Elsevier

Resuscitation

Volume 127, June 2018, Pages 51-57
Resuscitation

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

https://doi.org/10.1016/j.resuscitation.2018.03.028Get rights and content

Abstract

Background

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.

Objective

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

Methods

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).

Results

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).

Conclusions

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.

Introduction

The use of extracorporeal life support (ECLS) to treat hypothermic cardiac arrest is associated with a 10–50% improvement in survival [1] over the baseline rate of 10–37% [[2], [3], [4]], yielding a number needed to treat of approximately 2–5 to save one life. Some 400–1500 persons die annually from hypothermia in the United States [[5], [6], [7], [8]] yet most prehospital care systems and community hospitals do not have a protocol to identify and transfer appropriate hypothermic cardiac arrest patients to an ECLS center. With the increased use and availability of ECLS in the United States for treating cardiac arrest in the Emergency Department, this therapy has become increasingly accessible, making the appropriate triage of hypothermic patients particularly timely.

Clinical decision making regarding appropriate ECLS application can be challenging in situations where difficulty exists distinguishing between cardiac arrest victims who arrest and subsequently become hypothermic and those who cool prior to suffering cardiac arrest secondary to hypothermia. Indiscriminate use of ECLS in the resuscitation of all cardiac arrest patients who are cold would be costly and result in low survival rates. However overly restrictive ECLS criteria would result in patients with a reasonable probability of survival being denied a potentially lifesaving intervention. A reliable prognostication tool is currently lacking to assist in the appropriate allocation of ECLS therapy for hypothermic patients. Although poorly studied, this likely results in significant site-specific variability in hospital transfer policies and the application of this modality.

The primary purpose of this study was to identify factors independently associated with survival with good neurologic outcome in patients treated with ECLS for hypothermic cardiac arrest. Secondarily, if such factors could be identified, we sought to develop a scoring tool, using standard historical and/or clinical factors, to predict the probability of survival with good neurological outcome.

Section snippets

Methods

An individual patient data (IPD) meta-analysis with a multivariable prediction model component was performed using methods described in Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA-IPD) (Checklist, online Supplementary Data) and the Transparent Reporting of a Multivariate Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) guidelines [[9], [10]].

Results

Initial search of Pubmed, EMBASE and CINAHL identified 1172 potential studies. After exclusions, 84 manuscripts were selected for analysis (Fig. 1). No randomized studies were identified. All of the studies were observational designs comprised of 44 retrospective cohort studies and 40 individual case descriptions (Table 2, online Supplementary Data). The Cohen’s Kappa statistic for inter-annotator agreement was 0.993 (95% CI: 0.987, 0.999) and 0.987 (95% CI: 0.978, 0.996) for survival and

Discussion

The most important clinical outcome in hypothermic cardiac arrest resuscitation is survival with good neurologic outcome, typically viewed as a moderate or high level of cognition and independent functional status. Previously reported survival rates for hypothermic cardiac arrest treated with ECLS rewarming range from 10 to 100%. Our pooled data found a survival with good neurologic outcome rate of 40.3% and a relatively low proportion (5.6%) of survivors with a poor neurologic outcome.

After

Limitations

To our knowledge this is the most methodologically rigorous analysis of the accidental hypothermia patients treated with ECLS. However, a number of limitations of our study should be considered, the most important of which is potential publication bias. It is highly likely that cases successfully resuscitated with ECLS are reported and published more often than those that are unsuccessful, potentially leading to distortion of our estimates. Also, there are a number of clinical variables that

Conclusion

This meta-analysis is the largest and most comprehensive dataset of its kind; it pools individual patient data from all the published reports where ECLS was used to rewarm AH patients with cardiovascular collapse or severe cardiac instability. Given the low incidence of severe AH, the inability to ethically perform a randomized trial and the lack of a large registry, this data represents the most robust evidence available at this time.

The analysis shows a favourable survival with good

Conflict of interest

The authors declare that they have no competing interests.

Acknowledgments

We gratefully acknowledge the data provided by the following International Accidental Hypothermia Extracorporeal Life Support (ICE) Collaborators:

Champigneulle B1, Bellenfant-Zegdi F2, Follin A3, Lebard C3, Guinvarch A2, Thomas F2, Pirracchio R4, Journois D3. 1Surgical Intensive Care Unit, Georges Pompidou European Hospital, AP-HP, Paris, France; Paris Descartes University, Sorbonne Paris Cité, Paris, France. 2Surgical Intensive Care Unit, Georges Pompidou European Hospital, AP-HP, Paris,

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