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.

Predictors of severe outcome following opioid intoxication in children.

INTRODUCTION: While the opioid crisis has claimed the lives of nearly 500,000 in the U.S. over the past two decades, and pediatric cases of opioid intoxications are increasing, only sparse data exist regarding risk factors for severe outcome in children following an opioid intoxication. We explore predictors of severe outcome (i.e., intensive care unit [ICU] admission or in-hospital death) in children who presented to the Emergency Department with an opioid intoxication. METHODS: In this prospective cohort study we collected data on all children (0-18 years) who presented with an opioid intoxication to the 50 medical centers in the US and two international centers affiliated with the Toxicology Investigators Consortium (ToxIC) of the American College of Medical Toxicology, from August 2017 through June 2020, and who received a bedside consultation by a medical toxicologist. We collected relevant demographic, clinical, management, disposition, and outcome data, and we conducted a multivariable logistic regression analysis to explore predictors of severe outcome. The primary outcome was a composite severe outcome endpoint, defined as ICU admission or in-hospital death. Covariates included sociodemographic, exposure and clinical characteristics. RESULTS: Of the 165 (87 females, 52.7%) children with an opioid intoxication, 89 (53.9%) were admitted to ICU or died during hospitalization, and 76 did not meet these criteria. Seventy-four (44.8%) children were exposed to opioids prescribed to family members. Fentanyl exposure (adjusted OR [aOR] = 3.6, 95% CI: 1.0-11.6; p = 0.03) and age ≥10 years (aOR = 2.5, 95% CI: 1.2-4.8; p = 0.01) were independent predictors of severe outcome. CONCLUSIONS: Children with an opioid toxicity that have been exposed to fentanyl and those aged ≥10 years had 3.6 and 2.5 higher odds of ICU admission or death, respectively, than those without these characteristics. Prevention efforts should target these risk factors to mitigate poor outcomes in children with an opioid intoxication.

Systematic review on the use of activated charcoal for gastrointestinal decontamination following acute oral overdose.

INTRODUCTION: The use of activated charcoal in poisoning remains both a pillar of modern toxicology and a source of debate. Following the publication of the joint position statements on the use of single-dose and multiple-dose activated charcoal by the American Academy of Clinical Toxicology and the European Association of Poison Centres and Clinical Toxicologists, the routine use of activated charcoal declined. Over subsequent years, many new pharmaceuticals became available in modified or alternative-release formulations and additional data on gastric emptying time in poisoning was published, challenging previous assumptions about absorption kinetics. The American Academy of Clinical Toxicology, the European Association of Poison Centres and Clinical Toxicologists and the Asia Pacific Association of Medical Toxicology founded the Clinical Toxicology Recommendations Collaborative to create a framework for evidence-based recommendations for the management of poisoned patients. The activated charcoal workgroup of the Clinical Toxicology Recommendations Collaborative was tasked with reviewing systematically the evidence pertaining to the use of activated charcoal in poisoning in order to update the previous recommendations. OBJECTIVES: The main objective was: Does oral activated charcoal given to adults or children prevent toxicity or improve clinical outcome and survival of poisoned patients compared to those who do not receive charcoal?  Secondary objectives were to evaluate pharmacokinetic outcomes, the role of cathartics, and adverse events to charcoal administration. This systematic review summarizes the available evidence on the efficacy of activated charcoal. METHODS: A medical librarian created a systematic search strategy for Medline (Ovid), subsequently translated for Embase (via Ovid), CINAHL (via EBSCO), BIOSIS Previews (via Ovid), Web of Science, Scopus, and the Cochrane Library/DARE. All databases were searched from inception to December 31, 2019. There were no language limitations.  One author screened all citations identified in the search based on predefined inclusion/exclusion criteria. Excluded citations were confirmed by an additional author and remaining articles were obtained in full text and evaluated by at least two authors for inclusion. All authors cross-referenced full-text articles to identify articles missed in the searches. Data from included articles were extracted by the authors on a standardized spreadsheet and two authors used the GRADE methodology to independently assess the quality and risk of bias of each included study. RESULTS: From 22,950 titles originally identified, the final data set consisted of 296 human studies, 118 animal studies, and 145 in vitro studies. Also included were 71 human and two animal studies that reported adverse events. The quality was judged to have a Low or Very Low GRADE in 469 (83%) of the studies. Ninety studies were judged to be of Moderate or High GRADE. The higher GRADE studies reported on the following drugs: paracetamol (acetaminophen), phenobarbital, carbamazepine, cardiac glycosides (digoxin and oleander), ethanol, iron, salicylates, theophylline, tricyclic antidepressants, and valproate. Data on newer pharmaceuticals not reviewed in the previous American Academy of Clinical Toxicology/European Association of Poison Centres and Clinical Toxicologists statements such as quetiapine, olanzapine, citalopram, and Factor Xa inhibitors were included. No studies on the optimal dosing for either single-dose or multiple-dose activated charcoal were found. In the reviewed clinical data, the time of administration of the first dose of charcoal was beyond one hour in 97% (n = 1006 individuals), beyond two hours in 36% (n = 491 individuals), and beyond 12 h in 4% (n = 43 individuals) whereas the timing of the first dose in controlled studies was within one hour of ingestion in 48% (n = 2359 individuals) and beyond two hours in 36% (n = 484) of individuals. CONCLUSIONS: This systematic review found heterogenous data. The higher GRADE data was focused on a few select poisonings, while studies that addressed patients with unknown and or mixed ingestions were hampered by low rates of clinically meaningful toxicity or death.  Despite these limitations, they reported a benefit of activated charcoal beyond one hour in many clinical scenarios.

Acute pneumonitis associated with nickel carbonyl exposure in the workplace.

BACKGROUND: We describe the clinical course of one industrial technician occupationally exposed to nickel carbonyl (NiC). CASE REPORT: A 50-year-old male industrial technician presented with complaints of nausea, myalgia, and cough to a local clinic after suspected occupational exposure to nickel carbonyl. He has no history of lung disease or smoking. His initial urine nickel concentration was 692 ug/L. He had infiltrates on the initial chest X-ray (CXR) and an oxygen saturation (O2) of 97% on room air. The patient was started on disulfiram 1 g by mouth (PO), 500 mg six hours after the first dose, then 250 mg twice daily for five days with prednisone 60 mg by mouth for five days. He presented 48 hours later with worsening respiratory symptoms. His O2 saturation decreased to 85% despite two days of oral steroids, and he was admitted to a hospital. He received prednisone 60 mg/day PO, 4 L nasal O2, and disulfiram 500 mg twice daily. He was discharged on day 7 post-exposure with disulfiram and prednisone. Case discussions: NiC is a severe respiratory irritant. Disulfiram was used off-label and was based on an established company protocol. CONCLUSIONS: Inhalation exposure to NiC resulted in a delayed respiratory dysfunction which responded to disulfiram treatment.

Expert Consensus Guidelines for Stocking of Antidotes in Hospitals That Provide Emergency Care.

We provide recommendations for stocking of antidotes used in emergency departments (EDs). An expert panel representing diverse perspectives (clinical pharmacology, medical toxicology, critical care medicine, hematology/oncology, hospital pharmacy, emergency medicine, emergency medical services, pediatric emergency medicine, pediatric critical care medicine, poison centers, hospital administration, and public health) was formed to create recommendations for antidote stocking. Using a standardized summary of the medical literature, the primary reviewer for each antidote proposed guidelines for antidote stocking to the full panel. The panel used a formal iterative process to reach their recommendation for both the quantity of antidote that should be stocked and the acceptable timeframe for its delivery. The panel recommended consideration of 45 antidotes; 44 were recommended for stocking, of which 23 should be immediately available. In most hospitals, this timeframe requires that the antidote be stocked in a location that allows immediate availability. Another 14 antidotes were recommended for availability within 1 hour of the decision to administer, allowing the antidote to be stocked in the hospital pharmacy if the hospital has a mechanism for prompt delivery of antidotes. The panel recommended that each hospital perform a formal antidote hazard vulnerability assessment to determine its specific need for antidote stocking. Antidote administration is an important part of emergency care. These expert recommendations provide a tool for hospitals that offer emergency care to provide appropriate care of poisoned patients.

Position paper update: whole bowel irrigation for gastrointestinal decontamination of overdose patients.

CONTEXT: A position paper on the use of whole bowel irrigation (WBI) was first published in 1997 by the American Academy of Clinical Toxicology (AACT) and the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) and updated in 2004. The aims of this paper are to briefly summarize the content of the 2004 Position Paper and to present any new data and recommendations. METHODS: A systematic review of the literature from January 2003 to February 28, 2013 was conducted using multiple online databases for articles concerning WBI for gastrointestinal decontamination. An evidence table was created for applicable articles. The authors produced the initial draft that was reviewed by AACT and EAPCCT. RESULTS: The literature search produced 60 articles with the possibility of applicable human data. Based mainly on volunteer studies, WBI can be considered for potentially toxic ingestions of sustained-release or enteric-coated drugs particularly for those patients presenting later than 2 h after drug ingestion when activated charcoal is less effective. WBI can be considered for patients who have ingested substantial amounts of iron, lithium, or potassium as the morbidity is high and there is a lack of other potentially effective options for gastrointestinal decontamination. WBI can be considered for removal of ingested packets of illicit drugs in "body packers." However, controlled data documenting improvement in clinical outcome after WBI are lacking. WBI is contraindicated in patients with bowel obstruction, perforation, or ileus, and in patients with hemodynamic instability or compromised unprotected airways. WBI should be used cautiously in debilitated patients and in patients with medical conditions that might be further compromised by its use. The concurrent administration of activated charcoal and WBI might decrease the effectiveness of the charcoal. The clinical relevance of this interaction is uncertain. CONCLUSION: WBI can facilitate removal of select toxicants from the gastrointestinal tract in some patients, but there is no convincing evidence from clinical studies that it improves the outcome of poisoned patients. There is no new evidence that would require a major revision of the conclusions of the 2004 position statement.

Emergency department identification and critical care management of a Utah prison botulism outbreak.

STUDY OBJECTIVE: We report botulism poisoning at a state prison after ingestion of homemade wine (pruno). METHODS: This is an observational case series with data collected retrospectively by chart review. All suspected exposures were referred to a single hospital in October 2011. RESULTS: Twelve prisoners consumed pruno, a homemade alcoholic beverage made from a mixture of ingredients in prison environments. Four drank pruno made without potato and did not develop botulism. Eight drank pruno made with potato, became symptomatic, and were hospitalized. Presenting symptoms included dysphagia, diplopia, dysarthria, and weakness. The median time to symptom onset was 54.5 hours (interquartile range [IQR] 49-88 hours) postingestion. All 8 patients received botulinum antitoxin a median of 12 hours post-emergency department admission (IQR 8.9-18.8 hours). Seven of 8 patients had positive stool samples for type A botulinum toxin. The 3 most severely affected patients had respiratory failure and were intubated 43, 64, and 68 hours postingestion. Their maximal inspiratory force values were -5, -15, and -30 cm H2O. Their forced vital capacity values were 0.91, 2.1, and 2.2 L, whereas the 5 nonintubated patients had median maximal inspiratory force of -60 cm H2O (IQR -60 to -55) and forced vital capacity of 4.5 L (IQR 3.7-4.9). Electromyography abnormalities were observed in 1 of the nonintubated and 2 of the intubated patients. CONCLUSION: A pruno-associated botulism outbreak resulted in respiratory failure and abnormal pulmonary parameters in the most affected patients. Electromyography abnormalities were observed in the majority of intubated patients. Potato in the pruno recipe was associated with botulism.

Communication patterns for the most serious poison center calls.

CONTEXT. The communication demands faced by specialists in poison information (SPI) are unique in the health-care context. OBJECTIVES. (1) To describe SPI communication patterns for the highest risk poison exposure calls using cluster analysis, and (2) to describe variation in communication patterns or clusters. METHODS. A sample of 1 year of poison exposure calls to a regional poison control center with SPIs' perceived severity rating of major or moderate perceived was collected. Digital voice recordings were linked with medical records and were coded using the Roter Interaction Analysis System. Descriptive analyses were applied, and cluster-analytic techniques were used to assess variation in call communication and factors associated with that variation. RESULTS. Cases were described, and four communication styles were identified. The informational cluster represents calls with relatively high levels of SPI clinical information and caller questions. The Facilitative cluster represents calls with a pattern of relatively high SPI questions and caller information provision. The Planning cluster represents calls with relatively high levels of SPI relationship talk. The Emotional cluster represents calls with relatively high caller and SPI emotion. Further analyses revealed relationships between call characteristics, SPI identity, and cluster membership. CONCLUSION. This study provides a beginning step to understanding SPI communication behaviors. Our results suggest that SPIs are able to use a range of communication strategies that often involve not only information but also emotional responsiveness and rapport building. Findings also point to the opportunity for future communication training for SPIs to meet the needs of the heterogeneous caller population.

Black widow spider envenomation in pregnancy.

OBJECTIVE: Little data exist regarding the optimal treatment and outcomes of pregnancies complicated by black widow spider envenomation. Our objective is to evaluate the clinical effects, medical outcomes, and treatment differences between pregnant and nonpregnant women. METHODS: This observational study is based on a review of the database maintained by the American Association of Poison Control Centers from 2003 to 2007. RESULTS: Of the 12,640 human black widow spider envenomations reported at 61 poison centers in the United States, 3194 (25.3%) involved women of reproductive age, defined as age 15-45 years of age, with 97 (3.0% of reproductive-age women) being pregnant. Comparing pregnant and nonpregnant women, there were no significant differences in recommended or administered treatments. Pregnant women were more likely than nonpregnant women (OR: 1.84, 95% CI: 1.20-2.83) to have outcomes coded as minor, moderate, or major rather than no effect. Significantly higher percentages of pregnant patients were treated at a healthcare facility where they were either released (36.1% vs. 19.9%, p < 0.001) or admitted (13.4% vs. 4.0%, p < 0.001), than nonpregnant women. There were no documented pregnancy losses. CONCLUSIONS: Black widow spider envenomation is a rare occurrence in pregnant women and the short-term outcomes appear to be favorable.

Rapid urine drug screens: diphenhydramine and methadone cross-reactivity.

BACKGROUND: Rapid urine screens to detect drugs of abuse are often used in pediatric emergency departments (PEDs). A positive result may lead to further clinical testing, social evaluation, and increased stress/inconvenience. A PED patient with suspected diphenhydramine (DPH) ingestion had a positive methadone result on the rapid urine drug screen, One Step Multi-Drug, Multi-Line Screen Test Device (ACON Laboratories, San Diego, Calif). There was no history of methadone exposure so the patient was admitted while confirmatory testing was performed. Gas chromatography/mass spectroscopy testing of the urine failed to confirm the presence of methadone. We present this unreported false-positive methadone result and evaluation of the kit for cross-reactivity of DPH and methadone. METHODS: The same One Step urine drug screen was tested at an independent laboratory for cross-reactivity between methadone and DPH including the DPH metabolites. Drug-free urine was fortified with DPH, nordiphenhydramine, or dinordiphenhydramine at 0, 10, 25, 50, and 100 µg/mL for each analyte. One hundred microliters of the solutions were added to each of the 4 wells on test cassettes. Urine was allowed to migrate according to manufacturer instructions. Each cassette was interpreted by 2 analysts to ensure consistent interpretation and accurate data recording. RESULTS: In vitro laboratory testing results showed cross-reactivity between methadone and DPH but not for nordiphenhydramine or dinordiphenhydramine. CONCLUSIONS: Rapid urine drug screens using immunoassays based on the principle of competitive binding may show false-positive methadone results for patients who have ingested DPH. Product information for urine drug screens may not include all cross-reacting agents and should be used with caution when interpreting drug screen results in PED patients.

The abuse potential of propofol.

CONTEXT: Propofol is a sedative-hypnotic prescription medication that is widely used in anesthesia, long-term sedation, and conscious sedation. It is short acting, effective, and, when used appropriately, safe. It is not a controlled substance by the U.S. Drug Enforcement Administration, suggesting that it has little potential for abuse. The objective of this review was to evaluate the evidence for the abuse potential of propofol. METHODS: A systematic review of the medical literature was performed using the search terms: propofol, Diprivan, abuse, addiction, tolerance, misuse, and withdrawal. Six online literature citation databases and relevant bibliographies were searched for articles. RESULTS: Seventy-two articles were identified for review and 45 were relevant to the topic. These articles described propofol's biochemical and pharmacokinetic mechanisms of action that lend themselves to its abuse, propofol's physical and psychological effects that make it alluring as a recreational drug, the current evidence supporting the possibility of tolerance to and withdrawal from propofol, the risk involved in recreational propofol use, and the evidence supporting current abuse of this medication. We found evidence to support propofol's abuse potential from a pharmacological and experiential standpoint with multiple reports describing tolerance, dependence, withdrawal phenomena, abuse, and death from recreational use. CONCLUSIONS: Propofol has alluring and addictive properties that lend itself to potential recreational abuse and dependence. We recommend that the U.S. Drug Enforcement Administration and other international agencies should consider regulating propofol as a controlled substance.

Breath alcohol analyzer mistakes methanol poisoning for alcohol intoxication.

Breath alcohol analyzers are used to detect ethanol in motorists and others suspected of public intoxication. One concern is their ability to detect interfering substances that may falsely increase the ethanol reading. A 47-year-old-man was found in a public park, acting intoxicated. A breath analyzer test (Intoxilyzer 5000EN) measured 0.288 g/210 L breath ethanol, without an interferent noted. In the emergency department, the patient admitted to drinking HEET Gas-Line antifreeze, which contains 99% methanol. Two to three hours after ingestion, serum and urine toxicology screen results were negative for ethanol and multiple other substances. His serum methanol concentration was 589 mg/dL, serum osmolality 503 mOsm/kg, osmolar gap 193 mOsm/kg, and anion gap 17 mmol/L. The patient was treated with intravenous ethanol, fomepizole, and hemodialysis without complication. This is a unique clinical case of a breath alcohol analyzer reporting methanol as ethanol. Intoxilyzer devices have been shown to indicate some substances (acetone) as interferents in humans but not methanol. Increased serum concentrations of methanol can be reported as ethanol by a commonly used breath alcohol analyzer, which can result in a delayed diagnosis or misdiagnosis and subsequent methanol toxicity if antidotal treatment is not administered in a timely manner.

Specialist discrimination of toxic exposure severity at a poison control center.

BACKGROUND: Perceived severity has been shown to affect decision-making processes in telephone triage. However, the accuracy of specialists in poison information's (SPIs') perceptions of severity of poison exposures is unknown. OBJECTIVE: The purpose of this study was to describe the ability of SPIs to predict severity of medical outcome on the basis of the information obtained during the initial poison control center's phone call. METHODS: This study analyzed 22,576 cases of human poison exposure in one regional poison control center. At the time of the initial call, SPIs assigned a predicted severity rating. SPIs then assigned a medical outcome rating when closing each case. Animal exposures not coded, not followed, and confirmed nonexposures were excluded. RESULTS: For overall SPI's discrimination of more severe versus less severe cases, A(z) = 0.94 with asymmetric 95% confidence intervals (0.87, 0.97), indicating excellent discrimination. The sensitivity of SPIs in discriminating a major effect from any other effect was 0.62. The false-negative rate for discrimination of a moderate, major, or fatal effect from a minor effect or no effect was 0.32, with sensitivity = 0.68. CONCLUSIONS: The overall ability of the SPIs to predict exposure severity is excellent but less accurate with less frequently encountered, more severe cases. A better understanding of SPI's decision-making processes, including the relationship between perceived severity and decision-making strategies, is necessary for the development of educational strategies and decision support technologies.

Building knowledge for poison control: the novel pairing of communication analysis with data mining methods.

As information systems become increasingly integrated with health care delivery, vast amounts of clinical data are stored. Knowledge discovery and data mining methods are potentially powerful for the induction of knowledge models from this data relevant to nursing outcomes. However, an important barrier to the widespread application of these methods for induction of nursing knowledge models is that important concepts relevant to nursing outcomes are often unrepresented in clinical data. For instance, communication approaches are not necessarily consciously chosen by nurses, yet they are known to impact multiple clinical outcomes including satisfaction, pain and symptom response, recovery, physiological change (e.g., blood pressure), and adherence. Decisions about communication behaviors are likely intuitive and instantaneously made in response to cues offered by the patient. For this reason, among others, important choices and actions of nurses are not routinely documented. And so for many clinical outcomes relevant to nursing, important concepts such as communication are not represented in clinical data repositories. In studying poison control center outcomes, it is important to consider not only routinely documented clinical data, but the communication processes and verbal cues of both patient and SPI. In a novel approach, our current study of poison control center outcomes pairs a qualitative study of the communication patterns of SPIs and callers to a regional poison control center, with predictive modeling of poison control center outcomes using knowledge discovery and data mining methods. This three year study, currently in progress, pairs SPI-caller communication analysis with predictive models resulting from the application of knowledge discovery and data mining methods to three years' of archived clinical data. The results will form a hybrid model and the basis for future decision support interventions that leverage knowledge about both implicit and explicit factors that contribute to poison control center outcomes.

Requirements analysis for HL7 message development in poison control center.

HL7 is the commonly accepted messaging standard for achieving interoperability among information systems. Until now, no analysis has been done on how poison control data can be matched in HL7 messages. The purpose of this study was to create a preliminary domain analysis model which can be used to identify the data required to message poison control data in HL7 messages.