REVIEW OF PHYSIOLOGICAL-MECHANISMS IN RESPONSE TO ANEMIA

Objective: To determine the nature and quality of the physiologic evid ence regarding an ''optimum'' hemoglobin concentration in anemic patie nts or in patients with specific diseases. Literature search and selec tion: Searches of MEDLINE from January 1966 to December 1996 were comb ined with manual searches of the bibliographies and references from ex perts. Citations were chosen by 2 reviewers if they were related to re d blood cell transfusion practice and, more specifically, to physiolog ic 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 infer ences were derived from the literature. Results: Of the 160 articles i ncluded 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 st udies (56%) used a valid design with appropriate experimental and conc urrent control groups (graded as level I or II). The distribution of g rading was uniform throughout the categories. The quality of the evide nce was deemed weaker for laboratory studies evaluating cardiac adapta tion to anemia, largely because of a lack of reported concurrent contr ols in most studies. Inferences drawn from the literature were graded on a 4-point scale assessing the quality of the evidence; 13 of 18 sta tements were given the highest grade. The clinical significance of the Bohr effect and the shifts in the oxyhemoglobin curve following chang es in pH were thought to be poorly studied and were rated lowest. The studies evaluating maximum oxygen delivery in anemia were rated as wea k, partly because of conflicting reports. Of all identified studies, 5 6% were well designed and reported. Important adaptive responses to an emia 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 ra ted highly. The evidence also suggests that patients with cardiac dise ase are at risk of adverse events from anemia. Conclusions: There is a significant body of evidence supporting cardiovascular adaptive respo nses to anemia. However, there is a remarkable lack, in both quality a nd quantity, of clinical studies addressing how the ''normal'' physiol ogic adaptations may be affected by a variety of diseases. The physiol ogic evidence alone is insufficient to inform most decisions about red brood cell transfusion.