Intraoperative Voluven is Associated with Reduced Anastomotic Leakage Without Increasing Acute Kidney Injury in Gastrointestinal Surgery: A Retrospective Cohort Study

Technical Summary: Intraoperative Voluven and Anastomotic Leakage in Gastrointestinal Surgery

Problem Statement
The perioperative management of fluid therapy in gastrointestinal surgery remains a critical area of debate, specifically regarding the safety profile of synthetic colloids versus crystalloids. While hemodynamic instability is a primary driver of postoperative acute kidney injury (AKI), the use of hydroxyethyl starch (HES), particularly 6% HES 130/0.4 (Voluven), has been controversial due to concerns linking it to increased AKI risk, renal failure, and coagulopathy. Regulatory bodies have issued warnings restricting HES use in septic patients, yet data regarding its safety in elective gastrointestinal surgery remains inconclusive, often limited by small sample sizes or the pooling of different HES formulations. Furthermore, the impact of colloids on other surgical complications, such as anastomotic leakage, is not fully understood. This study addresses the uncertainty surrounding the intraoperative use of Voluven and succinylated gelatin (Gelofusine) compared to crystalloids alone, specifically investigating their association with postoperative AKI and anastomotic leakage.

Methodology
This was a single-center, retrospective cohort study conducted at Sun Yat-Sen Memorial Hospital involving patients who underwent gastrointestinal abdominal surgery under general anesthesia between January 1, 2019, and May 31, 2021.

• Population: The final analysis included 3,087 patients after applying strict inclusion and exclusion criteria (e.g., excluding patients with severe cardiac or renal insufficiency, preoperative hypotension, or those receiving both colloids).
• Grouping: Patients were categorized into three groups based on intraoperative fluid administration:
  1. Crystalloid Group: Received only crystalloids (n=698).
  2. Voluven Group: Received 6% HES 130/0.4 without gelatin (n=1,194).
  3. Gelofusine Group: Received 4% succinylated gelatin without HES (n=1,195).
• Outcomes:
  • Primary Outcome: Postoperative AKI within 7 days, defined by KDIGO criteria (increase in serum creatinine ≥26.5 µmol/L within 48 hours or ≥1.5 times baseline).
  • Secondary Outcomes: Anastomotic leakage, postoperative hemorrhage, infection, intestinal obstruction, gastrointestinal dysfunction, circulatory/respiratory complications, altered mental status, and length of stay.
• Statistical Analysis: To mitigate selection bias inherent in observational data, the authors employed Propensity Score Matching (PSM) and Inverse Probability of Treatment Weighting (IPTW). Multivariable logistic regression was used to calculate adjusted odds ratios (aOR) for outcomes, controlling for confounders such as age, comorbidities, surgical duration, and blood loss.

Key Contributions and Results

• Acute Kidney Injury (AKI): The study found no statistically significant association between the use of either Voluven or Gelofusine and an increased risk of postoperative AKI compared to crystalloids alone.
  • Voluven vs. Crystalloid: Adjusted OR = 1.12 (95% CI: 0.58–2.18; P=0.74).
  • Gelofusine vs. Crystalloid: Adjusted OR = 0.82 (95% CI: 0.44–1.52; P=0.53).
  • Subgroup analyses for patients with mild-to-moderate renal insufficiency and higher ASA physical status (III–IV) confirmed these findings, showing no significant difference in AKI incidence.
• Anastomotic Leakage: A significant finding was the association between Voluven use and a reduced risk of anastomotic leakage.
  • Voluven vs. Crystalloid: The adjusted odds ratio was 0.50 (95% CI: 0.29–0.87; P=0.014), indicating a 50% reduction in risk.
  • Gelofusine vs. Crystalloid: No significant association was observed (aOR = 0.78; P=0.18).
• Other Complications: No significant differences were observed between the groups regarding postoperative hemorrhage, infection, intestinal obstruction, gastrointestinal dysfunction, circulatory or respiratory complications, or altered mental status.
• Hospital Stay: While the median postoperative length of stay was slightly longer in the colloid groups (7 days) compared to the crystalloid group (6 days), the total hospital stay did not differ significantly among the three groups.

Significance and Claims
The authors claim that this study provides evidence that the intraoperative use of modern, third-generation HES (6% HES 130/0.4) does not increase the risk of postoperative AKI in patients undergoing gastrointestinal surgery, challenging previous concerns derived from studies in critically ill or septic populations.

Furthermore, the study suggests a potential protective benefit of Voluven regarding anastomotic healing, noting a significantly lower risk of anastomotic leakage. The authors propose that this may be attributed to HES's ability to improve microcirculation, reduce leukocyte adhesion, and attenuate systemic inflammation, thereby creating a favorable environment for wound healing.

The paper concludes that while Voluven appears to have a favorable safety profile regarding renal function and may offer benefits for anastomotic integrity, these findings are hypothesis-generating. The authors emphasize that the retrospective nature of the study limits causal inference and explicitly state that further prospective randomized trials are warranted to confirm these results before changing clinical practice guidelines.