Effect of different methods of cooling for targeted temperature management on outcome after cardiac arrest: a systematic review and meta-analysis (original) (raw)
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Journal of the American College of Cardiology, 2020
Background: Targeted Temperature Management (TTM) is a class I recommendation for the management of sudden cardiac arrest (SCA) patients with presumed brain injury. We aimed to study trends, predictors and outcomes in SCA patients from a nationally represented US population sample. Methods: We utilized the National Inpatient Sample from years 2005 to 2014 for the purpose of our study. Patients with SCA and anoxic brain injury were selected using relevant ICD-9 codes. Data were analyzed for trends over the years and key outcomes were assessed. Logistic regression analysis was done to determine predictors of TTM utilization in our study population. Results: A total of 78,465 patients with SCA and anoxic brain injury were identified from January 2005 to December 2014. Out of these, approximately 4,481 (5.7%) patients underwent TTM. Patients that underwent TTM were younger compared to patients without TTM utilization (60.67 vs. 63.27 years, P < 0.01). African Americans, Hispanics and women were less likely to undergo TTM. Myocardial infarction, electrolyte disorders and cardiogenic shock were associated with higher odds of TTM utilization. Sepsis, renal failure and diabetes were associated with underutilization of TTM. Inpatient mortality was higher in patients who did not undergo TTM when compared to patients who underwent TTM (67.30% vs. 65.10%, P < 0.01). Conclusions: Although TTM utilization increased over our study period, the overall application of TTM was still dismal. Factors that circumvent TTM utilization need to be addressed in future studies so more eligible patients could benefit from this life saving therapy.
Journal of Clinical Medicine, 2021
Target temperature management (TTM) in cardiac arrest (CA) survivors is recommended after hospital admission for its possible beneficial effects on survival and neurological outcome. Whether a lower target temperature (i.e., 32-34 • C) improves outcomes is unclear. We conducted a systematic review and meta-analysis on Pubmed and EMBASE to evaluate the effects on mortality and neurologic outcome of TTM at 32-34 • C as compared to controls (patients cared with "actively controlled" or "uncontrolled" normothermia). Results were analyzed via risk ratios (RR) and 95% confidence intervals (CI). Eight randomized controlled trials (RCTs) were included. TTM at 32-34 • C was compared to "actively controlled" normothermia in three RCTs and to "uncontrolled" normothermia in five RCTs. TTM at 32-34 • C does not improve survival as compared to normothermia (RR:1.06 (95%CI 0.94, 1.20), p = 0.36; I 2 = 39%). In the subgroup analyses, TTM at 32-34 • C is associated with better survival when compared to "uncontrolled" normothermia (RR: 1.31 (95%CI 1.07, 1.59), p = 0.008) but shows no beneficial effects when compared to "actively controlled" normothermia (RR: 0.97 (95%CI 0.90, 1.04), p = 0.41). TTM at 32-34 • C does not improve neurological outcome as compared to normothermia (RR: 1.17 (95%CI 0.97, 1.41), p = 0.10; I 2 = 60%). TTM at 32-34 • C increases the risk of arrhythmias (RR: 1.35 (95%CI 1.16, 1.57), p = 0.0001, I 2 = 0%). TTM at 32-34 • C does not improve survival nor neurological outcome after CA and increases the risk of arrhythmias.
Circulation Reports
for the J-PULSE-Hypo-DC Trial Study Group Background: The 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care recommend that comatose patients with return of spontaneous circulation after cardiac arrest have targeted temperature management (TTM). However, the duration of TTM remains to be elucidated. Methods and Results: We conducted a cluster randomized trial in 10 hospitals to compare 12-24 vs. 36 h of cooling in patients with cardiac arrest who received TTM. The primary outcome was the incidence, within 1 month, of complications including bleeding requiring transfusion, infection, arrhythmias, decreasing blood pressure, shivering, convulsions, and major adverse cardiovascular events. Secondary outcomes were mortality and favorable neurological outcome (Cerebral Performance Categories 1-2) at 3 months. Random-effects models with clustered effects were used to calculate risk ratios (RR). Data of 185 patients were analyzed (12-to 24-h group, n=100 in 5 hospitals; 36-h group, n=85 in 5 hospitals). The incidence of complications within 1 month did not differ between the 2 groups (40% vs. 34%; RR 1.04, 95% confidence interval [CI] 0.67-1.61, P=0.860). Favorable neurological outcomes at 3 months were comparable between the 2 groups (64% vs. 62%; RR 0.91, 95% CI 0.72-1.14, P=0.387). Conclusions: TTM at 34°C for 12-24 h did not significantly reduce the incidence of complications. This study did not show superiority of TTM at 34°C for 12-24 h for neurologic outcomes.
Resuscitation, 2021
Background: Therapeutic cooling initiated during cardiopulmonary resuscitation (intra arrest therapeutic hypothermia, IATH) provided diverging effect on neurological outcome of out-of-hospital cardiac arrest (OHCA) patients depending on the initial cardiac rhythm and the cooling methods used. Methods: We performed a systematic search of PubMed, EMBASE and the CENTRAL databases using established Medical Subject Headings (MeSH) terms for IATH and OHCA. Only studies comparing IATH to standard in-hospital targeted temperature management (TTM-control group) were selected. We used the revised Cochrane RoB-2 and the Newcastle-Ottawa scale tool to assess risk of bias of each study. Primary outcome was favorable neurological outcome (FO); secondary outcomes included return of spontaneous circulation (ROSC) rate and overall survival to hospital discharge. Two authors independently assessed the validity of included human studies and extracted data regarding characteristics of the studied cohorts and main outcomes. Results: Out of 20950 studies, 8 studies (n=3493 patients, including 4 randomized trials, RCTs) were included in the nal analysis. When compared to controls, the use of IATH was not associated with improved favorable neurological outcome (OR 0.96 [95% CIs 0.68-1.37]; p= 0.84), increased ROSC rate (OR 1.11 [95% CIs 0.83-1.49]; p= 0.46) or survival to hospital discharge (OR 0.91 [95% CIs 0.73-1.14]; p= 0.43). Signi cant heterogeneity among studies was observed only for the analysis of ROSC rate (I 2 =69%). Trans-nasal evaporative cooling and cold uids were explored in two RCTs each and no signi cant differences were observed on neurological outcome. However, trans-nasal evaporative cooling was associated with a higher probability of favorable neurological outcome when compared to controls in patients with an initial shockable rhythm (OR 1.62 [95% CI 1.00-2.64]; p=0.05]. Conclusions: In this meta-analysis, IATH was not associated with improved neurological outcome when compared to standard in-hospital TTM. However, there are considerable outcome differences depending on the methods used and the studied population that need to be explored in future trials.
Objective: This review aimed to compare the efficacy of endovascular cooling devices (ECD), such as Thermogard 1 , with surface cooling devices (SCD), such as Arctic Sun 1 , in reducing mortality and improving neurological status for patients with post-cardiac arrest undergoing targeted temperature management. Data sources: A systematic literature search was conducted using MEDLINE, EMBASE, and the Cochrane Library to identify randomized controlled trials (RCT) and observational studies (OS) comparing mortality and neurological status for patients treated with ECD or SCD. Results: The meta-analysis comprised 4,401 patients from 2 RCT and 7 OS. For mortality, the overall pooled analysis showed no statistically significant difference between ECD and SCD recipients (RR, 0.93; 95% CI 0.86À1.00; I 2 = 0%). Further, no statistically significant difference was observed between RCT (RR, 0.80; 95% CI 0.56À1.14; I 2 = 0%) and OS (RR, 0.94; 95% CI 0.85À1.04; I 2 = 18%) for in-hospital mortality. For good neurological status of survivors after TTM, the overall pooled analysis showed no statistically significant difference between ECD and SCD (RR, 1.08; 95% CI 0.99À1.18; I 2 = 71%). No statistically significant difference was found between ECD and SCD at hospital discharge in RCT (RR, 0.88; 95% CI 0.61À1.28; I 2 = 0%) and at 6 months in OS (RR, 1.03; 95% CI 0.99À1.09; I 2 = 32%). Conclusions: The study findings could not show that either ECD or SCD was more effective in terms of survival and improved neurological status for post-cardiac arrest patients. Systematic review registration number: CRD42019129770.
Critical Care, 2018
Background: The association between isolated admission heart rate (HR) and prognosis has been discussed, but not that between gross HR change and neurological outcome in patients with severe traumatic brain injury (TBI). In the acute phase of severe TBI, HR is influenced by several factors (e.g., pain, sympathetic activation, hypovolemia, fever, body temperature). Therefore, admission HR and gross HR change should be examined in patients with TBI treated with a well-designed protocol, such as was done in the Brain Hypothermia (B-HYPO) Study. Methods: This was a post hoc analysis of the B-HYPO Study, which was conducted as a prospective, multicenter, randomized controlled trial in patients with severe TBI receiving mild therapeutic hypothermia (MTH; 32.0°C-34.0°C) or fever control (35.5°C-37.0°C) in Japan. Patients with MTH were examined, and HR change (%HR) in the early MTH phase was calculated as follows: [admission HR-HR at day 1]/admission HR × 100. Patients were divided into six groups, using admission HR (< 80, 80-99, ≤ 100) and median of %HR; i.e., group (Admission HR < 80 and %HR ≥ 18.6); group (Admission HR < 80 and %HR < 18.6); group (Admission HR 80-99 and %HR ≥ 18.6); group (Admission HR 80-99 and %HR < 18.6); group (Admission HR ≥100 and %HR ≥ 18.6); and group (Admission HR ≥100 and %HR < 18.6). The primary outcome was an adjusted predicted probability of unfavorable neurological outcome at 6 months after TBI according to Glasgow Outcome Scale score, which is a measure of functional recovery and defined as severe disability, persistent vegetative state, and death.
American Journal of Emergency Medicine, 2021
Background: To date, no study has comprehensively analyzed the association between neuromuscular blockade (NMB) during target temperature management (TTM) and the neurological outcomes after out-of-hospital cardiac arrest (OHCA) using a multicenter dataset. We aimed to examine the association between NMB during TTM after cardiac arrest and neurological outcomes after OHCA. Methods: This study was a secondary analysis of the Japanese Population-based Utstein-style study with defibrillation and basic/advanced Life Support Education and implementation-Hypothermia (J-PULSE-HYPO) study registry. The exposure of the current study was the use of NMB during TTM. The primary outcome was favorable neurological outcome, i.e., a cerebral performance category of 1-2, at hospital discharge. Results: Of the 452 patients with OHCA enrolled in the J-PULSE-HYPO study, 431 were analyzed. NMB was used in 353 patients (81.9%). Multivariable logistic regression analysis revealed that NMB use was not independently associated with favorable outcomes [odds ratio (OR), 0.96; 95% confidence interval (CI), 0.42-2.18; p = .918)] or survival at discharge (OR, 0.83; 95% CI, 0.31-2.02; p = .688). After adjusting the covariates, the predicted probabilities did not reveal significant differences between NMB use and non-NMB use in the respective mean (95% CI) values for favorable neurological outcomes [53.6 (50.2-57.0) % vs. 58.0 (50.4-65.6) %, p = .304], and survival rates [77.1 (74.7-79.5) % vs. 75.8 (70.5-81.0) %, p = .647]. Conclusions: The NMB use during TTM was not associated with favorable neurological outcomes and survival rate in patients with OHCA.
Indian Journal of Critical Care Medicine
Background: Targeted temperature management (TTM) is a vital element of postresuscitation management after cardiac arrest. Though international guidelines recommend TTM, the supporting evidence is of low certainty. Aims and objectives: To estimate the effect of TTM strategy on mortality and neurological outcomes in postcardiac arrest survivors. Materials and methods: Randomized controlled trials (RCTs) published in English evaluating the use of TTM in adult comatose survivors of cardiac arrest were included. Studies were categorized into two groups, based on hypothermia vs normothermia. The main outcome was death due to any origin. The secondary outcome measures evaluated neurological outcome and complications associated with TTM. Outcomes were analyzed by calculating Odds Ratio (OR) of a worse outcome. ORs with 95% CIs in a forest plot were used to show the results of random-effects meta-analyses. Results: On pooled analysis of 11 RCTs, no difference was observed in death due to any origin rates in the hypothermia compared to the normothermia group (OR; 0.88, 95% CI: 0.39-1.16). Overall, no difference in poor neurological outcome was observed between the two groups (OR; 0.86, 95% CI: 0.66-1.12). Trial sequencing analysis for mortality and poor neurological outcome showed that number to achieve power to predict futility has been achieved in both the parameters. Conclusions: This meta-analysis showed that hypothermia compared to normothermia TTM strategies does not improve survival or neurologic outcomes.
Resuscitation, 2012
Background: The benefit of therapeutic hypothermia (TH) for comatose adult patients with return of spontaneous circulation after cardiac arrest (CA) with non-shockable initial rhythms is uncertain. We evaluated whether TH reduces mortality and improves neurological outcome in comatose adults resuscitated from non-shockable CA. Methods: We searched PubMed, EMBASE, CENTRAL, and BIOSIS through March 2010, to identify studies using TH after non-shockable CA. Randomized and non-randomized studies (RS and NRS) comparing survival or neurological outcome in TH and standard care or normothermia were selected. We corresponded with authors to clarify data missing from published articles. Individual and pooled statistics were calculated as risk ratios (RRs) with 95% confidence interval (CI). Both fixed-and random-effects models were used for both meta-analyses. Findings: Two RS and twelve NRS were included in the meta-analysis and separately analyzed. The pooled RR for 6-month mortality of two RS was 0.85 (95% CI 0.65-1.11). The pooled RR for in-hospital mortality for 10 NRS was 0.84 (95% CI 0.78-0.92) and for poor neurological outcome on discharge was 0.95 (95% CI 0.90-1.01) in random-effects model. In subgroup analysis for the NRS with out-of-hospital CA, the pooled RR for in-hospital mortality was 0.86 (95% CI 0.76-0.99) and for the poor neurological outcome on discharge was 0.96 (95% CI 0.90-1.02). For the prospective NRS, the pooled RR for in-hospital mortality was 0.76 (95% CI 0.65-0.89) and for the poor neurological outcome on discharge was 0.96 (95% CI 0.90-1.02). Most of studies had substantial risks of bias and overall quality of evidence was very low. Interpretation: TH is associated with reduced in-hospital mortality for adults patients resuscitated from non-shockable CA. However, most of the studies had substantial risks of bias and quality of evidence was very low. Further high quality randomized clinical trials would confirm the actual benefit of TH in this population.
Which Target Temperature for Post-Anoxic Brain Injury? A Systematic Review from “Real Life” Studies
Brain Sciences
There is a persistent debate on the optimal target temperature to use during cooling procedures in cardiac arrest survivors. A large randomized clinical trial (RCT) including more than 900 patients showed that targeted temperature management (TTM) at 33 °C had similar mortality and unfavorable neurological outcome (UO) rates as TTM at 36 °C in out-of-hospital cardiac arrest patients with any initial rhythm. Since then, several observational studies have been published on the effects of changes in target temperature (i.e., from 33 to 36 °C) on patients’ outcome. We performed a systematic literature search from 1 January 2014 to 4 December 2020 and identified ten retrospective studies (very low levels of certainty; high risk of bias), including 5509 patients, that evaluated TTM at 33 °C vs. TTM at 36 °C on the occurrence of UO (n = eight studies) and mortality (n = ten studies). TTM at 33 °C was associated with a lower risk of UO when studies assessing neurological outcome with the Ce...