Effects of terlipressin for mortality and abdominal bleeding in a severe uncontrolled hemorrhagic model of rat liver injury

STUDY OBJECTIVE:Hemorrhage is a common cause of mortality and morbidity for traumatic injury. However, the best fluid resuscitation strategy for uncontrolled hemorrhage has been unknown yet. The liver is the most commonly injured solid organ in blunt and penetrating injury. This study was designed to evaluate, the effects of terlipressin versus controlled fluid resuscitation on hemodynamic variables and abdominal bleeding in a rat model of uncontrolled hemorrhage from liver injury.METHODS:Twenty-one Wistar rats with average weights of 250±30gr were anesthetized with an uretan/chloralose (500mg/kg, 50mg/kg ip) in this study. Uncontrolled hemorrhagic experiments were initiated by creation of a standardized liver injury. A midline celiotomy was performed and approximately 65% of the median and left lateral lobes were removed with sharp dissection. No attempts for hemostasis were performed after the surgical procedure; abdominal cavity then was closed with stapler. After creation of the liver injury, rats were randomized to one of three resuscitation groups; the first group was the control group, in which terlipressin bolus dose equal to volume of saline placebo (500 µL) was given. The second group was LR group in which Lactated Ringer's solution bolus dose of 4 ml/kg was given after liver injury. The third group was Terlipressin group in which terlipressin was given in a bolus dose of 500 µL. Lactated Ringer's solution was given at an infusion rate of 2mL/kg/min in order to maintain a mean arterial blood pressure of 40 mmHg for the LR and Terlipressin groups. To all of the three groups, continuous supplemental LR infusion then was given for the next 75 minutes. Blood samples were taken from rats for arteriel blood gase analysis and determining serum lactate and Htc levels at 0, 30, and 90 minutes. At the end of the experiment, free intraperitoneal blood was collected on preweighed pieces of cotton, and the amount of free blood was determined by the difference in wet and dry weights.RESULTS:There were no differences between groups for MAP, heart rate, blood gases and lactat analysis, average weights and the percentage of liver excised at the preinjury time point. MAP decreased in all of the groups after the liver injury (p<0.001). In response to resuscitation, Terlipressin group demonstrated a significant elevation in MAP, averaged %190±61 approximately 4 minutes 30 seconds later. Blood loss was greater in the LR group compared with control group, there wasn?t any statistically significant difference between control and terlipressin groups (8.11±0.655mL, 12.76±1.927mL and 10.50±1.251mL; control group with RL and terlipressin groups respectively, p=0.041 and p=0.117). At the end of the study, 5 rats in control group, 5 rats in LR group and 2 rats in terlipressin group died, average survival times were 28.6%, 28.6% and 71.4%, respectively.CONCLUSION:IV terlipressin bolus after liver injury, contributed an increase at MAP and survival times without increasing abdominal bleeding compared with control group.KEY WORDS:Terlipressin, trauma, liver, hemorrhage