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Published in: Critical Care 6/2008

Open Access 01-12-2008 | Research

Metformin-associated lactic acidosis in an intensive care unit

Authors: Nicolas Peters, Nicolas Jay, Damien Barraud, Aurélie Cravoisy, Lionel Nace, Pierre-Edouard Bollaert, Sébastien Gibot

Published in: Critical Care | Issue 6/2008

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Abstract

Introduction

Metformin-associated lactic acidosis (MALA) is a classic side effect of metformin and is known to be a severe disease with a high mortality rate. The treatment of MALA with dialysis is controversial and is the subject of many case reports in the literature. We aimed to assess the prevalence of MALA in a 16-bed, university-affiliated, intensive care unit (ICU), and the effect of dialysis on patient outcome.

Methods

Over a five-year period, we retrospectively identified all patients who were either admitted to the ICU with metformin as a usual medication, or who attempted suicide by metformin ingestion. Within this population, we selected patients presenting with lactic acidosis, thus defining MALA, and described their clinical and biological features.

Results

MALA accounted for 0.84% of all admissions during the study period (30 MALA admissions over five years) and was associated with a 30% mortality rate. The only factors associated with a fatal outcome were the reason for admission in the ICU and the initial prothrombin time. Although patients who went on to haemodialysis had higher illness severity scores, as compared with those who were not dialysed, the mortality rates were similar between the two groups (31.3% versus 28.6%).

Conclusions

MALA can be encountered in the ICU several times a year and still remains a life-threatening condition. Treatment is restricted mostly to supportive measures, although haemodialysis may possess a protective effect.
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Literature
1.
go back to reference UK Prospective Diabetes Study (UKPDS) group: Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998, 352: 854-865. 10.1016/S0140-6736(98)07037-8.CrossRef UK Prospective Diabetes Study (UKPDS) group: Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998, 352: 854-865. 10.1016/S0140-6736(98)07037-8.CrossRef
2.
go back to reference Lebacq EG, Tirzmalis A: Metformin and lactic acidosis. Lancet. 1972, 1: 314-315. 10.1016/S0140-6736(72)90311-X.CrossRefPubMed Lebacq EG, Tirzmalis A: Metformin and lactic acidosis. Lancet. 1972, 1: 314-315. 10.1016/S0140-6736(72)90311-X.CrossRefPubMed
3.
go back to reference Misbin RI, Green L, Stadel BV, Gueriguian JL, Gubbi A, Fleming GA: Lactic acidosis in patients with diabetes treated with metformin. N Engl J Med. 1998, 338: 265-266. 10.1056/NEJM199801223380415.CrossRefPubMed Misbin RI, Green L, Stadel BV, Gueriguian JL, Gubbi A, Fleming GA: Lactic acidosis in patients with diabetes treated with metformin. N Engl J Med. 1998, 338: 265-266. 10.1056/NEJM199801223380415.CrossRefPubMed
4.
go back to reference Cusi K, Consoli A, DeFronzo RA: Metabolic effects of metformin on glucose and lactate metabolism in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1996, 81: 4059-4067. 10.1210/jc.81.11.4059.PubMed Cusi K, Consoli A, DeFronzo RA: Metabolic effects of metformin on glucose and lactate metabolism in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1996, 81: 4059-4067. 10.1210/jc.81.11.4059.PubMed
5.
go back to reference Owen MR, Doran E, Halestrap AP: Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J. 2000, 348: 607-614. 10.1042/0264-6021:3480607.PubMedCentralCrossRefPubMed Owen MR, Doran E, Halestrap AP: Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J. 2000, 348: 607-614. 10.1042/0264-6021:3480607.PubMedCentralCrossRefPubMed
6.
go back to reference El-Mir MY, Nogueira V, Fontaine E, Averet N, Rigoulet M, Leverve X: Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. J Biol Chem. 2000, 275: 223-228. 10.1074/jbc.275.1.223.CrossRefPubMed El-Mir MY, Nogueira V, Fontaine E, Averet N, Rigoulet M, Leverve X: Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. J Biol Chem. 2000, 275: 223-228. 10.1074/jbc.275.1.223.CrossRefPubMed
7.
go back to reference Barrueto F, Meggs WJ, Barchman MJ: Clearance of metformin by hemofiltration in overdose. J Toxicol Clin Toxicol. 2002, 40: 177-180. 10.1081/CLT-120004407.CrossRefPubMed Barrueto F, Meggs WJ, Barchman MJ: Clearance of metformin by hemofiltration in overdose. J Toxicol Clin Toxicol. 2002, 40: 177-180. 10.1081/CLT-120004407.CrossRefPubMed
8.
go back to reference Panzer U, Kluge S, Kreymann G, Wolf G: Combination of intermittent haemodialysis and the high-volume continous haemofiltration for the treatment of severe metformin-induced lactic acidosis. Nephrol Dial Transplant. 2004, 19: 2157-2158. 10.1093/ndt/gfh337.CrossRefPubMed Panzer U, Kluge S, Kreymann G, Wolf G: Combination of intermittent haemodialysis and the high-volume continous haemofiltration for the treatment of severe metformin-induced lactic acidosis. Nephrol Dial Transplant. 2004, 19: 2157-2158. 10.1093/ndt/gfh337.CrossRefPubMed
9.
go back to reference Heaney D, Majid A, Junor B: Bicarbonate haemodialysis as treatment of metformin overdose. Nephrol Dial Transplant. 1997, 12: 1046-1047. 10.1093/ndt/12.5.1046.CrossRefPubMed Heaney D, Majid A, Junor B: Bicarbonate haemodialysis as treatment of metformin overdose. Nephrol Dial Transplant. 1997, 12: 1046-1047. 10.1093/ndt/12.5.1046.CrossRefPubMed
10.
go back to reference Guo PY, Storsley LJ, Finkle SN: Severe lactic acidosis treated with prolonged hemodialysis: recovery after massive overdoses of metformin. Semin Dial. 2006, 19: 80-83. 10.1111/j.1525-139X.2006.00123.x.CrossRefPubMed Guo PY, Storsley LJ, Finkle SN: Severe lactic acidosis treated with prolonged hemodialysis: recovery after massive overdoses of metformin. Semin Dial. 2006, 19: 80-83. 10.1111/j.1525-139X.2006.00123.x.CrossRefPubMed
11.
go back to reference Gan SC, Barr J, Arieff AI, Pearl RG: Biguanide-associated lactic acidosis. Case report and review of the literature. Arch Intern Med. 1992, 152: 2333-2336. 10.1001/archinte.152.11.2333.CrossRefPubMed Gan SC, Barr J, Arieff AI, Pearl RG: Biguanide-associated lactic acidosis. Case report and review of the literature. Arch Intern Med. 1992, 152: 2333-2336. 10.1001/archinte.152.11.2333.CrossRefPubMed
12.
go back to reference Chalopin JM, Tanter Y, Besancenot JF, Cabanne JF, Rifle G: Treatment of metformin-associated lactic acidosis with closed recirculation bicarbonate-buffered hemodialysis. Arch Intern Med. 1984, 144: 203-205. 10.1001/archinte.144.1.203a.CrossRefPubMed Chalopin JM, Tanter Y, Besancenot JF, Cabanne JF, Rifle G: Treatment of metformin-associated lactic acidosis with closed recirculation bicarbonate-buffered hemodialysis. Arch Intern Med. 1984, 144: 203-205. 10.1001/archinte.144.1.203a.CrossRefPubMed
13.
go back to reference Charlson ME, Pompei P, Ales KL, MacKenzie CR: A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987, 40: 373-383. 10.1016/0021-9681(87)90171-8.CrossRefPubMed Charlson ME, Pompei P, Ales KL, MacKenzie CR: A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987, 40: 373-383. 10.1016/0021-9681(87)90171-8.CrossRefPubMed
14.
go back to reference Bellomo R, Kellum JA, Mehta R, Palevsky PM, Ronco C: Acute Dialysis Quality Initiative II: the Vicenza conference. Curr Opin Crit Care. 2002, 8: 505-508. 10.1097/00075198-200212000-00004.CrossRefPubMed Bellomo R, Kellum JA, Mehta R, Palevsky PM, Ronco C: Acute Dialysis Quality Initiative II: the Vicenza conference. Curr Opin Crit Care. 2002, 8: 505-508. 10.1097/00075198-200212000-00004.CrossRefPubMed
15.
16.
go back to reference Stacpoole PW, Wright EC, Baumgartner TG, Bersin RM, Buchalter S, Curry SH, Duncan CA, Harman EM, Henderson GN, Jenkinson S: A controlled clinical trial of dichloroacetate for treatment of lactic acidosis in adults. N Engl J Med. 1992, 327: 1564-1569.CrossRefPubMed Stacpoole PW, Wright EC, Baumgartner TG, Bersin RM, Buchalter S, Curry SH, Duncan CA, Harman EM, Henderson GN, Jenkinson S: A controlled clinical trial of dichloroacetate for treatment of lactic acidosis in adults. N Engl J Med. 1992, 327: 1564-1569.CrossRefPubMed
Metadata
Title
Metformin-associated lactic acidosis in an intensive care unit
Authors
Nicolas Peters
Nicolas Jay
Damien Barraud
Aurélie Cravoisy
Lionel Nace
Pierre-Edouard Bollaert
Sébastien Gibot
Publication date
01-12-2008
Publisher
BioMed Central
Published in
Critical Care / Issue 6/2008
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc7137

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