More blood tests in paracetamol overdose?
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ABSTRACT:
SUBMITTER: Owen R
PROVIDER: S-EPMC2083399 | biostudies-literature | 2007 Mar
REPOSITORIES: biostudies-literature
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More blood tests in paracetamol overdose?
Owen Ruth R Sammons Helen M HM
Archives of disease in childhood 20070301 3
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Project description: Not available
| S-EPMC6491303 | biostudies-literature
Project description:Paracetamol (acetaminophen (APAP)) is one of the most commonly used analgesics in the United Kingdom and the United States. However, exceeding the maximum recommended dose can cause serious liver injury and even death. Promising APAP toxicity biomarkers are thought to add value to those used currently and clarification of the functional relationships between these biomarkers and liver injury would aid clinical implementation of an improved APAP toxicity identification framework. The framework currently used to define an APAP overdose is highly dependent upon time since ingestion and initial dose; information that is often highly unpredictable. A pharmacokinetic/pharmacodynamic (PK/PD) APAP model has been built in order to understand the relationships between a panel of biomarkers and APAP dose. Visualization and statistical tools have been used to predict initial APAP dose and time since administration. Additionally, logistic regression analysis has been applied to histology data to provide a prediction of the probability of liver injury.
| S-EPMC6027737 | biostudies-literature
Project description: Not available
| S-EPMC1725876 | biostudies-literature
Project description:Background and Objectives: Over-the-counter availability and a good safety profile make paracetamol one of the most common analgesics in developed countries but also the leading cause of liver failure due to overdose. The objectives of the study were to identify modifiable risk factors for severe hepatotoxicity following paracetamol overdose in adults. Materials and Methods: A retrospective cohort study involved the consecutive adult patients hospitalized in a toxicological center over a period of seven years due to paracetamol overdose. Complete medical datasets of laboratory and anamnestic variables were analyzed and validated by means of logistic regression model. Results: A total of 185 patients entered the study, including 25 individuals who developed severe hepatotoxicity (plasma aminotransferases levels above 1000 UI/L) and 31 individuals with mild to moderate liver injury (plasma aminotransferases levels above upper normal range, but below 1000 UI/L). In the univariable analysis, significant hepatotoxicity risk factors were male gender, alcohol abuse, an ingested paracetamol dose, and a timespan from ingestion to hospital admission. The later one was the only significant risk factor in the multivariable model (adjusted odds ratio 1.08; 95% CI: 1.03-1.12). Conclusions: A delay in hospital admission, resulting in a delayed administration of disease-specific treatment outweighs any other known risk factors of paracetamol-induced hepatotoxicity.
| S-EPMC8402128 | biostudies-literature
Project description:AimIn cases of paracetamol (acetaminophen, APAP) overdose, an accurate estimate of tissue-specific paracetamol pharmacokinetics (PK) and ingested dose can offer health care providers important information for the individualized treatment and follow-up of affected patients. Here a novel methodology is presented to make such estimates using a standard serum paracetamol measurement and a computational framework.MethodsThe core component of the computational framework was a physiologically-based pharmacokinetic (PBPK) model developed and evaluated using an extensive set of human PK data. Bayesian inference was used for parameter and dose estimation, allowing the incorporation of inter-study variability, and facilitating the calculation of uncertainty in model outputs.ResultsSimulations of paracetamol time course concentrations in the blood were in close agreement with experimental data under a wide range of dosing conditions. Also, predictions of administered dose showed good agreement with a large collection of clinical and emergency setting PK data over a broad dose range. In addition to dose estimation, the platform was applied for the determination of optimal blood sampling times for dose reconstruction and quantitation of the potential role of paracetamol conjugate measurement on dose estimation.ConclusionsCurrent therapies for paracetamol overdose rely on a generic methodology involving the use of a clinical nomogram. By using the computational framework developed in this study, serum sample data, and the individual patient's anthropometric and physiological information, personalized serum and liver pharmacokinetic profiles and dose estimate could be generated to help inform an individualized overdose treatment and follow-up plan.
| S-EPMC4799923 | biostudies-literature
Project description:Paracetamol, or acetaminophen (N-acetyl-para-aminophenol, APAP), is an analgesic and antipyretic drug that is commonly used worldwide, implicated in numerous intoxications due to overdose, and causes serious liver damage. APAP can cross the blood-brain barrier and affects brain function in numerous ways, including pain signals, temperature regulation, neuroimmune response, and emotional behavior; however, its effect on adult neurogenesis has not been thoroughly investigated. We analyze, in a mouse model of hepatotoxicity, the effect of APAP overdose (750 mg/kg/day) for 3 and 4 consecutive days and after the cessation of APAP administration for 6 and 15 days on cell proliferation and survival in two relevant neurogenic zones: the subgranular zone of the dentate gyrus and the hypothalamus. The involvement of liver damage (plasma transaminases), neuronal activity (c-Fos), and astroglia (glial fibrillar acidic protein, GFAP) were also evaluated. Our results indicated that repeated APAP overdoses are associated with the inhibition of adult neurogenesis in the context of elevated liver transaminase levels, neuronal hyperactivity, and astrogliosis. These effects were partially reversed after the cessation of APAP administration for 6 and 15 days. In conclusion, these results suggest that APAP overdose impairs adult neurogenesis in the hippocampus and hypothalamus, a fact that may contribute to the effects of APAP on brain function.
| S-EPMC10888347 | biostudies-literature
Project description:BackgroundPrevious studies of paracetamol overdose treatment show that a 2-bag, 20-h intravenous (IV) acetylcysteine regimen decreased the incidence of non-allergic anaphylactic reactions compared to the 3-bag, 21 h IV regimen, but have not examined efficacy of the 20-h 2 bag regimen.MethodsThis was a multi-centre observational study of paracetamol overdose presentations treated with a 2-bag IV acetylcysteine regimen (200 mg/kg over 4 h, 100 mg/kg over 16 h) compared to a 3-bag regimen, performed from 2009 to 2019. Patients were referred from the emergency department to the inpatient toxicology units for continued management. For the primary non-inferiority analysis: subjects had single, acute ingestions, a serum paracetamol-concentration performed 4 to 8-h post-ingestion. The primary outcome was development of acute liver injury (ALI), defined as peak ALT>150 U/L; and > double admission baseline ALT (for presentations within 24 h post-overdose). Secondary outcomes included adverse reactions to acetylcysteine (cutaneous and systemic).FindingOut of 6419 paracetamol overdoses, 2763 received acetylcysteine. For the primary analysis, 1003 received the 2-bag and 783 the 3-bag acetylcysteine regimen. When presentation bloods were performed 4 to 8-h post-overdose, 21 (3.1%) developed ALI with the 2-bag regimen vs 16 (2.9%) with the 3-bag regimen (Difference: 0.2%, 95%CI:-1.6 to 2.2). The incidence of hepatotoxicity was: 1.2% (n = 8) with the two-bag regimen and 1.6% (n = 9) with the three-bag regimen (Difference -0.4%, 95%CI -1.75, 0.91). When presentation bloods were performed 8 to 24-h post-overdose, 70 (21%) developed ALI with the 2-bag regimen vs 46 (23%) with the 3-bag regimen (Difference: -2%, 95%CI -9.12 to 5.36). There were significantly less cutaneous and systemic non-allergic anaphylactic reactions recorded after treatment with the two-bag than the three-bag regimen (1.3% [n = 17] and 7.1% [n = 65], Difference: -5.8%, 95%CI -7.6 to -4.0, p < 0.0001), respectively.InterpretationA two-bag intravenous acetylcysteine regimen was found to be non-inferior to the three-bag regimen with regards to efficacy in preventing acute liver injury for early presentations of paracetamol overdose. No important differences were seen for any other presentations. The two-bag regimen also decreased the incidence of both non-allergic anaphylactic reactions and gastrointestinal adverse events from acetylcysteine treatment.FundingAW is funded by a National Health and Medical Research Council (NHMRC) Early Career Fellowship ID 1159907. GI is funded by a NHMRC Senior Research Fellowship ID 1061041. The NHMRC had no role in the design, writing of this manuscript. The corresponding author (AW) had full access to all the data in the study and final responsibility for the decision to submit the manuscript for publication.
| S-EPMC7082646 | biostudies-literature
Project description:BackgroundThe United Kingdom guideline for acute paracetamol overdose has recommended the use of '100-treatment line'. Emergency medical centers in some developing countries lack the resources for timely reporting of paracetamol concentrations, hence treatment depends on reported dose. This study aimed to examine whether using an reported dose is safe to predict concentration above the 100-line.MethodsData were retrieved from two emergency medical centers retrospectively, between 2010 and 2017. The inclusion criteria were single acute paracetamol overdose, presentation within 15 h, and age ≥ 14 years. Multiple linear regression was performed to determine the effect of ingested dose on paracetamol concentration. Subgroups were created based on ingested dose, rate of concentration above 100-line were investigated.ResultsOne hundred and seventy-two patients were enrolled in the primary analysis; median dose was 133.3 mg/kg and 46 (37.8%) had concentration above 100-line in the first test. Only dose per weight was moderately correlated with the first concentration (R2 = 0.410, p < 0.001). In the ≤200 mg/kg ingestion group, 18 patients showed concentration above 100-line and 8 showed acute liver injury. The cut-off value of 150 mg/kg showed 82.6% sensitivity and 73.8% specificity to predict concentration above 100-line.ConclusionWhere paracetamol concentration is not available and activated charcoal is readily used, following United Kingdom guideline, it is safe to use an ingested dose of > 150 mg/kg as the cut-off value for N-acetylcysteine treatment with risk stratification for hepatotoxicity if the patient is ≥14 years and visit the ED within 15 h after an acute paracetamol overdose.
| S-EPMC8734297 | biostudies-literature
Project description:BackgroundParacetamol overdose is common but patient stratification is suboptimal. We investigated the usefulness of new biomarkers that have either enhanced liver specificity (microRNA-122 [miR-122]) or provide mechanistic insights (keratin-18 [K18], high mobility group box-1 [HMGB1], and glutamate dehydrogenase [GLDH]). The use of these biomarkers could help stratify patients for their risk of liver injury at hospital presentation.MethodsUsing data from two prospective cohort studies, we assessed the potential for biomarkers to stratify patients who overdose with paracetamol. We completed two independent prospective studies: a derivation study (MAPP) in eight UK hospitals and a validation study (BIOPAR) in ten UK hospitals. Patients in both cohorts were adults (≥18 years in England, ≥16 years in Scotland), were diagnosed with paracetamol overdose, and gave written informed consent. Patients who needed intravenous acetylcysteine treatment for paracetamol overdose had circulating biomarkers measured at hospital presentation. The primary endpoint was acute liver injury indicating need for continued acetylcysteine treatment beyond the standard course (alanine aminotransferase [ALT] activity >100 U/L). Receiver operating characteristic (ROC) curves, category-free net reclassification index (cfNRI), and integrated discrimination index (IDI) were applied to assess endpoint prediction.FindingsBetween June 2, 2010, and May 29, 2014, 1187 patients who required acetylcysteine treatment for paracetamol overdose were recruited (985 in the MAPP cohort; 202 in the BIOPAR cohort). In the derivation and validation cohorts, acute liver injury was predicted at hospital presentation by miR-122 (derivation cohort ROC-area under the curve [AUC] 0·97 [95% CI 0·95-0·98]), HMGB1 (0·95 [0·93-0·98]), and full-length K18 (0·95 [0·92-0·97]). Results were similar in the validation cohort (miR-122 AUC 0·97 [95% CI 0·95-0·99], HMGB1 0·98 [0·96-0·99], and full-length K18 0·93 [0·86-0·99]). A combined model of miR-122, HMGB1, and K18 predicted acute liver injury better than ALT alone (cfNRI 1·95 [95% CI 1·87-2·03], p<0·0001 in the MAPP cohort; 1·54 [1·08-2·00], p<0·0001 in the BIOPAR cohort).InterpretationPersonalised treatment pathways could be developed by use of miR-122, HMGB1, and full-length K18 at hospital presentation for patient stratification. This prospective study supports their use for hepatic safety assessment of new medicines.FundingEdinburgh and Lothians Health Foundation, UK Medical Research Council.
| S-EPMC5777094 | biostudies-literature
Project description:BackgroundAssessment of paracetamol overdose in children and teenagers in the emergency department (ED) requires blood, taken 4 hours post ingestion. A commercial partner developed transdermal paracetamol measuring technology. This work aims to understand the acceptability of such a device, and potential market size.MethodsA questionnaire study was undertaken with children and parents attending Alder Hey Children's Hospital, and healthcare professionals (HCP) involved in their care. A retrospective audit of paracetamol ingestion presenting to a paediatric ED was undertaken.ResultsOne hundred forty-three questionnaires were distributed, and 139 returned (response rate 97.2%), comprising 55 children, 52 parents and 32 HCP (recruited between August-October 2019). Overall device acceptability, assessed by favourability of appearance and willingness to wear was high, at 60.0% and 81.5% respectively. Concerns raised included bulky size and weight, and concern regarding the duration younger children would tolerate wearing the device. All groups, including children, ranked accuracy of results as the most important device feature and device comfort the least important. Parents prioritised avoidance of blood tests more than children. One hundred twenty-seven children presented to ED with paracetamol ingestion (September 2017-August 2018), with 57 (44.9%) categorised as accidental overdose. Overall, 106 (83.4%) required paracetamol concentration measuring, and 25 (19.7%) of these required treatment with N-acetylcysteine. Extrapolating nationally, over 7000 children will present with accidental overdose per annum in the UK.ConclusionAcceptability of a non-invasive paracetamol sensor was high in all groups, provided accuracy could be assured.
| S-EPMC9902896 | biostudies-literature