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Observational Study
. 2017 Apr 25;12(4):e0176012.
doi: 10.1371/journal.pone.0176012. eCollection 2017.

Brainstem response patterns in deeply-sedated critically-ill patients predict 28-day mortality

Benjamin Rohaut  1   2   3   4 , Raphael Porcher  5 , Tarik Hissem  6 , Nicholas Heming  7 , Patrick Chillet  8 , Kamel Djedaini  9 , Guy Moneger  7 , Stanislas Kandelman  10 , Jeremy Allary  10 , Alain Cariou  11 , Romain Sonneville  12 , Andréa Polito  7 , Marion Antona  13 , Eric Azabou  14 , Djillali Annane  7 , Shidasp Siami  6 , Fabrice Chrétien  15   16 , Jean Mantz  15   17 , Tarek Sharshar  7   15 ; Groupe d’Exploration Neurologique en Réanimation (GENER)
Affiliations
Observational Study

Brainstem response patterns in deeply-sedated critically-ill patients predict 28-day mortality

Benjamin Rohaut et al. PLoS One. .

Abstract

Background and purpose: 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.

Methods: Observational 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.

Results: Two 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).

Conclusion: In 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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flow chart.
NMBA: neuromuscular-blocking agent; RASS: Richmond Assessment Sedation Scale.
Fig 2
Fig 2. Representation of homogeneous and heterogeneous profiles.
The percentage of abolition of each tested neurological responses in homogeneous and heterogeneous profiles are depicted. The heterogeneous profile is characterized by a greater and more heterogeneous abolition of neurological responses.
Fig 3
Fig 3. 28-day mortality probability according to the BRASS.
Mortality probability expressed in mean [95%CI], BRASS: Brainstem Responses Assessment Sedation Score.
See this image and copyright information in PMC

References

    1. Barr J, Fraser GL, Puntillo K, Ely EW, Gélinas C, Dasta JF, et al. Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit. Crit Care Med. 2013. January;41(1):278–80. - PubMed
    1. Shehabi Y, Bellomo R, Mehta S, Riker R, Takala J. Intensive care sedation: the past, present and the future. Crit Care. 2013;17(3):322 10.1186/cc12679 - DOI - PMC - PubMed
    1. Ely EW, Truman B, Shintani A, Thomason JWW, Wheeler AP, Gordon S, et al. Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale (RASS). JAMA. 2003. June 11;289(22):2983–91. 10.1001/jama.289.22.2983 - DOI - PubMed
    1. Shehabi Y, Bellomo R, Reade MC, Bailey M, Bass F, Howe B, et al. Early intensive care sedation predicts long-term mortality in ventilated critically ill patients. Am J Respir Crit Care Med. 2012. October 15;186(8):724–31. 10.1164/rccm.201203-0522OC - DOI - PubMed
    1. Grap MJ, Munro CL, Wetzel PA, Best AM, Ketchum JM, Hamilton VA, et al. Sedation in adults receiving mechanical ventilation: physiological and comfort outcomes. Am J Crit Care. 2012. May;21(3):e53–63. 10.4037/ajcc2012301 - DOI - PMC - PubMed

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