Flight Stressors: Pathophysiological Principles Guiding Safe Fixed-Wing Aeromedical Transport of Critically Ill Patients

International travel increases the chance of patients requiring aeromedical evacuation due to unexpected medical emergencies or worsening chronic medical conditions. Although critically ill patients are exclusively managed by specialized teams, all medics manage patients who may require air transfer after stabilization and first-tier management. These patients may face unpredictable and potentially harmful conditions at high altitudes. The aim of this study is to highlight in-flight factors that may negatively affect patients' well-being en route, providing useful information for all medics. A comprehensive literature search was conducted on PubMed and Google Scholar, up to March 2025, employing a multimethod approach to identify all relevant studies for this review. The search continued until no new citations emerged. Basic principles of physics are applied to clinical situations, demonstrating the relationship among pressure, volume, and temperature, which might affect pathophysiological processes of the human body under certain circumstances. Unique flight stressors, including the hypobaric aeronautical environment, thermal stress, gravitational forces, vibration, and noise, may adversely affect patients' health. In-flight hypoxia is the most important risk during air transfer. Other hazardous conditions include the tendency for increased risk of thromboembolic events, as well as the potential for gas embolism, gas expansion in normally pneumatized body cavities, and malfunction of pneumatically operated medical devices. Even small amounts of trapped gas can lead to serious complications. This narrative review provides valuable information regarding in-flight stressors and experiences that physicians must be aware of and predict for safe aeromedical evacuation of critically ill patients.