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Management of coma after cardiac arrest has improved during the past decade, allowing an increasing proportion of patients to survive, thus prognostication has become an integral part of post-resuscitation care. Neurologists are increasingly confronted with raised expectations of next of kin and the necessity to provide early predictions of long-term prognosis. During the past decade, as technology and clinical evidence have evolved, post-cardiac arrest prognostication has moved towards a multimodal paradigm combining clinical examination with additional methods, consisting of electrophysiology, blood biomarkers, and brain imaging, to optimise prognostic accuracy. Prognostication should never be based on a single indicator; although some variables have very low false positive rates for poor outcome, multimodal assessment provides resassurance about the reliability of a prognostic estimate by offering concordant evidence.

PurposeTo assess the ability of clinical examination, blood biomarkers, electrophysiology, or neuroimaging assessed within 7 days from return of spontaneous circulation (ROSC) to predict poor neurological outcome, defined as death, vegetative state, or severe disability (CPC 3–5) at hospital discharge/1 month or later, in comatose adult survivors from cardiac arrest (CA).MethodsPubMed, EMBASE, Web of Science, and the Cochrane Database of Systematic Reviews (January 2013–April 2020) were searched. Sensitivity and false-positive rate (FPR) for each predictor were calculated. Due to heterogeneities in recording times, predictor thresholds, and definition of some predictors, meta-analysis was not performed.ResultsNinety-four studies (30,200 patients) were included. Bilaterally absent pupillary or corneal reflexes after day 4 from ROSC, high blood values of neuron-specific enolase from 24 h after ROSC, absent N20 waves of short-latency somatosensory-evoked potentials (SSEPs) or unequivocal seizures on electroencephalogram (EEG) from the day of ROSC, EEG background suppression or burst-suppression from 24 h after ROSC, diffuse cerebral oedema on brain CT from 2 h after ROSC, or reduced diffusion on brain MRI at 2–5 days after ROSC had 0% FPR for poor outcome in most studies. Risk of bias assessed using the QUIPS tool was high for all predictors.ConclusionIn comatose resuscitated patients, clinical, biochemical, neurophysiological, and radiological tests have a potential to predict poor neurological outcome with no false-positive predictions within the first week after CA. Guidelines should consider the methodological concerns and limited sensitivity for individual modalities. (PROSPERO CRD42019141169)

The objective of the present study was to identify biological signatures of severe coronavirus disease 2019 (COVID-19) predictive of admission in the intensive care unit (ICU). Over 170 immunological markers were investigated in a ‘discovery’ cohort (n = 98 patients) of the Lausanne University Hospital (LUH-1). Here we report that 13 out of 49 cytokines were significantly associated with ICU admission in the three cohorts ( P  < 0.05 to P  < 0.001), while cellular immunological markers lacked power in discriminating between ICU and non-ICU patients. The cytokine results were confirmed in two ‘validation’ cohorts, i.e . the French COVID-19 Study (FCS; n = 62) and a second LUH-2 cohort (n = 47). The combination of hepatocyte growth factor (HGF) and C-X-C motif chemokine ligand 13 (CXCL13) was the best predictor of ICU admission (positive and negative predictive values ranging from 81.8% to 93.1% and 85.2% to 94.4% in the 3 cohorts) and occurrence of death during patient follow-up (8.8 fold higher likelihood of death when both cytokines were increased). Of note, HGF is a pleiotropic cytokine with anti-inflammatory properties playing a fundamental role in lung tissue repair, and CXCL13, a pro-inflammatory chemokine associated with pulmonary fibrosis and regulating the maturation of B cell response. Up-regulation of HGF reflects the most powerful counter-regulatory mechanism of the host immune response to antagonize the pro-inflammatory cytokines including CXCL13 and to prevent lung fibrosis in COVID-19 patients. Infection with SARS CoV2 results in the induction of multiple cytokine and inflammatory pathways. Here the authors demonstrate the association of HGF and CXCL13 production with increased severity and mortality in COVID-19 patients.

PurposePost-resuscitation guidelines recommend a multimodal algorithm for outcome prediction after cardiac arrest (CA). We aimed at evaluating the prevalence of indeterminate prognosis after application of this algorithm and providing a strategy for improving prognostication in this population.MethodsWe examined a prospective cohort of comatose CA patients (n = 485) in whom the ERC/ESICM algorithm was applied. In patients with an indeterminate outcome, prognostication was investigated using standardized EEG classification (benign, malignant, highly malignant) and serum neuron-specific enolase (NSE). Neurological recovery at 3 months was dichotomized as good (Cerebral Performance Categories [CPC] 1–2) vs. poor (CPC 3–5).ResultsUsing the ERC/ESICM algorithm, 155 (32%) patients were prognosticated with poor outcome; all died at 3 months. Among the remaining 330 (68%) patients with an indeterminate outcome, the majority (212/330; 64%) showed good recovery. In this patient subgroup, absence of a highly malignant EEG by day 3 had 99.5 [97.4–99.9] % sensitivity for good recovery, which was superior to NSE < 33 μg/L (84.9 [79.3–89.4] % when used alone; 84.4 [78.8–89] % when combined with EEG, both p < 0.001). Highly malignant EEG had equal specificity (99.5 [97.4–99.9] %) but higher sensitivity than NSE for poor recovery. Further analysis of the discriminative power of outcome predictors revealed limited value of NSE over EEG.ConclusionsIn the majority of comatose CA patients, the outcome remains indeterminate after application of ERC/ESICM prognostication algorithm. Standardized EEG background analysis enables accurate prediction of both good and poor recovery, thereby greatly reducing uncertainty about coma prognostication in this patient population.

This trial randomly assigned patients with coma after out-of-hospital cardiac arrest to undergo targeted hypothermia at 33°C or normothermia with treatment of fever. At 6 months, there were no significant between-group differences regarding death or functional outcomes.

PurposeTo assess the ability of quantitative pupillometry [using the Neurological Pupil index (NPi)] to predict an unfavorable neurological outcome after cardiac arrest (CA).MethodsWe performed a prospective international multicenter study (10 centers) in adult comatose CA patients. Quantitative NPi and standard manual pupillary light reflex (sPLR)—blinded to clinicians and outcome assessors—were recorded in parallel from day 1 to 3 after CA. Primary study endpoint was to compare the value of NPi versus sPLR to predict 3-month Cerebral Performance Category (CPC), dichotomized as favorable (CPC 1–2: full recovery or moderate disability) versus unfavorable outcome (CPC 3–5: severe disability, vegetative state, or death).ResultsAt any time between day 1 and 3, an NPi ≤ 2 (n = 456 patients) had a 51% (95% CI 49–53) negative predictive value and a 100% positive predictive value [PPV; 0% (0–2) false-positive rate], with a 100% (98–100) specificity and 32% (27–38) sensitivity for the prediction of unfavorable outcome. Compared with NPi, sPLR had significantly lower PPV and significantly lower specificity (p  < 0.001 at day 1 and 2; p  = 0.06 at day 3). The combination of NPi ≤ 2 with bilaterally absent somatosensory evoked potentials (SSEP; n = 188 patients) provided higher sensitivity [58% (49–67) vs. 48% (39–57) for SSEP alone], with comparable specificity [100% (94–100)].ConclusionsQuantitative NPi had excellent ability to predict an unfavorable outcome from day 1 after CA, with no false positives, and significantly higher specificity than standard manual pupillary examination. The addition of NPi to SSEP increased sensitivity of outcome prediction, while maintaining 100% specificity.

Objectives Recommendations for EEG monitoring in the ICU are lacking. The Neurointensive Care Section of the ESICM assembled a multidisciplinary group to establish consensus recommendations on the use of EEG in the ICU. Methods A systematic review was performed and 42 studies were included. Data were extracted using the PICO approach, including: (a) population, i.e. ICU patients with at least one of the following: traumatic brain injury, subarachnoid hemorrhage, intracerebral hemorrhage, stroke, coma after cardiac arrest, septic and metabolic encephalopathy, encephalitis, and status epilepticus; (b) intervention, i.e. EEG monitoring of at least 30 min duration; (c) control, i.e. intermittent vs. continuous EEG, as no studies compared patients with a specific clinical condition, with and without EEG monitoring; (d) outcome endpoints, i.e. seizure detection, ischemia detection, and prognostication. After selection, evidence was classified and recommendations developed using the GRADE system. Recommendations The panel recommends EEG in generalized convulsive status epilepticus and to rule out nonconvulsive seizures in brain-injured patients and in comatose ICU patients without primary brain injury who have unexplained and persistent altered consciousness. We suggest EEG to detect ischemia in comatose patients with subarachnoid hemorrhage and to improve prognostication of coma after cardiac arrest. We recommend continuous over intermittent EEG for refractory status epilepticus and suggest it for patients with status epilepticus and suspected ongoing seizures and for comatose patients with unexplained and persistent altered consciousness. Conclusions EEG monitoring is an important diagnostic tool for specific indications. Further data are necessary to understand its potential for ischemia assessment and coma prognostication.

BackgroundCurrent guidelines for the treatment of adult severe traumatic brain injury (sTBI) consist of high-quality evidence reports, but they are no longer accompanied by management protocols, as these require expert opinion to bridge the gap between published evidence and patient care. We aimed to establish a modern sTBI protocol for adult patients with both intracranial pressure (ICP) and brain oxygen monitors in place.MethodsOur consensus working group consisted of 42 experienced and actively practicing sTBI opinion leaders from six continents. Having previously established a protocol for the treatment of patients with ICP monitoring alone, we addressed patients who have a brain oxygen monitor in addition to an ICP monitor. The management protocols were developed through a Delphi-method-based consensus approach and were finalized at an in-person meeting.ResultsWe established three distinct treatment protocols, each with three tiers whereby higher tiers involve therapies with higher risk. One protocol addresses the management of ICP elevation when brain oxygenation is normal. A second addresses management of brain hypoxia with normal ICP. The third protocol addresses the situation when both intracranial hypertension and brain hypoxia are present. The panel considered issues pertaining to blood transfusion and ventilator management when designing the different algorithms.ConclusionsThese protocols are intended to assist clinicians in the management of patients with both ICP and brain oxygen monitors but they do not reflect either a standard-of-care or a substitute for thoughtful individualized management. These protocols should be used in conjunction with recommendations for basic care, management of critical neuroworsening and weaning treatment recently published in conjunction with the Seattle International Brain Injury Consensus Conference.

Background Elevated intracranial pressure (ICP) is frequent after traumatic brain injury (TBI) and may cause abnormal pupillary reactivity, which in turn is associated with a worse prognosis. Using automated infrared pupillometry, we examined the relationship between the Neurological Pupil index (NPi) and invasive ICP in patients with severe TBI. Methods This was an observational cohort of consecutive subjects with severe TBI (Glasgow Coma Scale [GCS] < 9 with abnormal lesions on head CT) who underwent parenchymal ICP monitoring and repeated NPi assessment with the NPi-200® pupillometer. We examined NPi trends over time (four consecutive measurements over intervals of 6 h) prior to sustained elevated ICP > 20 mmHg. We further analyzed the relationship of cumulative abnormal NPi burden (%NPi values < 3 during total ICP monitoring time) with intracranial hypertension (ICHT)—categorized as refractory (ICHT-r; requiring surgical decompression) vs. non-refractory (ICHT-nr; responsive to medical therapy)—and with the 6-month Glasgow Outcome Score (GOS). Results A total of 54 patients were studied (mean age 54 ± 21 years, 74% with focal injuries on CT), of whom 32 (59%) had ICHT. Among subjects with ICHT, episodes of sustained elevated ICP ( n  = 43, 172 matched ICP-NPi samples; baseline ICP [T − 6 h ] 14 ± 5 mmHg vs. ICPmax [T 0 h ] 30 ± 9 mmHg) were associated with a concomitant decrease of the NPi (baseline 4.2 ± 0.5 vs. 2.8 ± 1.6, p  < 0.0001 ANOVA for repeated measures). Abnormal NPi values were more frequent in patients with ICHT-r ( n  = 17; 38 [3–96]% of monitored time vs. 1 [0–9]% in patients with ICHT-nr [ n  = 15] and 0.5 [0–10]% in those without ICHT [ n  = 22]; p  = 0.007) and were associated with an unfavorable 6-month outcome (15 [1–80]% in GOS 1–3 vs. 0 [0–7]% in GOS 4–5 patients; p  = 0.002). Conclusions In a selected cohort of severe TBI patients with abnormal head CT lesions and predominantly focal cerebral injury, elevated ICP episodes correlated with a concomitant decrease of NPi. Sustained abnormal NPi was in turn associated with a more complicated ICP course and worse outcome.