Effects of Targeted Temperature Management in Patients with Post-Cardiac Arrest Syndrome after an Out-Of-Hospital Cardiac Arrest Caused by Hanging: A Prospective Observational Cohort Study in Japan

Background: Targeted temperature management (TTM) is recommended for unconscious patients after a cardiac arrest. However, its effectiveness in patients with post-cardiac arrest syndrome (PCAS) by hanging remains unclear. Therefore, this study aimed to investigate the relationship between TTM and favorable neurological outcomes in patients with PCAS by hanging.Methods: This study was a retrospective analysis of the Japanese Association for Acute Medicine out-of-hospital cardiac arrest (OHCA) registry between June 2014 and December 2017 among patients with PCAS admitted to the hospitals after an OHCA caused by hanging. A multivariate logistic regression analysis was performed to estimate the propensity score and to predict whether patients with PCAS by hanging receive TTM. We compared patients with PCAS by hanging who received TTM (TTM group) and those who did not (non-TTM group) using propensity score analysis.Results: A total of 199 patients with PCAS by hanging were enrolled in this study. Among them, 43 were assigned to the TTM group and 156 to the non-TTM group. Logistic regression model adjusted for propensity score revealed that TTM was not associated with favorable neurological outcome at 1-month (adjusted odds ratio [OR]: 1.38, 95% confidence interval [CI]: 0.27–6.96). Moreover, no difference was observed in the propensity score-matched cohort (adjusted OR: 0, 73, 95% CI: 0.10–4.71) and in the inverse probability of treatment weighting-matched cohort (adjusted OR: 0.63, 95% CI: 0.15–2.69).Conclusions: TTM was not associated with increased favorable neurological outcomes at 1-month in patients with PCAS after OHCA by hanging.

Differential Effectiveness of Hypothermic Targeted Temperature Management According to the Severity of Post-Cardiac Arrest Syndrome

International guidelines recommend targeted temperature management (TTM) to improve the neurological outcomes in adult patients with post-cardiac arrest syndrome (PCAS). However, it still remains unclear if the lower temperature setting (hypothermic TTM) or higher temperature setting (normothermic TTM) is superior for TTM. According to the most recent large randomized controlled trial (RCT), hypothermic TTM was not found to be associated with superior neurological outcomes than normothermic TTM in PCAS patients. Even though this represents high-quality evidence obtained from a well-designed large RCT, we believe that we still need to continue investigating the potential benefits of hypothermic TTM. In fact, several studies have indicated that the beneficial effect of hypothermic TTM differs according to the severity of PCAS, suggesting that there may be a subgroup of PCAS patients that is especially likely to benefit from hypothermic TTM. Herein, we summarize the results of major RCTs conducted to evaluate the beneficial effects of hypothermic TTM, review the recent literature suggesting the possibility that the therapeutic effect of hypothermic TTM differs according to the severity of PCAS, and discuss the potential of individualized TTM.

Evaluation of serum biomarkers and electroencephalogram to determine survival outcomes in pediatric post-cardiac arrest patients

Background Cardiac arrest causes primary and secondary brain injuries. We aimed to evaluate the association between neuron-specific enolase (NSE), serum S-100B (S100B), electroencephalogram (EEG) patterns, and post-cardiac arrest outcomes, including arrest duration and survival, in pediatric patients. Methods This prospective observational study was conducted in the pediatric intensive care unit of our hospital from January 2017 to December 2019 and included 41 post-cardiac arrest patients with different etiologies who underwent EEG and serum sampling for NSE and S100B. The participants were aged 1 month to 18 years who experienced cardiac arrest and underwent cardiopulmonary resuscitation after a sustained return of spontaneous circulation for ≥48 hours. We excluded immunocompromised patients, those with neurological diseases, hematological malignancies or solid tumors, or a history of head trauma. Results Approximately 19.5% (n=8) of patients survived until hospital discharge. Convulsions and sepsis—observed in 21.9% (n=9) and 82.9% (n=34) of patients, respectively—were significantly associated with higher mortality (relative risk: 1.33 [95% CI=1.09–1.6] and 1.99 [95% CI=0.8–4.7], respectively). Serum NSE and S100B levels were not statistically associated with outcome (P=0.278 and 0.693, respectively). NSE levels were positively correlated with arrest duration. EEG patterns were significantly associated with outcome (P=0.01). Non-epileptogenic EEG activity was associated with the highest survival rate. No patient with burst suppression survived. Conclusion Post-cardiac arrest syndrome is a serious condition with a high mortality rate. Management of sepsis and convulsions affects prognosis. NSE and S100B have no benefit in survival evaluation. EEG is recommended for all post-cardiac arrest patients.

Abstract 10169: Changes in Cytokine Responses by Treatment with Tocilizumab After Out-of-Hospital Cardiac Arrest - A Sub Study of the IMICA Trial

Background: Out-of-hospital cardiac arrest (OHCA) patients are at high risk of morbidity and mortality attributable to the post-cardiac arrest syndrome, in which systemic inflammation is a major component. Cytokines are involved in many processes, including inflammation. In the IMICA trial, treatment with the interleukin 6 receptor (IL-6R) antagonist tocilizumab in resuscitated comatose OHCA patients reduced systemic inflammation as characterized by a greatly reduced CRP response and lower levels of leukocytes as compared to placebo. Markers of myocardial injury were also reduced by treatment. Aim: To investigate changes in cytokine levels induced by blocking the IL-6-mediated signaling with tocilizumab after OHCA by employing a broad cytokine panel. Methods: We randomized 80 patients to a single infusion of tocilizumab 8 mg/kg or placebo after admission. Blood samples were drawn at 0, 24, 48, and 72 hours. Cytokines were measured using a 17-plex cytokine assay: G-CSF, GM-CSF, IFN-γ, MCP-1, MIP-1β, TNF-α, IL- 1β, 2, 4-8, 10, 12, 13, and 17. Data were log2 transformed and analyzed by constrained linear mixed models. Results: Most cytokines had temporal changes after OHCA. However, only for IL- 5, 6 (Figure) and 17 were the treatment-by-time interactions significant, all p<0.05. Circulating IL-5 and in particular IL-6 was markedly increased by inhibition of the IL-6R with tocilizumab as compared to the placebo group. For IL-17 the changes were less pronounced and only differed between groups at 72 hours. Conclusions: Treatment with the IL-6R antagonist, tocilizumab, did not alter the cytokine responses in general, however, IL-5 and IL-6 were markedly increased. Experimental data suggests that IL-5 may play a role in cardiac recovery after ischemia. Blockage of the IL-6R greatly increased the IL-6 levels, and as the CRP response was greatly reduced by tocilizumab, a response strongly associated with IL-6, it can be demonstrated that the function of IL-6 was blunted.

Circulatory trajectories after out-of-hospital cardiac arrest: a prospective cohort study

Background Circulatory failure frequently occurs after out-of-hospital cardiac arrest (OHCA) and is part of post-cardiac arrest syndrome (PCAS). The aim of this study was to investigate circulatory disturbances in PCAS by assessing the circulatory trajectory during treatment in the intensive care unit (ICU). Methods This was a prospective single-center observational cohort study of patients after OHCA. Circulation was continuously and invasively monitored from the time of admission through the following five days. Every hour, patients were classified into one of three predefined circulatory states, yielding a longitudinal sequence of states for each patient. We used sequence analysis to describe the overall circulatory development and to identify clusters of patients with similar circulatory trajectories. We used ordered logistic regression to identify predictors for cluster membership. Results Among 71 patients admitted to the ICU after OHCA during the study period, 50 were included in the study. The overall circulatory development after OHCA was two-phased. Low cardiac output (CO) and high systemic vascular resistance (SVR) characterized the initial phase, whereas high CO and low SVR characterized the later phase. Most patients were stabilized with respect to circulatory state within 72 h after cardiac arrest. We identified four clusters of circulatory trajectories. Initial shockable cardiac rhythm was associated with a favorable circulatory trajectory, whereas low base excess at admission was associated with an unfavorable circulatory trajectory. Conclusion Circulatory failure after OHCA exhibits time-dependent characteristics. We identified four distinct circulatory trajectories and their characteristics. These findings may guide clinical support for circulatory failure after OHCA. Trial registration ClinicalTrials.gov: NCT02648061