Hyperoxia after cardiac arrest may not increase ischemia-reperfusion injury

In the last decade, moderate hypothermia has become the mainstay of treatment in the post-resuscitation period. However, for the damaged brain, optimizing oxygen transport, including arterial oxygenation, may also be important. The current view states that hyperoxia in the immediate post-resuscitation period may worsen cerebral outcome, and international guidelines recommend a target arterial oxygen saturation of 94% to 98%. An article in the previous issue of Critical Care challenges this viewpoint. In an elegant study using a Cox proportional hazards model combined with sensitivity analyses and time period matching, the authors show no independent association between hyperoxia and in-hospital mortality. The present commentary discusses these contradictory findings and suggests a practical solution to solve these differences.

An article by Bellomo and colleagues [1] in the previous issue of Critical Care challenges the current view that hyperoxia in the immediate post-resuscitation period increases cerebral damage in cardiac arrest victims. Th ese fi ndings are at least remarkable and apparently contradict recent post-resuscitation guidelines.
Patients who initially survive an out-of-hospital cardiac arrest and are admitted to the ICU have a dismal prognosis. Despite the recent introduction of moderate therapeutic hypothermia, mortality is still approximately 65% to 70% [2]. Th e benefi cial eff ects of moderate hypothermia are partly explained by the mitigating eff ects on ischemia-reperfusion injury. Consequently, other measures that may attenuate ischemia-reperfusion injury have been suggested. Th is includes the prevention of postresuscitation hyperoxia as the current evidence suggests that hyperoxia may worsen cerebral injury [3]. Animal experiments apparently confi rm the detrimental eff ects of post-resuscitation hyperoxia on outcome. Hyperoxic reperfusion increases hippocampal neuronal death and induces behavioral defi cits in a rat global cerebral ischemia model [4]. In a canine ventricular fi brillation cardiac arrest model, hyperoxic reperfusion decreased the activity of the hippocampal pyruvate dehydrogenase complex, possibly due to an increase in peroxynitrite levels [5] and impaired oxidative energy metabolism [6]. Finally, a clinically applicable protocol designed to reduce post-resuscitative hyperoxia in dogs by using oximetry and aiming for an oxygen saturation as measured by pulse oximetry (SpO 2 ) of 95% signifi cantly reduced the number of injured CA1 neurons and improved the neuro logical defi cit score [7]. Th e British Th oracic Society recently recommended that the inspired oxygen concentration be targeted to an arterial oxygen saturation of 94% to 98% [8]. Th is is also advocated in the most recent guidelines from the European Resuscitation Council [9].
Why then did Bellomo and colleagues arrive at a diff erent conclusion? In an elegant retros pective analysis, they included 12,108 patients resuscitated from nontraumatic cardiac arrest. Hyperoxia was defi ned as an arterial partial pressure of oxygen (PaO 2 ) of greater than 300 mm Hg in the fi rst 24 hours after admission. Isolated hypoxemia was defi ned as a PaO 2 of less than 60 mm Hg. A total of 1,285 (10.6%) patients had hyperoxia and 1,168 (9.7%) had isolated hypoxemia. Mortality was higher in the hyperoxia group compared with the normoxia group (59% versus 47%) but not compared with hypoxemia patients. Patients with isolated hypoxemia had the lowest discharge home rate (19%). In a multivariate model, hyperoxia still had an odds ratio for hospital death of 1.2 (95% confi dence interval of 1.1 to 1.6), but a Cox pro portional hazards model combined with sensitivity analyses and time period matching showed no independent associa tion between hyperoxia and in-hospital mortality. In

Abstract
In the last decade, moderate hypothermia has become the mainstay of treatment in the post-resuscitation period. However, for the damaged brain, optimizing oxygen transport, including arterial oxygenation, may also be important. The current view states that hyperoxia in the immediate post-resuscitation period may worsen cerebral outcome, and international guidelines recommend a target arterial oxygen saturation of 94% to 98%. An article in the previous issue of Critical Care challenges this viewpoint. In an elegant study using a Cox proportional hazards model combined with sensitivity analyses and time period matching, the authors show no independent association between hyperoxia and in-hospital mortality. The present commentary discusses these contradictory fi ndings and suggests a practical solution to solve these diff erences.
contrast, in most of the models, isolated hypoxemia remained an independent risk factor for hospital mortality.
So where does this information leave us? Clearly, postresuscitation care is more than moderate hypothermia alone. Uncertainty still exists over the optimal blood pressure, the amount of cerebral blood fl ow, the hemoglobin level, the blood glucose regulation, and the partial pressure of arterial carbon dioxide (PaCO 2 ) and now also over the PaO 2 . Although the evidence up to now clearly suggested a detrimental eff ect of post-resuscitation hyperoxia, the weight of the present study raises serious doubts. Clearly, fear of hyperoxia should not lead to an indiscriminate decrease in inspired oxygen level, as hypoxemia is certainly bad for the damaged brain. On the other hand, hyperoxia had no proven benefi cial eff ects either. Th erefore, there is no reason to revise the current guidelines targeting a post-resuscitation arterial oxygen saturation of 94% to 98%.
Abbreviations ICU, intensive care unit; PaO 2 , arterial partial pressure of oxygen.