Scrutinizing Randomized Controlled Trials and Their Outcomes

Reference: Ye et al. Preoxygenation strategies before intubation in patients with acute hypoxic respiratory failure: a network meta-analysis. Frontiers in Medicine. 2025 Feb Date: June 12, 2025 Guest Skeptic:  Dr. Aine Yore is an Emergency Physician, practicing in the Seattle, Washington area for over twenty years. She is the former president of the Washington chapter of ACEP, and her career focus outside of clinical practice has been largely devoted to health care policy. Case: A 68-year-old woman presents in acute respiratory distress. She is febrile, hypoxemic, and meets criteria for sepsis. A chest x-ray reveals multilobar pneumonia. After managing her sepsis, her oxygenation remains poor, with saturations in the 88-92% range despite supplemental oxygen via a nonrebreather mask, and she now shows signs of worsening fatigue. You determine she requires endotracheal intubation, but note that she is at high risk for peri-intubation complications or even death, and wonder if there is a strategy you can utilize to reduce this risk? Background: Acute hypoxic respiratory failure (AHRF) represents a life-threatening emergency where pulmonary gas exchange becomes insufficient to maintain adequate oxygenation. It commonly arises from a variety of conditions, including pneumonia, acute respiratory distress syndrome (ARDS), sepsis, and exacerbations of chronic lung disease (ex, chronic obstructive lung disease). In such patients, intubation is often required, but the procedure itself introduces additional risk. Nearly 25% of patients undergoing emergency intubation in the context of AHRF experience profound desaturation (SpO₂ < 80%) during the procedure. Preoxygenation is a cornerstone of airway management, designed to extend the “safe apnea time” by denitrogenating the lungs and optimizing oxygen reservoirs. The aim is to minimize peri-intubation hypoxia, which is a known predictor of morbidity and mortality. Commonly used pre-oxygenation strategies include: Conventional oxygen therapy (COT), such as non-rebreather masks. High-flow nasal cannula (HFNC) provides warmed, humidified oxygen at high flow rates and can generate low levels of positive end-expiratory pressure (PEEP). Non-invasive ventilation (NIV) provides pressure support to enhance alveolar ventilation and decrease the work of breathing. Combinations of strategies like HFNC with NIV or bag-valve mask. Despite the widespread use of these techniques, clinical uncertainty persists regarding the most effective and safest strategy for preoxygenation in AHRF. This knowledge gap has led to multiple randomized controlled trials (RCTs) on the subject. Clinical Question: What is the optimal pre-oxygenation strategy in patients requiring intubation for acute hypoxic respiratory failure? Reference: Ye et al. Preoxygenation strategies before intubation in patients with acute hypoxic respiratory failure: a network meta-analysis. Frontiers in Medicine. 2025 Feb Population: Adults with AHRF defined as a respiratory rate >30/min, FiO₂ requirement ≥50% to maintain SpO₂ ≥90%, or PaO₂/FiO₂ < 300 mmHg within four hours of enrollment. Exclusions: Studies involving reviews, conference abstracts, case reports, or lacking full text. Intervention: Pre-oxygenation with Noninvasive Mechanical Ventilation, High Flow Oxygen via Nasal Cannula, or some combination of the above. Comparison: Conventional oxygen therapy (COT) or other preoxygenation. strategies. Outcome: There was no primary outcome explicitly stated. Outcomes included incidence of desaturation (SpO₂ < 80%) during intubation, lowest SpO2 during intubation, post-intubation complication rate, intensive care unit (ICU) length of stay (LOS) and ICU Mortality Type of Study: Network Meta-Analysis (NMA) Authors’ Conclusions: “Preoxygenation with HFNC appears to be the safest and most effective approach prior to intubation in patients with AHRF compared to other str...