Oxygen transport and cardiovascular effects of resuscitation from severe hemorrhagic shock using hemoglobin solutions

J Sprung, C F Mackenzie, G M Barnas, J E Williams, M Parr, R H Christenson, B H Hoff, R Sakamoto, A Kramer, M Lottes
Critical Care Medicine 1995, 23 (9): 1540-53

OBJECTIVE: To test the short-term efficacy of three hemoglobin solutions in restoring cardiac output, intravascular pressures, oxygen transport (DO2), and oxygen consumption (VO2) after resuscitation from severe hemorrhagic shock.

DESIGN: Prospective study.

SETTING: Research laboratory.

SUBJECTS: Beagle dogs.

INTERVENTIONS: After anesthesia and instrumentation, hemorrhagic shock was induced for 2 hrs by blood withdrawal to maintain systolic blood pressure at 50 mm Hg. Resuscitation then occurred with one of four different resuscitation fluids. One group of dogs was not resuscitated. Survival rate was monitored for 8 days.

MEASUREMENTS AND MAIN RESULTS: In 33 beagle dogs, cardiovascular variables (DO2 and VO2) were compared after resuscitation with 8% stroma-free hemoglobin, 4% or 8% pyridoxalated-hemoglobin-polyoxyethylene conjugate (PHP44 and PHP88, respectively), or autologous whole blood. The dogs were anesthetized, paralyzed, mechanically ventilated (FIO2 of 0.21), and instrumented with arterial and pulmonary artery catheters. An average of 63% of estimated blood volume was removed to maintain systolic blood pressure at 50 mm Hg for 2 hrs. The dogs then were either not resuscitated (n = 4) or resuscitated with 8% stroma-free hemoglobin (n = 7), PHP44 (n = 6), PHP88 (n = 8), or whole blood (n = 8), with a volume equivalent to the withdrawn blood. Cardiovascular variables, DO2, VO2, oxygen extraction ratios, and blood concentrations of lactic acid and catecholamines were determined before, and for < or = 6 hrs after, resuscitation from hemorrhagic shock. Blood smears were microscopically examined. In addition, the survival rate was monitored for 8 days after resuscitation. By 2 hrs of hemorrhagic shock, there was a large decrease in DO2 (p < .05) and an increase in oxygen extraction ratio from 0.27 to 0.70 (p < .05). There was a 3.5-fold increase in lactate concentrations and a 25-fold increase in catecholamine concentrations as compared with preshock values. All dogs not resuscitated died within 1.75 hrs after 2 hrs of shock. After resuscitation with whole blood, all cardiovascular and oxygen transport variables returned to approximately prehemorrhage values and remained so throughout the measurement period. After resuscitation with any hemoglobin solution, DO2 returned transiently to control values. However, recovery of DO2 was short-lived in all hemoglobin solution groups, and, by 4 hrs postresuscitation in all groups, DO2 was less than the DO2 of the dogs receiving whole blood (p < .05). These changes were associated with decreases in total hemoglobin concentrations compared with the values immediately before resuscitation (p < .05). In addition, with resuscitation using the PHP solutions, blood smears demonstrated aggregation of red blood cells and platelets. On day 8 after hemorrhagic shock, the survival rate was 100% for whole blood and PHP44, 86% for 8% stroma-free hemoglobin, and 33% for PHP88.

CONCLUSIONS: Resuscitation from severe hemorrhagic shock with 8% stroma-free hemoglobin, PHP44, or PHP88 is equally effective in restoring cardiac index and vascular pressures as using whole blood. However, resuscitation with the three hemoglobin solutions only transiently restored DO2 after hemorrhagic shock. The subsequent reduction of DO2 compared with the DO2 value using whole blood was due mostly to hemodilution. With the two PHP solutions, formation of red blood cell aggregates probably resulted in sequestration of red cell mass and additional loss of oxygen carrying capacity.

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