Multiple Causes of Anemia in Surgical Patients
Anemia is a concern for the surgical patient in two phases of treatment: before surgery and in the immediate perioperative period, which includes both the surgery itself and the time spent in the hospital during postoperative recovery. Surgery patients may develop preoperative anemia from acute or chronic blood loss (eg, trauma or peptic ulcer oozing), iron deficiency caused by poor nutrition or menstrual bleeding, renal insufficiency, malignancy, or chronic disease (eg, rheumatoid arthritis or inflammatory bowel disease).^1,2

Catastrophic bleeding during surgery may occur, but this is uncommon and usually can be controlled before significant anemia develops. Coagulation defects, either congenital or acquired, such as trauma-induced disseminated intravascular coagulation, may lead to anemia. Frequent phlebotomies and untreated bleeding episodes can also cause blood loss and contribute to anemia during surgery and recovery.² Furthermore, after surgery, the erythropoietic response may be severely blunted in anemic patients because of diminished iron availability and the inhibitory actions of inflammatory cytokines.¹ Reduced red cell life span and occult gastrointestinal bleeding may also contribute to anemia in surgical patients.

Anemia Prevalence Varies in Surgical Patients
It is difficult to estimate an overall prevalence of anemia in surgery patients, in part because of variations among patients undergoing different types of surgery as well as the variability in investigators’ anemia definitions. A recent review of the literature found 10 studies reporting the prevalence of anemia among surgery patients.³ In these studies, the prevalence ranged from a low of 5% (in female geriatric hip fracture patients) to almost 76% (in patients with Dukes’ stage D colon cancer). Clemens and Spivak found that 56% (49% of the women and 63% of the men) in a group of 84 elective surgery patients were anemic before surgery. Moreover, 66% of the women and 88% of the men were anemic after surgery. On postoperative day 5, the anemia frequency increased to 90% (80% of the women and all of the men), probably due to a blunted erythropoietic response.⁴ Dunne and colleagues recently reported that 33.9% of 6,301 patients scheduled for noncardiac surgery were anemic before surgery and 84.1% were anemic in the postoperative period.⁵

Some patients may be more susceptible than others to perioperative anemia. Clemens and Spivak reported that female or African American patients were more susceptible to surgery-induced suppression of erythropoiesis.⁴ In a study of nearly 7,000 patients undergoing coronary artery bypass graft (CABG) surgery, DeFoe and colleagues found that female patients and those with smaller body surface area were at increased risk of anemia compared to males and larger patients.⁶ Gruson and colleagues found that 180 of 395 patients (45.6%) who entered their hospital for repair of a hip fracture were anemic, suggesting that recent blood loss from a hip fracture may be superimposed on chronic anemia.⁷

Increased Postoperative Risk of Anemia
Findings of several studies suggest that perioperative anemia may increase the risk of postoperative morbidity and mortality.^8-10 However, the exact relationships among preoperative, intraoperative, and postoperative factors and how to measure anemia remain unclear. Below-normal preoperative Hb levels may or may not be a deciding factor.

Carson and colleagues demonstrated that the degree of anemia as measured by Hb and Hct values was associated with postoperative mortality in the nontransfused patient.¹¹ However, in the same patients the research group showed that the amount of surgical blood loss was more important than preoperative Hb or Hct value.¹² Upon analysis of a larger patient population, these researchers found that among patients with low preoperative Hb (<6 g/dL), the risk of death was more pronounced in those with cardiovascular disease than in those without (interaction P <0.03).¹³ Subsequent analyses have called into question the validity of preoperative Hb and Hct values as predictors of outcome other than an increased need for transfusion.^14-16

Other researchers have shown that preoperative Hb and Hct values can be used as predictors of outcome for specific types of patients, namely those undergoing CABG or orthopedic surgery.^17,18 The Northern New England Cardiovascular Disease Study Group has shown an association between nadir Hct during cardiopulmonary bypass and postoperative morbidity and mortality in 6,980 patients who underwent CABG.⁶ Female patients and those with a smaller body size were most susceptible to low intraoperative Hct, suggesting that excessive hemodilution may contribute to this problem. This same group previously showed that hemorrhage leading to re-exploration after CABG was associated with increased mortality, as one would expect.¹⁹ The findings of another study, which involved nearly 1,000 patients undergoing CABG, revealed that a measure combining age and red blood cell volume was an important determinant of postoperative morbidity, as indicated by either serious complications or increased length of hospital stay. The researchers concluded that older patients with preoperative anemia, low blood volume, and comorbidities were at increased risk for postoperative complications.⁸

Dunne and colleagues point out the clinical significance of perisurgical anemia by demonstrating a statistical relationship between anemia and increased morbidity, mortality, and length of stay.⁵ Overall length of stay and mortality up to 12 months after surgery were higher in the anemic group of patients in Gruson and colleagues’ study of hip fracture patients.⁷

In addition to influencing survival and morbidity in surgical patients, perioperative anemia may adversely affect quality of life (QOL), especially because of its contribution to fatigue.^20,21

Of particular relevance to surgery patients is the relationship between lowered Hb levels and the safety of general anesthesia. Some patients with lower perioperative Hb levels may be at increased risk of hypoxemia; therefore, the issue of safety should be considered in anemic patients undergoing anesthesia. ²² Anemia might also be one of several factors that can contribute to delirium during surgery.²³ In addition, red blood cells might play an important role as a supplier of phospholipids in the blood coagulation pathway; thus, anemia could represent a risk factor for hemorrhagic tendency.²⁴

Presurgical Strategies Correct Anemia
Multiple strategies can be used to correct perioperative anemia. These include allogeneic blood transfusion, the use of single transfusion alternatives, or combinations of the alternatives.^25,26 Allogeneic blood transfusion should be avoided whenever possible, not only because of associated risks but also because transfusion has not been proven to improve postoperative outcomes.²⁷ Transfusion risks include reactions, disease transmission, and immunomodulation.^28,29 Transfusion decisions must focus on patient characteristics, not Hb or Hct values alone.³⁰

The simplest approach is to avoid transfusion regardless of the level of preoperative anemia. This may be necessary in emergency cases or in patients who refuse transfusion. Ott and Cooley’s landmark report of successful cardiac surgery without blood transfusion in 542 Jehovah’s Witness patients was the first demonstration that surgery could be done using this strategy without excessive blood loss or mortality.³¹ The sine qua non of success using this approach is meticulous surgery to eliminate or reduce operative blood loss. This strategy entails accepting a lowered transfusion threshold, or trigger, and has been proven to be safe by several surgical groups.^25,32,33 The use of autologous blood either through preoperative donation or autotransfusion to return shed blood is also helpful.^28,29

In surgeries with an expected high blood loss (>1,000 mL), one of the major anesthetic techniques for avoiding allogeneic blood use is acute normovolemic hemodilution (ANH). ANH is a procedure that reduces the patient’s red blood cell mass by the controlled removal of whole blood and the simultaneous replacement with colloid, crystalloid, or both to maintain essential adequate circulatory volume. The purpose of ANH is to avoid allogeneic blood transfusions during and after surgery. ANH is a point-of-care technique that results in acute anemia, decreased blood viscosity, and preserved tissue perfusion.³⁴

While ANH is one cornerstone, other necessary blood conservation practices are pharmaceuticals (primarily erythropoietin plus iron) for enhancing Hb production, preoperative autologous donation, minimally invasive surgical techniques, new techniques for hemostasis, the staging of difficult surgical procedures, and intraoperative cell salvage. These are used selectively or in combination. Along with these specific techniques, a reasoned approach is necessary for a greater understanding of the implications of tolerating acute anemia.

Preoperative anemia often goes unrecognized and untreated unless the surgeon makes a particular effort to order Hb and Hct tests for review in advance of a planned operation. Therefore, the first step to be taken with the anemic patient is to establish the presence of the problem early enough to do something about it, if the risk is to be decreased by avoiding allogeneic blood.

Although alternative therapies have their own risks, these are typically minimal when compared to transfusion. Autologous predonation can be very effective in reducing reliance on allogeneic blood, but it has been shown to increase overall exposure to transfusion and to increase the chance of perioperative anemia.^28,29,35 This problem can be avoided by the use of iron replenishment and erythropoietin to facilitate autologous blood procurement before surgery.^36-38

Use of erythropoietin alone may eliminate the need for transfusion in some surgical patients, but when transfusion is indicated, the most effective approach may be to combine preoperative erythropoietin administration with procurement of autologous blood by methods such as ANH.³⁹

Erythropoietin use is also helpful in the postoperative period because it accelerates Hct recovery.⁴⁰ Erythropoietin has also been used in bloodless surgery, protecting patients from the possible hazards of allogeneic blood transfusion. ^1,21,41,42 In addition to reducing the need for transfusion, management of anemia with erythropoietin has been shown to accelerate erythropoiesis and to enhance QOL in surgery patients.^43,44

Beneficial Effects of Anemia Management
Early recognition of anemia allows the surgeon to offer patients proven, safe alternatives to allogeneic blood, thereby reducing risk. Blood transfusion has not been shown to reduce morbidity and mortality in surgical patients, but alternatives such as erythropoietin have. Sound management of anemia with combinations of alternatives avoids risk and appears to provide better outcomes.

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References

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