Anne Michelle Ruha

Comparison of F(ab')2 versus Fab antivenom for pit viper envenomation: A prospective, blinded, multicenter, randomized clinical trial

Abstract Background. Crotalidae Polyvalent Immune Fab (Ovine) has been the only antivenom commercially available in the US since 2007 for treatment of Crotalinae envenomation. Late coagulopathy can occur or recur after clearance of Fab antivenom, often after hospital discharge, lasting in some cases more than 2 weeks. There have been serious, even fatal, bleeding complications associated with recurrence phenomena. Frequent follow-up is required, and additional intervention or hospitalization is often necessary. F(ab’)2 immunoglobulin derivatives have longer plasma half life than do Fab. We hypothesized that F(ab’)2 antivenom would be superior to Fab in the prevention of late coagulopathy following treatment of patients with Crotalinae envenomation. Methods. We conducted a prospective, double-blind, randomized clinical trial, comparing late coagulopathy in snakebitten patients treated with F(ab’)2 with maintenance doses [F(ab’)2/F(ab’)2], or F(ab’)2 with placebo maintenance doses [F(ab’)2/placebo], versus Fab with maintenance doses [Fab/Fab]. The primary efficacy endpoint was coagulopathy (platelet count < 150 K/mm3, fibrinogen level < 150 mg/dL) between end of maintenance dosing and day 8. Results. 121 patients were randomized at 18 clinical sites and received at least one dose of study drug. 114 completed the study. Of these, 11/37 (29.7%) in the Fab/Fab cohort experienced late coagulopathy versus 4/39 (10.3%, p < 0.05) in the F(ab’)2/F(ab’)2 cohort and 2/38 (5.3%, p < 0.05) in the F(ab’)2/placebo cohort. The lowest heterologous protein exposure was with F(ab’)2/placebo. No serious adverse events were related to study drug. In each study arm, one patient experienced an acute serum reaction and one experienced serum sickness. Conclusions. In this study, management of coagulopathic Crotalinae envenomation with longer-half-life F(ab’)2 antivenom, with or without maintenance dosing, reduced the risk of subacute coagulopathy and bleeding following treatment of envenomation.

Urine Mercury Excretion Following meso-Dimercaptosuccinic Acid Challenge in Fish Eaters

CONTEXT Public awareness of methylmercury in fish has caused patients to seek testing for mercury poisoning. In some patients, the diagnosis of mercury poisoning has been made based on urine mercury excretions following oral dosing of meso-dimercaptosuccinic acid (DMSA), a metal chelator. However, studies comparing urine mercury excretion following DMSA in healthy non-fish eaters with healthy fish eaters could not be located. OBJECTIVES To describe urinary mercury excretion before and after DMSA in healthy fish eaters and non-fish eaters, and to determine whether urine mercury excretion after DMSA would rise above baseline levels to a greater extent in fish eaters. DESIGN A total of 24 healthy physicians were assigned to 1 of 3 groups based on fish consumption: non-fish eaters; 1 to 2 fish servings per week; and 3 or more servings per week. Blood mercury concentrations and 12-hour urine mercury and creatinine excretions were measured before and after oral ingestion of 30 mg of DMSA per kilogram of body weight. RESULTS A total of 24 subjects completed the study, and 2 subsequently were excluded. No difference in baseline urinary mercury excretion was detected between groups. All groups demonstrated an increase in urinary mercury excretion following DMSA, which was higher in fish eaters (P = .04). Multiple linear regression found that the best predictor of a rise in urine mercury excretion following DMSA challenge was the prechelation blood mercury concentration. CONCLUSIONS In this study of healthy physicians, oral DMSA produced a rise in urine mercury excretion both in non-fish eaters and fish eaters. The increase in chelated mercury excretion was higher in fish eaters. A simple rise in chelated mercury excretion over baseline excretion is not a reliable diagnostic indicator of mercury poisoning.

Epidemiology and clinical outcomes of snakebite in the elderly: a ToxIC database study*

Abstract Introduction: Epidemiologic studies of snakebites in the United States report typical victims to be young men. Little is known regarding other demographics including children and the elderly. The objective of this study was to describe the epidemiology and clinical manifestations of snake bite in elderly patients reported to the ToxIC (Toxicology Investigators Consortium) North American Snakebite Registry (NASBR) Methods: This was a multicenter analysis of a prospectively collected cohort of patients with snakebite reported to the ToxIC NASBR between 1 January 2013 and 31 December 2015. Inclusion criterion was age >65. Variables collected included patient demographics, medical comorbidities, medications, date the case was reported to the registry, location of exposure, bite location, snake species, clinical manifestations, outcomes, and management. Results: Of the 450 cases reported, 30 (6.7%) occurred in elderly patients, with an average age of 74 years. Rattlesnake envenomations were common (93.3%). The majority of patients were men (66.7%) and reported at least one medical comorbidity (83.3%). Most patients were on cardiac medications (60%) and use of antiplatelet or anticoagulant medications was common (33%). Hemotoxicity occurred in 30% of patients on initial presentation and 11.5% of patients on initial follow-up. No clinically significant early or late bleeding was observed. Conclusions: Elderly patients with North American snake envenomation are likely to have co-morbidities and to take medications that may increase their risk for hemotoxicity, however risk of bleeding or other complications was not increased in this group.

Gila monster (Heloderma suspectum) envenomation: Descriptive analysis of calls to United States Poison Centers with focus on Arizona cases

Abstract Background. The Gila monster (Heloderma suspectum) is a venomous lizard native to the deserts of southwestern United States (US) and northern Mexico. The purpose of this study was to describe human exposures to Gila monsters reported to US poison control centers (PCCs) with a focus on Arizona cases. Methods. The American Association of Poison Control Centers’ National Poison Data System (NPDS) was used to access and retrospectively review all calls to US PCCs, concerning Gila monsters between January 1, 2000 and October 31, 2011. In addition, detailed records from the two Arizona PCCs were reviewed for the same time period. Results. A total of 319 calls regarding Gila monsters were identified in the NPDS. Of these, 105 (33%) were human exposures; most (79%) occurred in males. A total of 71 (68%) of these 105 cases were referred to a health care facility (HCF); 30 (29%) were managed on-site. Of the 71 HCF referrals, 36 (51%) were discharged home and 17 (24%) were admitted. Most (65%) admissions were to an intensive care unit (ICU). Arizonas PCCs received 70 unique reports of Gila monster bite. Most (77%) of the bites in Arizona involved an upper extremity. Eight (11%) involved patients under the age of 18 years. Eleven (16%) Arizona cases were work-related. Twenty-eight (40%) of the 70 bites in Arizona were evaluated in a HCF, but not admitted. Eleven (16%) were admitted, of which five were to an ICU. Six patients had edema of airway structures; three required emergent airway management, one by cricothyrotomy. There were no deaths. Conclusion. Gila monster bites are uncommon. Many cases did not require hospitalization. Edema of airway structures is an infrequent, but life-threatening complication.