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Mixed opioid use the cause?
- Alfred P J Lake, Oksana L. Coates (10 February 2006)
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Balanced general anaesthesia including dexmedetomidine
- Olumuyiwa A Bamgbade (2 December 2005)
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Alfred P J Lake, Consultant in Anaesthesia and Pain Management Glan Clwyd Hospital, Oksana L. Coates
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We read this case report with considerable interest because, as dexmedetomidine is known to have as a specific advantage the lack of respiratory depressant effect, an alternative explanation for the occurrence might appropriately be advanced. The case reported is that of a female patient, average size without significant co-morbities or other confounding variables, who suffered central apnoea in the post-anaesthetic care unit. As a part of her anaesthesia care she received fentanyl 100 mcg together with morphine 7.5 mg which the authors calculate may be equivalent to 250 mcg and 19 mg respectively on the basis of the morphine-sparing effect of the co- administered α2 agonist. At the conclusion of surgery she is reported as breathing spontaneously with a frequency of 10 breaths per minute whilst continuing to receive the dexmedetomidine by infusion yet experiencing the reported apnoeic episode subsequently at which time no mention is made of pupillary size. The co-administration of more than one opioid with main action on the mu opioid receptor (MOP-R) may lead to complications. Morphine behaves differently with the MOP-R to activate it than do other agonists such as the fentanyl analogues (1) each filling the upper part of the receptor cavity in a particular way. Antagonists like naloxone act more deeply inside the receptor to sterically hinder its activation. Overall, the distinct receptor mediated pharmacological activity of any mu opioid will be the sum of actions at all MOP-R including any variants. The MOP-R is complex and has sub-types; this together with peripheral receptors, which, for example, may be involved in respiratory depression can explain noticable differences between mu agonists (2,3). Also, the receptor affinity, efficacy, dosage and pharmacokinetic characterisitcs of the drug used will affect the final outcome. Differences in the response of patients to the same opioid expressed either as analgesic effects or side effect profile have always been apparent clinically. As the authors state, the mutually enhancing respiratory depressant effect between opioids and sedating agents is well known and, indeed, the combination of morphine with fentanyl and dexmedetomidine may present a very significant problem in susceptible patients. Mixed opioid use during anaesthesia is a common practice, fentanyl is often administered at induction followed by a longer acting agent. This practice exposes the MOP-R to more than one exogenous ligand and, thereby, gives a mixed message. More common than previously realised, perhaps; potentially an unpredicatable problem for all patients and an unrecognised event in some. Unexpected respiratory depression, excess sedation and delayed recovery to an unusual degree may ensue. Without a good clinical reason it may be appropriate to avoid mixing and administer only a single opioid during each general anaesthetic. REFERENCES 1. Bot G. Blake AD. Li S. Reisine T. Fentanyl and its analogs desensitize the cloned mu opioid receptor. J Pharmacol Exper Ther1998; 285: 1207-18. 2. Bowdle TA. Adverse effects of opioid agonists and agonist- antagonists in anaesthesia. Drug Safety 1998; 19: 173-89. 3. Shook JE, Watkins WD, Camporesi EM. Differential roles of opioid receptors in respiration, respiratory disease, and opiate-induced respiratory depression. Amer Rev Resp Dis 1990; 142: 895-909. Conflict of Interest:None declared |
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Olumuyiwa A Bamgbade, Attending Anesthesiologist University of Michigan Hospital, Ann Arbor, USA.
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Editor- The article by Ho et al [1] describing a case report of postoperative apnoea attributed to the perioperative use of dexmedetomidine was interesting, but may be misleading. Dexmedetomidine is a highly selective alpha-2 adrenoceptor agonist that has analgesic, amnesic, sedative and sympatholytic properties; with the unique advantage of minimal cardiovascular and respiratory depression at recommended clinical doses or applications [2]. Although dexmedetomidine is only licensed for ICU sedation, its unique properties are employed perioperatively; as supplement or sole anaesthesia [3,4]. Ho et al used dexmedetomidine infusion as part of balanced general anaesthesia in an elderly patient, based on a protocol from a small study [5]: the study is not very reliable and requires further validation. The brief apnoea that occurred after tracheal extubation may be attributed to many factors. Despite coughing on the tracheal tube and attempting to open eyes to calls, the patient was probably not awake enough when she was extubated: she should have been extubated fully awake, especially being elderly. There is also the possibility of laryngospasm playing a role in this case of post-extubation apnoea. Intraoperative analgesia included significant doses of IV fentanyl 1.6mcg/kg and IV morphine 0.12mg/kg. Although the opioids were administered 90 minutes before extubation, their respiratory and central depressant effect persisted because the patient is opioid-naive, elderly, with reduced capacity for clearance of opioids and active metabolites. The assertion that ‘the combination of alpha-2 adrenoceptor agonists with opioids does not lead to respiratory depression’ is based on a review article that did not include studies on combined administration of dexmedetomidine and opioids [6]: the evidence is therefore unreliable. The dexmedetomidine infusion may have potentiated the depressant effect of the opioids, especially because the infusion was continued postoperatively. Dexmedetomidine is commonly used to supplement general anaesthesia at the University of Michigan hospital, usually at a dose of 0.4-0.5mcg/kg/h, but the infusion is discontinued before emergence and tracheal extubation. The patients usually wake up calm and cooperative, and there is no occurrence of post-extubation apnoea. There have been reports of inadvertent dexmedetomidine overdose in the perioperative setting [7]: this potentially dangerous problem should be avoided. Dexmedetomidine is a safe and effective anaesthesia supplement when used appropriately. References: [1] Ho AM-H, Chen S, Karmakar MK. Central apnoea after balanced general anaesthesia that included dexmedetomidine. Br J Anaesth 2005; 95: 773-5. [2] Hall JE, Uhrich TD, Barney JA, et al. Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusions. Anesth Analg 2000; 90: 699-705. [3] Fragen RJ, Fitzgerald PC. Effect of dexmedetomidine on the minimum alveolar concentration of sevoflurane in adults age 55 to 70 years. J Clin Anesth 1999; 11: 466-70. [4] Ramsay MA, Luterman DL. Dexmedetomidine as a total intravenous agent. Anesthesiology 2004; 101: 787-90. [5] Arain SR, Ruehlow RM, Uhrich TD, Ebert TJ. The efficacy of dexmedetomidine versus morphine for postoperative analgesia after major inpatient surgery. Anesth Analg 2004; 98: 153-8. [6] Khan ZP, Ferguson CN, Jones RM. Alpha-2 and imidazoline receptor agonists: their pharmacology and therapeutic role. Anaesthesia 1999; 54: 146-65. [7] Jorden VSB, Pousman RM, Sanford MM, et al. Dexmedetomidine overdose in the perioperative setting. Annals Pharmacother 2004; 38: 803-7. Conflict of Interest:None declared |
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