Personalizing Peri-Intubation Oxygenation in Patients at Risk of Acute Hypoxemic Respiratory Failure: A Phenotype-Driven Narrative Review of High-Flow Nasal Oxygen and Non-Invasive Ventilation.

Tracheal intubation in patients at risk of acute hypoxemic respiratory failure (AHRF) carries a high risk of life-threatening desaturation, and the choice of peri-intubation oxygenation strategy critically influences patient safety. This narrative review synthesizes current evidence on non-invasive oxygenation techniques-high-flow nasal oxygen (HFNO), non-invasive ventilation (NIV), and their combination-across the pre-oxygenation, apneic, and awake-intubation phases of airway management. We examine the physiological mechanisms underlying each modality, appraise landmark randomized trials and meta-analyses (including PREOXI, OPTINIV, and OPTIMASK), and address disease-specific considerations in chronic obstructive pulmonary disease, heart failure, interstitial lung disease, severe obesity, obstructive sleep apnea, and obstetric, pediatric, and trauma populations. The evidence supports a phenotype-driven hierarchy rather than a single dominant technique: NIV-optionally combined with HFNO for apneic oxygenation-is preferred in severely hypoxemic critically ill patients, whereas HFNO alone is adequate for many moderately hypoxemic or non-hypoxemic patients. Progressive hypercapnia limits apneic oxygenation, particularly in chronic CO2 retainers, underscoring the value of continuous CO2 monitoring. Persistent under-implementation of NIV-based pre-oxygenation reveals a gap between evidence and practice. Individualized, physiology-guided oxygenation-aligned with the goals of personalized peri-procedural medicine-offers the greatest potential to reduce peri-intubation morbidity.