Elsevier

Resuscitation

Volume 85, Issue 9, September 2014, Pages 1142-1148
Resuscitation

Review
The effect of hyperoxia on survival following adult cardiac arrest: A systematic review and meta-analysis of observational studies

https://doi.org/10.1016/j.resuscitation.2014.05.021Get rights and content

Abstract

Objective

Studies have shown the detrimental effect of hyperoxia in animals with return of spontaneous circulation (ROSC) after cardiac arrest. To maximize the value of existing clinical studies, we performed the systemic review and meta-analysis of human observational studies to examine the effect of hyperoxia on outcomes of post-ROSC patients.

Methods

We searched PubMed and Embase from the inception to October 2013. We selected adult observational studies that compared different levels of partial pressure of arterial oxygen (PaO2) in post-ROSC patients with mortality or neurological status at hospital discharge as outcome. Studies comparing hypoxia with normoxia only were excluded.

Results

Fourteen studies were identified from 2982 references. Odds ratio (OR) was used as effect estimate. OR was reconstructed if not provided in original articles. Hyperoxia was defined as a PaO2 >300 mmHg. Meta-analysis indicated that hyperoxia appeared to be correlated with increased in-hospital mortality (OR, 1.40; 95% CI, 1.02–1.93; I2, 69.27%; 8 studies) but not worsened neurological outcome (OR, 1.62; 95% CI, 0.87–3.02; I2, 55.61%; 2 studies). However, the results were inconsistent in subgroup and sensitivity analyses.

Conclusions

Hyperoxia appears to be correlated with increased in-hospital mortality of post-ROSC patients. This result should be interpreted cautiously because of the significant heterogeneity and limited number of studies analyzed. However, because exposure to hyperoxia had no obvious benefits, clinicians should monitor PaO2 closely and titrate oxygen administration cautiously.

Introduction

Cardiac arrest, either out-of-hospital or in-hospital, is a common and lethal emergency condition.1, 2 Even if return of spontaneous circulation (ROSC) is achieved, most patients do not survive to hospital discharge.1, 2 The high post-ROSC mortality may be attributed to post-cardiac arrest syndrome, which includes anoxic neurological injury, myocardial dysfunction, and systemic ischemic/reperfusion response.3

The 2010 European Resuscitation Council (ERC) Guidelines integrates the post-resuscitation care into the new chain of survival.4 The ERC recommends rapid application of therapeutic hypothermia for post-ROSC patients to improve survival to hospital discharge and neurological outcome because therapeutic hypothermia is thought to mitigate this systemic inflammatory response after ROSC.5

In the search for other modifiable post-ROSC factors that can improve outcomes, the role of supplemental oxygen in the pathogenesis of post-cardiac arrest syndrome has gained increasing attention recently. A meta-analysis of animal studies concluded that administration of 100% oxygen in the early post-ROSC period was associated with adverse neurological outcome.6

The only human randomized controlled trial compared the effects of administering 30% and 100% oxygen to post-ROSC patients.7 Although this study was not powered to show differences in long-term outcomes, subgroup analysis showed that 100% oxygen was associated with an increased level of neuron-specific enolase, a serum marker of neuronal injury.

It might be difficult to conduct a large-scale randomized controlled trial for examining the influence of high oxygen concentration on post-ROSC patients because of logistical and ethical difficulties. To maximize the value of existing evidence in the literature, we performed a meta-analysis of human observational studies to examine the effects of hyperoxia on outcomes of post-ROSC patients.

Section snippets

Data sources and searches

We performed this meta-analysis in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses8 and the Meta-Analysis of Observational Studies in Epidemiology.9 We searched PubMed and Embase from the inception through October 2013. We did not set any restrictions on publication year or language. We used 2 sets of search terms to represent the primary variable and population of interest. The search terms for the primary variable included “normox*,”

Search results and study characteristics

In the systematic review, we identified 14 observational studies, including 8 full-text articles18, 19, 20, 21, 22, 23, 24, 25 and 6 abstract-only articles26, 27, 28, 29, 30, 31 (Fig. 1 and Table 1). All studies were cohort studies and included patients between the years 2000 and 2012, encompassing a total of 49,951 patients.

Six studies used multicenter databases for analysis.18, 19, 20, 22, 25, 28 Two studies18, 20 utilized the Project IMPACT database; the later study20 was a secondary

Discussion

The systematic review identified 14 observational studies examining the relationship between hyperoxia and adverse outcomes in post-ROSC patients. The meta-analysis indicated that hyperoxia might be associated with increased in-hospital mortality (OR, 1.40; 95% CI, 1.02–1.93; I2, 69.27%). However, because of the great heterogeneity among studies, this conclusion should be interpreted with caution.

The timing and duration of exposure to hyperoxia were not controlled in each study, which might

Conclusions

Hyperoxia appears to be correlated with increased in-hospital mortality of post-ROSC patients. This result should be interpreted cautiously because of the significant heterogeneity and limited number of studies included in the analysis. However, because exposure to hyperoxia had no obvious benefits, clinicians should monitor PaO2 closely and titrate the oxygen administration cautiously.

Conflict of interest statement

The authors declare no conflicts of interest or sources of funding for this study.

References (40)

  • S. Girotra et al.

    Trends in survival after in-hospital cardiac arrest

    N Engl J Med

    (2012)
  • C. Sasson et al.

    Predictors of survival from out-of-hospital cardiac arrest: a systematic review and meta-analysis

    Circ Cardiovasc Qual Outcomes

    (2010)
  • D. Moher et al.

    Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

    Ann Intern Med

    (2009)
  • D.F. Stroup et al.

    Meta-analysis of observational studies in epidemiology: a proposal for reporting. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) group

    JAMA

    (2000)
  • L.B. Becker et al.

    Primary outcomes for resuscitation science studies: a consensus statement from the American Heart Association

    Circulation

    (2011)
  • S.H. Downs et al.

    The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions

    J Epidemiol Community Health

    (1998)
  • G.A. Wells et al.

    The Newcastle–Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses

    (2008)
  • E.E. Douzinas et al.

    Hypoxaemic reperfusion ameliorates the histopathological changes in the pig brain after a severe global cerebral ischaemic insult

    Intensive Care Med

    (2001)
  • E. Abraham et al.

    Consensus conference definitions for sepsis, septic shock, acute lung injury, and acute respiratory distress syndrome: time for a reevaluation

    Crit Care Med

    (2000)
  • J.P. Higgins et al.

    Measuring inconsistency in meta-analyses

    BMJ

    (2003)
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    A Spanish translated version of the abstract of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2014.05.021.

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