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Does This Patient Have a Severe Snake Envenomation?The Rational Clinical Examination Systematic Review

Educational Objective To identify the key clinical features of snake bites that predict severe envenomation and state the risks and potential benefits of antivenom treatment.
1 Credit CME
Key Points

Question  What clinical features risk-stratify patients with snakebite as having severe envenomations?

Findings  In this systematic review, the pooled prevalence of severe systemic envenomation, severe tissue injury, and severe hematologic venom effects was 14%, 14%, and 18%, respectively. Time from bite to care longer than 6 hours, patient age younger than 12 years, large snake size, and ptosis increased the likelihood of severe systemic envenomation, while envenomation by cottonmouth and copperhead (Agkistrodon) snakes (compared with rattlesnakes) decreases the likelihood of severe systemic envenomation and initial hypofibrinogenemia and thrombocytopenia increases the likelihood of severe hematologic venom effects.

Meaning  Physicians should evaluate patients with snakebites for these features to determine which are at increased likelihood of severe envenomation and should also be wary of progression from nonsevere to a severe envenomation.


Importance  Venomous snakebite severity ranges from an asymptomatic dry bite to severe envenomation and death. The clinical evaluation aids in prognosis and is essential to determine the risks and potential benefits of antivenom treatment.

Objectives  To identify historical features, clinical examination findings, basic laboratory testing, and clinical grading scales that will risk-stratify patients with pit viper snake envenomation for severe systemic envenomation, severe tissue injury, and/or severe hematologic venom effects.

Data Sources  We conducted a structured search of PubMed (1966-October 3, 2017) and Embase database (1980-October 3, 2017) to identify English-language studies that evaluated clinical features predictive of severe envenomation.

Study Selection  We included studies that evaluated the test performance of at least 1 clinical finding with an acceptable reference standard of severe envenomation for venomous snakes of the Western Hemisphere. Only studies involving the most common subfamily, Crotalinae (pit vipers), were evaluated. Seventeen studies with data were available for abstraction.

Data Extraction and Synthesis  The clinical features assessed and severity outcome measures were extracted from each original study. We assessed severity in 3 categories: systemic toxicity, tissue injury, and hematologic effects. Differences were resolved by author consensus.

Results  The pooled prevalence of severe systemic envenomation was 14% (95% CI, 9%-21%). The pooled prevalence of severe tissue injury and severe hematologic venom effects were 14% (95% CI, 12%-16%) and 18% (95% CI, 8%-27%), respectively. Factors increasing the likelihood of severe systemic envenomation included the time from bite to care of 6 or more hours (likelihood ratio [LR], 3.4 [95% CI, 1.1-6.4]), a patient younger than 12 years (LRs, 3.2 [95% CI, 1.5-7.1] and 2.9 [95% CI, 1.3-6.2]), large snake size (LR, 3.1 [95% CI, 1.5-5.7]), and ptosis (LRs, 1.4 [95% CI, 1.0-2.1] and 3.8 [95% CI, 1.8-8.3]). Envenomation by the genus Agkistrodon (copperhead and cottonmouth), as opposed to rattlesnakes, decreased the likelihood of severe systemic envenomation (LR, 0.28 [95% CI, 0.10-0.78]). Initial hypofibrinogenemia (LR, 5.1 [95% CI, 1.7-15.0]) and thrombocytopenia (LR, 3.7 [95% CI, 1.9-7.3]) increased the likelihood of severe hematologic venom effects. Other clinical features from history, physical examination, or normal laboratory values were not discriminative.

Conclusions  Clinical features can identify patients at increased risk of severe systemic envenomation and severe hematologic venom effects, but there are few features that are associated with severe tissue injury or can confidently exclude severe envenomation. Physicians should monitor patients closely and be wary of progression from nonsevere to a severe envenomation and have a low threshold to escalate therapy as needed.

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Article Information

Corresponding Author: Charles J. Gerardo, MD, MHS, Division of Emergency Medicine, Duke University School of Medicine, Box 3096 DUMC, Durham, NC 27710 (

Accepted for Publication: September 10, 2018.

Published Online: February 13, 2019. doi:10.1001/jamasurg.2018.5069

Author Contributions: Drs Gerardo and Evans had full access to all the data in the study and take full responsibility for the integrity of the data abstracted from the literature.

Concept and design: Gerardo, Lavonas.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Gerardo, Vissoci.

Critical revision of the manuscript for important intellectual content: Gerardo, Evans, Simel, Lavonas.

Statistical analysis: Vissoci, Evans, Simel.

Administrative, technical, or material support: Evans.

Supervision: Gerardo, Simel, Lavonas.

Conflict of Interest Disclosures: Drs Gerardo and Lavonas receive funding through their institutions from BTG International Inc, and Dr Lavonas’ institution has received research funding from Instituto Bioclon; both companies manufacture snake antivenom. Dr Simel receives honoraria for contributions to No further disclosures were reported.

Additional Contributions: The authors would like to acknowledge Bryn Mumma, MD, MAS, Department of Emergency Medicine, University of California Davis, and William Rushton, MD, Department of Emergency Medicine, University of Alabama at Birmingham, for contributions to early versions of the manuscript. They were not compensated for their contributions.

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