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Paper text:
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  
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 .
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 .
a rare but extremely serious adverse effect of this medication is lactic acidosis , which carries a staggering 50% mortality rate .
metformin is renally cleared and is known to accumulate in patients with chronic kidney disease .
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 .
identified risk factors for mala include acute kidney injury ( aki ) , hypoxemia , sepsis , alcohol abuse , liver failure , myocardial infarction , and shock .
medications that interfere with renal hemodynamic autoregulation ( that is , angiotensin - converting enzyme inhibitors , angiotensin receptor blockers , and non - steroidal anti - inflammatory drugs ) and volume depletion are frequently implicated in generating the aki leading to mala .
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 .
particular attention should be paid to normalizing the acid - base imbalance , eliminating offending medication , and treating concomitant disease .
renal replacement therapies , including conventional hemodialysis and continuous venovenous hemofiltration , have been successfully employed in mala [ 6 - 11 ] .
these allow for both isovolemic correction of the metabolic acidosis as well as removal of metformin and lactate .
peters and colleagues   performed a 5-year retrospective review of all patients admitted to their intensive care unit presenting with mala .
they defined mala as lactic acidosis ( lactate of greater than 5 mmol / l and bicarbonate of less than 22
mmol / l ) occurring in a patient who was chronically taking metformin or in the setting of a metformin overdose .
mala was part of the clinical presentation in this patient cohort rather than an admission diagnosis .
the definition of mala in this study did not duly account for people presenting primarily with tissue hypoperfusion as the likely cause of their lactic acidosis .
although metformin may interfere with lactate clearance in a shock state , it is not thought to be the primary cause of the acidosis .
restoration of hemodynamic stability rather than dialysis is the goal of therapy in these cases .
most of the patients who died in this study were admitted with shock , suggesting that hypoperfusion , rather than metformin , was the principal cause of their lactic acidosis . however , mala itself can present with hypotension due to negative inotropic effects and increased systemic vascular resistance with acidosis .
upon closer inspection of the data , those patients who were dialyzed were more acutely ill as they had higher values on the saps ii ( simplified acute physiology score ii ) .
furthermore , those who were dialyzed trended toward having a larger burden of comorbidity ( charlson index ) and more severe acidosis .
aki : acute kidney injury ; egfr : estimated glomerular filtration rate ; mala : metformin - associated lactic acidosis .
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 .