July 6, 2023
Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest
What was the research question (PICO format)?
Population: Adults with coma who had been resuscitated after out-of-hospital cardiac arrest.
Intervention: Targeted mild hypercapnia (Paco2, 50 to 55 mm Hg) for 24 hours.
Comparison: Targeted normocapnia (Paco2, 35 to 45 mm Hg) for 24 hours.
Outcome: The primary outcome was a favorable neurologic outcome at 6 months, assessed using the Glasgow Outcome Scale–Extended (GOS-E). Secondary outcomes included death within 6 months.
How did they do it?
The trial randomly assigned 1700 patients from 63 ICUs in 17 countries to either the targeted mild hypercapnia group woth (n=847) or the targeted normocapnia group (n=853).
The primary outcome was a favorable neurologic outcome (GOS-E score of 5 or higher) at 6 months. Secondary outcomes included death within 6 months.
What did they find?
The trial found that a favorable neurologic outcome at 6 months occurred in 43.5% of patients in the mild hypercapnia group and 44.6% in the normocapnia group.
The relative risk of a favorable neurologic outcome between the two groups was 0.98 (95% CI, 0.87 to 1.11; P=0.76), indicating no significant difference in neurologic outcomes.
Death within 6 months occurred in 48.2% of patients in the mild hypercapnia group and 45.9% in the normocapnia group, with a relative risk of 1.05 (95% CI, 0.94 to 1.16), again showing no significant difference.
The incidence of adverse events did not differ significantly between the two groups.
What are the limitations of the study?
Emergency department and ICU staff members were aware of the intervention assignments, potentially introducing bias.
Concomitant care was not fully specified in the protocol, which may have influenced outcomes.
Hypercapnia was common at randomization, possibly attenuating the difference between groups.
The trial included only patients with out-of-hospital cardiac arrest of presumed cardiac or unknown cause, limiting generalizability to other cardiac arrest causes.
Follow-up challenges during the pandemic resulted in missing data on the primary outcome for some patients.
What doe it mean?
The trial suggests that early mild hypercapnia is unlikely to induce clinically relevant improvement in cerebral blood flow to improve outcomes.
The findings complement other trials targeting physiological interventions in post-cardiac arrest patients.
It is recommended to continue following existing guidelines that recommend normocapnia for adults with coma after out-of-hospital cardiac arrest, as mild hypercapnia did not improve neurologic outcomes in this study.
Overall, the trial shows that targeted mild hypercapnia does not provide any additional benefit in terms of neurologic outcomes or mortality compared to targeted normocapnia for patients with coma after out-of-hospital cardiac arrest. The findings suggest that the use of mild hypercapnia should not be routinely adopted in this patient population.