Response by Roberts et al to Letters Regarding Article, “Association Between Early Hyperoxia Exposure After Resuscitation From Cardiac Arrest and Neurological Disability: Prospective Multicenter Protocol-Directed Cohort Study”
Authors: Brian W. Roberts, J. Hope Kilgannon, Stephen Trzeciak
Journal: Circulation (2018)

In Response:We thank Drs Russell, Nestelberger, Kong, and their colleagues for their interest in our recent article, 1 and for raising several important points regarding our results.Both Drs Russell and Nestelberger express some concern with our conclusion that increased risk of poor neurological outcome after resuscitation from cardiac arrest appears to begin at a partial pressure of arterial oxygen (Pao 2 ) of 300 mm Hg.We agree that our Figure 3 displaying varying cut points to define hyperoxia only demonstrates that Pao 2 >300 mm Hg is the lowest cutoff associated with a statistically significant risk of poor neurological outcome, and it is possible that there may be clinical harm at lower Pao 2 levels.In an effort to mitigate these concerns, we entered Pao 2 as a categorical variable (ie, ascending Pao 2 ranges: <100, 101-200, 201-300, and >300 mm Hg) into our original model with <100 mm Hg as the reference.We found no increased risk of poor neurological outcome at 101 to 200 or 201 to 300 mm Hg, relative risks 1.06 (95% CI, 0.76-1.47)and 0.93 (95% CI, 0.79-1.10),respectively, whereas Pao 2 >300 mm Hg remained statistically significant, relative risk 1.23 (95% CI, 1.08-1.40).Second, Dr Russell and colleagues appropriately note that 1 reason for the inability of Sao 2 to reliably rule out hyperoxia is likely poor plethysmographic waveforms, and that frequent phlebotomy to obtain serial arterial blood gas measurements is not without potential harm to patients.Based on these concerns, they offer using Sao 2 to rule our hyperoxia and to only obtain a Pao 2 measurement when in doubt about the waveform.This may be a reasonable approach; however, previous studies have demonstrated frequent hypoxic episodes when titrating down the fraction of inspired oxygen (Fio 2 ) based only on the Sao 2 after cardiac arrest. 2,3The oxyhemoglobin dissociation curve is, of course, not linear and, as such, it is not possible to know exactly where on the curve the patient is at the start of titration without a Pao 2 measurement.Our Figure I in the online-only Data Supplement also demonstrates that a proportion of patients with a high Sao 2 had a low Pao 2 , and it is possible that a small decrease in Fio 2 may result in a hypoxic exposure (ie, if the patient is on the steep part of the curve).Thus, not only are Pao 2 measurements important to identify hyperoxia exposure, but they may also help prevent hypoxia exposure during titration.An alternative approach to multiple arterial punctures is to place an arterial line for frequent Pao 2 measurements.In addition, arterial lines are advantageous for close blood pressure monitoring, and for rapid identification and reversal of hypotension, which is also associated with poor neurological outcome. 4hird, Dr Nestelberger and colleagues astutely note that, in our cohort, only 26% of patients with out-of-hospital, pulseless ventricular fibrillation/ventricular tachycardia cardiac arrest received percutaneous coronary intervention.For patients with a suspected cardiac etiology of cardiac arrest, the decision to take a patient for coronary angiography was made in conjunction with an interventional cardiologist.Among our entire cohort, 47 (17%) patients were identified to have