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Published in: Intensive Care Medicine 7/2020

Open Access 01-07-2020 | Original

Time to intra-arrest therapeutic hypothermia in out-of-hospital cardiac arrest patients and its association with neurologic outcome: a propensity matched sub-analysis of the PRINCESS trial

Authors: Akil Awad, Fabio Silvio Taccone, Martin Jonsson, Sune Forsberg, Jacob Hollenberg, Anatolij Truhlar, Mattias Ringh, Benjamin S. Abella, Lance B. Becker, Jean-Louis Vincent, Leif Svensson, Per Nordberg

Published in: Intensive Care Medicine | Issue 7/2020

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Abstract

Purpose

To study the association between early initiation of intra-arrest therapeutic hypothermia and neurologic outcome in out-of-hospital cardiac arrest.

Methods

A prespecified sub-analysis of the PRINCESS trial (NCT01400373) that randomized 677 bystander-witnessed cardiac arrests to transnasal evaporative intra-arrest cooling initiated by emergency medical services or cooling started after hospital arrival. Early cooling (intervention) was defined as intra-arrest cooling initiated < 20 min from collapse (i.e., ≤ median time to cooling in PRINCESS). Propensity score matching established comparable control patients. Primary outcome was favorable neurologic outcome, Cerebral Performance Category (CPC) 1–2 at 90 days. Complete recovery (CPC 1) was among secondary outcomes.

Results

In total, 300 patients were analyzed and the proportion with CPC 1–2 at 90 days was 35/150 (23.3%) in the intervention group versus 24/150 (16%) in the control group, odds ratio (OR) 1.92, 95% confidence interval (CI) 0.95–3.85, p = .07. In patients with shockable rhythm, CPC 1–2 was 29/57 (50.9%) versus 17/57 (29.8%), OR 3.25, 95%, CI 1.06–9.97, p = .04. The proportion with CPC 1 at 90 days was 31/150 (20.7%) in the intervention group and 17/150 (11.3%) in controls, OR 2.27, 95% CI 1.12–4.62, p = .02. In patients with shockable rhythms, the proportion with CPC 1 was 27/57 (47.4%) versus 12/57 (21.1%), OR 5.33, 95% CI 1.55–18.3, p = .008.

Conclusions

In the whole study population, intra-arrest cooling initiated < 20 min from collapse compared to cooling initiated at hospital was not associated with improved favorable neurologic outcome. In the subgroup with shockable rhythms, early cooling was associated with improved favorable outcome and complete recovery.
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Literature
1.
5.
go back to reference Jakkula P, Reinikainen M, Hastbacka J, Loisa P, Tiainen M, Pettila V, Toppila J, Lahde M, Backlund M, Okkonen M, Bendel S, Birkelund T, Pulkkinen A, Heinonen J, Tikka T, Skrifvars MB (2018) Targeting two different levels of both arterial carbon dioxide and arterial oxygen after cardiac arrest and resuscitation: a randomised pilot trial. Intensive Care Med 44(12):2112–2121. https://doi.org/10.1007/s00134-018-5453-9 CrossRefPubMedPubMedCentral Jakkula P, Reinikainen M, Hastbacka J, Loisa P, Tiainen M, Pettila V, Toppila J, Lahde M, Backlund M, Okkonen M, Bendel S, Birkelund T, Pulkkinen A, Heinonen J, Tikka T, Skrifvars MB (2018) Targeting two different levels of both arterial carbon dioxide and arterial oxygen after cardiac arrest and resuscitation: a randomised pilot trial. Intensive Care Med 44(12):2112–2121. https://​doi.​org/​10.​1007/​s00134-018-5453-9 CrossRefPubMedPubMedCentral
12.
go back to reference Kuboyama K, Safar P, Radovsky A, Tisherman SA, Stezoski SW, Alexander H (1993) Delay in cooling negates the beneficial effect of mild resuscitative cerebral hypothermia after cardiac arrest in dogs: a prospective, randomized study. Crit Care Med 21(9):1348–1358CrossRef Kuboyama K, Safar P, Radovsky A, Tisherman SA, Stezoski SW, Alexander H (1993) Delay in cooling negates the beneficial effect of mild resuscitative cerebral hypothermia after cardiac arrest in dogs: a prospective, randomized study. Crit Care Med 21(9):1348–1358CrossRef
13.
go back to reference Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, Pellis T, Stammet P, Wanscher M, Wise MP, Aneman A, Al-Subaie N, Boesgaard S, Bro-Jeppesen J, Brunetti I, Bugge JF, Hingston CD, Juffermans NP, Koopmans M, Kober L, Langorgen J, Lilja G, Moller JE, Rundgren M, Rylander C, Smid O, Werer C, Winkel P, Friberg H (2013) Targeted temperature management at 33°C versus 36°C after cardiac arrest. New Engl J Med 369(23):2197–2206. https://doi.org/10.1056/NEJMoa1310519 CrossRefPubMed Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, Pellis T, Stammet P, Wanscher M, Wise MP, Aneman A, Al-Subaie N, Boesgaard S, Bro-Jeppesen J, Brunetti I, Bugge JF, Hingston CD, Juffermans NP, Koopmans M, Kober L, Langorgen J, Lilja G, Moller JE, Rundgren M, Rylander C, Smid O, Werer C, Winkel P, Friberg H (2013) Targeted temperature management at 33°C versus 36°C after cardiac arrest. New Engl J Med 369(23):2197–2206. https://​doi.​org/​10.​1056/​NEJMoa1310519 CrossRefPubMed
16.
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, Olsufka M, Cobb LA (2014) Effect of prehospital induction of mild hypothermia on survival and neurological status among adults with cardiac arrest: a randomized clinical trial. JAMA 311(1):45–52. https://doi.org/10.1001/jama.2013.282173 CrossRefPubMed Kim F, Nichol G, Maynard C, Hallstrom A, Kudenchuk PJ, Rea T, Copass MK, Carlbom D, Deem S, Longstreth WT Jr, Olsufka M, Cobb LA (2014) Effect of prehospital induction of mild hypothermia on survival and neurological status among adults with cardiac arrest: a randomized clinical trial. JAMA 311(1):45–52. https://​doi.​org/​10.​1001/​jama.​2013.​282173 CrossRefPubMed
17.
go back to reference Bernard SA, Smith K, Finn J, Hein C, Grantham H, Bray JE, Deasy C, Stephenson M, Williams TA, Straney LD, Brink D, Larsen R, Cotton C, Cameron P (2016) 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 134(11):797–805. https://doi.org/10.1161/circulationaha.116.021989 CrossRefPubMed Bernard SA, Smith K, Finn J, Hein C, Grantham H, Bray JE, Deasy C, Stephenson M, Williams TA, Straney LD, Brink D, Larsen R, Cotton C, Cameron P (2016) 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 134(11):797–805. https://​doi.​org/​10.​1161/​circulationaha.​116.​021989 CrossRefPubMed
18.
go back to reference Debaty G, Maignan M, Savary D, Koch FX, Ruckly S, Durand M, Picard J, Escallier C, Chouquer R, Santre C, Minet C, Guergour D, Hammer L, Bouvaist H, Belle L, Adrie C, Payen JF, Carpentier F, Gueugniaud PY, Danel V, Timsit JF (2014) Impact of intra-arrest therapeutic hypothermia in outcomes of prehospital cardiac arrest: a randomized controlled trial. Intensive Care Med 40(12):1832–1842. https://doi.org/10.1007/s00134-014-3519-x CrossRefPubMed Debaty G, Maignan M, Savary D, Koch FX, Ruckly S, Durand M, Picard J, Escallier C, Chouquer R, Santre C, Minet C, Guergour D, Hammer L, Bouvaist H, Belle L, Adrie C, Payen JF, Carpentier F, Gueugniaud PY, Danel V, Timsit JF (2014) Impact of intra-arrest therapeutic hypothermia in outcomes of prehospital cardiac arrest: a randomized controlled trial. Intensive Care Med 40(12):1832–1842. https://​doi.​org/​10.​1007/​s00134-014-3519-x CrossRefPubMed
21.
go back to reference Castren M, Nordberg P, Svensson L, Taccone F, Vincent JL, Desruelles D, Eichwede F, Mols P, Schwab T, Vergnion M, Storm C, Pesenti A, Pachl J, Guerisse F, Elste T, Roessler M, Fritz H, Durnez P, Busch HJ, Inderbitzen B, Barbut D (2010) Intra-arrest transnasal evaporative cooling: a randomized, prehospital, multicenter study (PRINCE: Pre-ROSC IntraNasal Cooling Effectiveness). Circulation 122(7):729–736. https://doi.org/10.1161/circulationaha.109.931691 CrossRefPubMed Castren M, Nordberg P, Svensson L, Taccone F, Vincent JL, Desruelles D, Eichwede F, Mols P, Schwab T, Vergnion M, Storm C, Pesenti A, Pachl J, Guerisse F, Elste T, Roessler M, Fritz H, Durnez P, Busch HJ, Inderbitzen B, Barbut D (2010) Intra-arrest transnasal evaporative cooling: a randomized, prehospital, multicenter study (PRINCE: Pre-ROSC IntraNasal Cooling Effectiveness). Circulation 122(7):729–736. https://​doi.​org/​10.​1161/​circulationaha.​109.​931691 CrossRefPubMed
24.
go back to reference Nordberg P, Taccone FS, Truhlar A, Forsberg S, Hollenberg J, Jonsson M, Cuny J, Goldstein P, Vermeersch N, Higuet A, Jimenes FC, Ortiz FR, Williams J, Desruelles D, Creteur J, Dillenbeck E, Busche C, Busch HJ, Ringh M, Konrad D, Peterson J, Vincent JL, Svensson L (2019) Effect of trans-nasal evaporative intra-arrest cooling on functional neurologic outcome in out-of-hospital cardiac arrest: the PRINCESS randomized clinical trial. JAMA 321(17):1677–1685. https://doi.org/10.1001/jama.2019.4149 CrossRefPubMedPubMedCentral Nordberg P, Taccone FS, Truhlar A, Forsberg S, Hollenberg J, Jonsson M, Cuny J, Goldstein P, Vermeersch N, Higuet A, Jimenes FC, Ortiz FR, Williams J, Desruelles D, Creteur J, Dillenbeck E, Busche C, Busch HJ, Ringh M, Konrad D, Peterson J, Vincent JL, Svensson L (2019) Effect of trans-nasal evaporative intra-arrest cooling on functional neurologic outcome in out-of-hospital cardiac arrest: the PRINCESS randomized clinical trial. JAMA 321(17):1677–1685. https://​doi.​org/​10.​1001/​jama.​2019.​4149 CrossRefPubMedPubMedCentral
25.
go back to reference Perkins GD, Jacobs IG, Nadkarni VM, Berg RA, Bhanji F, Biarent D, Bossaert LL, Brett SJ, Chamberlain D, de Caen AR, Deakin CD, Finn JC, Grasner JT, Hazinski MF, Iwami T, Koster RW, Lim SH, Ma MH, McNally BF, Morley PT, Morrison LJ, Monsieurs KG, Montgomery W, Nichol G, Okada K, Ong ME, Travers AH, Nolan JP (2015) Cardiac Arrest and Cardiopulmonary Resuscitation Outcome Reports: Update of the Utstein Resuscitation Registry Templates for Out-of-Hospital Cardiac Arrest: A Statement for Healthcare Professionals From a Task Force of the International Liaison Committee on Resuscitation (American Heart Association, European Resuscitation Council, Australian and New Zealand Council on Resuscitation, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Southern Africa, Resuscitation Council of Asia); and the American Heart Association Emergency Cardiovascular Care Committee and the Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation. Resuscitation 96:328–340. https://doi.org/10.1016/j.resuscitation.2014.11.002 CrossRefPubMed Perkins GD, Jacobs IG, Nadkarni VM, Berg RA, Bhanji F, Biarent D, Bossaert LL, Brett SJ, Chamberlain D, de Caen AR, Deakin CD, Finn JC, Grasner JT, Hazinski MF, Iwami T, Koster RW, Lim SH, Ma MH, McNally BF, Morley PT, Morrison LJ, Monsieurs KG, Montgomery W, Nichol G, Okada K, Ong ME, Travers AH, Nolan JP (2015) Cardiac Arrest and Cardiopulmonary Resuscitation Outcome Reports: Update of the Utstein Resuscitation Registry Templates for Out-of-Hospital Cardiac Arrest: A Statement for Healthcare Professionals From a Task Force of the International Liaison Committee on Resuscitation (American Heart Association, European Resuscitation Council, Australian and New Zealand Council on Resuscitation, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Southern Africa, Resuscitation Council of Asia); and the American Heart Association Emergency Cardiovascular Care Committee and the Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation. Resuscitation 96:328–340. https://​doi.​org/​10.​1016/​j.​resuscitation.​2014.​11.​002 CrossRefPubMed
26.
go back to reference Jennett B, Bond M (1975) Assessment of outcome after severe brain damage. Lancet (London, England) 1(7905):480–484CrossRef Jennett B, Bond M (1975) Assessment of outcome after severe brain damage. Lancet (London, England) 1(7905):480–484CrossRef
28.
go back to reference den Hartog AW, de Pont AC, Robillard LB, Binnekade JM, Schultz MJ, Horn J (2010) Spontaneous hypothermia on intensive care unit admission is a predictor of unfavorable neurological outcome in patients after resuscitation: an observational cohort study. Crit Care 14(3):R121. https://doi.org/10.1186/cc9077 CrossRef den Hartog AW, de Pont AC, Robillard LB, Binnekade JM, Schultz MJ, Horn J (2010) Spontaneous hypothermia on intensive care unit admission is a predictor of unfavorable neurological outcome in patients after resuscitation: an observational cohort study. Crit Care 14(3):R121. https://​doi.​org/​10.​1186/​cc9077 CrossRef
29.
go back to reference Lascarrou JB, Merdji H, Le Gouge A, Colin G, Grillet G, Girardie P, Coupez E, Dequin PF, Cariou A, Boulain T, Brule N, Frat JP, Asfar P, Pichon N, Landais M, Plantefeve G, Quenot JP, Chakarian JC, Sirodot M, Legriel S, Letheulle J, Thevenin D, Desachy A, Delahaye A, Botoc V, Vimeux S, Martino F, Giraudeau B, Reignier J (2019) Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm. New Engl J Med. https://doi.org/10.1056/NEJMoa1906661 CrossRefPubMed Lascarrou JB, Merdji H, Le Gouge A, Colin G, Grillet G, Girardie P, Coupez E, Dequin PF, Cariou A, Boulain T, Brule N, Frat JP, Asfar P, Pichon N, Landais M, Plantefeve G, Quenot JP, Chakarian JC, Sirodot M, Legriel S, Letheulle J, Thevenin D, Desachy A, Delahaye A, Botoc V, Vimeux S, Martino F, Giraudeau B, Reignier J (2019) Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm. New Engl J Med. https://​doi.​org/​10.​1056/​NEJMoa1906661 CrossRefPubMed
31.
go back to reference Geocadin RG, Callaway CW, Fink EL, Golan E, Greer DM, Ko NU, Lang E, Licht DJ, Marino BS, McNair ND, Peberdy MA, Perman SM, Sims DB, Soar J, Sandroni C (2019) Standards for studies of neurological prognostication in comatose survivors of cardiac arrest: a scientific statement from the American Heart Association. Circulation 140(9):e517–e542. https://doi.org/10.1161/cir.0000000000000702 CrossRefPubMed Geocadin RG, Callaway CW, Fink EL, Golan E, Greer DM, Ko NU, Lang E, Licht DJ, Marino BS, McNair ND, Peberdy MA, Perman SM, Sims DB, Soar J, Sandroni C (2019) Standards for studies of neurological prognostication in comatose survivors of cardiac arrest: a scientific statement from the American Heart Association. Circulation 140(9):e517–e542. https://​doi.​org/​10.​1161/​cir.​0000000000000702​ CrossRefPubMed
Metadata
Title
Time to intra-arrest therapeutic hypothermia in out-of-hospital cardiac arrest patients and its association with neurologic outcome: a propensity matched sub-analysis of the PRINCESS trial
Authors
Akil Awad
Fabio Silvio Taccone
Martin Jonsson
Sune Forsberg
Jacob Hollenberg
Anatolij Truhlar
Mattias Ringh
Benjamin S. Abella
Lance B. Becker
Jean-Louis Vincent
Leif Svensson
Per Nordberg
Publication date
01-07-2020
Publisher
Springer Berlin Heidelberg
Published in
Intensive Care Medicine / Issue 7/2020
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-020-06024-3

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