Estudio multicéntrico sobre el tratamiento con N-acetilcisteína como antídoto en la intoxicación por paracetamol / N-acetylcysteine as an antidote for paracetamol poisoning: a multicenter study

Objetivo. Conocer los aspectos clínicos relacionados con el tratamiento del antídoto N-acetilcisteína (NAC) en las intoxicaciones por paracetamol. Método. Estudio observacional y retrospectivo de los pacientes atendidos por intoxicación por paracetamol en cuatro servicios de urgencias durante 3 años (2017-2019). Se analizan variables epidemiológicas, clínicas y asistenciales, así como la idoneidad y seguridad en el empleo del tratamiento antidótico. Resultados. Se incluyeron 332 intoxicaciones: 260 casos (78%) tenían más de 16 años y 242 (73%) fueron mujeres. Doscientos sesenta y ocho intoxicaciones (81%) fueron de causa voluntaria y la semivida de eliminación se determinó en 20 ocasiones (6%). La descontaminación digestiva se indicó de forma incorrecta en 39 ocasiones (28%). Se inició tratamiento con antídoto en 195 casos (58,7%). En 282 casos (85%) no hubo ninguna clínica de gravedad. La correlación entre la dosis referida ingerida y la paracetamolemia en los casos de ingesta voluntaria (R2 = 0,23) fue más fuerte que en los casos de ingesta accidental (R2 = 0,007). Existieron diferencias estadísticamente significativas al relacionar los criterios de gravedad con la dosis referida ajustada al peso (p = 0,001) y el intervalo desde la ingesta y la primera asistencia médica (p = 0,008). Conclusiones. Existe variabilidad en aspectos fundamentales del tratamiento antidótico en las intoxicaciones por paracetamol, a pesar de estar claramente protocolizado su manejo.

Objective. To identify the most common problems related to use of N-acetylcysteine to reverse the toxic effects of paracetamol poisoning. Methods. Retrospective descriptive observational study of clinical records for patients treated for paracetamol poisoning in 4 emergency departments during 3 years (2017-2019). We analyzed epidemiologic, clinical, and care variables, especially those related to the suitability and safety of using N-acetylcysteine as an antidote. Results. We included 332 cases of poisoning of 260 patients (78%) were over the age of 16 years, and 242 (73%) were female. Two hundred sixty-eight poisonings (81%) were the result of voluntary intake. The elimination half-life was determined in 20 cases (6%). Gastrointestinal decontamination was incorrectly prescribed on 39 occasions (28%). Treatment with the antidote was begun in 195 cases (58.7%). No serious clinical signs or symptoms were present in 282 cases (85%). The correlation of paracetamol levels in urine was stronger with the amount of drug ingested voluntarily (R2 = 0.23) than with accidental intake (R2 = 0.007). Predefined severity criteria were significantly related to reported dose ingested per body weight (P = .001) and the interval between intake and first medical assistance (P = .008). Conclusions. Even though clear protocols are available to guide the use of antidote treatment in cases of paracetamol poisoning, variability in fundamental aspects of management is excessive.

Amitriptyline accumulation in tissues after coated activated charcoal hemoperfusion-a randomized controlled animal poisoning model.

Amitriptyline poisoning (AT) is a common poisoning, and AT possess the ability to promote life-threatening complications by its main action on the central nervous and cardiovascular systems. The pharmacokinetic properties might be altered at toxic levels compared to therapeutic levels. The effect of coated activated charcoal hemoperfusion (CAC-HP) on the accumulation of AT and its active metabolite nortriptyline (NT) in various tissues was studied in a non-blinded randomized controlled animal trial including 14 female Danish Land Race piglets. All piglets were poisoned with amitriptyline 7.5 mg/kg infused in 20 min, followed by orally instilled activated charcoal at 30 min after infusion cessation. The intervention group received 4 h of CAC-HP followed by a 1-h redistribution phase. At study cessation, the piglets were euthanized, and within 20 min, vitreous fluid, liver tissue, ventricle and septum of the heart, diaphragm and lipoic and brain tissues were collected. AT and NT tissue concentrations were quantified by UHPLC-MS/MS. A 4-h treatment with CAC-HP did not affect the tissue accumulation of AT in the selected organs when tested by Mann-Whitney U test (p values between 0.44 and 0.73). For NT concentrations, p values were between 0.13 and 1.00. Although not significant, an interesting finding was that data showed a tendency of increased tissue accumulation of AT and NT in the CAC-HP group compared with the control group. Coated activated charcoal hemoperfusion does not significantly alter the tissue concentration of AT and NT in the AT-poisoned piglet.

Blue vitriol poisoning: a 10-year experience in a tertiary care hospital.

BACKGROUND AND AIM: Copper sulphate poisoning, while unusual in the West, is not rare in the Indian subcontinent, and mostly suicidal in intent. Unfortunately, data available on copper sulphate poisoning is limited. This study was planned to identify common presentations and complications of copper sulphate poisoning, and biochemical parameters that predict outcomes in these patients. MATERIALS AND METHODS: A retrospective analysis of 35 patients presenting with copper sulphate poisoning over a period of 10 years (2001-2010) was performed, based on review of their medical records. Paediatric cases and patients with concomitant poisoning with other substances were excluded. Clinical presentation, laboratory parameters, complications and treatment modalities were studied. RESULTS: Of the 35 cases, 23 were females (65.71%). Mean age was 29.18 ± 10.77 years. Vomiting was the commonest symptom (85.71%) followed by diarrhoea (45.71%), epigastric pain (42.86%) and rectal passage of blood (31.43%). Fourteen (40%) patients had pre-existing psychiatric disease. Medical signs included pallor (37.14%) and icterus (37.14%). Major complications included hemolysis (68.57%), renal failure (51.43%), acute hepatitis (45.71%) and upper gastrointestinal bleed (40%). Mean serum copper at presentation was 104.53 ± 56.67 µg/dL; mean methemoglobin level was 9.59 ± 8.28%. Twenty-seven patients survived yielding a mortality rate of 22.9%. Peak serum aspartate and alanine aminotransferases were significantly lower (223.8 ± 247.3 U/L, 66.3 ± 92.2 U/L) in survivors compared to non-survivors (489.6 ± 374.0 U/L, 192.9 ± 168.7 U/L; p = 0.03, p < 0.01, respectively). Analysis by receiver operating characteristic (ROC) curve showed sensitivities of 100% and 85.7%, and specificities of 73.1% and 69.2%, respectively for peak serum alanine aminotransferase levels greater than 55 U/L, and peak serum aspartate aminotransferase levels greater than 234 U/L in predicting mortality. CONCLUSION: Copper sulphate is a potent poison that can involve multiple organ systems. Elevated levels of serum aspartate and alanine aminotransferases beyond the aforementioned values can identify patients at greater risk of mortality, allowing for institution of aggressive treatment.

Calidad de los registros en las intoxicaciones voluntarias por fármacos en un Servicio de Urgencias / Quality of records in voluntary poisoning by drugs for an Emergency Department

Las consultas motivadas por los efectos secundarios de una intoxicación aguda suelen ser atendidas en los Servicios de Urgencias. Entre ellas se encuentran aquellas producidas por intoxicación voluntaria por fármacos. En el año 2006 se desarrollaron unos ítems para medir la calidad en la asistencia a las intoxicaciones agudas (CALITOX 2006). El objetivo de este estudio es evaluar el grado de cumplimiento de estos ítems en las intoxicaciones voluntarias por fármacos. Se ha llevado a cabo un estudio retrospectivo durante los años 2003 y 2004 de las intoxicaciones voluntarias por fármacos atendidas en nuestro Servicio de Urgencias. Se valora el grado de cumplimiento de una serie de ítems extraídos de CALITOX 2006. Durante el periodo de estudio se atendieron 1531 intoxicaciones, de las que 400 fueron voluntarias por fármacos. La edad media de los intoxicados fue de 36 (14) años, y el 59% eran mujeres. La frecuencia cardiaca fue la única constante vital que cumplía el estándar. Se encontraron deficiencias en los ítems referentes a administración de antídotos, tiempo de demora, porcentaje de descontaminaciones digestivas, realización de valoración psiquiátrica y emisión de parte judicial. El estándar establecido se cumplió en el resto de ítems. Por tanto, se puede concluir que se debe mejorar la calidad asistencial en las intoxicaciones voluntarias por fármacos. Una forma de conseguirlo sería la valoración sistemática de una serie de indicadores de calidad, lo que permitiría conocer en que aspectos se debe incidir para que el personal asistencial mejore tanto el proceso asistencial como la calidad de los informes (AU)

Subjects with side effects due to an acute intoxication, including voluntary drug ingestion, usually seek medical care at emergency services. A list of items to measure the quality of care provided in acute intoxications was developed in 2006 (CALITOX 2006). The objective of this study was to assess the level of adherence to these items in acute intoxications caused by voluntary ingestion of drugs. A retrospective study of all cases of acute intoxication due to voluntary ingestion of drugs attended in our Emergency Department during 2003 and 2004 was carried out. The degree of compliance with a series of items from CALITOX 2006 was analyzed. During the study period, a total of 1531 intoxications were recorded, 400 of which were voluntary ingestion of drugs. The mean (SD) age of the subjects was 36 (14) years; 59% were women. Heart rate was the only vital constant that met the established standard. There were differences in the items regarding antidote administration, delayed time, percentage of digestive decontaminations, psychiatric consultation, and judicial notification. Established standards were fulfilled for the remaining ítems. Care provided to subjects with acute intoxications associated with voluntary drug ingestion should be improved. Systematic assessment of a series of quality indicators would allow determining those aspects that merit particular attention by health care professionals I order to improve both the process of care and the quality of reports (AU)

Fomepizole for the treatment of pediatric ethylene and diethylene glycol, butoxyethanol, and methanol poisonings.

INTRODUCTION: The use and clinical efficacy of the alcohol dehydrogenase inhibitor fomepizole is well established for the treatment of ethylene glycol and methanol poisonings in adults. METHODS: A computerized search of the U.S. National Academy of medicine and EMBase databases was undertaken to identify published cases of patients treated with fomepizole. This search strategy identified 14 published cases related to the topic of this review: 10 due to ethylene glycol poisoning, 1 due to diethylene glycol poisoning, 1 due to butoxyethanol ingestion, and 2 due to methanol poisoning. The median age of these cases was 5.5 years old. FOMEPIZOLE IN GLYCOL AND GLYCOL ETHER POISONING: For the 10 ethylene glycol poisoned patients, the median recorded values of their arterial pH was 7.27 (range 7.03-7.38), serum bicarbonate concentration was 13 mEq/L (range 2-25), and ethylene glycol concentration was 2,140 mg/L (range 130-3,840). Eight of these patients were not hemodialyzed. The eight patients who were not hemodialyzed had ethylene glycol concentrations as high as 3,500 mg/L and serum bicarbonate concentrations as low as 4 mEq/L. All 10 patients had resolution of their metabolic acidosis and recovered without sequelae. The half-times of ethylene glycol elimination ranged from 9 to 15 h during fomepizole therapy, which is faster than the 19.7 h reported in adults. The two patients who ingested diethylene glycol or butoxyethanol all recovered without sequelae. The patient who ingested the butoxyethanol had a serum bicarbonate concentration of 13 mEq/L and was not hemodialyzed. FOMEPIZOLE IN METHANOL POISONING: One of the two children who ingested methanol was hemodialyzed. Both cases had a similar degree of severity. DOES FOMEPIZOLE OBVIATE THE NEED FOR HEMODIALYSIS?: Based on the experience reviewed herein it appears that, as in adults, hemodialysis may not be necessary in most cases of pediatric ethylene glycol poisoning if treated with fomepizole. FOMEPIZOLE PHARMACOKINETICS: Plasma fomepizole concentrations were measured in three cases and were found to be therapeutic with apparent Michaelis-Menton kinetics, having a zero-order elimination rate of 0.6-1 mg/L/h at higher concentrations and a first-order elimination with an apparent elimination half-time of 3.9 h at lower concentrations. FOMEPIZOLE REGIMEN: Most cases used the current U.S.-approved regimen. ADVERSE EFFECTS OF FOMEPIZOLE: The one adverse effect reported during fomepizole therapy was transient nystagmus in a 6-year-old with a serum ethylene glycol concentration of 130 mg/L and a serum bicarbonate concentration of 2 mEq/L; it is likely that ethylene glycol itself was the cause. COMPARISON OF FOMEPIZOLE WITH ETHANOL THERAPY: Two cases were originally treated with ethanol but switched to fomepizole because of adverse effects. In both cases, the adverse reactions to ethanol resolved once fomepizole treatment was initiated. CONCLUSIONS: The limited data available suggest that fomepizole, using the same dosage regimen as that used for adults, is efficacious and well tolerated in pediatric patients. In many cases of pediatric ethylene glycol poisoning treated with fomepizole, hemodialysis may not be necessary despite high concentrations and the presence of metabolic acidosis.

Pralidoxime safety and toxicity in children.

BACKGROUND: Currently, the safety of pralidoxime administration via adult autoinjectors for pediatric patients has not been established. Up until 2000, the published literature did not recommend its usage for children less than 12 kg or under the age of 10 years old. Since 2000, limited published articles have emerged validating adult autoinjector usage for the pediatric victim, in extreme circumstances. OBJECTIVE: We sought to determine whether adverse drug reactions (ADR) from pralidoxime administration to children occur. METHOD: Recurrent PubMed Medline literature search of all years were performed from 2001 to 2004 inclusive. The main search criteria were articles pertaining to U.S. children 16 years or younger who received pralidoxime. In addition, a review of 3 years (1999-2001) of detailed retrospective TESS exposure annual poison center data was obtained from the AAPCC. RESULTS: Eighty-one children met inclusion criteria and received pralidoxime for suspected organophosphate poisoning. Two children (2.5%) expired. Three children (3.7%) were identified as having a potential adverse drug reaction; all were mild. CONCLUSION: The author's recognize this study possesses limitations that require its findings be interpreted with caution. Our data suggest that adverse drug reactions to pralidoxime treatment in children are rare. However, further investigation is needed to more firmly establish the safety of this antidote in children and for its use in the prehospital environment.

Civilian adult self injections of atropine-trimedoxime (TMB4) auto-injectors.

INTRODUCTION: The clinical effects of self injections of atropine-trimedoxime auto-injectors distributed to the civilian population as a field antidote for nerve agent attack were assessed. METHODS: Data on self injections by adults (> or = 18 years) were collected from the Israel Poison Information Center and a hospital Emergency Department's records during a 2-year period. The data included demographics, time interval from injection, type of auto-injector, clinical manifestations and atropinization score. RESULTS: Sixty-five patients, all with unintentional self injections, were reported. Systemic atropine effects were observed in 24 patients, but no severe atropinization. The atropinization score was significantly higher in the 2 mg atropine dose group than in the two lower dose groups, which were in the normal range. No specific adverse effects attributable to trimedoxime were observed. Intravenous fluids and physostigmine were not required. CONCLUSION: Only mild reactions were observed following self-injection of atropine trimedoxime auto-injectors in adults, attesting to their relative safety under these conditions.

Pediatric poisoning from trimedoxime (TMB4) and atropine automatic injectors.

OBJECTIVE: To describe the effects of combined trimedoxime (TMB4) and atropine poisoning from automatic injectors (AI) in children. STUDY DESIGN: Data was collected from two sources: calls to the Israel Poison Information Center (IPIC) during a 1-year period and a cohort of children who presented to pediatric emergency departments (EDs) after unintentional injection of an AI. Demographic data and data regarding the type of AI, site and time of injection, and the clinical manifestations were abstracted. RESULTS: Data were available for 142 patients. The median age was 8.5 years (range 1.25-18 years). The dose of atropine and TMB4 was higher than the recommended dose for age in 22 (15.5%) cases. There were few side effects attributable to atropine: dilated pupils (26.7%), dryness of mucous membranes (24.6%), and tachycardia (22.5%). Compared with children injected with an age-appropriate dose, children injected with an AI that contained a dose that exceeds the recommended one were more likely to be symptomatic ( P = .029). There were no side effects characteristic to oximes, and no specific medical intervention was required. CONCLUSIONS: Unintentional pediatric atropine and TMB4 injection, even an adult dose in a small child, does not cause significant side effects.

Accidental injection of a U.S. Air Force aviator by a pralidoxime chloride auto-injector: a case report.

To counter the threat of organophosphate nerve agents, military personnel may be issued auto-injectors containing pralidoxime chloride. This drug helps to dephosphorylate the nerve agent-acetylcholinesterase complex and, thus, regenerate the enzyme. In non-poisoned persons, pralidoxime chloride is rapidly excreted by the kidneys and is fairly well tolerated. We present the first reported case of an accidental injection of an Air Force aviator by an auto-injector. The patient recovered well with no specific treatment needed. The pharmacology and toxicology of pralidoxime chloride are discussed.

Differential mechanisms in the effects of disulfiram and diethyldithiocarbamate intoxication on striatal release and vesicular transport of glutamate.

Intoxication with the alcohol-aversive drug disulfiram (Antabuse) and related dithiocarbamates may provoke neuropathies and, in some cases, damage the basal ganglia. Rats received a single administration of disulfiram (7 and 500 mg kg-1 i.p.) and equimolar doses (4 and 290 mg kg-1 i.p.) of its metabolite diethyldithiocarbamate (DDC), roughly corresponding to the daily maximum dose in alcohol abusers or to an estimated nonlethal overdose, respectively. The striatal, extracellular levels of glutamate in freely moving rats previously implanted with a microdialysis probe increased after low and intoxicating doses of disulfiram (126 +/- 3% and 154 +/- 10% of basal values, respectively) and DDC as well (135 +/- 10% and 215 +/- 14%, respectively), a partially Ca++-dependent effect. The prolonged (>7 hr) disulfiram-induced increase in glutamate observed in vivo may reflect the in vitro disulfiram-evoked release of glutamate from striato-cortical synaptic vesicles, where the drug nonspecifically inhibited (Ki approximately 4 microM) the uptake function and abolished the transmembrane proton gradient (DeltapH). In contrast, DDC did not seem to affect DeltapH. The prompt DDC-provoked increase in extracellular levels of glutamate was prevented by 7-nitroindazole, an in vivo specific inhibitor of neuronal nitric oxide synthase, which suggests that the thiol metabolite also acts via the nitric oxide synthesis. At variance, the short-acting 7-nitroindazole did not prevent the sustained in vivo effects of disulfiram and of DDC putatively formed with time. These findings provide new evidence for differential mechanisms underlying disulfiram- and DDC-induced increases in striatal glutamate release. Present glutamatergic changes, although not appearing dramatic enough to represent the only cause for neuronal damage from disulfiram overdose, might contribute to the drug neurotoxicity.

High-pressure injection injury involving a 2-PAM chloride autoinjector.

High-pressure injection injuries to the hand are often associated with severe morbidity and should be considered surgical emergencies. The severity of these injuries is usually due to vascular compromise and the inflammatory nature of the material injected, such as paint, grease, and solvents. We present a case of a high-pressure injection of 2-PAM chloride into the finger of a 3-year-old boy. In this case, operative treatment was not necessary and all symptoms resolved.