Victims are often afraid of dying. This anxiety must be reduced, which is best done by showing a professional approach. The bitten body part should be immobilised, ideally with a splint as for a broken limb. Immobilisation reduces absorption of the venom, which delays systemic effects. A tight elastic bandage is wrapped around the bitten limb (slower lymph flow). This technique was developed in 1979 in Australia and has proven to be effective for cobras and the Australian elapids (neurotoxic snakes). If a bite by a cytotoxic snake is involved, this might be contraindicated, because necrosis could increase locally. For immobilisation the elastic bandage and the splint are of equal importance. They must be applied as soon as possible. A tourniquet is not useful and can aggravate the injuries through ischaemia. Some sources say that it is only indicated when the medical centre is far away (> 1h) and when a bite from a cobra, mamba or sea snake is involved. Yet it is best to forgo an arterial tourniquet. The sudden removal of a tourniquet in the case of cobra bites can sometimes cause an acute worsening of the symptoms (situation e.g. after arrival in the hospital). It is best to transport patients lying on their side (danger of vomiting and aspiration). The airway must be kept free. Dangerous procedures such as incision, sustained suction pumps on the skin, amputation of a finger, prolonged tourniquet, etc. should be avoided. The commercial "Extractor" device consists of a syringe and a vacuum cup. If used within three minutes after the bite, it can remove up to 30% of the venom (the device remains on the site for 30 minutes). However, the underpressure of almost 1 atmosphere also causes a massive oedema. Whether there is a clinical benefit is by no means established (it might be counterproductive). Quickly sucking out (< 3 minutes after the bite) the bite wound can remove up to 50% of the venom, but the usefulness of this has not been demonstrated. With eye injuries, immediate and copious rinsing with any non-irritating liquid is indicated. Administering electroshocks with high voltage and low amperage is very controversial and is not advised. If possible and if this can be done without danger, it is best to bring the dead snake along for identification (note carefully: the bite reflex continues long after death, even after decapitation!). Attempting to kill the snake is dangerous and could lead to further bites. Correct species identification is often difficult, but it is of course important to have an idea of the family to which the animal belongs.

A plasma expander, steroids and an antihistamine must be available. Antivenom is given as indicated (see below). In case of vomiting an anti-emetic can be administered. Adrenaline (adult 0.5 ml of 0.1 % SC or IM ; for a child 0.01 ml/kg) can be used against angioedema. Endotracheal intubation may be required. If shock and inadequate response to 1 to 2 litres of IV-Ringer or 0.9% saline solution (adult dose), IV albumin is administered. Albumin remains in the bloodstream longer. No salicylate derivatives (aspirin) should be used for painkilling, due to the risk of haemorrhage. Tetanus vaccination must not be overlooked. The circumference of the bitten limb should be regularly monitored with a tape measure (an increase of 3 mm in the diameter of an arm or leg represents an increase of 1 cm in the circumference (= p d).

*

The venom in the victim’s serum can be quantified via enzyme immuno-assays in specialised laboratories, but given the great variability of venoms and their significant binding to various tissues coupled with their slow release from the site of injection, these techniques are seldom used.

*

Take blood for full blood count and cross matching (check for thrombocytopenia, spherocytosis, schistocytes, anaemia). Coagulation parameters must be determined, if possible. In under-equipped labs it is often impossible to perform conventional coagulation tests. Yet it is essential to determine whether there are blood coagulation problems. For this 2 ml of blood are taken in a dry clean glass tube. Normally blood coagulates and forms a clot within 15 minutes. If the blood has still not clotted after 20 minutes, then there is a haemotoxin present. This simple test can be repeated. If there are coagulation problems, antivenom should be given, if needed followed by or simultaneously with cryoprecipitate or fresh frozen plasma. Tranexamic acid, a fibrinolysis inhibitor, is normally not used in treatment. The thrombocytopenia which often develops is sometimes not corrected by antivenom. The aim is to attain normal clot formation within the first 24 hours (if not, extra antivenom must be given). The use of IV mannitol to ease a compartment syndrome and to avoid a fasciotomy must be further evaluated.

In case of respiratory paralysis, the patient must be artificially ventilated. On average this lasts 1 to 4 days if no antiserum is given, but longer periods of paralysis do occur. After release in the synaptic cleft, acetylcholine is normally very quickly broken down into choline and acetic acid by acetylcholinesterase. Sometimes it is possible to perform an edrophonium test, as with myasthenia gravis. This fast-acting anticholinesterase quickly produces an improvement in case of post-synaptic acting neurotoxins. A single dose of 10 mg IV (adults) is administered over 3-4 minutes. For children the dose is 0.25 mg/kg of body weight. An improvement can be expected within minutes: ptosis disappears and the respiratory capacity or peak flow (FEV₁₎ improves. Neostigmine is an acetylcholinesterase inhibitor. Its use ensures that more neurotransmitter is present, so more stimulus transmission can take place. In this way, neostigmine reduces the effect of certain types of neurotoxins (cobra, mamba). One ampoule (1 mg) is slowly injected IV and afterwards a neostigmine maintenance dose is infused. Neostigmine is broken down by plasma esterases. The metabolites are excreted via the urine. The half-life amounts to 1 to 2 hours. The normal dose is 25-100 m g/kg/hour IV. Unpleasant side effects (diarrhoea, intestinal cramps, excessive salivation, sweating) are attributable to stimulation of the parasympathetic nervous system (muscarinic receptors). In order to prevent this, the anticholinergic atropine as antidote (0.6 mg IV every 4 hours) is also given. Atropine is a competitive inhibitor of the muscarinic receptors (constipation, dry mouth, mydriasis). If no neostigmine is on hand, alternatives are distigmine, pyridostigmine (60 mg qds) or ambenomium (5 to 25 mg qds PO).

*

If the snake venom blocks the presynaptic release of acetylcholine, neostigmine will have little effect. In such cases the potassium channel blocker diaminopyridine sometimes produces an improvement. However, this substance is currently still experimental. It is also being studied for muscle strength improvement in cases of multiple sclerosis and Lambert-Eaton myasthenic syndrome.

Hyperkalaemia occurs primarily in sea snake bites with severe rhabdomyolysis (see above, muscle toxicity). In case of cardiac arrhythmia, 10 ml 10% calcium gluconate IV can save a life. This does not reduce the kalaemia, but counters the effects of potassium on the heart. Treatment is coupled with 250-500 ml of a 10% glucose-infusion together with 10-20 units of fast-acting insulin. Sodium bicarbonate (50-150 mmol or 40 ml of an 8.4% solution over 30´) can also be given, certainly if there is also severe acidosis (check Kussmaul respiration), yet there is doubt about its effectiveness. The principle behind the administration of bicarbonate is that a rising pH in the blood causes a potassium shift to intracellular. Watch out for provoking acute hypocalcaemia with tetany. Salbutamol or albuterol (b ₂-agonists) can be administered via inhalation to lower the kalaemia, since they also cause a potassium shift to intracellular. For salbutamol the target dose of 1200 to 1500 µg via aerosol (6 to 8 puffs of 200 µg each) applies, for albuterol the dose is 10 to 20 mg in 4 ml of physiological solution in a nebuliser. Albuterol and insulin are probably equally effective and may be given together. Insulin, salbutamol and bicarbonate do not remove potassium from the body, but only lower its concentration in the plasma. Kayexalate (sodium polystyrene sulphonate) is a potassium-binding ion-exchange resin that can be administered orally (25 grams in 20% sorbitol) or rectally (50 grams in 20% sorbitol). In case of persistent hyperkalaemia, peritoneal or haemodialysis is necessary. If peritoneal dialysis is possible, rapid rinsing (3-4 litres/hour) is required.

It was Calmette who introduced antivenom therapy one hundred years ago. To whom should antivenom (antiserum) be administered? The presence of "fang marks" - wounds caused by the fangs - is not per se an indication since dry bites also leave "fang marks". Antivenom is administered to patients with local symptoms of envenomation (progressive swelling, intense pain in and around the bite wound, haemorrhages which are difficult to stop, painful lymphadenopathy, blister formation) and/or when there are signs of systemic effects of the venom (muscle paralysis, blurred vision, difficulty in speaking, diffuse haemorrhages, respiratory problems, pulmonary oedema, shock, prolonged coagulation times). For some snakes (e.g. North American coral snakes > 50 cm) antiserum is given in any case. Prior to administration it is best to premedicate with a low dose of adrenaline (prevention of anaphylaxis symptoms) as well as steroids to prevent serum sickness (see below). With atopic patients and patients who have previously received antivenom-therapy, adrenaline, an H₁-antihistamine and an H₂-antihistamine e.g. cimethidine should also be given in advance. Antivenom is still useful up to more than one week after the bite. It is never too late to administer antivenom if there are symptoms of envenomation.

*

If possible, specific antivenom should be used, otherwise polyvalent antiserum is the next best alternative. It is best to use the regional antivenom, if it is in stock. Thus the Burmese antivenom will be more effective against the Burmese Russell´s viper than the Indian antivenom (which is prepared from the Indian Russell´s viper). Nevertheless, sometimes there is cross-protection. The antivenom against the Australian tiger snake (Notechis scutatus), in a dose of 3,000-6,000 units, will also be active against sea snake bites, as well as against bites by Notechis ater (Tasmanian Tiger snake), Notechis ater serventyi (Chappell Island Tiger snake), Austrelaps superbus (Australian Copperhead) and Tropidechis carinatus (Rough-scaled or Clarence River snake). The Australian antivenom against the Brown snake (1,000 units) is active against the various species of this genus: Eastern Brown snake (Pseudonaja textilis), Dugite (Pseudonaja affinis) and Gwardar (Pseudonaja nuchalis). The same applies for Black snake antivenom (6,000-18,000 units) against the genus Pseudoechis: Mulga or King Brown snake (Pseudoechis australis), Red-bellied black snake (Pseudoechis porphyriacus) and the Papuan Black snake (Pseudoechis papuanis).

*

The serum is exclusively administered IV because, due to the volume-effect, local administration (e.g. at the level of a finger) can turn a partial ischaemia into a total one (compression of blood vessels by increased tissue pressure secondary to the injected liquid). Administration is done slowly via IV injection (5 to 10 minutes) or better via infusion with normal saline over 30 minutes. If IM, large haematomas can develop and the absorption is erratic, certainly in the gluteus region. The same dose is administered to children as to adults. Usually 20 to 80 ml are given, possibly to be repeated. It is important to pay attention that the antibodies are correctly and cautiously brought into solution (this can take 30´ per vial, thus ask for help from your staff). Do not be too economical with antivenom. Sometimes very large quantities are necessary, such as with bites by a king cobra, black mamba, bushmaster or gaboon viper. The half-life of the classic IgG horse antiserum is 35-70 hours, Fab half-life is 12-18 hours, F(ab´)₂ half-life is 80-100 hours. This is sometimes shorter than the half-life of the venom. A favourable response can be expected within 15 minutes to 6h (respiration, blood pressure, coagulation). Otherwise a second antivenom dose might be indicated. The treatment with antivenom is effective for problems of blood coagulation, shock and specific neurotoxicity. For other problems (nephrotoxicity, local necrosis and some paralyses) the effect is a great deal less spectacular. Some recommend a skin test with 0.1 ml diluted antivenom intradermally, to check for allergy, but this is controversial.

Antivenom which is prepared from horse serum, contains foreign proteins and frequently produces side effects. Anaphylaxis (IgE-mediated type I reaction), anaphylactoid reactions (not IgE-mediated, but via complement activation through protein aggregates in the antivenom) and serum sickness (immune complex or type III reaction) can develop. Soon after administration, ±20% of the patients develop itching, urticaria, fever, cough, tachycardia, nausea and/or vomiting. Sometimes there are quite serious bronchospasms. The mortality rate is 1/1000. Fever often develops after 1 to 2 hours. In children these pyrogenic reactions sometimes lead to febrile convulsions. Antihistamines do not reduce the incidence or seriousness of these symptoms, in contrast to a low dose of adrenaline (0.25 ml SC of a 1/1000 solution). Hypertension, antecedents of CVA, angor or cardiac arrhythmia are relative contraindications. The performance of a skin test with a small quantity of antiserum has little value. There are many false positive and false negative results. With serious snakebites the diluted antiserum should still be given. Attention should be paid to the intravascular volume of the patient (it is best to give 2 l of normal saline over a fairly brief period).

*

Serum sickness as a result of immune complexes develops in 30 to 90% of the patients. It manifests itself after 5 to 24 days (average 7 days). The frequency depends on the dose of antivenom administered. Fever, itching, joint pain and periarticular swelling, lymphadenopathy, mononeuritis multiplex and immune complex nephritis with albuminuria characterise this disorder. When antivenom is given, steroids should be first administered to prevent these complications or reduce their seriousness. If serum sickness develops, steroids are given for 5 days.

When an adequate quantity of antivenom has been given, the following response can be expected:

• The patient rapidly feels better.
• Gum bleeding stops within 15 to 30 minutes.
• The coagulation test (20´ test) normalises within 3-9 hours, but the clinical haemorrhages stop much earlier.
• The blood pressure normalises within an hour. Cardiac arrhythmias disappear.
• Neurotoxic effects begin to disappear within 30 minutes, complete recovery takes much longer. Bites by kraits and sea snakes (presynaptic venom) improve slowly.
• Active haemolysis and rhabdomyolysis stop within several hours. Urine afterwards returns to its normal colour.

*

Indications to repeat antivenom:

• Persistence or recurrence of non-coagulability after 6 hours or new bleeding after 1-2 hours.
• Worsening neurotoxic or cardiovascular signs after 1-2 hours.

Supportive therapy therapy is necessary (fluid balance, analgetics, transfusion). Blood pressure, pulse, respiration, muscle functions, central venous pressure, urine production, blood coagulation and circumference of the bitten body part (leg, arm) must be monitored. Wound infections including tetanus must be prevented and combated. With bites by sea snakes, infections with unusual pathogens can follow, such as Aeromonas hydrophila. With a compartment syndrome, e.g. in the anterior tibial compartment, there is a very pronounced swelling of the area. There is a disproportionate amount of pain, which worsens upon passive stretching of the affected muscles. Weakness of the muscles and nerve compression with hypoaesthesia of the distal skin develop. The most reliable test is a direct pressure measurement in the compartment (cannulla linked with pressure transducer or mercury manometer; Stryker pressure monitor). Fasciotomy should only be considered in extreme cases (tissue pressure >40mm Hg.). It often does more harm than good. Surgical decompression of a very swollen finger might be needed. With local necrosis, operative intervention is necessary (wound debridement, skin grafts, amputation). Deep abscesses can develop and must be drained. After the acute episode scars are likely. Skin grafts might be needed. A Volkmann´s ischaemic contracture of the forearm can occur and requires intensive physiotherapy to regain some function. Kidney failure can sometimes make (peritoneal) dialysis necessary. Before it gets to that point, a strict fluid policy should be introduced in order to avoid any overload (fluid administration = fluid loss of previous day + 500-750 ml). Body weight must be monitored. Food must be low-protein and must contain little salt and potassium (no fruit or fruit juice). Nephrotoxic medicinal products including radiological contrast material are obviously contraindicated. With heavy myoglobinuria or haemoglobinuria an infusion of mannitol (200 ml of 20% over 20´) may be given and alkalinisation of the urine is advised. An adequate hydratation of the patient must be maintained. Muscle rest is obligatory if rhabdomyolysis is suspected.

*

Shock can be the result of anaphylaxis, direct vasodilatation due to the venom, cardiotoxicity with or without arrhythmia, hypovolaemia (fluid shift to extravascular and/or internal/external bleeding), respiratory failure, acute Addison crisis or septicaemia. Plasma expanders under continuous control of the central venous pressure (watch carefully for pulmonary oedema), dopamine and steroids can be necessary.

Snake venom probably penetrates the placenta. For a pregnant woman, ephedrine (25-50 mg IV) is a better choice than adrenaline, because ephedrine has no impact on uterine blood flow. Abruptio placenta can develop with haemostasis disturbances.

*

7.12 LIST OF ANTIVENOMS (HTTP://WWW.TOXINFO.ORG/ANTIVENOMS/INDEX_PRODUCT.HTML)

For Europe, see MAVIN (Münich Antivenom Index) at : http://www.toxinfo.org/antivenoms/
For Central America and eastern USA: see Miami-Dade Fire Rescue Antivenom Service: http://www.venomousreptiles.org/pages/antbnk

Australia, CSL, Poplar Road 45, 3052 Victoria Parkville
Tel:+61-3-93891911, Fax:+61-3-93891434
Homepage: www.csl.com.au

1. BLACK SNAKE ANTIVENOM®
2. BOX JELLYFISH ANTIVENOM®
3. BROWN SNAKE ANTIVENOM®
4. DEATH ADDER ANTIVENOM®
5. FUNNEL WEB SPIDER ANTIVENOM®
6. POLYVALENT SNAKE ANTIVENOM®
7. RED BACK SPIDER ANTIVENOM®
8. SEA SNAKE ANTIVENOM®
9. STONEFISH ANTIVENOM®
10. TAIPAN ANTIVENOM®
11. TICK ANTIVENOM®
12. TIGER SNAKE ANTIVENOM®

Belgium, Antwerpse Dierentuin - ZOO, Koningin Astridplein 26, 2018 Antwerpen
Tel. +32(0)3/202.45.40 - Fax +32(0)3/231.00.18
Antigif centrum : Tel: 00-32-(0)70.24.52.45

Brasil, Instituto Butantan, Av. Vital Brazil 1500, 05503-900 Sao Paulo (SP)
Tel:+55-11-3726-7222, Fax:+55-11-3726-1505
Email: instituto@butantan.gov.br, Homepage: www.butantan.gov.br

1. ANTI AFRICAN BEE SERUM® A
2. ANTI ARACHNIDIC SERUM®
3. ANTI ELAPIDIC SERUM®
4. ANTI LACHETIC SERUM®
5. ANTI LONAMIA SERUM®
6. SORO ANTICROTALICO®
7. SORO ANTIESCORPIONICO®
8. SORO BOTROPICO®

Costa Rica, Instituto Clodomiro, San Jose
Tel:+506-229-0344, Fax:+506-292-0485
Email: fchaves@cariari.ucr.ac.cr, Homepage: www.icp.urc.ac.cr

1. POLYVALENT ANTIVENOM®
2. SUERO ANTICORAL PANAMERICANO, LIOFILIZADO®

Croatia, Inst. of Immunology, Rockefellerova 2,P.O.Box 266, 41000 Zagreb
Tel:+385-1-4684500, Fax:+385-1-4684303, Telex:21864VACCHR

1. BLACK WIDOW SPIDER ANTISERUM®
2. EUROPEAN VIPER VENOM ANTISERUM®

France, Aventis Pasteur, avenue Pont Pasteur 2, Cedex 07, 69367 Lyon
Tel:+33-0437284199, Fax:+33-0437284458. Lille: 00.33.825.81.28.22
Homepage: www.aventispasteur.com

1. ANTIREPT PASTEUR®
2. FAV-AFRIQUE®
3. FAVIREPT®
4. IPSER AFRIQUE PASTEUR®
5. PASTEUR L.A.B.S. ANTISCORPION VENOM SERUM®
6. SCORPIFAV®
7. SCORPION ANTIVENOM SERUM®
8. VIPERFAV® (F(ab’)2 contre Vipera berus, V. ammodytes, V. aspis)

France, Pasteur Merieux, avenue Pasteur 3, 92430 Marnes la Coquette
Tel:+33-147958050, Fax:+33-147950921
Homepage: www.biam2.org/www/Lab61055.html

1. IPSER EUROPE®
2. SERUM ANTIVENIMEUX BITIS ECHIS NAJA PASTEUR®

Germany, Twyford, Knollstr. 50, 67061 Ludwigshafen
Tel:+49-621-589-0, Fax:+49-621-589-2896

1. NAJA NAJA SPUTATRIX®
2. SCORPION ANTIVENOM TWYFORD (NORTH AFRICA)®

Giftnotruf der Toxikologischen Abteilung der II. Med. Klinik
Klinikum Rechts der Isar der Technischen Universität München,
Tel : 00-(49)-89.19.240

India, Central Research Institute, 173204 Kasauli (H.P.)
Tel:+91-1-792-72114, Fax:+91-1-792-72049
Email: director@crikasauli.com, Homepage: www.crikasauli.com

1. MONOVALENT COBRA ANTIVENOM SERUM®
2. MONOVALENT KRAIT ANTIVENOM SERUM®
3. MONOVALENT RED SCORPION ANTIVENOM SERUM®
4. MONOVALENT RUSSELL'S VIPER ANTIVENOM SERUM®
5. MONOVALENT SAW-SCALED VIPER ANTIVENOM®
6. POLYVALENT SNAKE ANTIVENOM SERUM®

India, Haffkine, Acharya Donde Marg, Parel, 400012 Mumbai
Tel:+91-22-412-9320, Fax:+91-22-416-8578
Email: webmaster@vaccinehaffkine.com, Homepage: www.vaccinehaffkine.com

1. LYOPHILISED ANTI-SNAKE-VENOM SERUM®
2. SNAKE ANTIVENIN I.P.®

Indonesia, Bio Farma, Jl. Pasteur 28, Bandung 40161
Tel:+62-22-203-3755, Fax:+62-22-204-1306

1. ANTIVENIN POLYVALENT®

Israel, Felsenstein Medical Research , 49100 Petach Tikva
Tel:+972-3-9376741, Fax:+972-3-9247019

1. ANTI ECHIS COLORATUS®
2. ANTI VIPERA PALESTINAE®

Italy , Sclavo , Via Fiorentina 1, 53100 Siena
Tel:+39-0577293111

1. SIERO ANTIFIDICO TETRAVALENTE PURIFICATO SCALV®

Mexico, Myn Laboratories, Mexico City

1. CENTUROIDES SCORPION ANTIVENOM®

Poland, Biomed, Wytwornia Surowic i Szczepionek ul. Chelmska 30/34, 00-725 Warszawa
Tel:0048-22-414071

1. ANTITOXINUM VIPERICUM®

South Africa, SAIMR, Modderfontein Road 1, 2131 Sandringham
Tel:+27-11-531-8600, Fax:+27-11-531-8616
Email: cillaf@savp.co.za, Homepage: www.savp.co.za/default.htm

1. SAIMR BOOMSLANG ANTIVENOM®
2. SAIMR ECHIS ANTIVENOM®
3. SAIMR POLYVALENT SNAKE ANTIVENOM®
4. SAIMR SCORPION ANTIVENOM®

Switzerland, Schweizerisches Serum- und Impfinstitut, Rehhagstr. 79, 3018 Bern
Tel:+41-31-346111, Fax:+41-31-346775

1. SERUM BERNA®

Switzerland , Institut Serotherapique et Vaccinal Suisse, Bern

1. SERUM ANTIVENIN SERPENS EUROPEENS®

Taiwan, Nat.Inst.Prev.Med., Kun Yang Street 161, Taipei
Tel:+886-2-2785-0513, Fax:+886-2-2786-8908
Email: deliver@cdc.gov.tw, Homepage: www.cdc.gov.tw/en

1. AGKISTRODON ACUTUS®
2. ANTIVENIN BUNGARUS MULTIC. AND NAJA NAJA ATRA®

Thailand, Thai Red Cross, Rama VI Road 1871, Pathumwan, 10330 Bangkok
Tel:+66-2-252-0161, Fax:+66-2-254-0212

1. BANDED KRAIT ANTIVENIN®
2. COBRA ANTIVENIN®
3. GREEN PIT VIPER ANTIVENIN®
4. KING COBRA ANTIVENIN®
5. MALAYAN PIT VIPER ANTIVENIN®
6. RUSSELL'S VIPER ANTIVENIN®

USA, MSD, 19486-0004 West Point, Pennsylvania,
Tel:+1-800-396-6250, Fax:+1-800-637-2568
Homepage: www.merck.com

1. ANTIVENIN LATRODECTUS MACTANS®

USA, Wyeth, Wasp & Biddle Street, Marietta, Pennsylvania 17547
Tel:+1-717-426-1941
Homepage: www.wyeth.com

1. ANTIVENIN (CROTALIDAE) POLYVALENT®
2. ANTIVENIN (MICRURUS FULVIUS)®

USA, Protherics, 5214 Maryland Way, Suite 405, TN 37027 Brentwood
Tel:+1-615-3271027, Fax:+1-615-3201212
Homepage: www.protherics.com

1. CROFAB CROTALIDAE POLYVALENT IMMUNE FAB(OVINE)®
2. VIPERATAB®

USA, Miami-Dade Fire Resue, Venom Response Unit
ENVENOMATION EMERGENCY : Phone Number: (305) 596-8576
Non Emergency Phone Number: (786) 331-4444