Effects of Ketamine on Cardiovascular and Respiratory Responses to a Moderate 40 Percent Hemorrhage in Rats

Abstract

BackgroundCurrently, ketamine is recommended for analgesic use on the battlefield for Soldiers with severe hemorrhage. However, there have been few human or animal studies to support such use. Because of the dearth of controlled experimental evidence for use of ketamine as an analgesic during hypovolemia, the following study was conducted to determine effects of an intravascular analgesic dose of ketamine on cardiovascular and respiratory responses to a 40% hemorrhage in conscious rats.MethodsRats were randomly assigned to one of four treatment groups: 1) sham trauma plus 0.9% saline (STS; n=8); 2) sham trauma plus 5 mg/kg ketamine in saline (0.5 mg/100 μl) (STK; n=8); 3) trauma plus saline (TS; n=8); and 4) trauma plus ketamine (TK, n=7). All rats (male; ~ 360 grams) were surgically implanted with a Data Sciences International (DSI)Telemetry Device for measuring mean arterial pressure (MAP) and heart rate(HR), and two weeks later underwent a second surgery to implant a carotidcatheter. Then 24 hours later, rats were anesthetized briefly to undergo soft tissue injury (crushing of the right gastrocnemius and semimembranosus muscles with a Kelly forceps) and fibula fracture or underwent anesthesia without trauma (sham). Rats were allowed to awaken, and 90 minutes later all rats underwent aconscious ~40% hemorrhage via the indwelling carotid catheter. Hemorrhages were conducted after rats were placed in a DSI whole‐body plethysmography chamber for measures of respiration. At the end of hemorrhage, rats received either saline or ketamine injection via the carotid catheter. Rats were observed for 3.5 hr after injection.ResultsBy design, all rats survived this hemorrhage. By the end of hemorrhage, MAP decreased comparably in all groups by 58% (P<.0001). Within 40 minutes after injections, MAP increased similarly in all groups to a level 18% below pre‐hemorrhage, basal levels(P<.001) and remained thusly for the experimental duration. HR also decreased by the end of hemorrhage(32%; P <.01), and in all groups recovered to basal levels (P >.10) within 2 hrs. Three hours post hemorrhage, HR in STK rats (416±18 bpm) exceeded that in STS rats (354±18 bpm; P =.021). Trauma appeared to affect respiration as minute volume (MV) increased 40% (P<.01) during hemorrhage in only TS and TK rats. After hemorrhage and injections, MV decreased (P<.05) within 10 min in all groups, and remained below basal levels thereafter. Ketamine had no consistent effects on MV after hemorrhage.ConclusionsAt the analgesic dose given – previously shown to ameliorate behavioral indices of pain in rats (Xiang, unpublished observations) – ketamine had no deleterious effects on measured cardiovascular and respiratory function for up to 3.5 hours after severe hemorrhage. Modest positive effects of ketamine appeared dependent on trauma status.Support or Funding InformationFunding by USAMRMCThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.