In vivo neutralization of colchicine toxicity by a PASylated anticalin in a rat model.

We have investigated the pharmacokinetics (PK) and in vivo activity of an Anticalin exhibiting picomolar affinity towards colchicine, a plant toxin with low tolerable dose in humans. PK analysis of the 20-kDa "Colchicalin" protein in male Sprague Dawley rats (n = 3) revealed a very short plasma half-life (3.5 min), which was prolonged 21-fold via genetic fusion with a 200-residue Pro/Ala sequence (PASylation). The scavenging activity of the PASylated Colchicalin was investigated over 3.5 h via stoichiometric application following a sub-toxic i.v. dose of colchicine on anesthetized rats (n = 2) leading to a rapid rise in total plasma colchicine concentration. We then established a 14-day intoxication model in rats (n = 3) at a 30 mg/kg p.o. colchicine dose which was characterized by severe weight loss, elevated neutrophil-to-lymphocyte ratio and shortened survival. PASylated Colchicalin administration at 4.2% of the neutralizing dose (125 mg/kg/day daily for 12 consecutive days) resulted in faster relief of the symptoms in 2/3 of animals (n = 6) compared to the control group without Colchicalin treatment (n = 5). Nevertheless, 1/3 of the rats died suddenly after the first Colchicalin injection, probably due to a steep rise in the total colchicine plasma concentration, which suggests further improvement of the dosing scheme prior to potential application in acute human colchicine poisoning.

An internet-based survey of 96 German-speaking users of "bath salts": frequent complications, risky sexual behavior, violence, and delinquency.

OBJECTIVE: To define the demographics of German-speaking "bath salt" users. DESIGN: Prospective web-based survey of volunteer users of "bath salts". Subject recruitment/exclusion: Participation was solicited by posts in web forums frequented by users of synthetic cathinones. An invitation to participate was also disseminated via regional drug information centers. Responses were discarded if participants refused data analysis, provided incomplete surveys, were under 18 years of age (five cases), and in case of clearly improbable answers (i.e., two cases with profanity typed in free-form input fields). Overall 96 out of 180 participants provided complete questionnaires. These were further analyzed. RESULTS AND CONCLUSIONS: 74% of respondents were male. 41% were under the age of 30 and a further 38% between 30 and 39 years old. Cathinones were used on more than 10 days in the preceding year by 62% of study subjects. The nasal and intravenous routes of administration were most often used. About 80% of respondents reported binge use. There were frequent co-administrations of opioids and opiates. The most common complication was prolonged confusion (47%). 16% had been involuntarily confined. One third had thoughts of violence and 16% acted on these thoughts either against themselves or others. About 44% reported high-risk sexual activity under the influence of cathinones. About 31% had driven or ridden a bike while intoxicated. About 6% had problems with law-enforcement for selling cathinones and 16% for crimes committed under the influence of cathinones. In conclusion, cathinone users are typically young males in their twenties and thirties. Most are experienced drug users, particularly of alcohol and opiates/opioids. The impact on society is tremendous as evidenced by high rates of self-reported violence, high-risk sexual activity, crimes, and traffic violations.

Independent validation of the ICU requirement score in a cohort of acutely poisoned adults.

OBJECTIVE: To independently validate the predictive value of the intensive care requirement score (IRS) in unselected poisoned patients. DESIGN: Retrospective chart review. PATIENTS AND METHODS: Five hundred and seventeen out of 585 admissions for acute intoxications could be analyzed. Eleven were excluded for a condition already requiring intensive care unit (ICU) support at admission (e.g., preclinical intubation). A further 57 admissions were excluded due to missing data. The IRS was calculated using a point-scoring system including age, Glasgow Coma Scale, heart rate, type of intoxication, and preexisting conditions. It was then compared to a composite endpoint indicating an ICU requirement (death in hospital, vasopressors, need for ventilation). The endpoint and the point-scoring system were identical to the original publication of the score. RESULTS AND CONCLUSION: Twenty-three out of 517 patients had a complicated clinical course as defined by meeting the endpoint definition. Twenty-one out of 23 complicated courses had a positive IRS (defined as greater or equal 6 points), as compared to 255/494 patients with an uncomplicated clinical course (p < .001, Fisher's exact test). One patient (with a positive IRS) died. The negative predictive value of the IRS was 0.99 (95% CI: 0.97-1), the sensitivity was 0.91 and the specificity 0.48. In conclusion, the IRS is significantly linked to outcome. While a negative IRS virtually excludes the need for ICU care, a positive IRS has a positive predictive value too low to be used for risk stratification. The IRS could also be applied to unselected admissions of poisoned patients.

Ibuprofen plasma concentration profile in deliberate ibuprofen overdose with circulatory depression treated with therapeutic plasma exchange: a case report.

BACKGROUND: Inquiries relating to ibuprofen overdose have more than tripled in the last ten years in our poison control center. Although the vast majority of cases have a benign clinical course, there are few severe or even fatal cases present with refractory circulatory failure. CASE PRESENTATION: We describe a case of a 48 year-old male with suicidal mono-ingestion of approximately 72 g ibuprofen. Despite an initial rapid spontaneous drop in the total ibuprofen plasma concentration (IPC) from 550 to 275 mcg/mL within the first 5 h after admission, the patient developed a circulatory failure, refractory to aggressive fluid resuscitation and high doses of vasopressors. Due to ibuprofen's favorable pharmacokinetics (>95% bound to albumin, low volume of distribution) and in the absence of specific therapeutic alternatives thereby avoiding escalating vasopressor doses, therapeutic plasma exchange (TPE) for extracorporeal elimination of ibuprofen was considered as a therapeutic rescue option. An improvement of hemodynamics with a significant reduction of vasopressors was observed with TPE-initiation. However, neither the observed IPC-profile nor a pharmacokinetic (PK) simulation provided evidence for a quantitative effective elimination of ibuprofen by TPE. Based on PK-modeling we calculated an overall ibuprofen half-life of 17.2 h for the entire observation period over 5 days. CONCLUSIONS: To our knowledge this is the first report of a severe ibuprofen-mono intoxication treated with TPE and providing serial IPCs over a period of five days, indicating an estimated fivefold overall-elimination half-life of 17.2 h. Despite TPE clinically improved persistent hemodynamic instability, this procedure was neither consistent with the observed IPC-profile nor correlated with a meaningful quantitative elimination of ibuprofen.

Corrigendum to "Fatal Systemic Vasoconstriction in a Case of Metastatic Small-Intestinal NET".

[This corrects the article DOI: 10.1155/2017/9810194.].

Single dose activated charcoal for gut decontamination: Application by medical non-professionals -a prospective study on availability and practicability.

CONTEXT: Oral activated charcoal (AC) for toxin absorption should be applied as soon as possible. Extra-hospital AC-application on site by medical laypersons with pre-emptive obtained AC may save time, but may be inferior to AC-application by medical professionals. OBJECTIVE: 1) Availability and incidence of pre-emptive stockpiling of AC on site in the German region Bavaria 2) time saved by AC-stockpiling and application on site, 3) quality of AC-application defined by completeness of the applied AC-dose, time needed, incidence of side-effects in lay-care and in professional-care, considering confounding variables: AC-formulation/powder/tablets, recommended AC-dose, patient's age. METHOD: telephone-interviews in cases with AC-recommendation by a Poison Information Centre (PIC). Lay-care was suggested according to risk-assessment by PIC. Ingestion sites were classified as either apt for AC-stockpiling or not apt. RESULTS: 1) availability: In Bavaria only 20%-22% of eligible cases had AC on-hand, 2) time-saving was at least 14 min. 3) Lay-care/professional-care or patient's age had no significant influence on the completeness of the applied AC-dose, which was higher with AC as powder but negatively correlated with the recommended AC-dose. No significant difference was seen with time needed for application and incidence of side-effects. CONCLUSION: pre-emptive AC-stocking should be encouraged.

Fatal Systemic Vasoconstriction in a Case of Metastatic Small-Intestinal NET.

An increased release of serotonin secreted by ileal NETs is thought to be the major factor causing the carcinoid syndrome. However, in acutely arising carcinoid crisis also other vasoactive factors may lead to hazardous fluctuations in blood pressure and bronchial constriction. In rare cases, systemic vasoconstriction can be observed, probably caused by catecholamines or similar acting substances. Here, we report a fatal case of fulminant systemic vasoconstriction possibly caused by catecholamines in a patient with metastasized ileal NET. The vasospasm was detected by CT-angiography, and hemodynamic monitoring revealed a high systemic vascular resistance. Epinephrine, norepinephrine, and chromogranin A levels in plasma were elevated as was the urinary 5-hydroxyindoleacetic acid (5-HIAA). The cause of death was heart failure due to severe circulatory insufficiency. The progression of the tumor disease was confirmed by autopsy.

Synthetic cathinones in Southern Germany - characteristics of users, substance-patterns, co-ingestions, and complications.

OBJECTIVE: To define the characteristics of synthetic cathinone users admitted to hospital including clinical and laboratory parameters and the complications of use. DESIGN: Retrospective single-center study of patients treated for acute cathinone intoxication and complications of cathinone use between January 2010 and January 2016. SETTING: A specialized clinical toxicology unit at an academic tertiary care center in Southern Germany serving a population of about 4 million. PATIENTS AND METHODS: 81 consecutive patients with laboratory-confirmed use of cathinones who presented for acute intoxication or complications of cathinone use were retrospectively analyzed. RESULTS AND CONCLUSIONS: The patients were predominantly male (64%, 52/81) with a median age of 34 years. 60 were admitted for signs of acute intoxication while 21 suffered from complications of cathinone use. 70% of acutely intoxicated patients had an increased creatinine phosphokinase. Only a minority of patients presented with a sympathomimetic toxidrome. Three patients had infectious complications, 10 prolonged psychosis, 6 rhabdomyolyses and/or kidney failure, and two patients died. Based on presentations, cathinone use has increased with the first cases seen in 2010. Opiates/opioids are the main co-ingested drugs of abuse. The pattern of cathinone use shifted from methylone in 2010/2011 to 3,4-methylenedioxypyrovalerone (MDPV) and 3-methylmethcathinone (3-MMC) in 2014/2015. We conclude that in our setting "typical" cathinone users are males in their thirties. They are seldom drug naïve and regularly co-ingest illicit drugs. Preventive measures have to be tailored to these difficult to reach patients. Present efforts to educate young clubbers in their late teens may fail to reach the pertinent demographic.

Risk assessment of severe tricyclic antidepressant overdose.

Prognostic factors for severe complications in tricyclic antidepressant (TCA) overdose remain unclear. We therefore evaluated the value of clinical characteristics and electrocardiograph (ECG) parameters to predict serious events (seizures, arrhythmia, death) in severe TCA overdose of 100 patients using logistic regression models for risk assessment. The overall fatality rate was 6%, arrhythmia occurred in 21% and 31% of the patients developed seizures. Using an univariable logistic regression model, the maximal QRS interval (OR 1.22; 95% CI 1.06-1.41; p = .005), the time lag between ingestion and occurrence of first symptoms of overdose (OR 1.13; 95% CI 0.99-1.29; p = .072) and the age (OR 0.73; 95% CI 0.55-0.98; p = .038) were determined as the solely predictive parameters. In the multivariable logistic regression model, the QRS interval could not be established as independent predictor, however, the terminal 40-ms frontal plane QRS vector (T40) reached statistical significance regarding prediction of serious events (odds ration [OR] 1.70; 95% confidence interval [CI] 1.02-2.84; p = .041), along with age and time lag between ingestion and onset of symptoms of overdose with a sensitivity and specificity of 71% and 70%, respectively. Evaluation of both clinical characteristics and ECG-parameters in the early stage of TCA overdose may help to identify those patients who urgently need further aggressive medical observation and management.