Clinical paper| Volume 127, P51-57, June 2018

Prediction and risk stratification of survival in accidental hypothermia requiring extracorporeal life support: An individual patient data meta-analysis

  • Richard S. Saczkowski
    Corresponding author at: Department of Cardiac Sciences, Division of Cardiac Surgery, Kelowna General Hospital, Rm 1406, 2268 Pandosy Street, Kelowna, British Columbia, V1Y 1T2, Canada.
    Department of Cardiac Sciences, Division of Cardiac Surgery, Kelowna General Hospital, Kelowna, British Columbia, Canada
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  • Doug J.A. Brown
    Department of Emergency Medicine, University of British Columbia, New Westminster, British Columbia, Canada
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  • Riyad B. Abu-Laban
    Department of Emergency Medicine, University of British Columbia, Vancouver, British Columbia, Canada
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  • Guy Fradet
    Department of Cardiac Sciences, Division of Cardiac Surgery, Kelowna General Hospital, Kelowna, British Columbia, Canada
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  • Costas J. Schulze
    Department of Cardiac Sciences, Division of Cardiac Surgery, Kelowna General Hospital, Kelowna, British Columbia, Canada

    Department of Critical Care Medicine, Kelowna General Hospital, Kelowna, British Columbia, Canada
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  • Nick D. Kuzak
    Division of Cardiac Anaesthesia, Kelowna General Hospital, Kelowna, British Columbia, Canada

    Department of Emergency Medicine, Kelowna General Hospital, Kelowna, British Columbia, Canada

    Department of Anesthesiology and Pharmacology, University of British Columbia, Vancouver, British Columbia, Canada
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      Extra-corporeal life support (ECLS) is a life-saving intervention for patients with hypothermia induced cardiac arrest or severe cardiovascular instability. However, its application is highly variable due to a paucity of data in the literature to guide practice. Current guidelines and recommendations are based on expert opinion, single case reports, and small case series. Combining all of the published data in a patient-level analysis can provide a robust assessment of the influence of patient characteristics on survival with ECLS.


      To develop a prediction model of survival with good neurologic outcome for accidental hypothermia treated with ECLS.


      Electronic searches of PubMed, EMBASE, CINAHL were conducted with a hand search of reference lists and major surgical and critical care conference abstracts. Studies had to report the use of ECLS configured with a circuit, blood pump and oxygenator with an integrated heat exchanger. Randomized and observational studies were eligible for inclusion. Non-human, non-English and review manuscripts were deemed ineligible. Study authors were requested to submit patient level data when aggregate or incomplete individual patient data was provided in a study. Survival with good neurologic outcome was categorized for patients to last follow-up based on the reported scores on the Cerebral Performance Category (1 or 2), Glasgow Outcome Scale (4 or 5) and Pediatric Overall Performance Category (1 or 2). A one-stage, individual patient data meta-analysis was performed with a mixed-effects multi-level logistic regression model reporting odds ratio (OR) with a 95% confidence interval (CI).


      Data from 44 observational studies and 40 case reports (n = 658) were combined and analyzed to identify independent predictors of survival with good neurologic outcome. The survival rate with good neurologic outcome of the entire cohort was 40.3% (265 of 658). ECLS rewarming rate (OR: 0.93; 95% CI: 0.88, 0.98; p = .007), female gender (OR: 2.78; 95% CI: 1.69, 4.58; p < 0.001), asphyxiation (OR: 0.19; 95% CI: 0.11, 0.35; p < 0.001) and serum potassium (OR: 0.62; 95% CI: 0.53, 0.73; p < 0.001) were associated with survival with a good neurologic outcome. The logistic regression model demonstrated excellent discrimination (c-statistic: 0.849; 95% CI: 0.823, 0.875).


      The use of extracorporeal life support in the treatment of hypothermic cardiac arrest provides a favourable chance of survival with good neurologic outcome. When used in a weighted scoring system, asphyxiation, serum potassium and gender can help clinicians prognosticate the benefit of resuscitating hypothermic patients with ECLS.


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        • Brown D.
        • Brugger H.
        • Boyd J.
        • Paal P.
        Accidental hypothermia.
        N Engl J Med. 2012; 367: 1930-1938
        • Danzl D.
        • Pozos R.
        • Auerbach P.
        • et al.
        Multicenter hypothermia survey.
        Ann Emerg Med. 1987; 16: 1042-1055
        • Kornberger E.
        • Schwarz B.
        • Lindner K.
        • Mair P.
        Forced air surface rewarming in patients with severe accidental hypothermia.
        Resuscitation. 1999; 41: 105-111
        • Danzl D.
        • Hedges J.
        • Pozos R.
        Hypothermia outcome score: development and implications.
        Crit Care Med. 1989; 17: 227-231
        • Grey T.
        • Rolfs R.
        • Chambers M.
        • Niskar A.
        Hypothermia-related deaths: Utah, 2000, and United States, 1979–1998.
        Morbidity Mortal Wkly Rep. 2002; 51: 76-78
        • Dixon P.
        • Brummer D.
        • Hedquist B.
        • et al.
        Heat vs cold mortality: a study of conflicting databases in the US.
        B Am Meteorol Soc. 2005; : 937-943
        • Thacker M.
        • Lee R.
        • Sabogal R.
        • Anderson A.
        Overview of deaths associated with natural events, United States, 1979–2004.
        Disasters. 2008; 32: 305-315
        • Baumgartner E.
        • Belson M.
        • Rubin C.
        • Patel M.
        Hypothermia and other cold-related morbidity emergency department visits: united States, 1995–2004.
        Wilderness Environ Med. 2008; 19 (Winter): 233-237
        • Stewart L.
        • Clarke M.
        • Rovers M.
        • et al.
        PRISMA-IPD Development Group: preferred reporting items for systematic review and meta-analysis of individual participant data: the PRISMA-IPD statement.
        JAMA. 2015; 313: 1657-1665
        • Collins G.
        • Reitrma J.
        • Altman D.
        • Moons K.
        Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement.
        Ann Intern Med. 2015; 162: 55-63
        • He Y.
        Missing data analysis using multiple imputation: getting to the heart of the matter.
        Circ Cardiovasc Qual Outcomes. 2010; 3: 98-105
        • Downs S.
        • Black N.
        The feasibility of creating a checklist for the assessment of the methodological quality both of randomized and non-randomized studies of health care interventions.
        J Epidemiol Community Health. 1998; 52: 377-384
        • Riley R.
        • Lambert P.
        • Staessen J.
        • et al.
        Meta-analysis of continuous outcomes combining individual patient data and aggregate data.
        Statist Med. 2008; 27: 1870-1893
        • Van Houwelingen J.
        • Le Cessie S.
        Predictive value of statistical models.
        Statist Med. 1990; 9: 1303-1325
        • Sullivan L.
        • Massaro J.
        • D’Agostino R.
        Presentation of multivariate data for clinical use: the Framingham Study risk score functions.
        Statist Med. 2004; 23: 1631-1660
        • Wiberg S.
        • Kjaergaard J.
        • Kjeargaard B.
        • Moller B.
        • et al.
        The biomarkers neuron-specific enolase and S100b measured the day following admission for severe accidental hypothermia have high predictive value for poor outcome.
        Resuscitation. 2017; 121: 49-53
        • Mair P.
        • Brugger H.
        • Mair B.
        • Moroder L.
        • Ruttmann E.
        Is extracorporeal rewarming indicated in avalanche victims with unwitnessed hypothermic cardiorespiratory arrest?.
        High Alt Med Biol. 2014; 15: 500-503
        • Hilmo J.
        • Naesheim T.
        • Gilbert M.
        Nobody is dead until warm and dead: prolonged resuscitation is warranted in arrested hypothermic victims also in remote areas – a retrospective study from northern Norway.
        Resuscitation. 2014; 85: 1204-1211
        • Morita S.
        • Inokuchi S.
        • Yamagiwa T.
        • et al.
        Efficacy of a portable and percutaneous cardiopulmonary bypass rewarming versus that of conventional internal rewarming for patients with accidental deep hypothermia.
        Crit Care Med. 2011; 39: 1064-1068
        • Coskun K.
        • Popov A.
        • Schmitto J.
        • et al.
        Extracorporeal rewarming in drowning and near-drowning pediatric patients.
        Artif Organs. 2010; 34: 1026-1030
        • Ruttmann E.
        • Weissenbacher A.
        • Ulmer H.
        • et al.
        Prolonged extracorporeal membrane oxygenation-assisted support provides improved survival in hypothermic patients with cardiopulmonary arrest.
        J Thorac Cardiovasc Surg. 2007; 134: 595-600
        • Gregory J.
        • Bergstein J.
        • Aprahamian C.
        • Wittmann D.
        • Quebbeman E.
        Comparison of three methods of rewarming from hypothermia: advantages of extracorporeal blood warming.
        J Trauma. 1991; 31: 1247-1252
        • Svendsen O.S.
        • Grong K.
        • Andersen K.S.
        • Husby P.
        Outcome after rewarming from accidental hypothermia by use of extracorporeal circulation.
        Ann Thorac Surg. 2017; 103: 920-925
        • Debaty G.
        • Moustapha I.
        • Bouzat P.
        • et al.
        Outcome after severe accidental hypothermia in the French Alps: a 10-year review.
        Resuscitation. 2015; 93: 118-123
        • Jarosz A.
        • Darocha T.
        • Kosinski S.
        • Zietkiewicz M.
        • Drwila R.
        Extracorporeal membrane oxygenation in severe accidental hypothermia.
        Intensive Care Med. 2015; 41: 169-170
        • Sawamoto K.
        • Bird S.
        • Katayama Y.
        • et al.
        Outcome from severe accidental hypothermia with cardiac arrest resuscitated with extracorporeal cardiopulmonary resuscitation.
        Am J Emerg Med. 2014; 32: 320-324
        • Skarda D.
        • Barnhart D.
        • Scaife E.
        • Molitor M.
        • Meyers R.
        • Rollins M.
        Extracorporeal cardiopulmonary resuscitation (EC-CPR) for hypothermic arrest in children: is meaningful survival a reasonable expectation?.
        J Pediatr Surg. 2012; 47: 2239-2243
        • Sansone F.
        • Flocco R.
        • Zingarelli E.
        • et al.
        Hypothermic cardiac arrest in the homeless: what can we do?.
        JECT. 2011; 43: 252-257
        • Guenther U.
        • Varelmann D.
        • Putensen C.
        Wrigge Extended therapeutic hypothermia for several days during extracorporeal membrane-oxygenation after drowning and cardiac arrest. Two cases of survival with no neurological sequelae.
        Resuscitation. 2009; 80: 379-381
        • Silfvast T.
        • Pettila V.
        Outcome from severe accidental hypothermia in Southern Finland – a 10-year review.
        Resuscitation. 2003; 59: 285-290
        • Walpoth B.
        • Walpoth-Aslan B.
        • Mattle H.
        • et al.
        Outcome of survivors of accidental deep hypothermia and circulatory arrest treated with extracorporeal blood rewarming.
        N Engl J Med. 1997; 20: 1500-1505
        • Durrer B.
        • Brugger H.
        • Syme D.
        The medical on-site treatment of hypothermia: ICAR-MEDCOM recommendation.
        High Alt Med Biol. 2003; 4: 99-103
        • Topjian A.
        • Localio A.
        • Berg R.
        • et al.
        for the American Heart Association National Registry of Cardiopulmonary Resuscitation Investigators. Women of child-bearing age have better in-hospital cardiac arrest survival outcomes than do equal-aged men.
        Crit Care Med. 2010; 38: 1254-1260
        • Perers E.
        • Abrahamsson P.
        • Bång A.
        • et al.
        There is a difference in characteristics and outcome between women and men who suffer out of hospital cardiac arrest.
        Resuscitation. 1999; 40: 133-140
        • Kitamura T.
        • Iwami T.
        • Nichol G.
        • et al.
        Reduction in incidence and fatality of out-of-hospital cardiac arrest in females of the reproductive age.
        Eur Heart J. 2010; 31: 1365-1375
        • Wigginton J.
        • Pepe P.
        • Idris A.
        Rationale for routine and immediate administration of intravenous estrogen for all critically ill and injured patients.
        Crit Care Med. 2010; 38: S620-S629
        • Xiao G.
        • Wei J.
        • Yan W.
        • Wang W.
        • Lu Z.
        Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial.
        Crit Care. 2008; 12: 1-10
        • Grigore A.
        • Grocott H.
        • Mathew J.
        • et al.
        Neurologic Outcome Research Group of the Duke Heart Center: the rewarming rate and increased peak temperature alter neurocognitive outcome after cardiac surgery.
        Anesth Analg. 2002; 94: 4-10
        • Engelman R.
        • Baker R.A.
        • Likosky D.S.
        • et al.
        Society of Thoracic Surgeons; Society of Cardiovascular Anesthesiologists; American Society of ExtraCorporeal Technology. Clinical practice guidelines for cardiopulmonary bypass – Temperature management during adult cardiopulmonary bypass.
        Ann Thorac Surg. 2015; 100: 748-757