INTERACTIONS BETWEEN MIDAZOLAM AND REMIFENTANIL DURING MONITORED ANESTHESIA CARE

Background: Remifentanil, an ultra-short-acting opioid analgesic, may be useful as an intravenous adjuvant to local anesthesia for treating patient discomfort and pain during monitored anesthesia care (MAC), Ho wever, the remifentanil dose requirements, interactions with other com monly used sedative drugs (such as midazolam), and recovery characteri stics after ambulatory procedures have not been determined. Therefore, this study was designed to evaluate the safety and efficacy of remife ntanil alone and in combination with different doses of midazolam duri ng MAC. Methods: Eighty-one healthy consenting women scheduled for ele ctive breast biopsy procedures were randomly assigned to one of four t reatment groups according to an institutional review board-approved, d ouble-blind, placebo-controlled protocol, The study medication (contai ning either saline or 2 mg, 4 mg, or 8 mg of midazolam) was administer ed intravenously 5 min before starting an infusion of remifentanil at 0.1 mu g . kg(-1) . min(-1). The remifentanil infusion was subsequentl y adjusted in 0.025- and 0.05-mu g . kg(-1) . min(-1) increments to ma intain patient comfort and adequate ventilation during the operation. The level of sedation was assessed at 1- to 10-min intervals during th e procedure using the inverted observer's assessment of alertness/seda tion (OAA/S) scale, with a score of 1 = awake, alert to 5 = asleep, un arousable. Discomfort and pain were assessed using numerical rating sc ales, Hemoglobin oxygen saturation, respiratory rate, blood pressure ( systolic, diastolic, mean), and heart rate were monitored at 1- to 5-m in intervals. Intraoperative amnesia was assessed by asking patients t o recall a picture shown 5 min after the study medication was administ ered. Recovery was evaluated using the Aldrete score and the times to ''home readiness'' and actual discharge. Side effects and patient sati sfaction were assessed in a follow-up telephone interview on the first postoperative day. Results: Midazolam produced dose-dependent increas es in the median level of sedation, Remifentanil produced a greater re duction in respiratory rate in the 4-mg and 8-mg midazolam groups, How ever, there mere no significant differences in the hemodynamic variabl es or discharge times, Patients with OAA/S scores of 1 to 3 (''light'' sedation) 5 min after the study medication experienced a greater inci dence of intraoperative pruritus and postoperative nausea and vomiting (PONV) compared with those with OAA/S scores of 4 to 5 (''deep'' seda tion), Discharge times were prolonged for patients in the light sedati on group in whom PONV developed. Conclusions: Use of remifentanil alon e for MAC did not provide optimal sedation during local anesthesia, Ho wever, 0.05 to 0.1 mu g . kg(-1) . min(-1) remifentanil in combination with 2 mg midazolam given intravenously, provided effective sedation and analgesia during MAC in healthy patients classified as American So ciety of Anesthesiologists status 1 to 2. Midazolam also produced dose -dependent potentiation of remifentanil's depressant effect on respira tory rate. In outpatients receiving a combination of midazolam and rem ifentanil during local anesthesia, the level of sedation appears to in fluence the incidence of both intraoperative pruritus and PONV.