Response to Letter Regarding Article, “Association Between Postresuscitation Partial Pressure of Arterial Carbon Dioxide and Neurological Outcome in Patients With Post–Cardiac Arrest Syndrome”

We would like to thank Dr Eastwood and colleagues for their interest in our recent article.¹ In their letter, they raise concern that our results may reflect local practice and therefore should be interpreted with some caution. Our study was a single-center prospective study. We agree that a study of larger scope or of a different population could have found different results and that further research is needed to determine the optimal Paco₂ range during the initial post–cardiac arrest period. However, our finding that hypercapnia in the post–cardiac arrest period is associated with poor neurological outcome is consistent with previous findings of other brain-injured patients such as pediatric post–cardiac arrest and traumatic brain injury patients.^2,3

We are familiar with Dr Eastwood and colleagues’ recent article analyzing Paco₂ derangements in patients with post–cardiac arrest syndrome.⁴ Their paper was a large, well-performed registry study that found no difference in in-hospital mortality between hypercapnia and normocapnia patients overall; however, among survivors, they found hypercapnia to be associated with a greater likelihood of being discharged directly home as opposed being discharged to a rehabilitation center or transferred to another hospital. We agree that their findings, which are contrary to our findings and the other studies cited above, support that equipoise exists on this research question and provide the scientific rationale for future studies of Paco₂ optimization in post–cardiac arrest syndrome. We commend their group for moving forward with a clinical trial aimed at answering this important clinical question.

Before embarking on a clinical trial, we suggest careful consideration of a number of potentially important factors. On secondary analysis of our data, we found that the earliest exposure to Paco₂ derangements (ie, on initial postresuscitation arterial blood gas analysis) was associated with poor neurological function at hospital discharge, suggesting time sensitivity in achieving the optimal Paco₂ range. After resuscitation from cardiac arrest, there is often a time delay in identifying Paco₂ derangements (ie, time to initial arterial blood gas data being available). Although this period is usually brief, it is likely the time period when the injured brain is most susceptible to further damage. Therefore, rigorous research on ventilation strategies to prevent exposure immediately after resuscitation (ie, achievement of normocapnia on initial arterial blood gas) is warranted.

We also found that initial prescribed minute ventilation (ie, the minute ventilation set on the ventilator) had only a weak correlation with initial Paco₂ (R²=0.16), suggesting other important factors exist that influence the initial postresuscitation Paco₂. Therefore, simply prescribing ventilator settings in the hopes of rapidly achieving an ideal Paco₂, and not accounting for potential patient-related factors associated with Paco₂, could result in failure to rapidly achieve the target Paco₂ in a clinical trial. We hypothesize that the potentially important determinants of initial postresuscitation Paco₂ that also should be considered include treatment-related factors (ie, prescribed minute ventilation, use of neuromuscular blocking agents, duration and technique of bag ventilation by hand before initiation of mechanical ventilation) and patient-related factors (ie, cause of cardiac arrest, lung compliance, lung injury, intrinsic respiratory drive, persistent postresuscitation circulatory shock, dead space, body habitus).

We plan to use the infrastructure and information generated from an ongoing multicenter National Institutes of Health–sponsored cardiac arrest study⁵ to further elucidate the most crucial therapeutic time window and the Paco₂ range associated with good neurological outcome, as well as to determine the other factors associated with early postresuscitation Paco₂ derangements in patients with post–cardiac arrest syndrome.

• Received August 9, 2013.
• Accepted October 22, 2013.

• © 2014 American Heart Association, Inc.