The Challenges of Surrogate Outcomes in Clinical Trials

Reference: Gibbs et al. Noninvasive Ventilation for Preoxygenation during Emergency Intubation (The PREOXI trial). NEJM June 2024. Date: July 17, 2024 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 70-year-old man presents to the emergency department (ED) with an exacerbation of COPD. He is hypoxic on arrival with an oxygen saturation of 80% on room air. Although his oxygenation improves to 92% with supplemental oxygen by nasal cannula, he desaturates with minimal exertion and shows increasing fatigue indicating a need for greater respiratory support. He refuses non-invasive mechanical ventilation, as he has not tolerated it in the past, but is agreeable to intubation. His wife, who has been watching the monitors intently, says she is worried. “His oxygen levels keep dropping. How will you intubate him without them going too low?” Background: Preoxygenation is a critical step in the management of airway interventions, especially in critically ill patients undergoing tracheal intubation. This process involves the administration of supplemental oxygen before the induction of anesthesia to increase the oxygen reserves in the lungs, thereby reducing the risk of hypoxemia. Hypoxemia during intubation can lead to severe complications, including dysrhythmia, cardiovascular collapse, hypoxic brain injury, and death. Therefore, effective preoxygenation is essential to enhance patient safety during this high-risk procedure. Traditionally, preoxygenation has been achieved using an oxygen mask, which can deliver a high fraction of inspired oxygen (FiO2) under ideal conditions. However, oxygen masks have limitations. They do not provide positive pressure or ventilatory support, and the actual FiO2 delivered can be significantly lower than expected if the mask does not fit well. This can be particularly problematic in critically ill patients, who often present with compromised respiratory function and may not tolerate the procedure well. An alternative method of preoxygenation is the use of non-invasive ventilation (NIV), which includes devices like continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BiPAP). NIV offers several advantages over traditional oxygen masks. It delivers a high FiO2 and provides positive pressure support, which can help maintain airway patency and improve ventilation. This is particularly beneficial for patients who are critically ill, and the risk of desaturation is high. Despite its advantages, the use of NIV for preoxygenation is not without challenges. It requires more time to set up and may increase the risk of aspiration in certain patient populations. Recent studies have explored the efficacy of NIV compared to traditional oxygen masks in critically ill patients. The findings suggest that NIV significantly reduces the incidence of hypoxemia during intubation. These results are promising and may influence future guidelines and clinical practices, emphasizing the importance of optimizing preoxygenation strategies to improve outcomes in critically ill patients. However, the optimal preoxygenation strategy to reduce the risk of hypoxemia and potential harm from it has not yet been determined. Clinical Question: Among critically ill adults undergoing tracheal intubation, will preoxygenation with non-invasive positive pressure ventilation reduce the incidence of hypoxemia between induction to two minutes after tracheal intubation, compared to preoxygenation with facemask oxygen? Reference: Gibbs et al. Noninvasive Ventilation for Preoxygenation during Emergency Intubation (The PREOXI trial). NEJM June 2024. Population: Critically ill adults (18 years and older) undergoing tracheal intubation with a laryngoscope a...