Intravenous fluid selection during cardiopulmonary bypass (CPB) remains a critical and debated aspect of modern cardiac surgery. Colloid solutions are frequently used to maintain intravascular volume, optimize hemodynamics, and support organ perfusion during and after surgery. Among these, human albumin and synthetic hydroxyethyl starch (HES) solutions have been widely adopted, yet concerns persist regarding safety, cost, and long-term outcomes. The meta-analysis by Alqarni and colleagues provides an updated and comprehensive comparison of 6% HES 130/0.4 versus 5% albumin in patients undergoing cardiac surgery with CPB, offering clinically relevant insights grounded in randomized evidence.
The authors conducted a systematic review in accordance with PRISMA and Cochrane standards, searching major databases and grey literature through August 2025. Twelve randomized controlled trials involving 908 patients were included, with nearly equal representation in the HES and albumin groups. The studies encompassed a broad spectrum of cardiac surgical procedures, including coronary artery bypass grafting, valve surgery, complex adult cardiac surgery, and pediatric congenital heart repairs. Both fluids were used as priming solutions, intraoperative infusions, or postoperative volume replacement, reflecting real-world clinical practice.
One of the central findings of the meta-analysis is the overall similarity between HES 130/0.4 and albumin for most clinically important outcomes. Postoperative blood loss did not differ significantly between groups, nor did rates of packed red blood cell transfusion. These findings challenge earlier concerns that synthetic starches inevitably worsen bleeding risk, particularly with newer third-generation HES formulations designed to reduce coagulopathy. Similarly, there were no statistically significant differences in intensive care unit length of stay, total hospital stay, postoperative platelet counts, or short-term creatinine levels. Mortality rates were also comparable, although event numbers were low, limiting definitive conclusions.
Despite this apparent equivalence across many outcomes, the analysis identified a key safety signal: a significantly increased risk of acute kidney injury (AKI) associated with HES use. Patients receiving HES had approximately a 79% higher odds of developing AKI compared with those receiving albumin. Importantly, this association was observed with low heterogeneity, suggesting consistency across studies. While short-term creatinine levels did not differ significantly, the increased AKI incidence raises concerns about subclinical or evolving renal injury not fully captured by early laboratory values.
The renal findings are particularly relevant given the broader regulatory and clinical context surrounding HES solutions. Over the past decade, multiple studies in critically ill and septic populations have linked HES to renal dysfunction and increased mortality, prompting regulatory restrictions in several regions. Although elective cardiac surgery patients differ substantially from septic ICU populations, the observed AKI signal in this meta-analysis reinforces the need for caution, especially in patients with pre-existing renal impairment or other risk factors for kidney injury.
Methodologically, the study demonstrates several strengths. The authors adhered to rigorous systematic review standards, included recent trials, and performed detailed assessments of bias, heterogeneity, and publication bias. Meta-regression analyses explored whether baseline patient characteristics or surgical factors explained variability in bleeding or AKI outcomes, but no significant modifiers were identified. This suggests that the observed renal risk with HES may be intrinsic rather than confined to specific subgroups, although unmeasured confounders cannot be excluded.
Nonetheless, limitations must be acknowledged. Most included trials were small and single-center, with relatively short follow-up periods, often limited to the first 24–48 hours postoperatively. Definitions of AKI and bleeding varied across studies, potentially affecting outcome precision. Additionally, dosing strategies and timing of fluid administration were not uniform, reflecting clinical heterogeneity but complicating interpretation. These factors underscore the need for larger, multicenter trials with standardized outcome definitions and longer follow-up to fully characterize renal and long-term safety.
From a clinical perspective, the findings suggest that while both albumin and HES 130/0.4 can achieve effective volume expansion during cardiac surgery, they are not interchangeable from a safety standpoint. Albumin maintains a favorable renal safety profile but comes at higher cost and limited availability in some settings. HES offers economic and logistical advantages but carries a measurable risk of AKI that may outweigh its benefits in certain patients. Individualized fluid selection—considering patient comorbidities, renal risk, institutional protocols, and regulatory guidance—remains essential.
In conclusion, this meta-analysis contributes valuable, up-to-date evidence to the ongoing debate over colloid use in cardiac surgery. It supports the notion that 6% HES 130/0.4 and 5% albumin provide similar efficacy for volume management during CPB, but it also reinforces persistent concerns about HES-related renal injury. As perioperative care continues to evolve toward precision and safety, these findings emphasize the importance of thoughtful fluid stewardship and continued high-quality research in this high-risk population.
