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


METHODS
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.


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.
de Wit
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Division of Pulmonary and Critical Care Medicine, Virginia Commonwealth University, Medical College of Virginia Campus, Box 980050, Richmond, VA 23298-0050, USA. mdewit@vcu.edu
Best
A M
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Epstein
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Greenblatt
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D015331:Cohort Studies; D003243:Consciousness / Q000187:drug effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007362:Intensive Care Units; D008140:Lorazepam / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D012121:Respiration, Artificial
D006993:Hypnotics and Sedatives; D008140:Lorazepam