Effects of arginine vasopressin during resuscitation from hemorrhagic hypotension after traumatic brain injury

Objective: Two series of experiments were designed to evaluate whether early arginine vasopressin improves acute outcome following resuscitation from traumatic brain injury and severe hemorrhagic hypotension Design: Prospective randomized, blinded animal study. Setting: University laboratory. Subjects: Thirty-three swine. Interventions: In series 1 (n = 19), after traumatic brain injury with hemorrhage and 12 mins of shock (mean arterial pressure ≈20 mm Hg), survivors (n = 16) were initially resuscitated with 10 mL/kg crystalloid. After 30 mins, crystalloid and blood with either 0.1 unit·kg ^-1·hr ^-1 arginine vasopressin or placebo was titrated to a mean arterial pressure target ≥60 mm Hg. After 90 mins, all received mannitol and the target was cerebral perfusion pressure ≥60 mm Hg. To test cerebrovascular function, 7.5% inhaled CO ₂ was administered periodically. In series 2 (n = 14), the identical protocol was followed except the shock period was 20 mins and survivors (n = 10) received a bolus of either arginine vasopressin (0.2 units/kg) or placebo during the initial fluid resuscitation. Measurements and Main Results: In series 1, by 300 mins after traumatic brain injury with arginine vasopressin (n = 8) vs. placebo (n = 8), the fluid and transfusion requirements were reduced (both p < .01), intracranial pressure was improved (11 ± 1 vs. 23 ± 2 mmHg; p < .0001), and the CO ₂-evoked intracranial pressure elevation was reduced (7 ± 2 vs. 26 ± 3 mm Hg, p < .001), suggesting improved compliance. In series 2, with arginine vasopressin vs. placebo, cerebral perfusion pressure was more rapidly corrected (p < .05). With arginine vasopressin, five of five animals survived 300 mins, whereas three of five placebo animals died. The survival time with placebo was 54 ± 4 mins (p < .05 vs. arginine vasopressin). Conclusions: Early supplemental arginine vasopressin rapidly corrected cerebral perfusion pressure, improved cerebrovascular compliance, and prevented circulatory collapse during fluid resuscitation of hemorrhagic shock after traumatic brain injury.