Trends in intentional abuse and misuse ingestions in school-aged children and adolescents reported to US poison centers from 2000-2020.

CONTEXT: Childhood and adolescent misuse and abuse exposures remain a serious public health challenge in the United States. This study aimed to describe recent trends and patterns of intentional substance misuse and abuse exposures among school-aged children and adolescents in the United States. METHODS: This study was a retrospective cohort study of intentional misuse and abuse exposures in children 6 through 18 years reported to the National Poison Data System (NPDS) from January 1, 2000, through December 31, 2020. Demographic trends, reported clinical effects, treatments, management sites, and health outcomes were assessed overall and within four age categories: 6-9, 10-12, 13-15, and 16-18. RESULTS: Between 2000 and 2020, there were 338,727 cases regarding intentional misuse and abuse exposures for children ages 6 through 18 years old. Overall, misuse/abuse ingestions fluctuated over time, with a peak in 2011. The majority of intentional misuse/abuse ingestions occurred in males (58.3%), and more than 80% of all reported exposure cases occurred in youth aged 13 to 18. 32.6% of ingestions resulted in worse than minor clinical outcomes. Older age groups had a greater number of severe medical outcomes compared to younger age groups. Major or life-threatening exposures (including those resulting in death) were more common in males. Overall, deaths were rare (n = 450), 0.1%). Male sex, older age, abuse ingestions, exposure site of a public area or other residence, and multiple ingested substances were other factors associated with increased mortality. Marijuana exposure rates had the highest average monthly increase overall, with the most dramatic rise occurring from 2017 to 2020. Edible marijuana preparations accounted for the highest increase in call rates compared with all other forms of marijuana. DISCUSSION AND CONCLUSION: With over 330,000 poison center cases reported during the 20-year study period, intentional substance misuse and abuse exposures substantially impact the pediatric population. The substances most commonly misused/abused are more widely available substances such as over-the-counter medications, household products and pharmaceuticals commonly prescribed to youth. Differences in age and sex were evident, with males and adolescents more likely to abuse and misuse substances. Our study describes an upward trend in marijuana misuse/abuse exposures among youth, especially those involving edible products. These findings highlight an ongoing concern about the impact of rapidly evolving cannabis legalization on this vulnerable population.

Continuous extracorporeal clearance in metformin-associated lactic acidosis and metformin-induced lactic acidosis: a systematic review.

INTRODUCTION: Metformin poisoning with lactic acidosis is an uncommon yet clinically serious condition related to the inhibition of normal aerobic metabolism. Toxicity may occur after an acute overdose although it is much more common after a systemic insult, such as acute kidney injury, in the setting of chronic use. Hemodialysis is currently the preferred extracorporeal treatment modality (Grade 1D evidence) although some patients may be too hemodynamically unstable to tolerate it. Continuous renal replacement therapy is considered an alternative if hemodialysis is unavailable but an evaluation of survival amongst this specific treatment class is lacking. OBJECTIVES: To assess overall survival and provide an updated review of the toxicokinetic elimination parameters of patients receiving continuous renal replacement therapy for metformin poisoning. METHODS: A comprehensive search was performed using the EMBASE and MEDLINE libraries from inception until November 30, 2021. Data was extracted and findings were summarized. Toxicokinetic parameters were analyzed and confirmed for accuracy when data permitted. RESULTS: Eighty-three reports met inclusion criteria. These consisted of only low-quality evidence including 75 case reports, four case series, and four descriptive retrospective reviews. Overall survival among patients suffering from metformin toxicity who received continuous extracorporeal treatment was 85.8%. When stratified between metformin-induced lactic acidosis and metformin-associated lactic acidosis, survival was 75.0% and 87.4%, respectively. Available continuous renal replacement therapy toxicokinetic parameters were quite heterogeneous. Errors in previously published toxicokinetic calculations were noted in only two instances. The overall average and median peak metformin concentrations were 70.5 mg/L and 41.9 mg/L, respectively. The average and median extracorporeal clearance rates were 39.0 mL/min and 42.1 mL/min (range 9.0-58.7 mL/min). The average and median elimination half-life parameters were 27.5 h and median 23.0 h. Elimination half-life ranged from seven to 74 h. There was no meaningful relationship between peak metformin concentration and continuous extracorporeal treatment half-life at lower concentrations, though at very high concentrations (over 200 mg/L), there was a trend towards a half-life below 20 h. There is insufficient data to robustly evaluate overall survival in relation to the extracorporeal clearance rate. Finally, there was no relevant relationship between maximal lactate concentration and survival, nor nadir pH and survival, for patients with either type of metformin toxicity. CONCLUSIONS: This retrospective systematic analysis of published cases treating metformin related lactic acidosis with continuous renal replacement therapy notes an overall slightly greater survival percentage compared to previous publications of individuals requiring any modality of renal replacement therapy. Because of publication bias, these results should be interpreted with caution and serve as hypothesis generating for future research. Prospective study focusing on the most clinically meaningful endpoint - survival - will help elucidate if continuous modalities are non-inferior to intermittent hemodialysis in metformin toxicity.

Silibinin: a toxicologist's herbal medicine?

Silymarin is an herbal remedy, commonly called milk thistle, or St. Mary's Thistle, and has been used for over 2000 years. It has been available as a capsule of the plant extract in Europe since 1974 to treat hepatic disorders. To date toxicologists have relied on animal studies, human case series, or retrospective reviews to decide on its use. In the U.S. the ability to use IV silibinin, its pharmacologically active purified flavonolignan, is hindered by its lack of availability as a Food and Drug Administration approved pharmaceutical preparation. This commentary reviews the in vitro studies, animal studies, and human retrospective analyses which form the basis for its clinical use. Despite the numerous publications, summarized in this issue in a systematic review, the mortality rate from Amanita mushroom ingestion remains stubbornly the same over four decades of use, and hovers around 10%. Although in the retrospective systematic review the use of silibinin, or penicillin, compared to routine care is statistically significantly superior when the primary outcome is fatality. Despite this there is no quality randomized trial to definitively demonstrate its utility. While, intravenous silibinin has a low toxicity, unanswered is whether it is useful in protecting the liver in cases of amanitin-containing mushrooms toxicity, and whether earlier administration would likely improve outcomes.

Did hypervitaminosis A have a role in Mawson's ill-fated Antarctic exploration?

Douglas Mawson is a national hero of Australia, having led the Australasian Antarctic expedition of 1911, and survived. His three-man sledging team was beset by a series of catastrophes. First, expert skier Belgrave Ninnis died after he fell into a deep crevasse taking with him half the dogs and a sledge of essential food and supplies. The remaining two explorers immediately turned back to base which was 315 miles away. With their rations diminished they resorted to eating their remaining six dogs over 23 days. Xavier Mertz became progressively ill with diarrhea, delirium, vocal outbursts in rages, and finally several seizures. He died after another seizure. Mawson, alone with negligible food and no dogs for transportation, through his own sheer grit made it back to base camp a month later and was saved. His journal records medical complications with skin desquamation, alopecia, and muscle pain. It has been proposed that these symptoms in both Mertz and Mawson were the manifestations of hypervitaminosis A. They likely consumed greater than a 1,200,000 IU of vitamin A each day from the dog liver they decided was essential to eat to survive. Mertz, a vegetarian, possibly consumed more of the liver than muscle meat, and consequently suffered the more severe encephalopathy and seizures associated with acute vitamin A poisoning.

Nitrous oxide abuse induced subacute combined degeneration despite patient initiated B12 supplementation.

INTRODUCTION: Nitrous oxide (N2O) is a commonly used inhaled anesthetic that is legal to purchase as a food additive and is popular as a recreational euphoric drug. Abuse causes a functional B12 deficiency, leading to clinical features and imaging consistent with subacute combined spinal cord degeneration (SCD). CASES: Poison Center medical records from four patients are reviewed in this series. Four patients presented with lower extremity weakness, paresthesias and gait abnormalities in the setting of chronic N2O abuse. Each reported using 50-150 N2O cartridges ("whippets") almost daily for months to years, and reported supplementing with oral B12 at the recommendation of other users and online forums. None reported prior B12 deficiency or dietary restrictions, and none exhibited hematologic abnormalities. RESULTS: All patients had clinical signs of neurotoxicity including weakness and ataxia. Additionally, all had elevated methylmalonic acid and homocysteine concentrations with normal B12 indicating a functional B12 deficiency. Three had imaging consistent with SCD despite home supplementation The MRI in the fourth case was inconclusive due to movement artifact. CONCLUSION: We report four cases of subacute combined degeneration induced by recreational nitrous oxide abuse despite self-administered vitamin B12 supplementation.

Inhalational mercury toxicity from artisanal gold extraction reported to the Oregon poison center, 2002-2015.

CONTEXT: Mercury exposure has been described among small-scale gold mining communities in developing countries, but reports of inhalational mercury toxicity among home gold extractors in the US remain uncommon. OBJECTIVE: We sought to identify inhalational mercury exposures and toxicity among artisanal gold extractors. METHODS: This is an observational case series of a single Poison Center database from 2002-2015. We review all cases of "mercury" or "mercury inhalation" exposures, with detailed description of a recent representative case. RESULTS: Nine cases were reported, with patients' ages ranging 32-81 years. Eight (89%) patients were male. Seven of eight (88%) patients with acute exposures reported pulmonary symptoms consistent with mercury vapor inhalation such as dyspnea and cough; two (29%) patients had severe toxicity requiring intubation. Four of six (67%) patients had markedly elevated whole blood mercury concentrations up to 346 mcg/L; each received a different chelation regimen. Four (44%) patients used methamphetamines at the time of their exposure. The case report describes a patient with elevated mercury concentrations who required intubation for hypoxic respiratory failure. He received chelation therapy based on chelator availability, with decreasing 24-hour urine mercury concentrations. The house where he was exposed remains uninhabitable from elevated ambient mercury vapor concentrations. CONCLUSION: Artisanal gold extraction may be associated with inhalational mercury toxicity, including elevated blood mercury concentrations and acute hypoxic lung injury requiring intubation.

Poisonings Associated with Intubation: US National Poison Data System Exposures 2000-2013.

Patients may be intubated after exposure to a variety of substances because of respiratory failure, CNS sedation, pulmonary pathology, or cardiovascular instability. However, there is little data describing the types of substances that are associated with endotracheal intubation or the rates of intubation after these exposures. Evaluation of this association may inform future research on intubation after exposures to specific substances and guide poison prevention education. Our objective was to determine which exposures were commonly associated with intubation using the data from National Poison Data System (NPDS). The NPDS tracks data from potential exposures to substances reported to all American Association of Poison Control Centers. We performed a retrospective analysis of NPDS data from January 1st, 2000 to December 31st, 2013 to identify human exposures to substances that were associated with endotracheal intubation. Descriptive statistics were used to analyze the data. There were 93,474 single substance exposures and 228,507 multiple substance exposures that were associated with intubation. The most common exposures to substances that were associated with intubation were atypical antipsychotics (7.4 %) for single exposures and benzodiazepines (27.4 %) for multiple exposures. Within each age group, the most common known exposures to substances were for patients under 6 years, clonidine for single and multiple exposures; for patients aged 6-12 years, clonidine for single exposures and atypical antipsychotics for multiple exposures; for patients aged 13-19 years, atypical antipsychotics for single and multiple exposures; and for patients over 19 years, atypical antipsychotics for single exposures and benzodiazepines for multiple exposures. From 2000-2013, the exposures to substances most commonly associated with intubation varied by single versus multiple exposures and by age. This study helps clarify the exposures to substances that are associated with intubation reported to poison centers in the USA.

Acute kidney injury associated with smoking synthetic cannabinoid.

CONTEXT AND OBJECTIVES: Synthetic cannabinoids are illegal drugs of abuse known to cause adverse neurologic and sympathomimetic effects. They are an emerging health risk: 11% of high school seniors reported smoking them during the previous 12 months. We describe the epidemiology of a toxicologic syndrome of acute kidney injury associated with synthetic cannabinoids, review the toxicologic and public health investigation of the cluster, and describe clinical implications of the cluster investigation. MATERIALS AND METHODS: Case series of nine patients affected by the toxicologic syndrome in Oregon and southwestern Washington during May-October 2012. Cases were defined as acute kidney injury (creatinine > 1.3 mg/dL) among persons aged 13-40 years without known renal disease who reported smoking synthetic cannabinoids. Toxicology laboratories used liquid chromatography and time-of-flight mass spectrometry to test clinical and product specimens for synthetic cannabinoids, their metabolites, and known nephrotoxins. Public health alerts informed clinicians, law enforcement, and the community about the cluster and the need to be alert for toxidromes associated with emerging drugs of abuse. RESULTS: Patients were males aged 15-27 years (median, 18 years), with intense nausea and flank or abdominal pain, and included two sets of siblings. Peak creatinine levels were 2.6-17.7 mg/dL (median, 6.6 mg/dL). All patients were hospitalized; one required dialysis; none died. No alternate causes of acute kidney injury or nephrotoxins were identified. Patients reported easily purchasing synthetic cannabinoids at convenience, tobacco, and adult bookstores. One clinical and 2 product samples contained evidence of a novel synthetic cannabinoid, XLR-11 ([1-(5-fluoropentyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone). DISCUSSION AND CONCLUSION: Whether caused by direct toxicity, genetic predisposition, or an as-yet unidentified nephrotoxin, this association between synthetic cannabinoid exposure and acute kidney injury reinforces the need for vigilance to detect new toxicologic syndromes associated with emerging drugs of abuse. Liquid chromatography and time-of-flight mass spectrometry are useful tools in determining the active ingredients in these evolving products and evaluating them for toxic contaminants.

Lead toxicity and endoscopic removal of ingested firearm cartridges.

CONTEXT: Lead toxicity from the ingestion of a lead foreign body has been described in several case reports. Management of ingested live ammunition presents its own challenges due to the risk of accidental discharge. A safe and effective method of retrieving a live cartridge must be considered. CASE DETAILS: We present two cases of lead toxicity due to intact firearm cartridge ingestion with the removal of the cartridges via endoscopy. The first case is of severe pediatric lead toxicity due to the ingestion of 30-mm rifle cartridges. The second case is an adult ingestion of .22 caliber cartridges resulting in mild lead toxicity. DISCUSSION: These cases illustrate a diagnostic dilemma in both the diagnosis of lead toxicity and the removal of live ammunition from the stomach.

Acute arsenic trioxide ant bait ingestion by toddlers.

INTRODUCTION: Arsenic trioxide is available for home use in ant baits. Potential arsenic toxicity from unintentional pediatric ingestion is not well studied. The goal of this study is to describe the clinical course and urinary arsenic concentrations of children who ingested ant bait containing arsenic trioxide (0.46%). METHODS: This is a case series of pre-school children who unintentionally ingested arsenic trioxide ant bait gel bars in the home reported to two U.S. poison control centers from January 2003 to July 2007. RESULTS: Six children (age range, 8 months to 4 years) ingested varying portions of ant bait gel bars containing arsenic trioxide (0.46%). All vomited shortly after exposure. The initial, pre-chelation urine total arsenic concentrations ranged from 1,858 to 13,981 mcg/L. All children had resolution of symptoms and received chelation with succimer. Follow-up urine arsenic concentrations were in the normal range 14-35 days after chelation and no further clinical toxicity was noted. CONCLUSIONS: Children who ingest all or part of a household ant bait gel bar that contains relatively low concentration of arsenic trioxide can develop markedly elevated urine arsenic concentrations with minor initial symptoms. Prompt chelation with succimer is recommended for children with these exposures and continued until urine arsenic concentrations are normal.

Should transient loss of consciousness in blunt head trauma be a pre-hospital trauma triage criterion?

The objective of this study was to evaluate pre-hospital triage of patients with an isolated brief loss of consciousness (LOC) to a regional trauma center (RTC). Data from a 6-month period were retrospectively reviewed from an existing pre-hospital data collection set. Patients were included if either they or a witness claimed a LOC, but they had regained consciousness to at least a Glasgow Coma Score (GCS) > 13 by the time the paramedics arrived. Endpoints for need for trauma center services included positive head computed tomography (CT) scan, the occurrence of emergency non-orthopedic surgery in < 6 h, admission to a surgical intensive care unit (ICU), or a length of stay (LOS) greater than 3 days for surgical evaluation. There were 655 complete records available for 275 cases of vehicular trauma and 380 cases of non-vehicular trauma. There were 170 (62%) patients in the vehicular group, and 287 (76%) in the non-vehicular group evaluated in the emergency department and discharged. In the vehicular group, only one (0.4%) patient required operative intervention in less than 6 h, three (1.1%) had a positive head CT scan, 10 (3.6%) were admitted to a surgical ICU, and four (1.5%) had a LOS > 3 days. In the non-vehicular trauma group, only one (0.3%) had surgery in < 6 h, eight (2.1%) had a positive CT scan, six (1.6%) were admitted to a surgical ICU or had a LOS > 3 days. Overall, 19 (2.9%, CI 0.018-0.045) patients met any one of the end-point criteria for trauma center utilization; however, only one patient (0.2% CI < 0.0001-0.008) required immediate neurosurgical intervention. Transient LOC, in the absence of any other American College of Surgeons (ACS) trauma triage criteria, triaged 97% of patients to a trauma center, who did not require trauma center services based on our criteria.

Lead poisoning and chelation in a mother-neonate pair.

We report the case of a pregnant woman with chronic lead toxicity and a blood lead of 57 microg/dL (2.7 micromol/L) who gave birth to a healthy-appearing neonate with a cord blood lead of 126 microg/dL (6.08 micromol/L). The mother was prescribed a single course of oral succimer late in the third trimester of pregnancy, without any appreciable change in her blood lead. The neonate was initially treated with intramuscular dimercaprol and intravenous edetate calcium disodium. After 3 days, the neonate was then switched to oral 2,3-dimercaptosuccinic acid because the blood lead had declined. The child received two 19-day courses of 2,3-dimercaptosuccinic acid and had a blood lead level of 21.5 microg/dL (1.04 micromol/L) at 5 months of age. Despite extensive investigation, the precise source of the mother's lead toxicity remained undetermined.

The futility of hemoperfusion and hemodialysis in Amanita phalloides poisoning.

Amanita phalloides mushrooms are extremely toxic. A variety of treatments have been proposed based as often on anecdotal experience as on firm evidence. General consensus exists regarding some treatments, such as the use of silibinin, penicillin, and activated charcoal. The most polarized debate concerns the value of extracorporeal elimination. We describe a case of 2 adults with confirmed Amanita phalloides poisoning treated with hemodialysis (HD) immediately after arrival at our tertiary care hospital (23 h after ingestion) and later with hemoperfusion (HP); a series blood samples were taken to determine the clearance of the toxin by each method. No amatoxin was detected before treatment, after treatment, or in the HD/HP circuits. Neither HD nor HP contributed to the clearance of amatoxin.

Intermediate syndrome after malathion ingestion despite continuous infusion of pralidoxime.

CASE REPORT: A 33-year-old female ingested an unknown quantity of malathion in a suicide attempt. Cholinergic signs consistent with severe organ, phosphate intoxication developed and were treated within 6 hours of ingestion. Intravenous atropine and a continuous infusion of pralidoxime (400 mg/h) were administered. Prolonged depression of plasma and red blood cell cholinesterases were documented. Despite an initial clinical improvement and the presence of plasma pralidoxime concentrations exceeding 4 microg/mL, the patient developed profound motor paralysis consistent with the diagnosis of Intermediate Syndrome. In addition to the dose and frequency of pralidoxime administration, other factors including persistence of organophosphate in the body, the chemical structure of the ingested organophosphate, and the time elapsed between ingestion and treatment may limit the effectiveness of pralidoxime as an antidote in organophosphate ingestions. This case study suggests that these factors should be taken into account in assessing the risk of Intermediate Syndrome after intentional organophosphate ingestions.

Fatal cardiovascular collapse following acute colchicine ingestion.

BACKGROUND: A previously published prognostic rule predicts 100% survival after ingestion of cochicine doses less than 0.5 mg/kg and 100% mortality after ingestion of more than 0.8 mg/kg. This rule inaccurately predicted survival in a recent case. CASE REPORT: We present a case of fatal colchicine poisoning in an adult who ingested a maximum of 39.6 mg of colchicine (0.40 mg/kg). He subsequently developed hypotension which was refractory to fluid resuscitation and infusion of vasopressors. He died of cardiovascular collapse approximately 35 hours after ingestion. DISCUSSION: Fatal outcomes are possible even with colchicine doses less than 0.5 mg/kg. Physicians caring for colchicine-poisoned patients must be prepared for the possibility of acute cardiovascular collapse and ventricular dysrhythmias regardless of the reported dose of colchicine.