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1.
Lakartidningen ; 1162019 Nov 01.
Artigo em Sueco | MEDLINE | ID: mdl-31688944

RESUMO

Since the late 1970s N-acetylcystein has been used as an antidote after paracetamol intoxication. The treatment is traditionally given as three consecutive infusions for 20 hours and 15 minutes. The total dose given is 300 mg/kg. Half of this amount is given as a bolus during the first 15 minutes of treatment.  This regime has proven very efficient in avoiding liver injury. However, side effects, caused by histamine release, are common (10-15%). Symptoms as flush, urticaria and, in rare cases, bronchospasm, angioedema and circulatory shock typically appear during the bolus dose and may lead to interrupted and inadequate treatment. In addition, the regime is complicated leading to a risk of administration errors. During the last years several publications have described the use of a model with two infusions instead of three. The first and the second infusions are merged and given over four hours. The third infusion and the total dose are left unchanged. This modified regime has been shown to reduce side effects and seems not to increase the risk of liver injury. As of November 1, 2019, the Swedish Poisons Information Centre will change its recommendations to the new two-infusion protocol.


Assuntos
Acetaminofen/envenenamento , Acetilcisteína/administração & dosagem , Antídotos/administração & dosagem , Overdose de Drogas/tratamento farmacológico , Envenenamento/tratamento farmacológico , Acetilcisteína/efeitos adversos , Acetilcisteína/uso terapêutico , Administração Intravenosa , Antídotos/efeitos adversos , Antídotos/uso terapêutico , Humanos , Centros de Controle de Intoxicações , Guias de Prática Clínica como Assunto
2.
Lancet ; 394(10201): 869-881, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31498101

RESUMO

Acute liver failure is a rare and severe consequence of abrupt hepatocyte injury, and can evolve over days or weeks to a lethal outcome. A variety of insults to liver cells result in a consistent pattern of rapid-onset elevation of aminotransferases, altered mentation, and disturbed coagulation. The absence of existing liver disease distinguishes acute liver failure from decompensated cirrhosis or acute-on-chronic liver failure. Causes of acute liver failure include paracetamol toxicity, hepatic ischaemia, viral and autoimmune hepatitis, and drug-induced liver injury from prescription drugs, and herbal and dietary supplements. Diagnosis requires careful review of medications taken, and serological testing for possible viral exposure. Because of its rarity, acute liver failure has not been studied in large, randomised trials, and most treatment recommendations represent expert opinion. Improvements in management have resulted in lower mortality, although liver transplantation, used in nearly 30% of patients with acute liver failure, still provides a life-saving alternative to medical management.


Assuntos
Insuficiência Hepática Crônica Agudizada/etiologia , Acetaminofen/envenenamento , Insuficiência Hepática Crônica Agudizada/fisiopatologia , Insuficiência Hepática Crônica Agudizada/terapia , Adulto , Doença Hepática Crônica Induzida por Substâncias e Drogas/complicações , Feminino , Humanos , Transplante de Fígado , Masculino , Pessoa de Meia-Idade
3.
Lakartidningen ; 1162019 Jul 29.
Artigo em Sueco | MEDLINE | ID: mdl-31361324

RESUMO

Toxicological analysis is an important part of the acute treatment of various intoxications. Rapid laboratory responses are important for the patient to be assessed and treated correctly, and also to exclude poisoning and thus avoid unjustified and costly overtreatment. In Sweden, paracetamol (acetaminophen) is one of the most common pharmaceuticals in drug poisoning. Paracetamol overdose can cause severe liver damage unless treated early with the antidote acetylcysteine. A nation-wide initiative for improved laboratory measurement of paracetamol in plasma/serum samples has resulted in a marked reduction in the inter-laboratory coefficient of variation to generally below 10%. The introduction of a harmonized national reporting range for plasma/serum paracetamol covering at least 50-5 000 µmol/l was also recommended. This initiative will hopefully contribute to better healthcare from both a patient and health resource perspective in cases of paracetamol poisoning.


Assuntos
Acetaminofen , Analgésicos não Entorpecentes , Serviços de Laboratório Clínico/normas , Acetaminofen/sangue , Acetaminofen/envenenamento , Acetilcisteína/administração & dosagem , Acetilcisteína/uso terapêutico , Analgésicos não Entorpecentes/sangue , Analgésicos não Entorpecentes/envenenamento , Antídotos/administração & dosagem , Antídotos/uso terapêutico , Overdose de Drogas/diagnóstico , Overdose de Drogas/tratamento farmacológico , Humanos , Envenenamento/diagnóstico , Envenenamento/tratamento farmacológico , Guias de Prática Clínica como Assunto , Suécia , Fatores de Tempo
4.
Medicina (Kaunas) ; 55(5)2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31117289

RESUMO

Background and objectives: Ascorbic acid, alpha lipoic acid (ALA) and silymarin are well-known antioxidants that have hepatoprotective effects. This study aims to investigate the effects of these three compounds combined with attenuating drug-induced oxidative stress and cellular damage, taking acetaminophen (APAP)-induced toxicity in rats as a model both in vivo and in vitro. Materials and Methods: Freshly cultured primary rat hepatocytes were treated with ascorbic acid, ALA, silymarin and their combination, both with and without the addition of APAP to evaluate their in vitro impact on cell proliferation and mitochondrial activity. In vivo study was performed on rats supplemented with the test compounds or their combination for one week followed by two toxic doses of APAP. Results: Selected liver function tests and oxidative stress markers including superoxide dismutase (SOD), malondialdehyde (MDA) and oxidized glutathione (GSSG) were detected. The in vivo results showed that all three pretreatment compounds and their combination prevented elevation of SOD and GSSG serum levels indicating a diminished burden of oxidative stress. Moreover, ascorbic acid, ALA and silymarin in combination reduced serum levels of liver enzymes; however, silymarin markedly maintained levels of all parameters to normal ranges. Silymarin either alone or combined with ascorbic acid and ALA protected cultured rat hepatocytes and increased cellular metabolic activity. The subjected agents were capable of significantly inhibiting the presence of oxidative stress induced by APAP toxicity and the best result for protection was seen with the use of silymarin. Conclusions: The measured liver function tests may suggest an augmented hepatoprotection of the combination preparation than when compared individually.


Assuntos
Acetaminofen/efeitos adversos , Ácido Ascórbico/farmacocinética , Fatores de Proteção , Silimarina/farmacocinética , Ácido Tióctico/farmacocinética , Acetaminofen/envenenamento , Animais , Ácido Ascórbico/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/complicações , Modelos Animais de Doenças , Masculino , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Silimarina/uso terapêutico , Ácido Tióctico/uso terapêutico
5.
BMJ Case Rep ; 12(4)2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30954964

RESUMO

An 84-year-old woman presented to hospital with severe clinical and metabolic sequelaesequelae of a massive paracetamol overdose (concentration=822 mg/L). In spite of N-acetylcysteine therapy, she deteriorated with evidence of mitochondrial dysfunction. Although the EXtracorporeal TReatments In Poisoning group recommend adjunct haemodialysis (HD) in such a context, this was difficult to start due to haemodynamic instability. Instead, a trial of continuous venovenous haemodiafiltration (CVVHDF) was initiated in an attempt to restore normal mitochondrial function, normal pH and to actively remove the offending drug. Fortunately, plasma paracetamol levels fell exponentially over the subsequent 24-48 hours without the need to commence HD. The patient made a full recovery and was later discharged from the hospital. This case highlights that CVVHDF can be a reasonable alternative to HD for managing massive paracetamol overdoses in the context of mitochondrial dysfunction.


Assuntos
Acetaminofen/envenenamento , Analgésicos não Entorpecentes/envenenamento , Overdose de Drogas/terapia , Hemodiafiltração , Acetilcisteína/administração & dosagem , Idoso de 80 Anos ou mais , Antídotos/administração & dosagem , Overdose de Drogas/fisiopatologia , Feminino , Humanos , Tentativa de Suicídio , Resultado do Tratamento
6.
Hum Exp Toxicol ; 38(6): 646-654, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30838890

RESUMO

Paracetamol overdose is common and microRNA (miR)-122 expression is increased with liver injury. We aimed to measure miR-122 in the setting of an abbreviated paracetamol overdose treatment regimen. We compared miRNA expression in patients treated for paracetamol poisoning with an abbreviated 12-h intravenous acetylcysteine regimen (200 mg/kg over 4 h, 50 mg/kg over 8 h) or a 20-h regimen (200 mg/kg over 4 h, 100 mg/kg over 16 h) (NACSTOP trial). miR-122 expression is increased (decreased cycle threshold (Ct) values) with paracetamol liver injury. We assessed miR-122 expression in patients receiving the two acetylcysteine regimens and in a separate group with acute liver injury (ALI). We examined 121 blood samples in 38 patients. After 20 h of acetylcysteine, median alanine transaminase (ALT) was 12 U/L (18, 14) versus 16 U/L (11, 21) ( p = 0.17) and median miR-122 Ct was 30.1 (interquartile range (IQR): 28.9, 33.3) versus 31.4 (28.9, 33.9) ( p = 0.7) in the NACSTOP abbreviated and control groups, respectively. Median normalized miR-122 Ct after 20 h of acetylcysteine was 2.2 (IQR 1.9, 6.4), 1.1 (0.7, 2.9), 63.9 (2.5, 168), 123.2 (40.9, 207.8) in the NACSTOP-abbreviated, NACSTOP-control, ALI and hepatotoxicity groups, respectively. There was no significant difference in ALT or miRNA between NACSTOP treatment groups and no signal of increased liver injury from an abbreviated 12-h acetylcysteine regimen. These findings suggest that an abbreviated acetylcysteine regimen in low-risk patients who have overdosed on paracetamol is safe. Further study is required to validate this finding utilizing miRNA as a comparative biomarker.


Assuntos
Acetaminofen/envenenamento , Acetilcisteína/administração & dosagem , Analgésicos não Entorpecentes/envenenamento , Overdose de Drogas/tratamento farmacológico , MicroRNAs , Adolescente , Adulto , Overdose de Drogas/genética , Feminino , Humanos , Infusões Intravenosas , Masculino , Adulto Jovem
7.
Artigo em Inglês | MEDLINE | ID: mdl-30760194

RESUMO

OBJECTIVE: The aim of the study was to examine the impact of neonatal acetaminophen (APAP; paracetamol) administrations on the thyroid-liver axis in male Wistar rats. METHODS: APAP (100 or 350mg/kg) was orally administered to neonates from Postnatal Day (PND) 20 to 40. RESULTS: Both APAP doses elicited a substantial increase in serum TSH, albumin, AST, ALT, and ALP values, and a profound decrease in serum FT4 and FT3 values at PND 40 relative to those in the control group. Additionally, the hypothyroid state in both APAP-treated groups may increase the histopathological variations in the neonatal liver, such as destructive degeneration, fibrosis, fatty degeneration, fibroblast proliferation, haemorrhage, oedema, and vacuolar degeneration, at PND 40. Moreover, in the APAP groups, a marked depression was recorded in the t-SH and GSH levels and GPx and CAT activities at PND 40 in the neonatal liver compared to those in the control group. However, the levels of hepatic LPO, H2O2, and NO were increased in both APAP-treated groups at PND 40. All previous alterations were dose- dependent. CONCLUSION: Neonatal APAP caused a hypothyroidism and disturbed hepatic cellular components by increasing prooxidant markers and decreasing antioxidant markers, causing hepatotoxicity. Thus, neonatal administrations of APAP may act as a neonatal thyroid-liver disruptor.


Assuntos
Acetaminofen/efeitos adversos , Overdose de Drogas , Fígado/efeitos dos fármacos , Glândula Tireoide/efeitos dos fármacos , Acetaminofen/administração & dosagem , Acetaminofen/envenenamento , Animais , Animais Recém-Nascidos , Biomarcadores/análise , Biomarcadores/metabolismo , Overdose de Drogas/complicações , Overdose de Drogas/metabolismo , Crescimento e Desenvolvimento/efeitos dos fármacos , Fígado/crescimento & desenvolvimento , Fígado/fisiologia , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Ratos , Ratos Wistar , Glândula Tireoide/crescimento & desenvolvimento , Glândula Tireoide/fisiologia
8.
Biotech Histochem ; 94(5): 313-319, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30777790

RESUMO

Exposure to high doses of acetaminophen is the most common cause of drug induced liver injury. We investigated the protective effects of Hedera helix extract against acetaminophen induced oxidative stress and hepatotoxicity using a mouse model. We used two control groups: group A was given 0.9% NaCl, group B was an acetaminophen control that was given a single injection of 600 mg/kg acetaminophen. T1-T4 groups were pretreated orally with different doses of H. helix extract. The mice were sacrificed and blood samples were collected to estimate the levels of glutathione peroxidase (GPx), malondialdehyde (MDA), superoxide dismutase (SOD) and total bilirubin. Liver samples also were used for histopathological studies. We found that acetaminophen significantly increased the levels of serum ALP, ALT, AST and MDA, and also significantly reduced the antioxidant factors, CAT, GPX and SOD. H. helix extract treatment produced a significant reduction in the levels of ALP, ALT, AST and MDA in serum and restored the levels of CAT, GPX and SOD to control levels. The histopathological findings were consistent with the biochemical findings. H. helix extract exhibited antioxidant and hepatoprotective effects against acetaminophen induced liver damage.


Assuntos
Acetaminofen/farmacologia , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Hedera , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Acetaminofen/envenenamento , Alanina Transaminase/metabolismo , Animais , Antioxidantes/uso terapêutico , Aspartato Aminotransferases/metabolismo , Antagonismo de Drogas , Glutationa Peroxidase/metabolismo , Interações Ervas-Drogas , Fígado/enzimologia , Fígado/fisiopatologia , Malondialdeído/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Superóxido Dismutase/metabolismo
10.
Trials ; 20(1): 27, 2019 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-30621764

RESUMO

BACKGROUND: Paracetamol (acetaminophen) overdose (POD) is the commonest cause of acute liver failure in Europe and North America. Current treatment involves the use of the antidote N-acetylcysteine (NAC) in patients deemed at risk of liver damage. This regimen was introduced in the 1970s and has remained largely unchanged even though the initial NAC infusion is frequently associated with adverse reactions, in particular nausea, vomiting, and anaphylactoid reactions. NAC has reduced efficacy for preventing liver injury in those patients who present later after overdose. We designed a randomised study investigating the safety and tolerability of a superoxide dismutase (SOD) mimetic, calmangafodipir (PP100-01), co-treatment with a 12-h NAC regimen compared with NAC treatment alone in patients with POD. METHODS/DESIGN: We have designed an open-label, randomised, exploratory, rising dose design, NAC-controlled, phase 1 safety and tolerability study in patients treated with NAC for POD. A total of 24 patients will be assigned into one of three dosing cohorts of eight patients (n = 6 for PP100-01 and NAC; n = 2 for NAC alone). The doses of PP100-01 are 2, 5, and 10 µmol/kg. The primary outcome is the safety and tolerability of PP100-01 when co-administered with a 12-h NAC regimen compared with NAC treatment alone. Furthermore, the study will explore if PP100-01 has potential efficacy for the treatment of paracetamol-induced liver injury by measurement of conventional clinical and exploratory biomarkers. DISCUSSION: The aim of the study is to test the safety and tolerability of a SOD mimetic, PP100-01, in combination with a 12-h NAC regimen in patients presenting within 24 h of POD. This study will provide valuable data regarding the incidence of adverse events caused by the 12-h NAC plus PP100-01 regimen and may provide evidence of PP100-01 efficacy in the treatment of paracetamol-induced liver injury. TRIAL REGISTRATION: EudraCT, 2017-000246-21; ClinicalTrials.gov, NCT03177395 . Registered on 6 June 2017.


Assuntos
Acetaminofen/envenenamento , Acetilcisteína/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Ácido Edético/análogos & derivados , Fosfato de Piridoxal/análogos & derivados , Acetilcisteína/administração & dosagem , Comitês de Monitoramento de Dados de Ensaios Clínicos , Ensaios Clínicos Fase I como Assunto , Interpretação Estatística de Dados , Overdose de Drogas , Quimioterapia Combinada , Ácido Edético/administração & dosagem , Ácido Edético/efeitos adversos , Feminino , Humanos , Masculino , Fosfato de Piridoxal/administração & dosagem , Fosfato de Piridoxal/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
11.
J Affect Disord ; 246: 814-819, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30634113

RESUMO

BACKGROUND: Analgesics are used most frequently in fatal and non-fatal medicinal self-poisonings. Knowledge about their relative toxicity in overdose is important for clinicians and regulatory agencies. METHODS: Using data for 2005-2012 we investigated case fatality (number of suicides relative to number of non-fatal self-poisonings) of paracetamol, aspirin, codeine, dihydrocodeine, tramadol, paracetamol with codeine (co-codamol), paracetamol with dihydrocodeine (co-dydramol), ibuprofen and co-proxamol (paracetamol plus dextropropoxyphene; withdrawn in the UK in 2008 due to high toxicity). Data on suicides obtained from the Office for National Statistics and on non-fatal self-poisonings from the Multicentre Study of Self-harm in England. Case fatality was estimated for each drug, using paracetamol as the reference category. RESULTS: Compared to paracetamol and based on single drug deaths the case fatality index of dihydrocodeine was considerably elevated (odds ratio (OR) 12.81, 95% Confidence Interval (CI) 10.19-16.12). Case fatality indices for tramadol (OR 4.05, 95% CI 3.38-4.85) and codeine (OR 2.21, 95% CI 1.81-2.70) were also significantly higher than for paracetamol. The results when multiple drug deaths were included produced similar results. The relative toxicity of co-proxamol far exceeded that of the other analgesics. LIMITATIONS: Data on fatal self-poisonings were based on national data, whereas those for non-fatal poisonings were based on local data. CONCLUSIONS: Dihydrocodeine and tramadol are particularly toxic in overdose and codeine is also relatively toxic. They should be prescribed with caution, particularly to individuals at risk of self-harm.


Assuntos
Analgésicos/envenenamento , Overdose de Drogas/epidemiologia , Suicídio/estatística & dados numéricos , Acetaminofen/envenenamento , Adulto , Codeína/análogos & derivados , Codeína/envenenamento , Dextropropoxifeno/envenenamento , Combinação de Medicamentos , Inglaterra/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Br J Clin Pharmacol ; 85(1): 252-257, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30362143

RESUMO

Intravenous acetylcysteine is commonly prescribed as a course of three infusions for the management of paracetamol poisoning. Previous studies have demonstrated large variation in administered doses of intravenous acetylcysteine, which has been attributed to numerous factors, including inadequate mixing of infusion bags. The aim of this study was to determine whether the amount of mixing of infusion bags contributes significantly to this variation. Using acetylcysteine doses for a 60-69 kg patient, we added the appropriate volume of acetylcysteine to 5% glucose and subsequently inverted the infusion bags 0-5 times to mix the solutions. Infusion bags were then run through using an infusion pump and acetylcysteine concentrations measured at the beginning and end of the infusions. We found no significant difference between the beginning and end concentrations of acetylcysteine regardless of whether bags were mixed or not; infusion 1 (150 mg kg-1 ) showed beginning and end concentrations of 44.61 and 42.48 mg ml-1 respectively after 0 mixes, whilst beginning and end concentrations were 44.45 and 44.58 mg ml-1 respectively after five mixes. The same trend was observed for infusions 2 and 3. This confirmed that mixing does not play a substantial role in variation of drug concentrations; these are likely to be caused by an accumulation of small errors in infusion preparation.


Assuntos
Acetaminofen/envenenamento , Acetilcisteína/administração & dosagem , Composição de Medicamentos/métodos , Overdose de Drogas/tratamento farmacológico , Relação Dose-Resposta a Droga , Cálculos da Dosagem de Medicamento , Overdose de Drogas/etiologia , Humanos , Bombas de Infusão , Infusões Intravenosas/instrumentação , Infusões Intravenosas/métodos
13.
Basic Clin Pharmacol Toxicol ; 124(3): 341-347, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30248244

RESUMO

The use of extracorporeal treatments (ECTRs) for poisonings with four non-traditionally dialysed toxins (NTDTs) is increasing in the United States. This study evaluated whether ECTRs are prescribed for toxin removal or the treatment of other medical illnesses or complications. We performed a 2-Phase retrospective analysis evaluating the main indication for ECTRs in patients with poisoning from a NTDT (defined for this study as acetaminophen, opioids, tricyclic antidepressants (TCAs) or digoxin) and ECTR. The first phase assessed all cases from a single site (New York City Poison Control Center) between the years 2000 and 2016, and the second phase surveyed all United States Poison Control Centers (PCCs). In Phase 1, demographics, toxin ingested and main indication for ECTR were extracted. In Phase 2, a query to the National Poison Data System using the a pragmatic subset of inclusion criteria from Phase 1 restricted to single toxin ingestions over a narrower time frame (2014-2016) provided the cases for study. A structured online questionnaire was sent to all United States PCCs to request their database review regarding the indication for ECTR for their cases. In Phase 1, 92 cases met inclusion criteria. In Phase 2, 519 cases were screened and 425 met inclusion criteria. In Phase 1 91/92 (98.9%) and Phase 2 411/425 (96.7%), of extracorporeal treatments were used to treat underlying medical conditions or poisoning-related complications rather than accelerate toxin removal. The increasing number of ECTRs reported in patients who ingested one of the four NTDTs thus appears to be for medical indications rather than attempts at toxin removal, a distinction that is important.


Assuntos
Acetaminofen/envenenamento , Analgésicos Opioides/envenenamento , Antidepressivos Tricíclicos/envenenamento , Digoxina/envenenamento , Envenenamento/terapia , Diálise Renal/métodos , Bases de Dados Factuais , Humanos , Cidade de Nova Iorque/epidemiologia , Centros de Controle de Intoxicações/estatística & dados numéricos , Envenenamento/epidemiologia , Diálise Renal/estatística & dados numéricos , Estudos Retrospectivos , Inquéritos e Questionários , Estados Unidos/epidemiologia
14.
Transplantation ; 103(3): 544-551, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30028785

RESUMO

BACKGROUND: In adults, the absence of a preexisting chronic liver disease (CLD) is required to diagnose acute liver failure (ALF). The pediatric classification does not consider this aspect, thus previous studies pooled together children with ALF and children with unknown CLD presenting with acute hepatic decompensation (ALF-CLD). We aimed to compare prevalence, features, and outcome of children with ALF-CLD to those with a proper ALF. METHODS: Patients admitted between 1996 and 2017 because of ALF defined by Pediatric Acute Liver Failure criteria (raised transaminases, International Normal Ratio ≥2.0, no history of liver disease) were classified as ALF-CLD if diagnosed with autoimmune hepatitis, Wilson disease, Budd-Chiari syndrome, hepatitis B virus reactivation, inborn errors of metabolism. The others were classified as ALF. RESULTS: Seventy-four children (median age, 4 years; 1.0-8.8; male/female, 36/38] with ALF were found; 18 of <1 year of age were excluded. Fifty-six (median age, 6.6 years; 2.7-11.7; male/female, 23/33], 22 with ALF-CLD (autoimmune hepatitis, n = 14; Wilson disease, n = 6; inborn errors of metabolism, n = 2) and 34 with ALF (paracetamol overdose, n = 6; viral infections, n = 3; mushroom poisoning, n = 5; indeterminate, n = 20) were compared. In ALF-CLD, the median age at onset was higher, alanine aminotransferase, albumin, and International Normal Ratio levels were lower, splenomegaly, ascites, and cirrhosis were more common (all P < 0.01). On multivariate analysis, the diagnosis of ALF-CLD was an independent predictor of transplant-free survival (P = 0.006). CONCLUSIONS: In children, ALF-CLD is common, has peculiar features, and is associated with a favorable outcome. This study suggests the need to distinguish this entity from other forms of ALF in children.


Assuntos
Doença Hepática Terminal/diagnóstico , Falência Hepática Aguda/diagnóstico , Acetaminofen/envenenamento , Criança , Pré-Escolar , Doença Hepática Terminal/induzido quimicamente , Feminino , Sobrevivência de Enxerto , Encefalopatia Hepática , Hepatite Autoimune/terapia , Degeneração Hepatolenticular/terapia , Humanos , Lactente , Estimativa de Kaplan-Meier , Falência Hepática/epidemiologia , Falência Hepática/terapia , Falência Hepática Aguda/induzido quimicamente , Transplante de Fígado , Masculino , Erros Inatos do Metabolismo/terapia , Análise de Sobrevida , Resultado do Tratamento
15.
Pediatr Emerg Care ; 35(2): e42-e43, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29489610

RESUMO

Paracetamol is a common antipyretic often used to treat children with fever and pain. With the increasing administration of intravenous (IV) paracetamol, there will be the associated risk of medication dosing errors. We report a case of IV paracetamol overdose in a child with fever during hospital admission. A IV paracetamol dosing error occurred, with delayed recognition resulting in transient hepatotoxicity, with a peak alanine transaminase of 1946 IU/L and aspartate transaminase of 1633 IU/L.


Assuntos
Acetaminofen/envenenamento , Analgésicos não Entorpecentes/envenenamento , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Overdose de Drogas/complicações , Acetaminofen/administração & dosagem , Administração Intravenosa , Alanina Transaminase/sangue , Analgésicos não Entorpecentes/administração & dosagem , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Overdose de Drogas/diagnóstico , Feminino , Humanos , Lactente
16.
Cochrane Database Syst Rev ; 12: CD013230, 2018 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-30565220

RESUMO

BACKGROUND: Oral poisoning is a major cause of mortality and disability worldwide, with estimates of over 100,000 deaths due to unintentional poisoning each year and an overrepresentation of children below five years of age. Any effective intervention that laypeople can apply to limit or delay uptake or to evacuate, dilute or neutralize the poison before professional help arrives may limit toxicity and save lives. OBJECTIVES: To assess the effects of pre-hospital interventions (alone or in combination) for treating acute oral poisoning, available to and feasible for laypeople before the arrival of professional help. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, ISI Web of Science, International Pharmaceutical Abstracts, and three clinical trials registries to 11 May 2017, and we also carried out reference checking and citation searching. SELECTION CRITERIA: We included randomized controlled trials comparing interventions (alone or in combination) that are feasible in a pre-hospital setting for treating acute oral poisoning patients, including but potentially not limited to activated charcoal (AC), emetics, cathartics, diluents, neutralizing agents and body positioning. DATA COLLECTION AND ANALYSIS: Two reviewers independently performed study selection, data collection and assessment. Primary outcomes of this review were incidence of mortality and adverse events, plus incidence and severity of symptoms of poisoning. Secondary outcomes were duration of symptoms of poisoning, drug absorption, and incidence of hospitalization and ICU admission. MAIN RESULTS: We included 24 trials involving 7099 participants. Using the Cochrane 'Risk of bias' tool, we assessed no study as being at low risk of bias for all domains. Many studies were poorly reported, so the risk of selection and detection biases were often unclear. Most studies reported important outcomes incompletely, and we judged them to be at high risk of reporting bias.All but one study enrolled oral poisoning patients in an emergency department; the remaining study was conducted in a pre-hospital setting. Fourteen studies included multiple toxic syndromes or did not specify, while the other studies specifically investigated paracetamol (2 studies), carbamazepine (2 studies), tricyclic antidepressant (2 studies), yellow oleander (2 studies), benzodiazepine (1 study), or toxic berry intoxication (1 study). Eighteen trials investigated the effects of activated charcoal (AC), administered as a single dose (SDAC) or in multiple doses (MDAC), alone or in combination with other first aid interventions (a cathartic) and/or hospital treatments. Six studies investigated syrup of ipecac plus other first aid interventions (SDAC + cathartic) versus ipecac alone. The collected evidence was mostly of low to very low certainty, often downgraded for indirectness, risk of bias or imprecision due to low numbers of events.First aid interventions that limit or delay the absorption of the poison in the bodyWe are uncertain about the effect of SDAC compared to no intervention on the incidence of adverse events in general (zero events in both treatment groups; 1 study, 451 participants) or vomiting specifically (Peto odds ratio (OR) 4.17, 95% confidence interval (CI) 0.30 to 57.26, 1 study, 25 participants), ICU admission (Peto OR 7.77, 95% CI 0.15 to 391.93, 1 study, 451 participants) and clinical deterioration (zero events in both treatment groups; 1 study, 451 participants) in participants with mixed types or paracetamol poisoning, as all evidence for these outcomes was of very low certainty. No studies assessed SDAC for mortality, duration of symptoms, drug absorption or hospitalization.Only one study compared SDAC to syrup of ipecac in participants with mixed types of poisoning, providing very low-certainty evidence. Therefore we are uncertain about the effects on Glasgow Coma Scale scores (mean difference (MD) -0.15, 95% CI -0.43 to 0.13, 1 study, 34 participants) or incidence of adverse events (risk ratio (RR) 1.24, 95% CI 0.26 to 5.83, 1 study, 34 participants). No information was available concerning mortality, duration of symptoms, drug absorption, hospitalization or ICU admission.This review also considered the added value of SDAC or MDAC to hospital interventions, which mostly included gastric lavage. No included studies investigated the use of body positioning in oral poisoning patients.First aid interventions that evacuate the poison from the gastrointestinal tractWe found one study comparing ipecac versus no intervention in toxic berry ingestion in a pre-hospital setting. Low-certainty evidence suggests there may be an increase in the incidence of adverse events, but the study did not report incidence of mortality, incidence or duration of symptoms of poisoning, drug absorption, hospitalization or ICU admission (103 participants).In addition, we also considered the added value of syrup of ipecac to SDAC plus a cathartic and the added value of a cathartic to SDAC.No studies used cathartics as an individual intervention.First aid interventions that neutralize or dilute the poison No included studies investigated the neutralization or dilution of the poison in oral poisoning patients.The review also considered combinations of different first aid interventions. AUTHORS' CONCLUSIONS: The studies included in this review provided mostly low- or very low-certainty evidence about the use of first aid interventions for acute oral poisoning. A key limitation was the fact that only one included study actually took place in a pre-hospital setting, which undermines our confidence in the applicability of these results to this setting. Thus, the amount of evidence collected was insufficient to draw any conclusions.


Assuntos
Primeiros Socorros/métodos , Envenenamento/terapia , Acetaminofen/envenenamento , Analgésicos não Entorpecentes/envenenamento , Antidepressivos/envenenamento , Antídotos/uso terapêutico , Benzodiazepinas/envenenamento , Carbamazepina/envenenamento , Catárticos/uso terapêutico , Carvão Vegetal/uso terapêutico , Frutas/envenenamento , Humanos , Ipeca/uso terapêutico , Envenenamento/etiologia , Viés de Publicação , Ensaios Clínicos Controlados Aleatórios como Assunto , Thevetia/envenenamento
17.
Semin Respir Crit Care Med ; 39(5): 513-522, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30485882

RESUMO

Acute liver failure (ALF) is a condition that can rapidly progress to multiorgan failure. This article focuses on the diagnosis and management of ALF. We provide a detailed review of the common etiologies of ALF, including acetaminophen overdose, viral hepatitis, drug-induced liver injury, Wilson's disease, and autoimmune hepatitis. The article then addresses how to recognize ALF and reviews the role of common laboratory and imaging tests in establishing this diagnosis. The remainder of the article details the management of hepatic and extrahepatic organ dysfunctions in ALF. The article concludes with a discussion regarding the prognostication of patients with ALF and the criteria for considering liver transplantation.


Assuntos
Falência Hepática Aguda/diagnóstico , Falência Hepática Aguda/etiologia , Falência Hepática Aguda/terapia , Acetaminofen/envenenamento , Doença Hepática Induzida por Substâncias e Drogas , Cuidados Críticos , Overdose de Drogas , Hepatite Autoimune , Hepatite Viral Humana , Degeneração Hepatolenticular , Humanos , Testes de Função Hepática , Transplante de Fígado , Insuficiência Renal/complicações
18.
J Emerg Med ; 55(6): e141-e145, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30287134

RESUMO

BACKGROUND: Pediatric exposure to prazosin is unusual because it is most commonly indicated for the treatment of hypertension. Prazosin's increase in popularity as a treatment for posttraumatic stress disorder makes it important for emergency physicians to be aware of how to manage potential toxic ingestion because of prazosin overdose. CASE REPORT: A 16-year-old, 76-kg female presented after ingesting 110 mg of prazosin, 209.3 g of acetaminophen, and 55 g of naproxen. She was admitted to the pediatric intensive care unit for rapidly deteriorating hypotension (lowest blood pressure 47/19 mm Hg) refractory to aggressive fluid resuscitation and infusions of epinephrine and norepinephrine each at 0.5 mcg/kg/min. Stabilization of blood pressure was eventually achieved, and associated with use of a vasopressin infusion of 0.004 units/kg/min. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Because of the increasing exposure of children to prazosin, clinicians should be aware of the pharmacology behind alpha-1 antagonist overdose and consider treatment options, such as vasopressin, when hypotension is resistant to standard fluid and catecholamine therapy.


Assuntos
Acetaminofen/envenenamento , Analgésicos não Entorpecentes/envenenamento , Anti-Inflamatórios não Esteroides/envenenamento , Anti-Hipertensivos/envenenamento , Overdose de Drogas/terapia , Hipotensão/induzido quimicamente , Naproxeno/envenenamento , Prazosina/envenenamento , Adolescente , Feminino , Humanos , Tentativa de Suicídio
19.
Br J Gen Pract ; 68(675): e703-e710, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30201829

RESUMO

BACKGROUND: Globally, poisonings account for most medically-attended self-harm. Recent data on poisoning substances are lacking, but are needed to inform self-harm prevention. AIM: To assess poisoning substance patterns and trends among 10-24-year-olds across England DESIGN AND SETTING: Open cohort study of 1 736 527 young people, using linked Clinical Practice Research Datalink, Hospital Episode Statistics, and Office for National Statistics mortality data, from 1998 to 2014. METHOD: Poisoning substances were identified by ICD-10 or Read Codes. Incidence rates and adjusted incidence rate ratios (aIRR) were calculated for poisoning substances by age, sex, index of multiple deprivation, and calendar year. RESULTS: In total, 40 333 poisoning episodes were identified, with 57.8% specifying the substances involved. The most common substances were paracetamol (39.8%), alcohol (32.7%), non-steroidal anti-inflammatory drugs (NSAIDs) (11.6%), antidepressants (10.2%), and opioids (7.6%). Poisoning rates were highest at ages 16-18 years for females and 19-24 years for males. Opioid poisonings increased fivefold from 1998-2014 (females: aIRR 5.30, 95% confidence interval (CI) = 4.08 to 6.89; males: aIRR 5.11, 95% CI = 3.37 to 7.76), antidepressant poisonings three-to fourfold (females: aIRR 3.91, 95% CI = 3.18 to 4.80, males: aIRR 2.70, 95% CI = 2.04 to 3.58), aspirin/NSAID poisonings threefold (females: aIRR 2.84, 95% CI = 2.40 to 3.36, males: aIRR 2.76, 95% CI = 2.05 to 3.72) and paracetamol poisonings threefold in females (aIRR 2.87, 95% CI = 2.58 to 3.20). Across all substances poisoning incidence was higher in more disadvantaged groups, with the strongest gradient for opioid poisonings among males (aIRR 3.46, 95% CI = 2.24 to 5.36). CONCLUSION: It is important that GPs raise awareness with families of the substances young people use to self-harm, especially the common use of over-the-counter medications. Quantities of medication prescribed to young people at risk of self-harm and their families should be limited, particularly analgesics and antidepressants.


Assuntos
Acetaminofen/envenenamento , Analgésicos Opioides/envenenamento , Antidepressivos/envenenamento , Etanol/envenenamento , Educação em Saúde/organização & administração , Comportamento Autodestrutivo/induzido quimicamente , Adolescente , Criança , Estudos de Coortes , Inglaterra/epidemiologia , Feminino , Medicina Geral , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Incidência , Masculino , Papel do Médico , Vigilância da População , Comportamento Autodestrutivo/epidemiologia , Comportamento Autodestrutivo/prevenção & controle , Adulto Jovem
20.
Emerg Med J ; 35(10): 643-645, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30249712

RESUMO

A short-cut review was carried out to establish whether oral N-acetylcysteine is as effective as intravenous N-acetylcysteine in the management of paracetamol overdose. Seven studies were directly relevant to the question. The author, year and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is that oral N-acetylcysteine is a safe alternative in patients for whom the intravenous route is not an option.


Assuntos
Acetaminofen/efeitos adversos , Acetaminofen/envenenamento , Acetilcisteína/administração & dosagem , Acetilcisteína/farmacologia , Overdose de Drogas/tratamento farmacológico , Acetilcisteína/uso terapêutico , Administração Intravenosa , Administração Oral , Adolescente , Humanos , Masculino
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