Effects of Analgesic Doses of Opioids on Cardiorespiratory Responses and Survival to Hemorrhage and Trauma in Rats.

Abstract

Opioids are used for analgesia but questions persist about their safety following traumatic hemorrhage. We investigated analgesic doses of three opioids (morphine, fentanyl and sufentanil) on cardiorespiratory responses and survival to moderate or severe (37 and 50% blood volume) hemorrhage after trauma. A conscious hemorrhage model with extremity trauma (fibular fracture + soft tissue injury) was used; mean arterial pressure (MAP) and heart rate (HR) were measured by telemetry while minute volume (MV) was determined by whole body plethysmography. Male rats (n=10/group) received saline, morphine (2 mg/kg), fentanyl (10 µg/kg) or sufentanil (1 µg/kg) after traumatic hemorrhage. Neither survival times (for 37% hemorrhage: P=0.209; for 50% hemorrhage: P=0.88) nor survival percentages (for 37% hemorrhage: P=0.357; for 50% hemorrhage: P=1.0) differed among groups. For 37% hemorrhage, MAP of all opioid groups was higher than the saline-treated group 10 min post-injection. By 75 min post-injection, MAP after sufentanil was higher than saline; MAP for other opioids did not differ from saline. HR did not differ across treatments. Opioid injection decreased MV within 10 min but did not vary by treatment subsequently. For 50% hemorrhage, opioid injection did not immediately alter MAP but morphine and sufentanil were lower than saline at ≥75 min post-injection, with no treatment effects on HR. Fentanyl produced an immediate (5 min) decrease in MV with no treatment effects thereafter. Opioid effects on cardiorespiratory function were therefore modest and did not alter survival during a 4 hr observation period, supporting the judicious use of analgesic doses following traumatic hemorrhage.