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Published in: Critical Care 1/2018

Open Access 01-12-2018 | Research

The efficacy and safety of pre-hospital cooling after out-of-hospital cardiac arrest: a systematic review and meta-analysis

Authors: Patrick J. Lindsay, Danielle Buell, Damon C. Scales

Published in: Critical Care | Issue 1/2018

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Abstract

Background

Mild therapeutic hypothermia (TH), or targeted temperature management, improves survival and neurological outcomes in patients after out-of-hospital cardiac arrest (OHCA). International guidelines strongly support initiating TH for all eligible individuals presenting with OHCA; however, the timing of cooling initiation remains uncertain. This systematic review and meta-analysis was conducted with all available randomised controlled trials (RCTs) included to explore the efficacy and safety of initiating pre-hospital TH in patients with OHCA.

Methods

The MEDLINE and Cochrane databases were searched from inception to October 2017. Inclusion criteria for full-text review included RCTs comparing pre-hospital TH with no pre-hospital TH after cardiac arrest, patients > 14 years of age with documented cardiac arrest from any rhythm, and outcome data that included survival to hospital discharge and temperature at hospital arrival. Results of retrieved studies were compared through meta-analysis using random effects modelling.

Results

A total of 10 trials comprising 4220 patients were included. There were no significant differences between the two arms for the primary outcome of neurological recovery (risk ratio [RR] 1.04, 95% CI 0.93–1.15) or the secondary outcome of survival to hospital discharge (RR 1.01, 95% CI 0.92–1.11). However, there was a significantly lower temperature at hospital arrival in patients receiving pre-hospital TH (mean difference − 0.83, 95% CI − 1.03 to − 0.63). Pre-hospital TH significantly increased the risk of re-arrest (RR 1.19, 95% CI 1.00 to 1.41). No survival differences were observed among subgroups of patients who received intra-arrest TH vs post-arrest TH or who had shockable vs non-shockable rhythms.

Conclusions

Pre-hospital TH after OHCA effectively decreases body temperature at the time of hospital arrival. However, it does not improve rates of survival with good neurological outcome or overall survival and is associated with increased rates of re-arrest.
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Literature
1.
go back to reference Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346:549–56.CrossRef Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346:549–56.CrossRef
2.
go back to reference Arrich J, Holzer M, Havel C, Müllner M, Herkner H. Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation. Cochrane Database Syst Rev. 2016;2:CD004128.PubMed Arrich J, Holzer M, Havel C, Müllner M, Herkner H. Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation. Cochrane Database Syst Rev. 2016;2:CD004128.PubMed
3.
go back to reference Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, et al. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med. 2013;369:2197–206.CrossRefPubMed Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, et al. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med. 2013;369:2197–206.CrossRefPubMed
4.
go back to reference Howes D, Gray SH, Brooks SC, Boyd JG, Djogovic D, Golan E, Green RS, Jacka MJ, Sinuff T, Chaplin T, et al. Canadian guidelines for the use of targeted temperature management (therapeutic hypothermia) after cardiac arrest: a joint statement from the Canadian Critical Care Society (CCCS), Canadian Neurocritical Care Society (CNCCS), and the Canadian Critical Care Trials Group (CCCTG). Resuscitation. 2016;98:48–63.CrossRefPubMed Howes D, Gray SH, Brooks SC, Boyd JG, Djogovic D, Golan E, Green RS, Jacka MJ, Sinuff T, Chaplin T, et al. Canadian guidelines for the use of targeted temperature management (therapeutic hypothermia) after cardiac arrest: a joint statement from the Canadian Critical Care Society (CCCS), Canadian Neurocritical Care Society (CNCCS), and the Canadian Critical Care Trials Group (CCCTG). Resuscitation. 2016;98:48–63.CrossRefPubMed
5.
go back to reference Nikolaou NI, Arntz HR, Bellou A, Beygui F, Bossaert LL, Cariou A, Initial management of acute coronary syndromes section Collaborator. European Resuscitation Council Guidelines for Resuscitation 2015 Section 8. Initial management of acute coronary syndromes. Resuscitation. 2015;95:264–77.CrossRefPubMed Nikolaou NI, Arntz HR, Bellou A, Beygui F, Bossaert LL, Cariou A, Initial management of acute coronary syndromes section Collaborator. European Resuscitation Council Guidelines for Resuscitation 2015 Section 8. Initial management of acute coronary syndromes. Resuscitation. 2015;95:264–77.CrossRefPubMed
6.
go back to reference Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002;346:557–63.CrossRefPubMed Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002;346:557–63.CrossRefPubMed
7.
go back to reference Haugk M, Testori C, Sterz F, Uranitsch M, Holzer M, Behringer W, Herkner H, Time to Target Temperature Study Group. Relationship between time to target temperature and outcome in patients treated with therapeutic hypothermia after cardiac arrest. Crit Care. 2011;15:R101.CrossRefPubMedPubMedCentral Haugk M, Testori C, Sterz F, Uranitsch M, Holzer M, Behringer W, Herkner H, Time to Target Temperature Study Group. Relationship between time to target temperature and outcome in patients treated with therapeutic hypothermia after cardiac arrest. Crit Care. 2011;15:R101.CrossRefPubMedPubMedCentral
8.
go back to reference Lee BK, Jeung KW, Jung YH, Lee DH, Lee SM, Cho YS, Heo T, Yun JG, Min YI. Relationship between timing of cooling and outcomes in adult comatose cardiac arrest patients treated with targeted temperature management. Resuscitation. 2017;113:135–41.CrossRefPubMed Lee BK, Jeung KW, Jung YH, Lee DH, Lee SM, Cho YS, Heo T, Yun JG, Min YI. Relationship between timing of cooling and outcomes in adult comatose cardiac arrest patients treated with targeted temperature management. Resuscitation. 2017;113:135–41.CrossRefPubMed
9.
go back to reference Arrich J, Holzer M, Havel C, Warenits AM, Herkner H. Pre-hospital versus in-hospital initiation of cooling for survival and neuroprotection after out-of-hospital cardiac arrest. Cochrane Database Syst Rev. 2016;3:CD010570.PubMed Arrich J, Holzer M, Havel C, Warenits AM, Herkner H. Pre-hospital versus in-hospital initiation of cooling for survival and neuroprotection after out-of-hospital cardiac arrest. Cochrane Database Syst Rev. 2016;3:CD010570.PubMed
10.
go back to reference Huang FY, Huang BT, Wang PJ, Zuo ZL, Heng Y, Xia TL, Gui YY, Lv WY, Zhang C, Liao YB, et al. The efficacy and safety of prehospital therapeutic hypothermia in patients with out-of-hospital cardiac arrest: a systematic review and meta-analysis. Resuscitation. 2015;96:170–9.CrossRefPubMed Huang FY, Huang BT, Wang PJ, Zuo ZL, Heng Y, Xia TL, Gui YY, Lv WY, Zhang C, Liao YB, et al. The efficacy and safety of prehospital therapeutic hypothermia in patients with out-of-hospital cardiac arrest: a systematic review and meta-analysis. Resuscitation. 2015;96:170–9.CrossRefPubMed
11.
go back to reference Bernard SA, Smith K, Finn J, Hein C, Grantham H, Bray JE, Deasy C, Stephenson M, Williams TA, Straney LD, et al. Induction of therapeutic hypothermia during out-of-hospital cardiac arrest using a rapid infusion of cold saline: the RINSE Trial (Rapid Infusion of Cold Normal Saline). Circulation. 2016;134:797–805.CrossRefPubMed Bernard SA, Smith K, Finn J, Hein C, Grantham H, Bray JE, Deasy C, Stephenson M, Williams TA, Straney LD, et al. Induction of therapeutic hypothermia during out-of-hospital cardiac arrest using a rapid infusion of cold saline: the RINSE Trial (Rapid Infusion of Cold Normal Saline). Circulation. 2016;134:797–805.CrossRefPubMed
12.
go back to reference Scales DC, Cheskes S, Verbeek PR, Pinto R, Austin D, Brooks SC, Dainty KN, Goncharenko K, Mamdani M, Thorpe KE, et al. Prehospital cooling to improve successful targeted temperature management after cardiac arrest: a randomized controlled trial. Resuscitation. 2017;121:187–94.CrossRefPubMed Scales DC, Cheskes S, Verbeek PR, Pinto R, Austin D, Brooks SC, Dainty KN, Goncharenko K, Mamdani M, Thorpe KE, et al. Prehospital cooling to improve successful targeted temperature management after cardiac arrest: a randomized controlled trial. Resuscitation. 2017;121:187–94.CrossRefPubMed
14.
go back to reference van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke. 1988;19:604–7.CrossRefPubMed van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke. 1988;19:604–7.CrossRefPubMed
15.
go back to reference Brain Resuscitation Clinical Trial I Study Group. A randomized clinical study of cardiopulmonary-cerebral resuscitation: design, methods, and patient characteristics. Am J Emerg Med. 1986;4:72–86.CrossRef Brain Resuscitation Clinical Trial I Study Group. A randomized clinical study of cardiopulmonary-cerebral resuscitation: design, methods, and patient characteristics. Am J Emerg Med. 1986;4:72–86.CrossRef
16.
go back to reference Review Manager (RevMan) [computer program]. Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration; 2014. Review Manager (RevMan) [computer program]. Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration; 2014.
17.
go back to reference Bernard SA, Smith K, Cameron P, Masci K, Taylor DM, Cooper DJ, Kelly AM, Silvester W, Rapid Infusion of Cold Hartmanns (RICH) Investigators. Induction of therapeutic hypothermia by paramedics after resuscitation from out-of-hospital ventricular fibrillation cardiac arrest: a randomized controlled trial. Circulation. 2010;122:737–42.CrossRefPubMed Bernard SA, Smith K, Cameron P, Masci K, Taylor DM, Cooper DJ, Kelly AM, Silvester W, Rapid Infusion of Cold Hartmanns (RICH) Investigators. Induction of therapeutic hypothermia by paramedics after resuscitation from out-of-hospital ventricular fibrillation cardiac arrest: a randomized controlled trial. Circulation. 2010;122:737–42.CrossRefPubMed
18.
go back to reference Bernard SA, Smith K, Cameron P, Masci K, Taylor DM, Cooper DJ, Kelly AM, Silvester W, Rapid Infusion of Cold Hartmanns Investigators. Induction of prehospital therapeutic hypothermia after resuscitation from nonventricular fibrillation cardiac arrest. Crit Care Med. 2012;40:747–53.CrossRefPubMed Bernard SA, Smith K, Cameron P, Masci K, Taylor DM, Cooper DJ, Kelly AM, Silvester W, Rapid Infusion of Cold Hartmanns Investigators. Induction of prehospital therapeutic hypothermia after resuscitation from nonventricular fibrillation cardiac arrest. Crit Care Med. 2012;40:747–53.CrossRefPubMed
19.
go back to reference Kim F, Nichol G, Maynard C, Hallstrom A, Kudenchuk PJ, Rea T, Copass MK, Carlbom D, Deem S, Longstreth WT Jr, et al. Effect of prehospital induction of mild hypothermia on survival and neurological status among adults with cardiac arrest: a randomized clinical trial. JAMA. 2014;311:45–52.CrossRefPubMed Kim F, Nichol G, Maynard C, Hallstrom A, Kudenchuk PJ, Rea T, Copass MK, Carlbom D, Deem S, Longstreth WT Jr, et al. Effect of prehospital induction of mild hypothermia on survival and neurological status among adults with cardiac arrest: a randomized clinical trial. JAMA. 2014;311:45–52.CrossRefPubMed
20.
go back to reference Kim F, Olsufka M, Longstreth WT Jr, Maynard C, Carlbom D, Deem S, Kudenchuk P, Copass MK, Cobb LA. Pilot randomized clinical trial of prehospital induction of mild hypothermia in out-of-hospital cardiac arrest patients with a rapid infusion of 4°C normal saline. Circulation. 2007;115:3064–70.CrossRefPubMed Kim F, Olsufka M, Longstreth WT Jr, Maynard C, Carlbom D, Deem S, Kudenchuk P, Copass MK, Cobb LA. Pilot randomized clinical trial of prehospital induction of mild hypothermia in out-of-hospital cardiac arrest patients with a rapid infusion of 4°C normal saline. Circulation. 2007;115:3064–70.CrossRefPubMed
21.
go back to reference Kamarainen A, Virkkunen I, Tenhunen J, Yli-Hankala A, Silfvast T. Prehospital therapeutic hypothermia for comatose survivors of cardiac arrest: a randomized controlled trial. Acta Anaesthesiol Scand. 2009;53:900–7.CrossRefPubMed Kamarainen A, Virkkunen I, Tenhunen J, Yli-Hankala A, Silfvast T. Prehospital therapeutic hypothermia for comatose survivors of cardiac arrest: a randomized controlled trial. Acta Anaesthesiol Scand. 2009;53:900–7.CrossRefPubMed
22.
go back to reference Debaty G, Maignan M, Savary D, Koch FX, Ruckly S, Durand M, Picard J, Escallier C, Chouquer R, Santre C, et al. Impact of intra-arrest therapeutic hypothermia in outcomes of prehospital cardiac arrest: a randomized controlled trial. Intensive Care Med. 2014;40:1832–42.CrossRefPubMed Debaty G, Maignan M, Savary D, Koch FX, Ruckly S, Durand M, Picard J, Escallier C, Chouquer R, Santre C, et al. Impact of intra-arrest therapeutic hypothermia in outcomes of prehospital cardiac arrest: a randomized controlled trial. Intensive Care Med. 2014;40:1832–42.CrossRefPubMed
23.
go back to reference Castren M, Nordberg P, Svensson L, Taccone F, Vincent JL, Desruelles D, Eichwede F, Mols P, Schwab T, Vergnion M, et al. Intra-arrest transnasal evaporative cooling: a randomized, prehospital, multicenter study (PRINCE: Pre-ROSC IntraNasal Cooling Effectiveness). Circulation. 2010;122:729–36.CrossRefPubMed Castren M, Nordberg P, Svensson L, Taccone F, Vincent JL, Desruelles D, Eichwede F, Mols P, Schwab T, Vergnion M, et al. Intra-arrest transnasal evaporative cooling: a randomized, prehospital, multicenter study (PRINCE: Pre-ROSC IntraNasal Cooling Effectiveness). Circulation. 2010;122:729–36.CrossRefPubMed
24.
go back to reference Diao M, Huang F, Guan J, Zhang Z, Xiao Y, Shan Y, Lin Z, Ding L. Prehospital therapeutic hypothermia after cardiac arrest: a systematic review and meta-analysis of randomized controlled trials. Resuscitation. 2013;84:1021–8.CrossRefPubMed Diao M, Huang F, Guan J, Zhang Z, Xiao Y, Shan Y, Lin Z, Ding L. Prehospital therapeutic hypothermia after cardiac arrest: a systematic review and meta-analysis of randomized controlled trials. Resuscitation. 2013;84:1021–8.CrossRefPubMed
25.
go back to reference Hunter BR, O’Donnell DP, Allgood KL, Seupaul RA. No benefit to prehospital initiation of therapeutic hypothermia in out-of-hospital cardiac arrest: a systematic review and meta-analysis. Acad Emerg Med. 2014;21:355–64.CrossRefPubMed Hunter BR, O’Donnell DP, Allgood KL, Seupaul RA. No benefit to prehospital initiation of therapeutic hypothermia in out-of-hospital cardiac arrest: a systematic review and meta-analysis. Acad Emerg Med. 2014;21:355–64.CrossRefPubMed
26.
go back to reference Nie C, Dong J, Zhang P, Liu X, Han F. Prehospital therapeutic hypothermia after out-of-hospital cardiac arrest: a systematic review and meta-analysis. Am J Emerg Med. 2016;34:2209–16.CrossRefPubMed Nie C, Dong J, Zhang P, Liu X, Han F. Prehospital therapeutic hypothermia after out-of-hospital cardiac arrest: a systematic review and meta-analysis. Am J Emerg Med. 2016;34:2209–16.CrossRefPubMed
27.
go back to reference Elmer J, Torres C, Aufderheide TP, Austin MA, Callaway CW, Golan E, Herren H, Jasti J, Kudenchuk PJ, Scales DC, et al. Association of early withdrawal of life-sustaining therapy for perceived neurological prognosis with mortality after cardiac arrest. Resuscitation. 2016;102:127–35.CrossRefPubMedPubMedCentral Elmer J, Torres C, Aufderheide TP, Austin MA, Callaway CW, Golan E, Herren H, Jasti J, Kudenchuk PJ, Scales DC, et al. Association of early withdrawal of life-sustaining therapy for perceived neurological prognosis with mortality after cardiac arrest. Resuscitation. 2016;102:127–35.CrossRefPubMedPubMedCentral
28.
go back to reference Scales DC, Golan E, Pinto R, Brooks SC, Chapman M, Dale CM, Jichici D, Rubenfeld GD, Morrison LJ, Strategies for Post-Arrest Resuscitation Care Network. Improving appropriate neurologic prognostication after cardiac arrest: a stepped wedge cluster randomized controlled trial. Am J Respir Crit Care Med. 2016;194:1083–91.CrossRefPubMed Scales DC, Golan E, Pinto R, Brooks SC, Chapman M, Dale CM, Jichici D, Rubenfeld GD, Morrison LJ, Strategies for Post-Arrest Resuscitation Care Network. Improving appropriate neurologic prognostication after cardiac arrest: a stepped wedge cluster randomized controlled trial. Am J Respir Crit Care Med. 2016;194:1083–91.CrossRefPubMed
Metadata
Title
The efficacy and safety of pre-hospital cooling after out-of-hospital cardiac arrest: a systematic review and meta-analysis
Authors
Patrick J. Lindsay
Danielle Buell
Damon C. Scales
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2018
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-018-1984-2

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