Mini topic review: Total Intravenous Anaesthesia (TIVA)

By Dr David Mulvey, Consultant Anaesthetist, Royal Derby Hospital, Uttoxeter Road, Derby DE22 3NE Introduction Developments made over the last twenty five years have allowed total intravenous anaesthesia (TIVA) to become an everyday technique. These include the introduction of propofol and remifentanil into clinical practice, sophisticated mathematical modelling of plasma and brain drug concentrations, and infusion devices programmed with pharmacokinetic profiles. Drugs used for TIVA Theoretically any combination of intravenous hypnotic and opioid agents can be used in a synergistic/additive manner to achieve general anaesthesia. In practice, agents with fast onset and offset times prove most useful in maintaining a balance 1 between adequacy of anaesthesia/analgesia and rapid recovery. The decrement time of a drugs plasma concentration tends to increase with the duration of continuous administration (context sensitive half-time - CSHT).2 Of the hypnotic 1 agents with short CSHT, propofol has the least unwanted side effects making it the preferred choice. Remifentanil shows little CSHT in contrast to opioids such as alfentanil and fentanyl and is preferred in a TIVA technique.3 Some clinicians supplement intravenous infusions with inhaled nitrous oxide in order to reduce required plasma/brain concentrations and enhance awakening times, although strictly speaking this is not TIVA.3,4 Propofol-related infusion syndrome (PRIS) This is defined as metabolic acidosis plus cardiac dysfunction and =1 of rhabdomyolysis, hypertriglyceridemia or renal failure 5 occurring after the start of propofol therapy. The majority of reports concern paediatric and adult patients requiring support in an intensive care environment. The aetiology is unclear, but in a recent prospective study of 1017 adult patients an incidence of 1.1% was observed.6 Propofol is not recommended for sedation on paediatric ICU but is currently considered safe for TIVA in this age group.7 The same authors pointed out that the syndrome is not confined to the prolonged use of 7 propofol. Reports of perioperative lactic acidosis and/or hyperkalaemia in patients receiving propofol infusions as part of the anaesthetic technique have been published. It has been recommended that PRIS should be remembered as a possible complication of using propofol for anaesthesia.7 Hyperalgesia with Remifentanil Hyperalgesia after remifentanil infusion has been proposed8,9, and refuted10,11,12 but represents a potential disadvantage to using this agent for TIVA.13 The importance of administering morphine at least 40 minutes in advance of discontinuing 14 15 remifentanil infusion has been demonstrated , as well as the need for doses greater than 0.15 mg/kg. Target controlled infusion (TCI) Administration of hypnotic/opioid infusions can be performed manually using established dosing regimens to achieve clinically appropriate plasma drug concentrations. It is far easier for the anaesthetist to use a target controlled infusion (TCI) device which has pharmacokinetic data programmed into a microprocessor24. Additionally the use of TCI devices allows better control of anaesthesia, fewer haemodynamic side effects and a more predictable recovery than conventional infusions.16 However a systematic review found insufficient evidence to make firm recommendations about the advantage of 17 target controlled infusions in clinical practice. Pharmacokinetic models Most debate about pharmacokinetic models has centred on propofol infusions. The earliest TCI devices incorporated the Diprifusor module and accepted only syringes pre-filled with propofol by AstraZeneca. This module uses the pharmacokinetic data of Marsh and colleagues to achieve a target plasma concentration, adjusting the central volume of distribution according to weight. It is suggested that this model may lead to a relative overdosing of an elderly subject and 18 19 underdosing of the young fit patient , although it has proved robust in clinical practice. Subsequent investigators have broadened the models for propofol by encompassing a wider range of patient variables and currently ten data sets are available from an expert source20 (www.eurosiva.org). Whilst it is ideal to choose a model appropriate to the age and sex of the patients to be treated21, commercially available TCI devices offer a limited choice at present, namely the Marsh and Schnider adult models, and the Kataria and Paedfusor paediatric data sets. Current infusion devices accept syringes

filled with generic propofol (open TCI) offering a potential for cost saving. In addition, these open devices allow the use of a wider range of hypnotic/opioid agents and their relevant pharmacokinetic models to achieve a TCI. Another important difference is the ability to target the effect site (i.e. the brain) concentration of the drug, thereby limiting the delay between plasma and brain equilibration and reducing adverse cardiovascular effects in the elderly. This choice is available for both the Marsh and Schnider models for propofol in commercial devices. At present there is no evidence to suggest that the 22 choice of model or site of targeting has advantage in clinical practice. However it is recommend that the Marsh model is used in plasma target mode, and the Schnider model in effect site mode.22 Clinicians must exercise particular care when changing from models that target plasma to effect site concentration or vice versa. Varying masses of propofol are delivered into the patients circulation with the different models and this may lead to unexpected clinical consequences.23 In common 24 with inhalational anaesthesia, adjustments in TIVA dosing must be made on the basis of clinical response. The Minto model for remifentanil TCI is used most widely in clinical practice, both in plasma and effect site target modes. In common with propofol there is no evidence to show a benefit of effect-site targeting for remifentanil and the possibility of exaggerated haemodynamic effects which may be disadvantageous.25 Morbidly obese patients Anomalies arise with Schnider model for propofol and Minto model for remifentanil which use Lean Body Mass (LBM) as a limiting parameter on the infusion rate required with increasing total body weight. The calculation of LBM is by the James equation26 which gives a declining value for LBM when BMI exceeds 42 kg m-2 in males and 35 kg m-2 in females.27 This allows the pharmacokinetic model to deliver an exponential rise in infusion rate to maintain the target concentration with the potential for marked haemodynamic side effects. The TCI device manufacturers have prevented pump software from calculating an absurdly low LBM thereby limiting the use of the devices in patients with BMIs exceeding the critical values. It has been noted that the currently available pharmacokinetic models have not been validated for use in the morbidly 24 28,29 , but caution is urged if TIVA is given obese. . Some success has been obtained by empirical corrections of body mass 24 to this group of patients. Awareness It is often stated that TIVA is associated with an increased risk of awareness and that neuromuscular blocking agents should be avoided with this method of anaesthesia as a result. Relatively few patients are given TIVA compared to balanced 30 inhalational anesthesia (BIA) which makes comparison difficult. A further analytical complexity is the absence of standardisation of intravenous drug and dosing regimen used in published studies, and of a recognised end-point akin to minimal alveolar concentration for BIA. The susceptibility of TIVA to technical failures that result in awareness has been highlighted.31 In large prospective trial of propofol/alfentanil TIVA the incidence of awareness was similar to that with BIA, 30 although most TIVA cases were due to technical problems in delivery. In a prospective observational study of 4001 patients, the incidence of awareness in patients receiving TIVA-propofol was 1% versus 0.59% in the BIA group however no details of anaesthetic technique or additional drugs given to the TIVA-propofol group are available to allow detailed evaluation of these data.32 A small number of case reports of awareness in patients receiving TIVA administered as propofol/remifentanil TCI have been published but a large prospective trial is required to determine if extra risk truly exists. In studies using the isolated forearm technique and bispectral index endpoints for adequate anaesthesia, TIVA and BIA 33,34 Currently there is no provided similar numbers of patients able to respond to command with no difference in awareness. reason to believe that TIVA increases the risk of awareness, and good reasons to minimise the use of neuromuscular blocking agents in all modes of anaesthesia.35,36 Nausea and Vomiting In an early systematic review, propofol maintenance anaesthesia and omitting nitrous oxide in general anaesthesia had approximately the same effect on early and late post-operative nausea and vomiting (PONV) and the data were considered insufficient to recommend TIVA as the preferred method.37 Recent expert opinion emphasises the value of TIVA in a multimodal approach to patients at high risk for PONV.38 Daycase surgery The use of TIVA for ambulatory surgery seems to be increasing, with rapid, clear-headed emergence and low incidence of postoperative nausea and vomiting cited as advantages of the technique, in combination with simplicity of TCI 3,39 This contrasts administration, increased experience and declining costs with the propofol and remifentanil combination. 40 with a much earlier review which did not find TIVA to be cost-effective in this setting.

Anaesthesia for lung isolation

In a systematic review, there was no evidence of important differences in outcomes for anaesthesia maintained by 41 intravenous versus inhalational anaesthesia during one-lung ventilation. Nevertheless, TIVA is preferable for certain thoracic procedures incompatible with effective delivery of inhalational anaesthetics.42 Neurosurgical procedures TIVA appears to confer advantage over traditional anaesthetic techniques in patients with raised intracranial pressure43 and 44 those requiring intraoperative nuerophysiological monitoring but is the subject of ongoing studies. Conclusion TIVA is used in an ever widening range of clinical applications with quality of recovery considered the major advantage offered by the technique. More formal prospective clinical trials are required to determine the role of TIVA in modern anaesthetic practice. References 1. Sear J. Total Intravenous Anesthesia. Chapter 42, pp 897-916. in Anesthesiology. Longnecker D, Brown D, Newman M, Zapol W. 2008, McGraw-Hill. 2. Hughes MA, Glass PSA, Jacobs JR. Context-sensitive half-time in multicompartment pharmacokinetic models for intravenous anesthetic drugs. Anesthesiology 1992; 76:334-41. [Link to abstract] 3. Hitchcock M. Total Intravenous Anaesthesia (TIVA). Chapter 7, pp 65-77. in Practical Analgesia and Anesthesia for Day Case Surgery. Millar JM, Rudkin GE, Hitchcock M. 1997, BIOS Scientific Publishers Ltd. 4. Handa-Tsutsui F, Kodaka M. Effect of nitrous oxide on propofol requirement during target-controlled infusion for oocyte retrieval. Int J Obstet Anesth. 2007; 16(1):13-16. [Link to abstract] 5. Fudickar A, Bein B, Tonner P. Propofol infusion syndrome in anaesthesia and intensive care medicine. Curr Opin Anesthesiol. 2006; 19(4):404-10. [Link to abstract] 6. Roberts RJ, Barletta JF, Fong JJ et al. Incidence of propofol-related infusion syndrome in critically ill adults: a prospective, multicenter study. Crit Care 2009; 13(5): R169. Epub 2009 Oct 29. [Link to full text] 7. Fudickar A, Bein B. Propofol infusion syndrome: update of clinical manifestation and pathophysiology. Minerva Anestesiol. 2009; 75(5): 339-44. [Link to abstract] 8. Hood DD, Curry R, Eisenach JC. Intravenous remifentanil produces withdrawal hyperalgesia in volunteers with capsaicin-induced hyperalgesia. Anesth Analg. 2003; 97(3):810-5. [Link to abstract] 9. Crawford MW, Hickey C, Zaarour C et al. Development of acute opioid tolerance during infusion of remifentanil for pediatric scoliosis surgery. Anesth Analg. 2006; 102(6):1662-7. [Link to abstract] 10. Lahtinen P, Kokki H, Hynynen M. Remifentanil infusion does not induce opioid tolerance after cardiac surgery. J Cardiothorac Vasc Anesth. 2008; 22(2):225-9. [Link to abstract] 11. Cortinez LI, Brandes V, Munoz HR et al. No clinical evidence of acute opioid tolerance after remifentanil-based anaesthesia.Br J Anaes. 2001; 87(6): 866-9. [Link to abstract] 12. Hansen EG, Duedahl TH, Rmsing J et al. Intra-operative remifentanil might influence pain levels in the immediate post-operative period after major abdominal surgery. Acta Anaesthesiol Scand. 2005; 49(10):1464-70. [Link to abstract] 13. Singler B, Troster A, Manering N et al. Modulation of remifentanil-induced postinfusion hyperalgesia by propofol. Anesth Analg. 2007; 104(6): 1387-1403. [Link to abstract] 14. Munoz HR, Guerro ME, Brandes V et al. Effect of timing of morphine administration during remifentanil-based anaesthesia on early recovery from anaesthesia and postoperative pain. Br J Anaes. 2002; 88(6): 814-8. [Link to abstract] 15. Fletcher D, Pinaud M, Scherpereel P et al. The efficacy of intravenous 0.15 versus 0.25 mg/kg intraoperative morphine for immediate postoperative analgesia after remifentanil-based anesthesia for major surgery. Anesth Analg. 2000; 90(3): 666-71. [Link to abstract] 16. Moerman AT, Herregods LL, De Vos MM et al. Manual versus target-controlled infusion remifentanil administration in spontaneously breathing patients. Anesth Analg 2009; 108(3): 828-34. [Link to abstract] 17. Leslie K, Clavisi O, Hargrove J. Target-controlled infusion versus manually-controlled infusion of propofol for general anaesthesia or sedation in adults. Cochrane Database of Systematic Reviews 2008 Issue 3, John Wiley & Sons Ltd. [Link to full text] 18. Kazama T, Ikeda K, Morita M et al. Comparison of the effect-site k(eO)s of propofol for blood pressure and EEG bispectral index in elderly and younger patients. Anesthesiology 1999; 90(6): 1517-27. [Link to abstract] 19. Barakat AR, Sutcliffe N, Schwab M. Effect site concentration during propofol TCI sedation : a comparison of sedation score with two pharmacokinetic models. Anesthesia 2007; 62(7): 661-666. [Link to abstract] 20. European Society for Intravenous Anaesthesia (www.eurosiva.org) 21.. White M, Kenny G, Schraag S. Use of Target Controlled Infusion to Derive Age and Gender Covariates for

Propofol Clearance. Clin Pharmacokinetics 2008; 47(2): 119-127. [Link to abstract] 22. Absalom AR, Mani V, De Smet T, Struys MM. Pharmacokinetic models for propofol defining and illuminating the devil in the detail. Br J Anaes. 2009; 103(1): 26-37. [Link to abstract] 23. Enlund M. TCI:Target Controlled Infusion, or totally confused infusion? Call for an optomised population based pharmacokinetic model for propofol. Upsala J Med Sci 2008; 113(2): 161-170. [Link to abstract] 24. Coetzee JF. Total intravenous anaesthesia to obese patients: largely guesswork? Eur J Anaesthes. 2009; 26(5): 359-61. [Link to abstract] 25. Absalom AR, Struys MM. An overview of target controlled infusions and total intravenous anaesthesia. Chapter 2, pp 34. 2005, Academia Press. 26. James W. Research on obesity. London: Her Majestys Stationery Office; 1976. 27. Bouillon T, Shaffer SL. Does size matter? Anesthesiology 1998; 89(3): [Link to abstract] 28. Albertin A, Poli D, La Colla L et al. Predictive performance of Servins formula during BIS-guided propofolremifentanil infusion in morbidly obsess patients. Br J Anaes. 2007; 98(1): 66-75. [Link to abstract] 29. La Colla L, Albertin A, La Colla G et al. Predictive performance of the Minto remifentanil pharmacokinetic parameter set in morbidly obese patients ensuing from a new method of calculating lean body mass. Clin Pharmacokinetic. 2010; 49(2): 131-9. [Link to abstract] 30. Sandin R, Nordstrom O. Awareness during total intravenous anaesthesia. Br J Anaes. 1993; 71: 782-87. [Link to abstract] 31. Safe Anaesthesia Liaison Group. Guaranteeing Drug Delivery in Total Intravenous Anaesthesia. October 2009. salg@rcoa.ac.uk [Link to www.npsa.nhs.uk/nrls/improvingpatientsafety/anaesthesia-and-surgery/] 32. Errando CL, Sigl JC, Robles M et al. Awareness with recall during general anaesthesia: a prospective observational evaluation of 4001 patients. Br J Anaes. 2008; 101(2): 178-85. [Link to abstract] 33. Russell IF. BIS-guided isoflurane/relaxant anaesthesia monitored with the isolated forearm technique. Br J Anaes. 2008; 100(6): 875P. [Link to abstract] 34. Russell IF. BIS-guided TCI propofol/remifentanil anaesthesia monitored with the isolated forearm technique. (Proceedings of the 7th International Symposium Memory and Awareness in Anaesthesia) Br J Anaes. 2008; 100(6): 876P. [Link to full text] 35. Ponte J. Neuromuscular blockers during general anaesthesia. BMJ 1995; 310: 1218-19. [Link to abstract] 36. Ponte J. Neuromuscular blockers and awareness. Anesth Analg. 2001; 93(4): 1081-82. [Link to abstract] 37. Tramer M, Moore A, McQuay H. Meta-analytic comparison of prophylactic antiemetic efficacy for postoperative nausea and vomiting: propofol anaesthesia vs omitting nitrous oxide vs total i.v. anaesthesia with propofol. Br J Anaes. 1996; 76: 256-259. [Link to abstract] 38. Apfel CC, Kranke P, Piper S et al. Nausea and vomiting in the postoperative phase. Expert and evidence-based recommendations for prophylaxis and therapy. Anaesthesist 2007; 56(11):1170-80 [Link to abstract] 39. Eikaas H, Raedar J. Total intravenous anaesthesia techniques for ambulatory surgery. Curr Opin Anaesthesiol. 2009; 22(6):725-9. [Link to abstract] 40. Elliott RA, Payne K, Moore JK et al. Which anaesthetic agents are cost-effective in day surgery? Health Technol Assess. 2002; 6(30). [Link to abstract] 41. Bassi A, Milani WRO, El Dib R, Matos D. Intravenous versus inhalation anaesthesia for one-lung ventilation. Cochrane Database of Systematic Reviews 2008 Issue 2 John Wiley & Sons Ltd. [Link to full text] 42. Purugganan RV Intravenous anesthesia for thoracic procedures. Curr Opin Anaesthesiol. 2008; 21(1): 1-7. [Link to abstract] 43. Cole CD, Gottfried ON, Gupta DK, Couldwell WT. Total intravenous anesthesia: advantages for intracranial surgery. Neurosurgery 2007; 61(5 suppl2); 369-77. [Link to abstract] 44. Deiner S. Highlights of anesthetic considerations for intraoperative neuromonitoring. Semin Cardiothorac Vasc Anesth. 2010; 14(1): 51-53. [Link to abstract] Cite this resource: Mulvey D. Total Intravenous Anaesthesia (TIVA). NHS Evidence - surgery, anaesthesia, perioperative and critical care [published October 2010; downloaded (date of access)]. Available from: http://www.library.nhs.uk/Theatres/ViewResource.aspx?resID=387834 Disclaimer The content of this article represents the authors personal opinion and may not necessarily reflect that of their workplace, professional organisation or the National Library for Health. Your feedback is important to us, so if you have any comments about the review please Contact Us