Loxapine to control agitation during weaning from mechanical ventilation

Abstract

BackgroundWeaning 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.MethodsWe 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.ResultsThe 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).ConclusionsIn this prematurely stopped trial, loxapine did not significantly shorten weaning from MV. However, loxapine reduced the need for resuming sedation.Trial registrationClinicaltrials.gov, NCT01193816. Registered on 26 August 2010.

A systematic review of interventions to facilitate extubation in patients difficult-to-wean due to delirium, agitation, or anxiety and a meta-analysis of the effect of dexmedetomidine

“…These eight studies were all randomized-controlled trials and regrouped 437 patients. [28][29][30][31][32][33][34][35] One of the studies was only available in abstract form, and the authors were successfully contacted for missing data when needed. 35…”

“…The main characteristics of included studies are shown in the Table. All studies included adult patients, most reporting median ages in the fifties or sixties. Difficultto-wean patients were identified solely based on a clinicians' assessment without objective criteria in four trials, [30][31][32]35 while the others included patients who failed one spontaneous breathing trial 28,29,34 or failed an in-house extubation protocol. 33 Agitation was the reason for DTW in three studies and was measured using the Richmond Agitation Sedation Scale (RASS).…”

“…33 Agitation was the reason for DTW in three studies and was measured using the Richmond Agitation Sedation Scale (RASS). 30,32,34 Agitated delirium was an inclusion criteria in two studies and was assessed using a combination of a positive CAM-ICU and an evaluation with either the RASS 33 or the Mindful Attention Awareness Scale. 32 One study included patients that were DTW due to anxiety and used the State Anxiety Scale.…”

“…32 Another compared the effects of a single 150 mg dose of oral loxapine with placebo. 34 Biofeedback was the only non-pharmacologic intervention reported. 35 Biofeedback, which was compared with usual care, consisted of 20-min sessions that were performed four times per day and focused on diaphragmatic breathing.…”

“…Open-label acetaminophen, 28,29,33 non-steroidal antiinflammatory drugs, 33 benzodiazepines, 28,31,32,34 propofol, 31,32 or narcotic analgesics 32,34 were mentioned as permitted in both study groups in some trials. Open-label antipsychotics were permitted in one trial assessing dexmedetomidine.…”