INITIAL CLINICAL-EXPERIENCE WITH REMIFENTANIL, A NEW OPIOID METABOLIZED BY ESTERASES

Remifentanil is a new, esterase-metabolized opioid for anesthesia. Non specific esterases terminate the drug effect, with a context-sensitive half-time which plateaus at 3-4 min. This dose-ranging pilot study wa s designed to estimate the dose requirement of remifentanil for abolit ion of the responses to skin incision and intraoperative stimuli, and to determine the speed of recovery. Fifty-one unpremedicated patients took part at two centers. Anesthesia was induced with propofol, 67% ni trous oxide, and vecuronium. Remifentanil was then given (1 mu g/kg, p lus an infusion of 0.0125-1.0 mu g . kg(-1). min(-1)). Responses were defined as: >15% increase in systolic blood pressure or >20% increase in heart rate, tearing, sweating, movement, or coughing. Responses to incision or surgery were treated with 0.5 mu g/kg remifentanil boluses and a 50% increase in infusion rate, which could be done twice. Subse quent responses were treated with propofol or isoflurane. Remifentanil and nitrous oxide administration were terminated after the incision w as closed. ED50 for response to skin incision varied between the two s tudy sites (0.020 and 0.087 mu g . kg(-1). min(-1)). ED50 for response to all surgical stimuli was 0.52 mu g . kg(-1). min(-1). At 0.3 mu g . kg(-1). min(-1) or more, only 3 of 21 patients required isoflurane. Recovery was not longer in patients receiving larger doses to spontane ous ventilation (2.5-4.6 min), tracheal extubation (4.2-7.0 min), and response to verbal command (3.0-4.6 min). Postoperative pain was repor ted in most patients (92%) at a median time of 21 min. We conclude tha t remifentanil was effective and well tolerated as a component of nitr ous oxide-opioid-relaxant anesthesia. Over the 80-fold range of infusi on rates given, patients awoke, breathed, and were tracheally extubate d within a few minutes.