Rohaut Benjamin, Porcher Raphael, Hissem Tarik, Heming Nicholas, Chillet Patrick, Djedaini Kamel, Moneger Guy, Kandelman Stanislas, Allary Jeremy, Cariou Alain, Sonneville Romain, Polito Andréa, Antona Marion, Azabou Eric, Annane Djillali, Siami Shidasp, Chrétien Fabrice, Mantz Jean, Sharshar Tarek
Neurological Departement Intensive Care Unit, Assistance Publique - Hôpitaux de Paris (AP-HP), Pitié-Salpétrière Hospital, Paris, France.
Sorbonne University, UPMC Univ Paris 06, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
PLoS One. 2017 Apr 25;12(4):e0176012. doi: 10.1371/journal.pone.0176012. eCollection 2017.
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.
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.
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).
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.
深度镇静与急性脑功能障碍及死亡率增加相关。我们之前已经表明，早期评估的脑干反射可能预测深度镇静患者的预后。主要目的是确定脑干反射模式是否可预测深度镇静患者的死亡率。次要目的是生成一个预测这些患者死亡率的评分。
对148例非脑损伤的深度镇静患者进行观察性前瞻性多中心队列研究，这些患者由里士满镇静评估量表（RASS）<-3定义。在镇静后24小时内评估脑干反射和格拉斯哥昏迷量表，并使用潜在类别分析进行分类。还评估了无反应性全面量表（FOUR）评分。主要结局指标是28天死亡率。生成了一个“脑干反应评估镇静评分”（BRASS）。
确定了两种不同的亚表型，分别称为均匀和异质性脑干反应性（分别占患者的54.6%和45.4%）。均匀脑干反应性的特征是对伤害性刺激的反应性保留，以及脑干反射的部分且在地形上均匀的抑制。异质性脑干反应性的特征是与异质性脑干反射抑制相关的对伤害性刺激的反应性丧失。在调整简化急性生理学评分-II（SAPS-II）和RASS或序贯器官衰竭评估（SOFA）和RASS后，异质性亚表型是28天死亡率增加风险的预测指标（优势比[95%置信区间]=6.44[2.63-15.8]；p<0.0001）或（优势比[95%置信区间]=5.02[2.01-12.5]；p = 0.0005）。BRASS（以及勉强的FOUR）预测了28天死亡率（c指数[95%置信区间]分别为0.69[0.54-0.84]和0.65[0.49-0.80]）。
在这项前瞻性队列研究中，所有深度镇静的重症患者中约一半表现出一种早期特定的神经亚表型，可预测28天死亡率，这可能反映了脑干功能障碍。
