Optimal arterial carbon dioxide tension following cardiac arrest: Let Goldilocks decide?


Optimal arterial carbon dioxide tension following cardiac arrest: Let Goldilocks decide?

Ryan W. Morgan, Todd J. Kilbaugh

Article Outline

Despite initially successful cardiopulmonary resuscitation, a substantial proportion of patients who survive cardiac arrest die prior to hospital discharge and those that survive often have severe neurologic injury.Following arrest, the initial hours and days are defined by the post-cardiac arrest syndrome, with a significant inflammatory response, organ bioenergetic failure, and high risk of morbidity and mortality. This period of time requires vigilant monitoring and intervention, and is the subject of intense investigation to identify markers of ongoing neurologic injury and therapeutic development.

In cardiac arrest patients who achieve return of spontaneous circulation, 45–60% have hypocarbia or hypercarbia in the subsequent hours.,  Hypocarbia may be present soon after cardiac arrest due to inadvertent overventilation or due to a decreased metabolic rate precipitated by therapeutic hypothermia and other interventions., ,  Alternatively, hypercarbia immediately following cardiac arrest is often secondary to concomitant lung disease or asphyxia, or as a marker of limited pulmonary perfusion due to low cardiac output., 

Given the effects of PaCO2 on the cerebral circulation and the burden of severe anoxic injury following cardiac arrest, recent interest has been placed on the prognostic capabilities of PaCO2 in patients who are resuscitated from cardiac arrest., , , ,  In the present issue of Resuscitation, McKenzie et al. summarize the prognostic value of PaCO2 in their systematic review and meta-analysis. The authors identify nine prospective and retrospective cohort studies of out-of-hospital or in-hospital cardiac arrest for inclusion. Eight studies, with over 23,000 patients, are included in the meta-analysis. Despite being limited in conducting some analyses by excessive statistical heterogeneity between studies, the authors report improved hospital survival and improved neurologic outcomes with normocarbia as compared to hypercarbia; and improved rates of discharge home with normocarbia as compared to hypocarbia.

McKenzie et al. should be commended for this sophisticated meta-analysis. As the authors acknowledge, the analysis has some limitations. First, the authors reasonably define normocarbia as a PaCO2 of 35–45?mmHg, with values below and above this range being defined as hypocarbia and hypercarbia, respectively.However, these definitions were not consistent across all studies included in the meta-analysis. In fact, the authors excluded one study that differed from the set definitions of hypocarbia and hypercarbia as defined above, and this resulted in the loss of statistical significance in one analysis.

Additionally, the timing of blood gas acquisition varies from study to study. Whereas immediate post-resuscitation PaCO2 is indicative of the pre-arrest and intra-arrest state, PaCO2 values measured later in the post-arrest period likely reflect post-arrest pathophysiology and interventions. Knowledge of the relationship of these values to outcome is undoubtedly valuable, but the variability in when these values are obtained and what they represent limit how clinicians can or should employ this information in practice.

Another concern is that the majority of patients included in this review are from the Schneider et al. study, which includes 16,542 patients, approximately 71% of the patients included in the meta-analysis. This study is the primary factor influencing the conclusion that patients with normocarbia are more likely to survive to hospital discharge as compared to patients with hypercarbia. Interestingly, in Schneider’s original study, there was no difference between these groups in the adjusted analysis. Additionally, Schneider et al. found that hypercarbic patients were more likely to be discharged home than the normocarbic cohort. This finding provided the rationale for a randomized controlled trial between controlled normocarbia and mild hypercarbia, with a Phase II feasibility study demonstrating promising results for the potentially protective effects of therapeutic mild hypercarbia.

Hypocarbia has the potential to decrease cerebral blood flow by altering cerebral vascular resistance following cardiac arrest. Thus, current guidelines for the care of patients following successful resuscitation endorse the avoidance of hypocarbia except as a temporizing measure to inhibit intracranial hypertension. These guidelines also acknowledge an unclear link between hypercarbia and clinical outcome, but suggest a normocarbic goal “unless patient factors prompt more individualized treatment.” Intuitively, having a goal of maintaining normocarbia seems reasonable. The question still remains, are derangements in arterial carbon dioxide tension merely reflective of post-arrest pathophysiology or are they actually independent promotors of secondary injury. Likely, both are true.

With a large proportion of patients who survive their initial resuscitation suffering neurologic injury that results in death or permanent disability, resuscitation centers should be focused on the development of mutli-modal neuromonitoring platforms to assess ongoing injury and initiate early intervention. Armed with real-time data related to cerebral blood flow, cerebral oxygenation, and cerebral metabolism, ,  clinicians should be able to tailor therapies to the individual patient rather than to simply prognosticate across a population. Measurement and manipulation of arterial carbon dioxide is one piece of the complex management for post-cardiac arrest syndrome that deserves continued study.

Conflict of interest statement

The authors (Ryan Morgan and Todd Kilbaugh) report no relevant financial disclosures or conflicts of interest related to this editorial.


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