Saturday, April 24, 2010

Article 1


A Recent Advance in the First-Aid
The Management for Jelly-Fish Sting

(A Semi-technical Article for Light-Hearted Discussion)

By:


Lim Ju Boo

Regional Staff Officer for Training

I was reading an interesting article the other day on ‘vanilla as antidote for jellyfish sting’ which appeared on October 18, 1998 issue of the New Sunday Times. It was written by Theresa Manavalan (1), a journalist friend of mine, and I thought I should write a separate article on this myself giving my personal view for the interest of my SJAM readers. But before that, may I ask if any one of you have ever been stung by a jellyfish? I have. It was an experience to remember as a schoolboy of about 12 or 13 years old. I was having a picnic swimming in the sea, some 10 km from my hometown in Batu Pahat. The experience was one I can never forget as it was a very painful one. Suddenly out of the blues I felt like as if a mild electric shock had surged through the upper part of my body. I swam as fast as I could out of the shallow water with an intense excruciating pain all over my chest. Once out of water I could see a cluster of those jelly fish floating at the spot where I was swimming earlier. Then I saw my bare chest with those strings of punctuated red marks, made by the stinging cells (nematocytes) of the tentacles. The presentations were not different from those of herpes zoster (shingles) around the ribs or waist region, minus the vesicles.

Intense Pain:

The pain was terrifying and very smarting. I remember people in the crowd who milled around me, came out with all kinds of suggestions to help me. Some suggested I rub sand on my body, some said I should apply crushed paddy, others thought cooked porridge would be better, while another insisted that I smear my body with my own saliva or dust it with cigarette ash ?? I didn’t know anything about first-aid then, so I just sat there agonizing in pain. It wasn’t until when I went home my mother applied rice wine on my body. My mother did not know anything about first-aid either, but she being uneducated and illiterate (she could spell the word ‘cocoa’, and that was all the English word she spell) probably did what she thought was best – applying some rice wine on my body, a traditional remedy. Recalling what she did now, I don’t think she could have done better. She was actually applying alcohol on the affected parts, a remedy which is practiced by modern first-aiders. I could not remember what happened after that, except the tenderness and red marks remained for a day or two after the experience. Until today I am absolutely terrified being in the water with jelly fish.

According to the 6th edition first-aid manual of the British St John Ambulance, St. Andrew’s Ambulance Association and the British Red Cross (let us call them ‘British Ambulance Associations’ or BAA for convenience), they advised pouring alcohol or vinegar to incapacitate the stinging cells, and further on, they suggested the use of meat tenderizer (contains papain) to inactivate the venom (2). Like in all simple first-aid books, it does not tell much, or explain the mode of action alcohol has on the cells or the venom. This type of simplistic instruction is very frustrating to me. No further explanation, no rationale given. The only clue I suspect why they advocated that by analyzing their recommendations, is that brandy or any alcohol, such as the consumable alcohol (ethanol) in whisky, brandy and wine, or the poisonous industrial and surgical alcohol (methanol) or isopropyl alcohol, could denature the venom. The reason being, all venom is basically a serum (protein), and alcohol if strong enough, could denature protein by dehydrating and coagulating it, thus rendering it biologically inactive.

Meat tenderizer:

I believe it is exactly the same rational why the British St. John Ambulance further recommended the application of meat tenderizer which actually contains papain. Papain is actually a proteolytic enzyme (protease) which breaks down proteins, thus inactivating the venom. The problem for any first-aider is that, meat tenderiser is a bit difficult to get, and it is not every home kitchen that stocks them. Imagine looking for meat tenderiser along the seashore as a remedy for jelly fish sting? I think it is going to be a bit of a hassle. Instead, may I suggest something more readily available and practical to a first-aider in a tropical country like Malaysia? The milk from the leaves of papaya contains a very high content of papain. In fact the crush leaves of papaya or raw papaya rubbed over tough meat half an hour before cooking is traditionally used as a meat tenderiser in many home kitchens. Here we have a tropical local plant, very readily available as a substitute for papain solution. We already have this knowledge (phytochemistry) and some idea of its pharmacology, and I am very confident that should a clinical trial be done comparing meat tenderizer (suggested by BAA) and the milk from papaya leaves (suggested by me), there would be very little statistical difference between the two. Somehow I have an intuition how things will work out. For a first-aider, all we need is to be a little innovative, lots of common sense, and apply whatever scientific knowledge we have. There is no use frantically looking for papain solution in the wilderness of the sea just because it is prescribed in the book. Papain solution as suggested in the British St John Ambulance First-Aid Manual is almost non-existent along a sea beach except in some big supermarkets, and I don’t think we are likely to find any supermarket or pharmacy offering papain for sale to first-aiders along the seashores anywhere in the world, unless we bring a bottle from home deliberately to look for trouble. Might as well bring the victim straight to the hospital?

Natural protein digesters:

If we go along the same line of scientific reasoning that a proteolytic enzyme like papain can deactivate the protein of a serum, then even the juice from a raw pineapple could do the same job, as it contains bromelain, an equally powerful protein-breaking enzyme. In fact both papain and bromelain act not only as proteolytic agents, but they exhibit very powerful anti-microbial and anti-inflammatory properties. In the Philippines, South America and African countries, the crushed leaves of papaya are applied on wounds and intractable sores to accelerate the healing process because of their triple-action as anti-microbial (it breaks open the bacterial cell-walls), anti-inflammatory action, and debridement properties (removal of foreign matter and injured or infected tissue from a wound).

Toxico-dynamics:

Nevertheless, whether brandy, vinegar, papaya or pineapple juices, these measure are only meant for topical applications (local applications over the skin) provided the venom still remains at the site, and has not entered the systemic circulation as yet. Once the venom enters the blood stream, its toxicological effect on the body is entirely different. It is not just the local pain and swelling. The venom from a jelly-fish in fact contains three different types of toxins. The first one is a myotoxin (‘myo’ means muscles) which is responsible for much of the pain, swelling, skin rashes, and perhaps urticaria (nettle rash, and hives), a localised allergic reaction. More serious are the cardiotoxins. These toxins affect the heart muscles by reducing their contractility (anti-inotropic action) similar to some cardiac depressant drugs, causing pump failure and cardiogenic shock within 5 minutes of a bite. Fortunately this is rare in adults whose body weight is greater. The third categories are the neurotoxins that affect the nervous system. They act by attaching themselves to the receptor sites of the neurones and nerve endings, paralysing neurotransmission (anticholinergic action) to vital organs like the lungs (cholinergic crisis) and respiratory failure within 30 minutes of the venom entering the blood-stream. It can also act by paralysing the muscles, causing the swimmer to drown if he remains in the water long enough for the neurotoxin to act.

Shock possible:

If the sting is extensive, with the victims suffering several bites, most casualties would succumb to either cardiogenic shock, or anaphylactic shock or anaphylaxis (serum sickness). An anaphylactic shock is a very severe generalized Type I hypersensitive allergic reaction with widespread release of histamine, causing oedema (swelling with water and tissue fluid due to vascular permeability) of the mucous membrane of the mouth, throat, and glottis, constriction of the bronchioles, heart failure and circulatory collapse. Oedema of the throat and glottis is potentially fatal as the swelling block off the airways. These presenting features called angiooedema are very severe form of urticaria or allergic reaction that necessitates immediate medical management, and the earlier the victim is transported to a hospital where oxgyen, intramuscular 1:1000 adrenaline, hydrocortisone, aminophylline etc may be administered, the better it is for an uneventful recovery.

But what can a first-aider do in a pre-hospital environment, in the event an ambulance or transport to a hospital is delayed. The venom has spread into the systemic circulation. Obviously you can’t give the victim *brandy or vinegar to drink, or even papaya or pineapple juice. Spirit and vinegar described in the British St John Ambulance first-aid manual would only good for local (tropical) applications. In fact drinking alcohol or brandy makes the condition worse, as alcohol is a vasodilator, and in shock there is vasodilation causing the blood pressure to fall even further.

What to do:

Let us assume the victim is going into an anaphylactic shock (whatever the cause)? What can we do? The role of a first-aider is to treat conservatively. The first-aider’s first consideration is to ease breathing by supporting him (includes her) in a semi-sitting position called the Fowler’s or semi-Fowler’s position or in a position most comfortable to him (2). Of course loosen clothing around the neck, chest and waist (near the diaphragm) to ease breathing further. Once in the hospital, the victim is normally placed in the reverse position - Trendelenburg position (3,4), because by then they would have secured the airways with oropharyngeal or endotracheal intubation, if not short of a surgical airway (cricothyroidotomy and tracheostomy) if they fail to secure intubation due to pharyngeal oedema. The victim would have been ventilated with the maximum (6-10 litres/min.) amount oxygen. * The Fowler position eases breathing without mechanical aid in the pre-hospital stage, while the *Trendelenburg position (see foot-note) counteracts the shock once the airway is secured. Arrange for urgent transport to the nearest hospital as a priority, but be prepared for cardio-respiratory resuscitation (CPR) if necessary in the event of total cardio-pulmonary collapse from anaphylactic shock (see separate article on anaphylaxis and anaphylactic shock).

I have partly finished the brandy (alcohol) part of the story (except for the foot-notes).

Vinegar:

Now I shall comment on the vinegar part of the recommendation by the BAA in their 6th edition of their first-aid manual. Well, does vinegar work? Can we blindly adopt their recommendations and apply them here in the tropics or elsewhere in the world? According to a world-wide medical literature search I made a week ago, the BAA recommendation may be out-dated. In a paper published in 1993, Fenner and his colleagues disagreed that vinegar should be used to inhibit neomatocyst (the poison sting-cells of jellyfish) discharge in Chironex fleckeri the deadly north Australian box jellyfish. The application of vinegar has become the accepted first-aid, not only for box-jellyfish stings, but also for stings of other jellyfish as claimed by Frener and his colleagues.

The researchers in their paper published in the Medical Journal of Australia in 1993, have shown that in a newly differentiated species of Physalia in Australian waters which causes severe envenomation (the act of injecting a venom or poisonous material), the act of applying vinegar made matter worse as it was found to cause discharge in up to 30 % even more neomatocycsts into the body (5). The authors concluded that in treating these stings, the use of vinegar is not recommended as it increases, instead of decreasing envenomation.

Malaysian approach:

Stings from other species, such as from the single-tentacled Physalia utriculus (the “bluebottle”) are not severe, tentacles with unfired nematocysts rarely adhere to the victims’s skin, and vinegar dousing is not required. The paper concluded that vinegar treatment is therefore an unnecessary step in the first-aid management of any Physalia sting, but remain an essential first-aid treatment for the cubozoan jellyfish tested to date. So there we are. Should we in Malaysia adopt the joint British Ambulance Associations recommendation, without conducting some research on our own? Can we blindly accept another country’s guidelines just because we think their recommendations are more authoritative? (**See foot-notes on snake-bites.)

To answer that, we have to consider local (Malaysian) species of jellyfish in the warm waters of the tropics? Are they the same as those around the British Isles or Australia? Probably not I guess. The only local species reported in the newspaper, was one which caused two teenage deaths among three persons who were stung near Pantai Cenang in Pulau Langkawi on May 2, 1996. That fatal sting was believed to be from the Chiropsalmus spp. C.buitendjiki is, one of the most toxic cubomedusae (box jelly fish) known in Malaysian waters. According to a report, the only survivor was a 24 year old sibling who escaped with long nasty lacerations. Age, body weight and the health status of an individual could make a difference whether or not a victim could survive after a vicious sting. Most of the venom display high specificity of neuronal activities on the nervous system. Not all marine and jellyfish venoms are harmful. Some may even be used as future drugs. For instance, the venom omega-conotoxin from Conus geographus currently being researched may one day substitute calcium ion channels blockers like verapamil (a drug used for treating hypertension). Calcium ion channels blockers, like adrenoceptor and neurone blocking agents, including angiotensin converting enzyme (ACE) inhibitors. These are groups of drugs used in the management of hypertension.

Brief pharmacodynamics:

We will not go into their pharmacology or mode of action, except very briefly, it suffice to say that they all help in vasodilation by relaxing the muscles of the blood vessels, thus causing the blood pressure to fall. A list of such toxins acts as occluders, activators and stabilizers. They act on different ion-channels which are located in the ganglion and neurons. This toxin may be potential drugs of the future. The development of marine pharmacognosy is currently an area of interest to some pharmaceutical giants. Some of them have already undergone clinical trials prior to commercialization. Anyway, I am not a marine biologist, so I cannot comment on this subject any further.

Traditional remedy:

But according to the new Sunday times report on the 18th October, 1998, a team of researchers consisting of pharmacologists, biochemists, phytochemists and doctors from the Faculty of Medicine at the University of Malaya, led by Associate Professor Iekhsan, have been actively studying a common compound, vanillin as an antidote for jellyfish sting (1). Vanillin is the essence that gives vanilla-flavoured ice-cream and vanilla cake the distinctive flavour. Professor Iekhsan, a member of the international consortium of jellyfish stings has been actively hunting for an antidote for jellyfish sting since 1988 after learning of a folk remedy from northern peninsula fisherman. The fishermen apply a mash of crushed leaves from the local beach sand creeper called keledak laut (Ipomea pes caprae), a member of the sweet potato family onto the wounds of jellyfish stings.

Analgesic effect:

The fishermen claimed that the creeper relieves the pain instantly. The team investigated this claim, and sure enough, they found the plant not only has analgesic properties, but it also exhibit anti-inflammatory, and anti-bacterial properties as well. The team then zoomed in to identify and isolate the anti-venin in the keledak laut, and surprising it was nothing more than vanillin, chemically known as 4-hydroxy-3-methoxybenzaldehyde. Now the team found that the harmless, non-toxic vanillin, is not only a systemic antidote against jellyfish, but it can be used as its prophylaxis (prevention). This implies that a dose of vanillin taken orally would not only cure, but would have already protected us even before we are stung? That sounds interesting, because we would next ask whether or not taking vanilla ice-cream or a vanilla-flavoured sweets, chocolates, biscuits, cakes, drinks and other confectioneries, say half-an-hour before, or taking it after dipping into a jellyfish infested sea is going to confer us any immunity? Well, I do not know the answer to this question as this requires a clinical trial, and I am sure the University of Malaya team is looking into this.

My opinion:

First of all, I understand the research team is using natural vanillin probably from the sea plant, or from the pods of Vanilla planifolia, or even V. tahitensis, which actually contain, not just one form of vanillin, but a mixture of over 250 naturally occurring similar substances. So which, among the 250 compounds in a vanilla pod has the greatest efficacy as an anti-venin? The vanillin in your ice-cream are either one of the two pure synthetic compounds – lignin vanillin, which is actually a waste by-product of the paper-making industry, or ethyl vanillin which is three times stronger than lignin vanillin, and is derived from Guaiacol, a derivative of coal tar. (It is very distasteful and frightening to have all these substances added to our foods these days). The real natural vanillin from the plants is 200 times more expensive than the vanillin added to our cakes. The molecular orientation of natural and synthetic vanillin is quite different, and may have different actions. The fishermen make use of the natural plants of course, not the synthetic essence of vanilla from the shops. The mode of action may be different, because only the appropriate molecular structure of an anti-venin may fit into the receptor sites of the body cells to block off the venom from binding with it. Currently the only anti-venin for jellyfish sting is one produced by the Commonwealth Serum Laboratory in Melbourne, Australia. It uses immuno-globulins (IgE, IgG) to bind with the venom.

The ice-cream seller remedy:

Nevertheless, synthetic vanillin may work if the body can metabolically cleave off, for instance, the ethyl structure of vanillin to reduce the structure to the original vanillin, thus making it available to the body. These are some of the pharmacological possibilities. Anyway, I understand the team is now analyzing the structure of artificial and natural vanillin and other compounds in the vanilla pod, and studying their pharmao-kinetics (ways in which drugs are absorbed, distributed and metabolized in the body), with view of an eventual clinical application. If vanillin works even through topical application, as the local fishermen found by merely rubbing the mashed leaves onto the body, and if it should work as well for synthetic vanillin, well I must say rushing off to the nearest ice-cream seller, among the numerous ice-cream vendors that ply along the sea-beaches and sea-resorts on any hot day to get a vanilla ice-cream is probably not a problem.

Besides, it provides the best first-aid remedy for a jellyfish stung swimmer? I suspect even without the vanilla, the freezing temperature of the ice-cream itself may freeze more nematocysts from firing, besides the numbing and anaesthetic effect and anti-inflammatory properties ice, or ice-cream have on the affected area (remember the ‘i’ part of your R-I-C-E for soft tissue and sports injuries? This applies here as well). On the other hand, the application of cold itself may shut down the peripheral sub-cutaneous circulation (micro-circulation under the skin) to divert the blood into the deeper muscles, thus preventing the sub-cutaneous absorption of vanillin.

What other options?

Logically, I would suspect a few drops of the aromatic oil from a bottle of essence of vanilla applied on the affected part, and taken sublingually (under the tongue for rapid absorption through the mucosa into the circulation) would probably be better? I do not know the answer with certainty? A clinical research like this would be both interesting and worthwhile as a contribution medical research could play for the advancement of medicine and first-aid, and keeping our ideas and practice of first-aid up-to-date. Likewise hopefully, the university team can answer some of these questions as their answers could modify our modalities of current management. Well, knowledge, including medicine is after all rapidly advancing, and first-aid, which is actually the lay practice emergency medicine at level one, is no different.


Foot-notes:

* Strangely, I have not heard the terms, “Trendelenburg position” and “Fowler’s position” being used or mentioned, either in the Malaysian Red Crescent Society first-aid or in the first responder classes. Instead, lengthy descriptions like ‘elevating the legs below head level’ (Trendelenburg position) for the treatment of syncope and shock were taught and described. Similarly the term Fowler’s position, means placing the patient in a semi-sitting position – upper body 45-60 degrees angle above the horizontal level of stretcher were never taught by the Malysian Red Crescent Society. Actually these terms are normally applied to positions on a stretcher or hospital bed, but it does not matter. It can also be applied in the field. I am not too sure if these two terms were being taught in the first-aid classes conducted by SJAM? I have actually not attended any first-aid classes conducted by SJAM, but I did sit for their advanced first-aid examination directly without undergoing any of their training first, and of course I passed without any difficulty. I am introuducing these two terms as they come in very useful. Technical terms save repeating lengthy descriptions again and again.

** The same applies for snake-bites. At the Institute for Medical Research (where I was working in the various Divisions of Human Nutrition, Community Medicine, and Clinical Research for 25 years until I retired in 1994) tremendous amount of work had been done over the decades on the development of anti-venom sera against local snake-bites (for instance, the Malaysian pit-viper). As far as I understand, there are about 139 species of snakes found in the land and seas of Malaysia. Of these, only 39 are classified as very dangerous to man. These include cobra, kraits, vipers, sea snakes, and blue and banded coral snakes. In Malaysia, the neurotoxic effects comes from cobra, kraits and coral snakes, the myopathic effects (paralyses the muscles, e.g. of the heart and respiration) comes from the local sea snakes, and the haematological (blood) effect comes from the vipers. Other than these, the rest of the Malaysian snakes are less dangerous or non-poisonous. Anti-venom sera made for bites from ‘foreign’ snakes like adder (in the UK), saw-scale snakes (found in Middle East, Africa and elsewhere), or the American rattlesnakes may not necessary be effective for local snake bites. Even polyvalent antiserum against the venoms (chiefly constitutes haemotoxins / haemolysin (destroys the RBC), neurotoxins and vasculotoxins from the Viperidae spp.) of various other snakes would be more suitable for use in other countries where other species of snakes exist, unless of course the chemical structures of all their venoms are exactly the same as those from local snakes. Although the only solution against snake-bites (other than the normal first-aid – I need not elaborate) is to administer an antivenin, preferably a more specific monovalent antivenin, its greatest danger is the risk of anaphylactic shock for those previously sensitized, and who are prone to serum sickness. Anyway premedication with antihistamines and steroids are the precautions. Be prepared to resuscitate if necessary.

Foot-note:

Dr. Lim is Editor of The Malaysian Society for Traumatology and Emergency Medicine. He is also a Member of the Accident and Emergency Medicine Section, and a Member of two others Academic Sections of the Royal Society of Medicine (RSM) in London. He was admitted a Fellow on 1st March, 1994. He is also the Regional Staff Officer for Training of the St John Ambulance of Malaysia

What is RSM? Some of my friends thought that RSM stands for Royal School of Music, because of my association with music as a violinist. RSM does not stand for music, but for the Royal Society of Medicine in London which was founded in AD 1773, and it is probably the oldest and the largest of its kind in Europe with several chapters in the United States, and elsewhere in the world.

It was evolved under two Royal Charters, and currently it has 40 Specialists Sections, viz. from Accident and Emergency Medicine, Comparative Medicine, Cardiothoracic Surgery, History of Medicine, Laryngology and Rhinology, down to Urology, etc., etc. In addition, 13 more Fora Sections were added in recent years to cover advances in medicine in other sub-speciality in Angiology, Nutrition, Telemedicine, Medical Care of Catastrophies, to Sexual Medicine, etc. In its Registry, it recognizes over a hundred Medical Associations, as well as Specialist Medical and Surgical Societies throughout the world, especially those from the United States which is affiliated to the RSM. Its Rolls of Fellows are predominantly medical specialists from all areas of medicine.

In recent years, albeit to a lesser degree, specialists from other allied professions as well, such as veterinary surgeons, nutritionists and medical scientists who have contributed much to the advancement of medicine through research and publications, have also been admitted into the RSM Fellowship Rolls. Most of the Fellows are from the United States, Canada, Europe, Australia, and New Zealand. So RSM has nothing to do with music, although it also has an elaborate Club where some of its members are brilliant Chamber Orchestra Players.



References:

1. Manavalan, T. Vanilla As Antidote for Jellyfish Sting? New Sunday Times, October 18, 1998, page 7.

2. St John Ambulance, St. Andrew’s Ambulance Association, British Red Cross. First Aid Manul (6th edition, 1993), page 100, Dorling Kindersley, London

3. Brady Emergency Care, Grant, H.D, et al. (7th edition, 1995). Pages 45-46. Prentice-Hall International (UK) Ltd. London.

4. Feng, P.H., Fock, K.M., Eng, Philip. Handbook of Acute Medicine (5th edition, 1992), Pages 76-78. APAC Publishers, Singapore.

5. Fenner, P.J; Williamson, J.A; Burnett, J.W; Rifkin, J. First Aid Treatment of Jellyfish Stings in Australia. Response to a Newly Differentiated Species. Med. J Aust. 1993 Apr 5; 158 (7) : 498-501.

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