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

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