When a friend can become an enemy! Recognition and management of metformin-associated lactic acidosis

Patient 1: A 78-year-old woman presented with a 3-day history of abdominal pain, nausea, vomiting, and anorexia. Past medical history included type 2 diabetes mellitus, autoimmune hepatitis, hypertension, and ulcerative colitis with colectomy. Medications included metformin 1500mg twice daily (6 months), glyburide, rofecoxib, furosemide, levothyroxine, prednisone, azathioprine, and propanolol. On admission, she was hypothermic (34.4 degrees C), had blood pressure, 115/51mm Hg, pulse 104 beats/min, and trace of lower extremity edema. The rest of the physical examination was unremarkable. Arterial blood gases showed pH 7.0, pCO2 7mm Hg, tCO2 2mEq/ l. She was transferred to the intensive care unit and intubated for respiratory failure. Serum creatinine was 8.9mg/dl (baseline, 1.0mg/dl; estimated glomerular filtration rate (eGFR) 57 ml/ min/ 1.73 2 by the Modification of Diet in Renal Disease Study (MDRDS) formula); serum lactate 9.6mg/dl; serum metformin 17 mg/ml (therapeutic level 1-2 mg/ml). Liver enzymes were normal. Urinalysis: protein 2+ and moderate blood. Renal ultrasound ruled out obstruction. Echocardiogram showed normal left ventricular function and all fluid cultures were negative. Pertinent laboratory findings are shown in Table 1. Patient 2: A 64-year-old woman presented with nausea and vomiting. Past medical history included type 2 diabetes mellitus, hyperlipidemia, and hypertension. Medications included metformin 500mg twice daily (3 months), lisinopril, and ibuprofen for arthritis. On admission, she was hypothermic (34.5 degrees C), hypotensive blood pressure, 85/38mm Hg), and tachypneic (28 breaths/min). The rest of the physical examination was unremarkable. Arterial blood gases showed pH 6.78, pCO2 15mm Hg, and tCO2 3mEq/l. She was transferred to the intensive care unit and intubated for respiratory failure. Serum creatinine was 5.9mg/dl (1.0mg/ dl 8 months earlier and eGFR 59 ml/min/1.73(2) by the MDRDS formula); serum lactate 22mg/dl; serum metformin 31 mu g/ ml. Liver enzymes were mildly elevated. Urinalysis: blood 3+ and protein negative. All cultures and toxicology tests were negative. Non-contrast computer tomography showed no intra-abdominal or pelvic abscesses. Cardiac enzymes and electrocardiogram were not suggestive of myocardial injury. Pertinent laboratory findings are shown in Table 1.