Does therapeutic hypothermia benefit adult cardiac arrest patients presenting with non-shockable initial rhythms?: A systematic review and meta-analysis of randomized and non-randomized studies (original) (raw)

Comparative Effectiveness of Therapeutic Hypothermia After Out-of-Hospital Cardiac Arrest: Insight from a Large Data Registry

Therapeutic Hypothermia and Temperature Management, 2014

This study was done to determine the effectiveness of therapeutic hypothermia (TH) after out-of-hospital cardiac arrest (OHCA) among a large cohort of adults in the Cardiac Arrest Registry to Enhance Survival (CARES), with an emphasis on subgroups with a nonshockable first documented rhythm. This was an IRB approved retrospective cohort study. All adult index events at participating sites from November 2010 to December 2013 were study eligible. All patient data elements were provided. Summary statistics were calculated for all patients with and without TH. For multivariate adjustment, a multilevel (i.e., hierarchical), mixed-effects logistic regression (MLR) model was used with hospitals treated as random effects. Propensity score matching (PSM) on both shockable and nonshockable patients was done as a sensitivity analysis. After predefined exclusions, our final sample size was 6369 records for analysis: shockable = 2992 (47.0%); asystole = 1657 (26.0%); pulseless electrical activity = 1249 (19.6%); other unspecified nonshockable = 471 (7.4%). Unadjusted differences in neurological status at hospital discharge with and without TH were similar ( p = 0.295). After multivariate adjustment, TH had either no association with good neurological status at hospital discharge or that TH was actually associated with worse neurological outcome, particularly in patients with a nonshockable first documented rhythm (i.e., for NS patients, MLR odds ratio for TH = 1.444; 95% CI [1.039, 2.006] p = 0.029, and OR = 1.017, p = 0.927 via PSM). Highlighting our limitations, we conclude that when TH is indiscriminately provided to a large population of OHCA survivors with a nonshockable first documented rhythm, evidence for its effectiveness is diminished. We suggest more uniform and rigid guidelines for application.

Neurologic outcome in comatose patients resuscitated from out-of-hospital cardiac arrest with prolonged downtime and treated with therapeutic hypothermia

Resuscitation, 2014

Background: Previous reports have shown that prolonged duration of resuscitation efforts in out-ofhospital cardiac arrest (OHCA) is associated with poor neurologic outcome. This concept has recently been questioned with advancements in post-cardiac arrest care including the use of therapeutic hypothermia (TH). The aim of this study was to determine the rate of good neurologic outcome based on the duration of resuscitation efforts in OHCA patients treated with TH. Methods: This prospective, observational, study was conducted between January 2008 and September 2012. Inclusion criteria consisted of adult non-traumatic OHCA patients who were comatose after return of spontaneous circulation (ROSC) and received TH. The primary endpoint was good neurologic outcome defined as a cerebral performance category score of 1 or 2. Downtime was calculated as the length of time between the patient being recognized as pulseless and ROSC. Results: 105 patients were treated with TH and 19 were excluded due to unknown downtime, leaving 86 patients for analysis. The median downtime was 18.5 (10.0-32.3) min and 33 patients (38.0%) had a good neurologic outcome. When downtime was divided into four groups (≤10 min, 11-20 min, 21-30 min, >30 min), good neurologic outcomes were 62.5%, 37%, 25%, and 21.7%, respectively (p = 0.02). However, even with downtime >20 min, 22.9% had a good neurologic outcome, and this percentage increased to 37.5% in patients with an initial shockable rhythm. Conclusions: Although longer downtime is associated with worse outcome in OHCA patients, we found that comatose patients who have been successfully resuscitated and treated with TH have neurologically intact survival rates of 23% even with downtime >20 min.

Impact of therapeutic hypothermia during cardiopulmonary resuscitation on neurologic outcome: A systematic review and meta-analysis

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.

Predictors of death among cardiac arrest patients after therapeutic hypothermia: A non-tertiary care center's initial experience

Revista Portuguesa de Cardiologia, 2016

Introduction and Objectives: Therapeutic hypothermia (TH) is recommended for patients with return of spontaneous circulation (ROSC) after cardiac arrest (CA). There is still uncertainty about management, target temperature and duration of TH. In the present study we aim to describe the initial experience of a non-tertiary care center with TH after CA and to determine predictors of mortality. Methods: During the period 2011-2014, out of 2279 patients hospitalized in the intensive care unit, 82 had a diagnosis of CA with ROSC. We determined predictors of mortality and neurological outcome in comatose patients with ROSC after CA treated by TH. Results: A total of 15 patients were included, mean age 47.3±14 years, 10 (67.0%) male. CA occurred out-of-hospital (n=11; 73.3%) or in-hospital (n=4; 26.7%), in initial shockable (n=10; 66.7%) or non-shockable (n=5, 33.3%) rhythm. The mean time from CA to ROSC (CA-ROSC) was 44.7±36.5 min. All patients met the 24-hour TH target temperature of 33 • C. The mean neuronspecific enolase (NSE) level was 93.7±109.0 g/l. Seven patients (46.7%) were discharged with good cerebral performance and eight (53.3%) died. Patients who survived had lower median age (p=0.032), shorter CA-ROSC (p=0.048), lower NSE levels (p=0.020) and initial ventricular fibrillation rhythm (p=NS). Conclusions: The effectiveness of TH appears to be related to younger age, shockable initial rhythm and shorter CA-ROSC time. This results indicates some lines of inquiry that should be developed in appropriate prospective studies. The role of biomarkers as predictors of prognosis is an open question, with NSE potentially playing an important role.

Postresuscitation care with mild therapeutic hypothermia and coronary intervention after out-of-hospital cardiopulmonary resuscitation: a prospective registry analysis

Critical Care, 2011

Introduction: Mild therapeutic hypothermia (MTH) has been shown to result in better neurological outcome after cardiopulmonary resuscitation. Percutaneous coronary intervention (PCI) may also be beneficial in patients after out-of-hospital cardiac arrest (OHCA). Methods: A selected cohort study of 2,973 prospectively documented adult OHCA patients within the German Resuscitation Registry between 2004 and 2010. Data were analyzed by backwards stepwise binary logistic regression to identify the impact of MTH and PCI on both 24-hour survival and neurological outcome that was based on cerebral performance category (CPC) at hospital discharge. Odds ratios (95% confidence intervals) were calculated adjusted for the following confounding factors: age, location of cardiac arrest, presumed etiology, bystander cardiopulmonary resuscitation, witnessing, first electrocardiogram rhythm, and thrombolysis. Results: The Preclinical care dataset included 2,973 OHCA patients with 44% initial return of spontaneous circulation (n = 1,302) and 35% hospital admissions (n = 1,040). Seven hundred and eleven out of these 1,040 OHCA patients (68%) were also registered within the Postresuscitation care dataset. Checking for completeness of datasets required the exclusion of 127 Postresuscitation care cases, leaving 584 patients with complete data for final analysis. In patients without PCI (n = 430), MTH was associated with increased 24-hour survival (8.24 (4.24 to 16.0), P < 0.001) and the proportion of patients with CPC 1 or CPC 2 at hospital discharge (2.13 (1.17 to 3.90), P < 0.05) as an independent factor. In normothermic patients (n = 405), PCI was independently associated with increased 24-hour survival (4.46 (2.26 to 8.81), P < 0.001) and CPC 1 or CPC 2 (10.81 (5.86 to 19.93), P < 0.001). Additional analysis of all patients (n = 584) revealed that 24-hour survival was increased by MTH (7.50 (4.12 to 13.65), P < 0.001) and PCI (3.88 (2.11 to 7.13), P < 0.001), while the proportion of patients with CPC 1 or CPC 2 was significantly increased by PCI (5.66 (3.54 to 9.03), P < 0.001) but not by MTH (1.27 (0.79 to 2.03), P = 0.33), although an unadjusted Fisher exact test suggested a significant effect of MTH (unadjusted odds ratio 1.83 (1.23 to 2.74), P < 0.05). Conclusions: PCI may be an independent predictor for good neurological outcome (CPC 1 or CPC 2) at hospital discharge. MTH was associated with better neurological outcome, although subsequent logistic regression analysis did not show statistical significance for MTH as an independent predictor for good neurological outcome. Thus, postresuscitation care on the basis of standardized protocols including coronary intervention and hypothermia may

Effect of different methods of cooling for targeted temperature management on outcome after cardiac arrest: a systematic review and meta-analysis

Critical Care, 2019

Background: Although targeted temperature management (TTM) is recommended in comatose survivors after cardiac arrest (CA), the optimal method to deliver TTM remains unknown. We performed a meta-analysis to evaluate the effects of different TTM methods on survival and neurological outcome after adult CA. Methods: We searched on the MEDLINE/PubMed database until 22 February 2019 for comparative studies that evaluated at least two different TTM methods in CA patients. Data were extracted independently by two authors. We used the Newcastle-Ottawa Scale and a modified Cochrane ROB tools for assessing the risk of bias of each study. The primary outcome was the occurrence of unfavorable neurological outcome (UO); secondary outcomes included overall mortality. Results: Our search identified 6886 studies; 22 studies (n = 8027 patients) were included in the final analysis. When compared to surface cooling, core methods showed a lower probability of UO (OR 0.85 [95% CIs 0.75-0.96]; p = 0.008) but not mortality (OR 0.88 [95% CIs 0.62-1.25]; p = 0.21). No significant heterogeneity was observed among studies. However, these effects were observed in the analyses of non-RCTs. A significant lower probability of both UO and mortality were observed when invasive TTM methods were compared to non-invasive TTM methods and when temperature feedback devices (TFD) were compared to non-TFD methods. These results were significant particularly in non-RCTs. Conclusions: Although existing literature is mostly based on retrospective or prospective studies, specific TTM methods (i.e., core, invasive, and with TFD) were associated with a lower probability of poor neurological outcome when compared to other methods in adult CA survivors (CRD42019111021).

Factors predicting the use of therapeutic hypothermia and survival in unconscious out-of-hospital cardiac arrest patients admitted to the ICU

Critical Care, 2013

Introduction: Therapeutic hypothermia (TH) after out-of-hospital cardiac arrest (OHCA) was adopted early in Norway. Since 2004 the general recommendation has been to cool all unconscious OHCA patients treated in the intensive care unit (ICU), but the decision to cool individual patients was left to the responsible physician. We assessed factors that were associated with use of TH and predicted survival. Method: We conducted a retrospective observational study of prospectively collected cardiac arrest and ICU registry data from 2004 to 2008 at three university hospitals.

Therapeutic hypothermia after nonshockable cardiac arrest: the HYPERION multicenter, randomized, controlled, assessor-blinded, superiority trial

Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, 2015

Background: Meta-analyses of nonrandomized studies have provided conflicting data on therapeutic hypothermia, or targeted temperature management (TTM), at 33°C in patients successfully resuscitated after nonshockable cardiac arrest. Nevertheless, the latest recommendations issued by the International Liaison Committee on Resuscitation and by the European Resuscitation Council recommend therapeutic hypothermia. New data are available on the adverse effects of therapeutic hypothermia, notably infectious complications. The risk/benefit ratio of therapeutic hypothermia after nonshockable cardiac arrest is unclear.