Clinical PaperHyperOxic Therapy OR NormOxic Therapy after out-of-hospital cardiac arrest (HOT OR NOT): A randomised controlled feasibility trial☆
Introduction
Despite oxygen being a ubiquitous therapy in patients resuscitated from out-of-hospital cardiac arrest (OHCA), there is little high quality evidence to guide clinicians about how best to use oxygen in this patient group. With the exception of one pilot trial,1 no previous prospective study of different oxygen regimens following resuscitation from OHCA has been performed. There is a sound scientific basis supporting the hypothesis that avoidance of hyperoxia after resuscitation from OHCA might reduce neurological injury.2 On the other hand, although exposure to hyperoxia appears to be associated with increased in-hospital mortality in observational studies,3, 4, 5 significant heterogeneity in the results of the existing studies means that there is uncertainty about this association.6 Furthermore, even if the association proved to be robust, it is possible that arterial hyperoxia is a marker of illness severity rather than a determinant of outcome.7 For example, the presence of poor peripheral perfusion could potentially lead clinicians to increase the inspired oxygen concentration (FiO2) on the basis of spuriously low peripheral pulse oximetry (SpO2) recordings. Moreover, even if hyperoxia were truly harmful, any attempt to reduce oxygen exposure in post-resuscitation management may carry with it the potential risk of exposing patients to hypoxia which is also consistently associated with increased mortality risk.4, 7
As a result of the current uncertainty, a high quality prospective trial evaluating the effect of titrated oxygen therapy on patient outcomes after OHCA is a research priority.8 With the eventual objective of conducting such a trial, we undertook a feasibility study to evaluate whether or not an individualised oxygen titration regimen designed to limit exposure to hyperoxia in patients with return of spontaneous circulation (ROSC) after OHCA led to an effective reduction in oxygen exposure compared to standard care without exposing patients to a greater incidence and severity of hypoxia.
Section snippets
Trial design and setting
We performed a prospective, multi-centre, single-blind, parallel-groups, feasibility and safety randomised controlled trial (RCT) comparing titrated oxygen administration to standard care with high concentration oxygen in adults resuscitated from OHCA. This trial was conducted in New Zealand. We intended to enrol patients in Auckland, Christchurch, the Hutt Valley, and Wellington. However, at the time the trial was terminated, site initiation had not been completed in Auckland or Christchurch
Participants
Between 13/10/2012 and 21/09/2013 159 cardiac arrests were screened and 18 participants were randomised (Fig. 1). One non-eligible patient was randomised but received no study treatment and was not included in the analyses. Data for the primary end point were available for the other 17 participants. The trial was terminated early because ongoing review of accumulated data led the Data Safety Monitoring Board and the study management committee to conclude that safe delivery of titrated oxygen
Summary of principal findings
We conducted a multicentre feasibility study comparing titrated oxygen therapy to standard oxygen therapy in patients resuscitated from OHCA in New Zealand. The study was stopped early because preliminary data strongly suggested that our approach to delivering titrated oxygen therapy in the pre-hospital setting was not feasible. While targeting an SpO2 of 90–94% achieved significantly lower SpO2 measurements than standard care in the pre-hospital period, SpO2 recordings varied widely,
Conclusions
Titration of oxygen delivery to SpO2 following resuscitation from OHCA was not feasible in the pre-hospital setting. However, our preliminary data suggest that it may be possible to titrate oxygen after arrival in hospital. The safety and efficacy of any strategy to reduce oxygen exposure in hospital in OHCA patients should be further evaluated through prospective trials.
Conflicts of interest statement
The authors have no conflicts of interest to report.
Funding
This study was an investigator-initiated study funded by a Feasibility Grant provided by the Health Research Council of New Zealand (13/666). The study was conducted independently of the funder.
Acknowledgements
The authors would like to acknowledge the support for this study provided by the staff of Wellington Free Ambulance, St John Ambulance, Hutt Valley District Health Board, and Capital Coast District Health Board.
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A Spanish translated version of the summary of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2014.09.011.