Intramuscular Terlipressin as Monotherapy for Early Management of Uncontrolled Traumatic Hemorrhagic Shock: A Preliminary Study.

Abstract: Monotherapy using a single-dose vasopressor to maintain essential organ perfusion could be a viable alternative to restrictive fluid resuscitation in uncontrolled traumatic hemorrhagic shock (UTHS). This study evaluated the impact of intramuscular terlipressin on hemodynamics and organ injuries in UTHS. Adult male Sprague-Dawley rats, with eight rats in each group, were assigned to six distinct groups. Immediately after randomization, the rats in each group were exposed or not exposed to specific interventions over a 60-minute period, as follow: Sham, Shock, intramuscular terlipressin (5 μg/100 g), intravenous terlipressin (10 μg/100 g), normal saline (1.5 ml/100 g), and norepinephrine (0.3 μg/kg/min). The UTHS model was created by midline laparotomy, femoral artery bleeding, and tail amputation. After surgical hemostasis, resuscitated rats had a one-hour infusion of lost blood. Invasive blood pressure comparations and organ injury assessments were performed. Mean arterial pressure was increased starting 8 minutes post-intramuscular injection of terlipressin. The systemic perfusion pressure from intramuscular terlipressin was notably higher than that from normal saline and norepinephrine after 40 and 70 minutes, respectively. In comparison with rats treated with normal saline and norepinephrine, those receiving intramuscular terlipressin demonstrated improvements in biomarkers related to microcirculation dysfunction. Although there were no significant differences in multi-organ function markers among the groups, intramuscular terlipressin led to improvements in the pathological injury scores of the muscle, intestine, and kidney. Collectively, intramuscular administration of terlipressin improved early hemodynamics and multi-organ pathological injuries post-UTHS. Future investigations are warranted to elucidate the molecular mechanisms underpinning the protective effects of this treatment.