透明质酸酶对大鼠双光气中毒性肺水肿治疗的初步观察

本实验初步现察了HA对双光气中毒性肺水肿早期的治疗作用。结果提示,早期应用HA能显著延长动物存活时间,而治疗组与对照组动物在肺体指数、肺湿干重量比及肺含水量等项指标则未见显著差别。     

Adverse events related to the new psychoactive substance 3-fluorophenmetrazine – results from the Swedish STRIDA project

Background: New psychoactive substances (NPS) are often poorly pharmacologically documented and the production is unregulated, implying high risks for toxic side effects. This report from the STRIDA project describes analytically confirmed non-fatal intoxications involving the phenmetrazine analogue 3-fluorophenmetrazine (3-FPM).

Study design and methods: Observational case series of patients with suspected acute NPS exposure requiring hospital care. Blood and urine samples were collected from patients presenting in emergency departments (ED) or intensive care units (ICU), after consultation with the Swedish Poisons Information Centre (PIC). Laboratory analysis was performed by multi-component liquid chromatography–mass spectrometry. Clinical data were collected during PIC consultations and retrieved from medical records.

Results: From November 2014 to October 2015, eight cases were registered as 3-FPM or “phenmetrazine” intoxications at the PIC after consultation. During the same period, analysis of STRIDA project samples confirmed 3-FPM use in a total of 19 patients (84% men) aged 22–54 (median 30) years. 3-FPM was detected in 15 out of 19 serum (2.7–1416?ng/mL) and in 14 out of 14 urine (1.0–6857?μg/mmol creatinine) samples. All patients were also tested positive for other psychoactive substances, with benzodiazepines being most common (57% of the cases). Ten patients were monitored in the ED for <4?h, while six needed ICU monitoring of which five were graded as severe intoxications (Poisoning Severity Score 3). Prominent clinical signs were tachycardia (47%), depressed consciousness (42%), agitation/anxiety (37%), delirium (37%), dilated pupils (26%), and seizures (16%). All patients survived.

Conclusion: In 19 patients testing positive for 3-FPM, a high incidence of severe clinical features was demonstrated. However, as all patients had also used other psychoactive substances, it was difficult to identify a unique toxidrome for 3-FPM. The results further showed that many 3-FPM intoxications would have been missed, if relying solely on information from PIC consultations. These results emphasize the importance of performing bioanalytical investigation in cases of suspected NPS intoxication.     

Ingesta de cáusticos: análisis de la seguridad y beneficio de un protocolo menos agresivo

Introduction

The ingestion of a caustic agent is the most common cause of admission after being in contact with a domestic product. A group of patients could be considered low risk and not require aggressive procedures such a corticosteroid administration and endoscopy, especially in the paediatric population.

Occurrence and time course of NPS benzodiazepines in Sweden – results from intoxication cases in the STRIDA project

Context: In recent years, many unclassified benzodiazepines (BZD) have appeared through online sale as new psychoactive substances (NPS). This study describes bioanalytical and clinical data related to intoxications involving NPS BZD (“designer BZD”) in the Swedish STRIDA project.

Study design: Case series of consecutive patients with admitted or suspected intake of NPS presenting to hospitals all over Sweden for emergency treatment in 2012–2016.

Patients and method: Urine samples collected in the STRIDA project were analyzed for 28 NPS BZD, using immunoassay and liquid chromatography–high-resolution mass spectrometry . Data of patient’s age, gender, reported substance exposure, clinical signs, and treatment were obtained from medical and Poisons Information Center (PIC) records.

Results: A total of fifteen different NPS BZD were analytically confirmed in 217 of 1913 (11%) cases involving patients (81% men) aged 15–66 (mean 28) years. The frequency of positive samples increased from 4% in 2012 to 19% in 2015. Etizolam (20 cases) was the first detected NPS BZD (January 2012), and it was followed by metizolam (four cases), estazolam (two), pyrazolam (33), flubromazepam (33), nifoxipam (five), diclazepam (four), meclonazepam (26), bromazepam (one), flubromazolam (92), deschloroetizolam (one), clonazolam (16), 3-hydroxyphenazepam (eight), ketazolam (one), and phenazepam (one). Most cases (89%) also involved other drugs. Use of NPS BZD was rarely (15%) reported during PIC consultation. In 24 patients exposed only to NPS BZD, CNS depression was the most prominent clinical sign, seven were observed in the intensive care unit, and they responded positively to flumazenil treatment.

Conclusions: An increasing use of NPS BZD in Sweden was detected in acute intoxication cases, sometimes leading to intensive care monitoring and support needs.     

Lethal intoxications with morphine in Sweden 1966–1974

Summary Fatal intoxications with morphine derivatives have become increasingly common in Sweden. Toxicologic data and pathologic findings in 34 cases of morphine intoxications from 1966 to 1974 in Sweden are presented. From 1972 on when morphine the black market, lethal intoxication appeared on with morphine derivatives has become more common than lethal intoxications with centrally stimulating amines.

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Zusammenfassung Tödliche Vergiftungen mit Morphinderivaten haben in Schweden in letzter Zeit zugenommen. Toxikologische Daten und pathologische Befunde von 34 Fällen, die in Schweden zwischen 1966–1974 stattgefunden haben, wurden beschrieben. Seit 1972 ist die Anzahl der Fälle von Vergiftungen mit Morphinderivate mit tödlichem Ausgang höher als tödliche Vergiftungen mit zentralstimulierenden Aminen. Von dieser Zeit an waren die Morphinprodukte auf dem Schwarzmarkt zugänglich.

     

Carbamazepine Poisoning: Elimination Kinetics and Quantitative Relationship with Carbamazepine 10,11-Epoxide

Background: The optimal route and duration of administration for N–acetylcysteine in the management of acetaminophen (paracetamol) poisoning are controversial. It has been stated on the basis of a selected post-hoc analysis that oral N-acetylcysteine is superior to intravenous N-acetylcysteine in presentations later than 15 hours. Aim of Study: To investigate the efficacy of intravenous or oral N-acetylcysteine. Patients and Methods: We analyzed a series of acetaminophen poisonings treated with a protocol including activated charcoal and intravenous N-acetylcysteine. The outcomes assessed included use of N-acetylcysteine, adverse effects of intravenous N-acetylcysteine, and the occurrence of hepatotoxicity (transaminase >1000U/L). We incorporated these results in a meta-analysis of previously reported series of acetaminophen poisonings to compare the outcomes from intravenous and oral N-acetylcysteine use. Results: Of 981 patients admitted over 10 years, 4% (40) presented later than 24 hours and 10% (100) had concentrations of acetaminophen that indicated a probable or high risk of hepatotoxicity. The 30 patients who developed hepatotoxicity presented later, took larger amounts, had higher concentrations, and received N-acetylcysteine later than those who did not. No patients received a liver transplant but 2 patients died (one after referral to a transplant unit and one just before). Adverse reactions to intravenous N-acetylcysteine occurred in 6% (12/205) of patients but none prevented completion of the treatment. In the meta–analysis, those with probable or high risk concentrations had similar outcomes with intravenous (pooled n = 341) and oral N-acetylcysteine (pooled n = 1462) administration. Rates of hepatotoxicity for those treated within 10 hours (3 and 6%), late (10–24 hours: 30 and 26%), and overall (0–24 hours: 16 and 19%) were all similar. The proportion of patients classified as presenting later than 10 hours is much greater in the oral N-acetylcysteine studies (64%) than in many of the intravenous N-acetylcysteine studies (38%, 44%, and 63%).Conclusions: The differences claimed between oral and intravenous N-acetylcysteine regimes are probably artifactual and relate to inappropriate subgroup analysis. A shorter hospital stay, patient and doctor convenience, and the concerns over the reduction in bioavailability of oral N-acetylcysteine by charcoal and vomiting make intravenous N-acetylcysteine preferable for most patients with acetaminophen poisoning.     

Intoxications in the STRIDA project involving a panorama of psychostimulant pyrovalerone derivatives,MDPV copycats

Context: An increasing number of new psychoactive substances (NPS) of different chemical classes have become available through marketing and sale over the Internet. This report from the Swedish STRIDA project presents the prevalence, laboratory results, and clinical features in intoxications involving 11 stimulant pyrovalerone NPS derivatives over a 5-year period.

Study design: Case series of consecutive patients with admitted or suspected intake of NPS presenting to Swedish hospitals for emergency treatment from January 2011 to March 2016.

Patients and method: Blood and urine samples were collected from intoxicated patients presenting to hospitals all over Sweden. Analyses of NPS and other drugs of abuse were performed by immunochemical and liquid chromatography–mass spectrometry multi-component methods. Clinical data were collected during consultation with the Swedish Poisons Information Centre (PIC), and retrieved from medical records. The study involved analytically confirmed cases with 11 pyrovalerone drugs.

Results: During the study period, 114 intoxications were detected that involved any of 11 new pyrovalerone drugs. In addition to these new pyrovalerone derivatives, 3,4-methylenedioxypyrovalerone (MDPV) was detected in 17 of the cases and α-pyrrolidinovalerophenone (α-PVP) in 45 cases. Identification was made according to forensic standards and comprised the following substances: 4F-α-PVP, α-PHP, PV8, 4Me-PPP, α-PBP, 4F-PV8, α-PPP, MDPHP, α-PVT, 4Cl-α-PVP, and 4F-α-PHP. The three most frequently detected drugs were α-PBP, MDPHP, and 4F-α-PVP. The age range of patients was 16–66 (median 30) years and 84% were males. The substance concentrations in urine and serum were highly variable, ranging from 1?ng/mL to 300 µg/mL. Poly-drug use was common with only 8 of 114 cases (7%) involving one pyrovalerone drug. The additional substances comprised other NPS and classical psychoactive drugs. The patients showed a variety of clinical signs; agitation, delirium, hallucinations, excessive motor activity, seizures, tachycardia, hypertension, and/or hyperthermia.

Conclusions: In analytically confirmed NPS-related intoxications, 11 new pyrovalerone derivatives in addition to MDPV and α-PVP were found. The clinical features were consistent with a sympathomimetic toxidrome, but the urine and serum concentrations were highly variable. The results demonstrated that many novel pyrovalerone stimulants were introduced on the recreational NPS drugs market. Analytical investigations were necessary to obtain this information.     

Methadone in autopsy cases

Summary In the last year 5 oases of fatal methadone intoxications have been investigated. The mass spectrum of methadone and the results of the gas chromatographic determinations are presented. The variations in plasma half-life of methadone are discussed. Blood and tissue levels in fatal methadone intoxications are reported and discussed.

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Zusammenfassung Im letzten Jahr wurden insgesamt 5 Methadonvergiftungen untersucht. Das Massenspektrum von Methadon und die Ergebnisse von gaschromatographischen Untersuchungen werden angegeben. Die Variationen in Plasmahalbwertszeit sowie die Konzentration von Methadon im Blut und Gewebe bei tödlichen Vergiftungen werden angegeben und diskutiert.