Document Type : Case Report
Authors
Ankara Training and Research Hospital
Abstract
Introduction: Metformin-associated lactic acidosis is a rare, yet fatal condition, especially in the presence of risk factors. Therapeutic use of metformin may induce lactic acidosis. Gastrointestinal bleeding, dehydration, acute renal failure, and drugs are major risk factors that increase the mortality risk associated with metformin-associated lactic acidosis. In this regard, this case study aimed to present a patient, who died due to metformin-associated lactic acidosis despite treatment.
Method: This case study featured a 45-year-old diabetic patient with metformin use, who presented to the emergency department with the complaint of low back pain. He had acute renal failure, severe lactic acidosis, and shock findings.
Discussion: The primary purpose of metformin-associated lactic acidosis treatment is to restore acid-base balance and provide hemodynamic support. Hemodialysis reduces the mortality due to metformin-associated lactic acidosis by decreasing lactate clearance. Supportive therapies should be used. Nevertheless, mortality still occurs in approximately 50% of the cases.
Conclusion: Metformin overdose or even therapeutic levels of metformin use can cause MALA in the presence of various risk factors. MALA, a rare clinical condition, is associated with mortality rates of up to 50%. The most crucial step in treating MALA is hemodialysis/venous hemofiltration. Given that metformin is a frequently used medication, care should be taken in the follow-up of patients using metformin, considering MALA.
Keywords
Flory J, Lipska K. Metformin in 2019. JAMA. 2019 May 21;321(19):1926-1927.doi: 10.1001/jama.2019.3805.
- 2. DeFronzo R, Fleming GA, Chen K, Bicsak TA. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism. 2016 Feb;65(2):20-9.doi: 10.1016/j.metabol.2015.10.014.
3.Wang GS, Hoyte C. Review of Biguanide (Metformin) Toxicity. J Intensive Care Med. 2019 Nov-Dec;34(11-12):863-876.doi: 10.1177/0885066618793385.
- Doyle-Delgado K, Chamberlain JJ, Shubrook JH, Skolnik N, Trujillo J. Pharmacologic Approaches to Glycemic Treatment of Type 2 Diabetes: Synopsis of the 2020 American Diabetes Association's Standards of Medical Care in Diabetes Clinical Guideline. Ann Intern Med. 2020 Nov 17;173(10):813-821. doi: 10.7326/M20-2470.
- U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA revises warnings regarding use of the diabetes medicine metformin in certain patients with reduced kidney function
- Kuan IHS, Savage RL, Duffull SB, Walker RJ, Wright DFB. The Association between Metformin Therapy and Lactic Acidosis. Drug Saf. 2019 Dec;42(12):1449-1469. doi: 10.1007/s40264-019-00854-x.
7.Vural HZ, Koseoglu OF, Soylu S, Turkmen UA. Metformin-Associated Lactic Acidosis Developed as a Result of a Suicidal Attempt. Sisli Etfal Hastan Tip Bul. 2020 Jun 15;54(2):252-256.doi: 10.14744/SEMB.2018.35582
- 8. Mizock BA. Lactic acidosis. Dis Mon. 1989;35(4):233–300.doi: 10.1016/0011-5029(89)90021-7
- Rajasurya V, Anjum H, Surani S. Metformin Use and Metformin-associated Lactic Acidosis in Intensive Care Unit Patients with Diabetes. Cureus. 2019 May 23;11(5): e4739. doi: 10.7759/cureus.4739. doi: 10.7759/cureus.4739.
- DeFronzo R, Fleming GA, Chen K, Bicsak TA. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism. 2016 Feb;65(2):20-9. doi: 10.1016/j.metabol.2015.10.014.doi: 10.1016/j.metabol.2015.10.014.
- Cetinkaya A, Avci D, Erden A, Akca O, Ozer O, Kalan U et al. Clinical and Laboratory Features of Metformin Intoxication in Suicidal Patients Attending an Intensive Care Unit. Niger J Clin Pract. 2018 Feb;21(2):143-148. doi: 10.4103/njcp.njcp_343_16.
- Dell'Aglio DM, Perino LJ, Kazzi Z, Abramson J, Schwartz MD, 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 Dec;54(6):818-23. doi: 10.1016/j.annemergmed.2009.04.023.
- 13. Blumenberg A, Benabbas R, Sinert R, Jeng A, Wiener SW. Do Patients Die with or from Metformin-Associated Lactic Acidosis (MALA)? Systematic Review and Meta-analysis of pH and Lactate as Predictors of Mortality in MALA. J Med Toxicol. 2020 Apr;16(2):222-229. doi: 10.1007/s13181-019-00755-6.
14.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:R149. doi: 10.1186/cc7137.
15.Biradar V, Moran JL, Peake SL, Peter JV. Metformin-associated lactic acidosis (MALA): Clinical profile and outcomes in patients admitted to the intensive care unit. Crit Care Resusc 2010;12:191-5.PMID: 21261578.
- 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;36:733-46.doi: 10.1007/s40264-013-0038-6.
- Lalau JD. Lactic acidosis induced by metformin: incidence, management and prevention. Drug Saf. 2010 Sep 1;33(9):727-40. doi: 10.2165/11536790-000000000-00000.
- Pakkir Maideen NM, Jumale A, Balasubramaniam R. Drug Interactions of Metformin Involving Drug Transporter Proteins. Adv Pharm Bull. 2017;7(4):501-505. doi:10.15171/apb.2017.062
- Cooper DJ, Higgins AM, Nichol AD. Lactic acidosis. İn: Bersten AD, Soni N, editors. Oh’s Intensive Care Manual. Elsevier Ltd.; 2014. p. 158-64.
20.Barrueto F, Meggs WJ, Barchman MJ. Clearance of metformin by hemofiltration in overdose. J Toxicol Clin Toxicol 2002;40:177-80. doi: 10.1081/clt-120004407.
- Gura M, Devrim S, Sagiroglu A, Orhon Z, Sen B. Severe Metformin İntoxication With Lactic Acidosis İn An Adolescent: A Case Report. The Internet Journal of Anesthesiology 2009;27.2
22.Avcı D, Çetinkaya A, Karahan S, Oğuzhan N, Karagöz H, Başak M et al. Suicide commitment with metformin: our experience with five cases. Ren Fail. 2013 Jul;35(6):863-5. doi: 10.3109/0886022X.2013.801299
23.Johansen NJ, Christensen MB. A Systematic Review on Insulin Overdose Cases: Clinical Course, Complications and Treatment Options. Basic Clin Pharmacol Toxicol. 2018 Jun;122(6):650-659. doi: 10.1111/bcpt.12957.
- Serpa Neto A, Nassar AP, Cardoso SO et al.Vasopressin and terlipressin in adult vasodilatory shock: a systematic review and meta-analysis of nine randomized controlled trials. Crit Care. 2012 Aug 14;16(4):R154. doi: 10.1186/cc11469.
- Warrick BJ, Tataru AP, Smolinske S. A systematic analysis of methylene blue for drug-induced shock. Clin Toxicol (Phila). 2016 Aug;54(7):547-55. doi: 10.1080/15563650.2016.1180390.
)