KetAmine and Recovery After Mechanical VentilAtion ( KARMA )

The use of ketamine as an alternative sedative agent in ICU has garnered considerable attention in recent years. Ketamine has a rapid onset of action and a short duration of effect, potentially beneficial bronchodilatory effects, and minimal impact on hemodynamics or respiratory drive. It also provides effective analgesia. Due to its action on N-methyl-D-aspartate (NMDA) glutamatergic receptors, its mechanism of action differs from other commonly used agents such as propofol and benzodiazepines. Furthermore, emerging research suggests that ketamine may have anti-inflammatory/immunomodulatory and neuroprotective properties that could be advantageous in critically ill patients.

Recent observational studies utilizing low-dose ketamine have suggested an improvement in neurological complications in ICU (e.g., coma, delirium) while other authors have raised concerns about potential renal and hepatic toxicity associated with high doses of ketamine used for sedation. Despite its increasing use, there is currently a lack of high-quality data on the efficacy and safety of ketamine use for sedation in critically ill patients.

In this trial, we hypothesise that, critically ill patients requiring unplanned invasive mechanical ventilation, adjunctive treatment with low dose of ketamine will translate into better outcomes, with higher numbers of days alive outside of the hospital.

The study is a multicenter, randomised, double-blinded placebo-controlled superiority trial involving adult patients requiring unplanned mechanical ventilation, and sedation for more than 6 hours in the ICU. Patients will be randomised within 48 hours following initiation of mechanical ventilation adhering to a 1:1 allocation of ketamine or placebo.

Patients will be randomized to receive either intravenous ketamine or placebo as an adjunctive sedative agent during ICU stay for a maximum duration of 14 days.

Follow-up visits will be performed at day 3, day 14, ICU discharge, day 60, and day 90 after randomization.

The primary endpoint, "days alive and at home," will be assessed at day 60. The end of the research visit is the day 90 follow-up visit. If the patient has been discharged from the hospital, the day-90 visit will consist of telephone contact with the patient by a centralized research assistant and he also will complete the scales at D90.

Data collected by phone consist in Vital status, scales's results and Retrieval of Adverse Events if the patient has been discharged home or with the medical team of the healthcare structure if the patient has been discharged to another structure.