Perioperative Glycemic Management in Hepatobiliary Surgery: An Integrated Approach

Introduction

• Perioperative glycemic management is crucial in diabetic patients undergoing major hepatobiliary surgery.
• The liver plays a central role in glucose homeostasis and insulin clearance.
• Poor glycemic control is linked with higher morbidity and mortality.
• This article integrates molecular biology, anesthetic pharmacology, and surgical physiology to guide anesthetic practice in a 53-year-old insulin-dependent diabetic patient scheduled for hepatectomy [1,2].

Case Summary

• Patient: 53-year-old female with carcinoma gallbladder and duodenal infiltration, planned hepatectomy.
• Diabetes history: Type 2 diabetes, HbA1c 8.0%, on basal-bolus insulin (Actrapid 6-6-8 U + Lantus 14 U).
• Glucose range: 130–464 mg/dL.
• Key anesthetic issues:
• Stress-induced hyperglycemia.
• Altered hepatic metabolism.
• Variable insulin clearance [3,4].

Risks of Hyperglycemia in Hepatobiliary Surgery

• Clinical risks:
• Increased risk of infection and sepsis.
• Poor wound healing.
• Impaired liver regeneration.
• Molecular mechanisms:
• Advanced glycation end-products (AGEs) activate RAGE receptors.
• NF-κB pathway triggers pro-inflammatory cytokines (TNF-α, IL-6).
• Endothelial dysfunction due to inflammation.
• Mitochondrial ROS leads to hepatocyte and endothelial apoptosis.
• Insulin resistance from impaired IRS-1/PI3K/AKT signaling reduces glucose uptake [5,6].

Glycemic Challenges in Hepatectomy

• Liver functions in glucose control:
• Gluconeogenesis (enzymes: PEPCK, G6Pase).
• Glycogen storage.
• Insulin clearance via insulin-degrading enzyme.
• Impact of hepatectomy:
• Reduced insulin metabolism → risk of hyperinsulinemia.
• Depleted glycogen stores → risk of hypoglycemia.
• Reduced gluconeogenesis → impaired glucose maintenance post-resection [7,8].

Preoperative Glycemic Optimization

• Targets:
• Fasting glucose: 100–140 mg/dL.
• HbA1c <7% if time permits.
• Insulin adjustments:
• Continue basal insulin the night before.
• Replace SC prandial insulin with IV insulin on day of surgery.
• Other considerations:
• Stop metformin to avoid lactic acidosis.
• Correct potassium before surgery (insulin lowers K⁺).
• Molecular rationale:
• SC insulin absorption unreliable during anesthesia due to altered perfusion.
• IV insulin allows precise titration.
• Repeated hyperglycemia activates NF-κB and MAPK cascades [9,10].

Intraoperative Glycemic Management

• Monitoring:
• Hourly glucose.
• Potassium and magnesium every 4–6 hours.
• IV Insulin Infusion Protocol:
• 50 U regular insulin in 50 mL solution.
• Start at 1–2 U/hr with D5½NS at 100 mL/hr.
• Titration guidelines:
• <140 mg/dL: 0–0.5 U/hr.
• 141–180 mg/dL: 1 U/hr.
• 181–220 mg/dL: 2 U/hr.
• 221–260 mg/dL: 3 U/hr.

260 mg/dL: 4–6 U/hr plus review.

• Molecular impact of anesthesia and stress:
• Volatile agents suppress GSIS by impairing β-cell mitochondrial ATP.
• Propofol reduces ROS and systemic inflammation, preserving insulin signaling.
• Catecholamine and cortisol surges enhance gluconeogenesis and worsen insulin resistance via cytokine-mediated AKT inhibition [11–13].

Effects of Anesthetic Agents on Glucose Homeostasis

• Volatile agents:
• Disrupt β-cell Ca²⁺ homeostasis and ATP generation.
• Impair insulin secretion.
• May block hepatic AKT phosphorylation.
• Propofol:
• Antioxidant properties.
• Lowers IL-6 and IL-1β.
• Preserves mitochondrial function in β-cells.
• Opioids:
• Attenuate sympathetic response and stress hyperglycemia.
• Chronic use may impair insulin signaling via μ-receptor effects on hypothalamic centers [14–16].

Postoperative Glycemic Strategy

• Immediate goals:
• Continue IV insulin with D5½NS until oral intake resumes.
• Target glucose: 140–180 mg/dL.
• Transition to SC insulin:
• Overlap IV insulin with SC basal-bolus for 2 hours.
• Monitoring:
• Electrolytes and liver function.
• Sepsis markers (hyperglycemia can be an early sign).
• Molecular considerations:
• IL-6 and TNF-α continue driving insulin resistance postoperatively.
• Restored glucose control supports hepatocyte regeneration via PI3K/AKT/mTOR signaling.
• Avoid hypoglycemia to prevent neuroglycopenia and excitotoxic brain injury [17–19].

Case Interpretation from Glucose Chart

• Baseline: 464 mg/dL → marked hyperglycemia.
• After insulin infusion (~3.5 U/hr): glucose dropped to 180–200 mg/dL.
• Interpretation:
• SC basal-bolus regimen insufficient under surgical stress.
• Early IV insulin infusion is more effective for perioperative control [20].

Future Directions: Molecularly Guided Glycemic Targets

• Biomarkers and indices:
• C-peptide and HOMA-IR for endogenous insulin quantification.
• Hepatokines:
• FGF21, fetuin-A as indicators of liver–metabolic interactions.
• Genomic insights:
• IRS-1 gene variants for personalized insulin sensitivity assessment.
• Technological advances:
• Continuous glucose monitoring (CGM) integrated into OR practice [23–25].

Conclusion

• Optimal perioperative glycemic management requires integration of molecular biology, hepatic physiology, and anesthetic pharmacology.
• In this case, proactive IV insulin infusion, TIVA with propofol, and vigilant electrolyte monitoring improved outcomes.
• Future strategies may incorporate personalized molecular and genomic profiling for precision perioperative glucose control.