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

Abstract

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 1500 mg twice daily (6 months), glyburide, rofecoxib, furosemide, levothyroxine, prednisone, azathioprine, and propanolol. On admission, she was hypothermic (34.41C), had blood pressure, 115/51 mm 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, pCO 2 7 mm Hg, tCO 2 2 mEq/l. She was transferred to the intensive care unit and intubated for respiratory failure. Serum creatinine was 8.9 mg/dl (baseline, 1.0 mg/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 9.6 mg/dl; serum metformin 17 mg/ml (therapeutic level 1-2 mg/ml). Liver enzymes were normal. Urinalysis: protein 2 þ 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 500 mg twice daily (3 months), lisinopril, and ibuprofen for arthritis. On admission, she was hypothermic (34.

Metformin-Associated Lactic Acidosis (MALA): Case Files of the Einstein Medical Center Medical Toxicology Fellowship

“…While the incidence of MALA is low, its mortality is reported to approach 50 % [2,12,15,16,19,24,26]. The estimated incidence of lactic acidosis in chronic users of metformin is between three and nine cases per 100,000 patients-years [1,3,10,13,15,27]. However, a 2011 study found a MALA incidence of 47 cases per 100,000 patient-years-at least five times higher than the previously reported rates [13].…”

“…Though the mechanism is not well described, hypoglycemia and, less commonly, hyperglycemia have also been reported in severe poisonings [29]. Metforminassociated lactic acidosis with therapeutic dosing has up to a 50 % mortality rate [10,26]. However, the lactic acidosis resulting from intentional acute ingestions is less well understood.…”

“…Metformin causes an intracellular shift in oxidation-reduction reactions from aerobic to anaerobic metabolism, which results to lactic acid accumulation [3,7,10,18,23,24]. The developing lactic acidosis reduces intracellular pH, which continues a cycle of diminished activity of pyruvate carboxylase and decreased lactate uptake by the liver [11,24].…”

“…Steady-state levels are achieved within 24 to 48 h [9]. The half-life ranges between 2.5 and 4.9 h [10]. Metformin is excreted predominantly unchanged by the kidneys.…”

“…The elimination half-life is approximately 17 h, with 90 % of the dose ingested being renally cleared within 24 h [9]. The drug has high water solubility, minimal plasma protein binding, and a large volume of distribution, being concentrated primarily in the intestinal wall, salivary glands, kidneys, and liver [1,3,10,11].…”