Arterial oxygen and carbon dioxide tension and acute brain injury in extracorporeal cardiopulmonary resuscitation patients: Analysis of the extracorporeal life support organization registry

Abstract

Background: Acute brain injury (ABI) remains common after extracorporeal cardiopulmonary resuscitation (ECPR). Using a large international multicenter cohort, we investigated the impact of peri-cannulation arterial oxygen (PaO₂) and carbon dioxide (PaCO₂) on ABI occurrence.

Methods: We retrospectively analyzed adult (≥18 years old) ECPR patients in the Extracorporeal Life Support Organization registry from 1/2009 through 12/2020. Composite ABI included ischemic stroke, intracranial hemorrhage (ICH), seizures, and brain death. The registry collects 2 blood gas data pre- (6 hours) and post- (24 hours) cannulation. Blood gas parameters were classified as: hypoxia (<60mm Hg), normoxia (60-119mm Hg), and mild (120-199mm Hg), moderate (200-299mm Hg), and severe hyperoxia (≥300mm Hg); hypocarbia (<35mm Hg), normocarbia (35-44mm Hg), mild (45-54mm Hg) and severe hypercarbia (≥55mm Hg). Missing values were handled using multiple imputation. Multivariable logistic regression analysis was used to assess the relationship of PaO₂ and PaCO₂ with ABI.

Results: Of 3,125 patients with ECPR intervention (median age=58, 69% male), 488 (16%) experienced ABI (7% ischemic stroke; 3% ICH). In multivariable analysis, on-ECMO moderate (aOR=1.42, 95%CI: 1.02-1.97) and severe hyperoxia (aOR=1.59, 95%CI: 1.20-2.10) were associated with composite ABI. Additionally, severe hyperoxia was associated with ischemic stroke (aOR=1.63, 95%CI: 1.11-2.40), ICH (aOR=1.92, 95%CI: 1.08-3.40), and in-hospital mortality (aOR=1.58, 95%CI: 1.21-2.06). Mild hypercarbia pre-ECMO was protective of composite ABI (aOR=0.61, 95%CI: 0.44-0.84) and ischemic stroke (aOR=0.56, 95%CI: 0.35-0.89).

Conclusions: Early severe hyperoxia (≥300mm Hg) on ECMO was a significant risk factor for ABI and mortality. Careful consideration should be given in early oxygen delivery in ECPR patients who are at risk of reperfusion injury.

Keywords: ECPR; extracorporeal membrane oxygenation; neurological injury.

Figure 1.

Trends in the (a) utilization of extracorporeal cardiopulmonary resuscitation (ECPR) and incidence of acute brain injury (ABI), and (b) for the incidence of individual ABI types. Trends were assessed using Cuzick’s non-parametric trend test. Annual ECPR volume has increased (p-trend=0.003) while incidence of ABI has decreased (p-trend=0.023). Incidence of brain death decreased and ischemic stroke increased, while incidence of ICH and seizure have not changed over time.

Figure 2.

Histograms for (a) on-ECMO PaO₂ and (b) on-ECMO PaCO₂. Abbreviations – ECMO: extracorporeal membrane oxygenation.

Figure 3.

Forest plot for multivariable model of (a) acute brain injury (ABI), (c) ischemic stroke, and (c) intracranial hemorrhage (ICH). Dot represents adjusted odds ratio and brackets represent the 95% confidence intervals. Asterisks mark variables with a p<0.05.