Effects of Opioid Analgesics (Morphine, Fentanyl, and Sufentanil) and Trauma on Survival Time after Severe Conscious Hemorrhage in Rats

Abstract

BackgroundCurrently, opioid analgesics are not recommended for use on the battlefield for Soldiers with severe hemorrhage, although they are still used during such situations (Schauer et al., Prehosp Emerg Care 21: 744, 2017). Moreover, there have been few or no controlled, preclinical studies conducted using analgesic doses of fentanyl or sufentanil to support these guidelines. The current study was conducted to evaluate and compare effects of three opioid analgesics on survival after severe hemorrhage in conscious rats in the absence or presence of extremity trauma. We hypothesized that opioid drugs and trauma would both decrease survival time to severe hemorrhage.MethodsRats were randomly assigned to receive either 0.9% saline (S), 2.0 mg/kg morphine (M; 0.2 mg/100 μl), 10μg/kg fentanyl (F; 1 μg/100 μl) or 1μg/kg sufentanil (SuF; 0.1μg/100 μl). All rats (male; ~ 380grams) were surgically implanted with a carotid catheter. After 24 hours, rats were anesthetized briefly (10 min) to undergo soft tissue injury (crushing of the right gastrocnemius and semimembranosus muscles for 30 sec with forceps) and fibula fracture (T). Non‐trauma rats (NT) were anesthetized for 10 min only. Rats were allowed to awaken, and 90 min later underwent a conscious hemorrhage (~55% of blood volume) via the indwelling carotid catheter. At the end of hemorrhage, rats received either S, M, F, or SuF via the carotid catheter. Rats were observed for a maximum of 4 hr after the start of the 25 min hemorrhage.ResultsWithin each trauma group, neither survival times (p > 0.51) nor percent survival (p > 0.55) differed among treatment groups (Table 1). However, when combined across all treatment groups, T rats had a shorter (p = 0.013) survival time (137 min, SD 81, n = 24) and lower percent survival (33.3%; p = 0.02) than did NT rats (196 min, SD 72, n=23, 69.6%).ConclusionsAt the analgesic doses given–previously shown to ameliorate behavioral indices of pain in rats (Xiang, J Trauma Acute care Surg 85: S49, 2018) –opioid drugs tested did not affect survival after severe hemorrhage. Exacerbating effects of extremity trauma on survival after hemorrhage in our rat model portend the need for rapid treatment of patients with traumatic injury accompanied by hemorrhage.Support or Funding InformationFunding for this project was provided by the US Army CRMRP, JPC8, Applied Pain Research Programs, and USAMRMC.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.