In Reply: Drs Dotson and Peeters and Drs Wunsch and Meltzer correctly note that the pharmacokinetic properties of continuously infused lorazepam could have contributed to oversedation in the control group of our MENDS trial. However, such moderate to heavy use of sedatives continues to characterize usual practice.1,2 When designing and conducting a double-blind trial to evaluate dexmedetomidine, which is only administered via continuous infusion, we chose lorazepam as the control group in accordance with the guidelines of the Society of Critical Care Medicine for long-term sedation of ventilated patients.3 Despite the longer half-life of lorazepam, the majority of patients in both groups were sedated at the level targeted by the ICU team. When undersedation or agitation did occur, study drug boluses were not permitted because of potential adverse effects, but the infusions could be increased and fentanyl boluses were used if pain was suspected. In response to Wunsch and Meltzer, this may have helped preserve blinding, despite the possible inequality of the drug dose titration. A detailed cost-effectiveness analysis is underway, but such an analysis requires the consideration of a number of factors beyond the incidence of delirium or coma, such as organ failure and functional outcomes.
Pandharipande PP, Girard TD, Ely EW. Sedation With Dexmedetomidine vs Lorazepam in Mechanically Ventilated Patients—Reply. JAMA. 2008;299(13):1540-1542. doi:10.1001/jama.299.13.1542-a