Should dialysis be offered in all cases of metformin-associated lactic acidosis?

Abstract

Metformin is commonly used in diabetes mellitus type 2, with lactic acidosis being a rare but potentially fatal complication of this therapy. The management of metformin-associated lactic acidosis (MALA) is controversial. Treatment may include supportive care, activated charcoal, bicarbonate infusion, hemodialysis, or continuous venovenous hemofiltration. In the previous issue of Critical Care, Peters and colleagues systematically evaluated outcomes in MALA patients admitted to their intensive care unit. The mortality rate of patients who received dialysis was similar to that of patients who were not dialyzed. However, it was the more acutely and chronically ill patients who actually received dialysis. This suggests that hemodialysis was beneficial in preventing a higher mortality rate in those who required renal replacement therapy.The literature on the management of metformin-associated lactic acidosis (MALA) is sparse and consists of case reports and case series. In the previous issue of Critical Care, Peters and colleagues [1] presented a retrospective cohort study in patients with MALA. This study represents an important step forward in systematically evaluating outcomes in this rare but serious condition.Metformin is commonly used in type 2 diabetes mellitus and accounts for approximately one third of all prescriptions for oral hypoglycemic agents in the US [2]. The United Kingdom Prospective Diabetes Study demonstrated impressive reductions in diabetes-related endpoints and mortality in overweight patients with type 2 diabetes who used this drug [3]. A rare but extremely serious adverse effect of this medication is lactic acidosis, which carries a staggering 50% mortality rate [4].Metformin is renally cleared and is known to accumulate in patients with chronic kidney disease [4]. Current guidelines stipulate that it be used with caution in estimated glomerular filtration rates (eGFRs) of less than 60 mL/minute and not at all in eGFRs of less than 30 mL/minute [5]. Identified risk factors for MALA include acute kidney injury (AKI), hypoxemia, sepsis, alcohol abuse, liver failure, myocardial infarction, and shock [6]. Medications that interfere with renal hemodynamic autoregulation (that is, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and nonsteroidal anti-inflammatory drugs) and volume depletion are frequently implicated in generating the AKI leading to MALA [4]. The incidence of MALA is quoted at 1 to 5 cases per 100,000 patient-years but may be as high as 30 cases per 100,000 patient-years [4].The mainstay of MALA therapy is supportive care. Particular attention should be paid to normalizing the acid-base imbalance, eliminating offending medication, and treating concomitant disease [4]. Activated charcoal may also have a role, especially in cases of metformin overdose [6]. Intravenous sodium bicarbonate is commonly used to correct blood pH. Renal replacement therapies, including conventional hemodialysis and continuous venovenous hemofiltration, have been successfully...

Severe Metformin Associated Lactic Acidosis: A Case Series Of An Intensive Care Unit

“…We could speculate that the rapid correction of acidosis was not associated with total clearance of metformin from intracellular compartment and toxicity still exerts its effect in endomembrane system and proteins, resulting in late cell death. [21][22][23]. It is still unclear why some patients recover from severe MALA while others invariably die.…”

Metformin‐associated lactic acidosis following acute kidney injury. Efficacious treatment with continuous renal replacement therapy

“…Other combined therapeutic modalities were also reported to successfully treat severe cases [3,6,7,16]. Although Peters et al [1] later reported that they had failed to reduce the mortality rate among patients treated with haemodialysis compared with those who did not receive such treatment, Finkel's [20] observation that more severe patients were scheduled for haemodialysis rather than for non-haemodialysis therapy might explain the lack of success of Peters and colleagues. Thus, there are no conclusive data available to indicate which dialysis technique is superior.…”

Case Files from the University of California San Diego Health System Fellowship Coma and Severe Acidosis: Remember to Consider Acetaminophen

“…Although we felt MALA was unlikely, we could not exclude it. Fortunately, one of the critical interventions beyond supportive care for severe MALA appears to be hemodialysis [61], which we were preparing to do already for potential toxic alcohol poisoning.…”