Resuscitation from Hemorrhagic Shock With a Novel Protein Cocktail Restores Microvascular Perfusion and Protects Vital Organs

Carlos J Munoz; Daniela Lucas; Ivan S Pires; Thekla Cordes; Cynthia Muller; Krianthan Govender; Amanda Breton; Christian M Metallo; Andre F Palmer; Pedro Cabrales

doi:10.1097/SHK.0000000000002636

Resuscitation from Hemorrhagic Shock With a Novel Protein Cocktail Restores Microvascular Perfusion and Protects Vital Organs

Shock. 2025 Jun 23. doi: 10.1097/SHK.0000000000002636. Online ahead of print.

Authors

Carlos J Munoz¹, Daniela Lucas¹, Ivan S Pires², Thekla Cordes, Cynthia Muller¹, Krianthan Govender¹, Amanda Breton¹, Christian M Metallo, Andre F Palmer², Pedro Cabrales¹

Affiliations

¹ Department of Bioengineering, University of California San Diego, La Jolla, CA.
² William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH.

PMID: 40550505
DOI: 10.1097/SHK.0000000000002636

Abstract

Introduction: Low titer O positive Whole Blood (LTOWB) has been introduced in prehospital care to resuscitate patients; however, the logistical obstacles, cost of carrying LTOWB, and the availability of it in trauma situations are a point of concern. Therefore, fluids, like Lactated Ringer's (LR) and hydroxyethyl starch (HES) have been considered alternatives to LTOWB transfusion. Unfortunately, they dilute plasma proteins in the circulation and have unfavorable side effects. This study presents an alternative, a Protein Cocktail (PC). The PC combines human serum albumin, transferrin, haptoglobin, and hemopexin. This study compares the ability to resuscitate from hemorrhagic shock (HS) with Whole Blood (WB), LR, 6% HES, and PC.

Methods: Unanesthetized Golden Syrian hamsters instrumented with the dorsal window chambers were subjected to hemorrhage (50% blood volume), followed by 30 min hypovolemic shock, and resuscitated with 50% shed volume. The outcome was evaluated through systemic parameters, blood gases, microcirculatory hemodynamics, oxygen tension and saturation, metabolomics, and markers of organ injury/function. Additionally, to investigate the impact of the experimental solutions on the coagulation cascade, Sprague Dawley rats were subjected to an isovolemic exchange-infusion of 20% of the animal's blood volume.

Results: The PC showed favorable outcomes, restoring microvasculature hemodynamics comparable to resuscitation with Whole Blood and superior to Lactated Ringer's and HES. PC reduced acute inflammation, positively impacted organ function markers, and restore metabolomic homeostasis without coagulopathies observed with HES.

Conclusion: In conclusion, the Protein Cocktail (PC) shows some promise as a resuscitation from hemorrhagic shock when Whole Blood is not available, and superior to classic crystalloids and colloids (LR and HES). Further studies with the PC are needed to ensure its efficacy and safety in other experimental models.

Keywords: Coagulation; Hypovolemic Shock; Metabolites; Microcirculation; Oxygen Transport.