Elsevier

Resuscitation

Volume 91, June 2015, Pages 8-18
Resuscitation

Review article
Effects of in-hospital low targeted temperature after out of hospital cardiac arrest: A systematic review with meta-analysis of randomized clinical trials

https://doi.org/10.1016/j.resuscitation.2015.02.038Get rights and content

Abstract

Objective

We performed this systematic review to evaluate the effectiveness of in-hospital low targeted temperature in adult patients after out of hospital cardiac arrest on survival and neurologic performance.

Data source

We systematically searched MEDLINE and PUBMED from inception to April 2014.

Study selection

Citations were screened for studies evaluating the effect of in-hospital low targeted temperature in patients following out of hospital cardiac arrest.

Data extraction

We analyzed randomized control trials (RCTs) that included adult patients resuscitated from out of hospital cardiac arrest, reporting mortality at hospital discharge and comparing in-hospital low targeted temperature with a control group.

Data synthesis

This meta-analysis included 6 RCTs and 1418 adult patients. In-hospital low targeted (low T) temperature was associated to a reduction in mortality at hospital discharge and at 6 months when compared with in-hospital targeted and not targeted temperature while there was no reduction in mortality comparing low and high targeted temperature. In patients with initial ventricular fibrillation/ventricular tachycardia rhythm of out of hospital cardiac arrest, low T was associated with a reduction in short and long-term mortality when compared with no targeted temperature while not when compared to high targeted temperature. Low T was associated with good neurologic performance at hospital discharge compared with in-hospital high or not targeted temperature.

Conclusion

In-hospital low targeted temperature (<4 °C) improved short and long-term mortality when compared to no targeted temperature. In contrast, low T did not improve outcome compared with a slightly higher targeted temperature (≈36 °C).

Introduction

Out of hospital cardiac arrest (OHCA) is an increasing public-health concern in industrialized countries, with a reported incidence of 38 per 100,000 and a survival to hospital discharge of only 10.7%.1 Long-term survival and clinical outcome after cardiac arrest (CA) improved with years.2 However, many survivors suffer from a poor neurologic outcome, with low quality of life and an extended brain injury.3 After OHCA, post resuscitation care may significantly influence survival and neurologic outcome.4 Although, therapeutic hypothermia (TH) was included in the last guidelines on CA as a treatment for the post resuscitation phase,5 and it has been implemented as the standard of care in many countries, the evidences for its possible beneficial effects after OHCA are still debated.

From a pathophysiological point of view, TH may reduce the excitotoxin exposure and reduce the inflammatory response associated with the post cardiac arrest syndrome.5 On the other hand, TH has been associated with potential adverse side effects including pneumonia, cardiovascular instability and metabolic disturbance, which may further increase morbidity and mortality.6 In OHCA caused by ventricular fibrillation (VF), TH reduced mortality and improved 6-months neurological outcome.7, 8 In contrast, the efficacy of TH in the setting of other causes of cardiac arrest i.e. pulseless electrical activity and asystole, remains unclear.9, 10 A Cochrane review supported the use of TH after OHCA to improve survival and cerebral performance at hospital discharge.11 However, a recent target temperature management (TTM) trial did not show any difference in terms of survival and neurological outcome between OHCA patients treated with two levels of targeted temperature set at 33 and 36 °C.10

The aim of this systematic review and meta-analysis was to evaluate the effectiveness of in-hospital low targeted temperature (<34 °C, low T) compared to controls with both in-hospital not targeted temperature (no target T) and in-hospital targeted temperature (TT) in adult patients after OHCA on mortality and neurologic performance as main outcomes. The TTM study was not the first trial that randomized patients to receive two level of targeted temperature. Bernard et al., and Laurent et al., included a control group with targeted temperature.7, 9, 10 Keeping the patient's temperature stable at an established degree may avoid an uncontrolled increase of body temperature and its side effects.10 Given this, we hypothesized that a low targeted temperature (<34 °C) may have more beneficial effects over a slightly higher targeted temperature (≈36 °C). For this reason, we “a priori” planned a sub-analysis dividing the studies according the temperature management (targeted/not targeted) in different control groups. In addition, studies evaluating hypothermia after OHCA were mainly focused on patients with VF or ventricular tachycardia as initial rhythm.6, 7, 8, 9, 10 According to this, we “a priori” planned a further sub-group analysis of studies including mainly patients with shockable initial rhythm of OHCA.

Section snippets

Data sources and searches

We aimed to identify all randomized control trials (RCTs) assessing mortality at discharge after therapeutic induced hypothermia in adult cardiac arrest patients.

The electronic search strategy applied standard filters for identification of RCTs. Databases searched were the MEDLINE and PUBMED (from inception to April 2014). We applied English language restrictions. Our search included the following keywords: cardiac arrest, out of hospital cardiac arrest, in hospital cardiac arrest, circulatory

Study selection

We identified 1079 references and excluded 1043 after reading titles and abstracts for cardiac arrest, hypothermia, mortality and randomized clinical trials. We analyzed 36 articles in full paper format. Six references fulfilled our search criteria.7, 16, 17 Thirty references, including 3 RCTs evaluating the role of pre-hospital hypothermia, were excluded.18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 3, 43 Fig. 1 shows the study selection

Discussion

In this systematic review and meta-analysis we found that: (1) low T reduced mortality at hospital discharge and at 6 months when compared with no targeted T while there was no reduction in mortality comparing low T with TT; (2) in patients with initial VF/VT rhythm low T reduced short and long-term mortality when compared with no targeted T while not when compared to TT; (3) low T improved neurologic performance at hospital discharge compared with no targeted T.

The results of the present

Limitations

This systematic review and meta-analysis has some limitations, which need to be addressed. We included only full papers in English language and excluding abstracts, but only one of all trials showed overall low risk of bias. We found a substantial heterogeneity (I2 > 50%) according to Cochrane guidelines in 8 out of 17 considered outcomes. We were not able to divide the results according asystole/PEA initial rhythm of OHCA because of the lack of more than one study. Since the overall mortality

Conclusions

In-hospital low targeted temperature (<34 °C) was associated with beneficial effects on short and long-term mortality when compared to in-hospital not targeted temperature. At the same time, we are not able to demonstrate the same results when in-hospital low targeted temperature (<34 °C) was compared with in-hospital slightly higher targeted temperature (≈36 °C). Further studies are needed to establish the best targeted temperature and its potential beneficial effects, and determine how this

Funding

No funding was obtained for this manuscript.

Conflict of interest statement

BI and PP participate to target temperature management trial (TTM trial). VM SG, SY and RGR have no conflict of interest.

Acknowledgement

The authors would like to thank Professor John G Laffey for his contribution in manuscript editing and review.

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    A Spanish translated version of the abstract of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2015.02.038.

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