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CNS Adverse Effects of Opioids in Cancer Patients

Guidelines for Treatment

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Summary

Most of the adverse effects of Opioid analgesics are related to effects on the CNS. This article reviews the causes and treatment of the most frequent CNS adverse effects of Opioid analgesics prescribed for the relief of cancer-related pain. Such effects can occur during short term treatment of opioid-naive patients (e.g. sedation, nausea, vomiting, respiratory depression, mood changes, difficult micturition) and during long term treatment of patients in chronic pain (e.g. delirium, hyperalgesia, generalised myoclonus, tonic-clonic seizures), and can be classified according to their clinical relevance.

The symptoms can be associated with high concentrations of Opioids and their metabolites in CSF, but can also be caused by pharmacological interactions between Opioids and other drugs commonly used in clinical practice. Moreover, they may be related to the accumulation of active metabolites in patients with renal impairment.

Opioid rotation, hydration of the patient and suspension of drugs that can interfere with the pharmacokinetics of Opioids are suggested approaches to treatment. Psychostimulants can be used to treat opioid-induced sedation. Naloxone can be used to reverse severe respiratory depression caused by high doses of Opioids. Haloperidol and midazolam are useful for the treatment of opioid-induced hyperactive delirium.

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References

  1. Foley KM. The treatment of cancer pain. N Engl J Med 1984; 313: 84–95

    Google Scholar 

  2. Cleeland CS, Bruera E. Pain and symptom management. In: Love R, editor. Manual of clinical oncology. 6th ed. New York: Springer-Verlag, 1994: 556–69

    Google Scholar 

  3. Ellison NM. Opioid analgesics for cancer pain: toxicities and their treatments. In: Patt RB, editor. Cancer pain. Philadelphia: J.B. Lippincott Company, 1993: 185–94

    Google Scholar 

  4. Sjogren P, Eriksen J. Opioid toxicity. Curr Opin Anaesth 1994; 7: 465–9

    Google Scholar 

  5. World Health Organization. Cancer pain relief and palliative care. Report of a WHO Expert Committee. Geneva: World Health Organization, 1993

    Google Scholar 

  6. Bruera E, Macmillan K, Hanson J, et al. Palliative care in a cancer center: results in 1984 versus 1987. J Pain Sympt Manage 1990; 5(1): 1–5

    CAS  Google Scholar 

  7. Bruera E, Fox R, Chadwick S, et al. Changing patterns in the treatment of pain and other symptoms in advanced cancer patients. J Pain Symptom Manage 1987; 2(3): 139–45

    PubMed  CAS  Google Scholar 

  8. Leipzig RM, Goodman H, Gray G, et al. Reversible, narcotic-associated mental status impairment in patients with meta-static cancer. Pharmacology 1987; 35: 47–54

    PubMed  CAS  Google Scholar 

  9. MacDonald N, Der L, Allan S, et al. Opioid hyperexcitability: the application of alternate opioid therapy. Pain 1993; 53: 353–5

    PubMed  CAS  Google Scholar 

  10. Parkinson SK, Bailey SL, Little WL, et al. Myoclonic seizure activity with chronic high-dose spinal opioid administration. Anesthesiology 1990; 72: 743–5

    PubMed  CAS  Google Scholar 

  11. Sjogren P, Jonsson T, Jensen N-H, et al. Hyperalgesia and myoclonus in terminal cancer patients treated with continuous intravenous morphine. Pain 1993; 55: 93–7

    PubMed  CAS  Google Scholar 

  12. Sjogren P, Banning AM, Christensen CB, et al. Continuous reaction time after single dose, long-term oral and epidural opioid administration. Eur J Anaesthesiol 1994; 11: 95–100

    PubMed  CAS  Google Scholar 

  13. Bruera E, Macmillan K, Hanson J, et al. The cognitive effects of the administration of narcotic analgesics in patients with cancer pain. Pain 1989; 39: 13–6

    PubMed  CAS  Google Scholar 

  14. Vainio A, Ollila J, Matikainen E, et al. Driving ability in cancer patients receiving long-term morphine analgesia. Lancet 1995; 346: 667–70

    PubMed  CAS  Google Scholar 

  15. Banning A, Sjogren P, Kaiser F. Reaction time in cancer patients receiving peripherally acting analgesics alone or in combination with Opioids. Acta Anaesthesiol Scand 1992; 36: 480–2

    PubMed  CAS  Google Scholar 

  16. Banning A, Sjogren P. Cerebral effects of long-term oral Opioids in cancer patients measured by continuous reaction time. Clin J Pain 1990; 6: 91–5

    PubMed  CAS  Google Scholar 

  17. Saarialho-Kere U, Mattila MJ, Paloheimo M, et al. Psychomotor, respiratory and neuroendocrinological effects of buprenorphine and amitriptyline in healthy volunteers. Eur J Clin Pharmacol 1987; 33: 139–46

    PubMed  CAS  Google Scholar 

  18. MacDonald FC, Gough KJ, Nicoli RAG, et al. Psychomotor effects of ketorolac in comparison with buprenorphine and diclofenac. Br J Pharmacol 1989; 27: 453–9

    CAS  Google Scholar 

  19. Sjogren P, Banning A. Pain, sedation and reaction time during long-term treatment of cancer patients with oral and epidural opioids. Pain 1989; 39: 5–11

    PubMed  CAS  Google Scholar 

  20. Sjogren P, Banning AM, Larsen TK, et al. Postural stability during long-term treatment of cancer patients with epidural opioids. Acta Anaesthesiol Scand 1990; 34: 410–2

    PubMed  CAS  Google Scholar 

  21. Gordon N. Reaction-times of methadone treated ex-heroin addicts. Psychopharmacologia 1976; 16: 337–44

    Google Scholar 

  22. Lombardo WK, Lombardo B, Goldstein A. Cognitive functioning under moderate and low dosage methadone maintenance. Int J Addict 1976; 11: 389–401

    PubMed  CAS  Google Scholar 

  23. Rothenberg S, Schottenfeld S, Meyer RE, et al. Performance differences between addicts and non-addicts. Psychopharmacology 1977; 52: 299–307

    PubMed  CAS  Google Scholar 

  24. Joo S. Methadone substitution and driver ability: research findings and conclusions from a discussion of experts. J Traffic Med 1994; 22: 101–3

    Google Scholar 

  25. Bruera E, Fainsinger RL, Schoeller T, et al. Rapid discontinuation of hypnotics in terminal cancer patients: a prospective study. Ann Oncology 1996; 7: 855–6

    CAS  Google Scholar 

  26. Bruera E, Chadwick S, Weinlick A, et al. Delirium and severe sedation in patients with terminal cancer. Cancer Treat Rep 1987; 71(7/8): 787–8

    PubMed  CAS  Google Scholar 

  27. Osborne R, Joes S, Slevin M. Morphine intoxication in renal failure: the role of morphine-6-glucuronide. BMJ 1986; 292: 1548–9

    PubMed  CAS  Google Scholar 

  28. Osborne R, Joel S, Trew D, et al. Morphine and metabolite behaviour after different routes of morphine administration: demonstration of the importance of the active metabolite morphine-6-glucuronide. Clin Pharmacol 1990; 47: 12–9

    CAS  Google Scholar 

  29. Fainsinger R, Miller MJ, Bruera E. Morphine intoxication during acute reversible renal insufficiency. J Palliat Care 1990; 8(2): 52–3

    Google Scholar 

  30. Fainsinger R, Schoeller T, Briskin M, et al. Cognitive failure and coma after renal failure in a patient receiving Captopril and hydromorphone. J Palliat Care 1993; 3: 53–5

    Google Scholar 

  31. Bruera E, Brenneis C, Paterson AHG, et al. Use of methylphenidate as an adjuvant to narcotics analgesics in patients with advanced cancer. J Pain Symptom Manage 1989; 4: 3–6

    PubMed  CAS  Google Scholar 

  32. Bruera E, Brenneis C, Chadwick S, et al. Methylphenidate associated with narcotics for the treatment of cancer pain. Cancer Treat Rep 1987; 71: 67–70

    PubMed  CAS  Google Scholar 

  33. Wilwerding MB, Loprinzi CL, Mailliard JA, et al. A randomized, crossover evaluation of methylphenidate in cancer patients receiving strong narcotics. Support Care Cancer 1995; 3: 135–8

    PubMed  CAS  Google Scholar 

  34. Yee JD, Berde CB. Dextroamphetamine or methylphenidate as adjuvants to opioid analgesia for adolescents with cancer. J Pain Symptom Manage 1994; 9: 122–5

    PubMed  CAS  Google Scholar 

  35. Allan SG. Nausea and vomiting. In: Doyle D, Hanks GW, MacDonald N, editors. Oxford textbook of palliative medicine. Oxford: Oxford Medical Publications, 1993: 282–90

    Google Scholar 

  36. Clarke RS. Nausea and vomiting. Br J Anaesth 1984; 56: 19–27

    PubMed  CAS  Google Scholar 

  37. Blancquaert JP, LeFebvre RA, Willems JL. Emetic and antiemetic effects of Opioids in the dog. Eur J Rheumatol 1986; 128: 143–50

    CAS  Google Scholar 

  38. Ventafridda V, Oliveri E, Caraceni A, et al. A retrospective study on the use of oral morphine in cancer pain. J Pain Symptom Manage 1987; 2: 77–81

    Google Scholar 

  39. Peroutka SJ, Snyder SH. Antiemetics: neurotransmitter receptor binding predicts therapeutic actions. Lancet 1982; I: 658–9

    Google Scholar 

  40. Hagen NA, Foley KM, Cerbhone DJ, et al. Chronic nausea and morphine-6-glucuronide. J Pain Symptom Manage 1991; 6: 125–8

    PubMed  CAS  Google Scholar 

  41. Florez J, McCarty LE, Borison HL. A comparative study in the cat of the respiratory effects of morphine injected intravenously and into the cerebrospinal fluid. J Pharmacol Exp Ther 1968; 163: 448–55

    PubMed  CAS  Google Scholar 

  42. Inturrisi CE. Management of cancer pain: pharmacology and principles of management. Cancer 1989; 63: 2308–20

    PubMed  CAS  Google Scholar 

  43. Ling G, Spiegel K, Nishimura SL, et al. Dissociation of morphine’s analgesic and respiratory depressant actions. Eur J Pharmacol 1983; 86: 487–8

    PubMed  CAS  Google Scholar 

  44. Ling G, Spiegel K, Lockhart S, et al. Separation of opioid analgesia from respiratory depression: evidence for different receptor mechanisms. J Pharmacol Exp Ther 1985; 232(1): 149–55

    PubMed  CAS  Google Scholar 

  45. Walsh TD. Opiates and respiratory function in advanced cancer. Recent Results Cancer Res 1984; 89: 115–7

    PubMed  CAS  Google Scholar 

  46. Hanks GW, Twycross RG, Lloyd JW. Unexpected complication of successful nerve block. Anaesthesia 1981; 36: 37

    PubMed  CAS  Google Scholar 

  47. Wells CJ, Lipton S, Lahuerta J. Respiratory depression after percutaneous cervical anterolateral cordotomy in patients on slow-release oral morphine [letter]. Lancet 1984; I: 739

    Google Scholar 

  48. Paix A, Coleman A, Lees J, et al. Subcutaneous fentanyl and sufentanil infusion substitution for morphine intolerance in cancer pain management. Pain 1995; 63: 263–9

    PubMed  CAS  Google Scholar 

  49. Sjogren P, Jakobsen S, Valentin N. Respiratory depression during epidural morphine treatment. Acta Anaesthesiol Scand 1991; 35: 553–5

    PubMed  CAS  Google Scholar 

  50. Hunt G, Bruera E. Respiratory depression in a patient receiving oral methadone for cancer pain. J Pain Symptom Manage 1995; 10: 401–4

    PubMed  CAS  Google Scholar 

  51. Langlade A, Serrie A, Sandouk P, et al. Levels of morphine and metabolites in CSF during respiratory depression after intraventricular morphine injection. Pain 1991; 44: 175–8

    PubMed  CAS  Google Scholar 

  52. Peat SJ, Hanna MH, Woodham M, et al. Morphine-6-glucuronide: effects on ventilation in normal volunteers. Pain 1991; 43: 101–4

    Google Scholar 

  53. Hasselstrom J, Berg U, Lofgren A, et al. Long lasting respiratory depression induced by morphine-6-glucuronide? Br J Clin Pharmacol 1989; 27: 515–8

    PubMed  CAS  Google Scholar 

  54. Paulus DA, Paul WL, Munson ES. Neurologic depression after intrathecal morphine. Anesthesiology 1981; 54: 517–8

    PubMed  CAS  Google Scholar 

  55. Davies GK, Tolhurst-Cleaver CL, Terry LJ. CNS depression from intrathecal morphine. Anesthesiology 1980; 52: 280–1

    PubMed  CAS  Google Scholar 

  56. Lobato RD, Madrid JL, Fatela LV, et al. Intraventricular morphine administration for intractable cancer pain: rationale, methods, clinical results. Acta Anaesthesiol Scand 1987; 31 Suppl. 85: 68–74

    Google Scholar 

  57. Obbens EAMT, Hill CS, Leavens ME, et al. Intraventricular morphine administration for control of chronic cancer pain. Pain 1987; 28: 61–8

    PubMed  CAS  Google Scholar 

  58. Glynn CJ, Mather LE, Cousins MJ, et al. Spinal narcotics and respiratory depression. Lancet 1979; I: 356–7

    Google Scholar 

  59. Christensen V. Respiratory depression after extradural morphine. Br J Anaesth 1987; 52: 841–2

    Google Scholar 

  60. Scott DB, McLure J. Selective epidural analgesia. Lancet 1979; I: 1410–1

    Google Scholar 

  61. Rane A, Sawe J, Pacifici GM, et al. Regio-selective glucuronidation of morphine and interactions with benzodiazepines in human liver. Adv Pain Res Ther 1984; 8: 1297–300

    Google Scholar 

  62. Jacqz E, Ward S, Johnson R, et al. Extrahepatic glucuronidation of morphine in the dog. Drug Metab Dispos 1986; 14: 627–30

    PubMed  CAS  Google Scholar 

  63. Dahlstrom BE, Paalzow LK. Pharmacokinetic interpretation of the enterohepatic recirculation and first-pass elimination of morphine in the rat. J Pharmacokinetic Biopharm 1978; 6: 506–19

    Google Scholar 

  64. Hanks GW, Hoskin PJ, Aherne GW, et al. Entero-hepatic circulation of morphine. Lancet 1988; I: 469–71

    Google Scholar 

  65. Gong Q-L, Hedner J, Bjorkman R, et al. Morphine-3-glucuronide may functionally antagonize morphine-6-glucuronide induced antinociception and ventilatory depression in the rat. Pain 1992; 48: 249–55

    PubMed  CAS  Google Scholar 

  66. Bortolussi R, Fabiani F, Savron F, et al. Acute morphine intoxication during high-dose recombinant interleukin-2 treatment for metastatic renal cell cancer. Eur J Cancer 1994; 30A(12): 1905–7

    PubMed  CAS  Google Scholar 

  67. Bruera E, Miller L, McCallion J, et al. Cognitive failure (CF) in patients with terminal cancer: a prospective study. J Pain Symptom Manage 1992; 7(4): 192–5

    PubMed  CAS  Google Scholar 

  68. Stiefel F, Fainsinger R, Bruera E. Acute confusional states in patients with advanced cancer. J Pain Symptom Manage 1992; 7(2): 54–6

    Google Scholar 

  69. Fainsinger R, Young C. Palliative care round: cognitive failure in a terminally ill patient. J Pain Symptom Manage 1991; 6(8): 492–4

    PubMed  CAS  Google Scholar 

  70. Lipowski ZJ. Update on delirium. Psychiatr Clin North Am 1992; 15: 335–46

    PubMed  CAS  Google Scholar 

  71. Folstein MF, Folstein S, McHugh PR. ‘Mini-mental state’: a practical method for grading the cognitive state of patients for the clinician. J Psychosom Res 1975; 12: 189–98

    CAS  Google Scholar 

  72. Smith MJ, Breitbart WS, Platt MM. A critique of instruments and methods to detect, diagnose, and rate delirium. J Pain Symptom Manage 1995; 10(1): 37–77

    Google Scholar 

  73. Brizer D, Manning D. Delirium induced by poisoning with anticholinergic agents. Am J Psychiatry 1982; 139(10): 1343–4

    PubMed  CAS  Google Scholar 

  74. Tune LE, Carr S, Hoag E, et al. Anticholinergic effects of drugs commonly prescribed for the elderly: potential means for assessing risk of delirium. Am J Psychiatry 1992; 149: 1393–4

    PubMed  CAS  Google Scholar 

  75. Picotte-Prillmayer D, Di Maggio J, Baile WF. H2 blocker delirium. Psychosomatics 1995; 36(1): 74–7

    PubMed  CAS  Google Scholar 

  76. Goodwin JS, Regan M. Cognitive dysfunction associated with naproxen and buprofen in the elderly. Arthritis Rheum 1982; 25(8): 1013–5

    PubMed  CAS  Google Scholar 

  77. Stiefel FC, Breitbart WS, Holland JC. Corticosteroids in cancer: neuropsychiatric complications. Cancer Invest 1989; 7(5): 479–91

    PubMed  CAS  Google Scholar 

  78. Baile WF. Neuropsychiatric disorders in cancer patients. Curr Opin Oncology 1996; 8: 182–7

    CAS  Google Scholar 

  79. de Stoutz ND, Bruera E, Suarez-Almazor M. Opioid rotation for toxicity reduction in terminal cancer patients. J Pain Symptom Manage 1995; 10: 378–84

    PubMed  Google Scholar 

  80. de Stoutz ND, Tapper M, Fainsinger R. Reversible delirium in terminally ill patients. J Pain Symptom Manage 1995; 10: 249–53

    PubMed  Google Scholar 

  81. Ventafridda V, Ripamonti C, De Conno F, et al. Antidepressants increase bioavailability of morphine in cancer patients [letter]. Lancet 1987; I: 1204

    Google Scholar 

  82. McQuay HJ, Carroll D, Faura CC, et al. Oral morphine in cancer pain: influences on morphine and metabolite concentration. Clin Pharmacol Ther 1990; 48: 236–44

    PubMed  CAS  Google Scholar 

  83. Caraceni A, Martini C, De Conno F, et al. Organic brain syndromes and opioid administration for cancer pain. J Pain Symptom Manage 1994; 9: 527–33

    PubMed  CAS  Google Scholar 

  84. Lowe GR. The phenomenology of hallucinations as an aid to differential diagnosis. Br J Psychiatry 1973; 123: 621–33

    PubMed  CAS  Google Scholar 

  85. Bruera E, Miller MJ, Macmillan K, et al. Neuropsychological effects of methylphenidate in patients receiving a continuous infusion of narcotics for cancer pain. Pain 1992; 48: 163–6

    PubMed  CAS  Google Scholar 

  86. Massie MJ, Holland JC. The cancer patient with pain: psychiatric complications and their management. J Pain Symptom Manage 1992; 7: 99–109

    PubMed  CAS  Google Scholar 

  87. Levine PM, Silberfarb PM, Lipowski ZJ. Mental disorders in cancer patients: a study of 100 psychiatric referrals. Cancer 1978; 42: 1385–91

    PubMed  CAS  Google Scholar 

  88. Bruera E, Spachynski K, MacEachern T, et al. Cognitive failure in cancer patients in clinical trials. Lancet 1993; 341: 247–8

    PubMed  CAS  Google Scholar 

  89. Folstein MF, Fetting JH, Lobo A, et al. Cognitive assessment of cancer patients. Cancer 1984; Suppl. 10: 2250–7

    Google Scholar 

  90. Yue M, Fainsinger R, Bruera E. Cognitive impairment in a patient with a normal mini-mental state examination (MMSE). J Pain Symptom Manage 1994; 9: 51–3

    PubMed  CAS  Google Scholar 

  91. Marsden CD, Hallet M, Fahns S. The nosology and pathophysiology of myoclonus. In: Marsden CD, Fahns S, editors. Movement disorders. London: Butterworth, 1982: 196–248

    Google Scholar 

  92. Frenk H, Watkins LR, Mayer DJ. Differential behavioral effects induced by intrathecal microinjection of opiates: comparison of convulsive and cataleptic effects produced by morphine, methadone, and D-ala2-methionine-enkephalinamide. Brain Res 1984; 299: 31–42

    PubMed  CAS  Google Scholar 

  93. Glavina MJ, Robertshaw R. Myoclonic spasms following intrathecal morphine. Anaesthesia 1988; 43: 389–90

    PubMed  CAS  Google Scholar 

  94. De Conno F, Caraceni A, Martini C, et al. Hyperalgesia and myoclonus with intrathecal infusion of high-dose morphine. Pain 1991; 47: 337–9

    PubMed  Google Scholar 

  95. Krames ES, Gershow Y, Glassberg A. Continuous infusion of spinally administered narcotics for the relief of pain due to malignant disorders. Cancer 1985; 56: 696–702

    PubMed  CAS  Google Scholar 

  96. Glare PA, Walsh TD, Pippenger CE. Normorphine, a neurotoxic metabolite? Lancet 1990; 335: 725–6

    PubMed  CAS  Google Scholar 

  97. Sjogren P, Dragsted L. Myoclonic spasms during treatment with high doses of intravenous morphine in renal failure. Acta Anaesthesiol Scand 1993; 37: 780–2

    PubMed  CAS  Google Scholar 

  98. Eisele JH, Grigsby EJ, Dea G. Clonazepam treatment of myoclonic contractions associated with high-dose Opioids: case report. Pain 1992; 49: 231–2

    PubMed  Google Scholar 

  99. Babul N, Darte AC. Putative role of hydromorphone metabolites in myoclonus [letter]. Pain 1993; 51: 260–1

    Google Scholar 

  100. Szeto HH, Inturrisi CE, Houde R, et al. Accumulation of normeperidine, an active metabolite of meperidine, in patients with renal failure or cancer. Ann Intern Med 1977; 86: 738–41

    PubMed  CAS  Google Scholar 

  101. Kaiko RF, Foley KM, Grabinski PY, et al. Central nervous system excitatory effects of meperidine in cancer patients. Ann Neurol 1983; 13: 180–5

    PubMed  CAS  Google Scholar 

  102. Hochman MS. Meperidine-associated myoclonus and seizures in long-term hemodialysis patients [letter]. Ann Neurol 1983; 14(5): 27

    Google Scholar 

  103. Bowdle TA. Myoclonus following sufentanil without EEG seizure activity. Anesthesiology 1987; 67: 593–5

    PubMed  CAS  Google Scholar 

  104. Rao T, Mummaneni N. Convulsions: an unusual response to intravenous fentanyl administration. Anesth Analg 1982; 61: 1020–1

    PubMed  CAS  Google Scholar 

  105. Tommasino C, Maekawa T, Shapiro HM. Fentanyl-induced seizures activate subcortical brain metabolism. Anesthesiology 1984; 60: 283–90

    PubMed  CAS  Google Scholar 

  106. Pasternack GW, Bodmar RJ, Clark JA, et al. Morphine-6-glucuronide, a potent new agonist. Life Sci 1987; 41: 2845–9

    Google Scholar 

  107. Labella FS, Pinsky C, Havlicek V. Morphine derivates with diminished opiate receptor potency enhanced central excitatory activity. Brain Res 1979; 174: 263–71

    PubMed  CAS  Google Scholar 

  108. Hagen N, Thirlwell MP, Dhaliwal HS, et al. Steady-state pharmacokinetics of hydromorphone and hydromorphone-3-glucuronide in cancer patients after immediate and controlled-release hydromorphone. J Clin Pharmacol 1995; 35: 37–44

    PubMed  CAS  Google Scholar 

  109. Babul N, Hagen N, Baker T. Hydromorphone metabolite: accumulation in renal failure. J Pain Symptom Manage 1995; 10(3): 184–6

    PubMed  CAS  Google Scholar 

  110. Potter JM, Reid DB, Shaw RJ, et al. Myoclonus associated with treatment with high doses of morphine: the role of supplemental drugs. BMJ 1989; 299: 150–3

    PubMed  CAS  Google Scholar 

  111. International Association for the Study of Pain Subcommittee on Taxonomy. Classification of chronic pain: descriptions of chronic pain syndromes and definitions of pain terms. Pain 1986; 3: 217–9

    Google Scholar 

  112. Sjogren P, Jensen N-H, Jensen T-S. Disappearance of morphine-induced hyperalgesia after discontinuing or substituting morphine with other opioid agonists. Pain 1994; 59: 315–6

    Google Scholar 

  113. Ali NMK. Hyperalgesic response in a patient receiving high concentrations of spinal morphine [letter]. Anesthesiology 1986; 65: 449

    PubMed  CAS  Google Scholar 

  114. Stillman MJ, Moulin DE, Foley KE. Paradoxical pain following high-dose spinal morphine [abstract]. Pain 1987; 4: S389

    Google Scholar 

  115. Yaksh TL, Harty GJ. Pharmacology of the allodynia in rats evoked by high-dose intrathecal morphine. J Pharmacol Exp Ther 1987; 244: 501–7

    Google Scholar 

  116. Woolf CJ. Intrathecal high dose morphine produces hyperalgesia in the rat. Brain Res 1981; 209: 491–5

    PubMed  CAS  Google Scholar 

  117. Bruera E, Kuehn N, Miller MJ, et al. The Edmonton symptom assessment system (ESAS): a simple method for the assessment of palliative care patients. J Palliat Care 1991; 7: 6–9

    PubMed  CAS  Google Scholar 

  118. Bruera E, Schoeller T, Wenk R, et al. A prospective multicenter assessment of the Edmonton Staging System for cancer pain. J Pain Symptom Manage 1995; 10: 348–55

    PubMed  CAS  Google Scholar 

  119. Ewing J. Detection alcoholism: the CAGE Questionnaire. JAMA 1984; 252: 1905–7

    PubMed  CAS  Google Scholar 

  120. Lawlor P, Walker P, Bruera E. Severe opioid toxicity in a cancer patient coping chemically with psychosocial suffering. J Pain Symptom Manage. In press

  121. Robinson K, Bruera E. The management of pain in patients with advanced cancer: the importance of multidimensional assessments. J Palliat Care 1995; 11: 51–3

    PubMed  CAS  Google Scholar 

  122. Coyle N, Breitbart W, Weaver S. Delirium as a contributing factor to ‘crescendo’ pain: three case reports. J Pain Symptom Manage 1994; 9: 44–7

    PubMed  CAS  Google Scholar 

  123. Ripamonti C, Rodriguez C. Gastrointestinal motility disorders in advanced cancer patients. In: Portenoy RK, Bruera E, editors. Supportive care medicine. New York: Oxford University Press, 1996. In press

  124. Wamsley JK, Lewis MS, Young WS, et al. Autoradiographic localisation of muscarinic cholinergic receptors in rat brainstem. J Neurosci 1981; 1: 176–91

    PubMed  CAS  Google Scholar 

  125. Palacios JM, Wamsley JK, Kuhar MJ. The distribution of histamine H1-receptors in the rat brain: an autoradiographic study. Neuroscience 1981; 6: 15–7

    PubMed  CAS  Google Scholar 

  126. Bradberry JC, Raebel MA. Continuous infusion of naloxone in the treatment of narcotic overdose. Drug Intell Clin Pharm 1981; 15: 945–7

    PubMed  CAS  Google Scholar 

  127. Citron ML. How would you treat narcotic overdoses in cancer patients? Drug Therapy 1984; 9: 85–7

    Google Scholar 

  128. Osborne RJ, Joel SP, Trew D, et al. Analgesic activity of morphine-6-glucuronide [letter]. Lancet 1988; 2: 188

    Google Scholar 

  129. Forrest W, Brown B, Brown C, et al. Dextroamphetamine with morphine for the treatment of postoperative pain. New Engl J Med 1977; 296: 712–5

    PubMed  Google Scholar 

  130. Kreeger L, Duncan A, Cowap J. Psychostimulants used for opioid-induced drowsiness. J Pain Symptom Manage 1996; 11(1): 1–2

    PubMed  CAS  Google Scholar 

  131. Bruera E, Fainsinger R, MacEachern T, et al. The use of methyl-phenidate in patients with incident cancer pain receiving regular opiates: a preliminary report. Pain 1992; 50: 75–7

    PubMed  CAS  Google Scholar 

  132. Bruera E, Watanabe S. Psychostimulants as adjuvant analgesics. J Pain Symptom Manage 1994; 9: 412–5

    PubMed  CAS  Google Scholar 

  133. Fernandez F, Adams F, Levy JK, et al. Cognitive impairment due to AIDS-related complex and its response to psychostimulants. Psychosomatics 1988; 29: 38–46

    PubMed  CAS  Google Scholar 

  134. Wilens TE, Biederman J. The stimulants. Psychiatr Clin North Am 1992; 15(1): 191–222

    PubMed  CAS  Google Scholar 

  135. Breitbart W, Marotta R, Platt MM, et al. A double-blind trial of haloperidol, chlorpromazine, and lorazepam in the treatment of delirium in hospitalized AIDS patients. Am J Psychiatry 1996; 153: 231–7

    PubMed  CAS  Google Scholar 

  136. Settle EC, Ayd FJ. Haloperidol: a quarter century of experience. J Clin Psychiatry 1983; 44: 440–8

    PubMed  CAS  Google Scholar 

  137. Bottomley DM, Hanks GW. Subcutaneous midazolam infusion in palliative care. J Pain Symptom Manage 1990; 5: 259–61

    PubMed  CAS  Google Scholar 

  138. De Sousa E, Jepson BA. Midazolam in terminal care. Lancet 1988; 1: 67–8

    PubMed  Google Scholar 

  139. Morley JS, Miles JB, Bowsher D. Paradoxical pain [letter]. Lancet 1992; 340: 1045

    PubMed  CAS  Google Scholar 

  140. Smith MT, Watt JA, Cramond T. Morphine-3-glucuronide: a potent antagonist of morphine analgesia. Life Sci 1990; 47: 579–85

    PubMed  CAS  Google Scholar 

  141. Zaw Tun N, Bruera E. Active metabolites of morphine. J Palliat Care 1992; 8: 48–50

    PubMed  CAS  Google Scholar 

  142. Portenoy RK, Foley KM, Stulman J, et al. Plasma morphine and morphine-6-glucuronide during chronic morphine therapy for cancer pain: plasma profiles, steady state concentrations and the consequences of renal failure. Pain 1991; 47: 13–9

    PubMed  CAS  Google Scholar 

  143. Eisendrath SJ, Goldman B, Douglas J, et al. Meperidine-induced delirium. Am J Psychiatry 1987; 144: 1062–5

    PubMed  CAS  Google Scholar 

  144. Steimberg RB, Gilman DE, Johnson III F. Acute toxic delirium in a patient using transdermal fentanyl. Anesth Analg 1992; 75: 1014–6

    Google Scholar 

  145. Ripamonti C, Zecca E, Bruera E. An update on the clinical use of methadone for cancer pain. Pain 1997; 70: 109–15

    PubMed  CAS  Google Scholar 

  146. Bruera E, Pereira J, Watanabe S, et al. Opioid rotation in patients with cancer pain: a retrospective comparison of dose ratios between methadone, hydromorphone and morphine. Cancer 1996; 78(4); 852–7

    PubMed  CAS  Google Scholar 

  147. Fainsinger RL, MacEachern T, Miller MJ, et al. The use of hypodermoclysis for rehydration in terminally ill cancer patients. J Pain Symptom Manage 1994; 9: 298–302

    PubMed  CAS  Google Scholar 

  148. Billings JA. Comfort measures for the terminally ill: is dehydration painful? J Am Geriatr Soc 1985; 33: 808–10

    PubMed  CAS  Google Scholar 

  149. Printz LA. Is withholding hydration a valid comfort measure in the terminally ill? Geriatrics 1988; 43: 84–8

    PubMed  CAS  Google Scholar 

  150. Musgrave CF. Terminal dehydration: to give or not to give intravenous fluids? Cancer Nursing 1990; 13: 62–6

    PubMed  CAS  Google Scholar 

  151. Yan E, Bruera E. Case report: parenteral hydration of terminally ill cancer patients. J Palliat Care 1991; 7: 40–3

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Pain Therapy and Palliative Care Division, National Cancer Institute, Milan, Italy

    Carla Ripamonti

  2. Palliative Care Program, Grey Nuns Community Health Centre, 1100 Youville Drive West, Edmonton, Alberta, Canada, T6L 5X8

    Eduardo Bruera

Authors
  1. Carla Ripamonti
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  2. Eduardo Bruera
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Ripamonti, C., Bruera, E. CNS Adverse Effects of Opioids in Cancer Patients. CNS Drugs 8, 21–37 (1997). https://doi.org/10.2165/00023210-199708010-00003

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