Metformin intoxication in an adolescent

Abstract

To the Editor Metformin which belongs to the biguanide group is being used from the 1950 rsquo;s in diabetic patients who develop insulin resistance Metformin is an anti hyperglycemic agent and provides euglycemia The known toxic effect of biguanides is lactic acidosis in acute and chronic use Fenformin which belongs to the biguanides was recalled from market in USA in 1976 Lactic acidosis related to acute excessive metformin may be fatal 1 Here a patient who was followed up with metformin intoxication has been presented A 15 year old female patient was referred to our emergency department because of metformin intoxication Gastric irrigation was performed and activated charcoal was administered in the patient who had abdominal pain following ingestion of 40 tablets containing 1000 mg metformin with the objective of suicide At the same time intravenous dextrose was given as bolus since the blood glucose was found to be 28 mg dL On physical examination in the emergency department the consciousness was confused marked agitations were found occasionally and Kussmaul respiration became prominent The patient was internalized in the intensive care unit At the time of presentation the blood glucose was found to be 112 mg dL but decreased to 35 mg dL because of possible venous access problem Intravenous dextrose was given rapidly and 10 dextrose fluid therapy was continued Blood gases revealed the following: pH 6 99 HCO3 6 3 mmol L PCO2 27 3 mmHg BE 22 7 mmol L lactate level 134 mg dL 0 4 2 2 Laboratory findings were as follows: Hb 12 5 g dL WBC 17 000 mm3 platelets 389 000 mm3 urea 21 mg dL creatinine 1 97 mg dL sodium 123 mEq L potassium 3 1 mEq L Blood gases measured six hours after complementary bicarbonate treatment was started were as follows: pH 6 95 HCO3 5 4 mmol L PCO2 26 1 mmHg BE 27 3 mmol L The patient whose respiratory distress increased was intubated at the 8th hour of hospitalization Central venous dialysis catheter was inserted in the right jugular vein Dopamin treatment was started because of development of hypotension and continious veno venous hemodiafiltration was performed as 120 ml min The first hemodiafiltration procedure was performed using dialysis fluid for 10 hours The patient was extubated 8 hours after intubation On the second day of hospitalization lactate was found to be 93 3 mg dL urea was found to be 64 mg dL and creatinine was found to be 1 4 Veno venous hemodiafiltration was performed again using 120 ml min blood and dialysis fluid for 24 hours On the 4th day of hospitalization laboratory findings were as follows: pH 7 44 HCO3 22 mmol L PCO2 45 3 mmHg BE 1 5 mmol L lactate 7 mg dL urea 20 mg dL creatinine 0 53 sodium 135 mEq l potassium 3 7 mEq l The patient was discharged from the intensive care unit and on the 10th day of hospitalization was discharged from the hospital The effect of causing lactic acidosis in chronic use of metformin has been found in 1 10 100 000 patients The mortality rate was found to be 45 in a series of 49 patients who developed lactic acidosis after metformin treatment 2 In this study the variables which predicted mortality were reported to be liver failure and prolonged prothrombin time In our patient there was no liver failure and prolongation of prothrombin time Metformin related lactic acidosis is mostly related with acute overdose of metformin Blood gases and lactate values were shown to be the two possible variables which predicted mortality in a study In this study which evaluated 22 patients 16 patients who had a pH level above 6 9 and a lactate level below 225 mg dL survived while 5 of 6 patients who had a pH level below 6 9 and a lactate level above 225 mg dL died 3 In our patient blood pH level decreased to 6 95 and lactate level increased to 230 mg dL However lactate levels and blood gases became normal as a result of early and efficient hemodiafiltration intervention Hypoglycemic side effect of metformin may occur when used in combination with other oral antidiabetics In addition hypoglycemia may develop in metformin overdose Therefore attention should be paid to hypoglycemia in patients who present with metformin overdose In our patient marked hypoglycemia was observed for two times and the necessary intervention was performed Bicarbonate treatment is controversial in metformin related lactic acidosis Administration of bicarbonate may cause recurrent metabolic alkalosis serum potassium and calcium disorders and myocardial dysfunction Hemodialysis was shown to be efficient in treatment of metformin related lactic acidosis In patients with severe metabolic acidosis intensive bicarbonate treatment has been reported to be inefficient and hemodialysis has been recommended if pH lt;7 1 in patients with renal problems 4 In addition continuous veno venous hemodiafiltration has also been shown to be effective However hemodiafiltration has been reported to have a lower effect on the excretion of the drug compared to traditional hemodialysis 5 It should be performed in patients who can not tolerate hemodialysis and who have instable hemodynamics In our patient intensive bicarbonate treatment was not useful and hemodiafiltration was performed at the 10th hour of hospitalization In the literature four patients two from our country who developed lactic acidosis related to metformin intoxication have been reported 6 7 8 9 In female gender and patients aged 14 16 years lactic acidosis developed after ingestion of excessive doses of metformin 25 63 g One patient survived after bicarbonate treatment one patient survived after hemodialysis and 2 patients survived after continuous veno venous hemodiafiltration In recent years cases of obesity and hence type 2 diabetes have increased Increased use of metformin dictates that pediatricians and pediatric endocrinologists obtain more information about the side effects of this drug We would like to emphasize that bicarbonate treatment is not efficient and early hemodialysis or hemodiafiltration are life saving in patients who develop severe acidosis pH lt;7 1 Erdal Eren1 Mehmet Türe1 Veysi Almaz1 Tekin Bilgiç2 İhsan Yıldırım1 Tahsin Gider1 1Harran University Medical Faculty Department of Pediatrics Şanlıurfa Turkey 2Harran University Medical Faculty Department of Anesthesiology and Reanimation Şanlıurfa Turkey References 1 Lalau JD Mourlhon C Bergeret A Lacroix C Consequences of metformin intoxication Diabetes Care 1998; 21: 2036 7 2 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 84 3 Dell 39;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; 54: 818 823 4 Lalau JD Andrejak M Morini egrave;re P et al Hemodialysis in the treatment of lactic acidosis in diabetics treated by metformin: a study of metformin elimination Int J Clin Pharmacol Ther Toxicol 1989; 27: 285 288 5 Harvey B Hickman C Hinson G Ralph T Mayer A Severe lactic acidosis complicating metformin overdose successfully treated with high volume venovenous hemofiltration and aggressive alkalinization Pediatr Crit Care Med 2005; 6: 598 601 6 Lacher M Hermanns Clausen M Haeffner K Brandis M Pohl M Severe metformin intoxication with lactic acidosis in an adolescent Eur J Pediatr 2005; 164: 362 365 7 Harvey B Hickman C Hinson G Ralph T Mayer A Severe lactic acidosis complicating metformin overdose successfully treated with high volume venovenous hemofiltration and aggressive alkalinization Pediatr Crit Care Med 2005; 6: 598 601 8 Doğru O Koken R Bukulmez A Yurumez Y Ovalı F Metformin overdose: a case report Journal of the Indian Society of Toxicology 2005; 1: 41 45 9 Gura M Devrim S Sagıroglu AE Orhon Z Sen B Severe metformin intoxication with lactic acidosis in an adolescent: a case report The Internet Journal of Anesthesiology 2010; 27: 2

Keywords

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Bir ergende metformin zehirlenmesi

Öz

Biguanid grubundan olan Metformin 1950’li yıllardan bu yana insülin direnci gelişen diyabetli hastalarda kullanılmaktadır. Metformin hiperglisemi karşıtı ajan olup öglisemi sağlamaktadır. Biguanidlerin akut ve kronik kullanımında bilinen toksik etkisi laktik asidozdur. Biguanidlerden fenformin ciddi laktik asidoz etkisi nedeniyle 1976’da Amerika pazarından çekilmiştir. Akut aşırı metformine bağlı laktik asidoz ölümcül seyredebilmektedir (1). Burada kliniğimizde metformin zehirlenmesi ile izlenen bir olgu sunulmuştur. On beş yaşında kız hasta acil servisimize metformin zehirlenmesi nedeniyle yönlendirildi. İntihar amaçlı 40 adet 1000 mg metformin içeren tableti aldıktan sonra karın ağrısı başlayan olguya mide yıkaması ve aktif kömür uygulaması yapılmış ve aynı dönemde kan şekeri 28 mg/dL saptanması nedeniyle İV (damar içi) dekstroz hızla verilmişti. Acil servisteki muayenede bilinci dalgalanan, zaman zaman belirgin ajitasyonları saptanan ve Kussmaul solunumu belirginleşen hasta yoğun bakıma alındı.

Anahtar Kelimeler

• metformin
• zehirlenmesi
• Biguanid