Multiplying the serum aminotransferase by the acetaminophen concentration to predict toxicity following overdose The APAP × AT multiplication product

Context. The first available predictors of hepatic injury following acetaminophen (APAP) overdose are the serum APAP and aminotransferases [AT, i.e., aspartate (AST) aminotransferase or alanine (ALT) aminotransferase]. Objective. We describe the initial value, rate of change, and interrelationship between these biomarkers in patients who develop hepatotoxicity despite treatment following acute overdose. A new parameter, the APAP × AT multiplication product, is proposed for early risk stratification. Methods. We conducted a descriptive study of individuals selected from a multicenter retrospective cohort of patients hospitalized for APAP poisoning. We selected those acute APAP overdose patients who subsequently developed AT >1,000 IU/L. Rising serum AT values were compared to simultaneously measured (or estimated) falling serum APAP. The APAP × AT was expressed relative to initiation of acetylcysteine therapy and grouped by time to meeting hepatotoxicity criteria. Results. In the 94 cases studied, serum APAP concentrations were still appreciable Because serum AT rose rapidly (doubling time 9.5 h ) and APAP fell slowly (half-life 4.8 h), the multiplication product remained elevated during the first 12-24 h of antidotal therapy, especially among patients who developed earlier hepatotoxicity (AT > 1,000 IU/L). Discussion and conclusions. The APAP × AT multiplication product, calculated at the time of presentation and after several h of antidotal therapy, holds promise as a new risk predictor following APAP overdose. It requires neither graphical interpretation nor accurate time of ingestion, two limitations to current risk stratification

High risk clinical characteristics for subarachnoid haemorrhage in patients with acute headache: prospective cohort study

Objective To identify high risk clinical characteristics for subarachnoid haemorrhage in neurologically intact patients with headache

Acute Management and Outcomes of Patients with Diabetes Mellitus Presenting to Canadian Emergency Departments with Hypoglycemia

Objectifs: Cette vérification rétrospective des dossiers a permis d\u27examiner les données démographiques, les examens, la prise en charge et les résultats des patients adultes souffrant de diabète sucré qui se sont présentés aux services des urgences (SU) au Canada. Méthodes: Tous les sites ont mené une recherche dans leurs dossiers médicaux électroniques à l\u27aide des codes de la Classification internationale des maladies, dixième révision, pour relever les visites aux SU entre 2008 et 2010 qui étaient liées à l\u27hypoglycémie. Les caractéristiques des patients, les données démographiques, la prise en charge aux SU, les ressources des SU et les résultats sont rapportés. Résultats: Un total de 1039 patients de plus de 17 ans ont été inclus dans l\u27étude; 347 (33,4 %) ont été classifiés comme étant des cas de diabète de type 1 et 692 (66,6 %) ont été classifiés comme étant des cas de diabète de type 2. Les patients souffrant du diabète de type 2 étaient beaucoup plus âgés (73 ans vs 49 ans; p\u3c0,0001) et avaient plus d\u27affections chroniques inscrites à leur dossier (tous p\u3c0,001). La plupart des sujets arrivaient par ambulance, et 39 % des cas montraient des scores de triage qui révélaient des tableaux cliniques graves. Les traitements contre l\u27hypoglycémie étaient fréquents (75,7 %) durant le transport préhospitalier; 38,5 % recevaient du glucose et 40,1 % recevaient du glucagon par voie intraveineuse. Les traitements administrés dans les SU contre l\u27hypoglycémie comprenaient le glucose par voie orale (76,8 %), le glucose par voie intraveineuse (29,6 %) et en perfusion continue (27,7 %). Les examens diagnostiques (81,9 %) comprenaient fréquemment les électrocardiogrammes (51,9 %), la radiographie thoracique (37,5 %) et la tomodensitométrie crânienne (14,5 %). La plupart des patients (73,5 %) recevaient leur congé. Cependant, plus de sujets souffrant du diabète de type 2 nécessitaient une admission (30,3 vs 8,8 %). Les instructions de congé étaient étayées chez seulement 55,5 % des patients, et l\u27orientation vers des services de diabète se rencontrait chez moins de 20 % des cas. Une variation considérable dans la prise en charge de l\u27hypoglycémie existait entre les SU. Conclusions: Les patients souffrant de diabète qui se présentaient à un SU en raison d\u27une hypoglycémie consomment considérablement de ressources en soins de santé, puis une variation est observée dans la pratique. Les SU devraient élaborer des protocoles de prise en charge de l\u27hypoglycémie en portant une attention à la planification du congé pour réduire la récurrence

Sensitivity of computed tomography performed within six hours of onset of headache for diagnosis of subarachnoid haemorrhage: prospective cohort study

Objective To measure the sensitivity of modern third generation computed tomography in emergency patients being evaluated for possible subarachnoid haemorrhage, especially when carried out within six hours of headache onset

Assay precision and risk of misclassification at rule-out cut-offs for high-sensitivity cardiac troponin

Clinical trials and guidelines support the use of very low high-sensitivity cardiac troponin (hs-cTn) results to rule-out a myocardial infarction (MI) ( 1) ). The International Federation of Clinical Chemistry and Laboratory Medicine Committee on Clinical Applications of Cardiac Biomarkers committee, through a modeling approach, suggests assays need to have a lower limit near 3 ng/L and an analytical variation of 10% below 7 ng/L if these low values are to perform consistently in practice ( 2) ). Our objectives for the present study were to assess: i) if any type of instrument or individual instrument could achieve a coefficient of variation (CV) of ≤10% at very low hs-cTn cut-offs (i.e., targets) recommended in clinical pathways; ii) the frequency of results at the hs-cTn target, above the target and below the target, with the latter group representing potential misclassification to the low risk group where the target level would in the intermediate risk range.<br/

A descriptive analysis of aspartate and alanine aminotransferase rise and fall following acetaminophen overdose

<div><p><i>Context:</i> Risk prediction following acetaminophen (paracetamol, APAP) overdose is based on serum APAP, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels. One recently proposed risk stratification tool, the APAPxAT multiplication product, uses either AST or ALT, whichever is higher, yet their interrelation is not well known following APAP-induced hepatic injury. <i>Objective:</i> To describe the kinetics of AST and ALT release into and disappearance from the circulation following APAP overdose. <i>Materials and Methods:</i> An observational case series of adult patients with peak AST or ALT > 100 IU/L attributable to APAP toxicity. Cases were identified by electronic search of hospital laboratory database and by discharge diagnosis corroborated by structured explicit medical record review. <i>Results:</i> Of 68 cases identified (mean age (SD): 39 (18) years, 63% female, and 21% ethanol co-ingested), 28 (41%) developed hepatotoxicity (peak AST or ALT > 1000 IU/L), 28 (41%) coagulopathy (international normalized ratio or INR > 2), and 21 (31%) both. Three patients (4%) were transferred for liver transplantation and ultimately six (8.8%) died. Serum AST and ALT activity rose in a closely aligned 1:1 AST:ALT ratio, but fell at distinctly different rates: AST activity fell with a half-life (interquartile range [IQR]) of 15.1 (12.2, 19.4) hours, and ALT 39.6 (32.9, 47.6) hours. Using an aminotransferase falling to below 50% of peak as the basis for discontinuing acetylcysteine would have resulted in antidotal treatment being stopped 24 (IQR: 9.6, 40) hours earlier (and in no cases later) using AST rather than ALT. Only six patients had an AST:ALT ratio greater than 2:1 at the time of acetylcysteine administration; of these six, four died and one survivor developed coagulopathy. <i>Discussion:</i> AST and ALT release into the circulation appears tightly linked and numerically similar, except in the sickest patients. Once the aminotransferases peak, AST returns to baseline more quickly. <i>Conclusion:</i> Either AST or ALT can be used for early risk stratification tools when only one is known. Any criterion for N-AC discontinuation should be based on the decline of AST rather than ALT, with a potential benefit measured in days.</p></div

Accuracy of the paracetamol-aminotransferase product to predict hepatotoxicity in paracetamol overdose treated with a 2-bag acetylcysteine regimen

Introduction: Paracetamol concentration is a highly accurate risk predictor for hepatotoxicity following overdose with known time of ingestion. However, the paracetamol–aminotransferase multiplication product can be used as a risk predictor independent of timing or ingestion type. Validated in patients treated with the traditional, "three-bag" intravenous acetylcysteine regimen, we evaluated the accuracy of the multiplication product in paracetamol overdose treated with a two-bag acetylcysteine regimen. Methods: We examined consecutive patients treated with the two-bag regimen from five emergency departments over a two-year period. We assessed the predictive accuracy of initial multiplication product for the primary outcome of hepatotoxicity (peak alanine aminotransferase ≥1000IU/L), as well as for acute liver injury (ALI), defined peak alanine aminotransferase ≥2× baseline and above 50IU/L). Results: Of 447 paracetamol overdoses treated with the two-bag acetylcysteine regimen, 32 (7%) developed hepatotoxicity and 73 (16%) ALI. The pre-specified cut-off points of 1500 mg/L × IU/L (sensitivity 100% [95% CI 82%, 100%], specificity 62% [56%, 67%]) and 10,000 mg/L × IU/L (sensitivity 70% [47%, 87%], specificity of 97% [95%, 99%]) were highly accurate for predicting hepatotoxicity. There were few cases of hepatotoxicity irrespective of the product when acetylcysteine was administered within eight hours of overdose, when the product was largely determined by a high paracetamol concentration but normal aminotransferase. Conclusions: The multiplication product accurately predicts hepatotoxicity when using a two-bag acetylcysteine regimen, especially in patients treated more than eight hours post-overdose. Further studies are needed to assess the product as a method to adjust for exposure severity when testing efficacy of modified acetylcysteine regimens