The Association Between Neurological Prognosis and the Degree of Blood-Brain Barrier Disruption in Cardiac Arrest Survivors Who Underwent Target Temperature Management.

Abstract

This study aimed to compare day-specific associations of blood-brain barrier (BBB) disruption with neurological outcome in survivors of out-of-hospital cardiac arrest (OHCA) treated with target temperature management (TTM) and lumbar drainage. This retrospective single-center study included 68 survivors of OHCA who underwent TTM between April 2018 and December 2019. The albumin quotient (QA) was calculated as QA = albumincerebrospinal fluid/albuminserum immediately (day 1) and 24 (day 2), 48 (day 3), and 72h (day 4) after the return of spontaneous circulation. The degree of BBB disruption was weighted using the following scoring system: QA value of 0.007 or less (normal), QA value greater than 0.007-0.01 (mild), QA value greater than 0.01-0.02 (moderate), and QA value greater than 0.02 (severe). Points were assigned as follows: 0 (normal), 1 (mild), 4 (moderate), and 9 (severe). Neurological outcome was determined at 6months after the return of spontaneous circulation, as well as cerebral performance category (CPC), dichotomized as good (CPC score 1-2) and poor (CPC score 3-5) outcome. We enrolled 68 patients (48 men, 71%); 37 (54%) patients had a poor neurological outcome. The distributions of poor versus good outcomes at 6months in patients with moderate and severe BBB disruption were 19 of 22 (80%) vs. 18 of 46 (50%) on day 1, 31 of 37 (79%) vs. 6 of 31 (32%) on day 2, 32 of 37 (81%) vs. 5 of 31 (30%) on day 3, and 32 of 39 (85%) vs. 5 of 29 (30%) on day 4 (P < 0.001), respectively. Using receiver operating characteristic analyses, optimal cutoff values (sensitivity, specificity) of QA levels for the prediction of neurological outcome were as follows: day 1, greater than 0.009 (56.8%, 87.1%); day 2, greater than 0.012 (81.1%, 87.1%); day 3, greater than 0.013 (83.8%, 87.1%); day 4, greater than 0.013 (86.5%, 87.1%); the sum of all time points, greater than 0.039 (89.5%, 79.4%); and scoring system, greater than 9 (91.9%, 87.1%). In this proof of concept study, QA was associated with poor neurological outcome in survivors of OHCA treated with TTM with no contraindication to lumbar drainage. A large multicenter prospective study is needed to validate the utility of BBB disruption as a prognosticator of neurological outcome.