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Does Acute Normovolemic Hemodilution Reduce Perioperative Allogeneic Transfusion? A Meta-Analysis
PERIOPERATIVE CARE
287
removal of porous plastic tape and pectin based barriers (for stoma appliances) can be quite traumatic to neonatal skin. Currently, lipid rich barrier creams are being developed that provide better skin protection. The ideal forms of adhesives, and methods of tape and adhesive removal in premature neonates need to be standardized. Jack S. Elder, M.D.
PERIOPERATIVE CARE Perioperative Epoetin Alfa Increases Red Blood Cell Mass and Reduces Exposure to Transfusions: Results of Randomized Clinical Trials
M. A. GOLDBERG, Hematology I Oncology Division, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts Sem. Hematol., 34:41-47, 1997 To avoid the inherent risk of complications associated with perioperative allogeneic transfusion, preoperative autologous blood donation (PAD) is frequently employed by patients undergoing major elective surgical procedures. However, many patients are unable t o donate a sufficient quantity of blood prior to surgery. Recent studies have shown that epoetin alfa (ProcritB; Ortho-Biotech, Raritan, N J ) effectively increases red blood cell (RBC) mass when administered preoperatively and decreases the requirement for allogeneic transfusion. These studies also demonstrated that patients with baseline hemoglobin levels ranging from 10 to 13 g/dL have the highest risk for requiring allogeneic transfusions and appear to achieve the greatest benefit from epoetin alfa treatment. We evaluated several dosing regimens and schedules for perioperative epoetin alfa administration. In our initial study, the comparative efficacy of three different epoetin alfa regimens was assessed by hemoglobin concentration, hematocrit, and absolute reticulocyte counts. In addition, we analyzed the effect of accelerated erythropoiesis on iron indices and individual RBC hemoglobin content. Our study demonstrated that epoetin alfa is safe and effective in increasing RBC mass; however, iron stores considered sufficient for basal erythropoiesis may not optimally support the accelerated RBC production associated with epoetin alfa therapy. In a subsequent randomized multicenter trial, we compared weekly epoetin alfa dosing to daily dosing in patients undergoing elective major orthopedic surgery. The results of this study indicated that administering epoetin alfa on a weekly schedule for several weeks prior to surgery may be at least as effective and more convenient than perioperative daily epoetin alfa dosing. Editorial Comment: Recombinant epoetin a is functionally similar to endogenous erythropoietin, stimulates erythropoiesis and is being considered increasingly as a m e a n s to increase red blood cell m a s s before elective surgery. This report is of a series of clinical trials evaluating the use of erythropoietin f o r orthopedic surgery. The drug w a s effective in increasing red blood cell mass but whether this ultimately translates into a decreased transfusion requirement depends on the patient population and type of procedure. Iron stores are rapidly depleted with erythropoietin treatment and the authors found that oral ingestion of iron w a s less effective than intravenous administration. The optimal dosing regimen is still being explored but this s t u d y did show that daily dosing probably is not necessary. Joseph A. Smith, Jr., M.D.
Does Acute Normovolemic Hemodilution Reduce Perioperative Allogeneic Transfusion? A Meta-Analysis G. L. BRYSON, A. LAUPACIS AND G. A. WELLS FOR THE INTERNATIONAL STUDY OF PERIOPERATIVE TRANSFUSION, Department of Anaesthesia and Clinical Epidemiology Unit, Loeb Medical Research Institute, Ottawa Civic Hospital, Ottawa, Ontario, Canada Anesth. Analg., 8 6 9-15, 1998 The objective of this study was to systematically review the literature and to statistically summarize the evidence evaluating acute normovolemic hemodilution (ANH).Prospective, randomized, controlled trials of ANH that reported either the proportion of patients exposed to allogeneic blood or the units of allogeneic blood transfused were included. All types and languages of publication were eligible. Of 1573 identified publications, 24 trials (containing a total of 1218 patients) were included in the meta-analysis. When all trials were pooled, ANH reduced the likelihood of exposure to allogeneic blood (odds ratio [OR] 0.31,95% confidence interval [CI] 0.15, 0.62) and the total units of allogeneic blood transfused (weighted mean difference [WMD] -2.22 U, 95% CI -3.57, -0.86).However, there was marked heterogeneity of the results. In trials using a protocol to guide perioperative transfusion, ANH failed to reduce either the likelihood of transfusion (OR 0.64,95% CI 0.31,1.31)or the units administered (WMD -0.25 U, 95% CI -0.60,0.10).
288
PERIOPERATIVE CARE
Adverse events were incompletely reported. It is possible that biased experimental design is, in part, responsible for the reported efficacy of this technique. Implications: After a systematic literature review, 24 randomized trials examining the role of acute normovolemic hemodilution were identified, pooled, and summarized using statistical techniques. Many studies reported an impressive reduction in blood transfused. Closer examination suggests that these reductions in blood exposure may be due to flawed study design.
Editorial Comment: There are reports of the use of normovolemic hemodilution to decrease the transfusion requirement after radical prostatectomy. In this meta-analysis the authors evaluated 24 published trials on the use of normovolemic hemodilution. Does the procedure work in decreasing transfusion requirement? According to the authors, their meta-analysis ”provides the best estimate of the efficacy of acute normovolemic hemodilution now available.” They also state, “unfortunately, the results of this analysis are inconclusive.” The procedure may have some applicability at select centers with experience with the technique but there seems little reason to pursue new expertise at the centers that are not using normovolemic hemodilution. Joseph k Smith, Jr., M.D. Low Molecular Weight Heparin and Unfractionated Heparin in Thrombosis Prophylaxis After Major Surgical Intervention: Update of Previous Meta-Analyses
A. KOCH,S. BOUGES, S. ZIEGLER, H. DINKEL, J. P. DAURES AND N. VICTOR, Abteilung Medizinische Biometrie, Universitat Heidelberg, Heidelberg, Germany and Departement de l’lnformation Medicale, Centre Hospitalier Regional et Universitaire de Nimes, Nimes, France Brit. J. Surg., 84.750-759, 1997 Background Previous meta-analyses comparing low molecular weight heparin (LMWH) and unfractionated heparin for thrombosis prophylaxis after surgical interventions need updating. Methods This is a publication-based meta-analysis of 36 double-blind studies including 16 583 patients. Main outcome measures are incidence of deep vein thrombosis (efficacy) and wound haematoma (safety). Results In general surgery there is no increased efficacy in favour of LMWH (odds ratio (OR) 0-88,95 per cent confidence interval (c.i.)0.60-1.30) but there exists a higher incidence of bleeding complications (OR 1.47,95 per cent c.i. 1 07-2 01). Low-dose LMWH is equally efficacious (OR 1* 03,95 per cent c.i. 0.85-1. 26) but safer than unfractionated heparin (OR 0 68,95 per cent c.i. 0 .56-0 * 82). In orthopaedic surgery there is a trend towards an increased efficacy for LMWH (OR 0 . 83, 95 per cent c.i. 0 . 68-1 * 02) with equivalent safety (OR 0 . 96, 95 per cent c.i. 0 . 68-1 . 36). Conclusion A superiority of LMWH is suggested but heterogeneity might make generalizability t o future patients questionable. A meta-analysis on individual patient data should be the next step before randomizing additional patients in future trials.
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Editorial Comment: The efficacy of heparin in decreasing postoperative thromboembolic complications has been demonstrated repeatedly. The development of low molecular weight heparin compounds has led to multiple studies comparing low molecular weight heparin and unfractionated heparin. Often these studies are sponsored by a pharmaceutical company that owns the patent on a low molecular weight heparin compound. There has been little to suggest that low molecular weight heparin is more effective than unfractionated heparin but the hope has been that the risk of bleeding complications, which is relatively low with unfractionated heparin, is reduced even M h e r with low molecular weight heparin compounds. This meta-analysis did not substantiate a clear-cut superiority for low molecular weight heparin. The conclusion of the authors was that more studies need to be performed. However, 36 double-blind randomized trials have been published on this subject. Whatever difference exists must be relatively small and of questionable clinical relevance. Joseph k Smith, Jr., M.D.
A SpuriousCorrelation Between Hospital Mortality and Complication Rates. The Importance of Severity Adjustment J. H. SILBER AND P. R. ROSENBAUM, Leonard Davis Institute of Health Economics, Department of Pediatrics, University of Pennsylvania School of Medicine and Department of Statistics, Wharton School, University of Pennsylvania, Philadelphia, Pennsylvania Med. Care, 3 5 OS77-OS92, 1997 Objectives. When two outcome measures, such as mortality and complication rates, are intended to measure the same underlying quantity (in this case hospital quality of care), one expects they will be highly correlated. In addition, as data quality improves, one expects the correlation will increase. The authors show that these expectations are, in a significant way, mistaken. Methods. The authors study two outcomes (hospital mortality and complication rates after surgery) using three predictive models that vary in adjustment for severity of illness.
287
removal of porous plastic tape and pectin based barriers (for stoma appliances) can be quite traumatic to neonatal skin. Currently, lipid rich barrier creams are being developed that provide better skin protection. The ideal forms of adhesives, and methods of tape and adhesive removal in premature neonates need to be standardized. Jack S. Elder, M.D.
PERIOPERATIVE CARE Perioperative Epoetin Alfa Increases Red Blood Cell Mass and Reduces Exposure to Transfusions: Results of Randomized Clinical Trials
M. A. GOLDBERG, Hematology I Oncology Division, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts Sem. Hematol., 34:41-47, 1997 To avoid the inherent risk of complications associated with perioperative allogeneic transfusion, preoperative autologous blood donation (PAD) is frequently employed by patients undergoing major elective surgical procedures. However, many patients are unable t o donate a sufficient quantity of blood prior to surgery. Recent studies have shown that epoetin alfa (ProcritB; Ortho-Biotech, Raritan, N J ) effectively increases red blood cell (RBC) mass when administered preoperatively and decreases the requirement for allogeneic transfusion. These studies also demonstrated that patients with baseline hemoglobin levels ranging from 10 to 13 g/dL have the highest risk for requiring allogeneic transfusions and appear to achieve the greatest benefit from epoetin alfa treatment. We evaluated several dosing regimens and schedules for perioperative epoetin alfa administration. In our initial study, the comparative efficacy of three different epoetin alfa regimens was assessed by hemoglobin concentration, hematocrit, and absolute reticulocyte counts. In addition, we analyzed the effect of accelerated erythropoiesis on iron indices and individual RBC hemoglobin content. Our study demonstrated that epoetin alfa is safe and effective in increasing RBC mass; however, iron stores considered sufficient for basal erythropoiesis may not optimally support the accelerated RBC production associated with epoetin alfa therapy. In a subsequent randomized multicenter trial, we compared weekly epoetin alfa dosing to daily dosing in patients undergoing elective major orthopedic surgery. The results of this study indicated that administering epoetin alfa on a weekly schedule for several weeks prior to surgery may be at least as effective and more convenient than perioperative daily epoetin alfa dosing. Editorial Comment: Recombinant epoetin a is functionally similar to endogenous erythropoietin, stimulates erythropoiesis and is being considered increasingly as a m e a n s to increase red blood cell m a s s before elective surgery. This report is of a series of clinical trials evaluating the use of erythropoietin f o r orthopedic surgery. The drug w a s effective in increasing red blood cell mass but whether this ultimately translates into a decreased transfusion requirement depends on the patient population and type of procedure. Iron stores are rapidly depleted with erythropoietin treatment and the authors found that oral ingestion of iron w a s less effective than intravenous administration. The optimal dosing regimen is still being explored but this s t u d y did show that daily dosing probably is not necessary. Joseph A. Smith, Jr., M.D.
Does Acute Normovolemic Hemodilution Reduce Perioperative Allogeneic Transfusion? A Meta-Analysis G. L. BRYSON, A. LAUPACIS AND G. A. WELLS FOR THE INTERNATIONAL STUDY OF PERIOPERATIVE TRANSFUSION, Department of Anaesthesia and Clinical Epidemiology Unit, Loeb Medical Research Institute, Ottawa Civic Hospital, Ottawa, Ontario, Canada Anesth. Analg., 8 6 9-15, 1998 The objective of this study was to systematically review the literature and to statistically summarize the evidence evaluating acute normovolemic hemodilution (ANH).Prospective, randomized, controlled trials of ANH that reported either the proportion of patients exposed to allogeneic blood or the units of allogeneic blood transfused were included. All types and languages of publication were eligible. Of 1573 identified publications, 24 trials (containing a total of 1218 patients) were included in the meta-analysis. When all trials were pooled, ANH reduced the likelihood of exposure to allogeneic blood (odds ratio [OR] 0.31,95% confidence interval [CI] 0.15, 0.62) and the total units of allogeneic blood transfused (weighted mean difference [WMD] -2.22 U, 95% CI -3.57, -0.86).However, there was marked heterogeneity of the results. In trials using a protocol to guide perioperative transfusion, ANH failed to reduce either the likelihood of transfusion (OR 0.64,95% CI 0.31,1.31)or the units administered (WMD -0.25 U, 95% CI -0.60,0.10).
288
PERIOPERATIVE CARE
Adverse events were incompletely reported. It is possible that biased experimental design is, in part, responsible for the reported efficacy of this technique. Implications: After a systematic literature review, 24 randomized trials examining the role of acute normovolemic hemodilution were identified, pooled, and summarized using statistical techniques. Many studies reported an impressive reduction in blood transfused. Closer examination suggests that these reductions in blood exposure may be due to flawed study design.
Editorial Comment: There are reports of the use of normovolemic hemodilution to decrease the transfusion requirement after radical prostatectomy. In this meta-analysis the authors evaluated 24 published trials on the use of normovolemic hemodilution. Does the procedure work in decreasing transfusion requirement? According to the authors, their meta-analysis ”provides the best estimate of the efficacy of acute normovolemic hemodilution now available.” They also state, “unfortunately, the results of this analysis are inconclusive.” The procedure may have some applicability at select centers with experience with the technique but there seems little reason to pursue new expertise at the centers that are not using normovolemic hemodilution. Joseph k Smith, Jr., M.D. Low Molecular Weight Heparin and Unfractionated Heparin in Thrombosis Prophylaxis After Major Surgical Intervention: Update of Previous Meta-Analyses
A. KOCH,S. BOUGES, S. ZIEGLER, H. DINKEL, J. P. DAURES AND N. VICTOR, Abteilung Medizinische Biometrie, Universitat Heidelberg, Heidelberg, Germany and Departement de l’lnformation Medicale, Centre Hospitalier Regional et Universitaire de Nimes, Nimes, France Brit. J. Surg., 84.750-759, 1997 Background Previous meta-analyses comparing low molecular weight heparin (LMWH) and unfractionated heparin for thrombosis prophylaxis after surgical interventions need updating. Methods This is a publication-based meta-analysis of 36 double-blind studies including 16 583 patients. Main outcome measures are incidence of deep vein thrombosis (efficacy) and wound haematoma (safety). Results In general surgery there is no increased efficacy in favour of LMWH (odds ratio (OR) 0-88,95 per cent confidence interval (c.i.)0.60-1.30) but there exists a higher incidence of bleeding complications (OR 1.47,95 per cent c.i. 1 07-2 01). Low-dose LMWH is equally efficacious (OR 1* 03,95 per cent c.i. 0.85-1. 26) but safer than unfractionated heparin (OR 0 68,95 per cent c.i. 0 .56-0 * 82). In orthopaedic surgery there is a trend towards an increased efficacy for LMWH (OR 0 . 83, 95 per cent c.i. 0 . 68-1 * 02) with equivalent safety (OR 0 . 96, 95 per cent c.i. 0 . 68-1 . 36). Conclusion A superiority of LMWH is suggested but heterogeneity might make generalizability t o future patients questionable. A meta-analysis on individual patient data should be the next step before randomizing additional patients in future trials.
-
Editorial Comment: The efficacy of heparin in decreasing postoperative thromboembolic complications has been demonstrated repeatedly. The development of low molecular weight heparin compounds has led to multiple studies comparing low molecular weight heparin and unfractionated heparin. Often these studies are sponsored by a pharmaceutical company that owns the patent on a low molecular weight heparin compound. There has been little to suggest that low molecular weight heparin is more effective than unfractionated heparin but the hope has been that the risk of bleeding complications, which is relatively low with unfractionated heparin, is reduced even M h e r with low molecular weight heparin compounds. This meta-analysis did not substantiate a clear-cut superiority for low molecular weight heparin. The conclusion of the authors was that more studies need to be performed. However, 36 double-blind randomized trials have been published on this subject. Whatever difference exists must be relatively small and of questionable clinical relevance. Joseph k Smith, Jr., M.D.
A SpuriousCorrelation Between Hospital Mortality and Complication Rates. The Importance of Severity Adjustment J. H. SILBER AND P. R. ROSENBAUM, Leonard Davis Institute of Health Economics, Department of Pediatrics, University of Pennsylvania School of Medicine and Department of Statistics, Wharton School, University of Pennsylvania, Philadelphia, Pennsylvania Med. Care, 3 5 OS77-OS92, 1997 Objectives. When two outcome measures, such as mortality and complication rates, are intended to measure the same underlying quantity (in this case hospital quality of care), one expects they will be highly correlated. In addition, as data quality improves, one expects the correlation will increase. The authors show that these expectations are, in a significant way, mistaken. Methods. The authors study two outcomes (hospital mortality and complication rates after surgery) using three predictive models that vary in adjustment for severity of illness.