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| Year : 2015 | Volume
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| Issue : 1 | Page : 125-127 |
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| Metformin-related acidosis in a woman while performing Haj: A conservative approach |
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Riyazuddin S. H. Ansari, Ahmed Fouad Mady, Hatem Othman Qutub, Eidah Althomaly, Zainab Abdulaziz Alzayer, Amna A. R. Moulana
Intensive Care Department, King Faisal Hospital, Makkah, Kingdom of Saudi Arabia
Click here for correspondence address and email
| Date of Web Publication | 8-Jan-2015 |
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 Abstract | | |
Metformin is a first-line oral anti-hyperglycemic agent. It decreases insulin resistance, decreases hepatic glucose output and enhances peripheral glucose uptake. Metformin is used as a monotherapy in combination with other oral hypoglycemic agents. A major side-effect of metformin is lactic acidosis. The elimination of metformin is mainly through the kidneys, and raised plasma concentrations can cause lactic acidosis. Provided there is no overdose, metforminassociated lactic acidosis rarely develops in patients without co-morbidities such as renal or hepatic insufficiency, acute infection or severe dehydration. Herein, we report a case of metformin-induced metabolic acidosis occurring in a woman who was severely dehydrated after performing Haj and treated conservatively.
How to cite this article:
Ansari RS, Mady AF, Qutub HO, Althomaly E, Alzayer ZA, Moulana AA. Metformin-related acidosis in a woman while performing Haj: A conservative approach. Saudi J Kidney Dis Transpl 2015;26:125-7 |
How to cite this URL:
Ansari RS, Mady AF, Qutub HO, Althomaly E, Alzayer ZA, Moulana AA. Metformin-related acidosis in a woman while performing Haj: A conservative approach. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2021 Mar 7];26:125-7. Available from: https://www.sjkdt.org/text.asp?2015/26/1/125/148759 |
| Introduction | |  |
Metformin is a biguanide that enhances the release of glucose from the liver and the insulin effect on peripheral tissues thus decreasing the blood glucose. The most serious sideeffect of metformin is lactic acidosis due to inhibition of hepatic gluconeogenesis and/or reduction of conversion of lactic acid, pyruvic acid or alanine to glucose. The yearly incidence of lactic acidosis in previous reports was less than five episodes in every 100,000 treated individuals. Still, there is no particular antidote for metformin-induced lactic acidosis and its treatment mainly involves the correction of acidemia. [1] Considerable efficacy has been observed in the use of hemodialysis to treat the metformin-induced lactic acidosis. Hemodialysis application is currently recommended in patients with severe metabolic acidosis (pH < 7.1) and renal failure. It has been shown that plasma metformin concentrations are only slightly increased when the estimated glomerular filtration rate is ≥30 mL/ min/1.73 m2. [2]
We present a case of successful management of metformin-associated metabolic acidosis, treated simply with intravenous sodium bicarbonate and aggressive hydration and intensive monitoring. Our aim in presenting this article is to demonstrate that even normal doses of metformin can induce severe acidosis.
| Case Report | | |
A 55-year-old woman with type 2 diabetes mellitus presented to the emergency department (ED) with altered level of consciousness. The patient was on metformin 500 mg three times a day. Her respiratory rate was 30 breaths/min, non-invasive blood pressure was 90/50 mm Hg, heart rate was 90 beats/min and temperature was 37°C. The physical exam was otherwise unremarkable.
The laboratory investigations [Table 1] on admission revealed plasma creatinine: 12.72 mg/dL, blood urea nitrogen: 104 mg/dL; arterial blood gases pH: 7.14, PaCO 2 : 13.5 mm Hg, PaO 2 : 128 mm Hg on room air, bicarbonate: 7.7 mmol/L, potassium: 2.5 mmol/L, sodium: 143 mmol/L and chloride of 98 mmol/ L. The anion gap was 37 mmol/L. Blood lactate levels were not available in the hospital. Her white blood count was 13,320/mm 3 , hemoglobin 13.1 g/dL, platelets 209 lacs/mm 3 , random blood sugar 141 mg/dL, aspartate aminotransferase 38 IU/L, alanine aminotransferase 43 IU/L, alkaline phosphatase 80 IU/L, prothrombin time 13.1 s and partial thromboplastin time 31.09 s. The patient underwent an ultrasound scan of the abdomen that showed left-sided renal stone. As per the drug history and clinical and laboratory findings, the patient was admitted to the intensive care unit (ICU) with the suspicion of metformin-associated lactic acidosis. The patient was admitted to the ICU and treated with aggressive intravenous (i.v.) fluids of around 10 L of normal saline, sodium bicarbonate 8.4% boluses plus infusions with norepinephrine infusions (0.25 and 2 μg/kg/min). Endo-tracheal intubation was not performed as she had, by this time, adequate airway and respiratory status. In the ICU, she continued to have persistent metabolic acidosis. There were recurrent episodes of hypoglycemia, which were corrected with intra-venous dextrose infusion. Thereafter, the renal function tests and acidosis returned to normal levels after three days [Table 1]. The patient improved rapidly and was discharged to a medical ward after five days in the ICU.
| Discussion | | |
Lactic acidosis is an uncommon but severe side-effect of metformin treatment. Metformin blocks the conversion of lactate and pyruvate to glucose and results in anaerobic acidosis (type B). Metformin-associated lactic acidosis is defined as a lactate serum level >5 mmol/L and a bicarbonate serum level < 22 mmol/L in a patient on metformin medication or after metformin overdose. [3] However, our patient developed extreme metabolic acidosis in spite of therapeutic doses of metformin in the setting of acute renal failure induced by a prolonged episode of dehydration. In this patient, the history of exhaustion during the performance of Haj may have contributed to acute renal failure. Metformin is eliminated through renal excretion and impaired renal function results in the accumulation of the drug. Determination of the plasma metformin concentration may be useful to differentiate metformininduced lactic acidosis from other causes. If ketoacidosis, uremia and other causes of high anion gap acidosis are excluded, then intoxication due to metformin should be considered. [4] Protein binding of metformin is very low and enables its fast removal by hemodialysis and hemofiltration. Its half-life is around 6.5 h in patients with a normal renal function. Currently, the use of hemodialysis is recommended for the critically ill patients who have severe metabolic acidosis (pH < 7.1), failure of conservative treatment and development of renal failure. Plasma levels of metformin will only be raised when the glomerular filtration rate drops below 30 mL/min/1.73 m 2 . [5] Continuous venovenous hemofiltration (CVVH) is low in efficacy to conventional hemodialysis in removing drugs from the blood, [6] but its application is advised for patients with unstable hemodynamic status and in whom conventional hemodialysis cannot be initiated. Although continuous veno-venous hemodiafiltration (CVVHDF) also corrects acidosis, we chose to correct the metabolic acidosis simultaneously with intravenous infusions of sodium bicarbonate and normal saline. While bicarbonate therapy for lactic acidosis has been described previously, [7] bicarbonate therapy is not without risk, as it worsens intracellular acidosis, particularly in the setting of impaired ventilation.
High anion gap metabolic acidosis and increased serum lactate level in patients who are receiving metformin should alert for a metformin-associated lactic acidosis suspicion. In cases of metformin-induced severe refractory lactic acidosis, early hemodialysis or hemodiafiltration should be considered to correct acidosis and eliminate metformin. This approach is very effective and can be lifesaving. [8] However, in our index case, we successfully managed the metformin-associated lactic acidosis with intravenous sodium bicarbonate and intensive monitoring. This relatively non-invasive method is an effective treatment option. However, hemodialysis still has a valuable role in the management of acidosis that proves refractory to conservative treatment.
Finally, physicians starting treatment with metformin should assess renal function and instruct the patient to stop taking the drug and consult their physician in any situation where dehydration may occur or there may be comorbidities.
Conflict of interest: None
| References | | |
| 1. | Salpeter SR, Greyber E, Pasternak GA, Salpeter Posthumous EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev 2010;20:CD002967.  |
| 2. | Vasisht KP, Chen SC, Peng Y, Bakris GL. Limitations of metformin use in patients with kidney disease: Are they warranted? Diabetes Obes Metab 2010;12:1079-83. |
| 3. | Peters N, Jay N, Barraud D, et al. Metforminassociated lactic acidosis in an intensive care unit. Crit Care 2008;12:R149. |
| 4. | Chang CT, Chen YC, Fang JT, Huang CC. High anion gap metabolic acidosis in suicide: Don't forget metformin intoxication-two patients' experiences. Ren Fail 2002;24:671-5. |
| 5. | Frid A, Sterner GN, Londahl M, et al. Novel assay of metformin levels in patients with type 2 diabetes and varying levels of renal function: Clinical recommendations. Diabetes Care 2010;33:1291-3. |
| 6. | Barrueto F, Meggs WJ, Barchman MJ. Clearance of metformin by hemofiltration in overdose. J Toxicol Clin Toxicol 2002;40:177-80. |
| 7. | Heaney D, Majid A, Junor B. Bicarbonate haemodialysis as a treatment of metformin overdose. Nephrol Dial Transplant 1997;12:1046-7. |
| 8. | 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; 19:2157-8. [ PUBMED] |
Correspondence Address:
Dr. Riyazuddin S. H. Ansari
Intensive Care Department, King Faisal Hospital, P. O. Box 2043, Makkah 21955
Kingdom of Saudi Arabia
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DOI: 10.4103/1319-2442.148759 PMID: 25579731 
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