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Physiologic parameters at high altitudes vary from those at sea level. An understanding of flight and altitude physiology is essential to prevent pre-hospital fight-induced barotrauma. Boyle’s law explains that “the volume of a gas is inversely proportional to the pressure to which it is subjected.” Based on this law, pressure decreases with increased altitude, thereby causing an increase in the volume of gas.  These changes are demonstrated by the fact that atmospheric pressure at 10000 feet is 10.1 pounds per square inch (psi) (68 kPa), compared to 14.7 psi (101 kPa) at ground level.[1] These physiological factors affect both helicopter pre-hospital transport and aeromedical airplane transport. Federal regulations, such as those promulgated by the FAA, require cabin pressure to be below atmospheric pressure equal to the pressure at 8000 feet above sea level.[2][3] This setting is possible through in-cabin pressurization, thereby decreasing barotraumatic risks that would be in effect at higher altitudes. Fortunately, acceptable cabin altitude levels, or the atmospheric height experienced inside a flight cabin, have been safely increased over time due to aircraft and technologic improvements. [2] Another physiological factor that changes with altitude is the decrease in the partial pressure of oxygen as height above sea level increases; this leads to a reduction in FiO2 (fraction of inspired oxygen) at a higher altitude compared to sea level.  One report demonstrated a decrease of 32 mm Hg, from 159 at sea level to 127 at the height of 6200 feet.[4] In-flight hypoxia as altitude increases can have a marked clinical significance in the transport of the critically ill. Additional physiological factors of high altitude transport, the details of which are beyond the scope of this discussion, include decreasing temperatures, dehydration, and gravitational forces. A typical helicopter pre-hospital transport reaches altitudes of 1000 to 3500 feet above ground level, while airplane transport typically transports at altitudes of 10000 to 40000 ft above sea level. An understanding of flight physiology is essential, as even an increase of 1000 to 1500 feet above sea level can cause gas expansion leading to clinical significance in the critically ill.[1]