March 6, 2019

EJRC - A prospective multi-centre protocol-directed cohort study

Partial pressure of arterial carbon dioxide after resuscitation from cardiac arrest and neurological outcome


The neurological outcome remains one of the biggest concerns in patients who have survived cardiac arrest. Despite many studies and clinical interventions to improve this, the number of patients with poor neurological recovery has not substantially changed over the past decades [1].

Since partial pressure of carbon dioxide (PaCO2) is well recognised to influence the cerebral blood flow, current guidelines on post-cardiac arrest patients’ care recommend maintaining normocapnia in order to avoid hypocapnia induced cerebral vasoconstriction with decreased blood flow, as well as hypercapnia induced cerebral vasodilatation with possible increase in intracranial volume and pressure.

Studies aiming at establishing optimal PaCO2 ranges have yielded inconsistent results so far, with one of the most recent published in ICM pointing towards possible positive effects of high to normal PaCO2 [2].

Kilgannon and colleagues [3] aimed to overcome the limitations of previous studies published by their group and others, particularly the arbitrary cut points defining PaCO2 ranges. They therefore designed a prospective protocol-directed study and analysed PaCO2 as a continuous variable associating it with neurological outcome.

Using a multi-centre approach, they included comatose adult post cardiac arrest patients after Return Of Spontaneous Circulation (ROSC), who were undergoing targeted temperature management. The protocol mandated an initial arterial blood gas one hour after ROSC and a second one six hours after ROSC. The primary outcome was good neurological function at hospital discharge, defined by modified Rankin Scale, and was analysed in relationship to mean pCO2 levels during the first six hours after ROSC.

A total of 280 patients were analysed, with 30% of them showing a good neurological function at discharge. PaCO2 had a quadratic or inverted U-shaped association with every 5 mmHg increase, showing a 50% increase in the probability of good neurological outcome, up to a PaCO2 of 68 mmHg. Further PaCO2 increases reduced the likelihood of good neurological function.

A subgroup analysis of patients with metabolic acidosis showed that the quadratic association of PaCO2 with good neurological outcome was still present, yet attenuated, i.e. the quadratic curve was shifted to the left, with a PaCO2 of 51 mmHg being the transition point. Probability of good neurological outcome also increased with decreasing arterial pH as long as this remained above 7.19.



This study measured PaCO2 as a continuous variable, rather than categories therefore being able to calculate the turning point. The investigators included sensitivity analyses testing for possible impact of co-variables, such as ventilation parameters and tested confounders, as well as controlled for severity of illness.

Limitations are the relatively short time period of only six hours post-ROSC analysed. During this time, patients might still have been outside the intensive care unit for diagnostics, i.e. catheter lab, and protocols for ventilation not necessarily applied. This might also explain the relatively high mean FiO2 of 0.82 they reported.

Further limitations include the fact that it is an observational study and that it was not designed to show a causative effect, but association only.



This study provides another hint that mild to moderate hypercapnia is associated with good neurological outcome after ROSC in cardiac arrest. However, whether targeting hypercapnia improves neurological outcome needs to be examined in randomised controlled trials.


This article review was prepared and submitted by Dr Martina Bürge, Senior Clinical Fellow, Barts Health NHS Trust, London, on behalf of the ESICM Journal Review Club.



1)  Myat A. et al. (2018). Out-of-hospital cardiac arrest: current concepts. The Lancet, 393(10124), 970-979.

2) Jakkula P. et al. (2018). Targeting low-normal or high-normal mean arterial pressure after cardiac arrest and resuscitation: a randomised pilot trial. Intensive Care Medicine, 44(12), 2091-2101

3) Kilgannon JH. et al. (2019). Partial pressure of arterial carbon dioxide after resuscitation from cardiac arrest and neurological outcome: A prospective multi-center protocol-directed cohort study. Resuscitation, 135, 212-220

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