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1.
Medicine (Baltimore) ; 99(41): e22492, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031284

RESUMO

RATIONALE: Metformin-associated lactic acidosis (MALA) is a rare adverse effect that has significant morbidity and mortality. MALA is a high anion gap (AG), nonosmolar acidosis. Associated osmolar-gap (OG) is rarely reported, so finding an OG may make the diagnosis of MALA challenging. PATIENT CONCERNS: Forty-five years' old type II diabetic patient on metformin presented to emergency with a two-day history of vomiting, watery diarrhea, and mild abdominal discomfort. On examinations, he looked dehydrated. Investigation revealed acute kidney injury (AKI) with a high lactic acid (LA) level of 24 mmol/L, pH of 6.8, AG of 40, and an OG of 20 mOsm/kg DIAGNOSES:: The presence of an OG made the diagnosis challenging; the history was negative for alcohol, osmolar substance, or illicit drug ingestion or use. The toxicology screen was negative. After ruling out plausible causes of AG and OG, MALA was deemed the likely reason for his presentation likely precipitated by dehydration and AKI. INTERVENTIONS: He underwent two sessions of hemodialysis, afterward managed with fluid hydration. OUTCOMES: On day 3, he was in the polyuric phase suggestive of acute tubular necrosis. His serum creatinine improved afterward with improved acidosis; after 8 days, he was discharged in stable condition. LESSONS: MALA is a rare side effect of metformin therapy. Acute kidney injury is a known precipitant of MALA. In our review, we highlight the association of MALA and the presence of an OG. We believe that treating physicians should be aware of this relationship to avoid delaying or overlooking such an important diagnosis.


Assuntos
Acidose Láctica/sangue , Acidose Láctica/induzido quimicamente , Lesão Renal Aguda/complicações , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Concentração Osmolar , Desequilíbrio Ácido-Base , Acidose Láctica/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade
2.
Medicine (Baltimore) ; 99(33): e21743, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872062

RESUMO

INTRODUCTION: FOLFOX therapy is the main chemotherapy regimen for colorectal cancer. Peripheral neuropathy, hematotoxicity, and digestive symptoms are known to be the most frequent adverse events. Hyperammonemia and lactic acidosis rarely occur simultaneously during treatment with FOLFOX therapy; the number of case reports is limited worldwide. We report a case of disturbance of consciousness, considered to be caused by hyperammonemia and lactic acidosis that occurred during treatment with mFOLFOX6 therapy that was administered as postoperative adjuvant treatment for rectal cancer. PATIENT CONCERNS: This case was of a 71-year-old man who had been receiving oral treatment for chronic kidney disease and diabetes mellitus. Laparoscopic low anterior resection and artificial anal construction surgery were performed for stage III rectal cancer. As adjuvant postoperative therapy, mFOLFOX6 therapy was started but was followed by a disturbance of consciousness. DIAGNOSES: Results of the blood tests revealed notable hyperammonemia (ammonia level, 1,163 µg/dl) and lactic acidosis (pH 7.207; lactate, 17.56 mmol/L); however, imaging diagnosis did not reveal intracranial lesions that could cause disturbance of consciousness. INTERVENTIONS: For hyperammonemia, branched-chain amino acid agents and Ringers solution supplementation were administered. For acidosis, 7% sodium hydrogen carbonate was administered as treatment. OUTCOMES: The disturbance of consciousness improved within 12 hours of initiating the treatment, and the patient was discharged with no sequelae on 7th day after hospitalization. CONCLUSION: In patients with chronic kidney disease, FOLFOX regimen may confer risks of hyperammonemia and lactic acidosis.


Assuntos
Acidose Láctica/complicações , Antimetabólitos Antineoplásicos/efeitos adversos , Transtornos da Consciência/etiologia , Fluoruracila/efeitos adversos , Hiperamonemia/complicações , Acidose Láctica/induzido quimicamente , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Humanos , Hiperamonemia/induzido quimicamente , Masculino , Neoplasias Retais/tratamento farmacológico
3.
Cell Metab ; 32(4): 537-547.e3, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32861268

RESUMO

The safety and efficacy of anti-diabetic drugs are critical for maximizing the beneficial impacts of well-controlled blood glucose on the prognosis of individuals with COVID-19 and pre-existing type 2 diabetes (T2D). Metformin is the most commonly prescribed first-line medication for T2D, but its impact on the outcomes of individuals with COVID-19 and T2D remains to be clarified. Our current retrospective study in a cohort of 1,213 hospitalized individuals with COVID-19 and pre-existing T2D indicated that metformin use was significantly associated with a higher incidence of acidosis, particularly in cases with severe COVID-19, but not with 28-day COVID-19-related mortality. Furthermore, metformin use was significantly associated with reduced heart failure and inflammation. Our findings provide clinical evidence in support of continuing metformin treatment in individuals with COVID-19 and pre-existing T2D, but acidosis and kidney function should be carefully monitored in individuals with severe COVID-19.


Assuntos
Acidose/induzido quimicamente , Infecções por Coronavirus/complicações , Diabetes Mellitus Tipo 2/complicações , Metformina/efeitos adversos , Pneumonia Viral/complicações , Acidose Láctica/induzido quimicamente , Idoso , China/epidemiologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hospitalização , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Estudos Retrospectivos
4.
S Afr Med J ; 110(4): 313-319, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32657744

RESUMO

BACKGROUND: The goal of antiretroviral therapy (ART) is to suppress viral replication to undetectable levels. These low viral load (VL) levels may not be attained in some patients, a situation representing potential virological failure during the course of treatment. OBJECTIVES: To present the results of a Markov model exploring how virological failure and active tuberculosis (TB) affect the progression of HIV in patients on ART. METHODS: A continuous-time non-homogeneous Markov model was used to model the progression of HIV/AIDS in patients on combination ART (cART). We define seven states in our model. The first five states are based on VL levels and the other two are absorbing states: death and withdrawal from the study. The effects of TB co-infection, baseline VL, lactic acidosis and treatment failure on transition intensities were assessed. RESULTS: The model shows that VL-based transition intensities do not follow a constant rate; rather, there are two different trends in HIV/AIDS progression. The first trend is an increase in the prevalence of state 1 (undetectable VL levels) in the first 0.5 years of treatment. The second trend follows thereafter and shows a slow decrease. Within the first 0.5 years of therapeutic intervention, the undetectable VL state is therefore attainable from any VL state. However, when virological failure occurs, there is an increased risk of death. Developing active TB while on cART increases the risk of viral rebound from undetectable levels to VLs between 50 and 10 000 copies/mL by ~1.03-fold. From a VL between 10 000 and 100 000 copies/mL, developing TB while on cART increases the rate of viral rebound by ~2.5-fold. However, if TB is detected and treated at enrolment, rates of viral rebound from undetectable levels are reduced. CONCLUSIONS: The model confirms that virological failure, coupled with developing active TB while on cART, increases mortality rates irrespective of patient CD4+ count status. It also suggests that while TB at the time of cART initiation does not increase the risk of viral rebound, development of active TB after cART initiation does increase this risk. These findings highlight the importance of strengthening VL monitoring, which should be performed every 2 months, especially in patients with TB, and addressing unsuppressed VLs appropriately if they are detected.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Antituberculosos/uso terapêutico , Coinfecção , Infecções por HIV/tratamento farmacológico , Tuberculose/tratamento farmacológico , Acidose Láctica/induzido quimicamente , Síndrome de Imunodeficiência Adquirida/sangue , Síndrome de Imunodeficiência Adquirida/complicações , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Adolescente , Adulto , Idoso , Contagem de Linfócito CD4 , Progressão da Doença , Interações Medicamentosas , Farmacorresistência Viral , Feminino , Infecções por HIV/sangue , Infecções por HIV/complicações , Humanos , Tuberculose Latente/complicações , Masculino , Cadeias de Markov , Adesão à Medicação , Pessoa de Meia-Idade , Mortalidade , Doenças do Sistema Nervoso Periférico/induzido quimicamente , População Rural , África do Sul , Resposta Viral Sustentada , Falha de Tratamento , Tuberculose/complicações , Carga Viral , Adulto Jovem
5.
Ann Endocrinol (Paris) ; 81(2-3): 101-109, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: covidwho-380104

RESUMO

Diabetes is among the most frequently reported comorbidities in patients infected with COVID-19. According to current data, diabetic patients do not appear to be at increased risk of contracting SARS-CoV-2 compared to the general population. On the other hand, diabetes is a risk factor for developing severe and critical forms of COVID-19, the latter requiring admission to an intensive care unit and/or use of invasive mechanical ventilation, with high mortality rates. The characteristics of diabetic patients at risk for developing severe and critical forms of COVID-19, as well as the prognostic impact of diabetes on the course of COVID-19, are under current investigation. Obesity, the main risk factor for incident type 2 diabetes, is more common in patients with critical forms of COVID-19 requiring invasive mechanical ventilation. On the other hand, COVID-19 is usually associated with poor glycemic control and a higher risk of ketoacidosis in diabetic patients. There are currently no recommendations in favour of discontinuing antihypertensive medications that interact with the renin-angiotensin-aldosterone system. Metformin and SGLT2 inhibitors should be discontinued in patients with severe forms of COVID-19 owing to the risks of lactic acidosis and ketoacidosis. Finally, we advise for systematic screening for (pre)diabetes in patients with proven COVID-19 infection.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/terapia , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Acidose Láctica/induzido quimicamente , Acidose Láctica/epidemiologia , Acidose Láctica/virologia , Betacoronavirus/fisiologia , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Estado Terminal/epidemiologia , Estado Terminal/terapia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Cetoacidose Diabética/induzido quimicamente , Cetoacidose Diabética/epidemiologia , Cetoacidose Diabética/virologia , Humanos , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Metformina/uso terapêutico , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/terapia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Estado Pré-Diabético/complicações , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/terapia , Sistema Renina-Angiotensina/fisiologia , Fatores de Risco , Gestão de Riscos , Índice de Gravidade de Doença , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Suspensão de Tratamento
6.
Ann Endocrinol (Paris) ; 81(2-3): 101-109, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32413342

RESUMO

Diabetes is among the most frequently reported comorbidities in patients infected with COVID-19. According to current data, diabetic patients do not appear to be at increased risk of contracting SARS-CoV-2 compared to the general population. On the other hand, diabetes is a risk factor for developing severe and critical forms of COVID-19, the latter requiring admission to an intensive care unit and/or use of invasive mechanical ventilation, with high mortality rates. The characteristics of diabetic patients at risk for developing severe and critical forms of COVID-19, as well as the prognostic impact of diabetes on the course of COVID-19, are under current investigation. Obesity, the main risk factor for incident type 2 diabetes, is more common in patients with critical forms of COVID-19 requiring invasive mechanical ventilation. On the other hand, COVID-19 is usually associated with poor glycemic control and a higher risk of ketoacidosis in diabetic patients. There are currently no recommendations in favour of discontinuing antihypertensive medications that interact with the renin-angiotensin-aldosterone system. Metformin and SGLT2 inhibitors should be discontinued in patients with severe forms of COVID-19 owing to the risks of lactic acidosis and ketoacidosis. Finally, we advise for systematic screening for (pre)diabetes in patients with proven COVID-19 infection.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/terapia , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Acidose Láctica/induzido quimicamente , Acidose Láctica/epidemiologia , Acidose Láctica/virologia , Betacoronavirus/fisiologia , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Estado Terminal/epidemiologia , Estado Terminal/terapia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Cetoacidose Diabética/induzido quimicamente , Cetoacidose Diabética/epidemiologia , Cetoacidose Diabética/virologia , Humanos , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Metformina/uso terapêutico , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/terapia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Estado Pré-Diabético/complicações , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/terapia , Sistema Renina-Angiotensina/fisiologia , Fatores de Risco , Gestão de Riscos , Índice de Gravidade de Doença , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Suspensão de Tratamento
7.
Artigo em Alemão | MEDLINE | ID: mdl-32069482

RESUMO

Metformin-associated lactic acidosis (MALA) is a difficult to diagnose and potentially life-threatening disease. We report a rare case of severe MALA treated at our hospital's intensive care unit. Suspected diagnosis of MALA and quick initiation of an adequate therapy containing renal replacement therapy led to successful management of this complicated MALA-case.


Assuntos
Acidose Láctica , Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Metformina , Acidose Láctica/induzido quimicamente , Idoso , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hospitais , Humanos , Hipoglicemiantes/efeitos adversos , Unidades de Terapia Intensiva , Metformina/efeitos adversos , Terapia de Substituição Renal
8.
Aliment Pharmacol Ther ; 51(5): 565-575, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31960986

RESUMO

BACKGROUND: The FDA approved 'label' for metformin lists hepatic insufficiency as a risk for lactic acidosis. Little evidence supports this warning. AIMS: To investigate the safety and pharmacokinetics of metformin in patients with chronic liver disease (CLD). METHODS: Chronic liver disease patients with and without type 2 diabetes mellitus (T2DM) were studied by a cross-sectional survey of patients already prescribed metformin (n = 34), and by a prospective study where metformin (500 mg, immediate release, twice daily) for up to 6 weeks was prescribed (n = 24). Plasma metformin and lactate concentrations were monitored. Individual pharmacokinetics were obtained and compared to previously published values from healthy and T2DM populations without CLD. RESULTS: All plasma metformin and lactate concentrations remained below the putative safety thresholds (metformin, 5 mg/L; lactate, 5 mmol/L). Lactate concentrations were unrelated to average steady-state metformin concentrations. In patients with CLD, T2DM was associated with higher plasma lactate concentrations (48% higher than those without T2DM, P < 0.0001). CLD patients with cirrhosis had 23% higher lactate concentrations than those without cirrhosis (P = 0.01). The pharmacokinetics of metformin in CLD patients were similar to patients with T2DM and no liver disease. The ratio of apparent metformin clearance (CLMet /F) to creatinine clearance was marginally lower in CLD patients compared to healthy subjects (median, interquartile range; 12.6, 9.5-15.9 vs 14.9, 13.4-16.4; P = 0.03). CONCLUSIONS: The pharmacokinetics of metformin are not altered sufficiently in CLD patients to raise concerns regarding unsafe concentrations of metformin. There were no unsafe plasma lactate concentrations observed in CLD patients receiving metformin (ACTRN12619001292167; ACTRN12619001348145).


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Metformina/efeitos adversos , Metformina/farmacocinética , Acidose Láctica/sangue , Acidose Láctica/induzido quimicamente , Acidose Láctica/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Comorbidade , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Hipoglicemiantes , Ácido Láctico/sangue , Hepatopatias/complicações , Hepatopatias/epidemiologia , Hepatopatias/metabolismo , Masculino , Metformina/administração & dosagem , Metformina/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença
9.
J Med Case Rep ; 13(1): 371, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31842973

RESUMO

BACKGROUND: Metformin has been widely used as a first-line agent to treat type 2 diabetes mellitus. Lactic acidosis is a rare but serious adverse effect in patients treated with metformin. Recent studies noted a correlation between metformin accumulation and lactic acidosis. Continuous renal replacement therapy for the treatment of metformin-associated lactic acidosis has been documented in some case reports; however, there is currently no specific treatment for metformin-associated lactic acidosis. CASE PRESENTATION: A 70-year-old Japanese woman with type 2 diabetes mellitus presented to an emergency room with metformin-associated lactic acidosis. She was found to be hypotensive and laboratory examinations revealed severe lactic acidosis: pH 6.618, partial pressure of carbon dioxide in arterial blood 17.3 mmHg, bicarbonate 1.7 mmol/L, and lactate 18 mmol/L. Severe acidemia persisted despite supportive care including intravenously administered fluids, sodium bicarbonate, antibiotics, and vasopressors. Continuous renal replacement therapy was initiated in our intensive care unit. After dialysis for 3 days, her lactate level and pH value completely normalized. The concentration of metformin detected was 77.5 mg/L, which is one of the highest in metformin-associated lactic acidosis successfully treated without overdose. CONCLUSIONS: The present case had one of the highest metformin concentrations in metformin-associated lactic acidosis successfully treated with continuous renal replacement therapy, and serum metformin concentrations may be useful for the diagnosis of metformin-associated lactic acidosis. Metformin-associated lactic acidosis is a rare but important etiology of lactic acidosis. Continuous renal replacement therapy is advantageous for the treatment of hemodynamically unstable patients with metformin-associated lactic acidosis.


Assuntos
Acidose Láctica/terapia , Terapia de Substituição Renal Contínua , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Acidose Láctica/induzido quimicamente , Idoso , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Resultado do Tratamento
10.
Rev. esp. anestesiol. reanim ; 66(9): 483-486, nov. 2019.
Artigo em Espanhol | IBECS | ID: ibc-187757

RESUMO

La prevalencia mundial de diabetes mellitus (DM) ha aumentado drásticamente en las últimas 2 décadas, y esto afecta al 10-15% de la población quirúrgica1. La metformina representa el pilar de la terapia antihiperglucémica para la DM tipo 2, que proporciona numerosos efectos beneficiosos. Sin embargo, un efecto adverso raro, pero grave, es el desarrollo de acidosis láctica asociada a metformina (MALA) con una alta tasa de mortalidad. Describimos un caso grave de MALA en el período postoperatorio, que culminó en un paro cardíaco. Por lo tanto, los anestesistas deben tener conocimientos y ser expertos en el cuidado de pacientes con diabetes, siendo imperativo centrarse en la evaluación preoperatoria, la optimización, el tratamiento preexistente durante el período de inanición y la identificación de pacientes medicados con metformina en situación de riesgo de desarrollar MALA


The worldwide prevalence of diabetes mellitus (DM) has risen dramatically over the past two decades and this affects 10-15% of the surgical population1. Metformin represents the mainstay of anti-hyperglycaemic therapy for type 2 DM, providing numerous beneficial effects. However, a rare but severe adverse effect is the development of metformin-associated lactic acidosis (MALA) with high mortality rate. We describe a severe case of MALA in the postoperative period that culminated in cardiac arrest. Whereby anaesthetists should be knowledgeable and skilled in the care of patients with diabetes being imperative to focus on preoperative assessment, optimisation, management of pre-existing treatment during the starvation period and identification of patients medicated with metformin at risk of developing MALA


Assuntos
Humanos , Feminino , Idoso , Acidose Láctica/induzido quimicamente , Metformina/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Procedimentos Cirúrgicos em Ginecologia/métodos , Complicações Intraoperatórias/epidemiologia , Monitorização Intraoperatória/métodos , Suspensão de Tratamento , Insuficiência Renal Crônica/complicações
11.
Clin Lab ; 65(10)2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31625353

RESUMO

BACKGROUND: Lung involvement is rare in peripheral T cell lymphoma, and there is a lack of sufficient clinical study. The authors describe a rare case of lung involvement in a 40-year-old male patient with peripheral T cell lymphoma. METHODS: Hematological investigation, bone marrow aspirate, and lung biopsy were performed. RESULTS: The patient received 4 courses of CHOP regimen chemotherapy. He achieved partial response (PR) at the 2nd course, but showed disease progressive (PD) at the 4th course. Then he received 2 courses of GDP regimen chemotherapy. Unfortunately, the patient died of tumor overload with hyper-lactacidemia 6 months after the onset of the disease. CONCLUSIONS: Lung biopsy is important to confirm a diagnosis of primary pulmonary lymphoma. Lung involvement in peripheral T cell lymphoma as a prognostic factor needs further studies.


Assuntos
Neoplasias Pulmonares/patologia , Pulmão/patologia , Linfoma de Células T Periférico/patologia , Acidose Láctica/induzido quimicamente , Acidose Láctica/complicações , Acidose Láctica/diagnóstico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Evolução Fatal , Humanos , Ácido Láctico/sangue , Pulmão/efeitos dos fármacos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Linfoma de Células T Periférico/complicações , Linfoma de Células T Periférico/tratamento farmacológico , Masculino , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Vincristina/administração & dosagem , Vincristina/efeitos adversos
12.
Ir Med J ; 112(8): 992, 2019 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-31650826

RESUMO

Introduction Metformin is considered the first line oral hypoglycaemic agent for the treatment of type 2 diabetes. We report three cases of prospectively identified laboratory confirmed metformin-associated lactic acidosis admitted to our intensive care unit. Case 1 72-year-old female presented with lactic acidosis; pH 6.7, lactate 22.6mmol/L with elevated Metformin levels of 4.9mg/L. Case 2 56-year-old female presented with lactic acidosis; pH 7.2 and lactate 14.8mmol/L. Metformin levels elevated at 3.9mg/L. Case 3 72-year-old female presented with lactic acidosis, pH 6.95 and lactate of 27.6mmol/L with elevated Metformin levels of 48.7mg/L. Results All three cases were admitted to the intensive care unit to receive supportive care. Despite CVVHD, two patients died. Discussion Metformin is considered the first line oral hypoglycaemic agent. Confirmation of this diagnosis often proves difficult due to the scarcity of laboratory testing. Our case series highlights the issues of inappropriate prescription in specific patient populations.


Assuntos
Acidose Láctica/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Acidose Láctica/sangue , Acidose Láctica/terapia , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/sangue , Terapia de Substituição Renal Contínua , Evolução Fatal , Feminino , Humanos , Concentração de Íons de Hidrogênio , Hipoglicemiantes/sangue , Ácido Láctico/sangue , Metformina/sangue , Pessoa de Meia-Idade
13.
Diabetes Res Clin Pract ; 157: 107879, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31618624

RESUMO

Metformin, the first choice drug for type 2 diabetes treatment in all stages of therapy, and one of the most widely prescribed anti-hyperglycemic agents worldwide, represents a rare example of an old drug which continues to display new beneficial effects in various fields. However, lactic acidosis (LA) persists as a serious adverse effect. LA incidence is low and is not necessarily determined by the administration of metformin. Unfortunately, the concern for this complication has negatively affected the drug use, particularly in chronic kidney disease, which may impair drug excretion, and in congestive heart failure and chronic liver disease, which may promote lactate accumulation. This review describes how not only these historical contraindications have been considerably scaled back, though rather a recent large body of evidence supports a protective effect of biguanide on kidney, heart and liver and, maybe, against lactic acidosis itself. It is worthy to slow down both contraindications and precautions to metformin use, not to deprive a significant number of diabetic patients, as those with kidney, heart and liver comorbidities, from its potential benefits, and not to hamper in the near future the putative advantages in a wide spectrum of conditions outside of diabetes.


Assuntos
Acidose Láctica/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/efeitos adversos , Diabetes Mellitus Tipo 2/patologia , Humanos , Hipoglicemiantes/farmacologia , Metformina/farmacologia
15.
Drug Saf ; 42(12): 1449-1469, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31372935

RESUMO

INTRODUCTION AND OBJECTIVES: There is increasing evidence to suggest that therapeutic doses of metformin are unlikely to cause lactic acidosis. The aims of this research were (1) to formally evaluate the association between metformin therapy and lactic acidosis in published case reports using two causality scoring systems, (2) to determine the frequency of pre-existing independent risk factors in published metformin-associated lactic acidosis cases, (3) to investigate the association between risk factors and mortality in metformin-associated lactic acidosis cases, and (4) to explore the relationship between prescribed metformin doses, elevated metformin plasma concentrations and the development of lactic acidosis in cases with chronic renal impairment. METHODS: A systematic review was conducted to identify metformin-associated lactic acidosis cases. Causality was assessed using the World Health Organisation-Uppsala Monitoring Centre system and the Naranjo adverse drug reaction probability scale. Compliance to dosing guidelines was investigated for cases with chronic renal impairment as well as the association between steady-state plasma metformin concentrations prior to admission. RESULTS: We identified 559 metformin-associated lactic acidosis cases. Almost all cases reviewed (97%) presented with independent risk factors for lactic acidosis. The prescribed metformin dose exceeded published guidelines in 60% of cases in patients with impaired kidney function. Metformin steady-state plasma concentrations prior to admission were predicted to be below the proposed upper limit of the therapeutic range of 5 mg/L. CONCLUSIONS: Almost all cases of metformin-associated lactic acidosis reviewed presented with independent risk factors for lactic acidosis, supporting the suggestion that metformin plays a contributory role. The prescribed metformin dose, on average, exceeded the dosing recommendations by 1000 mg/day in patients with varying degrees of renal impairment but the predicted pre-admission plasma concentrations did not exceed the therapeutic range.


Assuntos
Acidose Láctica/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Acidose Láctica/epidemiologia , Causalidade , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Insuficiência Renal Crônica/complicações , Fatores de Risco
16.
BMJ Case Rep ; 12(7)2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31350229

RESUMO

While potassium cyanide poisoning has been well described, the toxicity of potassium gold cyanide is less well understood. This case describes an 84-year-old man who presented after an intentional ingestion of 0.5-1 teaspoons of potassium gold cyanide. Despite antidotal therapy, the patient rapidly developed severe lactic acidosis, multiorgan dysfunction and ultimately expired. While the patient's clinical findings were consistent with acute cyanide poisoning, a serum cyanide level was below the toxic threshold. Previous reports have suggested that gold toxicity may also contribute to the effects of potassium gold cyanide, and may have played a role in the patient's rapid decline. In addition to treatment of cyanide toxicity, management of acute gold toxicity should also be considered in potassium gold cyanide ingestion.


Assuntos
Acidose Láctica/induzido quimicamente , Cianatos/envenenamento , Compostos de Ouro/envenenamento , Ouro/envenenamento , Cianeto de Potássio/envenenamento , Suicídio , Idoso de 80 Anos ou mais , Humanos , Masculino
17.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 44(6): 714-719, 2019 Jun 28.
Artigo em Chinês | MEDLINE | ID: mdl-31304935

RESUMO

The incidence of telbivudine-related adverse reactions has been gradually increased. The increased levels of muscle enzymes and blood lactate are common. In this case, a 23-year-old male patient with long-term oral telbivudine had a rare serious adverse reaction. The main clinical manifestations were progressive myalgia, gradually progressed to mental disorder, and together with multiple organ dysfunction, in which the level of blood lactate was increased significantly and metabolic acidosis was extremely severe. Blood purification and sodium bicarbonate were given to correct acidosis, while ceftazidime was used to prevent infection. Telbivudine was discontinued, and tenofovir disoproxil fumarate and liver protective drug were used. The patient was discharged with a better health condition. Such patients are easily misdiagnosed as neuromuscular diseases in the early stage, which might delay the treatment and worsen medical conditions. Clinicians need to be cautious and obtain an early identification to avoid misdiagnosis.


Assuntos
Acidose Láctica , Telbivudina/efeitos adversos , Acidose Láctica/induzido quimicamente , Evolução Fatal , Humanos , Masculino , Insuficiência de Múltiplos Órgãos , Adulto Jovem
18.
Pharmacotherapy ; 39(9): 946-963, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31361914

RESUMO

Hyperlactatemia and lactic acidosis are two syndromes that are associated with morbidity and mortality. Medication-induced hyperlactatemia and lactic acidosis are diagnoses of exclusion and have the potential to be overlooked. The purposes of this systematic review are to identify published reports of medication-induced lactate level elevations to aid clinicians in diagnosing and comprehending the underlying mechanism of this rare adverse drug effect and to provide management strategies. The PubMed database was searched for case reports, case series, retrospective studies, and prospective studies describing cases of medication-induced lactate level elevation, including lactic acidosis and hyperlactatemia, published between January 1950 and June 2017. A standardized search strategy was used, and the articles identified underwent two rounds of independent evaluation by two reviewers to assess for inclusion. Articles were included if they described at least one patient older than 12 years with hyperlactatemia or lactic acidosis caused by a medication with United States Food and Drug Administration (FDA) approval and if alternative etiologies for an elevated lactate level were ruled out. Metformin and nucleoside/nucleotide reverse transcriptase inhibitors were excluded since the pathophysiology and incidence of lactic acidosis have been well established for these agents. Overall, 1918 articles were identified, and 101 met inclusion criteria. A total of 286 patients experienced medication-induced lactate level elevations, from which 59 unique medications were identified. The most commonly identified agents were epinephrine and albuterol. Medication-induced lactate level elevation was classified as lactic acidosis (64.0%), hyperlactatemia (31.1%), or not specified (4.9%). The doses ingested included FDA-labeled doses (86%), intentional overdoses (10.8%), or prescribed doses exceeding the FDA-labeled dose (3.1%). Medications were continued without a change (40.8%), were permanently discontinued (34.4%), were continued with a dosage reduction (11.6%), or were initially withheld then resumed after lactate level normalized (2.9%); medication management for the remaining 10.0% was not reported. Forty-six patients died (16%). Six deaths were attributed by treating clinicians to be secondary to medication-induced lactic acidosis. Management strategies were heterogeneous, and treatment included supportive care, exogenous bicarbonate therapy, medication specific antidotes, and decontamination strategies. Unexplained lactate level elevations should prompt clinicians to assess for medication-induced lactate level elevations. Pharmacists are members of the health care team that are well positioned to serve as experts in the diagnosis and management of medication-induced lactate level elevations.


Assuntos
Acidose Láctica/induzido quimicamente , Hiperlactatemia/induzido quimicamente , Medicamentos sob Prescrição/efeitos adversos , Relação Dose-Resposta a Droga , Overdose de Drogas/epidemiologia , Humanos , Uso Indevido de Medicamentos sob Prescrição/estatística & dados numéricos , Estados Unidos
19.
Rev. clín. esp. (Ed. impr.) ; 219(5): 236-242, jun.-jul. 2019. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-186557

RESUMO

Antecedentes y objetivos: Estudio observacional sobre la diferencia entre el número de casos diagnosticados en situación clínica habitual de acidosis con hiperlactacidemia sospechosa de ser causada por metformina y su incidencia según la ficha técnica. Adicionalmente se exploró la relación con la función renal de la acidosis hiperlactacidémica por metformina. Pacientes: Se identificaron los casos de acidosis entre los años 2013 y 2014 mediante el análisis del CMBD y las peticiones al laboratorio. Se seleccionó a los pacientes que presentaban lactato venoso > 2,7 mmol/L en el momento de ser atendidos y para los que constaba el uso ambulatorio de metformina. La relación causal con la metformina fue evaluada independientemente por varios investigadores. Los casos incidentes se calcularon con base en el número de pacientes a los que se les había dispensado un medicamento que contuviera metformina durante el mismo periodo en el área estudiada. Resultados: Se identificaron 476 casos de acidosis, de los que en 20 se consideró que la metformina era sospechosa de causar el cuadro de acidosis con hiperlactacidemia, lo que supone una incidencia de 6,57/10.000 pacientes. El 85% de los casos presentaban insuficiencia renal aguda. Conclusiones: La incidencia aparente de acidosis con hiperlactacidemia en pacientes tratados con metformina es mayor que la establecida en la ficha técnica (inferior a 1/10.000). El desarrollo de acidosis con hiperlactacidemia por metformina está relacionado con el deterioro agudo de la función renal


Background and objectives: Observational study on the difference between the number of cases of acidosis with hyperlactacidaemia suspected of being caused by metformin diagnosed in standard clinical practice and the incidence of this condition according to the datasheet. The study also explored the relationship between renal function and metformin-associated hyperlactacidaemia acidosis. Patients: We identified cases of acidosis between 2013 and 2014 by analysing the minimum basic data set and laboratory requests. We selected patients who presented venous lactate levels >2.7 mmol/L at the time they were treated and for whom the use of outpatient metformin was confirmed. The causal relationship with metformin was independently evaluated by several researchers. The incident cases were calculated based on the number of patients who had been dispensed a drug containing metformin during the same period in the study area. Results: We identified 476 cases of acidosis. Metformin was suspected of causing the condition of acidosis with hyperlactacidaemia in 20 of these cases, which represents an incidence rate of 6.57/10,000 patients. Eighty-five percent of the cases presented acute renal failure. Conclusions: The apparent incidence of acidosis with hyperlactacidaemia in patients treated with metformin is greater than that established in the datasheet (<1/10,000). The onset of metformin-associated hyperlactacidaemia acidosis is related to acute renal impairment


Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Hiperlactatemia/induzido quimicamente , Metformina/efeitos adversos , Lesão Renal Aguda/epidemiologia , Acidose Láctica/induzido quimicamente , Testes de Função Renal/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Acidose Láctica/epidemiologia , Insuficiência Renal Crônica/epidemiologia
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