Review of physiologic mechanisms in response to anemia

Objective: To determine the nature and quality of the physiologic evidence regarding an "optimum" hemoglobin concentration in anemic patients or in patients with specific diseases. Literature search and selection: Searches of MEDLINE from January 1966 to December 1996 were combined with manual searches of the bibliographies and references from experts. Citations were chosen by 2 reviewers if they were related to red blood cell transfusion practice and, more specifically, to physiologic adaptation to anemia. Disagreement was resolved through consensus. Literature synthesis: The articles selected from the literature search were classified by study design and topic areas. Evidence-based inferences were derived from the literature. Results: Of the 160 articles included in this review, 58 (36%) were human studies and 102 (64%) were laboratory studies. Most studies (84) fell into the "hemodilution" category, and were predominantly in animal models (70). Overall, 90 studies (56%) used a valid design with appropriate experimental and concurrent control groups (graded as level I or II). The distribution of grading was uniform throughout the categories. The quality of the evidence was deemed weaker for laboratory studies evaluating cardiac adaptation to anemia, largely because of a lack of reported concurrent controls in most studies. Inferences drawn from the literature were graded on a 4-point scale assessing the quality of the evidence; 13 of 18 statements were given the highest grade. The clinical significance of the Bohr effect and the shifts in the oxyhemoglobin curve following changes in pH were thought to be poorly studied and were rated lowest. The studies evaluating maximum oxygen delivery in anemia were rated as weak, partly because of conflicting reports. Of all identified studies, 56% were well designed and reported. Important adaptive responses to anemia consist of an elevation of cardiac output and its redistribution to favour the coronary and cerebral circulations at the expense of the splanchnic vascular beds; studies supporting these statements were rated highly. The evidence also suggests that patients with cardiac disease are at risk of adverse events from anemia. Conclusions: There is a significant body of evidence supporting cardiovascular adaptive responses to anemia. However, there is a remarkable lack, in both quality and quantity, of clinical studies addressing how the "normal" physiologic adaptations may be affected by a variety of diseases. The physiologic evidence alone is insufficient to inform most decisions about red blood cell transfusion.