Initial clinical experience with remifentanil, a new opioid metabolized by esterases

Remifentanil is a new, esterase-metabolized opioid for anesthesia. Nonspecific esterases terminate the drug effect, with a context-sensitive half-time which plateaus at 3-4 min. This dose-ranging pilot study was designed to estimate the dose requirement of remifentanil for abolition 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% nitrous oxide, and vecuronium. Remifentanil was then given (1 μg/kg, plus an infusion of 0.0125-1.0 μg · 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 μg/kg remifentanil boluses and a 50% increase in infusion rate, which could be done twice. Subsequent responses were treated with propofol or isoflurane. Remifentanil and nitrous oxide administration were terminated after the incision was dosed. ED50 for response to skin incision varied between the two study sites (0.020 and 0.087 μg · kg^-1 · min^{- 1}). ED50 for response to all surgical stimuli was 0.52 μg · kg^-1 · min^-1. At 0.3 μg · kg^-1 · min^-1 or more, only 3 of 21 patients required isoflurane. Recovery was not longer in patients receiving larger doses to spontaneous 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 reported in most patients (92%) at a median time of 21 min. We conclude that remifentanil was effective and well tolerated as a component of nitrous oxide-opioid-relaxant anesthesia. Over the 80-fold range of infusion rates given, patients awoke, breathed, and were tracheally extubated within a few minutes.