Mild Hypercapnia in Coma Patients Following Out-of-Hospital Cardiac Arrest

Targeted mild hypercapnia, compared with targeted normocapnia, does not improve neurologic outcomes at 6 months in patients with coma resuscitated after out-of-hospital cardiac arrest, according to findings published in The New England Journal of Medicine.

Researchers aimed to assess if targeted mild hypercapnia (partial pressure of arterial carbon dioxide [Paco₂], 50-55 mm Hg) vs targeted normocapnia (Paco₂, 35-45 mm Hg) would improve neurologic outcomes at 6 months in adults with coma who had been resuscitated after out-of-hospital cardiac arrest. Favorable neurologic outcome at 6 months was the primary outcome. Death within 6 months was the secondary outcome. Favorable neurologic outcome was defined as a score of at least 5/8 (1=death; 8=the best neurologic outcome) using the Glasgow Outcome Scale-Extended.

The researchers conducted the TAME  (Targeted Therapeutic Mild Hypercapnia After Resuscitated Cardiac Arrest; ClinicalTrials.gov Identifier: NCT03114033) trial, which included 1700 patients from 63 intensive care units (ICUs) in 17 countries. Patients had coma and were at least 18 years of age. Patients resuscitated after out-of-hospital cardiac arrest with sustained return of spontaneous circulation for at least 20 minutes without chest compressions were randomly assigned in a 1:1 ratio to either 24 hours of targeted mild hypercapnia (n=847) beginning at randomization, or to targeted normocapnia (n=853). Patients with greater than 180 minutes between the return to spontaneous circulation and screening were excluded. At the time of randomization, PaCO₂ values were similar between groups.

Patients were predominantly middle-aged men with histories of hypertension (33.8%), diabetes (17.9%), or percutaneous coronary intervention (14.0%). Cardiac arrest occurred either in residence or public, with 88.1% witnessed by a bystander and 80.5% with a bystander who performed CPR. Median time from cardiac arrest to randomization was 151 minutes.

Assessors of prognosis and neurologic outcome were not aware of the intervention assignment nor were study authors during data analysis, however attending clinicians were aware. Data was missing for 7.6% of patients.

Researchers found that 332 of 764 patients in the mild hypercapnia group and 350 of 784 patients in the normocapnia group achieved a favorable neurologic outcome at 6 months (relative risk [RR], 0.98; 95% CI, 0.87-1.11; P =.76).

After randomization, death within 6 months occurred in 393 of 816 patients in the mild hypercapnia group and in 382 of 832 patients in the normocapnia group (RR, 1.05; 95% CI, 0.94-1.16). Researchers found no significant between-group differences in death due to cerebral causes or incidence of death before neurologic prognostication.

No significant between-group differences were found in the incidence of adverse events, and mild hypercapnia did not increase the incidence of adverse events.

Results suggest targeted mild hypercapnia did not improve neurologic outcomes at 6 months in this patient population, and greater understanding of the effect of PaCO₂ on cerebrovascular control is necessary.

Study limitations include lack of blinding of emergency department and ICU staff members to intervention assignments, and hypercapnia was common at randomization possibly attenuating between-group differences.

“In patients with coma who were resuscitated after out-of-hospital cardiac arrest, targeted mild hypercapnia did not lead to better neurologic outcomes at 6 months than targeted normocapnia,” the researchers wrote. Researchers added that targeted mild hypercapnia did not improve the risk of death within 6 months, or health-related quality of life.