Time to development of metformin-associated lactic acidosis

Objective: Metformin-associated lactic acidosis (MALA) is a complication of metformin overdose. Recommendations for observation time after an acute ingestion to monitor for MALA vary. The aim of this study was to characterize the time to development of MALA after an acute metformin overdose.Methods: Utilizing Crystal Reports (Version 11.0), all metformin cases reported to the Illinois Poison Center (IPC) with a National Poison Data System (NPDS) clinical effects code of "acidosis" or "anion gap" were retrospectively queried over a 14-year period (2001-2014). Demographic data, time to MALA, co-ingestants, therapeutic modality use, and case outcome were extracted. Interrater reliability was assessed using kappa analysis.Results: A total of 88 cases were identified of which 44 met criteria for MALA; 40 were acute, acute on chronic, or unknown ingestions. The remaining four were chronic ingestions which were excluded. The mean age was 41 years (range 19-79 years). Most were female (55.0%) and over half (62.5%) were acute on chronic ingestions. Hypoglycemia was seen in three ingestions of metformin only. Of the 40 MALA cases, 18 developed MALA less than or equal to 6 h after ingestion, 9 between 6-12 h, 3 after 12 h, and 10 patients had an unknown time to MALA. The only death in the cohort had MALA detected beyond the typical 6-h observation period. Of the exposures when time to MALA was known, 40% (12/30) developed MALA greater than 6 h post ingestion.Conclusion: A 6-h observation period after a single acute ingestion of metformin may be inadequate, as a significant portion of exposures developed MALA beyond this time. We recommend a minimum of 12 h of observation following an acute overdose. Further study defining prospectively the time to development of MALA may improve management of this population.