Precipitated opioid withdrawal in a patient started on olanzapine/samidorphan.

BACKGROUND: Olanzapine/Samidorphan (Lybalvi®) is a novel oral agent for the treatment of schizophrenia and bipolar I disorder. It was designed to reduce weight gain associated with olanzapine. Samidorphan is an analog of naltrexone, initially intended to treat substance use disorders by antagonizing mu, delta, and kappa opioid receptors. CASE REPORT: We present the case of a 36-year-old who took their first dose of olanzapine/samidorphan shortly before calling for emergency services. The patient took diphenhydramine and an epinephrine autoinjector for what they thought was an allergic reaction but continued to have symptoms. EMS reported involuntary muscle movements thought to be due to dystonia from olanzapine. In the ED, they experienced generalized muscle spasms lasting for several seconds and diaphoresis. Initially, the staff treated for a presumed dystonic reaction to olanzapine and administered diphenhydramine 25 mg IV, diazepam 2 mg IV, midazolam 5 mg IV, and benztropine 1 mg IV without improvement. It was later determined that the patient took 16 mg of buprenorphine SL daily. With this information, precipitated opioid withdrawal was felt to be the likely cause of symptoms. The patient received 16 mg of buprenorphine for an initial Clinical Opiate Withdrawal Scale (COWS) score of 11 with repeat COWS of 6. Why should an emergency physician be aware of this? Initiating olanzapine/samidorphan in the setting of chronic opioid therapy may result in precipitated opioid withdrawal. Additional SL buprenorphine may be a reasonable treatment modality.

Systemic toxicity from subcutaneous brimonidine injection successfully treated with naloxone.

Brimonidine is a topical ophthalmic alpha-2 adrenergic agonist solution used to treat glaucoma. The toxidrome includes drowsiness, lethargy, hypotension, bradycardia, and respiratory depression when ingested in infants. We report a case of intentional subcutaneous injection of brimonidine in an elderly patient resulting in hypotension and CNS depression that responded to naloxone. A 73-year-old female with a past medical history significant for glaucoma, hypertension, and indwelling pacemaker presented to the emergency department after injecting her brimonidine tartrate ophthalmic solution subcutaneously (SQ). The patient was not taking any antihypertensive medications or opioids. Initial presentation consisted of lethargy, a paced rhythm of 60 bpm, and blood pressure of 91/24 mmHg with a MAP of 46. Due to central nervous system depression, 3 mg of intranasal naloxone was administered. The patient was treated with intravenous fluids and escalating doses of naloxone and required a continuous infusion. Mental status and vital signs subsequently improved. The patient was admitted to the ICU and naloxone was subsequently weaned over 12 h. Systemic central alpha-2 adrenergic agonist toxicity resulted from SQ brimonidine injection. Central alpha-2 adrenergic agonist overdoses present as sympatholytic effects including CNS depression, bradycardia, hypotension, and may mimic the opioid toxidrome. Brimonidine SQ injection has not previously been reported and this case has similar findings to other central alpha-2 adrenergic agonist poisonings. Naloxone has previously shown variable reversal of CNS depression in central alpha-2 overdose. In this case, high-dose naloxone was useful for reversing CNS depression and hemodynamic instability.

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%.

Evaluation of prehospital hydroxocobalamin use in the setting of smoke inhalation.

BACKGROUND: The indications for prehospital hydroxocobalamin are not well defined. The aim of this study was to evaluate prehospital signs and symptoms in patients who received hydroxocobalamin to improve future use. METHODS: In this retrospective study, all patients who received prehospital Hydroxocobalamin at a tertiary care burn center from December 2012 to March 2018 were reviewed. Each case was evaluated for evidence of suspected cyanide toxicity: hypotension, syncope, CNS depression/altered mentation, seizures, respiratory or cardiac arrest. A determination was made whether or not hydroxocobalamin was indicated. RESULTS: In this study, EMS providers administered hydroxocobalamin to 42 patients between December 2012 and March 2018. The majority (71%) of suspected cyanide exposures were from house fires. The most common prehospital findings were coma or depressed CNS (36%), followed by hypotension (16%) and cardiac arrest (12%). Sixty percent of patients treated with hydroxocobalamin had none of the six clinical indicators for potential cyanide toxicity. Carboxyhemoglobin and serum lactate were significantly different in patients that had a clinical indication for hydroxocobalamin compared to those who did not. CONCLUSIONS: Prehospital hydroxocobalamin was used empirically however, indications are unclear. Using defined clinical indications may provide greater clarity for providers and reduce unnecessary use of hydroxocobalamin.

Outbreak of Severe Hypoglycemia After Ingestion of a Male Enhancement Supplement - Virginia, August-November 2019.

In August 2019, the Virginia Poison Center (VPC) and the Blue Ridge Poison Center (BRPC) were contacted concerning patients experiencing repeated episodes of marked hypoglycemia following ingestion of a male enhancement supplement tablet marketed as "V8" in convenience stores in central Virginia. Over the following 3 months, the Virginia Department of Agriculture and Consumer Services (VDACS) and the Virginia Department of Health (VDH) conducted an investigation and identified 17 patients meeting the case definition (severe hypoglycemia within 48 hours of consuming an over-the-counter male enhancement supplement in a man with no history of use of insulin or other medication used to control blood glucose). Analysis of the V8 tablets revealed that most contained glyburide, a sulfonylurea oral hypoglycemic used in the treatment of diabetes and associated with prolonged hypoglycemia following overdose (1). To stem this outbreak, V8 was removed from stores when found, and public service announcements were released. The public health implications of V8 use include the potential for substantial morbidity from hypoglycemic episodes and the potential for mortality if health care services are not accessed in a timely manner when hypoglycemia occurs. The presence of V8 in the market poses a serious threat to public health because of its potentially life-threatening adverse effects.

Causative Agents in Clinically Significant Methemoglobinemia: A National Poison Data System Study.

BACKGROUND: Recognition of the agents most commonly implicated in causing methemoglobinemia can provide context for making therapeutic decisions and inform the diagnostic process. We evaluated the etiologic agents most commonly implicated in clinically significant methemoglobinemia using data from the National Poison Data System (NPDS). STUDY QUESTION: What are the most frequent etiologic agents associated with clinically significant methemoglobinemia. STUDY DESIGN: This was a retrospective cross-sectional chart review using electronic data from the NPDS. The NPDS database was queried to identify cases from July 1, 2007, to June 30, 2017, that were coded as methylene blue treatment recommended and/or performed. Cases were excluded if the substance(s) have never been known to cause methemoglobin or the substances suggested methylene blue was used adjunctively for refractory shock (eg, calcium channel or beta blocker). Multiple substance exposures were reviewed and substances not known to cause methemoglobinemia were excluded. MEASURES AND OUTCOMES: The primary end point was to summarize the most frequent etiologic agents associated with the administration of methylene blue for clinically significant methemoglobinemia. RESULTS: There were 2563 substances reported in 1209 cases. After excluding coingestants and cases not associated with methemoglobinemia, there were 1236 substances. The top 4 substance categories were benzocaine, phenazopyridine, dapsone, and nitrates/nitrites. CONCLUSIONS: This study reveals the relative contribution of various drugs and chemicals associated with methylene blue administration. Over two-thirds of all cases were associated with benzocaine, phenazopyridine, dapsone, and nitrates/nitrites.

Unintentional Epinephrine Auto-injector Injuries: A National Poison Center Observational Study.

BACKGROUND: Epinephrine is the only first-line therapeutic agent used to treat life-threatening anaphylaxis. Epinephrine auto-injectors are commonly carried by patients at risk for anaphylaxis, and reported cases of unintentional auto-injector injury have increased over the last decade. Modifications of existing designs and release of a new style of auto-injector are intended to reduce epinephrine auto-injector misuse. STUDY QUESTION: The aim of the study was to characterize reported cases of unintentional epinephrine auto-injector exposures from 2013 to 2014 and compare demographics, auto-injector model, and anatomical site of such exposures. METHODS: The American Association of Poison Control Center's National Poison Data System was searched from January 1, 2013, to December 31, 2014, for cases of unintentional epinephrine auto-injector exposures. Anatomical site data were obtained from all cases reported to the Virginia Poison Center and participating regional poison center for Auvi-Q cases. RESULTS: A total of 6806 cases of unintentional epinephrine auto-injector exposures were reported to US Poison Centers in 2013 and 2014. Of these cases, 3933 occurred with EpiPen, 2829 with EpiPen Jr, 44 with Auvi-Q, and no case reported of Adrenaclick. The most common site of unintentional injection for traditional epinephrine auto-injectors was the digit or thumb, with 58% of cases for EpiPen and 39% of cases with EpiPen Jr. With Auvi-Q, the most common site was the leg (78% of cases). CONCLUSIONS: The number of unintentional epinephrine auto-injector cases reported to American Poison Centers in 2013-2014 has increased compared with previous data. Most EpiPen exposures were in the digits, whereas Auvi-Q was most frequently in the leg. Because of the limitations of Poison Center data, more research is needed to identify incidence of unintentional exposures and the effectiveness of epinephrine auto-injector redesign.

Topical Benzocaine and Methemoglobinemia.

Methemoglobinemia can cause life-threatening hypoxia associated with cyanosis and dyspnea not responsive to oxygen. We present a case of recurrent methemoglobinemia because of occult use of topical benzocaine to the vulva. A 47-year-old female with medical history of vulvar cancer and HIV undergoing chemoradiation was sent by the oncology clinic to the emergency department for worsening dyspnea, fatigue, hypoxia to 78% on room air, and gradual onset of cyanosis over the past week. A methemoglobin (MetHb) level was 49%. She received methylene blue, and repeat MetHb levels initially decreased but later increased to 56% despite continued treatment. Additional interviews with the patient revealed she was applying vagicaine (20% benzocaine), an over the counter preparation to the vulvar area for analgesia, and she continued application while hospitalized. She received a total of 6 mg/kg methylene blue and underwent vaginal lavage with 60 mL of sterile saline and cleansed with soapy water. Cyanosis, hypoxia, and dyspnea resolved, and the MetHb level decreased to 5.4% on the day of discharge. Benzocaine is a frequent cause of iatrogenic methemoglobinemia. In this case, additional medication inquiries were helpful in making the diagnosis. Many patients do not consider over-the-counter medications to be potentially harmful. Methemoglobinemia from occult topical benzocaine administration to the vulva is an uncommon exposure route. Occult medication use can be a source of methemoglobinemia.

Activated Charcoal Does Not Reduce Duration of Phenytoin Toxicity in Hospitalized Patients.

Phenytoin toxicity frequently results in a prolonged inpatient admission. Several publications avow multidose activated charcoal (MDAC) will enhance the elimination of phenytoin. However, these claims are not consistent, and the mechanism of enhanced eliminaiton is unproven. The aim of this investigation is to compare the time to reach a clinical composite end point in phenytoin overdose patients treated with no activated charcoal (NoAC), single-dose activated charcoal (SDAC), and MDAC. This was a retrospective study using electronic poison center data. Patients treated in a health care facility with phenytoin concentrations >20 mg/L were included. Patients were grouped by use of SDAC, MDAC, and NoAC. The primary end points were either time to resolution of symptoms, hospital discharge, or the case was closed by a toxicologist. After applying inclusion and exclusion criteria, 132 cases were included for analysis. There were 88 NoAC, 13 SDAC, and 31 MDAC cases. The groups were similar in symptomatology, age, and chronicity of expsoure. Mean peak phenytoin concentrations (SD) were 42 mg/L (12), 41 mg/L (11), and 42 mg/L (11) for NoAC, SDAC, and MDAC, respectively. Mean time to reach the study end point was 39 hours [95% confidence interval (CI), 31-48], 52 hours (95% CI, 36-68), and 60 hours (95% CI, 45-75) for NoAC, SDAC, and MDAC, respectively. The groups appeared similar with respect to peak phenytoin concentrations and prevalence of signs and symptoms. In this observational series, the use of activated charcoal was associated with increased time to reach the composite end point of clinical improvement.

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.

Lack of adverse effects from flumazenil administration: an ED observational study.

BACKGROUND: Flumazenil is an effective benzodiazepine (BZD) antagonist. Empiric use of flumazenil in the emergency department (ED) is not widely recommended due to concerns of seizures, which are commonly associated with coingestants and BZD withdrawal. OBJECTIVE: The objective of the study is to assess adverse events and clinical outcomes of flumazenil administration in known and suspected BZD overdose in an ED at a tertiary academic medical center. METHODS: This is a retrospective observational study of adult patients administered flumazenil for known or suspected BZD overdose in the ED over 7 years. Outcomes included mental status improvement, the incidence of seizures, and intubation of the trachea after flumazenil administration. RESULTS: Twenty-three patients were included in the analysis, of which 15 (65%) of patients experienced some type of clinically significant mental status improvement. No seizures were identified despite 7 (35%) reported proconvulsant coingestants. One patient required intubation of the trachea but was subsequently extubated in the ED. CONCLUSIONS: A majority of patients had improved mental status after the administration of flumazenil. No patient experienced seizures. Additional studies that clarify the role of flumazenil for ED patients with suspected BZD toxicity are warranted.

Airway compromise in children exposed to single-use laundry detergent pods: a poison center observational case series.

INTRODUCTION: Single-use laundry detergent pods (LDPs) were introduced to the United States in 2010 but had been available in Europe as early as 2001. Case reports of unintentional exposures noted vomiting, ocular injuries, respiratory depression, and central nervous system depression. We summarize clinical effects from unintentional LDP exposures reported to a single poison center over 15 months. METHODS: Electronic poison center records were searched using verbatim field and both product and generic codes to identify laundry pod exposures from January 1, 2012, through April 9, 2013. Clinical effects were abstracted to a database and summarized using descriptive statistics. RESULTS: We identified 131 cases between March 2012 and April 2013. Median (interquartile range) age was 2.0 (1.5) years with 4 adult cases; all were coded as unintentional. The most common route was ingestion (120) followed by ocular (14) and dermal (6). Some patients had multiple routes of exposure. Of ingestion exposures, 79 (66%) were managed at home; and 41 (34%) were evaluated in a hospital, of which 9 patients were admitted. The median (interquartile range) age of admitted patients was 1.4 (1.1) years. Relevant findings in these admitted children included emesis (78%), central nervous system depression (22%), upper airway effects (56%), lower respiratory symptoms (33%), seizure (n = 1), and intubation (67%). One child with emesis initially managed at home was subsequently intubated for respiratory distress. DISCUSSION: Exposure to LDP can cause significant toxicity, particularly in infants and toddlers. Compared to traditional detergents, clinicians should be aware of the potential for airway compromise following exposure to LDP.

Recalcitrant Supraventricular Tachycardia: Occult Albuterol Toxicity Due to a Factitious Disorder.

BACKGROUND: We report a case of a factitious disorder presenting with recurrent episodes of supraventricular tachycardia (SVT). CASE REPORT: A 26-year-old woman presented with recurrent episodes of SVT. Medical history included SVT, asthma, anxiety, depression, type 2 diabetes, and migraine headaches. The patient had frequent emergency department (ED) visits with complaints of chest pain, palpitations, and heart rates typically between 130 and 150 beats/min. Electrocardiograms revealed sinus tachycardia; laboratory studies were consistently normal except for periodic episodes of hypokalemia. Over the 3 years, the patient had more than 50 visits for health care and underwent multiple diagnostic evaluations, including comprehensive laboratory testing, echocardiography, Holter monitoring, and event monitoring. Given the constellation of clinical features, a plasma albuterol concentration was obtained during an ED visit for SVT, which was 17 ng/mL (reference range for peak plasma concentration after 0.04-0.1-mg inhaler dose = 0.6-1.4 ng/mL). A subsequent ED visit with a similar presentation revealed a plasma albuterol level of 11 ng/mL. The patient adamantly denied using this medication. Due to concerns about a factitious disorder, a multidisciplinary hospital discussion was planned for subsequent interventions; however, the patient was lost to follow-up. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This is a compelling case report of a factitious disorder and occult albuterol abuse resulting in recalcitrant SVT with numerous ED visits and interventions. Patients with factitious disorders can have multiple visits for emergency care and are challenging to evaluate and treat. Albuterol toxicity can present with pronounced sinus tachycardia, fine tremor, and often with transient hypokalemia.

Prolonged venom-induced consumptive coagulopathy following Mangshan pit viper (Protobothrops mangshanensis) envenomation despite Hemato Polyvalent antivenom administration.

This case report summarizes an envenomation by the Mangshan pit viper (Protobothrops mangshanensis), a rare, endangered, venomous snake endemic to Mount Mang of China, and the first reported use of Hemato Polyvalent antivenom (HPAV) for this species. The snakebite occurred in a United States zoo to a 46-year-old male zookeeper. He presented via emergency medical services to a tertiary center after sustaining a single P. mangshanensis bite to the abdomen and was transported with antivenom from the zoo. Within 2 hours of envenomation, he developed oozing of sanguineous fluid and ecchymosis at the puncture site, and about 4 hours post-bite, was treated with HPAV. His coagulation profile fluctuated with the following pertinent peak/nadir laboratory values and corresponding hospital day (HD): undetectable fibrinogen levels, d-dimer 8.89 mg/L and 7.43 mg/L, and INR 2.97 and 1.46 on HD zero and three, respectively. Other peak/nadir values included hemoglobin 9.7 g/dL and creatinine phosphokinase 2410 U/L on HD four and platelets 81 × 109/L on HD seven. The patient received a total of 30 vials of HPAV over 5 days and 1 unit of cryoprecipitate on HD six. Upon discharge on HD eight, laboratory studies were normalizing, except for platelets, and edema stabilized. This case describes an acute, recurrent, and prolonged venom-induced consumptive coagulopathy despite prompt administration and repeated doses of HPAV.