The pharmacokinetics of remifentanil.
Opioids decrease the sympathetic and somatic responses to noxious stimulation and can be given in high doses without negative inotropic effects, even in patients with impaired cardiac function. With currently available opioids, precise titration of dose to effect is difficult, and high doses result in drug accumulation and prolonged respiratory depression. Remifentanil is a new synthetic opioid with direct action on mu-opioid receptors. It has a rapid onset and short latency to peak effect. It is rapidly inactivated by esterases in both blood and tissues, resulting in a very short duration of action. The context-sensitive half-life remains very short (3 to 4 minutes), independent of the duration of infusion. These characteristics facilitate titration of dose to effect and also allow the use of very high doses (ED99) without prolonging recovery from its effects. The duration of action of remifentanil has been found to be short, even in patients with renal or hepatic failure, although only low doses have been used in the studies published to date. The hydrolysis of remifentanil produces a metabolite with very weak opioid receptor activity that does not contribute to the effects of remifentanil. Possible disadvantages of the drug include (1) the need to mix the lyophilized drug with a diluent, (2) administration as a continuous infusion, (3) risk of rapid loss of analgesic and anesthetic effects if the infusion is interrupted accidentally, and (4) difficulty in judging the dose of another, longer lasting opioid that will be required to control postoperative pain without producing excessive ventilatory depression. Remifentanil is likely to be more expensive than other opioids, but its use may reduce overall costs if prompt recovery from its effects results in shorter stays in the operating room and recovery units.
Michelsen
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Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Hug
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D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000493:pharmacokinetics*; D000762:Anesthesia Recovery Period; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000493:pharmacokinetics; D003365:Costs and Cost Analysis; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006801:Humans; D006868:Hydrolysis; D007262:Infusions, Intravenous; D009200:Myocardial Contraction / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects; D010149:Postoperative Pain / Q000517:prevention & control; D010880:Piperidines / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000493:pharmacokinetics*; D011930:Reaction Time; D017450:Receptors, Opioid, mu / Q000187:drug effects; D000077208:Remifentanil; D012119:Respiration / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects
D000701:Analgesics, Opioid; D018686:Anesthetics, Intravenous; D010880:Piperidines; D017450:Receptors, Opioid, mu; D000077208:Remifentanil