Irreversible Shock Is Not Irreversible: A New Model of Massive Hemorrhage and Resuscitation

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Abstract
Existing shock models do not address the patient with massive hemorrhage (> 1 blood volume). Such patients often die from irreversible shock. This model simulates the clinical scenario of massive hemorrhage and resuscitation (MHR) to determine if irreversible shock can be reversed. Lewis rats were bled at a rate of 1 estimated blood volume (EBV) per hour for 2 hours with simultaneous infusion of resuscitation mixture (RM) consisting of red blood cells and crystalloid. Blood pressure was maintained at a mean arterial pressure (MAP) of 50 mm Hg during the 2 hours of hemorrhage. Hemorrhage was stopped and resuscitation continued for 1 hour until 6, 8, or 10 × EBV of RM was infused. Control animals were subjected to a traditional fixed pressure hemorrhage to MAP of 50 mm Hg for 2 hours followed by resuscitation to MAP > 90 mm Hg for 1 hour with crystalloid alone. Two-week survival was compared using a χ2 test. Control animals (n = 13) were hemorrhaged 48% ± 5% of EBV and had a mortality rate of 23%. MHR animals had severity and duration of hypotension identical to that of controls but were hemorrhaged 214% ± 8% of EBV. Despite receiving 390 mL/kg of RM and a final hematocrit of 37%, 14 of 15 animals resuscitated with 6 × EBV died from “irreversible” shock (mortality, 93%;p < 0.001 vs. controls). When very large volumes of resuscitation were used, survival rates improved significantly. The 10 × EBV group received 120% of lost red blood cells and 530 mL/kg of crystalloid and had 64% survival at 2 weeks (p < 0.01 vs. 6 × EBV group). This MHR model is much more lethal than a traditional severe hemorrhage model and reproduces the clinical picture of irreversible shock. This irreversible shock can be reversed with very large volumes of resuscitation.

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