Patient Handgrip Strength and Vigor After Total Joint Arthroplasty

Patients undergoing total joint arthroplasty often experience significant blood loss and may need allogeneic blood transfusions. To avoid these risks, patients will often donate autologous blood before surgery, a practice known as preoperative autologous donation (PAD). PAD does carry some risks, including anemia and allergic reactions. Alternatively, recombinant human erythropoietin (EPO) dosing prior to surgery has shown promise in reducing the need for postoperative transfusions. Thus, a randomized, open-label clinical study was undertaken to assess the postoperative effects of PAD versus EPO dosing in patients before elective orthopedic surgery.

In the study, 251 adult patients with baseline hemoglobin levels of 11-14 g/dL received EPO (600 IU/kg once weekly for 4 doses, n=130) or PAD (n=121) and were assessed for postoperative vigor and handgrip strength after undergoing total joint arthroplasty. Reliable questionnaires were used to assess vigor, while handgrip strength was measured using a JAMAR Hand Dynamometer. Hemoglobin levels and the need for transfusions were also monitored postoperatively. All patients were screened for baseline exclusion criteria which included hypertension, pregnancy, presence of seizure disorders, deep vein thrombosis, gastrointestinal bleeding, and other cardiovascular or pulmonary disorders not well controlled.

Based on previous EPO studies predicting an improvement in energy and quality of life, this trial originally hypothesized a postoperative increase in both vigor and handgrip strength in patients receiving EPO prior to surgery. A univariate analysis of vigor and handgrip strength showed no statistical difference between the EPO and PAD groups 21 days postoperatively. However, a multivariate analysis that controlled for baseline factors showed a significant overall increase in vigor (p=.011) in EPO patients, but not a significant increase in handgrip strength (p=.245). In an analysis of hemoglobin levels, patients in the EPO group showed a significantly higher hemoglobin level (p<.001) at every postoperative visit compared to the PAD group. The mean hemoglobin level at postoperative day 21 was 12.0 g/dL in the EPO group, compared to 11.1 g/dL in the PAD group. The need for postoperative transfusions was also monitored, with four EPO patients (3%) and 79 PAD patients (65%) requiring transfusions during the operation or postoperatively.

According to the study, EPO certainly seems to have clinical potential for patients undergoing total joint arthroscopy, especially in raising hemoglobin levels and reducing the need for postoperative transfusions. However, more work needs to be done to better assess interfering factors such as the presence of anemia after PAD or insufficiently sensitive hand dynamometers.

Please reference the source article:
A randomized, parallel-group, open-label trial of recombinant human erythropoietin vs preoperative autologous donation in primary total joint arthroplasty: effect on postoperative vigor and handgrip strength Keating EM. Callaghan JJ. Ranawat AS. Bhirangi K. Ranawat CS. Journal of Arthroplasty. 22(3):325-33, 2007 Apr.

NAAC Expert Commentary:
The article by Keating et al. compares erythropoietin versus preoperative autologous blood donation for patients with total joint arthroplasty. This open-label study concludes that erythropoietin improves "vigor" but does not affect grip strength. However, several significant issues should be considered before accepting these conclusions. First, the study’s measurement of "vigor" does not directly examine important functional issues by using a fully validated measure such as the HAQ disability index or some other validated measure. The study questionnaire contained some relatively general questions and questions not even directly related to this somewhat amorphous word—“vigor.” In addition, the study does not address an important issue such as fatigue or examine quality of life using a fully validated instrument (such as the SF 36 or Quality of Well-Being scale).

After controlling for baseline hemoglobin, the erythropoietin group had a significantly greater improvement in "vigor". However if one looks carefully at the patients’ hemoglobin levels, it is clear that these hemoglobin levels were significantly lower in the patients with transfusions (prior to receiving any transfusions if they required them) and, consequently, it is not a great surprise that these patients have less "vigor," baseline compensation notwithstanding.

The authors also had assumed a 5% attrition rate. However, the study actually had a 10% to 14% attrition rate, making this study somewhat underpowered to discern whether a real difference existed or not.

The authors have stated that cost effectiveness was beyond the scope of the study. However, it is really only here that one might expect to see any clinically significant difference. Overall, this study does not expand our knowledge with respect to the usefulness of erythropoietin versus transfusions-as-needed, although it does provides some tantalizing data.

Improved Patient Outcomes in Appropriate Clinical Settings

According to reports from the National Health and Nutrition Examination Survey, 20 million people in the United States may have chronic kidney disease (CKD). Anemia is a common complication associated with CKD, and often leads to adverse cardiovascular events and decreased health-related quality of life. Recently, a study evaluating a multidisciplinary clinical treatment approach was undertaken at university-affiliated CKD clinics. The goal of the study was to assess how a reengineered clinic and redefined clinical roles of the health care team could improve the care of patients by meeting the National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (K/DOQI).

In the study, 166 patients with anemia of CKD received darbepoetin alfa dosed on an every-other-week basis, as well as oral iron supplements. Dosage amount and frequency were adjusted to achieve the K/DOQI targets for hemoglobin (>11.0 g/dL) and iron measures (transferrin saturation of 20% or greater; ferritin of 100ng/ml or greater). Primary outcome was measured as the number of patients with at least 30 days of treatment who achieved the target hemoglobin level or greater. Of the patients in the study, 52% were female, and most were Caucasian (50%) or African-American (45%) with a mean age of 62 years. The multidisciplinary team included a clinical pharmacist, a supervising nephrologist, a clinical nurse, a vascular access nurse, and data managers.

Of the original 166 patients, 128 patients received at least 30 days of treatment. In this treatment group, 100 (78%) reached the target hemoglobin level. Also, 99 of the original 128 patients were naïve to previous attempts of recombinant human erythropoietin therapy. Of these 99 patients, 77 (78%) achieved the hemoglobin target in an average of 7 weeks. Furthermore, 60% of patients receiving oral iron administration throughout the 30-day treatment and beyond reached K/DOQI targets in hemoglobin, ferritin, and transferrin levels.

The results of this study show how a reengineered clinical practice using a multidisciplinary treatment team can improve the management of CKD. A multidisciplinary approach can better assure timely therapy with darbepoetin alfa and oral iron, increase the appropriateness of patient referrals, and improve monitoring of laboratory tests. The continuity of care is increased in a multidisciplinary approach because patients tend to see their clinic providers more frequently than their primary care provider and receive prompt dosage adjustments and vigilant monitoring of hemoglobin and iron levels. This approach provides a well-planned and directed clinic that offers improved patient care in not only anemic patients, but in all CKD-related complications.

Please reference the source article:
Reengineering clinical operations in a medical practice to optimize the management of anemia of chronic kidney disease Joy MS. Candiani C. Vaillancourt BA. Chin H. Hogan SL. Falk RJ. Pharmacotherapy. 27(5):734-44, 2007 May.

NAAC Expert Commentary:
The authors of this publication have provided us with evidence for concepts that would normally be intuitively expected. In this time of evidenced based medical decision making, this type of study is helpful because it turns intuitive assumptions into actual outcome proven facts.

Chronic kidney disease (CKD) affects over 20 million Americans, and the associated co-morbidity of anemia is a common complication, which carries with it the additional increased risk of cardiac compromise and reduced quality of life. The authors' goal of modifying the university-based clinic structure to test the premise that this would improve anemia management was successfully born out.

The study of 166 CKD patients with anemia demonstrates that in a clinical setting where designated staff members have described responsibilities, including attention to anemia care, the patient outcomes improve. The clinical setting described brought to bear an impressive team of healthcare providers whose goal was to monitor and intervene in order to resolve the anemia demonstrated in these CKD patients.

This clinic concept should be helpful to private sector therapists involved in managing CKD anemia. However, modifications to the study approach would likely be required because of the difference in resource availability and the economic realities of private practice patient care. Prospective studies evaluating patient outcomes in private practice clinics where similar efforts were undertaken would be useful in providing evidence which might demonstrate cost savings and encourage third-party payers to adopt and promote similar care models. This study, in order to increase attention, would benefit from a larger patient sampling. This wider audience would increase its care planning impact and the degree of its influence on anemia intervention.

Careful Treatment for Acute Coronary Syndrome Patients

Acute coronary syndromes (ACSs) result from imbalances between myocardial oxygen supply and demand. Although some studies have shown conflicting results, anemia has been shown to exacerbate ACS imbalances by causing decreases in oxygen-carrying capacity. However, not much is known about the prognostic value of blood transfusions in this setting. Thus, a recent study has examined the impact of red blood cell transfusions in anemic patients presenting with ACSs and non-ST-elevation myocardial infarctions (MIs).

This observational study included 370 anemic patients with hemoglobin levels of <11.5 g/dL. These patients were predominantly white (70.9%) and male (99.1%). The study determined 30-day event rates by review of electronic medical records with a primary end-point of combined incidence of death or new MI within 30 days of the index hospitalization. All patients received a thorough physical examination prior to inclusion in the study to screen for exclusion criteria such as pulmonary edema or persistent ST elevations.

Of the study population, 110 patients (29.7%) received blood transfusions. In this group, 37 patients (33.6%) experienced adverse effects (MI or death), compared to 38 patients (14.2%) in the non-transfusion group (n=260). A multivariate analysis showed that patients receiving blood transfusions had a higher rate of 30-day recurrent MI or death (odds ratio 3.05, 95% confidence interval 1.80 to 5.17, p<.001). This analysis indicates a strong association between blood transfusions and adverse 30-day outcomes. Also, the transfusion group showed a lower hemoglobin level (8.9 g/dL) than the non-transfusion group (9.2 g/dL).

The results of this study indicate that anemic patients carry a 2.5-fold higher risk of adverse effects after receiving red blood cell transfusions. However, several limitations point out the need for further studies. For example, the study population was predominantly male with a mean age of 70 years. Women and younger patients may tolerate lower hematocrit levels differently, and therefore the risk-benefit ratio of transfusions may be skewed toward higher risk with an elderly male population. Also, due to the observational nature of the study, precise, unmeasured clinical factors may have impacted the results. More studies need to be done to assess thresholds at which transfusions become beneficial for anemic patients.

Please reference the source article:
Impact of blood transfusions in patients presenting with anemia and suspected acute coronary syndrome Singla I. Zahid M. Good CB. Macioce A. Sonel AF. American Journal of Cardiology. 99(8):1119-21, 2007 Apr 15.

NAAC Expert Commentary:
The large TIMI database has established that both anemia and polycythemia (too many red cells) are risk factors for adverse 30-day outcomes in patients who have an acute myocardial infarction. Whether anemia is a marker or mediator of an increased risk remains unclear, but risk could be due to inflammation that results in anemia. In this case, treatment of the marker anemia would not prevent the adverse risk of the mediator,(the inflammation) unless treatment also lowers inflammation. In any case, effective treatments for anemia in patients with an acute myocardial infarction remain unknown.

In this retrospective study, the authors evaluated whether treatment of anemia by transfusion was associated with improved outcomes. They observed damage in patients with admission hemoglobins above 9.0 g/dL, suggesting that transfusions may be neutral or possibly beneficial in patients with hemoglobins below 9.0 g/dL. The study’s major limitation was the absence of nadir hematocrit data and data to explain the reasons for transfusion, whether GI bleeding or groin hematoma related to a cardiac catheterization/PCI. Assuming that the institution did not perform CABG procedures—known to be associated with transfusions and an increased 30-day risk—the reason for an increased risk in adverse outcomes could be due to the underlying complication rather than the transfusion. Similarly, the nadir hemoglobin is another potential trigger for transfusion that was not reported. Another possibility is that a transfusion could have occurred after a 10.0 g/dL admission hemoglobin decreased to 7.0 g/dL. In this case, the higher risk would likely be due to the hemoglobin of 7.0 g/dL, rather than the transfusion itself.

It is also unknown if erythropoietic stimulating proteins are beneficial in patients with anemia and an acute myocardial infarction. Some animal studies, which may not be applicable to humans, have suggested that these agents may have an anti-apoptotic effect if administered early after the myocardial infarction. Moreover, recent trials with chronic renal disease patients, comparing conservative vs. aggressive hemoglobin targets, suggested an increased risk of myocardial infarctions when attempting to raise the hemoglobin level above 12.0 g/dL.

It seems reasonable to evaluate the cause of the anemia (including occult blood loss) in acute myocardial infarction patients and to treat with oral iron, vitamin B12, and folate if appropriate. It is likely that acute inflammation will resolve over the next several months and that the anemia may improve, as well. This article suggests it is prudent to avoid transfusion for hemoglobin levels of greater than 9.0, unless there is ongoing ischemia that is refractory to other interventions.