Perioperative management of opioid-tolerant chronic pain patients


  • Dima Rozen, MD
  • Noah P. DeGaetano, MD



opioids, opioid tolerance, chronic pain, perioperative, anesthesia


Opioids occupy a position of unsurpassed clinical utility in the treatment of many types of painful conditions. In recent years there has been a noticeable shift regarding the use of opioids for the treatment of both benign and malignancy-related pain. As acceptance of the prescribing of opioids for chronically painful conditions has grown, many more opioid-tolerant patients are presenting for surgical procedures. It is therefore imperative that practicing anesthesiologists become familiar with currently available opioid formulations, including data regarding drug interactions and side effects, in order to better plan for patients’ perioperative anesthetic needs and management. Unfortunately, there is a lack of scientifically rigorous studies in this important area, and most information must be derived from anecdotal reports and the personal experience of anesthesiologists working in this field. In this review, we shall discuss current chronic pain management and the impact of opioid use and tolerance on perioperative anesthetic management.

Author Biographies

Dima Rozen, MD

Assistant Professor of Anesthesiology, Director of Neuromodulation, Department of Anesthesiology and Pain Medicine, Mount Sinai Medical Center, New York, New York.

Noah P. DeGaetano, MD

Department of Psychiatry, Mount Sinai Medical Center, New York, New York.


Elliott AM, Smith BH, Penny KI, et al.: The epidemiology of chronic pain in the community. Lancet. 1999; 354(9186): 1248-1252.

Ballantyne JC, Mao J: Opioid therapy for chronic pain. N Engl J Med. 2003; 349(20): 1943-1953.

Portenoy RK: Chronic opioid therapy in nonmalignant pain. J Pain Symptom Manage. 1990; 5(1 Suppl): S46-S62.

Portenoy RK: Opioid therapy for chronic nonmalignant pain: A review of the critical issues. J Pain Symptom Manage. 1996; 11(4): 203-217.

Haddox JD, Joranson DE, Angarola RT, et al.: Consensus statement from the American Academy of Pain Medicine and American Pain Society: The use of opioids for the treatment of chronic pain. Clin J Pain. 1997; 13: 6-11.

Collett BJ: Chronic opioid therapy for non-cancer pain. Br J Anaesth. 2001; 87: 133-143.

Clark JD: Chronic pain prevalence and analgesic prescribing in a general medical population. J Pain Symptom Manage. 2002; 23(2): 131-137.

Peng PW, Tumber PS, Gourlay D: Review article: Perioperative pain management of patients on methadone therapy. Can J Anaest. 2005; 52(2): 513-523.

O’Brien CP: Drug addiction and drug abuse. In Hardman JG, Limbird LE (eds.): Pharmacological Basis of Therapeutics. New York: McGraw-Hill, 2001.

Wikler A: Recent progress in research on the neurophysiologic basis of morphine addiction. Am J Psychiatry. 1948; 105: 329-338.

Taub A: Opioid analgesics in the treatment of chronic intractable pain of non-neo-plastic origin. In Kitahata LM, Collins JG (eds.): Narcotic Analgesics in Anaesthesiology. London: Williams and Wilkins, 1982.

Kreek MJ: Medical safety and side effects of methadone in tolerant individuals. JAMA. 1973; 223: 665-668.

Savage SR: Long-term opioid therapy: Assessment of consequences and risks. J Pain Symptom Manage. 1996; 11(5): 274-286.

Chu LF, Clark DJ, Angst MS: Opioid tolerance and hyperalgesia in chronic pain patients after one month of oral morphine therapy: A preliminary prospective study. J Pain. 2006; 7(1): 43-48.

Etches RC: Patient-controlled analgesia. Surgery Clinic of North America. 1999; 79: 297-312.

Schmid RL, Sandler AN, Katz J: Use and efficacy of low-dose ketamine in the management of acute postoperative pain: A review of current techniques and outcomes. Pain. 1999; 82: 111-125.

Weinbroum AA: A single small dose of postoperative ketamine provides rapid and sustained improvement in morphine analgesia in the presence of morphine-resistant pain. Anesth Analg. 2003; 96: 789-795.

Gomar C, Carrero EJ: Delayed arousal after general anesthesia associated with baclofen. Anesthesiology. 1994; 81: 1306-1307.

Wallden J, Thorn SE, Wattwil M: The delay of gastric emptying induced by remifentanil is not influenced by posture. Anesth Analg. 2004; 99(2): 429-434, table of contents.

Thorn SE, Wattwil M, Lindberg G, et al.: Systemic and central effects of morphine on gastroduodenal motility. Acta Anaesthesiol Scand. 1996; 40(2): 177-186.

Murphy DB, Sutton JA, Prescott LF, et al.: A comparison of the effects of tramadol and morphine on gastric emptying in man. Anaesthesia. 1997; 52(12): 1224-1229.

Murphy DB, Sutton JA, Prescott LF, et al.: Opioid-induced delay in gastric emptying: A peripheral mechanism in humans. Anesthesiology. 1997; 87(4): 765-770.

Walker PW, Klein D, Kasza L: High dose methadone and ventricular arrhythmias: A report of three cases. Pain. 2002; 103: 321-324.

Gil M, Sala M, Anguera I, et al.: QT prolongation and Torsades de Pointes in patients infected with human immuno-deficiency virus and treated with methadone. Am J Cardiol. 2003; 92(8): 995-997.

Kornick CA, Kilborn MJ, Santiago-Palma J, et al.: QTc interval prolongation associated with intravenous methadone. Pain. 2003; 105: 499-506.

Krantz MJ, Lefkowiez L, Hays H, et al.: Torsades de pointes associated with very-high dose methadone. Ann Intern Med. 2002; 137: 501-504.

Martell BA, Arnsten JH, Ray B, et al.: The impact of methadone induction on cardiac conduction in opiate users. Ann Intern Med. 2003; 139: 154-155.

Cruciani RA, Portenoy RK, Homel P: Drug-induced prolongation of QT interval. N Engl J Med. 2004; 350: 2618-2621.

Makkar RR, Fromm BS, Steinman RT, et al.: Female gender as a risk factor for torsades de pointes associated with cardiovascular drugs. JAMA. 1993; 270(21): 2590-2597.

Kay GN, Plumb VJ, Arciniegas JG, et al.: Torsade de pointes: The long-short initiating sequence and other clinical features: Observations in 32 patients. J Am Coll Cardiol. 1983; 2(5): 806-817.

Rebeiz AG, Al-Khatib SM: A case of severe ischemia-induced QT prolongation. Clin Cardiol. 2001; 24(11): 750.

Reardon M, Malik M: QT interval change with age in an overtly healthy older population. Clin Cardiol. 1996; 19(12): 949-952.

Ahnve S, Vallin H: Influence of heart rate and inhibition of autonomic tone on the QT interval. Circulation. 1982; 65(3): 435-439.

Ahnve S: QT interval prolongation in acute myocardial infarction. Eur Heart J. 1985; 6(Suppl D): 85-95.

Roden DM: Drug-induced prolongation of the QT interval. N Engl J Med. 2004; 350: 1013-1022.

Al-Khatib SM, Allen LaPointe NM, Kramer JM, et al.: What clinicians should know about the QT interval. JAMA. 2003; 289: 2120.

Viskin S: Long QT syndromes and torsades de pointes. Lancet. 1999; 354: 1625-1633.

Moss AJ: Measurement of the QT interval and the risk associated with QTc interval prolongation: A review. Am J Cardiol. 1993; 72: 23B-25B.

Cruciani RA, Sekine R, Homel P, et al.: Measurement of QTc in patients receiving chronic methadone therapy. J Pain Symptom Manage. 2005; 29: 385-391.

Krantz MJ, Lewkowiez L, Hays H, et al.: Torsade de pointes associated with very-high-dose methadone. Ann Intern Med. 2002; 137(6): 501-504.

Gourlay GK, Kowalski SR, Plummer JL, et al.: The transdermal administration of fentanyl in the treatment of postoperative pain: Pharmacokinetics and pharmacodynamic effects. Pain. 1989; 37: 193-202.

Duthie DR, Rowbotham DJ, Wyld R, et al.: Plasma fentanyl concentrations during transdermal delivery of fentanyl to surgical patients. Br J Anaesth. 1988; 60: 614-618.

Frolich MA, Giannotti A, Modell JH: Opioid overdose in a patient using a fentanyl patch during treatment with a warming blanket. Anesth Analg. 2001; 93(3): 647-648.

Pettifer GR, Hosgood G: The effect of rectal temperature on perianesthetic serum concentrations of transdermally administered fentanyl in cats anesthetized with isoflurane. Am J Vet Res. 2003; 64(12): 1557-1561.

Pettifer GR, Hosgood G: The effect of inhalant anesthetic and body temperature on peri-anesthetic serum concentrations of transdermally administered fentanyl in dogs. Vet Anaesth Analg. 2004; 31(2): 109-120.

Rose PG, Macfee MS, Boswell MV: Fentanyl transdermal system overdose secondary to cutaneous hyperthermia. Anesth Analg. 1993; 77(2): 390-391.

Shomaker TS, Zhang J, Ashburn MA: Assessing the impact of heat on the systemic delivery of fentanyl through the transdermal fentanyl delivery system. Pain Med. 2000; 1(3): 225-230.

Newshan G: Heat-related toxicity with the fentanyl transdermal patch. J Pain Symptom Manage. 1998; 16(5): 277-278.

Thompson JP, Bower S, Liddle AM, et al.: Perioperative pharmacokinetics of transdermal fentanyl in elderly and young adult patients. Br J Anaesth. 1998; 81(2): 152-154.

Murray JM, Rowlands BJ, Trinick TR: Indocyanine green clearance and hepatic function during and after prolonged anaesthesia: Comparison of halothane with isoflurane. Br J Anaesth. 1992; 68(2): 168-171.

Gelman S, Fowler KC, Smith LR: Liver circulation and function during isoflurane and halothane anesthesia. Anesthesiology. 1984; 61(6): 726-730.

Grundmann U, Zissis A, Bauer C, et al.: In vivo effects of halothane, enflurane, and isoflurane on hepatic sinusoidal microcirculation. Acta Anaesthesiol Scand. 1997; 41(6): 760-765.

Greenblatt EP, Loeb AL, Longnecker DE: Endotheliumdependent circulatory control—a mechanism for the differing peripheral vascular effects of isoflurane versus halothane. Anesthesiology. 1992; 77(6): 1178-1185.

Landau R, Cahana A, Smiley RM, et al.: Genetic variability of mu-opioid receptor in an obstetric population. Anesthesiology. 2004; 100(4): 1030-1033.

Kim H, Neubert JK, San Miguel A, et al.: Genetic influence on variability in human acute experimental pain sensitivity associated with gender, ethnicity and psychological temperament. Pain. 2004; 109(3): 488-496.

Lipkowski AW, Carr DB, Silbert BS, et al.: Non-deterministic individual responses to receptor-selective opioid agonists. Pol J Pharmacol. 1994; 46(1-2): 29-35.

Weinrieb RM, Barnett R, Lynch KG, et al.: A matched comparison study of medical and psychiatric complications and anesthesia and analgesia requirements in methadone-maintained liver transplant recipients. Liver Transpl. 2004; 10(1): 97-106.

Peng PW, Sandler AN: A review of the use of fentanyl analgesia in the management of acute pain in adults. Anesthesiology. 1999; 90: 576-599.

Gourlay GK, Kowalski SR, Plummer JL, et al.: Fentanyl blood concentrations-analgesic response relationship in the treatment of postoperative pain. Anesth Analg. 1988; 67: 329-337.

Davis JJ, Johnson KB, Egan TD, et al.: Preoperative fentanyl infusion with pharmacokinetic simulation for anesthetic and perioperative management of an opioid-tolerant patient. Anesth Analg. 2003; 97(6): 1661-1662.

Rapp SE, Ready LB, Nessly ML: Acute pain management in patients with prior opioid consumption: A case-controlled retrospective review. Pain. 1995; 61: 195-201.

Jage J, Bey T: Postoperative analgesia in patients with substance use disorders. Acute Pain. 2000; 92: 140-155.

Hord AH: Postoperative analgesia in the opioid-dependent patient. In Sinatra RS, Hord AH, Ginsberg B, et al. (eds.): Acute Pain: Mechanisms and Management. St. Louis: Mosby Yearbook, 1992.

Saberski L: Postoperative pain management for the patient with chronic pain. In Sinatra RS, Hord AH, Ginsberg B, et al. (eds.): Acute Pain: Mechanisms and Management. St. Louis: Mosby Yearbook, 1992.

May JA, White HC, Lenard-White A, et al.: The patient recovering from alcohol or drug addiction: Special issues for the anesthesiologist. Anesth Analg. 2001; 92: 160-161.

Higa KD, Ho T, Boone KB, et al.: Narcotic withdrawal syndrome following gastric bypass—a difficult diagnosis. Obesity Surgery. 2001; 11(5): 631-634.




How to Cite

Rozen, MD, D., and N. P. DeGaetano, MD. “Perioperative Management of Opioid-Tolerant Chronic Pain Patients”. Journal of Opioid Management, vol. 2, no. 6, Nov. 2006, pp. 353-6, doi:10.5055/jom.2006.0052.



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