<abstract xmlns="http://www.w3.org/1999/xhtml">

<sec>
<h3>Introduction</h3>
<p>The risk-benefit profile of therapeutic hypothermia is controversial with several randomized controlled trials providing conflicting results.</p>
</sec>
<sec>
<h3>Aim of Study</h3>
<p>The purpose of this systematic review and meta-analysis was to determine if therapeutic hypothermia provides beneficial neurologic outcomes relative to adverse effects.</p>
</sec>
<sec>
<h3>Material and Methods</h3>
<p>MEDLINE and EMBASE databases were searched for randomized controlled trials of post-cardiac arrest patients comparing therapeutic hypothermia (<sup>~</sup>33 degrees Celsius) to normothermia or the standard of care (36 - 38 degrees Celsius). Data were collected using the Covidence systematic review software. Statistical analysis was performed by Review Manager software. Risk of bias, sensitivity, and heterogeneity were analyzed using the Cochran’s Collaboration tool, trial sequential analysis (TSA) software, and I2 statistic respectively.</p>
</sec>
<sec>
<h3>Results</h3>
<p>A total of 1825 studies were screened and 5 studies (n=3614) were included. No significant differences existed between the hypothermia group and normothermia for favorable neurologic outcome (risk ratio [RR] 1.17, 95% confidence interval [CI] 0.97 to 1.41) or all-cause mortality (RR 0.97, 95% CI 0.89 to 1.05). When compared to normothermia, the hypothermia group had greater risk of adverse effects (RR 1.16, 95% CI 1.04 to 1.28), which was driven by the onset of arrhythmias. Subgroup analyses revealed that therapeutic hypothermia provided greater neurologic benefit in trials with a higher percentage of subjects with shockable rhythms (RR 0.73, 95% CI 0.6 to 0.88). Trial sequential analysis revealed statistical futility for therapeutic hypothermia and favorable neurologic outcome, mortality, and adverse effects.</p>
</sec>
<sec>
<h3>Conclusions</h3>
<p>Therapeutic hypothermia does not provide consistent benefit in neurologic outcome or mortality in the general cardiac arrest population. Patients with shockable rhythms may show favorable neurologic outcome with therapeutic hypothermia and further investigation in this population is warranted. Any potential benefit associated with therapeutic hypothermia must be weighed against the increased risk of adverse effects, particularly the onset of arrhythmias.</p>
</sec>
</abstract>

Introduction
The risk-benefit profile of therapeutic hypothermia is controversial with several randomized controlled trials providing conflicting results.


Aim of Study
The purpose of this systematic review and meta-analysis was to determine if therapeutic hypothermia provides beneficial neurologic outcomes relative to adverse effects.


Material and Methods
MEDLINE and EMBASE databases were searched for randomized controlled trials of post-cardiac arrest patients comparing therapeutic hypothermia (~33 degrees Celsius) to normothermia or the standard of care (36 - 38 degrees Celsius). Data were collected using the Covidence systematic review software. Statistical analysis was performed by Review Manager software. Risk of bias, sensitivity, and heterogeneity were analyzed using the Cochran’s Collaboration tool, trial sequential analysis (TSA) software, and I2 statistic respectively.


Results
A total of 1825 studies were screened and 5 studies (n=3614) were included. No significant differences existed between the hypothermia group and normothermia for favorable neurologic outcome (risk ratio [RR] 1.17, 95% confidence interval [CI] 0.97 to 1.41) or all-cause mortality (RR 0.97, 95% CI 0.89 to 1.05). When compared to normothermia, the hypothermia group had greater risk of adverse effects (RR 1.16, 95% CI 1.04 to 1.28), which was driven by the onset of arrhythmias. Subgroup analyses revealed that therapeutic hypothermia provided greater neurologic benefit in trials with a higher percentage of subjects with shockable rhythms (RR 0.73, 95% CI 0.6 to 0.88). Trial sequential analysis revealed statistical futility for therapeutic hypothermia and favorable neurologic outcome, mortality, and adverse effects.


Conclusions
Therapeutic hypothermia does not provide consistent benefit in neurologic outcome or mortality in the general cardiac arrest population. Patients with shockable rhythms may show favorable neurologic outcome with therapeutic hypothermia and further investigation in this population is warranted. Any potential benefit associated with therapeutic hypothermia must be weighed against the increased risk of adverse effects, particularly the onset of arrhythmias.

Therapeutic Hypothermia Following Cardiopulmonary Arrest: A Systematic Review and Meta-Analysis with Trial Sequential Analysis

University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences

The Journal of Critical Care Medicine

This work is licensed under the Creative Commons Attribution 4.0 International License.

Introduction
The risk-benefit profile of therapeutic hypothermia is controversial with several randomized controlled trials providing conflicting...

Study	Mild Hypothermia	Standard of Care	Initial Shockable Rhythm	Out-of-Hospital Arrest	Median Time to ROSC	Bystander CPR	Duration of Cooling	Surface Cooling
Bernard. HACA. 2002.	32 to 34	Normothermia	96%	87%	22	46%	24	100%
Bernard. OHCA. 2002.	33	Normothermia	100%	100%	26	58%	18	100%
Nielsen. TTM. 2013.	33	36	80%	100%	25	73%	28	76%
Lascarrou. HY PERION. 2019.	33	37	0%	73%	NR	70%	24	85%
Dankiewicz. TTM2. 2021.	33	37.5	74%	100%	25	80%	28	70%

Adverse Effect	Hypothermia	Normothermia	Absolute Difference	Fragility Index^b
Arrhythmias	306/1389(22%)	227/1390 (16.3%)	5.7%	38
Bleeding	95/1389 (6.8%)	89/1391 (6.4%)	0.4%	0
Seizures	77/463 (16.6%)	83/464 (17.9%)	−1.3%	0
Infection	593/1388 (42.7%)	544/1391 (39.1%)	3.6%	0

Therapeutic Hypothermia Following Cardiopulmonary Arrest: A Systematic Review and Meta-Analysis with Trial Sequential Analysis

Article Category: Review

Publicado en línea: 08 may 2023

Páginas: 64 - 72

Recibido: 28 dic 2022

Aceptado: 26 abr 2023

DOI: https://doi.org/10.2478/jccm-2023-0015

Palabras clave
targeted temperature, therapeutic hypothermia, cardiac arrest, cardiopulmonary arrest, neurology, arrhythmia

© 2023 Robert Maclaren et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

Fig. 1.

Fig. 2.

Fig. 3.

Characteristics of Included Studies

Absolute Percentages of Adverse Effects at the Participant Levela

Therapeutic Hypothermia Following Cardiopulmonary Arrest: A Systematic Review and Meta-Analysis with Trial Sequential Analysis

Article Category: Review

Publicado en línea: 08 may 2023

Páginas: 64 - 72

Recibido: 28 dic 2022

Aceptado: 26 abr 2023

DOI: https://doi.org/10.2478/jccm-2023-0015

Palabras clavetargeted temperature, therapeutic hypothermia, cardiac arrest, cardiopulmonary arrest, neurology, arrhythmia

© 2023 Robert Maclaren et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

Fig. 1.

Fig. 2.

Fig. 3.

Characteristics of Included Studies

Absolute Percentages of Adverse Effects at the Participant Levela

Palabras clave
targeted temperature, therapeutic hypothermia, cardiac arrest, cardiopulmonary arrest, neurology, arrhythmia