title: Metformin-associated lactic acidosis treated with continuous renal replacement therapy.
abstract: BACKGROUND
  Lactic acidosis is an infrequent complication of metformin therapy for diabetes mellitus. The presence of clinical conditions, such as renal failure, increases the risk of metformin-associated lactic acidosis (MALA). We present a case of lactic acidosis in a patient with diabetes treated with metformin, complicated by acute renal failure in preexisting chronic nephropathy.
  
  
  METHODS
  A 70-year-old white male, weighing 77 kg, with diabetes mellitus, coronary heart disease, congestive heart failure (New York Heart Association class III), moderate essential hypertension (stage 2), and renal dysfunction (serum urea, 90 mg/dL; serum creatinine, 1.5 mg/dL; creatinine clearance, 49.8 mL/min/1.73 m2) presented to the emergency department of the General Hospital of Rhodes (Rhodes, Greece), complaining of malaise, respiratory distress, myalgias, disorientation, abdominal discomfort, and increasing somnolence of insidious onset. The patient's regimen included isosorbide mononitrate 60 mg QD, furosemide 40 mg QD, quinapril 20 mg QD, and metformin 850 mg TID. Before this hospitalization, he had received a 2-week course of oral diclofenac sodium 25 mg TID for low back pain. Preliminary laboratory evaluation found leukocytosis (27,300/mm3), severe renal failure (serum urea, 215 mg/dL; serum creatinine, 7.4 mg/dL; calculated creatinine clearance, 10.1 mL/min/1.73 m2), and a high anion gap metabolic acidosis (pH, 6.95; anion gap, 33 mEq/L) in arterial blood gas analysis. His medical and drug history, the clinical and laboratory findings, and the determination of lactate in samples of plasma (7.8 mEq/L), aroused the suspicion of MALA. The Naranjo algorithm scores for metformin and diclofenac sodium were 6 and 7, respectively. The patient received a single session of bicarbonate-buffered continuous venovenous hemodiafiltration (CWHDF) that lasted 16 hours. Ultimately, he was stabilized, and progressive restoration of acid-base balance and renal function was observed.
  
  
  CONCLUSIONS
  We suspect that lactic acidosis may have been related to the use of metformin, the presence of heart and renal failure (contributing to metformin toxicity), and previous use of diclofenac sodium. CVVHDF has an advantage over conventional intermittent hemodialysis in that it corrects acidosis and removes lactate and metformin without risk of hypernatremia or fluid overload.
  
  
  CONCLUSIONS
  MALA should be strongly suspected in diabetic patients presenting with high anion gap metabolic acidosis and increased serum lactate level. In the case described, prompt recognition of lactic acidosis and early application of bicarbonate-buffered CVVHDF produced successful results.
authors.affiliation: Department of Nephrology, General Hospital of Rhodes, Rhodes, Greece. polal@otenet.gr
authors.forename: Polichronis
authors.initials: P
authors.lastname: Alivanis
authors.forename: Ioannis
authors.initials: I
authors.lastname: Giannikouris
authors.forename: Christos
authors.initials: C
authors.lastname: Paliuras
authors.forename: Antonios
authors.initials: A
authors.lastname: Arvanitis
authors.forename: Maria
authors.initials: M
authors.lastname: Volanaki
authors.forename: Agelos
authors.initials: A
authors.lastname: Zervos
mesh_terms: D000140:Acidosis, Lactic / Q000139:chemically induced* / Q000628:therapy*; D000368:Aged; D003920:Diabetes Mellitus / Q000188:drug therapy; D017583:Hemodiafiltration / Q000379:methods*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects*; D051437:Renal Insufficiency / Q000209:etiology / Q000628:therapy
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin