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 microgram/kg, plus an infusion of 0.0125-1.0 micrograms.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 micrograms/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 closed. ED50 for response to skin incision varied between the two study sites (0.020 and 0.087 microgram.kg-1.min-1). ED50 for response to all surgical stimuli was 0.52 microgram.kg-1.min-1. At 0.3 microgram.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.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of ketorolac tromethamine on bleeding and on requirements for analgesia after total knee arthroplasty.

The effect of ketorolac tromethamine, a non-steroidal anti-inflammatory drug, on postoperative blood loss and on the requirement for morphine was assessed after total knee arthroplasty, an operation in which blood loss is mainly measured rather than estimated. The purpose of this prospective, randomized, double-blind clinical trial was to determine whether administration of ketorolac in the perioperative period would increase bleeding related to the operation. Fifty-nine patients who had a total knee arthroplasty received either thirty milligrams of ketorolac or a placebo consisting of saline solution, intravenously, every six hours, in four doses. The first dose was administered about an hour before the end of the operation. Blood loss and use of morphine for pain control were measured for the first twenty-four hours postoperatively. The per cent change in the hematocrit and the amount of transfused blood were also recorded. The patients who received ketorolac used 27 per cent less morphine than those who received the placebo (40.0 +/- 23.4 milligrams compared with 55.1 +/- 23.5 milligrams [mean and standard deviation]); this difference was significant (p < 0.05). On the first day after the operation, the hematocrit decreased from 0.364 +/- 0.043 preoperatively to 0.278 +/- 0.032 in the patients who received ketorolac and from 0.363 +/- 0.046 to 0.298 +/- 0.030 in the patients who received the placebo. The 6 per cent greater decrease in the group that received ketorolac was significant (p < 0.05) but not clinically important.(ABSTRACT TRUNCATED AT 250 WORDS)