Hemorrhage is the leading cause of battlefield and civilian trauma deaths. Given that a hemorrhagic injury on the battlefield is usually associated with pain, it is paramount that the administered analgesic does not disrupt the physiological mechanisms that are beneficial towards the maintenance of blood pressure and vital organ blood perfusion during that hemorrhagic insult. Current guidelines from the US Army‘s Committee on Tactical Combat Casualty Care (CoTCCC) for the selection of pain medications administered to a hemorrhaging soldier are based upon limited scientific evidence, with the majority of supporting studies being conducted on anesthetized animals. Specifically, the influence of fentanyl, one of three analgesics employed in the pre-hospital setting by the US Army, on hemorrhagic tolerance in humans is entirely unknown.

Purpose: The aim of this study is to test the hypothesis that fentanyl impairs the capacity for a conscious human to tolerate a simulated hemorrhagic insult.Methods: Fourteen subjects (8 females, 27±7 years old, 173±9 cm, 77±12 kg) participated in this double-blinded, randomized, placebo-controlled crossover investigation. Following intravenous administration of fentanyl (75 µg —consistent with the US Army‘s CoTCCC guidelines) or placebo (saline), tolerance to a simulated hemorrhage was performed using a progressive lower-body negative pressure (LBNP) protocol to pre-syncope. Tolerance was quantified as a cumulative stress index (CSI), which is the sum of products of the LBNP stage and the duration at that stage [e.g., (40 mmHg•3 min) + (50 mmHg•3 min) ⋯]. Results: Mean tolerance to the simulated hemorrhagic challenge was not different between the fentanyl and placebo trials (CSI: 585±406 mmHg•min and 626±267 mmHg•min respectively, P=0.67).
Conclusions: These data, the first to be obtained in conscious humans, demonstrate that administration of the US Army‘s CoTCCC recommended dose of fentanyl does not compromise tolerance to a simulated hemorrhagic insult. These findings may be insightful in choosing the most suitable analgesic medication in the pre-hospital setting during a hemorrhagic injury.