Beneficial effects of loxapine on agitation and breathing patterns during weaning from mechanical ventilation

Abstract

Introduction: Interruption of sedation during weaning from mechanical ventilation often leads to patient agitation because of withdrawal syndrome. We tested the short-term efficacy and tolerance of loxapine in this situation.

Methods: Nineteen mechanically ventilated patients with marked agitation after sedation withdrawal were included. Three agitation scales, the Richmond Agitation Sedation Scale (RASS), the Motor Activity Assessment Scale (MAAS), and the Ramsay and physiological variables (respiratory rate, airway occlusion pressure during the first 0.1 second of inspiration (P0.1), heart rate and systolic arterial blood pressure) were recorded before and after loxapine administration.

Results: Loxapine dramatically improved all agitation scores (RASS and MASS decreased from 2 +/- 0 to -1.1 +/- 2.3, and 5.4 +/- 0.5 to 2.7 +/- 1.6, respectively; Ramsay increased from 1.0 +/- 0 to 3.5 +/- 1.5, 60 minutes after loxapine administration, P < 0.05 for all scores) as well as P0.1 (6 +/- 4.2 to 1.8 +/- 1.8 cm H2O; P < 0.05) and respiratory rate (from 31.2 +/- 7.2 to 23.4 +/- 7.8; P < 0.05) without hemodynamic adverse events. No side effects occurred. Sixteen (84%) patients were successfully managed with loxapine, sedation was resumed in two others, and one patient self-extubated without having to be reintubated.

Conclusions: Loxapine was safe and effective in treating agitation in a small group of mechanically ventilated patients and improved respiratory physiologic parameters, enabling the weaning process to be pursued. A multicenter trial is under way to confirm these promising results.

Figure 1

Values for three sedation/agitation scores before agitation, at the time of agitation, and at 60, 90, 120, and 180 minutes after loxapine (LXP) administration. Marked alteration of the three scores was initially observed. Loxapine administration resulted in normalization of the three scores after 1 hour. This normalization persisted for several hours. Significance of differences: *P < 0.0001 versus all other conditions; † P < 0.005 versus all other conditions.

Figure 2

Breathing-pattern scores before agitation, at the time of agitation, and at 60, 90, 120, and 180 minutes after loxapine (LXP) administration. The dramatic increase in both respiratory rate and P0.1 observed during agitation normalized after loxapine administration. Significance of differences: *P < 0.0001 versus all other conditions; † P < 0.05 versus values observed before agitation.