Toxic Tetrahydrocannabinol (THC) Dose in Pediatric Cannabis Edible Ingestions.

OBJECTIVE: The study characterizes cannabis toxicity in relation to tetrahydrocannabinol (THC) dose in pediatric edible cannabis ingestions. METHODS: This is a retrospective review of children aged <6 years presenting with edible cannabis ingestions of known THC dose within a pediatric hospital network (January 1, 2015-October 25, 2022). Cannabis toxicity was characterized as severe if patients exhibited severe cardiovascular (bradycardia, tachycardia/hypotension requiring vasopressors or intravenous fluids, other dysrhythmias), respiratory (respiratory failure, apnea, requiring oxygen supplementation), or neurologic (seizure, myoclonus, unresponsiveness, responsiveness to painful stimulation only, requiring intubation or sedation) effects. Cannabis toxicity was characterized as prolonged if patients required >6 hours to reach baseline. The relationship between THC dose and severe and prolonged toxicity was explored using multivariable logistic regression and receiver operator characteristic curve analyses. RESULTS: Eighty patients met inclusion. The median age was 2.9 years. The median THC ingestion was 2.1 mg/kg. Severe and prolonged toxicity was present in 46% and 74%, respectively. THC dose was a significant predictor of severe (adjusted odds ratio 2.9, 95% confidence interval: 1.8-4.7) and prolonged toxicity (adjusted odds ratio 3.2, 95% confidence interval: 1.6-6.5), whereas age and sex were not. Area under the curve was 92.9% for severe and 87.3% for prolonged toxicity. THC ingestions of ≥1.7 mg/kg can predict severe (sensitivity 97.3%) and prolonged toxicity (sensitivity 75.4%). CONCLUSIONS: The THC dose of edible cannabis correlates to the degree of toxicity in children <6 years old. The threshold of 1.7 mg/kg of THC may guide medical management and preventive regulations.

Impact of Cannabis-Based Medicine on Alzheimer's Disease by Focusing on the Amyloid ß-Modifications: A Systematic Study.

Deposition of Amyloid-beta (Aß) peptide in the brain is the leading source of the onset and progression of Alzheimer's Disease (AD). Recent studies have suggested that anti-amyloidogenic agents may be a suitable therapeutic strategy for AD. The current review was proposed to address the beneficial effects of cannabis-based drugs for the treatment of AD, focusing primarily on Aß modifications. Keywords related to AD, Aß, and cannabis-based on MeSH were identified and were searched in PubMed, Google Scholar, Scopus, Ovid-Medline, and Web of Science from inception until 15 March 2020. The full text of identified papers was obtained and assessed based on exclusion and inclusion criteria. The review is based on articles that have focused on AD and the amyloidogenic pathway. A total of 17 studies were identified based on the inclusion criteria; however, nine studies qualified for this systematic review. The maximum and minimum cannabis dosages, mostly CBD and THC in animal studies, were 0.75 and 50 mg/kg, respectively. Cannabis (CBD and THC) was injected for 10 to 21 days. The findings of the 9 articles indicated that cannabis-based drugs might modulate Aß modifications in several AD models. Our findings establish that cannabis-based drugs inhibited the progression of AD by modulating Aß modifications.

Review of Biguanide (Metformin) Toxicity.

In the 1920s, guanidine, the active component of Galega officinalis, was shown to lower glucose levels and used to synthesize several antidiabetic compounds. Metformin (1,1 dimethylbiguanide) is the most well-known and currently the only marketed biguanide in the United States, United Kingdom, Canada, and Australia for the treatment of non-insulin-dependent diabetes mellitus. Although phenformin was removed from the US market in the 1970s, it is still available around the world and can be found in unregulated herbal supplements. Adverse events associated with therapeutic use of biguanides include gastrointestinal upset, vitamin B12 deficiency, and hemolytic anemia. Although the incidence is low, metformin toxicity can lead to hyperlactatemia and metabolic acidosis. Since metformin is predominantly eliminated from the body by the kidneys, toxicity can occur when metformin accumulates due to poor clearance from renal insufficiency or in the overdose setting. The dominant source of metabolic acidosis associated with hyperlactatemia in metformin toxicity is the rapid cytosolic adenosine triphosphate (ATP) turnover when complex I is inhibited and oxidative phosphorylation cannot adequately recycle the vast quantity of H+ from ATP hydrolysis. Although metabolic acidosis and hyperlactatemia are markers of metformin toxicity, the degree of hyperlactatemia and severity of acidemia have not been shown to be of prognostic value. Regardless of the etiology of toxicity, treatment should include supportive care and consideration for adjunct therapies such as gastrointestinal decontamination, glucose and insulin, alkalinization, extracorporeal techniques to reduce metformin body burden, and metabolic rescue.

Pediatric jellyfish envenomation in the Mediterranean Sea.

BACKGROUND: Several species of jellyfish native to the western Indian Ocean have entered the Mediterranean Sea through the Suez Canal. Since the late 1980s, each summer Rhopilema nomadica forms swarms as long as 100 km in the southeastern Levant and since the millennium aggregations of additional nonnative jellyfish have been sighted. The aim of this study was to evaluate children seen in the emergency department after jellyfish envenomations and to establish patterns of toxicity associated with this organism. METHODS: A retrospective chart review was performed of all children presenting after jellyfish envenomations to the pediatric emergency department during the jellyfish swarming seasons (June-August) between 2010 and 2015. Extracted data included age, location of envenomation, pain scores, local and systemic manifestations, treatment provided in the emergency department and hospital, and disposition. RESULTS: Forty-one patients fulfilled the inclusion criteria; their ages ranged from 1 to 16 years and the median age was 9.4 years. Clinical manifestations were evident in all patients. Pain, present in 100% of patients, and an erythematous, whip-like, linear rash present in 87.8%, were the most common manifestations. The majority of 'burns' associated with jellyfish stings were first and second degree. The upper limb was affected in 34% and the lower limb was affected in 61% of cases. One patient suffered a sting to the abdomen and three patients suffered a sting to the face. Treatment in the emergency department included pain control, with nonsteroidal anti-inflammatory drugs and opiates, and antihistamines and topical corticosteroids in some cases. Nearly 49% of patients were seen during the summer of 2015 alone and seven patients in this group needed hospitalization. Reasons for hospitalization included systemic symptoms such as fever, chills, tachycardia, and muscle spasms. Two patients developed severe cellulitis, one patient had an anaphylactic reaction, and one was admitted to the ICU after suffering an anaphylactic reaction to a sting sustained while surfing. CONCLUSION: The prevalence of the jellyfish swarms and the severity of clinical manifestations because of their envenomations suggest that it should be considered as a health hazard in the Mediterranean Sea. We call for public health authorities in affected countries to initiate a health hazards database, familiarize medical and healthcare staff with the clinical syndromes, train medical and healthcare staff` in appropriate treatment, and initiate and continue public awareness campaigns.

Treatment of pediatric black widow spider envenomation: A national poison center's experience.

BACKGROUND: Black widow species (Latrodectus species) envenomation can produce a syndrome characterized by painful muscle rigidity and autonomic disturbances. Symptoms tend to be more severe in young children and adults. We describe black widow spider exposures and treatment in the pediatric age group, and investigate reasons for not using antivenom in severe cases. METHODS: All black widow exposures reported to the Rocky Mountain Poison Center between January 1, 2012, and December 31, 2015, were reviewed. Demographic data were recorded. Patients were divided into 2 groups. Group 1: contact through families from their place of residence, public schools and/or cases where patients were not referred to healthcare facilities. Group 2: patient contact through healthcare facilities. RESULTS: 93 patients were included. Forty (43%) calls were in Group 1 and 53 (57%) in Group 2. Symptoms were evident in all victims; 43 (46.2%) were grade 1, 16 (17.2%) grade 2 and 34 (36.5%) grade 3, but only 14 patients (41.1%) of this group received antivenom. Antivenom use was associated with improvement of symptoms within minutes, and all treated patients were discharged within hours, without an analgesic requirement or any complications. Reasons for not receiving antivenom included: skin test positive (2/20), strong history of asthma or allergies (2/20), physician preference (2/20), non-availability of the antivenom at the health care facility (14/20). CONCLUSION: In our study, most symptomatic black widow envenomations were minor. Relatively few patients received antivenom, but antivenom use was associated with shorter symptom duration among moderate and major outcome groups.

Anaphylaxis to black widow spider antivenom.

Black widow spider envenomation is commonly reported to poison centers. Black widow spider envenomation produces a clinical syndrome, known as latrodectism, characterized by headache, nausea, vomiting, several muscle cramping and pain, joint stiffness, hypertension, and regional diaphoresis. Black widow spider antivenom (Merck & Co, Inc, West Point, PA USA) is an effective and relatively safe treatment option. There is 1 clear case of anaphylaxis secondary to black widow spider antivenom reported in the medical literature. Here, we report a case of anaphylaxis to antivenom. A 12-year-old boy presented to the emergency department (ED) with diffuse, severe pain 2 1/2 hours after being bitten by a black widow spider on the right lower extremity. In the ED, the patient failed analgesic therapy with fentanyl and was given black widow spider antivenom. Within 45 minutes, he exhibited signs and symptoms consistent with anaphylaxis, including wheezing, chest tightness, pruritus, and urticarial rash. The patient was given standard therapy for anaphylaxis, and all of his signs and symptoms (including the pain secondary to the black widow envenomation) resolved over 6 hours of observation. Leading experts agree that the use of antivenom is indicated in cases of severe envenomation not responsive to standard therapy. Despite concern that the antivenom is an equine-derived whole IgG and can precipitate early hypersensitivity reactions, there is only 1 other reported case of anaphylaxis to the antivenom in the medical literature.