Interact CardioVasc Thorac Surg 2009;8:373-376. doi:10.1510/icvts.2008.195354
© 2009 European Association of Cardio-Thoracic Surgery
Brief communication - Cardiopulmonary bypass |
Retrograde autologous priming and allogeneic blood transfusions: a meta-analysis
Richard Saczkowskia,*,
Pierre-Luc Berniera,
Christo I. Tchervenkova and
Ramiro Arellanob
a Department of Cardiovascular Surgery, McGill University, Montreal Children's Hospital, 2300 Tupper Street, Montreal, Quebec, Canada
b Department of Anesthesiology, Queen's University, Kingston General Hospital, Kingston, Ontario, Canada
Received 1 October 2008;
received in revised form 24 November 2008;
accepted 25 November 2008
*Corresponding author. Fax: +1-514-412-4330.
E-mail address: richard.saczkowski{at}gmail.com (R. Saczkowski).
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Abstract
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A literature review and meta-analysis were undertaken to assess the clinical effectiveness of retrograde autologous priming of the cardiopulmonary bypass circuit to reduce allogeneic packed red blood transfusions in adult cardiac surgery. Structured searches of Medline, Embase, Cochrane Collaboration Library, Scopus, Cumulative Index to Nursing and Allied Health Literature and Science Direct were performed to identify randomized trials comparing retrograde autologous priming to a prospective control group. A total of 21,643 studies were identified and eighteen trials were retrieved for full-text review. Six trials met eligibility criteria. Pooled estimates demonstrated that retrograde autologous priming significantly reduced the number of patients receiving intraoperative packed red cell transfusions (OR=0.36; 95% CI: 0.13, 0.94; P=0.04, I2=47.5%), total hospital stay packed red cell transfusions (OR=0.26; 95% CI: 0.13, 0.52; P=0.0001, I2=0%), and the number of units transfused of total hospital stay packed red blood cells (WMD=–0.60; 95% CI: –0.90, –0.31; P=0.0001, I2=0%). Retrograde autologous priming, however, did not provide a clinical benefit in reducing the number of units transfused of intraoperative packed red blood cells (WMD=–0.29; 95% CI: –0.59, 0.01; P=0.05). The combined patient population studied in the six trials was mainly primary isolated coronary artery bypass surgery. Assessing the safety of retrograde autologous priming was not possible due to limited data.
Key Words: On-pump; Blood conservation; Blood transfusions; Cardiopulmonary bypass
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1. Introduction
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Retrograde autologous priming (RAP) of the cardiopulmonary bypass (CPB) circuit has been reported to reduce allogeneic blood transfusions [1–6]. RAP reduces hemodilution through passive exsanguination of the arterial and venous lines prior to the initiation of CPB. Autologous blood displaces the prime solution from the circuit and sequesters it in a collection bag. Additional prime volume reduction can be achieved by actively forcing prime into an attached collection bag with the use of the main arterial or cardioplegia pump. The available studies reporting the effectiveness of RAP are limited by small sample size. Therefore, a meta-analysis was undertaken to assess the effect of RAP on reducing allogeneic packed red cell (RBC) transfusions in adult cardiac surgery.
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2. Materials and methods
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Structured searches of MEDLINE (1966–2007), EMBASE (1978–2007), Cochrane Library (2007), SCOPUS (2006), CINAHL (2007), and Science Direct (2007) were performed. Keyword search methodology was used for each database with the following structure: ‘Retrograde AND Autologous AND Prime OR Priming’; ‘Retrograde AND Prime OR Priming’; ‘Reduction AND Prime OR Priming’; ‘Volume AND Prime OR Priming’; ‘Cardiopulmonary AND Bypass AND Prime OR Priming’; ‘Transfusion AND Prime OR Priming’. Only randomized clinical trials comparing RAP to a prospective control group reporting RBC transfusion rates as an outcome were eligible for inclusion. A reference list review of selected papers was performed to assist in the procurement of all relevant articles. Information from each study was recorded on a standardized data collection form. Discrepancies between author entries were resolved by consensus. The Jadad scoring methodology was applied to each trial, rating a score to a minimum of 0 and a maximum of 5 [7]. Points are given for proper randomization methodology; appropriate blinding techniques, and a description of withdrawals and dropouts. Dichotomous transfusion data were used to generate an odds ratio (OR), while continuous transfusion data produced a weighted mean difference (WMD) value. Both outcome measures are reported with a 95% confidence interval (CI) and a test of significance (P). The OR and WMD were created by an inverse variance-weighted random-effects model. Statistical heterogeneity was assessed with the I2 test statistic with a value exceeding 50% being significant. Mean data were expressed with a standard deviation. A two-tailed Student's t-test of significance was applied as appropriate. Sensitivity analysis was performed by eliminating each trial one by one from the pooled estimate.
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3. Results
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The primary keyword literature searches identified 21,643 trials. Of these, 18 studies were retrieved for full-text review, which resulted in six trials meeting eligibility criteria for inclusion. The characteristics of the six studies are depicted in Table 1. The median Jadad score was 1.5 (range: 0–2). The mean prime volume for the control and RAP group was 1519.8±116.9 ml and 596.5±171.3 ml, respectively (P<0.0001). Intraoperative mean fluid balance was not significantly different between the RAP (1574.6±864.9 ml) and control groups (2016.2±1028.5 ml) (P=0.44). Five trials implemented a strict transfusion protocol [1, 3–6]. Three trials report the routine use of antifibrinolytics [2–4]. Intraoperative autologous blood transfusion devices were employed in every cardiac surgery case in three studies [1–3]. The vast majority of patients underwent primary coronary artery bypass grafting (CABG) (RAP=91%, control=91%). The remaining procedures were valve surgery (RAP=3%, control=3%), reoperation (RAP= 6%, control=3%) and ‘other cardiac surgery’ (RAP=0.8%, control=2%). Vasopressor administration during RAP depicts no additional benefit in decreasing the mean post-RAP prime volume (P=0.73). Pooled estimates of the six trials representing 557 patients demonstrate that RAP confers a 64% reduction in the number of patients transfused intraoperative RBC (OR=0.36; 95% CI: 0.13, 0.94; P=0.04, I2=47.5%), and a 74% reduction in the number of patients transfused RBC over the total hospital stay (OR=0.26; 95% CI: 0.13, 0.52; P=0.0001, I2=0%) (Fig. 1, upper panel). Similarly, a pooled estimate for the number of units transfused of RBC over the total hospital stay (WMD=–0.60; 95% CI: –0.90, –0.31; P=0.0001, I2=0%) (Fig. 1, lower panel) demonstrate a clinically important reduction for RAP allocated patients. The one study reporting the number of units transfused of intraoperative RBC (WMD=–0.29; 95% CI: –0.59, 0.01; P=0.05) (Fig. 1, lower panel), showed no reduction with the application of RAP. The sequential removal of Rosengart et al. [1] (OR=0.43; CI: 0.16, 1.21; P=0.11, I2=49%) and Rousou et al. [3] (OR=0.52; CI: 0.19, 1.39; P=0.19, I2=21%) from the pooled estimate of the number of patients transfused RBC negated the clinical benefit of RAP. The remaining sensitivity analysis did not alter the results substantially.
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Fig. 1. Packed red blood cell transfusion: RAP compared to control. Upper panel: Number of patients. Lower panel: Number of units. CI, confidence interval; df, degrees of freedom; I2, heterogeneity test; OR, odds ratio; RBC, packed red blood cells; random, random effects model; RAP, retrograde autologous priming; S.D., standard deviation; WMD, weighted mean difference.
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4. Discussion
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The appeal of RAP over other blood conservation strategies is that it is inexpensive. All CPB circuits can be readily modified to accommodate RAP. The procedure can be applied with similar prime volume reduction without the use of vasopressors. Primary coronary artery bypass grafting (CABG) patient population was the most prevalent group studied, which represents a relatively lower transfusion risk. Whether RAP confers a similar benefit across the spectrum of the adult cardiac surgical population remains uncertain. An attempt to elucidate the safety of RAP was not possible in this analysis. The paucity of information pertaining to adverse outcomes limits comment. However, the six trials do not report any significant detrimental effects from the application of RAP. The results from the sensitivity analysis question the robustness of the clinical benefit of RAP. This was paralleled in a retrospective study depicting RAP's ineffectiveness in reducing RBC transfusions, which is the largest reported series on RAP (n=545) [8]. However, addition of this trial into the summary effect measure for the number of patients transfused intraoperative RBC (OR=0.50; CI: 0.28, 0.90; P=0.02, I2=47.5%) and the total hospital stay number of patients transfused RBC (OR=0.41; CI: 0.18, 0.94; P=0.04, I2=72%) did not mitigate the clinical benefit of RAP. A sensitivity analysis to assess the effect of autologous cell salvaging could not be performed due to the limited number of trials implementing this modality.
The number needed to treat (NNT) for the number of patients receiving intraoperative RBC transfusions and total hospital stay RBC transfusions are 11 and 4, respectively. Assuming a mean adjusted cost per unit for transfused allogeneic RBC's of $2000 US dollars [9] and one unit of RBC's avoided with the application of RAP. It is possible that a five hundred case cardiac program could reduce costs by $90,900.00 per year in intraoperative RBC transfusions and $250,000.00 per year in total hospital stay RBC transfusions with the application of RAP. These figures are not inconsequential but the results drawn from the economic framework depend on the robust conclusions of the meta-analysis. Therefore, it is important to highlight that this meta-analysis does pose inherent limitations. The aggregate sample sizes for the RAP and control groups were small, which imply caution in interpreting the results. Two of the six trials were originally undertaken as pilot studies to assess the feasibility of RAP [1, 5]. This point is particularly relevant with regards to the sensitivity analysis. It is important to state, however, that the heterogeneity of the pooled estimate was below 50% for all groups. This adds to the confidence in the combinability of the studies in a meta-analysis. The median Jadad score was low resulting from the methods instituted for randomization and blinding raising the suspicion of bias across the six trials. A Jadad score of two or less is generally considered a poor quality study and may over estimate the true treatment effect [7].
This study is the first meta-analysis of randomized, controlled trials pertaining to RAP. It shows that RAP significantly reduces allogeneic blood transfusions in adults; however, the six trials reviewed may be biased and safety could not be assessed.
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References
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- Shapira OM, Aldea GS, Treanor PR, Chartrand RM, DeAndrade KM, Lazar HL, Shemin RJ. Reduction of allogenic blood transfusions after open-heart operations by lowering cardiopulmonary bypass prime volume. Ann Thorac Surg 1998;65:724–730.[Abstract/Free Full Text]
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Abstract
1. Introduction