Outcome Related to Level of Targeted Temperature Management in Postcardiac Arrest Syndrome of Low, Moderate, and High Severities: A Nationwide Multicenter Prospective Registry

Abstract

OBJECTIVES: The optimal target temperature during targeted temperature management for patients after cardiac arrest remains under debate. The aim of this study was to evaluate the association between targeted temperature management at lower target temperatures and the neurologic outcomes among patients classified by the severity of postcardiac arrest syndrome. DESIGN: A multicenter observational study from the out-of-hospital cardiac arrest registry of the Japanese Association for Acute Medicine, which is a nationwide prospective registry of out-of-hospital cardiac arrest patients. SETTING: A total of 125 critical care medical centers or hospitals with an emergency care department across Japan. PATIENTS: A total of 1,111 out-of-hospital cardiac arrest patients who had received targeted temperature management. MEASUREMENTS AND MAIN RESULTS: We divided all 1,111 postcardiac arrest syndrome patients treated with targeted temperature management into two groups: those who received targeted temperature management at a lower target temperature (33–34°C) and those who received targeted temperature management at a higher target temperature (35–36°C). In regard to classification of the patients, we divided the patients into three categories of severity (low, moderate, and high severities) using the risk classification tool, post-Cardiac Arrest Syndrome for Therapeutic hypothermia, which was previously validated. The primary outcome was the percentage of patients with a good neurologic outcome at 30 days, and the secondary outcome was the survival rate at 30 days. Multivariate analysis showed that targeted temperature management at 33–34°C was significantly associated with a good neurologic outcome and survival at 30 days in the moderate severity (odds ratio, 1.70 [95% CI, 1.03–2.83] and 1.90 [95% CI, 1.15–3.16], respectively), but not in the patients of low or high severity (pinteraction = 0.033). Propensity score analysis also showed that targeted temperature management at 33–34°C was associated with a good neurologic outcome in the moderate-severity group (p = 0.022). CONCLUSIONS: Targeted temperature management at 33–34°C was associated with a significantly higher rate of a good neurologic outcome in the moderate-severity postcardiac arrest syndrome group, but not in the low- or high-severity group.

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

“…Thus, the patient group that is especially likely to derive benefit from hypothermic TTM is the group with PCAS of moderate severity ( Figure 2 ). This hypothesis is partly supported by the two recent clinical studies mentioned above [ 41 , 42 ], while additional RCT(s) would be needed to confirm this hypothesis.…”

“…We evaluated the association between the core temperature setting for TTM and the neurologic outcomes in PCAS patients classified according to the rCAST score as having PCAS of high, moderate, and low severity, and examined the effect of TTM at 33–34 °C on the neurological outcome in each group [ 42 ]. Among the patients with PCAS of moderate severity, those undergoing TTM at 33–34 °C showed a better neurological prognosis than patients undergoing TTM at 35–36 °C, while no such difference in the prognosis according to the core temperature setting was observed in patients with mild or severe PCAS.…”

Temperature control after cardiac arrest: friend or foe

“…Patients with severe cerebral oedema or a highly malignant EEG had poor outcomes (98.4 and 96.3% mortality, respectively) regardless of temperature control strategy. In an observational study from Japan, temperature control at 33–34 o C compared with temperature control at 35–36 o C was associated with a significantly higher rate of a good functional outcome in the moderate-severity postcardiac arrest syndrome group (defined using a validated risk classification tool, but not in the low-severity or high-severity group [35 ▪ ]). Whilst these studies show an association between temperature control at 33–34 o C and better outcomes than temperature control at 36 o C among those with severe hypoxic–ischaemic injury (excluding those with the most severe disease), there are likely to be multiple confounders unaccounted for in the analyses and causality is unproven.…”

The effectiveness of targeted temperature management following cardiac arrest may depend on bystander cardiopulmonary resuscitation rates

“…Each patient should be evaluated individually but development of detailed unit-specific protocols has facilitated safe practice by reducing the complications associated with use of multiple agents. 2 Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that is often used for its sedative and analgesic effects. Its dissociative anaesthetic properties, coupled with cardiovascular stability and minimal respiratory depression make it a versatile anaesthetic agent.…”

“…It is recommended for procedures in a range of specialties, such as anaesthesiology, intensive care, emergency medicine as well as psychiatry. [2][3][4] Psychotropic effects, such as hallucinations can be minimised by concomitant administration of benzodiazepine drugs. [3][4][5][6] In the USA, ketamine is the most frequently used analgosedative for burn injuries, with 50% of centres using this agent.…”