Choosing the optimal fluid for cardiopulmonary bypass (CPB) in cardiac surgery remains a critical clinical decision, influencing outcomes such as hemodynamic stability, bleeding, transfusion requirements, renal function, and mortality. This systematic review and meta-analysis provides a contemporary and comprehensive comparison between 6% hydroxyethyl starch (HES 130/0.4) and 5% human albumin, two commonly used colloid solutions in cardiac surgical practice.Â
The study followed rigorous PRISMA and Cochrane methodology, analyzing data from 12 studies encompassing 908 patients—455 receiving HES and 453 receiving albumin. These studies included both randomized controlled trials and controlled observational designs, spanning a range of cardiac procedures such as coronary artery bypass grafting, valve surgery, and congenital heart repairs. As illustrated in the PRISMA flow diagram on page 6, over 800 records were screened before narrowing to the final 12 studies, highlighting the thorough selection process.
A key finding of this meta-analysis is the overall equivalence between HES and albumin across multiple clinically important outcomes. There were no statistically significant differences in postoperative blood loss, packed red blood cell transfusion rates, ICU length of stay, hospital length of stay, platelet counts, or mortality. For example, postoperative blood loss differed by only 42.4 mL on average and was not statistically significant. Similarly, mortality rates were nearly identical between groups, reinforcing the comparable efficacy of both fluids in supporting perioperative hemodynamics.
However, a crucial distinction emerges when examining renal outcomes. The analysis found that HES was associated with a significantly higher risk of acute kidney injury (AKI), with an odds ratio of 1.79. This finding was consistent across studies with low heterogeneity (I² = 0%), suggesting a robust and reliable signal rather than a statistical anomaly. Importantly, meta-regression analysis did not identify patient demographics, comorbidities, or procedural factors as drivers of this increased risk, implying that the association may be intrinsic to the properties of HES itself.
From a physiological perspective, this increased AKI risk aligns with longstanding concerns regarding synthetic colloids. HES solutions have been associated with renal tubular injury, osmotic nephrosis-like lesions, and altered microcirculatory dynamics. While newer-generation HES formulations such as 130/0.4 were developed to mitigate these risks, this meta-analysis suggests that renal safety concerns persist even with modern preparations.
The findings also challenge historical assumptions about bleeding risk. Earlier studies suggested that HES increased postoperative bleeding and coagulopathy. However, as shown in the forest plots on page 8, this analysis found no significant difference in bleeding outcomes or transfusion requirements. This may reflect improvements in HES formulations, better perioperative management, or variability in study designs across time.
Another important consideration is cost and resource utilization. Albumin, a natural plasma-derived product, is significantly more expensive than HES. In resource-limited settings, HES has often been favored due to its lower cost and availability. However, the potential for increased AKI—and its associated complications, prolonged hospitalization, and need for renal replacement therapy—may offset any initial cost savings. Thus, economic evaluations should consider not only upfront costs but also downstream clinical consequences.
The quality assessment of included studies revealed moderate overall evidence strength. According to the risk-of-bias table on page 5, five studies had low risk of bias, while the remaining had some concerns but none were high risk. The GRADE assessment further indicated high certainty for key outcomes such as AKI, transfusion, and mortality, although some outcomes like hospital length of stay had lower certainty due to heterogeneity and imprecision.
Despite its strengths, the study has limitations. Most included trials were single-center with relatively small sample sizes, which may limit generalizability. Additionally, variations in dosing regimens, timing of administration, and definitions of outcomes such as AKI could introduce heterogeneity. Follow-up durations were also relatively short, often limited to the immediate postoperative period, potentially missing longer-term renal effects.
Regulatory considerations further complicate interpretation. The European Medicines Agency has recommended restrictions or suspension of HES use in certain populations due to safety concerns, particularly in critically ill or septic patients. While this meta-analysis focuses on elective cardiac surgery, these broader safety concerns reinforce the need for cautious and individualized decision-making.
In clinical practice, the implications are clear: while HES and albumin provide similar efficacy for volume expansion in cardiac surgery, the increased risk of AKI with HES cannot be ignored. For patients with pre-existing renal dysfunction, diabetes, or other risk factors for kidney injury, albumin may represent a safer option despite its higher cost. Conversely, in low-risk patients where cost constraints are significant, HES may still have a role, provided careful monitoring is in place.
Ultimately, this study underscores the importance of personalized medicine in perioperative care. Fluid choice should not be based solely on tradition or cost but should incorporate patient-specific risk factors, institutional protocols, and evolving evidence. Future large-scale, multicenter randomized trials with standardized definitions and longer follow-up are needed to further clarify the long-term safety profiles of these fluids.
