With the introduction of intrathecal and epidural opioids came the hope that, due to binding with specific spinal cord receptors, pain relief would be produced without adverse side effects (Chapter 60). However, respiratory depression although not common, is a recognizable complication of this technique. It occurs as an "early" or "late" phenomenon and depends to some extent, on the lipid solubility of the agent.
The spread of the lipid-soluble opioids, eg. fentanyl and sufentanil, has been thought to be more limited than that of morphine(1) with a presumed lower risk of severe respiratory depression. This has been recently questioned (2, 3) as the incidence of 0.6% is similar to that of morphine (4). The large epidural doses required for analgesic effect are similar to intravenous doses for fentanyl and even higher for sufentanil supporting the theory that early respiratory depression, if it occurs, is the result of systemic absorption from the epidural veins with these agents. Following intrathecal administration, respiratory depression within 15-30 minutes has been reported with both fentanyl (5) and sufentanil (6).
Morphine crosses the dura slowly with peak CSF concentrations seen at 90-120 minutes after epidural administration. CSF morphine concentration remains high due to prolonged elimination (7) and cephalad spread to the medullary respiratory center is probably the cause of late respiratory depression. Intrathecal doses are markedly reduced to avoid this complication which may also be precipitated if parenteral opioids are given at this time. Dose-dependent depression of CO2 response curves has also been demonstrated (9).
Respiratory depression and other systemic effects have been treated with a low dose of naloxone such that epidural analgesia is not reversed. Other longer-acting antagonists are currently being investigated. Results with agonist-antagonists, eg. nalbuphine, are conflicting (9).
All patients who receive spinal opioids should be observed carefully for at least the first 12 hours. This has been done successfully on surgical wards provided that nursing staff are well trained and monitoring includes respiratory rate and degree of sedation (10). Continuous pulse oximetry has been advocated but is not mandatory. If these measures are implemented, respiratory depression is a rare event and neuraxial narcotics are probably safer than parenteral opioids (where the frequency of monitoring is traditionally lower) (11).
References:
1. Bromage PR, Camporesi E, Leslie J. Epidural narcotics in volunteers: Sensitivity to pain and to carbon dioxide. Pain 9: 145-160, 1990
2. Colten SE, Lasaille T, Benhamou D, Levron JC Respiratory effects of epidural sufentanil after cesarean section. Anesth Analg 74:677-82, 1992.
3. Brockway MS, Noble DW, Sharwood-Smith GH, McClure JH Profound respiratory depression after extradural fentanyl. Br J Anaes 64:243-5, 1990,
4. Weightman WM Respiratory arrest during epidural infusion of bupivacaine and fentanyl. Anaes Intensive Care 19:282-284, 1991,
5. Belzarena SD. Clinical effects of intrathecally administered fentanyl in patients undergoing cesarean section. Anesth Analg 74:653-659, 1992.
6. Palmer CM Early respiratory depression following intrathecal fentanyl-morphine combination. Anesthesiology 74:1153-1155, 1991.
7. Nordberg G, Hedner T, Mellstrand T et al Pharmacokinetics of epidural morphine in man. Eur J Clin Pharm 26:233-237, 1984.
8. Rawal N, Wattwil M. Respiratory depression following epidural morphine: an experimental and clinical study. Anesth Analg 63:8-14, 1984.
9. Etches RC, Sandler AN, Lawson SL A comparison of the analgesic and respiratory effects of epidural nalbuphine or morphine in post thoracotomy patients. Anesthesiology 74:9-14, 1991.
10. Ready LB, Loper KA, Nessly M, Wild L. Postoperative epidural morphine is safe on surgical wards. Anesthesiology 75:452-456, 1991.
11. Hughes SC. The safety of intraspinal narcotics in obstetric patients. Survey of Anesthesia 33:261-264, 1989.