Hydroxyethyl starch (HES) versus other fluid therapies: effects on kidney function

Fluid resuscitation is a standard intervention in critical care to restore intravascular volume. While hydroxyethyl starches (HES) are widely used as synthetic colloids, concerns have emerged about their impact on kidney function. Prior research has shown that HES may not be neutral in renal outcomes. However, uncertainty remained about the extent of this risk across different patient populations and HES formulations. Earlier studies lacked consistency in defining acute kidney injury (AKI) and in controlling for confounding variables. This gap motivated a systematic review to clarify the comparative safety of HES versus other fluids. The need for standardized definitions and larger datasets became apparent as early studies were retracted or excluded due to incomplete data. Recent trials have provided more robust evidence but still require synthesis. The lack of consensus on HES safety has driven the need for updated meta-analyses. This uncertainty has also prompted clinical guidelines to reconsider the use of HES in fluid management.

This updated Cochrane review aimed to evaluate the effects of HES on kidney function compared to alternative fluid therapies. The study focused on determining whether HES increases the risk of acute kidney injury (AKI) and the need for renal replacement therapy (RRT). The goal was to synthesize evidence from randomized controlled trials (RCTs) and quasi-RCTs to inform clinical practice. The review considered different patient populations and HES formulations to identify patterns in renal outcomes. The authors sought to address inconsistencies in prior studies by using standardized definitions like RIFLE criteria. They also aimed to assess whether subgroup analyses could clarify risks in sepsis versus non-sepsis patients. The motivation was to provide a comprehensive and updated analysis of HES safety. The study aimed to guide clinicians in choosing safer alternatives when appropriate.

The researchers conducted a systematic review and meta-analysis of RCTs and quasi-RCTs comparing HES with other fluids. They searched multiple databases including Cochrane Library, MEDLINE, and EMBASE up to November 2012. Two authors independently screened, selected, and extracted data using standardized forms. The primary outcomes were RRT, author-defined kidney failure, and AKI as per RIFLE criteria. Data were analyzed using relative risk (RR) and 95% confidence intervals (CI). Authors were contacted for missing data when necessary. Subgroup and sensitivity analyses were performed using a random-effects model. The review included 42 studies involving 11,399 patients, with 19 from the original 2010 review and 23 new studies added.

The meta-analysis found that HES treatment significantly increased the risk of requiring renal replacement therapy (RRT) compared to other fluids (RR 1.31, 95% CI 1.16 to 1.49). HES also increased the risk of author-defined kidney failure (RR 1.59, 95% CI 1.26 to 2.00). The risk of AKI based on RIFLE-F criteria was elevated in HES-treated patients (RR 1.14, 95% CI 1.01 to 1.30). However, urine output-based RIFLE-R criteria showed a lower risk of AKI with HES (RR 0.95, 95% CI 0.91 to 0.99). When RIFLE-R urine output data were excluded, the risk of AKI favored other fluids (RR 1.05, 95% CI 0.97 to 1.14). The RIFLE-I outcome showed a significant increase in AKI with HES (RR 1.22, 95% CI 1.08 to 1.37). No differences were found between HES subgroups for RRT or RIFLE-F outcomes. Subgroup analyses for sepsis versus non-sepsis patients showed differences in RIFLE-R and RIFLE-I outcomes.

The authors concluded that HES solutions increase the risk of acute kidney injury (AKI) and the need for renal replacement therapy (RRT) across all patient populations. They emphasized that a safe volume of HES has not been established. The findings suggest that the risks of HES likely outweigh any benefits in most clinical settings. The authors recommend considering alternative fluid therapies instead of HES. They noted that subgroup analyses revealed differences in RIFLE-R and RIFLE-I outcomes between sepsis and non-sepsis patients. This may reflect varying renal responses to fluid resuscitation in different clinical contexts. The authors did not propose new mechanisms or future research directions. They reiterated that the current evidence supports avoiding HES in favor of safer alternatives.