Influence of Blood Pressure Targets on Inflammation and Associations Between Inflammatory Markers and Vasopressor Usage after Cardiac Arrest - a Substudy of a Randomized Clinical Trial

Abstract Background Following resuscitation from cardiac arrest, a profound systemic inflammatory response may develop. In observational studies of critically ill patients an association between levels of inflammation and vasopressor usage has been found. Higher levels of inflammation may lead to higher vasopressor needs due to vasoplegia and cardiac dysfunction, however, catecholamines, including vasopressors also have immune modulatory effects. In the Blood Pressure and Oxygenation Targets in Post resuscitation Care (BOX) trial patients were randomized to a high or low blood pressure target, and vasopressor usage was increased in the high blood pressure target group. Therefore, the inflammatory response evoked by cardiac arrest, may have been altered by differences in vasopressor usage according to blood pressure target in this trial. Purpose To determine if differences in vasopressor and inotropy usage associated with randomization to a high compared to a low blood pressure target affects the inflammatory response after OHCA, and to investigate the association between inflammation and vasopressor and inotropy usage. Methods In the BOX trial, comatose OHCA patients with a presumed cardiac etiology were randomized to a blinded intervention of either a high (77mmHg) or a low blood pressure target (63mmHg). The inflammatory markers of leukocytes and CRP were measured at 0, 24, 48, and 72 hours. The average Vasoactive-Inotropic Score (VIS) was determined during initial 72 hours. The associations between average CRP, leukocytes, and VIS during initial 72 hours were determined by Spearman’s correlation analysis. Results The BOX trial included 789 resuscitated comatose OHCA patients, and 788 patients had at least 1 measurement of leukocytes and CRP. The median age was 64 (IQR 54-73), females constituted 19%, 1 year mortality was 36%. There was no difference in leukocytes and CRP at admission between the high and low blood pressure target groups (Figure 1). Leukocytes were slightly higher at 24 hours (p<0.01) in the high blood pressure target group, but no group differences were found at 48 and 72 hours, and CRP levels did not differ at 24, 48, or 72 hours. The average VIS was 19 (11-32) and 11 (5-19), p<0.01, in the two groups, with VIS being consistently higher at all timepoints beyond ICU admission (all p<0.01, data not shown) in patients with a high blood pressure target. Both average CRP and leukocytes were weakly correlated with average VIS at 0-72 hours for both blood pressure targets, r=0.17 and r=0.20, respectively for a high target (both p<0.01), and r=0.17 and r=0.20, respectively for a low target (both p<0.01). Conclusions In conclusion, increased vasopressor and inotropy usage in this randomized, blinded study of blood pressure targets after OHCA, did not lead to clinically relevant changes in inflammation. Inflammatory markers and VIS were correlated to a similar degree for both blood pressure targets.Figure 1, LeukocytesFigure 2, CRP