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Emergency medical service (EMS) providers initiate care for critical patients in precarious environments daily. Gas- and fire-related accidents are especially complex and require careful management considerations to optimize patient care. In particular, asphyxiation from gas and smoke exposure poses a significant threat to both patient and provider safety. Inhalation injuries are easy to overlook and complicate burns in approximately 10% to 20% of patients.[1][2][3][4] Smoke is a heterogeneous mixture of compounds and has deleterious effects on the body via 4 separate mechanisms. Simple asphyxiants such as carbon dioxide and methane cause hypoxia by displacing oxygen in the lungs and lowering inspiratory oxygen concentrations. Chemical irritants such as hydrochloric acid, ammonia, and formaldehyde interact directly with mucous membranes and cause direct injury to the eyes and respiratory tract. Furthermore, physical exposure to heat causes direct thermal mucosal injury, and the deposition of particulate matter, such as soot or debris, may impair proper gas exchange in the alveoli. Lastly, chemical asphyxiants such as carbon monoxide (CO) and cyanide (CN) produce systemic ischemia and metabolic acidosis by interfering with mitochondrial oxidative phosphorylation. CO and CN gas may be the most insidious of these destructive mechanisms. These 2 gases are lethal byproducts of combustion and increase short-term mortality rates by 30% to 50% when there is concomitant exposure. Thus, it is imperative for EMS to quickly identify patients at increased risk for asphyxiation and initiate prompt life-saving interventions.