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Fluid resuscitation-related coagulation impairment in a porcine hemorrhagic shock model.

ABSTRACT: Background:Fast and effective treatment of hemorrhagic shock is one of the most important preclinical trauma care tasks e.g., in combat casualties in avoiding severe end-organ damage or death. In scenarios without immediate availability of blood products, alternate regimens of fluid resuscitation represent the only possibility of maintaining sufficient circulation and regaining adequate end-organ oxygen supply. However, the fluid choice alone may affect the extent of the bleeding by interfering with coagulation pathways. This study investigates the impact of hydroxyethyl starch (HES), gelatine-polysuccinate (GP) and balanced electrolyte solution (BES) as commonly used agents for fluid resuscitation on coagulation using a porcine hemorrhagic shock model. Methods:Following approval by the State and Institutional Animal Care Committee, life-threatening hemorrhagic shock was induced via arterial blood withdrawal in 24 anesthetized pigs. Isovolumetric fluid resuscitation with either HES, GP or BES (n = 3 × 8) was performed to compensate for the blood loss. Over four hours, hemodynamics, laboratory parameters and rotational thromboelastometry-derived coagulation were analyzed. As secondary endpoint the porcine values were compared to human blood. Results:All the agents used for fluid resuscitation significantly affected coagulation. We measured a restriction of laboratory parameters, clot development and clot firmness, particularly in HES- and GP-treated animals. Hemoglobin content dropped in all groups but showed a more pronounced decline in colloid-treated pigs. This effect was not maintained over the four-hour monitoring period. Conclusion:HES, GP, and BEL sufficiently stabilized the macrocirculation, but significantly affected coagulation. These effects were most pronounced after colloid and particularly HES administration. Despite suitability for rapid hemodynamic stabilization, colloids have to be chosen with caution, because their molecular properties may affect coagulation directly and as a consequence of pronounced hemodilution. Our comparison of porcine and human coagulation showed increased coagulation activity in pig blood.

SUBMITTER: Ziebart A

PROVIDER: S-EPMC7017792 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Fluid resuscitation-related coagulation impairment in a porcine hemorrhagic shock model.

Ziebart Alexander A Ruemmler Robert R Möllmann Christian C Kamuf Jens J Garcia-Bardon Andreas A Thal Serge C SC Hartmann Erik K EK

PeerJ 20200210

<h4>Background</h4>Fast and effective treatment of hemorrhagic shock is one of the most important preclinical trauma care tasks e.g., in combat casualties in avoiding severe end-organ damage or death. In scenarios without immediate availability of blood products, alternate regimens of fluid resuscitation represent the only possibility of maintaining sufficient circulation and regaining adequate end-organ oxygen supply. However, the fluid choice alone may affect the extent of the bleeding by inte ...[more]

PMID: 32095322

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Project description:BackgroundCurrent research suggests that administration of vasopressin to patients with uncontrolled hemorrhagic shock (UHS) can avoid the detrimental effects associated with aggressive fluid resuscitation. However, vasopressin has a short half-life of 10~35 minutes in in vivo use and precludes its use in the pre-hospital setting. To increase the half-life of vasopressin, we proposed to synthesize liposome-encapsulated vasopressin and test it in a rat model of UHS.MethodsThe film hydration method was used to prepare liposomal vasopressin consisting of: Dipalmitoylphosphatidylcholine, cholesterol, and dipalmitoyl phosphatidylethanolamine (20:20:1 mole ratio). 42 rats were subjected to UHS and randomly received 5 different treatments (vasopressin, liposomal vasopressin, lactate ringer (LR), liposome only and sham). Outcome of UHS were measured using 4 common prognostic tests: mean arterial pressure (MAP), serum lactate level, inflammatory profile and pulmonary edema.ResultsThe dynamic light scattering results confirmed that we had prepared a successful liposomal vasopressin complex. Comparing the serum vasopressin concentration of liposomal vasopressin and vasopressin treated animals by ELISA, we found that the concentration of vasopressin for the liposomal vasopressin treated group is higher at 60 minutes. However, there was no significant difference between the MAP profile of rats treated with vasopressin and liposomal vasopressin in UHS. We also observed that animals treated with liposomal vasopressin performed indifferently to vasopressin treated rats in serum lactate level, inflammatory profile and edema profile. For most of our assays, the liposome only control behaves similarly to LR resuscitation in UHS rats.ConclusionWe have synthesized a liposomal vasopressin complex that can prolong the serum concentration of vasopressin in a rat model of UHS. Although UHS rats treated with either liposomal vasopressin or vasopressin showed no statistical differences, it would be worthwhile to repeat the experiments with different liposomal compositions.

Project description:Subject-specific mathematical models for prediction of physiological parameters such as blood volume, cardiac output, and blood pressure in response to hemorrhage have been developed. In silico studies using these models may provide an effective tool to generate pre-clinical safety evidence for medical devices and help reduce the size and scope of animal studies that are performed prior to initiation of human trials. To achieve such a goal, the credibility of the mathematical model must be established for the purpose of pre-clinical in silico testing. In this work, the credibility of a subject-specific mathematical model of blood volume kinetics intended to predict blood volume response to hemorrhage and fluid resuscitation during fluid therapy was evaluated. A workflow was used in which: (i) the foundational properties of the mathematical model such as structural identifiability were evaluated; (ii) practical identifiability was evaluated both pre- and post-calibration, with the pre-calibration results used to determine an optimal splitting of experimental data into calibration and validation datasets; (iii) uncertainty in model parameters and the experimental uncertainty were quantified for each subject; and (iv) the uncertainty was propagated through the blood volume kinetics model and its predictive capability was evaluated via validation tests. The mathematical model was found to be structurally identifiable. Pre-calibration identifiability analysis led to splitting the 180 min of time series data per subject into 50 and 130 min calibration and validation windows, respectively. The average root mean squared error of the mathematical model was 12.6% using the calibration window of (0 min, 50 min). Practical identifiability was established post-calibration after fixing one of the parameters to a nominal value. In the validation tests, 82 and 75% of the subject-specific mathematical models were able to correctly predict blood volume response when predictive capability was evaluated at 180 min and at the time when amount of infused fluid equals fluid loss.

Dataset Information

Fluid resuscitation-related coagulation impairment in a porcine hemorrhagic shock model.

Publications

Fluid resuscitation-related coagulation impairment in a porcine hemorrhagic shock model.

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