Editor's Choice-Effects of targeted temperature management on mortality and neurological outcome: A systematic review and meta-analysis.
Topic: Hyperthermia

The purpose of this study was to conduct a systematic review, and where applicable meta-analyses, examining the evidence underpinning the use of targeted temperature management following resuscitation from cardiac arrest.

PICO
Population: Patients resuscitated from cardiac arrest
Intervention: Targeted temperature management
Comparison: Standard care or alternative treatment
Outcomes: Mortality and neurological outcome

Included studies:
title: A comparison of intravascular and surface cooling techniques in comatose cardiac arrest survivors.
abstract: Mild therapeutic hypothermia after out-of-hospital cardiac arrest is usually achieved either by surface cooling or by core cooling via the patient's bloodstream. We compared modern core (Coolgard) and surface (Arctic Sun) cooling devices with a zero hypothesis of equal cooling, complications, and neurologic outcomes.
title: Invasive versus non-invasive cooling after in- and out-of-hospital cardiac arrest: a randomized trial.
abstract: Mild induced hypothermia (MIH) is indicated for comatose survivors of sudden cardiac arrest (SCA) to improve clinical outcome. In this study, we compared the efficacy of two different cooling devices for temperature management in SCA survivors.
title: Induction of therapeutic hypothermia by paramedics after resuscitation from out-of-hospital ventricular fibrillation cardiac arrest: a randomized controlled trial.
abstract: Therapeutic hypothermia is recommended for the treatment of neurological injury after resuscitation from out-of-hospital cardiac arrest. Laboratory studies have suggested that earlier cooling may be associated with improved neurological outcomes. We hypothesized that induction of therapeutic hypothermia by paramedics before hospital arrival would improve outcome.
title: Does induction of hypothermia improve outcomes after in-hospital cardiac arrest?
abstract: Hypothermia improves neurologic recovery compared to normothermia after resuscitation from out-of-hospital ventricular fibrillation, but may or may not be beneficial for patients resuscitated from in-hospital cardiac arrest. Therefore, we evaluated the effect of induced hypothermia in a large cohort of patients with in-hospital cardiac arrest.
title: Pilot randomized clinical trial of prehospital induction of mild hypothermia in out-of-hospital cardiac arrest patients with a rapid infusion of 4 degrees C normal saline.
abstract: Although delayed hospital cooling has been demonstrated to improve outcome after cardiac arrest, in-field cooling started immediately after the return of spontaneous circulation may be more beneficial. The aims of the present pilot study were to assess the feasibility, safety, and effectiveness of in-field cooling.
title: Impact of intra-arrest therapeutic hypothermia in outcomes of prehospital cardiac arrest: a randomized controlled trial.
abstract: Mild therapeutic hypothermia (TH) is recommended as soon as possible after the return of spontaneous circulation to improve outcomes after out-of-hospital cardiac arrest (OHCA). Preclinical data suggest that the benefit of TH could be increased if treatment is started during cardiac arrest. We aimed to study the impact of intra-arrest therapeutic hypothermia (IATH) on neurological injury and inflammation following OHCA.
title: Is hypothermia after cardiac arrest effective in both shockable and nonshockable patients?: insights from a large registry.
abstract: Although the level of evidence of improvement is significant in cardiac arrest patients resuscitated from a shockable rhythm (ventricular fibrillation or pulseless ventricular tachycardia [VF/Vt]), the use of therapeutic mild hypothermia (TMH) is more controversial in nonshockable patients (pulseless electric activity or asystole [PEA/asystole]). We therefore assessed the prognostic value of hypothermia for neurological outcome at hospital discharge according to first-recorded cardiac rhythm in a large cohort.
title: Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest.
abstract: Cardiac arrest with widespread cerebral ischemia frequently leads to severe neurologic impairment. We studied whether mild systemic hypothermia increases the rate of neurologic recovery after resuscitation from cardiac arrest due to ventricular fibrillation.
title: Influence of neonatally-administered monosodium glutamate on the neuroendocrine regulation of prolactin cell activity in adult Syrian hamsters.
abstract: The effects of MSG on PRL cell activity in hamsters was assessed by injecting either MSG (8 mg/g body weight) or saline into male and female hamsters on day 8 of the neonatal period. One-hundred and three days later, the anterior pituitaries were removed for the analysis of PRL synthesis and storage. Serum PRL levels were also determined by radioimmunoassay as an index of in vivo PRL secretion. Blood levels of PRL were decreased by 74% in female and 88% in male hamsters treated with MSG as compared with vehicle controls. In females, glutamate induced a drop in PRL storage (90%) and synthesis (82%) while in male animals glutamate caused a non-significant decrease in PRL storage (48%) and synthesis (31%) as compared with controls. These results indicate that MSG-induced arcuate nucleus lesions inhibit PRL cell activity in the hamster.
title: Amplification systems in immunity.
title: Therapeutic hypothermia after cardiac arrest: a retrospective comparison of surface and endovascular cooling techniques.
abstract: Therapeutic hypothermia (32-34 degrees C) is recommended for comatose survivors of cardiac arrest; however, the optimal technique for cooling is unknown. We aimed to compare therapeutic hypothermia using either surface or endovascular techniques in terms of efficacy, complications and outcome.
title: Intra-arrest transnasal evaporative cooling: a randomized, prehospital, multicenter study (PRINCE: Pre-ROSC IntraNasal Cooling Effectiveness).
abstract: Transnasal evaporative cooling has sufficient heat transfer capacity for effective intra-arrest cooling and improves survival in swine. The aim of this study was to determine the safety, feasibility, and cooling efficacy of prehospital transnasal cooling in humans and to explore its effects on neurologically intact survival to hospital discharge.
title: Targeted temperature management at 33°C versus 36°C after cardiac arrest.
abstract: Unconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever.
title: Therapeutic hypothermia after out-of-hospital cardiac arrest in Finnish intensive care units: the FINNRESUSCI study.
abstract: We aimed to evaluate post-resuscitation care, implementation of therapeutic hypothermia (TH) and outcomes of intensive care unit (ICU)-treated out-of-hospital cardiac arrest (OHCA) patients in Finland.
title: The relationship between shocks and survival in out-of-hospital cardiac arrest patients initially found in PEA or asystole.
abstract: To describe survival rates from out-of-hospital cardiac arrest for patients who present with pulseless electrical activity or asystole according to whether they remained in a non-shockable rhythm or converted to ventricular fibrillation and were shocked appropriately.
title: Comparative Effectiveness of Therapeutic Hypothermia After Out-of-Hospital Cardiac Arrest: Insight from a Large Data Registry.
abstract: 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 (
title: Neurological benefit of therapeutic hypothermia following return of spontaneous circulation for out-of-hospital non-shockable cardiac arrest.
abstract: Although therapeutic hypothermia is an effective therapy for comatose adults experiencing out-of-hospital shockable cardiac arrest, there is insufficient evidence that is also applicable for those with out-of-hospital non-shockable cardiac arrest.
title: Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia.
abstract: Cardiac arrest outside the hospital is common and has a poor outcome. Studies in laboratory animals suggest that hypothermia induced shortly after the restoration of spontaneous circulation may improve neurologic outcome, but there have been no conclusive studies in humans. In a randomized, controlled trial, we compared the effects of moderate hypothermia and normothermia in patients who remained unconscious after resuscitation from out-of-hospital cardiac arrest.
title: High-volume hemofiltration after out-of-hospital cardiac arrest: a randomized study.
abstract: The study examined the effect of isovolumic high-volume hemofiltration (HF) alone or combined with mild hypothermia (HT) on survival after out-of-hospital cardiac arrest (OHCA) with initial ventricular fibrillation or asystole.
title: A randomized controlled trial comparing the Arctic Sun to standard cooling for induction of hypothermia after cardiac arrest.
abstract: Hypothermia improves neurological outcome for comatose survivors of out-of-hospital cardiac arrest. Use of computer controlled high surface area devices for cooling may lead to faster cooling rates and potentially improve patient outcome.
title: The influence of post-rewarming temperature management on post-rewarming fever development after cardiac arrest.
abstract: We evaluated the influence of post-rewarming temperature management (PRTM) on post-rewarming fever development and determined the association between the temperature in the immediate post-targeted temperature management (TTM) period and outcomes.
title: Effect of Therapeutic Hypothermia on Survival to Hospital Discharge in Out-of-hospital Cardiac Arrest Secondary to Nonshockable Rhythms.
abstract: Therapeutic hypothermia has been shown to improve neurologic outcome and survival in out-of-hospital cardiac arrest (OHCA) following return of spontaneous circulation (ROSC), and current guidelines recommend therapeutic hypothermia for all comatose survivors of OHCA. However, recommendations for nonshockable rhythms are not as strongly supported. Our study aims to provide further evidence on the use of therapeutic hypothermia in nonshockable rhythms.
title: Post-hypothermia fever is associated with increased mortality after out-of-hospital cardiac arrest.
abstract: Post-cardiac arrest fever has been associated with adverse outcome before implementation of therapeutic hypothermia (TH), however the prognostic implications of post-hypothermia fever (PHF) in the era of modern post-resuscitation care including TH has not been thoroughly investigated. The aim of the study was to assess the prognostic implication of PHF in a large consecutive cohort of comatose survivors after out-of-hospital cardiac arrest (OHCA) treated with TH.
title: Targeted Temperature Management for 48 vs 24 Hours and Neurologic Outcome After Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial.
abstract: International resuscitation guidelines recommend targeted temperature management (TTM) at 33°C to 36°C in unconscious patients with out-of-hospital cardiac arrest for at least 24 hours, but the optimal duration of TTM is uncertain.
title: Induction of prehospital therapeutic hypothermia after resuscitation from nonventricular fibrillation cardiac arrest*.
abstract: To evaluate the effects on temperature and outcome at hospital discharge of a pre-hospital rapid infusion of large volume, ice-cold intravenous Hartmann's solution in patients with out-of-hospital cardiac arrest and an initial cardiac rhythm of asystole or pulseless electrical activity.