PEG-20k IV Resuscitation Improves Survival and Microvascular Perfusion in Rat Model of Septic Shock

Introduction: Microvascular perfusion defects have been increasingly linked to sepsis pathogenesis. Recent studies in hemorrhagic and splanchnic shock resuscitation showed improved microvascular perfusion using new IV solutions containing cell impermeants polyethylene glycol (PEG). Our objective was to translate this success to septic shock, with the hypothesis that PEG-20k resuscitation will decompress the ischemic microvasculature by transferring water from swollen cells to the capillary, both improving perfusion and survival.


Methods: A rodent model of septic shock using Sprague-Dawley male rats (n=5/group) was established using IV lipopolysaccharide (LPS) infusion. When mean arterial blood pressure (MAP) decreased below 75% of baseline, an IV bolus of lactated Ringer’s (LR) or PEG-20k at 6.8 ml/kg was given over 5 minutes with or without constant infusion of norepinephrine (NE) thereafter (5 mcg/kg/min at 0.02 ml/min). The main outcomes were survival time, MAP, plasma expansion (measured hemoglobin dilution), lactate, and orthogonal polarization spectral imaging (OPSI), which directly images microcirculation.


Results: PEG-20k with NE had the best mean survival among all groups (219 min), followed by PEG-20k only (150 min), LR-NE (75 min), LR only (42 min), and LPS-only control (34 min). PEG-20k resulted in greater vascular expansion than LR (37% vs 7%). Although every group’s lactate level increased after resuscitation, only PEG-20k groups survived past 75 minutes and had stable lactate levels up to 120 minutes after resuscitation. Septic shock significantly decreased OPSI parameters, and only improved with PEG resuscitation.


Conclusions: In this LPS rodent model of septic shock, PEG-20k resuscitation resulted in greater survival benefit, intravascular volume expansion, lactate stability, and microvascular perfusion (via OPSI) as compared to crystalloid resuscitation with and without vasopressor support, which appears to be synergistic with the PEG-20k effect. Thus, improved mortality with PEG-20k in this model is likely due to the ability of PEG-20k to decompress the microcirculation and improve end-organ perfusion. By targeting the microcirculation (not just macrocirculation) early in septic shock, we hope to prevent or delay multiorgan dysfunction and poor outcomes.