Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 102
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Nefrología (Madrid) ; 39(1): 35-43, ene.-feb. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-181907

RESUMO

Objetivos: Conocer la incidencia de casos de acidosis láctica por metformina durante el periodo enero de 2014 y marzo de 2017 en el Área Sanitaria III de Aragón. Analizar los factores clínicos y analíticos asociados y la mortalidad. Resultados: Treinta y un casos (61,3% varones). Incidencia: 79,76 casos/100000 pacientes-año; edad media 75,39 ± 9,34 años; 23 de ellos con niveles séricos de metformina (21,91 ± 15,52 mcg / mL); miligramos/día de metformina ingeridos: 1790,32 ± 499; 96,8% de casos en el contexto de fracaso renal agudo; 11 casos con antecedentes de enfermedad renal crónica (35,5%); 12 requirieron UCI (38,7%); 13 requirieron tratamiento depurador (41,9%; 3 hemodiafiltración, 10 hemodiálisis) Existió correlación significativa entre: miligramos diarios ingeridos de metformina y niveles del fármaco; niveles de metformina y: creatinina pico, pH y lactato. La mortalidad fue del 25,8%. Solo hubo diferencias significativas entre los fallecidos y los supervivientes respecto a la duración de la estancia y la creatinina final. La regresión logística multivariante no detectó ninguna variable del estudio asociada con la mortalidad. Conclusiones: La incidencia en nuestra área sanitaria es más elevada que en otras series, con 25,8% de mortalidad. Prácticamente todos los casos en el contexto de fracaso renal agudo de origen prerrenal. En un 29% de los casos hubo sobredosificación. Es necesario advertir a los pacientes de las situaciones más frecuentes potencialmente inductoras de acidosis láctica, especialmente la deshidratación, si siguen tomando el fármaco durante las mismas


Objectives: To determine the incidence of metformin-induced lactic acidosis during the period January 2014 to March 2017 in Aragon Healthcare Area III. To analyse the associated clinical and analytical factors and mortality. Results: A total of 31 cases (61.3% males). Incidence: 79.76 cases/100,000 patients-year; mean age 75.39±9.34 years; 23 of them with levels of serum metformin (21.91 ± 15.52 mcg/ ml); milligrams/day of metformin ingested: 1790.32 ± 499; 96.8% of cases in the context of acute kidney failure; 11 cases with a history of chronic kidney disease (35.5%); 12 required intensive care (38.7%); 13 required purification treatment (41.9%; 3 haemodiafiltration, 10 haemodialysis). There was a significant correlation between daily milligrams of metformin ingested and drug levels; levels of metformin; and peak creatinine, pH and lactate. Mortality was 25.8%. There were only significant differences between the deceased and survivors regarding the duration of stay and final creatinine. Multivariate logistic regression did not detect any study variables associated with mortality. Conclusions: The incidence in our healthcare area is higher than in other series, with a 25.8% mortality rate. Virtually all cases were in the context of prerenal acute kidney failure. In 29% of cases, there was an overdose. Patients must be warned about the most common lactic acidosis-inducing situations, especially dehydration, if they continue taking the drug at such times


Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Acidose Láctica/induzido quimicamente , Acidose Láctica/mortalidade , Metformina/efeitos adversos , Atenção Terciária à Saúde , Fatores de Risco , Espanha/epidemiologia , Incidência
2.
Chin Med J (Engl) ; 132(3): 269-274, 2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30681492

RESUMO

BACKGROUND: Studies on the relationship between antiepileptic drug (AED) administration and clinical outcomes in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) remain scarce. Levetiracetam (LEV) is an AED that is neuroprotective in various neurologic disorders. This study aimed to determine the impact of LEV on the outcome of MELAS. METHODS: A retrospective, single-center study was performed based on a large cohort of patients with MELAS with a history of seizures (n = 102). Decisions on antiepileptic therapies were made empirically. Patients were followed up for 1 to 8 years (median, 4 years) and divided into 2 groups based on whether LEV was administered (LEV or non-LEV). The modified Rankin scale (mRS) scores and mortality risks were analyzed in all patients. RESULTS: LEV, carbamazepine, benzodiazepines, topiramate, oxcarbazepine, valproate, and lamotrigine were administered in 48, 37, 18, 13, 11, 9, and 9 patients, singly or in combination, respectively. The mean mRS score of the LEV group (n = 48) was lower than that of the non-LEV group (n = 54; mean ±â€Šstandard deviation, 2.79 ±â€Š1.47 vs. 3.83 ±â€Š1.93, P = 0.006) up to the end of the study. Nevertheless, there was no difference in the proportion of subjects without disability (mRS ranging 0-1) between the groups (P = 0.37). The multivariate regressions revealed that LEV treatment was associated with lower mRS scores (odds ratio 0.32, 95% confidence interval [CI] 0.15-0.68, P = 0.003) and mortality rates (hazard ratio 0.24, 95% CI 0.08-0.74, P = 0.013). There was a significant difference in the Kaplan-Meier survival curves between the groups (χ = 4.29, P = 0.04). CONCLUSIONS: The LEV administration is associated with lower mortality in patients with MELAS in this retrospective study. Further laboratory research and prospective cohort studies are needed to confirm whether LEV has neuroprotective effects on patients with mitochondrial diseases.


Assuntos
Acidose Láctica/tratamento farmacológico , Acidose Láctica/mortalidade , Anticonvulsivantes/uso terapêutico , Levetiracetam/uso terapêutico , Encefalomiopatias Mitocondriais/tratamento farmacológico , Encefalomiopatias Mitocondriais/mortalidade , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/mortalidade , Adolescente , Carbamazepina/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Lamotrigina/uso terapêutico , Levetiracetam/administração & dosagem , Masculino , Oxcarbazepina/uso terapêutico , Estudos Prospectivos , Estudos Retrospectivos , Topiramato/uso terapêutico , Ácido Valproico/uso terapêutico
3.
Nefrologia ; 39(1): 35-43, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30060893

RESUMO

OBJECTIVES: To determine the incidence of metformin-induced lactic acidosis during the period January 2014 to March 2017 in Aragon Healthcare Area III. To analyse the associated clinical and analytical factors and mortality. RESULTS: A total of 31 cases (61.3% males). Incidence: 79.76 cases/100,000 patients-year; mean age 75.39±9.34 years; 23 of them with levels of serum metformin (21.91±15.52 mcg/ ml); milligrams/day of metformin ingested: 1790.32±499; 96.8% of cases in the context of acute kidney failure; 11 cases with a history of chronic kidney disease (35.5%); 12 required intensive care (38.7%); 13 required purification treatment (41.9%; 3 haemodiafiltration, 10 haemodialysis). There was a significant correlation between daily milligrams of metformin ingested and drug levels; levels of metformin; and peak creatinine, pH and lactate. Mortality was 25.8%. There were only significant differences between the deceased and survivors regarding the duration of stay and final creatinine. Multivariate logistic regression did not detect any study variables associated with mortality. CONCLUSIONS: The incidence in our healthcare area is higher than in other series, with a 25.8% mortality rate. Virtually all cases were in the context of prerenal acute kidney failure. In 29% of cases, there was an overdose. Patients must be warned about the most common lactic acidosis-inducing situations, especially dehydration, if they continue taking the drug at such times.


Assuntos
Acidose Láctica/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Acidose Láctica/epidemiologia , Acidose Láctica/mortalidade , Acidose Láctica/terapia , Idoso , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Incidência , Modelos Logísticos , Masculino , Metformina/administração & dosagem , Distribuição por Sexo , Espanha/epidemiologia , Centros de Atenção Terciária
4.
Medicine (Baltimore) ; 97(36): e12114, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30200095

RESUMO

BACKGROUND: In recent years, linezolid is increasingly used in multidrug-resistant bacteria therapy. At the same time, linezolid-induced lactic acidosis has been continually reported as a serious side effect. Notably, to our knowledge, there are limited available literatures that evaluate risk factors for linezolid-induced lactic acidosis, and there is no highly reliable study on the relationship between linezolid-induced lactic acidosis and age or gender. However, clinicians need relevant information to advice on the use of linezolid. Therefore, we report on a case of life-threatening lactic acidosis after 3 doses of linezolid exposure and evaluate the risk factors of linezolid-induced lactic acidosis. METHODS: Cases of linezolid-induced lactic acidosis reported in PubMed were searched. Several characteristics and data of case numbers and deaths were extracted for analysis. RESULTS: A total of 35 articles including 47 cases were included in this study. Twelve patients (25.5%) died due to linezolid-induced lactic acidosis. At the cut-offs of 7, 14, and 28 days, the mortalities were 27.3%, 20%, and 27.3%. No statistically significant difference was observed according to age and gender. However, the proportion (27.7% and 29.8%) and mortality (30.8% and 35.7%) of male patients were much higher than females in both ≥65 and <65 years old groups (proportion: 15.2% and 23.9%; mortality: 14.3% and 18.2%). CONCLUSION: The mortality of linezolid-induced lactic acidosis was relatively high. The duration of linezolid use and age might not be risk factors. Gender (specifically, male) might be related to the mortality of linezolid-induced lactic acidosis.


Assuntos
Acidose Láctica/induzido quimicamente , Antibacterianos/efeitos adversos , Linezolida/efeitos adversos , Acidose Láctica/mortalidade , Antibacterianos/uso terapêutico , Evolução Fatal , Humanos , Linezolida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fatores de Risco
5.
Dtsch Med Wochenschr ; 143(15): 1082-1085, 2018 08.
Artigo em Alemão | MEDLINE | ID: mdl-30060277

RESUMO

Severe hyperlactaemia in intensive care patients is most often due to underlying sepsis or septic, cardiogenic or haemorrhagic shock. Hyperlactaemia is an independent predictor of death in various groups of critically ill patients. With serum lactate values > 10 mmol/l 80 % of the patients die in intensive care, and if the severe lactic acidosis persists for 48 hours, all patients die. Increased lactate levels require immediate diagnostic work-up and classification. The new sepsis definition requires a serum lactate > 2 mmol/l for septic shock with adequate volume substitution and vasopressor administration in order to achieve a mean arterial pressure in persistent hypotension ≥ 65 mmHg. The 1-hour bundle of the Surviving Sepsis Campaign published in 2018 recommends as a first measure the determination of the lactate serum concentrations, and increased values should be closely monitored. In addition, blood culture sampling, broad-spectrum antibiotics, fluid resuscitation and vasopressor administration are recommended within the first hour. Large amounts of crystalloids should be given for increased lactate levels (≥ 4 mmol/l) and refractory hypotension, the administration of fluids can be adjusted according to lactate clearance. Lactate metabolism is prolonged in patients with liver function impairment. Lactate levels on admission to intensive care are significantly associated with the number of failing organs and mortality in patients with cirrhosis. 12-hour lactate clearance has a strong predictive prognosis for survival in patients with baseline lactate levels above 5 mmol/l, the latter remains an independent predictor for the severity of the underlying disease even after correction. The greater the decrease in lactate during the initial therapy, the better the outcome.


Assuntos
Acidose Láctica/diagnóstico , Acidose Láctica/terapia , Cuidados Críticos , Acidose Láctica/etiologia , Acidose Láctica/mortalidade , Humanos , Ácido Láctico/sangue , Hepatopatias/complicações , Hepatopatias/diagnóstico , Hepatopatias/mortalidade , Hepatopatias/terapia , Taxa de Depuração Metabólica/fisiologia , Prognóstico , Fatores de Risco , Sepse/complicações , Sepse/diagnóstico , Sepse/mortalidade , Sepse/terapia , Choque Séptico/complicações , Choque Séptico/diagnóstico , Choque Séptico/mortalidade , Choque Séptico/terapia , Taxa de Sobrevida
6.
Mil Med Res ; 5(1): 13, 2018 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-29695298

RESUMO

Type A lactic acidosis resulted from hypoxic mitochondrial dysfunction is an independent predictor of mortality for critically ill patients. However, current therapeutic agents are still in shortage and can even be harmful. This paper reviewed data regarding lactic acidosis treatment and recommended that pyruvate might be a potential alkalizer to correct type A lactic acidosis in future clinical practice. Pyruvate is a key energy metabolic substrate and a pyruvate dehydrogenase (PDH) activator with several unique beneficial biological properties, including anti-oxidant and anti-inflammatory effects and the ability to activate the hypoxia-inducible factor-1 (HIF-1α) - erythropoietin (EPO) signal pathway. Pyruvate preserves glucose metabolism and cellular energetics better than bicarbonate, lactate, acetate and malate in the efficient correction of hypoxic lactic acidosis and shows few side effects. Therefore, application of pyruvate may be promising and safe as a novel therapeutic strategy in hypoxic lactic acidosis correction accompanied with multi-organ protection in critical care patients.


Assuntos
Acidose Láctica/tratamento farmacológico , Ácido Pirúvico/farmacocinética , Acidose Láctica/mortalidade , Antiácidos/farmacocinética , Antiácidos/uso terapêutico , Bicarbonatos , Eritropoetina/análise , Eritropoetina/sangue , Hidratação/métodos , Humanos , Hipóxia/tratamento farmacológico , Subunidade alfa do Fator 1 Induzível por Hipóxia/análise , Subunidade alfa do Fator 1 Induzível por Hipóxia/sangue , Ácido Pirúvico/uso terapêutico , Lactato de Ringer/farmacocinética , Lactato de Ringer/uso terapêutico
7.
J Surg Res ; 226: 173-180, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29661284

RESUMO

BACKGROUND: A novel pyruvate-based oral rehydration salt (Pyr-ORS) was demonstrated of superiority over bicarbonate- or citrate-based one to preserve organ function and correct lactic acidosis in rehydration of lethal shock in animals. This study further compared these effects between low-osmolar Pyr-ORS and equimolar citrate-based counterpart. METHODS: Eighty rats, using a fatal burn shock model, were randomized into four groups (two subgroups per group: n = 10): the sham group (group SR), Pyr-ORS group (group PR), WHO-ORS III group (group CR), and no rehydration group. ORS was delivered by manual gavage during 24 h following burns. Oral administration consisted of half of counted volume in the initial 8 h plus the rest in the later 16 h. Systemic hemodynamics, visceral organ surface blood flow, organ function, and metabolic acidosis were determined at 8 h and 24 h after burn. Another set of rats with identical surgical procedures without tests was observed for survival. RESULTS: Survival was markedly improved in the groups PR and CR; the former showed a higher survival rate than the latter at 24 h (40% versus 20%, P < 0.05). Systemic hemodynamics, visceral blood flow, and function of heart, liver, and kidney were greatly restored in group PR, compared with group CR (all P < 0.05). Hypoxic lactic acidosis was efficiently reversed in group PR, instead of group CR, (pH 7.36 versus 7.11, base excess 2.1 versus -9.1 mmol/L, lactate 4.28 versus 8.18 mmol/L; all P < 0.05) at 24 h after injury. CONCLUSIONS: Pyruvate was advantageous over citrate in low-osmolar ORS for protection of organs and survival; pyruvate, but not citrate, in the ORS corrected hypoxic lactic acidosis in rats subjected to lethal burn shock in 24 h.


Assuntos
Acidose Láctica/terapia , Queimaduras/complicações , Hidratação/métodos , Ácido Pirúvico/administração & dosagem , Soluções para Reidratação/administração & dosagem , Choque/terapia , Acidose Láctica/etiologia , Acidose Láctica/mortalidade , Administração Oral , Animais , Bicarbonatos/administração & dosagem , Queimaduras/diagnóstico , Queimaduras/mortalidade , Ácido Cítrico/administração & dosagem , Modelos Animais de Doenças , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Concentração Osmolar , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Soluções para Reidratação/química , Índice de Gravidade de Doença , Choque/etiologia , Choque/mortalidade , Resultado do Tratamento
8.
Clin Toxicol (Phila) ; 56(7): 622-625, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29301418

RESUMO

IMPORTANCE: Acetaminophen toxicity is common and is characterized by hepatic failure. In cases that are not improving with standard medical therapy with N-acetylcysteine, some patients may require hepatic transplant. While there are various criteria to predict patients who might benefit from transplant, the King's College criteria remain one of the most widely used. However, the King's College criteria have several limitations and do not incorporate glucose, an important marker of hepatic function. OBJECTIVE: The primary objective of this study is to compare the presence of hypoglycemia, coagulopathy, and metabolic acidosis with the King's College criteria for predicting a composite endpoint of death or transplant. DESIGN: This study is a retrospective cohort study of adult patients admitted with a discharge diagnosis of acetaminophen-induced liver failure. SETTING: The patients were admitted at one of six university-affiliated teaching hospitals in the United States. RESULTS: A total of 334 subjects were identified who met inclusion criteria. Fifty-one subjects (15.3%) met the composite endpoint of death or transplant. Ninety-six (28.7%) subjects met the King's College criteria for transplant. The presence of hypoglycemia increased the odds of reaching the composite endpoint by 3.39-fold. This model performed better than the King's College criteria (pseudo R2 for the area under the curve of 0.93 vs. 0.20 for the King's College criteria). CONCLUSIONS: The combination of hypoglycemia, coagulopathy, and lactic acidosis performed better than the King's College criteria for predicting death or transplant.


Assuntos
Acetaminofen/toxicidade , Acidose Láctica/mortalidade , Doença Hepática Induzida por Substâncias e Drogas/mortalidade , Hipoglicemia/mortalidade , Falência Hepática/mortalidade , Transplante de Fígado , Adulto , Transtornos da Coagulação Sanguínea/mortalidade , Doença Hepática Induzida por Substâncias e Drogas/cirurgia , Feminino , Humanos , Falência Hepática/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
9.
J Crit Care ; 44: 101-110, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29080515

RESUMO

BACKGROUND: Quantitative relationships among plasma [Lactate], [Pi], [Albumin], unmeasured anions ([UA]) and the anion gap (AGK) in lactic acidosis (LA) are not well defined. METHODS: A mathematical model featuring compensatory potassium and chloride shifts and respiratory changes in LA demonstrated: (1) AGK=[Lactate]+Zp×[Pi]+2.4×[Albumin]+constant1+e, where Zp is a function of pH, and e reflects unmeasured anions and cations plus pH-related variations. Eq. (1) can be algebraically rearranged to incorporate the albumin-corrected anion gap, cAGK: (2) cAGK=[Lactate]+Zp×[Pi]+constant2+e. Eq. (1) was tested against 948 data sets from critically ill patients with [Lactate] 4.0mEq/L or greater. AGK and cAGK were evaluated against 12,341 data sets for their ability to detect [Lactate]>4.0mEq/L. RESULTS: Analysis of Eq. (1) revealed r2=0.5950, p<0.001. cAGk>15mEq/L exhibited a sensitivity of 93.0% [95% CI: 91.3-94.5] in detecting [Lactate]>4.0mEq/L, whereas AGK>15mEq/L exhibited a sensitivity of only 70.4% [67.5-73.2]. Additionally, [Lactate]>4.0mEq/L and cAGK>20mEq/L were each strongly associated with intensive care unit mortality (χ2>200, p<0.0001 for each). CONCLUSIONS: In LA, cAGK is more sensitive than AGK in predicting [Lactate]>4.0mEq/L.


Assuntos
Acidose Láctica/sangue , Ânions/sangue , Ácido Láctico/sangue , Fósforo/sangue , Albumina Sérica/análise , Equilíbrio Ácido-Base , Acidose Láctica/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Valor Preditivo dos Testes , Análise de Regressão , Sensibilidade e Especificidade , Adulto Jovem
10.
BMC Nephrol ; 18(1): 229, 2017 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-28693440

RESUMO

BACKGROUND: The current practice concerning timing, mode, and dose of renal replacement therapy (RRT) in patients with metformin-associated lactic acidosis (MALA) with renal failure remains unknown. To investigate whether serum lactate level and prescription pattern of RRT are associated with mortality in patients with MALA requiring RRT. METHODS: We searched PubMed/Medline and EMBASE from inception to Sep 2014 and applied predetermined exclusion criteria. Case-level data including case's demographics and clinical information related to MALA were abstracted. Multiple logistic regression modeling was used to examine the predictors of mortality. RESULTS: A total of 253 unique cases were identified with cumulative mortality of 17.2%. Eighty-seven percent of patients had acute kidney injury. Serum lactate level was significantly higher in non-survivors (median 22.5 mmol/L) than in survivors (17.0 mmol/L, p-value <0.01) and so did the median blood metformin concentrations (58.5 vs. 43.9 mg/L, p-value = 0.05). The survival advantage was not significantly different between the modalities of RRT. The adjusted odds ratio of mortality for every one mmol/L increase in serum lactate level was 1.09 (95% CI 1.02-1.17, p-value = 0.01). The dose-response curve indicated a lactate threshold greater than 20 mmol/L was significantly associated with mortality. CONCLUSIONS: Our study suggests that predialysis level of serum lactate level is an important marker of mortality in MALA patients requiring RRT with a linear dose-response relationship. To better evaluate the optimal prescription of RRT in MALA, we recommend fostering an international consortium to support prospective research and large-scale standardized case collection.


Assuntos
Acidose Láctica/sangue , Acidose Láctica/mortalidade , Hipoglicemiantes/efeitos adversos , Ácido Láctico/sangue , Metformina/efeitos adversos , Terapia de Substituição Renal/mortalidade , Acidose Láctica/induzido quimicamente , Lesão Renal Aguda/sangue , Lesão Renal Aguda/mortalidade , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Terapia de Substituição Renal/tendências
11.
BMC Nephrol ; 18(1): 163, 2017 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-28526011

RESUMO

BACKGROUND: Whether metformin precipitates lactic acidosis in patients with chronic kidney disease (CKD) remains under debate. We examined whether metformin use was associated with an increased risk of acute kidney injury (AKI) as a proxy for lactic acidosis and whether survival among those with AKI varied by metformin exposure. METHODS: All individuals with type 2 diabetes and available prescribing data between 2004 and 2013 in Tayside, Scotland were included. The electronic health record for diabetes which includes issued prescriptions was linked to laboratory biochemistry, hospital admission, death register and Scottish Renal Registry data. AKI events were defined using the Kidney Disease Improving Global Outcomes criteria with a rise in serum creatinine of at least  26.5 µmol/l or a rise of greater than 150% from baseline for all hospital admissions. Cox Regression Analyses were used to examine whether person-time periods in which current metformin exposure occurred were associated with an increased rate of first AKI compared to unexposed periods. Cox regression was also used to compare 28 day survival rates following first AKI events in those exposed to metformin versus those not exposed. RESULTS: Twenty-five thousand one-hundred fourty-eight patients were included with a total person-time of 126,904 person years. 4944 (19.7%) people had at least one episode of AKI during the study period. There were 32.4 cases of first AKI/1000pyrs in current metformin exposed person-time periods compared to 44.9 cases/1000pyrs in unexposed periods. After adjustment for age, sex, diabetes duration, calendar time, number of diabetes drugs and baseline renal function, current metformin use was not associated with AKI incidence, HR 0.94 (95% CI 0.87, 1.02, p = 0.15). Among those with incident AKI, being on metformin at admission was associated with a higher rate of survival at 28 days (HR 0.81, 95% CI 0.69, 0.94, p = 0.006) even after adjustment for age, sex, pre-admission eGFR, HbA1c and diabetes duration. CONCLUSIONS: Contrary to common perceptions, we found no evidence that metformin increases incidence of AKI and was associated with higher 28 day survival following incident AKI.


Assuntos
Acidose Láctica/mortalidade , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/mortalidade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/mortalidade , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/mortalidade , Metformina/uso terapêutico , Acidose Láctica/etiologia , Distribuição por Idade , Idoso , Estudos de Coortes , Comorbidade , Feminino , Humanos , Incidência , Masculino , Metformina/efeitos adversos , Pessoa de Meia-Idade , Fatores de Risco , Escócia/epidemiologia , Distribuição por Sexo , Taxa de Sobrevida , Resultado do Tratamento
12.
Intern Emerg Med ; 12(8): 1225-1233, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27677616

RESUMO

Accidental hypothermia has a low incidence, but is associated with a high mortality rate. Knowledge about concomitant factors, complications, and length of hospital stay is limited. A retrospective cohort study on patients with accidental hypothermia admitted to Oulu University Hospital in Finland, over a 5-year period. Patients were categorized as short-stay patients (7 days or less) and long-stay patients (more than 7 days) according to their length of stay in hospital. From a total of 105 patients, 67 patients were included in the analyses. Alcohol abuse was the most common concomitant factor (54 %). Median length of hospital stay was 4 days, and 16 patients (24 %) stayed in hospital over 7 days (median 15 days). Thirty-day mortality was low (14/105, 13 %). Patients with long-term hospitalization had a lower initial temperature (28.4 versus 31.2 °C, p = 0.011), a lower level of consciousness (GCS score 8.4 versus 12.8, p = 0.003), more severe acidosis (pH 7.08 versus 7.28, p = 0.005, and lactate 7.2 versus 3.9, p = 0.043), and a lower level of platelets (183 versus 242, p = 0.041) on admission compared with short-stay patients. Thirty-six patients (54 %) had at least one complication, and this prolonged median hospital treatment for 2.5 days (p < 0.001). Alcohol is the most common concomitant factor and every fourth patient spends more than 7 days in hospital. Long-term hospitalization is related to a lower core temperature, lower consciousness, more severe lactic acidosis, lower platelet level and infections, rhabdomyolysis, and renal failure.


Assuntos
Hospitalização/estatística & dados numéricos , Hipotermia/mortalidade , Prognóstico , Acidose Láctica/etiologia , Acidose Láctica/mortalidade , Adolescente , Adulto , Idoso , Distribuição de Qui-Quadrado , Estudos de Coortes , Feminino , Finlândia , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/complicações , Insuficiência Renal/mortalidade , Estudos Retrospectivos , Rabdomiólise/complicações , Rabdomiólise/mortalidade , Estatísticas não Paramétricas
13.
Clin Genet ; 91(4): 629-633, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27905109

RESUMO

Short-chain enoyl-CoA hydratase (SCEH) is a mitochondrial enzyme involved in the oxidation of fatty acids and the catabolic pathway of valine and, to a lesser extent, isoleucine. Deficiency of this enzyme was recently shown to cause an early childhood Leigh syndrome phenotype. The few reported patients were compound heterozygotes for two missense or missense with truncating variants in ECHS1 that encodes SCEH. We describe two siblings with severe refractory lactic acidosis and death within the first 2 days of life. Following negative clinical whole-exome and whole-genome sequencing, we resorted to autozygome/exome analysis on research basis and identified a homozygous splice site mutation (c.88+5G>A) in the two cases. Analysis of cDNA confirmed complete replacement of the normal transcript with an aberrant transcript (r.88_89ins 88+1_88+11) predicting premature truncation of the protein [p.(Ala31Glufs*23)]. Furthermore, quantitative reverse transcriptase polymerase chain reaction (RTPCR) showed marked reduction in ECHS1, most likely nonsense-mediated decay (NMD)-mediated. This is the first report of homozygosity for a truncating mutation in ECHS1, which may explain the severe phenotype. Our report highlights the need to consider SCEH deficiency in patients with lethal neonatal lactic acidosis, and the potentially limited sensitivity of untargeted genomic sequencing towards non-canonical splicing mutations, which may explain at least some of the 'negative' cases on clinical exome/genome sequencing.


Assuntos
Acidose Láctica/genética , Enoil-CoA Hidratase/genética , Acidose Láctica/mortalidade , Acidose Láctica/fisiopatologia , Enoil-CoA Hidratase/deficiência , Exoma/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Homozigoto , Humanos , Recém-Nascido , Doença de Leigh/genética , Doença de Leigh/fisiopatologia , Masculino , Mutação , Linhagem , Fenótipo , Sítios de Splice de RNA/genética , Irmãos
14.
Medicine (Baltimore) ; 95(46): e4998, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27861334

RESUMO

AIMS: The principal objective of this study was to retrospectively review a series of cases of lactic acidosis (LA) in patients with type 2 diabetes mellitus (T2DM) and examine the relationship with the use of metformin. More generally, the study enabled an investigation of the profiles of patients diagnosed with LA and clinical variables associated with in-hospital mortality. METHODS: All patients admitted to the Royal Hobart Hospital in Tasmania with LA (lactate >5.0 mmol/L and pH <7.35) over a 4-year period were included. Data extracted included patient demographics, medical history, medications, acute and chronic conditions associated with LA, and relevant pathology results. Multivariate logistic regression analysis was used to identify predictors for in-hospital mortality in patients with LA. RESULTS: A total of 139 patients with LA were included in this study. Of these, 23 patients had T2DM and 11 patients were taking metformin. All metformin-treated patients had at least 1 additional medical condition (either chronic or acute) associated with an increased risk for LA. More than half (n = 72, 51.8%) of the patients with LA died during hospitalization. Multivariate logistic regression revealed older age and lower pH as the significant independent predictors (P < 0.05) for in-hospital mortality. CONCLUSION: LA was associated with high in-hospital mortality, with older age and lower pH as the significant risk factors for mortality. In patients with LA, approximately half of the patients with T2DM were receiving metformin. All the patients treated with metformin had other medical conditions that were risk factors for developing LA. The role of LA in patients treated with metformin is seemingly overemphasized.


Assuntos
Acidose Láctica/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Acidose Láctica/mortalidade , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Mortalidade Hospitalar , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
Emergencias (St. Vicenç dels Horts) ; 28(1): 38-40, feb. 2016. tab
Artigo em Espanhol | IBECS | ID: ibc-148465

RESUMO

El objetivo de este estudio es la detección de parámetros analíticos asociados a la mortalidad en los pacientes con diabetes mellitus tipo 2 (DM2) con tratamiento crónico con metformina que acuden a urgencias por un cuadro clínico agudo con presencia de acidosis láctica. Se trata de un estudio observacional-analítico retrospectivo realizado en un hospital de tercer nivel. Se recogieron datos clínicos y analíticos en una serie de pacientes con acidosis láctica, estratificada por gravedad, y tratamiento con metformina para DM2. Se compararon los resultados en función de la mortalidad o supervivencia del episodio. De 16 pacientes estudiados, con una edad media de 70 años (rango de 60 a 77), el 75% presentó sintomatología gastrointestinal los 5 días previos a su ingreso. La mortalidad total observada fue del 19%, que se asoció a la presencia de sepsis al ingreso, leucocitosis con neutrofilia, plaquetopenia, elevación de proteína C reactiva (PCR), valores altos de procalcitonina y la comorbilidad con una o más patologías crónicas. Las cifras sé- ricas de metformina no se correlacionaron significativamente con la mortalidad. Se concluye que en pacientes con acidosis láctica y tratamiento con metformina pueden ser factores asociados a la mortalidad la presencia de criterios de sepsis, neutrofilia con plaquetopenia, elevación de PCR y de procalcitonina y la existencia de una o más patologías comórbidas (AU)


To identify analytical factors associated with mortality in patients with type-2 diabetes under long-term treatment with metformin who come to the emergency department with acute symptoms of lactic acidosis. Retrospective observational analysis of patient records in a referral hospital. We collected clinical data and laboratory results for a series of metformin-treated patients with type-2 diabetes who developed lactic acidosis, stratified by severity. Factors related to the episode were analyzed for associations with mortality or survival. Of 16 patients studied (mean age 70 years; range, 60-77 years), 75% had gastrointestinal symptoms in the 5 days before they came to the emergency department. Mortality (19%) was associated with sepsis on arrival; elevated white blood cell counts, particularly neutrophil counts; low platelet counts; high C-reactive protein (CRP) and procalcitonin levels; and 1 or more chronic concomitant diseases. Metformin concentration was not significantly associated with mortality. Signs of sepsis, high neutrophil counts with low platelet counts, elevated CRP and procalcitonin levels, and the presence of 1 or more concomitant diseases may be risk factors for death in metformin-treated patients with lactic acidosis (AU)


Assuntos
Humanos , Diabetes Mellitus Tipo 2/complicações , Acidose Láctica/mortalidade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Metformina/uso terapêutico , Serviço Hospitalar de Emergência/estatística & dados numéricos , Tratamento de Emergência/métodos , Estudos Retrospectivos
17.
J Nephrol ; 29(6): 783-789, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26800971

RESUMO

Metformin (MF) accumulation during acute kidney injury is associated with high anion gap lactic acidosis type B (MF-associated lactic acidosis, MALA), a serious medical condition leading to high mortality. Despite dose adjustment for renal failure, diabetic patients with chronic kidney disease (CKD) stage III-IV are at risk for rapid decline in renal function by whatever reason, so that MF toxicity might arise if the drug is not timely withdrawn. Sixteen consecutive patients were admitted to our Hospital's Emergency Department with clinical findings consistent with MALA. Fifteen had prior history of CKD, 60 % of them with GFR between 30 and 60 ml/min. Of these, 5 required mechanical ventilation and cardiovascular support; 3 promptly recovered renal function after rehydration, whereas 10 (62 %) required continuous veno-venous renal replacement treatment. SOFA and SAPS II scores were significantly related to the degree of lactic acidosis. In addition, lactate levels were relevant to therapeutic choices, since they were higher in dialyzed patients than in those on conservative treatment (11.92 mmol/l vs 5.7 mmol/l, p = 0.03). The overall death rate has been 31 %, with poorer prognosis for worse acidemia, as serum pH was significantly lower in non-survivors (pH 6.96 vs 7.16, p > 0.04). Our own data and a review of the literature suggest that aged, hemodynamically frail patients, with several comorbidities and CKD, are at greater risk of MALA, despite MF dosage adjustment. Moreover, renal replacement therapy rather than simple acidosis correction by administration of alkali seems the treatment of choice, based on eventual renal recovery and overall outcome.


Assuntos
Acidose Láctica/induzido quimicamente , Diabetes Mellitus/tratamento farmacológico , Nefropatias Diabéticas/fisiopatologia , Hipoglicemiantes/efeitos adversos , Rim/fisiopatologia , Metformina/efeitos adversos , Insuficiência Renal Crônica/fisiopatologia , Equilíbrio Ácido-Base , Acidose Láctica/mortalidade , Acidose Láctica/fisiopatologia , Acidose Láctica/terapia , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus/mortalidade , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/mortalidade , Nefropatias Diabéticas/terapia , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Registros Médicos , Pessoa de Meia-Idade , Diálise Renal , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/terapia , Estudos Retrospectivos , Fatores de Risco , Roma , Resultado do Tratamento
18.
J Intensive Care Med ; 31(3): 187-92, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24733810

RESUMO

INTRODUCTION: Although magnesium plays an important role in aerobic metabolism and magnesium deficiency is a common phenomenon in critical illness, the association between magnesium deficiency and lactic acidosis in the intensive care unit (ICU) has not been defined. METHODS: This was a retrospective, cross-sectional study conducted at a 77 ICU bed tertiary medical center. Data pertaining to the first unique admission of any ICU patient between 2001 and 2008 were extracted from the Multiparameter Intelligent Monitoring in Intensive Care database. Hypomagnesemia was defined as serum magnesium <1.6 mg/dL. Mild and severe lactic acidosis were defined as lactate concentrations of >2 and > 4 mmol/L, respectively. Multivariate modeling was used to explore the association between magnesium and lactate concentrations. RESULTS: Of 8922 critically ill patients, 22.6% were hypomagnesemic. Hypomagnesemia was associated with an increased adjusted risk of mild lactic acidosis (odds ratio [OR] 1.71, 95% confidence interval [95%CI] 1.51-1.94, P < .001) and severe lactic acidosis (OR 1.56, 95%CI 1.32-1.84, P < .001) than the reference quartile. The association between hypomagnesemia and mild lactic acidosis was stronger in those at risk of magnesium deficiency, including diabetics (OR 2.02, 95%CI 1.51-2.72, P < .001) and alcoholics (OR 1.92, 95%CI 1.16-3.19, P = .01). As an internal model control, hypokalemia was not associated with an increased risk of lactic acidosis. CONCLUSIONS: Magnesium deficiency is a common finding in patients admitted to the ICU and is associated with lactic acidosis. Our findings support the biologic role of magnesium in metabolism and raise the possibility that hypomagnesemia is a correctable risk factor for lactic acidosis in critical illness.


Assuntos
Acidose Láctica/etiologia , Estado Terminal , Deficiência de Magnésio/complicações , Acidose Láctica/sangue , Acidose Láctica/mortalidade , Estado Terminal/mortalidade , Estudos Transversais , Feminino , Hospitalização , Humanos , Unidades de Terapia Intensiva , Deficiência de Magnésio/sangue , Deficiência de Magnésio/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco
19.
J Crit Care ; 31(1): 243-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26507640

RESUMO

PURPOSE: The purpose was to determine prognosis of patients presenting extreme acidosis (pH <7) on admission to the intensive care unit (ICU) and to identify mortality risk factors. MATERIALS AND METHODS: We retrospectively analyzed all patients who presented with extreme acidosis within 24 hours of admission to a polyvalent ICU in a university hospital between January 2011 and July 2013. Multivariate analysis and survival analysis were used. RESULTS: Among the 2156 patients admitted, 77 patients (3.6%) presented extreme acidosis. Thirty (39%) patients suffered cardiac arrest before admission. Although the mortality rate predicted by severity score was 93.6%, death occurred in 52 cases (67.5%) in a median delay of 13 (5-27) hours. Mortality rate depended on reason for admission, varying between 22% for cases linked to diabetes mellitus and 100% for cases of mesenteric infarction (P = .002), cardiac arrest before admission (P < .001), type of lactic acidosis (P = .007), high Simplified Acute Physiology Score II (P = .008), and low serum creatinine (P = .012). CONCLUSIONS: Patients with extreme acidosis on admission to ICU have a less severe than expected prognosis. Whereas mortality is almost 100% in cases of cardiac arrest before admission, mortality is much lower in the absence of cardiac arrest before admission, which justifies aggressive ICU therapies.


Assuntos
Acidose Láctica/terapia , Acidose Respiratória/terapia , Oxigenação por Membrana Extracorpórea , Diálise Renal , Respiração Artificial , Bicarbonato de Sódio/uso terapêutico , Vasoconstritores/uso terapêutico , Acidose/mortalidade , Acidose Láctica/induzido quimicamente , Acidose Láctica/mortalidade , Acidose Respiratória/mortalidade , Adulto , Idoso , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Feminino , Parada Cardíaca/epidemiologia , Hemorragia/epidemiologia , Mortalidade Hospitalar , Hospitalização , Hospitais Universitários , Humanos , Hipoglicemiantes/efeitos adversos , Infarto/epidemiologia , Unidades de Terapia Intensiva , Masculino , Isquemia Mesentérica/epidemiologia , Metformina/efeitos adversos , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Análise de Sobrevida
20.
PLoS One ; 10(12): e0145181, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26692209

RESUMO

INTRODUCTION: Initial lactate level, lactate clearance, C-reactive protein, and procalcitonin in critically ill patients with sepsis are associated with hospital mortality. However, no study has yet discovered which factor is most important for mortality in severe sepsis patients with lactic acidosis. We sought to clarify this issue in patients with lactic acidosis who were supplementing with sodium bicarbonate. MATERIALS AND METHODS: Data were collected from a single center between May 2011 and April 2014. One hundred nine patients with severe sepsis and lactic acidosis who were supplementing with sodium bicarbonate were included. RESULTS: The 7-day mortality rate was 71.6%. The survivors had higher albumin levels and lower SOFA, APACHE II scores, vasopressor use, and follow-up lactate levels at an elapsed time after their initial lactate levels were checked. In particular, a decrement in lactate clearance of at least 10% for the first 6 hours, 24 hours, and 48 hours of treatment was more dominant among survivors than non-survivors. Although the patients who were treated with broad-spectrum antibiotics showed higher illness severity than those who received conventional antibiotics, there was no significant mortality difference. 6-hour, 24-hour, and 48-hour lactate clearance (HR: 4.000, 95% CI: 1.309-12.219, P = 0.015) and vasopressor use (HR: 4.156, 95% CI: 1.461-11.824, P = 0.008) were significantly associated with mortality after adjusting for confounding variables. CONCLUSIONS: Lactate clearance at a discrete time point seems to be a more reliable prognostic index than initial lactate value in severe sepsis patients with lactic acidosis who were supplementing with sodium bicarbonate. Careful consideration of vasopressor use and the initial application of broad-spectrum antibiotics within the first 48 hours may be helpful for improving survival, and further study is warranted.


Assuntos
Acidose Láctica , Mortalidade Hospitalar , Ácido Láctico/sangue , Sepse , Bicarbonato de Sódio/administração & dosagem , Acidose Láctica/sangue , Acidose Láctica/tratamento farmacológico , Acidose Láctica/mortalidade , Idoso , Proteína C-Reativa/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sepse/sangue , Sepse/tratamento farmacológico , Sepse/mortalidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA