A fatal case of desvenlafaxine and paroxetine poisoning.

Desvenlafaxine (O-desmethylvenlafaxine) and paroxetine are antidepressants that inhibit serotonin reuptake. Despite their relatively safe profiles, several serious side effects, including serotonin syndrome, bleeding, mania, and high blood pressure, are observed. We report the confirmation of the death of a 41-year-old female, with an overdose of desvenlafaxine and paroxetine suspected as the main cause of death. To quantify the level of desvenlafaxine and paroxetine in whole blood and urine, solid phase extraction combined with liquid chromatography-tandem mass spectrometry was developed and validated. Calibration curves were linear with coefficients of determination (r2) >0.999 for desvenlafaxine and paroxetine. The limits of detection and the limits of quantification for both desvenlafaxine and paroxetine were 0.001 µg/mL and 0.02 µg/mL, respectively. Desvenlafaxine and paroxetine were detected in the postmortem samples, along with various psychiatric drugs, and the blood alcohol content level was below 0.010%. The concentrations of desvenlafaxine and paroxetine in the heart blood were 11.0 µg/mL and 2.1 µg/mL, respectively, indicating lethal concentrations. In the urine, the concentrations of desvenlafaxine and paroxetine were 87.7 µg/mL and 3.5 µg/mL, respectively. This is the first report to determine the blood concentration of desvenlafaxine in a fatal intoxication caused by an overdose of desvenlafaxine single formulation.

[Epidemiological Characterization of Benzodiazepine and Antidepressant Poisonings in Chile]. / Intoxicaciones por benzodiacepinas y antidepresivos, una realidad preocupante.

INTRODUCTION: Poisonings are a worldwide preventable public health problem that affects the general population. OBJECTIVE: To epidemiologically characterize BZ and AD poisonings registered in Chile between 2002 and 2019. METHODS: An observational retrospective study of poisonings registered in the medical outcome report system of the Chilean Ministry of Health was conducted. The World Health Organization International Classification of Disease codes T42.2, T43.0 and T43.2 were included. RESULTS: 22,807 poisonings associated with BZ or AD were identified, representing 0.08% of all hospitalizations. Poisoning rates distribution were established at regional and national level. There were 9.8% of accidental events, 63.7% of intentional events, and 26.5% of undetermined cases. The highest accidental and intentional poisoning rates were estimated at the ages of 0 to 4 and 15 to 19 years old respectively. Poisoned patients remained hospitalized on average for 3.4 days. 0.3% of cases were related to death of patients. CONCLUSIONS: Poisoning events were characterized according to the studied variables. National poisoning rates decreased over the years with prevalence of those intentional events linked to women. Efforts should be made in creating poisoning prevention campaigns focused on age-based groups in the general population.

Intentional suspected suicide exposures by poisoning among adolescents from 2009 to 2018 reported to the Georgia Poison Center and compared nationally.

This retrospective chart review aimed to report the incidence and characteristics of intentional suspected suicide among 13- to 19-year-olds reported to the Georgia Poison Center (GPC) and compared nationally from 2009 to 2018. Of the 19 733 cases reported to the GPC, 74.9% were females. The total number of cases more than doubled from 2009 to 2018, increasing annually by 10%. Majority (90.1%) of the cases occurred in the home, and 60.4% of the cases resulted in either no effect or minor effect. More than half (66.5%) of the cases involved only one substance. Pharmaceuticals made up 94.5% of the substances used, with analgesics accounting for 42.10% and antidepressants at 20.77%. A significant difference was found in substances used between males and females (P < .001). Females were more likely to use analgesics (45.17% vs 32.90%), and males were more likely to use sedatives/hypnotics/antipsychotics (20.45% vs 13.58%). While the majority of the GPC patients were females, the GPC was more likely to have fewer female patients (74.7% vs 75.7%) and more male patients (25.3% vs 24.3%) than other poison centers. Intentional suspected suicide exposures by poisoning are on the rise and higher among females, demonstrating a need for strengthened intervention and prevention strategies.

Evidence of repeated mirtazapine poisoning in children by hair analysis.

Mirtazapine is an antidepressant drug, used to treat depression, but also, in some specific conditions, to treat obsessive-compulsive disorder and anxiety. Although mirtazapine is not a hypnotic, it can make the subject feel drowsy. Children under the age of 18 should not take mirtazapine, but for some very special diseases, a physician can prescribe it for a limited period of time. The authors report a case involving 2 children (7- and 9-year-old) who were administered mirtazapine without consent by the mother, who was under daily therapy with this antidepressant. Hair specimens, collected from the children were tested by liquid chromatography coupled to tandem mass spectrometry for mirtazapine and its metabolite, N-desmethylmirtazapine, on 3 × 1 cm segments. The hair test results (3 × 1 cm segments) have demonstrated that both children have been repetitively exposed to mirtazapine for approximately the last 3 months before hair collection, with concentrations in the range 1.32-3.79 and 0.64-2.54 ng/mg for mirtazapine and N-desmethylmirtazapine, respectively. Environmental contamination was ruled out as the measured concentrations are highly variable according to the pattern of drug distribution and the washes were negative. Hair testing for drugs appears as an excellent diagnostic tool for child protection toward drug exposure.

Drug Poisoning Deaths Among Women: A Scoping Review.

OBJECTIVE: Drug poisoning deaths among women remain a challenge for public health policy and have increased at a higher rate relative to men. Although biological, social, and psychological differences between men and women can have an influence on drug poisoning deaths, sex is rarely considered. The objective of this study is to explore the extent, range, and nature of evidence in relation to drug poisoning deaths among women. METHOD: A scoping review was conducted according to the Arksey and O'Malley framework. A comprehensive search was performed using MEDLINE, Embase, CINAHL, and Web of Science, supplemented by gray literature, including national and international reports and government documents and consultation with experts. Publications in English from June 1, 1998, to November 2, 2019, were included. Two reviewers independently screened publications for inclusion. RESULTS: The search identified 5,316 individual publications, and 61 met the inclusion criteria (46% from Europe; n = 28). The main candidate factors identified as contributing factors to drug poisoning deaths among women included age; opioid drugs, especially prescription opioids; other prescription drugs, particularly antidepressants; mental health issues; barriers to treatment; victim of violence; alcohol use; polydrug use; and history of imprisonment. CONCLUSIONS: The majority of studies on drug poisoning deaths among women involved descriptive epidemiological data, primarily prevalence estimates, with limited in-depth analyses of factors explaining these trends. To inform policies and practices to prevent drug poisoning deaths among women, more evidence is required on risk factors specifically related to women.

Non-Opioid Substances Acute Poisonings with Suicidal Intent in Patients with Opioid Use Disorder.

INTRODUCTION: Several epidemiological studies have evaluated the role of illicit drug use in suicide behaviour. AIM: To assess patients with opioid use disorder and suicidal intent related to behavior, severity of acute poisoning and the most commonly used non-opioid substances. MATERIALS AND METHODS: This cross sectional study included 67 patients diagnosed with opioid use disorder. The study was conducted at the University Clinic of Toxicology in Skopje over a 5-year period (2013-2017). The following variables were examined: gender, age, duration and route of opioid administration, duration of hospitalization, and types of substances used in acute poisoning. Assessment of patients' behavior and severity of poisoning was made by using the Suicide Behaviours Questionnaire-Revised and the Poison severity score. RESULTS: The majority of patients were male (88.1%). The mean age of patients was 30±6.1 years. The average duration of opioid use disorder was 8.5±3.9. A single poisoning was found in 62.7%, double poisoning in 25.4%, and triple poisoning in 11.9% of participants. Benzodiazepines were most commonly used by the patients (55.2%). The largest number of patients (32.8%) had minor Poison severity score (PSS), and only 17.9% had severe PSS. None of the patients had a fatal suicide attempt. 86.6% of patients had a score of ≥7 indicating a high risk of repeat suicide attempts. CONCLUSION: Benzodiazepines were most commonly used as a single or combined substance in patients with opioid use disorder. PSS indicated that most of the participants were with minor PSS and with high risk of a repeat suicide attempt.

Hospital-treated deliberate self-poisoning in the older adult: Identifying specific clinical assessment needs.

BACKGROUND: Hospital-treated deliberate self-poisoning is common, with a median patient age of around 33 years. Clinicians are less familiar with assessing older adults with self-poisoning and little is known about their specific clinical requirements. OBJECTIVE: To identify clinically important factors in the older-age population by comparing older adults (65+ years) with middle-aged adults (45-64 years) during an index episode of hospital-treated deliberate self-poisoning. METHODS: A prospective, longitudinal, cohort study of people presenting to a regional referral centre for deliberate self-poisoning (Calvary Mater Newcastle, Australia) over a 10-year period (2003-2013). We compared older-aged adults with middle-aged adults on demographic, toxicological and psychiatric variables and modelled independent predictors of referral for psychiatric hospitalisation on discharge with logistic regression. RESULTS: There were (n = 157) older-aged and (n = 925) middle-aged adults. The older-aged group was similar to the middle-aged group in several ways: proportion living alone, reporting suicidal ideation/planning, prescribed antidepressant and antipsychotic drugs, and with a psychiatric diagnosis. However, the older-aged group were also different in several ways: greater proportion with cognitive impairment, higher medical morbidity, longer length of stay, and greater prescription and ingestion of benzodiazepines in the deliberate self-poisoning event. Older age was not a predictor of referral for psychiatric hospitalisation in the multivariate model. CONCLUSION: Older-aged patients treated for deliberate self-poisoning have a range of clinical needs including ones that are both similar to and different from middle-aged patients. Individual clinical assessment to identify these needs should be followed by targeted interventions, including reduced exposure to benzodiazepines.

Bradyarrhythmia due to mirtazapine overdose: A case of serious adverse event in a suicidal patient.

There are a limited number of studies on postoverdose clinical findings of mirtazapine in the literature. Our case presented an unlikely junctional rhythm, which we have not seen in the previous studies, in a patient who had bradycardia and hypotension following mirtazapine intake. A 37-year old male was admitted to the emergency department (ED) after his suicide attempt with 300 mg PO of mirtazapine tablets. He took the drug 2 h prior to his ED visit. He did not have any complaints after the mirtazapine intake. His complete physical examination and electrocardiography (ECG) revealed no pathological findings. He was observed in the ED. The results were in the normal range in his blood test and he has 0 mg/dl of blood ethanol. He experienced dizziness after 5 h and 30 min. The blood pressure was 60/30 mmHg. The heart rate was 34 beats/min. The simultaneous ECG showed junctional bradycardia. 0.5 mg atropine IV was given two times at intervals. Norepinephrine infusion was initiated after normal saline therapy. Forty-five minutes later, he did not have any clinically significant complaint. There are no pathological findings in his follow-up ECG and physical examination. He was discharged of his own accord 10 h after his ED admission. His initial mirtazapine level was 145 ng/ml when he came to the ED. Mirtazapine was known to have a safe cardiac profile both for regular dose and overdose. However, physicians should consider that it might induce a life-threatening bradyarrhythmia.

Clinical predictors of adverse cardiovascular events for acute pediatric drug exposures.

Context: Risk factors for adverse cardiovascular events (ACVE) from drug exposures have been well-characterized in adults but not studied in children. The objective of the present study is to describe the incidence, characteristics, and risk factors for in-hospital ACVEs among pediatric emergency department (ED) patients with acute drug exposures.Methods: This is a prospective cohort design evaluating patients in the Toxicology Investigators Consortium (ToxIC) Registry. Pediatric patients (age <18 years) who were evaluated at the bedside by a medical toxicologist for a suspected acute drug exposure were included. The primary outcome was in-hospital ACVE (myocardial injury, shock, ventricular dysrhythmia, or cardiac arrest). The secondary outcome was in-hospital death. Multiple logistic regression analyses were performed to examine novel clinical risk factors and extrapolate adult risk factors (bicarbonate <20 mEq/L; QTc ≥500 ms), for the primary/secondary outcomes.Results: Among the 13,097 patients (58.5% female), there were 278 in-hospital ACVEs (2.1%) and 39 in-hospital deaths (0.3%). Age and drug class of exposure (specifically opioids and cardiovascular drugs) were independently associated with ACVE. Compared with adolescents, children under 2 years old (OR: 0.41, 95% CI: 0.21-0.80), ages 2-6 (OR: 0.37, 95% CI: 0.21-0.80), and ages 7-12 (OR: 0.51, 95% CI: 0.27-0.95) were significantly less likely to experience an ACVE. Serum bicarbonate concentration <20 mEq/L (OR: 2.31, 95% CI: 1.48-3.60) and QTc ≥ 500 ms (OR: 2.83, 95% CI: 1.67-4.79) were independently associated with ACVE.Conclusion: Previously derived clinical predictors of ACVE from an adult drug overdose population were successfully extrapolated to this pediatric population. Novel associations with ACVE and death included adolescent age and opioid drug exposures. In the midst of the opioid crisis, these findings urgently warrant further investigation to combat adolescent opioid overdose morbidity and mortality.

[Analysis of risk factors, etiology and treatment standard of lithium poisoning]. / Analyse zu Risikofaktoren, Ätiologie und Behandlungsstandard der Lithiumintoxikation.

Despite unlimited access to therapeutic drug monitoring lithium poisoning is still a common and potentially life-threatening but in most cases preventable complication of lithium treatment; however, it is still considered to be the gold standard in the treatment of affective disorders. The necessity of drug monitoring and potential lithium toxicity substantiate the skepticism of many therapists with respect to this often very effective treatment. This therefore limits the use of lithium although the unique therapeutic effects and high efficiency are well known. This retrospective data analysis of risk factors and etiology of lithium poisoning cases identified 58 cases of lithium poisoning, which were treated internally in this hospital between 2010 and 2014. Of the patients 67.2% were female and the majority were classified as chronic poisoning (66.1%). The most relevant patient-related risk factor seemed to be insufficient self-management as 26% of cases of lithium poisoning occurred during febrile infections or exsiccosis. Regarding practitioner-related risk factors, an insufficient consideration of drug interactions, insufficient therapeutic drug monitoring after dose increase and a paucity of experience and knowledge concerning lithium treatment were most relevant. This study illustrates the most important risk factors for lithium poisoning and their frequencies and contributes to raise awareness for this highly relevant topic. These data can help to prevent further cases of lithium poisoning. Furthermore, the results enable a comparison between the actual treatment reality and currently available evidence for the treatment of lithium poisoning.

Vilazodone poisoning: a systematic review.

Introduction: Vilazodone is a novel antidepressant approved for the treatment of major depressive disorder. It acts as a serotonin reuptake inhibitor and 5-HT1A partial agonist. It may lead to a more rapid rise in serotonin concentration in the synaptic cleft than selective serotonin reuptake inhibitors (SSRIs), which could potentially cause more severe toxicity in overdose.Methods: We performed a systematic review of the medical literature to identify all available peer reviewed evidence regarding vilazodone poisoning.Results: We identified nine unique articles describing vilazodone poisoning. These included eleven unique case reports of vilazodone poisoning, three reviews of data from the National Poison Data System, and one review of data from the Toxicology Investigators Consortium. Children were frequently symptomatic, and many developed seizures and/or serotonin syndrome. Adults and adolescents also developed serotonin syndrome after single-substance ingestion of vilazodone. ICU admission, endotracheal intubation, and parenteral benodiazepines were frequently required.Discussion: Vilazodone, unlike SSRIs, may frequently cause serotonin syndrome in single-substance ingestions. Children ingesting as little as the minimum daily dose of vilazodone, 10 mg, suffered major clinical toxicity.Conclusion: Vilazodone poisoning may produce serious clinical effects, including serotonin syndrome and seizures. Young children are at particularly high risk and may become critically ill after ingestion of very small amounts of vilazodone. Admission of poisoned children to a monitored setting and prolonged clinical observation of poisoned adults may be reasonable.

Nonopioid Overdose Death Rates Rose Almost As Fast As Those Involving Opioids, 1999-2016.

The number of Americans dying from drug overdoses has risen rapidly, but the contribution of nonopioid drugs to this growth is not well understood. Using vital statistics data from the universe of deaths among US residents in the period 1999-2016, I calculated levels of and increases in overall nonopioid fatal overdose rates and those for subgroups stratified by manner of death, sex, race/ethnicity, and age. Mortality rates were also calculated separately for sedatives, stimulants, antidepressants, and cocaine. Recently developed methods were used to correct for the incomplete reporting of drug involvement on death certificates. From 1999 to 2016 the number of nonopioid drug deaths rose 274 percent, and deaths per 100,000 population rose by 223 percent. Over the same period, opioid-involved fatality counts and rates grew by 371 percent and 307 percent, respectively. Fatal overdose rates involving stimulants increased more than tenfold, with slower growth but higher rates for deaths involving sedatives and cocaine. Midlife non-Hispanic whites generally experienced the highest levels and rise in nonopioid death rates, but cocaine fatality rates were particularly common among nonwhite or Hispanic males ages 40-59. Policies designed to curb the opioid epidemic are probably helpful in reducing nonopioid deaths, but targeted interventions may also be needed.

Cardiac arrest induced by the intentional ingestion of boric acid and mirtazapine treated by percutaneous cardiopulmonary bypass: a case report.

BACKGROUND: Mirtazapine has a good tolerability and safety profile that demonstrates several benefits over other antidepressants and it is associated with few fatalities. Boric acid is an odorless white powder that is generally not recognized as a poisonous substance. We report a case of cardiac arrest induced by the intentional ingestion of mirtazapine, boric acid, and sennosides, by a patient who required percutaneous cardiopulmonary bypass. CASE PRESENTATION: Our patient was a 49-year-old Japanese woman with a history of depression; she was found in an unconscious state after ingesting boric acid (unknown amount), mirtazapine (1950 mg), and sennosides (780 mg). On arrival, she was in a deep coma with marked hypotension induced by atrial fibrillation, tachycardia, and diffuse hypokinetic cardiac motion. She had systemic diffuse erythema. Her serum concentrations of boric acid and mirtazapine on arrival were 560.49 mg/L and 1270 ng/mL, respectively. She experienced repeated cardiac arrest, and was therefore treated with tracheal intubation, mechanical ventilation, percutaneous cardiopulmonary bypass, and continuous hemodialysis filtration. Stable circulation and respiration and a normal kidney function were finally obtained and she was transferred to a local medical facility in a persistent unconscious state. CONCLUSIONS: This is the first case of a return of spontaneous circulation after cardiac arrest induced by the intentional ingestion of boric acid and mirtazapine, requiring percutaneous cardiopulmonary bypass for survival. To maintain cerebral perfusion during percutaneous cardiopulmonary bypass, even in a prolonged state of cardiac arrest induced by overdose, is medically, ethically, and economically challenging.

A quasi-experimental evaluation of partnerships for success's impact on community-level ethanol and prescription drug poisoning rates.

The emerging dual threats of underaged drinking (UAD) and prescription drug misuse (PDM) require sustained prevention efforts across multiple levels of interventions. In response to the continuing proliferation of UAD and PDM among youth and young adults, the Substance Abuse and Mental Health Services Administration (SAMHSA) developed the Partnerships for Success (PFS) program. Across five cohorts funded from 2012 to 2016, PFS created linkages between health care providers, treatment and prevention services providers, government agencies, and nonprofit organizations for the delivery of multiple sets of services (e.g., prevention education, community activities, screening) targeted toward UAD and PDM. This paper reports on the impact of the PFS program on reductions in ethanol and prescription drug poisoning exposures as reported from data in the National Poisoning Data System (NPDS). Across 35 States, communities targeted by PFS interventions were compared to non-targeted communities using a non-equivalent comparison groups design and propensity score weighting. Using propensity-weighted, multilevel latent growth modeling, steeper reductions in ethanol and prescription drug poisoning exposure call rates were observed in States which had a higher proportion of communities participating in PFS. Grantee-level longitudinal analogs to Cohen's d effect sizes ranged from -0.24 to -0.97, whereas PFS' effects on individual communities (net of Statewide effects) were negligible. The study serves as a unique exemplar of using the NPDS to extract community-level intervention effects that might otherwise be "hidden" within epidemiological data while underscoring the cumulative effects of PFS' community-level efforts in stemming the tide on underaged drinking and prescription drug misuse.

Is Capillary Electrophoresis a New Tool to Monitor Acute Lithium Poisoning in Human?†.

A 38-year-old man was admitted in the intensive care unit (ICU) after supposed ingestion of 504 sustained-release tablets of Theralithe™ corresponding ~200 g of lithium carbonate. At the admission, ~19.5 h after ingestion, the patient was conscious with trembling limbs, intense thirst, profuse sweats and vomiting and lithium serum concentration was 14.2 mmol/L. Toxicological screenings performed in urine and serum, were negative. Patient was treated with continuous extrarenal epuration by continue veno-venous hemodiafiltration starting (CCVHDF) 24 h post-admission and was carried on until 64 h. After 11 days in ICU, the patient was dismissed to the service without sequelae, and transferred to a psychiatric unit. To follow lithium concentrations in serum, urines and dialysates, we developed a simple, rapid and reliable method by capillary zone electrophoresis (CZE). Separation was achieved in 7 min. The method was linear between 0.14 and 1.44 mmol/L for serum samples, and between 0.07 and to 1.44 mmol/L for urines and dialysates. Limits of quantification were 0.15 mmol/L and 0.07 mmol/L for serum and others fluids, respectively. Intra- and inter-day precisions expressed as CV were systematically inferior to 12.1% for serum and 8.2% for other fluids. Results obtained regarding precision, accuracy, recovery and stability were satisfying, with recoveries ranging from 91.0 to 102.0%. Serum, urine and dialysate samples were measured using CZE and flame photometry. We observed a strong correlation between both methods as assessed by linear regression and Bland-Altman analysis. For the intoxicated patient, the assay was successfully applied to serum, urine and dialysates to determine the amount of lithium present in circulation and excreted. Lithium amounts in dialysates were estimated to correspond to 89% of total lithium excreted during CCVHF session while urine excretion account only for 11%.

Prolonged QRS Widening After Aripiprazole Overdose.

BACKGROUND: Aripiprazole is an atypical antipsychotic with a long half-life. Overdose can result in protracted somnolence and cardiac disturbances, particularly QT interval prolongation. METHODS: This is a single case report of a 14-year-old boy who took an overdose of aripiprazole and developed QRS widening. CASE: A 14-year-old boy intentionally ingested 20 tablets of aripiprazole (5 mg). He was brought to the emergency department when his ingestion was discovered. The patient's vital signs were as follows: temperature, 37.7°C; heart rate, 108 beats/min; blood pressure, 138/98 mm Hg; and respirations, 16 breaths/min. Activated charcoal was administered within 90 minutes of ingestion. Initial electrocardiogram (EKG) showed sinus tachycardia, with a QRS of 138 ms and QT interval of 444 ms. QRS duration was 90 ms on an EKG performed 3 months earlier. A bolus of sodium bicarbonate was administered, and the patient was transferred to the pediatric intensive care unit. Repeat EKG demonstrated a QRS of 156 ms, and a sodium bicarbonate infusion was initiated. The patient continued to have QRS prolongation for the next 8 days, reaching a peak of 172 ms 3 days postingestion. Despite aggressive treatment with sodium bicarbonate, there was persistent QRS prolongation; however, the patient did not have any dysrhythmias and remained hemodynamically stable. The patient was discharged 9 days postingestion when the QRS duration normalized to 82 ms. Genetic testing revealed that the patient was a CYP2D6 poor metabolizer. CONCLUSIONS: This case suggests that aripiprazole toxicity may possibly be associated with QRS prolongation without associated dysrhythmias or cardiovascular compromise. In addition, toxicity may be prolonged in patients who are CYP2D6 poor metabolizers.

Acetaminophen and Acetylsalicylic Acid Exposure in a Preterm Infant after Maternal Overdose.

Here, we review the case of a 26 1/7 weeks' gestation premature female infant born to a mother who intentionally ingested a large quantity of Tylenol, aspirin, quetiapine, and prenatal vitamins. The neonate subsequently had markedly elevated levels of both Tylenol and aspirin when checked on the first day of life. While overall clinically stable, the neonate did demonstrate coagulopathy as evidenced by abnormal coagulation studies. Both poison control and a pediatric gastroenterologist/hepatologist were consulted. She successfully tolerated a course of N-acetylcysteine; her subsequent Tylenol level was markedly decreased and the neonate exhibited no further effects of toxicity. The salicylate level decreased on its own accord. To our knowledge, this is the first report of a neonate at 26 weeks' gestation that has been successfully managed for supratherapeutic concentrations of acetaminophen and acetylsalicylic acid secondary to maternal ingestion. While rare, this case may serve as a reference for the effectiveness of N-acetylcysteine in premature infants in such instances.

First aid interventions by laypeople for acute oral poisoning.

BACKGROUND: Oral poisoning is a major cause of mortality and disability worldwide, with estimates of over 100,000 deaths due to unintentional poisoning each year and an overrepresentation of children below five years of age. Any effective intervention that laypeople can apply to limit or delay uptake or to evacuate, dilute or neutralize the poison before professional help arrives may limit toxicity and save lives. OBJECTIVES: To assess the effects of pre-hospital interventions (alone or in combination) for treating acute oral poisoning, available to and feasible for laypeople before the arrival of professional help. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, ISI Web of Science, International Pharmaceutical Abstracts, and three clinical trials registries to 11 May 2017, and we also carried out reference checking and citation searching. SELECTION CRITERIA: We included randomized controlled trials comparing interventions (alone or in combination) that are feasible in a pre-hospital setting for treating acute oral poisoning patients, including but potentially not limited to activated charcoal (AC), emetics, cathartics, diluents, neutralizing agents and body positioning. DATA COLLECTION AND ANALYSIS: Two reviewers independently performed study selection, data collection and assessment. Primary outcomes of this review were incidence of mortality and adverse events, plus incidence and severity of symptoms of poisoning. Secondary outcomes were duration of symptoms of poisoning, drug absorption, and incidence of hospitalization and ICU admission. MAIN RESULTS: We included 24 trials involving 7099 participants. Using the Cochrane 'Risk of bias' tool, we assessed no study as being at low risk of bias for all domains. Many studies were poorly reported, so the risk of selection and detection biases were often unclear. Most studies reported important outcomes incompletely, and we judged them to be at high risk of reporting bias.All but one study enrolled oral poisoning patients in an emergency department; the remaining study was conducted in a pre-hospital setting. Fourteen studies included multiple toxic syndromes or did not specify, while the other studies specifically investigated paracetamol (2 studies), carbamazepine (2 studies), tricyclic antidepressant (2 studies), yellow oleander (2 studies), benzodiazepine (1 study), or toxic berry intoxication (1 study). Eighteen trials investigated the effects of activated charcoal (AC), administered as a single dose (SDAC) or in multiple doses (MDAC), alone or in combination with other first aid interventions (a cathartic) and/or hospital treatments. Six studies investigated syrup of ipecac plus other first aid interventions (SDAC + cathartic) versus ipecac alone. The collected evidence was mostly of low to very low certainty, often downgraded for indirectness, risk of bias or imprecision due to low numbers of events.First aid interventions that limit or delay the absorption of the poison in the bodyWe are uncertain about the effect of SDAC compared to no intervention on the incidence of adverse events in general (zero events in both treatment groups; 1 study, 451 participants) or vomiting specifically (Peto odds ratio (OR) 4.17, 95% confidence interval (CI) 0.30 to 57.26, 1 study, 25 participants), ICU admission (Peto OR 7.77, 95% CI 0.15 to 391.93, 1 study, 451 participants) and clinical deterioration (zero events in both treatment groups; 1 study, 451 participants) in participants with mixed types or paracetamol poisoning, as all evidence for these outcomes was of very low certainty. No studies assessed SDAC for mortality, duration of symptoms, drug absorption or hospitalization.Only one study compared SDAC to syrup of ipecac in participants with mixed types of poisoning, providing very low-certainty evidence. Therefore we are uncertain about the effects on Glasgow Coma Scale scores (mean difference (MD) -0.15, 95% CI -0.43 to 0.13, 1 study, 34 participants) or incidence of adverse events (risk ratio (RR) 1.24, 95% CI 0.26 to 5.83, 1 study, 34 participants). No information was available concerning mortality, duration of symptoms, drug absorption, hospitalization or ICU admission.This review also considered the added value of SDAC or MDAC to hospital interventions, which mostly included gastric lavage. No included studies investigated the use of body positioning in oral poisoning patients.First aid interventions that evacuate the poison from the gastrointestinal tractWe found one study comparing ipecac versus no intervention in toxic berry ingestion in a pre-hospital setting. Low-certainty evidence suggests there may be an increase in the incidence of adverse events, but the study did not report incidence of mortality, incidence or duration of symptoms of poisoning, drug absorption, hospitalization or ICU admission (103 participants).In addition, we also considered the added value of syrup of ipecac to SDAC plus a cathartic and the added value of a cathartic to SDAC.No studies used cathartics as an individual intervention.First aid interventions that neutralize or dilute the poison No included studies investigated the neutralization or dilution of the poison in oral poisoning patients.The review also considered combinations of different first aid interventions. AUTHORS' CONCLUSIONS: The studies included in this review provided mostly low- or very low-certainty evidence about the use of first aid interventions for acute oral poisoning. A key limitation was the fact that only one included study actually took place in a pre-hospital setting, which undermines our confidence in the applicability of these results to this setting. Thus, the amount of evidence collected was insufficient to draw any conclusions.