Preoxygenation When Standard Approaches Fail: Phenotype-Based Strategies for High-Risk Emergent Intubations

Emergent tracheal intubation in critically ill patients is a common, yet high-risk, intervention. It is frequently complicated by peri-intubation hypoxemia, hemodynamic instability, and metabolic derangements that increase the risk of arrhythmias, hypotension, cardiac arrest, and death. Because the highest-risk interval often occurs in the minutes surrounding induction, when apnea, derecruitment, and abrupt cardiopulmonary shifts converge, oxygenation failure frequently reflects a mismatch between preoxygenation strategy and the underlying physiology rather than inadequate oxygen delivery alone. This review proposes a phenotype-based approach to peri-intubation oxygenation and focuses on four high-risk phenotypes in whom standard preoxygenation strategies commonly fail: obesity, neuromuscular disease, right ventricular dysfunction or pulmonary hypertension, and post-operative respiratory failure with altered respiratory mechanics or airway anatomy. We summarize the key mechanisms that shorten safe apnea time, including reduced functional residual capacity, intrapulmonary shunt, elevated oxygen consumption, rapid derecruitment after induction, and impaired oxygenation–hemodynamics coupling. We then compare preoxygenation modalities as physiologic tools, including facemask oxygen, high-flow nasal cannula (HFNC), noninvasive ventilation (NIV), and controlled bag-mask ventilation (BMV), and integrate contemporary randomized trial evidence that informs bedside selection and combination of these approaches. Finally, we synthesize these concepts into a practical, physiology-informed framework to guide clinicians in choosing and troubleshooting preoxygenation strategies in high-risk patients undergoing emergent intubation.