Captive Black Mamba (Dendroaspis Polylepis) Bite Leading to Respiratory Failure.

BACKGROUND: Of the 8000-10,000 snake envenomations evaluated in U.S. emergency departments (ED) annually, approximately 1% are due to non-native snakes. We describe a 26-year-old man who was bitten by his captive black mamba (Dendroaspis polylepis) as he was packing it up for transport to another snake collector. CASE REPORT: The patient presented to the ED 1 h after being bitten on the forearm, complaining of left arm pain, oral paresthesias, and dyspnea. His vital signs: heart rate 96 beats/min, blood pressure 167/101 mm Hg, temperature 36.7°C (97.9°F), respiratory rate 20 breaths/min, and room air oxygen saturation 100%. Two mildly tender puncture wounds without swelling or ecchymosis were found on the posterior aspect of the forearm. Over the ensuing 30 min his dyspnea worsened, and he developed objective weakness. He was intubated and placed on mechanical ventilation. He was treated with atropine 2 mg for bronchorrhea. Five vials of South African Vaccine Producers (Johannesburg, South Africa) polyvalent antivenom were administered 2.5 h post-bite and the patient was admitted to the intensive care unit. He was extubated 18 h post-envenomation and discharged the following day. He has remained asymptomatic since leaving the hospital. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The primary manifestations of D. polylepis envenomings are neurological. Initial signs may include paresthesias, dysarthria, dysphagia, and ptosis. Progressive descending paralysis leading to respiratory failure develops within 60 min. Muscarinic features are frequently observed. Cardiotoxicity and hematologic laboratory abnormalities may be present. Although pain is common, significant local tissue injury does not occur. In addition to supportive care, several non-native antivenoms are indicated for D. polylepis envenomations. Black mamba envenomings differ from the native snakebites with which U.S. physicians are familiar. Rapid, progressive neurological toxicity and muscarinic features are most common. Treatment consists of supportive care and appropriate antivenom administration.

Anticonvulsant fatalities reported to the American Association of Poison Control Centers 2000 - 2019.

BACKGROUND: Anticonvulsants are frequently prescribed, and exposures are commonly reported to American Association of Poison Control Centers sites. The purpose of this study was to describe the epidemiology of fatalities associated with oral anticonvulsant use, including patient demographics, specific medications, and the circumstances surrounding the deaths. METHODS: This was a retrospective analysis of cases coded with oral anticonvulsants as a single substance and associated with a fatal outcome reported to the AAPCC National Poison Data System from 2000 to 2019. Polydrug ingestions and parenteral exposures were excluded. Patient characteristics, circumstances of the ingestion, specific medication, and chronicity of use were described. RESULTS: We identified 126 cases that were classified as fatalities associated with single anticonvulsant use. The five most implicated anticonvulsants were carbamazepine, gabapentin, lamotrigine, phenytoin, and valproic acid. The majority (68.3%) of fatal cases were suicides. Phenytoin was implicated in eight (89%) adverse reactions and seven (70%) therapeutic errors. Valproic acid caused one (11.1%) adverse reaction and was associated with one (10%) therapeutic error. Three (75%) unintentional fatalities were caused by carbamazepine. The plurality (42.1%) of fatal ingestions occurred in acute-on-chronic use. An additional 40 (31.7%) were acute. Chronic use accounted for 15 (11.9%) of fatal exposures, including 5/10 of fatalities attributed to therapeutic error. The chronicity of medication use was unknown in 18 (14.3%) of fatal ingestions. Narrative summaries were available in 14 cases. Four of the patients presented to the emergency department with minimal symptoms. The other 10 had varying degrees of central nervous system (CNS) depression. Seizures were observed in six cases. Hyperammonemia was reported in seven of nine valproic acid ingestions. CONCLUSIONS: Fatalities associated with isolated anticonvulsant use are uncommon and typically occur following intentional overdoses. Fatal adverse reactions and therapeutic errors are most associated with phenytoin use and disproportionately affect elderly patients.

Predictors of severe outcome following opioid intoxication in children.

INTRODUCTION: While the opioid crisis has claimed the lives of nearly 500,000 in the U.S. over the past two decades, and pediatric cases of opioid intoxications are increasing, only sparse data exist regarding risk factors for severe outcome in children following an opioid intoxication. We explore predictors of severe outcome (i.e., intensive care unit [ICU] admission or in-hospital death) in children who presented to the Emergency Department with an opioid intoxication. METHODS: In this prospective cohort study we collected data on all children (0-18 years) who presented with an opioid intoxication to the 50 medical centers in the US and two international centers affiliated with the Toxicology Investigators Consortium (ToxIC) of the American College of Medical Toxicology, from August 2017 through June 2020, and who received a bedside consultation by a medical toxicologist. We collected relevant demographic, clinical, management, disposition, and outcome data, and we conducted a multivariable logistic regression analysis to explore predictors of severe outcome. The primary outcome was a composite severe outcome endpoint, defined as ICU admission or in-hospital death. Covariates included sociodemographic, exposure and clinical characteristics. RESULTS: Of the 165 (87 females, 52.7%) children with an opioid intoxication, 89 (53.9%) were admitted to ICU or died during hospitalization, and 76 did not meet these criteria. Seventy-four (44.8%) children were exposed to opioids prescribed to family members. Fentanyl exposure (adjusted OR [aOR] = 3.6, 95% CI: 1.0-11.6; p = 0.03) and age ≥10 years (aOR = 2.5, 95% CI: 1.2-4.8; p = 0.01) were independent predictors of severe outcome. CONCLUSIONS: Children with an opioid toxicity that have been exposed to fentanyl and those aged ≥10 years had 3.6 and 2.5 higher odds of ICU admission or death, respectively, than those without these characteristics. Prevention efforts should target these risk factors to mitigate poor outcomes in children with an opioid intoxication.

Monocled Cobra (Naja kaouthia) Envenomations Requiring Mechanical Ventilation.

BACKGROUND: Bites from nonnative snakes are uncommon, accounting for 1.1% of envenomations reported to poison centers between 2015 and 2018. Here we discuss two monocled cobra (Naja kaouthia) envenomations resulting in respiratory failure. CASE REPORTS: A 30-year-old man and a 40-year-old man were bitten by their captive monocled cobras. At the first hospital, the first patient was mildly hypotensive, transiently bradycardic, and confused. He was intubated for respiratory distress. He was hypertensive to 211/119 mm Hg upon arrival to the second hospital. In the Emergency Department, cobra antivenom was administered. He was admitted to the medical intensive care unit (MICU) and had an additional bradycardic episode that corrected with atropine. He was extubated after 35 h. He was observed for an additional 9 h prior to going home, where he recovered without incident. The second patient developed abdominal pain, blurry vision, and dyspnea within 90 min of the bite. He was intubated at the first hospital. At the second hospital he received cobra antivenom and was admitted to the MICU. He was extubated after 9 h and discharged the following day with no further symptoms. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Envenomations after N. kaouthia bites are characterized by local tissue injury and various neurotoxic effects. Nonspecific signs and symptoms are common. Hematologic toxicity and cardiovascular manifestations are uncommon. Antivenom is the specific treatment for snake envenomation, but only certain antivenoms are indicated for N. kaouthia. Cholinesterase inhibitors may reduce toxicity from postsynaptic alpha toxins by increasing acetylcholine concentrations.

Epidemiology of fatal snakebites in the United States 1989-2018.

BACKGROUND: There are 5000-10,000 snake envenomations annually in the United States. Fortunately, few are fatal. In this study we review the epidemiology of fatal snakebites. METHODS: Native snakebite cases from the American Association of Poison Control Centers (AAPCC) National Poison Data System from 1989 to 2018 were reviewed. Additional cases that were not reported to the AAPCC were identified by reviewing Wikipedia and by searching PubMed and online news outlets using various combinations of relevant keywords. RESULTS: We identified 101 fatal bites from native snakes. Rattlesnakes accounted for 74 (90.2%) of the 82 deaths for which the species was known or which occurred where rattlesnakes are the only native crotalids. There were five fatalities attributed to copperheads, two due to cottonmouths, and one caused by an eastern coral snake. Males were disproportionately affected. The median age for victims was 40 years old. In cases for which data were available, many of the snake interactions were intentional, e.g. religious services, animal husbandry, and attempting to kill the snake. CONCLUSIONS: Death following envenomation from a native U.S. snake is unlikely, particularly if medical attention is sought promptly. Rattlesnake envenomations are more likely to be fatal than bites from other species. Intentionally engaging with a venomous snake raises the risk of incurring a fatal bite, as does concurrent alcohol or drug use. Age less than 12 years old does not appear to be a risk factor for a fatal outcome, while elderly patients may have a slightly increased risk of death.

Validity and reliability of telephone administration of the patient-specific functional scale for the assessment of recovery from snakebite envenomation.

OBJECTIVES: Although more than 1.8 million people survive snakebite envenomation each year, their recovery is understudied. Obtaining long-term follow-up is challenging in both high- and low-resource settings. The Patient-Specific Functional Scale (PSFS) is an easily administered, well-accepted patient-reported outcome that is validated for assessing limb recovery from snakebite envenomation. We studied whether the PSFS is valid and reliable when administered by telephone. METHODS: This is a secondary analysis of data from a randomized clinical trial. We analyzed the results of PSFS collected in-person on days 3, 7, 14, 21, and 28 and by telephone on days 10, 17, and 24. We assessed the following scale psychometric properties: (a) content validity (ceiling and floor effects), (b) internal structure and consistency (Cronbach's alpha), and (c) temporal and external validity using Intraclass Correlation Coefficient (ICC). Temporal stability was assessed using Spearman's correlation coefficient and agreement between adjacent in-person and telephonic assessments with Cohen's kappa. Bland Altman analysis was used to assess differential bias in low and high score results. RESULTS: Data from 74 patients were available for analysis. Floor effects were seen in the early post-injury time points (median: 3 (IQR: 0, 5) at 3 days post-enrollment) and ceiling effects in the late time points (median: 9 (IQR: 8, 10). Internal consistency was good to excellent with both in-person (Cronbach α: 0.91 (95%CI 0.88, 0.95)) and telephone administration (0.81 (0.73, 0.89). Temporal stability was also good (ICC: 0.83 (0.72, 0.89) in-person, 0.80 (0.68, 0.88) telephone). A strong linear correlation was found between in-person and telephone administration (Spearman's ρ: 0.83 (CI: 0.78, 0.84), consistency was assessed as excellent (Cohen's κ 0.81 (CI: 0.78, 0.84), and Bland Altman analysis showed no systematic bias. CONCLUSIONS: Telephone administration of the PSFS provides valid, reliable, and consistent data for the assessment of recovery from snakebite envenomation.

Validity and reliability of telephone administration of the patient-specific functional scale for the assessment of recovery from snakebite envenomation

Objectives Although more than 1.8 million people survive snakebite envenomation each year, their recovery is understudied. Obtaining long-term follow-up is challenging in both high- and low-resource settings. The Patient-Specific Functional Scale (PSFS) is an easily administered, well-accepted patient-reported outcome that is validated for assessing limb recovery from snakebite envenomation. We studied whether the PSFS is valid and reliable when administered by telephone. Methods This is a secondary analysis of data from a randomized clinical trial. We analyzed the results of PSFS collected in-person on days 3, 7, 14, 21, and 28 and by telephone on days 10, 17, and 24. We assessed the following scale psychometric properties: (a) content validity (ceiling and floor effects), (b) internal structure and consistency (Cronbach’s alpha), and (c) temporal and external validity using Intraclass Correlation Coefficient (ICC). Temporal stability was assessed using Spearman’s correlation coefficient and agreement between adjacent in-person and telephonic assessments with Cohen’s kappa. Bland Altman analysis was used to assess differential bias in low and high score results. Results Data from 74 patients were available for analysis. Floor effects were seen in the early post-injury time points (median: 3 (IQR: 0, 5) at 3 days post-enrollment) and ceiling effects in the late time points (median: 9 (IQR: 8, 10). Internal consistency was good to excellent with both in-person (Cronbach a: 0.91 (95%CI 0.88, 0.95)) and telephone administration (0.81 (0.73, 0.89). Temporal stability was also good (ICC: 0.83 (0.72, 0.89) in-person, 0.80 (0.68, 0.88) telephone). A strong linear correlation was found between in-person and telephone administration (Spearman’s Ró: 0.83 (CI: 0.78, 0.84), consistency was assessed as excellent (Cohen’s capa 0.81 (CI: 0.78, 0.84), and Bland Altman analysis showed no systematic bias. Conclusions Telephone administration of the PSFS provides valid, reliable, and consistent data for the assessment of recovery from snakebite envenomation.

Validity and reliability of telephone administration of the patient-specific functional scale for the assessment of recovery from snakebite envenomation

Objectives Although more than 1.8 million people survive snakebite envenomation each year, their recovery is understudied. Obtaining long-term follow-up is challenging in both high- and low-resource settings. The Patient-Specific Functional Scale (PSFS) is an easily administered, well-accepted patient-reported outcome that is validated for assessing limb recovery from snakebite envenomation. We studied whether the PSFS is valid and reliable when administered by telephone. Methods This is a secondary analysis of data from a randomized clinical trial. We analyzed the results of PSFS collected in-person on days 3, 7, 14, 21, and 28 and by telephone on days 10, 17, and 24. We assessed the following scale psychometric properties: (a) content validity (ceiling and floor effects), (b) internal structure and consistency (Cronbach’s alpha), and (c) temporal and external validity using Intraclass Correlation Coefficient (ICC). Temporal stability was assessed using Spearman’s correlation coefficient and agreement between adjacent in-person and telephonic assessments with Cohen’s kappa. Bland Altman analysis was used to assess differential bias in low and high score results. Results Data from 74 patients were available for analysis. Floor effects were seen in the early post-injury time points (median: 3 (IQR: 0, 5) at 3 days post-enrollment) and ceiling effects in the late time points (median: 9 (IQR: 8, 10). Internal consistency was good to excellent with both in-person (Cronbach a: 0.91 (95%CI 0.88, 0.95)) and telephone administration (0.81 (0.73, 0.89). Temporal stability was also good (ICC: 0.83 (0.72, 0.89) in-person, 0.80 (0.68, 0.88) telephone). A strong linear correlation was found between in-person and telephone administration (Spearman’s Ró: 0.83 (CI: 0.78, 0.84), consistency was assessed as excellent (Cohen’s capa 0.81 (CI: 0.78, 0.84), and Bland Altman analysis showed no systematic bias. Conclusions Telephone administration of the PSFS provides valid, reliable, and consistent data for the assessment of recovery from snakebite envenomation.

Effervescent N-Acetylcysteine Tablets versus Oral Solution N-Acetylcysteine in Fasting Healthy Adults: An Open-Label, Randomized, Single-Dose, Crossover, Relative Bioavailability Study.

BACKGROUND: Oral solution N-acetylcysteine (NAC) is an antidote for acetaminophen overdose, but its unpleasant taste and aroma can impede delivery even after the coadministration of antiemetic medications. Flavored effervescent NAC tablets dissolved in water might be a more palatable formulation than oral solution NAC diluted with soft drink. OBJECTIVES: To evaluate the relative bioavailability of these 2 formulations and assess subjective preferences between them. METHODS: Thirty healthy adult volunteers (mean [SD] = 35.2 [9.14] years) were enrolled in this open-label, randomized, single-dose, crossover study, with a 7-day washout period. Volunteers were randomized to receive 11 g effervescent test formulation or the reference product under fasting conditions, after which 19 serial blood samples were collected over 48 hours. Total plasma NAC concentrations were evaluated by LC-MS, and pharmacokinetic parameters were calculated. The 2 formulations were considered bioequivalent if the 90% CIs of log-transformed ratios of pharmacokinetic parameters were within the predetermined bioequivalence range (80%-125%) established by the US Food and Drug Administration. Within 15 minutes of dosing, subjects were also asked to rank formulation attributes on a 5-point hedonic scale, with mean group differences analyzed by Wilcoxon signed rank test. Safety-profile assessment included treatment-emergent adverse events, physical examination, chemistry, and hematology parameters. RESULTS: The concentration-versus-time profiles were similar for the 2 formulations, with mean Cmax of 26.5 µg/mL for effervescent NAC tablets and 28.4 µg/mL for oral solution NAC. The 90% CIs for the pharmacokinetic parameters met the criteria for concluding bioequivalence, and subjects preferred effervescent NAC tablets in terms of taste (P = 0.0247), flavor (P = 0.0082), texture (P = 0.009), and overall likeability (P = 0.0012), but there was no difference for smell (P = 0.0533). All treatment-emergent adverse events were mild, with no differences between the treatment groups. CONCLUSIONS: Data from this study of a single dose of 11 g oral NAC demonstrated that effervescent NAC tablets and oral solution NAC met the regulatory criteria for bioequivalence in fasting healthy adult subjects. Effervescent NAC tablets appear to be a more palatable alternative for treatment of acetaminophen overdose. ClinicalTrials.gov identifier: NCT02723669. (Curr Ther Res Clin Exp. 2016; 83C:1-7) © 2016 Elsevier HS Journals, Inc.