Metformin-associated lactic acidosis: Difference between revisions

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*Stimulates anaerobic glucose metabolism in splanchnic bed → increased lactate production
*Stimulates anaerobic glucose metabolism in splanchnic bed → increased lactate production
*Inhibits mitochondrial respiratory chain → decreased gluconeogensis from lactate → lactate accumulation
*Inhibits mitochondrial respiratory chain → decreased gluconeogensis from lactate → lactate accumulation
*Associated with overdose, renal failure, liver disease, acute infection as precipitants
*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
*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>
*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
**Lactate only predictive of mortality in overdose patients, not in incidental metformin accumulation
**Elevated PT associated with increased mortality
**Elevated PT associated with increased mortality
**pH > 6.9, lactate > 25 → 5 out of 6 mortality in case series <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>
**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==
==Clinical Features==

Revision as of 14:22, 18 October 2015

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[1]
  • Acidosis onset several hours after acute ingestion
  • Mortality rate 45%[2]
    • 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[3]

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[4]
  • Hemodialysis
    • Metformin can be cleared with hemodialysis and CVVH (continuous venovenous hemofiltration)[5]
      • Former preferred
      • CVVH should be used in unstable patient
    • Reduction in metformin levels following acute ingestion reported to require prolonged HD[6]
    • Consider if:
      • pH <7.1
      • Renal insufficiency
    • Mortality benefits mainly from improving acidosis than from removing Metformin

References

  1. ↑ Goldfrank, Lewis R. Goldfrank's Toxicologic Emergencies. 9th Ed. New York: McGraw-Hill, 2011
  2. ↑ Seidowsky, A., Nseir, S., Houdret, N., & Fourrier, F. (2009). Metformin-associated lactic acidosis: a prognostic and therapeutic study. Critical care medicine, 7, 2191–2196.
  3. ↑ 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.
  4. ↑ Kruse, J. A. (2001). Metformin-associated lactic acidosis. The Journal of emergency medicine, 3, 267–272.
  5. ↑ Barrueto, F., Meggs, W. J., & Barchman, M. J. (2002). Clearance of metformin by hemofiltration in overdose. Journal of toxicology. Clinical toxicology, 2, 177–180.
  6. ↑ Rifkin, S. I., McFarren, C., Juvvadi, R., & Weinstein, S. S. (2011). Prolonged hemodialysis for severe metformin intoxication. Renal failure, 4, 459–461.
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