Acute severe isovolemic anemia impairs cognitive function and memory in humans

Background, Erythrocytes are transfused to prevent or treat inadequate oxyg en delivery resulting from insufficient hemoglobin concentration. Previous studies failed to find evidence of inadequate systemic oxygen delivery at a hemoglobin concentration of 5 g/dl. However, in those studies, sensitive, specific measures of critical organ function were not used. This study test ed the hypothesis that acute severe decreases of hemoglobin concentration a lters human cognitive function. Methods: Nine healthy volunteers, age 29 +/- 5 yr (mean +/- SD), were teste d with verbal memory and standard, computerized neuropsychologic tests befo re and after acute isovolemic reduction of their hemoglobin to 7, 6, and 5 g/dl and again after transfusion of their autologous erythrocytes to return their hemoglobin concentration to 7 g/dL To control for duration of the ex periment, each volunteer also completed the same tests on a separate day, w ithout alteration of hemoglobin, at times of the day approximately equivale nt to those on the experimental day. Results: No test showed any change in reaction time or error rate at hemogl obin concentration of 7 g/dl compared with the data at the baseline hemoglo bin concentration of 14 g/dl, Reaction time, but not error rate, for horizo ntal addition and digit-symbol substitution test (DSST) increased at hemogl obin 6 g/dl (mean horizontal addition, 19%; 95% confidence interval [CI], 4 -34%; mean DSST, 10%; 95% CI, 4-17%) and further at 5 g/dl (mean horizontal addition, 43%; 95% CI, 6-79%; mean DSST, 18%; 95% CI, 4-31%). Immediate an d delayed memory was degraded at hemoglobin 5 g/dl but not at 6 g/dl. Retur n of hemoglobin to 7 g/dl returned all tests to baseline, except for the DS ST, which significantly improved, and returned to baseline the following mo rning after transfusion of all autologous erythrocytes. Conclusion: Acute reduction of hemoglobin concentration to 7 g/dl does not produce detectable changes in human cognitive function. Further reduction o f hemoglobin level to 6 and 5 g/dl produces subtle, reversible increases in reaction time and impaired immediate and delayed memory. These are the fir st prospective data to demonstrate subtle degraded human function with acut e anemia of hemoglobin concentrations of 6 and 5 g/dl, This reversibility o f these decrements with erythrocyte transfusion suggests that our model can be used to test the efficacy of erythrocytes, oxygen therapeutics, or othe r treatments for acute anemia.