Loxapine to control agitation during weaning from mechanical ventilation

Background: Weaning from mechanical ventilation (MV) may be impeded by the occurrence of agitation. Loxapine has the ability to control agitation without affecting spontaneous ventilation. The aim of this study was to establish whether loxapine would reduce MV weaning duration in agitated patients. Methods: We performed a multicentre, double-blind, placebo-controlled, parallel group, randomised trial. Patients who were potential candidates for weaning but exhibited agitation (Richmond Agitation-Sedation Scale score?=?2) after sedation withdrawal were randomly assigned to receive either loxapine or placebo. In case of severe agitation, conventional sedation was immediately resumed. The primary endpoint was the time between first administration of loxapine or placebo and successful extubation. Results: The trial was discontinued after 102 patients were enrolled because of an insufficient inclusion rate. Median times to successful extubation were 3.2 days in the loxapine group and 5 days in the placebo group (relative risk 1.2, 95% CI 0.75-1.88, p = 0.45). During the first 24 h, sedation was more frequently resumed in the placebo group (44% vs 17%, p = 0.01). Conclusions: In this prematurely stopped trial, loxapine did not significantly shorten weaning from MV. However, loxapine reduced the need for resuming sedation.