Acidosis láctica en un paciente usuario de metformina / Metformin-associated lactic acidosis

Metformin is a hypoglycemic agent used as the first line for the treatment of non-insulin dependent Diabetes Mellitus. While it is a generally safe drug, it has an infrequent adverse reaction called lactic acidosis. We report a 49 year-old patient with non-insulin-requiring type 2diabetes who developed an acute kidney failure injury along with severe metabolic acidosis secondary to pneumonia during treatment.

La metformina es un agente hipoglucemiante que se ocupa de primera línea para el tratamiento de la Diabetes Mellitus no insulino dependiente. Si bien es un medicamento bien tolerado, tiene una reacción adversa bastante infrecuente que es la acidosis láctica. Reportamos el caso de una paciente de 49 años insulino no dependiente que desarrolló una injuria renal aguda junto con acidosis metabólica severa secundaria a una neumonía en tratamiento.

MALA: Acidosis láctica asociado al uso de metformina, una revisión a propósito de casos clínicos / MALA: Lactic acidosis associated with the use of metformin, review of clinical cases

La metformina es el fármaco preferido en el manejo inicial de la diabetes mellitus tipo 2 (DMT2). Aunque se recomienda su uso ampliamente, se debe tener precaución al prescribirla a poblaciones susceptibles a condiciones de riesgo de hipoperfusión sistémica, ya que puede provocar acumulación en el organismo y alteraciones metabólicas que desemboquen en acidosis láctica asociada a metformina, una complicación grave que a menudo es subdiagnosticada. Con el propósito de promover un mejor conocimiento sobre este tema, la presente revisión se centra en el análisis de la clínica, fisiopatología, diagnóstico y manejo de la acidosis láctica asociada a metformina, prestando especial atención al manejo mediante terapias de reemplazo renal. El análisis se basará en la experiencia de una serie de casos de acidosis láctica asociada a metformina atendidos en un centro clínico hospitalario en Chile.

Metformin is the preferred medication for the initial management of type 2 diabetes mellitus (T2DM). Although its use is widely recommended, caution should be exercised when prescribing it to populations susceptible to systemic hypoperfusion conditions, as it can lead to accumulation in the body and metabolic disturbances that may result in metformin-associated lactic acidosis. This severe complication is often underdiagnosed. To promote a better understanding of this topic, the present review focuses on the analysis of the clinical, pathophysiological, diagnostic, and management aspects of metformin-associated lactic acidosis, with particular attention to management through renal replacement therapies. The analysis will be based on the experience of a series of cases of metformin-associated lactic acidosis treated at a hospital clinical center in Chile.

Acidosis láctica asociada a metformina: caso clínico / Metformin-associated lactic acidosis: report of one case

Metformin-associated lactic acidosis is a severe and infrequent adverse event. Early diagnosis is essential to start an early treatment, which often has favorable results. We report a 56 years old non-insulin-requiring type 2 diabetic female who developed a severe metabolic acidosis associated with metformin in relation to an acute renal failure secondary to infectious diarrhea. Early treatment with bicarbonate and continuous hemofiltration allowed a quick improvement of the patient. Metformin-associated lactic acidosis has an elevated mortality (50-80%) and has a specific and effective treatment. Therefore, the condition must be born in mind.

Acid-base balance in sheep with experimentally induced acute ruminal lactic acidosis / Equilíbrio ácido-base em ovinos com acidose láctica ruminal aguda induzida experimentalmente

This study aimed to investigate the changes in the acid-base balance of sheep with experimentally induced acute ruminal lactic acidosis (ARA). Ten ewes orally received 15 grams of sucrose per kilogram of body mass. Arterial blood samples for blood gas analysis were obtained at the following intervals: before the induction of ARA (control), and 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 48, 72, 96, 120 and 144 hours after sucrose administration. Urine samples for pH measurement were obtained at the following times: -15 days, -7 days, and immediately before sucrose administration, then at 24, 48, 72, 96, 120 and 144 hours. Thereafter, both blood and urine samples were obtained on the 2nd, 3rd, and 4th following weeks. From 4 hours after the induction, elevation of the pH, bicarbonate and base excess on the arterial blood was observed. After 12 hours, the animals showed a decrease of these parameters, as well as urine acidification, which are symptomatic of metabolic acidosis. Within 28 hours, all parameters were normalized except the base excess, which only returned to normal after 72 hours. Despite the occurrence of acidemia, there was no need for medication and no animals died.(AU)

Este trabalho objetivou estudar as alterações referentes ao equilíbrio ácido-base de ovinos com acidose láctica ruminal aguda (ARA) induzida experimentalmente. Dez ovelhas receberam oralmente 15 gramas de sacarose por quilograma de peso corporal. Amostras de sangue arterial para realização da hemogasometria foram obtidas nos seguintes intervalos: antes da indução da ARA (controle), duas, quatro, seis, oito, 10, 12, 16, 20, 24, 28, 32, 36, 48, 72, 96, 120, 144 horas após a administração da sacarose. Amostras de urina para análise do pH urinário foram obtidas nos seguintes momentos: 15 dias, sete dias e imediatamente antes da administração da sacarose, 24, 48, 72, 96, 120 e 144 horas. Posteriormente, tanto as amostras de sangue quanto de urina foram obtidas na segunda, terceira e quarta semanas seguintes. A partir de quatro horas da indução, elevação do pH, do bicarbonato e excesso de base no sangue arterial foram observados. Após 12 horas, os animais apresentaram diminuição dos parâmetros acima citados, como também acidificação da urina, que são sintomas de acidose metabólica. Decorridas 28 horas, todos os parâmetros retornaram à normalidade, exceto o EB, que somente retornou à normalidade após 72 horas. Apesar da ocorrência da acidemia, não houve necessidade de tratamento medicamentoso e nenhum animal veio a óbito.(AU)

Hiperpotasemia extrema no fatal en un caso de acidosis láctica por sobreingesta de metformina / Non-fatal hyperkalemia in lactic acidosis due to metformin overdose. Report of one case

We report a 74-year-old man with diabetes mellitus type 2 and hypertension, who recently underwent coronary bypass surgery due to severe triple vessel disease receiving cardiological and combined antidiabetic therapy, including metformin 4 g/day. He was admitted with abdominal pain, nausea, vomiting, diarrhea and loss of consciousness. At admission, he was disoriented and agitated with signs of poor perfusion. His blood pressure was 80/70 mmHg, pulse rate 40 beats/min, respiratory rate 20-breaths/min, and axillary temperature 35°C. Biochemical profile revealed an extreme hyperkalemia of 15.4 mEq/L (double checked), elevated creatinine, uremia and brain natriuretic peptide; hypoglycemia (blood glucose 68 mg/dl) and normal C Reactive Protein. Arterial blood gases revealed severe lactic acidemia. The electrocardiogram showed sinus bradycardia, simple AV block, widened QRS with prominent T wave and prolonged QT. He was admitted to the Intensive Care Unit (ICU) with the suspicion of lactic acidosis associated with metformin, receiving fluid management, intravenous hypertonic glucose plus insulin and sodium bicarbonate, mechanical ventilation, vasopressor therapy, a temporary pacemaker lead, in addition to continuous venovenous hemodiafiltration. Two days later, the patient experienced a significant clinical improvement with normalization of the acid-base status, plasma lactate and potassium levels. On day 9, diuresis was recovered, creatinine and uremia returned to normal levels and the patient was discharged from the ICU.

Reported survival with severe mixed acidosis and hyperlactemia after toluene poisoning

Lactic acidosis is a recognized complication of the inhalant abuse such as toluene, especially in patients with renal insufficiency. We report a case of severe metabolic acidosis and hyperlactemia due to toluene sniffing. The favorable outcome, despite extremely poor clinical symptoms, signs, laboratory and radiological findings, was unexpected. Specific aspects of the clinical course are addressed. Toluene sniffing should be considered in evaluating sever metabolic acidosis. Favorable outcome could be achieved with early diagnosis and proper interventions

Acidosis láctica severa asociada a infusión de propofol: Caso clínico / Severe lactic acidosis caused by propofol infusion: Report of one case

Propofol infusion syndrome (PRIS) is a rare but potentially lethal complications. This disorder is triggered under unknown circumstances by a propofol infusion of more than 5 mg/kg/h for more than 48 h. PRIS is characterized by a multiorgan failure and rhabdomyolysis and is induced by a disturbance in mitochondrial long chain fatty acid oxidation. We report a 43 year-old woman who underwent brain surgery due to a vascular malformation. In the immediate postoperative period, she had an unexplained and severe lactic acidosis. During anaesthesia, she received a propofol infusion of 7 mg/kg/h that continued in the UCI at a rate of 3.5 mg/kg/h, for 8 hours more. The suspicion of PRIS motivated immediate discontinuation of propofol with rapid correction of lactic acidosis and full recovery of the patient.

HIV-associated neuromuscular weakness syndrome in Brazil: report of the two first cases

We describe two Brazilian patients with HIV-associated neuromuscular weakness syndrome (HANWS), a unique clinical toxic syndrome that was recently reported in developed countries. Both patients were women, used stavudine and had hyperlactatemia, one of them with lactic acidosis. Eletrophysiological studies were consistent with axonal neuropathy. After discontinuation of antiretroviral therapy the patients had significant improvement in neurologic manifestations, and normalization of lactate levels. To our knowledge, this is the first report of HANWS in developing countries. Growing use of antiretroviral therapy in this setting, particularly stavudine, make it likely that similar cases will be observed.

Os autores descrevem dois pacientes brasileiros com a síndrome da fraqueza neuromuscular associada ao HIV, uma síndrome tóxica, clínicamente particular, que foi recentemente relatada em países desenvolvidos. Ambas pacientes eram do sexo feminino, usavam estavudina e apresentaram hiperlactatemia, uma delas com acidose láctica. Os exames electrofisiológicos foram consistentes com neuropatia axonal. As pacientes melhoraram significativamente das alterações neurológicas, assim como normalizaram os níveis de lactato, após descontinuar o uso dos antiretrovirais. Até onde sabemos, este é o primeiro relato da síndrome de fraqueza neuromuscular associada ao HIV em países em desenvolvimento. Nesse contexto, o uso crescente de antiretrovirais, particularmente a estavudina, possibilitarão que casos similares sejam observados.

Lactic acidosis in HIV-I infected patients receiving antiretroviral therapy.

Highly active antiretroviral therapy (HAART) has resulted in dramatic declines in morbidity and mortality in HIV-I infected patients in the developed world. However, with the availability of generic antiretroviral treatments (ART) in India, a large number of patients now receive ART. Increase in experience with ART has led to the detection of drug-related toxicities. We report herein potentially fatal side effects associated with the use of nucleoside analogues in HIV treatment--hyperlactatemia and lactic acidosis/hepatic steatosis.

A Case of Lactic Acidosis Caused by Stavudine in an AIDS Patient

Nucleoside reverse transcriptase inhibitors (NRTIs), which are used for the treatment of human immunodeficiency virus (HIV) infection have been associated with a wide spectrum of clinical manifestations, including hepatic steatosis, lipodystrophy, myopathy, and lactic acidosis. Such adverse effects are postulated to result from the inhibition of mitochondrial DNA gamma polymerase, which causes the depletion of mitochondrial DNA and eventual the disruption of oxidative phosphorylation. Although cases of severe decompensated lactic acidosis are rare, this syndrome is associated with a high mortality rate. We report upon the first Korean case, of severe lactic acidosis in an acquired immunodeficiency syndrome (AIDS) patient receiving stavudine, an anti-HIV drug.

Lactic acidosis associated with the usual theophylline dose in a patient with asthma

Metabolic and electrolyte abnormalities, including hypokalemia, hyperglycemia and lactic acidosis, are associated with theophylline overdose. However, we report an unusual case of sinus tachycardia, lactic acidosis, hypokalemia and hyperglycemia associated with the usual theophylline dose in a patient with asthma. The theophylline dose was 200 mg orally twice daily. Three hours after administration of the third dose, the patient experienced palpitation. An electrocardiogram showed a sinus tachycardia. Arterial blood gas analysis revealed a mixed metabolic acidosis and respiratory alkalosis. Serum lactate level was 51 mmol/L (normal 0.7~2.1 mmol/L). Biochemistry results were sodium 136 mEq/L, chloride 99 mEq/L, potassium 1.9 mEq/L and glucose 204 mg/dL. Our case suggests that a possibility of theophylline-associated metabolic abnormalities should be considered when an asthmatic patient given the usual theophylline dose presents with lactic acidosis, hypokalemia and hyperglycemia of unknown etiology.

Acidosis láctica fatal en paciente con síndrome de inmunodeficiencia adquirido y tratamiento antiretroviral de alto grado de actividad: comunicación de un caso / Fatal lactic acidosis in a patient with acquired immunodeficiency syndrome treated with highly active antiretroviral therapy: case report

Type B lactic acidosis occurs without any evidence of cellular hypoxia and is associated with the use of drugs or toxins. We report a 36 years old woman with acquired immunodeficiency syndrome that was admitted to the hospital with a severe lactic acidosis. She had been treated with didanosine, stavudine and efavirenz for four months prior to admission. Despite the use of high bicarbonate doses and vasoactive drugs, the patient had a catastrophic evolution and died in shock and multiple organ failure, 68 hours after admission

Efeitos dos fármacos vasoativos na acidose lática consequente à circulaçäo extracorpórea em cirurgia cardíaca / Effects of vasoactive drugs in lactic acidosis as a consequence of extracorporeal circulation in cardiac surgery

Justificativa e objetivos: a circulaçäo extracorpórea (CEC) pode reduzir a liberaçäo de oxigênio aos tecidos causando acidose metabólica lática. Os fármacos vasoativos utilizados frequentemente para controlar a pressäo arterial, modificam a resistência vascular periférica e podem interfirir na ocorrência da acidose lática. Os objetivos deste estudo foram: 1) determinar os fatores no desenvolvimento da acidose tipo A consequente à CEC; 2) avaliar os efeitos dos fármacos vasoativos como fatores coadjuvantes ou näo desta acidose. Método: participaram do estudo trinta pacientes submetios à revascularizaçäo do miocárdio e distribuídos em três grupos: I - näo utilizou agentes vasoativos; grupo II - utilizou epidefrina; grupo III - utilizou nitroprussiato de sódio e droperidol. Foram avaliados os parâmetros fisiológicos, oxigenaçäo tecidual, equilíbrio ácido-base e osmolalidade plasmática nos períodos: pré-CEC; CEC-32ºC; CEC-37ºC e pós-CEC. Resultados: o transporte e consumo de oxigênio foram reduzidos durante a CEC. Também ocorreu reduçäo significativa no pH arterial e bicarbonato plasmático associados ao aumento do lactato sanguíneo nos grupos I e II, durante e após a CEC. No grupo I as variaçöes destes parâmetros näo foram significativas quando conparados aos grupos II e III. A osmolalidade plasmática näo olterou significativamente nos grupos. Conclusäo: a acidose lática tipo A consequente à CEC, provalvelmente ocorreu por hipoperfusäo tecidual e näo hipoxemia. Foi observada acidose lática no grupo I devido aos efeitos da hipotermia, hemodiluiçäo e baixo fluxo de perfusäo. No grupo II, a norepinefrina parece ter acentuado a acidose lática tipo A. No grupo III, a administraçäo dos fármacos vasodilatodores durante a CEC parece ter contribuído favoravelmente com a redistribuiçäo do fluxo tecidual, prevenindo-se a acidose lática tipo A

Biguanidas (metformin) y acidosis láctica. Reporte de un caso y revisión de la literatura / Biguanides (metformin) and lactic acidosis. case report

Introducción. El metformin puede desencadenar acidosis láctica en presencia de insuficiencia renal aguda. Objetivo. Reportar un caso de acidosis láctica secundaria a metformin en presencia de función renal normal. Reporte del caso. Un paciente de 45 años de edad con historia de diabetes mellitus no insulino-dependiente, tipo 2, ingresó a una ICU. Tenía vómito y debilidad después de 13 días de tratamiento con metformin (2,000 mg/d). Al ingreso tenía TA 80/40, FC 110/min. FR 32/min. Laboratorio: pH 6.77, PaCO2 10mmHg, PaO2 300 mmHg, glucosa 79 mg/dL, urea 191 mg/dL, creatinina 9.5 mg/dL, ácido láctico 34 mmol/L. Se realizaron maniobras enérgicas que incluyeron ventilación mecánica, administración de líquidos y diálisis peritoneal; se recuperó rápidamente y se dio de alta a su domicilio cinco días depués