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Zolpidem is a widely prescribed hypnotic Z-drug used to treat short-term insomnia. However, a growing number of individuals intentionally overdose on these drugs. This study aimed to develop a predictive tool for physicians to assess patients with zolpidem overdose. A population pharmacokinetic (PK) model was established using digitized data obtained from twenty-three healthy volunteers after a single oral administration of zolpidem. Based on the final PK model, a web application was developed using open-source R packages such as rxode2, nonmem2rx, and shiny. The final model was a one-compartment model with first-order absorption and elimination with PK parameters, including clearance (CL, 16.9 L/h), absorption rate constant (Ka, 5.41 h-1), volume of distribution (Vd, 61.7 L), and lag time (ALAG, 0.394 h). Using the established population PK model in the current study, we developed a web application that enables users to simulate plasma zolpidem concentrations and visualize their profiles. This user-friendly web application may provide essential clinical information to physicians, ultimately helping in the management of patients with zolpidem intoxication.

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Pediatric population represents the most vulnerable and at risk for unintentional poisoning, with children younger than 6 years old accounting for nearly half of poison exposures. Poisoning is a time-dependent emergency. The need to reach a scientific agreement on diagnostic protocol and treatment seems to be crucial to reduce morbidity and mortality. Starting from a buprenorphine pediatric intoxication case, this article highlights the limits and pitfalls of the traditional diagnostic approach. Diagnosis of drug intoxication was achieved after several days when an in-depth diagnostic investigation became necessary and complete forensic toxicological analyses were performed. Results evidenced an alarming lack of an unequivocal diagnostic protocol in case of suspect intoxication in structures not provided with a forensic toxicological service/unit. Collection of biological specimens according to forensic protocols at hospitalization plays a paramount role in the definitive diagnosis of intoxication. A diagnostic algorithm that focuses on medical history and biological specimen collection timing is herein proposed, in order to unify emergency approaches to the suspected poisoned child.

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INTRODUCTION: This study evaluates the implications of drug intoxication (DI) on donor utilization and outcomes in liver transplantation (LT). METHODS: The UNOS STAR database was evaluated for all potential donors and adult, first-time, whole LT between 2005 and 2019. Logistic regression analyses evaluated liver utilization; proportional hazards modeling assessed risk of 1-year graft loss. RESULTS: A total of 132 783 potential donors (10 205, 7.7% from DI), and 90 612 adult LT were identified (7490, 8.3% from DI). DI donors had median age 32 years (IQR 26-40 years, p < .001), were 42.6% female (n = 4346), and 15.5% were DCD donors (n = 1583). Utilization of DI donors changed over time, such that by 2015-2019 they were the most likely donor cause of death (COD) to be utilized. Among LT recipients, there were insignificant differences (<2% variance) in age, gender, ethnicity, and etiology of liver disease according to donor COD. Recipients with MELD scores >30 more frequently received grafts from donors with trauma (23.8%) and DI (21.8%) versus cardiovascular (20.0%) and CVA/stroke (19.9%, p < .001). Among DBD donors, DI-COD was associated with superior 1-year graft survival compared to donors from trauma (HR 1.172, 95% CI 1.057-1.300) and CVA/stroke (HR 1.404, 95% CI 1.264-1.561, p < .001). Donor COD was not significantly associated with 1-year graft loss among DCD donors. CONCLUSIONS: There is an increased likelihood of donor utilization when COD is drug overdose and an increased likelihood of 1-year graft survival compared to donors from trauma, CVA/stroke, and other COD.

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Acute lung injury following fentanyl overdose is an unusual presentation. Pulmonary edema has been associated with opioid and naloxone use. However, to our knowledge, there have been no previous reports of inhaled fentanyl-associated acute lung injury presenting with acute hypoxic respiratory failure secondary to severe acute respiratory distress syndrome. We report a case of inhaled fentanyl-related severe acute respiratory distress syndrome which presented immediately after snorting fentanyl. This patient developed hypoxia requiring 100% oxygen on non-rebreather mask, and acute respiratory distress syndrome was confirmed on chest X-ray and computed tomography on admission. He was successfully treated with steroids with recovery in 48 hours. Naloxone was used in this patient, which has been associated with pulmonary edema in case reports and series, but clinical findings were more consistent with acute respiratory distress syndrome rather than pulmonary edema. The mechanism for this clinical presentation is not well known. Proposed mechanisms include lung injury from inhalation against an obstruction in a manner similar to post-obstructive pulmonary edema. Although our patient rapidly responded to symptomatic treatment and steroid course, our case also highlights the need for further study to elucidate the various clinical presentations associated with fentanyl use-related lung toxicity including acute respiratory distress syndrome.

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OBJECTIVE: To assess the ability of intranasal atipamezole to reverse sedative effects of xylazine in dogs. DESIGN: Prospective proof-of-concept study. SETTING: University research laboratory. ANIMAL: Six healthy, staff-owned dogs. INTERVENTIONS: Dogs were sedated with 1.1 mg/kg of xylazine intravenously. The sedation score of each dog was recorded every 5 minutes until they achieved a sedation score of >13/21 for 3 readings. Once achieved, 0.3 mg/kg of atipamezole was administered intranasally using a mucosal atomization device. Sedation scores continued to be recorded every 5 minutes until successful reversal was achieved (<4/21). MEASUREMENTS AND MAIN RESULTS: Average times to standing and normal wakefulness after administration of intranasal atipamezole were 6 minutes, 30 seconds and 7 minutes, 20 seconds, respectively. CONCLUSIONS: Intranasal atipamezole successfully reversed the sedation effects of xylazine. The findings of this study provide justification for future controlled prospective studies into the potential use of intranasal atipamezole in a variety of settings including exposure to xylazine in operational canines as well as bioavailability studies for optimal dosing.

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This report describes a case of shock symptoms in a 72-year-old woman with epilepsy who had been in a state of polypharmacy, taking multiple antipsychotic drugs. After receiving a normal dose of periciazine, she exhibited impaired consciousness, hypothermia, and hypotension and was admitted to hospital. Despite poor response to vasopressors, conservative treatment led to gradual improvement. Subsequent pharmacokinetic analysis showed non-toxic blood concentrations of periciazine, suggesting that even small doses of phenothiazines could result in toxic symptoms. This case highlights the importance of monitoring for adverse reactions when prescribing multiple antipsychotic drugs, particularly in older polypharmacy patients.

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BACKGROUND: Medication poisoning in children is a severe condition that can endanger a child's life. Although drug intoxications are easily preventable, awareness of the proper handling of drugs and their safe storage out of the reach of children is not widespread among the general public. In this work, we investigated the demographic and clinical data of children admitted to the Department of Pediatrics of the University Hospital Olomouc for acute drug-induced intoxication. We also selected several case reports to illustrate the wide range of both presentations and outcomes in individual patients. METHOD: Cases of drug-induced intoxications were selected from a group of patients under the age of 19 years admitted to the hospital for poisoning between January 1, 2010, and December 31, 2019. Medical records of these patients were prospectively evaluated, and overview tables and graphs of predefined research objectives were created. RESULTS: During the given time period, 162 children with suspected drug intoxications were hospitalized at the Department of Pediatrics, University Hospital Olomouc. Of these, 108 cases were reported in girls and 54 in boys (66.7% vs. 33.3%). In 16 cases (9.9%), there was a severe intoxication requiring follow-up intensive care. There was also one case of fatal accidental intoxication. Most poisonings were seen in toddlers (65; 40.1%). Intoxication with suicidal ideation was found in 44 cases (27.2%), with a higher incidence of suicide attempts in girls (40 vs. 4). Repeated intoxication was recorded in nine cases. Analgesics were the most common drug group (61; 37.7%), with paracetamol (28; 17.3%) being the leading drug. In 154 cases (95.1%), the drugs were taken orally, most often in the form of tablets. CONCLUSION: Accidental drug intoxications most frequently occurred in the age group from one to three years old. The second highest incidence was among adolescents most of which were suicide attempts. Analgesics and psychoactive agents accounted for the majority of cases. Medications should be kept in places where children cannot reach them.

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Background Acutely agitated patients are common in the emergency department (ED). Given the myriad aetiologies of the clinical conditions that can produce agitation, such a high prevalence is unsurprising. Agitation is a symptomatic presentation, not a diagnosis, secondary to a psychiatric, medical, traumatic, or toxicological condition. Most literature on the emergency management of agitated patients is from psychiatric populations, not generalised to EDs. Benzodiazepines, antipsychotics, and ketamine have been used to treat acute agitation. However, a clear consensus is lacking. Objectives The objectives are to study the effectiveness of intramuscular (IM) olanzapine as a first-line treatment for rapid tranquillisation in undifferentiated acute agitation in the ED and compare the effectiveness of sedatives to control agitation in etiologically divided groups per the following preassigned protocols: Group A: Alcohol/drug intoxication (olanzapine vs haloperidol), Group B: Traumatic brain injury (TBI) with or without alcohol intoxication (olanzapine vs haloperidol), Group C: Psychiatric conditions (olanzapine vs haloperidol and lorazepam), and Group D: Agitated delirium, organic causes (olanzapine vs haloperidol). Methods This 18-month prospective study included acutely agitated ED patients between 18 and 65. Results A total of 87 patients between 19 and 65 were included, all with a Richmond Agitation Sedation Scale (RASS) score between +2 and +4 at presentation. Nineteen of the 87 patients were managed as acute undifferentiated agitation, and 68 were assigned to one of the four groups. In acute undifferentiated agitation, IM olanzapine 10 mg effectively sedated 15 (78.9%) patients within 20 minutes, whereas the remaining four (21.1%) were sedated with a repeat IM olanzapine 10 mg over the next 25 minutes. In 13 patients with agitation due to alcohol intoxication, zero out of three with olanzapine and four out of 10 (40%) with IM haloperidol 5 mg were sedated within 20 minutes. In patients with TBI, two out of eight (25%) receiving olanzapine and four out of nine (44.4%) receiving haloperidol were sedated within 20 minutes. In acute agitation secondary to psychiatric disease, olanzapine sedated nine out of 10 (90%), and haloperidol with lorazepam sedated 16 out of 17 (94.1%) within 20 minutes. In patients with agitation secondary to organic medical conditions, olanzapine rapidly sedated 19 out of 24 (79.1%), whereas haloperidol sedated one out of four (25%). Interpretation and conclusion IM olanzapine 10 mg is effective for rapid sedation in acute undifferentiated agitation. Olanzapine is superior to haloperidol in agitation secondary to organic medical conditions and is as efficacious as haloperidol with lorazepam in agitation due to psychiatric diseases. However, in agitation due to alcohol intoxication and TBI, haloperidol 5 mg is slightly better, although not statistically significant. Olanzapine and haloperidol were well tolerated by Indian patients in the current study, with minimal side effects.

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The Portuguese Poison Information Center (from Portuguese-CIAV) is a call center that offers medical assistance in case of possible intoxication with any kind of product, including medicines. This center´s main goal is to inform and guide the general public and health professionals. This work aimed to analyze and compare data corresponding to the telephone calls from the Algarve region (South of Portugal), received by CIAV during 2019 and 2020, regarding potential intoxications with medicines. To this end, data provided by CIAV on possible cases of medication intoxication in the Algarve region were collected, including the number of calls received, the place of origin of the call, the age group and sex of the intoxicated individual, the route of exposure to the drug, the circumstances of contact with the substance, the existence of symptoms, and the drug or drugs involved in the potential intoxication. The results showed that the number of cases slightly decreased in 2020 (n = 1261) compared with 2019 (n = 1340), with a high number of cases of intoxication in children between one and four years old in both years (21.2%; n = 152 in 2019; 16.4%; n = 115 in 2020). The drugs belonging to the locomotor system group (paracetamol and ibuprofen) were the main drugs involved, followed by the central nervous system pharmacotherapeutic group, namely benzodiazepines (diazepam and alprazolam). Paracetamol was the main drug responsible for the calls to CIAV (n = 71 in 2019; n = 63 in 2020), while for the remaining drugs there were fluctuations in their positions between both years. In some cases, this swinging may be explained by the possible changes in therapy due to potential interactions with drugs used for the treatment of symptoms of COVID-19 or perhaps related to misleading information released by the media about the use of some drugs, such as ibuprofen, during lockdown periods. Although there has been a decrease in calls to report possible drug intoxication in the Algarve region, the profile of calls was very similar. Paracetamol was the drug with the highest number of reported cases and the group of psychotropic drugs showed the largest increase between 2019 and 2020.

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Background Drug overdose is a significant healthcare issue and remains a common phenomenon in the emergency department (ED). The incidents have increased over the last few years worldwide. There are a few studies about drug overdose in Saudi Arabia in general and Jeddah city specifically. We aimed to describe the pattern of drug overdoses in the emergency department at an academic hospital in Jeddah between 2015-2022. Methodology A retrospective record review study was done in 2022 at an academic hospital in Jeddah between 2015-2021, where charts were reviewed for all reported patients presenting to the ED with drug overdose, including all ages and both genders. A careful review of their medical records, data collection, and processing was done using Google Forms (Google, Mountain View, California) and Microsoft Excel (Microsoft, Redmond, Washington), respectively. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) version 26 software (IBM Inc. Armonk, New York). Results Seventy-eight patients were identified, meeting the criteria from the medical records. Most of the patients were children under 12 years of age. Most patients were clinically stable when they arrived at the emergency department. Gastrointestinal symptoms were the most common clinical presentations, followed by drowsiness, while some patients were non-symptomatic. Analgesics and nonsteroidal were the most common causes of drug overdose. Conclusion We concluded from this limited study that the most commonly used causative agent in drug overdoses was nonsteroidal and analgesics. Moreover, children younger than 12 years of age constituted the majority of drug overdose patients, and accidental overdose represented the majority of cases. Therefore, it is important to increase public awareness of proper child supervision and keep drugs out of children's reach. More research using larger and more representative data is needed to identify patterns of drug overdose in the community.

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Mitochondria are central organelles in the homeostasis of the cardiovascular system via the integration of several physiological processes, such as ATP generation via oxidative phosphorylation, synthesis/exchange of metabolites, calcium sequestration, reactive oxygen species (ROS) production/buffering and control of cellular survival/death. Mitochondrial impairment has been widely recognized as a central pathomechanism of almost all cardiovascular diseases, rendering these organelles important therapeutic targets. Mitochondrial dysfunction has been reported to occur in the setting of drug-induced toxicity in several tissues and organs, including the heart. Members of the drug classes currently used in the therapeutics of cardiovascular pathologies have been reported to both support and undermine mitochondrial function. For the latter case, mitochondrial toxicity is the consequence of drug interference (direct or off-target effects) with mitochondrial respiration/energy conversion, DNA replication, ROS production and detoxification, cell death signaling and mitochondrial dynamics. The present narrative review aims to summarize the beneficial and deleterious mitochondrial effects of common cardiovascular medications as described in various experimental models and identify those for which evidence for both types of effects is available in the literature.

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Hyposphagma or subconjunctival hemorrhage is extensive confluent bleeding located between the conjunctiva and episclera. It can develop after trauma or the Valsalva maneuver and hemorrhagic diathesis and vascular diseases, hypertension, arteriosclerosis, and diabetes are the predisposing causes. It may also appear as part of the so-called congestion syndrome of the face and neck in crush or mechanical asphyxia and ligature strangulation, as well as in head-down positional asphyxia. We present two cases of heavily intoxicated individuals who were both, at the time of death, in the position with their trunks bent at the waist over their thighs and their heads down between the legs. They both had severe facial congestion with pronounced hyposphagma. The formation of extensive subconjunctival bleeding or hyposphagma resulted in hemodynamic dysregulation, a consequence of the head-down position, with a decreased venous return of blood to the heart. Since it requires preserved circulation, this finding cannot be considered solely as a mere postmortem phenomenon. Thus, in the presented cases, and especially in other cases where the blood level of psychoactive substances alone may be insufficient to explain the death, positional asphyxia, including the head-down position, could be considered a contributing cause. In such cases, hyposphagma could prove to be a valuable marker of positional asphyxia.

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We report the case of a young man, a former heroin addict, found dead at home by the Police Forces in an advanced state of decomposition. Numerous blisters and unpacked tablets of medications were found all over the bed and on the floor of the room. Multiple injuries to the face, left arm and neck of the deceased were noted. The latter damages were attributed to post-mortem dog bites, since no indications of a possible defense against the animal were observed. The autopsy findings were unremarkable. Toxicological investigations performed on peripheral blood and urine by gas chromatography-mass spectrometry (GC-MS) technique showed the presence of acetaminophen, citalopram and trazodone. Combined drug intoxication was proposed as the cause of death since acetaminophen and trazodone concentrations were comparable with the ones found in fatal cases. Moreover, citalopram concentration in peripheral blood was above the toxic range and in accordance with levels found in fatalities due to poly-drug intoxication.

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OBJECTIVE: The aim: This study is aimed at conducting a comprehensive analysis of the Ukrainian legislation regulating the alcohol testing procedure for drivers, investigating the practice of its implementation, reviewing international experience in this field, and elaborating proposals for its improvement. PATIENTS AND METHODS: Materials and methods: During the writing of the article, the current legislation of Ukraine is regulated, which regulates the procedure for medical examination to establish the state of intoxication of drivers, namely the Code of Ukraine on Administrative Offenses. This work meets the requirements of the Declaration of Helsinki. Methodology of the study includes general scientific methods (dialectic method, inductive and deductive approaches), special investigative techniques. CONCLUSION: Conclusions: Our study has underlined the necessity to improve the legal regulation for more effective alcohol testing program for drivers in Ukraine. This implies the elaboration of guideline for alcohol testing procedure and its approval by the Ministry of Health of Ukraine; to specify and legislate maximum permissible indicator values of blood alcohol concentration; to set the list of drugs and other substances through regulation; to adopt administrative responsibility for driving while intoxicated with alcohol (from 0.2 ppm to 1.1), and criminal liability for driving under severe alcoholic intoxication (1.1 ppm and above).

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The best evidence provided in the literature worldwide suggests the importance of harmonizing the investigation in drug-related fatalities. In this study, the application of a multidisciplinary approach in eight cases of drug-related deaths is presented. Although death scene findings could be highly suggestive of drug intoxication, external examination and toxicological screening test alone are insufficient. There are several variables, and it is not always easy to give the proper interpretation of the drug detection. A complete autopsy is necessary to correctly complete organ and tissues sampling for further histological and toxicological studies and obtain body fluids. The use of peripheral blood is recommended to avoid artifacts. The collection of many specimens is warranted to get more responses. The sampling aims to provide a picture of the distribution of the substance in the body. The sample and the selection of the drugs and the matrices to investigate are case-dependent. The presented diagnostic algorithm provides the coroner with all the elements to investigate drug-related deaths and cooperate with toxicologists. Toxicological forensic diagnosis is still extremely heterogeneous in regional and national contexts. Funding for method development, research, networking, facilities, and technologies improvement is mandatory to standardize the toxicological investigation.

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The intoxicated patient is a frequent situation in the emergency department (ED). Assessment and monitoring of somatic risk must be a priority, especially if there is any doubt about the treatments ingested. The risk of suicide, assessed on the patient's arrival, can lead to increased monitoring. Because of the strong interaction between serious psychiatric pathologies and drug intoxication, a psychiatric assessment should be systematically carried out. This is done at a distance from the intoxication, when the patient's condition allows it. In the case of alcohol intoxication associated with psychiatric symptoms or complaints, the assessment should be carried out after a period of sobering up, defined between the ED and psychiatry teams.

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OBJECTIVE: To describe the clinical features of rhabdomyolysis due to albuterol toxicosis in a Greyhound. CASE SUMMARY: A 4-year-old neutered male Greyhound was presented for albuterol toxicosis leading to severe hypokalemia and respiratory paralysis. After 3 hours of mechanical ventilation, pigmenturia and marked enlargement, firmness, and pain of the left thigh muscles were noted. Severe hyperkalemia and cardiac arrhythmias were identified after turning the patient. After discontinuation of mechanical ventilation, other muscles became involved, and the patient developed acute kidney injury and concern for multiple organ dysfunction syndrome over the next 5 days. On day 6, the patient was euthanized, and necropsy revealed myocardial and skeletal muscle necrosis, myoglobinuria, and acute tubular degeneration. NEW OR UNIQUE INFORMATION PROVIDED: To the authors' knowledge, this is the first case of albuterol toxicosis leading to rhabdomyolysis.

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OBJECTIVES: Traffic accidents, falls, assaults, occupational accidents, intoxications, burns, electric shock, lightning strike, all cases of asphyxia, penetrating and firearm injuries, suspected or definite cases of sexual abuse, and suicide attempts should be evaluated in the forensic category. In this study, we aimed to present our intensive care experiences in forensic cases. METHODS: We retrospectively evaluated forensic cases admitted to our Pediatric Intensive Care Unit between 1 February 2017 and 1 September 2018. RESULTS: This study included 153 children, 65 (42.5%) boys and 88 (57.5%) girls. The forensic causes of hospitalizations in the intensive care unit included drug intoxication with a rate of 54.9%, followed by suicide attempts with 24.2%, falling from a high place with 5.2%, child abuse with 5.2%, pedestrian (out-of-vehicle) traffic accidents with 2.6%, drowning in water with 2.6%, road (in-vehicle) traffic accidents with 2%, electric shocks with 2%, and CO (carbon monoxide) poisoning with 1.3%. The drug intoxication was caused by drugs prescribed to the mother and the child with a rate of 40.6% and 27.1%, respectively. Analgesic anti-inflammatory drugs (33.1%) and antidepressant drugs (22.3%) were identified as major causes of intoxication. In addition, paracetamol was the most common cause of intoxication, with a rate of 21.9% among all intoxication cases and 72.5% in the analgesic group. Amitriptyline was the most common agent in the antidepressant group (59.2%). The admission rate to the intensive care unit between 08:00 and 14:00 was 35.1% for suicide attempts and 16.4% for non-suicide attempts, with a statistically significant difference (p=0.025; p<0.05, respectively). CONCLUSION: Drug intoxications had the highest rate of forensic cases followed in our pediatric intensive care unit. The majority of these intoxications (69.4%) arose from accidental drug ingestion. Therefore, we believe that there may be a significant decrease in the number of hospitalizations of forensic cases associated with drug intoxications in pediatric intensive care units by preventing children's access to drugs.

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A 49-year-old man transferred to our hospital for dyspnea that developed while transporting significant loads of dry ice, which may have caused potential carbon dioxide intoxication. On admission, he presented hyperventilation and disorientation. Transthoracic echocardiography showed the reduced motion of the anterior wall of the left ventricle with decreased left ventricular ejection fraction. The patient underwent coronary angiography, which did not show apparent coronary arterial stenosis. The electrocardiogram revealed T-wave change and echocardiography results showed the subsided changes on the third hospital day. He was discharged without any symptoms on the fourth hospital day. Our case demonstrates the potential association between carbon dioxide intoxication and Takotsubo cardiomyopathy. Our experience may inform emergency physicians in formulating diagnostic/therapeutic approaches for similar patients experiencing cardiac failure following carbon dioxide intoxication.

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Background Childhood poisoning is a major health problem. Mostly, it is accidental and associated with low morbidity and mortality. The association between sociodemographic factors and childhood injury rates could be used for improvement to prevent and reduce such injuries. Childhood poisoning is preventable through appropriate education and judicious storage of drugs and household chemicals that might help in reducing and eliminating the accidental ingestion of toxic materials at home. Objectives To recognize the potential risk factors that might be associated with childhood home poisoning in Riyadh City, Kingdom of Saudi Arabia. Design A survey-based questionnaire study. Setting A tertiary care teaching hospital in Riyadh City. Patients and methods A structured questionnaire was created, which included questions on the poisoning incidence, home medication history, and possible risk factors for poisoning and the sociodemographic characteristics, and was disseminated to individuals who visited the King Khalid University Hospital. Main outcome measures Demographic characteristics of participants and risk factors related to childhood poisoning. Results The study included 152 randomly selected participants, 62 men (40.79%) and 90 women (59.21%). Self-ingestion was reported to be the most common mode of poisoning 28/44 (63.6%). The appearance of clinical manifestations suggesting poisoning was reported to be the most frequent method of discovery of children poisoning 20/44 (45.5%). Thirty-six out of the 44 respondents (81.8%) with a positive history of childhood poisoning in their family transferred their children to a hospital immediately. Drugs were the most common causative agent reported for poisoning among the respondents 21/44 (47.7%). Conclusion Accidental and non-intentional self-ingestion still presents as a major mode of childhood home poisoning. Despite the significant advancement in the lifestyle among the majority of Saudi Arabian regions, especially the capital city Riyadh, childhood poisoning remains a significant cause of morbidity and possible mortality. Creating health education and prevention programs might help to prevent such serious preventable problems. Limitations The limited number of participants may not reflect the whole population living in Riyadh City, hence, interpretation of the study results might be taken cautiously. Conflict of interest There was no conflict of interest.