View source for Metformin-associated lactic acidosis

==Background==
*Acute and chronic use of metformin can lead to rare complication of Metformin-associate lactic acidosis (MALA)
*Excreted (unmetabolized) in proximal tubules
*Stimulates anaerobic glucose metabolism in splanchnic bed → increased lactate production
*Inhibits mitochondrial respiratory chain → decreased gluconeogensis from lactate → lactate accumulation
*Associated with overdose, renal failure, liver disease, and septicemia<ref>Goldfrank, Lewis R. ''Goldfrank's Toxicologic Emergencies''. 9th Ed. New York: McGraw-Hill, 2011</ref>
*Acidosis onset several hours after acute ingestion
*Mortality rate 45%<ref>Seidowsky, A., Nseir, S., Houdret, N., & Fourrier, F. (2009). Metformin-associated lactic acidosis: a prognostic and therapeutic study. Critical care medicine, 7, 2191–2196.</ref>
**Lactate only predictive of mortality in overdose patients, not in incidental metformin accumulation
**Elevated PT associated with increased mortality
**pH >6.9, lactate >25 portends a poor prognosis<ref>Dell'Aglio, D. M., Perino, L. J., Kazzi, Z., Abramson, J., Schwartz, M. D., & Morgan, B. W. (2009). Acute metformin overdose: examining serum pH, lactate level, and metformin concentrations in survivors versus nonsurvivors: a systematic review of the literature. Annals of emergency medicine, 6, 818–823.</ref>

==Clinical Features==
*Nausea
*Vomiting
*Diarrhea
*Altered mental status 
*Dyspnea
*Hypotension
*Tachycardia
*Tachypnea

==Diagnosis==
*FS
*[ASA]
*[APAP]
*EKG
*bHCG
*ABG
*Chem
*Lactate

==Management==
*If intubated, maintain minute ventilation so as to not remove respiratory compensation for acidosis
*Activated charcoal if peri-ingestion/AMS appropriate
*Metformin should not cause hypoglycemia and, if present, should lead to work up of cause
*Sodium Bicarbonate 
**No evidence to support its use in MALA patients<ref>Kruse, J. A. (2001). Metformin-associated lactic acidosis. The Journal of emergency medicine, 3, 267–272.</ref>
*Hemodialysis
**Metformin can be cleared with hemodialysis and CVVH (continuous venovenous hemofiltration)<ref>Barrueto, F., Meggs, W. J., & Barchman, M. J. (2002). Clearance of metformin by hemofiltration in overdose. Journal of toxicology. Clinical toxicology, 2, 177–180.</ref>
***Former preferred
***CVVH should be used in unstable patient
**Reduction in metformin levels following acute ingestion reported to require prolonged HD<ref>Rifkin, S. I., McFarren, C., Juvvadi, R., & Weinstein, S. S. (2011). Prolonged hemodialysis for severe metformin intoxication. Renal failure, 4, 459–461.</ref>
**Consider if:
***pH <7.1
***Renal insufficiency
**Mortality benefits mainly from improving acidosis than from removing Metformin

==References==
<references/>

[[Category:Tox]]