Cytotoxicity

The presence of significant local pain OR progressive edema OR signs of tissue destruction (bruising, blistering, necrosis) is an indication for initial administration of antivenom.1,47,48,79,100–105  If any of these criteria (or other systemic signs and symptoms) are present, treat immediately and do not wait for irreversible damage to occur before deciding to give antivenom. Note that the progression of edema at any treatment interval is an indication to administer additional antivenom; however, edema may not begin to noticeably decrease for several days and severe edema may take 1 - 2 weeks or longer to completely resolve. WORSENING edema is therefore a treatment criteria, persistence of edema without any progression IS NOT a treatment criteria. Worsening pain that increases significantly in severity or moves proximally up the limb is another indicator for antivenom treatment.

Neurotoxicity

The onset, persistence, or resumption of systemic neurotoxic signs of envenomation (dyspnea, neck flexor muscle weakness, bulbar muscle weakness, reduced level of consciousness, ↓ respiratory muscle function, etc.) at any of the antivenom treatment intervals is always an indication to administer or re-administer antivenom.1,50,107–109  Monitor respiratory function using negative inspiratory force (NIF) or forced vital capacity (FVC), single breath count test (SBC), capnography, spirometry, peak flow meters, etc.1,54,72  In patients who have not reached the late stages of respiratory distress/arrest, the first indications that paralysis is improving may be apparent within 30 - 60 minutes once the right dose of antivenom has been achieved. In patients who are already intubated, it may take hours for reversal to occur after antivenom. This typically occurs within 1 - 3 hours, but may take 6 - 12 hours or longer in some patients. There are numerous documented cases of patients who did not receive antivenom and required prolonged mechanical ventilation ranging from several days up to 13 weeks before recovery. Antivenom typically either reverses the syndrome before it progresses or dramatically shortens the duration of paralysis.

Bleeding

The onset, persistence, or resumption of any active local or systemic bleeding at any of the standard assessment intervals (0, 2, 4, 6, 12, 24 hours) is always an indication to administer or re-administer antivenom regardless of the WBCT result at the time.1,70,78,106,109–111  All external and internal bleeding will cease when the appropriate dose of antivenom has been given and actively circulating venom has been neutralized.

WBCT/Coagulation Tests

Tests of coagulation usually normalize within 2 - 6 hours after the effective dose of antivenom has been achieved but in some cases it may take longer for these labs to fully normalize after antivenom therapy.78,112–120  WBCT procedure and interpretation is covered in Appendix A: Whole Blood Clotting Test (WBCT) for Venom-Induced Consumptive Coagulopathies (VICC).

There are three situations where an abnormal WBCT or other abnormal laboratory tests of coagulation (e.g. fibrinogen, PT/PTT/INR, etc) should be treated with antivenom:

  1. Initial assessment at H0: Coagulopathy after a snakebite is an indication to give antivenom. If the coagulation test is abnormal but the patient is otherwise asymptomatic, repeat the test using a new glass tube to confirm the result prior to antivenom administration.78,111,113,114,121
  2. H2, H4, H6, H12, H24: a previously normal coagulation test that changes to abnormal in the presence of any new symptoms meets criteria to administer an additional dose of antivenom. This also applies to a WBCT that was abnormal, normalized several hours after antivenom, but then changes to abnormal again later (recurrent envenomation).78
  3. Coagulopathy remains abnormal at H24: If WBCT or other tests of coagulation remain abnormal at H24, administer an additional dose of antivenom and repeat every 24 hours until resolution of coagulopathy has occurred.

Sudden Collapse Syndrome

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