Antivenoms for snake bite

These are the 7 snake antivenoms commercially available in Australia: Tiger snake, Brown snake, Taipan, Black snake, Death adder, Sea snakes and Polyvalent snake antivenom. Administration of some of these antivenoms for other snake bites can sometimes help control envenomation in the patient. Identification of the offending snake will aid in the choice of the appropriate antivenom and alert clinicians to particular features characteristic of envenomation by that type of snake. In cases of snakebite involving zoo staff, herpetologists or other experienced snake handlers, the snake’s identity may be known (although this cannot always be relied upon, particularly in the case of enthusiastic amateurs). Identification of snakes by the general public or by hospital staff is frequently unreliable. Sometimes, the snake is not seen or is only glimpsed in retreat.
Supportive Care Envenomed patients should be admitted to hospital and observed for a period of at least 24 hours, depending on the clinical circumstances. Regular (i.e., at least hourly) neurological observations and repeated pathology studies should be performed to monitor progression of the illness. The frequency at which clotting studies should be repeated is uncertain. After circulating antivenom has been neutralised, it may be several hours (4-6 hours) before reconstitution of plasma clotting factors has occurred sufficiently to return clotting times towards normal. A lack of improvement in clotting times on retesting may therefore represent insufficient antivenom or insufficient time before re-testing. Improvement in clotting times may represent the efficacy of antivenom or the natural history of the disease. Worsening of coagulopathy on testing, however, is an indication that circulating procoagulants remain un-neutralised, and that further antivenom is required. Other treatments such as analgesia (avoid sedating agents such as morphine if possible), plasma volume expanders and fresh frozen plasma may be required. In severe envenomations resulting in respiratory compromise, supplemental oxygen and sometimes mechanical ventilation are indicated. Incipient renal failure may be treated with volume replacement and diuretics, but haemodialysis may occasionally be required, particularly in cases where treatment has been delayed. Hyperkalaemia secondary to rhabdomyolysis may be treated with calcium, insulin and glucose and resonium. All patients should receive appropriate tetanus prophylaxis and consideration should be given to antibiotic prophylaxis if the bite wound is contaminated. Rarely, the snake’s fangs may break and become embedded in the wound, acting as a foreign body and a nidus for infection. Indications for Antivenom Many cases of snakebite do not need antivenom because often the snake injects very little venom. Fang marks alone are not an indication for antivenom. Antivenoms should not be used unless there is evidence of systemic envenomation. Presentation of envenomation may include:
  • headache, nausea, vomiting
  • abdominal pain
  • collapse, unconsciousness (may be transient), coma
  • painful, tender muscles (myolysis)
  • blurred vision
  • irritability, confusion
  • dark urine (myoglobinuria, haematuria)
  • ptosis, dysarthria, weakness/paralysis, dyspnoea
  • respiratory failure (neurotoxicity)
  • hypotension
  • cardiorespiratory arrest
The symptoms and signs of envenomation, and the time course they follow, vary enormously between individual patients, being influenced by such factors as body weight, amount of venom injected, age and state of health of the patient time elapsed since the bite and site of the bite. Variation between snakes is also important. The size and maturity of the snake and the time since it last injected venom will influence the severity of the envenomation. Some features of envenomation are more prominent in bites from certain species of snakes. Myolysis, for example, is particularly prominent in sea snake and tiger snake envenomations, while death adder venom is predominantly neurotoxic in action. Myolysis may lead to renal failure, which probably accounted for the delayed deaths at 2-7 days described in the past. Several Australian snake venoms, including tiger snake and taipan venoms, contain post-synaptic as well as pre-synaptic neurotoxins, the latter being difficult to reverse if the patient is not treated promptly. Coagulation disturbance, usually related to secondary afibrinogenaemia, is common after bites from most Australian venomous snakes, although severe haemorrhage is rarely seen. There have been 7 published fatal cases of intracerebral haemorrhage related to snakebite in Australia . When Envenomation is Not Indicated Presentation of a snake bite may include:
  • Puncture marks (usually on limbs). These may be difficult to see, and may consist of a single or double puncture or scratch marks or multiple punctures. They may be bleeding or oozing.(NB care should be taken with puncture of arterial or central venous sites in the presence of potential coagulopathy)
  • Regional tender lymphadenopathy (NB this may also be present after bites from non-venomous snakes, and is not by itself an indication for antivenom)
Differential Diagnosis of Venomous Snakebite
  • non-venomous snakebite
  • bite or sting by other venomous creature (arthropod (including spider), octopus, jellyfish)
  • CVA
  • ascending neuropathy e.g., Guillain-Barre Syndrome
  • AMI
  • allergic reaction
  • hypoglycaemia/hyperglycaemia
  • drug overdose
  • closed head injury
Premedication The issue of premedication prior to the administration of antivenoms has been controversial. However, a recent publication from Sri Lanka provides good evidence from a randomised controlled trial that premedication with subcutaneous adrenaline reduced the rate of allergic reactions to snake antivenom from 43% (placebo) to 11% (adrenaline). There were reported to be no adverse effects related to the use of adrenaline (Premawardhena, C.E. et al, B.M.J. 318: 1041-1043, 17 April 1999). Premedication appears to be most clearly indicated in rural settings where staff and other resources are limited. If premedication is to be given, it should always be by the subcutaneous route prior to the intravenous administration of Australian snake antivenoms. Adults should receive 0.25-0.3mg of adrenaline by the subcutaneous route (0.005-0.01 mg/kg for a child). Adrenaline as a premedicant should never be given intravenously, in order to avoid hypertension in the coagulopathic patient with the potential for bleeding. Similarly, it should not be administered intramuscularly, as this may also lead to hypertension, as well as to haematoma formation in the presence of coagulopathy. Although traditional, the role of antihistamines in premedication is unclear. There is some overseas evidence to suggest that the incidence of allergic reactions to snake antivenom is not reduced by antihistamine. In addition, the only currently available parenteral antihistamine in Australia, promethazine, has sedative effects which may be undesirable in envenomed patients. AVRU does not currently recommend antihistamines as a premedication to antivenom use. Administration of Antivenoms for Australian Snakebite Australian antivenoms are amongst the safest in the world. Many patients, such as snake handlers, even those with a past history of reaction to equine proteins have had minimal or no problems with repeat antivenom therapy after premedication. They are, however, foreign protein, and the possibility of allergic reactions, including life threatening anaphylaxis, should always be considered and facilities be made available for dealing with such complications before the administration of antivenoms. Adrenaline is the treatment of choice for anaphylactic and anaphylactoid reactions, in conjunction with bronchdilators, fluid replacement, etc. Most antivenoms are given by the intravenous route, although redback spider antivenom and box jellyfish antivenom are more often used intramuscularly. Skin testing for allergy to antivenom is not recommended, as it is unreliable and may delay urgent therapy. Antivenoms that are given intravenously should be diluted in at least 100ml of normal saline, 5% dextrose or Hartmann’s solution immediately prior to administration. It should initially be administered slowly while the patient is observed for signs of allergic reaction. If no reaction is observed, then the rate of infusion may be increased. If the patient reacts to the antivenom, the rate may be slowed or the infusion ceased temporarily. If the reaction is more severe, then treatment with adrenaline, plasma volume expanders and beta agonists should be undertaken as required. The decision to recommence antivenom should be based on the clinical state of the patient. In the case of the patient with a known allergy to antivenom or to horse serum, the decision as to whether to withhold antivenom should again be clinically based, bearing in mind the resuscitation facilities available. The initial doses of antivenom recommended are included in the table above, and are based on the average amount of venom injected by each of the snakes concerned. There is evidence, however, that these doses may be insufficient to reverse coagulopathy associated with the bites of several Australian venomous snakes, notably the brown snake and the taipan. Larger initial doses should be considered if there is evidence of severe envenomation (multiple bites, rapidly progressive symptoms, large snakes). The dose of antivenom for children should not be reduced according to their weight, since the amount of venom injected by the snake is independent of the victim’s size. Initial recommended doses of antivenom for Australian snake bites are given in the linked PDF gallary article. Note: the antivenom requirements of patients will vary considerably. Some patients with minimal envenoming will require no antivenom, whereas others may require multiple doses of antivenom. Detailed information on the use of antivenoms is packaged with the individual antivenoms. If you require additional advice, contact the Australian Venom Research Unit on (03) 8344 7753, Poison Information Centres on 13 11 26 (Australia wide) or CSL Ltd on (03) 9389 1911. Serum Sickness Serum sickness, due to the deposition of immune complexes, is a recognized complication of the administration of foreign protein solutions such as antivenoms. The symptoms include fever, rash, arthralgia and flu-like illness. Serum sickness following the administration of Australian antivenoms was reported in 3 out of a total of 70 cases in one series, although this is may be an underestimate due to loss to follow up of some patients. The possibility of serum sickness, and the symptoms and signs should be discussed with the patient prior to discharge, so that it may be recognized and treated early. Corticosteroids should be considered if a large volume of antivenom, such as polyvalent snake antivenom or multiple ampoules of monovalent snake antivenom, is administered, or if the patient has a past history of exposure to equine protein. Both the incidence and severity of delayed serum sickness may be markedly reduced by the administration of prednisolone, 50 mg (adult dose) for five days after the administration of antivenoms. Methods for Investigating Envenomation Include:
  • Venom Detection Kit (bite site, urine or blood)
  • Clotting studies INR/PT, APTT, ACT, D-dimer, X-FDP, fibrinogen. In remote areas where sophisticated clotting tests are unavailable, a sample of the patient’s blood in a plain tube should clot within a few minutes in the absence of coagulopathy
  • Creatine kinase for myolysis
  • Urinalysis for haemoglobin, myoglobin
  • Renal function may be impaired secondary to myoglobinuria or other mechanisms WCC is usually only mildly elevated. A significantly raised WCC may indicate other pathology.
Australia is the only country in the world that has snake venom detection kits. They consist of a rapid two step enzyme immunoassay in which wells are coated with antibodies to the various snake venoms. A swab from the bite site, blood, or urine helps to select the type of snake antivenom which may have to be used. Note that the primary purpose of the venom detection kit is not to decide whether envenomation has occurred (i.e., whether antivenom is indicated), but to help to choose the appropriate antivenom if required. About Snake Venom Detection Kits (VDKs): A positive VDK result is not an indication for antivenom. Venom detected at the bite site may be present in insufficient quantity in the circulation to cause significant illness. A negative VDK result does not mean that envenomation has not occurred. The venom may have been washed off or diluted at the bite site, or may not have reached the urine, but still be present in the circulation. Bite site swabs are considered to be the most reliable sample for use in venom detection kits. Venom may also be obtained from clothing, or even from the fangs of dead snakes. Note that very high concentrations of venom in the sample may cause inaccuracies in the venom detection kit result. If this occurs, the sample should be diluted and the test repeated. Blood and urine samples may also be used in the venom detection kit, but are generally thought to be less reliable than bite site swabs. Urine in particular may be used if there has been some delay in presentation, or if no bite site can be identified. Venom Detection Kits should be used in conjunction with other information (such as clinical presentation, knowledge of snakes in the geographic area, identification of snakes brought to hospital with the patient) to determine which antivenom to use if the patient is significantly envenomed. If a reliable identification cannot be made,then polyvalent snake antivenom (or the appropriate combination of monovalent antivenoms in Victoria and Tasmania) should be used. Snake venom is a complex mixture of toxic and non-toxic substances, mostly proteins. Australian snake venoms display neurotoxic, haemolytic, pro-coagulant and usually weak cytotoxic properties. Some also contain potent myotoxic activity. The composition of particular venoms influences the clinical presentation of particular snakebites.