Combination of intermittent haemodialysis and high-volume continuous haemofiltration for the treatment of severe metformin-induced lactic acidosis

Sir,

Metformin has been used for many decades as an effective glucose-lowering medication in the treatment of type 2 diabetes mellitus. Recent studies clearly demonstrated that metformin reduced secondary complications of diabetes mellitus type 2 without promoting weight gain, which is in contrast to treatment with insulin and/or sulphonylurea [1]. Lactic acidosis is a serious side effect observed with metformin treatment and an incidence rate of 9 lactic acidoses per 100 000 person-years of metformin treatment, as has been calculated [2]. This side effect is usually found in patients receiving metformin despite major contraindications, such as renal insufficiency and/or cardiopulmonary instability. The mortality in metformin-induced lactic acidosis is very high and has been estimated to be >50% [3]. Only a small number of cases of metformin overdoses with lactic acidosis have been described in the literature [4].

We report the case of a patient with severe lactic acidosis and cardiocirculatory arrest caused by metformin intoxication. Despite a plasma metformin concentration of 191 mg/l (to our knowledge the highest reported value in the literature), the patient recovered totally after treatment with a combination of intermittent haemodialysis and high-volume continuous haemofiltration.

A 42-year-old man was admitted with nausea and vomiting. The patient declared that he wanted to kill himself, but denied that he had taken any medications or drugs. His past medical history included type 2 diabetes that was treated with initial unknown types of oral hypoglycaemics. On admission, the patient was in a stable condition and initial routine laboratory workup was normal.

Four hours later, the patient complained of severe dyspnoea. Laboratory studies revealed a metabolic acidosis (pH 7.20, pCO2 37 mmHg, bicarbonate 15.8 mmol/l, anion gap 18) and a lactate concentration of 8.9 mmol/l. The patient was transferred to the intensive care unit (ICU), where he developed respiratory insufficiency and severe hypotension, resulting in intubation, mechanical ventilation and administration of dopamine and noradrenaline infusion. Laboratory workup showed further progression of the lactic acidosis (pH 6.89, pCO2 30 mmHg, bicarbonate 6.7 mmol/l, lactate 21.6 mmol/l) and a serum creatinine of 1.8 mg/dl. Urine analysis was negative for ketones.

In the meantime, a relative reported that metformin is part of the patient's medication. This information in combination with the patient's initial declaration of intending to harm himself led to the assumption of a metformin-induced lactic acidosis.

We started intermittent haemodialysis for 11 h (with 1 h interruption) in order to remove metformin and lactate as fast as possible and to correct acidosis. However, blood lactate levels remained very high and progressive haemodynamic instability occurred. Haemodialysis treatment was stopped and continuous veno-venous haemofiltration (CVVH) with bicarbonate substitute was started. Because of a further rise in the lactate level (25.8 mmol/l) and the poor clinical course of the patient, we intensified the extracorporeal elimination treatment using a second CVVH machine with a femoral catheter access. Under this high-volume CVVH (blood flow 300 ml/min, ultrafiltration 5 l/h) for 16 h (Figure 1), lactic acidosis improved, the haemodynamic situation of the patient stabilized and he was discharged from the ICU.



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Fig. 1. Follow-up plasma lactate concentration (mmol/l) (grey squares) and plasma metformin concentration (mg/l) (black circles). IHD, intermittent haemodialysis therapy.

 
In conclusion, metformin intoxication should be considered in the differential diagnosis for patients with lactic acidosis in the absence of obvious tissue hypoxia [5]. Only early treatment, even in a suspicious case of metformin intoxication, is able to reduce the high mortality rates in these patients. This case report demonstrates the usefulness of the combination of intermittent haemodialysis with high-volume CVVH using two vascular access sites in the treatment of a patient with severe metformin-induced lactic acidosis and extremely high serum metformin concentrations.

Conflict of interest statement. None declared.

Ulf Panzer1, Stefan Kluge2, Georg Kreymann2 and Gunter Wolf1

1 Medizinische Klinik IV2 Medizinische Klinik I Universitätsklinikum Hamburg Eppendorf Germany Email: panzer{at}uke.uni-hamburg.de

Notes

The authors wish to be known that, in their opinion, the first two authors contributed equally to this work.

References

  1. UK Prospective Diabetes Study 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[CrossRef][ISI][Medline]
  2. Stang MR, Wysowski DK, Butler-Jones D. Incidence of lactic acidosis in metformin users. Diabetes Care 1999; 22: 925–927[Abstract]
  3. Lalau JD, Race JM. Lactic acidosis in metformin-treated patients. Prognostic value of arterial lactate levels and plasma metformin concentrations. Drug Saf 1999; 20: 377–384[ISI][Medline]
  4. Heaney D, Majid A, Junor B. Bicarbonate haemodialysis as a treatment of metformin overdose. Nephrol Dial Transplant 1997; 12: 1046–1047[Abstract]
  5. Luft FC. Lactic acidosis update for critical care clinicians. J Am Soc Nephrol 2001; 12: 15–19[CrossRef]




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