Incidence of Adverse Events Using Flumazenil in Patients With Iatrogenic Benzodiazepine Delirium: A Retrospective Study.

BACKGROUND: Flumazenil is a competitive benzodiazepine (BZD) antagonist most used for treating delirium in BZD overdoses. Since its introduction, many have expressed concerns about its safety secondary to the risk of inducing BZD withdrawal and refractory seizures. STUDY QUESTION: What is the incidence of adverse drug events after the administration of flumazenil in patients with suspected iatrogenic BZD delirium? STUDY DESIGN: This is a retrospective cross-sectional study of patients from a single center from 2010 to 2013. Patients experiencing delirium after receiving BZDs in the hospital were included if they had a bedside toxicology consult and were administered flumazenil. Patients were excluded if they were given BZDs for ethanol withdrawal or if they did not have mental status documentation before and after flumazenil administration. Descriptive statistics were calculated. MEASURES AND OUTCOMES: The primary outcome was the incidence of adverse drug events after flumazenil administration. The secondary outcome was the efficacy of flumazenil determined by the patient's mental status. RESULTS: A total of 501 patient records were reviewed, and 206 patients were included in the final analysis. Of those patients, 172 (83.5%) experienced an objective improvement in their mental status within 1 hour after flumazenil administration. A total of 5 patients experienced adverse events (2.4%), 95% confidence interval (0.78, 5.54). Of these, 3 patients experienced minor agitation or restlessness without pharmacologic intervention. Two patients experienced moderate agitation or restlessness that resolved with haloperidol or physostigmine administration. No patients had a reported seizure, 95% confidence interval (0.0, 1.77). CONCLUSIONS: Flumazenil seems to be a safe and effective intervention for the reversal of delirium secondary to iatrogenic BZD administration.

Patterns of transaminase elevation in rhabdomyolysis versus acetaminophen toxicity.

BACKGROUND: Transaminase elevations can occur from liver injury or in the setting of rhabdomyolysis. The goal of this study is to evaluate indices that could differentiate acetaminophen toxicity from muscle injury in the setting of transaminase elevations. METHODS: A retrospective chart review of consecutive cases reported to our regional poison center. Patients with transaminase (AST and ALT) elevation were grouped as those with acetaminophen exposure (AT) and those with elevated creatine phosphokinase (CPK) without evidence of acetaminophen exposure (RHB). RESULTS: Of the 345 patients included in the study, elevated AST/ALT levels were attributed to rhabdomyolysis in 168 patients and attributed to acetaminophen toxicity in 177 patients. The median AST: ALT values also differed between groups, with patients in the RHB group had higher median ratios (p < 0.001). Using an AST: ALT value of 2.02 as a diagnostic cutoff produced a specificity of 0.52 (95% CI: 0.37, 0.64) and sensitivity of 0.84 (95% CI: 0.73, 0.94) for acetaminophen detection in the test dataset (N = 104). CONCLUSIONS: Elevated transaminases due to liver injury from acetaminophen ingestion had a different pattern than elevated transaminases due to rhabdomyolysis. Lower AST:ALT ratios were found in acetaminophen cases, however, the specificity using a ratio threshold of ≤1 would be 83%.

An algorithm for identifying mothball composition.

INTRODUCTION: Unintentional mothball ingestions may cause serious toxicity in small children. Camphor, naphthalene, and paradichlorobenzene mothballs are difficult to distinguish without packaging. Symptoms and management differ based on the ingested compound. Previous studies have used a variety of antiquated, impractical and potentially dangerous techniques to identify the mothballs. The goal of this study is to discover a simplified identification technique using materials readily available in an emergency department. METHODS: Mothballs made of naphthalene and paradichlorobenzene along with camphor tablets were tested. Each material was tested both intact and after being fragmented to simulate a partially ingested mothball. Each of these six sample types were then immersed in 40 ml each of 11 fluids: water, 0.45% NaCl, 0.9% NaCl, lactated Ringer's, 5% dextrose in water, 5% dextrose in 0.9% NaCl, 50% dextrose in water, 8.4% NaHCO3, 3% H2O2, 70% isopropanol, and 91% isopropanol. All tests were conducted in standard urinalysis sample cups to replicate available materials. Three toxicologists blinded to the identities of samples and solutions visually evaluated each sample. Observations included assessing response to immersion: sink, float, or dissolve. RESULTS: All evaluators agreed in their description of 62/66 (94%) of the samples, with all four disagreements being on sinking and dissolving versus sinking only. A two-fluid algorithm utilizing 50% dextrose and water was sufficient to distinguish the sample types. Camphor will float in water while both paradichlorobenzene and naphthalene will sink. In 50% dextrose, both naphthalene and camphor will float while paradichlorobenzene will sink. CONCLUSION: Mothball materials can be distinguished by immersion in water and 50% dextrose. Limitations of this study include using camphor tablets as a substitute for mothballs given lack of availability.

Survival After Cardiac Arrest: ECMO Rescue Therapy After Amlodipine and Metoprolol Overdose.

Extracorporeal membrane oxygenation (ECMO) use in poisoned patients is increasing, but is rare post cardiac arrest. We report a case of ECMO use with complete recovery in a patient who arrested twice after a cardiotoxicant overdose. A 17-year-old male presented after an unknown overdose. He rapidly became hypotensive and bradycardic and received aggressive supportive care without improvement. He was transferred to our institution and suffered a cardiac arrest shortly after arrival. Six minutes of advanced cardiac life support resulted in return of spontaneous circulation. High-dose insulin, lipid emulsion, and ECMO were initiated. While awaiting ECMO deployment, he again became pulseless. Compressions resumed, and after 30 min, ROSC was achieved, and he was cannulated for veno-arterial ECMO. Within 48 h, he was decannulated, and then weaned off epinephrine 2 days later. Upon extubation, he was neurologically intact. Amlodipine and metoprolol were later confirmed in serum. Adolescent poisoned patients represent an ideal population for ECMO due to lack of comorbidities. As experience with ECMO in overdose increases, additional research is needed to determine appropriate indications and timing for its use. ECMO is an option for patients poisoned with a cardiotoxicant drug, even following witnessed cardiac arrest.

A Case Series of Clenbuterol Toxicity Caused by Adulterated Heroin.

BACKGROUND: Adulteration of drugs of abuse may be done to increase profits. Some adulterants are relatively innocuous and others result in significant toxicity. Clenbuterol is a ß2-adrenergic agonist with veterinary uses that has not been approved by the U.S. Food and Drug Administration for human use. It is an infrequently reported heroin adulterant. We describe a cluster of hospitalized patients with laboratory-confirmed clenbuterol exposure resulting in serious clinical effects. CASE SERIES: Ten patients presented with unexpected symptoms shortly after heroin use. Seven evaluated by our medical toxicology service are summarized. Presenting symptoms included chest pain, dyspnea, palpitations, and nausea/vomiting. All patients were male, with a median age of 40 years (interquartile range [IQR] 38-46 years). Initial vital signs included a heart rate of 120 beats/min (IQR 91-137 beats/min), a respiratory rate of 20 breaths/min (IQR 18-22 breaths/min), a temperature of 36.8°C (IQR 36.7-37.0°C), a systolic blood pressure of 107 mm Hg (IQR 91-131 mm Hg), and a diastolic blood pressure of 49 mm Hg (IQR 40-70 mm Hg). Serum potassium nadir was 2.5 mEq/L (IQR 2.2-2.6 mEq/L), initial glucose was 179 mg/dL (IQR 125-231 mg/dL), initial lactate was 9.4 mmol/L (IQR 4.7-10.5 mmol/L), and peak creatine phosphokinase was 953 units/L (IQR 367-10,363 units/L). The median peak troponin level in six patients was 0.7 ng/mL (IQR 0.3-2.4 ng/mL). Three patients underwent cardiac catheterization and none had significant coronary artery disease. Clenbuterol was detected in all patients after comprehensive testing. All patients survived with supportive care. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Atypical presentations of illicit drug intoxication may raise concern for drug adulteration. In the case of heroin use, the presence of adrenergic symptoms or chest pain with hypokalemia, lactic acidosis, and hyperglycemia suggests adulteration with a ß-agonist, such as clenbuterol, and patients presenting with these symptoms often require hospitalization.

Methanol Kinetics in Chronic Kidney Disease After Fomepizole: A Case Report.

Methanol is a common toxicant in the United States, especially from automotive products. Its kinetics have been described previously and typically involve little urinary excretion. We present a case of prolonged methanol half-life in a patient with chronic kidney disease. An 80-year-old male with a baseline glomerular filtration rate of 24 mL·min·1.73 m was transferred to our facility after unintentional methanol ingestion. The original facility had treated him with an oral ethanol load; upon arrival to our facility, he was immediately loaded with fomepizole. His initial serum methanol concentration was 66.1 mg/dL. After a risk/benefit discussion, we decided not to perform hemodialysis on the patient and he was treated with fomepizole and supportive care. After 6 days as an inpatient, the patient's methanol level had declined to 22 mg/dL, fomepizole was discontinued, and the patient was able to be discharged without apparent complications. Based on the exponential best fit line for the patient's methanol concentrations, his methanol half-life during fomepizole treatment was approximately 70 hours, significantly longer than the 30-50 hours typically reported. The reasons for this difference are unclear. This report is limited by being a single case. Further study on the kinetics of methanol in the setting of chronic kidney disease is needed.

Comparison of Preloaded Bougie versus Standard Bougie Technique for Endotracheal Intubation in a Cadaveric Model.

INTRODUCTION: We compared intubating with a preloaded bougie (PB) against standard bougie technique in terms of success rates, time to successful intubation and provider preference on a cadaveric airway model. METHODS: In this prospective, crossover study, healthcare providers intubated a cadaver using the PB technique and the standard bougie technique. Participants were randomly assigned to start with either technique. Following standardized training and practice, procedural success and time for each technique was recorded for each participant. Subsequently, participants were asked to rate their perceived ease of intubation on a visual analogue scale of 1 to 10 (1=difficult and 10=easy) and to select which technique they preferred. RESULTS: 47 participants with variable experience intubating were enrolled at an emergency medicine intern airway course. The success rate of all groups for both techniques was equal (95.7%). The range of times to completion for the standard bougie technique was 16.0-70.2 seconds, with a mean time of 29.7 seconds. The range of times to completion for the PB technique was 15.7-110.9 seconds, with a mean time of 29.4 seconds. There was a non-significant difference of 0.3 seconds (95% confidence interval -2.8 to 3.4 seconds) between the two techniques. Participants rated the relative ease of intubation as 7.3/10 for the standard technique and 7.6/10 for the preloaded technique (p=0.53, 95% confidence interval of the difference -0.97 to 0.50). Thirty of 47 participants subjectively preferred the PB technique (p=0.039). CONCLUSION: There was no significant difference in success or time to intubation between standard bougie and PB techniques. The majority of participants in this study preferred the PB technique. Until a clear and clinically significant difference is found between these techniques, emergency airway operators should feel confident in using the technique with which they are most comfortable.