Hyperoxia Post-Cardiac Arrest Increases Mortality

Hyperoxia in patients recovering in the intensive care unit (ICU) after cardiac arrest increases the risk of in-hospital death, a study from the Project IMPACT database shows [1].

Dr J Hope Kilgannon (Cooper University Hospital, Camden, NJ) and colleagues analyzed the outcomes of patients in ICUs following cardiopulmonary resuscitation after cardiac arrest at 120 centers. Results of the study, supported by the National Institutes of Health and the Emergency Medicine Foundation, appear in the June 2, 2010 issue of the Journal of the American Medical Association. It is the first large multicenter study documenting the association between postresuscitation hyperoxia and poor clinical outcome, according to the authors.

Of the 6326 patients in the study, 1156 were hyperoxic–defined as arterial blood pressure (PaO₂) ≥300 mm Hg within 24 hours after arriving in the ICU; 3999 were hypoxic (PaO₂ <60 mm Hg); and 1171 were normoxic.

In-hospital mortality was 63% in the hyperoxic group, significantly higher than the 57% mortality in the hypoxic group and 45% mortality in the normoxic group (p<0.001). Hyperoxia was also associated with a lower likelihood of independent functional status at hospital discharge.

Kilgannon created a statistical model controlling for potential cofounders such as age, preadmission functional status, comorbid conditions, vital signs, and other factors and found that hyperoxia was associated with almost twice the risk of in-hospital mortality as normoxia (odds ratio 1.8; 95% CI 1.5–2.2).

“Reperfusion after an ischemic insult is associated with a surge of reactive oxygen species, which may overwhelm host natural antioxidant defenses,” the Kilgannon et al suggest. “The oxidative stress from the reactive oxygen species formed after reperfusion may lead to increased cellular death by diminishing mitochondrial oxidative metabolism, disrupting normal enzymatic activities, and damaging membrane lipids through peroxidation.”

In an accompanying editorial [2], Drs Patrick Kochanek and Hulya Bayir (University of Pittsburgh, PA) point out that the study also found a link between hypoxia and mortality after cardiopulmonary arrest. “This complicates the ability to make sweeping recommendations against the use of 100% oxygen early in resuscitation.” They suggest that measuring brain oxygen pressure may help optimize oxygen levels in postresuscitation patients but note that this approach is untested.

Study coauthor Dr Stephen Trzeciak (Cooper University Hospital) reported that he receives material support for research from Ikaria and consults for Spectral Diagnostics but receives no remuneration from any commercial interest. None of the other authors reported disclosures.

References

1. Kilgannon H, Jones A, Shapiro N, et al. Association between arterial hyperoxia following resuscitation from cardiac arrest and in-hospital mortality. JAMA 2010; 303:2165-2171.
2. Kochanek P and Bayir H. Titrating oxygen during and after cardiopulmonary resuscitation. JAMA 2010; 303:2190-2191.

Clinical Context

Mortality rate from sudden cardiac arrest is extremely high even when resuscitation is successful, with only approximately 60% of patients surviving to hospital discharge after return of spontaneous circulation from cardiac arrest. Factors contributing to high mortality rate include global ischemia reperfusion injury, myocardial stunning, anoxic brain injury, and other components of the postcardiac arrest syndrome.

The role of supplemental oxygen, often given in high concentrations to patients after cardiac arrest, is controversial. Exposure to hyperoxia after resuscitation from cardiac arrest may worsen anoxic brain injury, based on evidence from laboratory studies. To date, however, clinical data describing the effects and clinical correlates of exposure to hyperoxia are lacking.

Study Highlights

• The goal of this multicenter cohort study from the Emergency Medicine Shock Research Network (EMShockNet) Investigators was to evaluate the association between postresuscitation hyperoxia and increased mortality rate.
• Between 2001 and 2005, patients were identified from the Project IMPACT critical care database of ICUs at 120 US hospitals.
• Inclusion criteria were age older than 17 years, nontraumatic cardiac arrest, cardiopulmonary resuscitation 24 hours or less before arrival to the ICU, and arterial blood gas tested at 24 hours or less after ICU admission.
• PaO₂ on the first arterial blood gas tested in the ICU was used to divide patients into 3 groups.
• Hyperoxia was defined a priori as a PaO₂ of at least 300 mm Hg, hypoxia as a PaO₂ of less than 60 mm Hg (or ratio of PaO₂ to fraction of inspired oxygen < 300), and normoxia as neither hyperoxia nor hypoxia.
• The primary study endpoint was in-hospital mortality rate.
• Hyperoxia was present in 1156 (18%) of 6326 patients, hypoxia in 3999 (63%), and normoxia in 1171 (19%).
• Nearly 1 in 5 patients had exposure to hyperoxia (PaO₂ ≥ 300 mm Hg), and almost half of these patients had a PaO₂ of at least 400 mm Hg.
• In-hospital mortality rate was significantly higher in the hyperoxia group (732/1156; 63%; 95% confidence interval [CI], 60% – 66%) vs the normoxia group (532/1171 [45%; 95% CI, 43% - 48%]; proportion difference, 18% [95% CI, 14% - 22%]) or the hypoxia group (2297/3999 [57%; 95% CI, 56% - 59%]; proportion difference, 6% [95% CI, 3% - 9%]).
• For hyperoxia exposure, the odds ratio for death was 1.8 (95% CI, 1.5 – 2.2), after controlling for age, preadmission functional status, comorbid conditions, vital signs, other physiologic indices, hospital factors, and other potential confounders.
• Among hospital survivors, hyperoxia was associated with a lower likelihood of independent functional status at hospital discharge vs normoxia.
• The investigators concluded that among patients admitted to the ICU after resuscitation from cardiac arrest, arterial hyperoxia was independently associated with increased in-hospital mortality rate vs either hypoxia or normoxia.
• They also suggest that these data support the hypothesis that both hyperoxia and hypoxia are harmful, mandating clinical trials of controlled reoxygenation in adults who are resuscitated from cardiac arrest.
• Limitations of this study include observational design, preventing determination of causation; arbitrary definition of hyperoxia as a PaO₂ of at least 300 mmHg; inclusion of the ratio of PaO₂ to FIO₂ in the definition for hypoxia; possible unmeasured confounders; and lack of data on whether therapeutic hypothermia was attempted.

Clinical Implications

• Exposure to hyperoxia is common among adult patients admitted to the ICU after resuscitation from cardiac arrest, based on a large, multicenter cohort study using the Project IMPACT critical care database.
• Exposure to hyperoxia was an independent predictor of in-hospital mortality among adult patients admitted to the ICU after resuscitation from cardiac arrest, based on the current study. These data support the hypothesis that postresuscitation hyperoxia could be harmful and suggest the need for clinical trials of controlled reoxygenation after cardiac resuscitation.

Tags: Rianimazione