Acute Metformin Overdose

Article Outline

• References
• Copyright

To the Editor:

Enthusiastically, we read the recent work by Dell'Aglio et al.¹ Perhaps the most powerful tool in the physician's armamentarium is the ability to render a prognosis. This is particularly true in the setting of metformin overdose where survival is possible despite profound acidemia. The opportunity to render a few comments is appreciated.

We salute this effort to identify factors associated with good outcomes in acute metformin overdoses. However, we are concerned that the conclusions are not generalizable and potentially misleading when determining prognosis. The data is not representative of the general population of metformin overdoses for several reasons.

First, Dell'Aglio et al's selection criterion was quite restrictive and excluded the vast majority of metformin overdoses in the literature. Dell'Aglio's requirement that all cases have a reported metformin concentration limits the analysis of applicable cases because in most metformin overdoses serum concentrations are never measured.

Several of the patients included in the review did not have supratherapeutic metformin concentrations, hyperlactatemia or acidosis. Of the 22 cases extracted from the world's literature, 3 had subtherapeutic metformin concentrations despite reported ingestions >23 grams, 6 did not have lactic acidosis (lactate >5 mmol/L), 2 had lactate concentrations <2, 8 had a nadir pH of >7.34, and 1 had lactic acidosis unrelated to metformin.²

Third, contrary to the results of this paper, recent data suggests that metformin concentrations do not correlate with mortality. Seidowsky et al³ recently published a series of 42 patients with metformin-associated lactic acidosis, 13 of which were acute overdoses. Though a statistical difference in lactate levels and pH was noted between survivors and non-survivors, no statistically significant difference was noted with plasma metformin levels. Additionally, 31 of these patients were dialyzed within 12 hours of presentation, a treatment factor that may have greater prognostic implication than either lactate or pH.

Lastly, the authors state that no patient in their comprehensive review died if they had a reported metformin concentration less than 50 mcg/mL, a lactate <25 mmol/L, and a nadir pH of >6.9. Unfortunately, they also describe a case of their own that failed this prognostic triad and both Seidowsky et al³ and Suchard and Grostky⁴ present cases that fail this as well.

Should we think of the “chronic” metformin-associated lactic acidosis differently than the “acute” overdose much as we do for aspirin? Taking either metformin or aspirin chronically at the appropriate doses rarely leads to acidosis or mortality unless an underlying risk factor, such as renal insufficiency, occurs. In both acute metformin and aspirin overdoses, however, acidosis is the rule rather than the exception. For both, no clear guideline exists as when to offer dialysis as the life-saving modality. It would be interesting to recalculate survivability from Dell'Aglio's series with the variable of dialysis before shock occurred versus after shock occurred. Until these questions are answered, physicians should use caution in adapting the criteria proposed for false reassurance exists in using serum ph >6.9, metformin levels <50 and lactate levels <25 in the setting of metformin overdose.

Back to Article Outline

References 

1. Dell'Aglio DM, Perino LJ, Kazzi Z, et al. Acute metformin overdose: examining serum pH, lactate level, and metformin concentrations in survivors versus nonsurvivors: A systematic review of the literature. Ann Emerg Med. 2009;12:818–823
   • View In Article
2. Lalau JD, Mourhlhon C, Bergeret A, et al. Consequences of metformin intoxication. Diabetes Care. 1998;21:2036–2037
   • View In Article
   • MEDLINE
   • CrossRef
3. Seidowsky A, Nseir S, Houdret N, et al. Metformin-associated lactic acidosis: A prognostic and therapeutic study. Crit Care Med. 2009;37:2191–2196
   • View In Article
   • CrossRef
4. Suchard JR, Grostky TA. Fatal metformin overdose presenting with progressive hyperglycemia. Western Journal of Emergency Medicine. 2008;9:160–164
   • View In Article