Project Summary: Retrospective Cohort Study

1. Core ObjectiveThe primary goal is to determine if the volume of Hydroxyethyl Starch (HES) 130/0.4 (specifically Voluven® or Volulyte®) administered during the removal of giant meningiomas (tumors > 5 cm) increases the risk of postoperative complications.

2. Research Question

   Does the volume of intraoperative HES solution influence the rate of re-bleeding (requiring a second surgery within 48 hours) or the development of Acute Kidney Injury (AKI) within 7 days after the initial craniotomy?Outcomes:

3. Outcomes Primary: Incidence of re-bleeding at the tumor bed requiring re-operation within 48 hours Secondary: New-onset postoperative AKI within 7 days (defined by KDIGO criteria)

Background & Rationale

HES Properties: HES is a synthetic colloid used to maintain blood volume during surgery. While newer "third-generation" HES (130/0.4) is designed to be safer, it may still interfere with blood clotting.

Coagulation Concerns: HES can reduce levels of Factor VIII and von Willebrand factor (vWF) by 50-80%, potentially leading to "dilutional coagulopathy" where the blood cannot clot effectively.

Knowledge Gap: Current evidence is inconclusive regarding whether low-to-moderate doses of HES are truly safe during the removal of large, vascular brain tumors like giant meningiomas.

Study Methodology Study Population: Adult patients (> 18 years) who underwent craniotomy for a giant meningioma (> 5 cm) at Maharaj Nakorn Chiang Mai Hospital between January 1, 2016, and December 31, 2024.

Data Collection: Researchers will review electronic medical records to extract data on:

Patient demographics (age, sex, ASA physical status). Surgical details (operation time, estimated blood loss). Fluid management (volume of HES, crystalloids, and blood products given). Laboratory results (pre- and post-operative Serum Creatinine)

Ethical Considerations and Privacy: As a retrospective review of existing records, there is no direct patient contact. Data will be coded to maintain strict confidentiality.Benefits: The findings will help anesthesiologists optimize fluid therapy to improve patient safety and reduce surgical risks.

Statistical Analysis Plan

1. Grouping and ComparisonIn a cohort design, patients will be grouped based on their exposure to Hydroxyethyl Starch (HES) Voluven® or Volulyte® 130/0.4:

   Exposed Group: Patients who received HES during surgery. Non-Exposed Group: Patients who did not receive HES (received only crystalloids or other fluids).

   Dose-Response Analysis: Patients may also be categorized by the volume of HES received (e.g., < 500 ml vs. 500-1,000 ml vs. > 1,000 ml) to see if higher doses correlate with higher bleeding risk.

2. Primary and Secondary Outcomes

   Primary Outcome: The cumulative incidence of re-bleeding and required re-craniotomy within 48 hours.

   Secondary Outcome: The incidence of new-onset postoperative Acute Kidney Injury (AKI) within 7 days, defined by the KDIGO criteria (Serum Creatinine increase > 0.3 mg/dl or > 1.5x baseline).

3. Analytic StatisticsRisk Estimation: We will primarily report Relative Risk (RR) or Hazard Ratios (HR) to describe the risk of bleeding in the HES group compared to the non-HES group.

Confounder Adjustment: We will use Multivariable Logistic Regression or Cox Proportional Hazards Regression to adjust for potential confounders such as age, sex, ASA grade, tumor size, and total blood loss.

Handling Continuous Data: Factors like the volume of HES and estimated blood loss (EBL) will be analyzed using mean/standard deviation and compared using t-tests or Mann-Whitney U tests.

Sample Size Consideration for Cohort Study

For a cohort study, the sample size is determined by the expected incidence of re-bleeding in the unexposed group versus the exposed group.Based on our previous data, the incidence of re-operation is approximately 1.5% to 1.6%.With we planned 9-year data collection (2016-2024), we aim to include all eligible giant meningioma cases (> 5 cm) to maximize the power of the study.

Inclusion Criteria:

• Inclusion CriteriaTo be included in the study, participants must meet all of the following requirements:Age: Patients must be at least 18 years old.

Diagnosis: Patients must be diagnosed with a meningioma. Tumor Size: The tumor must be classified as "giant," defined as having a diameter of 5 cm or larger as seen on a CT scan.

Surgery Type: Patients must have undergone a craniotomy to remove the tumor. Timeframe: The surgery must have occurred between the years 2016 and 2024

Exclusion Criteria:

• Exclusion CriteriaPatients will be excluded from the study if they meet any of the following conditions:

Recurrent Cases: Patients with a recurrent meningioma (rather than a first-time surgery).

Emergency Cases: Patients requiring an emergency craniotomy. Pregnancy: Any patient who is pregnant. Major Complications: Patients who experienced cardiac arrest during the surgery.

Adult patients diagnosed of giant meningiomas, diameter of at least 5 cm. They were scheduling for craniotomy during 2016-2024.

Withdrawal Criteria: There are no specific withdrawal criteria listed for this study.

Ethical Consideration: Since this is a retrospective study using existing hospital electronic records, individual informed consent is not required.

This is a retrospective cohort study using electronic medical records from a single center.To protect patient privacy and maintain strict confidentiality, only the research team has authorized access to the data.The data is recorded using research codes instead of hospital identification numbers to ensure anonymity.Currently, there is no established protocol or administrative framework for sharing these specific patient records with external researchers