Approach to the Poisoned Patient.

Audience: This video lecture is appropriate for emergency medical providers who are not comfortable with initial assessment of poisoned patients. Ideal learners include medical students and residents. Introduction: Poisoning is the leading cause of injury-related mortality in the United States, with more than 40,000 deaths annually.1 Of all ED injury-related visits, 2.4% are related to poisoning.2 While providers may have access to support services (poison control center, medical toxicology consulting service), they are often responsible for the initial evaluation of poisoned patients. While a large portion of poisoned patients have good outcomes regardless of the care they receive, inappropriate risk assessment and lack of knowledge about basic interventions can put patients at risk. A standardized approach as outlined in the video will help evaluate and treat the vast majority of poisoned patients. Educational Objectives: By the end of the lecture, learners should be able to: 1) initiate the evaluation of a poisoned patient, 2) identify key interventions to support airway, breathing, and circulation, 3) identify the three components of risk assessment in the poisoned patient, 4) list the four options for gastric decontamination, and 5) select standard diagnostic labs and tests commonly used in evaluating poisoned patients. Educational Methods: This is an enhanced live action greenscreen recording with video animation. Research Methods: This video has been made available for a variety of learners on social medial (Facebook and YouTube) and written feedback has been collected on YouTube. Results: The video has been seen over three thousand times and has received positive comments on social media (Facebook, YouTube). Comments include "dropping some tox knowledge bombs, proving yet again that #ToxRocks," and "This is an excellent talk, thank you very much, but I think it would be worth mentioning antidotes." Discussion: The goal is to expose learners to basic concepts in approaching poisoned patients and focusses on cognitive knowledge and diagnostic frameworks. The learner may watch the on-demand video as part of a flipped classroom experience with clinical cases, or as a just-in-time resource before seeing a patient who has been poisoned. Topics: Poisoning, resuscitation, risk assessment, gastric decontamination, occult ingestion, supportive care.

Serum Acetaminophen Protein Adduct Concentrations in Pediatric Emergency Department Patients.

OBJECTIVES: Acetaminophen toxicity is a common cause of pediatric liver failure. The diagnosis may be limited by the short window of detection of acetaminophen in serum. Recently acetaminophen protein adducts (APAP-CYS) have been used as a biomarker with a longer duration of detection. The objective of this study was to describe the serum concentrations of APAP-CYS in pediatric patients with and without reported therapeutic acetaminophen exposure. METHODS: A cross-sectional study of children age 1 to <12 years presenting to a pediatric emergency department. Subjects were stratified by recent acetaminophen use and had serum APAP-CYS measured using LC/MS. RESULTS: One hundred patients were enrolled. All of the patients whose caregivers denied acetaminophen exposure had nondetectable APAP-CYS. Fifty-two percent of subjects who were reported to have taken acetaminophen in the preceding 2 weeks had detectable serum APAP-CYS. The APAP-CYS concentrations were positively correlated with higher overall dose and more recent ingestion. CONCLUSIONS: APAP-CYS is detectable in the majority of children taking acetaminophen and not detected in the majority of children who are not exposed to acetaminophen.

Cyclic vomiting presentations following marijuana liberalization in Colorado.

OBJECTIVES: Case reports have described a syndrome of cyclic vomiting associated with chronic marijuana use, termed cannabinoid hyperemesis syndrome. The primary objective was to determine the prevalence of patients presenting with cyclic vomiting before and after the liberalization of medical marijuana in Colorado in 2009. The secondary objective was to describe the odds of marijuana use among cyclic vomiting visits in these same time periods. METHODS: This was a cross-sectional study of cyclic vomiting visits to the emergency department (ED) before and after marijuana liberalization. ED visits with International Classification of Diseases, ninth revision, coding for cyclic vomiting or that met diagnostic criteria for cyclic vomiting by the Rome III criteria were included. RESULTS: The authors reviewed 2,574 visits and identified 36 patients diagnosed with cyclic vomiting over 128 visits. The prevalence of cyclic vomiting visits increased from 41 per 113,262 ED visits to 87 per 125,095 ED visits after marijuana liberalization, corresponding to a prevalence ratio of 1.92 (95% confidence interval [CI] = 1.33 to 2.79). Patients with cyclic vomiting in the postliberalization period were more likely to have marijuana use documented than patients in the preliberalization period (odds ratio = 3.59, 95% CI = 1.44 to 9.00). CONCLUSIONS: The prevalence of cyclic vomiting presentations nearly doubled after the liberalization of medical marijuana. Patients presenting with cyclic vomiting in the postliberalization period were more likely to endorse marijuana use, although it is unclear whether this was secondary to increased marijuana use, more accurate marijuana reporting, or both.

The effect of CYP2D6 drug-drug interactions on hydrocodone effectiveness.

OBJECTIVES: The hepatic cytochrome 2D6 (CYP2D6) is a saturable enzyme responsible for metabolism of approximately 25% of known pharmaceuticals. CYP interactions can alter the efficacy of prescribed medications. Hydrocodone is largely dependent on CYP2D6 metabolism for analgesia, ondansetron is inactivated by CYP2D6, and oxycodone analgesia is largely independent of CYP2D6. The objective was to determine if CYP2D6 medication coingestion decreases the effectiveness of hydrocodone. METHODS: This was a prospective observational study conducted in an academic U.S. emergency department (ED). Subjects were included if they had self-reported pain or nausea and were excluded if they were unable to speak English, were less than 18 years of age, had liver or renal failure, or carried diagnoses of chronic pain or cyclic vomiting. Detailed drug ingestion histories for the preceding 48 hours prior to the ED visit were obtained. The patient's pain and nausea were quantified using a 100-mm visual analog scale (VAS) at baseline prior to drug administration and following doses of hydrocodone, oxycodone, or ondansetron. We used a mixed model with random subject effect to determine the interaction between CYP2D6 drug ingestion and study drug effectiveness. Odds ratios (ORs) were calculated to compare clinically significant VAS changes between CYP2D6 users and nonusers. RESULTS: A total of 250 (49.8%) of the 502 subjects enrolled had taken at least one CYP2D6 substrate, inhibitor, or inducing pharmaceutical, supplement, or illicit drug in the 48 hours prior to ED presentation. CYP2D6 drug users were one-third as likely to respond to hydrocodone (OR = 0.33, 95% confidence interval [CI] = 0.1 to 0.8) and more than three times as likely as nonusers to respond to ondansetron (OR = 3.4, 95% CI = 1.3 to 9.1). There was no significant difference in oxycodone effectiveness between CYP2D6 users and nonusers (OR = 0.53, 95% CI = 0.3 to 1.1). CONCLUSIONS: CYP2D6 drug-drug interactions appear to change effectiveness of commonly prescribed drugs in the ED. Drug-drug interaction should be considered prior to prescribing CYP2D6 drugs.

Acetylcysteine for acetaminophen overdose in patients who weigh >100 kg.

N-Acetylcysteine (NAC) dosing for acetaminophen (APAP) overdose is weight based (150 mg/kg intravenous or 140-mg/kg oral loading dose) and, in the United States, the dosing protocol recommends using a maximum patient weight of 100 and 110 kg, respectively. Little clinical data describe the use of NAC for APAP poisoning in patients weighing >100 kg. The aim of this study was to describe the demographics, outcomes, and adverse event (AE) rates of patients weighing >100 kg treated with oral or IV NAC for APAP poisoning. Patients were identified from a multicenter retrospective NAC safety study for APAP overdose. We included patients with a recorded weight. Trained chart abstractors used a standardized form. Selected data included age, gender, weight, serum alanine transaminase, and aspartate transaminases, coingestants, NAC administration route, ingestion type, AEs, and outcome [hepatotoxicity (alanine transaminase > 1000 U/L), liver transplant, or death]. Descriptive statistics were used. Of 503 study patients, 37 (7.4%) had recorded weights >100 kg. The median (range) weight was 110 kg (101-160). The median (range) dosing for patients treated with oral NAC was 140 mg/kg (127-143 mg/kg) and 150 (108-168) mg/kg for IV NAC. Hepatotoxicity occurred in 12/36 (33.3%) patients. Death occurred in 4/36 (11.1%) patients. Thirteen NAC-related AEs occurred in 8 patients (1.6 per person). All AEs were related to NAC and were rated nonserious by the reviewer. Clinicians use an actual weight-based NAC dose rather than a maximum weight cutoff dose. Hepatotoxicity was common in our cohort. AEs were relatively common but not serious.

Unintentional pediatric exposures to central alpha-2 agonists reported to the National Poison Data System.

OBJECTIVE: To investigate national trends in unintentional pediatric exposures to 3 common alpha-2 agonists: clonidine, guanfacine, and tizanidine. Secondary objectives were to describe outcomes, symptoms, treatments, and death. STUDY DESIGN: Retrospective chart review from the American Association of Poison Control Centers National Poison Data System from January 2000 to December 2011 for unintentional exposure to clonidine, guanfacine, and tizanidine in children ≤ 12 years of age. RESULTS: From 2000-2011, there was a significant increase (5.9% per year, CI 3.6, 8.2) in unintentional pediatric exposures to National Poison Data System for central alpha-2 agonists. There were 27,825 clonidine exposures (67.3% male, median age: 4 years), 6143 guanfacine exposures (69.8% male, median age: 6 years), and 856 tizanidine exposures (51.9% male, median age: 2 years). Guanfacine had the greatest proportional increase among the medications. Clonidine was associated with the most respiratory (799, 2.9%) and central nervous system symptoms (12,612, 45.3%), as well as the most episodes of bradycardia (2847, 10.2%) and hypotension (2365, 8.5%). Seven-hundred twenty-eight (2.0%) patients were intubated, and 141 patients (0.5%) were administered vasopressors. There were 7 cardiac arrests and 3 deaths from clonidine. CONCLUSIONS: The number of unintentional pediatric exposures to alpha-2 agonists increased from 2000-2011. Clonidine exposures were the most commonly reported, more symptomatic, and associated with 3 deaths. Despite central nervous system depression, bradycardia, and hypotension being common, the need for intubation and vasopressors was rare.

Fatal cesium chloride toxicity after alternative cancer treatment.

BACKGROUND: Cesium chloride (CsCl) is sold as a treatment for several types of cancers. The purported mechanism of action is alkalinization of relatively acidic neoplastic cells. The efficacy of CsCl has not been demonstrated in controlled experiments. Oral and intravenous CsCl use has been associated with seizures, cardiotoxicity, syncope, and death. Although intratumoral treatment with various antineoplastic agents is described, no cases of intratumoral cancer treatment with CsCl have been found in the medical literature. The case described here appears to be of the first reported patient with CsCl toxicity secondary to subcutaneous exposure after attempted intratumoral injection. CASE DETAILS: A 61-year-old woman presented in cardiac arrest 20 hours after injecting 9 mL of an oral CsCl preparation around a mass in her breast. She had been taking the CsCl orally for approximately 1 year to treat her breast mass. The patient had a headache and nausea for several hours after injection and then experienced ventricular tachycardia arrest at home. She received advanced cardiac life support care and multiple antiarrhythmic medications and underwent electrical cardioversion early in the course of the arrest. After stabilization, her electrocardiogram revealed QT interval prolongation to >700 milliseconds. Upon discovery of her CsCl exposure, she was treated with Prussian blue. Her initial whole blood cesium level was 100,000 µg/L (reference range <10 µg/L). Her QT prolongation resolved after several days, but she experienced no meaningful postarrest neurologic recovery and died at home less than a week after exposure. DISCUSSION: CsCl is sold as an alternative treatment for cancer. There is no demonstrable efficacy, and clear evidence shows life-threatening toxicity. Reported here is a case of fatal CsCl toxicity after attempted intratumoral injection.

The effect of amiodarone pretreatment on survival of mice with cocaine toxicity.

INTRODUCTION: Cocaine is a common drug of abuse and use has been associated with ventricular dysrhythmias. Published guidelines suggest that amiodarone is the first line antidysrhythmic for ventricular tachycardia and fibrillation. However, the effects amiodarone in the setting of cocaine toxicity are unknown and unstudied. The purpose of this study was to evaluate the safety and efficacy of amiodarone pretreatment in a murine model of acute cocaine toxicity. METHODS: This was a randomized, blinded, placebo controlled investigation using male CF-1 mice weighing 29-37 g. First, the safety of an intraperitoneal dose of amiodarone (40 mg/kg) was confirmed in 5 mice. Second, based on preliminary investigations, an approximate intraperitoneal LD50 dose of cocaine (110 mg/kg) was identified and used as the cocaine dose in this study. Animals were then randomized to 2 groups. The control group received 0.5 mL of intraperitoneal 0.9% saline 30 minutes before cocaine. The study group received 40 mg/kg of intraperitoneal amiodarone (40 mg/kg) 30 minutes before cocaine. A blinded observer monitored mice for 2 hours after cocaine administration. RESULTS: No mice in the amiodarone-only group developed any signs of toxicity or died. In the saline + cocaine group 31/32 (96.9%; 95% CI 83.8 to 99.9) mice seized with a median time to seizure of 2.5 minutes, and 23/32 (71.9%; 95% CI 52.3 to 86.3) died with a median time to death of 5.5 minutes. In the amiodarone + cocaine group 31/33 (93.9%; 95% CI 79.0 to 99.3) mice seized with a median time to seizure of 2.0 minutes, and 24/33 (72.7%; 95% CI 54.5 to 86.7) died with a median time to death of 6.0 minutes. All animals that died did so within 9 minutes. The difference in the proportion of animals dying in the amiodarone + cocaine group compared to the saline + cocaine group was 0.008 (-21 to 22%). CONCLUSIONS: In this study, pretreatment with amiodarone in cocaine poisoned mice resulted in no change in seizure incidenceor mortality. However, definite conclusions about the reason for these findings cannot be drawn from this model.