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Alternatives to Intrathecal Morphine
- Clinton Z. Kakazu, MD, Maurice Lippmann MD, Inderjeet Julka, MD (21 April 2009)
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Clinton Z. Kakazu, MD, Anesthesiologist Harbor-UCLA Medical Center, Maurice Lippmann MD, Inderjeet Julka, MD
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To the Editor: We read with interest the recent article by Meylam et al(1) dealing with the use of intrathecal morphine during major surgeries under general anesthesia and wish to commend the authors for their review of the literature and meta-analysis. Although the authors point out the advantages and disadvantages for intrathecal morphine the use of this anesthesia technique still persist throughout the anesthesia community. Given the fact morphine is a mu receptor agonist and can cause respiratory depression post-operatively soon after a surgical procedure, this adverse affect can persist even up to 48 hours later. The technique poses a certain degree of risk as the authors mentioned. Puritis, is another unwanted side effect as well as urinary retention. The author’s summary stated that the use of intrathecal morphine should be abandoned because of the risk posed by respiratory depression and apnea with only a slight improvement in pain relief. But what are the alternatives? Well, there are other analgesics that anesthesiologist can use intrathecally that do not pose the mu receptor side effects of respiratory depression. Mixed agonist/antagonist narcotics offer an alternative to morphine. These drugs do not cause puritis, have a ceiling affect on respiration depression, resulting in a safer side-effect profile. For example, butorphanol (2, 3), an agonist/antagonist, offers excellent pain relief that can be used intrathecally. Nalbuphine (4) is another such drug that is safer and has equivalent analgesic potency. While both drugs are devoid of mu receptor affinity, their narcotic kappa receptor affinity offers a safer side effect profile in terms of respiratory depression, yet preserving analgesic effects warrants significant consideration. Another mixed agonist/antagonist narcotic, buprenorphine (5) attaches to the mu receptor (6-8) similar to morphine without kappa receptor activity, has even more powerful analgesic potency compared to morphine, but yet possesses less respiratory adverse side effects as well. Since clinicians want good outcomes for their patients, the use of intrathecally administered agonist/antagonist drugs should be promulgated rather than pure agonist such as morphine. These mixed agonist/antagonist administered intrathecally offer the primary advantage of excellent analgesic results without major side effects, particularly respiratory depression and apnea. It is important to note that the aforementioned agonist/antagonist drugs have not been sanctioned by the United States Federal Food and Drug Administration for intrathecal use. Yet, many other narcotics are used intrathecally as “off label” including: fentanyl, sufentanil, and hydromorphone. Another safety consideration of these “off labeled” drugs administered intrathecally are the preservatives added in its preparation which maybe toxic to the CNS. Sincerely, Maurice Lippmann, MD, Professor of Anesthesiology Clinton Z. Kakazu, MD, Assistant Professor of Anesthesiology, Director of Regional Anesthesia Inderjeet Julka, MD, Assistant Professor of Anesthesiology, Director of Pain Management David Geffen School of Medicine at UCLA Harbor-UCLA Medical Center, Torrance CA Department of Anesthesiology References: 1. Meylan N, Elia N, Lysakowski C, Tramer MR: Benefit and risk of intrathecal morphine without local anaesthetic inpatients undergoing major surgery: metaanalysis of randomized trials. BJA 102(2): 156-67,2009. 2. Tsai, SK, Mok MS, Lippmann M: Subarachnoid administration of butorphanol for the relief of post-operative pain. Regional Anesthesia 7(2):73. 3. Tsai SK, Lee TY, Mok MS, Lippmann M: Subarachnoid administration of butorphanol for the relief of postoperative pain. Southeast Asia Journal of Surgery 8(2):212-213. 4. Mok MS, Tsai SK, Chan KH, Lee TY, Lippmann M: Analgesic effect of intrathecal stadol, nubaine, meperidine, morphine, and fentanyl: A comparative study. 8th World Congress, Book of Abstracts Vol II, A213, 1984. 5. Ginsburg RS, Lippmann M: Buprenorphine: A k-receptor agonist? Anesth Analg 72:713-8, 1991. 6. Mather LE, Pharmacology of opiods. Med J Aust 144:424-7, 1986. 7. Boas RA, Villiger JW: Clinical actions of fentanyl and buprenorphine: the significance of receptor binding. Br J Anaesth 57:192-6, 1985. 8. Rance MJ: Multiple opiate receptors – their occurrence and significance. Clin Anaesthesiol 1:183-99, 1983. Conflict of Interest:None declared |
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