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Assessment of brainstem responses is feasible in sedated critically ill patients and loss of selected responses is predictive of mortality and altered mental status.

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.

BackgroundSomatosensory (SSEP) and brainstem auditory (BAEP) evoked potentials are neurophysiological tools which, respectively, explore the intracranial conduction time (ICCT) and the intrapontine conduction time (IPCT). The prognostic values of prolonged cerebral conduction times in deeply sedated patients have never been assessed. Sedated patients are at risk of developing new neurological complications, undetected. In this prospective observational bi-center pilot study, we investigated whether early impairment of SSEP’s ICCT and/or BAEP’s IPCT could predict in-ICU mortality or altered mental status (AMS), in deeply sedated critically ill patients.MethodsSSEP by stimulation of the median nerve and BAEP were assessed in critically ill patients receiving deep sedation on day 3 following ICU admission. Deep sedation was defined by a Richmond Assessment sedation Scale (RASS) <−3. Mean left- and right-side ICCT and IPCT were measured for each patient. Primary and secondary outcomes were, respectively, in-ICU mortality and AMS defined as the occurrence of delirium and/or delayed awakening after discontinuation of sedation.ResultsEighty-six patients were studied of which 49 (57%) were non-brain-injured and 37 (43%) were brain-injured. Impaired ICCT was a predictor of in-ICU mortality after adjustment on the global Sequential Organ Failure Assessment score (SOFA) [OR (95% CI) = 2.69 (1.05–6.85); p = 0.039] and on the non-neurological SOFA components [2.67 (1.05–6.81); p = 0.040]. IPCT was more frequently delayed in the subgroup of patients who developed post-sedation AMS (24%) compared those without AMS (0%). However, this difference did not reach statistical significance (p = 0.053). Impairment rates of ICCT and IPCT were not found to be significantly different between non-brain- and brain-injured subgroups of patients.ConclusionIn critically ill patients receiving deep sedation, early ICCT impairment was associated with mortality. Somatosensory and brainstem auditory evoked potentials may be useful early warning indicators of brain dysfunction as well as prognostic markers in deeply sedated critically ill patients.

Background: Mismatch negativity (MMN) is the neurophysiological correlate of cognitive integration of novel stimuli. Although MMN is a well-established predictor of awakening in non-sedated comatose patients, its prognostic value in deeply sedated critically ill patients remains unknown. The aim of this prospective, observational pilot study was to investigate the prognostic value of MMN for subsequent awakening in deeply sedated critically ill patients. Methods: MMN was recorded in 43 deeply sedated critically ill patients on Day 3 of ICU admission using a classical 'oddball' paradigm that delivers rare deviant sounds in a train of frequent standard sounds. Individual visual analyses and a group level analysis of recordings were performed. MMN amplitudes were then analysed according to the neurological status (awake vs not awake) at Day 28. Results: Median (inter-quartile range) Richmond Assessment Sedation Scale (RASS) at the time of recording was À5 (range, from À5 to À4.5). Visual detection of MMN revealed a poor inter-rater agreement [kappa¼0.17, 95% confidence interval (0.07e0.26)]. On Day 28, 30 (70%) patients had regained consciousness while 13 (30%) had not. Quantitative group

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