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.

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.

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.

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.

Clinically Significant Envenomation From Postmortem Copperhead (Agkistrodon contortrix).

Over 14,000 copperhead (Agkistrodon contortrix) bites were reported to United States poison centers between 1983 and 2008, and 1809 cases were reported to poison centers in 2014. The copperhead is primarily found in the southeastern United States and belongs to the pit viper subfamily Crotalinae, which also includes the water moccasin (Agkistrodon piscivorus) and rattlesnakes (Crotalus and Sistrurus genera). Postmortem rattlesnakes have been reported to cause clinically significant envenomation; we report a case of a postmortem copperhead causing clinically significant envenomation after inadvertent puncture with the deceased copperhead fang. The copperhead was transected twice, leaving the snake in 3 separate pieces. While handling the snake head, an inadvertent puncture occurred on the right index finger followed by pain and swelling in the affected extremity necessitating antivenom administration. Care should be taken when handling deceased pit vipers due to the continued risk of envenomation.

Collaborative Public Health Investigation of Clenbuterol-Adulterated Heroin Outbreak-Richmond, Virginia, March-April 2015.

CONTEXT: In March 2015, the Virginia Department of Health (VDH) was alerted by the Virginia Poison Center of a 6-patient cluster treated for severe clinical presentations after using heroin. Patients' symptoms were atypical for heroin use, and concern existed that patients were exposed to heroin that had been adulterated with or replaced by another substance. OBJECTIVE: To understand the extent and characterization of the outbreak and implement response measures to prevent further cases. The purpose of this report is to highlight the collaborative nature of a public health investigation among a diverse group of stakeholders. DESIGN: Active surveillance and retrospective case finding. SETTING: Richmond metro area community and hospitals. PARTICIPANTS: Regional poison centers, the Division of Consolidated Laboratory Services, the Department of Behavioral Health and Developmental Services, community partners, local law enforcement, and multiple VDH divisions. INTERVENTION: Outbreak investigation, communication to public health professionals, clinicians, and the community, and liaising with the local law enforcement. MAIN OUTCOME MEASURES: Outbreak control. RESULTS: Laboratory confirmation of clenbuterol in clinical specimens implicated it as the heroin adulterant. Thirteen patients met clinical and epidemiologic criteria for exposure to clenbuterol-adulterated heroin. All patients were associated with a localized area within Richmond, and patient interviews elucidated heroin supplier information. VDH collaborated with local law enforcement agents who investigated and arrested the supplier, leading to cessation of the outbreak. CONCLUSION: This outbreak highlights the value of policies and practices that support an integrated outbreak response among public health practitioners, poison center staff, laboratorians, clinicians, law enforcement agents, community groups, and other agencies. Collaboration enabled implementation of effective control measures-including those outside the purview of the health department-and should be standard practice in future outbreaks involving illicit substances.

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.

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.

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.

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.

Peri-mortem rigidity in a fatal case of severe salicylate poisoning.

INTRODUCTION: There has been a previous case report of peri-arrest muscle rigidity in the setting of severe salicylate poisoning (serum salicylate concentration 1,500 mg/L), described as paratonia or rapid rigor mortis. We present an image of rapid rigor mortis in another fatal salicylate poisoning. CASE SUMMARY: We report a 42-year-old male with severe salicylate poisoning (peak salicylate concentration 1,600 mg/L). During the peri-arrest period, the patient developed isotonic flexion of the upper and lower extremities, the clinical signs of rapid-occurring rigor mortis. Despite resuscitative efforts, the patient died. IMAGE: Our patient is exhibiting peri-arrest rigidity in the upper extremities. DISCUSSION: Peri-mortem rigidity is due to depletion of adenosine triphosphate. Severe salicylate poisoning causes uncoupling of oxidative phosphorylation which prevents the production of adenosine triphosphate, which is required to release myosin from actin to allow the muscle to relax. A limitation of our report is that we did not definitively exclude other uncouplers of oxidative phosphorylation, such as 2,4-dinitrophenol. However, the history of aspirin ingestion was provided by the patient and corroborated by his mother, and it was confirmed by measurement of his salicylate concentration. CONCLUSION: We hypothesize that in our patient, rapid-occurring rigor mortis likely resulted from depletion of adenosine triphosphate. This occurred as a result of uncoupling of oxidative phosphorylation in the mitochondria from severe salicylate poisoning, as adenosine triphosphate is required for muscle relaxation.

The Clinical Toxicology Recommendations Collaborative: purpose, organization, and methodology.

INTRODUCTION: Scientific societies aim to provide a collective voice and unified stance on important issues. The Clinical Toxicology Recommendations Collaborative was formed in 2016 to develop evidence- and consensus-based recommendations for the management of patients exposed to common and/or serious poisonings for which the management is unclear or controversial. ORGANIZATION: The Clinical Toxicology Recommendations Collaborative is led jointly by the American Academy of Clinical Toxicology, the Asia Pacific Association of Medical Toxicology, and the European Association of Poison Centres and Clinical Toxicologists. The Governance Committee is chaired by a Past-President of one of these Societies and comprised of the six Presidents and Immediate Past-Presidents of the three Societies. A Steering Committee oversees the process of each project workgroup. METHODOLOGY: The overall process is guided by standards set forth by the Institute of Medicine for developing trustworthy guidelines and the Appraisal of Guidelines for Research and Evaluation Instrument. Systematic reviews are produced using the framework set in the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology. Workgroup members jointly review the evidence and prepare statements on which they vote anonymously using a 9-point Likert scale. A two-round modified Delphi method is used to reach a consensus on clinical recommendations using the RAND/UCLA Appropriateness Method. Final recommendations are approved by unanimous consent of the workgroup and are expressed as both levels of evidence and strength of recommendations. LIMITATIONS: The major limitations of the Clinical Toxicology Recommendations Collaborative process centre around the amount and quality of evidence, the assessment of that evidence, and the voting of the panel. CONCLUSIONS: By using a transparent evidence- and consensus-based approach to produce systematic reviews and clinical recommendations, the Clinical Toxicology Recommendations Collaborative aims to create an international framework for clinical toxicology education and decision-making and foster positive change for the benefit of poisoned patients.