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

PLoS One. 2020 Jul 2;15(7):e0235084. doi: 10.1371/journal.pone.0235084. eCollection 2020.

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, SvO2, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cerebrovascular Circulation / drug effects
  • Disease Models, Animal
  • Fluid Therapy
  • Hemodynamics / drug effects*
  • Male
  • Resuscitation
  • Saline Solution / therapeutic use*
  • Shock, Hemorrhagic / blood
  • Shock, Hemorrhagic / physiopathology
  • Shock, Hemorrhagic / therapy*
  • Swine
  • Terlipressin / therapeutic use*
  • Vasoconstrictor Agents / therapeutic use*

Substances

  • Saline Solution
  • Vasoconstrictor Agents
  • Terlipressin

Grant support

This work was partially supported by Basque Government Grant (GIU19/026) to VEM and Spanish Society of pediatric critical care (Ruza Grant 2017) to JG.