Atezolizumab-induced Autoimmune Diabetes in a Patient with Metastatic Breast Cancer: A Case Report.

INTRODUCTION: Immune checkpoint inhibitors (ICI) are a class of immunotherapy drugs used increasingly in the treatment of multiple types of cancer. Major side effects include immune-related adverse effects, potentially resulting in damage to normal tissue across multiple different organ systems. CASE REPORT: A 74-year-old woman with a history of triple negative metastatic breast cancer treated with the ICI atezolizumab presented with new-onset autoimmune diabetes in diabetic ketoacidosis. She required fluid resuscitation, insulin infusion, vasopressors, and initial hospitalization in the intensive care unit. The patient was subsequently discharged on bolus dose insulin and remained an insulin-dependent diabetic at three-month follow-up. CONCLUSION: Autoimmune diabetes is a rare, but life-threatening, adverse event associated with ICIs such as atezolizumab. To our knowledge this is the only case report of atezolizumab causing autoimmune diabetes in the setting of metastatic breast cancer. As ICIs become more common in the treatment of cancer, emergency physicians should remain vigilant for the various immune-mediated complications associated with this class of immunotherapy drugs.

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.

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.

Blast Injuries Caused by Vape Devices: 2 Case Reports.

Vaporizing devices have become a popular alternative to conventional nicotine products. They are thought to be safer as they produce aerosolized nicotine powered by a lithium ion battery. Many people have used these electronic devices as a tool to quit smoking; however, the batteries can be unstable and explode.We present 2 case reports where explosions of electronic vapor devices caused significant injuries. The first patient sustained a combustion injury to the maxilla resulting in bone and anterior maxillary tooth loss requiring reconstruction. The second patient had a severe blast injury to the hand which ultimately resulted in loss of a digit. Toxicology was consulted due to concerns for systemic absorption of metals in the soft tissue of the hand. Cobalt and manganese were initially elevated but decreased after surgical debridement. The patient did not have any systemic symptoms.Currently, there is no federal regulation of electronic cigarettes or vape devices in the United States. With the increasing use of these devices and no standard regulations, we anticipate more blast injuries occurring in the future. Medical providers will need to be able to be prepared to manage the devastating clinical injuries that ensue.

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.

Safety and efficacy of flumazenil for reversal of iatrogenic benzodiazepine-associated delirium toxicity during treatment of alcohol withdrawal, a retrospective review at one center.

Both alcohol withdrawal syndrome (AWS) and benzodiazepines can cause delirium. Benzodiazepine-associated delirium can complicate AWS and prolong hospitalization. Benzodiazepine delirium can be diagnosed with flumazenil, a GABA-A receptor antagonist. By reversing the effects of benzodiazepines, flumazenil is theorized to exacerbate symptoms of AWS and precludes its use. For patients being treated for alcohol withdrawal, flumazenil can diagnose and treat benzodiazepine delirium without precipitating serious or life-threatening adverse events. Hospital admission records were retrospectively reviewed for patients with the diagnosis of AWS who received both benzodiazepines and flumazenil from December 2006 to June 2012 at a university-affiliated inpatient toxicology center. The day of last alcohol consumption was estimated from available blood alcohol content or subjective history. Corresponding benzodiazepine, flumazenil, and adjunctive sedative pharmacy records were reviewed, as were demographic, clinical course, and outcome data. Eighty-five patients were identified (average age 50.3 years). Alcohol concentrations were detectable for 42 patients with average 261 mg/dL (10-530 mg/dL). Eighty patients were treated with adjunctive agents for alcohol withdrawal including antipsychotics (n = 57), opioids (n = 27), clonidine (n = 35), and phenobarbital (n = 23). Average time of flumazenil administration was 4.7 days (1-11 days) after abstinence, and average dose was 0.5 mg (0.2-1 mg). At the time of flumazenil administration, delirium was described as hypoactive (n = 21), hyperactive (n = 15), mixed (n = 41), or not specified (n = 8). Response was not documented in 11 cases. Sixty-two (72.9 %) patients had significant objective improvement after receiving flumazenil. Fifty-six patients required more than one dose (average 5.6 doses). There were no major adverse events and minor adverse effects included transiently increased anxiety in two patients: 1 patient who received 0.5 mg on abstinence day 2 and another patient who received 0.2 mg flumazenil on abstinence day 11. This is the largest series diagnosing benzodiazepine delirium after AWS in patients receiving flumazenil. During the treatment of AWS, if delirium is present on day 5, a test dose of flumazenil may be considered to establish benzodiazepine delirium. With the limited data set often accompanying patients with AWS, flumazenil diagnosed benzodiazepine delirium during the treatment of AWS and improved impairments in cognition and behavior without serious or life-threatening adverse events in our patients.