Carbon Monoxide Toxicity.

Carbon monoxide accounts for thousands of deaths worldwide each year. Clinical effects can be diverse and include headache, dizziness, nausea, vomiting, syncope, seizures, coma, dysrhythmias, and cardiac ischemia, and severe toxicity generally affects the nervous and cardiovascular systems. Because of its complex pathophysiology, effects of toxicity can be acute or delayed. The diagnosis can be elusive, as carboxyhemoglobin levels do not always correlate with the degree of poisoning. Even when the diagnosis is certain, appropriate therapy is widely debated. Normobaric oxygen is the standard therapy, and the efficacy of hyperbaric oxygen is unclear.

Consensus Development of a Core Content for a Standardized Medical Toxicology Curriculum for Medical Students.

BACKGROUND: Currently, no standardized core content in medical toxicology exists for medical students. The goals of this study were to (1) assess the current state and needs of medical toxicology clerkships and (2) develop a consensus-derived list of core topics that should be covered during a medical toxicology clerkship. METHODS: We assembled a task force established by the American College of Medical Toxicology (ACMT) of nine experts in medical toxicology or emergency medicine. We developed a needs assessment survey that was sent to all medical student clerkship directors in medical toxicology. Based on their responses, we used a modified Delphi process to develop a consensus of core topics that should be covered during a medical student clerkship. RESULTS: Nineteen out of 42 (45%) clerkship directors completed the survey; 18 met inclusion criteria. The majority of clerkships were 4 weeks in duration with an average of 15 students/year. The three most common teaching methods used were bedside teaching (n = 17/18), classroom teaching (n = 17/18), and journal club (n = 14/18). All the clerkship directors (n = 18/18) reported they would use a standardized curriculum as well as educational content developed by ACMT. There was overwhelming consensus on the core topics which included, but were not limited to, pharmacology/toxicology; drugs; drugs of abuse; natural products; pharmacological basis of antidote use; toxicologic syndromes; vital sign abnormalities; initial management; supportive and other care; withdrawal syndrome management; industrial, household, and environmental toxins; differential diagnosis by clinical findings; and ABCs-resuscitation. CONCLUSION: The ACMT task force developed a medical toxicology clerkship core content. The task force also identified a need for shared resources among clerkships.

Acute Cytotoxic Cerebellar Edema Subsequent to Fentanyl Patch Intoxication in an Infant.

The opioid epidemic continues to have devastating consequences for children and families across the United States with rising prevalence of opioid use and abuse. Given the ease of access to these medications, accidental ingestion and overdose by children are becoming increasingly more common. The recognition of opioid-induced neurotoxicity and the associated life-threatening complication of acute cerebellar cytotoxic edema are crucial, as are the high morbidity and mortality without timely intervention. We discuss an infant with acute cytotoxic cerebellar edema following mucosal exposure to a transdermal fentanyl patch.

The Toxicology Investigators Consortium Case Registry-the 2018 Annual Report.

The Toxicology Investigators Consortium (ToxIC) Registry was established by the American College of Medical Toxicology (ACMT) in 2010. The Registry collects data from participating sites with the agreement that all bedside medical toxicology consultation will be entered. The objective of this ninth annual report is to summarize the Registry's 2018 data and activity with its additional 7043 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from 1 January to 31 December 2018. Detailed data was collected from these cases and aggregated to provide information which included demographics, reason for medical toxicology evaluation, agent and agent class, clinical signs and symptoms, treatments and antidotes administered, mortality, and whether life support was withdrawn. A total of 51.5% of cases were female, 48% were male, and 0.6% transgender. Non-opioid analgesics were the most commonly reported agent class, followed by antidepressants and opioids. Acetaminophen was once again the most common agent reported. There were 106 fatalities, comprising 1.5% of all registry cases. Major trends in demographics and exposure characteristics remained similar to past years' reports. Sub-analyses were conducted to describe exposures in elderly patients, addiction consultation practices, and risk factors for bupropion-induced seizures. The launch of the ToxIC Qualified Clinical Data Registry (TQCDR) is also described.

Ibogaine Consumption With Seizure-Like Episodes, QTc-Prolongation, and Captured Cardiac Dysrhythmias.

BACKGROUND: Ibogaine is a psychoactive indole alkaloid that has been investigated for use as a treatment for opioid addiction. While not commercially available in the United States, it is available via Internet suppliers. Ibogaine use has been associated with significant cardiac and neurologic effects, such as QT-segment prolongation, cardiac dysrhythmias, hallucinations, seizures, and central nervous system depression. We present a case of verified ibogaine exposure with associated QTc prolongation and torsade de pointes with qualitative analysis of the ingested substance, and examine the history, social context, availability, and perceptions of ibogaine's effects and safety. CASE REPORT: A 34-year-old white woman with medical history significant for heroin and cocaine use disorder presented with reported seizures 1 day after ingestion of 2 g ibogaine powder purchased from an Internet supplier. Shortly after ingestion, she experienced hallucinations and was reported by family to have four to five seizure-like episodes, at one point becoming apneic. In the emergency department, she was noted to have QTc prolongation and several episodes of torsade de pointes. Qualitative analysis confirmed the presence of ibogaine in the empty foil packages containing the ingested substance. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: As increasing numbers of opioid-dependent patients attempt to curtail their substance use disorders, we anticipate a rise in ibogaine exposures, necessitating awareness by front-line clinicians in recognizing and treating a drug exposure that can rapidly become life-threatening.

Role of dantrolene in dinitrophenol (DNP) overdose: A continuing question?

BACKGROUND: 2,4-Dinitrophenol (DNP) is a known uncoupler of oxidative phosphorylation that clinically results in hyperthermia, tachycardia, tachypnea, and metabolic acidosis. Overdoses of DNP are often fatal and there is no specific reversal therapy. Dantrolene interferes with calcium release in skeletal muscle and is traditionally used to treat malignant hyperthermia. There has been limited published data on its use in DNP toxicity. We present two cases of DNP toxicity that were treated with dantrolene. CASE 1: A 22-year-old male presented following an overdose of his bodybuilding supplements including DNP. He became altered, tachycardic, and hyperthermic to 40.0C. He required intubation and aggressive cooling. He received multiple doses of dantrolene over the initial 36 h with resolution of his hyperthermia. He was extubated and discharged home on hospital day 6. CASE 2: A 20-year-old male presented following a staggered ingestion of DNP. He was tachypneic and tachycardic on arrival. He became hyperthermic to 40.2C and required intubation. He underwent aggressive cooling and received 200 mg of IV dantrolene. His temperature normalized, however, he expired 4 h after ED arrival. CONCLUSION: DNP toxicity has limited treatment options. Dantrolene may ameliorate the hypermetabolic state in DNP toxicity by lessening excitation-contraction coupling in muscle cells and improving the associated hyperthermia. Our cases demonstrate the hyperthermia reducing effects of dantrolene in DNP toxicity and contribute to the existing literature on this topic. Being aware of the possible use of dantrolene to treat the associated hyperthermia could assist emergency physicians in the treatment of DNP toxicity.

Correction to: The Toxicology Investigators Consortium Case Registry-The 2017 Annual Report.

Please note the Collaborators for this article listed in the Acknowledgements.

The Toxicology Investigators Consortium Case Registry-the 2017 Annual Report.

The Toxicology Investigators Consortium (ToxIC) Case Registry was established by the American College of Medical Toxicology in 2010. The Registry collects data from participating sites with the agreement that all bedside medical toxicology consultations will be entered. The objective of this eighth annual report is to summarize the Registry's 2017 data and activity with its additional 7577 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from 1 January to 31 December 2017. Detailed data was collected from these cases and aggregated to provide information which includes demographics (e.g., age, gender, race, ethnicity), reason for medical toxicology evaluation (e.g., intentional pharmaceutical exposure, envenomation, withdrawal from a substance), agent and agent class, clinical signs and symptoms (e.g., vital sign abnormalities, organ system dysfunction), treatments and antidotes administered, fatality, and life support withdrawal data. Females were involved in 50.4% of cases. Transgender demographic information collection was initiated in 2017 to better represent the population and there were 36 cases involving transgender patients. Adults aged 19-65 were the most commonly reported age group. Non-opioid analgesics were the most commonly reported agent class, with acetaminophen again the most common agent reported. There were 93 fatalities reported in 2017. Treatment interventions were frequently reported with 30.6% receiving specific antidotal therapy. Major trends in demographics and exposure characteristics remained similar to past years' reports. While treatment interventions were commonly required, fatalities were rare.

Baclofen overdose mimicking brain death.

CONTEXT: Brain death guidelines should be used with caution in patients with drug intoxication. It is often suggested that physicians use five half-lives of a drug when observing a patient with an overdose. We report two cases of baclofen intoxication where brain death was entertained as an explanation for prolonged coma, with arousal seen days later, suggesting that routine use of a 5-half-life observation period is insufficient with baclofen intoxication. CASE PRESENTATION: A 40-year-old woman was found unresponsive by her family. Baclofen was found to be the responsible overdose. The patient had absent brain stem reflexes and was intubated and in the ICU for several days. Although EEG and Apnea test were inconclusive, the patient was thought to be brain dead and organ procurement was arranged. On hospital day 5, the patient started having purposeful movements. The patient had progressive arousal and was eventually transferred without neurologic sequelae to psychiatry. The second patient also had a massive baclofen overdose, had absence of almost all brain stem reflexes and was also intubated and in the ICU. Brain death was felt to be imminent, but the patient began to awake on hospital day 7. DISCUSSION: Our two cases suggest that baclofen intoxication may result in very prolonged and profound coma and may, in fact, mimic brain death. Conclusion. The determination of brain death in the comatose overdose patient must proceed with caution. An adequate period of time to allow drug clearance must be allowed.

Benzodiazepine-associated atrioventricular block.

Dysrhythmias, although common in overdose situations, are not often seen after benzodiazepine exposures. We report two cases of transient atrioventricular block after benzodiazepine misuse. Case 1 is a 4-year-old boy who was found unresponsive after an ingestion of clonazepam. An electrocardiogram (EKG) performed on emergency department presentation demonstrated first-degree atrioventricular block (PR 206 ms). After flumazenil administration, he developed second-degree atrioventricular block (Mobitz Type 1). EKG abnormalities resolved by morning. Serum clonazepam was 478 ng/mL (laboratory clonazepam reference range, 10-75 ng/mL with a dose of up to 6 mg/day) 5 hours after being found unresponsive. Case 2 is a 23-year-old man who presented to the emergency department after ingesting risperidone, combination hydrocodone/acetaminophen, and alprazolam. On arrival, his EKG demonstrated sinus bradycardia with a PR interval of 182 msec. He subsequently developed second-degree atrioventricular block (Mobitz Type I). Sinus bradycardia with resolution of his atrioventricular block (PR 200 ms) was seen on a third EKG performed 5 hours after presentation. These two patients demonstrated transient first- and second-degree atrioventricular block after benzodiazepine exposure. Benzodiazepines have been shown to alter L-type Ca2+ channel function. This alteration in function may account for the dysrhythmias seen in our patients. Together, these cases serve to remind clinicians of this rare but potentially serious complication associated with benzodiazepine exposure.

A multicenter comparison of the safety of oral versus intravenous acetylcysteine for treatment of acetaminophen overdose.

UNLABELLED: Oral and intravenous (IV) N-acetylcysteine (NAC) are used for the treatment of acetaminophen poisoning. The objective of this multicenter study was to compare the safety of these two routes of administration. METHODS: We conducted a multicenter chart review of all patients treated with NAC for acetaminophen poisoning. The primary safety outcome was the percentage of patients with NAC-related adverse events. RESULTS: A total of 503 subjects were included in the safety analysis (306 IV-only, 145 oral-only, and 52 both routes). There were no serious adverse events related to NAC for either route. Nausea and vomiting were the most common related adverse events and were more common with oral treatment (23 vs. 9%). Anaphylactoid reactions were more common with IV administration (6 vs. 2%). CONCLUSIONS: IV and oral NAC are generally mild adverse drug reactions.

Heavy metal poisoning: management of intoxication and antidotes.

Of the known elements, nearly 80% are either metals or metalloids. The highly reactive nature of most metals result in their forming complexes with other compounds such oxygen, sulfide and chloride. Although this reactivity is the primary means by which they are toxic, many metals, in trace amounts, are vital to normal physiological processes; examples include iron in oxygen transport, manganese and selenium in antioxidant defense and zinc in metabolism. With these essential metals toxicity occurs when concentrations are either too low or too high. For some metals there are no physiological concentrations that are beneficial; as such these metals only have the potential to cause toxicity. This chapter focuses on four of these: arsenic, mercury, lead and thallium.

The MALAdy of metformin poisoning: Is CVVH the cure?

Inadvertent or intentional metformin overdose can result in death from refractory lactic acidosis. We report a death from metformin-induced refractory lactic acidosis despite aggressive care. A 49-year-old hypertensive diabetic female presented 1 hour after ingesting 60 tablets of 500 mg metformin and 20 combination tablets of 12.5 mg hydrochlorothiazide/20 mg lisinopril. She was awake and alert, with a blood glucose of 579 mg/dL. Chemistry panel revealed lactic acidosis and acute renal failure (arterial blood gas pH, 7.18; pCO(2), 15 mm Hg; pO(2), 127 mm Hg; HCO(3), 6 mmol/L; lactate, 9.6 mmol/L; and creatinine, 1.2 mg/dL [0.8 mg/dL previously]). She received normal saline, sodium bicarbonate, and insulin. On arrival to the intensive care unit she was obtunded, with a blood pressure of 40/25 mm Hg and had worsening acidosis and poor oxygenation (arterial blood gas pH, 6.79; pCO(2), 55; pO(2), 57; HCO(3), 8.4; and base excess of -25 on 100% fractional inspired oxygen). She was intubated and received additional fluid boluses, bicarbonate, and norepinephrine. Continuous veno-venous hemofiltration (CVVH) was started 6 hours after her ingestion. Metformin was 380 microg/mL on CVVH initiation. The patient developed pulseless electrical activity 30 hours after her ingestion, which recurred 20 minutes later. The family requested no further resuscitation. She died 31.5 hours after her ingestion. Metformin concentrations decreased to 97 microg/mL 28 hours after the ingestion on CVVH, with a first-order elimination half-life of 11.3 hours (r(2) = 0.99) and a clearance of 56.2 mL/min. Further investigations on the place of CVVH in the management of the poisoned patient with MALA unable to hemodynamically tolerate conventional hemodialysis may be needed.