Brainstem Dysfunction is Associated With Mortality in Deeply Sedated Critically Ill Patients

Background and objectives – Absent cough reflex is associated with mortality intensive care unit (ICU) patients requiring deep sedation, suggesting that lower brainstem dysfunction contributed to adverse outcomes. We conducted a multicenter observational cohort study to confirm this hypothesis by assessing the peak latency (PL) of the lower brainstem-generated P14 evoked potential (EP), which is slightly increased by sedatives. We aimed to demonstrate that a P14-PL> 16 ms is independently associated with day-28 mortality. Patients and methods - Mechanically ventilated adult patients, comatose or deeply sedated, brain-injured or not, were included. At day 3, EPs were performed in patients remaining unconscious. The Simplified Acute Physiological Score (SAPSII), initial Glasgow Coma Scale (GCS), sedation depth and brainstem reflexes were collected. The primary outcome was 28-day mortality. The secondary outcomes were delayed awakening and delirium after sedation discontinuation. Results - Between 2015 and 2019, 322 patients were included. EPs were performed in 264 (82%) patients, including 140 (53%) brain-injured and 251 (95%) deeply sedated patients. The median age, SAPSII and initial GCS were 62 years [50; 71], 49 [40; 62] and 11 [6; 15], respectively. A P14-PL > 16ms was found in 76 (29%) patients and was associated with day-28 mortality (adjusted hazard ratio, 3.0; 95% confidence interval, [1.7-5.2]). Absent cough and pupillary light reflexes were associated with death. Only absent oculocephalogyre reflex was associated with delayed awakening (adjusted odds ratio, 2.1, 95%CI, [1.1 - 3.7]). Interpretation – Impaired neurological and neurophysiological lower brainstem responses are associated with mortality in deeply sedated patients. Funded by the French Ministry of Health; PRORETRO; n° P120915; ClinicalTrials.gov registry: NCT02395861; date: 24 March 2015