APPENDIX E: INDOPACOM TREATMENT GUIDELINES

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

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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.