Epidemiology of cannabidiol related cases reported in the National Poison Data System - 2019-2020.

INTRODUCTION: Cannabidiol (CBD) has become a popular supplement in consumer products in recent years, resulting in part from normalization of the cultivation of low THC cannabis in 2018. However, the actual content of CBD-labeled products is frequently uncertain, as oversight of such products is minimal. To date, there is little pragmatic knowledge regarding exposures to products labeled as containing CBD. METHODS: Cases reported to Poison Control Centers from April 1, 2019 and March 31, 2020, the first year in which CBD was identified uniquely as a substance in the National Poison Data System, were analyzed for demographic, temporal, and clinical trends. RESULTS: Poison Control Centers handled 1581 cases exposures to CBD-containing products between April 1, 2019 and March 31, 2020. There was a significant trend of over 5 additional cases related to this substance per month (linear regression coefficient = 5.2, 95% CI: 1.52-8.98). Patients under age 13 years made up 44.0% of reported exposures. Mild CNS depression (10.3%), tachycardia (5.7%), dizziness/vertigo (5.3%), vomiting (4.9%), nausea (4.5%), and agitation (4.4%) were the most frequently reported symptoms. 13% of cases were coded as having "moderate" or "severe" medical outcomes. There were no fatalities. CONCLUSIONS: Cases reported to Poison Control Centers regarding exposures to CBD-labeled products have been increasing, representing an emerging trend of interest to Poison Control Center professionals, clinicians, and public health officials. Further monitoring of this trend is recommended.

Acute Phenobarbital Poisoning for the Management of Seizures in Newborns and Children; A Systematic Literature Review.

OBJECTIVES: While phenobarbital (PB) is commonly used for the management of seizures in newborns and pediatrics, its administration may accompany acute poisoning. We aimed to review the literature to find out the frequency of PB poisonings in newborns and children with seizures. METHOD: A literature search was performed by two independent reviewers to find relevant articles about PB toxicity in neonates and pediatrics that were treated for the seizure. RESULTS: 18 articles met the inclusion criteria and were included in this systematic review. The main reasons for PB poisoning in studied patients were therapeutic intoxication. Reported signs of PB poisoning were lethargy, sedation, lack of sucking, fever, skin rash, hepatic inflammation and alopecia. Moreover, respiratory depression, encephalopathy, myocardial failure, syndrome of inappropriate antidiuretic hormone, and coma were among the complications of acute PB toxicity in children and infants. CONCLUSION: PB therapy for the management of seizures in newborns and children might be associated with poisoning. Although supportive and symptomatic treatments are available for PB overdose, it should be administered with caution, using drug monitoring to avoid toxicity.

Pediatric perampanel poisoning.

There is no pediatric overdose information available for perampanel. We present twocases involving children 2 years of age. A female ingested 0.77mg/kg perampanel anddeveloped drowsiness and ataxia within an hour, followed by bradycardia after 6 hours.She was admitted to the pediatric intensive care unit and given fluids and was thendischarged after 20 hours. The other case involved a male who ingested 0.25mg/kgperampanel and developed ataxia within an hour, eventually he was discharged after 6hour observation in the emergency department without any treatment.

Calcium Channel Blocker Toxicity Causing Acute Respiratory Distress Syndrome: A Commonly Used Drug Triggering a Life-Threatening Condition.

INTRODUCTION: Calcium channel blockers (CCBs) are commonly used but have the potential to cause substantial toxicity. One such underreported toxicity of CCB use is the development of acute respiratory distress syndrome (ARDS). CASE PRESENTATION: 44-year-old previously healthy woman presented to the emergency department (ED) having taken 60 tablets of 125 mg extended-release verapamil and 90 tablets of 0.25 mg clonazepam with the intent to commit suicide. On presentation to the ED, she was sedated and intubated for airway protection. She received aggressive medical resuscitation and was ventilated using low tidal volume mechanical ventilation. The hospital course was complicated by worsening hypoxia and a chest x-ray demonstrating bilateral patchy geographic areas of airspace opacities consistent with ARDS. On day 5 of hospitalization, the patient's clinical status improved significantly, and she was subsequently weaned off vasopressors and extubated. DISCUSSION: CCB toxicity can result in profound hypotension, shock, bradycardia, and conduction blocks, as well as hyperglycemia, acidosis and acute kidney injury, and ARDS. It is important for clinicians to understand the signs and symptoms of CCB toxicity, as well as how to treat it.

Meropenem as an antidote for intentional valproic acid overdose.

Valproic acid (VPA) is a broad-spectrum antiepileptic drug indicated for monotherapy and adjunctive therapy of seizures, and complex manic episodes associated with bipolar disorder [1]. While uncommon due to monitoring, VPA can cause toxicity at supratherapeutic levels [1, 2]. Traditional treatment for VPA toxicity is primarily supportive care, however activated charcoal, l-carnitine, and hemodialysis have been successful in removing free VPA [2]. An interaction between carbapenem antibiotics and VPA is well-established and listed in respective package inserts as a combination to be avoided due to decreased VPA efficacy [1, 3]. Recent literature suggests co-administration of meropenem with VPA reduces mean plasma VPA levels by 50-80% [4, 6]. This case report describes the successful use of carbapenems to intentionally lower toxic VPA levels in a 42 year old female that presented to the emergency department with VPA toxicity from an overdose with divalproex sodium.

Α Simple Method for the Determination of Lacosamide in Blood by GC-MS.

Lacosamide is a functionalized amino acid with antiepileptic function. Therapeutic drug monitoring (TDM) in patients for lacosamide is critical as it allows clinicians to control epileptic seizures. A single liquid-liquid extraction step was applied for the extraction of lacosamide from whole blood samples which were thereafter analyzed by GC-MS. Optimum extraction conditions were selected on the basis of experiments with various solvents at different pHs, indicating ethyl acetate at pH 12 as the most efficient parameters for the extraction of lacosamide. Method exhibited linearity from 2 to 100 µg/mL with R2  = 0.998. Accuracy and precision were evaluated at three concentrations and found to be within acceptable limits. LOD and LOQ were determined at 0.1 and 0.5 µg/mL, respectively. Lacosamide was found to be stable at storage conditions. The developed method was applied successfully in clinical samples and postmortem blood sample from an overdose case.

Pregabalin and Its Involvement in Coronial Cases.

Pregabalin is an anticonvulsant and analgesic designed to treat neuropathic pain and partial seizure disorders and has been available in Australia as a prescription medication since 2005. Studies have found high rates of polydrug use associated with pregabalin and it is reportedly used recreationally for its euphoric and relaxing effects as well as to self-manage opioid withdrawal symptoms. A robust analytical method for the analysis of pregabalin using protein precipitation and LC/MS/MS was developed, validated and employed in routine case work. In recent years a substantial increase in pregabalin detections in coronial case submissions had been noted. This study examines the case characteristics and outcomes of 332 coronial cases submitted to the laboratory and analyzed for pregabalin between 2015 and 2017. Pregabalin was identified in approximately 5% of all coronial cases submitted during this time. A high rate of concurrent drug use with pregabalin was evident with the predominant classes being opioids, benzodiazepines and anti-depressants. Post-mortem blood pregabalin concentrations ranged from <0.05 to 140 mg/kg (median 5.5 mg/kg); however, limited interpretation of levels could be achieved as the drug was rarely identified in the absence of other drugs. Cause of death (COD) was found to be drug related in 58% of all cases, with mixed drug toxicity specifically mentioned as related to COD in 40% of cases.

Cardiac Collapse Secondary to Phenytoin Toxicity in a Neonate Treated with Extracorporeal Membrane Oxygenation Support (ECMO).

INTRODUCTION: Although medication toxicity is uncommon in neonates, there are several medications used in this population that pose a risk. Phenytoin has an increased risk of toxicity given its narrow therapeutic window and variations in drug elimination. CASE REPORT: We describe the case of a 3-day-old male infant who developed cardiovascular collapse secondary to severe phenytoin toxicity (max phenytoin level 86 µg/mL) and was placed on extracorporeal membrane oxygenation support (ECMO). Several ancillary treatments were utilized in an attempt to decrease serum phenytoin concentrations and limit toxicity including albumin boluses, phenobarbital administration, intravenous lipid infusion, and folic acid supplementation. DISCUSSION: Although uncommon, drug toxicity should be considered in patients with acute changes who are exposed to medications with potential toxicity. With elevated levels of phenytoin, the half-life can be prolonged resulting in longer exposure to elevated levels of the drug as seen in our patient. This case report highlights the importance of ECMO utilization for cardiac support in neonates with medication toxicity and other potential ancillary treatments to decrease serum phenytoin concentrations.

Carbamazepine-induced hyperglycemia: A rare case report.

Carbamazepine is a commonly used iminostilbene antiepileptic medication and it is estimated that 46.9% of the total antiepileptic drug overdose in the United Kingdom is because of this drug. The overdose of Carbamazepine can show negative effects on multiple systems, these include neurologic (ataxia, seizures, and altered sensorium), cardiac (tachycardia, hypotension) and metabolic manifestations. We reported a case of a 17-year-old girl had an increase in glucose levels after voluntary ingestion carbamazepine tablets. After ingestion, her gross random blood sugar level was increased, then physician suspected that she might be a Type I diabetic,but HbA1C[glycosylated hemoglobin] levels was found normal.Carbamazepine was discontinued and patient received symptomatic therapy. The patient had decreased levels of blood sugar level,after removal of the drug within the next day after ingestion of carbamazepine. A Naranjo assessment was obtained, indicating a definite relationship between the patient's increased in blood glucose levels and her use of carbamazepine.

Lacosamide: a Study of Exposures Reported to US Poison Centers over a 9-Year Period.

BACKGROUND: Lacosamide (Vimpat®) is an anticonvulsant used to treat partial-onset seizures. Little is known about the characteristics and outcomes of patients exposed to lacosamide. OBJECTIVE: To characterize lacosamide exposures reported to US poison centers with regard to patient demographics, clinical effects, and outcomes. METHODS: This retrospective observational study queried the National Poison Data System (NPDS) for single substance lacosamide exposures from January 2008 to December 2016. Variables of interest included age, gender, medical outcome, management site, level of healthcare facility, reason for exposure, and clinical effects. RESULTS: Lacosamide exposures were identified in 1124 patients, ranging from ages 2 months to 99 years. Six hundred and twenty-two patients (55.3%) were female. Nine hundred and seventy-six patients (86.8%) had minimal or no toxic effects. Life-threatening exposures numbered 30 cases (2.7%). There was one death. Five hundred and forty-eight patients (48.8%) did not require healthcare management while 537 (47.7%) were either referred to or already at a hospital. Among those treated at a healthcare facility, 269 (50.1%) did not require admission. Thirty-three patients (6.1%) were admitted to a psychiatric facility, 68 (12.7%) to a non-critical care unit, and 93 (17.3%) to a critical care unit. Six hundred and thirty-two exposures (56.2%) were due to therapeutic error. Suicide attempts numbered 168 (14.9%). Neurologic, gastrointestinal, and cardiovascular symptoms were commonly encountered. CONCLUSION: Lacosamide exposures infrequently cause death or disability; however, a considerable proportion of the study population required intensive care. Exposed patients with symptoms require healthcare evaluation.

Management of lamotrigine overdose using hemodialysis.

Lamotrigine [LTG] is primarily an anti-epileptic drug used to treat seizure disorders, depression, and bipolar disease. It is generally well tolerated with limited side effects reported during routine use. Adverse events after overdose include neurotoxicity in the form of sedation and seizure activity, as well as cardiopulmonary toxicity in the form of sodium-channel blockade and cardiovascular collapse. There is no consensus regarding the role of hemodialysis (HD) in management of lamotrigine toxicity. Based on pharmacological properties, LTG is a candidate for extracorporeal removal, however, the successful use of HD for the treatment of this poisoning is not well described. We report the case of a 44 year-old female after a LTG overdose that experienced prolonged sedation that was ultimately treated with HD with an excellent response.

Levocarnitine for the Treatment of Valproic Acid-Induced Hyperammonemic Encephalopathy in Children: The Experience of a Large, Tertiary Care Pediatric Hospital and a Poison Center.

BACKGROUND: Although rare, symptomatic hyperammonemia is sometimes associated with valproic acid (VPA), especially in children. L-carnitine (levocarnitine), sometimes classified as an essential amino acid, is vital to mitochondrial utilization of fatty acids and can be helpful in treating this condition. The data supporting this, however, are limited. STUDY QUESTION: The aim of the study was to illustrate the role of L-carnitine in the treatment of patients with VPA-induced hyperammonemic encephalopathy (VPE) at 2 different institutions. METHODS: Medical records of affected patients were reviewed; data collected included exposure history, clinical manifestations, physical examination, and laboratory values. RESULTS: There were 13 cases of VPE; 12 were associated with therapeutic dosing and 1 with an overdose. The maximum ammonia concentration was 557 µmol/L, and blood concentrations of VPA ranged from 68 to 600 µg/mL (therapeutic range 50-100 µg/mL). In all cases, liver function tests were normal or only mildly increased. In this study, 12 patients received a daily dose of L-carnitine 100 mg/kg, and 1 received 200 mg/kg (intravenous infusion over 30 minutes) divided every 8 hours until clinical improvement. All patients made a full recovery. None developed adverse effects or reactions, and no cases of toxicity were reported. CONCLUSION: Our series suggests that intravenous L-carnitine, at a dose of 100 mg·kg·d in 3 divided doses each over 30 minutes until clinical improvement occurs, is a safe and effective treatment in the management of VPE in children.

Drugs that Can Kill a Toddler with One Tablet or Teaspoonful: A 2018 Updated List.

BACKGROUND AND OBJECTIVE: Young children may be accidentally exposed to adult dose forms of medications, some of which can be fatal, even with a single dose. As numerous new medications have been introduced, we herein update a 2004 list of potentially toxic drugs that can be lethal for toddlers when taking one adult dose unit. METHODS: We reviewed all medications available in North America and identified their reported fatal doses per kilogram in children, or in adults if no pediatric data were available. For each drug we identified the largest dose unit available on the market and calculated how many dose units would be fatal to a 10 kg toddler. RESULTS: Since 2004, the list of potentially fatal drugs for toddlers has doubled and now includes new anticoagulants, a phosphodiesterase-5 inhibitor, new antiepileptic drugs, antidiabetic medications, drugs for multiple sclerosis, and second-generation antipsychotic drugs, among others. CONCLUSION: With the development of potent new medications, an increasing number of drugs are dangerous upon accidental exposure to toddlers and young children. The present 2018 list of documented fatal drugs has doubled compared with 2004, and special labeling of these medications is urgently needed to avoid such calamities.

Effects of three infusion fluids with different sodium chloride contents on steady-state serum concentrations of bromide in dogs.

Potassium bromide overdose (bromism) in the management of canine epilepsy has been known. However, a protocol to reduce bromide concentrations rapidly has not been previously established. The effects of three infusion fluids with different chloride contents on the steady-state serum concentrations of bromide in beagles were determined. After stabilization of the serum bromide concentrations, seven dogs were infused with saline (Na+ 154 mmol/L; Cl- 154 mmol/L), lactated Ringer's (Na+ 131 mmol/L; Cl- 110 mmol/L), or maintenance solutions (Na+ 35 mmol/L; Cl- 35 mmol/L) at a rate of 2 or 10 ml kg-1  hr-1 for 5 hr. Serum and urine were collected hourly, and the bromide concentrations were measured. When saline and lactated Ringer's solutions were infused at a rate of 10 ml kg-1  hr-1 for 5 hr, serum bromide concentrations were decreased by 14.24% and urine bromide concentrations by 17.63%, respectively. Of all compositions of infusion fluids, only sodium and chloride contents were associated with the decreased serum concentrations and the increased renal clearance of bromide. In summary, saline and lactated Ringer's solutions reduced serum bromide concentrations in a sodium chloride-dependent manner in dogs were found when infused at 10 ml kg-1  hr-1 for 5 hr.

Risk of Unnatural Mortality in People With Epilepsy.

Importance: People with epilepsy are at increased risk of mortality, but, to date, the cause-specific risks of all unnatural causes have not been reported. Objective: To estimate cause-specific unnatural mortality risks in people with epilepsy and to identify the medication types involved in poisoning deaths. Design, Setting, and Participants: This population-based cohort study used 2 electronic primary care data sets linked to hospitalization and mortality records, the Clinical Practice Research Datalink (CPRD) in England (from January 1, 1998, to March 31, 2014) and the Secure Anonymised Information Linkage (SAIL) Databank in Wales (from January 1, 2001, to December 31, 2014). Each person with epilepsy was matched on age (within 2 years), sex, and general practice with up to 20 individuals without epilepsy. Unnatural mortality was determined using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes V01 through Y98 in the Office for National Statistics mortality records. Hazard ratios (HRs) were estimated in each data set using a stratified Cox proportional hazards model, and meta-analyses were conducted using DerSimonian and Laird random-effects models. The analysis was performed from January 5, 2016, to November 16, 2017. Exposures: People with epilepsy were identified using primary care epilepsy diagnoses and associated antiepileptic drug prescriptions. Main Outcomes and Measures: Hazard ratios (HRs) for unnatural mortality and the frequency of each involved medication type estimated as a percentage of all medication poisoning deaths. Results: In total, 44 678 individuals in the CPRD and 14 051 individuals in the SAIL Databank were identified in the prevalent epilepsy cohorts, and 891 429 (CPRD) and 279 365 (SAIL) individuals were identified in the comparison cohorts. In both data sets, 51% of the epilepsy and comparison cohorts were male, and the median age at entry was 40 years (interquartile range, 25-60 years) in the CPRD cohorts and 43 years (interquartile range, 24-64 years) in the SAIL cohorts. People with epilepsy were significantly more likely to die of any unnatural cause (HR, 2.77; 95% CI, 2.43-3.16), unintentional injury or poisoning (HR, 2.97; 95% CI, 2.54-3.48) or suicide (HR, 2.15; 95% CI, 1.51-3.07) than people in the comparison cohort. Particularly large risk increases were observed in the epilepsy cohorts for unintentional medication poisoning (HR, 4.99; 95% CI, 3.22-7.74) and intentional self-poisoning with medication (HR, 3.55; 95% CI, 1.01-12.53). Opioids (56.5% [95% CI, 43.3%-69.0%]) and psychotropic medication (32.3% [95% CI, 20.9%-45.3%)] were more commonly involved than antiepileptic drugs (9.7% [95% CI, 3.6%-19.9%]) in poisoning deaths in people with epilepsy. Conclusions and Relevance: Compared with people without epilepsy, people with epilepsy are at increased risk of unnatural death and thus should be adequately advised about unintentional injury prevention and monitored for suicidal ideation, thoughts, and behaviors. The suitability and toxicity of concomitant medication should be considered when prescribing for comorbid conditions.

Antiepileptic drugs: Role in paediatric poisoning.

Intoxications, both accidental and intentional, are common in children and adolescents and often require hospitalisation and intensive treatment. Antiepileptic drugs are a possible cause of poisoning and intoxications because this category of medications has shown a rising trend in recent years. They might be responsible for multi-organ dysfunctions of variable severity, ranging from subtle symptoms to life-threatening complications. No guidelines on the management of these intoxications in the paediatric population are currently available, and treatment is mainly supportive. Activated charcoal administration and extracorporeal circulation techniques for drug removal have been proposed. Facing the complexity of this clinical scenario, it is of utmost importance to maintain a high index of suspicion to guarantee a prompt intervention and ensure the best possible management for the patient.

Complete Recovery After Acute Zonisamide Overdose in an Adolescent Female.

Zonisamide is a sulfonamide drug used primarily for the treatment of partial seizures in adults. We describe the case of a 15-year-old woman with a mood disorder who survived without complications after ingestion of an estimated 7.5 g of zonisamide. To the best of our knowledge, there are 4 case reports of individuals with intentional ingestion of more than 4 g of zonisamide as a single agent. Our patient developed coma and hypotension 4 hours after ingestion and was treated with a catecholamine infusion, endotracheal intubation, and mechanical ventilation. She had mild electrocardiographic abnormalities and fully recovered after 4 days. This report contributes to the understanding of acute zonisamide poisoning.