BACKGROUND: Randomized trials have shown that trans-nasal evaporative cooling initiated during CPR (i.e. intra-arrest) effectively lower core body temperature in out-of-hospital cardiac arrest patients. However, these trials may have been underpowered to detect significant differences in neurologic outcome, especially in patients with initial shockable rhythm. METHODS: We conducted a post hoc pooled analysis of individual data from two randomized trials including 851 patients who eventually received the allocated intervention and with available outcome ("as-treated" analysis). Primary outcome was survival with favourable neurological outcome at hospital discharge (Cerebral Performance Category [CPC] of 1-2) according to the initial rhythm (shockable vs. non-shockable). Secondary outcomes included complete neurological recovery (CPC 1) at hospital discharge. RESULTS: Among the 325 patients with initial shockable rhythms, favourable neurological outcome was observed in 54/158 (34.2%) patients in the intervention and 40/167 (24.0%) in the control group (RR 1.43 [confidence intervals, CIs 1.01-2.02]). Complete neurological recovery was observed in 40/158 (25.3%) in the intervention and 27/167 (16.2%) in the control group (RR 1.57 [CIs 1.01-2.42]). Among the 526 patients with initial non-shockable rhythms, favourable neurological outcome was in 10/259 (3.8%) in the intervention and 13/267 (4.9%) in the control group (RR 0.88 [CIs 0.52-1.29]; p = 0.67); survival and complete neurological recovery were also similar between groups. No significant benefit was observed for the intervention in the entire population. CONCLUSIONS: In this pooled analysis of individual data, intra-arrest cooling was associated with a significant increase in favourable neurological outcome in out-of-hospital cardiac arrest patients with initial shockable rhythms. Future studies are needed to confirm the potential benefits of this intervention in this subgroup of patients.

Department of Emergency Medicine University Hospital of Freiburg Faculty of Medicine University of Freiburg Freiburg Germany

Department of Intensive Care Hopital Erasme Université Libre de Bruxelles Route de Lennik 808 1070 Bruxelles Belgium

Department of Medicine Center for Resuscitation Science Karolinska Institute Solna Sweden

Emergency Department SAMU Centre Hospitalier Régional Universitaire de Lille Lille France

Emergency Medical Services of the Hradec Kralove Region Hradec Kralove University Hospital Hradec Kralove Czech Republic

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Goraya TY, Jacobsen SJ, Kottke TE, et al. Coronary heart disease death and sudden cardiac death: a 20-year population-based study. Am J Epidemiol. 2003;157:763–770. doi: 10.1093/aje/kwg057. PubMed DOI

Gul SS, Cohen SA, Becker TK, et al. Patient, Neighborhood, and Spatial Determinants of Out-of-Hospital Cardiac Arrest Outcomes Throughout the Chain of Survival: A Community-Oriented Multilevel Analysis. Prehosp Emerg Care. 2019;5:1–12. PubMed PMC

Lemiale V, Dumas F, Mongardon N, et al. Intensive care unit mortality after cardiac arrest: the relative contribution of shock and brain injury in a large cohort. Intensive Care Med. 2013;39(11):1972–1980. doi: 10.1007/s00134-013-3043-4. PubMed DOI

The HACA Study group Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346:549–556. doi: 10.1056/NEJMoa012689. PubMed DOI

Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002;346:557–563. doi: 10.1056/NEJMoa003289. PubMed DOI

Nolan JP, Morley PT, Hoek TL, et al. Therapeutic hypothermia after cardiac arrest. An advisory statement by the advancement life support task force of the international Liaison committee on resuscitation. Resuscitation. 2003;57:231–235. doi: 10.1016/S0300-9572(03)00184-9. PubMed DOI

Lascarrou JB, Merdji H, Le Gouge A, et al. Targeted temperature management for cardiac arrest with nonshockable rhythm. N Engl J Med. 2019;381(24):2327–2337. doi: 10.1056/NEJMoa1906661. PubMed DOI

Kim F, Olsufka M, Longstreth WT, et al. 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;115:3064–3070. doi: 10.1161/CIRCULATIONAHA.106.655480. PubMed DOI

Bernard SA, Smith K, Cameron P, et al. Rapid Infusion of Cold Hartmann’s (RICH) investigators: induction of therapeutic hypothermia by paramedics after resuscitation from out-of-hospital ventricular fibrillation cardiac arrest: a randomized controlled trial. Circulation. 2010;122:737–742. doi: 10.1161/CIRCULATIONAHA.109.906859. PubMed DOI

Annoni F, Peluso L, Fiore M, et al. Impact of therapeutic hypothermia during cardiopulmonary resuscitation on neurologic outcome: a systematic review and meta-analysis. Resuscitation. 2021 doi: 10.1016/j.resuscitation.2021.01.029. PubMed DOI

Garrett JS, Studnek JR, Blackwell T, et al. The association between intra-arrest therapeutic hypothermia and return of spontaneous circulation among individuals experiencing out of hospital cardiac arrest. Resuscitation. 2011;82:21–25. doi: 10.1016/j.resuscitation.2010.09.473. PubMed DOI

Bernard SA, Smith K, Finn J, 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(11):797–805. doi: 10.1161/CIRCULATIONAHA.116.021989. PubMed DOI

Castrén M, Nordberg P, Svensson L, et al. Intra-arrest transnasal evaporative cooling: a randomized, prehospital, multicenter study (PRINCE: Pre-ROSC IntraNasal Cooling Effectiveness) Circulation. 2010;122:729–736. doi: 10.1161/CIRCULATIONAHA.109.931691. PubMed DOI

Nordberg P, Taccone FS, Truhlar A, et al. Effect of trans-nasal evaporative intra-arrest cooling on functional neurologic outcome in out-of-hospital cardiac arrest: The PRINCESS randomized clinical trial. JAMA. 2019;321(17):1677–1685. doi: 10.1001/jama.2019.4149. PubMed DOI PMC

Olasveengen TM, Wik L, Sunde K, Steen PA. Outcome when adrenaline (epinephrine) was actually given vs. not given—post hoc analysis of a randomized clinical trial. Resuscitation. 2012;83(3):327–332. doi: 10.1016/j.resuscitation.2011.11.011. PubMed DOI

Tripepi G, Chesnaye NC, Dekker FW, Zoccali C, Jager KJ. Intention to treat and per protocol analysis in clinical trials. Nephrology (Carlton) 2020;25(7):513–517. doi: 10.1111/nep.13709. PubMed DOI

Kirkegaard H, Søreide E, de Haas I, et al. Targeted Temperature Management for 48 vs 24 Hours and Neurologic Outcome After Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA. 2017;318(4):341–350. doi: 10.1001/jama.2017.8978. PubMed DOI PMC

Hirlekar G, Karlsson T, Aune S, et al. Survival and neurological outcome in the elderly after in-hospital cardiac arrest. Resuscitation. 2017;118:101–106. doi: 10.1016/j.resuscitation.2017.07.013. PubMed DOI

Gässler H, Fischer M, Wnent J, Seewald S, Helm M. Outcome after pre-hospital cardiac arrest in accordance with underlying cause. Resuscitation. 2019;138:36–41. doi: 10.1016/j.resuscitation.2019.02.039. PubMed DOI

Malta Hansen C, Kragholm K, Pearson DA, et al. Association of bystander and first-responder intervention with survival after out-of-hospital cardiac arrest in North Carolina, 2010–2013. JAMA. 2015;314(3):255–264. doi: 10.1001/jama.2015.7938. PubMed DOI

Neumar RW, Shuster M, Callaway CW, et al. Part 1: executive summary: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2015;132(18 Suppl 2):S315–S367. doi: 10.1161/CIR.0000000000000252. PubMed DOI

Wang H, Barbut D, Tsai MS, Sun S, Weil MH, Tang W. Intra-arrest selective brain cooling improves success of resuscitation in a porcine model of prolonged cardiac arrest. Resuscitation. 2010;81(5):617–621. doi: 10.1016/j.resuscitation.2010.01.027. PubMed DOI

Riter HG, Brooks LA, Pretorius AM, Ackermann LW, Kerber RE. Intra-arrest hypothermia: both cold liquid ventilation with perfluorocarbons and cold intravenous saline rapidly achieve hypothermia, but only cold liquid ventilation improves resumption of spontaneous circulation. Resuscitation. 2009;16:561–566. doi: 10.1016/j.resuscitation.2009.01.016. PubMed DOI PMC

Yu T, Barbut D, Ristagno G, et al. Survival and neurological outcomes after nasopharyngeal cooling or peripheral vein cold saline infusion initiated during cardiopulmonary resuscitation in a porcine model of prolonged cardiac arrest. Crit Care Med. 2010;16:916–921. doi: 10.1097/CCM.0b013e3181cd1291. PubMed DOI

Debaty G, Maignan M, Savary D, et al. Impact of intra-arrest therapeutic hypothermia in outcomes of prehospital cardiac arrest: a randomized controlled trial. Intensive Care Med. 2014;40(12):1832–1842. doi: 10.1007/s00134-014-3519-x. PubMed DOI

Grave MS, Sterz F, Nürnberger A, et al. Safety and feasibility of the RhinoChill immediate transnasal evaporative cooling device during out-of-hospital cardiopulmonary resuscitation: a single-center, observational study. Medicine (Baltimore) 2016;95(34):e4692. doi: 10.1097/MD.0000000000004692. PubMed DOI PMC

Raina KD, Rittenberger JC, Holm MB, Callaway CW. Functional outcomes: one year after a cardiac arrest. Biomed Res Int. 2015;2015:283608. doi: 10.1155/2015/283608. PubMed DOI PMC

Haywood K, Whitehead L, Nadkarni VM, et al. COSCA (Core Outcome Set for Cardiac Arrest) in adults: an advisory statement from the international liaison committee on resuscitation. Circulation. 2018;137(22):e783–e801. doi: 10.1161/CIR.0000000000000562. PubMed DOI

Kim F, Nichol G, Maynard C, 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(1):45–52. doi: 10.1001/jama.2013.282173. PubMed DOI

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