KetAmine and Recovery After Mechanical VentilAtion ( KARMA )

Invasive mechanical ventilation of critically ill patients in the intensive care unit (ICU) is associated with significant morbidity and mortality, as well as a severe prognosis in survivors, in terms of functional, psychological, and cognitive sequelae. During the initial phase, invasive mechanical ventilation aims to promote oxygenation and reduce respiratory effort, with most patients receiving continuous intravenous sedation comprising gamma-aminobutyric acid (GABA) agonists (propofol, midazolam), and opioids. This continuous intravenous sedation is associated with complications, particularly hemodynamic issues (e.g., hypotension, vasopressor dependency), and neurological concerns (e.g., coma, delayed awakening, withdrawal syndrome upon discontinuation of sedation) during the acute phase and is linked to prolonged mechanical ventilation and long-term neurocognitive sequelae. 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 i