The Tanta University risk model could help identify patients with acute poisoning who would require intensive care unit level of care.

OBJECTIVE: To independently validate the negative predictive value of the Tanta University risk model for intensive care requirements in poison center telephone consultations with other physicians. METHODS: This study included 400 consecutive patients with acute poisoning. Clinical and laboratory parameters were recorded during the initial consultation with the poison center. Patients who were already ventilated or on vasopressors at the time of consultation were excluded. The Tanta University risk model score was calculated from the data according to the following equation: Tanta University risk model score = 1.966*Glasgow Coma Scale + 0.329*oxygen saturation (percent) + 0.212*diastolic blood pressure (mmHg) - 0.27*respiratory rate (breaths/minute) + 0.33*standard bicarbonate (mmol/L). Twenty-four hours later, the patients' courses were followed up by telephone. The Tanta University risk model was then compared to a composite endpoint indicating the requirement for admission to an intensive care unit (vasopressors, need for intubation, or death). RESULTS: Four hundred patients with acute poisoning were included. Thirty-seven patients had a complicated clinical course as defined by the composite endpoint. Receiver operating characteristic analysis revealed the area under the curve to be 0.87 (95 percent confidence interval 0.83-0.90). An unfavorable Tanta University risk model score was defined as less than 73.46, using a cut-off derived from a previous study of an unrelated series of patients with acute poisoning admitted to our service. Thirty-one of 37 patients with complicated courses had an unfavorable Tanta University risk model score compared to six patients with complicated courses among 306 patients with a favorable Tanta University risk model score (P < 0.0002, Fisher's exact test). Sixty-three patients had an unfavorable Tanta University risk model score but an uneventful course. The negative predictive value of the Tanta University risk model was 0.98 (95 percent confidence interval 0.96-0.99), sensitivity was 0.84, and specificity 0.83. CONCLUSIONS: In the present study of poison center telephone consultations, the Tanta University risk model was significantly related to the outcomes in patients with acute poisoning. Patients with a favorable Tanta University risk model score (greater than or equal to 73.46) were unlikely to need intensive care unit level of care.

Independent validation of the Tanta University Risk Model for intensive care requirement in acutely poisoned adults.

OBJECTIVE: To independently validate the predictive value of the Tanta University Risk Model for intensive care requirement in unselected poisoned patients. METHOD: Retrospective chart review of 293 poisoned patients. The Tanta University Risk Model was calculated as follows: Tanta University Risk Model = -1.966*Glasgow Coma Scale - 0.329*oxygen saturation - 0.212*diastolic blood pressure + 0.27*respiratory rate - 0.33*standard bicarbonate. It was then compared to a composite endpoint indicating an intensive care unit requirement (death in hospital, vasopressors, need for intubation). RESULTS: Nineteen of 293 patients had a complicated clinical course as defined by meeting the primary endpoint definition. Receiver operating characteristic analysis revealed the area under the curve to be 0.79 (95% confidence interval 0.73-0.83). A positive Tanta University Risk Model was defined >-73.46. Fifteen out of 84 patients with a positive Tanta University Risk Model had a complicated course, while four of 209 patients with a negative Tanta University risk model had a complicated course (P<0.0001, Fisher's exact test). The negative predictive value of the Tanta University Risk Model was 0.98 (95% confidence interval 0.95-0.99), the sensitivity was 0.79 and that specificity was 0.75. CONCLUSION: Poisoned patients with a negative Tanta University Risk Model score are unlikely to need an intensive care unit level of care.

ToxNet: an artificial intelligence designed for decision support for toxin prediction.

BACKGROUND: Artificial intelligences (AIs) are emerging in the field of medical informatics in many areas. They are mostly used for diagnosis support in medical imaging but have potential uses in many other fields of medicine where large datasets are available. AIM: To develop an artificial intelligence (AI) "ToxNet", a machine-learning based computer-aided diagnosis (CADx) system, which aims to predict poisons based on patient's symptoms and metadata from our Poison Control Center (PCC) data. To prove its accuracy and compare it against medical doctors (MDs). METHODS: The CADx system was developed and trained using data from 781,278 calls recorded in our PCC database from 2001 to 2019. All cases were mono-intoxications. Patient symptoms and meta-information (e.g., age group, sex, etiology, toxin point of entry, weekday, etc.) were provided. In the pilot phase, the AI was trained on 10 substances, the AI's prediction was compared to naïve matching, literature matching, a multi-layer perceptron (MLP), and the graph attention network (GAT). The trained AI's accuracy was then compared to 10 medical doctors in an individual and in an identical dataset. The dataset was then expanded to 28 substances and the predictions and comparisons repeated. RESULTS: In the pilot, the prediction performance in a set of 8995 patients with 10 substances was 0.66 ± 0.01 (F1 micro score). Our CADx system was significantly superior to naïve matching, literature matching, MLP, and GAT (p < 0.005). It outperformed our physicians experienced in clinical toxicology in the individual and identical dataset. In the extended dataset, our CADx system was able to predict the correct toxin in a set of 36,033 patients with 28 substances with an overall performance of 0.27 ± 0.01 (F1 micro score), also significantly superior to naïve matching, literature matching, MLP, and GAT. It also outperformed our MDs. CONCLUSION: Our AI trained on a large PCC database works well for poison prediction in these experiments. With further research, it might become a valuable aid for physicians in predicting unknown substances and might be the first step into AI use in PCCs.

Characteristics and predictive factors of severe or fatal suicide outcome in patients hospitalized due to deliberate self-poisoning.

Prediction of clinical course of intoxication is essential for timely initiation of appropriate medical treatment in patients hospitalized due to suicidal self-poisoning. In this retrospective single-centre study in patients hospitalized due to suicidal poisoning in a specialized clinical toxicology unit, we aimed to identify predictive factors associated with severe or fatal course of self-poisoning. All patients underwent at least one psychiatric exploration during their inpatient stay. Severity of poisoning was assessed on admission and after 24 hours according to the Poison Severity Score index (PSS). Spearman's rank correlation coefficient was used to test the association of PSS with sociodemographic, anamnestic and (pre-)clinical parameters. Multivariable binomial logistic regression analysis was performed to determine predictive factors for severe and/or fatal self-poisoning. 1090 patients were included in the study. Median age was 39 years (range 13-91), 66.7% of patients were female. PSS was classified in the majority as "minor" (n = 558, 51.2%) or "moderate" (n = 264, 24.2%). 61 patients (5.6%) had PSS "severe"; 14 patients (1.3%) died. A higher severity of poisoning positively correlated with duration of inpatient therapy (p<0.001, Spearman's rho = 0.454) and duration of ventilation (p<0.001, rho = 0.474), and it inversely correlated with initial Glasgow Coma Scale (GCS) score (p<0.001, rho = -0.437). Multivariable analysis identified no alcohol co-ingestion (OR 3.23; 95%CI 1.3, 8.07; p = 0.012) and self-poisoning with non-medicinal substances (OR 5.4; 95%CI 1.78, 16.34; p = 0.003) as factors predictive for "severe" or "fatal" suicide outcome. In contrast, female gender (OR 0.4; 95%CI 0.2, 0.81; p = 0.011), not using an antidepressant as the method for self-poisoning (OR 0.27; 95%CI 0.12, 0.59; p = 0.001) and a higher initial GCS score (OR 0.79; 95%CI 0.73, 0.85; p<0.001) reduced the risk of a severe or fatal course of self-poisoning. The conclusion for clinical practice is that male patients hospitalized due to self-poisoning, with a low initial GCS score, who did not co-ingest alcohol, attempted suicide with non-pharmaceutical substances or antidepressants are at a higher risk of severe/fatal outcome of suicide. Determination of these risk factors at admission could be potentially used to guide treatment intensification in patients hospitalized due to deliberate self-poisoning.

Socio-demographic and psychiatric profile of patients hospitalized due to self-poisoning with suicidal intention.

OBJECTIVE: To identify the psychiatric profile of patients hospitalized due to self-intoxication associated with suicide-related behavior (SRB). METHODS: In this retrospective single-center study, records of consecutive patients treated for suicidal poisoning in our Clinical Toxicology unit between 1st January 2012 and 31st December 2016, who received at least one psychiatric exploration during their inpatient stay, were analyzed with regard to epidemiological data, ingested substances, psychiatric and somatic comorbidities, suicidal circumstances and follow-up therapy. RESULTS: Out of 1289 hospitalized patients, 1090 patients with complete data were analyzed. Mean age was 40.5 ± 17.2 years, 66.7% were female. 32.0% of patients had previously engaged in SRB, in 76.3% intention was suicidal. 64.7% of patients had a pre-existing psychiatric disorder (PD). Patients with a pre-existing PD more often displayed prior SRB than those without PD (40.7% vs 15.3%; p < 0.001; Fisher's exact test), used long-term/on demand medication (70.2% vs 38.9%; p < 0.001), distanced themselves from the current suicide attempt (65.9% vs 50.8%; p < 0.001) and had no detectable trigger (38.7% vs 18.1%; p < 0.001). Partnership conflict was the most commonly named trigger, and it was documented more often in patients without than in those with PD (41.6% vs 25.6%). After psychiatric reevaluation, most patients were diagnosed with mood disorders (29.7%) and stress disorders (17.0%); 32.8% of patients had a combination of two or more PDs. CONCLUSION: Hospitalization due to self-poisoning is associated with pre-existing PD, prior SRB and access to psychiatric medication. Detection of these risk factors could allow timely introduction of effective preventive measures tailored to particularly vulnerable subgroups and appropriate relief. However, lack of a detectable trigger in many cases may hamper the identification of those at risk.

Clinical effect of ethanol co-use in patients with acute drug toxicity involving the use of central nervous system depressant recreational drugs.

BACKGROUND AND IMPORTANCE: Patients who use recreational drugs frequently co-ingest ethanol, which is considered a central nervous system (CNS) depressant. The clinical relevance of this in acute toxicity involving other CNS depressants is not well described. OBJECTIVE: To assess the clinical impact of ethanol co-use in patients presenting to the emergency department (ED) with acute toxicity involving the use of CNS depressant drugs. DESIGN, SETTINGS AND PARTICIPANTS: A retrospective multicentre study using data from the Euro-DEN Plus database from January 2014 to December 2019. OUTCOMES MEASURE AND ANALYSIS: Comparison of epidemiologic and clinical characteristics, ED and hospital management of patients with CNS depressant intoxication with or without ethanol co-use. MAIN RESULTS: Although 7644 (17.5%) of the 43 633 presentations were included, ethanol was co-ingested in 3811 (49.9%). In total 53.3% required medical treatment, 14 patients died. Patients with ethanol co-use more frequently presented with a Glasgow Coma Scale (GCS) ≤8 (34.1% vs. 22.4%; P < 0.001), vomiting (8.1% vs. 4.6%; P < 0.001), anxiety (12 % vs. 6.4%; P < 0.001), agitation/aggression (22% vs. 14.7%; P < 0.001), seizures (3.8% vs. 2.4%; P < 0.001) and hypotension (7.5% vs. 4.6%; P < 0.001). They more often required ambulance transport (85.5% vs. 76.5%; P < 0.001), medical treatment (57.3% vs. 48.0%; P < 0.001), hospitalization (27.7% vs. 18.9%; P < 0.001), and admission to intensive care (12.2% vs. 4.0%; P < 0.001). Subgroup analysis showed that GCS ≤8 was particularly common in patients who combined ethanol with opioids or gamma-hydroxybutyrate (GHB)/gamma-butyrolactone (GBL). CONCLUSION: Co-use of ethanol with CNS-depressant drugs appears to increase the risk of adverse effects and is associated with a higher need for medical treatment, especially when ethanol is combined with opioids or GHB/GBL.

Lessons to be learned: identifying high-risk medication and circumstances in patients at risk for suicidal self-poisoning.

BACKGROUND: Although the total number of suicides decreased since the beginning of the 1980s, the number of suicide-related behaviors using self-intoxication increased. Therefore, research on the characteristics of individuals committing self-intoxication becomes of growing importance for risk assessments and the development of preventive measures. METHODS: In this prospective, observational, monocentric cohort study, all incoming calls at our Poisons Control Centre reporting suicide-related behaviors through self-intoxication, were analyzed via a standardized questionnaire over 12 months. Both univariate and bivariate analyses were performed. RESULTS: 1238 cases of deliberate intoxication were included in the study. The majority of cases occurred in the age group between 18 and 44 (n = 607/49%), two-thirds were female (n = 817/66%). The main substances used were antidepressants (n = 420/34%), peripheral analgesics (n = 322/26%) and neuroleptics (n = 282/23%). The majority of patients ingested substances from their prescribed medication (n = 640/82%) with the highest proportion in those aged over 64 years (n = 72/113; 91%, p < 0.001). Substance use was reported for the minority of patients (n = 175/23%). For 704 cases (79%), a psychiatric disorder was documented. Factors associated with recurrent suicide-related behaviors were an underlying psychiatric disorder (OR = 6.2; 95% CI 3.8-10.4), substance use (OR = 2.4; 95% CI 1.5-3.8), and ingestion of neuroleptics (OR = 2.1, 95% CI 1.4-3.0) or antidepressants (OR = 1.6; 95% CI 1.2-2.3). CONCLUSION: This study might contribute to identifying individuals with an increased risk of suicide-related behaviors by deliberate intoxication and to developing preventive strategies for future suicide attempt(s).

A case report of severe pirimiphos-methyl intoxication: Clinical findings and cholinesterase status.

A 63-year-old male was admitted to a district hospital after ingesting ethanol and pirimiphos-methyl (PM) with suicidal intentions. History included alcoholic cirrhosis with alcoholism, adiposity, diabetes with cerebral microangiopathy, chronic renal insufficiency, heparin-induced thrombocytopenia, and status post necrotizing fasciitis. Emergency medical service reported an alert patient without signs of cholinergic crisis; activated charcoal and atropine were administered. Upon hospital arrival, he received fluid resuscitation, activated charcoal, and atropine. He was transferred to a toxicology unit the next day. On admission, he had no cholinergic signs (dry mucous membranes, warm skin, and mydriatic pupils) requiring small atropine doses (0.5 mg per hour). Four hours after admission, he developed bradycardia and respiratory distress, necessitating intubation. He received atropine by continuous infusion for 7 days (248 mg total) and obidoxime (bolus and continuous infusion). PM, pirimiphos-methyl-oxon (PMO), and phosphorylated tyrosine (Tyr) adducts derived from human serum albumin were analyzed in vivo. Cholinesterase status (acetylcholinesterase (AChE), butyrylcholinesterase (BChE), inhibitory activity of patient plasma and reactivatability, and phosphorylated BChE-derived nonapeptides) was measured in vivo. Obidoxime and atropine were monitored. PM and PMO were detectable, PM with maximum concentration ∼24 h post admission (p.a.) and PMO at ∼18 h p.a. Tyr adducts were detectable. AChE in vivo was suppressed on admission, increased continuously after starting obidoxime, and reached maximum activity after ∼30 h. AChE in vivo and reactivatability remained at the same level until the end of monitoring. BChE was already suppressed on admission; termination of the antidote treatment was possible after BChE had recovered to 1/5th of its normal value and extubation was possible after BChE had recovered to 2/5th. While a substantial part of BChE was already aged on admission, aging continued peaking at ∼24 h p.a. After initiating obidoxime treatment, plasma levels increased until obidoxime plasma levels reached a steady state. On admission, plasma atropine level was low; it increased with the start of the continuous infusion. Afterward, the level dropped to a steady state. The clinical course was characterized by bouts of pneumonia, necessitating re-intubation and prolonged ventilation, sepsis, delirium, and a peripheral neuropathy. After psychiatric evaluation, the patient was discharged to a neurological rehabilitation facility after 77 days of hospital care.

Choking agents and chlorine gas - History, pathophysiology, clinical effects and treatment.

INTRODUCTION: Choking agent exposure, among them chlorine gas, occurs in household or industrial accidents, chemical warfare and terrorist attacks. AIMS: Review of published animal and human data regarding the history, pathophysiology, clinical effects and management of chlorine exposure. PATHOPHYSIOLOGY: Highly soluble agents cause quick upper respiratory tract symptoms. Chlorine gas has a medium solubility, also causing delayed lower airway symptoms, mainly due to its oxidizing potential by releasing hypochlorous and hydrochloric acid, but also by interacting with Transient Receptor Potential channels. SYMPTOMS: Eyes may show conjunctival injection, abrasions and corrosions. Burns of the oronasal mucosa and trachea can occur. Dyspnea, bronchospasm and possible retrosternal pain occur frequently. Glottis edema or laryngospasm are acute life-threatening emergencies. Chlorine gas can cause toxic pneumonitis, lung edema and acute respiratory distress syndrome (ARDS). MANAGEMENT: General management includes physical examination, pulse oximetry and arterial blood gases. Eyes should be irrigated, humidified oxygen and inhalative bronchodilators administered. An EKG, cardiac enzymes and complete-blood-count should be obtained if there is retrosternal pain. Routine chest x-ray is not recommended - except if pulmonary edema is suspected. Laryngoscopy should be performed if glottis edema is suspected. Sodium bicarbonate inhalation after chlorine gas inhalation is discussed controversially. Mechanical ventilation with continuous-positive-airway-pressure or intubation/tracheotomy with high positive-end-expiratory-pressure may be necessary. Glucocorticoids for prevention of pulmonary edema should be applied restrictively. Prophylactic antibiotics are not recommended. In severe ARDS, extracorporeal membrane oxygenation (ECMO) can be considered. CONCLUSION: Treatment is mainly symptom oriented. New and promising therapies are in development.

The Use of Activated Charcoal to Treat Intoxications.

BACKGROUND: In 2016, according to the German Federal Statistical Office, 178 425 cases of intoxication (poisoning) were treated in German hospitals. The poison control centers in the German-speaking countries gave advice in a total of 268 787 instances of poisoning in that year, and use of activated charcoal was recommended in 4.37% of cases. The application of activated charcoal plays a major role in both primary and secondary detoxification. This article serves as an overview of the mechanism of action, indications, contraindications, modes of application, and dosing of activated charcoal. METHODS: This review is based on pertinent publications retrieved by a selective search in PubMed. The opinions of experts from the poison control centers in the German-speaking countries were considered in the interpretation of the data. RESULTS: The administration of activated charcoal is indicated to treat moderately severe to life-threatening intoxication. It should be carried out as soon as possible, within the first hour of the ingestion; timed-release preparations can be given up to 6 hours after the ingestion. An important contraindication is impaired consciousness with the danger of aspiration in a patient whose air- way has not yet been secured. Activated charcoal is ineffective or inadequately effective in cases of poisoning with acids or bases, alcohols, organic solvents, inorganic salts, or metals. The proper dosage consists of an amount that is 10 to 40 times as much as that of the intoxicating substance, or else 0.5-1 g/kg body weight in children or 50 g in adults. Repeated application is indicated for intoxications with agents that persist for a longer time in the stomach and for intoxications with timed-release drugs or drugs with a marked enterohepatic or entero-enteric circulation. The routine combination of activated charcoal with a laxative is not recommended. CONCLUSION: Even though intoxications are common, there is still no internationally valid guideline concerning the administration of activated charcoal. A precise analysis of the risks and benefits is needed for each administration, and a poison control center should be consulted for this purpose.

[Alarming Pregabalin Abuse in Munich: Prevalence, Patterns of Use and Complications]. / Alarmierender Pregabalin-Missbrauch: Prävalenz im Münchener Raum, Konsummuster und Komplikationen.

Background Pregabalin is used e. g. for the treatment of neuropathic pain and anxiety disorder. Recently, its potential for abuse and addiction has become apparent. Methods From 2008 - 2015, we searched our database for the term "Pregabalin", including all patients treated in our department and all calls to the Poison Information Centre (PIC) Munich.From October 2013 to September 2014, all patients were included in a cohort study who either were admitted with a drug intoxication or who presented themselves for a course of detoxification (except ethanol). Results From 2008 - 2015, 263 patients with Pregabalin abuse were treated. The number of cases per year increased from 0 - 5 in 2008 - 2011 to 105 in 2015. In 2008, the PIC received 3 calls concerning Pregabalin abuse, in 2015 the number of calls was 71. From 2013 - 2014, 80 out of 370 patients had consumed Pregabalin. It was the fifth most frequently abused substance. Pregabalin users had consumed more additional substances than other patients (median 4 1 2 3 4 5 6 vs. 2 1 2 3 4 5 6, p < 0.001) and they were more often in an opioid substitution treatment (41.2 vs. 21.7 %, p < 0.001).The most co-abused drugs were benzodiazepines (66.3 %), methadone (48.8 %), buprenorphine (32.5 %) and heroin (22.5 %). 88.0 % of all intoxicated patients had moderate to severe symptoms of intoxication like impaired consciousness (74.0 %), respiratory distress, (40.0 %), agitation/aggressiveness (28.0 %), restlessness (14.0 %), hallucinations (8.0 %) or seizures (8.0 %).The semi-quantitative urine concentration was 51.4 ± 66.0 mg/g Creatinine for intoxicated patients and 26.1 ±â€Š23.0 for patients admitted for detoxification (n = 58; p = 0.034). Discussion Pregabalin abuse increases continuously and constitutes a significant health issue. Particularly patients with a history of substance abuse are vulnerable. Physicians should be aware of the substantial potential of Pregabalin for abuse and addiction and they should know the dangers of an intoxication.

Dementia, epilepsy and polyneuropathy in a mercury-exposed patient: investigation, identification of an obscure source and treatment.

We present a patient aged 54 years with early onset of dementia, epilepsy and peripheral polyneuropathy. A mercury intoxication was diagnosed in 2010, chelation therapy with 2,3-dimercaptopropane-1-sulfonate had failed. A source of exposure could not be identified. MRI showed unspecific hyperintense brain lesions in 2015. She was referred for diagnosis and treatment. Neuropsychological testing indicated severe memory loss and nerve conduction speed measurements showed chronic neurogenically changed potentials. Mercury levels in blood and urine and neuron-specific enolase (NSE) were elevated. A detailed patient history revealed a daily application of mercury-containing skin lightening creams for 6 years. Treatment with 2,3-dimercaptosuccinic acid (DMSA) was started, blood mercury levels were falling during treatment. She was discharged with DMSA prescriptions. A renewed MRI revealed unchanged brain lesions. Blood and urine mercury levels and NSE were falling. Memory function had improved qualitatively and quantitatively.