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.

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.

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.

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.

A Mixed Presentation of Serotonin Syndrome vs Neuroleptic Malignant Syndrome in a 12-Year-Old Boy.

BACKGROUND: Neuroleptic malignant syndrome (NMS) and serotonin syndrome (SS) are serious medical conditions associated with commonly prescribed psychiatric medications. Although the mechanisms differ, they can be clinically difficult to distinguish. We report a case of a pediatric patient with complicated psychiatric history that developed features of both syndromes in the setting of polypharmacy. CASE: A 12-year-old boy with a history of developmental delay, attention-deficit hyperactivity disorder, and posttraumatic stress disorder presented to the emergency department with behavior changes consisting of delayed reactions, gait instability, drooling, and slowed movements. Ten days before presentation, his outpatient psychiatrist had made multiple medication changes including discontinuation of cyproheptadine (an appetite stimulant) and initiation of aripiprazole. On arrival, the patient was noted to be tachycardia and hypertensive for age. He was disoriented, intermittently agitated, and tremulous with increased tonicity, clonus in the lower extremities, and mydriasis. He was supportively treated with lorazepam and intravenous fluids while discontinuing potential offending agents. His course was complicated by hypertension and agitation managed with dexmedetomidine infusion and benzodiazepines. His mental status, tremors, and laboratory values began to improve over the next 2 days, and eventually transitioned to the inpatient psychiatric unit on hospital day 7. DISCUSSION: Diagnosis of NMS or SS can be difficult when there is overlap between syndromes, particularly in the setting of multiple potential offending agents or underlying developmental delay. In addition, pediatric patients may present atypically as compared with adult patients with the same condition. CONCLUSION: The use of antipsychotic medications for young children with behavioral problems has risen dramatically in the last decade, increasing their risk for developing SS or NMS.

A 10-year review of single medication double-dose ingestions in the nation's largest poison control system.

BACKGROUND: Most Americans take at least one medication on a daily basis. Inadvertently ingesting a double-dose of a medication with a narrow therapeutic index may lead to adverse effects. When a patient or medical professional contacts the local poison center after an overdose, a poison specialist fields the incoming information and, depending on the caller, provides specific recommendations. We sought to determine which medication classes were most likely to lead to significant adverse outcomes when an extra dose was ingested. METHODS: This was a retrospective review of all double-dose medication ingestions reported to the California Poison Control System (CPCS) between January 2006 and December 2015. Inclusion criteria were single-instance, single-medication ingestions where the dose was known. All ages and both sexes were included. We evaluated generalized outcomes per AAPCC criteria stratified as no effect, minor, moderate, major or death. We also documented specific symptoms and interventions noted by the poison control specialists. RESULTS: Out of 1286 cases, 876 ingestions met the inclusion criteria. Medications with antihypertensive and behavior modulating effects each accounted for over a third of all moderate and major effects. The medications/medication classes implicated in the 12 major outcomes included propafenone, beta blockers (ßBs), calcium channel blockers (CCBs), bupropion, and tramadol. Of these, vasoactive medications were associated with the most severe effects requiring cardiac pacing and vasopressor drips. Analgesics, antimicrobials, and anti-allergy medications were well tolerated. There were no deaths. CONCLUSIONS: Major adverse outcomes after a double dose ingestion were rare. Most double dose medication ingestions can be safely monitored at home, albeit with a few exceptions. Vigilance is warranted in cases of ßB and CCB ingestion due to the risk of hemodynamic collapse or seizures with tramadol and bupropion.

Loperamide Trends in Abuse and Misuse Over 13 Years: 2002-2015.

STUDY OBJECTIVE: With the increasing amount of information available on the Internet describing techniques for using loperamide either for self-treatment of opioid withdrawal syndromes or for recreational use (so-called legal highs), the objective was to describe a statewide poison control system's experience with loperamide misuse and abuse, with specific interest in cases of cardiotoxicity, and to determine if reported loperamide misuse or abuse cases have recently increased. DESIGN: Retrospective review. DATA SOURCE: Statewide poison control system electronic database. PATIENTS: A total of 224 adults who presented or were referred to a health care facility between January 1, 2002, and November 10, 2015, for intentional ingestions of loperamide, and whose cases were reported to the poison control system by either physicians or nurses at the bedside. MEASUREMENTS AND MAIN RESULTS: Between 2002 and 2013, the number of yearly calls to the poison control system regarding loperamide cases ranged from 12-19 (mean 16.4, median 17.5 calls). In 2014, a sharp increase to 41 calls was noted. On completion of the study (November 10, 2015), 27 calls had been recorded. Medical outcomes of loperamide exposure for each patient were classified in accordance with the American Association of Poison Control Center's classification system as minor, moderate, or severe. For those patients with known outcomes, 3 resulted in death, 9 had major effects, 49 had moderate effects, and 36 had minor effects. We identified nine reports of patients who developed cardiotoxicity, with eight of them occurring between 2012 and 2015. A spike in the number of cases of loperamide toxicity reported in 2014 and 2015 coincided with an abundance of online instructions on how to abuse this drug. Almost all cases of recorded cardiotoxicity occurred over the last 3 years. Cardiotoxicity from loperamide abuse has only recently been recognized as a potential complication during the last few years, so earlier cases of cardiotoxicity resulting from loperamide abuse were likely missed. CONCLUSION: Our data suggest that loperamide may be increasing in popularity as a drug of abuse and for treatment of opioid withdrawal symptoms. Given the potential for significant toxicity with loperamide exposure, including life-threatening cardiac dysrhythmias, clinicians should consider obtaining a screening electrocardiogram for patients presenting after acute or chronic high-dose ingestions of loperamide. In addition, increased control over the availability of loperamide may be warranted.

A Case of 3,4-Dimethoxyamphetamine (3,4-DMA) and 3,4-Methylenedioxymethamphetamine (MDMA) Toxicity with Possible Metabolic Interaction.

We present a case of "ecstasy" ingestion revealing 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-dimethoxyamphetamine (3,4-DMA) and absence of cytochrome P450 (CYP)-2D6 MDMA metabolites. CASE REPORT: A 19-year-old presented following a seizure. Initial vital signs were normal. Laboratories were normal with the exception of sodium 127 mEq/L and urine drugs of abuse screen positive for amphetamines. Twelve hours later, serum sodium was 114 mEq/L and a second seizure occurred. After receiving hypertonic saline (3%), the patient had improvement in mental status and admitted to taking "ecstasy" at a rave prior to her initial presentation. Liquid chromatography-time-of-flight mass spectrometry (LC-TOF/MS) of serum and urine revealed MDMA, 3,4-DMA, and the CYP-2B6 MDMA metabolites 3,4-methylendioxyamphetamine (MDA) and 4-hydroxy-3-methoxyamphetamine (HMA). The CYP2D6 metabolites of MDMA, 3,4-dihydromethamphetamine (HHMA) and 4-hydroxy-3-methoxymethamphetamine (HMMA), were detected at very low levels. CONCLUSION: This case highlights the polypharmacy which may exist among users of psychoactive illicit substances and demonstrates that concurrent use of MDMA and 3,4-DMA may predispose patients to severe toxicity. Toxicologists and other healthcare providers should be aware of this potential toxicity.

Single Versus Multiple Hyperbaric Sessions for Carbon Monoxide Poisoning in a Murine Model.

Hyperbaric oxygen (HBO) has been advocated for treatment of acute carbon monoxide (CO) poisoning. There exists considerable debate as to whether HBO prevents delayed neurologic sequelae (DNS) due to CO poisoning. Additionally, existing data in the literature supporting HBO efficacy do not identify an optimal number of HBO treatments. We sought to determine in a mouse model whether there is a difference between one versus multiple HBO sessions for the prevention of DNS. Fifty mice were randomized into five groups of ten mice each: (1) control, receiving no CO exposure or treatment; (2) CO poisoned, receiving no treatment (CO group); (3) CO poisoned, receiving normobaric oxygen for 58 min following the end of exposure (CO + NBO group); (4) CO poisoned, followed by one session of HBO(CO + HBO1); and (5) CO poisoned, followed by three HBO treatment sessions, one every 6 h (CO + HBO3). Prior to poisoning, all animals were trained in step-down latency (SDL) and step-up latency (SUL) tasks. One week after exposure and treatment, all five groups were retested to evaluate the retention of this training. There was no difference detected among groups in SDL (p = 0.67 among all groups) when evaluated using a Kruskal-Wallis test. There was a significant difference among groups in SUL (p = 0.027 among all groups) when evaluated using a Kruskal-Wallis test. When individual groups were compared using a Wilcoxon signed-rank test with Bonferroni correction, there were no statistically significant differences in either SDL or SUL. There was no difference between groups treated with either one or three HBO sessions. One possibility to explain this might be that HBO sessions administered some time after a CO exposure may enhance the lipid peroxidation cascade and worsen neurologic outcomes; alternatively, HBO may simply impart no benefit when compared to NBO.