The Efficacy of Antivenin Latrodectus (Black Widow) Equine Immune F(ab')2 Versus Placebo in the Treatment of Latrodectism: A Randomized, Double-Blind, Placebo-Controlled, Clinical Trial.

STUDY OBJECTIVE: The antivenom currently available for treatment of systemic black widow envenomation (latrodectism) is composed of equine whole immunoglobin. Although considered effective, it has been associated with anaphylaxis and 2 reported fatalities. We test the efficacy and safety of new equine antivenom composed of purified F(ab')2 antibody fragments. METHODS: A randomized, double-blind, placebo-controlled trial was conducted at 16 sites across the United States. Subjects aged 10 years or older with moderate to severe pain because of black widow spider envenomation received F(ab')2 antivenom or placebo. The primary outcome measure was treatment failure, which was defined as failure to achieve and maintain clinically significant reduction in pain for 48 hours posttreatment. Secondary measures of pain intensity differences and summed pain intensity difference were computed. Adverse events were recorded. RESULTS: Sixty patients were treated (29 antivenom and 31 placebo). The mean age was 39 years and 68% were male. There were 15 treatment failures in the antivenom group and 24 in the placebo group (P=.019). Differences in pain intensity difference between groups were lower at each postbaseline point, and the mean summed pain intensity difference was greater for the antivenom group (difference 2,133; 95% confidence interval 177 to 4,090). No deaths or serious drug-related adverse events were detected. CONCLUSION: The F(ab')2 antivenom met the predefined primary outcome of reduced treatment failures. Secondary outcomes of pain intensity difference and summed pain intensity difference also supported efficacy. The rate of symptom improvement in the placebo group was higher than expected, which may be related to enrollment criteria or placebo effect.

Epidemiology of the reported severity of cottonmouth (Agkistrodon piscivorus) snakebite.

OBJECTIVE: The goal of this study was to analyze trends in the annual rates of reported medical outcomes of cottonmouth (Agkistrodon piscivorus) snakebites in the United States, published in the annual reports of the American Association of Poison Control Centers in the course of 29 years. METHODS: This was a retrospective analysis of medical outcomes for cottonmouth snakebite victims who developed fatal, major, moderate, minor, or no effects. The annual rates for these medical outcomes were calculated by dividing the annual number of patients in each outcome category by the total annual number of people reported as being bitten by cottonmouths. Negative binomial regression was used to examine trends in annual rates. RESULTS: From 1985 through 2011, after controlling for the availability of CroFab, the annual incidence rate of cottonmouth snakebites causing no effect decreased significantly by 7.3%/year (incidence rate ratio [IRR] 0.927, 95% confidence interval [CI] 0.885-0.970), the incidence rate of minor outcomes did not change significantly (IRR 0.989, CI 0.974-1.006), the incidence rate of moderate outcomes increased significantly by 2.3%/year (IRR 1.023, CI 1.004-1.042), and the incidence rate of major outcomes did not change significantly (IRR 0.987, CI 0.935-1.041). One fatality was reported in 2011. CONCLUSIONS: Annual rates of cottonmouth snakebites producing no effects decreased significantly, those producing minor outcomes did not change significantly, those producing moderate outcomes increased significantly, and those producing major outcomes did not change significantly, from 1985 through 2011.

Epidemiology of the reported severity of copperhead (Agkistrodon contortrix) snakebite.

OBJECTIVE: The goal of this study was to analyze trends in the annual rates of reported medical outcomes of US copperhead (Agkistrodon contortrix) snakebites published in the annual reports of the American Association of Poison Control Centers in the course of 26 years. METHODS: This was a retrospective analysis of medical outcomes for copperhead snakebite victims who developed fatal, major, moderate, minor, or no effects. The annual rates for these medical outcomes were calculated by dividing the annual number of patients in each outcome category by the total annual number of people reported as being bitten by copperheads. Poisson and negative binomial regression were used to examine trends in annual rates. RESULTS: From 1983 through 2008, the incidence rate of copperhead snakebites causing no effect significantly decreased by 12.1%/year (incidence rate ratio [IRR] 0.879; 95% confidence interval [CI] 0.848-0.911]. From 1985 through 2008, the incidence rate of minor outcomes significantly decreased by 2.3%/year (IRR 0.977; 95% CI 0.972-0.981), whereas the rate of moderate outcomes significantly increased by 2.8%/year (IRR 1.028; 95% CI 1.024-1.033). The rate of major outcomes did not significantly change. One fatality was reported in 2001. CONCLUSIONS: Annual rates of copperhead snakebites producing no effects and minor outcomes significantly decreased, those producing moderate outcomes significantly increased, and those producing major outcomes did not significantly change in a 26-year period.

Temporal analyses of coral snakebite severity published in the American Association of Poison Control Centers' Annual Reports from 1983 through 2007.

INTRODUCTION: The only U.S. Food and Drug Administration-approved coral snake antivenom was officially discontinued in 2007, causing ever-diminishing supplies. This study describes the severity of U.S. coral snakebites during the last 25 years to determine trends in annual rates of these bites' medical outcomes. METHODS: This study retrospectively analyzed all human coral snakebites voluntarily reported by the public and/or health care professionals to poison centers that were subsequently published in the Annual Reports of the American Association of Poison Control Centers (AAPCC) from 1983 through 2007. Annual rates of medical outcomes from coral snakebites were calculated by dividing the annual number of people bitten by coral snakes who developed fatal, major, moderate, minor, or no effect outcomes by the total annual number of people bitten by coral snakes. Negative binomial regression was used to examine trends in annual rates. RESULTS: From 1983 through 2007, the incidence rate of coral snakebites producing no effects significantly decreased by 4.7% per year [incidence rate ratio (IRR) = 0.953; 95% confidence interval (CI) = 0.920-0.987]. From 1985 through 2007, the incidence rates of minor and major outcomes did not significantly change; however, moderate outcomes significantly increased by 3.4% per year (IRR = 1.034; 95% CI = 1.004-1.064). No fatalities were reported from 1983 through 2007. CONCLUSION: Annual rates of coral snakebites producing no effects significantly decreased and those producing moderate outcomes significantly increased in our analyses of data from the last 25 years of published AAPCC Annual Reports. This study has important limitations that must be considered when interpreting these conclusions.

Epidemiology of severe and fatal rattlesnake bites published in the American Association of Poison Control Centers' Annual Reports.

INTRODUCTION: No study has focused on the nationwide epidemiology of severe and fatal rattlesnake bites during the last 25 years. We examined rates and temporal trends of severe and fatal rattlesnake bites across the United States. Our hypothesis was that nationwide annual rates of both severe and fatal outcomes from rattlesnake bites have remained unchanged over time. METHODS: This study retrospectively analyzed all human rattlesnake bites published in the Annual Reports of the American Association of Poison Control Centers from 1983 through 2007. Annual rates of severe (major) and fatal rattlesnake bites were calculated using the annual number of major outcomes and fatalities as respective numerators and the total annual number of single rattlesnake bites (exposures) as denominators. Negative binomial and Poisson regressions were used to examine trends of severe and fatal rattlesnake bites over time. RESULTS: Annually, from 1985 to 2007, the incidence rate of major outcomes decreased by 2% per year (incidence rate ratio = 0.980; CI = 0.967-0.993), corresponding to an absolute annual rate decrease of two major outcomes per 1,000 bites per year. Annual rates of fatalities showed no statistically significant change from 1983 through 2007. CONCLUSION: This is the first study to examine rates and trends of published severe and fatal rattlesnake bites across the United States over the past 25 years. Annual rates of severe rattlesnake bites, derived from the published Annual Reports of the American Association of Poison Control Centers, have significantly decreased over time, whereas rates of fatal rattlesnake bites have remained unchanged.

Serum levels and urine detection of Centruroides sculpturatus venom in significantly envenomated patients.

INTRODUCTION: Envenomation by Centruroides sculpturatus can cause systemic signs and symptoms requiring treatment. The toxicokinetics of C. sculpturatus venom has not been described. METHODS: Venom components were separated for cross-reactivity testing. Serum and urine collected from three patients envenomated by C. sculpturatus had venom levels determined by sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: Western blot analysis indicated recognition of C. sculpturatus venom by Alacramyn, an equine F(ab')(2) antivenom developed against Centruroides scorpion venoms, including C. sculpturatus. Serum venom levels in ng/mL with post-envenomation times in minutes (min) were as follows: 85-year-old woman = 8.2 (approximately 150), 2.8 (515), 1.6 (1,200); 14-month-old girl = 29.7 (approximately 50), 5.0 (729); 3-year-old girl = 11.1 (approximately 313), urine venom level of 9.0 (approximately 490). CONCLUSION: There is sufficient venom cross-antigenicity among different Centruroides species to allow this ELISA technique with Alacramyn to determine serum and urine C. sculpturatus venom concentrations in envenomated patients.

Toxicologic information resources for reptile envenomations.

The United States is the largest importer of reptiles in the world, with an estimated 1.5 to 2.0 million households keeping one or more reptiles. Snakes account for about 11% of these imports and it has been estimated that as many as 9% of these reptiles are venomous. Envenomations by nonindigenous venomous species are a rare but often serious medical emergency. Bites may occur during the care and handling of legitimate collections found in universities, zoos, or museums. The other predominant source of exotic envenomation is from amateur collectors participating in importation, propagation, and trade of non-native species. This article provides toxicologic information resources for snake envenomations.

Resistance of antivenom proteins to foaming-induced denaturation.

Reconstitution of lyophilized antivenom is usually accomplished by gentle swirling for sometimes as much as 45min. Gentle resuspension is employed in order to avoid foaming the antivenom, which could have a variety of consequences including unfolding and denaturation of the protein, thus rendering it inactive. However, foaming of antivenom might cause only a small portion of the total protein to unfold or the protein may refold as foaming subsides. In this report, the effects of intentional severe foaming of three antivenom preparations are tested. Samples of gently resuspended antivenoms were subject to severe foaming by mechanical means, then tested for precipitation by examining the amounts of protein remaining in solution, for structural changes by circular dichroism spectroscopy and for activity changes by ELISA. In all cases, either no or minimal changes in antivenom properties were observed. These results indicate that severe intentional foaming does not substantially affect the properties of the antivenoms. It may be possible to employ more vigorous resuspension methods without affecting the efficacy of the antivenom. This could lead to a significant decrease in the time between envenomation and administration of antivenom.

Combined evidence-based literature analysis and consensus guidelines for stocking of emergency antidotes in the United States.

STUDY OBJECTIVE: To develop guidelines for the stocking of antidotes at hospitals that accept emergency admissions using combined evidence-based and consensus methods. METHODS: Study participants were 12 medical care providers from disciplines that are affected by insufficient stocking of emergency antidotes (clinical pharmacology, critical care, clinical pharmacy, emergency medicine, hospital pharmacy, internal medicine, managed care pharmacy, clinical toxicology, pediatrics, poison control centers, pulmonary medicine, regulatory medicine). Selection of individuals for the study panel was based on evidence of previous antidote research or perspective regarding the purchase and use of antidotes. The literature regarding each antidote was systematically amassed using pre-1966 literature files, current MEDLINE searches, the reference lists of major medical textbooks, and citations solicited from the consensus panel. Articles relevant to 4 defined core questions were included. These articles formed the basis of an evidence-based analysis performed by the principal investigator. After literature analysis, a literature summary and proposed guidelines for antidote stocking were submitted to the panel. Consensus was formed by electronic iterative presentation of alternatives to each panel member using a modified Delphi method. All panel members participated in 5 rounds of guideline analysis of 20 antidotes. RESULTS: Of the 20 antidotes, 16 antidotes were ultimately recommended for stocking (N -acetylcysteine, atropine, Crotalid snake antivenin, calcium gluconate and chloride, cyanide antidote kit, deferoxamine, digoxin immune Fab, dimercaprol, ethanol, fomepizole, glucagon, methylene blue, naloxone, pralidoxime, physostigmine, sodium bicarbonate), 2 were not recommended for stocking (black widow antivenin, ethylenediamine tetraacetic acid), and consensus could not be reached for 2 antidotes (flumazenil, physostigmine). CONCLUSION: These guidelines provide a tool to be used in revising or creating policies and procedures with regard to the stocking of antidotes in hospitals that accept emergency patients.