Metformin-Associated Lactic Acidosis following Intentional Overdose Successfully Treated with Tris-Hydroxymethyl Aminomethane and Renal Replacement Therapy

Lam, Ngan N.; Sekhon, Gurbir; House, Andrew A.

doi:10.1155/2012/671595

Cited by 11 publications

(14 citation statements)

References 24 publications

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“…Other reports indicate a comparably low incidence of MALA, but all are consistent in that most cases occurred in patients with pre-disposing conditions or intercurrent precipitating events that predispose to lactic acidosis [3,8,9,27,28,72]. Cases of lactic acidosis with "normal" metformin levels have been reported in patients with [33,49,[73][74][75][76][77][78][79][80][81][82][83] and without a history of diabetes [73,80,81,[84][85][86].…”

mentioning

confidence: 78%

Metformin-associated lactic acidosis: Current perspectives on causes and risk

DeFronzo

Fleming²,

Chen³

et al. 2016

Metabolism

462

333

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Although metformin has become a drug of choice for the treatment of type 2 diabetes mellitus, some patients may not receive it owing to the risk of lactic acidosis. Metformin, along with other drugs in the biguanide class, increases plasma lactate levels in a plasma concentration-dependent manner by inhibiting mitochondrial respiration predominantly in the liver. Elevated plasma metformin concentrations (as occur in individuals with renal impairment) and a secondary event or condition that further disrupts lactate production or clearance (e.g., cirrhosis, sepsis, or hypoperfusion), are typically necessary to cause metformin-associated lactic acidosis (MALA). As these secondary events may be unpredictable and the mortality rate for MALA approaches 50%, metformin has been contraindicated in moderate and severe renal impairment since its FDA approval in patients with normal renal function or mild renal insufficiency to minimize the potential for toxic metformin levels and MALA. However, the reported incidence of lactic acidosis in clinical practice has proved to be very low (<10 cases per 100,000 patient-years). Several groups have suggested that current renal function cutoffs for metformin are too conservative, thus depriving a substantial number of type 2 diabetes patients from the potential benefit of metformin therapy. On the other hand, the success of metformin as the first-line diabetes therapy may be a direct consequence of conservative labeling, the absence of which could have led to excess patient risk and eventual withdrawal from the market, as happened with earlier biguanide therapies. An investigational delayed-release metformin currently under development could potentially provide a treatment option for patients with renal impairment pending the results of future studies. This literature-based review provides an update on the impact of renal function and other conditions on metformin plasma levels and the risk of MALA in patients with type 2 diabetes.

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mentioning

confidence: 78%

Metformin-associated lactic acidosis: Current perspectives on causes and risk

DeFronzo

Fleming²,

Chen³

et al. 2016

Metabolism

462

333

View full text Add to dashboard Cite

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“…In such cases, a depressed level of consciousness may occur following several hours of lucidity, although typically it is in the setting of cardiovascular instability [47,[52][53][54][55][56]. Hypothermia, as observed in our patient, has also been well described in acute metformin overdoses [47,54,[57][58][59][60]. Similar to ethylene glycol, at most institutions including our own, metformin measurements are send out tests, with results being available days after empiric clinical management decisions are necessary.…”

Section: Could This Be Metformin-associated Lactic Acidosis?mentioning

confidence: 76%

Case Files from the University of California San Diego Health System Fellowship Coma and Severe Acidosis: Remember to Consider Acetaminophen

Villano

O'Connell

et al. 2015

J. Med. Toxicol.

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A 28-year-old man was brought to the Emergency Department (ED) for evaluation of a depressed level of consciousness that developed while in jail. Sixteen hours previously, he had been arrested on charges of murder. The patient's mental status was reported as normal at the time of arrest, and it had remained so during several hours of interrogation and during the booking process at jail. Following interrogation, the patient was placed into a cell with no other inmates. During the jail intake process, the patient had not reported any history of medical problems nor was he prescribed with any medications. Paramedics arrived to find him unresponsive, but maintaining airway reflexes and hemodynamically stable. They measured a blood glucose of 300 mg/dL and noted one episode of blood-tinged emesis during transport to the ED. No seizure activity was witnessed.On arrival to the ED, vital signs were: heart rate 132/min, blood pressure 129/74 mmHg, temperature 35.3°C (95.5°F), respiratory rate 24/min, and 100 % oxygen saturation on 15 l/ min of oxygen delivered by non-rebreather face mask.Physical examination was notable for a depressed level of consciousness. His eyes remained closed to pain, he withdrew all extremities equally to pain, and he was non-verbal. He had no signs of trauma, and his pupils were normal in size and reactive. Rapid sequence tracheal intubation was performed for airway protection. An electrocardiogram was normal except for sinus tachycardia at a rate of 111/min. An initial peripherally drawn arterial blood gas obtained immediately after intubation revealed: pH 6.97, pCO 2 40 mmHg, pO 2 215 mmHg. A computed tomography scan of the brain was normal. Initial blood chemistry panel was significant for a serum bicarbonate of 7 mEq/L, glucose of 362 mg/dL, and a normal potassium, blood urea nitrogen (BUN), creatinine, and calcium. The initial serum anion gap was 34 mEq/L. Measured serum osmolality was 320 mOsm/kg, yielding an osmol gap of 9 mOsm/kg (using formula of [2(Na)+BUN/2.8+glu-cose/18] for calculated serum osmolarity). Initial lactate was 156.5 mg/dL (normal reference range 4.5-19.8 mg/dL) and beta-hydroxybutyrate (βHB) 2.9 mg/dL (normal reference range 0.0-2.8 mg/dL). Initial liver panel included an aspartate aminotransferase (AST) of 64 U/L, alanine aminotransferase (ALT) of 27 U/L, and bilirubin of 0.4 mg/dL. Prothrombin time was 13.1 s (reference range 9.7-12.5), and lipase was normal at 25 U/L. Initial creatinine phosphokinase (CK) was slightly elevated at 373 U/L (0-175). Urinalysis was positive for small ketones and crystals were not present. Measurements of acetone and acetoacetate were not performed. Serum ethanol and salicylate levels were undetectable, and a urine drug of abuse panel by immunoassay was negative for amphetamines as a class, barbiturates as a class, benzodiazepines as a class, benzoylecgonine (cocaine metabolite), methadone, opiates as class, oxycodone, phencyclidine, and tetrahydrocannabinoids. Iron concentration was normal at 87 mcg/dL.Over the first hour of management,...

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“…Some authors advocated the use of bicarbonate prior to dialysis for treatment of lactic acidosis [17,18]. Others have reported the use of tris-hydroxymethyl aminomethane with CRRT [19]. Our therapeutic approach was immediate high-volume CVVHDF with bicarbonate buffered solution from Fresenius HF BIC ® , in order to remove the offending drug and correct high anion gap metabolic acidosis.…”

Section: Discussionmentioning

confidence: 99%

Severe Metformin Associated Lactic Acidosis: A Case Series Of An Intensive Care Unit

et al. 2015

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Background: Severe metformin-associated lactic acidosis (MALA) is a rare but potentially fatal side effect of metformin. The clinical presentation is often unspecific, thus hindering early recognition. We aimed to assess the prevalence of MALA in an intensive care unit (ICU) and describe the demographic and clinical characteristics according to patient outcome. Methods:We conducted a 13-year single-center retrospective study, including all patients admitted in ICU with a high anion-gap metabolic acidosis and hyperlactatemia secondary to therapeutic use of metformin, after excluding other medical causes of acidosis.Results: Twenty one patients were admitted in ICU due to severe MALA (less than 1% of all admissions) with an ICU mortality rate of 23.8% (N=5). The baseline clinical characteristics were similar in survivors and nonsurvivors, both with a high prevalence of cardiovascular comorbidities as well as frequent concomitant therapy with angiotensin-converting-enzyme inhibitors and diuretics. All patients were treated with continuous renal replacement therapy (CRRT) and other organ failure support. Normal acid-base balance was achieved in all survivors in the first 24 hours. At baseline, the clinical and laboratory features of nonsurvivors were undistinguishable from survivors. Conclusions:Severe MALA is a rare cause of admission in the ICU.Although early institution of supportive therapy, MALA can progress to severe multiple-organ failure, especially when diagnosis and CRRT are delayed. Clinicians should suspect of MALA in all diabetic patients taking metformin with unexplained high anion-gap metabolic acidosis and hyperlactatemia.

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Metformin-Associated Lactic Acidosis following Intentional Overdose Successfully Treated with Tris-Hydroxymethyl Aminomethane and Renal Replacement Therapy

Cited by 11 publications

References 24 publications

Metformin-associated lactic acidosis: Current perspectives on causes and risk

Metformin-associated lactic acidosis: Current perspectives on causes and risk

Case Files from the University of California San Diego Health System Fellowship Coma and Severe Acidosis: Remember to Consider Acetaminophen

Severe Metformin Associated Lactic Acidosis: A Case Series Of An Intensive Care Unit

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