Sedation during mechanical ventilation: a trial of benzodiazepine and opiate in combination.

Objective: To compare the efficacy of continuous intravenous sedation with midazolam alone vs. midazolam plus fentanyl ("co-sedation") during mechanical ventilation.

Design: A randomized, prospective, controlled trial.

Setting: A ten-bed medical intensive care unit at a university hospital.

Patients: Thirty patients with respiratory failure who were expected to require >48 hrs of mechanical ventilation and who were receiving a sedative regimen that did not include opiate pain control.

Interventions: An intravenous infusion of either midazolam alone or co-sedation was administered by a nurse-implemented protocol to achieve a target Ramsay Sedation Score set by the patient's physician. Study duration was 3 days, with a brief daily "wake-up."

Measurements And Main Results: We recorded the number of hours/day that patients were "off-target" with their Ramsay Sedation Scores, the number of dose titrations per day, the incidence of patient-ventilator asynchrony, and the time required to achieve adequate sedation as measures of sedative efficacy. We also recorded sedative cost in U.S. dollars and adverse events including hypotension, hypoventilation, ileus, and coma. Compared with the midazolam-only group, the co-sedation group had fewer hours per day with an "off-target" Ramsay Score (4.2 +/- 2.4 and 9.1 +/- 4.9, respectively, p < .002). Fewer episodes per day of patient-ventilator asynchrony were noted in the co-sedation group compared with midazolam-only (0.4 +/- 0.1 and 1.0 +/- 0.2, respectively, p < .05). Co-sedation also showed nonsignificant trends toward a shorter time to achieve sedation, a need for fewer dose titrations per day, and a lower total sedative drug cost. There was a trend toward more episodes of ileus with co-sedation compared with midazolam-only (2 vs. 0).

Conclusions: In mechanically ventilated patients, co-sedation with midazolam and fentanyl by constant infusion provides more reliable sedation and is easier to titrate than midazolam alone, without significant difference in the rate of adverse events.