Association of deranged cerebrovascular reactivity with brain injury following cardiac arrest: a post-hoc analysis of the COMACARE trial

Background: Impaired cerebrovascular reactivity (CVR) is one feature of post cardiac arrest encephalopathy. We studied the incidence and features of CVR by near infrared spectroscopy (NIRS) and associations with outcome and biomarkers of brain injury.

Methods: A post-hoc analysis of 120 comatose OHCA patients continuously monitored with NIRS and randomised to low- or high-normal oxygen, carbon dioxide and mean arterial blood pressure (MAP) targets for 48 h. The tissue oximetry index (TO_x) generated by the moving correlation coefficient between cerebral tissue oxygenation measured by NIRS and MAP was used as a dynamic index of CVR with TO_x > 0 indicating impaired reactivity and TO_x > 0.3 used to delineate the lower and upper MAP bounds for disrupted CVR. TO_x was analysed in the 0-12, 12-24, 24-48 h time-periods and integrated over 0-48 h. The primary outcome was the association between TO_x and six-month functional outcome dichotomised by the cerebral performance category (CPC1-2 good vs. 3-5 poor). Secondary outcomes included associations with MAP bounds for CVR and biomarkers of brain injury.

Results: In 108 patients with sufficient data to calculate TO_x, 76 patients (70%) had impaired CVR and among these, chronic hypertension was more common (58% vs. 31%, p = 0.002). Integrated TO_x for 0-48 h was higher in patients with poor outcome than in patients with good outcome (0.89 95% CI [- 1.17 to 2.94] vs. - 2.71 95% CI [- 4.16 to - 1.26], p = 0.05). Patients with poor outcomes had a decreased upper MAP bound of CVR over time (p = 0.001), including the high-normal oxygen (p = 0.002), carbon dioxide (p = 0.012) and MAP (p = 0.001) groups. The MAP range of maintained CVR was narrower in all time intervals and intervention groups (p < 0.05). NfL concentrations were higher in patients with impaired CVR compared to those with intact CVR (43 IQR [15-650] vs 20 IQR [13-199] pg/ml, p = 0.042).

Conclusion: Impaired CVR over 48 h was more common in patients with chronic hypertension and associated with poor outcome. Decreased upper MAP bound and a narrower MAP range for maintained CVR were associated with poor outcome and more severe brain injury assessed with NfL. Trial registration ClinicalTrials.gov, NCT02698917 .