Case Presentation: An 84-year-old male with a past medical history significant for improving chronic kidney disease stage 3 (baseline creatinine of 0.72 mg/dL) and prediabetes presented to the emergency department with altered mental status and poor oral intake from a low resource facility. Patient was recently hospitalized for perforated diverticulitis after sigmoidectomy and ostomy complicated by intra-abdominal abscesses treated with antibiotics and drainage by interventional radiology. Initial blood tests were notable for potassium of 6.7 mmol/L, lactate of 7.69 mmol/L, pH of 7.2, creatinine of 5.54 mg/dL, pCO2 of 24 mmHg and a white blood cell count to 16.4 x 10^3/mcL.Patient was initially managed for hyperkalemia with calcium, insulin, and dextrose, and broad-spectrum antibiotics were started. Patient’s lactate continued to rise to 12.4 mmol/L and had a pure anion gap metabolic acidosis with anion gap of 32 with CO2 level of 10 mmol/L. Patient was worked up for potential bacteremia however a computed tomography scan of the abdomen and pelvis without contrast revealed no obstruction concern, worsening abscess, or hydronephrosis. Blood cultures were ultimately negative. After patient was stabilized, a discussion with the low resource facility where he resided for 2 months since previous hospital discharge revealed that he was started on metformin 500mg daily and escalated to 500mg twice daily and had also received furosemide for leg swelling daily for 1 week prior to presentation. At this facility, labs were only drawn once weekly. Serum creatinine obtained at the facility after a week of furosemide revealed a stage 1 AKI, yet metformin was continued at 1000mg total daily.Nephrology was consulted because of the rising lactate and worsening metabolic acidosis. Patient was also not producing urine. Patient was started on a sodium bicarbonate drip as preparations for intermittent hemodialysis were implemented. There was a concern for MALA with the significantly elevated lactate and recent initiation of metformin. Metformin levels were drawn 12 hours after presentation prior to starting hemodialysis due to delay in receiving collateral information. The metformin levels returned elevated at 22 mcg/mL (therapeutic range: 1-2 mcg/mL) and decreased to 13 mcg/mL after dialysis. After two weeks spent in the ICU and the medical wards, the patient was not able to recover and later passed away at a hospice care treatment facility after family decided to transition to comfort care.
Discussion: This case emphasizes the importance of considering MALA when patients are admitted for altered mental status, lactic acidosis, and concurrent renal failure. Patient’s at risk of developing worsening kidney function should avoid nephrotoxins that might accumulate. While there is no antidote for metformin toxicity, management is primarily supportive and includes stopping the drug, sodium bicarbonate drip, and intermittent hemodialysis.
Conclusions: Clinicians should keep MALA on their differential in patients that have a metabolic acidosis and high lactate levels and are on metformin. Patients who have a history of kidney disease, on multiple nephrotoxic agents, and are at high risk for renal failure should be closely monitored when starting metformin.