RESUMEN
In 2014, health staff who were vaccinating children in rebel-held northern Syria accidentally administered a muscle relaxant, atracurium, to up to 75 children, killing 15 of them. An investigation found that the drug was given to the children instead of a solution used to mix measles vaccines because the packaging was similar.
Asunto(s)
Atracurio , Vacuna Antisarampión , Errores Médicos , Fármacos Neuromusculares no Despolarizantes , Atracurio/administración & dosificación , Atracurio/envenenamiento , Niño , Humanos , Fármacos Neuromusculares no Despolarizantes/administración & dosificación , Fármacos Neuromusculares no Despolarizantes/envenenamiento , SiriaAsunto(s)
Pena de Muerte , Ética Médica , Hipnóticos y Sedantes/envenenamiento , Hipnóticos y Sedantes/provisión & distribución , Rol del Médico , Códigos de Ética , Industria Farmacéutica , Humanos , Fármacos Neuromusculares no Despolarizantes/envenenamiento , Fármacos Neuromusculares no Despolarizantes/provisión & distribución , Pentobarbital/envenenamiento , Cloruro de Potasio/envenenamiento , Cloruro de Potasio/provisión & distribución , Sociedades Médicas , Tiopental/envenenamiento , Tiopental/provisión & distribución , Estados UnidosAsunto(s)
Analgésicos Opioides/envenenamiento , Anestésicos/envenenamiento , Homicidio , Relajantes Musculares Centrales/envenenamiento , Adulto , Androstanoles/envenenamiento , Femenino , Fentanilo/envenenamiento , Humanos , Masculino , Midazolam/envenenamiento , Persona de Mediana Edad , Fármacos Neuromusculares Despolarizantes/envenenamiento , Fármacos Neuromusculares no Despolarizantes/envenenamiento , Pancuronio/envenenamiento , Rocuronio , Succinilcolina/envenenamiento , Adulto JovenRESUMEN
Long lasting polemics about the mechanisms of the action of curare took place at the Société de Biologie over thirty years. After a period during which poisoning protocols were developed on various animal species, where Claude Bernard, Vulpian and their colleagues were involved, German electrophysiology combined its results with new histological data about motor end-plates, elaborating a theory in which young physiologists fought against Claude Bernard's views and finally managed to convince him. According to the new theory proposed by Vulpian, curare blocked transmission between end-plate and muscle. This first draft of the neurotransmission theory helps us to understand the rise of a novel physiology in the context of the school of Claude Bernard with a better integration of disciplines and a more prominent faith in reductionism and materialism.
Asunto(s)
Curare/historia , Fármacos Neuromusculares no Despolarizantes/historia , Fisiología/historia , Animales , Curare/farmacología , Curare/envenenamiento , Electrofisiología/historia , Electrofisiología/métodos , Francia , Historia del Siglo XIX , Humanos , Fármacos Neuromusculares no Despolarizantes/farmacología , Fármacos Neuromusculares no Despolarizantes/envenenamiento , Neurofisiología/historia , Neurofisiología/métodosRESUMEN
One of the most erroneous and repeated assertion in the history of pharmacology for anaesthetists is to say that "the curare was introduced in Europe by Sir Walter Raleigh under the name of ourari". On the contrary, the names to be reminded are: Lawrence Keymis for the first citation of the word ourari, José Gumilla for the word curare and the description of its effects, Charles-Marie de La Condamine for the import of the first known samples. The mistake was initiated by Alexander von Humboldt and developed by the physiologist Münter, a student of Johannes Müller, quoted by Claude Bernard. The repetition of this error was facilitated by the world diffusion of Claude Bernard's work.
Asunto(s)
Curare/historia , Expediciones/historia , Fármacos Neuromusculares no Despolarizantes/historia , Curare/envenenamiento , Europa (Continente) , Historia del Siglo XV , Historia del Siglo XVI , Historia del Siglo XVII , Historia del Siglo XVIII , Historia del Siglo XIX , Humanos , Indígenas Sudamericanos/historia , Bloqueo Neuromuscular/historia , Fármacos Neuromusculares no Despolarizantes/envenenamiento , América del SurRESUMEN
The muscle relaxant rocuronium and the hypnotics etomidate, diazepam and midazolam were candidate poisons in a case of a suspected series of fatal intoxications in a hospital. A robust, specific and sensitive multi-target screening procedure was established to identify unequivocally the parent compounds and diagnostic metabolites and artefacts in putrefied specimens, obtained from exhumed bodies. The analytical findings of relevant compounds could be traced partially back to authorised therapeutic measures, whereas the identification of rocuronium proved potentially lethal intoxications in 13 (of a total number of 42) cases. Moreover, the detection of certain hypnotics revealed an improper administration of these compounds in another nine cases, which suggested manipulation but was not indicative of fatal intoxications. Quantitative estimations of substance concentrations were highly correlated with the post-mortem time intervals and did not reveal any information on doses, initial serum concentrations or toxicological effects.
Asunto(s)
Androstanoles/envenenamiento , Cromatografía Líquida de Alta Presión/métodos , Hipnóticos y Sedantes/envenenamiento , Espectrometría de Masas en Tándem/métodos , Androstanoles/farmacocinética , Autopsia/métodos , Diazepam/farmacocinética , Diazepam/envenenamiento , Etomidato/farmacocinética , Etomidato/envenenamiento , Exhumación , Hospitales , Humanos , Hipnóticos y Sedantes/farmacocinética , Midazolam/farmacocinética , Midazolam/envenenamiento , Fármacos Neuromusculares no Despolarizantes/farmacocinética , Fármacos Neuromusculares no Despolarizantes/envenenamiento , Rocuronio , Toxicología/métodosRESUMEN
BACKGROUND: Intermediate syndrome (IMS) is a major cause of death from respiratory failure following acute organophosphate poisoning. The objective of this study was to determine repetitive nerve stimulation (RNS) predictors of IMS that would assist in patient management and clinical research. METHODS AND FINDINGS: Seventy-eight consenting symptomatic patients with organophosphate poisoning were assessed prospectively with daily physical examination and RNS. RNS was done on the right and left median and ulnar nerves at 1, 3, 10, 15, 20, and 30 Hz. The study was conducted as a prospective observational cohort study in the Central Province, Sri Lanka. IMS was diagnosed in ten out of 78 patients using a priori clinical diagnostic criteria, and five of them developed respiratory failure. All ten patients showed progressive RNS changes correlating with the severity of IMS. A decrement-increment was observed at intermediate and high frequencies preceding the onset of clinical signs of IMS. As the patient developed clinical signs of IMS, decrement-increment was progressively noted at low and intermediate frequencies and a combination of decrement-increment and repetitive fade or severe decrement was noted at high frequencies. Severe decrement preceded respiratory failure in four patients. Thirty patients developed forme fruste IMS with less severe weakness not progressing to respiratory failure whose RNS was characterized by decrement-increment or a combination of decrement-increment and repetitive fade but never severe decrements. CONCLUSIONS: Characteristic changes in RNS, preceding the development of IMS, help to identify a subgroup of patients at high risk of developing respiratory failure. The forme fruste IMS with the characteristic early changes on RNS indicates that IMS is a spectrum disorder. RNS changes are objective and precede the diagnosis and complications of IMS. Thus they may be useful in clinical management and research.
Asunto(s)
Enfermedades de la Unión Neuromuscular/inducido químicamente , Enfermedades de la Unión Neuromuscular/diagnóstico , Intoxicación por Organofosfatos , Plaguicidas/envenenamiento , Estudios de Cohortes , Femenino , Humanos , Masculino , Debilidad Muscular/inducido químicamente , Debilidad Muscular/patología , Enfermedades de la Unión Neuromuscular/patología , Fármacos Neuromusculares no Despolarizantes/envenenamiento , Estudios Prospectivos , Insuficiencia Respiratoria/inducido químicamente , Insuficiencia Respiratoria/patología , Sri Lanka , SíndromeAsunto(s)
Eutanasia/legislación & jurisprudencia , Recien Nacido Prematuro , Mala Praxis/legislación & jurisprudencia , Pediatría/legislación & jurisprudencia , Consultores , Humanos , Recién Nacido , Fármacos Neuromusculares no Despolarizantes/envenenamiento , Pancuronio/envenenamiento , Reino UnidoRESUMEN
UNLABELLED: Pediatric populations are at risk for medication errors that may be associated with mortality and disability. The purpose of this study was to describe the clinical manifestations of seven newborns following an event of accidental intramuscular injection of atracurium and to assess the impact on neurodevelopmental outcome. This study enrolled seven newborns who were accidentally administered 10 mg of atracurium, equivalent to 2.6-3.3 mg/kg, in a local perinatal clinic. Accident reports and hospital records were reviewed to obtain the history and medical data for the event. The survivors were prospectively examined for their growth, health and neurodevelopment until 24 months of age. All newborns showed immediate apnea and cyanosis requiring resuscitation after atracurium injection and presented with respiratory failure and flaccid paralysis on arrival for emergency medical services. One newborn was asystolic despite resuscitation and died of multiple organ failure. Of the five survivors available for follow-up, all achieved favorable growth outcomes. However, four showed mild to significant delay in development; and two manifested mild hypomyelination of cerebral white matter on the brain magnetic resonance imaging. CONCLUSION: Newborns accidentally injected with high doses of atracurium are at risk of death and neurodevelopmental delay. The serious clinical manifestations, developmental delay and cerebral hypomyelination were most likely due to insufficient immediate respiratory assistance following atracurium injection.
Asunto(s)
Atracurio/envenenamiento , Encéfalo/efectos de los fármacos , Discapacidades del Desarrollo/inducido químicamente , Errores Médicos , Fármacos Neuromusculares no Despolarizantes/envenenamiento , Atracurio/administración & dosificación , Bradicardia/inducido químicamente , Encéfalo/patología , Cianosis/inducido químicamente , Sobredosis de Droga , Femenino , Estudios de Seguimiento , Humanos , Hipoxia/inducido químicamente , Recién Nacido , Inyecciones Intramusculares , Imagen por Resonancia Magnética , Masculino , Destreza Motora/efectos de los fármacos , Fármacos Neuromusculares no Despolarizantes/administración & dosificación , Salas Cuna en HospitalRESUMEN
The case report of a serial killer who worked at several hospitals as a respiratory therapist is presented. The suspect was initially labeled a benevolent Angel of Death who ended the suffering of elderly patients through mercy killing. However, his subsequently declared motive for homicide was very different from other similar cases in medical settings. The application of new analysis techniques for the detection of pancuronium bromide in a series of aged exhumation tissues gave positive results and led to the resultant conviction of the therapist.
Asunto(s)
Eutanasia , Homicidio , Fármacos Neuromusculares no Despolarizantes/farmacocinética , Pancuronio/farmacocinética , Cambios Post Mortem , Adulto , Anciano , Anciano de 80 o más Años , Autopsia , Exhumación , Femenino , Medicina Legal/métodos , Cromatografía de Gases y Espectrometría de Masas , Humanos , Masculino , Persona de Mediana Edad , Fármacos Neuromusculares no Despolarizantes/envenenamiento , Pancuronio/envenenamiento , Personal de Hospital , Terapia RespiratoriaAsunto(s)
Industria Farmacéutica/legislación & jurisprudencia , Fármacos Neuromusculares Despolarizantes/química , Fármacos Neuromusculares no Despolarizantes/química , Pancuronio/química , Succinilcolina/química , Embalaje de Medicamentos , Ciencias Forenses/métodos , Homicidio , Hospitales , Humanos , Isótopos , Fármacos Neuromusculares Despolarizantes/análisis , Fármacos Neuromusculares Despolarizantes/envenenamiento , Fármacos Neuromusculares no Despolarizantes/análisis , Fármacos Neuromusculares no Despolarizantes/envenenamiento , Pancuronio/análisis , Pancuronio/envenenamiento , Succinilcolina/análisis , Succinilcolina/envenenamientoRESUMEN
Suicides by intravenous injection of an overdose of medicaments are uncommon. In this paper, we present the case of a suicide by rocuronium-bromide injection in combination with an oral overdose of metoprolol. Unfortunately, in Belgrade, there is no toxicological laboratory capable of detecting rocuronium. The interpretation of autopsy and toxicological data in this case was made difficult due to the extreme putrefaction of the body of the deceased. So, by forensic investigation, the case was solved indirectly, through circumstantial evidence: an empty ampoule of rocuronium found near the body, as well as a plastic syringe and cloth-bandage found in the left hand of the deceased.
Asunto(s)
Androstanoles/envenenamiento , Fármacos Neuromusculares no Despolarizantes/envenenamiento , Suicidio , Adulto , Femenino , Humanos , Inyecciones Intravenosas , Metoprolol/envenenamiento , RocuronioRESUMEN
The present study was designed to determine the stability of pancuronium in postmortem blood and liver during storage. Results were obtained using the method by Kerskes et al. [C.H.M. Kerskes, K.J. Lusthof, P.G.M. Zweipfenning, J.P. Franke, The detection and identification of quaternary nitrogen muscle relaxants in biological fluids and tissues by ion-trap LC-ESI-MS, J. Anal. Toxicol. 26 (2002) 29-34.], modified and validated in our laboratory. Target analytes were isolated after enzymatic hydrolysis followed by solid phase extraction (BondElut C18 column). Internal standardisation was carried out using laudanosine and the target ions were monitored by LC-ESI-MS (monitoring ions m/z 358 for IS and 286 for pancuronium). Materials were taken from a 46-year-old woman, who had been found dead. A syringe (2 ml) and an empty ampoule of Pavulon (4 mg/2 mL) were found in her hand. The residual volume of fluid in the syringe was 0.7 ml. An autopsy was performed six days after death. It revealed a needle mark on the left thigh. Postmortem materials (muscle from the injection site, blood and liver) and the syringe with fluid were stored for four months in a freezer at -20 degrees C. The initial pancuronium concentrations were 81 ng/mL in blood and 532 ng/g in liver. The analyte was stable when stored at -20 degrees C in blood even up to seven months. In liver samples its concentrations were variable. Pancuronium in blood stored at 20 degrees C underwent degradation very rapidly. After three months of storage these blood samples had concentrations not greater about 10% of the initial value. The degradation patterns of pancuronium depended on temperature and the biological matrix.
Asunto(s)
Hígado/química , Fármacos Neuromusculares no Despolarizantes/análisis , Pancuronio/análisis , Estabilidad de Medicamentos , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Inyecciones Intramusculares , Persona de Mediana Edad , Fármacos Neuromusculares no Despolarizantes/envenenamiento , Pancuronio/envenenamiento , Reproducibilidad de los Resultados , Insuficiencia Respiratoria/inducido químicamente , Manejo de Especímenes , Temperatura , MusloAsunto(s)
Curare/historia , Fármacos Neuromusculares no Despolarizantes/historia , Curare/envenenamiento , Curare/uso terapéutico , Etnobotánica/historia , Historia del Siglo XVI , Historia del Siglo XVIII , Historia del Siglo XIX , Historia del Siglo XX , Humanos , Indígenas Norteamericanos/historia , Fármacos Neuromusculares no Despolarizantes/envenenamiento , Fármacos Neuromusculares no Despolarizantes/uso terapéutico , Fitoterapia/historia , Extractos Vegetales/historia , Extractos Vegetales/envenenamiento , Extractos Vegetales/uso terapéutico , América del SurRESUMEN
Quaternary nitrogen muscle relaxants pancuronium, rocuronium, vecuronium, gallamine, suxamethonium, mivacurium, and atracurium and its metabolites were extracted from whole blood and other biological fluids and tissues by using a solid-phase extraction procedure. The extracts were examined by using high-performance liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS). The drugs were separated on a ODS column in a gradient of ammonium acetate buffer (pH 5.0) and acetonitrile. Full-scan mass spectra of the compounds showed molecular ions, and MS-MS spectra showed fragments typical of the particular compounds. LC-ESI-MS allowed an unequivocal differentiation of all muscle relaxants involved. The method was applied in a case of rocuronium and suxamethonium administration in a Caesarian section and in a case of intoxication by pancuronium injection. In both cases, the administered drugs could be detected and identified in the supplied samples.
Asunto(s)
Relajantes Musculares Centrales/análisis , Compuestos de Nitrógeno/análisis , Adulto , Androstanoles/análisis , Androstanoles/envenenamiento , Bilis/química , Líquidos Corporales/química , Tampones (Química) , Femenino , Medicina Legal , Humanos , Indicadores y Reactivos , Hígado/química , Masculino , Espectrometría de Masas , Relajantes Musculares Centrales/sangre , Relajantes Musculares Centrales/orina , Fármacos Neuromusculares Despolarizantes/análisis , Fármacos Neuromusculares no Despolarizantes/análisis , Fármacos Neuromusculares no Despolarizantes/envenenamiento , Compuestos de Nitrógeno/sangre , Compuestos de Nitrógeno/orina , Pancuronio/análisis , Pancuronio/envenenamiento , Intoxicación/diagnóstico , Embarazo , Estándares de Referencia , Rocuronio , Espectrometría de Masa por Ionización de Electrospray , Succinilcolina/análisis , Succinilcolina/envenenamientoRESUMEN
A case is presented involving an acute fatality resulting from self-administration of atracurium, a muscle relaxant by a 45-year-old nurse. In the body, atracurium undergoes a spontaneous non-enzymatic degradation to laudanosine and an acrylate moiety. Laudanosine was quantified using gas chromatography coupled to mass spectrometry after extraction with chloroform-isopropanol-n-heptane (50:17:33 v/v) at pH 9.5 and separation on a HP5-MS capillary column. Laudanosine was subject to postmortem redistribution due to release from drug-rich tissues such as the lung and heart. The heart blood (917 ng/ml) to peripheral blood (390 ng/ml) ratio was 2.4. No other drugs, including ethanol were detected.