Metformin-associated lactic acidosis
Background
- Acute and chronic use of metformin can lead to rare complication of Metformin-associated lactic acidosis (MALA)
- Excreted (unmetabolized) in proximal tubules
- Stimulates anaerobic glucose metabolism in splanchnic bed → increased lactate production
- Inhibits mitochondrial respiratory chain → decreased gluconeogenesis 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
Differential Diagnosis
Lactic acidosis
By Type
- Type A (tissue hypoperfusion)
- Type B (decreased utilization)
- Alcoholism
- ↓ Lactate utilization secondary to hepatic dysfunction
- ↓ NAD+/NADH ratio leads to ↑ conversion of pyruvate to lactate
- Metformin
- DKA
- Mainly due to D-lactate production, though hypovolemia contributes
- Liver disease (decreased clearance)
- Adrenergic receptor agonism; viz., albuterol, epinephrine, etc
- Malignancy
- Carbon Monoxide poisoning
- Cyanide poisoning
- Alcoholism
- Type D
- episodes of encephalopathy and metabolic acidosis typically following high carbohydrate meals in patients with short bowel syndrome
- metabolic acidosis and high serum anion gap, normal lactate level, short bowel syn or other forms of malabsorption, and characteristic neurologic findings
- Type D lactate is not detected with standard lactate levels
Complete List
- Any shock state
- SIRS; lactate may be 2-5 mEq/L
- Thiamine deficiency; more often seen in ICU settings; Thiamine is a co-factor for pyruvate dehydrogenase
- Seizure
- Dead gut
- Hepatic failure
- Malignancy
- Exercise
- Albuterol and other beta agonists[4][5]
- Toxicologic Causes:
- Cyanide
- Carbon Monoxide
- Metformin
- Didanosine
- Stavudine
- Zidovudine
- Linezolid
- Strychnine
- Emtriva
- Rotenone (Fish Poison
- NaAzide (Lab Workers)
- APAP (if Liver Fx)
- Phospine (rodenticide)
- NaMonofluoroacetate (Coyote Poison‐ give Etoh as antidote)
- INH (if patient seizes)
- Hemlock
- Valproate
- Hydrogen Sulfide
- Nitroprusside (if cyanide toxic)
- Ricin & Castor Beans
- Propofol
- Sympathomimetics (cocaine, methamphetamine)
- Jequirty peas (Abrus precatorius)
- Prunus Amygdalus plants
- Crab tree apple seeds & cassava (yucca)
- HAART-induced lactic acidosis
Evaluation
Management
- If intubated, maintain minute ventilation so as to not remove respiratory compensation for acidosis
- Activated charcoal if peri-ingestion/mental status 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[6]
- Hemodialysis
- Metformin can be cleared with hemodialysis and CVVH (continuous venovenous hemofiltration)[7]
- Former preferred
- CVVH should be used in unstable patient
- Reduction in metformin levels following acute ingestion reported to require prolonged HD[8]
- Consider if:
- pH <7.1
- Renal insufficiency
- Mortality benefits mainly from improving acidosis than from removing Metformin
- Metformin can be cleared with hemodialysis and CVVH (continuous venovenous hemofiltration)[7]
See Also
References
- ↑ Goldfrank, Lewis R. Goldfrank's Toxicologic Emergencies. 9th Ed. New York: McGraw-Hill, 2011
- ↑ Seidowsky, A., Nseir, S., Houdret, N., & Fourrier, F. (2009). Metformin-associated lactic acidosis: a prognostic and therapeutic study. Critical care medicine, 7, 2191–2196.
- ↑ 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.
- ↑ Dodda V and Spiro P. Albuterol, an Uncommonly Recognized Culprit in Lactic Acidosis. Chest. 2011;140.
- ↑ . Zitek T, Cleveland N, Rahbar A, et al. Effect of nebulized albuterol on serum lactate and potassium in healthy subjects. Acad Emerg Med 2016;23:718–21.
- ↑ Kruse, J. A. (2001). Metformin-associated lactic acidosis. The Journal of emergency medicine, 3, 267–272.
- ↑ Barrueto, F., Meggs, W. J., & Barchman, M. J. (2002). Clearance of metformin by hemofiltration in overdose. Journal of toxicology. Clinical toxicology, 2, 177–180.
- ↑ Rifkin, S. I., McFarren, C., Juvvadi, R., & Weinstein, S. S. (2011). Prolonged hemodialysis for severe metformin intoxication. Renal failure, 4, 459–461.