Metabolism in resuscitated out-of-hospital cardiac arrest and the effect of Tozilizumab

Abstract

Abstract Background Out-of-Hospital Cardiac Arrest (OHCA) is a leading cause of death. The mortality and morbidity for initially comatose patients remain high even after successful resuscitation. The conquest of attenuating the damage caused by ischemia and reperfusion is ongoing. In a double-blinded clinical trial, comatose resuscitated OHCA patients (n=80) were randomized 1:1 to receive tocilizumab (interleukin-6 receptor antagonist) or placebo at arrival to the intensive care unit to reduce systematic inflammation (Figure 1). Tocilizumab markedly reduced the immunological response invested by high-sensitive C-reactive-protein and white blood count and further significantly lowered both troponin and NT-pro-BNP levels. Aim To describe circulating metabolites in out-of-hospital cardiac arrest patients and how tocilizumab affects the metabolism. Methods Accordingly, using ultra-performance-liquid-mass-spectrometry, we detected more than 3000 plasma metabolites in samples from arrival at the hospital (before tocilizumab infusion) and 48 hours later. We had prespecified 61 metabolites for quantification. Results The level of poly-unsaturated free fatty acids was associated with activated partial thromboplastin time (rho=0.77), while metabolites from the tricarboxylic acid cycle were associated with time to return of spontaneous circulation (rho=0.32) and interleukin-6 levels (rho=0.37) upon arrival. Furthermore, medium- and long-chain acylcarnitines were associated with increasing age (rho=0.32), eGFR (rho=-0.46), and NT-pro-BNP level (rho=0.47) Tocilizumab treatment increased the levels of several amino acids and free fatty acids more than 1.5 times (Figure 2). A possible interpretation would suggest a downregulated systemic protein synthesis in the tocilizumab group, possibly due to reduced systemic inflammation. Conclusion In this study, we have described the alterations in metabolites following OHCA and, for the first time, described the effect of tocilizumab on metabolism in critically ill patients.IMICA TrialVolcano Plot - Effect of tocilizumab