Impact of environmental stressors on tolerance to hemorrhage in humans

Hemorrhage is a leading cause of death in military and civilian settings, and ~85% of potentially survivable battlefield deaths are hemorrhage-related. Soldiers and civilians are exposed to a number of environmental and physiological conditions that have the potential to alter tolerance to a hemorrhagic insult. The objective of this review is to summarize the known impact of commonly encountered environmental and physiological conditions on tolerance to hemorrhagic insult, primarily in humans. The majority of the studies used lower body negative pressure (LBNP) to simulate a hemorrhagic insult, although some studies employed incremental blood withdrawal. This review addresses, first, the use of LBNP as a model of hemorrhage-induced central hypovolemia and, then, the effects of the following conditions on tolerance to LBNP: passive and exercise-induced heat stress with and without hypohydration/dehydration, exposure to hypothermia, and exposure to altitude/hypoxia. An understanding of the effects of these environmental and physiological conditions on responses to a hemorrhagic challenge, including tolerance, can enable development and implementation of targeted strategies and interventions to reduce the impact of such conditions on tolerance to a hemorrhagic insult and, ultimately, improve survival from blood loss injuries.