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.

Intramuscular versus Intraosseous Delivery of Nerve Agent Antidote Pralidoxime Chloride in Swine.

OBJECTIVE: Exposure to nerve agents requires prompt treatment. We hypothesized that intraosseous (IO) injections of drug antidotes into the vascularized bone marrow will provide a more rapid and effective means to treat exposure to nerve agents than standard intramuscular (IM) injections. We compared the pharmacokinetics of IM and IO administration of pralidoxime chloride (2-PAM Cl) during normovolemia and hypovolemia, as well as their combined administration during normovolemia in swine. METHODS: Ten normovolemic swine were randomly administered 2 mL, 660 mg 2-PAM Cl via the IM or IO route and monitored for 180 minutes. IM versus IO also was compared in 8 hypovolemic swine bled to a mean arterial pressure of 50 mmHg. In a combined group, an IO injection was administered followed by an IM injection 60 minutes later. Blood samples were collected at times over a 180-minute period to calculate standard pharmacokinetic variables to compare the 2 routes of administration. RESULTS: In the normovolemic swine, IM injection achieved therapeutic levels (4 µg/mL) in 2 minutes, whereas IO infusion achieved these levels in less than 15 seconds. 2-PAM-Cl concentrations fell below these levels at 60 minutes post-injection in both groups. In the hypovolemic swine, IM injection achieved therapeutic levels in 4 minutes compared to less than 15 seconds in the IO group. 2-PAM-Cl concentrations fell below therapeutic levels at 12 and 90 minutes post-injection in the IM and IO groups, respectively. In the combined IO-IM treatment, plasma levels remained above therapeutic levels for the entire experiment and had two concentration peaks that corresponded to IO and IM injections. CONCLUSIONS: The IO route for the delivery of 2-PAM Cl provides a significant time and high initial blood concentrations advantage compared to the IM route for the prehospital treatment of nerve agent exposure even under hypovolemic conditions. The initial concentration peak associated with IO, but not IM, may provide greater initial therapy at the most critical time.

The use and tolerability of Crotalidae Polyvalent Immune FAB (Ovine) in pediatric envenomations.

There are limited data on the use of Crotalidae Polyvalent Immune FAB-Ovine (CroFab) in the management of crotalid envenomations in children. Thus, the primary objective of this retrospective chart review was to evaluate the safety and tolerability of CroFab in a pediatric population. Over an 8-year time period at this institution, there were 204 admissions for snakebite of which 82 received CroFab. Children who received CroFab were more often associated with bites to the hands and fingers and tended to have more significant envenomations as indicated by longer hospital stays, greater tissue injury, and a tendency to require surgery more often. Six (7.3%) of the 82 patients who received CroFab experienced an adverse drug reaction. Reactions consisted of allergic symptoms that were mild, responded to minimal interventions, and did not limit the subsequent use of CroFab. It is concluded that CroFab use is typically well tolerated in pediatric patients.

Fever and antipyretic use in children.

Fever in a child is one of the most common clinical symptoms managed by pediatricians and other health care providers and a frequent cause of parental concern. Many parents administer antipyretics even when there is minimal or no fever, because they are concerned that the child must maintain a "normal" temperature. Fever, however, is not the primary illness but is a physiologic mechanism that has beneficial effects in fighting infection. There is no evidence that fever itself worsens the course of an illness or that it causes long-term neurologic complications. Thus, the primary goal of treating the febrile child should be to improve the child's overall comfort rather than focus on the normalization of body temperature. When counseling the parents or caregivers of a febrile child, the general well-being of the child, the importance of monitoring activity, observing for signs of serious illness, encouraging appropriate fluid intake, and the safe storage of antipyretics should be emphasized. Current evidence suggests that there is no substantial difference in the safety and effectiveness of acetaminophen and ibuprofen in the care of a generally healthy child with fever. There is evidence that combining these 2 products is more effective than the use of a single agent alone; however, there are concerns that combined treatment may be more complicated and contribute to the unsafe use of these drugs. Pediatricians should also promote patient safety by advocating for simplified formulations, dosing instructions, and dosing devices.

The development of a competency-based assessment rubric to measure resident milestones.

BACKGROUND: The outcomes-based assessment rubric is a novel systematic instrument for documenting improvement in clinical learning. APPROACH: This article describes the development of a rubric aimed at introducing specific performance indicators to measure the Accreditation Council for Graduate Medical Education competencies. RESULTS: The potential benefits and implications for medical education include specifying performance indicators and outcomes, ensuring that assessment is coherent and consistent for all residents, measuring resident outcomes based on real-life criteria, providing opportunities for residents to demonstrate proficiency in a specific competency and outcome level, and improving the quality of assessment.

Incorporating the ACGME educational competencies into morbidity and mortality review conferences.

BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME) mandates that residents be trained in six core educational competencies. Practice-based learning and improvement (PBLI), one of the six competencies, is defined as the investigation and evaluation of one's own patient care. Morbidity and Mortality Conference, a frequently used venue to review the clinical outcome of hospitalized patients, provides the opportunity to teach and assess PBLI. DESCRIPTION: We report an approach to Morbidity and Mortality Conference that includes a systematic analysis of the ACGME core competencies and their application to a clinical case, a regular review of the factors that defines high-quality patient care, and a focused discussion of the PBLI competency. EVALUATION: Preliminary data indicate that our residents preferred this revised method for conducting Morbidity and Mortality Conference. CONCLUSION: Our adaptation to Morbidity and Mortality Conference provides a systematic review of the core competencies and their relevance to clinical decision making, with the ultimate goal of improving patient care.

Cytokines and toxicity in acetaminophen overdose.

Several cytokines have been reported to have hepatoprotective properties in animal models of acetaminophen toxicity. To investigate the relationships of cytokines and toxicity in acetaminophen overdose, blood samples were collected from patients following acute ingestions of acetaminophen. Samples for cytokine analysis were collected at the time of routine clinical monitoring in 111 patients (90 females; mean age 13.6 years). Plasma concentrations of interleukin 6, interleukin 8, interleukin 10, and monocyte chemoattractant protein 1 were analyzed by enzyme-linked immunosorbent assay. Patients were stratified by toxicity severity, defined by the maximal values of hepatic transaminase elevation. Levels of interleukin 6, interleukin 8, and monocyte chemoattractant protein 1 were higher in patients with serum alanine aminotransferase > 1000 IU/L, and monocyte chemoattractant protein 1 had the strongest association with toxicity. Monocyte chemoattractant protein 1 values were higher in patients with greater delays in N-acetylcysteine treatment and in patients with higher values of prothrombin time. Monocyte chemoattractant protein 1 elevation in acetaminophen overdose may represent an innate, immunomodulary response of the liver to earlier events in the toxicity. An understanding of the role of cytokine responses in acetaminophen overdose may be relevant to the future development of new therapies for acetaminophen toxicity.

Validation of a liquid chromatographic method for the determination of ibuprofen in human plasma.

A simple, rapid method of determining the ibuprofen concentration in small volumes of human plasma (50 microl) by HPLC was developed. The sample was prepared for injection using a solid-phase extraction method, with naproxen as the internal standard. A 96-well extraction plate was used, easing sample preparation and allowing the simultaneous extraction of multiple plasma samples directly into the HPLC injection vials. Samples were stable at room temperature for at least 48 h prior to injection. The HPLC method used an ultraviolet detector with a 5-min run time and measured concentrations across the range typically seen with the clinical use of this drug. The calibration curve was linear across the concentration range of 0.78-100 microg/ml with a limit of quantitation (LOQ) of 1.56 microg/ml. The coefficient of variation for intra-day and inter-day precision was 6% or less with accuracies within 2% of the nominal values for low (4.5 microg/ml), medium (40 microg/ml) and high (85 microg/ml) ibuprofen concentrations. For ibuprofen concentrations at the LOQ, the intra-day and inter-day precision and accuracy were within 10 and 15%, respectively. Recovery was 87% or greater for ibuprofen. This method was used to analyze plasma samples for unknown ibuprofen concentrations in bioequivalence and limited food effect studies of different formulations of ibuprofen. Thus, this method has been fully validated and used in the analysis of unknown plasma samples for ibuprofen.

Predictors of outcome after acetaminophen poisoning in children and adolescents.

OBJECTIVE: Shortened courses of N-acetylcysteine may be acceptable in patients with acetaminophen poisoning who are at low risk for toxicity. The goal of this study was to determine which clinical findings best identified patients at lowest risk for acetaminophen-related hepatotoxicity after an acute overdose. STUDY DESIGN: This was a retrospective analysis, throughout 10 years, of hospital admissions for acute acetaminophen poisoning, with inclusion criteria being an acetaminophen concentration above the possible toxicity line by nomogram, arrival within 24 hours, and an initial prothrombin time (PT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) measured within 24 hours of ingestion. Clinical parameters capable of identifying patients most and least likely to have hepatotoxicity were evaluated by using sensitivity and specificity testing. RESULTS: Of 95 patient charts identified, 41 met all inclusion criteria, with 16 patients having hepatotoxicity. PT, AST, and ALT within the first 24 hours postingestion did not identify all patients who had hepatotoxicity. The best predictor of a low risk of toxicity was the presence of normal values for the PT, AST, or ALT within 48 hours of ingestion. CONCLUSIONS: These data suggest that all patients with an acute acetaminophen overdose should be observed and treated for at least 48 hours postingestion.