A Systematic Review and Meta-analysis of the Safety of the Apnea Test in Adults and the Case for Maintaining Positive Airway Pressure

Background/Objective: The apnea test is indispensable for determining brain death/death by neurologic criteria but may be aborted for hypoxemia or hemodynamic instability. We quantified its safety in adults and tested whether maintaining positive airway pressure, rather than tracheal insufflation, reduces the risk of an aborted test. Methods: Systematic review of five databases to July 2026 including studies of ≥10 apnea tests in adults with extractable safety outcomes. Proportions were pooled with a generalized linear mixed model with 95% prediction intervals (PI). In studies comparing techniques within the same center or patient, the odds of an aborted test with positive pressure versus insufflation were pooled with the Peto method. Results: Forty-six studies were included. In 24 studies (2774 tests) the test was aborted because of an adverse event in 4.56% (95% CI 2.85–6.71; PI 0.8–22.5%). Severe events were rare (<1%), with no cardiac arrest in 391 tests. In six within-study comparisons (one crossover, five cohorts), the test was aborted in 3 of 389 tests with positive pressure and 16 of 448 with insufflation (Peto OR 0.26, 95% CI 0.10–0.66; P = 0.004; I² = 0%; risk difference −2.9%), and hypoxemia occurred in 0 of 262 versus 14 of 363 (OR 0.13, 0.04–0.38) without loss of diagnostic performance. The effect persisted after excluding the crossover and the sequential-design study (OR 0.25, 0.08–0.77). Pre-test acidemia (pH ≤7.33), systolic pressure ≤105 mmHg and impaired oxygenation (alveolar–arterial gradient >556 mmHg) predicted failure. Conclusions: About 1 in 20 tests is aborted, but within-study comparisons consistently show an approximately fourfold lower risk when positive airway pressure is maintained; ventilator disconnection appears to be the principal modifiable determinant of failure. We propose a pre-test optimization and stratification pathway, with positive pressure as the default technique, for prospective validation. Evidence is observational and of low certainty.