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Can a Therapeutic Strategy for Hypotension Improve Cerebral Perfusion and Oxygenation in an Experimental Model of Hemorrhagic Shock and Severe Traumatic Brain Injury?

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An Invited Commentary to this article was published on 03 August 2023

Abstract

Background

Restoration of brain tissue perfusion is a determining factor in the neurological evolution of patients with traumatic brain injury (TBI) and hemorrhagic shock (HS). In a porcine model of HS without neurological damage, it was observed that the use of fluids or vasoactive drugs was effective in restoring brain perfusion; however, only terlipressin promoted restoration of cerebral oxygenation and lower expression of edema and apoptosis markers. It is unclear whether the use of vasopressor drugs is effective and beneficial during situations of TBI. The objective of this study is to compare the effects of resuscitation with saline solution and terlipressin on cerebral perfusion and oxygenation in a model of TBI and HS.

Methods

Thirty-two pigs weighing 20–30 kg were randomly allocated into four groups: control (no treatment), saline (60 ml/kg of 0.9% NaCl), terlipressin (2 mg of terlipressin), and saline plus terlipressin (20 ml/kg of 0.9% NaCl + 2 mg of terlipressin). Brain injury was induced by lateral fluid percussion, and HS was induced through pressure-controlled bleeding, aiming at a mean arterial pressure (MAP) of 40 mmHg. After 30 min of circulatory shock, resuscitation strategies were initiated according to the group. The systemic and cerebral hemodynamic and oxygenation parameters, lactate levels, and hemoglobin levels were evaluated. The data were subjected to analysis of variance for repeated measures. The significance level established for statistical analysis was p < 0.05.

Results

The terlipressin and saline plus terlipressin groups showed an increase in MAP that lasted until the end of the experiment (p < 0.05). There was a notable increase in intracranial pressure in all groups after starting treatment for shock. Cerebral perfusion pressure and cerebral oximetry showed no improvement after hemodynamic recovery in any group. The groups that received saline at resuscitation had the lowest hemoglobin concentrations after treatment.

Conclusions

The treatment of hypotension in HS with saline and/or terlipressin cannot restore cerebral perfusion or oxygenation in experimental models of HS and severe TBI. Elevated MAP raises intracranial pressure owing to brain autoregulation dysfunction caused by TBI.

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Funding

This study was funded by FAPESP (Fundação de Amparo ao Ensino e Pesquisa do Estado de São Paulo), the São Paulo state research support foundation (Award Number: 2013/07832-1), and the grant recipient was Luiz Marcelo Sá Malbouisson, PhD, the last author of this article.

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Authors and Affiliations

  1. Anesthesiology Department, Hospital das Clinicas SP, School of Medicine, University of São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 255, Cerqueira César, São Paulo, SP, 05403-000, Brazil

    Ana Paula de Carvalho Canela Balzi & Luiz Marcelo Sá Malbouisson

  2. Medical Research Laboratory -LIM-08, Anesthesiology Department, School of Medicine, University of São Paulo, São Paulo, Brazil

    Denise Aya Otsuki

  3. Nephrology Department, Hospital das Clinicas SP, School of Medicine, University of São Paulo, São Paulo, Brazil

    Lucia Andrade

  4. Neurosurgery Department, Hospital das Clinicas SP, School of Medicine, University of São Paulo, São Paulo, Brazil

    Wellingson Paiva

  5. Medical Research Laboratory, Nephrology Department, School of Medicine, University of São Paulo, São Paulo, Brazil

    Felipe Lima Souza

  6. Pathology Department, Hospital das Clinicas SP, School of Medicine, University of São Paulo, São Paulo, Brazil

    Luiz Guilherme Cernaglia Aureliano

  7. Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

    Ana Paula de Carvalho Canela Balzi, Denise Aya Otsuki, Lucia Andrade, Wellingson Paiva, Felipe Lima Souza, Luiz Guilherme Cernaglia Aureliano & Luiz Marcelo Sá Malbouisson

  8. Divisão de Anestesia do ICHC, UTI Cirúrgica Pediátrica, Av. Enéas Carvalho de Aguiar, 255 – 8° Andar, Cerqueira César, São Paulo, SP, 05403-900, Brazil

    Ana Paula de Carvalho Canela Balzi

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Contributions

All authors made a substantial contribution to the concept and design of the study, interpreted the data, and reviewed the article. APCCB and DAO initiated the study. APCCB and LMSM performed data extraction and analyses. APCCB, LMSM, FLS, and LGCA drafted the first version of the article. LA and WP critically reviewed the article and revised it. The final manuscript was approved by all authors.

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Correspondence to Ana Paula de Carvalho Canela Balzi.

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The authors confirm adherence to ethical guidelines and ethical (institutional review board) approval by CEUA (Comissão de Ética no Uso de Animais), whose purpose is to deliberate on the approval or not of research projects for studies in which the experimental protocols require animals in Brazil (approval number: CEUA/ FMUSP – 120/16).

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Balzi, A.P.d.C.C., Otsuki, D.A., Andrade, L. et al. Can a Therapeutic Strategy for Hypotension Improve Cerebral Perfusion and Oxygenation in an Experimental Model of Hemorrhagic Shock and Severe Traumatic Brain Injury?. Neurocrit Care 39, 320–330 (2023). https://doi.org/10.1007/s12028-023-01802-5

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