Polyethylene glycol‐20 ameliorates tissue ischemia and improves renal function following traumatic shock

Abstract

The “Golden Hour” policy used for US Troops in Iraq and Afghanistan has contributed to the highest survival rates for combat injury in history. Anticipated future combat operations require more options to optimize combat casualty care by extending “the Golden Hour” to “the Golden Day.” Low volume resuscitation with polyethylene glycol‐20K (PEG) has been shown to decrease mortality following hemorrhagic shock, however, the effect of PEG on tissue perfusion and renal function has not been determined. We hypothesized that PEG can ameliorate ischemia and prevent renal injury during prolonged traumatic shock. Anesthetized rats received extremity trauma (soft tissue injury and fracture in one hindlimb) and pressure‐controlled hemorrhage, with mean arterial pressure (MAP) maintained at 55mmHg. MAP, heart rate, renal blood flow (RBF, perivascular ultrasonic transit time flow probe), peripheral skeletal muscle microcirculatory flow and tissue oxygen partial pressure (OxyLite needle probes), blood gases, and electrolytes were monitored throughout the experiment. Glomerular filtration rate (GFR) was recorded using a non‐invasive Fluorescein isothiocyanate‐sinistrin transcutaneous technique. After 45 minutes of shock with MAP at 55mmHg, rats were randomly treated with an intravenous bolus of either 7.5% PEG or saline (1.3 ml/kg, n = 5/group). Measurements were continued from the 45th to the 165th minute without MAP control or any other treatment. Compared with saline, PEG markedly improved MAP recovery (P < 0.001) and survival (P < 0.01) (Figures 1A and 1B). Microcirculatory perfusion and oxygen partial pressure were markedly decreased after hemorrhage and saline treatment elicited no additional effect. However, with PEG, the decreases in capillary flow and tissue oxygen levels were significantly attenuated (P = 0.04 and 0.03, respectively) (Figure 2A). Moreover, blood lactate levels continuously increased in the saline group but returned to levels comparable to baseline within 30 minutes after PEG treatment (P < 0.001) (Figure 2B). In the saline group, RBF markedly decreased concomitantly with a sustained increase in renal vascular resistance (RVR) during the shock period. PEG treatment rapidly restored RBF (P < 0.001) to levels comparable to baseline along with a normalized RVR. GFR was diminished in the saline‐treated rats but was improved in the PEG‐treated group (0.07 ± 0.05 vs. 0.67 ± 0.06 ml/min/100g, respectively; P < 0.001). These results provide strong evidence that PEG rapidly improves macro‐ and microcirculatory hemodynamics ameliorates tissue ischemia, and minimize renal injury and mortality following prolonged traumatic shock.