Severe hemodilutional anemia increases cerebral tissue injury following acute neurotrauma

Abstract

Anemia may worsen neurological outcomes following traumatic brain injury (TBI) by undefined mechanisms. We hypothesized that hemodilutional anemia accentuates hypoxic cerebral injury following TBI. Anesthetized rats underwent unilateral TBI or sham injury (n > or = 7). Target hemoglobin concentrations between 50 and 70 g/l were achieved by exchanging 40-50% of the blood volume (1:1) with pentastarch. The effect of TBI, anemia, and TBI-anemia was assessed by measuring brain tissue oxygen tension (Pbr(O(2))), regional cerebral blood flow (rCBF), jugular venous oxygen saturation (Sjv(O(2))), cerebral contusion area, and nuclear staining for programmed cell death. Baseline postinjury Pbr(O(2)) values in the TBI and TBI-anemia groups (9.3 +/- 1.3 and 11.3 +/- 4.1 Torr, respectively) were lower than the uninjured controls (18.2 +/- 5.2 Torr, P < 0.05 for both). Hemodilution caused a further reduction in Pbr(O(2)) in the TBI-anemia group relative to the TBI group without anemia (7.8 +/- 2.7 vs. 14.8 +/- 3.9 Torr, P < 0.05). The rCBF remained stable after TBI and increased comparably after hemodilution in both anemia and TBI-anemia groups. The Sjv(O(2)) was elevated after TBI (87.4 +/- 8.9%, P < 0.05) and increased further following hemodilution (95.0 +/- 1.6%, P < 0.05). Cerebral contusion area and nuclear counts for programmed cell death were increased following TBI-anemia (4.1 +/- 3.0 mm(2) and 686 +/- 192, respectively) relative to TBI alone (1.3 +/- 0.3 mm(2) and 404 +/- 133, respectively, P < 0.05 for both). Hemodilutional anemia reduced cerebral Pbr(O(2)) and oxygen extraction and increased cell death following TBI. These results support our hypothesis that acute anemia accentuated hypoxic cerebral injury after neurotrauma.

Reassessing the risk of hemodilutional anemia: Some new pieces to an old puzzle

“…7 Evaluation of co-oximetry data (delta hemoglobin and methemoglobin) is presented from five previously published experimental studies. 13,[65][66][67]95 An expected strong positive correlation was observed between the change in hemoglobin and blood oxygen content in control (no hemodilution) or 50% hemodiluted rats (positive control, Upper Panel). A positive correlation was also observed between the change in hemoglobin and methemoglobin levels, suggesting that hemodilutional anemia led to a proportional increase in methemoglobin levels (Lower Panel)…”

“…In support of this hypothesis, a review of data from previously published hemodilution studies has demonstrated a positive correlation between the reduction in absolute hemoglobin and the % increase in MetHb level ( Figure 7). 13,[65][66][67]95 In addition, the increase in MetHb occurred after hemodilution with either 5% albumin or 10% pentastarch, suggesting that the effect was independent of the type of colloid used (Figure 8). In these experiments, the amount of MetHb formed was proportional to the degree of hemodilution with 5% albumin, suggesting a causal link between blood oxygen content and the amount of MetHb formed.…”

“…In this model of hemodilutional anemia, blood volume exchange (1:1 with 10% pentastarch) is acutely associated with increased or maintained central venous pressures. 67 However, the influence of subsequent reduction in blood volume with clearance of the pentastarch at 18-24 hr cannot be ruled out entirely. Interestingly, these changes in gene expression occurred in the absence of any increase in blood lactate levels, suggesting that local ''tissue hypoxia'' occurs without overt evidence of anerobic metabolism in the systemic circulation.…”

“…In an experimental model of acute hemodilutional anemia, we have observed that whole blood methemoglobin (MetHb) levels are increased consistently by approximately 1-2%. 13,[65][66][67]95 Figure 6). Thus, although the anemia-induced increase in MetHb concentration is small relative to the total Hb, its generation may provide evidence of increased vascular NO bioavailability following acute hemodilution.…”

Impact of Acute Normovolemic Hemodilution in Organ and Cell Structure

“…Available data regarding safe hematocrit levels for the nervous system derive mostly from experimental studies and a few clinical studies that associate anemia with neurological outcome after cardiopulmonary bypass (Hare et al, 2007). In healthy young human subjects, ANH to hemoglobin of 5.7 g/dL elicited subtle cognitive dysfunction and memory deficits that were reversible with erythrocyte transfusion or increase in oxygen concentration (Weiskopf et al, 2002).…”