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Effects of resuscitation with 0.9% saline solution and terlipressin on cerebral oxygenation and perfusion in a model of traumatic brain injury and hemorrhagic shock

Grant number: 13/07832-1
Support type:Regular Research Grants
Duration: February 01, 2017 - July 31, 2019
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Luiz Marcelo Sá Malbouisson
Grantee:Luiz Marcelo Sá Malbouisson
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers: Ana Paula de Carvalho Canela Balzi ; Denise Aya Otsuki ; Lucia da Conceição Andrade ; Wellingson Silva Paiva

Abstract

Introduction: The restoration of tissue perfusion of the brain is a determining factor in neurological outcome in patients who suffer traumatic brain injury (TBI) and hemorrhagic shock (HS). In a porcine model of hemorrhagic shock without neurologic injury (FAPESP research n°2011/00348-1), it was observed that the use of fluids or vasoactive drugs were equally effective in restoring cerebral perfusion. However, only terlipressin was equally effective in restoring cerebral oxygenation, to lower brain markers expression of edema and apoptosis compared to saline group. Nevertheless, it is unclear whether the use of vasopressors is effective and beneficial for situations of traumatic brain injury. Objective: Compare the effects of resuscitation with 0.9% saline solution (SS) and terlipressin (TLP) on cerebral oxygenation and perfusion in a model of traumatic brain injury and hemorrhagic shock. Methodology: The brain damage will be induced by lateral fluid percussion injury in 32 pigs of 20-30 kg, followed by bleeding pressure-controlled for 20 minutes, aiming to mean arterial pressure target of 40 mmHg. The animals will be randomized into four groups with 8 animals each one. The first one known as control group and, the other ones, would be the resuscitation strategies implementation: Saline Group (SS), Terlipressin Group (TLP) and Saline plus Terlipressin Group (SS + TLP). Systemic and cerebral hemodynamics, perfusion and oxygenation parameters will be evaluated at baseline, 20 minutes after start withdraw of blood, when median arterial pressure is 40 mmhg (HS20), 30 minutes after last sample (after HS20, named HS50) and 30, 60, 90 and 120 minutes after treatment. At the end of the study the animals will be submitted further euthanasia following the current guidelines for use of animals in laboratory research. Samples of brain tissue, lung and kidney will be collected for histological analysis. Data will be submitted to analysis of variance for repeated measures followed by the Tukey test. The degree of statistical significance was set to be p <0.05. (AU)