Comprehensive Summary
This health economic evaluation examined whether maintaining mild hypercapnia after out-of-hospital cardiac arrest (OHCA) is cost-effective compared with maintaining normocapnia. Using data from the large multinational TAME randomized controlled trial, the analysis included 1,586 patients treated across 63 intensive care units in 17 countries. The primary outcome was cost per quality-adjusted life-year (QALY), derived from healthcare costs and patient-reported quality-of-life scores six months after the arrest. The study found no significant difference in cost-effectiveness between mild hypercapnia and normocapnia at the commonly used $50,000 per QALY willingness-to-pay threshold. The estimates were highly imprecise, with wide confidence intervals spanning both cost savings and increased costs. Subgroup and sensitivity analyses, including 24-month follow-up data from New Zealand, reinforced the substantial uncertainty around the economic benefit of mild hypercapnia. Although probabilistic analyses suggested a greater than 60% chance that mild hypercapnia could be cost-effective at very high willingness-to-pay thresholds, this did not translate into a clear economic advantage. Overall, the results remained too uncertain to support routine adoption based on cost considerations.
Outcomes and Implications
Out-of-hospital cardiac arrest is associated with high mortality, substantial long-term disability, and significant healthcare costs, making even small improvements in neurologic outcomes or resource use clinically meaningful. Although the TAME trial showed no clinical benefit of mild hypercapnia over normocapnia, its low implementation cost made it an important candidate for economic evaluation. This study found that mild hypercapnia does not provide a reliable cost-effectiveness advantage within six months, and its estimated economic impact is highly uncertain due to wide confidence intervals and inconsistent findings across sensitivity analyses. While the intervention is simple and inexpensive to apply in the ICU, the absence of demonstrable improvements in survival, neurologic recovery, or cost savings means it cannot be recommended as a routine post-resuscitation strategy at this time. Future large-scale and long-term studies may help clarify whether specific patient subgroups could derive economic or clinical benefit, but until then, maintaining normocapnia remains the standard of care for targeted temperature and ventilation management after OHCA.