Superior survival, hemodynamics, and metabolic recovery using PEG-20k-based low volume resuscitation in a polytrauma...

Hemorrhagic shock is a major cause of preventable civilian and military trauma death. Although whole blood and blood products remain the standard of care, field‑stable alternatives are needed for resource‑limited environments and supply‑chain disruptions. Blood‑based resuscitation may also fail to optimally restore microvascular perfusion despite improved macrohemodynamics, contributing to ongoing ischemia-reperfusion injury, dysfunctional molecular cell dynamics, and capillary cell swelling. Prior controlled hemorrhage studies in rats and swine demonstrated superior survival, mean arterial pressure (MAP), and lactate clearance with polyethylene glycol 20,000 (PEG‑20k) compared with crystalloid, colloid, and whole blood controls. These beneficial effects are attributed to the capacity of PEG-20k to augment water transfer from swollen ischemic cells into the vascular space, thereby decompressing capillary beds and restoring effective tissue perfusion. This study evaluated PEG‑20k in a severe polytrauma rat model with combined controlled and uncontrolled hemorrhage.

Adult male Sprague-Dawley rats (250-400-g) underwent a midline laparotomy, 75% tail amputation, and dual splenic transections. The spleen bled freely into the closed abdomen (uncontrolled, non-compressible hemorrhage), while the tail was intermittently clamped (controlled, compressible hemorrhage) to maintain MAP > 30-mmHg until plasma lactate reached 7.5-10-mM. A tail tourniquet was then placed, and animals were resuscitated with 6.1-ml/kg IV fluid over 5-minutes using either lactated Ringer's (LR), 6%-hetastarch in LR (Hextend, HXT), or 10%-PEG-20k in LR (PEG). Outcomes included survival, blood loss, MAP, and lactate. The study concluded at subject death from shock or at 4-hours after treatment.

Baseline and post-hemorrhage characteristics were similar across groups (n = 4/group; hemorrhage volume 51.3% ±6.8% of total blood volume, p = 0.4088). Survival times for PEG-20k, HXT, and LR were 240-min ±0, 59.0-min ±21.2, and 36.3-min ±10.8, respectively (p < 0.0001). PEG-20k normalized MAP within 5-minutes and remained > 90-mmHg throughout the 240-min period. Terminal lactates for PEG-20k, HXT, and LR were 3.2-mM ±0.5, 10.3-mM ±1.7, and 11.7-mM ±0.5, respectively (p < 0.0001).

PEG-20k low-volume resuscitation markedly improved survival, MAP, and lactate clearance without increasing uncontrolled bleeding in a severe polytrauma hemorrhagic shock model. This shelf-stable IV fluid may enhance resuscitation during prolonged prehospital care and in resource-limited settings where blood products are unavailable. Future studies will evaluate PEG-20k in translational models of uncontrolled hemorrhage and polytrauma, and as a potential preemptive adjunct to blood-based resuscitation.