This study aims to assess the efficacy of a drug (loxapine, a neuroleptic) in calming patients down in a situation of restlessness during mechanical ventilation weaning. This drug is used for several years to quieten restless patients. Its purpose is to restore spontaneous breathing sooner and therefore to reduce the risks of intubation and mechanical ventilation.

This study aims to assess the efficacy of a drug (loxapine, a neuroleptic) in calming patients down in a situation of restlessness during mechanical ventilation weaning. This drug is used for several years to quieten restless patients. Its purpose is to restore spontaneous breathing sooner and therefore to reduce the risks of intubation and mechanical ventilation. 300 patients will participate in the study and will be randomized, after informed consent, to receive either loxapine or a placebo.Patients whose proxies refuse participation will be sedated according to standard care procedures.

Inclusion Criteria:

• age ≥ 18 years,
• sedated
• under mechanical ventilation through intubation probe for more than 48 hours
• no contra-indication to naso-gastric probe- with criteria for potential weaning
• with social security
• important restlessness at sedation withdrawal, defined as RASS score (Richmond Agitation Sedation Scale)= 2. This restlessness has no potential danger for the patient but requires a level of sedation. This re-sedation implies administration of morphinomimetics and benzodiazepines at dosages that does not allow to pursue mechanical ventilation weaning attempts.

Exclusion Criteria:

• extreme restlessness at sedation withdrawal ((RASS>2)
• allergy to loxapine or one of its component
• dopaminergic agonists
• extubation planned in the following 24 hours
• antecedent of comitiality
• known pregnancy at admission
• proxies opposed to study participation