RESUMO
BACKGROUND: Acetaminophen toxicity remains one of the most common causes of liver failure and is treated with a course of n-acetylcysteine (NAC). This exceptionally effective medication is traditionally administered using a complicated three-bag protocol that is prone to administration errors. OBJECTIVE: We aimed to assess whether switching to a novel two-bag protocol (150 mg/kg over 1 h followed by 150 mg/kg over 20 h) reduced administration errors while not increasing liver injury or anaphylactoid reactions. METHODS: This was a retrospective chart review of hospital encounters for patients with acetaminophen toxicity, comparing outcomes before and after the change from a three-bag protocol to a two-bag protocol at two affiliated institutions. The primary outcome was incidence of medication errors with secondary outcomes including acute liver injury (ALI) and incidence of non-anaphylactoid allergic reactions (NAAR). The study was approved by the health system's Institutional Review Board. RESULTS: 483 encounters were included for analysis (239 in the three-bag and 244 in the two-bag groups). NAAR were identified in 11 patients with no difference seen between groups. Similarly, no differences were seen in ALI. Medication administration errors were observed significantly less often in the two-bag group (OR 0.24) after adjusting for confounders. CONCLUSION: Transitioning to a novel two-bag NAC regimen decreased administration errors. This adds to the literature that two-bag NAC regimens are not only safe but also may have significant benefits over the traditional NAC protocol.
Assuntos
Acetaminofen , Acetilcisteína , Doença Hepática Induzida por Substâncias e Drogas , Erros de Medicação , Humanos , Acetilcisteína/uso terapêutico , Acetilcisteína/administração & dosagem , Estudos Retrospectivos , Feminino , Masculino , Adulto , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Pessoa de Meia-Idade , Erros de Medicação/prevenção & controle , Analgésicos não Narcóticos , Antídotos/administração & dosagem , Antídotos/efeitos adversos , Antídotos/uso terapêutico , Resultado do Tratamento , Esquema de Medicação , Embalagem de MedicamentosRESUMO
INTRODUCTION: Children are at higher risk of medication errors due to the complexity of drug prescribing and administration in this patient group. Intravenous (IV) paracetamol overdose differs from overdose by ingestion as there is no enteral absorptive buffering. We provide the first national UK data focusing on paediatric IV paracetamol poisoning. METHODS: All telephone enquiries to the National Poisons Information Service between 2008 and 2021 regarding children less than 18 years old in the UK concerning IV paracetamol overdose were extracted from the UK Poisons Information Database (UKPID). Data were analysed using descriptive statistics. RESULTS: Enquiries were made concerning 266 children, mostly involving children under the age of 1 year (n=145; 54.5%). Acute and staggered overdoses were the most frequent types of exposure. Common error themes included 10-fold overdose in 45 cases (16.9%) and inadvertent concomitant oral and IV dosing in 64 cases (24.1%). A high proportion of cases were asymptomatic (87.1%), with many calls regarding overdoses below the treatable dose of 60 mg/kg (41.4%). Treatment with the antidote acetylcysteine was advised in 113 cases (42.5%). CONCLUSIONS: Inadvertent IV paracetamol overdose appears to occur more frequently in young children. A significant proportion were calculation errors which were often 10-fold errors. While these errors have the potential for causing serious harm, thankfully most cases were asymptomatic. Errors with IV paracetamol might be reduced by electronic prescribing support systems, better communication regarding administration and consideration of whether other routes are more appropriate.
Assuntos
Acetaminofen , Analgésicos não Narcóticos , Overdose de Drogas , Erros de Medicação , Centros de Controle de Intoxicações , Humanos , Acetaminofen/intoxicação , Acetaminofen/administração & dosagem , Erros de Medicação/estatística & dados numéricos , Criança , Lactente , Pré-Escolar , Overdose de Drogas/epidemiologia , Reino Unido/epidemiologia , Adolescente , Centros de Controle de Intoxicações/estatística & dados numéricos , Feminino , Masculino , Analgésicos não Narcóticos/intoxicação , Analgésicos não Narcóticos/administração & dosagem , Administração Intravenosa , Antídotos/administração & dosagem , Antídotos/efeitos adversos , Antídotos/uso terapêutico , Acetilcisteína/administração & dosagem , Acetilcisteína/efeitos adversos , Acetilcisteína/uso terapêutico , Recém-NascidoRESUMO
INTRODUCTION: Physostigmine fell out of widespread use in the 1980s due to safety concerns; however, more recent research has demonstrated that its safety profile is better than previously thought. These studies have mainly included adults. We theorized that improved safety data may lead to more acceptance. Our objectives, therefore, were to characterize current frequency of use of physostigmine in pediatric patients as well as to study adverse effect rates in a national pediatric patient population. METHODS: The National Poison Data System was queried for cases of patients aged 0-18 years that involved single-substance exposures to antimuscarinic xenobiotics that were reported to a poison center between January 1, 2000, and December 31, 2020. Cases were stratified into groups by therapy received: benzodiazepines alone, benzodiazepines and physostigmine, physostigmine alone, or no physostigmine or benzodiazepines. Patient demographics, clinical effects, and medical outcomes were analyzed. RESULTS: A total of 694,132 cases were reviewed, and 150,075 were included for analysis. Nearly 5% (7562/150,075) of patients received specific pharmacological therapy with benzodiazepines, physostigmine, or both. A benzodiazepine as a single agent was the most frequently used pharmacologic therapy (92% of 7562). Among patients receiving any pharmacological therapy, only 8.3% (n = 627) of patients received physostigmine. Frequency of serious outcomes significantly increased across the study period among patients receiving benzodiazepines alone or with physostigmine. There was no increase in serious outcomes among patients receiving only physostigmine. CONCLUSIONS: Physostigmine frequency of use was low overall, but when used, was associated with less severe outcomes when compared to benzodiazepines.
Assuntos
Benzodiazepinas , Antagonistas Muscarínicos , Fisostigmina , Centros de Controle de Intoxicações , Humanos , Fisostigmina/uso terapêutico , Criança , Pré-Escolar , Adolescente , Lactente , Feminino , Masculino , Antagonistas Muscarínicos/uso terapêutico , Benzodiazepinas/intoxicação , Estudos Retrospectivos , Recém-Nascido , Inibidores da Colinesterase/intoxicação , Estados Unidos , Antídotos/uso terapêutico , Antídotos/efeitos adversos , Bases de Dados FactuaisRESUMO
And Then There Were None and Sparkling Cyanide, two of Agatha Christie's famous novels describe potassium cyanide-induced deaths. Cyanide, a tasteless, odorless, strongly alkaline poison is a powerful gastrointestinal irritant, following oral ingestion. It reacts with hydrochloric acid in the gastric juice to produce hydrogen cyanide gas, which is absorbed and inhibits the mitochondrial electron transfer system and consequently suppresses adenosine triphosphate (ATP) production. Therefore, the central nervous system, which consumes a large amount of ATP, is first affected and symptoms of poisoning manifest as dizziness, disorientation, coma, and convulsions. The orally lethal dose is approximately 300 mg.
Assuntos
Antídotos , Cianetos , Humanos , Cianetos/efeitos adversos , Antídotos/efeitos adversos , Convulsões , Trifosfato de Adenosina/efeitos adversosRESUMO
BACKGROUND ThinPrep Cytolyt is a methanol-based cell preservation solution frequently used to fix tissue samples immediately following endobronchial ultrasound-guided fine-needle aspiration. Currently, no published reports describe an iatrogenic exposure to Cytolyt. We report the only known case of an accidental intraoperative administration of a methanol solution, with corresponding plasma concentrations, and successful treatment with fomepizole. CASE REPORT A 70-year-old woman with a history of stage IIIA rectal adenocarcinoma was referred for evaluation of a newly identified lung mass. During the procedure, a bronchoalveolar lavage (BAL) of the right upper lobe was performed. After BAL, the proceduralist was informed that the syringe used to instill fluid for the BAL contained Cytolyt rather than saline. The Department of Medical Toxicology was contacted immediately, and the patient received a 15 mg/kg dose of fomepizole. The first plasma methanol level, before fomepizole administration, was elevated to 21 mg/dL. The methanol level was 13 mg/dL 3 h after fomepizole treatment and even lower thereafter; therefore, no additional fomepizole was required. The patient did not develop signs of systemic toxicity and was discharged on hospital day 3. CONCLUSIONS Following methanol exposures, patients can exhibit metabolic acidosis, with potential for blindness, hemodynamic instability, and possibly death if untreated. Fomepizole (4-methylpyrazole) inhibits alcohol dehydrogenase and is a mainstay of treatment. Preventing medical errors is key in ensuring optimal patient care and decreasing adverse events. Providers using CytoLyt and any similar products should be aware of this potential error and approach the possibility of methanol toxicity as they would other routes of methanol exposure.
Assuntos
Antídotos , Metanol , Feminino , Humanos , Idoso , Fomepizol , Antídotos/efeitos adversos , Pirazóis/uso terapêutico , Dimercaprol , Doença IatrogênicaRESUMO
INTRODUCTION: Although not a potentially life-threatening poisoning, benzodiazepine (BZD) intoxication may be life-threatening in special situations/populations or those with background diseases. AREAS COVERED: The aim of this review is to evaluate all possible treatment options available in the literature for the management of benzodiazepine poisoning with special attention to antidote administration. We conducted a literature search using PubMed, Google Scholar, EMBASE, and Cochrane central register from 1 January 1980 to 10 November 2021 using keywords 'benzodiazepine,' 'poisoning,' 'toxicity,' 'intoxication,' and 'treatment.' EXPERT OPINION: Careful patient selection, ideally by a clinical toxicologist, may decrease the complications of flumazenil and add to its efficacy. The cost-to-benefit ratio should be considered in every single patient who is a candidate for flumazenil administration. In case a decision has been made to administer flumazenil, careful consideration of the possible contraindications is essential. We recommend slow administration of low doses of flumazenil (0.1 mg/minute) to avoid complications or withhold the administration with development of first signs of adverse effects. The main treatment of benzodiazepine toxicity is conservative with administration of activated charcoal, monitoring of the vital signs, prevention of aspiration and development of deep vein thrombosis due to prolonged immobilization, and respiratory support.
Assuntos
Overdose de Drogas , Flumazenil , Antídotos/efeitos adversos , Benzodiazepinas/efeitos adversos , Overdose de Drogas/tratamento farmacológico , Flumazenil/efeitos adversos , HumanosRESUMO
BACKGROUND: Historically, the first step in treating cyanide (CN-) toxicity utilized antidotes to induce methemoglobinemia. This is concerning in patients who are already hypoxemic or have elevated carboxyhemoglobin. Hydroxocobalamin (OHCbl) is now the first-line antidote for CN- toxicity and is not known to induce methemoglobinemia. We observed elevated methemoglobin (MetHb) levels in several patients treated with OHCbl and sought to investigate the incidence of MetHb formation following administration of OHCbl. METHODS: Chart review: A single-center, retrospective case series of patients who received 5 or 10 g of hydroxocobalamin from 01/01/2011 through 04/30/2019. Data was analyzed using descriptive statistics. In-vitro study: Discarded blood was separated into whole blood and plasma samples. OHCbl and normal saline was added to reach 0×, 1×, 2×, and 4× peak therapeutic concentrations and analyzed at times 0, 2, and 4 h after administration. RESULTS: Chart review: Twenty-seven cases of OHCbl administration were identified. The median age was 53 years (IQR 38 - 64) and 20 (74.1%) were male. Exposure to a house fire or smoke inhalation was the reason for OHCbl administration in 21 (77.8%) patients. Five (18.5%) patients received 10 g of OHCbl while the rest received 5 g. Six (22.2%) patients developed methemoglobinemia, all after 5 g OHCbl administration; four had been exposed to fire and smoke, two received the medication for severe acidosis of unknown etiology not related to fire or smoke. The median peak level was 7.1% (IQR 2.2 - 16.4%) at a median time of 11.4 h post-administration. Two patients received methylene blue (MB), neither responded. Death occurred in 17 (63%) cases. In-vitro study: We observed a dose dependent elevation in total hemoglobin but did not detect any increase in MetHb. CONCLUSION: We observed a noteworthy temporal association between the formation of methemoglobinemia and the administration of hydroxocobalamin. This does not appear to be an artifact of the CO-oximeters. This could have profound implications for patients who are already hypoxemic or have impaired oxygen carrying capacity from carboxyhemoglobin.
Assuntos
Hidroxocobalamina , Metemoglobinemia , Adulto , Antídotos/efeitos adversos , Carboxihemoglobina/análise , Cianetos , Feminino , Humanos , Hidroxocobalamina/uso terapêutico , Masculino , Metemoglobina/análise , Metemoglobinemia/induzido quimicamente , Metemoglobinemia/tratamento farmacológico , Azul de Metileno , Pessoa de Meia-Idade , Oxigênio , Estudos Retrospectivos , Solução Salina , FumaçaRESUMO
Activated charcoal (AC) is a potential candidate antidote against dioxins. However, it is difficult to take AC as a supplement on a daily basis, because its long-term ingestion causes side effects such as constipation and deficiency of fat-soluble essential nutrients and hypocholesterolemia. Alginate-coated AC, termed Health Carbon (HC), was developed to decrease the side effects of AC, but its pharmacological effects, including side effects, remains unclear. Here, we show that HC enhanced fecal excretion of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and decreased some side effects of unmodified AC, such as hypocholesterolemia, in male mice. Basal diet mixed with HC or unmodified AC at various concentrations was fed to mice for 16 days following a single intraperitoneal administration of [3H]TCDD. Both HC and unmodified AC at 3% or more significantly increased fecal excretion of [3H]TCDD in comparison with the control basal diet. Consistent with this, [3H]TCDD radioactivity in the liver-a major TCDD storage organ-was markedly decreased by HC at concentrations of 3% and 10%. In an examination of potential side effects, unmodified AC at 10% or more caused significant body weight reduction and at 20% caused significant hypocholesterolemia. In contrast, HC caused weight gain reduction only at a concentration of 20%, and there was no evidence of hypocholesterolemia at any dietary HC concentration. HC not only retains the ability of AC to enhance fecal excretion of TCDD but also reduces some of the side effects of AC.
Assuntos
Alginatos , Antídotos/efeitos adversos , Antídotos/farmacologia , Carvão Vegetal/efeitos adversos , Carvão Vegetal/farmacologia , Fezes , Dibenzodioxinas Policloradas/metabolismo , Administração Oral , Alginatos/administração & dosagem , Animais , Antídotos/administração & dosagem , Carvão Vegetal/administração & dosagem , Colesterol/sangue , Constipação Intestinal/induzido quimicamente , Masculino , Camundongos Endogâmicos , Redução de PesoRESUMO
INTRODUCTION: Acetylcysteine is the standard treatment for preventing hepatotoxicity caused by acetaminophen overdose. Several novel approaches to the management of acetaminophen overdose have been suggested to improve patient safety by reducing adverse drug reactions and dosing errors. This article reviews these alternative treatment regimens and intends to offer a detailed assessment of the available options to assist providers in managing cases of acetaminophen overdose. AREAS COVERED: This review article covers observational and experimental studies that assessed the efficacy and safety of alternative intravenous acetylcysteine regimens for acetaminophen overdose. A literature search was conducted using PubMed, ProQuest, and Scopus to identify the studies, which included results through April 2021. The assessment of alternative regimens consists of a discussion on the limitations and benefits, barriers to implementation, and important considerations for each regimen. EXPERT OPINION: Several alternative regimens have been studied and implemented in various institutions. Many of these dosing regimens have supporting safety data but most lack robust data. A reduction in infusion-related side effects is an important outcome, but established efficacy, local poison center familiarity with the regimen, institutional resources, and patient-specific factors should be equally considered when deciding on implementing and using an alternative dosing strategy.
Assuntos
Acetaminofen/intoxicação , Acetilcisteína/administração & dosagem , Antídotos/administração & dosagem , Acetilcisteína/efeitos adversos , Administração Intravenosa , Analgésicos não Narcóticos/intoxicação , Antídotos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Overdose de Drogas/tratamento farmacológico , HumanosRESUMO
Copper sulfate immersion is common for the prevention and treatment of Cryptocaryon irritans during quarantine of marine teleosts. The National Aquarium in Baltimore has followed a consistent copper sulfate protocol for marine teleost quarantine since 2004. The protocol used copper sulfate pentahydrate as a slow drip to increase copper ions over 3-5 days to a level of 0.18-0.21 mg/L. This level was maintained for 21 days, and then copper ions were rapidly removed with activated carbon filtration and water changes. Quarantine records from 2004-2016 were used to examine mortality of marine teleosts during copper treatment and identify factors that might have influenced mortality. The following records were excluded: brackish and freshwater teleosts (salinity <25 g/L); long-term treatment at subtherapeutic levels (<0.18 mg/L); intentional short courses (<14 days); and use outside of quarantine. Species, system volume, temperature, parasitic outbreaks, concurrent medications, and water quality concerns were evaluated. During this period, 4,835 individual teleosts belonging to 347 different species were treated. From 2004 to 2016, mortality during copper treatment was 4.1% (199/4,835 individuals) and was higher when treatment was started during the first week of quarantine (7.7%, 68/884) rather than later (3.3%, 131/3,951 individuals). Of the mortalities, 24.1% (48/199) occurred during the initial subtherapeutic period, and 75.9% (151/199) occurred during the therapeutic period. No mortalities occurred in 75.5% (262/347) of species during copper treatment. When using a similar methodology, copper sulfate is a safe immersion for quarantine of marine teleosts. Mortalities during copper treatment can be reduced by increasing copper ion levels to therapeutic ranges more slowly (e.g., over 7 days) and starting copper treatment after the first week of quarantine.
Assuntos
Antídotos/farmacologia , Antiparasitários/farmacologia , Sulfato de Cobre/farmacologia , Doenças dos Peixes/parasitologia , Animais , Animais de Zoológico , Antídotos/administração & dosagem , Antídotos/efeitos adversos , Antiparasitários/administração & dosagem , Baltimore , Sulfato de Cobre/administração & dosagem , Sulfato de Cobre/efeitos adversos , Doenças dos Peixes/prevenção & controle , Peixes , QuarentenaRESUMO
INTRODUCTION: Anaphylactoid reactions are well-documented adverse events associated with the intravenous administration of N-acetylcysteine (NAC) in patients with acetaminophen overdose. Most reactions are mild, occurring within the first 1-5 hours of initiation. This report presents the case of an adolescent with a delayed, life-threatening anaphylactoid reaction 24.5 hours after starting NAC, where discontinuing NAC could have resulted in fulminant hepatic failure (FHF) and death. CASE REPORT: A 17-year-old previously healthy female presented with nausea, vomiting, and abdominal pain 10 hours after an acute acetaminophen ingestion. Her 11-hour serum acetaminophen concentration was above the treatment line (149 µg/mL), and she had elevated transaminases (AST = 202 U/L, ALT = 284 U/L). She was treated with intravenous NAC, which was suspended for 3 hours after she developed an apparent life-threatening anaphylactoid reaction with angioedema and respiratory distress 24.5 hours after treatment initiation. Given her high risk of progression to FHF, NAC was resumed at double the previous rate along with scheduled corticosteroids and antihistamines after resolution of her symptoms. Her AST increased to 10,927 U/L, and INR peaked at 3.6, but she had no further anaphylactoid symptoms. She was discharged in her normal state of health after 6 days. DISCUSSION: Discontinuing NAC in this case of severe, delayed anaphylactoid reaction could have resulted in FHF requiring liver transplant. The reason for her reaction is unclear but could be related to patient risk factors or medication error. Guidelines for reinitiation of NAC after development of delayed anaphylactoid reactions are not well-established. Close observation beyond the first 1-5 hours of NAC administration is warranted.
Assuntos
Acetaminofen/intoxicação , Acetilcisteína/efeitos adversos , Analgésicos não Narcóticos/intoxicação , Anafilaxia/induzido quimicamente , Antídotos/efeitos adversos , Hipersensibilidade a Drogas/etiologia , Overdose de Drogas/tratamento farmacológico , Acetilcisteína/administração & dosagem , Adolescente , Corticosteroides/uso terapêutico , Anafilaxia/diagnóstico , Anafilaxia/tratamento farmacológico , Antídotos/administração & dosagem , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/tratamento farmacológico , Overdose de Drogas/diagnóstico , Feminino , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Infusões Intravenosas , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Sodium bicarbonate therapy (SBT) is currently indicated for the management of a variety of acute drug poisonings. However, SBT effects on serum potassium concentrations may lead to delayed QTc prolongation (DQTP), and subsequent risk of adverse cardiovascular events (ACVE), including death. Emergency department (ED)-based studies evaluating associations between SBT and ACVE are limited; thus, we aimed to investigate the association between antidotal SBT, ECG changes, and ACVE. METHODS: This was a secondary data analysis of a consecutive cohort of ED patients with acute drug overdose over 3 years. Demographic and clinical data as well as SBT bolus dosage and infusion duration were collected, and outcomes were compared with an unmatched consecutive cohort of patients with potential indications for SBT but who did not receive SBT. The primary outcome was the occurrence of ACVE, and secondary outcomes were delayed QTc (Bazett) prolongation (DQTP), and death. Propensity score and multivariable adjusted analyses were conducted to evaluate associations between adverse outcomes and SBT administration. Planned subgroup analysis was performed for salicylates, wide QRS (> 100 ms), and acidosis (pH < 7.2). RESULTS: Out of 2365 patients screened, 369 patients had potential indications for SBT, of whom 31 (8.4%) actually received SBT. In adjusted analyses, SBT was found to be a significant predictor of ACVE (aOR 9.35, CI 3.6-24.1), DQTP (aOR 126.7, CI 9.8-1646.2), and death (aOR 11.9, CI 2.4-58.9). Using a propensity score model, SBT administration was associated with ACVE (OR 5.07, CI 1.8-14.0). Associations between SBT and ACVE were maintained in subgroup analyses of specific indications for sodium channel blockade (OR 21.03, CI 7.16-61.77) and metabolic acidosis (OR: 6.42, 95% CI: 1.20, 34.19). CONCLUSION: In ED patients with acute drug overdose and potential indications for SBT, administration of SBT as part of routine clinical care was an independent, dose-dependent, predictor of ACVE, DQTP, and death. This study was not designed to determine whether the SBT or acute overdose itself was causative of ACVE; however, these data suggest that poisoned patients receiving antidotal SBT require close cardiovascular monitoring.
Assuntos
Antídotos/efeitos adversos , Overdose de Drogas/tratamento farmacológico , Sistema de Condução Cardíaco/efeitos dos fármacos , Síndrome do QT Longo/induzido quimicamente , Bicarbonato de Sódio/efeitos adversos , Potenciais de Ação/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Overdose de Drogas/diagnóstico , Overdose de Drogas/mortalidade , Serviço Hospitalar de Emergência , Feminino , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Humanos , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/mortalidade , Síndrome do QT Longo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
ABSTRACT: Although using direct oral anticoagulants increases patient risk for hemorrhagic events, FDA-approved options for reversing anticoagulant effects are limited. This article discusses one of the more recent FDA-approved antidotes, andexanet alfa, and provides guidelines for its safe and effective use.
Assuntos
Antídotos/administração & dosagem , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Fator Xa/administração & dosagem , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Proteínas Recombinantes/administração & dosagem , Antídotos/efeitos adversos , Contraindicações de Medicamentos , Fator Xa/efeitos adversos , Humanos , Guias de Prática Clínica como Assunto , Proteínas Recombinantes/efeitos adversos , Risco , Prevenção Secundária , Tromboembolia Venosa/prevenção & controleAssuntos
Carbamazepina/intoxicação , Carvão Vegetal/administração & dosagem , Carvão Vegetal/efeitos adversos , Ácido Láctico/sangue , Idoso , Antídotos/administração & dosagem , Antídotos/efeitos adversos , Feminino , Humanos , Hiperlactatemia/induzido quimicamente , Intubação Gastrointestinal , Propilenoglicol/efeitos adversosRESUMO
INTRODUCTION: Acetaminophen (APAP) hepatotoxicity is the leading cause of acute liver failure in the western world. Despite extensive investigations into the mechanisms of cell death, only a single antidote, N-acetylcysteine, is in clinical use. However, there have recently been more efforts made to translate mechanistic insight into identification of therapeutic targets and potential new drugs for this indication. AREAS COVERED: After a short review of the key events in the pathophysiology of APAP-induced liver injury and recovery, the pros and cons of targeting individual steps in the pathophysiology as therapeutic targets are discussed. While the re-purposed drug fomepizole (4-methylpyrazole) and the new entity calmangafodipir are most advanced based on the understanding of their mechanism of action, several herbal medicine extracts and their individual components are also considered. EXPERT OPINION: Fomepizole (4-methylpyrazole) is safe and has shown efficacy in preclinical models, human hepatocytes and in volunteers against APAP overdose. The safety of calmangafodipir in APAP overdose patients was shown but it lacks solid preclinical efficacy studies. Both drugs require a controlled phase III trial to achieve regulatory approval. All studies of herbal medicine extracts and components suffer from poor experimental design, which questions their clinical utility at this point.
Assuntos
Acetaminofen/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Falência Hepática Aguda/induzido quimicamente , Acetaminofen/administração & dosagem , Acetilcisteína/administração & dosagem , Animais , Antídotos/administração & dosagem , Antídotos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Overdose de Drogas , Ácido Edético/administração & dosagem , Ácido Edético/efeitos adversos , Ácido Edético/análogos & derivados , Fomepizol/administração & dosagem , Fomepizol/efeitos adversos , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Humanos , Falência Hepática Aguda/tratamento farmacológico , Falência Hepática Aguda/fisiopatologia , Fosfato de Piridoxal/administração & dosagem , Fosfato de Piridoxal/efeitos adversos , Fosfato de Piridoxal/análogos & derivadosRESUMO
INTRODUCTION: Direct thrombin inhibitor, dabigatran and factor Xa inhibitors, apixaban, edoxaban, and rivaroxaban (DOACs/NOACs), are currently the first-choice drugs in some indications. Life-threatening bleeding occurring during DOACs treatment may benefit from the use of reversal agents, however there are some concerns regarding potential rebound thrombotic events. In this systematic review we aimed to estimate the incidence of thrombotic events in patients treated with idarucizumab or andexanet alfa. METHODS: This systematic review included all prospective and retrospective studies, enrolling patients that received specific antidotes (idarucizumab, andexanet alfa and cirapantag) for anticoagulation reversal, published until October 2019 in CENTRAL, MEDLINE and PsycINFO. Studies in healthy individuals and those with less than 10 patients were excluded. The primary outcome was the incidence of thrombotic events and the secondary outcome was all-cause mortality. Studies screening and data extraction was performed in duplicate by reviewers. A random-effects meta-analysis was performed using the Freeman-Tukey transformation of the data. The results are expressed in percentages, with 95%-confidence intervals (CI), limited between 0 and 100% due to the data transformation. RESULTS: Overall 16 studies with 1774 patients were included (13 studies enrolling 1384 patients that received idarucizumab; 3 studies enrolling 390 patients that received andexanet alfa; cirapantag studies were not found). The pooled incidence rate of thrombotic events in the patients treated with specific antidote was 5.5% (95% CI 2.0-10.1%) until 30-90 days. The incidence of all-cause mortality was 13.3% (95% CI 9.6-17.5%). CONCLUSIONS: In patients requiring idarucizumab or andexanet alfa to reach haemostasis, our data shows that there were 5.5% thrombotic events. The causality of harm associated to antidotes remains to be established due to the design of studies without a control group.
Assuntos
Anticoagulantes , Fator Xa , Administração Oral , Anticorpos Monoclonais Humanizados , Anticoagulantes/efeitos adversos , Antídotos/efeitos adversos , Inibidores do Fator Xa , Humanos , Incidência , Estudos Prospectivos , Proteínas Recombinantes , Estudos RetrospectivosRESUMO
PURPOSE: Drug-induced liver injury (DILI) that progresses to acute liver failure (ALF) has a high mortality rate, and therapeutic options are limited. Acetylcysteine has a labeled indication for use as an antidote for acetaminophen toxicity and has also been used with limited success in treatment of non-acetaminophen-induced liver injury, with small clinical trials indicating an increase in transplant-free survival. Recommendations for management of non-acetaminophen-induced DILI include withdrawal of the offending agent and supportive care. Treatment guidelines generally discourage a rechallenge with an offending medication, except in cases where there are no other therapeutic options for management of a serious disease, such as active tuberculosis (TB). SUMMARY: This case report describes the reversal of ALF due to DILI in a patient receiving antitubercular agents for active TB. After withdrawal of initially prescribed antitubercular agents, the patient was switched to a less hepatotoxic anti-TB regimen and intravenous acetylcysteine pending results of antimicrobial susceptibility testing. After stabilization of the patient's liver enzyme levels, intravenous acetylcysteine was discontinued and oral acetylcysteine was continued for 5 days without an increase in hepatic enzyme levels or clinical deterioration. After 5 days, oral acetylcysteine was discontinued due to patient-reported nausea and vomiting. CONCLUSION: Given the limited number of therapeutic interventions shown to be beneficial in ALF and data suggesting a protective effect against DILI with initiation of acetylcysteine at the start of treatment with anti-TB medications, acetylcysteine can be considered for patients with anti-TB - associated DILI.