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Effects of albumin and crystalloid priming strategies on red blood cell transfusions in on-pump cardiac surgery: a network meta-analysis
Wang, T., Wang, J., Zhang, M., Zhang, H., Zhang, Q., Liu, G., Dong, W., Wang, Y., Ji, B.
BMC anesthesiology. 2024;24(1):26
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Editor's Choice
Abstract
BACKGROUND In on-pump cardiac surgery, the albumin priming strategy could maintain colloid osmotic pressure better than crystalloid solutions and reduce excessive perioperative fluid balance. However, a high-quality meta-analysis is required to compare the safety of these approaches in perioperative red blood cell (RBC) transfusions. Owing to limited direct evidence, we conducted a network meta-analysis (NMA) to increase the pool of studies and provide indirect evidence. METHODS The pre-defined primary outcomes were intraoperative and the first 24 h postoperative RBC transfusion volume in units. The pre-defined secondary outcome was postoperative blood loss (the first 24 h). We reviewed all randomized controlled trials comparing albumin, crystalloid, and artificial colloid priming strategies. Studies that only displayed pre-defined outcomes could be included. A pairwise meta-analysis was performed on studies that directly compared the pre-defined outcomes between albumin and crystalloids. Additionally, a random-effects network meta-analysis (NMA) model was employed to generate indirect evidence for the pre-defined outcomes between albumin and crystalloids. RESULTS The literature search identified 830 studies,10 of which were included in the final analysis. Direct meta-analysis indicated that crystalloid priming significantly decreased total perioperative RBC transfusions (MD: -0.68U; 95%CI: -1.26, -0.09U; P = 0.02) and intraoperative RBC transfusions (MD: -0.20U; 95%CI: -0.39, -0.01U; P = 0.03) compared to albumin. Postoperative RBC transfusions showed a decreasing trend in the crystalloid group; however, the difference was not statistically significant. (MD: -0.16U; 95%CI: -0.45, 0.14U; P = 0.30). After including indirect evidence, the NMA results continued to demonstrate a higher RBC receiving with the albumin priming strategy compared to crystalloids, although the differences did not reach statistical significance. For postoperative blood loss, direct evidence showed no significant differences between albumin and crystalloid priming strategies. However, NMA evidence displayed that albumin exist higher probability of reducing postoperative blood loss than crystalloid. CONCLUSION Both direct and NMA evidence indicated that the albumin priming strategy resulted in more perioperative RBC transfusions than crystalloids. Considering the additional blood management burden, the application of an albumin-priming strategy in on-pump cardiac surgery still needs more consideration.
PICO Summary
Population
Adult patients undergoing cardiovascular surgery with cardiopulmonary bypass (10 randomised controlled trials).
Intervention
Network meta-analysis (NMA) to perform direct comparisons, including albumin vs. artificial colloid and artificial colloid vs. crystalloid, and to obtain indirect evidence for the comparisons between albumin and crystalloid priming strategies.
Comparison
Outcome
Direct meta-analysis indicated that crystalloid priming significantly decreased total perioperative red blood cell (RBC) transfusions (MD -0.68U; 95% CI [-1.26, -0.09U]) and intraoperative RBC transfusions (MD -0.20U; 95% CI [-0.39, -0.01U]) compared to albumin. Postoperative RBC transfusions showed a decreasing trend in the crystalloid group; however, the difference was not statistically significant (MD -0.16U; 95% CI: [-0.45, 0.14U]). After including indirect evidence, the NMA results continued to demonstrate a higher RBC receiving with the albumin priming strategy compared to crystalloids, although the differences did not reach statistical significance.
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Effect of 5% albumin on endothelial glycocalyx degradation during off-pump coronary artery bypass
Nan, Z., Soh, S., Shim, J. K., Kim, H. B., Yang, Y. S., Kwak, Y. L., Song, J. W.
Canadian journal of anaesthesia = Journal canadien d'anesthesie. 2023
Abstract
PURPOSE The integrity of the endothelial glycocalyx (EG), a critical player in vascular homeostasis, reportedly influences the outcomes of critically ill patients. We investigated the effect of 5% albumin, which preserved EG integrity in preclinical studies, vs balanced crystalloid solution on EG degradation in patients undergoing off-pump coronary surgery. METHODS Patients were randomized to receive either 5% albumin (N = 51) or balanced crystalloid solution (Plasma-Lyte [Baxter Incorporated, Seoul, Republic of Korea]; N = 53) for intravenous volume replacement during surgery (double-blinded). The primary outcome was plasma syndecan-1 concentration, a marker of EG degradation, measured after anesthetic induction (baseline), completion of grafting, and sternal closure. Secondary outcomes were atrial natriuretic peptide (ANP), tumour necrosis factor (TNF)-α, soluble thrombomodulin, and perioperative fluid balance. RESULTS The mean (standard deviation) fluid requirements were 833 (270) mL and 1,323 (492) mL in the albumin and Plasma-Lyte group, respectively (mean difference, -489 mL; 95% confidence interval [CI], -643 to -335; P < 0.001). Plasma syndecan-1 concentration increased after completion of grafting (median difference, 116 ng·mL(-1); 95% CI, 67 to 184; P < 0.001) and sternal closure (median difference, 57 ng·mL(-1); 95% CI, 36 to 80; P < 0.001) compared with those at baseline, without any intergroup differences. Atrial natriuretic peptide, TNF-α, and soluble thrombomodulin concentrations were similar between the two groups. The amount of chest tube drainage was greater in the albumin group than that in the Plasma-Lyte group (median difference, 190 mL; 95% CI, 18 to 276; P = 0.03). CONCLUSION Off-pump coronary surgery was associated with significant EG degradation. Yet, intraoperative fluid therapy with 5% albumin could not ameliorate EG degradation when compared with balanced crystalloid solution. TRIAL REGISTRATION ClinicalTrials.gov (NCT03699462); first posted 9 October 2018.
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Intravenous albumin in cardiac and vascular surgery: a systematic review and meta-analysis
Skubas, N. J., Callum, J., Bathla, A., Keshavarz, H., Fergusson, D., Wu, B., Stanworth, S., Shehata, N.
British journal of anaesthesia. 2023
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Editor's Choice
Abstract
BACKGROUND Intravenous albumin is commonly utilised in cardiovascular surgery for priming of the cardiopulmonary bypass circuit, volume replacement, or both, although the evidence to support this practice is uncertain. The aim was to compare i.v. albumin with synthetic colloids and crystalloids for paediatric and adult patients undergoing cardiovascular surgery for all-cause mortality and other perioperative outcomes. METHODS A systematic review and meta-analysis of randomised controlled trials (RCTs) of i.v. albumin compared with synthetic colloids and crystalloids on the primary outcome of all-cause mortality was conducted. Secondary outcomes included renal failure, blood loss, duration of hospital or intensive care unit stay, cardiac index, and blood component use; subgroups were analysed by age, comparator fluid, and intended use (priming, volume, or both). We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CCRT) from 1946 to November 23, 2022. RESULTS Of 42 RCTs, mortality was assessed in 15 trials (2711 cardiac surgery patients) and the risk difference was 0.00, 95% confidence interval (CI) -0.01 to 0.01, I(2)=0%. Among secondary outcomes, i.v. albumin resulted in smaller fluid balance, mean difference -0.55 L, 95% CI -1.06 to -0.4, I(2)=90% (nine studies, 1975 patients) and higher albumin concentrations, mean difference 7.77 g L(-1), 95% CI 3.73-11.8, I(2)=95% (six studies, 325 patients). CONCLUSIONS Intravenous albumin use was not associated with a difference in morbidity and mortality in patients undergoing cardiovascular surgery, when compared with comparator fluids. The lack of improvement in patient-important outcomes with albumin and its higher cost suggests it should be used restrictively. SYSTEMATIC REVIEW PROTOCOL PROSPERO; CRD42020171876.
PICO Summary
Population
Paediatric and adult patients undergoing cardiovascular surgery (42 randomised controlled trials).
Intervention
Intravenous albumin.
Comparison
Synthetic colloids and crystalloids.
Outcome
Primary outcome of all-cause mortality. Secondary outcomes included renal failure, blood loss, duration of hospital or intensive care unit stay, cardiac index, and blood component use. Mortality was assessed in 15 trials (n= 2,711) and the risk difference was 0.00; 95% confidence interval (CI) [-0.01, 0.01] I(2)= 0%. Among secondary outcomes, intravenous albumin resulted in smaller fluid balance, mean difference -0.55 L; 95% CI [-1.06, -0.4], I(2)= 90% (nine studies, n= 1,975) and higher albumin concentrations, mean difference 7.77 gL(-1); 95% CI [3.73, 11.8], I(2)= 95% (six studies, n= 325). Intravenous albumin use was not associated with a difference in morbidity and mortality in patients undergoing cardiovascular surgery, when compared with comparator fluids.
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Albumin Infusion and Blood Loss after Cardiac Surgery
Talvasto A, Ilmakunnas M, Raivio P, Vlasov H, Hiippala S, Suojaranta R, Wilkman E, Petäjä L, Helve O, Juvonen T, et al
The Annals of thoracic surgery. 2023
Abstract
BACKGROUND In the recent ALBICS trial (ALBumin In Cardiac Surgery), 4% albumin used for cardiopulmonary bypass priming and volume replacement increased perioperative bleeding, compared to Ringer's acetate. In the present exploratory study, albumin-related bleeding was further characterized. METHODS Ringer's acetate and 4% albumin were compared in a randomized, double-blinded fashion in 1386 on-pump adult cardiac surgical patients. The study endpoints for bleeding were the Universal Definition of Perioperative Bleeding (UDPB) class and its components. RESULTS The UDPB bleeding grades were higher in the albumin than the Ringer group: "insignificant" (albumin vs. Ringer: 47.5% vs. 62.9%), "mild" (12.7% vs. 8.9%), "moderate" (28.7% vs. 24.4%), "severe" (10.2% vs. 3.2%), "massive" (0.9% vs. 0.6%), p<0.001. Patients in the albumin group received red blood cells (45.2% vs. 31.5%, p<0.001, odds ratio (OR) 1.80, 95% confidence interval (CI) 1.44-2.24), platelets (33.3% vs.21.8%, p<0.001, OR 1.79, CI 1.41-2.28), and fibrinogen (5.6% vs. 2.6%, p<0.05, OR 2.24: CI 1.27-3.95), and underwent resternotomy (5.3% vs. 1.9%, p<0.001, OR 2.95, CI 1.55-5.60) more often than patients in the Ringer group. The strongest predictors of bleeding were albumin group allocation (OR 2.18, CI 1.74-2.74) and complex- (OR 2.61, CI 2.02-3.37) and urgent surgery (OR 1.63, CI 1.26-2.13). In interaction analysis, the effect of albumin on the risk of bleeding was stronger in patients on preoperative acetylsalicylic acid. CONCLUSIONS Perioperative administration of albumin, compared to Ringer´s acetate, resulted in increased blood loss and higher UDBP class. The magnitude of this effect was similar to the complexity and urgency of the surgery.
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Albumin and Cardioprotection in On-Pump Cardiac Surgery-A Post Hoc Analysis of a Randomized Trial
Vlasov, H., Talvasto, A., Hiippala, S., Suojaranta, R., Wilkman, E., Rautamo, M., Helve, O., Petäjä, L., Raivio, P., Juvonen, T., et al
Journal of cardiothoracic and vascular anesthesia. 2023
Abstract
OBJECTIVES To study the quantitative potency of plasma albumin on cardioprotection in terms of creatinine kinase-myocardial band mass (CK-MBm) in on-pump cardiac surgery. DESIGN Post hoc analysis of a double-blinded randomized clinical trial. SETTING Single-center study in the Helsinki University Hospital. PARTICIPANTS A total of 1,386 adult on-pump cardiac surgical patients. INTERVENTION Administration of 4% albumin (n = 693) or Ringers acetate (n = 693) for cardiopulmonary bypass priming and volume replacement intraoperatively and postoperatively during the first 24 hours. MEASUREMENTS AND MAIN RESULTS Albumin concentration was measured preoperatively and intraoperatively (after protamine administration), and CK-MBm on the first postoperative morning. Multivariate linear regression analyses were measured in the whole cohort and the Ringer group. Plasma albumin concentration did not differ between the groups preoperatively (Ringer v albumin: 38.3 ± 5.0 g/L v 38.6 ± 4.5 g/L; p = 0.171) but differed intraoperatively (29.5 ± 5.2 g/L v 41.5 ± 6.0 g/L; p < 0.001). Creatinine kinase-myocardial band mass was higher in the Ringer (32.0 ± 34.8 μg/L) than in the albumin group (24.3 ± 33.0 μg/L) (p < 0.001). Aortic cross-clamping time associated with CK-MBm in the whole cohort (standardized β = 0.376 [95% CI 0.315-0.437], p < 0.001) and the Ringer group (β = 0.363 [0.273-0.452]; p < 0.001). Albumin administration in the whole cohort (β = -0.156 [-0.201 to -0.111]; p < 0.001) and high intraoperative albumin concentration in the Ringer group (β = -0.07 [-0.140 to -0.003]; p = 0.04) associated with reduced CK-MBm. Compared with ischemia-induced increase in CK-MBm, albumin's potency to reduce CK-MBm was 41% in the whole cohort (β-value ratio of -0.156/0.376) and 19% in the Ringer group (β-value ratio of -0.07/0.363). CONCLUSION Both endogenous and exogenous albumin appear to be cardioprotective regarding CK-MBm release in on-pump cardiac surgery.
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Safety and Efficacy of Albumin for Pump Priming in Cardiac Surgery: A Meta-Analysis
Yin, J., Sun, M., Zeng, Y., Cai, M., Liu, H., Jin, Y.
Journal of cardiothoracic and vascular anesthesia. 2023
Abstract
OBJECTIVES To assess the efficacy and safety of albumin as pump priming fluid in cardiac surgery. DESIGN Meta-analysis of randomized controlled trials. SETTING Each study was conducted in a surgical center or intensive care unit. PARTICIPANTS Adult and pediatric patients undergoing cardiac surgery with cardiopulmonary bypass who received circuit priming fluids. INTERVENTIONS Extracorporeal circuit priming with either albumin or crystalloid. MEASUREMENTS AND RESULTS Fourteen eligible randomized controlled trials with 741 patients were included in the present meta-analysis. Albumin prime had lower bleeding (CI -202.20 to -142.88 mL, p < 0.00001) and showed a greater advantage in preserving platelet counts (CI 14.85-21.48 × 10(3) mm(-3), p < 0.00001), maintaining colloid osmotic pressure and sustaining negative fluid balance. No significant differences were found in the remaining study outcomes. CONCLUSIONS Albumin was shown to be safe and efficacious in extracorporeal circulation perfusion. However, its clinical advantages were not clearly highlighted, as there were no significant differences in the number of deaths, length of hospital stay, or intensive care unit duration. The results should be interpreted cautiously, as most included studies were small in scale, and the total number of participants was limited.
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Effect of 4% Albumin Solution vs Ringer Acetate on Major Adverse Events in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass: A Randomized Clinical Trial
Pesonen, E., Vlasov, H., Suojaranta, R., Hiippala, S., Schramko, A., Wilkman, E., Eränen, T., Arvonen, K., Mazanikov, M., Salminen, U. S., et al
Jama. 2022;328(3):251-258
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Abstract
IMPORTANCE In cardiac surgery, albumin solution may maintain hemodynamics better than crystalloids and reduce the decrease in platelet count and excessive fluid balance, but randomized trials are needed to compare the effectiveness of these approaches in reducing surgical complications. OBJECTIVE To assess whether 4% albumin solution compared with Ringer acetate as cardiopulmonary bypass prime and perioperative intravenous volume replacement solution reduces the incidence of major perioperative and postoperative complications in patients undergoing cardiac surgery. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, single-center clinical trial in a tertiary university hospital during 2017-2020 with 90-day follow-up postoperatively involving patients undergoing on-pump coronary artery bypass grafting; aortic, mitral, or tricuspid valve surgery; ascending aorta surgery without hypothermic circulatory arrest; and/or the maze procedure were randomly assigned to 2 study groups (last follow-up was April 13, 2020). INTERVENTIONS The patients received in a 1:1 ratio either 4% albumin solution (n = 693) or Ringer acetate solution (n = 693) as cardiopulmonary bypass priming and intravenous volume replacement intraoperatively and up to 24 hours postoperatively. MAIN OUTCOMES AND MEASURES The primary outcome was the number of patients with at least 1 major adverse event: death, myocardial injury, acute heart failure, resternotomy, stroke, arrhythmia, bleeding, infection, or acute kidney injury. RESULTS Among 1407 patients randomized, 1386 (99%; mean age, 65.4 [SD, 9.9] years; 1091 men [79%]; 295 women [21%]) completed the trial. Patients received a median of 2150 mL (IQR, 1598-2700 mL) of study fluid in the albumin group and 3298 mL (IQR, 2669-3500 mL) in the Ringer group. The number of patients with at least 1 major adverse event was 257 of 693 patients (37.1%) in the albumin group and 234 of 693 patients (33.8%) in the Ringer group (relative risk albumin/Ringer, 1.10; 95% CI, 0.95-1.27; P = .20), an absolute difference of 3.3 percentage points (95% CI, -1.7 to 8.4). The most common serious adverse events were pulmonary embolus (11 [1.6%] in the albumin group vs 8 [1.2%] in the Ringer group), postpericardiotomy syndrome (9 [1.3%] in both groups), and pleural effusion with intensive care unit or hospital readmission (7 [1.0%] in the albumin group vs 9 [1.3%] in the Ringer group). CONCLUSIONS AND RELEVANCE Among patients undergoing cardiac surgery with cardiopulmonary bypass, treatment with 4% albumin solution for priming and perioperative intravenous volume replacement solution compared with Ringer acetate did not significantly reduce the risk of major adverse events over the following 90 days. These findings do not support the use of 4% albumin solution in this setting. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02560519.
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Effect of 6% Hydroxyethyl Starch 130/0.4 on Inflammatory Response and Pulmonary Function in Patients Having Cardiac Surgery: A Randomized Clinical Trial
Lee MJ, Tannenbaum C, Mao G, Jia Y, Leung S, Yilmaz HO, Ince I, Soltesz E, Duncan AE
Anesthesia and analgesia. 2021
Abstract
BACKGROUND Cardiac surgery with cardiopulmonary bypass induces a profound inflammatory response that, when severe, can lead to multiorgan system dysfunction. Preliminary data suggest that administration of hydroxyethyl starch (HES) solutions may mitigate an inflammatory response and improve pulmonary function. Our goal was to examine the effect of 6% HES 130/0.4 versus 5% human albumin given for intravascular plasma volume replacement on the perioperative inflammatory response and pulmonary function in patients undergoing cardiac surgery. METHODS This was a subinvestigation of a blinded, parallel-group, randomized clinical trial of patients undergoing elective aortic valve replacement surgery at the Cleveland Clinic main campus, titled "Effect of 6% Hydroxyethyl Starch 130/0.4 on Kidney and Haemostatic Function in Cardiac Surgical Patients." Of 141 patients who were randomized to receive either 6% HES 130/0.4 or 5% human albumin for intraoperative plasma volume replacement, 135 patients were included in the data analysis (HES n = 66, albumin n = 69). We assessed the cardiopulmonary bypass-induced inflammatory response end points by comparing the 2 groups' serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and macrophage migration inhibitory factor (MIF), measured at baseline and at 1 and 24 hours after surgery. We also compared the 2 groups' postoperative pulmonary function end points, including the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (Pao2:Fio2 ratio), dynamic lung compliance, oxygenation index (OI), and ventilation index (VI) at baseline, within 1 hour of arrival to the intensive care unit, and before tracheal extubation. The differences in the postoperative levels of inflammatory response and pulmonary function between the HES and albumin groups were assessed individually in linear mixed models. RESULTS Serum concentrations of the inflammatory markers (TNF-α, IL-6, MIF) were not significantly different (P ≥ .05) between patients who received 6% HES 130/0.4 or 5% albumin, and there was no significant heterogeneity of the estimated treatment effect over time (P ≥ .15). The results of pulmonary function parameters (Pao2:Fio2 ratio, dynamic compliance, OI, VI) were not significantly different (P ≥ .05) between groups, and there was no significant heterogeneity of the estimated treatment effect over time (P ≥ .15). CONCLUSIONS Our investigation found no significant difference in the concentrations of inflammatory markers and measures of pulmonary function between cardiac surgical patients who received 6% HES 130/0.4 versus 5% albumin.
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Albumin in adult cardiac surgery: a narrative review
Hanley C, Callum J, Karkouti K, Bartoszko J
Canadian journal of anaesthesia = Journal canadien d'anesthesie. 2021
Abstract
PURPOSE Intravascular fluids are a necessary and universal component of cardiac surgical patient care. Both crystalloids and colloids are used to maintain or restore circulating plasma volume and ensure adequate organ perfusion. In Canada, human albumin solution (5% or 25% concentration) is a colloid commonly used for this purpose. In this narrative review, we discuss albumin supply in Canada, explore the perceived advantages of albumin, and describe the clinical literature supporting and refuting albumin use over other fluids in the adult cardiac surgical population. SOURCE We conducted a targeted search of PubMed, Embase, Medline, Web of Science, ProQuest Dissertations and Theses Global, the Cochrane Central Register of Controlled trials, and the Cochrane Database of Systematic Reviews. Search terms included albumin, colloid, cardiac surgery, bleeding, hemorrhage, transfusion, and cardiopulmonary bypass. PRINCIPAL FINDINGS Albumin is produced from fractionated human plasma and imported into Canada from international suppliers at a cost of approximately $21 million CAD per annum. While it is widely used in cardiac surgical patients across the country, it is approximately 30-times more expensive than equivalent doses of balanced crystalloid solutions, with wide inter-institutional variability in use and no clear association with improved outcomes. There is a general lack of high-quality evidence for the superiority of albumin over crystalloids in this patient population, and conflicting evidence regarding safety. CONCLUSIONS In cardiac surgical patients, albumin is widely utilized despite a lack of high- quality evidence supporting its efficacy or safety. A well-designed randomized controlled trial is needed to clarify the role of albumin in cardiac surgical patients.
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The comparison of albumin and 6% hydroxyethyl starches (130/0.4) in cardiac surgery: a meta-analysis of randomized controlled clinical trials
Wei, L., Li, D., Sun, L.
BMC surgery. 2021;21(1):342
Abstract
BACKGROUND Fluid administration is a key tool in the maintenance of normovolemia in patients with cardiac surgery. The trials that evaluated the safety of 6% hydroxyethyl starch (HES) 130/0.4 in cardiac surgical patients were inconsistent. It is necessary to compare the efficacy and safety of albumin and 6% HES (130/0.4). METHOD We searched for the randomized controlled clinical trials that compared human albumin with 6% HES (130/0.4) in cardiac surgery in PubMed, Cochrane, and Embase. RESULTS Ten studies involved a total of 1567 patients were included in our meta-analysis. For the efficiency, there was no difference in total volume of infusion between compared groups [P = 0.64, Fixed Effect Model (FEM): standardized mean difference (SMD) = 0.04, 95% confidence interval (CI) (- 0.12, 0.20)]. As for safety, the albumin show more risk than hydroxyethyl starch 130/0.4 in blood loss [P = 0.02, FEM: SMD: 0.22, 95% CI (0.03, 0.41)]. There was no difference in the frequency of transfusions (P = 0.20, RR = 1.11; 95% CI (0.95, 1.27)) between the two groups. No difference was observed for the days in intensive care unit [P = 0.05, FEM: SMD = - 0.18, 95% CI (- 0.36, 0.00)], and the days in hospital [P = 0.32, FEM: SMD = - 0.11, 95% CI (- 0.32, 0.10)]. Furthermore, both the incidence of AKI, RRT, and mortality were comparable in the two groups. CONCLUSION This study provided evidence that the 6% HES (130/0.4) might be the substitute for HA, which reduced the economic burden for patients with cardiac surgery. However, the effect of 6% HES (130/0.4) and HA on AKI still needs to be further studied.