Urgent Reference

If you are currently OCONUS with a snakebite patient, contact the DoD ADVISOR Hotline (+1-833-238-7756), and refer to the NEURO Algorithm, HEMO/CYTO Algorithm, or ASYMPTOMATIC Algorithm to start treatment. For adverse reactions, see REACTION Algorithm and CPG sections on pretreatment and treatment of reactions.

Pre-Mission Planning: Always familiarize yourself with the specific antivenoms needed for your area of operation prior to deployment. For specific regional antivenom and dose recommendations, start with the Regional Antivenom Selection Flowcharts, then the Antivenom Dosing by Product table in Appendix H.

Summary of Changes

Major revision for enhanced usability including:

1. New ACLS-style STAT treatment algorithms with streamlined bedside decision-making.
2. Expanded and updated antivenom profiles, dosing guidance, and BB-IND usage instructions in addition to FDA considerations.
3. New printable rapid-reference tools to enhance usability in austere environments including Antivenom Dosing by Product and Pre-Mission AV selection flowcharts.
4. Reorganized guidelines by CCMD for faster pre-mission planning and point-of-care use, including a suggested packing checklist.
5. INDOPACOM expanded + enhanced coverage with new dedicated regional pathways for Taiwan, Japan, Korean Peninsula, China / East Asia, and elsewhere.

This CPG provides comprehensive guidance on how to manage snakebites in all geographic Combatant Commands (CCMD), with clear steps for providers of all levels to follow in the field, and the clinic.

“How do I examine and treat snake envenomation patients?”

Perform a rapid snakebite exam to determine if the patient is currently symptomatic (NEURO vs HEMO/CYTO syndromes) or asymptomatic for snake envenomation, then follow the appropriate STAT treatment algorithms below:

Symptomatic treatment algorithms:

1. NEURO dominant syndrome = refer to Symptomatic NEURO Algorithm
2. HEMO and/or CYTO dominant syndrome = refer to Symptomatic HEMO/CYTO Algorithm

NOTE: For specific Antivenom doses, refer to Appendix H, Table 1: Antivenom Dosing by Product

Asymptomatic (suspected dry bite or non-venomous snake):

1. Refer to Asymptomatic Algorithm
2. Once a symptomatic patient begins to improve and control is achieved after the correct dose of antivenom, follow the Control Algorithm for assessment pathway and disposition guidance.

Within the CPG text, review Universal Approach, Initial Priorities, and Focused Assessment for a more detailed guide to identifying the syndrome, determining severity, managing ABCs, and trending.

“How do I know when I have given the right dose of antivenom?”

Keep giving antivenom until key S/Sx stop getting worse (initial control) - pain will begin to improve; edema will stop progressing; all active bleeding will stop; vision, speaking, swallowing, and breathing will begin to improve; and systemic instability will stabilize. For a detailed list of clinical endpoints indicating that initial control has been achieved, see Figure 4 - Identifying Initial Control by Syndrome. Once initial control has been achieved, follow the Control Algorithm.

“How do I find which antivenom(s) and doses I need for deployment?”

1. To select the appropriate regional antivenoms, refer to the regional antivenom selection flowcharts.
2. To find the High and Low Doses recommended for each product, refer to Appendix H: Antivenom Dosing by Product or find the short form regional entries in the regional section for each CCMD.

Detailed product pages containing additional information (coverage, formulation, preparation, administration, etc) can be found in the regional sections (Appendix B – G). Both the NEURO Algorithm and HEMO/CYTO Algorithm contain blank boxes and are designed to print and fill in the details for the products you need.

“What do I do to prevent or treat reactions to antivenom?”

See Pretreatment to Prevent Reactions, Treatment of Adverse Reactions, Antivenom Reactions Algorithm.

“If my patient arrives with a tourniquet or constricting band, how should I remove it?”

Tourniquets and constricting bands may worsen snakebite outcomes and must be removed according to the Tourniquet Algorithm. 

“What if I do not have antivenom (yet), or used it all?”

Reference Special Circumstances for full explanation. They have a very high morbidity and high mortality rate, and may require Supportive Care for weeks to months, if they survive.

Pre-Mission Planning: Review & Print Prior to Deployment

“What parts of the CPG should I reference and print to prepare for use while deployed?”

If you are deploying, everyone should print at a minimum Appendix A – STAT treatment algorithms (NEURO, HEMO/CYTO, Asymptomatic, Control, and Tourniquet algorithm) + your specific CCMD Appendix.

• Print for AFRICOM - Appendix A + Appendix B
• Print for CENTCOM - Appendix A + Appendix C
• Print for EUCOM - Appendix A + Appendix D
• Print for INDOPACOM - Appendix A + Appendix E
• Print for NORTHCOM - Appendix A + Appendix F
• Print for SOUTHCOM - Appendix A + Appendix G
• Print for ALL CCMDS: Appendix I - Class VIII Medical Material

If need for antivenom dosing by product for all CCMDs simultaneously - Print Appendix H, Table 1: Antivenom Dosing by Product + Appendix H, Pre-Mission Flowcharts: Regional Antivenom Selection

Print & Fill Your Own Doses – When you print the NEURO Algorithm and HEMO/CYTO Algorithm, fill in the blanks for High and Low dosing from the products listed in Appendix H: Antivenom Dosing by Product. If you need more than 1 antivenom for either syndrome to obtain coverage in your region, print & copy the blank symptomatic algorithm pages you need and fill them in for all antivenoms you are carrying.

STAT TREATMENT ALGORITHMS

• Symptomatic NEURO Algorithm
• Symptomatic HEMO/CYTO Algorithm
• ASYMPTOMATIC Algorithm
• Control Algorithm
• Tourniquet Algorithm
• Antivenom Reactions Algorithm

NEURO Algorithm

HEMO/CYTO Algorithm

ASYMPTOMATIC Algorithm

CONTROL Algorithm

TOURNIQUET Algorithm

ANTIVENOM REACTIONS Algorithm

Snakebite, recently declared a neglected tropical disease and global health priority by the World Health Organization (WHO), results in an estimated 2.5 million envenomations, 138,000 deaths and over 500,000 cases of permanent disability worldwide every year.^1–10 Snake, spider, and scorpion envenomations are a common environmental and occupational hazard for military forces worldwide.^11–46 The consequences of an envenomation range from mild local effects to permanent disability or death, and the outcome is largely determined by the time to antivenom treatment and the level of training of the medical providers involved. Clinical outcomes and survival of the snakebite patient require administering antivenom quickly and immediate care by trained medics or medical professionals. Antivenom and appropriate early care are critical to saving lives and preventing long-term complications like amputations, blindness, or loss of limb function.

Venomous snakebites can induce a range of clinical syndromes, largely categorized by the primary type of toxin in the venom. Cytotoxic venoms, found in snakes like spitting cobras, copperheads, and puff adders cause severe localized tissue damage. This manifests as painful progressive swelling that starts at the bite site and can spread rapidly, leading to complications such as blistering, tissue death (necrosis), and compartment syndrome, a condition where swelling cuts off blood circulation. Hemotoxic venoms, on the other hand, disrupt the body's ability to clot blood, leading to bleeding from various sites, including the gums, nose, and the bite wound itself. Snakes such as Russell's vipers, saw-scaled vipers, and boomslangs possess hemotoxic venom, which can cause coagulopathy, a condition of abnormal blood clotting, and in severe instances, disseminated intravascular coagulation (DIC).

Neurotoxic venoms primarily affect the nervous system, causing progressive weakness and paralysis. Symptoms of neurotoxic envenomation include drooping eyelids (ptosis), blurred vision, difficulty breathing, and can advance to paralysis of the respiratory muscles, which can be fatal. Cobras, kraits, and mambas are well-known for their neurotoxic venom. Systemic instability is a broader category of effects that can result from various types of snake venoms and their systemic impacts. This can include a mix of syndromes (eg HEMO + CYTO), such as painful progressive swelling combined with bleeding, as seen in bites from many vipers including rattlesnakes, gaboon vipers, the Fer-de-lance, and others. It can also manifest as life-threatening systemic complications like dangerously low blood pressure (hypotension), shock, acute kidney injury, and acute respiratory distress syndrome (ARDS), which can be triggered by fluid loss from cytotoxic effects, widespread bleeding from hemotoxic effects, or direct shock-inducing venom components.

Once a snakebite occurs, it is a race against time to prevent severe local tissue damage and deadly systemic symptoms. Some types of necrosis caused by cytotoxic venoms cannot be reversed but can be prevented by early antivenom administration (or arrested before further damage can occur in cases of late antivenom treatment).^1,7,47-49 Hemotoxic venoms can induce bleeding and clotting abnormalities within minutes, which progresses over hours or days into widespread external and internal bleeding. Neurotoxic venoms can act rapidly and be fatal. When a neurotoxic snake bite occurs, rapid antivenom administration prior to the onset of respiratory failure can arrest the progression of descending paralysis before serious systemic manifestations develop.^1,50,51 In many cases paralysis will reverse rapidly. When paralysis cannot be reversed before mechanical ventilation is needed (e.g. late-presenting krait envenomations), antivenom still plays a key role: clearance of unbound circulating venom, which permits recovery of damaged nerve terminals and reduces time to extubation to an average of 2 – 5 days versus weeks of ventilation in untreated patients. Every hour wasted between bite and antivenom administration is strongly associated with sharp increases in mortality and the development of chronic or permanent sequelae including amputation, disfigurement, PTSD, blindness, kidney injury, infections, and partial or complete loss of function of the bitten limb.^{4,7,8,52–58}

This CPG provides comprehensive guidance on how to manage snakebites in all geographic CCMDs, with clear steps for providers of all levels to follow in the field and the clinic.

Don’t try to ID the snake. You don’t need to know the snake’s species to treat the patient. Trying to catch or kill the snake is dangerous and wastes time. Focus on the patient’s symptoms.

Venomous snakebites fall into three main types (syndromes) plus an additional can’t miss HALO diagnosis: neurotoxic (paralyzes the nervous system), hemotoxic (affects blood), cytotoxic (destroys tissue), and systemic instability/sudden collapse. Every dangerous snakebite will show at least one sign from these syndromes, and those signs will continue to worsen until antivenom is given to neutralize the threat. Treatment depends on the presence and progression of clinical signs, not the snake’s identity.

For patients who present with rapid instability / sudden collapse syndrome, refer to Sudden Collapse Syndrome section for more information.

CLINICAL PEARLS ON SNAKEBITES & ANTIVENOM TREATMENT

1. Treat based on symptoms, not the snake.

Even if a patient says they were bitten by a dangerous snake (like a mamba), don’t give antivenom unless they show signs of envenomation (e.g., swelling, bleeding, or weakness). If a patient has symptoms but thinks the snake was harmless, treat them based on what you see.

2. Antivenom is the main treatment.

• Antivenoms are safe and effective and carry a low risk of allergic reactions compared to the high risk of venom damage. Many can be carried in the field at ambient tropical temperatures with no special storage required – these products are labeled as FREEZE-DRIED/UNREFRIGERATED in the antivenom product pages later in this document.

3. Use IV or IO routes only (not IM or SQ, even if the package says so). IV is best, but IO works in emergencies^.54,59

4. Antivenom dosage is not weight-based and there is no difference in dosing between adults and children.

5. Follow the dosing recommended in this CPG unless instructed otherwise by a DoD ADVISOR Toxicologist or other approved snakebite expert. DO NOT follow the package insert, as they rarely reflect clinical or evidence-based best practices.

6. Keep giving antivenom until symptoms stop getting worse (INITIAL CONTROL) – see Identifying Initial Control by Syndrome): pain will begin to improve; edema will stop progressing; all active bleeding will stop; vision, speaking, swallowing, and breathing will improve; and systemic instability will stabilize. Overdosing isn’t a concern, but watch for late allergic reactions (e.g., rash or fever) 1–3 weeks later, which can be treated with antihistamines or steroids.

7. Some snakebite patients will experience secondary recurrences (similar to polyphasic anaphylaxis) where control is lost and symptoms suddenly begin to worsen and progress again. This is usually within the first 0 - 6 hours after initial control but rarely can occur 24 – 48 hours later.

• This is why the control algorithm stacks more frequent assessments in the first hours after control is achieved: reassess q30 minutes for the first two hours after initial control is achieved

8. When control is lost and recurrence occurs, give additional doses of antivenom according to the appropriate treatment algorithm (NEURO or HEMO/CYTO).

• When control is achieved again, restart the 48-hour clock on the Control Algorithm for assessment intervals and disposition decisions. Symptoms must be controlled for 48 hours without signs of worsening progression before disposition can be achieved. When in doubt, consult a DoD toxicologist via the ADVISOR line.

9. DO NOT give test doses to check for allergies; they don’t work and waste time.^60–63 Pretreatment with IM epinephrine is the only effective means of reducing reaction risk, see Pretreatment to Prevent Reactions.

10. Track progression / evolution of symptoms over time. Write down the following:

• When the bite occurred (time/date) + time elapsed prior to arrival
• Speed and degree of progression between bite à presentation
• Time when the first dose of antivenom is given (defined as Hour 0, written as H0)
• Assessment and disposition instructions (including timing of repeated assessments) is detailed in the Control Algorithm.

11. Snakebites can change fast.

• A patient might start with only local pain or swelling (cytotoxic) but later develop systemic bleeding (hemotoxic) or progressive weakness (neurotoxic). Check for all three syndrome types at every assessment and adjust treatment as needed (see rapid assessment box in treatment/assessment algorithms). Consult a Medical Toxicologist as soon as possible.
• Within the United States, a Medical Toxicologist can be reached via a Poison Control Center by calling 800-222-1222. Within the Department of Defense, a Medical Toxicologist can be reached via the Advanced Virtual Support for Operational Forces (ADVISOR) teleconsultation service by calling 833-ADVSRLN (833-238-7756)/ DSN: 312-429-9089 and requesting a toxicology consult.

12. If a reaction occurs, see Antivenom Reactions Algorithm and Treatment of Adverse Reactions.

Qualifications

Antivenom administration should be performed by medical providers capable of providing advanced life support and trained to a minimum level of paramedic (or DoD equivalent) and higher (i.e., 68W3P, SOCM, 18D, PJ, IDC, IDMT, RN, PA, MD or DO, etc).

Circumstances

All qualified medical providers who may be responsible for treatment of a snakebite casualty OCONUS, with ground CASEVAC times exceeding 60 minutes to facilities equipped with appropriate regional antivenoms in sufficient quantities, should carry the equivalent of 2 high doses or 4 low doses of the appropriate regional antivenoms to enable timely definitive treatment with antivenoms at the point of injury. 

Following repeated questions to JTS about using non-FDA-approved antivenoms after publication of the Global Snake Envenomation Management CPG (2020), the JTS Working Group consulted with FDA’s Center for Biologics Evaluation and Research (CBER) to provide clarification and guidance regarding the regulatory framework for DoD medical providers, procurement officers, and commanders who need to obtain the foreign antivenoms listed in this CPG.

Snakebite treatment OCONUS requires the use of non-FDA-approved foreign antivenoms through the Biological-Based Investigational New Drug (BB-IND) pathway.

Non-FDA-approved antivenoms are the only options for treating snakebites outside the United States. None of the 26 foreign antivenoms recommended for OCONUS use in this CPG are FDA-approved, and the FDA does not expect or require them to obtain approval because they are indicated for exotic snakes that are not native to the United States. Instead, the FDA provides a specific legal pathway to facilitate lawful importation, storage, and use of these products: the Biological IND (BB-IND) with Expanded Access under 21 CFR 312 Subpart I. The antivenom BB-IND pathway has been utilized for decades by zoos and private snake keepers, allowing U.S. citizens to procure and administer these lifesaving products with required annual reporting.

DoD is already utilizing the BB-IND pathway to support use of foreign antivenoms.

In AFRICOM, INDOPACOM, SOUTHCOM, EUCOM, and part of NORTHCOM (Mexico), first-line therapy for snakebite utilizes non-FDA-approved antivenoms obtained through the BB-IND/Expanded Access program. The Surgeon General-Department of the Army (TSG-DA) holds the BB-INDs for all antivenoms listed in this CPG, and the Defense Health Agency’s Office of Regulated Activities and Force Health Protection (FHP) Division oversees importation, compliance tracking, and regulatory oversight. Logistics and procurement should follow this established pathway to meet the standard of care and JTS Performance Improvement (PI) objectives.

What type of reporting and documentation is required by the FDA for BB-IND?

Antivenoms accessed through BB-IND require annual and case-specific reporting to FDA CBER. Annual reports are filed each year (FDA Form 1571) and detail whether any antivenom was used in the previous 12 months. When a patient is treated, FDA Form 1572 (found on the FDA website: https://www.fda.gov/about-fda-reports-manuals-forms/forms) is submitted in the annual report and a case report is filed as well. As the BB-IND holder for the US military, the ORA, acting on behalf of TSG-DA is responsible for submitting these reports to the FDA. If any antivenom is administered, please contact a Medical Toxicologist via the Advanced Virtual Support for Operational Forces (ADVISOR) teleconsultation service by calling 833-ADVSRLN (833-238-7756)/ DSN: 312-429-9089 and the Toxicologist will assist in ensuring compliance with FDA guidelines for the use of antivenoms with an IND or in submitting an emergency IND number if one does not already exist.

Who should I contact with questions about obtaining antivenom for my local formulary?

Contact Force Health Protection (FHP) with questions regarding antivenom procurement via the FHP 24/7 Emergency Phone: 301-401-2768 or e-mail: usarmy.detrick.medcom-usammda.mbx.force-health-protection@health.mil.

The U.S. Food and Drug Administration (FDA) does not adjudicate nor approve antivenoms required outside the United States. Code of Federal Regulations (CFR) Title 21 Part 312 classifies these pharmaceuticals as Investigational New Drugs (IND). Therefore, sourcing of these antivenoms occurs through alternate pharmaceutical supply chains. Oversight for IND falls under the Department of Health Operational Medical Systems (DHA OPMED) Force Health Protection (FHP) Division (https://dha.mil/Offices-and-Programs/OPMED/FHP) with regulatory support provided by U.S. Army Medical Research and Development Command’s (MRDC) Office or Regulated Activities (ORA). However, the antivenoms will need to be purchased and acquired by the Combatant Command or on the local market by medical personnel. We recommend contacting the appropriate Geographical Combatant Command Surgeon General’s Office to assist in acquiring and stocking antivenom if there is the credible risk of snake envenomation for which the risks and costs of maintaining and storing said antivenom are appropriate. If medical personnel must acquire the appropriate antivenom on the local economy, it is advised that great caution is taken to ensure the antivenom is legitimate, unexpired, and appropriately stored given that selling and marketing of fraudulent antivenom does occur in developing countries.

INITIAL PRIORITIES

1. Focus on ABCs (Airway, Breathing, Circulation) and antivenom.

a. Check ABCs first and fix any immediate life threats (e.g., trouble breathing or shock).

b. If the patient has sudden collapse (shock, swelling, confusion, or bleeding within 30 minutes), follow the Sudden Collapse Syndrome Treatment Protocol.

c. Establish IV or IO access in a non-bitten limb for antivenom or fluids.

d. Treat emergent secondary issues that may be present (such as anaphylaxis or hypovolemic shock) according to standard clinical protocols.

e. Establish IV or IO access in a non-bitten limb before proceeding.

2. DO NOT apply constricting bandages or tourniquets as these may worsen local tissue injury and increase the risk of permanent disability.^64–66

If a tourniquet is already in place, see Tourniquet Algorithm. Do not remove it until you are ready to treat and resuscitate the patient as a rapid decompensation can occur.^67,68  

3. If and when conditions allow, minimize patient activity, and loosely immobilize the bitten limb to reduce movement without constricting tissues.

a. If antivenom isn’t available, get the patient to a facility with antivenom as fast as safely possible, even if they have to walk.

b. If conditions allow during transport, maintain the bitten limb in a position of comfort that is elevated below the level of the heart.

c. Once the patient has arrived at a medical facility with antivenom, aggressively elevate the bitten limb (aim for a minimum 60º angle in a supine patient if possible and tolerated by patient) to reduce oncotic pressure on swollen tissues.

4. Evaluate for specific signs and symptoms of snake envenomation. Refer to the STAT treatment algorithms in Appendix A for specific criteria for initial antivenom treatment and repeat doses for additional information.

5. Consult a Medical Toxicologist as soon as possible. Within the United States, a Medical Toxicologist can be reached via a Poison Control Center by calling 800-222-1222. Within the Department of Defense, a Medical Toxicologist can be reached via the Advanced Virtual Support for Operational Forces (ADVISOR) teleconsultation service by calling 833-ADVSRLN (833-238-7756)/ DSN: 312-429-9089.

FOCUSED ASSESSMENT & EXAMINATION

Perform a physical examination and history focused on identifying signs and symptoms of neurotoxic, hemotoxic, cytotoxic, and systemic instability envenomation syndromes. General approach is to identify syndrome à determine severityà administer initial LOW, MEDIUM, or HIGH DOSE antivenom based on syndrome AND current severityà reassess and retreat as needed based on response of key STOP/GO criteria for additional doses.

1. Mark the bite site. Circle the site of the bite wound and write the specific time that it occurred with a permanent marker on the patient. Don’t rely on fang marks—bites may look like punctures, scratches, or nothing at all.

2. Check for cytotoxic signs (tissue damage). Look for pain, swelling, or tissue destruction. Mark the edge of pain (dashed line) and swelling (solid line) with a marker and note the time.

3. Check for hemotoxic signs (bleeding). Look for bleeding at the bite that lasts over 30 minutes or bleeding from gums or other areas (mouth, gums or other mucosa).^1,69–72

4. Check for neurotoxic signs (nerve issues).

5. Rapid examination for signs of neuromuscular weakness (neurotoxic syndrome)

• Evaluate respiratory muscle weakness by single breath count (SBC) testing ⁷² and repeat periodically to trend improvement or deterioration in respiratory function over time.
  • Ask the patient to take a deep breath and count out loud as high as they can without breathing again and repeat periodically to trend improvement or deterioration in respiratory function over time.
  • Normal SBC is approximately 50 and SBC < 20 is associated with the need for mechanical ventilation.
    • If spirometry is available, this can be used in place of the single breath count test by evaluating the negative inspiratory force (NIF) and/or forced vital capacity (FVC).
• Conduct gross assessment and pay particular attention to the following:
  • Signs and symptoms of descending flaccid paralysis: Ptosis (upper eyelid drooping), diplopia (double vision), neck flexor muscle weakness, bulbar weakness, difficulty speaking, difficulty swallowing, etc.^1,54,73
    • Signs and symptoms of parasympathetic / cholinergic crisis: SLUDGE mnemonic - Salivation, Lacrimation, Urination, Defecation, GI distress, Emesis.

6. Perform and/or check the clinical laboratory tests listed below (if available).

• Complete Blood Count (CBC), Hemoglobin, or Hematocrit.
• Clotting tests (PT, PTT, INR, Fibrinogen).
  • Simple coagulation test for austere environments: Use the Whole Blood Clotting Test (WBCT) as described in Appendix J to diagnose and monitor coagulopathy if advanced labs not available.
• Comprehensive Metabolic Panel (CMP) and Creatine Kinase (CK).

LAB TESTS

Advanced laboratory tests include:

• Complete Blood Count (CBC)
• Hemoglobin (Hb) or Hematocrit (HCT) if no CBC but separate testing for either Hb or HCT is available
• Prothrombin Time (PT), Partial Thromboplastin Time (PTT), and International Normalized Ratio (INR)
• Fibrinogen
• Comprehensive Metabolic Panel (CMP)
• Creatine Kinase (CK)

Simple coagulation test for austere environments: Use the Whole Blood Clotting Test (WBCT) as described in Appendix J to diagnose and monitor coagulopathy if advanced labs are not available.

TRANSPORT FACTORS

1. If the patient is being medically evacuated from the field or between roles of care, confirm that the receiving facility has an adequate supply of the appropriate regionally specific antivenoms listed in this CPG to ensure treatment coverage against local species of concern. Alternatively, have the antivenom transported to the patient.

NOTE: Evacuation is not an alternative to antivenom administration. A patient whose snakebite warrants evacuation will require antivenom. The earlier it is given the greater the chance of full recovery without permanent disability. DO NOT delay administration of antivenom in the field to a patient with an envenomation.

2. If clinical evidence of envenomation is present and treatment is occurring in a hospital setting, always admit to a bed with continuous vital sign monitoring if available. If treating in the field, continuously monitor patient trends for signs of progression, improvement, or deterioration.

3. If no initial clinical evidence of envenomation, follow the Asymptomatic Algorithm for assessment intervals and disposition guidance.

In rare cases, a patient may rapidly deteriorate in the first 5 - 30 minutes after the bite and present with profound hypotension, tachycardia, angioedema, altered level of consciousness, etc.^1,122–130 These patients should be aggressively treated for severe anaphylaxis and severe envenomation simultaneously. Treat anaphylaxis aggressively according to anaphylaxis protocols. Treat the envenomation with an initial high dose (at least 6 vials) of antivenom by rapid IV push, and support the patient with airway management, fluids, and other interventions as appropriate.^{122,123,125,131,132} Most patients presenting with hypotension or angioedema are responsive to epinephrine, but may require IV epinephrine infusions to achieve this effect if they are unresponsive to IM epinephrine.¹²²

SUDDEN COLLAPSE SYNDROME TREATMENT PROTOCOL

Patient presents within 30 minutes of the bite with rapid onset shock (hypotension with inadequate tissue perfusion) ± angioedema, altered mental status, systemic bleeding, and/or diarrhea.¹ Stabilize with IM or IV epinephrine and fluids as per anaphylaxis protocols.

4. Intubate for airway edema if not rapidly responsive to epinephrine.

5. Follow epinephrine immediately with a high dose of the appropriate regional antivenom given by rapid IV or IO push during the resuscitation.

6. Maintain blood pressure with IV or IO fluids and epinephrine until antivenom has taken effect to reverse the hypotension.

Signs and symptoms differentiating mild, moderate, and severe presentations of neurotoxic, hemotoxic, and cytotoxic syndromes are detailed below. Rapid reference criteria for determining severity by syndrome is included in the STAT treatment algorithms for symptomatic patients with NEURO and HEMO/CYTO envenomations.

Clinical Pearl: Worsening progressive pain may be present with any syndrome. Increasing pain severity and/or ascending pain up the bitten limb may be present for all snake envenomations and is an early diagnostic indicator of envenomation. Edema and/or blistering with progressive pain is the definition of the cytotoxic syndrome. If there is worsening pain with hemotoxic or neurotoxic symptoms, chart it and expect improvement after the appropriate antivenom dose.

Clinical Pearl: Treatment Endpoint = Control. Snakebite treatment is dynamic and the total dose of antivenom needed is determined by the amount of venom injected into the patient.  Continue administering antivenom according to the STAT treatment algorithms until Initial Control has been achieved – refer to Defining Initial Control by Syndrome for specific clinical endpoints indicating that initial control has been achieved. When initial control is maintained through all the assessment points detailed in the control algorithm, then permanent control has been achieved.

DEFINING INITIAL CONTROL BY SYNDROME: CLINICAL ENDPOINTS INDICATING ADEQUATE ANTIVENOM DOSING HAS BEEN ACHIEVED

Antivenom dosing, preparation, and administration recommendations vary by product. Coverage, initial dosing, preparation, and administration of antivenoms are included in this CPG. Each antivenom recommended in the CPG has a rapid reference on dosing and key notes needed in the Regional Sections as well as in Appendix H: Antivenom Dosing by Product. Each antivenom also has a detailed product page with dosing, mixing / administration instructions, and additional information within its respective regional section (Appendices B – E). 

Note on Antivenom Infusions versus Direct IV/IO Push:

For most first line antivenoms in this CPG, administration using either a) 100, 250, or 500 mL IV bag of isotonic fluids (0.9% NS ideal; Lactated Ringers is acceptable) with 10-minute IV/IO infusion or b) direct IV push is recommended in order to get a full dose of antivenom onboard as quickly as possible and neutralize venom before further damage has occurred.

However, if this is not possible, it is acceptable to dilute antivenom in any size bag of isotonic solution you have available and give over 10 – 30 minutes.

While the amount of antivenom given should not change based upon the patient’s size, smaller volumes of isotonic fluids may be indicated (especially in pediatric patients) to avoid volume overload or worsening dependent edema of bitten limb.

SUPPORTIVE CARE & ONGOING MANAGEMENT

Provide supportive care and address secondary issues related to the envenomation as follows:

1. Anticipate the need for aggressive airway management with intubation and prolonged ventilation in all patients presenting with neurotoxic envenomation, particularly those who present late with impending respiratory failure or fail to respond to antivenom. Ptosis is an early sign of central neurotoxicity indicating need for antivenom and likely progression to respiratory failure without timely antivenom administration.

• For any neurotoxic snakebite producing a cholinergic crisis, consider atropine 0.5 mg IV/IO titrated by auscultation to dry up bronchial and oral hypersecretions posing a risk to airway or breathing.

Repeat original dose every 5 minutes until resolution of crackles, rales, and bronchospasm has been achieved. Pediatric atropine doses should be weight based at a dose of 0.01 mg/kg, up to 0.5 mg.

• For neurotoxic snakebites in the Middle East, North Africa, and Central Asia without cholinergic crisis, but causing ptosis and respiratory muscle weakness, consider administering, in addition to antivenom, a trial dose of 0.5 mg atropine followed by 1.0 mg neostigmine IV/IO to temporarily reverse neuromuscular weakness and delay the need for intubation. Pediatric doses should be weight based at a dose of 0.01 mg/kg, up to a maximum of 0.25 mg atropine with 0.5 mg neostigmine.^54,74–77

Not all patients will respond, but those who do will show temporary improvement (reversal of ptosis, increased respiratory muscle strength, etc.). If no response to neostigmine, do not readminister. If positive response is achieved, repeat every 1 - 4 hours as needed (maximum dose in 24 hours = 10 mg adults / 5 mg pediatric) until antivenom has definitively reversed the paralysis. 

2. For hemotoxic envenomations, all internal and external active bleeding should cease within 30 – 60 minutes of antivenom administration once the appropriate dose has been given. Packed red blood cell or whole blood transfusion can be considered if the patient is in hemorrhagic shock.^{17,69,70, 78-82} Platelets, fresh frozen plasma, cryoprecipitate, TXA, and other agents are not effective in these cases due to the mechanism of the venoms.

3. Ketamine and fentanyl are preferable for analgesia. Histamine release from morphine may mimic signs of an allergic reaction or worsen hypotension. Acetaminophen may be used but NSAIDs are contraindicated.

4. It is important to keep the limb significantly elevated (> 60º is ideal) whenever possible to limit dependent edema and swelling.

5. DO NOT routinely de-roof or aspirate blisters, bullae, or blebs unless they are causing significant discomfort or uncontrolled rupture appears imminent. If abscess is suspected, treat according to existing protocols for abscess management.

6. Avoid fasciotomy for snakebites unless absolutely necessary. Compartment syndrome is rare in snakebites, and evidence suggests that patients treated with antivenom alone – without fasciotomy – generally experience better outcomes, including shorter recovery times and reduced long-term morbidity.^83–86 Appropriate use of antivenom should typically resolve elevated intracompartmental pressures caused by envenomation. However, in deployed settings, constraints such as limited antivenom supplies due to delayed procurement or depletion during evacuation may complicate management. In such cases (prior to performing a fasciotomy), consult a DoD ADVISOR toxicologist to guide decision-making and ensure the best possible outcomes.

7. DO NOT routinely administer PROPHYLACTIC ANTIBIOTICS unless signs and symptoms of an infection are present. Direct infections are rare from most snakebites when prompt, appropriate treatment is given (washing with soap and water).⁵⁴ Bites from certain snakes (Asian cobras) have higher rates of infection.

8. ADMINISTER ANTIBIOTICS FOR SUSPECTED INFECTIONS, which may be common in local nationals with late-presenting bites who arrive with significant secondary infections due to unsanitary traditional treatments, poor hygiene conditions + widespread tissue compromise.

ONGOING MONITORING & NEED FOR ADDITIONAL ANTIVENOM

1. Monitor the patient closely for signs of progression every 30 minutes in the initial hours of treatment until initial control of symptoms has been achieved (see Defining Initial Control by Syndrome). Detailed intervals for assessment and treatment are included in the new ACLS-style NEURO, HEMO/CYTO, and Asymptomatic algorithms.

2. After initial control, reassess for signs and symptoms of NEURO and HEMO/CYTO syndromes according to the appropriate Control Algorithm in Appendix A.

3. In the new treatment protocols, providers are instructed to contact DoD ADVISOR to discuss need for additional antivenom after the equivalent of TWO high doses or FOUR low doses have been given to patient (a high dose for most recommended products is defined as ~10 vials and a low dose is ~5 vials, meaning that providers are strongly advised to seek toxicology consult if considering more than 20 vials).

This recommendation exists for several reasons:

a. Most products recommended in the CPGs are high potency and rarely require more than 20 vials equivalent.

b. In some cases, providers may not realize that control has been achieved (e.g. inappropriately re-dosing for persistent laboratory coagulopathy without clinical bleeding). In others, there may be a need to switch to an alternative 2nd line antivenom or the patient is an exceptional case with very large amounts of venom injected requiring higher than usual antivenom dosing (e.g. multiple bites, very large snake that bit and held on, etc.).

4. Persistent coagulopathy without bleeding: If coagulopathy persists (without bleeding) 24 hours after antivenom was given, contact DoD ADVISOR toxicologist to discuss need for additional antivenom.

5. Continuous monitoring for recurrence of symptoms must be performed. Occasionally, pockets of venom can be trapped in swollen tissue compartments and escape into the bloodstream once circulation has improved. This is called recurrence and is most common within the first 6 - 24 hours after a severe bite with extensive swelling and blistering.^78,87–93 Recurrence is addressed in the symptomatic NEURO & HEMO/CYTO and Control algorithms.

a. Continuous clinical monitoring includes hourly checks of vital signs, urine output, and detailed assessment for new or worsening signs of neurotoxic, hemotoxic, or cytotoxic envenomation.

b. Serial laboratory studies including CBC, CMP, PT/PTT/INR, CK, fibrinogen levels (or WBCT if no advanced testing available) may be repeated every 2 hours while signs of envenomation persist.

c. If indications of recurrence are detected, treat according to the recurrence pathways in the symptomatic NEURO and HEMO/CYTO algorithms.

d. When control has been achieved again, return to the Control Algorithm and restart the 48-hour timer to disposition decision. Control must be maintained for a full 48h without recurrence to discharge a previously symptomatic snakebite. Contact DoD ADVISOR toxicologist for advice in these cases.

DISCHARGE RECOMMENDATIONS:  CONTROL  &  ASYMPTOMATIC  ALGORITHMS

1. If patients were ever symptomatic, they should be held for at least 48 hours after resolution of all signs and symptoms, and the following steps should be completed prior to discharge (Control Algorithm):

a. Repeat blood tests before releasing the patient to ensure resolution of coagulopathy.

b. Administer a booster dose of tetanus toxoid if needed.

c. Patients should be instructed to return if any new or worrying signs or symptoms develop.

d. Patients with significant hemotoxic envenomations require 2 weeks of bleeding precautions and serial labs showing normalization before return to duty!

e. If patient has polyphasic recurrence, restart treatment algorithm and timeline to discharge.

2. Serum sickness is characterized by flu-like symptoms ± rash that typically develops between 1 - 3 weeks after antivenom administration. It is rare with highly purified modern antivenoms but may occur more frequently with some of the second and third line antivenoms listed in this CPG.^94–97 Serum sickness may be uncomfortable but is not dangerous. Management is either symptomatic, or, in the case of significant discomfort, can be treated with oral antihistamines and/or oral steroids if needed.^{94,95,97–99}

3. If patients were asymptomatic for 6 hours, they can leave the clinic but should remain within 1 hour distance and must return every 6 hours for reassessment until hour 48 or snake ID confirmed as non-venomous by expert as detailed in the asymptomatic algorithm. Symptoms usually begin 6 hours after bite but may have delayed onset on the order of days.

Refer to the Asymptomatic Algorithm for detailed assessment intervals and disposition guidance.

PRETREATMENT WITH EPINEPHRINE TO PREVENT EARLY REACTIONS

Epinephrine is the only prophylactic treatment (pretreatment) that has been shown to effectively reduce the incidence of early adverse reactions (EARs) such as anaphylaxis.^{60,98,133–136} See Antivenom Reactions Algorithm.

1. DO NOT pretreat with steroids or antihistamines, as they not only have no benefit prior to a reaction but may reduce the efficacy of epinephrine as a pretreatment for EARs.^134,273

2. DO NOT administer test doses of antivenom to check for hypersensitivity.^60–63

Relative contraindications to epinephrine pretreatment include age > 70, hypertension, ischemic heart disease, history of stroke, suspected or confirmed intracranial hemorrhage. No absolute contraindications.

1. Pretreatment with epinephrine prior to antivenom administration is not indicated by default for all antivenoms, and is recommended only under the following circumstances:

a. Unstable snakebite patients with signs of shock.

b. Known history of atopy (asthma, eczema, etc.), equine hypersensitivity, or severe reactions to antivenom in the past.

c. Use of certain second or third line antivenom due to the high rate of serious EARs associated with these products.

2. Standard epinephrine pretreatment protocol:

a. Adult dose is 0.25 mg of 1:1000 epinephrine given by IM injection several minutes prior to antivenom administration.

b. Pediatric doses should be weight based at a dose of 0.01 mg/kg, up to 0.25 mg.^{60,134,135,137,138}

c. Alternatively, consider establishing two intravenous catheters (one for the antivenom and one for epinephrine) and preparing an epinephrine infusion that can be immediately initiated in the event an allergic reaction to the antivenom occurs.

ALPHA-GAL SYNDROME AND INCREASED RISK OF EARLY ADVERSE REACTIONS

Practice implication: Alpha-gal Syndrome is not a contraindication to antivenom when envenomation is life or limb threatening but warrants pre-treatment with epinephrine and up-tiering of risk management (infusion strategy, ICU capable monitoring, product selection). There are NO absolute contraindications to antivenom for a patient with a significant symptomatic envenomation).

Early but compelling clinical evidence suggests that patients with Alpha-Gal syndrome (a mammalian meat allergy) may experience higher rates of reaction in response to antivenoms due to conservation of the alpha-gal epitope in mammalian antibody proteins. Some early studies from the United States indicated higher rates of reactions with with the F(ab’)² Anavip versus CroFab which is a F(ab), but other studies have shown that patients who reacted to CroFab tolerated Anavip.^274–276 Regardless, pretreatment should be considered for patients with elevated risk factors (patient from high prevalence area, medical Hx suspicious for alpha-gal, etc) and in patients with known or suspected alpha-gal syndrome. If both CroFab and Anavip are available for a CONUS bite with a known history or high risk of alpha-gal, it may be worth discussing CroFab as first line if available due to possible lower risk of reaction with a medical toxicologist. If a patient had a reaction to CroFab or Anavip CONUS, it may be worth discussing switching to the alternative product with a medical toxicologist.

While additional research is needed, the key points are as follows:

1. In US servicemembers and other patients with a known or suspected history of alpha-gal syndrome, pretreatment with 1:1000 epinephrine prior to antivenom may be advisable due to early evidence indicating higher incidence of EARs including anaphylaxis. Pretreatment with epinephrine has not been proven to reduce the incidence of these reactions, but has strong evidence base to support its use in typical EARs and the MAST cell stabilization resulting from epinephrine may also benefit these patients.
2. If a patient with known or suspected alpha-gal syndrome has a reaction to one antivenom and a second line alternative exists, it may be appropriate to try a different product if additional doses are needed.
3. In all cases, it is advisable to contact DoD advisor line and consult a toxicologist (or contact poison control if CONUS) in cases where an alpha-gal sensitivity is known or suspected.
4. In all cases, antivenom should not be delayed for patients suffering from instability or other possible threats to life or limb due to envenomation. Be prepared to treat the reaction if it occurs but do not delay antivenom for sick patients.

TREATMENT OF ADVERSE REACTIONS PRINCIPLES OF EARLY ADVERSE REACTION (EAR) MANAGEMENT

Most EARs to antivenom are mild and limited to either skin and mucosal signs, gastrointestinal signs, or both. In some cases, patients may experience a severe reaction (anaphylaxis), this can be life-threatening and should be treated aggressively. Refer to the Antivenom Reactions Algorithm for a stepwise approach to management of mild, moderate, and severe reactions.

When a reaction has occurred but is mild, simply increasing the antivenom’s dilution (for example, moving the remaining dose from a 50 mL bag of NS into 100 mL of NS), increase the duration of infusion (for example, from 15 mins to 30 mins) and treating the skin/mucosal or GI signs with antihistamines or antiemetics may resolve the problem. With mild reactions, start by either increasing the dilution of the antivenom (add more fluid to the antivenom infusion), decreasing the rate of infusion, or both. When a severe reaction such as anaphylaxis occurs, pause the antivenom infusion, treat the reaction, then resume it using twice the volume of dilution and half the rate of administration. In most cases, epinephrine given to treat a severe reaction will also reduce the risk of subsequent reactions for up to 48 hours. Always contact DoD ADVISOR if you have questions about reaction management.

NOTE: Refer to the detailed Antivenom Reactions Algorithm for guidance on the approach to reactions.

MILD OR MODERATE REACTION DURING INFUSION

1. Manage mild or moderate reactions (e.g. nausea, vomiting, urticaria, pruritus, chills, fever, etc.) symptomatically as needed with antiemetics, antihistamines, steroids, etc. as shown in the Antivenom Reactions Algorithm.
2. Consider increasing the volume of dilution of the antivenom and/or slowing the rate of infusion. You may be able to treat symptomatically with antiemetics, antihistamines, etc. without the need to stop the infusion. If the patient fails to improve to first line medications or appears to be worsening, consider giving a dose of IM epinephrine and then resuming at a slower rate once the symptoms are improving.
3. If the infusion was paused, reassess the patient once the reaction has been controlled; if the antivenom treatment criteria for cytotoxic, hemotoxic, or neurotoxic syndromes have not resolved completely then resume the infusion at a slower rate over 30 minutes.
4. If giving via push, dilute the remaining dose of antivenom in a 100 - 500 mL bag of normal saline and give as 30-minute infusion.

SEVERE REACTION (ANAPHYLAXIS) DURING INFUSION

1. Pause the infusion and treat according to the anaphylaxis treatment protocol and the Antivenom Reactions Algorithm.
2. Reassess the patient once the reaction has been controlled; if the antivenom treatment criteria for cytotoxic, hemotoxic, or neurotoxic syndromes have not resolved completely then resume the infusion at a slower rate or larger volume of fluid (e.g., if 250 bag, dilute in 500 cc) over 30 minutes.
3. If giving via push, dilute the remaining dose of antivenom in a 100-250 mL bag of normal saline and give as 30-minute infusion.
4. If the reaction occurs, stop the infusion, and consult a physician expert via telemedicine to discuss next steps for management.

ANAPHYLAXIS TREATMENT PROTOCOL

NOTE: Intubate for airway edema not rapidly responsive to epinephrine.

If anaphylaxis occurs after antivenom administration, treat according to the following protocol (also refer to the Antivenom Reactions Algorithm):

1. First line treatment of anaphylaxis is rapid administration of 1:1000 epinephrine (initial adult dose = 0.5 mg IM (0.01 mg/kg IM in pediatric patients) in the lateral thigh for rapid absorption). Epinephrine can be repeated as needed until the patient has stabilized and/or an intravenous or intraosseous infusion administered as per standard protocols if the patient fails to respond to IM doses.

Epinephrine should always be given prior to antihistamines or steroids to counter the immediate life-threats of bronchospasm and vasodilation.

2. After epinephrine has been given:

a. Give methylprednisolone 125 mg IV (2 mg/kg IV in pediatric patients).

b. Give diphenhydramine 50 mg IV (1-2 mg/kg IV in pediatric patients).

c. Consider adding an H2 antihistamine such as famotidine.

If anaphylaxis occurs during administration of antivenom, stop the antivenom administration to treat the reaction, then resume the antivenom administration as described below. ^{15,61,95,99,128,129,140–146}

LATE REACTIONS TO ANTIVENOM (SERUM SICKNESS)

1. Serum sickness is characterized by flu-like symptoms ± rash that typically develops between 1-3 weeks after antivenom administration. Serum sickness may be uncomfortable, but it is not dangerous.
2. Management is either symptomatic with antihistamines, acetaminophen, or with a course of oral steroids for patients who are in significant discomfort.^{94,95,97–99}

IF ANTIVENOM IS UNAVAILABLE

1. Antivenom is the gold standard of care for symptomatic snake envenomations. Early treatment is the best strategy to prevent death, amputation, or other serious disability. Management of snake envenomations when antivenom is not available should be directed at getting the patient to the antivenom (or vice versa) as quickly as possible to prevent irreversible damage to organs and tissues.
2. Mission planning before deployment should include research and procurement of the appropriate regionally specific antivenom(s) recommended in this CPG for your area of operation. If currently deployed without antivenom, efforts to acquire the appropriate antivenom(s) recommended in this CPG for your area of operations should be initiated through proper channels as fake or low-quality antivenoms are frequently found in local pharmacies throughout Africa and elsewhere in the developing world.
3. For specific management until antivenom can be obtained, follow the checklist and skip the steps related to antivenom administration until it has been obtained.

Refer to Supportive Care measures for specific recommendations. Without antivenom, prognosis is poor. Expect high mortality, permanent disability, and supportive care for weeks or longer.

MILITARY WORKING DOGS / MULTIPURPOSE CANINES

All antivenoms can be administered to military working dogs (MWD) and multipurpose canines according to the treatment criteria and initial doses listed in this CPG; other management should be based on the Arachnid and Snake Envenomation, MWD CPG.

LATE PRESENTATIONS & TREATMENT DELAYS

There is no defined time limit to antivenom therapy for a symptomatic snakebite. Early antivenom within the first minutes or hours after a bite is the best means of preventing morbidity or mortality, but antivenom remains effective at resolving reversible issues like coagulopathy and preventing further irreversible tissue damage even in patients who present many hours or days after the snakebite.^{56,69,78,146,147}

OUTDATED INTERVENTIONS THAT SHOULD NOT BE PERFORMED

1. DO NOT cut, suck, electrocute, burn, or use chemicals on the envenomation site.

2. DO NOT apply constricting bandages, tourniquets, or other circulation-reducing intervention!  

3. DO NOT use venom extractors or other commercial snakebite first aid kits.^148–152

4. DO NOT administer test doses of antivenom to check for hypersensitivity as these are ineffective and waste both time and antivenom.^60–63

5. DO NOT administer antihistamines or steroids as prophylactic pretreatment for prevention of anaphylaxis or other early adverse reactions (EARs) to antivenom as neither is effective as a premedication.^133,134

Spitting cobras have modified fangs that allow them to spray venom into the eyes of a predator or perceived threat.^153–155  The snakes aim at the glint of sunlight reflecting off of the target’s eyes and the venom spray widens like buckshot. The venom is harmless unless it enters the eyes (causing instantaneous burning, lacrimation, blurred vision, etc.) or the bloodstream by injection (such as a bite), through open wounds on the skin or inside of the mouth, or by ingestion (such as drinking a glass of venom with an ulcer). If a significant amount of venom enters the bloodstream through an open wound and produces typical symptoms of a snakebite, it is treated with antivenom like any other envenomation. For ocular exposure alone without signs of systemic envenomation, antivenom is not indicated and the management is like any ocular chemical exposure with copious irrigation. Spitting cobras can also deliver a venomous bite, so it is important to rule out an actual snakebite in patients who have encountered one of these snakes.

SIGNS AND SYMPTOMS

Immediate signs and symptoms of venom ophthalmia include intense local pain, swelling and/or spasms of the eyelid, lacrimation, and leukorrhea.¹⁵⁶  The primary concern is corneal epithelial injury which can lead to blindness by secondary infection or scarring if not treated correctly.^{7,25,54,156–158}  Treatment of venom ophthalmia is relatively simple and similar to managing a patient who has been splashed in the eyes with a harmful chemical solution.

FIRST AID

Confirm that the patient did not experience a snakebite in addition to the ophthalmia. Immediately irrigate the eye with copious quantities of water, normal saline, or a bland fluid such as milk if nothing else is available. Remove clothing and decontaminate the patient from head to toe with soap and water to prevent second re-exposure to dried venom.⁵⁴

CLINICAL MANAGEMENT

Apply topical anesthetic eye drops (tetracaine) to facilitate thorough irrigation and examination of the affected eyes. Irrigate the eyes thoroughly using water or normal saline for ≥ 15 minutes.¹⁵⁶

Fluorescein stain and examination using a slit lamp or ophthalmoscope for corneal injury. If present, treat with antimicrobial eye drops (such as ofloxacin or moxifloxacin) or ointments and mydriatics. Reassess daily with slit lamp or ophthalmoscope examination. If absent, consider benefits vs risks of antimicrobial eye drops.

ADDITIONAL TREATMENTS TO CONSIDER

Topical eye drops containing either epinephrine (1:1000) or phenylephrine (10%) are reported to immediately relieve the burning sensation produced by the venom.^54,156

CONTRAINDICATED TREATMENTS

Antivenom (topical or systemic) IS NOT indicated for patients with ocular exposure to snake venom.^54,156,159 Topical steroids are contraindicated for these patients.

Providers should adhere to the 29 antivenoms and dosing recommended in this CPG for use by military personnel, which have been evaluated by a multidisciplinary, mixed panel of leading civilian and military subject matter experts for safety, efficacy, and suitability for use in the unique environment of operational and austere medicine.

Note: If unable to source the recommended antivenoms and considering use of a non-recommended antivenom in an emergency context (or in the case of any general questions regarding antivenom use), contact the DoD ADVISOR line (+1 (833) 238-7756 (1-833-ADVSRLN) DSN: (312) 429-9089) and request toxicology consult ASAP. Many non-recommended products carry significant risks and toxicology consult is critical to avoiding preventable death or disability.

The global landscape of antivenoms is complex, fragmented, and characterized by a wide range of safety, efficacy, tolerability, and clinical evidence across the more than 110 distinct antivenoms currently manufactured worldwide.²⁶⁴ This is further complicated by the logistical and ethical barriers which make it extraordinarily difficult to conduct randomized clinical trials and nearly impossible to do so with placebo control, the lack of universal definitions of severity (making it difficult to interpret the context of efficacy when studies are performed), and many other challenges.²⁶⁵ The end result is chaotic, poorly controlled, and difficult to interpret: some products are widely relied upon by local clinicians and experts despite the lack of any formal trials; others are marketed as safe and effective based solely off of preclinical “test tube” studies conducted despite well-documented translational gaps between preclinical findings and real world effectiveness; some local formulations may enter the market without any studies whatsoever.^266,267 Unfortunately, this has led to widespread confusion, frequent misinformation, and sensationalistic media reports which inaccurately characterize effective products as ineffective (despite published clinical evidence demonstrating otherwise) or ineffective and potentially dangerous products as effective (despite either a lack of any clinical data or the existence of initial data indicating inefficacy and potentially dangerous dose-dependent toxicity).^268–271

RISKS OF USING NON-RECOMMENDED ANTIVENOMS & PROCUREMENT OUTSIDE OF RECOMMENDED CHANNELS

POPULATION OF INTEREST

All patients bitten by snakes.

INTENT (EXPECTED OUTCOMES)

1. All patients bitten by a snake will be managed according to the steps outlined in the Universal Approach to Snakebite Assessment, Diagnosis, and Treatment section, with an emphasis on the clinical syndrome of envenomation, and not on the identity of the snake species.
2. When a broad-spectrum antivenom does not exist for a given syndrome in a given area, the regional algorithms will be used to determine the most appropriate antivenom therapy.
3. Appropriate antivenom will be given at the earliest possible role of care, including in the pre-hospital setting if available, with appropriate documentation of dosage, preparation, administration procedures, and qualified performing provider.
4. Rapid patient assessment and frequent reassessment will be documented.
5. Tetanus prophylaxis will be given to all patients.
6. When antivenom is unavailable, patient will be evacuated urgently to capable role of care, and lack of capability and mitigation strategy is documented.
7. Fasciotomy for suspected compartment syndrome will be avoided unless absolutely necessary (delayed evacuation or depletion of antivenom supply), and DoW ADVISOR Toxicology consultation will be performed and documented prior to fasciotomy.
8. Documented DoW ADVISOR Toxicology telemedicine consult will be performed for any questions, concerns, or unusual manifestations that arise.

PERFORMANCE/ADHERENCE METRICS

1. Patients with clinical syndromes of envenomation who received administration of antivenom at the earliest available role of care.
2. Documentation of antivenom dosage, preparation, administration procedures, and qualified performing provider.
3. Rapid assessment and frequent reassessment is performed, with attention to clinical signs and symptoms of envenomation.
4. Patients urgently evacuated to capable role of care when antivenom unavailable.
5. Tetanus prophylaxis administered.
6. Elevated compartment pressures are managed with repeated administration of antivenom, and fasciotomy is avoided if possible
7. DoD ADVISOR Toxicology telemedicine consultation performed for all questions, concerns, or unusual manifestations that arise.

DATA SOURCES

• Patient Record
• Department of Defense Trauma Registry (DoDTR)

SYSTEM REPORTING & FREQUENCY

The above constitutes the minimum criteria for PI monitoring of this CPG. System reporting will be performed annually; additional PI monitoring and system reporting may be performed as needed. The system review and data analysis will be performed by the Joint Trauma System (JTS) Chief and the JTS PI Branch.

RESPONSIBILITIES

It is the trauma team leader’s responsibility to ensure familiarity, appropriate compliance and PI monitoring at the local level with this CPG.

There are several different antivenoms included in this CPG for snakebite treatment in African Command (AFRICOM), Central Command (CENTCOM), Indonesia-Pacific Command (INDOPACOM), European Command (EUCOM), Northern Command (NORTHCOM), and Southern Command (SOUTHCOM). The coverage, initial dosing, preparation, and administration vary between products and details for each of them are included. Simplified algorithms for selecting and dosing each antivenom are also included in each regional section below.

Whenever possible, broad-spectrum, field-stable antivenoms are recommended to enable syndromic diagnosis and treatment at the point of injury without the need to identify the species responsible for the bite. Citations of the relevant literature on safety, efficacy, and dosing for each product are provided in the references section.

Determine the appropriate first line antivenom for your area of operations prior to deployment using this section, then refer back to the Universal Approach to Snakebite Assessment, Diagnosis, and Treatment earlier in the document for detailed instructions and a stepwise approach to snakebite management throughout the course of care. Abbreviated antivenom guidelines for each regional combatant command are included below.

CATEGORIZATION OF MEDICALLY SIGNIFICANT SNAKE SPECIES

The World Health Organization (WHO) classifies the risk posed by various venomous snakes by designating each species as either Category 1 or Category 2 as described below. WHO guidelines state that the “species listed in Category 1 within a country, territory or area should be considered as being of highest priority for antivenom production on the basis that available knowledge implicates them as being responsible for the greater burden in that particular setting.” ¹⁶⁰

WHO Category 1: Venomous Snakes of Highest Medical Importance

Defined as “highly venomous snakes which are common or widespread and cause numerous snakebites, resulting in high levels of morbidity, disability or mortality.”

WHO Category 2: Venomous Snakes of Secondary Medical Importance

Defined as “highly venomous snakes capable of causing morbidity, disability or death, for which exact epidemiological or clinical data may be lacking; and/or which are less frequently implicated (due to their activity cycles, behavior, habitat preferences or occurrence in areas remote to large human populations).”

NOTE: Antivenom Infusion versus Direct Push: For most first line antivenoms in this CPG, administration using either a) 100, 250, or 500 mL IV bag of isotonic fluids (0.9% NS ideal; Lactated Ringers is acceptable) with 10-minute IV/IO infusion or b) direct IV push is recommended in order to get a full dose of antivenom onboard as quickly as possible and neutralize venom before further damage has occurred. However, if this is not possible you may dilute antivenom in any size bag of isotonic solution and give over 10 – 30 minutes. While the amount of antivenom given should not change based upon the patient’s size, smaller volumes of fluids may be indicated in pediatric patient’s to avoid volume overload.

CONTACT: For emergency consultations, or additional information about snake bite management or this CPG, call the ADVISOR telemedicine hotline 833-ADVSRLN (833-238-7756) / DSN: 312-429-9089 and select toxicology from the phone menu.

Symptomatic NEURO Algorithm

Symptomatic HEMO/CYTO Algorithm

Asymptomatic Algorithm

Control Algorithm

Tourniquet Algorithm

Antivenom Reactions Algorithm

Safe and effective broad-spectrum, field-stable antivenoms are available for all three syndromes of snake envenomation in this AOR and treatment does not require identification of the species responsible. Snakebite treatment at the point of injury is recommended for AFRICOM due to prolonged evacuation times, high incidence of snakebites, and the high risk of death or permanent disability from many venomous snakes in the AOR if early antivenom treatment is not available.

Adverse Reaction Management

• If a mild or moderate reaction occurs, slow the infusion and treat symptomatically with antihistamines, steroids, and/or antiemetics as needed. Refer to management of adverse reactions for specific instructions.
• If a severe reaction such as anaphylaxis occurs, stop the infusion and treat according to the antivenom reactions algorithm listed elsewhere in the CPG. Reassess the patient once the reaction has been controlled and resume the infusion at a slower rate if any of the specific criteria for antivenom treatment listed elsewhere in the CPG have not completely resolved.

AFRICOM Antivenom Selection Flowchart 

AFRICOM - Short Form Antivenom Guide

AFRICOM – Long Form Antivenom Guide

Sub-Saharan Africa/North Africa

North Africa

Sub Saharan Africa

Sub Saharan Africa

Sub Saharan Africa

North Africa

Safe and effective broad-spectrum, field-stable antivenoms are available for all three syndromes of snake envenomation in this AOR and treatment does not require identification of the species responsible. Snakebite treatment at the point of injury is recommended for CENTCOM due to potential for prolonged evacuation times, high incidence of snakebites, and the high risk of death or permanent disability from many venomous snakes in the AOR if early antivenom treatment is not available.

Adverse Reaction Management

• If a mild or moderate reaction occurs, slow the infusion and treat symptomatically with antihistamines, steroids, and/or antiemetics as needed.
• If a severe reaction such as anaphylaxis occurs, stop the infusion and treat according to the anaphylaxis protocol listed elsewhere in the CPG. Reassess the patient once the reaction has been controlled and resume the infusion at a slower rate if any of the specific criteria for antivenom treatment listed elsewhere in the CPG have not completely resolved.

CENTCOM - First Line Antivenoms

CONTACT

For emergency consultations, or additional information about snake bite management or this CPG, call the ADVISOR telemedicine hotline 833-ADVSRLN (833-238-7756) / DSN: 312-429-9089 and select toxicology from the phone menu. 

CENTCOM Antivenom Selection Flowchart

CENTCOM- Short Form Antivenom Guide

CENTCOM-Long Form Antivenom Guide

Middle East/Central Asia

Arabian Peninsula

Central Asia

Middle East/Central Asia

Safe and effective broad-spectrum, refrigerated antivenoms are available for all three syndromes of snake envenomation due to European viper species in this AOR and treatment does not require identification of the species responsible. Snakebite treatment at the point of injury is not routinely recommended for EUCOM. This section provides specifics about antivenoms use in this region.

Adverse Reaction Management

• If a mild or moderate reaction occurs, slow the infusion and treat symptomatically with antihistamines, steroids, and/or antiemetics as needed.
• If a severe reaction such as anaphylaxis occurs, stop the infusion and treat according to the anaphylaxis protocol listed elsewhere in the CPG. Reassess the patient once the reaction has been controlled and resume the infusion at a slower rate if any of the specific criteria for antivenom treatment listed elsewhere in the CPG have not completely resolved.

EUCOM - First Line Antivenoms

EUCOM Antivenom Selection Algorithm

EUCOM – Short Form Antivenom Guide

EUCOM –Long Form Antivenom Guide

Outside UK or Scandinavia

UK or Scandinavia

UK or Scandinavia

Outside UK or Scandinavia

Snakebite management in Asia is complicated by a high diversity of venomous snakes, many narrow-spectrum local antivenoms that require snake ID and cold-chain storage, and only two broad-spectrum, field-stable polyvalents (TRC-NPAV and TRC-HPAV) which provide only partial coverage outside of Southeast Asia. Critically, TRC-HPAV and TRC-NPAV fail to cover many of the highest threat venomous snakes in Taiwan, Japan, the Korean Peninsula, China, and several other areas.^277-292 As a result, in these areas providers may need to make an educated guess as to the genus or species responsible. Refer to the Appendix: Snake Identification (ID) Tips – INDOPACOM for more detailed guidance on snake identification. Always start with the Antivenom Selection Flowchart: INDOPACOM and Antivenom Dosing by Product Table in Appendix H, which are designed to help you through this process with excerpted images below and detailed explanation in appendix. For rapid bedside decision making support when antivenom selection depends on snake ID, reference the Bedside Snake ID Workflow.

INDOPACOM Snake ID Legend

Adverse Reaction Management

• If a mild or moderate reaction occurs, slow the infusion and treat symptomatically with antihistamines, steroids, and/or antiemetics as needed. Refer to the Antivenom Reactions Algorithm.
• If a severe reaction such as anaphylaxis occurs, stop the infusion, and treat according to the anaphylaxis protocol listed elsewhere in the CPG. Reassess the patient once the reaction has been controlled and resume the infusion at a slower rate if any of the specific criteria for antivenom treatment listed elsewhere in the CPG have not completely resolved.

CONTACT

For emergency consultations, or additional information about snake bite management or this CPG, call the ADVISOR telemedicine hotline 833-ADVSRLN (833-238-7756) / DSN: 312-429-9089 and select toxicology from the phone menu.

INDOPACOM – First Line Antivenoms

INDOPACOM Antivenom Selection Flowchart

INDOPACOM - Short Form Antivenom Guide

CPG Revision: Approach to Snakebite in Asia

The CPG revision approaches snakebite management in Asia by prioritizing coverage against highest threat species causing the most bites and the species which are most likely to cause severe injury and death. We have selected antivenoms with favorable efficacy, safety, and sourcing that give the broadest species coverage with the fewest possible products. Taking the species and the antivenoms into account, we have subdivided Asia into the following regions: 1) Southeast Asia, 2) Southeast China/Northern Laos/Northern Vietnam, 3) Taiwan, 4) Japan, and 5) Korean Peninsula/Northeast China.

Venomous Asian snakes fall into 2 broad categories, elapids (primarily neurotoxic), and vipers (primarily hemotoxic/cytotoxic). Exceptions exist, however, and the most notable is that several Asian cobras (elapids) cause primarily cytotoxic effects with minimal neurotoxicity. Other Asian cobras, however, are severely neurotoxic. The available neuro antivenom products, such as Thai Red Cross Neuro Polyvalent (TRC-NPAV), and Taiwan Neuro Polyvalent (NIPM-NBB) are indicated for both neurotoxic and cytotoxic cobra syndromes. The primary clinical implication of this is that a patient presenting with a neurotoxic bite or a cytotoxic cobra bite (severe pain, signs of tissue damage, absence of hemorrhage) should receive a neuro polyvalent antivenom. In general, the Thai polyvalent antivenoms provide excellent coverage for most of the venomous snakes found in SE Asia (Thailand, Myanmar, Cambodia, Laos, Vietnam, Malaysia, Indonesia, and Brunei). As such, monovalent antivenoms are not needed in this region.

CPG Revision: East Asia (China, Japan, Korean Peninsula, Borders)

SE China, Northern Laos, and Northern Vietnam:

The venomous snake fauna in this region is very similar to Taiwan. A notable exception is the presence of the king cobra in China and adjacent southern countries. King cobras are large elapids that produce a mixed clinical syndrome of severe neurotoxicity (main life threat) and cytotoxic tissue damage; which is covered by TRC-NPAV. The Thai polyvalent antivenoms are indicated in this region but notably do not cover other important snakes like the Habu (Protobothrops) and the Sharp-nosed viper (Deinagkistrodon). These special cases are addressed with the Taiwan antivenoms (NIPM-PTBV and NIPM-SNV) in the algorithm.

Japan, Korean Peninsula, NE China:

The venomous snakes of Japan, the Korean Peninsula, and NE China are similar and vipers like the Mamushi (Gloydius spp.) predominate.^284-292 Japanese and Korean antivenoms provide good coverage for these snakes. An exception is the Okinawa region and adjacent smaller southern Japanese islands, where the Habu (Protobothrops) is found.²⁸³ This is also addressed in the algorithm with Japanese Habu antivenom (CSTRI-HABU).

Sea Snake Envenomation:

Finally, sea snakes are present throughout the Indo-Pacific region in oceans and aquatic coastal regions. These snakes can produce severe neurotoxic effects. Bites are extremely rare from sea snakes and usually only occur to fishermen removing the snakes from their nets. Australia produces the only antivenom for sea snakes (CSL-SS) and this is reflected as a special case in the algorithm. In cases where the clinical envenomation syndrome is unclear and/or the culprit snake is in question, the clinician should contact the DOD Advisor Line.

INDOPACOM - Long Form Antivenom Guide

Southeast Asia

Southeast Asia

Marine Environments

Maluku/West Papua Islands

Japan (Okinawa Region)

Japan (Not in Okinawa Region)

Japan/China/N Korea/Vietnam/E Russia

Korean Peninsula/NE China

Taiwan

East Asia: SE China, N Vietnam, LaosTaiwan: Rocky Slopes, Montane Forest 100m-1500m

South and East Taiwan: Coastal Zone

INDOPACOM – Snake Identification Tips

In some parts of Asia, bedside antivenom selection sometimes depends on a presumptive snake ID. When ID is required, the objective is not perfect certainty - it is to make a timely and evidence-based “best guess” that allows treatment to proceed. Do not delay lifesaving antivenom in pursuit of 100% certainty. Providers are advised to contact the DoD ADVISOR line and request a toxicology consult as soon as possible.              

DoD ADVISOR: +1 (833) 238-7756 / DSN: (312) 429-9089 |Request Toxicology Consult

Core principles

• Safety first: Never encourage patients, bystanders, or staff to chase, capture, kill, or handle a snake to aid identification. Even a severed head can reflex bite and inject venom for hours. Treat any snake—alive or dead—as capable of causing envenomation.
• If photos or a specimen available: contact DoD advisor toxicologist for ID assist.
• Don’t let ID delay care. Stabilize airway, breathing, and circulation; start syndrome guided management; and use the regional algorithm. Reassess the presumptive ID as new information emerges.
• Use a weighted evidence approach. When photos or a specimen are not available, combine: (1) place (geography, habitat, elevation), (2) snake description/behavior if seen, (3) circumstances of the bite, and (4) clinical syndrome at the bedside. The combination is usually more reliable than any single element.
• Start with the info embedded in the AV Rapid Reference table and the regional Antivenom Algorithm: INDOPACOM AOR within the CPG (see next section for details and screenshots).

CPG Revision: Dedicated Coverage Pathways for Taiwan

Dedicated Coverage Paths: The following species cause nearly all snake envenomations in Taiwan: Chinese cobra (Naja atra - cytotoxic), many-banded krait (Bungarus multicinctus -severely neurotoxic), Habu (Protobothrops mucrosquamatus - hemotoxic/cytotoxic), green tree viper (Trimeresurus stejnegeri - hemotoxic/cytotoxic), sharp-nosed viper (Deinagkistrodon acutus - hemotoxic/cytotoxic), and eastern Russell’s viper (Daboia siamensis - hemotoxic/cytotoxic). Photographs of these snakes are included below.

Four different antivenom products are produced in Taiwan, two are polyvalent and two are monovalent. All are effective for their covered species. The polyvalent neuro product (NIPM-NBB) covers kraits and cobras, and the bivalent hemorrhagic product (NIPM-PTBV) covers the Habu and green pit viper. Monovalent products cover the sharp-nosed viper (NIPM-SNV) and Russell’s viper (NIPM-RV).

How to Use Taiwanese Antivenoms

Taiwan’s multi-antivenom approach relies on knowing the species responsible for the bite. Identifying the culprit species in Asia is more useful than in any other region. Taiwanese clinicians use snake-identification posters and venom detection kits to help choose the proper antivenom. A detailed history from the victim regarding the behavior and appearance of the snake is important. Description of the habitat (mountainous, coastal flats, agricultural, etc.) is also important and can help identify the culprit. For assistance in identifying Taiwan venomous snakes, refer to the above images.

The Taiwan bivalent viper antivenom (NIPM-PTBV) will likely be used most frequently, followed by the Taiwan neuro bivalent (NIPM-NBB; indicated not only for neurotoxic krait bites but also cytotoxic cobra bites). The monovalent antivenoms will be needed for bites from suspected sharp-nosed vipers (NIPM-SNV) and Russell’s vipers (NIPM-RV) and this is addressed in the algorithm.

Start at Regional Antivenom Flowchart: INDOPACOM and Antivenom Dosing By Product Table (in CPG)

Because broad-spectrum, field stable polyvalents (TRC-NPAV and TRC-HPAV) have gaps outside Southeast Asia, the CPG includes region tailored decision points for Taiwan, Japan, the Korean Peninsula, East China, and other areas where local monovalents or mixed coverage strategies may be required. In these subsections, location/elevation/habitat plus syndrome often narrows to a logical presumptive ID even when the snake was not seen. Use those boxes first when working in these areas.

INDOPACOM AOR Antivenom Algorithm

INDOPACOM AV Rapid Reference Guide

Bedside Snake ID Workflow (When Antivenom Choice Depends on ID)

1. Stabilize ABCs; start syndrome guided care (airway equipment ready for neurotoxicity; pressure immobilization only when indicated; analgesia).

2. If snake photos (or dead snake) AVAILABLE:

a. Contact DoD Advisor at +1 (833) 238-7756, request toxicology, tell them you have photos or a dead snake with the patient.

b. Ideally, photos show the full body/pattern as well as several clear angles of the head (top, front, sides). Ventral side photos can be helpful but dorsal more important.

c. DO NOT take risks to obtain photos! Never touch the head with your hands - even a decapitated snake head can bite and inject venom >24 hours after the bite.

3. If snake photos (or dead snake) NOT AVAILABLE:

a. Ask the patient about where the bite occurred (location / estimated elevation), what type of habitat it was (e.g., dry rocky hillside, wading through creek), what the patient was doing when the bite occurred, what the snake looked like, and if they remember anything about how it behaved (e.g., rose up and hooded its neck).

b. Review ID tips (habitat/location) in Antivenom Algorithm: INDOPACOM AOR in the CPG regional pages for INDOPACOM. Review the location/habitat text on the sub-regional arrows for your area, this may provide an answer.

c. Review snake description and habitat/location tips in the AV RAPID REFERENCE table in the CPG: Antivenoms that require species ID have tips for identification based on location/habitat and snake description.

d. Classify the syndrome(s): NEURO, HEMO, CYTO, or mixed (e.g. HEMO/CYTO). If mixed, identify the dominant syndrome.

e. Scan history / description for strong signals (hooding/spitting; sea exposure; nocturnal bed bite with minimal local signs).

4. Make a presumptive ID à Select antivenom per regional algorithm for the most likely group à treat without delay.

5. Reassess frequently: If the clinical course and labs do not improve after adequate dosing, reopen the differential and switch antivenom per algorithm or after DoD ADVISOR consultation.

6. Sometimes, it may be necessary to try more than one antivenom in these cases – this is often done in Taiwanese hospitals.

Safe and effective antivenoms are available for all neurotoxic/hemo/cytotoxic pit viper envenomations and for neurotoxic coral snake envenomations in this AOR. Treatment does not require identification of the species responsible. Snakebite treatment at the point of injury is not routinely recommended for NORTHCOM.

For all NORTHCOM antivenoms, refer to the package insert in the antivenom box for specific usage instructions as per FDA regulations for domestically approved products. Also see Unified treatment algorithm for the management of crotaline snakebite in the U.S. (Lavonas et al. 2011) for dosing and management guidelines on pit viper bites.¹⁰¹ This section provides specifics about antivenoms use in this region.

Adverse Reaction Management

• If a mild or moderate reaction occurs, slow the infusion, and treat symptomatically with antihistamines, steroids, and/or antiemetics as needed.
• If a severe reaction such as anaphylaxis occurs, stop the infusion, and treat according to the anaphylaxis protocol listed elsewhere in the CPG. Reassess the patient once the reaction has been controlled and resume the infusion at a slower rate if any of the specific criteria for antivenom treatment listed elsewhere in the CPG have not completely resolved.

CONTACT

For emergency consultations, or additional information about snake bite management or this CPG, call the ADVISOR telemedicine hotline 833-ADVSRLN (833-238-7756) / DSN: 312-429-9089 and select toxicology from the phone

First Line Antivenoms – NORTHCOM

NORTHCOM Antivenom Selection Flowchart

NORTHCOM – Short Form Antivenom Guide

NORTHCOM –Long Form Antivenom Guide

United States & Canada

United States & Canada

United States  & Canada (USA: AL, AR, AZ, FL, GA, LA, MS, NM, NC, OK, SC, TX)

Mexico

Mexico

Mexico

Safe and effective antivenoms are available for all hemo/cytotoxic pit viper envenomations and for neurotoxic coral snake envenomations in this AOR. Treatment does not require identification of the species responsible but does require identification of the syndrome. Snakebite treatment at the point of injury is recommended for SOUTHCOM. This section provides specifics about antivenoms use in this region.

Adverse Reaction Management

• If a mild or moderate reaction occurs, slow the infusion, and treat symptomatically with antihistamines, steroids, and/or antiemetics as needed.
• If a severe reaction such as anaphylaxis occurs, stop the infusion, and treat according to the anaphylaxis protocol listed elsewhere in the CPG. Reassess the patient once the reaction has been controlled and resume the infusion at a slower rate if any of the specific criteria for antivenom treatment listed elsewhere in the CPG have not completely resolved.

SOUTHCOM First Line Antivenoms

CONTACT

For emergency consultations, or additional information about snake bite management or this CPG, call the ADVISOR telemedicine hotline 833-ADVSRLN (833-238-7756) / DSN: 312-429-9089 and select toxicology from the phone

SOUTHCOM – Antivenom Selection Flowchart

SOUTHCOM – Short Form Antivenom Guide

SOUTHCOM – Long Form Antivenom

First Line Northern Central America

Second Line Southern Central America/South America

First Line Southern Central America/South America 

Second Line Northern Central America

Second Line South America

First Line Central America

Second line South America

First Line South America

Second Line Central America

APPENDIX H – REGIONAL ANTIVENOM SELECTION FLOWCHARTS

APPENDIX H, TABLE 1 –ANTIVENOM DOSING BY PRODUCT

JTS recommended HIGH/LOW doses are listed in this table and supersede any package inserts or dosing provided by the manufacturer.

For additional information including National Stock Number (NSN), please contact dha.ncr.med-log.list.lpr-cps@health.mil

DISCLAIMER: This is not an exhaustive list. These are items identified to be important for the care of combat casualties.

Whole Blood Clotting Test for Venom-Induced Consumptive Coagulopathies

The whole blood clotting test (WBCT) is a simple but critical bedside gross examination used in the assessment, diagnosis, and therapeutic monitoring of snakebite patients in the developing world and remote environments.^1-10 Refer to the diagram below regarding instructions for performing the test. At minutes 20 and 30, the tube is gently picked up and tilted 90 degrees; a stable solid clot retained within the tube is scored “Grade 0” and indicates normal coagulation. Abnormal results are scored “Grade 1” for a partial, semisolid clot that breaks apart and detaches from the glass tube shortly after it is turned or “Grade 2” for completely incoagulable liquid blood that pours out of the tube immediately. Attempting to score the test earlier than 20 minutes will not yield accurate results due to the consumptive mechanism of the coagulopathy. Using a healthy donor as a control is ideal to confirm questionable findings.

Continue WBCT testing throughout the course of care to monitor for secondary resumption of venom-induced consumptive coagulopathy.^11-13 After control of the envenomation has been achieved, reassess WBCT every 24 hours throughout the course of hospitalization. It is important to remember that the WBCT must be interpreted in the context of the larger clinical picture. If a patient has improved in all parameters except for a persistent abnormal WBCT, it may reflect an inertia in replenishment of depleted clotting factors after a severe hemotoxic envenomation.¹ If the venom is active then hematocrit should continue to decrease or signs of ongoing hemolysis or bleeding should be present.

This revision of the Joint Trauma System (JTS) Snakebite Envenomation Clinical Practice Guidelines followed the established JTS framework for updating existing CPGs, with emphasis on operational relevance and improved bedside usability for providers at all levels across the continuum of care (prehospital through Role 3). The update was conducted as a focused, expert-driven revision of the original CPG ID 81 (2020) to achieve the following:

1. Improving bedside usability as a clinical reference tool and enabling rapid, time-critical decision-making through streamlined ACLS-style STAT treatment algorithms.
2. Enhancing operational relevance, pre-mission planning, and force health protection in deployed settings globally.
3. Simplified syndrome and severity-driven antivenom dosing guidance designed to reduce preventable deaths and disabilities through rapid initiation of treatment at the POI and early consultation with DoD Advisor toxicologists.
4. Printable rapid-reference tools optimized for austere and resource-limited environments including dosing tables, antivenom coverage algorithms, and suggested antivenom treatment packing checklist.
5. Expanded INDOPACOM algorithms with dedicated regional management pathways to address coverage gaps in Taiwan, Japan, the Korean Peninsula, China/East Asia, and other high-risk geographic regions.

Antivenom Recommendations

Antivenom selection was based on a combination of published evidence and expert experience. Authors prioritized antivenoms which offered broad-spectrum regional coverage of medically significant species, enabled syndromic treatment without reliance on species identification, could be carried for extended periods in field conditions without cold chain, and demonstrated low rates of adverse reactions in peer-reviewed studies or firsthand applications. Due to the lack of high quality studies on many antivenoms globally, whenever possible first line antivenoms were selected from manufacturer product platforms which have been used extensively by the authors in comparable operational environments. Strategic considerations, including supply chain reliability and security risks (e.g. deprioritization of products manufactured by adversarial states) were also considered.

This Clinical Practice Guideline (CPG) was developed to provide pragmatic clinical guidance for military medical providers managing snakebite envenomations in far-forward, expeditionary settings.

Recognizing the ethical and logistical challenges of conducting rigorous clinical trials for time-critical envenomations on the battlefield, the recommendations herein are based on the best available evidence. Where high-quality published data is limited, the guidance reflects a synthesis of available literature, author experience, and expert recommendations. The methodology incorporates SME opinion, operational experience, observational studies, and unpublished data to address gaps in military or civilian literature.

In line with Joint Trauma System (JTS) policy, this CPG prioritizes operational relevance, speed, and real-time performance improvement. Therefore, it does not adhere to all standards of the National Academy of Sciences, Engineering, and Medicine, such as formal strength-of-evidence grading. Final adjudication was achieved through a structured, iterative expert review and consensus of selected senior authors, rather than a formal Delphi methodology. While potentially useful for civilian providers in austere environments, this CPG is specifically tailored to the unique capabilities and needs of military medical personnel.

Roles & Responsibilities

The development and revision of this CPG were managed through a structured process involving a working group leader, section authors, and a senior author group.

• Working Group Leader: The first author (JM) led the JTS Snakebite Envenomation Working Group, defined the scope, provided revisions, and ensured compliance with JTS development standards.
• Senior Author Group: A senior group composed of JMB, BG, CD, EB, AF, and JM conducted a secondary review and iterative revisions of all draft sections. This group represented key stakeholders across the continuum of care, including conventional and special operations paramedics, emergency medicine physicians, toxicologists, and non-toxicologist experts in austere envenomations.
• Additional Subject Matter Experts: JMB and BG also consulted with DR, MC, JL, CP, NB, BW, KM, and SG as additional domain SMEs on specialized topics throughout the process.

The original CPG was divided into the following sections for initial review and revision:

Approval & Finalization

Draft sections were extensively reviewed by the senior author group to ensure clinical validity and operational feasibility. Once consensus was achieved, the recommendations were passed to the first author (JM) for final review. The consolidated document was then reviewed by designated DoD toxicology reviewers and advanced through the formal JTS review and approval pathway.

Several investigational drugs currently under study for snakebite treatment have received significant public and media attention in recent years.^263,264 The most promising are small-molecule therapeutics (SMTs), notably the phospholipase A₂ (PLA₂) inhibitor varespladib and the snake-venom metalloprotease (SVMP) inhibitor marimastat. However, they have been frequently mischaracterized in press reports as “universal antivenoms” when they are neither universal nor antivenoms, leading to significant confusion among medical providers and policymakers. In some cases, this confusion has complicated the efforts of medical providers seeking to obtain CPG recommended antivenoms for deployments OCONUS, negatively impacting Force Health Protection. It is therefore critical to clarify the position of the Joint Trauma System on investigational drugs for snakebite treatment.

1. The only definitive treatment for a snake envenomation is the timely administration of appropriate antivenom at the appropriate dose required to neutralize circulating venom compounds. SMTs may eventually prove useful as adjunct therapies to be given in addition to recommended antivenoms, but not as replacements. Due to the complexity of snake venoms and envenomations, this is unlikely to change in the next 20+ years.
2. The utility of SMTs lies not in replacing antivenoms, but in supporting them as adjunct therapies much like TXA, either in prehospital settings when ALS-capable providers are not available to administer IV/IO antivenoms or, in some cases, potentially as co-administered medications given with antivenom to improve outcomes where coverage may be lacking. In all cases, the best outcome depends on timely administration of the appropriate antivenom to the patient. Definitive treatment with antivenoms given at the earliest opportunity will remain the single most important factor in determining patient outcomes in these cases.
3. While some SMTs have shown early promise, their safety, tolerability, and efficacy must be demonstrated in rigorous, peer‑reviewed clinical trials before any consideration for inclusion in the Clinical Practice Guidelines can be made. This process will likely take years and the outcome is uncertain. The JTS Snakebite Envenomation Working Group will continue to monitor advances in snakebite therapies and will incorporate new treatments into the guidelines when it is appropriate to do so based on rigorous scientific evidence and clinical best practices.

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Purpose                                                                                                                       

The purpose of this Appendix is to ensure an understanding of DoD policy and practice regarding inclusion in CPGs of “off-label” uses of U.S. Food and Drug Administration (FDA)–approved products. This applies to off-label uses with patients who are armed forces members. 

Background

Unapproved (i.e. “off-label”) uses of FDA-approved products are extremely common in American medicine and are usually not subject to any special regulations. However, under Federal law, in some circumstances, unapproved uses of approved drugs are subject to FDA regulations governing “investigational new drugs.” These circumstances include such uses as part of clinical trials, and in the military context, command required, unapproved uses. Some command requested unapproved uses may also be subject to special regulations. 

Additional Information Regarding Off-Label Uses in CPGs

The inclusion in CPGs of off-label uses is not a clinical trial, nor is it a command request or requirement. Further, it does not imply that the Military Health System requires that use by DoD health care practitioners or considers it to be the “standard of care.” Rather, the inclusion in CPGs of off-label uses is to inform the clinical judgment of the responsible health care practitioner by providing information regarding potential risks and benefits of treatment alternatives. The decision is for the clinical judgment of the responsible health care practitioner within the practitioner-patient relationship.

Additional Procedures

Balanced Discussion

Consistent with this purpose, CPG discussions of off-label uses specifically state that they are uses not approved by the FDA. Further, such discussions are balanced in the presentation of appropriate clinical study data, including any such data that suggest caution in the use of the product and specifically including any FDA-issued warnings.

Quality Assurance Monitoring

With respect to such off-label uses, DoD procedure is to maintain a regular system of quality assurance monitoring of outcomes and known potential adverse events. For this reason, the importance of accurate clinical records is underscored.

Information to Patients

Good clinical practice includes the provision of appropriate information to patients. Each CPG discussing an unusual off-label use will address the issue of information to patients. When practicable, consideration will be given to including in an appendix an appropriate information sheet for distribution to patients, whether before or after use of the product. Information to patients should address in plain language: a) that the use is not approved by the FDA; b) the reasons why a DoD health care practitioner would decide to use the product for this purpose; and c) the potential risks associated with such use.