ADJUNCT TREATMENTS, SUPPORTIVE CARE, ONGOING MONITORING, AND ADDITIONAL ANTIVENOM DOSES

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.

Figure 5. Timeline of Assessments After Control

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.