, and feet, and 2
1.3% grams for elbows, wrists, and hands. Lightly rub until absorbed. Use up to 4
topical times a day. Maximum total daily dose 32 grams.
patch Patch: apply to intact skin at most painful site twice a day.

Ibuprofen* 5% gel Squeeze 50–125 milligrams (4–10 cm) of the gel from the tube and lightly
rub into the a ected area until absorbed. Apply up to 4 times per day.

Ketoprofen* 2.5% gel Squeeze 2–4 grams (5–10 cm) of the gel from the tube and lightly rub into
the a ected area until absorbed. Apply 2–4 times per day.

Lidocaine 5% gel Gel: apply a moderately thick layer to the a ected area (approximately 1/8
5% topical inch thick). Allow time for numbness to develop. Best results obtained 20
patch min to 1 hour a er application.
Patch: apply to intact skin to cover the most painful area. Use only once for
up to 12 h within a 24-h period.

Capsaicin 0.025% Cream and gel: apply to a ected area not more than 3–4 times daily.
cream Massage into area until thoroughly absorbed.
0.075% Patch: only for postherpetic neuralgia. Requires physician or healthcare
cream professional application. Applied for 60 min. Treatment may be repeated
0.1% gel every 3 months.
8% patch

*Not available in the United States.

The primary adverse reaction of topical medications is local burning, particularly seen with capsaicin,
which is derived from chili peppers. Rare cases of localized burns have been reported with topical muscle
and joint pain relievers.57 Most of the serious burns were associated with agents containing menthol (>3%
concentration) and/or methyl salicylate (>10% concentration).

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ROUTE OF ADMINISTRATION

Systemic pain medications can be given by multiple routes (Table 35-12). Oral administration is convenient,
inexpensive, and appropriate once the patient can tolerate oral intake; it is a mainstay of pain management
in the ambulatory ED population.

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TABLE 35-12
Delivery Routes of Systemic Analgesia

Method Advantages Disadvantages

PO Ease Unreliable GI absorption

Painless Requires gastric motility
Minimal cost Slow onset
No technical skill Titration less reliable
required
Patient acceptability

IV Rapid onset Venous access required

Titratable Potential for overdose
Usually easier to reverse

IM or SC Convenient Painful
Titration di icult and requires repeated injections
Absorption variable
More expensive than PO route

PR (transmucosal) No first-pass hepatic Requires patient acceptance and cooperation

metabolism Variable absorption
No reliance on gastric
motility

Buccal/nasal Ease Di icult to control dose

(transmucosal) Painless Can irritate nasal mucosa
Available buccal mucosal fentanyl preparations are
no bioequivalent

Transdermal Ease Variable dose and duration

Painless Di icult to titrate
Slow onset
Prolonged duration a er removal

Inhalational Rapid onset and o set Requires patient cooperation

Scavenger equipment required

Intra-articular Direct action Only in major joints

No systemic side e ects Risk of joint infection
Can last up to 48 h

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IV opioids are suitable for bolus administration or continuous infusion and are preferred to intermittent IM
injections. IM injections are painful, do not allow for easy titration, and have no clinically relevant
advantage over PO medications. Absorption can be variable, especially in sickle cell patients (due to
scarring) and hypotensive or volume-depleted patients. Patient-controlled IV analgesic systems are
particularly e ective for ED patients with acute abdominal pain and in addicts with pain when compared
with the usual approach of intermittent nurse-administered parenteral medications.58,59,60 Intra-articular
analgesia using opioids or bupivacaine can provide sustained relief during the immediate postoperative
period following hip and knee surgery.61,62,63 Nasal and buccal preparations of fentanyl are available
primarily for breakthrough pain in opioid-tolerant cancer patients, and these routes may have a role in
prehospital and ED acute pain management.64 Sublingual buprenorphine is described as e ective for ED
management of acute pain from fractures.65

DOSAGE AND PRECAUTIONS

Safe and e ective use of opioids is facilitated by choosing an appropriate initial dose66 and subsequently
titrating additional doses toward the desired e ect, thus avoiding overmedication and minimizing
unwanted e ects. In unmonitored opioid-naïve patients, excessive doses of opioids can result in
respiratory depression and decreased levels of consciousness. Hypotension is infrequent, is almost always
due to histamine release with the first dose of medication, and is usually of short duration. With
comorbidities, such as altered mental status, hemodynamic instability, respiratory dysfunction, or
multisystem trauma, initial dosing should be decreased, and dose titration is important for achieving
satisfactory pain relief.

The Elderly

Acute pain management for the elderly can be a challenge; these patients may have more than one source
of pain and/or multiple comorbidities and are at increased risk for drug–drug and drug–disease
interactions.67 Opioid-naïve elderly patients are more sensitive to the analgesic e ects of opioid drugs,
because they experience a higher peak and longer duration of pain relief. Moreover, they are more sensitive
to sedation, respiratory depression, and cognitive and neuropsychiatric dysfunction. Initial IV opioid doses
in the elderly are typically half those used in younger adults (e.g., morphine 0.05 milligram/kg and
hydromorphone 0.0075 milligram/kg), although single doses may not achieve adequate pain control for
elderly patients with acute severe pain.68

Addiction and Dependence

Addiction is the misuse of a medication or drug to the detriment of the patient's well-being. Dependence
infers that abrupt cessation of a medication will result in acute withdrawal symptoms. Dependence on
opioids requires regular daily usage for 4 to 6 weeks in most patients, whereas addiction may occur a er
one use of heroin. Care should be taken to assess a patient's risk for addiction or diversion of prescription
medications, but when uncertainty exists, the general approach is to err on the side of acute pain control,
although management in opioid-tolerant patients can be a challenge.69 Contemporary and rigorous
evidence is that dependence and addiction occur in up to one-third of patients on chronic opioid therapy,70
but there is little knowledge regarding the risk of short-term (<2 weeks) opioid therapy following an ED visit
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for an acute injury or temporary illness. Although EDs are not where most cases of opioid abuse originate,
they are perceived as a potential perpetuator of misuse.71 Distinguishing patient requests for medications
because of oligoanalgesia from addiction o en requires multiple patient assessments over time; subjective
assessment in the ED during a single visit is usually inaccurate for identifying addiction versus aberrant
behavior due to oligoanalgesia.72 Use of an assessment tool such as the Drug Abuse Screening Test may
provide a more objective means of screening for addiction.73

Renal and Hepatic Dysfunction

Because most analgesics are metabolized by the liver or kidney, take care when using opioids in patients
with impaired hepatic or renal function. Renal excretion is a major route of elimination for such
pharmacologically active opioid metabolites such as norpropoxyphene, normeperidine, morphine-6-
glucuronide, and dihydrocodeine. Mild renal failure can impede excretion of the metabolites of many
opioids, resulting in clinically significant narcosis and respiratory depression. In patients with renal failure,
hydromorphone and fentanyl are the preferred opioids. Mild hepatic dysfunction has little e ect on opioid
metabolism. In patients with severe hepatic dysfunction, titration with low doses of analgesics will
minimize the risk of overdose.

Respiratory Insu iciency

Patients with respiratory insu iciency and those with chronic obstructive pulmonary disease, cystic
fibrosis, and neuromuscular disorders a ecting respiratory e ort (e.g., muscular dystrophy and
myasthenia gravis) are particularly vulnerable to the respiratory depressant e ects of opioids and nitrous
oxide. Careful dose titration and monitoring of oxygenation and ventilation are necessary. Ketamine may
be a useful alternative agent in such cases.

Drug Interactions

Opioids may have adverse synergistic sedative e ects in patients with psychiatric illnesses taking
anxiolytics or other psychoactive drugs. The use of monoamine oxidase inhibitors with meperidine is
associated with severe adverse reactions, including death as the result of precipitating a serotonin
syndrome (see chapter 178, Atypical and Serotonergic Antidepressants). The cyclic antidepressants
clomipramine and amitriptyline may increase morphine levels and potentiate the opioid e ects.

NONPHARMACOLOGIC MODALITIES
Traditionally, nonpharmacologic techniques of pain management in the ED have been limited to
application of heat or cold and immobilization and elevation of injured extremities. Other techniques may
be useful in the ED and a er discharge. Cognitive-behavioral techniques can be e ective in reducing pain
and anxiety, may control mild pain when used alone, and can enhance patient satisfaction. Such
techniques include reassurance, explanation, relaxation, music, psychoprophylaxis, biofeedback, guided
imagery, hypnosis, and distraction. They are a useful adjunct to pharmacologic management of moderate
to severe pain. Successful application of these therapies requires a cognitively intact patient and skilled
personnel, but many of the techniques require only a few minutes to teach the patient.

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Physical nonpharmacologic agents are becoming increasingly relevant to acute pain management. In
addition to the traditional techniques noted above, less commonly used physical modalities, such as
transcutaneous electrical nerve stimulation and acupuncture, may have some potential role in the ED.
Although specific technical skills and equipment are required, there is no need for IV access, and there is no
systemic e ect such as respiratory depression or altered mental status.

SPECIFIC SITUATIONS
ABDOMINAL PAIN

Early administration of IV opioids is safe for the treatment of acute abdominal pain in the ED and does not
a ect the accuracy of the evaluation, diagnosis, or management.74,75,76,77 The dogma against the use of
opioids for patients with acute abdominal pain stated in previous editions of Cope's Early Diagnosis of the
Acute Abdomen was revised in 2000.78 The one valid concern regarding analgesia and abdominal pain is
that reduction in pain does not indicate improvement in pathophysiology. Analgesia without proper
evaluation is as inappropriate as proper evaluation without analgesia.

MIGRAINE

There is no one, consistent, best analgesic agent for the management of a patient with migraine headache
in the ED.11,12,14 Opioid use for acute migraine treatment has lost favor due to poor performance in clinical
trials, but can be considered if other agents have been ine ective.14 The high success rates with
promethazine, chlorpromazine, and prochlorperazine are tempered by the extrapyramidal side e ects,
seen in as many as 45% of patients, and occasional intense dysphoria (see chapter 165, Headache).13

TRAUMA

Patients in shock and those with trauma, burns, and hemodynamic or respiratory instability need judicious
use of opioids.2 Fentanyl, first as a bolus and then as an infusion, may be the opioid of choice due to its
lesser impact on hemodynamic function. Use of regional analgesia is encouraged.29 Nonsteroidal anti-
inflammatory drugs should not be given to patients with major trauma due to the risks of excessive
bleeding from platelet dysfunction and gastric stress ulcers and the potential for acute renal failure in a
volume-depleted patient.

DISPOSITION
Although rare, intractable acute pain can be a primary reason for hospital admission. Otherwise, most
patients may be safely discharged with a plan for pain management that includes instructions for use of
short-acting analgesics (i.e., those with a duration of action of up to 6 hours). Persistent pain a er ED
discharge is common.79,80,81 Prescriptions for long-acting agents (e.g., methadone, controlled-release
preparations of morphine or oxycodone) are generally avoided upon ED discharge but are sometimes used
for special patients, such as those with cancer in whom short-acting agents are no longer e ective (see
chapter 38, Chronic Pain).

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Patients should be counseled to take subsequent doses on a regular basis or when their pain begins to
return, rather than when it approaches its peak. Patients with recurrence of severe pain or changes in the
quality of pain should be told to return to the ED for reassessment. It is best to prescribe only a few days'
worth of analgesics, because conditions with a longer duration of pain require follow-up with the primary
care physician. If opioids are prescribed to the elderly or those naïve to narcotics, home observation by a
responsible adult is recommended so that adverse e ects can be quickly recognized. Discharge
instructions for those given opioids should include instructions to avoid making important decisions while
medicated and to avoid driving, operating machinery, climbing or working from heights, and so on, and
should also include instructions for treatment of constipation. Education about securing opioid
prescriptions is important because up to 85% of prescription opioids misused by adolescents come from
their parents' medication cabinet.

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