Recovery from Copperhead Snake Envenomation: Role of Age, Sex, Bite Location, Severity, and Treatment

  • Eric J. LavonasEmail author
  • Randy I. Burnham
  • John Schwarz
  • Eugenia Quackenbush
  • Brandon Lewis
  • S. Rutherfoord Rose
  • Spencer Greene
  • Eric A. Toschlog
  • Nathan P. Charlton
  • Michael E. Mullins
  • Richard Schwartz
  • David Denning
  • Kapil Sharma
  • Kurt Kleinschmidt
  • Sean P. Bush
  • Victoria E. Anderson
  • Adit A. Ginde
  • Charles J. Gerardo
Original Article



Few data exist to understand the recovery phase of pit viper envenomation. A recently published placebo-controlled clinical trial affords this opportunity. The purpose of this study is to examine the time course of recovery from copperhead snake (Agkistrodon contortrix) envenomation patients managed with and without the use of antivenom, stratified by age, sex, anatomic site of envenomation, initial severity of envenomation, and geographic region.


This is a post-hoc subgroup analysis of data from a multi-center double-blinded clinical trial of Fab antivenom (FabAV) vs. placebo. Outcomes were the Patient-Specific Functional Scale (PSFS) score at 3, 7, 10, and 14 days after envenomation. Least-squares mean PSFS score curves were calculated for each subgroup, and repeated measures ANOVA was used to estimate between-group comparisons.


Seventy-two subjects were included, of whom 44 received FabAV. Males demonstrated better overall recovery than females (model predicted PSFS score 6.18 vs 4.99; difference 1.19; 95% CI 0.12 to 2.25; p = 0.029). No sex difference was found in response to FabAV. Overall recovery and effect of FabAV were similar in adult vs adolescent patients, patients with upper vs lower extremity envenomation, and patients with initially mild vs moderate envenomation signs. Analysis by geographic location was not successful due to ANOVA mode instability.


Male victims of copperhead snake envenomation demonstrate slightly better recovery than females, but response to Fab antivenom overall is similar across all subgroups studied.


Envenomation Snake Agkistrodon Antivenins Snake Fab Copperhead 


Compliance with Ethical Standards

Conflict of Interest

This clinical trial and the subsequent subgroup analysis were funded by BTG International, Inc. In addition, the Denver Health and Hospital Authority (EJL, RJB, JS, and VJA) has research, consulting, and call center agreements with BTG International, Inc., and has completed research arrangements with the manufacturer of a competing antivenom. Duke University (CJG) has received research funding from BTG for projects beyond the current trial. Dr. Green has received income from BTG for professional consulting. No other author has received personal funds or has other conflicts to disclose.

Supplementary material

13181_2019_733_MOESM1_ESM.pdf (114 kb)
Online Resource 1 Mean scores on the Patient-Specific Functional Scale During Recovery from Copperhead Snake Envenomation, by Sex, Age Group, Envenomated Extremity, and Initial Severity, Divided by Treatment. Raw mean Patient Specific Functional Scale (PSFS) scores and standard error for each time point (days after treatment) and treatment group. FabAV = Fab antivenom. (PDF 113 kb)
13181_2019_733_MOESM2_ESM.png (31 kb)
Online Resource 2 Mean Scores on the Patient-Specific Functional Scale During Recovery from Copperhead Snake Envenomation in Patients Treated at The Three Highest-Enrolling Study Sites. Raw mean Patient Specific Functional Scale (PSFS) scores and standard error for each time point (days after treatment) and treatment group. FabAV = Fab antivenom. (PNG 31 kb)


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Copyright information

© American College of Medical Toxicology 2019

Authors and Affiliations

  • Eric J. Lavonas
    • 1
    • 2
    • 3
    Email author
  • Randy I. Burnham
    • 1
  • John Schwarz
    • 1
  • Eugenia Quackenbush
    • 4
  • Brandon Lewis
    • 5
  • S. Rutherfoord Rose
    • 6
  • Spencer Greene
    • 7
  • Eric A. Toschlog
    • 8
  • Nathan P. Charlton
    • 9
  • Michael E. Mullins
    • 10
  • Richard Schwartz
    • 11
  • David Denning
    • 12
  • Kapil Sharma
    • 13
  • Kurt Kleinschmidt
    • 13
  • Sean P. Bush
    • 14
  • Victoria E. Anderson
    • 1
  • Adit A. Ginde
    • 3
  • Charles J. Gerardo
    • 15
  1. 1.Rocky Mountain Poison and Drug CenterDenver Health and Hospital AuthorityDenverUSA
  2. 2.Department of Emergency MedicineDenver Health and Hospital AuthorityDenverUSA
  3. 3.Department of Emergency MedicineUniversity of Colorado School of MedicineAuroraUSA
  4. 4.Department of Emergency MedicineUniversity of North Carolina School of MedicineChapel HillUSA
  5. 5.Texas A&M Health Science CenterCollege StationUSA
  6. 6.Department of Emergency MedicineVirginia Commonwealth UniversityRichmondUSA
  7. 7.Henry J. N. Taub Department of Emergency MedicineBaylor College of MedicineHoustonUSA
  8. 8.Department of SurgeryBrody School of Medicine at East Carolina UniversityGreenvilleUSA
  9. 9.Division of Medical ToxicologyUniversity of VirginiaCharlottesvilleUSA
  10. 10.Division of Emergency MedicineWashington University School of MedicineSt. LouisUSA
  11. 11.Department of Emergency Medicine and Hospital ServicesMedical College of GeorgiaAugustaUSA
  12. 12.Department of SurgeryMarshall HealthHuntingtonUSA
  13. 13.Department of Emergency MedicineUniversity of Texas Southwestern Medical CenterDallasUSA
  14. 14.Department of Emergency MedicineBrody School of Medicine at East Carolina UniversityGreenvilleUSA
  15. 15.Division of Emergency Medicine, Department of SurgeryDuke University School of MedicineDurhamUSA

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