Cannabinoid toxicity in pediatrics.

PURPOSE OF REVIEW: The advent of legalized cannabis in multiple regions of the United States has rendered the drug more accessible to pediatric patients. Pediatricians and Pediatric Emergency Medicine Providers face new challenges in counseling both patients and their parents, diagnosing exploratory ingestions of cannabinoids in toddlers, and managing complications of prolonged, heavy cannabis use in adolescents. The purpose of this review article is to provide clinicians a succinct summary of recent literature regarding tetrahydrocannabinol (THC) pharmacokinetics, pharmacodynamics, impacts on development, as well as presentations of acute and chronic toxicity. RECENT FINDINGS: Many young children being admitted to the hospital for cannabis toxicity have been exposed to high concentration products, such as edibles, resins, or vaping fluid. These products contain extremely high concentrations of cannabinoids, and lead to sedation, respiratory depression, and other adverse effects. Chronic toxicity associated with cannabis consumption includes neurocognitive changes and cannabinoid hyperemesis syndrome. SUMMARY: Clinicians should provide guidance for pediatric patients and their caregivers to reduce the risk of accidental cannabis exposure, particularly with high concentration products. In addition, clinicians should consider chronic cannabis exposure when evaluating certain complaints, such as chronic vomiting or educational performance at school.

Development of a predictive algorithm for patient survival after traumatic injury using a five analyte blood panel.

Severe trauma can induce systemic inflammation but also immunosuppression, which makes understanding the immune response of trauma patients critical for therapeutic development and treatment approaches. By evaluating the levels of 59 proteins in the plasma of 50 healthy volunteers and 1000 trauma patients across five trauma centers in the United States, we identified 6 novel changes in immune proteins after traumatic injury and further new variations by sex, age, trauma type, comorbidities, and developed a new equation for prediction of patient survival. Blood was collected at the time of arrival at Level 1 trauma centers and patients were stratified based on trauma level, tissues injured, and injury types. Trauma patients had significantly upregulated proteins associated with immune activation (IL-23, MIP-5), immunosuppression (IL-10) and pleiotropic cytokines (IL-29, IL-6). A high ratio of IL-29 to IL-10 was identified as a new predictor of survival in less severe patients with ROC area of 0.933. Combining machine learning with statistical modeling we developed an equation ("VIPER") that could predict survival with ROC 0.966 in less severe patients and 0.8873 for all patients from a five analyte panel (IL-6, VEGF-A, IL-21, IL-29, and IL-10). Furthermore, we also identified three increased proteins (MIF, TRAIL, IL-29) and three decreased proteins (IL-7, TPO, IL-8) that were the most important in distinguishing a trauma blood profile. Biologic sex altered phenotype with IL-8 and MIF being lower in healthy women, but higher in female trauma patients when compared to male counterparts. This work identifies new responses to injury that may influence systemic immune dysfunction, serving as targets for therapeutics and immediate clinical benefit in identifying at-risk patients.

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.

The Potential Proconvulsant Effects of Cannabis: a Scoping Review.

INTRODUCTION: Cannabis' effect on seizure activity is an emerging topic that remains without consensus and merits further investigation. We therefore performed a scoping review to identify the available evidence and knowledge gaps within the existing literature on cannabis product exposures as a potential cause of seizures in humans. METHODS: A scoping review was conducted in accordance with the PRISMA Extension for Scoping Reviews guidelines. The PubMed and Scopus databases were searched over a 20-year period from the date of the database query (12/21/2020). Inclusion criteria were (1) English language original research articles, (2) inclusion of human subjects, and (3) either investigation of seizures as a part of recreational cannabinoid use OR of exogenous cannabinoids as a cause of seizures. RESULTS: A total of 3104 unique articles were screened, of which 68 underwent full-text review, and 13 met inclusion/exclusion criteria. Ten of 11 studies evaluating acute cannabis exposures reported a higher seizure incidence than would be expected based on the prevalence of epilepsy in the general and pediatric populations (range 0.7-1.2% and 0.3-0.5% respectively). The remaining two studies demonstrated increased seizure frequency and/or seizure-related hospitalization in recreational cannabis users and those with cannabis use disorder. CONCLUSIONS: This scoping review demonstrates that a body of literature describing seizures in the setting of cannabis exposure exists, but it has several limitations. Ten identified studies showed a higher than expected incidence of seizures in populations exposed to cannabis products. Based on the Bradford Hill criteria, delta-9 tetrahydrocannabinol (THC) may be the causative xenobiotic for this phenomenon.

Opioid Use and Driving Performance.

INTRODUCTION: The USA is in an opioid epidemic, with an increased number of individuals taking psychoactive drugs while executing the tasks of everyday life, including operating a motor vehicle. The pharmacology of opioids has been widely studied, but the effects of opioids on psychomotor function, driving performance, and the risk of motor vehicle collision remain less clear. Clinicians are faced with the challenge of controlling patient pain while also reconciling conflicting messages from the literature about how safe it is for their patients taking opioids to engage in potentially dangerous routine tasks. DISCUSSION: This review assesses the current literature regarding opioids as they relate to neurocognitive function, driving performance, and accident risk. Manuscripts are categorized by study context and subject matter: controlled experimental administration, illicit use, prescription use, retrospective forensic toxicology, and polydrug consumption. CONCLUSION: Illicit use, initiation of therapy, and opioid use in combination with other psychoactive medications are contexts most clearly associated with impairment of driving-related functions and/or operation of a motor vehicle. Clinicians should counsel patients on the risk of impairment when initiating therapy, when co-prescribing opioids and other psychoactive drugs, or when a patient is suspected of having an opioid use disorder.

SARS-CoV-2 Seroprevalence and Drug Use in Trauma Patients from Six Sites in the United States.

In comparison to the general patient population, trauma patients show higher level detections of bloodborne infectious diseases, such as Hepatitis and Human Immunodeficiency Virus. In comparison to bloodborne pathogens, the prevalence of respiratory infections such as SARS-CoV-2 and how that relates with other variables, such as drug usage and trauma type, is currently unknown in trauma populations. Here, we evaluated SARS-CoV-2 seropositivity and antibody isotype profile in 2,542 trauma patients from six Level-1 trauma centers between April and October of 2020 during the first wave of the COVID-19 pandemic. We found that the seroprevalence in trauma victims 18-44 years old (9.79%, 95% confidence interval/CI: 8.33 - 11.47) was much higher in comparison to older patients (45-69 years old: 6.03%, 4.59-5.88; 70+ years old: 4.33%, 2.54 - 7.20). Black/African American (9.54%, 7.77 - 11.65) and Hispanic/Latino patients (14.95%, 11.80 - 18.75) also had higher seroprevalence in comparison, respectively, to White (5.72%, 4.62 - 7.05) and Non-Latino patients (6.55%, 5.57 - 7.69). More than half (55.54%) of those tested for drug toxicology had at least one drug present in their system. Those that tested positive for narcotics or sedatives had a significant negative correlation with seropositivity, while those on anti-depressants trended positive. These findings represent an important consideration for both the patients and first responders that treat trauma patients facing potential risk of respiratory infectious diseases like SARS-CoV-2.

Drug-induced hyperlactatemia.

BACKGROUND: Hyperlactatemia is common in critically ill patients and has a variety of etiologies. Medication toxicity remains an uncommon cause that providers often fail to recognize. In this article, we review several medications that cause hyperlactatemia in either therapeutic or supratherapeutic dosing. When known, the incidence, mortality, pathophysiology, and treatment options are discussed. METHODS: We performed a literature search using PUBMED and Google Scholar for English language articles published after 1980 regarding medication induced hyperlactatemia and its management. Our search string resulted in 798 articles of which 138 articles met inclusion criteria and were relevant to the topic of our review. CONCLUSIONS: Hyperlactatemia is a relatively rare but life-threatening toxicity of various medication classes. Discontinuation of the drug is always advised, and some toxicities are subject to specific antidotal treatment. If there is no apparent medical cause for hyperlactatemia (sepsis, hypotension, hypoxia), clinicians should consider a toxicological etiology.

Macrophage response to cross-linked and conventional UHMWPE.

To prevent wear debris-induced osteolysis and aseptic loosening, cross-linked ultra-high molecular weight polyethylene's (UHMWPE) with improved wear resistance have been developed. Hip simulator studies have demonstrated very low wear rates with these new materials leading to their widespread clinical use. However, the biocompatibility of this material is not known. We studied the macrophage response to cross-linked UHMWPE (XLPE) and compared it to conventional UHMWPE (CPE) as well as other clinically used orthopaedic materials such as titanium-alloy (TiAlV) and cobalt-chrome alloy (CoCr). Human peripheral blood monocytes and murine macrophages, as surrogates for cells mediating peri-implant inflammation, were cultured onto custom designed lipped disks fabricated from the test materials to isolate cells. Culture supernatants were collected at 24 and 48h and analyzed for cytokines such as IL-1alpha, IL-1beta, TNF-alpha and IL-6. Total RNA was extracted from adherent cells and gene expression was analyzed using qualitative RT-PCR. In both in vitro models, macrophages cultured on cross-linked and conventional polyethylene released similar levels of cytokines, which were also similar to levels on control tissue culture dishes. Macrophages cultured on TiAlV and CoCr-alloy released significantly higher levels of cytokines. Human monocytes from all donors varied in the magnitude of cytokines released when cultured on identical surfaces. The variability in individual donor responses to TiAlV and CoCr surfaces may reflect how individuals respond differently to similar stimuli and perhaps reveal a predisposed sensitivity to particular materials.

Medical marijuana and driving: a review.

Medical marijuana remains a highly debated treatment regimen despite removal of state penalties against care providers prescribing the drug and patients treated with the drug in many areas of the USA. The utility of marijuana in specific medical conditions has been studied at length, but its effects on driving performance and risk of motor vehicle collision remain unclear. As with other medications that affect psychomotor function, the healthcare provider should be informed of the potential risks of driver safety prior to prescribing this psychotropic drug to give appropriate anticipatory guidance for appropriate use. The goal of this narrative review is to assess the current literature regarding marijuana as it relates to driving performance and traffic safety. With a foundation in the pharmacology of cannabinoids, we consider the limitations of testing cannabinoid and metabolite concentration. In addition, we will review studies on driving performance and epidemiological studies implicating marijuana in motor vehicle collisions. The increasing prevalence of medical marijuana laws in the USA suggests that clinicians should be aware of marijuana's influence on public safety. Patients should abstain from driving for 8 h if they achieve a subjective "high" from self-treatment with smoked marijuana and should be aware of the cumulative effects of alcohol and other psychoactive xenobiotics.

Sodium acetate as a replacement for sodium bicarbonate in medical toxicology: a review.

Sodium bicarbonate is central to the treatment of many poisonings. When it was placed on the FDA drug shortage list in 2012, alternative treatment strategies to specific poisonings were considered. Many hospital pharmacies, poison centers, and medical toxicologists proposed sodium acetate as an adequate alternative, despite a paucity of data to support its use in medical toxicology. The intention of this review is to educate the clinician on the use of sodium acetate and to advise them on the potential adverse events when given in excess. We conducted a literature search focused on the pharmacology of sodium acetate, its use as a buffer in pathologic acidemia and dialysis baths, and potential adverse events associated with excess sodium acetate infusion. It appears safe to replace sodium bicarbonate infusion with sodium acetate on an equimolar basis. The metabolism of acetate, however, is more complex than bicarbonate. Future prospective studies will be needed to confirm the efficacy of sodium acetate in the treatment of the poisoned patient.