Sean H. Rhyee

Acetaminophen-cysteine adducts during therapeutic dosing and following overdose

BackgroundAcetaminophen-cysteine adducts (APAP-CYS) are a specific biomarker of acetaminophen exposure. APAP-CYS concentrations have been described in the setting of acute overdose, and a concentration >1.1 nmol/ml has been suggested as a marker of hepatic injury from acetaminophen overdose in patients with an ALT >1000 IU/L. However, the concentrations of APAP-CYS during therapeutic dosing, in cases of acetaminophen toxicity from repeated dosing and in cases of hepatic injury from non-acetaminophen hepatotoxins have not been well characterized. The objective of this study is to describe APAP-CYS concentrations in these clinical settings as well as to further characterize the concentrations observed following acetaminophen overdose.MethodsSamples were collected during three clinical trials in which subjects received 4 g/day of acetaminophen and during an observational study of acetaminophen overdose patients. Trial 1 consisted of non-drinkers who received APAP for 10 days, Trial 2 consisted of moderate drinkers dosed for 10 days and Trial 3 included subjects who chronically abuse alcohol dosed for 5 days. Patients in the observational study were categorized by type of acetaminophen exposure (single or repeated). Serum APAP-CYS was measured using high pressure liquid chromatography with electrochemical detection.ResultsTrial 1 included 144 samples from 24 subjects; Trial 2 included 182 samples from 91 subjects and Trial 3 included 200 samples from 40 subjects. In addition, we collected samples from 19 subjects with acute acetaminophen ingestion, 7 subjects with repeated acetaminophen exposure and 4 subjects who ingested another hepatotoxin. The mean (SD) peak APAP-CYS concentrations for the Trials were: Trial 1- 0.4 (0.20) nmol/ml, Trial 2- 0.1 (0.09) nmol/ml and Trial 3- 0.3 (0.12) nmol/ml. APAP-CYS concentrations varied substantially among the patients with acetaminophen toxicity (0.10 to 27.3 nmol/ml). No subject had detectable APAP-CYS following exposure to a non-acetaminophen hepatotoxin.ConclusionsLower concentrations of APAP-CYS are detectable after exposure to therapeutic doses of acetaminophen and higher concentrations are detected after acute acetaminophen overdose and in patients with acetaminophen toxicity following repeated exposure.

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

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.

Sulfur Mustard Exposure Presenting to a Community Emergency Department

We report dermal exposure to a chemical warfare agent, sulfur mustard, in a 28-year-old commercial fisherman. Chemical warfare agents such as sulfur mustard are considered potential terrorist weapons, and suspected exposure requires notification of federal authorities. We address potential pitfalls when alerting authorities and methods to avoid such obstacles, and we describe the clinical management of sulfur mustard toxicity.

Serotonin toxicity association with concomitant antidepressants and rasagiline treatment: retrospective study (STACCATO).

The serotonin toxicity syndrome (STS) is a potential risk with concurrent use of the monoamine oxidase type‐B inhibitor rasagiline and antidepressants.

Acute barium toxicity from ingestion of “snake” fireworks

IntroductionIngestion of fireworks has been infrequently reported in the medical literature. We describe a case of acute barium poisoning following firework ingestion.Case ReportA 35-year-old male with a history of severe mental retardation presented with vomiting and diarrhea following ingestion of 16 small fireworks (“color snakes” and “black snakes”). His condition rapidly deteriorated and he developed obtundation, wide complex dysrhythmias, and respiratory failure. Approximately 12 hours following ingestion, his serum potassium level was 1.5 mmol/L with a serum barium level of 20,200 μg/mL (reference range<200 μg/L). The patient eventually recovered with ventilatory support and potassium supplementation.DiscussionAlthough firework ingestion is uncommon, clinicians should be prepared for potentially severe complications. In the case of barium poisoning, treatment consists of potassium supplementation, along with respiratory and hemodynamic support.

Clinical course of repeated supratherapeutic ingestion of acetaminophen.

Background. Repeated supratherapeutic ingestion (RSTI) of acetaminophen (APAP) is recognized as an important cause of APAP-related morbidity and mortality. This study describes the characteristics and clinical course of patients with RSTI, and identifies the risk factors for developing hepatotoxicity and death. Methods. This secondary analysis of a multicenter retrospective chart review studied patients treated with IV and/or oral N-acetylcysteine for acetaminophen poisoning. For this analysis, we included all subjects coded as RSTIs, defined as ingestions of greater than 4 g of APAP per 24 h over a period longer than 8 h. Data collected include demographics, coingestants, comorbidities, presenting laboratory data, and outcomes. The analysis includes descriptive statistics and associations of demographic and clinical factors with patient outcome. Results. Of the 503 patients enrolled, 119 (23.7%) were RSTI. The mean age was 39.6 years (SD ± 15); 63.9% of the patients were females, 60.5% Caucasians, 27.7% alcoholics, 5% malnourished, 10.9% had viral hepatitis, and 3.4% had other liver diseases. Coingestants included ethanol, opioids, and antihistamines (17.6, 48.7, and 19.3%, respectively). Among this group, 44 patients developed hepatotoxicity, two received liver transplants, and four died (37.0, 1.7, and 3.4%, respectively). The risk for hepatotoxicity increased with a history of alcoholism, viral hepatitis, and other liver diseases. A history of alcoholism and an elevated presenting serum creatinine were associated with increased risk for death/transplant. The lowest presenting ALT levels in a subject who developed hepatotoxicity and who died were 252 and 426 IU/l, respectively. Conclusion. RSTI-induced hepatotoxicity and poor outcomes can be predicted at the patients presentation. All patients with RSTI who developed hepatotoxicity presented with an abnormal ALT. A history of alcoholism and an elevated creatinine at presentation are markers of increased risk for hepatotoxicity and death.

Acute respiratory distress associated with inhaled hydrocarbon

BACKGROUND Pneumonitis is a well-known complication following aspiration of ingested liquid hydrocarbons. There are few data about acute pulmonary toxicity from unintentional hydrocarbon inhalation; most human cases involve products containing a fluoropolymer in combination with hydrocarbons. METHODS Case report of a 45-year-old male who presented with respiratory distress after a 15-min inhalational exposure to a canvas waterproofing spray containing liquefied petroleum gas, ethylene glycol monobutyl ether, and isopropanol. RESULTS Patients had symptoms, exam findings, and chest X-ray that were consistent with an acute pneumonitis. CONCLUSION Acute pulmonary injury can occur after a short exposure to an inhaled hydrocarbon and associated symptoms appear to respond to supportive measures, including oxygen, corticosteroids, and bronchodilators.

Prolonged delirium after quetiapine overdose

Quetiapine is an atypical antipsychotic agent increasingly used to treat schizophrenia and bipolar disorder in pediatric patients. Few published data exist concerning quetiapines effects in therapeutic settings or short-term overdose in pediatric and adolescent populations. In this report, we describe a 15-year-old adolescent girl who experienced continued delirium 5 days after an overdose of quetiapine, trazodone, and clonidine. The patient initially presented with sedation and stable vital signs. After 3 days of gradual improvement, she experienced episodes of delirium coinciding with an increase in resting heart rate. On the basis of suspicion for quetiapine-associated antimuscarinic effects, the patient was administered intravenously with physostigmine on the fifth day after ingestion. Treatment resulted in a brief resolution of symptoms. Serum quetiapine levels measured 1 day and 5 days after ingestion were 3400 and 4800 ng/mL, respectively. The use of physostigmine and interpretation of serum levels are discussed further.

Acute kidney injury due to intravenous bleach injection

IntroductionSodium hypochlorite is the active ingredient in bleach, a ubiquitous household disinfectant, and has known toxicities depending on route of exposure and amount. Acute kidney injury due to sodium hypochlorite exposure has never been reported. Patients that did develop nephrotoxicity following bleach exposure did so due to development of other risk factors for kidney injury such as volume depletion or sepsis.DiscussionWe report a patient who presented with black urine after parenteral self-administration of a large quantity of bleach. We review the clinical presentation, laboratory and biopsy findings, and outcome as well as discuss possible mechanisms of sodium hypochlorite toxicity and management strategies.

Status epilepticus in a child secondary to ingestion of skin-lightening cream

The popularity of the Internet and online media has led to the increased availability of prescription-strength, skin-lightening products contributing to a rise in their use among people with various skin pigment disorders. These products may contain a wide variety of active ingredients such as heavy metals, hydroquinone, and corticosteroids that can be highly toxic, especially after prolonged application. For decades, there have been case reports of both corticosteroid and heavy metal toxicity related to skin-lightening cream use. We report a case of a child who developed status epilepticus after ingesting a skin-lightening solution containing 2% hydroquinone. The toxicodynamics of hydroquinone and its effects on the central nervous system are discussed.