Indications for the Use of Intraspinal Opioids

  • Narinder Rawal
Part of the Current Management of Pain book series (CUMP, volume 6)


Following identification of highly specific opioid receptors in the brain and spinal cord of animals and man in 1973 [1,2], it was demonstrated in 1976 that intrathecal morphine produced antinociception in rats [3]. The first clinical use of the technique for the treatment of cancer pain was reported in 1979 [4]. Today, ten years and several hundred international publications later, the technique of injecting opioids epidurally and intrathecally for the management of acute and chronic pain is well established. Although this modality is not the panacea early reports appeared to promise, its place as a major advance in the management of acute and chronic pain is beyond doubt. This chapter will attempt to provide the current indications for the use of epidural and intrathecal opioids.


Respiratory Depression Postoperative Analgesia Intrathecal Administration Epidural Morphine Intrathecal Morphine 
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  1. 1.
    Pert CB, Synder SH. 1973. Opiate receptor: Demonstration in nervous tissue. Science 179:1947–1949.CrossRefGoogle Scholar
  2. 2.
    Terenius L. 1973. Characteristics of the “receptor” for narcotic analgesia in synaptic plasma membrane fractions from rat brain. Acta Pharmacol Toxicol 33:337–384.Google Scholar
  3. 3.
    Yaksh TL, Rudy TA. 1976. Analgesia mediated by a direct spinal action of narcotics. Science 192:1357–1358.PubMedCrossRefGoogle Scholar
  4. 4.
    Wang KH, Nauss LA, Thomas JE. 1979. Pain relief by intrathecally applied morphine in man. Anesthesiology 50:149–151.PubMedCrossRefGoogle Scholar
  5. 5.
    Rawal N, Arnér S, Gustafsson LL, Alvin R. 1987. Present state of epidural and intrathecal opiate analgesia — a nationwide follow-up survey in Sweden. Br J Anaesth 59:791–799.PubMedCrossRefGoogle Scholar
  6. 6.
    Cousins JD, Mather LE. 1984. Intrathecal and epidural administration of opioids. Anesthesiology 61:276–310.PubMedCrossRefGoogle Scholar
  7. 7.
    Müller H, Borner U, Zierski J, Hempelmann G. 1987. Intrathecal baclofen for treatment of tetanus-induced spasticity. Anesthesiology 66:76–79.PubMedCrossRefGoogle Scholar
  8. 8.
    Erickson DL, Blacklock JB, Michaelson M, Sperling UB, Lo JN. 1985. Control of spasticity by implantable continuous flow morphine pump. Neurosurgery 16:215–217.PubMedCrossRefGoogle Scholar
  9. 9.
    Caplan RA, Ready LB, Olsson GL, Nessley ML. 1986. Transdermal delivery of fentanyl for postoperative pain control. Anesth Analg 65:195.CrossRefGoogle Scholar
  10. 10.
    Slowey HF, Reynolds AD, Mapleson WW, Vickers MD. 1985. Effect of premedication with controlled-release oral morphine on postoperative pain. Anaesthesia 40:438–440.PubMedCrossRefGoogle Scholar
  11. 11.
    Streisand JB, Hague B, Vreeswijk HV, Ho GH, Pace NL, Clissold M, Nelson P, East KA, Standley TO, Stanley TH. 1987. Oral transmucosal fentanyl premedication in children. Anesth Analg 66:S170.CrossRefGoogle Scholar
  12. 12.
    Carl P, Crawford ME, Madsen NBB, Ravlo O, Bach V, Larsen AI. 1987. Pain relief after major abdominal surgery: A double blind controlled comparison of sublingual buprenor-phine, intramuscular buprenorphine and intramuscular meperidine. Anesth Analg 66:142–146.PubMedCrossRefGoogle Scholar
  13. 13.
    Chrubasik J, Geller E, Niv D, Zindler M. 1987. Morphine inhalation versus intravenous infusion in pain treatment after abdominal surgery. Anesth Analg 66.S29.CrossRefGoogle Scholar
  14. 14.
    Tamsen A, Hartvig P, Fagerland C. 1982. Patient controlled analgesic therapy: Individual anlagesic demand and analgesic plasma concentrations of pethidine in postoperative pain. Clin Pharmacokinet 7:164–175.PubMedCrossRefGoogle Scholar
  15. 15.
    Murphy DF. 1983. Continuous intercostal nerve blockade for pain relief following cholecystectomy. Br J Anaesth 55:521–524.PubMedCrossRefGoogle Scholar
  16. 16.
    Seltzer JL, Larijain GE, Goldberg ME, Marr AT, Rocci ML. 1986. A kinetic and dynamic evaluation of intrapleural bupivacaine for subcostal incisional pain. Anesthesiology 65:A213.CrossRefGoogle Scholar
  17. 17.
    Patel JM, Lanzaframe RJ, Williams JS, Muller BV, Hinshaw JR. 1983. The effect of incisional infiltration of bupivacaine hydrochloride upon pulmonary functions, atelectasis, and narcotic need following elective cholecystectomy. Surg Gynecol Obstet 157:338–340.PubMedGoogle Scholar
  18. 18.
    Raj PP, Denson DD. 1986. Prolonged analgesia techniques with local continuous brachial plexus block anesthetics. In Raj PP (ed): Practical Management of Pain. Chicago: Year Book Medical Publishers, pp. 687–700.Google Scholar
  19. 19.
    Tuominen MK, Pitkänen MT, Rosenberg PH. 1986. Continuous interscalene brachial plexus block with bupivacaine for postoperative pain relief. Anesthesiology 65:A197.CrossRefGoogle Scholar
  20. 20.
    Scott DB. 1982. Postoperative pain relief. Reg Anaesth 7:S110–113.Google Scholar
  21. 21.
    Utting JE, Smith JM. 1979. Postoperative analgesia. Anaesthesia 34:320–322.PubMedCrossRefGoogle Scholar
  22. 22.
    Postoperative pain. Editorial. 1978. Br Med J 2:517–518.Google Scholar
  23. 23.
    Weis O, Srivatankul K, Alloza JL, Weintraub M, Lasagna L. 1983. Attitudes of patients, house staff, and nurses toward postoperative analgesic care. Anesth Analg 62:70–74.PubMedGoogle Scholar
  24. 24.
    Rawal N, Sjöstrand UH, Dahlström B, Nydahl PA, Östelius J. 1982. Epidural morphine for postoperative pain relief: A comparative study with intramuscular narcotic and intercostal nerve block. Anesth Analg 61:93–98.PubMedCrossRefGoogle Scholar
  25. 25.
    Aun C, Thomas D, St John-Jones L, Colvin MP, Savege TM, Lewis CT. 1985. Intrathecal morphine in cardiac surgery. Eur J Anaesthesiol 2:419–426.Google Scholar
  26. 26.
    Gray JR, Fromme GA, Nauss LA, Wang JK, Duane MI. 1986. Intrathecal morphine for post-thoracotomy pain. Anesth Analg 65:873–876.PubMedCrossRefGoogle Scholar
  27. 27.
    Hyde NH, Harrison DM. 1986. Intrathecal morphine in a parturient with cystic fibrosis. Anesth Analg 65:1357–1358.PubMedCrossRefGoogle Scholar
  28. 28.
    Brizgys RV, Shnider SM. 1984. Hyperbaric intrathecal morphine analgesia during labor in a patient with Wolff—Parkinson—White Syndrome. Obstet Gynecol 64:445–465.Google Scholar
  29. 29.
    Rawal N, Sjostrand U, Christoffersson E, Rydman H., Arvill A. 1984. Comparison of intramuscular and epidural morphine for postoperative analgesia in the grossly obese: Influence on postoperative ambulation and pulmonary function. Anesth Analg 63:583–592.PubMedGoogle Scholar
  30. 30.
    Brownridge P, Frewin D. 1985. A comparative study of techniques of postoperative analgesia following caesarean section and lower abdominal surgery. Anaesthe Intensive Care 13: 123–130.Google Scholar
  31. 31.
    Harrison DM, Sinatra RS, Morgese L, Chung JH, Mandel ALZ. 1986. Epidural and patient controlled analgesia for post-cesarean section pain relief. Anesthesiology 65:A364.CrossRefGoogle Scholar
  32. 32.
    Purves PG, Sperring SJ, Dykes V, Stanley TD. 1987. Improved postoperative analgesia: Epidural vs patient controlled intravenous morphine. Anesth Analg 66:SI43.Google Scholar
  33. 33.
    Hjortsø ND, Lund C, Mogensen T, Bigler D, Kehlet H. 1986. Epidural morphine potentiates pain relief and maintains sensory analgesia during continuous epidural bupivacaine after abdominal surgery. Anesth Analg 65:1033–1036.PubMedGoogle Scholar
  34. 34.
    Abouleish E, Rawal N, Fallon K, Hernandez D. 1988. Combined intrathecal morphine and bupivacaine for cesarean section. Anesth Analg 67:370–374.PubMedCrossRefGoogle Scholar
  35. 35.
    Rawal N, Sjöstrand U, Dahlström B. 1981. Postoperative pain relief by epidural morphine. Anesth Analg 60:726–731.PubMedCrossRefGoogle Scholar
  36. 36.
    Isacsson IJ, Weitz FI, Berry AJ, Knos GB, Venner DS. 1987. Intrathecal morphine’s effect on the postoperative course of patients undergoing abdominal aortic surgery. Anesth Analg 66:S86.CrossRefGoogle Scholar
  37. 37.
    Johnston JR, McCaughey W. 1980. Epidural morphine: A method of management of multiple fractured ribs. Anaesthesia 35:155–159.PubMedCrossRefGoogle Scholar
  38. 38.
    Rawal N, Tandon B. 1985. Epidural and intrathecal morphine in intensive care units. Intensive Care Med 11:129–133.PubMedCrossRefGoogle Scholar
  39. 39.
    Miller Jones CMH, Williams JH. 1980. Sedation for ventilation. Anaesthesai 35:1104–1106.CrossRefGoogle Scholar
  40. 40.
    Abboud TK, Shnider SM, Raya J A, Grobler NM, Sadri S, Khoo SS, De Souza B, Baysinger CL, Miller F. 1984. Intrathecal administration of hyperbaric morphine for the relief of pain in labour. Br J Anaesth 56:1351–1360.PubMedCrossRefGoogle Scholar
  41. 41.
    Gustafsson LL, Schildt B, Jacobsen KJ. 1982. Adverse effects of epidural and intrathecal opiates: Report of a nationwide study in Sweden. Br J Anaesth 54:479–486.PubMedCrossRefGoogle Scholar
  42. 42.
    Chadwick HS, Ready LB. 1987. Comparison of intrathecal and epidural morphine sulphate for post-cesarean section analgesia. Reg Anaesth 12:40–41.Google Scholar
  43. 43.
    Nordberg G. 1984. Pharmacokinetic aspects of spinal morphine analgesia. Acta Anaesthesiol Scand Suppl 28:1.CrossRefGoogle Scholar
  44. 44.
    Bengtsson M, Löfström JB, Merits H. 1983. Postoperative pain relief with intrathecal morphine after major hip surgery. Reg Anesth 8:139.Google Scholar
  45. 45.
    Glass PSA, Biagi B, Sischy S, Camporesi E. 1985. Analgesic action of very low dose intrathecal morphine (0.1 mg) as compared to higher doses (0.2–0.4 mg). Anesthesiology 65:A236.CrossRefGoogle Scholar
  46. 46.
    Samii J, Chauvin M, Viars P. 1981. Postoperative spinal analgesia with morphine. Br J Anaesth 53:817–820.PubMedCrossRefGoogle Scholar
  47. 47.
    Duckett JE, McDonnell T, Zebrowski M, Witte M. 1987. Lumbar versus thoracic continuous epidural sufentanil for postoperative analgesia after upper abdominal surgery. Anaesth Analg 66:S45.CrossRefGoogle Scholar
  48. 48.
    Matthew EB, Henderson SK, Avram MJ, Glassenberg R, Cohen H. 1987. Epidural hydromorphine versus epidural morphine in postcesarean section analgesia. Anaesth Analg 66:S112.CrossRefGoogle Scholar
  49. 49.
    Palacios QT, Jones MM, Tessem J, Adenwala J, Longmire S. 1987. Comparison of epidural butorphanol and morphine for analgesia after cesarean section. Anesth Analg 66:S133.CrossRefGoogle Scholar
  50. 50.
    Chauvin M, Salbaing J, Perrin D, Leuron JC, Viars P. 1985. Clinical assessment and plasma pharmacokinetics associated with intramuscular or extradural alfentanil. Br J Anaesth 57: 886–891.PubMedCrossRefGoogle Scholar
  51. 51.
    Bilsbach P, Rolly G, Tampubolon O. 1985. Efficacy of the extradural administration of alfentanil, buprenorphine or saline in the management of postoperative pain. Br J Anaesth 57:943–948.CrossRefGoogle Scholar
  52. 52.
    Rao U, Campbell IT, Catley DM, Sutherst JR. 1985. Epidural meptazinol for pain relief after lower abdominal surgery. Anaesthesia 40:754–758.PubMedCrossRefGoogle Scholar
  53. 53.
    Kalia PK, Madan R, Saksena R, Batra RK, Gode GR. 1983. Epidural pentazocine for post-operative pain relief. Anesth Analg 62:949–950.PubMedCrossRefGoogle Scholar
  54. 54.
    Paterson GMC, McQuay HJ, Bullingham RES, Moore RA. 1984. Intradural morphine and diamorphine. Anaesthesia 39:113–117.PubMedCrossRefGoogle Scholar
  55. 55.
    Evron S, Samueloff A, Simon A, Drenger B, Magora A. 1985. Urinary function during epidural analgesia with methadone and morphine in post-cesarean section patients. Pain 23:135–144.PubMedCrossRefGoogle Scholar
  56. 56.
    Knape JTA. 1986. Early respiratory depression resistant to naloxone following epidural buprenorphine. Anesthesiology 64:382–384.PubMedCrossRefGoogle Scholar
  57. 57.
    Wang BC, Hillman DE, Spielholz N, et al. 1984. Subarachnoid blockade by sodium met-abisulfite. Reg Anesth 9:45.Google Scholar
  58. 58.
    Gissen AJ, Datta S, Lambert D. 1984. The chloroprocaine controversy. II. Is chloroprocaine neurotoxic? Reg Anesth 9:135.Google Scholar
  59. 59.
    Saiki JH, Thompson S, Smith F, et al. 1972. Paraplegia following intrathecal chemotherapy. Cancer 29:370PubMedCrossRefGoogle Scholar
  60. 60.
    Craig DB, Habib GG. 1977. Flaccid paraparesis following obstetrical epidural anesthesia: Possible role of benzyl alcohol. Anesth Analg 56:219–221.PubMedGoogle Scholar
  61. 61.
    Feasby TE, Hahn AF, Gilbert JJ. 1983. Neurotoxicity of bacteriostatic water. N Engl J Med 308:966.PubMedGoogle Scholar
  62. 62.
    Brock-Utne JG, Mankowitz E, Kalhichurum S, Downing JW. 1982. Effects of intrathecal saline and ketamine with and without preservative on the spinal nerve roots of monkeys. S Afr Med J 61:360–361.PubMedGoogle Scholar
  63. 63.
    Ahuja BR. 1983. Analgesic effect of intrathecal ketamine in rats. Br J Anaesth 55:991–995.PubMedCrossRefGoogle Scholar
  64. 64.
    Eisenach JC. 1988. Demonstrating safety of subarachnoid calcitonin: patients or animals. Anesth Analg 67:298.PubMedCrossRefGoogle Scholar
  65. 65.
    Gaumann DM, Yaksh TL. 1988. Spinal administration of somatostatin in animals and humans. Anesthesiology 69:808–810.CrossRefGoogle Scholar
  66. 66.
    Abouleish R, Barmada MA, Nemoto EM, et al. 1981. Acute and chronic effects on intrathecal morphine in monkeys. Br J Anaesth 53:1027–1032.PubMedCrossRefGoogle Scholar
  67. 67.
    Meier FA, Coombs DW, Saunders RL, et al. 1982. Pathologic anatomy of constant morphine infusion by intraspinal silastic catheter. Anesthesiology 57:A206.CrossRefGoogle Scholar
  68. 68.
    Yaksh TL. 1981. Spinal opiate analgesia: Characteristics and principles of action. Pain 11: 293–346.PubMedCrossRefGoogle Scholar
  69. 69.
    King FG, Baxter AD, Mathieson G. 1984. Tissue reaction of morphine applied to the epidural space of dogs. Can Anaesth Soc J 31:268–271.PubMedCrossRefGoogle Scholar
  70. 70.
    Gordh T, Post C, Olsson Y. 1986. Evaluation of the toxicity of subarachnoid clonidine, guanfacine and a substance P-antagonist on rat spinal cord and nerve roots: Light and electron microscopic observations after chronic intrathecal administration. Anesth Analg 65:1303–1311.PubMedGoogle Scholar
  71. 71.
    Mollenholt P, Post C, Rawal N, Friedman J, Hökfelt T, Paulsson I. 1988. Antinociception and neurotoxicity of intrathecal somatostatin in the rat. Pain 32:95–105.PubMedCrossRefGoogle Scholar
  72. 72.
    Robinson SJS, Lenis S, Elliot M. 1984. Accidental epidural narcotic overdose. Can Anaesth Soc J 31:594–596.PubMedCrossRefGoogle Scholar
  73. 73.
    Arnér S, Rawal N, Gustafsson LL. 1988. Clinical experience of long term treatment with extradural and intrathecal opioids — a nationwide survey. Acta Anaesth Scand 32:253–259.PubMedCrossRefGoogle Scholar
  74. 74.
    Negre I, Gueneron JP, Ecoffey C, Lerron JC, Samii K. 1985. CO2 sensitivity after epidural fentanyl. Anesthesiology 63:A507.CrossRefGoogle Scholar
  75. 75.
    Duckett JE, McDonnell T, Zebrowski M, Witte M. 1987. Lumbar versus thoracic continuous epidural sufentanil for postoperative analgesia after upper abdominal surgery. Anesth Analg 66:S45CrossRefGoogle Scholar
  76. 76.
    Penon C, Negre I, Ecoffey C, Gross JB, Samii K. 1986. Influence of naloxone infusion on respiratory depression following epidural alfentanil. Anesthesiology 65.A173.CrossRefGoogle Scholar
  77. 77.
    Rawal N. 1988. Spinal opioids — clinical aspects. In Lofstrom B, Sjostrand U (eds): Monographs in Anesthesiology. Local Anesthesia and Regional Blockade, Vol. 15. Amsterdam: Elsevier Publishing B.V.Google Scholar
  78. 78.
    Matthew EB, Henderson SK, Auram MJ, Glassenberg R, Cohen H. 1987. Epidural hydromorphone versus epidural morphine for postcesarean section analgesia. Anesth Analg 66.S112.CrossRefGoogle Scholar
  79. 79.
    Palacios QT, Jones MM, TessemJ, Aden wale J, Longmire S, Joyce TH. 1987. Comparison of epidural butorphanol and morphine for analgesia after cesarean section. Anesth Analg 66:S133.CrossRefGoogle Scholar
  80. 80.
    Fischer R, Lubenow T, Liceaga A, McCarthy RJ, Ivankovich AD. 1987. A comparison of continuous epidural narcotic /local anesthetic mixtures for postoperative analgesia. Anesth Analg 66:S56.CrossRefGoogle Scholar
  81. 81.
    Bion JF. 1984. Intrathecal ketamine for way surgery. A preliminary study under field conditions. Anaesthesia 39:1023–1028.PubMedCrossRefGoogle Scholar
  82. 82.
    Carli P, Ecoffey C, ChrubasikJ, Bendabed M, Gross JB, Samii K. 1986. Spread of analgesia and ventilatory response to CO2 following epidural somatostatin. Anesthesiology 65:A216.CrossRefGoogle Scholar
  83. 83.
    Coombs DW, Sanders R, Lachance D. 1985. Intrathecal morphine tolerance: Use of intrathecal clonidine, DADLE, and intraventricular morphine: A representative case and review. Anesthesiology 62:216–221.CrossRefGoogle Scholar
  84. 84.
    Mirelles FS, Lopez-Soriano F, Perez D, Lopez-Rodriguez F, Puig MM. 1986. Subarachnoid administration of calcitonin produces postoperative analgesia. Anesthesiology 65:A199.CrossRefGoogle Scholar
  85. 85.
    Yaksh TL. 1983. The principles behind the use of spinal narcotics. In Clinics in Anesthesiology. Philadelphia: W.B. Saunders Company, pp. 219–232.Google Scholar
  86. 86.
    Chrubasik J, Meynadier J, Scherperell P, Wunch E. 1985. The effect of epidural somatostatin on postoperative pain. Anesth Analg 4:1085–1088.Google Scholar
  87. 87.
    Gaumann D, Yaksh TL. 1988. Intrathecal somatostatin in rats: antinociception only in the presence of toxic effects. Anesthesiology 68:733–742.PubMedCrossRefGoogle Scholar
  88. 88.
    Gaumann D, Yaksh TL, Post C, Wilcox GL, Pierce M, Rodriguez M. In Press. Intrathecal somatostatin in cat and mouse. Studies on pain, motor behavior and morphology. Anesth Analg.Google Scholar
  89. 89.
    Bromage PR, Camporesi EM, Durant PA, Nielsen CH. 1983. Influence of epinephrine as an adjunct to epidural morphine. Anesthesiology 58:257–262.PubMedCrossRefGoogle Scholar
  90. 90.
    Parker EO, Brookshire GL, Bartel SJ, Menard RG, Culverhouse ED, Ault LC. 1985. Effects of epinephrine on epidural fentanyl, sufentanil and hydromorphone for postoperative analgesia. Anesthesiology 63:A235.CrossRefGoogle Scholar
  91. 91.
    Rauck R, Knarr D, Denson R, Raj P. 1986. Comparison of the efficacy of epidural morphine given by intermittent injection or continuous infusions for the management of postoperative pain. Anesthesiology 65:A201.CrossRefGoogle Scholar
  92. 92.
    Raj PP, Knarr D, Vigdorth E, Gregg R, Denson D, Hopson CN. 1985. Comparative study of continuous epidural infusions versus systemic analgesics for postoperative pain relief. Anesthesiology 63:A238.CrossRefGoogle Scholar
  93. 93.
    Cullen ML, Staren ED, El-Ganzouri A, Logas WG, Ivankovich AD, Economou SG. 1985. Continuous epidural infusion for analgesia after major abdominal operations: A randomized prospective, double blind study. Surgery 98:718–728.PubMedGoogle Scholar
  94. 94.
    Cohen SE, Tan S, Albright GA, Halpern J. 1986. Epidural fentanyl/bupivacaine combinations for labor analgesics. Effect of varying doses. Anesthesiology 65:A368.CrossRefGoogle Scholar
  95. 95.
    Naulty JS, Malinow A, Hunt CO, Hausheer J, Datta S, Lema MJ, Ostheimer GW. 1986. Epidural butorphanol—bupivacaine for analgesia during labor and delivery. Anesthesiology 65:A369.CrossRefGoogle Scholar
  96. 96.
    Chrubasik J, Wiemers K. 1985. Contrinuous-plus-on demand epidural infusion of morphine for postoperative pain relief by means of a small externally worn device. Anesthesiology 65:263–267.CrossRefGoogle Scholar

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© Kluwer Academic Publishers 1990

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  • Narinder Rawal

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