Restoring microcirculatory perfusion in a preclinical model of severe hemorrhagic shock: The role of microcirculatory function.

BACKGROUND: No reflow in capillaries (no reflow) is the lack of tissue perfusion that occurs once central hemodynamics are restored. This prevents oxygen transfer and debt repayment to vital tissues after shock resuscitation. Since metabolic swelling of cells and tissues can cause no reflow, it is a target for study in shock. We hypothesize no reflow secondary to metabolic cell swelling causes the problem not addressed by current strategies that increase central hemodynamics alone. METHODS: Anesthetized swine were bled until plasma lactate reached 7.5 mM to 9 mM. Intravenous low volume resuscitation solutions were administered (6.8 mL/kg over 5 minutes) consisting of; (1) lactated Ringer (LR), (2) autologous whole blood, (3) high-dose vitamin C (200 mg/kg), or (4) 10% PEG-20k, a polymer-based cell impermeant that corrects metabolic cell swelling. Outcomes were macrohemodynamics (MAP), plasma lactate, capillary flow in the gut and tongue mucosa using orthogonal polarization spectral imaging (OPSI), and survival to 4 hours. RESULTS: All PEG-20k resuscitated swine survived 240 minutes with MAP above 60 mm Hg compared with 50% and 0% of the whole blood and LR groups, respectively. The vitamin C group died at just over 2 hours with MAPs below 40 and high lactate. The LR swine only survived 30 minutes and died with low MAP and high lactate. Capillary flow positively correlated ( p < 0.05) with survival and MAP. Sublingual OPSI correlated with intestinal OPSI and OPSI was validated with a histological technique. DISCUSSION: Targeting micro-hemodynamics in resuscitation may be more important than macrohemodynamics. Fixing both is optimal. Sublingual OPSI is clinically achievable to assess micro-hemodynamic status. Targeting tissue cell swelling that occurs during ATP depletion in shock using optimized osmotically active cell impermeants in crystalloid low volume resuscitation solutions improves perfusion in shocked tissues, which leverages a primary mechanism of injury.

Effects of polyethylene glycol-20k IV solution on donor management in a canine model of donor brain death.

BACKGROUND: Traditionally, vasopressors and crystalloids have been used to stabilize brain dead donors; however, the use of crystalloid is fraught with complications. This study aimed to investigate the effectiveness of a newly developed impermeant solution, polyethylene glycol-20k IV solution (PEG-20k) for resuscitation and support of brain dead organ donors. METHODS: Brain death was induced in adult beagle dogs and a set volume of PEG-20k or crystalloid solution was given thereafter. The animals were then resuscitated over 16 h with vasopressors and crystalloid as necessary to maintain mean arterial pressure of 80-100 mmHg. The kidneys were procured and cold-stored for 24 h, after which they were analyzed using the isolated perfused kidney model. RESULTS: The study group required significantly less crystalloid volume and vasopressors while having less urine output and requiring less potassium supplementation than the control group. Though the two groups' mean arterial pressure and lactate levels were comparable, the study group's kidneys showed less preservation injury after short-term reperfusion indexed by decreased lactate dehydrogenase release and higher creatinine clearance than the control group. CONCLUSIONS: The use of polyethylene glycol-20k IV solution for resuscitating brain dead donors decreases cell swelling and improves intravascular volume, thereby improving end organ oxygen delivery before procurement and so preventing ischemia-reperfusion injury after transplantation.