When should metformin be stopped and restarted for a patient undergoing anesthesia or surgery, considering operative risk, renal function, and postoperative oral intake?

Metformin and Anesthesia: Perioperative Management

Direct Recommendation

Stop metformin the night before surgery and do not restart until 48 hours postoperatively, after confirming adequate renal function (eGFR ≥60 mL/min/1.73m²) and ensuring the patient is eating and drinking normally. 1, 2, 3

Timing of Discontinuation

For Elective Surgery

• Discontinue metformin the evening before surgery for patients with normal renal function, which allows adequate drug clearance given metformin's plasma half-life of 6.2 hours 2, 3
• For minor or ambulatory surgery, metformin can be continued except in cases of severe renal failure 1
• For major surgery, always stop metformin the night before regardless of renal function 1

For Emergency Surgery

• Proceed with surgery without delay if metformin cannot be stopped in advance 3
• Alert the surgical and anesthesia team to metformin use 3
• Monitor lactate levels and renal function closely perioperatively 2, 4
• Ensure adequate fluid resuscitation with balanced crystalloids 5
• Be prepared for hemodialysis if metformin-associated lactic acidosis develops 6

Rationale: Risk of Lactic Acidosis

Metformin-associated lactic acidosis (MALA) is rare but carries catastrophic mortality rates of 30-50%. 1, 6

• The incidence is 2-9 cases per 100,000 patients/year 1, 7
• In France, cases increased from 10 to 72 per year between 2005-2010, with 20% mortality 1
• Almost all cases involved acute renal failure 1
• Most affected patients were elderly (68% over age 65) taking high doses (mean 2600 mg/day) 1

Why Surgery Increases MALA Risk

Surgery creates multiple risk factors simultaneously: 3, 5

• Hemodynamic instability and tissue hypoperfusion
• Perioperative fasting and volume depletion
• Acute kidney injury from surgical stress
• Potential hypoxemia and metabolic stress

Risk Factors Requiring Extra Caution

Identify these high-risk conditions preoperatively, as they mandate strict adherence to discontinuation protocols: 1

• Renal impairment (creatinine clearance <60 mL/min) 1, 6
• Severe heart failure (left ventricular ejection fraction <30%) 1
• Administration of iodinated contrast agents 1, 6
• Conditions altering renal function: dehydration, fasting, or concurrent medications (ACE inhibitors, ARBs, diuretics, NSAIDs) 1
• Elderly patients (age ≥65 years) require more frequent renal function assessment 2, 6
• Hepatic impairment or alcoholism due to impaired lactate clearance 6

Criteria for Restarting Metformin

Do not restart metformin until ALL of the following criteria are met: 2, 3

1. Minimum 48 hours have elapsed after major surgery 1, 2, 3
2. eGFR ≥60 mL/min/1.73m² confirmed by laboratory testing 2, 3, 6
3. Patient is eating and drinking normally 2, 3
4. No ongoing clinical instability: no dehydration, vasopressor requirement, acute heart failure, sepsis, or respiratory insufficiency 2
5. Adequate renal perfusion has been maintained postoperatively 1

Special Considerations for Restarting

• For minor/ambulatory surgery, metformin can be restarted sooner if renal function is normal and patient is stable 1
• Patients with baseline eGFR 30-60 mL/min/1.73m² require more conservative management and longer observation before restarting 3, 6
• Check renal function at 48 hours postoperatively before making the decision to restart 3, 5

Practical Perioperative Algorithm

Preoperative Phase

• Stop metformin the night before elective surgery 1, 2, 3
• Check baseline eGFR and identify high-risk patients 1, 3
• Ensure adequate hydration status 3, 5
• Review concurrent medications (ACE inhibitors, ARBs, diuretics, NSAIDs) that increase MALA risk 1

Intraoperative Phase

• Use balanced crystalloids for fluid resuscitation 5
• Maintain mean arterial pressure ≥65 mmHg (≥70 mmHg if hypertensive) to preserve renal perfusion 1
• Monitor for signs of tissue hypoperfusion 5
• Consider hemodynamic monitoring for major/hemorrhagic surgery 1

Postoperative Phase

• Check renal function at 48 hours postoperatively 3, 5
• Assess clinical stability: volume status, hemodynamics, oral intake 2, 3
• Restart metformin only if all criteria met (see above) 2, 3
• Monitor for signs of MALA: unusual weakness, muscle pain, respiratory distress, abdominal symptoms, hypothermia, bradycardia 6

Important Caveats and Pitfalls

Contrast-Enhanced Procedures

Stop metformin at the time of or prior to iodinated contrast imaging in patients with: 6

• eGFR 30-60 mL/min/1.73m²
• History of hepatic impairment, alcoholism, or heart failure
• Intra-arterial contrast administration planned
• Re-evaluate eGFR 48 hours after imaging before restarting 6

Evolving Evidence

Recent data suggest metformin may not be as strongly associated with lactic acidosis as previously feared 2, 8, 9, and some studies show continuation does not raise lactate to clinically relevant levels 8. However, consensus guidelines from major societies (American College of Cardiology, American Heart Association, European Society of Cardiology) continue to recommend perioperative discontinuation due to the catastrophic consequences when MALA does occur 2, 3, 5. The conservative approach remains standard practice given the 30-50% mortality rate 1, 6.

Glucose Management During Metformin Interruption

• Use basal-bolus insulin coverage perioperatively rather than reactive sliding scale alone 2
• For patients on insulin who are fasting, establish glucose infusion if blood glucose drops below acceptable range 1
• Do not administer glucose infusion if blood glucose >16.5 mmol/L (297 mg/dL) 1