To assess the clinical consequences of acute tolerance to remifentanil, Guignard et al. recruited 50 adult patients scheduled for major abdominal surgery. On the evening before surgery, patients were instructed regarding the use of a 10-cm visual analog scale, a four-point verbal rating scale, and a patient-controlled analgesia system. After induction of anesthesia with use of thiopental and tracheal intubation, patients were randomized for administration of either remifentanil titrated to autonomic responses (with desflurane kept constant at 0.5 minimum alveolar concentration [MAC]) or desflurane titrated to autonomic responses (with remifentanil 0.1 mg · kg−1· min−1). All patients were administered a bolus of 0.15 mg/kg morphine approximately 40 min before completion of skin closure. The total dose of remifentanil administered to each patient was recorded, as were any complications, such as respiratory depression or shivering. Behavioral pain assessment (0 = calm, 2 = intensive manifestation of pain) was performed 5, 10, and 15 min after tracheal extubation.
In the postanesthesia care unit and in the surgical unit, nurses blind to patient group assignment or intraoperative remifentanil dose assessed patient pain intensity using a visual analog scale and a verbal response scale, and they initially treated patient postoperative pain with morphine administered intravenously at a rate of 3 mg at 5-min intervals until the behavioral pain score was less than 1. Time to first request for postoperative morphine was also recorded, as were anesthetic-related complications, such as nausea, vomiting, or pruritus. Within 3 h after tracheal extubation, patients were connected to a patient-controlled analgesia device set to deliver 1 mg morphine as an intravenous bolus, with a lock-out interval of 5 min.
Patients in the remifentanil group had higher verbal response scores for pain, and greater visual analog scale scores, at 30 min and 3 h and 4 h after extubation, than did those in the desflurane group. The cumulative dose of morphine administered intravenously by nurses in the postanesthetic care unit was significantly greater in the remifentanil group; by adding the cumulative patient-controlled analgesia morphine dosages, it can be seen that patients in the remifentanil group received almost double the amount of morphine.