A double-blind, randomized comparison of IV lorazepam versus midazolam for Sedation of ICU patients via a pharmacologic model

摘要: Background: Benzodiazepines, such as lorazepam and midazolam, are frequently administered to surgical intensive care unit (ICU) patients for postoperative sedation. To date, the pharmacology of in critically ill has not been described. The aim current study was characterize compare pharmacokinetics pharmacodynamics midazolam continuous intravenous infusions sedation ICU patients. Methods: With Institutional Review Board approval, 24 consenting adult were given either or a double-blind fashion (together with fentanyl epidural morphine analgesia) through target-controlled titrated maintain moderate level 12‐72 h postoperatively. Moderate defined Ramsay Sedation Scale score 3 4. scores measured, together benzodiazepine plasma concentrations. Population pharmacokinetic pharmacodynamic parameters estimated using nonlinear mixed-effects modeling. Results: A two-compartment model best described both midazolam. predicted depth 76% accuracy. sedative potency twice that C50,ss (plasma concentrations where P(Sedation > ss) 5 50%) values (sedation [SS] n, n Score 2, ,...6 )were 68, 101, 208, 304, 375 ng/ml. corresponding 34, 51, 104, 152, 188 ng/ml, respectively. Age, administration, resolving effects surgery anesthesia significant covariates relative amnestic 4 (observed). emergence times from after 72-h infusion light (SS 3) deep 5) typical patient 3.6 14.9 11.9 31.1 infusions, Conclusions: differs significantly This results delays compared when