A randomized, double-blind trial comparing the effect of two blood pressure targets on global brain metabolism after out-of-hospital cardiac arrest

Abstract

Purpose This study aimed to assess the effect of different blood pressure levels on global cerebral metabolism in comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA). Methods In a double-blinded trial, we randomly assigned 60 comatose patients following OHCA to low (63 mmHg) or high (77 mmHg) mean arterial blood pressure (MAP). The trial was a sub-study in the Blood Pressure and Oxygenation Targets after Out-of-Hospital Cardiac Arrest-trial (BOX). Global cerebral metabolism utilizing jugular bulb microdialysis (JBM) and cerebral oxygenation (rSO2) was monitored continuously for 96 h. The lactate-to-pyruvate (LP) ratio is a marker of cellular redox status and increases during deficient oxygen delivery (ischemia, hypoxia) and mitochondrial dysfunction. The primary outcome was to compare time-averaged means of cerebral energy metabolites between MAP groups during post-resuscitation care. Secondary outcomes included metabolic patterns of cerebral ischemia, rSO2, plasma neuron-specific enolase level at 48 h and neurological outcome at hospital discharge (cerebral performance category). Results We found a clear separation in MAP between the groups (15 mmHg, p < 0.001). Cerebral biochemical variables were not significantly different between MAP groups (LPR low MAP 19 (16–31) vs. high MAP 23 (16–33), p = 0.64). However, the LP ratio remained high (> 16) in both groups during the first 30 h. During the first 24 h, cerebral lactate > 2.5 mM, pyruvate levels > 110 µM, LP ratio > 30, and glycerol > 260 µM were highly predictive for poor neurological outcome and death with AUC 0.80. The median (IQR) rSO2 during the first 48 h was 69.5% (62.0–75.0%) in the low MAP group and 69.0% (61.3–75.5%) in the high MAP group, p = 0.16. Conclusions Among comatose patients resuscitated from OHCA, targeting a higher MAP 180 min after ROSC did not significantly improve cerebral energy metabolism within 96 h of post-resuscitation care. Patients with a poor clinical outcome exhibited significantly worse biochemical patterns, probably illustrating that insufficient tissue oxygenation and recirculation during the initial hours after ROSC were essential factors determining neurological outcome.

Post-Cardiac Arrest Syndrome

“…There was no difference in the primary outcome (a composite of death or poor functional outcome at 90 d) which occurred in 34% of those in the 77 mm Hg group compared with 32% in the 63 mm Hg group (hazard ratio, 1.08; 95% CI, 0.84–1.37; P =0.56). In a sub-analysis of this study, lactate-to-pyruvate ratios in jugular venous blood, markers of global brain metabolism, were also no different between the groups 24. The mean difference in achieved MAP between the 2 groups was 10.7 mm Hg, which may have been too small to affect clinical outcomes.…”

“…In a sub-analysis of this study, lactate-to-pyruvate ratios in jugular venous blood, markers of global brain metabolism, were also no different between the groups. 24 The mean difference in achieved MAP between the 2 groups was 10.7 mm Hg, which may have been too small to affect clinical outcomes.…”

The agreement between jugular bulb and cerebrospinal fluid lactate levels in patients with out-of-hospital cardiac arrest

“…In a study investigating the impact of mean arterial blood pressure regulation on the neurological prognosis of OHCA patients through JB based brain metabolism monitoring, lactate/pyruvate ratio exceeding 16 was defined as ischemia when pyruvate is below 70 μM, and exceeding 70 μM was defined as mitochondrial dysfunction. The study reported that mean arterial blood pressure regulation does not improve neurological prognosis in patients with OHCA 28 . In this study, no significant agreement was observed between CSF and JB lactate levels in patients with a good neurological prognosis.…”

General Critical Care, Temperature Control, and End-of-Life Decision Making in Patients Resuscitated from Cardiac Arrest

“…In critically ill patients, mean arterial pressure (MAP) represents the entry pressure for the perfusion of most organs and should be maintained >65–70 mmHg [ 116 , 117 , 118 ]. Although higher MAP levels may be required in patients with brain injury or persistent hypoperfusion (e.g., progressing acute kidney injury or altered mental status) [ 119 , 120 ], adequate circulatory volume, absence of left ventricular outflow tract obstruction, and microcirculatory flow and responsiveness (if possible) should be ideally assessed before using a vasopressor challenge, especially in patients treated with TTM [ 77 , 121 , 122 , 123 ].…”