Use of recombinant hemoglobin solution in reversing lethal hemorrhagic hypovolemic oxygen debt shock

To compare recombinant hemoglobin solution (rHb1.1) with colloid/blood (CB) resuscitation in a hemorrhagic shock (HS) model based on oxygen debt (O2D).

Twenty-two anesthetized canines (weight 23.3 +/- 0.2 kg) were bled to an O2D of 99.9 +/- 2.1 mL/kg over 60 minutes (estimated lethal dose 31%), blood loss 65.9 +/- 2.3% of estimated blood volume, - 199 g hemoglobin (Hgb). Prospectively randomized resuscitation done in 20 minutes with 120% of shed blood volume, either colloid 60%/blood 60% shed blood volume (CB), 118 g Hgb, or 120% shed blood volume as 5% rHb1.1, 85 g Hgb, and fall in O2D was quantified over 80 minutes. Six animals died during HS, one after CB resuscitation (32% actual mortality). Blood lactate (L) and base deficit (BEA) were related to O2D.

Both lactate (L) and BEA quantified O2D during hemorrhage: L = 0.0671 (O2D) + 1.209; r2 = 0.90, p < 0.0001; BEA = 0.1313 (O2D) + 1.764; r2 = 0.90, p < 0.0001, but L was a better indicator than BEA of fall in O2D during resuscitation (L = 0.069 (O2D) + 1.083; r2 = 0.80). Both groups were followed for 7 days after HS and had normal renal and hepatic function by day 7. However, at equal resuscitation volume, rHb1.1 resuscitation with 41% of Hgb loss produced a more rapid initial fall in O2D than CB at 60% of Hgb loss (p < 0.002). rHb1.1 resuscitation also caused a more complete washout of metabolic acids than CB.

Lactate and BEA accurately quantify O2D in HS and resuscitation. rHb1.1 replacement is as good as CB with regard to survival, but leads to a more uniform reperfusion and produces a more complete resolution of ischemic acidosis.