Whole-bowel irrigation in cases of poisoning: A retrospective multicentre study of feasibility, tolerability, and effectiveness.

BACKGROUND: Whole-bowel irrigation (WBI) is a strategy of gastrointestinal decontamination, recommended by several European and American learned societies, which may be used in the management of the poisoned patients. OBJECTIVES: The objectives of this study were to describe the feasibility and tolerability of this technique and to compare the clinical outcome of a group of poisoned patients treated with WBI versus that of an untreated group. METHODS: This was a retrospective and observational study of data recorded by the Angers Poison Control Centre (PCC) between 2012 and 2018. All cases for which the PCC advised WBI were included. The association between outcomes (clinical deterioration after WBI advised by a PCC, length of hospitalisation), WBI treatment, and relevant associated risk factors was determined using univariate and multivariate logistic regression. RESULTS: A total of 257 patients were included. One hundred forty-one patients were treated with WBI with clearly successful induction of diarrhoea in 47 cases (31%). WBI was not initiated in 89 patients. WBI was initiated but unsuccessful (no diarrhoea) in nine cases. The median age is 46 years (interquartile range: 32-55 years), with a sex ratio (M/F) of 1.3. A total of 27 of 150 patients (18%) who underwent WBI had adverse effects possibly linked to WBI, mainly vomiting (n=23). The patients with clinical deterioration (n=49) were irrigated significantly less often (95% confidence interval: 0.13-0.52; p<0.001). After adjustment for sex, age, time to implementation of WBI, type of substance ingested, and admission to intensive care, patients who were treated with WBI were less likely to deteriorate clinically than patients who were not treated with WBI (p<0.001). CONCLUSION: Despite a low rate of completion of this procedure, WBI appeared to provide clinical benefits in patients treated in comparison of an untreated group and is associated with an acceptably low risk of direct complications.

Poisoning exposure from non-pharmaceutical products in residents of structured living facilities.

OBJECTIVE: The objectives of this study were to describe poisonings occurring in older or disabled patients residing in structured living facilities, identify risk factors, and propose preventive measures. METHOD: This was a prospective and observational study, covering all cases of poisoning occurring in structured living facilities in the Brittany region of France. All calls were received at the Grand Ouest Poison Control Centre (PCC) of Angers and were recorded from 1 February 2019 to 31 January 2020. The clinical severity of the poisonings was assessed using the Poisoning Severity Score (PSS). Clinical severity was compared by univariate and multivariate analyses using the following dependent variables: PSS score < 2 and PSS ≥ 2. RESULTS: This study included 158 residents with a median age of 83 years (5-116 years old). The average number of residents supervised by a member of the supervisory staff was 11 (+/-10.7). The substance ingested was a personal hygiene product or a cleaning product in 48% and 25% of cases, respectively. The most frequently ingested product was a bar of soap (n = 20). All moderate to severe cases (4.6%, n = 8 including one death) occurred in residents with dementia living in nursing homes for elderly patients, and 9% of residents required hospital treatment. In more than 50% of cases (n = 83), the product was provided by the facility and in 23% (n = 40), it was brought in by the family. Ingestion of a bar of soap or a product brought in by the family was significantly associated with higher poisoning severity (PSS ≥ 2). After adjustment for age, sex and the number of residents per supervisor, the severity of poisoning was significantly greater after ingestion of a bar of soap (OR = 12.33, CI95 [2.12, 71.63], p = 0.005). CONCLUSION: Older adults residing in medical facilities who have a history of dementia and/or cognitive impairment are more at risk of non-medicinal product poisoning. Clinical severity and the hospitalisation rate were greater when bar soap was ingested.

Difficulties interpreting concentrations in fatal cases: example of 2,5-dimethoxy-4-chloroamphetamine.

PURPOSE: Death related to the use of drugs is evident when drugs are detected in biological matrices within toxic levels, but sometimes it can be less obvious. Intoxications after 2,5-dimethoxy-4-chloroamphetamine (DOC) use are occurring but up to date, only one fatality has been reported. Here we present the case of a young woman admitted to hospital as she presented vomiting, convulsions and cardiorespiratory arrest. METHODS: Blood ethanol concentration was determined using gas chromatography with flame ionization detection and toxicological screenings (blood, gastric content and hair samples) were performed using liquid chromatography with diode array detection, gas chromatography or liquid chromatography with mass spectrometry detection. RESULTS: Her health state declined with cardiac troubles, organs failure and cerebral edema till death occurring 4 days later. The autopsy revealed the presence of hemorrhagic infiltration inside the left ventricle, pulmonary edema and hemorrhagic infiltration of the terminal ileum. The analysis of biological fluids confirmed the presence of DOC (< 10 ng/mL in cardiac blood sample), buprenorphine, cocaine and cannabis metabolites. The analysis of hair highlighted a history of drugs abuse. CONCLUSION: In the absence of evident identified cause, the hypothesis of a death due to acute drugs use within a history of chronic consumption of drugs has been put forward. The concentration of some substances such as new psychoactive substances can be low in biological matrices but the toxic effects can be additive and lead to death even within young people, hence the importance of the knowledge of consumption history.

Poison control centres and alternative forms of communication: comparison of response rates between text message and telephone follow-up.

INTRODUCTION: In recent years, the number of patients managed by poison control centres (PCCs) has increased without a proportional increase in the number of physicians. To improve efficiency without neglecting patient follow-up, some PCCs have begun using text messages. We evaluated the difference in response rates between text messaging and traditional telephone follow-up. MATERIALS AND METHODS: This retrospective, monocentric, non-randomised cohort study was conducted using data from calls made by the New Aquitaine PCC between February 27, 2019, and March 31, 2019. Patients were contacted up to three times by a phone call or short message service (SMS). RESULTS: For the analysis, 823 patients were included. At the end of follow-up, the response rates were similar in the phone call and SMS group (94 vs. 94%; p = 0.76) with median [interquartile range] response times of 0 min [0; 27 min] and 29 min [6; 120 min], respectively. The response rates did not differ in subgroups stratified according to sex, self-poisoning vs. relative response, age class, and solicitation during working hours vs. outside of working hours (all p > 0.5). Moreover, health practitioners required 2.4-fold more time to call than to send text messages (p < 0.001), and all practitioners were satisfied or very satisfied with text messaging implementation. CONCLUSION: Patients had good adherence to text messages. Text messages are easy to use, rapid, and allow the physician to easily prioritise follow-up without occupying the emergency line. Additionally, the costs of installation and maintenance are low for text message systems; these low costs facilitate the implementation of such services in various medical situations.

Pediatric cannabis poisonings in France: more and more frequent and severe.

CONTEXT: Accidental pediatric cannabis poisonings are an incidental effect of cannabis use. The average THC content of cannabis resin and the number of consumers are rising sharply in the USA and in most European countries. The objective is to study the evolution of prevalence and severity of pediatric exposures to cannabis in France. METHOD: This is a retrospective observational study of cases detected by French poison centers between January 1st 2010 and December 31st 2017 of cannabis exposure by ingestion in children aged ten or younger. The clinical severity was assessed using the Poisoning Severity Score (PSS). The criteria used for assessing the overall severity were as follows: PSS ≥ 2, admission to pediatric intensive care, coma and respiratory depression (univariate and multivariate logistic regression). RESULTS: A total of 965 cases of poisoning were covered. The annual average number of cases was 93 between 2010 and 2014 and 167 between 2015 and 2017. The median age was 15 months (range, 6 months-10 years) and the sex ratio was 1:1. The form of cannabis ingested was mainly resin (75%). During the period covered by the study, 26.1% of children (n = 252) presented with a PSS ≥ 2, 4.5% (n = 43) coma, 4.6% (n = 44) with respiratory depression and 11.7% (n = 113) were admitted into pediatric intensive care (out of 819 hospitalizations). No fatal cases were reported. In comparison to the 2010-2014 period, the length of hospital stays was significantly higher (p < 0.0001) and the comas were significantly deeper (lower score on the Glasgow coma scale, p < 0.005) in 2015-2017. Following adjustments made for the sex, age and weight of the children, the data show that the severity of the poisonings was significantly greater in 2015-2017 in terms of PSS score, the number of comas and monitoring in intensive care (p < 0.001). CONCLUSION: The data indicates a significant increase in the number of cases of pediatric exposure to cannabis and a rise in the seriousness of poisonings between 2010 and 2017.

High silver concentrations in biological samples following different exposures: Two case reports.

BACKGROUND: Silver is used in various industrial applications, but also in confectioneries and for therapeutic use due to its antibiotic properties. Its toxicity is not well documented and most often only in the context of professional exposure. AIM: Here we report two cases of high silver concentrations in biological samples in two women: the first patient presented grey marks around her cuticles, probably due to her consumption of silvered sweets and the second patient presented agranulocytosis and thrombocytopenia occurring within 24 h after the topical application of a cream containing sulfadiazine and silver to burns over a large surface area. METHODS: Silver concentrations were determined in blood and urine samples and sweets using inductively coupled plasma- mass spectrometry (ICP-MS). RESULTS: The silver concentrations were elevated compared to population reference values and confirmed the hypotheses for the patients: the significant consumption of sweets coated with silver nanoparticles and the topical application of a cream containing silver to burns over a large area. DISCUSSION-CONCLUSION: After initial questioning by the dermatologist, Patient 1 explained that she consumed more than 30 bags of the sweets per year. She decreased her consumption of the sweets and the control performed one year later showed a plasma silver concentration of 1.5 µg/L. For Patient 2, the absorption of silver through burns over a large area appeared relatively significant, whereas it is very low through undamaged skin. The haematological cells counts returned to normal levels quickly and no other major effects were highlighted. To apply these findings to a larger population, further investigation to determine sulfadiazine and silver concentrations in plasma and urine have been initiated in a cohort of patients with burns over a large area.

A Protocol for the Use of Case Reports/Studies and Case Series in Systematic Reviews for Clinical Toxicology.

Introduction: Systematic reviews are routinely used to synthesize current science and evaluate the evidential strength and quality of resulting recommendations. For specific events, such as rare acute poisonings or preliminary reports of new drugs, we posit that case reports/studies and case series (human subjects research with no control group) may provide important evidence for systematic reviews. Our aim, therefore, is to present a protocol that uses rigorous selection criteria, to distinguish high quality case reports/studies and case series for inclusion in systematic reviews. Methods: This protocol will adapt the existing Navigation Guide methodology for specific inclusion of case studies. The usual procedure for systematic reviews will be followed. Case reports/studies and case series will be specified in the search strategy and included in separate sections. Data from these sources will be extracted and where possible, quantitatively synthesized. Criteria for integrating cases reports/studies and case series into the overall body of evidence are that these studies will need to be well-documented, scientifically rigorous, and follow ethical practices. The instructions and standards for evaluating risk of bias will be based on the Navigation Guide. The risk of bias, quality of evidence and the strength of recommendations will be assessed by two independent review teams that are blinded to each other. Conclusion: This is a protocol specified for systematic reviews that use case reports/studies and case series to evaluate the quality of evidence and strength of recommendations in disciplines like clinical toxicology, where case reports/studies are the norm.

Second-generation antihistamines: a study of poisoning in children.

Background and objectives: The toxicity of second-generation antihistamines after an overdose by a child is still unknown. The objective of this study is to use data from Poisons Centres in France to describe the toxicity profile of second-generation antihistamines for children and to compare the severity of poisoning observed from these with a first-generation antihistamine.Method: This was a retrospective, multi-centre and observational study focusing on human cases of single-substance exposure to a second-generation antihistamine and to mequitazine, reported between 1 January 2001 and 31 December 2016 in Poisons Centres in France.Results: From a total of 9403 children included, 5980 were exposed to a second-generation antihistamine and 3423 were exposed to mequitazine. The severity of exposure to second-generation antihistamines in children is low: among the children followed until a known outcome, 9% of children were symptomatic and in 97% of cases, the symptoms shown were of a minor-level severity (primarily drowsiness or restlessness). Depending on the substance, children who ingested doses 16 to 69 times the maximum recommended therapeutic dose remained asymptomatic. No deaths or severe symptoms were observed. No cases of lengthening of the QT interval or arrhythmias were identified. Mequitazine led to more symptoms than other substances (14.8% symptomatic children vs. 7.5%, Odd ratio (OR): 2.3 (2.0-2.6), p < 0.0001), more symptoms of moderate intensity (1.4 vs. 0.2%, OR: 8.3 (4.1-18.5), p < 0.0001) and more hospitalisation (19.1 vs. 8.7%, OR: 2.5, 95% CI: (2.2-2.8), p < 0.0001).Conclusion: The severity of poisoning from second-generation antihistamines appears to be low among children and considerably lower than poisoning caused by mequitazine.

Severe poisoning with naproxen causing coagulopathy.

Non-steroidal anti-inflammatory drugs (NSAIDs) are well known for their most frequent side effects (digestive, renal and metabolic disorders) but are lesser known for other effects, such as coagulation disturbances. In this issue, we report the case of a 58-year-old woman who ingested 26 g of naproxen in a suicidal attempt and developed cardiovascular shock, hypocoagulability and thrombopenia. Her outcome was positive (extubation 3 days after admission [D3], correction of haemostatic disruptions on D5 and of thrombopenia on D6). Naproxen plasma concentration was at a toxic concentration of 1320 mg/L at 6 hours after drug ingestion. Only few cases of hypocoagulopathy are reported with the NSAIDs, and this is the first case that can be attributed to naproxen. A possible explanation of this phenomenon following naproxen ingestion is an inhibition of thromboxane A2, usually attributed to NSAIDs, combined with an inhibition of activation of downstream the cascade.

Ingestion of bar soap may produce serious injury: clinical effects and risk factors.

INTRODUCTION: Most household and body soaps have an alkaline pH (9-12). In addition to their foaming effect, they irritate the skin. This study aims to review soap exposure reported to the Angers Poison Control Centre. METHOD: A retrospective study of accidental or deliberate oral exposure to solid soaps reported to the Angers Poison Control Centre between 1 January 2000 and 1 April 2015. Poisoning severity was reassessed for each case according to the Poisoning Severity Score (PSS). RESULTS: 553 cases of exposure were recorded. In more than 40% of cases (n = 226), exposure occurred in community settings (retirement homes, nursing homes). Patients had a history of dementia in 220 cases (40%). The most common symptoms were labial oedema (28%, n = 153), oropharyngeal irritation (10%, n = 56), salivation (10%, n = 53), vomiting (9%, n = 48) and cough (8%, n = 45). Among symptomatic patients (n = 276), one patient died from aspiration pneumonia and one patient died from a cardiogenic shock following oropharyngeal oedema, vomiting, cough and bronchial obstruction. Patients with dementia were more often symptomatic (75% vs 34%, p < .001) and more frequently hospitalised (22% vs 0.8%, p < .001). They experienced more moderate to severe symptoms (8% vs 0%, p < .001). Mildly severe (PSS2, n = 14), highly severe (PSS3, n = 1) and fatal (PSS4, n = 2) poisoning were observed only in patients with dementia. CONCLUSION: Ingestion of soap bars is potentially serious, especially in patients with dementia. This type of soap should not be available to them in community settings and close monitoring should be considered in the event of oral exposure.

Enzalutamide and analytical interferences in digoxin assays.

Objective: We report two cases of elevated digoxin plasma levels in patients receiving enzalutamide. Cases reported: The first patient, an 84-year-old male treated with enzalutamide, was hospitalized due to deterioration in his general state. Atrial fibrillation was discovered and treatment with digoxin was initiated. Supratherapeutic digoxin concentrations (4 µg/L and 3.5 µg/L 3 days later) led to treatment being stopped despite the lack of clinical or biological signs of overdose. The second patient, an 84-year-old male treated with digoxin and enzalutamide, was hospitalized for the same reasons. Digoxin concentration upon admission was 2.8 µg/L. Despite stopping treatment, digoxin blood levels were observed to have increased on D3 and D7 following admission (3 and 3.6 µg/L, respectively). However, no clinical or biological findings indicated an overdose. Blood samples were sent to the Pharmacology and Toxicology Laboratory for analysis. Methods: The second patient's digoxin plasma level was determined using the chemiluminescent microparticle immunoassay (CMIA®, Abbott, Illinois) method. Enzalutamide levels were determined using HPLC-UV/DAD method. An interference study was performed using different assay methods by adding enzalutamide to control plasma at various concentrations from a Xtandi® (40mg) capsule. Results: Plasma concentration of digoxin at D7 for patient 2 was identical in both laboratories (3.5 vs. 3.6 µg/L). Enzalutamide was found in the patient's plasma (12,5 mg/L). Adding 4, 10, 20, and 40 mg/L of enzalutamide to the untreated plasma showed that the plasma concentration of digoxin was positive (from 0.35 to 3.69 µg/L) using the CMIA method. Conclusions: Our results highlight the analytical interferences of enzalutamide with digoxin assays using the CMIA method.

New evidence for oxetorone toxicity.

CONTEXT: Oxetorone is a serotonin antagonist antimigraine drug but literature relating to its toxic properties is poor. The aim of this study is to describe the toxicological profile of oxetorone and to highlight any relationship between clinical and analytical findings. MATERIALS AND METHODS: This is a retrospective and observational study of cases exposure to oxetorone, reported to the Angers Poison and Toxicovigilance Centre between January 2002 and May 2016. Severity was assessed using the Poisoning Severity Score (PSS). Cases where data were incomplete, where oxetorone was deemed not accountable, where clinical signs were linked mainly to a co-ingested drug or where the plasma concentration of oxetorone was negative were all excluded. RESULTS: We included 43 cases of exposure, 31 of whom were suicide attempts. The assumed ingested dose (60-3600 mg) was correlated to severity (rs = 0.45, p = 0.01). Symptoms of moderate severity (PSS2 = drowsiness, hypertonia, myosis, convulsions, arterial hypotension, QRS widening, QTc prolongation) were observed following ingestion of more than 600 mg of oxetorone (median dose =1200 mg) and severe symptoms (PSS 3 = coma, convulsions, QTc prolongation, QRS widening, ventricular tachycardia, arterial hypotension, cardiogenic shock) were observed starting from 1800 mg (median dose =2700 mg). In four cases, a secondary worsening of symptoms 10-48 h following ingestion was observed. Plasma oxetorone was measured in four patients. Severe symptoms were observed in the event of a concentration over 0.3 mg/L and the highest measured serum oxetorone level was delayed by 20-48 h following the ingestion for two cases. CONCLUSIONS: Several clinical and paraclinical parameters strongly point towards membrane-stabilising properties of the molecule and the risk of a delayed occurrence of symptoms or a secondary worsening.

Parachuting: a dangerous trend in recreational psychoactive substance delivery.

INTRODUCTION: Medicine diversion for recreational use is a constant concern for health authorities. Parachuting, also refered to as bombing, is used in order to increase the expected effect, to accelerate time-to-onset and to create mixtures of medicines and substances. Aeras covered: Firstly, we analyzed all available scientific literature (PRISMA) and internet forums without any limiting timeframe. Secondly, we collected cases of parachuting reported in the west of France by the addictovigilance and poison control centres. Our study confirms the reality of this emerging issue associated with a higher medical risk (60% of intoxication cases were moderate-to-severe in our study). The substances involved in parachuting were primarily stimulants, with a majority of MDMA, although the use of diverted medication and psychotropes is also of concern. Expert opinion: Parachuting is a dangerous way of using substances and of diverting medicines. This type of administration gives users a certain pharmacokinetic latitude to 'play' with respect to substances and medicines. Medicine abuse deterrent formulations do not seem to be sufficient in preventing diversions. This dangerous method of using substances and of diverting medicines should drive pharmaceutical companies to innovate in the interest of public health and safety.

Recreational phenethylamine poisonings reported to a French poison control center.

OBJECTIVES: Over the last decade, use of phenethylamines has become increasingly prevalent. This study aimed to describe typical aspects of phenethylamine poisoning in order to better inform patient care. METHODS: Phenethylamine poisoning cases reported to the Poison Control Center of Angers, France, from January, 2007 to December, 2013 were examined. Clinical findings were examined in 105 patients, including phenethylamine used, symptoms and final outcome. Patients were predominantly male (80%), with mean age 26±8 years. RESULTS: MDMA (38%), amphetamine (18%) and methamphetamine (14%) were the most commonly reported. Synthetic cathinones (10%) and the 2C series (7%) were also found. Substances most commonly associated with phenethylamine poisoning were cannabis (27%), ethanol (20%) and cocaine (9%). The most frequently reported symptoms included anxiety and hallucinations (49%), mydriasis and headache (41%), tachycardia (40%) and hypertension (15%). Complications such as seizures (7%), cardiac arrest (5%), toxic myocarditis (1%) and hemorrhagic stroke (1%) were also observed. Of the cases, the Poison Severity Score was: null or low, 66%, moderate, 21%, severe or fatal, 13%. Of the patients, 77% received hospital care and 12.4% were admitted to an intensive care unit. Analytical confirmations were obtained for all severe cases. While 93% of patients recovered, there were 5 deaths and 2 patients presented with neurological sequelae. CONCLUSIONS: Phenethylamine poisonings may be severe in young and healthy individuals. Physicians, toxicologists and analysts should be aware of new phenethylamine consumption trends in order to inform management of patient care and to contribute to a more responsive drug policy.

European viper envenomings: Assessment of Viperfav™ and other symptomatic treatments.

UNLABELLED: The treatment of European viper envenomings is based on IV antivenom infusions. Viperfav™ contains purified F(ab')(2) fragments of equine antibodies, and a 4 ml vial can neutralize 500-1000 mouse LD50 of Vipera aspis, V. ammodytes and V. berus venoms and is known to be safe and efficient. Assessments of Viperfav™ (dosage and timing of infusions) and of symptomatic treatments such as low-molecular-weight heparin (LWHM), corticosteroids and the routine use of antibiotic therapy have not as yet been reported. OBJECTIVES: The objective was to compare the efficacy and safety of Viperfav™ as a function of the time to infusion and to assess other symptomatic treatments given for European viper bites such as antibiotics, corticosteroids and LWMH. METHODS: A prospective case review study of viper envenomings treated with Viperfav™ was compiled by the Angers Poisons Centre. The endpoints chosen were as follows: duration of hospital stay, complications (haematoma, infection) and persistent functional discomfort on day 15. Statistical studies were based on multivariate data analysis (MVA). RESULTS: 268 moderate or severe envenomings (Grades II and III) recorded in adults and children between 1999 and 2009 were included in the study. A time to the Viperfav™ infusion < 10 h after the bite (179 patients vs. 72) significantly reduced the incidence of haematomas (OR 2.3; p < 0.006), functional discomfort (OR 3.7; p < 10 - 4) and length of hospital stay (OR 2.1; p < 0.03). Multiple doses of Viperfav™ (2 or 3 vials in 22 patients vs. 246 treated with 1 vial) did not improve the selected endpoints. Routine antibiotic therapy was prescribed in 102 patients (vs. 166 patients without) and no significant difference was seen with respect to the endpoints. Moreover, no local or systemic infections were recorded in the non-antibiotic group. Corticosteroids were prescribed in 36 patients (vs. 232 without) but they did not significantly improve the endpoints or oedema. LMWH in 32 patients (vs. 236 without) increased the length of hospital stay (OR 3.2; p < 0.009 and the level of significantly persistent functional discomfort at day 15 (OR 3.7; p < 0.003). CONCLUSIONS: A single infusion of Viperfav™ (one vial) was effective whatever the grade of envenomation, and multiple doses did not improve the outcome. Viperfav™ was most effective when given soon (< 10 h) after envenoming. The routine use of antibiotic therapy was not necessary. Corticosteroids did not improve the endpoints selected, and we do not recommend the use of LMWH as this increased persistent functional discomfort and the length of hospital stay.

Hypoglycaemia: a little known effect of Venlafaxine overdose.

We report the case of a 39-year-old woman who presented with serotonin syndrome and hypoglycaemia likely due to intoxication with a very high dose of venlafaxine. This case of venlafaxine-associated hypoglycaemia was treated first by glucose perfusion, but despite large doses, hypoglycaemia recurred. Blood glucose normalized after injection of octreotide, eliminating the need for hypertonic glucose. Octreotide has been shown to decrease glucose requirements and the number of hypoglycaemic episodes in patients with sulfonylurea-induced hypoglycaemia but, to our knowledge, its ability to resolve hypoglycaemic episodes due to massive venlafaxine overdose has not yet been described.