Hostname: page-component-848d4c4894-nr4z6 Total loading time: 0 Render date: 2024-05-31T13:27:58.103Z Has data issue: false hasContentIssue false
  • English
  • Français

Opioid-related side-effects after intrathecal morphine: a prospective, randomized, double-blind dose–response study

Published online by Cambridge University Press:  01 March 2006

W. Raffaeli ,
G. Marconi ,
G. Fanelli ,
S. Taddei ,
G. B. Borghi  and
A. Casati
W. Raffaeli
Affiliation:
Cure Palliative, Department of Terapia Antalgica, AUSL Rimini, Rimini, Italy
G. Marconi
Affiliation:
Università degli Studi di Modena e Reggio, Department of Anesthesiology, Azienda Ospedaliera di Modena, Emilia, Italy
G. Fanelli
Affiliation:
Università degli Studi di Parma, Department of Anesthesiology, Azienda Ospedaliera di Parma, Parma, Italy
S. Taddei
Affiliation:
Università degli Studi di Bologna, Department of Anesthesiology, Ospedale Sant'Orsola, Bologna, Italy
G. B. Borghi
Affiliation:
Università degli Studi di Bologna, Department of Anesthesiology, Ospedale Sant'Orsola, Bologna, Italy
A. Casati
Affiliation:
Università degli Studi di Parma, Department of Anesthesiology, Azienda Ospedaliera di Parma, Parma, Italy
Get access

Extract

Summary

Background and objective: The aim of this prospective, randomized, double-blind investigation was to assess the dose–effect characteristics of postoperative nausea and vomiting after intrathecal administration of small doses of morphine (from 0.015 to 0.25 mg) in opioid-naïve, non-surgical patients. Methods: With Ethic Committee approval and written informed consent 144 opioid-naïve patients suffering from non-cancerous chronic back-pain, and receiving intrathecal morphine as diagnostic test for their chronic pain, were randomly allocated to receive intrathecal injection of 0.015 mg (Group I, n = 25), 0.03 mg (Group II, n = 30), 0.06 mg (Group III, n = 31) or 0.25 mg (Group IV, n = 33) morphine. The control group consisted in 25 further patients not included in the dose–effect study and receiving a placebo injection of normal saline in the interspinous ligament. A blinded observer recorded the occurrence of pruritus, nausea, vomiting, urinary retention and respiratory depression (respiratory rate < 6 bpm) at 2, 4 and 24 h after injection. Results: Clinically significant pain relief was observed in all patients receiving intrathecal morphine but only six patients (25%) of the control group (P = 0.0005). The incidence of pruritus was lower in patients of Groups III (6%) and IV (3%) than in Groups I (12%) and II (20%) (P = 0.002). The incidence of nausea and vomiting was higher at 2- and 4-h observation times, and decreased 24 h after intrathecal injection. Surprisingly, nausea was more frequent in Groups I (56%) and II (50%) than in Groups III (33%) and IV (24%) (P = 0.0005). Vomiting was higher in patients receiving morphine than in control group, but without differences among the four doses. No urinary retention was observed in the control group, while 2 h after intrathecal injection urinary retention was observed in 20–40% of cases, and decreased to less than 10% 24 h after spinal injection without differences among the four doses. Conclusions: The onset and incidence of minor opioid-related side-effects after intrathecal morphine administration do not depend on its dose, occurring with even very small doses of morphine. Accordingly, they can be considered as a patient-dependent effect of the drug, suggesting the presence of a primary dose-independent excitatory component that might be related to the theory of the bimodal activation of opioid receptors. The very low incidence major respiratory depression prevents us from drawing any conclusion about the dose–effect relationship for this side-effect, and further properly powered studies should be advocated to evaluate major respiratory depression after spinal morphine.

Keywords

ANAESTHESIA SPINAL, ANALGESICS OPIOID, morphine, intrathecalBACK PAIN, chronicADVERSE EFFECTSRANDOMIZED-CONTROLLED TRIAL
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 23 , Issue 7 , July 2006 , pp. 605 - 610
Copyright
© 2006 European Society of Anaesthesiology

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Hines R, Barash PG, Watrous G, O'Connor T. Complications occurring in the postanesthesia care unit: a survey. Anesth Analg 1992; 74: 503–509.Google Scholar
Habib AS, White WD, Eubanks S, Pappas TN, Gan TJ. A randomized comparison of a multimodal management strategy vs. combination antiemetics for the prevention of postoperative nausea and vomiting. Anesth Analg 2004; 99: 77–81.Google Scholar
Standl T, Eckert S, Esch ISA. Postoperative complaints after spinal and thiopentone–isoflurane anesthesia in patients undergoing orthopaedic surgery: spinal versus general anaesthesia. Acta Anaesthesiol Scand 1996; 40: 222–226.Google Scholar
Borgeat A, Ekatodramis G, Schenker CA. Postoperative nausea and vomiting in regional anesthesia. Anesthesiology 2003; 98: 530–547.Google Scholar
Pavlin DJ, Rapp SE, Polissar NL, Malmgren JA, Koerschgen M, Keyes H. Factors affecting discharge time in adult outpatients. Anesth Analg 1998; 87: 816–826.Google Scholar
Bailey PL, Rhondeau S, Schager PG et al. Dose–response pharmacology of intrathecal morphine in human volunteers. Anesthesiology 1993; 79: 49–59.Google Scholar
Dahl JB, Jeppesen IS, Jorgensen H, Wetterslev J, Moiniche S. Intraoperative and postoperative analgesic efficacy and adverse effects of intrathecal opioids in patients undergoing Cesarean section with spinal anesthesia. A qualitative and quantitative systematic review of randomized controlled trials. Anesthesiology 1999; 91: 1919–1927.Google Scholar
Krames ES, Olson K. Clinical realities and economic considerations: patient selection in intrathecal therapy. J Pain Symptom Manage 1997; 14 (Suppl 3): S3–S13.Google Scholar
Krames ES. Intrathecal infusional therapies for intractable pain: patient management guidelines. J Pain Symptom Manage 1993; 8: 36–46.Google Scholar
Martin R, Salbaing J, Blaise G, Tetrault JP, Tetreault L. Epidural morphine for postoperative pain relief: a dose–response curve. Anesthesiology 1982; 56: 423–426.Google Scholar
Connelly NR, Rahimi A, Parker RK. Nalmefene or naloxone for preventing intrathecal opioid mediated side-effects in Cesarean delivery patients. Int J Obstet Anesth 1997; 6: 231–234.Google Scholar
Barkshire K, Russell R, Burry J, Popat M. A comparison of bupivacaine–fentanyl–morphine with bupivacaine–fentanyl–diamorphine for Caesarean section under spinal anaesthesia. Int J Obstet Anesth 2001; 10: 4–10.Google Scholar
Habib AS, Muir HA, White WD, Spahn TE, Olufolabi AJ, Breen TW. Intrathecal morphine for analgesia after postpartum bilateral tubal ligation. Anesth Analg 2005; 100: 239–243.Google Scholar
Shen KF, Crain SM. Chronic selective activation opioid receptor functions in sensory neurons results in opioid ‘dependence’ without tolerance. Brain Res 1992; 597: 74–83.Google Scholar
Wattwil M. Postoperative pain relief and gastrointestinal motility. Acta Chir Scand 1988; 550 (Suppl): 140–145.Google Scholar
Levy M. Pharmacologic treatment of cancer pain. New Engl J Med 1996; 335: 1124–1132.Google Scholar
Ruskis AF. Effects of narcotics on the gastrointestinal tract, liver and kidneys. In: Kitahata LM, Colins JG, eds. Narcotic Analgesics in Anesthesiology. 1st edn. Baltimore/London: Williams & Wilkins, 1982: 143–156.
Ummenhofer WC, Arends RH, Shen DD, Bernards CM. Comparative spinal distribution and clearance kinetics of intrathecally administered morphine, fentanyl, alfentanil, and sufentanil. Anesthesiology 2000; 92: 739–753.Google Scholar
Roberts LJ, Finch PM, Goucke CR, Price LM. Outcome of intrathecal opioids in chronic non cancer-pain. Eur J Pain 2001; 5: 353–361.Google Scholar
Abouleish E, Rawal N, Rashad MN. The addition of 0.2 mg subarachnoid morphine to hyperbaric bupivacaine for Cesarean delivery: a prospective study of 856 cases. Reg Anesth 1991; 16: 137–140.Google Scholar
Wen ZH, Chang YC, Cherng CH et al. Increasing of intrathecal CSF excitatory amino acids concentration following morphine challenge in morphine-tolerant rats. Brain Res 2004; 9 (995): 253–259.Google Scholar
Wong CS, Chang YC, Huang GS, Cherng CH. Loss of intrathecal morphine analgesia in terminal cancer patients is associated with high levels of excitatory amino acids in the CSF. Can J Anaesth 2002; 49: 561–565.Google Scholar