А HIGH ANION GAP METABOLIC ACIDOSIS IN SEVERE DELIBERATE POISONING WITH METFORMIN – SUCCESSFUL TREATMENT WITH 2.5-HOUR CONVENTIONAL HEMODYALISIS
Acute metformin poisoning
Metformin-associated lactic acidosis is a rare, life-threatening condition with a high mortality rate, that could occur both with therapeutic use and in metformin overdose. Clinical manifestations may be nonspecific, with severe anion gap metabolic acidosis and elevated lactate levels being the most prominent laboratory findings; hence, delaying the diagnosis and treatment. Renal replacement therapy plays a key role in the treatment of severe metformin poisoning. We herewith present a case with intentional metformin poisoning successfully treated with one session of hemodialysis in combination with parenteral sodium bicarbonate therapy. A 17-year-old non-diabetic woman ingested 25 grams of metformin in a suicide attempt. She developed vomiting and diarrhoea and was brought to the local emergency unit, and shortly after admittance she became nonresponsive. Glasgow coma scale was 7/15 (E2, V1, M4), glucose level was 3.4 mmol/L and blood pressure was 90/60 mmHg. The first arterial blood gas analysis demonstrated a severe metabolic acidosis with high lactate level (pH = 6.778, BE -31.7, lactate 18 mmol/L, anion gap 39.8 mmol/L), and, subsequently, she developed a non-oliguric renal failure. Lactic acidosis was successfully treated with a combination of a conventional 2.5-hour bicarbonate HD and early administration of intravenous bicarbonate. The arterial pH steadily increased back to normal levels, lactic acidosis improved and kidney function recovered completely. It could be concluded that even a single session of timely applied conventional HD in combination with parenteral administration of bicarbonates allows simultaneous drug removal, lactate reduction and acid-base correction and should be a treatment of choice in hemodynamically stable patients with severe metformin poisoning.
Keywords:metformin poisoning, lactic acidosis, renal replacement therapy.
recommendations from the extracorporeal treatments in poisoning workgroup. Crit Care Med.
2015;43(8):1716-30. doi: 10.1097/CCM.0000000000001002.
2. Balley CJ, Turner RC. Metformin. N England J Med. 1996; 334: 574-579.
3. Seidowsky A, Nseir S, Houdret N, Fourrier F. Metfformin associated lactic acidosis: A prognostic and
therapeutic study. Crit Care Med. 2009; 37:2191-2196.
4. Boucaud-Maitre D, Ropers J, Porokhov B, et al. Lactic acidosis: relationship between metformin levels, lactate
concentrations and mortality. Diabet Med. 2016;(11):1536-1543.
5. Spiller HA, Quadrani DA. Toxic effects from metformin exposure. Ann Pharmacother. 2004; 38: 776-780.
6. Spiller HA, Sawyer TS. Toxicology of oral antidiabetic medications. Am J Heath-Syst Pharm. 2006; 63: 29-38.
7. Dell`Aglio DM, Perino IJ, Kazzi Z, Abramson J, Schwartz MD, Morgan BW. Acute metformin overdose: examing
serum pH, lactate level, and metformin concentrations in survivors versus nonsurvivors: a systematic review of
the literature. Ann Emerg Med. 2009;54(6):818-823.
8. Guo PY, Storsley LJ, Finkle SN. Severe lactic acidosis treated with prolonged hemodialysis: recovery after
massive overdoses of metformin. Semin Dial. 2006 Jan-Feb;19(1):80-3.
9. Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical
Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management
algorithm. 2016 Executive summary. Endocr Pract. 2016;22(1):84-113
10. Graham GG, Punt J, Arora M, et al. Clinical pharmacokinetics of metformin. Clin Pharmacokinet. 2011;
11. Chang CT, Chen YC, Fang JT, Huang CC. Metformin-associated lactic acidosis: case reports and literature
review. J Nephrol. 2002;15(4):398-402.
12. Leonaviciute D, Madsen B, Schmedes A, Buus NH, Rasmussen BS. Severe Metformin Poisoning Successfully
Treated with Simultaneous Venovenous Hemofiltration and Prolonged Intermittent Hemodialysis. Case Rep
Crit Care. 2018 May 8;2018:3868051. doi: 10.1155/2018/3868051. PMID: 29854476; PMCID: PMC5964555.
13. Lalau JD, Lacroix C, Compagnon P, et al. Role of metformin accumulation in metformin-associated lactic
acidosis. Diabetes Care. 1995; 18(6):779-84.
14. Lalau JD, Race JM. Lactic acidosis in metformin-treated patients. Prognostic value of arterial lactate levels and
plasma metformin concentrations. Drug Saf. 1999; 20(4):377-84
15. Manini AF, Kumar A, Olsen D, Vlahov D, Hoffman RS. Utility of serum lactate to predict drug-overdose fatality.
Clin Toxicol (Phila). 2010 Aug;48(7):730-6. doi: 10.3109/15563650.2010.504187. PMID: 20704455; PMCID:
16. Weil MH, Rackow EC, Trevino R, Grundler W, Falk Jl, Griffel MI. Difference in acid-base state between venous
and arterial blood during cardiopulmonary resuscitation. N Engl J Med. 1986; 315: 153-6.
17. Sabatini S, Kurtzman NA. Bicarbonate therapy in severe metabolic acidosis. J Am Soc Nephrol. 2009; 20(4):
18. Calello D, Liu KD, Wiegand TJ, et al. Extracorporeal treatment for metformin poisoning: systematic review and
recommendations from the extracorporeal treatments in poisoning workgroup. Crit Care Med. 2015;
19. Brochard L, Abroug F, Brenner M et al. An official ATS/ERS/ESICM/SCCM/SRLF statement: prevention and
management of acute renal failure in th ICU patient: an international consensus conference in intensive care
medicine. Am J Respir Crit Care Med. 2010; 181(10): 1128-55. Doi: 10.1164/rccm.200711-1664ST.
20. Regolisti G, Antoniotti R, Fani F, Greco P, Fiaccadori E. Treatment of Metformin Intoxication Complicated by
Lactic Acidosis and Acute Kidney Injury: The Role of Prolonged Intermittent Hemodialysis. Am J Kidney Dis.
2017;70(2):290-296 doi: 10.1053/j.ajkd.2016.12.010