New low-volume resuscitation solutions containing PEG-20k

Abstract

Background Hypovolemic shock reduces oxygen delivery and compromises energy dependent cell volume control. Consequent cell swelling compromises microcirculatory flow, which reducing oxygen exchange further. The importance of this mechanism is highlighted by the effectiveness of cell impermeants in low volume resuscitation (LVR) solutions in acute studies. The objective of this study was to assess impermeants in survival models and compare them to commonly used crystalloid solutions. Methods Adult rats were hemorrhaged to a pressure of 30–35 mm Hg, held there until the plasma lactate reached 10 mM, and given an LVR solution (5–10% blood volume) with saline alone (control), saline with various concentrations of Polyethylene glycol-20k (PEG-20k), hextend or albumin. When lactate again reached 10 mM following LVR, full resuscitation was started with crystalloid and red cells. Rats were either euthanized (acute) or allowed to recover (survival). The LVR time, which is the time from the start of the LVR solution until the start of full resuscitation was measured as was survival and diagnostic labs. In some studies, the capillary oncotic reflection coefficient was determined for PEG-20k to determine its relative impermeant and oncotic effects. Results PEG-20k (10%) significantly increased LVR times relative to saline (8 fold), hextend, and albumin. Lower amounts of PEG-20k (5%) were also effective but less so than 10% doses. PEG-20k maintained normal arterial pressure during the low volume state. Survival of a 180 minute LVR time challenge was 0% in saline controls and 100% in rats given PEG-20k as the LVR solution. Surviving rats had normal labs 24 hours later. PEG-20k had an oncotic reflection coefficient of 0.65, which indicates that the molecule is a hybrid cell impermeant with significant oncotic properties. Conclusions PEG-20k based LVR solutions are highly effective for inducing tolerance to the low volume state and for improving survival.

Low-volume resuscitation using polyethylene glycol-20k in a preclinical porcine model of hemorrhagic shock

“…The rodent model of severe hemorrhagic shock was translated to a parallel porcine model for pre-clinical testing of novel PEG-20k based resuscitation solutions (8;9). There are some differences between the two models.…”

“…Since no further bleeding or loss of RBCs was allowed to occur after the end of hemorrhage (because it was a controlled bleed model), the hemoglobin concentration reduction likely represents a proportional dilution effect with non-hemoglobin containing fluid from outside of the vascular compartment. The remaining 50% non-dilutional drop in plasma lactate that was observed after PEG-20k LVR likely represents a combination of clearance by renal filtration into the urine and by the metabolic oxidation of lactate to pyruvate by LDH as the peripheral microcirculation opens (8;9) and aerobic metabolism resumes.…”

“…As such, our comparative data amplifies the significance and effectiveness of the PEG-20k component. In the future, clinically relevant studies will be performed where PEG-20k will be compared to traditional low volume resuscitation fluids in the pig model as was done recently in rodent studies where PEG-20k LVR solutions were compared to both Hextend and albumin (8). …”

“…If lactate decreased and did not reach the target of 7–8 mM/L by 240 minutes, the maximum LVR time was arbitrarily set at 240 minutes. The LVR time is a surrogate for tolerance to the low volume or shock state (8;9). Clinically, it would be similar to the length of time that a patient can safely remain in the low volume state until definitive care and full resuscitation are needed, i.e.…”

“…Parrish et al have demonstrated reduced ischemia-induced cell swelling, increased tolerance to the low volume state, improved capillary blood flow, and higher survival with administration of a low volume solution containing polyethylene glycol-20k (PEG-20k) compared to saline in a rodent model of severe hemorrhagic shock (8;9). The resuscitation effects were extraordinary in this model.…”