Analgesics in the Pre‐Hospital Setting: Simulated Hemorrhagic Tolerance in Humans is not Impaired by Ketamine Administration

Abstract

Hemorrhage is the leading cause of battlefield and civilian trauma deaths. Given that a hemorrhagic injury on the battlefield is virtually always associated with pain, it is paramount that the administered pain medication does not disrupt the physiological mechanisms that are beneficial towards the maintenance of blood pressure and vital organ blood flow 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 clear majority of supporting studies being conducted on anesthetized animals. Specifically, the influence of ketamine, one of three analgesics employed in the pre‐hospital setting by the US Army, on hemorrhagic tolerance in humans is entirely unknown. Thus, the purpose of this study is to test the hypothesis that ketamine will impair the capacity for a conscious human to tolerate a simulated hemorrhagic insult. Twelve subjects (4 females, 29±7 years old, 181±6 cm, 84±10 kg) participated in this double‐blinded, randomized, placebo‐controlled investigation. Tolerance to a simulated hemorrhage was performed using a progressive lower body negative pressure (LBNP) protocol to pre‐syncope following intravenous administration of Ketamine (20 mg—consistent with the US Army's CoTCCC guidelines) or placebo (saline). Tolerance was quantified as a cumulative stress index (CSI, mmHg•min). Tolerance to the LBNP challenge was not different between the ketamine and placebo trials (CSI: 746±368 mmHg•min and 795±316 mmHg•min respectively, P=0.61). These data, the first to be obtained in conscious humans, demonstrate that administration of ketamine 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 insult.Support or Funding InformationFunding: Department of Defense – US Army, W81XWH1820012This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.