Lorazepam concentrations, pharmacokinetics and pharmacodynamics in a cohort of mechanically ventilated ICU patients

Abstract

Objectives: To evaluate plasma concentrations, pharmacokinetics and pharmacodynamics of lorazepam in a cohort of mechanically ventilated patients.

Interventions: Patients underwent simultaneous measurement of lorazepam concentration and sedation assessments using the Sedation-Agitation Scale (SAS) and Bispectral Index (BIS). Lorazepam administration was classified as either continuous intravenous infusion (CIVS) or bolus.

Main results: A total of 124 observations were made in 13 patients. The median concentration was 59 ng/ml, interquartile range 23 - 93 ng/ml, range 0 - 1,072 ng/ml. Clearance was preserved at 92 +/- 71 ml/min. Higher concentrations were associated with deeper sedation determined by both SAS and BIS. Two patients were managed with CIVS and received more lorazepam than those managed without (288 +/- 53.5 versus 55 +/- 25.2 mg, p-value < 0.005). CIVS administration was associated with higher concentrations (629 +/- 36 versus 49 +/- 15 ng/ml, p-value < 0.001) and deeper sedation by both SAS and BIS.

Conclusions: Lorazepam clearance was preserved with a wide range of concentrations. Higher concentrations were associated with deeper sedation and use of CIVS. Elevated concentrations during CIVS were attributable to administration of larger doses.