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Antivenom treatment - Adverse reactions - Prevention

See also "Essentials of the management of envenoming and poisoning: 9. How is the appropriate antivenom chosen? When is it administered?".

Indications for administration of antivenom

See "Who requires antivenom?" in the "General practitioner / health post" sections of Diagnosis & Treatment for the relevant group of venomous or poisonous animals.

Choice of appropriate antivenom

See "How is the appropriate antivenom chosen?" in the "General practitioner / health post" sections of Diagnosis & Treatment for the relevant group of venomous or poisonous animals.

Follow-up investigations following administration of antivenom

See "Monitoring of the patient. 1. After administration of antivenom" in the "Hospital" sections of Diagnosis & Treatment for the relevant group of venomous or poisonous animals.


Table 5.5 Antivenom administration: practical approach


Treatment step
Procedure Comments
 Sensitivity test  no Apart from the rare cases of a pre-existing sensitivity, e.g. to horse serum, sensitivity tests (intradermal, intraconjunctival) have no predictive value for an antivenom reaction (Malasit et al. 1986)
 Pre-medication adrenaline s.c., antihistamine i.v. plus corticosteroids i.v. Indication: patients with a history of atopy (asthma, hay fever, food or drug allergy) and those who had developed a reaction to horse serum on previous occasions; they have an increased risk of developing a severe reaction (Warrell 1990b)
Mode of administration i.v. Antivenoms are most effective when administered i.v.; in rare cases antivenoms can be administered i.m.; however, this is associated with a loss of efficacy, and there is a danger of intramuscular bleeding in the case of envenoming with haemostatically active venom components; i.m. administration should thus only be applied if i.v. administration is not possible for technical reasons (Warrell 1990b); further exceptions: Chironex antivenom, F(ab) antivenom (see: "Essentials of the management of envenoming and poisoning: 9. How is the appropriate antivenom chosen? When is it administered?").
Form and speed of administration

i.v. injection of approx. 5 ml/min,

i.v. infusion with isotonic saline solution over 30–60 min

Dose see Biomedical database, provided that there have been clinical studies on the relevant antivenom;


children receive the same or a larger dose than adults;


repeated doses may be necessary

Information from the manufacturer is often based on mouse assays, which can differ from clinical results;

Repeated doses may be necessary, even if there is initial normalisation of crucial parameters; this can be explained by continued absorption of venom from a depot in the region of venom application;


Recurrent envenoming was common when rapidly cleared Fab antivenoms were introduced: EchiFab, Micropharm, London, UK for envenoming by Nigerian saw-scaled viper, ProlongaTab, Micropharm for envenoming by Sri Lankan Russell's viper (D. russelli), and CroFab, BTG, London, UK for envenoming by American rattlesnakes. Possible mechanisims: (a) continued absorption of antivenom from the bite site after antivenom has been cleared or has complexed with venom and (b) redistribution of venom after dissociation of the venom-antivenom complexes (Warrell 2010).

Repetition of the initial dose with snakebites if, for example, severe cardiovascular or neurological symptoms persist for longer than 30 min and if blood is incoagulable for more than 6 h (Warrell 1990b)


monitoring of the patient during and after antivenom administration; constant monitoring during the first 10–15 min after the start of antivenom administration (see below, Table 5.6 Antivenom reactions);

in the case of envenoming with impaired haemostasis ensuring that there is no persistent bleeding from the site of venipuncture, possibly compression bandage

The likelihood of the occurrence of early antivenom reactions is greatest during the first 15 min; however, so-called "early" reactions may also first appear after a period of hours; thus it is necessary to monitor the patient for several hours following antivenom administration

Identification and treatment of antivenom reactions see below, Table 5.6 Antivenom reactions

see below, Table 5.6 Antivenom reactions

Efficacy of antivenom see Biomedical database, provided that there have been clinical studies on the relevant antivenom for general information see "Essentials of the management of envenoming and poisoning: 9b".




Table 5.6  Antivenom reactions: types, mechanisms, treatment


Type/Characteristics Mechanism Treatment
Early anaphylactoid/anaphylactic reactions

approx. 10–60 minutes
after starting antivenom treatment (Warrell 1990b)

the mechanisms have not yet been clearly elucidated;

complement activation by immune complexes (aggregates)?

rarely a type I hypersensitivity reaction to horse sera

adrenaline: 0.5–1.0 mg for adults (0.01 mg/kg BW for children), i.e. for adults 0.5–1.0 ml (for children 0.01 ml/kg BW) of adrenaline solution diluted 1:1,000 i.m.; repetition every 10 min, corresponding measurement of blood pressure and pulse until the patient's condition improves; in less severe cases the first dose can be given s.c. upon initial signs of an antivenom reaction;


antihistamines, e.g. chlorpheniramine: adults 10 mg, children 0.2 mg/kg BW, slowly i.v., beginning after adrenaline administration for 24–48 h;

if a patient continues to deteriorate despite this treatment, additional treatment with i.v. fluid replacement, aminophylline i.v., β₂-receptor stimulators, oxygen and assisted ventilation (Warrell 1990b, BNF 1995)

early anaphylactoid reactions, which make up the great majority of the early reactions, cannot be predicted with a sensitivity test (Malasit et al. 1986)


mild reactions: urticaria, nausea, vomiting, diarrhoea, headache, fever (Malasit et al. 1986)

severe (systemic) reactions: bronchospasm, arterial hypotension, angio-oedema (Malasit et al. 1986)

the more purified the antivenom used, the lower the incidence of such reactions (see "Essentials of the management of envenoming and poisoning": Table 2.1)

Pyrogenic reactions

approx. 1
2 hours after starting antivenom treatment (Warrell 1990b)

contamination of the antivenom by endotoxin-like substances

prevention of postural arterial hypotension;

reducing fever through cooling and antipyretics (paracetamol 15 mg/kg BW) (Warrell 1990b)


signs and symptoms: fever, chills, vasodilatation, arterial hypotension (febrile seizures can occur in children)

Late reactions (serum sickness)

approx. 7 days (5
24 days) after antivenom treatment (Warrell 1990b)

type III hypersensitivity mild reaction
chlorpheniramine: adults 4 × daily 2 mg, children 0.2 mg/kg BW/day in evenly distributed doses (alternative: terfenadine);

severe reactions
prednisolone: adults 4 × 5 mg for 5 days, children 0.7 mg/kg BW/day in evenly distributed doses for 5 days (Warrell 1990b)

signs and symptoms: pruritus, urticaria, fever, arthralgia, lymphadenopathy, peri-articular swelling, albuminuria, neurological impairment (mononeuritis multiplex, rarely encephalopathy);


the incidence and speed with which the reaction develops are greater the higher the dose of antivenom administered (Warrell 1990b)




Asita de Silva et al (2011) Low-Dose Adrenalin, Promethazine, and Hydrocortisone in the Prevention of Acute Adverse Reactions to Antivenom Snakebite: A Randomized, Double-Blind, Placebo-Controlled Trial (PLoS Med 8(5): e1000435. doi:10.1371/journal.pmed.1000435) In total, 1,007 patients were randomized, using a 2×2×2 factorial design, in a double-blind, placebo-controlled trial of adrenaline (0.25 ml of a 1:1,000 solution subcutaneously), promethazine (25 mg intravenously), and hydrocortisone (200 mg intravenously), each alone and in all possible combinations.

In total, 752 (75%) patients had acute reactions to antivenom: 9% mild, 48% moderate, and 43% severe; 89% of the reactions occurred within 1 h; and 40% of all patients were given rescue medication (adrenaline, promethazine, and hydrocortisone) during the first hour. Compared with placebo, adrenaline significantly reduced severe reactions to antivenom by 43% (95% CI 25–67) at 1 h and by 38% (95% CI 26–49) up to and including 48 h after antivenom administration; hydrocortisone and promethazine did not. Adding hydrocortisone negated the benefit of adrenaline.


Conclusions: Pretreatment with low-dose adrenaline was safe and reduced the risk of acute severe reactions to snake antivenom. This may be of particular importance in countries where adverse reactions to antivenom are common, although the need to improve the quality of available antivenom cannot be overemphasized.


Guidelines on Production, Control, and Regulation of Antivenom