Addition of terlipressin to initial volume resuscitation in a pediatric model of hemorrhagic shock improves hemodynamics and cerebral perfusion

Abstract

Hemorrhagic shock is one of the leading causes of mortality and morbidity in pediatric trauma. Current treatment based on volume resuscitation is associated to adverse effects, and it has been proposed that vasopressors may be used in the pharmacological management of trauma. Terlipressin has demonstrated its usefulness in other pediatric critical care scenarios and its long half-life allows its use as a bolus in an outpatient critical settings. The aim of this study was to analyze whether the addition of a dose of terlipressin to the initial volume expansion produces an improvement in hemodynamic and cerebral perfusion at early stages of hemorrhagic shock in an infant animal model. We conducted an experimental randomized animal study with 1-month old pigs. After 30 minutes of hypotension (mean arterial blood pressure [MAP]<45 mmHg) induced by the withdrawal of blood over 30 min, animals were randomized to receive either normal saline (NS) 30 mL/kg (n = 8) or a bolus of 20 mcg/kg of terlipressin plus 30 mL/kg of normal saline (TP) (n = 8). Global hemodynamic and cerebral monitoring parameters, brain damage markers and histology samples were compared. After controlled bleeding, significant decreases were observed in MAP, cardiac index (CI), central venous pressure, global end-diastolic volume index (GEDI), left cardiac output index, SvO 2 , intracranial pressure, carotid blood flow, bispectral index (BIS), cerebral perfusion pressure (CPP) and increases in systemic vascular resistance index, heart rate and lactate. After treatment, MAP, GEDI, CI, CPP and BIS remained significantly higher in the TP group. The addition of a dose of terlipressin to initial fluid resuscitation was associated with hemodynamic improvement, intracranial pressure maintenance and better cerebral perfusion, which would mean protection from ischemic injury. Brain monitoring through BIS was able to detect changes caused by hemorrhagic shock and treatment.

Characterization of cerebral blood flow during open cardiac massage in swine: Effect of volume status

“…The goal of initial trauma resuscitation should be to rescue the cardiopulmonary system but while doing so, preserve and protect the central nervous system. Cerebral perfusion is an important resuscitation endpoint to assess the neurological status of survivors ( van den Brule et al, 2018 ; Lorusso and Bělohlávek, 2020 ; Gil-Anton et al, 2020 ). Computed tomography perfusion (CTP) scanning offers a non-invasive method to assess for cerebral perfusion ( Abdou et al, 2021 ; Abdou et al, 2022 ).…”

Terlipressin combined with conservative fluid management attenuates hemorrhagic shock-induced acute kidney injury in rats

“…Terlipressin has been studied as a vasoactive drug for the management of catecholamine-resistant arterial hypotension in septic shock 46 , liver failure 25 , and acute gastrointestinal bleeding 26 . The effects of terlipressin consist of vasoconstrictor activity in vascular smooth muscle cells and pronounced vasoconstriction within the splanchnic circulation, having been shown to redistribute blood flow in order to restore perfusion pressure to organs such as the liver, kidneys, and brain 27 , as well as to increase survival rates in animal models of HS 47 . In the HS model employed in the present study, we found that treatment with terlipressin and conservative fluid management increased post-HS survival.…”

Terlipressin Attenuates Hemorrhagic Shock-Induced Acute Kidney Injury in Rats

“…Terlipressin has been studied as a vasoactive drug for the management of catecholamineresistant arterial hypotension in septic shock [46], liver failure [25], and acute gastrointestinal bleeding [26]. The effects of terlipressin consist of vasoconstrictor activity in vascular smooth muscle cells and pronounced vasoconstriction within the splanchnic circulation, having been shown to redistribute blood ow in order to restore perfusion pressure to organs such as the liver, kidneys, and brain [27], as well as to increase survival rates in animal models of HS [47]. In the HS model employed in the present study, we found that treatment with terlipressin increased post-HS survival.…”