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Metformin Intoxications Requiring Admission to the Pediatric Intensive Care Unit

Year 2020, Volume: 14 Issue: 3, 231 - 235, 29.05.2020
https://doi.org/10.12956/tchd.723600

Abstract

Objective: To identify the demographics of patients admitted with metformin intoxication and characterize their clinical courses and treatment options in pediatric intensive care unit.
Material and Methods: The records of patients admitted to the pediatric intensive care unit due to metformin intoxication between 2013 and 2019 were retrospectively evaluated.
Results: There were 22 acute metformin overdose cases. Mean age of the patients was 13.04±5.46 years (1-18 years), 18 were female. Ingested metformin dose ranged from 1.7 gr to 85 gr (mean 19±22.6 gr, median 10 gr), with coingestants taken in 12 patients. Nausea and/or vomiting were present in 16 (72.7%) of the patients. Hyperlactatemia (lactate > 2mmol/L) was present in 13 (59%) of the patients. Mean peak lactate level was 5.1±5.7 mmol/L (0.9-21 mmol/L). Acidosis was present in 12 (54.5%) of the patients. Mean lowest pH level was 7.28±0.16 (6.9-7.45). There was a positive correlation between lactate level and ingested dose (r = 0.816; P < 0.001) while pH was inversely related to dose (r = −0.873; P < 0.001). Six (27%) patients required renal replacement therapy because of profound lactic acidosis despite the intravenous fluid support. Hemodialysis was applied to 5 patients and high dose continuous venovenous hemodiafiltration was applied to 2 patients. 16 years old female patient who ingested 85 g metformin died despite prolonged hemodialysis.
Conclusion: Lactic acidosis associated with metformin intoxication is a potentially fatal condition. Both renal replacement therapies hemodialysis and continuous venovenous hemodiafiltration are effective in the treatment of metformin associated lactic acidosis. Most of the patients with severe metformin associated lactic acidosis require repetitive and prolonged hemodialysis sessions.

References

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  • 2. Aljada A and Mousa SA, Metformin and neoplasia: implications and indications. Pharmacol Ther, 2012. 133(1): 108-15.
  • 3. Berstein LM, Metformin in obesity, cancer and aging: addressing controversies. Aging (Albany NY), 2012. 4(5): 320-9.
  • 4. Viollet B, Guigas B, Sanz Garcia N, Leclerc J, Foretz M, and Andreelli F, Cellular and molecular mechanisms of metformin: an overview. Clin Sci (Lond), 2012. 122(6): 253-70.
  • 5. Mowry JB, Spyker DA, Cantilena LR, Jr., Bailey JE, and Ford M, 2012 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 30th Annual Report. Clin Toxicol (Phila), 2013. 51(10): 949-1229.
  • 6. Salpeter SR, Greyber E, Pasternak GA, and Salpeter EE, Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev, 2010(4): CD002967.
  • 7. Suchard JR and Grotsky TA, Fatal metformin overdose presenting with progressive hyperglycemia. West J Emerg Med, 2008. 9(3): 160-4.
  • 8. Timbrell S, Wilbourn G, Harper J, and Liddle A, Lactic acidosis secondary to metformin overdose: a case report. J Med Case Rep, 2012. 6: 230.
  • 9. Peters N, Jay N, Barraud D, Cravoisy A, Nace L, Bollaert PE, et al., Metformin-associated lactic acidosis in an intensive care unit. Crit Care, 2008. 12(6): R149.
  • 10. Dell'Aglio DM, Perino LJ, Kazzi Z, Abramson J, Schwartz MD, and Morgan BW, 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. 54(6): 818-23.
  • 11. Spiller HA, Weber JA, Winter ML, Klein-Schwartz W, Hofman M, Gorman SE, et al., Multicenter case series of pediatric metformin ingestion. Ann Pharmacother, 2000. 34(12): 1385-8.
  • 12. Soyoral YU, Begenik H, Emre H, Aytemiz E, Ozturk M, and Erkoc R, Dialysis therapy for lactic acidosis caused by metformin intoxication: presentation of two cases. Hum Exp Toxicol, 2011. 30(12): 1995-7.
  • 13. Ali S and Fonseca V, Overview of metformin: special focus on metformin extended release. Expert Opin Pharmacother, 2012. 13(12): 1797-805.
  • 14. Scheen AJ, Clinical pharmacokinetics of metformin. Clin Pharmacokinet, 1996. 30(5): 359-71.
  • 15. Seidowsky A, Nseir S, Houdret N, and Fourrier F, Metformin-associated lactic acidosis: a prognostic and therapeutic study. Crit Care Med, 2009. 37(7): 2191-6.
  • 16. Carvalho C, Correia S, Santos MS, Seica R, Oliveira CR, and Moreira PI, Metformin promotes isolated rat liver mitochondria impairment. Mol Cell Biochem, 2008. 308(1-2): 75-83.
  • 17. Turkcuer I, Erdur B, Sari I, Yuksel A, Tura P, and Yuksel S, Severe metformin intoxication treated with prolonged haemodialyses and plasma exchange. Eur J Emerg Med, 2009. 16(1): 11-3.
  • 18. Duong JK, Furlong TJ, Roberts DM, Graham GG, Greenfield JR, Williams KM, et al., The Role of Metformin in Metformin-Associated Lactic Acidosis (MALA): Case Series and Formulation of a Model of Pathogenesis. Drug Saf, 2013.
  • 19. Lalau JD and Race JM, Metformin and lactic acidosis in diabetic humans. Diabetes Obes Metab, 2000. 2(3): 131-7.
  • 20. Yang PW, Lin KH, Lo SH, Wang LM, and Lin HD, Successful treatment of severe lactic acidosis caused by a suicide attempt with a metformin overdose. Kaohsiung J Med Sci, 2009. 25(2): 93-7.
  • 21. Nguyen HL and Concepcion L, Metformin intoxication requiring dialysis. Hemodial Int, 2011. 15 Suppl 1: S68-71.
  • 22. Giuliani E, Albertini G, Vaccari C, and Barbieri A, pH 6.68--surviving severe metformin intoxication. QJM, 2010. 103(11): 887-90.
Year 2020, Volume: 14 Issue: 3, 231 - 235, 29.05.2020
https://doi.org/10.12956/tchd.723600

Abstract

References

  • 1. Prikis M, Mesler EL, Hood VL, and Weise WJ, When a friend can become an enemy! Recognition and management of metformin-associated lactic acidosis. Kidney Int, 2007. 72(9): 1157-60.
  • 2. Aljada A and Mousa SA, Metformin and neoplasia: implications and indications. Pharmacol Ther, 2012. 133(1): 108-15.
  • 3. Berstein LM, Metformin in obesity, cancer and aging: addressing controversies. Aging (Albany NY), 2012. 4(5): 320-9.
  • 4. Viollet B, Guigas B, Sanz Garcia N, Leclerc J, Foretz M, and Andreelli F, Cellular and molecular mechanisms of metformin: an overview. Clin Sci (Lond), 2012. 122(6): 253-70.
  • 5. Mowry JB, Spyker DA, Cantilena LR, Jr., Bailey JE, and Ford M, 2012 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 30th Annual Report. Clin Toxicol (Phila), 2013. 51(10): 949-1229.
  • 6. Salpeter SR, Greyber E, Pasternak GA, and Salpeter EE, Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev, 2010(4): CD002967.
  • 7. Suchard JR and Grotsky TA, Fatal metformin overdose presenting with progressive hyperglycemia. West J Emerg Med, 2008. 9(3): 160-4.
  • 8. Timbrell S, Wilbourn G, Harper J, and Liddle A, Lactic acidosis secondary to metformin overdose: a case report. J Med Case Rep, 2012. 6: 230.
  • 9. Peters N, Jay N, Barraud D, Cravoisy A, Nace L, Bollaert PE, et al., Metformin-associated lactic acidosis in an intensive care unit. Crit Care, 2008. 12(6): R149.
  • 10. Dell'Aglio DM, Perino LJ, Kazzi Z, Abramson J, Schwartz MD, and Morgan BW, 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. 54(6): 818-23.
  • 11. Spiller HA, Weber JA, Winter ML, Klein-Schwartz W, Hofman M, Gorman SE, et al., Multicenter case series of pediatric metformin ingestion. Ann Pharmacother, 2000. 34(12): 1385-8.
  • 12. Soyoral YU, Begenik H, Emre H, Aytemiz E, Ozturk M, and Erkoc R, Dialysis therapy for lactic acidosis caused by metformin intoxication: presentation of two cases. Hum Exp Toxicol, 2011. 30(12): 1995-7.
  • 13. Ali S and Fonseca V, Overview of metformin: special focus on metformin extended release. Expert Opin Pharmacother, 2012. 13(12): 1797-805.
  • 14. Scheen AJ, Clinical pharmacokinetics of metformin. Clin Pharmacokinet, 1996. 30(5): 359-71.
  • 15. Seidowsky A, Nseir S, Houdret N, and Fourrier F, Metformin-associated lactic acidosis: a prognostic and therapeutic study. Crit Care Med, 2009. 37(7): 2191-6.
  • 16. Carvalho C, Correia S, Santos MS, Seica R, Oliveira CR, and Moreira PI, Metformin promotes isolated rat liver mitochondria impairment. Mol Cell Biochem, 2008. 308(1-2): 75-83.
  • 17. Turkcuer I, Erdur B, Sari I, Yuksel A, Tura P, and Yuksel S, Severe metformin intoxication treated with prolonged haemodialyses and plasma exchange. Eur J Emerg Med, 2009. 16(1): 11-3.
  • 18. Duong JK, Furlong TJ, Roberts DM, Graham GG, Greenfield JR, Williams KM, et al., The Role of Metformin in Metformin-Associated Lactic Acidosis (MALA): Case Series and Formulation of a Model of Pathogenesis. Drug Saf, 2013.
  • 19. Lalau JD and Race JM, Metformin and lactic acidosis in diabetic humans. Diabetes Obes Metab, 2000. 2(3): 131-7.
  • 20. Yang PW, Lin KH, Lo SH, Wang LM, and Lin HD, Successful treatment of severe lactic acidosis caused by a suicide attempt with a metformin overdose. Kaohsiung J Med Sci, 2009. 25(2): 93-7.
  • 21. Nguyen HL and Concepcion L, Metformin intoxication requiring dialysis. Hemodial Int, 2011. 15 Suppl 1: S68-71.
  • 22. Giuliani E, Albertini G, Vaccari C, and Barbieri A, pH 6.68--surviving severe metformin intoxication. QJM, 2010. 103(11): 887-90.
There are 22 citations in total.

Details

Primary Language English
Subjects ​Internal Diseases
Journal Section ORIGINAL ARTICLES
Authors

Selman Kesici 0000-0003-4746-6986

Benan Bayrakçı 0000-0003-3307-0948

Publication Date May 29, 2020
Submission Date April 20, 2020
Published in Issue Year 2020 Volume: 14 Issue: 3

Cite

Vancouver Kesici S, Bayrakçı B. Metformin Intoxications Requiring Admission to the Pediatric Intensive Care Unit. Turkish J Pediatr Dis. 2020;14(3):231-5.


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