Continuous intravenous infusions of lorazepam versus midazolam for sedation during mechanical ventilatory support: a prospective, randomized study

A S Pohlman, K P Simpson, J B Hall
Critical Care Medicine 1994, 22 (8): 1241-7

OBJECTIVE: To evaluate the efficacy of continuous infusions of lorazepam vs. midazolam for sedation in the intensive care unit (ICU).

DESIGN: Prospective, randomized study.

SETTING: Large, urban university hospital.

PATIENTS: Twenty adult medical ICU patients receiving mechanical ventilatory support.

INTERVENTIONS: Patients were randomized to receive either lorazepam or midazolam. The infusion rate was adjusted at the bedside by the ICU nurse according to a standardized study protocol to achieve and maintain sedation at Ramsay's sedation level 2 or 3.

MEASUREMENTS AND MAIN RESULTS: Ten patients were randomized to receive lorazepam and ten to receive midazolam. The groups were similar in demographics, Acute Physiology and Chronic Health Evaluation (APACHE) II scores, ICU admission diagnosis, underlying disease processes, and supplemental analgesic administration. The mean time to achieve initial adequate sedation was 124 mins for lorazepam and 105 mins for midazolam. The mean infusion rate at the point of initial sedation was 0.06 mg/kg/hr for lorazepam and 0.15 mg/kg/hr for midazolam. The maximum and mean infusion rates for the entire study period were 0.1 and 0.06 mg/kg/hr, respectively, for lorazepam and 0.29 and 0.24 mg/kg/hr, respectively, for midazolam. The number of infusion rate adjustments per day was 1.9 mg/kg/hr for lorazepam and 3.6 mg/kg/hr for midazolam. Of the surviving patients, the mean time to return to baseline mental status after discontinuation of the benzodiazepine infusion was 261 mins for lorazepam and 1815 mins for midazolam. The mean volume of fluid per day required to deliver the maximum dose of benzodiazepine was 1.2 L for lorazepam (maximum 2.4 L) and 1.3 L for midazolam (maximum 3.6 L).

CONCLUSIONS: While there was a tendency to a longer time required for return to baseline mental status in patients receiving midazolam, this was not statistically significant. Findings of interest concerning both midazolam and lorazepam were: a) time to achieve sedation in medical ICU patients is often prolonged; b) actual dose requirements necessary to maintain sedation in this patient population are larger than the current literature describes; c) time to awaken after discontinuation of the infusion was occasionally delayed for > 24 hrs; d) large volumes of fluid were required to deliver these doses of drug via this route of administration.

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