Cannabis use and measurement of cannabinoids in plasma and breast milk of breastfeeding mothers.

BACKGROUND: Information on cannabinoids in breast milk and maternal cannabis use is limited. We quantified cannabinoids in plasma and breast milk of breastfeeding mothers and assessed cannabis use patterns. METHODS: This is a prospective study at a university hospital in a state with legal medical and recreational cannabis. Breast milk and plasma samples along with survey data were collected from volunteers using cannabis in the last 48 h at 2 weeks and 2 months postpartum. RESULTS: Twenty subjects were enrolled. Median age (IQR) was 27 (24-34) years. Median (IQR) instances of cannabis use in the last 7 days were visit 1: 17 (6-29) and visit 2: 23 (15-45). Median (IQR) tetrahydrocannabinol (THC) concentrations were: plasma 3.7 ng/ml (0.8-56.8) and breast milk 27.5 ng/ml (0.8-190.5). Median (IQR) cannabidiol (CBD) concentrations were: plasma 0.6 ng/ml (0.5-6.4) and breast milk 1.2 ng/ml (0.5-17.0). Median (IQR) THC M/P: 7.0 (1.8-34.6) and CBD M/P: 2.6. Median breast milk THC concentration increased from visit 1 to visit 2 by 30.2 ng/ml (95% CI 3.05-69.3 ng/ml). CONCLUSIONS: THC and CBD accumulate in breast milk. Breastfeeding mothers used cannabis frequently and increased use in the early postpartum period. Research on the effects of infant exposure to cannabinoids in breast milk is urgently needed. IMPACT: Cannabis use is increasing in the general population and many nursing mothers use cannabis. THC has been previously detected in breast milk but little is known on how it concentrates relative to plasma. Data on cannabinoids other than THC, reasons for cannabis use, and patterns of use in breastfeeding women are also limited. We detected THC and CBD in breast milk. Both concentrate in breast milk relative to plasma. We showed that breastfeeding mothers increased cannabis use in the weeks after childbirth. Further research is needed to evaluate infant exposure to cannabinoids via breast milk and effects on infant health.

Toxicologic Confounders of Brain Death Determination: A Narrative Review.

The aim of this narrative review is to describe the toxicologic confounders of brain death currently reported in the literature to offer guidance for physicians assessing brain death after a toxic exposure. We established an a priori definition of a "brain death mimic" as an unresponsive, intubated patient missing some, but not all brainstem reflexes. We completed a review of the literature utilizing MEDLINE and EMBASE to find case reports of patients of all ages in English, French, and Spanish meeting the criteria and hand searched the references of the results. We recorded xenobiotic dose, duration of physical exam suggesting brain death, and how the cases failed to meet full brain death criteria, when available. Fifty-six cases representing 19 different substances met the a priori definition of brain death mimic. Xenobiotic toxicities included: snake envenomation (13), baclofen (11), tricyclic antidepressants (8), bupropion (7), alcohols (4), antiepileptic agents (3), barbiturates (2), antidysrhythmics (2), organophosphates (2), and one case each of magnesium, succinylcholine, tetrodotoxin, and zolpidem. All patients except one survived to discharge and the majority at their baseline physical health. The most common means by which the cases failed brain death examination prerequisites was via normal neuroimaging. The xenobiotics in this review should be considered in cases of poisoning resulting in loss of brainstem reflexes and addressed before brain death determination. Brain death diagnosis should not be pursued in the setting of normal cerebral imaging or incomplete evaluation of brain death prerequisites.

Serotonin Toxicity: Associated Agents and Clinical Characteristics.

BACKGROUND: Serotonin toxicity is a common cause of drug-induced altered mental status. However, data on the causes of serotonin toxicity, symptomatology, complications, and rate of antidotal treatment are limited. METHODS: This study evaluated cases of serotonin toxicity in the ToxIC registry, an international database of prospectively collected cases seen by medical toxicologists. Serotonin toxicity was diagnosed by bedside evaluation of medical toxicology specialists and explicit criteria were not used. The database was searched for "serotonin syndrome" between January 1, 2010, and December 31, 2016. RESULTS: There were 1010 cases included. Females made up 608 (60%) cases. Ages are as follows: younger than 2 years (3, 0.3%), 2 to 6 years (8, 0.8%), 7 to 12 years (9, 0.9%), 13 to 18 years (276, 27.3%), 19 to 65 years (675, 67%), older than 66 years (33, 3.4%), unknown (6, 0.6%). Reasons for encounter: intentional (768, 76%), adverse drug event/reaction (127, 12.6%), unintentional (66, 6%), and unknown (55, 5.4%). Signs/symptoms: hyperreflexia/clonus/myoclonus (601, 59.5%), agitation (337, 33.4%), tachycardia (256, 25.3%), rigidity (140, 13.9%), seizures (139, 13.7%), and hyperthermia (29, 2.9%). COMPLICATIONS: rhabdomyolysis (97, 9.7%), dysrhythmias (8, 0.8%), and death (1, 0.1%). TREATMENTS: benzodiazepines 67% (677/1010), cyproheptadine 15.1% (153/1010). There were 192 different xenobiotics reported with 2046 total exposures. Antidepressants were most common (915, 44.7%) with bupropion the most frequent overall (147, 7.2%). Common non-antidepressants were dextromethorphan (95, 6.9%), lamotrigine (64, 3.1%), and tramadol (60, 2.9%). DISCUSSION: Serotonin toxicity most often occurred in adult patients with intentional overdose. Antidepressants were the most common agents of toxicity. Interestingly, bupropion, a norepinephrine/dopamine reuptake inhibitor, was the most frequently mentioned xenobiotic. Though often cited as a potential antidote, only 15% of patients received cyproheptadine. Severe toxicity was rare. A single death was reported.

Adolescent Intentional Abuse Ingestions: Overall 10-Year Trends and Regional Variation.

OBJECTIVE: Adolescent intentional ingestions remain a significant public health problem in the United States with little research to date on the over-the-counter or prescription medicines that adolescents abuse. These data are important for anticipatory guidance by primary care providers, preventive health, and poison center outreach. METHODS: This was an observational study using the American Association of Poison Control Centers National Poison Data System. The study population consisted of all cases of patients aged 13 to 19 years from 2004 to 2013 with a coding of "intentional abuse." RESULTS: There were 95,695 patient calls that were coded for intentional abuse between 2004 and 2013 for adolescents aged 13 to 19 years. The most common agent reportedly ingested in intentional-abuse cases was antihistamine and/or decongestant with dextromethorphan, and this agent remained the most common throughout the 10-year study period. The next 4 most common agents remained similar across the study period as well and included ethanol, benzodiazepines, dextromethorphan alone, and marijuana. These 5 agents remained the most commonly reported across the study period for all US regions (West, Midwest, South Northeast, and US territories). CONCLUSIONS: Over a recent 10-year period, common cough preparations remain the most commonly reported intentional abuse ingestion among all years and regions for adolescents.

Unintentional Pediatric Ingestion of Electronic Cigarette Nicotine Refill Liquid Necessitating Intubation.

Liquid nicotine used in electronic cigarette devices is highly concentrated, unreliably packaged, and poorly regulated. We present a case report of a 6-year-old female who developed severe toxicity and required intubation after an unintentional oral ingestion of approximately 703 mg (35 mg/kg) of liquid nicotine, with accompanying serum and urine concentrations of nicotine and its metabolites. Analysis of the ingested liquid suggests a nicotine concentration of 140.6 mg/mL in the purchased commercial product, or 234% of its labeled concentration. Clinicians should be aware of these products and the potential severity of toxicity they may incur.

Outcomes After High-Concentration Peroxide Ingestions.

STUDY OBJECTIVE: In cases of high-concentration peroxide ingestion reported to US poison centers, we describe medical outcomes, examine the role of hyperbaric oxygen, and review the use of endoscopy. METHODS: The study was a retrospective analysis of a structured database, the National Poison Data System. The chart for each poison center case of a high-concentration (>10%) peroxide ingestion was obtained and abstracted in a standardized fashion; 1,054 cases were initially considered and 294 cases met inclusion criteria. The primary outcome of possible embolic event was defined as seizure, altered mental status, respiratory distress, hypoxia, hemodynamic instability, ECG changes, radiographic evidence of cerebrovascular accident, focal neurologic deficit on examination, pulmonary embolism, cardiac emboli, elevated troponin level, physician bedside diagnosis, or rapid improvement after hyperbaric oxygen therapy. Both descriptive statistics and logistic regression models were used to analyze the data. RESULTS: In the 10-year study period, 41 of 294 patients (13.9%; 95% confidence interval 10.2% to 18.4%) with symptoms after high-concentration peroxide ingestion demonstrated evidence of embolic events, and 20 of 294 (6.8%; 95% confidence interval 4.2% to 10.3%) either died or exhibited continued disability when the poison center chart was closed. Improved outcomes were demonstrated after early hyperbaric oxygen therapy. Endoscopy revealed grade 3 or 4 lesions in only 5 cases. CONCLUSION: Symptomatic high-concentration peroxide exposures had a high incidence of associated embolic events in this cohort. Patients with evidence of embolic events had a high rate of death. Early hyperbaric oxygen therapy may be useful, but routine endoscopy is unlikely to be of benefit.

Delayed Salicylate Toxicity in a 17-Year-Old Girl With Initially Undetectable Salicylate Concentration 3.9 Hours After Ingestion.

We report the case of a 17-year-old girl with a 126-mg/kg nonenteric coated aspirin ingestion with nontoxic salicylate concentrations at 1.5 and 3.9 hours postingestion, who developed tinnitus and vomiting an estimated 8 hours postingestion, and who was subsequently found to have a toxic salicylate concentration at 22.7 hours postingestion. This case, as well as previous cases of delayed aspirin therapy, may prompt providers to consider educating patients and their care providers regarding the need to return for further testing if symptoms, such as vomiting or tinnitus, develop after an aspirin ingestion.

Respiratory depression in the intoxicated trauma patient: are opioids to blame?

Providing effective pain management to acutely intoxicated trauma patients represents a challenge of balancing appropriate pain management with the risk of potential respiratory depression from opioid administration. The objective of this study was to quantify the incidence of respiratory depression in trauma patients acutely intoxicated with ethanol who received opioids as compared with those who did not and identify potential risk factors for respiratory depression in this population. Retrospective medical record review was conducted for subjects identified via the trauma registry who were admitted as a trauma activation and had a detectable serum ethanol level upon admission. Risk factors and characteristics compared included demographics, Injury Severity Score, Glasgow Coma Score, serum ethanol level upon arrival, urine drug screen results, incidence of respiratory depression, and opioid and other sedative medication use. A total of 233 patients were included (78.5% male). Patients who received opioids were more likely to have a higher Injury Severity Score and initial pain score on admission as compared with those who did not receive opioids. Blood ethanol content was higher in patients who did not receive opioids (0.205 vs 0.237 mg/dL, P = .015). Patients who did not receive opioids were more likely to be intubated within 4 hours of admission (1.7% vs 12.1%, P = .02). Opioid administration was not associated with increased risk of respiratory depression (19.7% vs 22.4%, P = .606). Increased cumulative fentanyl dose was associated with increased risk of respiratory depression. Increased cumulative fentanyl dose, but not opioid administration alone, was found to be a risk factor for respiratory depression.

Endotracheal Intubation for Toxicologic Exposures: A Retrospective Review of Toxicology Investigators Consortium (ToxIC) Cases.

BACKGROUND: Endotracheal intubation remains a cornerstone of early resuscitation of the poisoned patient, but little is known about which substances are associated with intubation. OBJECTIVES: Our objective was to describe patient exposures to substances reported to the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC) that were managed with intubation between 2010 and 2014. METHODS: We performed a retrospective review of cases managed with endotracheal intubation in the ACMT ToxIC Registry from January 1, 2010 through December 31, 2014. Descriptive statistics were used to describe patient exposures. RESULTS: A total of 2724 exposures to substances were managed with endotracheal intubation. Intubated patients were 52% male and 82% adults. For all ages taken together, the most common known single-substance exposures managed with intubation were sedative hypnotics (9.8%), antidepressants (8.7%), and opioids (8.0%). The most common single ingestions associated with intubation in various age groups were: opioids (<2 years old), alpha-2 agonists (2-6 years old), antidepressants (7-18 years old), sedative-hypnotics (19-65 years old), and cardiac medications (>65 years old). Multiple substances were involved in 29.0% of exposures. Decontamination and elimination processes were used in 12.8% of patients. CONCLUSIONS: The most common substances involved in single- and multiple-substance exposures managed with intubation varied by age group. Most patients were managed with supportive care. Knowledge of substances commonly involved in exposures managed with intubation may inform triage and resource planning in the emergency department resuscitation of critically ill poisoned patients.

Association of Overall Opioid Prescriptions on Adolescent Opioid Abuse.

BACKGROUND: Opioid abuse is a public health epidemic in the United States. Much literature has focused on the prescribing practices of physicians and opioid misuse by adults. However, there are limited data on the effect of opioid prescriptions on adolescent recreational ingestion of these medications. OBJECTIVES: The objective of this study was to assess for a relationship between opioid prescribing practices across the United States and adolescent opioid ingestion calls to poison centers. METHODS: This was an observational study using the National Poison Data System. The study population consisted of poison center calls regarding adolescents between 2005 and 2010 in the database with a coding of "intentional abuse" and an opioid ingestion. National opioid prescription estimates were generated using nationally representative outpatient and inpatient databases. RESULTS: There were 4186 adolescent opioid ingestion calls during the study period. There was a general increase between 2005 and 2010 in both teen opioid abuse calls (617 in 2005 to 782 in 2010) and national opioid prescriptions (approximately 78 million in 2005 to 108 million in 2010). For each opioid prescription increase per 100 persons per year, the annual teen opioid abuse calls increased by 1.8% (95% confidence interval 0.9-2.8%), equivalent to an absolute increase of about 0.04 to 0.05 calls per 100,000 teens annually. CONCLUSIONS: There appears to be an association between opioid prescriptions nationally and poison center calls for adolescent opioid ingestions. This is particularly important in this patient population because of impulsivity and early exposure to substance abuse. Providers should be aware of the nonmedical use of opioids by adolescents and educate patients accordingly.

Impact of social media "challenges" on poison center case volume for intentional ingestions among school-aged children: an observational study.

INTRODUCTION: Mental health problems among youth have escalated over the past decade, with increased rates of self-harm, including suicide attempts by ingestion. Social media use has been linked to youth mental health, including "challenges" urging youth to ingest substances for recreational and other purposes. We hypothesized that social media challenges for particular substances would temporally correspond with increased ingestions of these substances. METHODS: We identified peak Google Trends search times for social media ingestion challenges involving diphenhydramine, laundry pods, nutmeg, and cinnamon, and used data from America's Poison Centers National Poison Data System to plot reported ingestions 3 months before and after peak searches in school-aged children. RESULTS: There were 2,169 individuals in the analysis. Diphenhydramine was the most frequently reported ingestion for misuse/abuse and suicidal purposes (n = 266 and 1,609, respectively). For all ingestions together, 45 percent (n = 979) had a moderate health effect, and 6.35 percent (n = 137) had a major health effect. Time of peak searches corresponded with increased ingestions for each substance. DISCUSSION: We found a temporal relationship between peak Google Trends searches for ingestion challenges and ingestions of that substance reported to United States poison centers. Compared to misuse/abuse ingestions, most suicidal ingestions peaked 1-2 months later, suggesting a public health opportunity for intervention. LIMITATIONS: This retrospective observational study does not establish causal effect. All data are a result of self-reporting of the exposures, which may lead to a reporting bias. Google Trends is not the only search engine and likely underestimates the true incidence of social media posts. CONCLUSIONS: Additional research is needed on the relationship between social media and youth mental health, particularly around "challenges" that place youths' health at risk. There may be opportunities for intervention to decrease medical and mental health sequelae of these challenges.

Methamphetamine-related psychiatric visits to an urban academic emergency department: an observational study.

BACKGROUND: Methamphetamine, a stimulant of abuse, is associated with a significant number of Emergency Department (ED) visits. Methamphetamine use may produce psychiatric symptoms including acute psychosis, depression, and anxiety disorders. STUDY OBJECTIVES: To characterize psychiatric emergencies either directly or indirectly attributable to methamphetamine use in an urban academic ED. METHODS: We analyzed a database of patients determined to have an ED visit that was either methamphetamine related or non-methamphetamine related. We retrospectively reviewed the records of the subset of ED visits from this database with psychiatric diagnoses. We compared the characteristics of patients with methamphetamine-related psychiatric visits (MRPVs) and non-methamphetamine-related psychiatric visits (non-MRPVs). RESULTS: We identified 130 patients with MRPVs. This represented 7.6% (130 of 1709) of all psychiatric visits. Patients with MRPV, compared to non-MRPV patients, were younger (34.4 years vs. 39.1 years, respectively, p = 0.0005), more likely to be uninsured (55% vs. 37%, respectively, p = 0.001), and less likely to have a past history of depression (10% vs. 19%, respectively, p = 0.011). Many characteristics between the two groups (MRPV vs. non-MRPV) were similar: likelihood of patient being placed on a psychiatric hold; hospital charges; previous histories of psychiatric visits; and history of anxiety, bipolar disorder, or schizophrenia. CONCLUSIONS: Methamphetamine may be related to a significant proportion (7.6%) of psychiatric ED visits. Furthermore, patients with methamphetamine-associated psychiatric visits are younger, have lower rates of depression, are more likely to be uninsured, and are less likely to have a substance abuse-related chief complaint than patients with non-methamphetamine-associated ED psychiatric visits.

Kratom: History, pharmacology, current user trends, adverse health effects and potential benefits.

Kratom (Mitragyna speciosa Korth.) is a tree native to Southeast Asia with dose-dependent stimulant and opioid-like effects. Dried, powdered leaf material is among the kratom products most commonly consumed in the US and Europe, but other formulations also exist including enriched extracts, resins, tinctures, and edibles. Its prevalence in the US remains debated and the use pattern includes self-treatment of mood disorders, pain, and substance use disorders. Most of the adverse effects of kratom and its alkaloid mitragynine have been reported in the literature as case reports or part of surveys necessitating confirmation by clinical trials. Toxicities associated with kratom consumption have focused on hepatic, cardiac, and CNS effects with the potential to cause fatalities primarily as part of polydrug exposures. Kratom may also present with drug-drug interactions primarily through CYP 3A4 and 2D6 inhibition, although the clinical significance remains unknown to date. The variability in composition of commercially available kratom products complicates generalization of findings and requires further investigation by employing clinical trials. Healthcare professionals should remain cautious in counseling patients on the use of kratom in a therapeutic setting.

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.

Management of Acetaminophen Poisoning in the US and Canada: A Consensus Statement.

Importance: The US and Canada currently have no formal published nationwide guidelines for specialists in poison information or emergency departments for the management of acetaminophen poisoning, resulting in significant variability in management. Objective: To develop consensus guidelines for the management of acetaminophen poisoning in the US and Canada. Evidence Review: Four clinical toxicology societies (America's Poison Centers, American Academy of Clinical Toxicology, American College of Medical Toxicology, and Canadian Association of Poison Control Centers) selected participants (n = 21). Led by a nonvoting chairperson using a modified Delphi method, the panel created a decision framework and determined the appropriate clinical management of a patient with acetaminophen poisoning. Unique to this effort was the collection of guidelines from most poison centers in addition to systematic collection and review of the medical literature. Comments from review by external organizations were incorporated before the guideline was finalized. The project began in March 2021 and ended in March 2023. Findings: The search retrieved 84 guidelines and 278 publications. The panel developed guidelines for emergency department management of single or repeated ingestion of acetaminophen. In addition, the panel addressed extended-release formulation, high-risk ingestion, coingestion of anticholinergics or opioids, age younger than 6 years, pregnancy, weight greater than 100 kg, and intravenous acetaminophen use. Differences from current US practice include defining acute ingestion as an ingestion presentation from 4 to 24 hours after overdose was initiated. A revised form of the Rumack-Matthew nomogram was developed. The term massive ingestion was replaced with the term high-risk ingestion and denoted by a specific nomogram line. Other recommendations include specific criteria for emergency department triage, laboratory evaluation and monitoring parameters, defining the role of gastrointestinal decontamination, detailed management of acetylcysteine treatment, associated adverse effects, and stopping criteria for acetylcysteine treatment, as well as criteria for consultation with a clinical toxicologist. Finally, specific treatment considerations, including acetylcysteine dosing, fomepizole administration, and considerations for extracorporeal elimination and transplant evaluation, were addressed. Conclusions and Relevance: This qualitative study provides a consensus statement on consistent evidence-based recommendations for medical, pharmacy, and nursing education and practice to optimize care of patients with acetaminophen poisoning.

Lipid emulsion therapy during management of the critically-ill poisoned patient: a prospective cohort study.

BACKGROUND: Despite conflicting data, intravenous lipid emulsion has emerged as a potential antidote. The "lipid sink" theory suggests that following intravenous administration of lipid, lipophilic drugs are sequestered in the vascular compartment, thereby reducing their tissue concentrations. This study sought to determine if survival is associated with the intoxicant's degree of lipophilicity. METHODS: We reviewed all cases in the Toxicology Investigators Consortium's lipid sub-registry between May 2012 through December 2018. Information collected included demographics, exposure circumstances, clinical course, management, disposition, and outcome. The primary outcome was survival after lipid emulsion therapy. Survival was stratified by the log of the intoxicant's octanol-water partition coefficient. We also assessed the association between intoxicant lipophilicity and an increase in systolic blood pressure after lipid emulsion administration. RESULTS: We identified 134 patients, including 81 (60.4%) females. The median age was 40 years (interquartile range 21-75). One hundred and eight (80.6%) patients survived, including 45 (33.6%) with cardiac arrest during their intoxication. Eighty-two (61.2%) were hypotensive, and 98 (73.1%) received mechanical ventilation. There was no relationship between survival and the log of the partition coefficient of the intoxicant on linear analysis (P = 0.89) or polynomial model (P = 0.10). Systolic blood pressure increased in both groups. The median (interquartile range) systolic blood pressure before lipid administration was 68 (60-78) mmHg for those intoxicants with a log partition coefficient < 3.6 compared with 89 (76-104) mmHg after lipid administration. Among those drugs with a log partition coefficient > 3.6, the median (interquartile range) was 69 (60-84) mmHg before lipid and 89 (80-96) mmHg after lipid administration. CONCLUSION: Most patients in this cohort survived. Lipophilicity was not correlated with survival or the observed changes in blood pressure. The study did not address the efficacy of lipid emulsion.