Why should metformin (biguanide oral hypoglycemic) be stopped before surgery?

Why Metformin Should Be Stopped Before Surgery

Metformin must be stopped before surgery to prevent metformin-associated lactic acidosis (MALA), a rare but life-threatening complication with a 30-50% mortality rate that occurs when surgery-induced renal impairment, tissue hypoperfusion, or hemodynamic instability causes metformin accumulation. 1, 2, 3

The Core Problem: Lactic Acidosis Risk

Metformin-associated lactic acidosis is rare (2-9 cases per 100,000 patients/year) but catastrophic when it occurs. 4, 1, 5 The mechanism is straightforward:

• Metformin is eliminated exclusively by the kidneys, so any perioperative renal impairment causes drug accumulation 3
• Surgery creates multiple conditions that trigger lactic acidosis: hemodynamic instability, tissue hypoperfusion, dehydration from fasting, acute kidney injury, and volume depletion 1, 2
• The drug interferes with lactate metabolism, and when lactate production increases (from tissue hypoxia during surgery) while clearance decreases (from renal dysfunction), lethal acidosis develops 3

Current Guideline Recommendations

The American College of Cardiology, American Heart Association, and European guidelines recommend stopping metformin the night before elective surgery and not restarting until 48 hours post-surgery, only after confirming adequate renal function (eGFR ≥60 mL/min/1.73m²). 1, 2, 6

Timing of Discontinuation

• For normal renal function: Stop metformin the evening before surgery, which allows adequate clearance given metformin's 6.2-hour plasma half-life 1, 2
• For baseline renal impairment (eGFR 30-60 mL/min/1.73m²): Stop at least 24 hours before surgery 2
• For emergency surgery: Proceed without delay but alert the surgical/anesthesia team to metformin use and monitor lactate levels closely 1

High-Risk Surgical Situations Requiring Extra Vigilance

Certain procedures carry particularly high risk for MALA:

• Procedures involving iodinated contrast administration, especially with history of liver disease, alcoholism, heart failure, or intra-arterial contrast use 2, 3
• Major abdominal surgery due to higher risk of hemodynamic instability and acute kidney injury 2, 7
• Any surgery with expected significant blood loss or hemodynamic instability 4

Risk Factors That Amplify MALA Risk

The FDA label and guidelines identify specific patient factors that dramatically increase perioperative MALA risk: 3

• Renal impairment (creatinine clearance <60 mL/min) - the primary risk factor 4, 1
• Severe heart failure (LVEF <30%) or acute cardiac conditions 1, 3
• Liver disease or alcoholism (impairs lactate clearance) 3
• Concurrent use of ACE inhibitors, ARBs, diuretics, or NSAIDs (increase acute kidney injury risk) 4, 2
• Age ≥65 years (higher likelihood of organ impairment) 3
• Dehydration or fasting status 3

When to Restart Metformin: The 48-Hour Rule

Do not restart metformin until 48 hours post-surgery, and only if ALL of the following criteria are met: 1, 2, 6

• eGFR ≥60 mL/min/1.73m² (must be measured, not assumed)
• Patient eating and drinking normally
• No ongoing clinical instability (no vasopressor requirement, dehydration, acute heart failure, sepsis, or respiratory insufficiency)
• Hemodynamically stable

The 48-hour waiting period exists because surgery-induced renal impairment may not be immediately apparent on postoperative day 1, and transient perioperative kidney injury is common. 1, 2

Clinical Recognition of MALA

If MALA develops postoperatively, recognize these symptoms immediately: 3

• Unexplained hyperventilation or dyspnea
• Severe muscle pain (myalgias)
• Unusual somnolence or altered mental status
• Unexplained nausea, vomiting, or abdominal pain
• Feeling cold, especially in extremities
• Slow or irregular heartbeat

Laboratory findings: pH <7.35, lactate >5 mmol/L (>45 mg/dL), increased anion gap 5, 7

Management of MALA

If MALA is suspected: 3, 7

• Discontinue metformin immediately
• Prompt hemodialysis is the definitive treatment (metformin is dialyzable with clearance up to 170 mL/min) 3
• Provide vasopressor support and fluid resuscitation as needed 7
• Continuous veno-venous hemodialysis with citrate and calcium (CVVHD-CiCa) has been successful in case reports 7

Common Pitfalls to Avoid

• Do not restart metformin too early - the 48-hour rule exists for a reason, as renal function may appear normal on day 1 but deteriorate 1, 6
• Do not assume normal renal function without measuring eGFR before restarting 2
• Do not continue metformin in patients with baseline eGFR 30-45 mL/min/1.73m² undergoing major surgery 3
• Do not forget to stop metformin before contrast-enhanced imaging studies in at-risk patients 2, 3

Evolving Perspective

Recent data suggest metformin may not be as strongly associated with lactic acidosis as previously feared, and the 2024 AHA/ACC guidelines acknowledge this. 1, 6 However, the conservative approach of perioperative discontinuation remains standard practice because when MALA does occur, it is often fatal, and surgery creates the exact conditions (renal impairment, tissue hypoxia, hemodynamic instability) that trigger this complication. 4, 7, 8