Childhood Victims of Snakebites: 2000–2013 Joann Schulte, DO, MPH,A Kristina Domanski, MD, a Eric Anthony Smith, MS,A Annelle Menendez, MD, a Kurt C

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Childhood Victims of Snakebites: 2000–2013 Joann Schulte, DO, MPH,a Kristina Domanski, MD, a Eric Anthony Smith, MS,a Annelle Menendez, MD, a Kurt C. Kleinschmidt, MD,b Brett A. Roth, MDa,b

BACKGROUND: Snakebites are not a reportable condition (to state health departments), and 1 abstract major assessment of US children with snakebites was published 50 years ago. Increasing urbanization, population shifts south and west, newer antivenom therapy, and the importation of exotic snakes may have changed snakebites. Poison control centers are often consulted on treatment and collect surveillance data. METHODS: Generic codes for venomous, nonvenomous, and unknown snakebites were used to characterize victims aged ≤18 years reported to US poison control centers between 2000 and 2013. Data included demographic characteristics, snake types, and outcomes. RESULTS: Callers reported 18 721 pediatric snakebites (annual mean, 1337). Two-thirds were male (n = 12 688 [68%]), with a mean age of 10.7 years. One-half of the snakebites were venomous (n = 9183 [49%]), with copperheads (n = 3602 [39%]) and rattlesnakes (n = 2859 [31%]) the most frequently identified. Reported copperhead bites increased 137% and unknown crotalids (venomous) increased 107%. Exotic (nonnative) exposures were reported in 2% of cases. All 50 states reported snakebites, but one-quarter occurred in Texas and Florida. Rates for total snakebites and venomous snakebites were highest in West Virginia, Oklahoma, and Louisiana. One-fifth required ICU admission. Limited data for 28% of bites for antivenom treatment suggests increasing use. Four victims died. CONCLUSIONS: The epidemiology of pediatric snakebites is changing. One-half of the reported exposures were venomous, and copperhead bites and exotic species are being reported more frequently. Although snakebite-related deaths are rare, ICU admission is common. Antivenom treatment is incompletely reported, but its use is increasing.

a North Texas Poison Control Center, Parkland Health & Hospital System, Dallas, Texas; and bDivision of Medical WHAT'S KNOWN ON THIS SUBJECT: Few Toxicology, Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas, Texas comprehensive assessments of pediatric snakebites Dr Schulte conceptualized and designed the study, obtained institutional review board approval, have been published. obtained the data, performed the data analysis, interpreted the data, and drafted the initial WHAT THIS STUDY ADDS: Reported snakebites manuscript and revisions; Mr Smith performed data analysis and helped draft the initial average 1300 annually. One-half of the 18 721 manuscript and revisions; Dr Domanski assisted in interpretation of data, helped draft the initial snakebites reported were venomous, and 2% manuscript, and critically revised the manuscript for important intellectual content; Dr Menendez assisted in interpretation of data and helped draft the initial manuscript; Dr Kleinschmidt involved exotic snakes. Antivenom treatment of bites assisted in design of the study, assisted in interpretation of data, and critically revised the from copperheads and unknown snake types has manuscript for important intellectual content; Dr Roth assisted in design of the study, oversaw increased. About 20% required ICU admission, and data analysis, helped draft the initial manuscript, and critically revised the manuscript for 4 deaths were reported. important intellectual content; and all authors approved the ﬁ nal manuscript as submitted and agree to be accountable for all aspects of the work. DOI: 10.1542/peds.2016-0491 Accepted for publication Aug 24, 2016 To cite: Schulte J, Domanski K, Smith EA, et al. Childhood Address correspondence to Joann Schulte, DO, MPH, North Texas Poison Control Center, Parkland Victims of Snakebites: 2000–2013. Pediatrics. 2016;138(5): Hospital, 5201 Harry Hines Blvd, Dallas, TX 75235. E-mail: [email protected] e20160491

Downloaded from www.aappublications.org/news by guest on September 23, 2021 PEDIATRICS Volume 138 , number 5 , November 2016 :e 20160491 ARTICLE Snakebites are not a reportable calculate population-based rates (137109), and exotic snake unknown condition (to state health for total snakebites and venomous if poisonous (137110). departments), and few snakebites. 10 comprehensive surveillance Antivenom Therapy assessments exist. One often- Data Selection and Conditions cited study assessing snakebites NPDS data were obtained for all During the study period, antivenom among US children was published single snakebite exposures among therapy for domestic snakebites in 1965 (50 years ago) and used data persons with a known age of ≤18 evolved. Before 2000, the major from individual hospitals in years that were reported to any antivenom used for all domestic 10 states. 1 Since that date, increasing US poison control center between venomous snakes (except coral) was urbanization, population shifts to the calendar years 2000 and 2013. 9 a polyvalent product of equine origin southern and western states, 2, 3 Cases were limited to those in which manufactured by Wyeth (US Food development of new antivenom the victim was in or referred to a and Drug Administration, personal treatments, 4 and the emergence health care facility (HCF). communication, 2016). The last lot of exotic snakes as an industry5, 6 of that antivenom expired in March have altered the population and the As a condition of obtaining the 2007, and it was generally only used circumstances in which snakebites national data, we agreed not to in severe envenomations because may occur. Increasing numbers of US contact any individual poison it could produce serious adverse households are estimated to own a control center to request free text or effects, including anaphylaxis and snake, 5 which can lead to bites and charts at any poison control center. serum sickness. 12, 13 Concurrent even death. 7, 8 We were able to obtain the death use of epinephrine to treat possible The main objective of the present abstracts of the 4 cases because such anaphylaxis was common. A separate study was to characterize snakebites cases are forwarded to American Wyeth antivenom, specific to coral to children and adolescents aged Association of Poison Control Centers snakes, had been available in ≤18 years reported to US poison and are reviewed and published in limited supply with an expiration 9 control centers between 2000 and annual reports. date of May 2016 (US Food and 2013. We investigated the trends in, Drug Administration, personal and epidemiologic characteristics of, Snakebite Variables communication, 2016). pediatric snakebites and the resulting Snakebites are defined with NPDS consequences, including hospital generic codes9, 11 identifying The Fab antivenom that has become admissions and possible antivenom venomous, nonvenomous, and the therapeutic cornerstone for many treatment. unknown snakes, both species US snakebites, including those to 4 indigenous to the United States children, was granted approval by and exotic varieties that are the US Food and Drug Administration METHODS nonnative to the United States. 9 in 2000. This Fab antivenom (CroFab [BTG International Inc, Data Sources Specific codes for the domestic snakes are unknown types of snake West Conshohocken, PA]) is derived This study was based on data envenomation (13700); unknown from sheep and is considered less collected in the National Poison Data or known nonpoisonous snakebites antigenic because it lacks the Fc System (NPDS), which is maintained 4, 13 (137102); rattlesnake envenomation antibody fragment. In this article, by the American Association of (137103); coral snake envenomation the newer antivenom is referred to Poison Control Centers. Poison (137104); copperhead envenomation as Fab antivenom. The older Wyeth control centers offer 24-hour advice (137106); cottonmouth/water antivenoms are called polyvalent and consultation for individuals moccasin envenomation (137107); antivenom and coral snake and hospitals using an 800 number, and unknown crotalid envenomation antivenom and, collectively, as older with calls routed on the basis of (137105). Rattlesnakes, copperheads, antivenoms. the caller’s area code. The collected and cottonmouths/water moccasin documentation for each call includes Collected information on antivenoms are all pit vipers and are classified as exposure (in this study, type of is coded as recommended, unknown crotalids if not specifically snake), basic demographic data on performed, recommended and identified. the exposed person, subsequent performed, and recommended, medical information related to the Codes for the exotic snakes, known not performed. We exposure, and other information nonnative to the United States, consolidated those categories into regarding the incident. 9 US include exotic snake poisonous treated and any consideration of Census Bureau data were used to (137108), exotic snake nonpoisonous antivenom on use.

Downloaded from www.aappublications.org/news by guest on September 23, 2021 2 SCHULTE et al Deﬁ nition of Treatable Envenomation

Most snakebites, whether venomous or not, will have some type of local tissue effect, including minor pain and erythema. Venomous snakebites may cause a variety of symptoms, including pain, swelling, tissue necrosis, low blood pressure, convulsions, hemorrhage, respiratory paralysis, kidney failure, coma, and death. 1, 3, 9 However, not all venomous snakes are identified as such, and unknown snakes can be venomous FIGURE 1 but unrecognized. Pediatric snakebite study ﬂ owchart. The decision to treat a specific bite Additional variables analyzed were made between 7:00 and with antivenom is made by a treating included children’s sex, age, and 10:00 PM. Most patients (n = 14 980 provider, often in consultation with month and year of exposure. 11 [80%]) were in an HCF when the a poison control center. Antivenom Exposure, case, and call were used as poison control center was called. treatment may be administered for interchangeable terms. victims bitten by known venomous Deaths snakes or bites in which an unknown Statistical Analysis and Ethical snake type produces serious Considerations Four separate deaths of children complications in the provider’s were reported; 3 by rattlesnakes SAS version 9.3 (SAS Institute, Inc, judgment. (Texas, Georgia, and Florida) and Cary, NC) and Epi Info (Centers for 1 by an unknown type of snake Disease Control and Prevention, A potentially treatable envenomation (Florida). All deaths were considered Atlanta, GA) were used for data was defined as one in which a bitten directly related to the snakebites. patient was at risk for complications analysis. The institutional review because the bite involved an board at UT Southwestern approved A 2-year-old girl who died in Texas identified domestic venomous snake this study. in 2010 had 2 bites on her ankle; or an unknown domestic snake a rattlesnake was found at the (n = 15 422) ( Fig 1). The domestic lake where she visited. She had a RESULTS venomous snakes considered generalized seizure before transport included rattlesnakes, copperheads, Demographic Characteristics of to a hospital 2 hours away where she cottonmouths, coral snakes, and Bitten Children and Adolescents was given 6 vials of Fab antivenom unknown crotalids. and admitted to the ICU. She was Poison control centers received 18 721 started on vasopressor agents but reports of snakebites to children and became hypotensive and pulseless. Other Variables ≤ adolescents aged 18 years during the She died 5 hours after being bitten. Geographic location is the state study period. More than two-thirds n A 3-year-old boy was bitten in where the snakebite occurred. 11 of those bitten were male ( = 12 688 Georgia in 2000 by a rattlesnake, Exposure site was collapsed to [68%]), with a mean age of 10.7 years. received 36 vials of polyvalent residence (either the child’s own Bite numbers were highest among n crotalid antivenom, and developed home or another) versus all other children aged 3 to 9 years ( = 6717 n disseminated intravascular sites. In NPDS, level of treatment [36%]) and 10 to 14 years ( = 5917 coagulopathy. He died within several at an HCF is categorized as seen at [32%]). Four deaths were reported. hours of the envenomation. HCF, no HCF treatment, and patient Exposures were reported in all refused referral/did not arrive at months, with one-third in June In 2000, a 2-year-old boy from the HCF. The description of being and July (n = 6461 [33%]). Most Florida was bitten on the knee by a seen at HCF includes admission to a exposures were in residential home rattlesnake and received 90 vials of critical care unit (ICU), admitted to settings (n = 14 824 [89%]). Calls polyvalent crotalid antivenom. He a noncritical care unit (floor), being were distributed equally among the had only 1 fang mark and bled from treated/evaluated, and released 7 weekdays, and more than one- a cutdown site, oral orifices, and the (<24-hour stay). quarter of calls (n = 5048 [27%]) gastrointestinal tract. He received

Downloaded from www.aappublications.org/news by guest on September 23, 2021 PEDIATRICS Volume 138 , number 5 , November 2016 3 vasopressor agents and transfusions but had had no response to pain within 24 hours and was declared brain dead. A 17-year-old female, bitten on the right hand by an unknown type of snake in 2001 in Florida, was initially seen at a fire station. She was thought to be having an allergic reaction and given epinephrine. She had 2 puncture marks on her right hand, with no local swelling or ecchymosis. She had a seizure en route to the emergency department and became hypotensive. She was intubated, received a total of 34 vials of Fab antivenom, and had no response to vasopressor agents. She died on day 5 of hospitalization. FIGURE 2 Rates of total snakebites per 1 million according to state, ages 0 to 18 years, 2000 to 2013. Geographic Distribution of All Snakebites An annual mean of 1337 snakebites were reported (range, 1184–1527). One-half of all the reported snakebites (domestic and exotic) were venomous (n = 9182 [49%]). Other totals were nonvenomous (n = 3156 [17%]) and unknown type of snake (n = 6382 [34%]). Among the venomous snakes, copperheads (n = 3602 [39%]) and rattlesnakes (n = 2859 [31%]) were most common. Lower numbers were reported for unknown crotalids (n = 1853 [20%]), cottonmouths (n = 511 [6%]), coral snakes (n = 232 [3%]), and exotic n venomous snakes ( = 126 [1%]). FIGURE 3 Rates of venomous snakebites per 1 million population according to state, ages 0 to 18 years, 2000 Snakebites were reported in 50 to 2013. states, Washington, DC, and Puerto Rico, but 39% (n = 7238) were Puerto Rico. Forty percent (n = bites (Fig 3) were highest in West reported by 4 states: Texas (n = 2627 3789) of snakebites were reported Virginia (421.4), Oklahoma (383.2), [14%]), Florida (n = 2199 [12%]), in 4 states: Texas (n = 1431 [16%]), and Louisiana (354). Georgia (n = 1237 [7%]), and North Florida (n = 895 [10%]), North Carolina (n = 1174 [6%]). Prevalence Carolina (n = 815 [9%]), and California Trends in Reported Snakebite rates per 1 million population ( Fig 2) (n = 648 [7%]). Texas and North Exposures and Antivenom Use for all snakebites were highest in Carolina reported one-third of the West Virginia (762.3), Louisiana copperhead bites (n = 1203). Arizona Use of any antivenom therapy was (625.5), and Oklahoma (557.5). and California reported 40% (n = considered in 5279 (28%) reported 1154) of the rattlesnake bites. Florida snakebites and administered in 4817 Geographic Distribution of reported 60% of coral snake bites (25.7%) exposures. During the study Venomous Snakebites (n = 160) and 25% of cottonmouth period, Fab antivenom use increased Venomous snakebites were reported bites (n = 124). Prevalence rates per 298%, spiking after the last lot of in 48 states, Washington, DC, and 1 million populations for venomous polyvalent antivenom expired.

Downloaded from www.aappublications.org/news by guest on September 23, 2021 4 SCHULTE et al Figure 4 shows trends in reported exposures for domestic snakes (venomous and unknown) that might be treated with antivenom therapy (as discussed in the Definition of Treatable Envenomation section). Between 2000 and 2013, copperhead reports increased 137% and unknown crotalid reports increased 107%. Figures 5, 6, and 7 show trends in reported snakebites and antivenom use for rattlesnake, copperhead, and unknown crotalid bites, respectively. In each case, the Fab antivenom drove most of the increase and increased markedly starting in 2007.

Level of Health Care and Treatment FIGURE 4 Almost 40% (n = 7106 [38%]) of Pediatric snakebites reported to US poison control centers, 2000 to 2013. pediatric cases caused hospital admissions, and 1 in 5 reported cases were admitted to ICUs (n = 3541 [19%]). One-half of the patients (n = 9397) were treated and released, and <1% (n = 11) were admitted to a psychiatric facility. Antivenom use ( Table 1) was highest for rattlesnake bites (n = 1181 [41%]). More than one-third of bites by copperheads (n = 1278 [34%]), cottonmouths (n = 175 [35%]), and unknown crotalids (n = 684 [37%]) were treated with antivenom. Lower treatment percentages were reported for coral snakes (n = 36 [20%]) and unknown types of snakes (n = 1816 [28%]).

Among 15 422 patients with FIGURE 5 potentially treatable snakebites, Reported rattlesnake bites and antivenom use, 2000 to 2013. rattlesnake victims were 3.8 times (odds ratio, 3.80 [95% confidence Exotic Snakes admitted to the hospital, and 4% interval, 3.48–4.13]) more likely (n = 37) were ICU admissions. to be admitted to an HCF than Two percent (n = 368) of the those patients bitten by all other exposures reported involved exotic DISCUSSION types of snakes. Children bitten by snakes. Almost one-half of the exotic rattlesnakes were 3.9 times (odds snakes were boa constrictors (n = The last comprehensive assessment ratio, 3.92 [95% confidence interval, 182 [49%]), and 31 different exotic of epidemiology of snakebites among 3.53–4.35]) more likely to be venomous species were reported. children and adolescents of which admitted to an HCF than those bitten Nine percent of children (n = 76) we are aware was published in 1965 by copperheads. with exotic snake encounters were when inpatient hospital records

Downloaded from www.aappublications.org/news by guest on September 23, 2021 PEDIATRICS Volume 138 , number 5 , November 2016 5 in 10 states were reported. 1 The present study provides data from 50 states, Puerto Rico, and Washington, DC, and finds both similarities and differences. Copperheads and rattlesnakes remain the most common domestic venomous snakes reported; most snakebites are reported during summer months; and few deaths occurred. More than 1100 children and adolescents are bitten each year, and ∼20% of victims require ICU admission. Almost 50% of the reported snakebites were venomous, but 84% of all domestic snakebites could have been potentially treated with antivenom therapy. Every state reported snakebite FIGURE 6 Reported copperhead bites and antivenom use, 2000 to 2013. victims, but copperhead reports were focused in the southeastern US and rattlesnakes in the west. Three for briefer time periods.4, 14 Much charges for just the antivenom can be states (West Virginia, Oklahoma, of the augmented use is driven by almost $100 000. 18 and Louisiana) had the highest copperhead bites, which increased Our study also prompts questions prevalence rates of both total bites 107% during the study period; use concerning the data regarding and venomous bites. These findings of Fab antivenom for those bites antivenom treatment. We had data on suggest the potential benefit of increased 775%. Traditionally, antivenom therapy for only 28% of prevention efforts tailored to antivenom treatment of copperheads pediatric reports, but up to 83% of all states reporting large numbers of was less common because their domestic snakebites were potentially snakebites (Texas, Florida, Georgia, venom is less toxic, producing treatable with antivenom according North Carolina, Arizona, and milder symptoms than bites by to our estimates. The seeming California) or have high prevalence rattlesnakes or cottonmouths. 15, 16 discrepancy may be explained by rates (Oklahoma, West Virginia, and More recent studies have found the variation in bites and symptoms Louisiana). that residual copperhead venom that the bites produce. Up to 20% of We found that the use of antivenom effects, including swelling, pain, and venomous snakebites are dry,19, 20 and for rattlesnake, copperhead, and functional disability, may persist for the amount of venom injected varies unknown crotalid bites increased 13 days.17 Treatment with the newer among bites. Dry bites occur because during the study period, especially Fab antivenom has become more a specific snake may have hunted after 2006. This finding is common and can be expensive. Initial and used all venom supplies. The similar to those of earlier studies treatment requires at least 4 to 6 severity of clinical manifestations can examining the use of antivenom vials of antivenom, and the patient’s vary greatly, with minimal symptoms

TABLE 1 Characteristics and Treatment of Venomous and Unknown Snakebites, 2000 to 2013 Patient Characteristic Rattlesnake Copperhead Cottonmouth Coral (n = 232) Unknown Crotalid Unknown Snake (n = 2859) (n = 3602) (n = 511) (n = 1853) (n = 6382) Mean age, y 10.6 10.8 12.2 12.2 10.7 10.6 Male 2035 (71) 2325 (65) 396 (78) 187 (81) 1194 (64) 4289 (67) HCF admit 1361 (48) 798 (22) 123 (24) 98 (42) 466 (25) 634 (10) ICU admit 500 (17) 363 (10) 121 (24) 29 (13) 566 (31) 944 (15) Antivenom treatment Fab antivenom 958 (34) 1110 (31) 135 (26) NA 571 (31) 823 (13) Older antivenoma 223 (8) 168 (5) 40 (8) 36 (16) 113 (6) 993 (16) Any antivenom 1181 (41) 1278 (36) 175 (34) NA 684 (37) 1816 (28) Data are presented as n (%) unless indicated otherwise. NA, not applicable. a Either polyvalent crotalid or monovalent coral snake.

Downloaded from www.aappublications.org/news by guest on September 23, 2021 6 SCHULTE et al of envenomation, or the amount of antivenom used in treatment. HCFs may treat snakebites and not consult with a poison center, especially if the treating physician chooses not to use antivenom. Some data may be miscoded. In addition, our data likely do not completely reflect the time of day when the snakebite occurred. The national data collection includes time of call but no data regarding time of exposure. In addition, snakes may be improperly identified or not identified at all. NPDS data use voluntary self-reporting from health care providers, patients, FIGURE 7 and friends and family who have Reported unknown crotalid bites and antivenom use, 2000 to 2013. varying levels of knowledge, and the follow-up of cases may not to life-threatening complications, is also changing. Fifty years ago, be complete. However, NPDS and they may not develop or no exotic species were reported. 1 data are the most comprehensive progress slowly or rapidly. Systemic In our report, only 2% of pediatric and accurate database for such manifestations, usually attributed to exposures were exotic species, but exposures. venomous bites, can include rapid pet industry groups have estimated swelling, ecchymosis, and progression that 846 000 households own to hypotension, altered sensorium, snakes. 4 Some exotic species (all CONCLUSIONS tachycardia, respiratory distress, and of them constrictors) have been Our study found changes in the severe coagulation abnormalities restricted from further importation venomous snakebites reported, with and require admission to the ICU. In and from interstate transport by increased numbers of copperhead bites 22 many exposures, the exact snake is the federal government. It is reported, an increased use of newer unidentified. This fact can complicate reasonable to expect that the antivenom therapy for species beyond decisions about whether to use calls to poison control centers about rattlesnakes, and the emergence of antivenom. exotic snakes will become more exotic species. Educational prevention common. efforts should focus on states reporting We found only 4 pediatric victims large numbers of snakebites or high who died during the study period. The present study has a number of prevalence rates. This finding is consistent with earlier limitations. Our assessment was based assessments that ∼5 persons of all on described exposures reported to US ages die each year of snakebites in poison control centers by voluntary ABBREVIATIONS callers, which does not capture all the United States. 21 HCF: health care facility incidents. The NPDS also does not NPDS: National Poison Data The type of snakebites that poison capture detailed information on the System control centers are consulted about anatomic site of the bite, the degree

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2016 by the American Academy of Pediatrics FINANCIAL DISCLOSURE: Dr. Kleinschmidt has received funding for the North American Snakebite Registry that is supported by the American College of Medical Toxicology through an unrestricted grant from BTG Pharmaceuticals. This registry has no relationship to the National Poison Data System (the data source for the study). The other authors have indicated they have no ﬁ nancial relationships relevant to this article to disclose. FUNDING: No external funding. POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conﬂ icts of interest to disclose.

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