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Acute Normovolemic Hemodilution Reduces Allogeneic Red Blood Cell Transfusion in Cardiac Surgery: A Systematic Review and Meta-analysis of Randomized Trials

Barile, Luigi MD*†; Fominskiy, Evgeny MD, PhD; Di Tomasso, Nora MD*; Alpìzar Castro, Ligia Elena MD§; Landoni, Giovanni MD*†; De Luca, Monica MD*; Bignami, Elena MD*; Sala, Alessandra MD; Zangrillo, Alberto MD*†; Monaco, Fabrizio MD*

doi: 10.1213/ANE.0000000000001609
Hemostasis
Free
SDC

BACKGROUND: To better understand the role of acute normovolemic hemodilution (ANH) in a surgical setting with high risk of bleeding, we analyzed all randomized controlled trials (RCTs) in the setting of cardiac surgery that compared ANH with standard intraoperative care. The aim was to assess the incidence of ANH-related number of allogeneic red blood cell units (RBCu) transfused. Secondary outcomes included the rate of allogeneic blood transfusion and estimated total blood loss.

METHODS: Twenty-nine RCTs for a total of 2439 patients (1252 patients in the ANH group and 1187 in the control group) were included in our meta-analysis using PubMed/MEDLINE, Cochrane Controlled Trials Register, and EMBASE.

RESULTS: Patients in the ANH group received fewer allogeneic RBCu transfusions (mean difference = −0.79; 95% confidence interval [CI], −1.25 to −0.34; P = .001; I2 = 95.1%). Patients in the ANH group were overall transfused less with allogeneic blood when compared with controls (356/845 [42.1%] in the ANH group versus 491/876 [56.1%] in controls; risk ratio = 0.74; 95% CI, 0.62 to 0.87; P < .0001; I2 = 72.5%), and they experienced less postoperative blood loss (388 mL in ANH versus 450 mL in control; mean difference = −0.64; 95% CI, −0.97 to −0.31; P < .0001; I2 = 91.8%).

CONCLUSIONS: ANH reduces the number of allogeneic RBCu transfused in the cardiac surgery setting together with a reduction in the rate of patients transfused with allogeneic blood and with a reduction of bleeding.

Published ahead of print September 23, 2016.

From the *Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Cardiac Surgery, Vita-Salute San Raffaele University, Milan, Italy; Department of Anesthesia and Intensive Care, Academician EN Meshalkin Novosibirsk State Budget Research Institute of Circulation Pathology, Novosibirsk, Russia; and §Department of Anesthesia, Mexico Hospital, San Josè, Costa Rica.

Published ahead of print September 23, 2016.

Accepted for publication August 5, 2016.

Funding: None.

The authors declare no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website.

Address correspondence to Fabrizio Monaco, MD, Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, Milano, 20132 Italy. Address e-mail to monaco.fabrizio@hsr.it.

In cardiac surgery, postoperative bleeding is one of the most relevant complications and, within a national blood supply range, it accounts for 15% to 20% of total transfusion requests. Allogeneic blood transfusions are associated with a worse short- and long-term outcome.1,2 Most of the transfusions are represented by red blood cell units (RBCu), and, for each unit transfused, there is an additive risk of mortality and cardiac adverse events.3–5 Careful control of major bleeding and management of blood losses can reduce the proportion of transfused patients and the number of surgical reinterventions.6 Despite current guideline indications and despite numerous approaches to reduce bleeding and to reduce hemoglobin transfusion threshold, >50% of the patients undergoing cardiac surgery receive transfusions.7–9 This calls for different approaches, and acute normovolemic hemodilution (ANH) could be a valid alternative. However, doubts remain as to whether ANH is capable of reducing the need for allogeneic blood and for exerting a positive effect on morbidity and mortality.

ANH is performed by drawing a specific amount of blood volume from the patient, hydrating the patient to maintain isovolemia, storing patient’s blood in storing bags at room temperature with anticoagulants, and readministering it during surgery, usually after cardiopulmonary bypass (CPB) or according to the patient’s need. The beneficial effects of ANH are reduced risk of adverse reactions related to transfusion of allogeneic blood products, preservation of erythrocytes from CPB damage, enhancing coagulation with the possibility of readministering the patient’s whole blood containing clotting factors and platelets, and improved perfusion during CPB through a decrease of blood viscosity resulting in an increased tissue oxygen delivery above the critical anaerobic threshold.10,11 ANH also is a simple and low-cost procedure, with no evidence of coagulation, hemolysis, fibrinolysis, or immunological activity in the collected blood.11

Cardiac surgery can be the ideal setting for ANH.13,14 In fact, administering fresh whole blood after CPB allows prevention of the alteration induced by heparin administration, cardiotomy suction, and cellular activation during CPB, which typically results in hemolysis, platelet activation and consumption, complement activation, and stimulation of the inflammatory cascade.15–17 Furthermore, a reduction in blood viscosity during CPB seems to improve blood flow through stenotic and collateral vessels of the myocardium and counteracts the reduced blood oxygen–carrying capacity because of hemodilution.18,19

Our study is the first meta-analysis of randomized controlled trials (RCTs) conducted in adult patients undergoing any type of cardiac surgery aimed at comparing the intraoperative use of ANH versus control patients treated according to standard intraoperative care.

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METHODS

Search Strategies

A systematic review using PubMed/MEDLINE, Cochrane Controlled Trials Register, and EMBASE was performed by 4 trained investigators.20 Additional studies were identified by manual research of references identified from original studies. In addition, authors employed backward snowballing (scanning through references of retrieved articles and pertinent reviews) and contacted international experts. Corresponding authors were contacted for missing data. The full PubMed search strategy was developed according to Biondi-Zoccai et al21 using the following key words: ANH, intraoperative anemia, intraoperative autologous blood donation and cardiac surgery, and search strategies are found in Supplemental Digital Content 1 (Supplemental Appendix 1, updated November 2015, http://links.lww.com/AA/B513). No language restrictions were enforced.

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Study Selection

References were initially examined independently, by 4 investigators, at the title and abstract level. Divergences were resolved by consensus, and potentially relevant articles were retrieved in full formats. Inclusion criteria were as follows: human studies performed in cardiac surgery (all types of procedures), random allocation to treatment, and comparison of ANH versus standard treatment.

Figure 1.

Figure 1.

Exclusion criteria were as follows: overlapping publications, studies not conducted in adult population, and non-RCT studies. Two investigators independently assessed compliance with selection criteria and isolated the studies for final analysis (Figure 1). The authors’ judgments regarding methodological quality for each included study are described in Supplemental Digital Content 2 (Supplemental Table 1, http://links.lww.com/AA/B514).

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Data Extraction

The primary end point of this review was the number of allogeneic RBCu transfused for each patient. Secondary end points were the rate of allogeneic blood transfusion and estimated total blood loss.

Computations were performed with Stata (release 11, College Station, TX).22 This study was performed in compliance with PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses).23,24 Statistical heterogeneity hypothesis was tested with statistical significance set at 2-tailed 0.1 levels, whereas the extent of statistical consistency was measured with Higgins and Thompson I2. According to Higgins et al,25I2 values around 25%, 50%, and 75% were considered to represent low, moderate, and severe statistical heterogeneity, respectively. We performed sensitivity analyses by sequentially removing each study one at a time and then repeating a separate analysis for the rest of the studies. We also performed sensitivity analyses including groups of studies with a different amount of blood removed with ANH, different type of blood replacement, different type of surgery, different number of participants, the presence or absence of a transfusion protocol, different year of publication, and different amount of perioperative total blood loss. Finally, we tested the interaction between these subgroups. We reported unadjusted P values throughout the article. Study-specific risk ratio (RR) and its 95% confidence intervals (CIs) were calculated for binary outcomes, whereas continuous variables were analyzed to compute study-specific mean differences with 95% CI. Pooled data were analyzed using the inverse variance method, either with a fixed-effect model in cases of low-moderate (I2 < 50%) statistical inconsistency or with a random-effect model in case of moderate-high (I2 > 50%) statistical inconsistency.26 Publication bias was assessed by visually inspecting funnel plots of primary outcomes, by analytical appraisal based on the Begg adjusted rank correlation test and the Egger linear regression test (a 2-sided P value of .10 or less was regarded as significant).

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RESULTS

Characteristics of the Included Studies

Table 1.

Table 1.

Table 2.

Table 2.

Twenty-nine randomized control trials for a total of 2439 patients (1252 patients in the ANH group and 1187 patients in the control group) were selected.27–55 Baseline characteristics in ANH and control group were similar in all included studies. All but 1 study included only elective patients with Herregods et al38 enrolling semiurgent coronary artery bypass graft (CABG). None of the studies mentioned the enrollment of patients with risk factors for increased risk of bleeding in cardiac surgery as per blood conservation guidelines.16 Sixteen RCTs included only CABG interventions,30,31,33,36–39,44–47,49–51,54,55 5 included combined CABG and valve operations,27,28,35,40,52 3 focused on heart valve interventions,41,48,53 1 studied CABG and aortic arch repair patients,34 and 4 took into account all types of cardiac surgery procedures.29,32,42,43 Two CABG studies focused on “off-pump” patients,46,50 2 studies did not specify if “off- or on-pump” CABG procedures were performed,35,37 whereas all other studies analyzed procedures performed with CPB. Methods used to perform ANH were different among the analyzed studies; only 1 among all RCTs analyzed 2 types of ANH methods, low- and high-volume hemodilution.29 Volume replacement was performed with colloids in the majority of studies,29–31,33,37–39,42–45,47,48,50–54 crystalloids in 3 studies,35,49,55 a combination of crystalloids and colloids in 2 studies,34,46 crystalloids and/or plasma protein fraction in 2 other cases,27,28 and albumin in 2 studies.27,32 Eight studies27–29,33,37,38,41,55 did not use specific transfusion protocols. In 2 studies, hemodilution was done after heparin infusion.36,41 Characteristics of the included studies are described in Table 1 and baseline data in Table 2.

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Data Synthesis

Primary Outcome

Number of Allogeneic Red Blood Cell Units Transfused.

In the 21 studies reporting these data and including overall 1852 patients, the ANH group received fewer RBCu transfusions (mean difference = −0.79; 95% CI, −1.25 to −0.34; P = .001; I2 = 95.1%; Figure 2).

Figure 2.

Figure 2.

Visual inspection of the funnel plot did not reveal asymmetry (Figure 3) and the Begg test was nonsignificant (P < .174), suggesting that studies with little precision (studies with few participants) did not give different results from studies with greater precision (studies with more participants). The Egger test (P < .074) became nonsignificant (P = .404) after the exclusion of an outlier trial (Hurpe et al29).

Figure 3.

Figure 3.

Sensitivity analyses showed that sequentially removing each study one at a time and then repeating a separate analysis for the rest of the studies did not change the overall mean difference of number of RBCu transfused: from a minimum of −0.76 (95% CI, −1.11 to −0.41; P < .0001) to a maximum of −0.51 (95% CI, −0.95 to −0.13; P = .01).

In exploring the reasons for heterogeneity across RCTs, we found differences between subgroups that could partially explain the observed heterogeneity, in the following categories: amount of blood removed with ANH, the type of surgery, the year of publication, and the presence or absence of a transfusion protocol. The test for differences between subgroups did not reveal variability in effect estimates within the following categories: type of blood replacement, the number of participants, and the amount of blood loss. P values for the interaction between subgroups are reported in Supplemental Digital Content 3 (Supplemental Table 2, http://links.lww.com/AA/B515).

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Secondary Outcomes

Rate of Perioperative Allogeneic Blood Transfusion.

Fewer ANH patients received allogeneic blood transfusions compared with controls, 356 of 845 (42.1%) in the ANH group versus 491 of 876 (56.1%) in controls, RR = 0.74; 95% CI, 0.62 to 0.87; P < .0001; I2 = 72.5%, with Begg test P = .940 and Egger test P = .015, in 18 studies with 1721 patients included (Supplemental Digital Content 4, Supplemental Figure 1, http://links.lww.com/AA/B516)

Sensitivity analyses showed that sequentially removing each study one at a time and then repeating a separate analysis for the rest of the studies did not change the overall RR of patients transfused with allogeneic red blood cells: from a minimum of 0.71 (95% CI, 0.56 to 0.91; P = .005) to a maximum of 0.78 (95% CI, 0.64 to 0.94; P < .001).

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Estimated Total Blood Loss.

Patients managed with ANH had less estimated total blood loss, 388 mL in ANH versus 450 mL in control, mean difference = −0.64; 95% CI, −0.97 to −0.31; P < .0001; I2 = 91.8%, with Begg test P = .013 and Egger test P = .061, according to 23 studies analyzed, which included 2043 patients (Supplemental Digital Content 5, Supplemental Figure 2, http://links.lww.com/AA/B517).

Sensitivity analyses showed that sequentially removing each study one at a time and then repeating a separate analysis for the rest of the studies did not change the overall mean differences of total amount of blood loss: from a minimum of −92 mL (95% CI, −121.92 to −63.21), P < .00001, to a maximum of −72 mL (95% CI, −102.36 to −43.51), P < .00001.

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DISCUSSION

To the best of our knowledge, the present meta-analysis, including 29 RCTs and investigating ANH use versus standard treatment in cardiac surgery, is the first performed specifically in this setting and focusing on patients’ need for allogeneic RBCu. The main identified finding is a clinically relevant reduction in RBCu transfusions in patients receiving ANH. Further findings are a decrease in the rate of patients transfused with allogeneic blood and a reduction in estimated total blood loss. These findings are of paramount importance and may have a great clinical and economic impact. Transfusions of blood products are known to be cost-intensive and to significantly increase the risk of perioperative complications, including mortality, prolonged hospitalization, and increased hospital resource utilization.56,57 In particular, cardiac and pulmonary dysfunction, neurological impairment, renal failure (50% of patients have a significant increase in serum creatinine and, among these, 5% need renal replacement therapy), and infections (nosocomial infections occur in 10%–20% of cardiac surgery patients) are increased in patients receiving transfusions and are associated with an overall worse outcome, higher in-hospital mortality, longer hospitalizations, and a higher rate of discharge to chronic care facilities.3,4 Therefore, a strategy like ANH able to minimize the exposure to blood products may reduce costs and morbidity. Moreover, as reported by Grant et al,14 cardiac surgery is the most appropriate setting in which ANH may play a relevant role because transfusion requirements remain high despite compelling evidence of many adverse effects and the advances in perioperative blood conservation techniques.6–9 Data on ANH in cardiac surgery were still greatly conflicting and inconclusive before performing this meta-analysis. As observed by Goldberg et al58 in a recent observational study on patients undergoing cardiac surgery, only 17% of patients received ANH. Although several studies have examined the role of ANH in cardiac surgery and guidelines proposed ANH as an approved practice in selected patients with adequate preoperative hemoglobin levels (class IIb, level B), to date, there have been no large randomized studies or meta-analyses that systematically review the role of this technique in the cardiac surgery field.16,59

Previous meta-analyses established a limited usefulness of ANH in terms of outcome. Bryson et al,60 in 1998, performed a systematic review and meta-analysis, regarding ANH management in cardiac and noncardiac surgery and concluded that ANH reduces the need for allogeneic red blood cell transfusions (odds ratio, 0.31; 95% CI, 0.15–0.62) in all areas, but with a less compelling evidence in cardiac surgery (odds ratio, 0.51; 95% CI, 0.26–0.99). Bryson’s meta-analysis considered only 11 RCTs performed in cardiac surgery.

Another meta-analysis performed in 2004 by Segal et al61 that compared ANH with standard of care in all surgical settings suggested a small benefit of ANH but failed to perform a specific subcategory analysis in cardiac surgery.

Recently, Zhou et al13 showed that ANH is effective in reducing allogeneic blood loss transfusion, with a significant heterogeneity and publication bias, and only when surgical blood loss is 1 L or when it exceeds 20% of the patients’ blood volume. However, the authors included in their meta-analysis a case-mixed population confirming, ultimately, the findings of previous meta-analyses. Moreover, Zhou’s meta-analysis considered only 23 RCTs in cardiac surgery.

In the present meta-analysis, to be more exhaustive and to further validate safety and reliability of ANH practice, the rate of patients transfused with allogeneic blood transfusion and the estimated total blood loss were considered.

We confirmed a significant reduction in the number of allogeneic RBCu transfused. These data are coherent with the study by Goldberg et al,58 in which a significant reduction in RBCu transfusions was observed in patients undergoing cardiac surgery in whom ANH protocol was adopted. The forest plot of RBCu transfused clearly demonstrated that, in our meta-analysis, there is strong consistency in the direction of the estimated effect among all analyzed studies, and the vast majority of our subanalyses confirmed the results of the primary analysis. Different magnitude of the effect among studies could partially explain the observed heterogeneity together with the observed differences in several subgroups: trials with different quantities of blood removed, trials published before and after the year 2000, trials with valve surgery and CABG surgery, and trials with or without a transfusion protocol.

When a great volume of blood was removed (>650 mL), there was a more pronounced reduction in RBCu transfusion, in agreement with the report of Goldberg et al.58 Recent trials show a reduced benefit from ANH probably because of reduced blood loss in modern cardiac surgery because of the widespread use in cardiac surgery of blood conservation techniques. We also found a reduction in the number of RBCu transfused in the ANH patients versus control in the subgroup of CABG surgery versus valve surgery, probably related to different tendency to bleed of these types of patients; ultimately, the use of a transfusion protocol could also influence the risk of RBCu transfusion. For the primary outcome, we noted an absence of publication bias, absence of small study effect, confirmative results from most sensitivity analyses, by sequentially removing each study one at a time, and also repeating analysis for specific groups of studies. We therefore concluded that the reason for heterogeneity was due to different magnitude in the estimated effect and by the differences between subgroups of trials.

The rate of patients transfused with allogeneic blood and the estimated total blood loss were also decreased in the ANH group, confirming the beneficial effects of ANH on clinically relevant outcomes. These findings are consistent with those reported in the study by Goldberg et al,58 in which an overall decrease in red blood cell transfusion was reported in the ANH group.

To date, this meta-analysis included the largest cardiac surgery population ever studied. Nonetheless, conclusive data are still lacking, and to obtain definitive data and demonstrate a reduction in RBCu transfusion with the use of ANH versus standard care in cardiac surgery, we will probably need a large RCT designed for a specific surgery setting (CABG or valve surgery), in which the amount of blood removed is at least 650 mL and that utilizes a precise transfusion protocol.

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Limitations

The following limitations of the present meta-analysis are acknowledged: only a restricted number of trials used the same hemodilution procedure and performed volume replacement with the same substance; colloids were extensively used for volume replacement in the ANH group and because they increase the risk of bleeding when compared with crystalloids, they might have worsened the coagulation, resulting in decreased ANH efficacy.62 In 2 studies, ANH was performed after heparin infusion,36,41 even though no differences in the results were found with sensitivity analyses. Heterogeneity was observed for the primary and secondary outcomes, suggesting that large, high-quality RCTs are necessary to reach more conclusive results.

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CONCLUSIONS

This meta-analysis is the most comprehensive review regarding all RCTs on ANH published in cardiac surgery and provides an extensive evaluation of the efficacy of such technique in this setting in decreasing the number of allogeneic RBCu transfused. This is in agreement with the observed reduction in the rate of patients requiring transfusions with allogeneic blood and in the estimated total blood loss. ANH can be considered a valid technique to reduce allogeneic red blood cell transfusions in the cardiac surgery setting.

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DISCLOSURES

Name: Luigi Barile, MD.

Contribution: This author helped design the study, conduct the study, collect the data, analyze the data, and prepare the manuscript.

Name: Evgeny Fominskiy, MD, PhD.

Contribution: This author helped collect the data, analyze the data, and prepare the manuscript.

Name: Nora Di Tomasso, MD.

Contribution: This author helped collect the data and prepare the manuscript.

Name: Ligia Elena Alpìzar Castro, MD.

Contribution: This author helped collect the data and prepare the manuscript.

Name: Giovanni Landoni, MD

Contribution: This author helped prepare the manuscript.

Name: Monica De Luca, MD.

Contribution: This author helped prepare the manuscript.

Name: Elena Bignami, MD.

Contribution: This author helped prepare the manuscript.

Name: Alessandra Sala, MD.

Contribution: This author helped prepare the manuscript.

Name: Alberto Zangrillo, MD.

Contribution: This author helped prepare the manuscript.

Name: Fabrizio Monaco, MD.

Contribution: This author helped design the study, conduct the study, collect the data, analyze the data, and prepare the manuscript.

This manuscript was handled by: Roman Sniecinski, MD.

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REFERENCES

1. Engoren MC, Habib RH, Zacharias A, Schwann TA, Riordan CJ, Durham SJ. Effect of blood transfusion on long-term survival after cardiac operation. Ann Thorac Surg. 2002;74:1180–1186.
2. Paone G, Likosky DS, Brewer R, et al.; Membership of the Michigan Society of Thoracic and Cardiovascular Surgeons. Transfusion of 1 and 2 units of red blood cells is associated with increased morbidity and mortality. Ann Thorac Surg. 2014;97:87–93.
3. Stephens RS, Whitman GJ. Postoperative critical care of the adult cardiac surgical patient. Part I: routine postoperative care. Crit Care Med. 2015;43:1477–1497.
4. Stephens RS, Whitman GJ. Postoperative critical care of the adult cardiac surgical patient. Part II: procedure-specific considerations, management of complications, and quality improvement. Crit Care Med. 2015;43:1995–2014.
5. Koch CG, Li L, Sessler DI, et al. Duration of red-cell storage and complications after cardiac surgery. N Engl J Med. 2008;358:1229–1239.
6. Kozek-Langenecker SA, Afshari A, Albaladejo P, et al. Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology. Eur J Anaesthesiol. 2013;30:270–382.
7. American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies. Practice guidelines for perioperative blood transfusion and adjuvant therapies: an updated report by the American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies. Anesthesiology. 2006;105:198–208.
8. Bennett-Guerrero E, Zhao Y, O’Brien SM, et al. Variation in use of blood transfusion in coronary artery bypass graft surgery. JAMA. 2010;304:1568–1575.
9. Stehling L, Zauder HL. Controversies in transfusion medicine. Perioperative hemodilution: pro. Transfusion. 1994;34:265–268.
10. Goodnough LT, Monk TG, Brecher ME. Acute normovolemic hemodilution should replace the preoperative donation of autologous blood as a method of autologous-blood procurement. Transfusion. 1998;38:473–476.
11. Flom-Halvorsen HI, Øvrum E, Øystese R, Brosstad F. Quality of intraoperative autologous blood withdrawal used for retransfusion after cardiopulmonary bypass. Ann Thorac Surg. 2003;76:744–748.
12. Triulzi DJ, Ness PM. Intraoperative hemodilution and autologous platelet rich plasma collection: two techniques for collecting fresh autologous blood. Transfus Sci. 1995;16:33–44.
13. Zhou X, Zhang C, Wang Y, Yu L, Yan M. Preoperative acute normovolemic hemodilution for minimizing allogeneic blood transfusion: a meta-analysis. Anesth Analg. 2015;121:1443–155.
14. Grant MC, Resar LM, Frank SM. The efficacy and utility of acute normovolemic hemodilution. Anesth Analg. 2015;121:1412–1414.
15. Reents W, Babin-Ebell J, Misoph MR, Schwarzkopf A, Elert O. Influence of different autotransfusion devices on the quality of salvaged blood. Ann Thorac Surg. 1999;68:58–62.
16. The Society of Thoracic Surgeons Blood Conservation Guideline Task Force and the Society of Cardiovascular Anesthesiologists Special Task Force on Blood Transfusion.. Perioperative Blood Transfusion and Blood Conservation in Cardiac Surgery: The Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists Clinical Practice Guideline. Ann Thorac Surg. 2007;83:S27–S86.
17. Kreimeier U, Messmer K. Hemodilution in clinical surgery: state of the art 1996. World J Surg. 1996;20:1208–1217.
18. Mirhashemi S, Ertefai S, Messmer K, Intaglietta M. Model analysis of the enhancement of tissue oxygenation by hemodilution due to increased microvascular flow velocity. Microvasc Res. 1987;34:290–301.
19. Pries AR, Secomb TW. Rheology of the microcirculation. Clin Hemorheol Microcirc. 2003;29:143–148.
20. Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions, Version 5.0.0. The Cochrane Collaboration; updated February 2008. http://handbook.cochrane.org/. Accessed May 2009
21. Biondi-Zoccai GG, Agostoni P, Abbate A, Testa L, Burzotta F. A simple hint to improve Robinson and Dickersin’s highly sensitive PubMed search strategy for controlled clinical trials. Int J Epidemiol. 2005;34:224–225.
22. Fleiss JL. The statistical basis of meta-analysis. Stat Methods Med Res. 1993;2:121–145.
23. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151:264–269, W64.
24. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med. 2009;151:W65–W94.
25. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–560.
26. Higgins JPT, Green S. 2011. Cochrane Handbook for Systematic Reviews of Interventions. http://handbook.cochrane.org/. Accessed June 2014
27. Hallowell P, Bland JH, Buckley MJ, Lowenstein E. Transfusion of fresh autologous blood in open-heart surgery. A method for reducing bank blood requirements. J Thorac Cardiovasc Surg. 1972;64:941–948.
28. Kaplan JA, Cannarella C, Jones EL, Kutner MH, Hatcher CR Jr, Dunbar RW. Autologous blood transfusion during cardiac surgery. A re-evaluation of three methods. J Thorac Cardiovasc Surg. 1977;74:4–10.
29. Hurpe JM, Zerr C, Lebreton P, et al. [Contribution of autologous blood transfusion in cardiac surgery in the adult]. Ann Fr Anesth Reanim. 1987;6:11–16.
30. Dietrich W, Barankay A, Dilthey G, Mitto HP, Richter JA. Reduction of blood utilization during myocardial revascularization. J Thorac Cardiovasc Surg. 1989;97:213–219.
31. Boldt J, Kling D, Weidler B, et al. Acute preoperative hemodilution in cardiac surgery: volume replacement with a hypertonic saline-hydroxyethyl starch solution. J Cardiothorac Vasc Anesth. 1991;5:23–28.
32. Vedrinne C, Girard C, Jegaden O, et al. Reduction in blood loss and blood use after cardiopulmonary bypass with high-dose aprotinin versus autologous fresh whole blood transfusion. J Cardiothorac Vasc Anesth. 1992;6:319–323.
33. Herregods L, Foubert L, Moerman A, François K, Rolly G. Comparative study of limited intentional normovolaemic haemodilution in patients with left main coronary artery stenosis. Anaesthesia. 1995;50:950–953.
34. Triulzi DJ, Gilmor GD, Ness PM, Baumgartner WA, Schultheis LW. Efficacy of autologous fresh whole blood or platelet-rich plasma in adult cardiac surgery. Transfusion. 1995;35:627–634.
35. Helm RE, Klemperer JD, Rosengart TK, et al. Intraoperative autologous blood donation preserves red cell mass but does not decrease postoperative bleeding. Ann Thorac Surg. 1996;62:1431–1441.
36. Kochamba GS, Pfeffer TA, Sintek CF, Khonsari S. Intraoperative autotransfusion reduces blood loss after cardiopulmonary bypass. Ann Thorac Surg. 1996;61:900–903.
37. Spahn DR, Schmid ER, Seifert B, Pasch T. Hemodilution tolerance in patients with coronary artery disease who are receiving chronic beta-adrenergic blocker therapy. Anesth Analg. 1996;82:687–694.
38. Herregods L, Moerman A, Foubert L, et al. Limited intentional normovolemic hemodilution: ST-segment changes and use of homologous blood products in patients with left main coronary artery stenosis. J Cardiothorac Vasc Anesth. 1997;11:18–23.
39. Kahraman S, Altunkaya H, Celebioğlu B, Kanbak M, Paşaoğlu I, Erdem K. The effect of acute normovolemic hemodilution on homologous blood requirements and total estimated red blood cell volume lost. Acta Anaesthesiol Scand. 1997;41:614–617.
40. Nuttall GA, Oliver WC, Ereth MH, et al. Comparison of blood-conservation strategies in cardiac surgery patients at high risk for bleeding. Anesthesiology. 2000;92:674–682.
41. Zhang S, Yao S. Effects of intraoperative autologous blood donation and tepid temperature cardiopulmonary bypass on blood system. J Tongji Med Univ. 2000;20:151–153.
42. Casati V, Speziali G, D’Alessandro C, et al. Intraoperative low-volume acute normovolemic hemodilution in adult open-heart surgery. Anesthesiology. 2002;97:367–373.
43. Höhn L, Schweizer A, Licker M, Morel DR. Absence of beneficial effect of acute normovolemic hemodilution combined with aprotinin on allogeneic blood transfusion requirements in cardiac surgery. Anesthesiology. 2002;96:276–282.
44. McGill N, O’Shaughnessy D, Pickering R, Herbertson M, Gill R. Mechanical methods of reducing blood transfusion in cardiac surgery: randomised controlled trial. BMJ. 2002;324:1299
45. Durmus M, Karaaslan K, But AK, Erdem TB, Sezgin N, Ersoy MO. The effects of acute normovolemic hemodilution on coagulation parameters in coronary artery bypass surgery. Anestezi Dergisi. 2003;11:201–206.
46. Casati V, Benussi S, Sandrelli L, Grasso MA, Spagnolo S, D’Angelo A. Intraoperative moderate acute normovolemic hemodilution associated with a comprehensive blood-sparing protocol in off-pump coronary surgery. Anesth Analg. 2004;98:1217–1223.
47. Licker M, Ellenberger C, Sierra J, Kalangos A, Diaper J, Morel D. Cardioprotective effects of acute normovolemic hemodilution in patients undergoing coronary artery bypass surgery. Chest. 2005;128:838–847.
48. Licker M, Sierra J, Kalangos A, Panos A, Diaper J, Ellenberger C. Cardioprotective effects of acute normovolemic hemodilution in patients with severe aortic stenosis undergoing valve replacement. Transfusion. 2007;47:341–350.
49. Jalali A, Naseri MH, Chalian M, Dolatabadi HL. Acute normovolaemic haemodilution with crystalloids in coronary artery bypass graft surgery: a preliminary survey of haemostatic markers. Acta Cardiol. 2008;63:335–339.
50. Ela Y, Emmiler M, Kocogullari CU, Terzi Y, Sivaci RG, Cekirdekci A. Advantages of autologous blood transfusion in off-pump coronary artery bypass. Heart Surg Forum. 2009;12:E261–E265.
51. Mahoori A, Heshmati F, Noroozinia H, Mehdizadeh H, Salehi S, Rohani M. Intraoperative minimal acute normovolemic hemodilution in patients undergoing coronary artery bypass surgery. Middle East J Anaesthesiol. 2009;20:423–429.
52. Zisman E, Eden A, Shenderey A, et al. The effect of acute autologous blood transfusion on coagulation dysfunction after cardiopulmonary bypass. Eur J Anaesthesiol. 2009;26:868–873.
53. Virmani S, Tempe DK, Pandey BC, et al. Acute normovolemic hemodilution is not beneficial in patients undergoing primary elective valve surgery. Ann Card Anaesth. 2010;13:34–38.
54. Momeni M, Liistro G, Baele P, et al. An increase in endogenous erythropoietin concentrations has no cardioprotective effects in patients undergoing coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth. 2012;26:251–257.
55. Soltanzadeh M, Ebadi A, Tabatabaiee SK, et al. Quantitative comparison of blood and blood products requirement between two groups with and without auto-transfusion following coronary artery bypass grafting surgery. Life Sci J. 2012;9:905–907.
56. Despotis G, Eby C, Lublin DM. A review of transfusion risks and optimal management of perioperative bleeding with cardiac surgery. Transfusion. 2008;48:2S–30S.
57. Levi M, Cromheecke ME, de Jonge E, et al. Pharmacological strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically relevant endpoints. Lancet. 1999;354:1940–1947.
58. Goldberg J, Paugh TA, Dickinson TA, et al.; PERForm Registry and the Michigan Society of Thoracic and Cardiovascular Surgeons Quality Collaborative. Greater volume of acute normovolemic hemodilution may aid in reducing blood transfusions after cardiac surgery. Ann Thorac Surg. 2015;100:1581–1587.
59. The Society of Thoracic Surgeons Blood Conservation Guideline Task Force, the Society of Cardiovascular Anesthesiologists Special Task Force on Blood Transfusion and the International Consortium for Evidence Based Perfusion. 2011 Update to The Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists Blood Conservation Clinical Practice Guidelines. Ann Thorac Surg. 2011;91:944–982.
60. Bryson GL, Laupacis A, Wells GA. Does acute normovolemic hemodilution reduce perioperative allogeneic transfusion? A meta-analysis. The International Study of Perioperative Transfusion. Anesth Analg. 1998;86:9–15.
61. Segal JB, Blasco-Colmenares E, Norris EJ, Guallar E. Preoperative acute normovolemic hemodilution: a meta-analysis. Transfusion. 2004;44:632–644.
62. Kozek-Langenecker SA. Fluids and coagulation. Curr Opin Crit Care. 2015;21:285–291.

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