Fatal metformin overdose: Case report and postmortem biochemistry contribution

International Journal of Legal Medicine

Volumn 128, Issue 3, 2014, Pages 483-492

  Bonsignore, Alessandro ^a   Pozzi, Fulvia ^b   Fraternali Orcioni, Giulio ^c   Ventura, Francesco ^a   Palmiere, Cristian ^d  

^a UNIVERSITY OF GENOA   (Italy)

^b UNIVERSITY OF PAVIA   (Italy)

^c UNIVERSITY OF GENOA   (Italy)

^d UNIVERSITY CENTER OF LEGAL MEDICINE   (Switzerland)

Author keywords

Fatal intoxication; Lactic acidosis; Metformin; Metformina associated lactic acidosis; Renal function

Indexed keywords

ANTIDIABETIC AGENT; METFORMIN;

AGED; BLOOD; CASE REPORT; CHEMICALLY INDUCED; COMPLICATION; DIABETES MELLITUS, TYPE 2; DRUG OVERDOSE; FATALITY; FEMALE; HEART ARREST; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; KIDNEY FAILURE; LACTIC ACIDOSIS;

ACIDOSIS, LACTIC; AGED; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DIABETES MELLITUS, TYPE 2; DRUG OVERDOSE; FATAL OUTCOME; FEMALE; HEART ARREST; HUMANS; HYPOGLYCEMIC AGENTS; METFORMIN; RENAL INSUFFICIENCY;

EID: 84902441891     PISSN: 09379827     EISSN: 14371596     Source Type: Journal    
DOI: 10.1007/s00414-013-0927-3     Document Type: Article

References (39)

1. Al-Abri SA, Hayashi S, Thoren KL, Olson KR (2013) Metformin overdose-induced hypoglycemia in the absence of other antidiabetic drugs. Clin Toxicol (Phila) 51(5):444-447
2. Moore KA, Levine B, Titus JM, Fowler DR (2003) Analysis of metformin in antemortem serum and postmortem specimens by a novel HPLC method and application to an intoxication case. J Anal Toxicol 27(8):592-594
3. Dell'Aglio DM, Perino LJ, Kazzi Z, Abramson J, Schwartz MD, Morgan BW (2009) Acute metformin overdose: examining serum pH, lactate level, and metformin concentrations in survivors versus nonsurvivors: a systematic review of the literature. Ann Emerg Med 54(6):818-823
4. Suchard JR, Grotsky TA (2008) Fatal metformin overdose presenting with progressive hyperglycemia. West J Emerg Med 9(3):160-164
5. 2 of 140 mmHg in a venous line? Acta Biomed 80(3):262-264
6. Lalau JD (2010) Lactic acidosis induced by metformin: incidence, management and prevention. Drug Saf 33(9):727-740
7. Eurich DT, Majumdar SR, McAlister FA, Tsuyuki RT, Johnson JA (2008) Levels of evidence needed for changing indications, contraindications, and Food and Drug Administration labeling: the case of metformin. Arch Intern Med 171(11):1042-1043
8. Nye HJ, Herrington WG (2011) Metformin: the safest hypoglycaemic agent in chronic kidney disease? Nephron Clin Pract 118(4):c380-c383
9. Krzymień J, Karnafel W (2013) Lactic acidosis in patients with diabetes. Pol Arch Med Wewn 123(3):91-97
10. Spiller HA, Sawyer TS (2006) Toxicology of oral antidiabetic medications. Am J Health Syst Pharm 63(10):929-938
11. Mujtaba M, Geara AS, Madhrira M, Agarwala R, Anderson H, Cheng JT, Mohan S (2012) Toxicokinetics of metformin-associated lactic acidosis with continuous renal replacement therapy. Eur J Grud Metab Pharmacokinet 37(4):249-253
12. Wills BK, Bryant SM, Buckley P, Seo B (2010) Can acute overdose of metformin lead to lactic acidosis? Am J Emerg Med 28(8):857-861
13. Spiller HA, Quadrani DA (2004) Toxic effects from metformin exposure. Ann Pharmacother 38(5):776-780
14. Lalau JD, Mourlhon C, Bergeret A, Lacroix C (1998) Consequences of metformin intoxication. Diabetes Care 21(11):2036-2037
15. Duong JK, Furlong TJ, Roberts DM, Graham GG, Greenfield JR, Williams KM, Day RO (2013) The role of metformin in metformin-associated lactic acidosis (MALA): case series and formulation of a model of pathogenesis. Drug Saf. doi: 10.1007/s40264-013-0038-6
16. Lacher M, Hermanns-Clausen M, Haeffner K, Brandis M, Pohl M (2005) Severe metformin intoxication with lactic acidosis in an adolescent. Eur J Pediatr 164(6):362-365
17. Cantrell LF, Nelson CL, Gary RD, McIntyre IM (2012) Fatal metformin intoxication with markedly elevated blood and liver concentrations. J Anal Toxicol 36(9):657-659
18. Gambaro V, Dell'acqua L, Farè F, Fidani M, Froldi R, Saligari E (2007) A case of fatal intoxication from metformin. J Forensic Sci 52(4):988-991
19. Nisse P, Mathieu-Nolf M, Deveaux M, Forceville X, Combes A (2003) A fatal case of metformin poisoning. J Toxicol Clin Toxicol 41(7):1035-1036
20. Hermann LS, Magnusson S, Möller B, Casey C, Tucker GT, Woods HF (1981) Lactic acidosis during metformin treatment in an elderly diabetic patient with impaired renal function. Acta Med Scand 209(6):519-520
21. Sánchez-Rubio Ferrández L, Martínez Iturriaga S, Hurtado Gómez MF, Apiñaniz Apiñaniz R (2013) Suicide to massive ingestion of metformin (85 g): lactic acidosis followed by rhabdomyolysis with fatal heart damage. Farm Hosp 37(2):166-167
22. Orban JC, Giunti C, Levraut J, Grimaud D, Ichai C (2003) Metformin-associated lactic acidosis remains a serious complication of metformin therapy. Ann Fr Anesth Reanim 22(5):461-465
23. Bronstein AC, Spyker DA, Cantilena LR Jr, Rumack BH, Dart RC (2012) 2011 annual report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 29th annual report. Clin Toxicol (Phila) 50(10):911-1164
24. Perrone J, Phillips C, Gaieski D (2011) Occult metformin toxicity in three patients with profound lactic acidosis. J Emerg Med 40(3):271-275
25. Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Dart RC (2011) 2010 annual report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 28th annual report. Clin Toxicol (Phila) 49(10):910-941
26. Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Giffin SL (2010) 2009 annual report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 27th annual report. Clin Toxicol (Phila) 48(10):979-1178
27. Arroyo AM, Walroth TA, Mowry JB, Kao LW (2010) The MALAdy of metformin poisoning: is CVVH the cure? Am J Ther 17(1):96-100
28. Barrueto F, Meggs WJ, Barchman MJ (2002) Clearance of metformin by hemofiltration in overdose. J Toxicol Clin Toxicol 40(2):177-180
29. Bismuth C, Gaultier M, Conso F, Assan R, Heuclin C (1976) Lactic acidosis induced by excessive ingestion of metformin. Eur J Toxicol Environ Hyg 9(1):55-57
30. Assan R, Heuclin C, Ganeval D, Bismuth C, George J, Girard JR (1977) Metformin-induced lactic acidosis in the presence of acute renal failure. Diabetologia 13(3):211-217
31. Ortega Carnicer J, Ambrós Checa A, Martín Rodríguez C, Ruiz Lorenzo F, Portilla Botelho M, Gómez Grande L (2007) Overdose of metformin secondary to acute renal insufficiency: a report of six cases. Med Intensiva 31(9):521-525
32. Dell'Aglio DM, Perino LJ, Todino JD, Algren DA, Morgan BW (2010) Metformin overdose with a resultant serum pH of 6.59: survival without sequelae. J Emerg Med 39(1):e77-e80
33. Kosmalski M, Drozdowska A, Sliwinska A, Drzewoski J (2012) Inappropriate metformin prescribing in elderly type 2 diabetes mellitus (T2DM) patients. Adv Med Sci 57(1):65-70
34. Tschöpe D, Hanefeld M, Meier JJ, Gitt AK, Halle M, Bramlage P, Schumm-Draeger PM (2013) The role of co-morbidity in the selection of antidiabetic pharmacotherapy in type-2 diabetes. Cardiovasc Diabetol 12:62
35. Lipska KJ, Bailey CJ, Inzucchi SE (2011) Use of metformin in the setting of mild-to-moderate renal insufficiency. Diabetes Care 34(6):1431-1437
36. Devetzis V, Passadakis P, Panagoutsos S, Theodoridis M, Thodis E, Georgoulidou A, Vargemezis V (2011) Metformin-related lactic acidosis in patients with acute kidney injury. Int Urol Nephrol 43(4):1243-1248
37. Boulagnon C, Garnotel R, Fornes P, Gillery P (2011) Postmortem biochemistry of vitreous humor and glucose metabolism: an update. Clin Chem Lab Med 49(8):1265-1270
38. Zilg B, Alkass K, Berg S, Druid H (2009) Postmortem identification of hyperglycemia. Forensic Sci Int 185(1-3):89-95
39. Palmiere C, Sporkert F, Vaucher P, Werner D, Bardy D, Rey F, Lardi C, Brunel C, Augsburger M, Mangin P (2012) Is the formula of Traub still up to date in antemortem blood glucose level estimation? Int J Legal Med 126(3):407-413