Addition of Drag-Reducing Polymers to Colloid Resuscitation Fluid Enhances Cerebral Microcirculation and Tissue Oxygenation After Traumatic Brain Injury Complicated by Hemorrhagic Shock

Abstract

Hemorrhagic shock (HS) is a severe complication of traumatic brain injury (TBI) that doubles mortality due to severely compromised microvascular cerebral blood flow (mvCBF) and oxygen delivery reduction, as a result of hypotension. Volume expansion with resuscitation fluids (RF) for HS does not improve microvascular CBF (mvCBF); moreover, it aggravates brain edema. We showed that the addition of drag-reducing polymers (DRP) to crystalloid RF (lactated Ringer’s) significantly improves mvCBF, oxygen supply, and neuronal survival in rats suffering TBI+HS. Here, we compared the effects of colloid RF (Hetastarch) with DRP (HES-DRP) and without (HES). Fluid percussion TBI (1.5 ATA, 50 ms) was induced in rats and followed by controlled HS to a mean arterial pressure (MAP) of 40 mmHg. HES or HES-DRP was infused to restore MAP to 60 mmHg for 1 h (prehospital period), followed by blood reinfusion to a MAP of 70 mmHg (hospital period). In vivo two-photon microscopy was used to monitor cerebral microvascular blood flow, tissue hypoxia (NADH), and neuronal necrosis (i.v. propidium iodide) for 5 h after TBI+HS, followed by postmortem DiI vascular painting. Temperature, MAP, blood gases, and electrolytes were monitored. Statistical analyses were done using GraphPad Prism by Student’s t-test or Kolmogorov-Smirnov test, where appropriate. TBI+HS compromised mvCBF and tissue oxygen supply due to capillary microthrombosis. HES-DRP improved mvCBF and tissue oxygenation (p < 0.05) better than HES. The number of dead neurons in the HES-DRP was significantly less than in the HES group: 76.1 ± 8.9 vs. 178.5 ± 10.3 per 0.075 mm3 (P < 0.05). Postmortem visualization of painted vessels revealed vast microthrombosis in both hemispheres that were 33 ± 2% less in HES-DRP vs. HES (p < 0.05). Thus, resuscitation after TBI+HS using HES-DRP effectively restores mvCBF and reduces hypoxia, microthrombosis, and neuronal necrosis compared to HES. HES-DRP is more neuroprotective than lactated Ringer’s with DRP and requires an infusion of a smaller volume, which reduces the development of hypervolemia-induced brain edema.