How should I manage a patient with end‑stage renal disease who was inadvertently started on metformin and now presents with hypoglycemia‑induced chorea and ballismus secondary to metformin‑associated lactic acidosis?

Management of Metformin-Associated Lactic Acidosis with Hypoglycemia-Induced Movement Disorders in End-Stage Renal Disease

Immediate Life-Saving Interventions

Discontinue metformin immediately and initiate urgent hemodialysis—this is the definitive treatment for metformin-associated lactic acidosis (MALA) and often reverses symptoms, with metformin being dialyzable at clearances up to 170 mL/min under good hemodynamic conditions. 1

• Metformin is absolutely contraindicated when eGFR < 30 mL/min/1.73 m² and must never be prescribed in end-stage renal disease (ESRD). 2, 1
• The patient's MALA occurred because metformin is eliminated unchanged in the urine, making drug accumulation inevitable in ESRD, with toxic levels causing life-threatening lactic acidosis. 2, 3
• Hemodialysis should be performed promptly in a hospital setting to correct the acidosis and remove accumulated metformin; this has resulted in reversal of symptoms and recovery in reported cases. 1, 4

Addressing the Hypoglycemia

• Administer intravenous dextrose (D50W 25–50 mL bolus, then D10W infusion) to correct hypoglycemia immediately, targeting blood glucose 100–180 mg/dL. 3
• Monitor blood glucose every 1–2 hours during the acute phase, as metformin itself rarely causes hypoglycemia but the combination of ESRD, lactic acidosis, and potential malnutrition creates high risk. 2, 3

Managing the Movement Disorder (Chorea/Ballismus)

• The chorea and ballismus are secondary to hypoglycemia affecting the basal ganglia (particularly the striatum and subthalamic nucleus), which are highly metabolically active and vulnerable to glucose deprivation. 3
• These involuntary movements typically resolve spontaneously within days to weeks once normoglycemia is restored and the metabolic derangement (lactic acidosis) is corrected. 3
• Obtain urgent brain MRI (T1-weighted sequences) to document hyperintensity in the basal ganglia, which is characteristic of hypoglycemia-induced chorea and helps exclude other causes such as stroke or structural lesions. 3
• If movements are severe and persist beyond 48–72 hours despite glucose correction, consider symptomatic treatment with haloperidol 0.5–2 mg PO/IV every 8 hours or tetrabenazine 12.5–25 mg PO twice daily, though these are rarely needed as the movements usually resolve with metabolic correction. 3

Supportive Management of Lactic Acidosis

• Do NOT administer sodium bicarbonate unless pH < 7.15 with severe acidosis causing catecholamine receptor resistance and refractory hypotension—bicarbonate does not improve hemodynamics or survival at pH ≥ 7.15 and may cause harm by increasing lactate production, hypernatremia, volume overload, and CO₂ generation. 3, 1
• Restore tissue perfusion with isotonic saline 15–20 mL/kg/h if hypotension is present, targeting mean arterial pressure ≥ 65 mmHg. 3
• If hypotension persists despite fluid resuscitation, initiate norepinephrine as first-line vasopressor. 3
• Treat any concurrent sepsis aggressively with source control and antibiotics within 3 hours if infection is suspected. 3

Monitoring During Acute Phase

• Check arterial blood gas, serum lactate, and anion gap every 2–4 hours until lactate < 2 mmol/L and pH normalizes. 3
• The patient's lactate level indicates life-threatening severity (normal < 2 mmol/L; > 5 mmol/L abnormal; > 10 mmol/L associated with 46–80% mortality). 3
• Monitor for complications of severe lactic acidosis including respiratory failure, cardiac arrhythmias, and hemodynamic collapse. 3
• Assess for rhabdomyolysis by checking creatine kinase and myoglobin, as severe metabolic acidosis can cause muscle breakdown. 3

Alternative Glucose-Lowering Therapy After Recovery

• Once the patient stabilizes, use insulin therapy as the primary option for glycemic control in ESRD—reduce total daily insulin dose by 25–50% compared to patients with normal renal function because insulin half-life is prolonged due to reduced renal degradation. 2
• DPP-4 inhibitors are second-line alternatives: sitagliptin 25 mg daily (requires dose reduction in ESRD) or linagliptin 5 mg daily (no dose adjustment needed at any eGFR level). 2
• Never restart metformin in this patient—it remains absolutely contraindicated for life in ESRD. 2, 1

Critical Pitfalls to Avoid

• Do not delay hemodialysis while attempting supportive measures alone—prompt dialysis is the definitive treatment and significantly improves survival in MALA. 1, 4
• Do not assume the movement disorder requires specific neurological treatment—it is a metabolic complication that resolves with correction of hypoglycemia and acidosis. 3
• Do not use metformin in any patient on peritoneal dialysis or hemodialysis, even if some studies suggest PD may provide partial clearance—the risk of fatal MALA remains unacceptably high. 2, 4, 5
• Do not rely on serum creatinine alone to assess renal function in future patients—always calculate eGFR, as creatinine-based cutoffs are outdated and may miss significant renal impairment, especially in elderly or small-statured patients. 2

Prognosis and Expected Recovery

• With prompt hemodialysis and supportive care, most patients survive MALA, though mortality rates range from 30–50% depending on severity and delay in treatment. 3, 6
• The chorea/ballismus typically resolves within 2–4 weeks of metabolic correction, though residual mild movements may persist for several months in severe cases. 3
• Neuroimaging abnormalities (basal ganglia hyperintensity) usually resolve on follow-up MRI within 3–6 months. 3