Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest

N Engl J Med. 2023 Jul 6;389(1):45-57. doi: 10.1056/NEJMoa2214552. Epub 2023 Jun 15.


Background: Guidelines recommend normocapnia for adults with coma who are resuscitated after out-of-hospital cardiac arrest. However, mild hypercapnia increases cerebral blood flow and may improve neurologic outcomes.

Methods: We randomly assigned adults with coma who had been resuscitated after out-of-hospital cardiac arrest of presumed cardiac or unknown cause and admitted to the intensive care unit (ICU) in a 1:1 ratio to either 24 hours of mild hypercapnia (target partial pressure of arterial carbon dioxide [Paco2], 50 to 55 mm Hg) or normocapnia (target Paco2, 35 to 45 mm Hg). The primary outcome was a favorable neurologic outcome, defined as a score of 5 (indicating lower moderate disability) or higher, as assessed with the use of the Glasgow Outcome Scale-Extended (range, 1 [death] to 8, with higher scores indicating better neurologic outcome) at 6 months. Secondary outcomes included death within 6 months.

Results: A total of 1700 patients from 63 ICUs in 17 countries were recruited, with 847 patients assigned to targeted mild hypercapnia and 853 to targeted normocapnia. A favorable neurologic outcome at 6 months occurred in 332 of 764 patients (43.5%) in the mild hypercapnia group and in 350 of 784 (44.6%) in the normocapnia group (relative risk, 0.98; 95% confidence interval [CI], 0.87 to 1.11; P = 0.76). Death within 6 months after randomization occurred in 393 of 816 patients (48.2%) in the mild hypercapnia group and in 382 of 832 (45.9%) in the normocapnia group (relative risk, 1.05; 95% CI, 0.94 to 1.16). The incidence of adverse events did not differ significantly between groups.

Conclusions: 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. (Funded by the National Health and Medical Research Council of Australia and others; TAME number, NCT03114033.).

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Carbon Dioxide / blood
  • Cardiopulmonary Resuscitation*
  • Coma* / blood
  • Coma* / etiology
  • Critical Care
  • Hospitalization
  • Humans
  • Hypercapnia* / blood
  • Hypercapnia* / etiology
  • Out-of-Hospital Cardiac Arrest* / blood
  • Out-of-Hospital Cardiac Arrest* / complications
  • Out-of-Hospital Cardiac Arrest* / therapy


  • Carbon Dioxide

Associated data