Abstract
Background and purposeDeep sedation is associated with acute brain dysfunction and increased mortality. We had previously shown that early-assessed brainstem reflexes may predict outcome in deeply sedated patients. The primary objective was to determine whether patterns of brainstem reflexes might predict mortality in deeply sedated patients. The secondary objective was to generate a score predicting mortality in these patients.MethodsObservational prospective multicenter cohort study of 148 non-brain injured deeply sedated patients, defined by a Richmond Assessment sedation Scale (RASS) <-3. Brainstem reflexes and Glasgow Coma Scale were assessed within 24 hours of sedation and categorized using latent class analysis. The Full Outline Of Unresponsiveness score (FOUR) was also assessed. Primary outcome measure was 28-day mortality. A “Brainstem Responses Assessment Sedation Score” (BRASS) was generated.ResultsTwo distinct sub-phenotypes referred as homogeneous and heterogeneous brainstem reactivity were identified (accounting for respectively 54.6% and 45.4% of patients). Homogeneous brainstem reactivity was characterized by preserved reactivity to nociceptive stimuli and a partial and topographically homogenous depression of brainstem reflexes. Heterogeneous brainstem reactivity was characterized by a loss of reactivity to nociceptive stimuli associated with heterogeneous brainstem reflexes depression. Heterogeneous sub-phenotype was a predictor of increased risk of 28-day mortality after adjustment to Simplified Acute Physiology Score-II (SAPS-II) and RASS (Odds Ratio [95% confidence interval] = 6.44 [2.63–15.8]; p<0.0001) or Sequential Organ Failure Assessment (SOFA) and RASS (OR [95%CI] = 5.02 [2.01–12.5]; p = 0.0005). The BRASS (and marginally the FOUR) predicted 28-day mortality (c-index [95%CI] = 0.69 [0.54–0.84] and 0.65 [0.49–0.80] respectively).ConclusionIn this prospective cohort study, around half of all deeply sedated critically ill patients displayed an early particular neurological sub-phenotype predicting 28-day mortality, which may reflect a dysfunction of the brainstem.
Highlights
Current guidelines recommend that sedation be monitored, titrated and discontinued as soon as possible and that benzodiazepines be avoided in critically ill patients [1,2]
Homogeneous brainstem reactivity was characterized by preserved reactivity to nociceptive stimuli and a partial and topographically homogenous depression of brainstem reflexes
Heterogeneous brainstem reactivity was characterized by a loss of reactivity to nociceptive stimuli associated with heterogeneous brainstem reflexes depression
Summary
Current guidelines recommend that sedation be monitored, titrated and discontinued as soon as possible and that benzodiazepines be avoided in critically ill patients [1,2]. Deep sedation is associated with delayed awakening, increased mortality [4,6,9], acute brain dysfunction [10,11,12] and a long-term impact on mental health [13]. We hypothesized that brainstem dysfunction might be involved, as early abolition of the cough and oculocephalic reflexes is associated with mortality and delirium [14]. In order to further improve our understanding of the interaction between sedation, critical illness and brainstem reflexes, we sought to define particular neurological sub-phenotypes in non-brain injured, deeply sedated, critically ill patients. Deep sedation is associated with acute brain dysfunction and increased mortality. We had previously shown that early-assessed brainstem reflexes may predict outcome in deeply sedated patients. The primary objective was to determine whether patterns of brainstem reflexes might predict mortality in deeply sedated patients. The secondary objective was to generate a score predicting mortality in these patients
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