Treatment for Snake Bites

Sorry for the delay. I kinda forgot that we have PCL until a few hours ago...Well..Better late than never.


HOW IS ANTIVENOM ADMINISTERED?
Snake antivenoms must be given by the intravenous route. In dire circumstances, if a vein cannot be cannulated, antivenom may be given intraosseously, particularly in young children. The intramuscular route is useless in emergencies as absorption is slow, and there is a large volume of fluid to be administered. If required for small children, the dilution may be less to prevent excessive fluid administration.
In emergencies the antivenom may be infused quickly in high concentration. A test dose of antivenom to determine allergy should not be given since it is unreliable and a waste of precious time.

Freeze-dried (lyophilised) antivenoms are reconstituted, usually with 10 ml of sterile water for injection per ampoule. The freeze-dried protein may be difficult to dissolve. Two methods of administration are recommended:
i) Intravenous "push" injection: reconstituted freeze-dried antivenom or neat liquid antivenom is given by slow intravenous injection (not more than 2 ml/minute). This method has the advantage that the doctor/nurse/dispenser giving the antivenom must remain with the patient during the time when some early reactions may develop. It is also economical, saving the use of intravenous fluids, giving sets, cannulae etc.
ii) Intravenous infusion: reconstituted freeze-dried or neat liquid antivenom is diluted in approximately 5-10 ml of isotonic fluid per kg body weight (ie 250-500 ml of isotonic saline or 5% dextrose in the case of an adult patient) and is infused at a constant rate over a period of about one hour.

Patients must be closely observed for at least one hour after starting intravenous antivenom administration, so that early anaphylactic antivenom reactions can be detected and treated early with epinephrine (adrenaline).

Local administration of antivenom at the site of the bite is not recommended!
Although this route may seem rational, it should not be used as it is extremely painful, may increase intracompartmental pressure and has not been shown to be effective.

Intramuscular injection of antivenom
Antivenoms are large molecules (F(ab0)2 fragments or sometimes whole IgG) which, after intramuscular injection, are absorbed slowly via lymphatics. Bioavailability is poor, especially after intragluteal injection and blood levels of antivenom never reach those achieved rapidly by intravenous administration. Other disadvantages are the pain of injection of large volumes of antivenom and the risk of haematoma formation in patients with haemostatic abnormalities.
Antivenom must never be given by the intramuscular route if it could be given intravenously.
Situations in which intramuscular administration might be considered :
-at a peripheral first aid station, before a patient with obvious envenoming is put in an ambulance for a journey to hospital that may last several hours;
-on an expedition exploring a remote area very far from medical care;
-when intravenous access has proved impossible.
Although the risk of antivenom reactions is less with intramuscular than intravenous administration, epinephrine (adrenaline) must be readily available.
Under these unusual circumstances, the dose of antivenom should be divided between a number of sites in the upper anterolateral region of both thighs. A maximum of 5-10 ml should be given at each site by deep intramuscular injection followed by massage to aid absorption. Local bleeding and haematoma formation is a problem in patients with incoagulable blood.
Finding enough muscle mass to contain such large volumes of antivenom is particularly difficult in children.

Antivenom should never be injected into the gluteal region (upper outer quadrant of the buttock) as absorption is exceptionally slow and unreliable and there is always the danger of sciatic nerve damage when the injection is given by an inexperienced operator.


Amount/dose
Test patient's sensitivity to antivenom by giving 0.2 ml subcutaneously first, then observe for 30 minutes. If no adverse reactions occur, administer the required amount of antivenom diluted in 200 ml of saline or 5%D by slow IV drip over 1 hour.
If anaphylaxis occur, adrenaline 0.5 ml of 1:1000 should be drawn up. Reaction may develop despite negative sensitivity but can be controlled by adrenaline subcutaneously with or without antihistamines and steroids. Routine anti-histamine, SC adrenaline and hydrocortisone may be given prior to infusion to prevent reaction to antivenom.
For a patient with a known allergic history, two lines should be set up. One for the antivenom; the other line for adrenaline and hydrocortisone. Adrenaline and hydrocortisone should not be mixed in the same bottle but the same line can be used for infusion (e.g via Y-connector).
For a patient with positive skin reaction, consultation with the nearest hospital with medical specialist as regards next course of action should be made.
For children, it is recommended that half to two- thirds of adult dose should be given.
If there is no improvement after the first dose of antivenom, a repeat treatment may be given an hour later. Antivenom is probably of less value after 12 hours; however, it can be effective, particularly for clotting defects, even after 24 hours.

Snakes inject the same dose of venom into children and adults. Children must therefore be given exactly the same dose of antivenom as adults.
Manufacturers’ recommendations are usually based on inappropriate animal tests in which venom and antivenom are incubated before being injected into the test animal. The recommended dose is often the amount of antivenom required to neutralise the average venom yield when captive snakes are milked of their venom. In practice, the choice of an initial dose of antivenom is usually empirical.
Antivenom manufacturers, health institutions and medical research organisations should encourage and promote the proper clinical testing of antivenoms as with other therapeutic agents. This is the only reliable guide to the initial dose (and safety) of an antivenom.
Since the neutralising power of antivenoms varies from batch to batch, the results of a particular clinical trial may soon become obsolete if the manufacturers change the strength of the antivenom.


SHOULD ADRENALINE BE ADMINISTERED FIRST?
Antivenom serum is the most effective, if not the only effective, treatment available for management of snake bite envenomation. Adverse effects of the serum are common, and anaphylaxis can be fatal. Increasing the safety of treatment with antivenom serum for snake bite victims is, therefore, a matter of high priority.

Adrenaline is the drug of choice in the treatment of anaphylaxis, and it is likely to be useful in the prevention of such acute reactions to serum. There is a general reluctance to use adrenaline because of potential side effects and lack of clear guidelines on use. The only available data on use of adrenaline before treatment with antivenom serum are from a few uncontrolled retrospective studies from Australia. These data suggest that adrenaline is safe and effective in reducing acute adverse reactions.

What WHO says:

At the earliest sign of a reaction:
i) Antivenom administration must be temporarily suspended
ii) Epinephrine (adrenaline) (0.1% solution, 1 in 1,000, 1 mg/ml) is the effective treatment for early anaphylactic and pyrogenic antivenom reactions

Epinephrine (adrenaline) is given intramuscularly (into the deltoid muscle or the upper lateral thigh) in an initial dose of 0.5 mg for adults, 0.01 mg/kg body weight for children. Severe, life-threatening anaphylaxis can evolve very rapidly and so epinephrine (adrenaline) should be given at the very first sign of a reaction, even when only a few spots of urticaria have appeared or at the start of itching, tachycardia or restlessness. The dose can be repeated every 5-10 minutes if the patient’s condition is deteriorating.

The routine mode of administration of adrenaline should be the subcutaneous route because it does not cause significant hypertension. However, in a moribund or critically ill patient when it is essential to administer antivenom as soon as possible, adrenaline may be given intramuscularly or even intravenously in smaller doses. In general, intramuscular and intravenous routes are not recommended since they may induce hypertension which in the presence of venom-induced coagulopathy could cause an intracerebral haemorrhage.

Next paragraph is from http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=27835
Based on a research published in British Medical Journal:

The prophylactic use of 1:1000 adrenaline in a dose of 0.25ml given subcutaneously immediately before infusion of antivenom serum significantly reduces the risk of acute adverse reactions.

There is no clear scientific evidence or uniform policy for the use of premedication to prevent acute adverse reactions to antivenom serum.

A major concern regarding the use of adrenaline as premedication is the potential risk of intracerebral haemorrhage; a result of the combination of the ability of certain snake venoms to cause coagulopathy and the risk of hypertension with use of adrenaline. This has led to a reluctance to use adrenaline.

Few studies have analysed the risk of cerebral haemorrhage after use of adrenaline. Of seven cases of fatal intracerebral haemorrhage after snake bite documented in Australia, only three patients had received adrenaline as premedication, making the evidence incriminating adrenaline as the cause of cerebral haemorrhage weak. Fears of development of hypertension after low dose adrenaline also seem unfounded.

From http://www.flyingdoctor.net/monographs/snakebite.pdf
by: Dr Struan Keith Sutherland & Dr James Tibballs
It is not prudent to forgo premedication and elect to treat anaphylaxis if it occurs. Iatrogenic anaphylaxis has a high mortality despite vigorous and expert resuscitation. If there is no adverse reaction to the first ampoule of antivenom, subsequent doses do not need to be preceded by adrenaline.


SERUM SICKNESS
What is serum sickness?
Serum sickness is a reaction similar to an allergy. Specifically, it is an immune system reaction to certain medications, injected proteins used to treat immune conditions, or antiserum, the liquid part of blood that contains antibodies that help protect against infectious or poisonous substances.

Serum sickness is a reaction by the immune system against large amounts of foreign protein that have entered the bloodstream. A common source of such foreign protein is horse serum, an ingredient present in many venom antidotes (antivenoms) that are used to treat poisonous snake and spider bites and scorpion stings.

Symptoms of serum sickness include fever, rash, joint pains and sometimes swollen lymph nodes. Rarely, kidney damage and death can occur.

Doctors treat serum sickness with antihistamines, such as diphenhydramine Some Trade Names BENADRYL, and corticosteroids. Antivenoms that do not contain horse serum are unlikely to result in serum sickness.

Corticosteroid creams or ointments or other soothing skin medications may relieve discomfort from itching and rash.
Antihistamines may shorten the length of illness and help ease rash and itching.
Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen or naproxen, may relieve joint pain. Corticosteroids taken by mouth (such as prednisone) may be prescribed for severe cases.

Prevention of serum reaction: before injecting the antivenom
-Enquire whether patient has been given serum injections before (eg the old ATS but not ATT).
-Patient has personal or family history of allergy
-Test sensitivity of patient to serum by intradermal injection of 0.1 ml of serum diluted 1:10. Observe for 30 minutes for local and general reactions. If these occur, consider giving IV diphenhydramine, IV corticosteroids and/or IM adrenaline 1:1,000 or IV adrenaline 1:10,000.
-Inject antivenom in allergic or sensitive patients under cover of antihistamines and hydrocortisone given 15-30 minutes before administration of the antivenom.
-Give anticholinesterases for patient with severe neurotoxic symptoms, administer test dose of IV edrophonium chloride (Tensilon) 10 mg with IV atropine 0.6 mg. If response is convincing, administer IV neostigmine. Consultation with a neurologist is advised.


References:
http://74.125.153.132/search?q=cache:u0Zd8aFc5Q8J:www.moh.gov.my/MohPortal/DownloadServlet%3Fid%3D2100%26type%3D2+management+snakebite&cd=4&hl=en&ct=clnk&gl=my

http://www.flyingdoctor.net/monographs/snakebite.pdf

http://www.searo.who.int/EN/Section10/Section17/Section53/Section1024_3900.htm

http://www.merck.com/mmhe/sec24/ch298/ch298d.html

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=27835 (research paper by british medical journal. quite interesting.)

All about serum sickness:
http://www.nlm.nih.gov/medlineplus/ency/article/000820.htm#visualContent

http://emedicine.medscape.com/article/887954-overview