"Tianeptine abuse via novel, extended-release, star-shaped, drug delivery device".

We report a rare domestic case of exposure to tianeptine and use of a novel, extended-release, six-armed, star-shaped, drug delivery capsule. A 40-year-old male with a history of depression, anxiety, ethanol, opioid, cannabis, and tobacco use disorders presented to the emergency department (ED) from a substance abuse residential recovery treatment program after developing hypertension, tachycardia, and tremor for two day. He used an extended-release, six-armed, star-shaped, drug delivery device he purchased online, filling each arm with 15 mg of tianeptine (90 mg total). His intention was to mitigate the symptoms of kratom/opioid withdrawal through this extended-release method while simultaneously undergoing formal treatment for ethanol withdrawal. Tianeptine is an atypical tricyclic antidepressant that exerts complex mechanisms of action including serotonin (5-HT) neuromodulation as well as full µ-opioid and ∂-opioid receptor agonism. The capsule itself is made of caprolactone, which is a bioabsorbable material similar to absorbable sutures, initially developed as a long-term enteral antimalarial delivery method and is not FDA approved for human use. Over the course of the patients two day hospitalization course he developed symptoms consistent with uncomplicated ethanol withdrawal, which were treated with as-needed phenobarbital. No clinical manifestations of opioid or serotonin toxicity developed. Serial EKGs and telemetry monitoring remained unchanged. The patient was then medically cleared and discharged back to the residential recovery treatment program.

Severe outcomes following pediatric cannabis intoxication: a prospective cohort study of an international toxicology surveillance registry.

INTRODUCTION: An increasing number of jurisdictions have legalized recreational cannabis for adult use. The subsequent availability and marketing of recreational cannabis has led to a parallel increase in rates and severity of pediatric cannabis intoxications. We explored predictors of severe outcomes in pediatric patients who presented to the emergency department with cannabis intoxication. METHODS: In this prospective cohort study, we collected data on all pediatric patients (<18 years) who presented with cannabis intoxication from August 2017 through June 2020 to participating sites in the Toxicology Investigators Consortium. In cases that involved polysubstance exposure, patients were included if cannabis was a significant contributing agent. The primary outcome was a composite severe outcome endpoint, defined as an intensive care unit admission or in-hospital death. Covariates included relevant sociodemographic and exposure characteristics. RESULTS: One hundred and thirty-eight pediatric patients (54% males, median age 14.0 years, interquartile range 3.7-16.0) presented to a participating emergency department with cannabis intoxication. Fifty-two patients (38%) were admitted to an intensive care unit, including one patient who died. In the multivariable logistic regression analysis, polysubstance ingestion (adjusted odds ratio = 16.3; 95% confidence interval: 4.6-58.3; P < 0.001)) and cannabis edibles ingestion (adjusted odds ratio = 5.5; 95% confidence interval: 1.9-15.9; P = 0.001) were strong independent predictors of severe outcome. In an age-stratified regression analysis, in children older than >10 years, only polysubstance abuse remained an independent predictor for the severe outcome (adjusted odds ratio 37.1; 95% confidence interval: 6.2-221.2; P < 0.001). As all children 10 years and younger ingested edibles, a dedicated multivariable analysis could not be performed (unadjusted odds ratio 3.3; 95% confidence interval: 1.6-6.7). CONCLUSIONS: Severe outcomes occurred for different reasons and were largely associated with the patient's age. Young children, all of whom were exposed to edibles, were at higher risk of severe outcomes. Teenagers with severe outcomes were frequently involved in polysubstance exposure, while psychosocial factors may have played a role.

Mobitz type I as manifestation of acute lithium cardiotoxicity.

Lithium induced cardiotoxicity is associated with several electrocardiographic (ECG) findings. The most commonly observed cardiac effects include QT prolongation, Twave abnormalities, and to lesser extent SA node dysfunction and ventricular arrythmias. We present a case of a 13-year-old female with acute lithium overdose whodeveloped Mobitz I, a manifestation of lithium associated cardiotoxity not previously reported. The patient had no significant past medical history and presented to the emergency department 1 h after intentional overdose of 10 tablets of unknown drug. Parents reported that the patient had visited her grandmother, who "regularly took many different kinds of medications," earlier that same evening. On physical examination the patient had reassuring vital signs, was in no acute distress,cardiopulmonary examination was normal, had clear sensorium, and no evidence of a toxidrome. On serological examination complete blood count, chemistries panel, and liver function tests did not show significant derangements. 4 h post-ingestion acetaminophen concentration was 28 mcg/ml and below indication for n-acetylcysteine antidote therapy. During her ED course she showed evidence of Mobitz I (Wenckebach) on 12-lead ECG. No prior ECGs were available for comparison. Medical toxicology was consulted at that time given concern for potential cardiotoxicity from an unknown xenobiotic. Serum dioxin and lithium concentrations were subsequently requested. Serum digoxin concentration was undetectable. Serum lithium concentrations was 1.7 mEq/L (0.6-1.2 mEq/L therapeutic range). The patient was treated with intravenous hydration at twice maintenance rate. Repeat lithium concertation 14 h post-ingestion was undetectable. During her admission, the patient remained hemodynamically stable and asymptomatic despite occasional episodes of Mobitz I, lasting seconds to minutes. Repeat 12-lead ECG obtained 20 h post-ingestion showed normal sinus rhythm. Cardiology recommendations included ambulatory Holter monitoring upon discharge and follow-up in clinic within two weeks. The patient was medically cleared after 36 h of monitoring and discharged after psychiatric evaluation. Our case demonstrates that patients who develop a new Mobitz I atrioventricular block of unclear etiology in the setting of acute ingestion should be screened for lithium exposure, even if otherwise free of more typical manifestations of lithium toxicity.

Oral Capecitabine Exposures and Use of Uridine Triacetate: A 20-Year Retrospective Analysis.

BACKGROUND AND OBJECTIVES: Capecitabine is an oral prodrug of 5-fluorouracil. Toxicity can occur during therapy as well as acutely with overdose and particular genetic susceptibilities. Uridine triacetate is an effective antidote if given within 96 h of exposure. This study seeks to characterize accidental and intentional capecitabine exposures and uridine triacetate use, about which little has been published. METHODS: A retrospective review of capecitabine exposures from 30 April 2001 to 31 December 2021 reported to a statewide poison control center was performed. All single-substance oral exposures were included. RESULTS: In total, 81 of 128 reviewed cases were included, with a median age of 63 years. In total, 49 were acute-on-chronic exposures and 32 were acute exposures in capecitabine-naïve patients, 29 of which were accidental. Fifty-six (69%) were managed at home. Of these, none later recontacted the poison control center to report symptoms or were known to have later had healthcare facility evaluations. Of the 25 cases presenting for healthcare facility evaluation, 4 were acutely symptomatic. Thirteen were eligible for uridine triacetate, and six received it; no new or progressive toxicity was reported after. Three developed mild latent toxicity; otherwise, no morbidity or mortality was reported. CONCLUSIONS: Accidental acute-on-chronic and acute ingestions of capecitabine appear to be well tolerated; most cases were managed at home. Unfortunately, little is known regarding the threshold at which toxicity may present following exposures. The threshold may vary individually given genetic susceptibilities. Management was heterogeneous, likely reflecting inadequate guidelines. Further research is needed to better delineate at-risk populations and treatment strategies.

Reversible Neurotoxicity Due To Excessive Use of Ethyl Chloride.

BACKGROUND: Ethyl chloride is commercially available as a DVD/VCR cleaner, and can be found as a gasoline additive and topical anesthetic. There is an emerging trend of recreational huffing to enhance sexual relations. Neurotoxicity from repeated abuse is uncommon. CASE REPORT: A 36-year-old man with a history of intermittent ethyl chloride use for 15 years presented to the Emergency Department with an inability to walk for 4 days after frequent use for 1 week. The patient reported a rapid titration of inhalation from zero to eight cans of 4.6 oz ethyl chloride aerosol per day over a 1-week period. Initial vital signs were heart rate 88 beats/min, blood pressure 147/60 mm Hg, temperature 37.2°C (99°F), and respiratory rate 16 breaths/min. Physical examination was notable for slurred speech, ptosis, a wide-based and ataxic gait with short strides, inability to stand without support, loss of toe/finger proprioception, horizontal and vertical nystagmus, and dysmetria on coordination testing. Strength and sensation were preserved. His work-up included computed tomography and magnetic resonance imaging of the brain, cervical, thoracic, and lumbar spine that demonstrated no acute abnormalities. On hospital day 9, the patient was able to ambulate with mild difficulty. WHY SHOULD AN EMERGENY PHYSICIAN BE AWARE OF THIS?: Toxicity from excessive ethyl chloride huffing has been rarely reported. The toxicity was characterized with cerebellar findings, no attributable laboratory abnormalities, and no radiographic abnormalities on computed tomography/magnetic resonance imaging. The neurotoxicity resolved with supportive care. This case of excessive huffing of ethyl chloride presenting with neurotoxicity and ataxia further characterizes a rare complication of ethyl chloride toxicity that is gaining popularity.

Oral Chemotherapeutic Ingestions Reported to a Poison Control Center Treated in a Health Care Facility.

BACKGROUND: The approach to cancer chemotherapy has changed in recent years, and there are several new oral chemotherapeutics that offer convenience to patients. These medications have toxicity, which may be particularly amplified in an overdose. STUDY DESIGN: This was a retrospective review of all oral chemotherapy overdoses reported to the California Poison Control System between January 2009 and December 2019. Inclusion criteria were all ingestions coded as "antineoplastic, monoclonal antibody, or thalidomide" that were evaluated at a health care facility. We evaluated outcomes per AAPCC criteria (stratified as death, major, moderate, mild, or no effect) as well as symptoms and interventions. RESULTS: There were 314 total cases reported; 169 single-substance ingestions (54%) and 145 cases with coingestant(s) (46%). One hundred eighty cases were female (57%) and 134 male (43%). Age ranges were as follows: ages 1-10 years old (87 cases); ages 11-19 years old (26 cases); 20-59 years old (103 cases); ages 60 and older (98 cases). The majority of cases were unintentional ingestions (199, 63%). The most common medication reported was methotrexate with 140 cases (45%), followed by anastrozole (32 cases) and azathioprine (25 cases). One hundred thirty-eight cases were admitted to the hospital for further care (ICU 63 cases; non-ICU 75 cases). Eighty-four of the methotrexate cases received the antidote leucovorin (60%). Five of the capecitabine ingestions received uridine (36%). Outcomes included 124 cases with no effect, 87 cases with minor effect, 73 case with moderate effect, 26 cases with major effect, and 4 deaths. CONCLUSION: Although methotrexate is the most common oral chemotherapeutic agent involved in overdoses reported to the California Poison Control System, there are many other oral chemotherapeutics from various drug classes, which can lead to toxicity. Although deaths are rare, further studies are needed to determine if particular drugs or drug classes warrant more scrutiny.

Neurotoxicity Associated With the Southern Pacific Rattlesnake (Crotalushelleri).

The Southern Pacific rattlesnake (Crotalus helleri) is commonly encountered throughout Southern California. Typical toxicity includes tissue injury and hematologic toxicity. However, neurotoxicity is not commonly reported with rattlesnake envenomations, other than infrequently with select species, including the Mojave rattlesnake (Crotalus scutulatus scutulatus). Importantly, clinical neurotoxicity has not been well described with the Southern Pacific rattlesnake, the only rattlesnake in the city of Los Angeles, along with the Southern and coastal regions of Los Angeles County. In this case series, 7 patients envenomated by the Southern Pacific rattlesnake with significant neurotoxicity, including dysarthria, ataxia, and myokymia, are presented. Clinicians practicing in this region should be aware of evolving patterns of toxicity associated with the Southern Pacific rattlesnake.

A Retrospective Review of Hospitalized Patients Receiving a Higher than Maximum Dose of Acetaminophen.

BACKGROUND: Although the 3 to 4 gram per 24 hours dose recommended for daily use are generally safe, case reports and some series raise concerns about nonacute excessive doses in some individuals. OBJECTIVE: To assess the safety of dosing more than 4 grams of acetaminophen in a 24-hour period in hospitalized patients and develop a method to evaluate the ongoing practice of acetaminophen dosing. Methods: We performed a retrospective chart review of supratherapeutic doses of acetaminophen over a 2-year period. Outcomes included death and the need for liver transplant. A "best practices alert" (BPA) was then developed in our EMR when more than 4 grams of acetaminophen was either prescribed or administered in a 24- hour period. Twelve months of alerts were then retrospectively reviewed and evaluated. RESULTS: 152 cases of dosing more than 4 grams were initially identified. No cases of death related to liver failure or liver transplant were found in any of these patients. 482 cases were identified after a BPA was put in place where the alert was overridden. There were no deaths and no cases that required liver transplantation due to liver failure. The majority of overrides were due to the allowed window of timing for nursing administration of acetaminophen for scheduled doses and overlap with as needed dosing. CONCLUSION: Supratherapeutic dosing of acetaminophen in our patients did not lead to death or liver transplant. A BPA in our EMR has allowed better evaluation of patterns of acetaminophen use at our university health system.

Envenomation by the Green Bush Viper Atheris squamigera.

The Green Bush Viper, Atheris squamigera, is native to West and Central Africa and has few well reported envenomations. Bite victims experience dizziness, nausea, headache, regional lymphadenopathy, and localized edema. Most reports also detail severe effects including thrombocytopenia, coagulopathy, hemolysis, hemorrhage, or renal failure. Fatalities are reported, but poorly described. There is no specific antivenom for A. squamigera, but non-species specific antivenom has been reported helpful in several cases. We report the case of a 36-year-old woman who was bitten by a green bush viper and was treated with several non-species specific antivenoms. There were no complications to antivenom administration and the patient experienced a milder envenomation than detailed in previous reports.

Accidental organophosphate poisoning: A case series of 2 pediatric coumaphos exposures.

Introduction: Pediatric organophosphate insecticide poisonings are rare in the United States, and life-threatening toxicity is rarely seen. We report 2 accidental ingestions of the organophosphate insecticide coumaphos that resulted in life-threatening symptoms. Case Reports: A 7-year-old boy and 10-year-old girl both presented from home after accidental ingestion of 1 "spoonful" of coumaphos 20% liquid (Asuntol; Bayer de Mexico, S.A. de C.V., Mexico D.F., Mexico). There were no other known ingestions. Both became rapidly symptomatic, with the boy developing dyspnea, vomiting, and depressed mental status and the girl developing headache and nausea. Soon afterward, the boy had witnessed cardiopulmonary arrest and the girl developed altered mental status and flaccid paralysis. Both were treated initially with atropine, but required no additional doses. On arrival to the pediatric intensive care unit (ICU), both patients received pralidoxime with subsequent plasma exchange and continuous venovenous hemodiafiltration (CVVHDF). Transient anemia, coagulopathy, transaminitis, and hyperglycemia developed in both patients. The girl was extubated on hospital day 6 and the boy on hospital day 11. The girl's course was complicated by aspiration pneumonia and an isolated seizure. The boy's course was complicated mainly by anoxic brain injury, associated seizures, neuroagitation, spasticity, and autonomic instability. The girl was discharged on hospital day 16 and remains asymptomatic 32 days after ingestion. As of 90 days after ingestion, the boy remains admitted to inpatient rehabilitation. Discussion: The clinical benefit of pralidoxime, plasma exchange, and CVVHDF is uncertain in these cases. The optimal treatment regimen for organophosphate insecticide toxicity remains poorly defined.

Massive Nonfatal Hydroxychloroquine Ingestion in a Pediatric Patient.

BACKGROUND: Hydroxychloroquine overdose is rare but potentially lethal. Hydroxychloroquine overdose symptoms are characterized by central nervous system toxicity, cardiac toxicity, and hypokalemia. Recommended treatment consists of epinephrine, high-dose diazepam, and careful potassium repletion. Few pediatric hydroxychloroquine overdoses have been reported. CASE REPORT: We describe a 14-year-old girl who ingested 10 g (172 mg/kg) of hydroxychloroquine. She developed tachycardia, hypotension, and hypokalemia. She was intubated and treated with diazepam and epinephrine infusions and potassium supplementation. Her serum hydroxychloroquine concentration obtained 10 h after ingestion was 13,000 ng/mL (reference range 500-2000 ng/mL). The patient made a full medical recovery. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Pediatric hydroxychloroquine overdoses are reported rarely, and the toxic and lethal doses of hydroxychloroquine ingestion have not been established. This case of a teenaged patient who ingested 10 g of hydroxychloroquine and survived provides additional information that may be used to help establish toxic and lethal doses of ingestion.

Delayed-Onset Portal Venous Thrombosis After Ingestion of 3% Hydrogen Peroxide.

BACKGROUND: Identification of portal venous gas on radiographic imaging is well documented after the ingestion of hydrogen peroxide, as is its resolution after hyperbaric therapy. Although hyperbaric therapy may resolve the gastrointestinal symptoms associated with the presence of portal venous gas, the principle rationale for performing hyperbaric therapy is to prevent subsequent central nervous system oxygen embolization. CASE REPORT: We describe a patient with portal venous gas identified by computed tomography after the ingestion of 3% hydrogen peroxide, managed without hyperbaric therapy, who subsequently developed portal venous thrombosis. We are not aware of this complication being previously described from hydrogen peroxide ingestion. The case is complicated by the coexistence of a self-inflicted stab wound, leading to exploratory laparotomy in a patient predisposed to arterial vascular occlusion. Why Should an EmergencyPhysicianBeAware of This? Emergency physicians will encounter patients after the ingestion of hydrogen peroxide who, despite not having symptoms of central nervous system emboli, have portal venous gas identified on radiographic imaging. Being aware that the principle rationale for prophylactic utilization of hyperbaric therapy is to prevent subsequent central nervous system emboli, and that in at least one case, delayed-onset portal venous thrombosis has occurred without hyperbaric therapy may help contribute to clinical decision-making.

Severe Perampanel Toxicity in a Pediatric Patient With Prolonged Symptoms.

BACKGROUND: Perampanel is a new antiepileptic used to treat partial-onset seizures and generalized tonic-clonic seizures in people older than 12 years old. Perampanel is a selective, non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, with a prolonged half-life of approximately 105 hours. Few cases of significant toxicity have been reported, and effects in overdose are poorly understood. CASE REPORT: This case describes a 20-month-old healthy female who ingested 8 mg of perampanel. She presented to a pediatric emergency department 1 hour after ingestion with ataxia, irritability, and somnolence. Vital signs were: heart rate 130 beats per minute, blood pressure 112/97 mmHg, temperature 99°F, respiratory rate 30 breaths per minute. She was admitted to the pediatric intensive care unit. During the hospitalization, she developed hypotension and bradycardia which improved with stimulation and fluid resuscitation. Intermittent bradycardia persisted for 32 hours after ingestion. Physical examination was notable for somnolence and truncal ataxia with irritability when aroused, all of which improved throughout the hospitalization. A quantitative level obtained on hospital day 3 (HD) was 750ng/ml. On HD 3 the patient was noted to be ataxic but otherwise had an age-appropriate neurologic examination. She was discharged on HD 4 with normal vital signs, return to baseline mental status, and baseline gait. The patient's cardiovascular, neurologic, and behavioral symptoms were attributed to perampanel toxicity. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS ?: Toxicity from a perampanel overdose is poorly understood both in adults and pediatric patients with significant cardiovascular, behavioral, and central nervous system abnormalities.

Accidental Arthrotomy Causing Aseptic Monoarthritis Due to Agave Sap: A Case Report.

INTRODUCTION: Aseptic inflammatory arthritis has been reported from thorns or cactus needles after inadvertent arthrotomy. Agave sap irritants may cause an aseptic inflammatory arthritis mimicking a septic joint. CASE REPORT: A 27-year-old male presented with left knee pain and swelling two hours after suffering an accidental stab wound to his left lateral knee by an agave plant spine. Synovial fluid white blood cell count was 92,730 mm3 with 75% neutrophils and no crystals. Surgical washout was remarkable for turbid fluid and no foreign body. Synovial fluid and blood cultures remained without growth. At two-week follow-up, the patient had recovered. CONCLUSION: Penetrating injuries from agave thorns can cause an inflammatory arthritis that mimics septic arthritis.

Despair in the time of COVID: A look at suicidal ingestions reported to the California Poison Control System during the pandemic.

BACKGROUND: Despite concern that the global pandemic will worsen depression and suicide rates, there remain little data on its actual effect. The purpose of this study was to determine the effect of the COVID-19 pandemic on suicidal ingestions reported to the California Poison Control System (CPCS). METHODS: This was a cross-sectional comparison of suicidal ingestions reported to the CPCS during the 2020 COVID-19 pandemic compared to suicidal ingestions reported during the same period in 2018 and 2019. RESULTS: The CPCS received 19,607 call for suicidal ingestions during the study periods, of which 13,800 were in the pre-COVID era (2018 and 2019) and 5,807 were in the COVID era. The median (IQR) number of suicidal ingestions per month decreased from 2,286 (2,240-2,364) to 1,940 (1,855-2,045; p = 0.02). This decrease was consistent and significant across all age groups except those age 70 or older. Ingestions without adverse events decreased by 101 cases/month (95% confidence interval [CI] = 136.8 to 65; p = 0.0003), minor outcomes decreased by 156.6 cases/month (95% CI = 226.2 to 87.1; p = 0.001), and moderate outcomes decreased by 96 cases/month (95% CI = 143.9 to 48.1; p = 0.00021). Major outcomes decreased from 793 (4.99%) cases in the pre-COVID era to 315 (4.60%) cases in the COVID era (risk ratio = 0.92, 95% CI = 0.81 to 1.05). The number of deaths decreased by 3.7 cases/month (95% CI = -8.3 to 0.92, p = 0.10). CONCLUSIONS: Despite concern for worsening suicidality, calls regarding suicidal ingestions to the nation's largest poison control center decreased during the COVID era compared to the pre-COVID era. This study provides evidence that the pandemic's effects on modern society remain difficult to predict. Further effort is needed to understand how pandemic will affect American's mental health.

Two Cases of Thyrotoxicosis due to Redotex Ingestion, a Mexican Weight Loss Drug.

BACKGROUND: Redotex™ is a Mexican weight-loss supplement that is not U.S. Food and Drug Administration-approved. It consists of the following five ingredients: tri-iodothyronine 75 µg, atropine 0.36 mg, diazepam 8 mg, aloin 16 mg, and d-norpseudoephedrine 50 mg per tablet. There are few case reports with clinically severe ingestions. We report two cases of clinical thyrotoxicosis due to use of Redotex. CASE REPORTS: A 29-year-old woman presented to the emergency department (ED) with anxiety and palpitations. She reported taking Redotex daily for 1 week. Her temperature was 37.1°C, blood pressure (BP) was 166/104 mm Hg, and heart rate (HR) was 140 beats/min. Laboratory analysis was significant for a bicarbonate level of 20 mmol/L (reference 22-29 mmol/L), free T4 0.75 ng/dL (reference 0.93-1.70 ng/dL), and thyroid-stimulating hormone (TSH) 0.05 uIU/mL (reference 0.27-4.20 uIU/mL). She was treated with 2 mg i.v. lorazepam and 20 mg oral propranolol. A 37-year-old woman presented with chest pain, palpitations, and nausea after taking Redotex 1 to 2 tablets daily for 6 weeks. Her HR was 134 beats/min and BP was 130/66 mm Hg. Thyroid function tests on initial presentation showed a TSH of 0.013 uU/mL, free T4 of 0.24 ng/dL, and free T3 of >30 pg/mL. She was treated with propranolol 1 mg i.v. twice per day and 2 doses of lorazepam 1 mg. Both patients had resolution of their symptoms. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: When taken chronically and at recommended doses, Redotex can present with clinically significant T3 thyrotoxicosis. This has not been seen in prior reports.