Project 463291

Acute respiratory failure is the most common organ failure in the intensive care unit. Patients with acute respiratory failure commonly develop acute signs of brain dysfunction (delirium). Survivors often exhibit cognitive impairment long after the resolution of their lung failure. Acute respiratory failure may lead to elevated carbon dioxide (CO2) levels in the blood. Patients with elevated CO2 frequently need to be supported with mechanical ventilation. The amount of CO2 in the blood is inversely proportional to the amount of air an individual breathes in every minute. Heavily sedated, invasively mechanically ventilated patients do not control the amount of air they breathe. It is controlled by the parameters set by the multidisciplinary critical care teams, generally aiming to normalize CO2 levels. However, this could injure the brain. Indeed, CO2 drops reduce the diameter of cerebral blood vessels, which can dangerously decrease blood flow to the brain. Patients with the most extreme forms of acute respiratory failure can be supported extracorporeal membrane oxygenation (ECMO). In previous work, we demonstrated a strong association between large reductions in CO2 with ECMO initiation and the development of brain injury. Whether drastic changes in CO2 similarly occur and harm patients on invasive mechanical ventilation without ECMO remains to be determined. With this grant, we propose to study this question by assessing if patients who develop large reductions in CO2 levels while invasively mechanically ventilated more commonly develop delirium, seizures, brain bleeds and strokes. To do so, we will analyze three large North American databases involving 270 000 patients using causal inference methods. Our findings could lead to significant changes in how multidisciplinary critical care teams adjust mechanical ventilator parameters. This could improve both short- and long-term neurological outcomes that affect acute respiratory failure patients' quality of life.