Metformin Intoxication Research Articles

Methylene Blue in Metformin Intoxication: Not Just Rescue But Also Initial Treatment.

Metformin (MTF) is a widely used oral antidiabetic medication. Regardless the reason, high doses of MTF cause lactic acidosis as a result of its effects on mitochondrial ATP production and no-mediated vascular smooth muscle relaxation. Metformin-associated lactic acidosis can be life-threatening despite all treatments. Methylene blue (MB) has the potential to reverse the toxic effects of MTF through its effects on both the mitochondrial respiratory chain and nitric oxide production. The use of MB in MTF intoxication has only been reported in a limited number of cases. Herein, we present a 16-year-old female patient who attempted suicide by ingesting high doses of MTF. Supportive treatments, such as vasopressor, inotropic treatments, and sodium bicarbonate, were started in the patient who developed fluid-resistant hypotension after pediatric intensive care unit admission. Because of rising lactate levels, Continuous renal replacement therapy (CRRT) was started immediately. Despite all treatments, hypotension and hyperlactatemia persisted; MB was given as a rescue therapy. Noticeable hemodynamic improvement was observed within 30 minutes of initiating MB infusion, allowing a gradual decrease in the doses of inotropic infusions within the first hour of therapy. Patient's cardiovascular support was discontinued on the second day, and she was discharged on the fifth day. We speculate that, considering the mechanisms of MTF toxicity and the mechanisms of action of MB, it is suggested that early administration of MB, not only as a rescue treatment but as the initial approach to MTF poisoning in combination with other treatments, may result in improved outcomes.

GC–MS analysis of 4-hydroxyproline: elevated proline hydroxylation in metformin-associated lactic acidosis and metformin-treated Becker muscular dystrophy patients

Metformin (N,N-dimethylbiguanide), an inhibitor of gluconeogenesis and insulin sensitizer, is widely used for the treatment of type 2 diabetes. In some patients with renal insufficiency, metformin can accumulate and cause lactic acidosis, known as metformin-associated lactic acidosis (MALA, defined as lactate ≥ 5 mM, pH < 7.35, and metformin concentration > 38.7 µM). Here, we report on the post-translational modification (PTM) of proline (Pro) to 4-hydroxyproline (OH-Pro) in metformin-associated lactic acidosis and in metformin-treated patients with Becker muscular dystrophy (BMD). Pro and OH-Pro were measured simultaneously by gas chromatography–mass spectrometry before, during, and after renal replacement therapy in a patient admitted to the intensive care unit (ICU) because of MALA. At admission to the ICU, plasma metformin concentration was 175 µM, with a corresponding lactate concentration of 20 mM and a blood pH of 7.1. Throughout ICU admission, the Pro concentration was lower compared to healthy controls. Renal excretion of OH-Pro was initially high and decreased over time. Moreover, during the first 12 h of ICU admission, OH-Pro seems to be renally secreted while thereafter, it was reabsorbed. Our results suggest that MALA is associated with hyper-hydroxyprolinuria due to elevated PTM of Pro to OH-Pro by prolyl-hydroxylase and/or inhibition of OH-Pro metabolism in the kidneys. In BMD patients, metformin, at the therapeutic dose of 3 × 500 mg per day for 6 weeks, increased the urinary excretion of OH-Pro suggesting elevation of Pro hydroxylation to OH-Pro. Our study suggests that metformin induces specifically the expression/activity of prolyl-hydroxylase in metformin intoxication and BMD.

P-29 Metformin poisoning without lactic acidosis: Case report

Abstract Introduction Metformin is the most widely used oral antidiabetic, which belongs to the biguanide pharmacological group. Metformin-associated lactic acidosis (MALA) is a rare event with an incidence of approximately 19 cases per 100,000 patient-years. The risk of developing lactic acidosis, when taking metformin is enhanced by several factors such as: age &amp;gt; 65 years; concomitant diseases that have the ability to induce hypoxemia (chronic renal failure, congestive heart failure, cardiogenic shock, severe lung disease, sepsis, advanced liver disease, history of lactic acidosis); an excessive alcohol consumption; an administration of iodinated contrast agents. Clinical Case A 46-year-old man was urgently admitted with the following symptoms: drowsiness, repeated vomiting, lethargy, dizziness. The symptoms started after he administered outpatient and at own initiative 50 tablets of metformin, each tablet contains a dose of 500 mg (total dose 25g). Concomitant pathologies: diagnosed with Type 2 Diabetes for 8 years; Toxic liver cirrhosis, compensated Child-Pugh A (recently diagnosed); hypertension; CKD G3aA2 KDIGO. The patient's condition at admission was assessed as extremely serious, Glasgow scale - 11 points, mild hypertension, tachycardia, tachypnea. The paraclinical investigations revealed the presence of metabolic acidosis, but with lactate &amp;lt;5 mmol/l; the progressive renal dysfunction with creatinine values in the first 24 hours up to 1184 µmol/l, urea – 24.5 mmol/l; a severe hypoglycemia - 1.68 mmol/l; a moderate cytolytic syndrome; a cholestatic syndrome, an inflammatory and hepatoprive syndrome; coagulation disorders; a pancreatic dysfunction. In the context of the evident increase of urea and creatinine, the decision was made to initiate the intermittent hemodialysis, a total of 14 sessions were required during hospitalization. The particularity of this case is represented by the absence of lactic acidosis, despite metformin intoxication with altered neurological status, acute renal failure, developed due to chronic kidney disease, liver cirrhosis of toxic etiology and severe hypoglycemia. Conclusion Metformin should be administered with caution in patients with multiple comorbidities. Metformin intoxication can induce lactic acidosis with an increased risk of serious, potentially fatal adverse events. It is essential to identify metformin intoxication as early as possible, with prompt initiation of renal replacement measures and dynamic monitoring of biochemical parameters.

Calcium-Citrate Anticoagulation during Continuous Renal Replacement Therapy in Patients with Metformin Intoxication: A Case Series, Mathematical Estimation of Citrate Accumulation, and Literature Review

Plain Language SummaryMetformin intoxication is a potentially life-threatening condition characterized by severe metabolic acidosis that could require intensive care unit admission and renal replacement therapy (RRT) for metformin removal. According to current guidelines, a citrate solution is commonly administered to generate regional anticoagulation in RRT due to its effect on chelating ionized calcium, an essential element of the coagulation pathway. Citrate metabolism can be impaired during metformin intoxication, and its administration could lead to accumulation worsening the metabolic acidosis. Citrate is not routinely measured, and its accumulation is clinically diagnosed by the ratio between total and ionized plasma calcium concentration (T/I calcium ratio) >2.5 or estimating the presence of unmeasured anions (UA), calculating the strong ion gap (SIG), i.e., the difference between the strong anions and cation, and the concentration of bicarbonate, dissociated albumin, and phosphates. We compared our results obtained from a case series of three patients with a theoretical model of citrate accumulation. Finally, we reviewed the literature to unveil clinical practice in this scenario. Our results support that diluted citrate can be safely used for RRT in patients with metformin toxicity, and the SIG is a valuable tool to estimate the presence of UA and can be used to detect and monitor citrate accumulation in this context.

A Case Report of Metformin Related Lactic Acidosis

Metformin is an oral antidiabetic drug of the biguanide classused in type 2 diabetic patients with normal renal function. The mortality rate is high in cases of lactic acidos is developing in metformin intoxication. In the emergency department, metformin intoxication should be considered in the differential diagnosis of patients whouse metformin and have high anion gap metabolic acidosis (lactic acidosis). The most important and effective treatment with early diagnosis is correction of metabolic acidosis with hemodialysis or hemofiltration methods, bicarbonate treatment, adjustment of blood glucose level. Cardiovascular system support therapy significantly reduces morbidity/mortality. In this case report, we present the early diagnosis and successful treatment of a patient with lactic acidosis due to metformin intoxication.

Acute Pancreatitis After a Late Period of Metformin Intoxication in a Non-diabetic Patient "Pancreatitis and Metformin"

Acute Pancreatitis After a Late Period of Metformin Intoxication in a Non-diabetic Patient "Pancreatitis and Metformin"

Postmortem Metabolomics of Insulin Intoxications and the Potential Application to Find Hypoglycemia-Related Deaths

Postmortem metabolomics can assist death investigations by characterizing metabolic fingerprints differentiating causes of death. Hypoglycemia-related deaths, including insulin intoxications, are difficult to identify and, thus, presumably underdiagnosed. This investigation aims to differentiate insulin intoxication deaths by metabolomics, and identify a metabolic fingerprint to screen for unknown hypoglycemia-related deaths. Ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry data were obtained from 19 insulin intoxications (hypo), 19 diabetic comas (hyper), and 38 hangings (control). Screening for potentially unknown hypoglycemia-related deaths was performed using 776 random postmortem cases. Data were processed using XCMS and SIMCA. Multivariate modeling revealed group separations between hypo, hyper, and control groups. A metabolic fingerprint for the hypo group was identified, and analyses revealed significant decreases in 12 acylcarnitines, including nine hydroxylated-acylcarnitines. Screening of random postmortem cases identified 46 cases (5.9%) as potentially hypoglycemia-related, including six with unknown causes of death. Autopsy report review revealed plausible hypoglycemia-cause for five unknown cases. Additionally, two diabetic cases were found, with a metformin intoxication and a suspicious but unverified insulin intoxication, respectively. Further studies are required to expand on the potential of postmortem metabolomics as a tool in hypoglycemia-related death investigations, and the future application of screening for potential insulin intoxications.

Factors Favoring the Toxic Effects of Metformin in Subjects with Type 2 Diabetes in Two Referral Hospital in Douala, Cameroon

Introduction: The Metformin is a first line agent for the treatment of type 2 diabetes that can be used alone or in combination with sulfonylureas thiazolidinediones, incretin-based drugs, sodium/glucose cotransporter-2 inhibitors, or other hypoglycemic agents. Metformin is the most used anti-hyperglycemic agent for the treatment of Type 2 Diabetes Mellitus. It is considered as a very good drug, with low risk and high benefit. The Metformin liver and pancreatic intoxication can be due to massive ingestion or to a progressive accumulation due to renal failure, hence an elevated blood amylase and transaminases levels. Fatal cases due to metformin intoxication have been described.&#x0D; Methods: The study was an analytical cross sectional study which was carried out in the Douala General Hospital and the Douala Laquintinie Hospital from the 1st of March 2021 to the 30th of May 2021. Our study population included type 2 diabetic patients above 40years of age who are strictly on oral antidiabetic drugs who came to consult in the Douala General Hospital and the Douala Laquintinie Hospital, the exclusion criteria were; Patients infected with hepatitis A, B or hepatitis C, diabetic patients suffering from other pathologies like fatty liver disease and cirrhosis, liver cancer and others, patients suffering from terminal renal failure, patients who have been on NSAI drugs for long period and also taking alcohol or those with hemolyzed blood. For ethical consideration, after presenting and filling of the consent form, 5ml of blood was collected from each participant for the analyses, serum was conserved at a temperature of -15 to -20oC and the samples were finally analyzed in 2 series on the Biotecnica 1500 chemistry analyzer. Statistical analysis was done on Microsoft Excel 2013 version.&#x0D; Results: A total of 102 participants were enrolled, female gender was dominant, and the mean age was 69 years. Most of participants felt under neurological clinical effects (tiredness, dizziness, and tingling sensation). We had an average GOT of 28.3, with a minimum of 7.0 and a maximum of 207, an average GPT of 19.8 with a minimum of 5.9 and a maximum of 90.7 and an average amylase was 45.7 with a minimum value of 11.5 and a maximum value of 470. On the other hand, our average GFR was 74.3 with a minimum of 12.8 and a maximum of 153.2. From the study population, 90 where on metformin among which 79 were on stages 2-5 of kidney failure.&#x0D; Conclusion: This study highlights the risk of liver toxicity for diabetic patient under metformin surfing from renal failure.

Prognostic Factors in Metformin Intoxication; A Case Control Study

Background: Metformin is one of the most orally used antidiabetic agents. Intentional and unintentional overdose of metformin can be associated with life threatening condition. In this study we evaluate prognostic factors for metformin intoxication. Methods: This case-control study was performed on patients referred to Loghman Hakim toxicology emergency department due to metformin intoxication. The patient’s information and lab data were subsequently extracted from their medical file and data processing and analysis performed. Results: There was a significant difference between two groups in multiple items, patients in died group had higher age, blood sugar, BUN, Cr, PT, INR, WBC, on the other hand this group had lower blood pressure, O2 saturation, pH, HCO3 and PTT. Receiver operating characteristic curve showed that five items including: Bp, O2sat, pH, HCO3 and Cr had ability to predict the risk of mortality in patients with metformin poisoning. Univariate as well as multivariate analysis showed, factors including: BP 1.15 (P=0.0216) were related to patient’s mortality. Discussion and conclusion: Our study showed that mentioned clinical and laboratory findings may have an important role in determining the prognosis of patients with metformin poisoning. Extracorporeal treatments may be considered sooner in those who have poorer prognostic factors since admission.

Cholinergic and metabolic effects of metformin in mouse brain

Metformin is widely used as a first-line treatment for type 2 diabetes, but central effects of metformin have received little attention. When metformin (200 mg/kg i.p.) was administered to C57Bl6 mice, metformin concentration in cerebrospinal fluid peaked at 29 μM after 30 min but dropped quickly and was low at 90 min. In mouse hypothalamus sampled by microdialysis, systemically administered metformin caused minor and transient increases of acetylcholine, glucose and lactate while choline levels decreased. When metformin (0.2−10 mM) was locally infused via retrodialysis, there was a short-lasting increase of acetylcholine in the hypothalamus. Extracellular lactate levels in hypothalamus showed a massive increase upon metformin infusion while glucose levels decreased. In isolated mitochondria of mouse brain, metformin inhibited oxygen consumption and the activity of complex I. Inhibition of mitochondrial respiration likely explains lactate formation in the brain during metformin infusion which may cause lactic acidosis during metformin intoxication. The changes of cholinergic activity in the hypothalamus may be associated with appetite suppression observed during metformin treatment.

The importance of hemodialysis in intoxications with 3 case reports

Introduction: While many intoxication cases are cured with medical treatment, antidote therapy and symptomatic treatment; some cases may need hemodialysis treatment or even invasive mechanical ventilation support. We aimed to examine the place of hemodialysis in three rare intoxication cases seen in our hospital.&#x0D; Case Reports: 43-year-old male patient was admitted to the emergency service with metformin intoxication . The patient with type B lactic acidosis was treated with urgent hemodialysis After a session of hemodialysis, the clinical and laboratory data returned to normal. 19-year-old female patient admitted to the emergency service with theophylline intoxication. The blood theophylline level was toxic.The patient with symptoms of intoxication (tachycardia, hypokalemia, severe nausea and vomiting, etc.) regressed after a session of hemodialysis . 22-year-old mental retarded male patient was admitted to the emergency service with loss of consciousness. The patient with metabolic acidosis was taken to the intensive care unit with coma of unknown cause. 4 sessions of hemodialysis was applied to the patient who developed acute renal failure. It was learned that the patient drank ethylene glycol (antifreeze).&#x0D; Result: All our patients could be discharged with full recovery.Hemodialysis treatment has an important place in the treatment of intoxication cases.

Increased ratio of P[v-a]CO2 to C[a-v]O2 without global hypoxia: the case of metformin-induced lactic acidosis

The ratio of venoarterial CO2 tension to arteriovenous O2 content difference (P[v-a]CO2/C[a-v]O2) increases when lactic acidosis is due to inadequate oxygen supply (hypoxia); we aimed to verify whether it also increases when lactic acidosis develops because of mitochondrial dysfunction (dysoxia) with constant oxygen delivery. Twelve anaesthetised, mechanically ventilated pigs were intoxicated with IV metformin (4.0 to 6.4 g over 2.5 to 4.0 h). Saline and norepinephrine were used to preserve oxygen delivery. Lactate and P[v-a]CO2/C[a-v]O2 were measured every one or two hours (arterial and mixed venous blood). During metformin intoxication, lactate increased from 0.8 (0.6−0.9) to 8.5 (5.0−10.9) mmol/l (p < 0.001), even if oxygen delivery remained constant (from 352 ± 78 to 343 ± 97 ml/min, p = 0.098). P[v-a]CO2/C[a-v]O2 increased from 1.6 (1.2–1.8) to 2.3 (1.9−3.2) mmHg/ml/dl (p = 0.004). The intraclass correlation coefficient between lactate and P[v-a]CO2/C[a-v]O2 was 0.72 (p < 0.001). We conclude that P[v-a]CO2/C[a-v]O2 increases when lactic acidosis is due to dysoxia. Therefore, a high P[v-a]CO2/C[a-v]O2 may not discriminate hypoxia from dysoxia as the cause of lactic acidosis.

Severe metformin intoxication in an adolescent: A case report

Severe metformin intoxication in an adolescent: A case report

Metformin Intoxications Requiring Admission to the Pediatric Intensive Care Unit

Objective: To identify the demographics of patients admitted with metformin intoxication and characterize their clinical courses and treatment options in pediatric intensive care unit. Material and Methods: The records of patients admitted to the pediatric intensive care unit due to metformin intoxication between 2013 and 2019 were retrospectively evaluated. Results: There were 22 acute metformin overdose cases. Mean age of the patients was 13.04±5.46 years (1-18 years), 18 were female. Ingested metformin dose ranged from 1.7 gr to 85 gr (mean 19±22.6 gr, median 10 gr), with coingestants taken in 12 patients. Nausea and/or vomiting were present in 16 (72.7%) of the patients. Hyperlactatemia (lactate > 2mmol/L) was present in 13 (59%) of the patients. Mean peak lactate level was 5.1±5.7 mmol/L (0.9-21 mmol/L). Acidosis was present in 12 (54.5%) of the patients. Mean lowest pH level was 7.28±0.16 (6.9-7.45). There was a positive correlation between lactate level and ingested dose (r = 0.816; P < 0.001) while pH was inversely related to dose (r = −0.873; P < 0.001). Six (27%) patients required renal replacement therapy because of profound lactic acidosis despite the intravenous fluid support. Hemodialysis was applied to 5 patients and high dose continuous venovenous hemodiafiltration was applied to 2 patients. 16 years old female patient who ingested 85 g metformin died despite prolonged hemodialysis. Conclusion: Lactic acidosis associated with metformin intoxication is a potentially fatal condition. Both renal replacement therapies hemodialysis and continuous venovenous hemodiafiltration are effective in the treatment of metformin associated lactic acidosis. Most of the patients with severe metformin associated lactic acidosis require repetitive and prolonged hemodialysis sessions.

Mortal Seyreden Nadir Bir Metformin İntoksikasyonu Olgusu

Metformin-associated lactic acidosis is a rare side effect in metformin poisoning. There is conflicting data about mortality rates changing from 3% to 83%. We aimed to discuss a case that developed lactic acidosis and acute renal failure progressing to mortality due to metformin intoxication. A 33 year-old female patient was admitted to the emergency department, with nausea and vomiting after taking 30 tablets of 1000 mg metformin. In the 2nd hour of follow-up, patient was observed to develop lactic acidosis which did not recover despite the infusion replacement treatments and hemodialysis. Following the development of respiratory failure, under mechanical ventilation, the patient developed cardiac arrest at the 48th hour of her admission. In metformin intoxications, it should be remembered that acidosis deepens very quickly and can progress with mortality despite optimal supportive therapy. More specific recommendations and further studies are required for the management and treatment of acute metformin-associated lactic acidosis.

A rare combination of severe lactic acidosis and acute pancreatitis due to metformin intoxication: A case report

A rare combination of severe lactic acidosis and acute pancreatitis due to metformin intoxication: A case report

Metformin – Postmortem fatal and non-fatal reference concentrations in femoral blood and risk factors associated with fatal intoxications

Background & objectivesTo improve the interpretation of fatal intoxications by establishing fatal and non-fatal reference concentrations of metformin in postmortem femoral blood and to further evaluate risk factors associated with fatal metformin intoxication. MethodsAll forensic autopsies in Sweden where metformin was detected in femoral blood 2011–2016 were identified in the National Board of Forensic Medicine databases (NFMD). The cases were classified as single substance intoxications, A (n = 22), multiple substance intoxications, B (N = 7) and postmortem controls, C (N = 13). The control group consisted of cases where metformin was detected, but the cause of death excluded the incapacitation by metformin or other substances. Strict inclusion criteria were used, and all postmortem cases were assessed by two independent reviewers. All other cases where the inclusion criteria of groups A–C where not met formed group O (N = 78). The forensic findings logged in the NFMD where linked to national registers whereby information on comorbidities, dispensed drugs and clinical data could be obtained. ResultsThe mean age was 66 ± 10 years in the total study population and did not differ between the groups. The proportion of men was 64% in group A, 71% in B, 77% in C and 74% in group O. The median values of metformin in group A (48.5 μg/g; range 13.0–210 μg/g) and B (21.0 μg/g; range 4.40–95.0 μg/g) were significantly (p < 0.001 and p = 0.015 respectively) higher than those of the control group C (2.30 μg/g ; range 0.70–21.0 μg/g). The median concentration of metformin in group A and B was also significantly higher than in group O (4.60 μg/g; range 0.64–54.0 μg/g) (p < 0.001 and p = 0.040 respectively). The results suggest that intoxication with metformin as a cause of death should be considered when the postmortem femoral blood level exceeds about 10 μg/g, although higher levels may be seen in postmortem in cases without incapacitation. The metformin intoxication was confirmed to be intentional in 23% (n = 5) of the single intoxications. Underlying factors identified as important for the remaining fatal metformin intoxications included living alone, any contraindication for the use of metformin, known alcohol abuse and a history of stroke or cardiovascular disease. ConclusionsThe reported post mortem femoral blood concentrations of metformin can hopefully contribute to a better interpretation of results in suspected poisonings and obscure cases. Living in a single household, history of cardiovascular disease and contraindications, predominantly alcohol abuse, were associated with fatal metformin intoxication.

Severe lactic acidosis and hypoglycemia due to acute metformin intoxication in a dog

To report a case of severe lactic acidosis and hypoglycemia due to acute metformin intoxication in a dog. A female neutered Rat Terrier was presented for an acute onset of seizure-like episodes, weakness, and vomiting approximately 14 hours after ingestion of 198 mg/kg of metformin. The dog was found to be laterally recumbent, paddling, and unresponsive shortly before presentation. On physical exam, the dog was in hypovolemic shock and hypothermic. Blood work revealed severe lactic acidosis and hypoglycemia. The dog was volume resuscitated with intravenous crystalloids and dextrose, followed by a continuous infusion of intravenous fluids and dextrose, as well as administration of isotonic sodium bicarbonate. Repeat blood work showed minimal improvement of the hyperlactatemia for 3 hours despite resolution of hypovolemia and hypoglycemia followed by gradual improvement over the next 9 hours of hospitalization. High performance liquid chromatography/tandem mass spectrometry analysis showed markedly increased plasma metformin concentrations at 3.9 μg/mL. The dog was discharged from the hospital within 24 hours and showed no recurrence of clinical signs one year following discharge. Metformin-associated lactic acidosis and hypoglycemia is a severe complication in human patients, but has not been reported in veterinary medicine. Aggressive treatment with supportive care including IV fluids and dextrose administration resulted in resolution of the clinical signs in this patient. Metformin toxicosis should be considered in dogs with severe hyperlactatemia and hypoglycemia of unknown etiology.

Efficiency of Hemodiafiltration in Severe Lactic Acidosis Due to Metformin Intoxication: Case Report

Efficiency of Hemodiafiltration in Severe Lactic Acidosis Due to Metformin Intoxication: Case Report

Range of therapeutic metformin concentrations in clinical blood samples and comparison to a forensic case with death due to lactic acidosis

Due to a lack of reference values for blood concentration of metformin in the literature, the forensic evaluation of metformin findings in blood samples is difficult. Interpretations with regard to the assessment of blood concentrations as well as an estimation of the ingested metformin amounts are often vague. Furthermore, post mortem evaluation of death due to lactic acidosis because of metformin is difficult since renal performance or lactate concentrations can not always reliably be determined after death.To describe a concentration range in clinical samples after chronic use of metformin, metformin serum concentrations were determined in serum samples of 95 diabetic patients receiving daily doses of 500mg–3000mg of metformin. The analyses of metformin was carried out using a validated high performance liquid chromatograph coupled to triple quadrupole mass spectrometry (LC–QQQ-MS).On average, metformin concentrations were 1846ng/mL (<LoQ—5560ng/mL) and independent of the prescribed daily dose. There was no correlation between plasma concentration and glomerular filtration rate except for the 1700mg daily dose collective (R2=0.707). Results of the herein presented study are useful for the interpretation of analytical metformin findings in forensic toxicology. The utility of the described concentration range is demonstrated by discussing a death case involving a fatal lactate acidosis after metformin intake and renal failure. Usefulness of the parameters metformin blood concentration, lactate concentration and glomerular filtration rate in post mortem cases of lactic acidosis due to metformin intoxication are discussed.