Thromboelastographic analysis of novel polyethylene glycol based low volume resuscitation solutions

PLoS One. 2018 Nov 15;13(11):e0207147. doi: 10.1371/journal.pone.0207147. eCollection 2018.

Abstract

Background: Low volume resuscitation (LVR) in shock prevents deleterious effects of crystalloid loading in pre-hospital settings. Polyethylene glycol 20,000 (PEG-20k) based LVR solutions are 20-fold more effective at maintaining perfusion and survival in shock compared to conventional crystalloids. The aim of this study was to determine coagulation and platelet function of whole blood treated with 10% PEG-20k.

Methods: Citrated blood from volunteers (n = 25) or early admission severely injured trauma patients (n = 9) were diluted 10% with various LVR solutions in a matched design with a paired volume control (saline), and studied using thromboelastography (TEG).

Findings: In healthy volunteers and patients, 10% PEG-20k significantly increased clot amplification time (k), decreased propagation (angle), maximal clot size and strength (MA), and the overall coagulation index (CI), but not clot initiation (R) or fibrinolysis (Ly30), relative to paired saline dilutional controls. Clinically, K, angle, and MA were just outside of the normal limits in volunteers but not in patients. No statistical differences existed between PEG-20k and Hextend (HES) in either patient population. In a dose response series using volunteer blood, all effects of 10% PEG-20k on TEG were reversed and normalized by lower concentrations (7.5% and 5%). Furthermore, 7.5% PEG-20k produced similar resuscitation effects as 10% PEG in rodent hemorrhagic shock models (n = 5).

Conclusions: In conclusion, PEG-20k based LVR solutions produced a dose-dependent minor hypocoagulative state, possibly associated with changes in clot propagation and platelet function, which can be reversed by dose reduction in concentration while providing superior LVR, microvascular rescue, and lactate clearance compared to saline or starch.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Blood Coagulation / drug effects
  • Blood Platelets / drug effects
  • Blood Volume
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Fibrinolysis / drug effects
  • Fluid Therapy
  • Humans
  • Male
  • Middle Aged
  • Polyethylene Glycols / administration & dosage*
  • Rats, Sprague-Dawley
  • Rehydration Solutions / administration & dosage*
  • Shock / therapy*
  • Shock, Hemorrhagic / drug therapy
  • Solutions
  • Thrombelastography
  • Young Adult

Substances

  • Rehydration Solutions
  • Solutions
  • Polyethylene Glycols

Grants and funding

This work was supported by Department of Defense, W81XWH-16-2-0040, Polyethylene glycol polymers in low volume resuscitation, PI, Martin Mangino; Department of Defense, W81XWH-17-1-0602, Treatment of Spinal Cord Ischemia with Cell Impermeant-Based Resuscitation, PI, Martin Mangino; Department of Defense, W81XWH-12-1-0599, Cell impermeants in low volume resuscitation, PI, Martin Mangino. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.