Level III, retrospective comparative series.
IMPORTANCE Brain injury biomarkers released into circulation from the injured neurovascular unit are important prognostic tools in patients with cardiac arrest who develop hypoxic ischemic brain injury (HIBI) after return of spontaneous circulation (ROSC).OBJECTIVE To assess the neuroprognostic utility of bloodborne brain injury biomarkers in patients with cardiac arrest with HIBI.DATA SOURCES Studies in electronic databases from inception to September 15, 2021. These databases included MEDLINE, Embase, Evidence-Based Medicine Reviews, CINAHL, Cochrane Database of Systematic Reviews, and the World Health Organization Global Health Library.STUDY SELECTION Articles included in this systmatic review and meta-analysis were independently assessed by 2 reviewers. We included studies that investigated neuron-specific enolase, S100 calcium-binding protein β, glial fibrillary acidic protein, neurofilament light, tau, or ubiquitin carboxyl hydrolase L1 in patients with cardiac arrest aged 18 years and older for neurologic prognostication. We excluded studies that did not (1) dichotomize neurologic outcome as favorable vs unfavorable, (2) specify the timing of blood sampling or outcome determination, or (3) report diagnostic test accuracy or biomarker concentration.DATA EXTRACTION AND SYNTHESIS Data on the study design, inclusion and exclusion criteria, brain biomarkers levels, diagnostic test accuracy, and neurologic outcome were recorded. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline.MAIN OUTCOMES AND MEASURES Summary receiver operating characteristic curve analysis was used to calculate the area under the curve, sensitivity, specificity, and optimal thresholds for each biomarker. Risk of bias and concerns of applicability were assessed with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. RESULTSWe identified 2953 studies, of which 86 studies with 10 567 patients (7777 men [73.6] and 2790 women [26.4]; pooled mean [SD] age, 62.8 [10.2] years) were included. Biomarker analysis at 48 hours after ROSC demonstrated that neurofilament light had the highest predictive value for unfavorable neurologic outcome, with an area under the curve of 0.92 (95% CI, 0.84-0.97). Subgroup analyses of patients treated with targeted temperature management and those who specifically had an out-of-hospital cardiac arrest showed similar results (targeted temperature management, 0.92 [95% CI, 0.86-0.95] and out-of-hospital cardiac arrest, 0.93 [95% CI, 0.86-0.97]).CONCLUSIONS AND RELEVANCE Neurofilament light, which reflects white matter damage and axonal injury, yielded the highest accuracy in predicting neurologic outcome in patients with HIBI at 48 hours after ROSC.
PURPOSE: Following return of spontaneous circulation after cardiac arrest, hypoxic ischemic brain injury is the primary cause of mortality and disability. Goal-directed care using invasive multimodal neuromonitoring has emerged as a possible resuscitation strategy. We evaluated whether goal-directed care was associated with improved neurologic outcome in hypoxic ischemic brain injury patients after cardiac arrest. DESIGN: Retrospective, single-center, matched observational cohort study. SETTING: Quaternary academic medical center. PATIENTS: Adult patients admitted to the ICU following return of spontaneous circulation postcardiac arrest with clinical evidence of hypoxic ischemic brain injury defined as greater than or equal to 10 minutes of cardiac arrest with an unconfounded postresuscitation Glasgow Coma Scale of less than or equal to 8. INTERVENTIONS: We compared patients who underwent goal-directed care using invasive neuromonitoring with those treated with standard of care (using both total and matched groups). MEASUREMENTS AND MAIN RESULTS: Goal-directed care patients were matched 1:1 to standard of care patients using propensity scores and exact matching. The primary outcome was a 6-month favorable neurologic outcome (Cerebral Performance Category of 1 or 2). We included 65 patients, of whom 21 received goal-directed care and 44 patients received standard of care. The median age was 50 (interquartile range, 35–61), 48 (74%) were male, and seven (11%) had shockable rhythms. Favorable neurologic outcome at 6 months was significantly greater in the goal-directed care group (n = 9/21 [43%]) compared with the matched (n = 2/21 [10%], p = 0.016) and total (n = 8/44 [18%], p = 0.034) standard of care groups. Goal-directed care group patients had higher mean arterial pressure (p < 0.001 vs total; p = 0.0060 vs matched) and lower temperature (p = 0.007 vs total; p = 0.041 vs matched). CONCLUSIONS: In this preliminary study of patients with hypoxic ischemic brain injury postcardiac arrest, goal-directed care guided by invasive neuromonitoring was associated with a 6-month favorable neurologic outcome (Cerebral Performance Category 1 or 2) versus standard of care. Significant work is required to confirm this finding in a prospectively designed study.
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