Fluid therapy in uncontrolled hemorrhage – what experimental models have taught us

Abstract

Intravenous fluid is life-saving in hypovolemic shock, but fluid sometimes aggravates the bleeding. During the past 25 years, animal models have helped our understanding of the mechanisms involved in this unexpected effect. A key issue is that vasoconstriction is insufficient to arrest the bleeding when damage is made to a major blood vessel. ‘Uncontrolled hemorrhage’ is rather stopped by a blood clot formed at the outside surface of the vessel, and the immature clot is sensitive to mechanical and chemical interactions. The mortality increases if rebleeding occurs. In the aortic tear model in swine, hemorrhage volume and the mortality increase from effective restoration of the arterial pressure. The mortality vs. amount of fluid curve is U-shaped with higher mortality at either end. Without any fluid at all, irreversible shock causes death provided the hemorrhage is sufficiently large. Crystalloid fluid administered in a 3 : 1 proportion to the amount of lost blood initiates serious rebleeding. Hypertonic saline 7.5% in 6% dextran 70 (HSD) also provokes rebleeding resulting in higher mortality in the recommended dosage of 4 ml/kg. Uncontrolled hemorrhage models in rats, except for the ‘cut-tail’ model, confirm the results from swine. To avoid rebleeding, fluid programs should not aim to fully restore the arterial pressure, blood flow rates, or blood volume. For a hemorrhage of 1000 ml, computer simulations show that deliberate hypovolemia (−300 ml) would be achieved by infusing 600–750 ml crystalloid fluid over 20–30 min or 100 ml of HSD over 10–20 min in an adult male

Comparisons of normal saline and lactated Ringer’s resuscitation on hemodynamics, metabolic responses, and coagulation in pigs after severe hemorrhagic shock

“…It is likely the on-going bleeding from uncontrolled hemorrhage will exaggerate the impact of vasodilation effects from NS, with higher volumes infused and more hemodilution and coagulation impairment. Considering that restriction on resuscitation fluid has been shown improving survival in uncontrolled bleeding patients [35] and animals [36], a larger volume of NS, as compared to LR, would increase bleeding with resultant higher morbidities and mortality in trauma patients.…”

Understanding volume kinetics

“…Computer simulations and animal experiments show that the recommended dose of hypertonic saline in dextran to combat hemorrhage (4 mL/kg) is too large. Hypervolemia is produced, and re‐bleeding occurs in nearly all animals with uncontrolled hemorrhage.…”

Is There a Place for Crystalloids and Colloids in Remote Damage Control Resuscitation?

“…The relationship between mortality and the amounts of fluids given is U-shaped in animal models of uncontrolled hemorrhage (8). Usually, small aliquots of fluids (e.g., 50 Y 100 mL of hydroxyethyl starch (HES) or 250 mL of Ringer's lactate solution) are given in repeated doses to maintain a palpable radial pulse or a systolic blood pressure of 90 mmHg.…”