Jellyfish
Drugs

Author: Sonia Guarguagli
Date: 20/02/2013

Description

INTRODUCTION

Jellyfish stings are hazardous for anyone who enters a marine environment anywhere in the world. Jellyfish are most common in the tropics, but are found in waters ranging from tropical to arctic. Stings are more common in the summer months due to the increased recreational exposure to the marine environment as well as the seasonal patterns of jellyfish.

Touching or being touched by a jellyfish can be very uncomfortable, sometimes requiring medical assistance: sting effects range from no effect to extreme pain to death. Stings of the jellyfish could have several very severe consequences, due to its cardio toxic (effect on the heart), neurotoxic (damage to the nerves) and dermatonecrotic (effect on the skin) components. Jellyfish tentacles in contact with human skin can produce pain swelling and redness. The pain is due to discharge of jellyfish nematocysts and associated toxins and discharge can be caused by a variety of mechanical and chemical stimuli. In the event of extensive contact with its tentacles cardiac arrest is likely to result within minutes. The statistics vary with numbers of recorded fatalities quoted as being over 5500 deaths. In the Phillipine Islands there are reports of 20 to 40 deaths per year as a result of Jellyfish stings.

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A series of tests were carried out with chemicals traditionally used to treat jellyfish stings e.g. acetic acid, ammonia, meat tenderizer, baking soda and urea to determine if these chemicals stimulated or inhibited nematocyst discharge and if they brought relief to testers who were exposed to jellyfish tentacles. Hot water and topical lidocaine appear more universally beneficial in improving pain symptoms and are preferentially recommended. In particular lidocaine, in addition to acting as an anesthetic on skin, in contact with jellyfish tentacles inhibited nematocyst discharge possibly by blocking sodium and/or calcium channels of the nematocytes. Unfortunately, it may be difficult to obtain at the site of envenomation, such as the beach or diving sites. In these instances, removing the nematocysts and washing the area with saltwater may be considered.

JELLYFISH ANATOMY

Jellyfish, or coelenterates, are marine invertebrates belonging to the Scyphozoan class, and in turn the phylum Cnidaria. They are related to corals, hydra and sea anemones.
They are typified as free-swimming marine animals consisting of a gelatinous umbrella-shaped bell and trailing tentacles. The bell can pulsate for locomotion, while stinging tentacles can be used to capture prey.

Most jellyfish do not have specialized digestive, osmoregulatory, central nervous, respiratory or circulatory systems. The manubrium is a stalk-like structure hanging down from the centre of the underside, with the mouth at its tip. This opens into the gastrovascular cavity, where digestion takes place and nutrients are absorbed. It is joined to the radial canals which extend to the margin of the bell. Jellyfish do not need a respiratory system since their skin is thin enough that the body is oxygenated by diffusion. They have limited control over movement, but can use their hydrostatic skeleton to navigate through contraction-pulsations of the bell-like body.
The body of an adult jellyfish is composed of a bell-shaped, jellylike substance enclosing its internal structure, from which the creature's tentacles suspend. Each tentacle of the jellyfish is covered with stinging cells (cnidocytes) that can sting or kill other animals: most jellyfish use them to secure prey or as a defense mechanism.
They have tentacles or oral arms coated with thousands of the stinging cells called cnidocytes containing a microscopic, toxin-filled harpoon, a nematocysts. Generally, each nematocyst has a "trigger" (cnidocil) paired with a capsule containing a coiled stinging filament, as well as barbs on the exterior. Upon contact, the filament will swiftly unwind, launch into the target, and inject toxins. It can then pull the victim into its mouth, if appropriate. In addition to discharging toxin, the nematocysts activate the surrounding cnidocytes to increase the total volume of venom injected. Importantly, the nematocysts are still able to function when separated from the jellyfish, making deactivation and removal of these stingers a key element of treatment.

WHERE TO FIND JELLYFISH

Jellyfish are found in every ocean, from the surface to the deep sea. A few jellyfish inhabit also freshwater. Large and often colorful, they are common in coastal zones worldwide.
Although most serious envenomations occur in the waters of the Indo-Pacific region, North American and European waters also provide a habitat for jellyfish, with stings reported. Even nonfatal jellyfish stings can be extremely painful. Occasionally, anaphylaxis and death occur.
The map above shows the areas of main concentration of the jellyfish and in turn strength of venom are found around Australia, the Philippines, off the Indonesian Coast, Hawaii, Vietnam, the Caribbean and other tropical areas including off the coast of Africa and the Indian Ocean Islands.

Recent increases in the jellyfish population have made jellyfish stings a more frequent occurrence and a more common concern for swimmers. Some marine scientists attribute the recent proliferation of jellyfish to mankind's impact on marine life; jellyfish may merely be taking the place of already overfished creatures. Since jellyfish feed on the same kinds of prey as many species of fishes, depletion of fish populations allows jellyfish to move in. Sampling sea life in certain heavily fished regions has shown that jellyfish have actually overtaken fish in terms of the biomass they contribute to these ocean regions. Additionally, increased nutrients in the water, ascribed to agricultural runoff and urban by-products, may also be a factor in the recent proliferation of jellyfish numbers.

VENOM

Whereas poison is transmitted passively through ingestion or absorption, venom is actively injected. As a general rule, poison is used primarily for defensive purposes (by prey), and venom is used for offensive purposes (by predators). In addition, most venomous animals can produce their own deadly concoction, whereas poisonous creatures usually acquire their toxicity through their diet.
A poisonous animal can only transfer its toxins if another animal comes into physical contact with it or eats it (a sort of posthumous revenge).
Venomous animals, on the other hand, have a device to actively deliver their lethal cocktail.

Jellyfish are efficient predators which prey on crabs, fish larvae, and small fish. Their venoms consist of various toxins including neurotoxins that paralyse prey organisms immediately. One possible mode of action of neurotoxins is the blockage of voltage-gate.
Jellyfish venoms are composed of potent proteinaceous porins (cellular membrane pore-forming toxins), neurotoxic peptides, bioactive lipids and other small molecules whilst the tubules contain ancient collagens, chitins and other compounds that together are highly antigenic. Other effects of jellyfish venoms appear to be linked to their proteolytic activities and possibly their synergistic actions.

Hyunkyoung Lee; Eun-sun Jung; Changkeun Kang; Won Duk Yoon; Jong-Shu Kim; Euikyung Kim. Scyphozoan jellyfish venom metalloproteinases and their role in the cytotoxicity, 2011

Some venomous animals are well known (black widows, rattlesnakes..). One of the world's most venomous animals is one you may never even see. The venom of this pale blue, almost transparent, invertebrate is among the most deadly in the world, capable of killing a human in under five minutes (box jellyfish venom has a median lethal dose of 40 mcg/kg, which makes it the most potent marine toxin).
Each tentacle contains about 5,000 stinging nematocysts, housed in cnidoblasts. Nematocysts are like little stinging darts that fire whenever the tentacle comes in contact with chemicals on the surface of its prey.
With up to 15 tentacles growing from each corner of the jelly's bell, and each one reaching a possible 3 meters, that's a lot of miniharpoons ready to deliver venom into a victim's body. A single encounter can leave thousands of stings, and the powerful venom doesn't waste any time getting to work. Many victims stung at sea go into shock or die of heart failure before they can even reach the shore.

STING EFFECTS

Although a jellyfish can kill a small aquatic animal, its sting is not usually fatal to humans. It tends to cause pain, skin rashes, fever and muscle cramps. Effects range from severe burning pain with localised skin erythema, through mild systemic upset, to severe systemic reactions involving vomiting, chest pain, convulsions, and respiratory failure.
The degree of pain and reaction to a jellyfish sting can depend on the species: larger jellyfish have larger cnidoblasts that can penetrate deeper into the skin and some jellyfish have stronger venom than others. Extremely toxic species such as the box jellyfish (Chironex fleckeri) and Irukandji (Carukia barnesi) are found in tropical Australian and Indo- Pacific waters.

The most severe envenomations can occasionally induce systemic responses such as nausea, headache, and chills and even more rarely can induce severe systemic reactions such as cardiac arrhythmia, respiratory dysfunction, psychosis, and muscular spasm. Yet the major feature of most stings is the rash and associated pain, which is caused by a combination of several elements of the venom. Most envenomations result in pain that can be severe, but is usually self-limited.

The duration of the symptoms of minor stings ranges from a few minutes to several hours, weeks, or longer depending upon the jellyfish species, the extent of the sting, the presenting symptoms, and the physiology of the individual. Most of the effects, both mild and severe, are caused by the actions of the venom, not an allergic reaction. The local reaction to most jellyfish envenomations includes local reactions such as pain, pruritus, paresthesias such as numbness, burning, or throbbing, inflammatory rash, blistering, and swelling.

Healthy 13 years old boy, who was attacked by a jellyfish at a Caribbean beach. The patient had burning and pain in the left half of the face and left shoulder and linear lesions with erythema and swelling.

REMEDIES

A therapeutically effective amount refers to that amount which has the effect of

  • reducing the amount of pain associated with the sting,
  • inhibiting (that is, slowing to some extent, preferably stopping) any further firing by the nematocysts, and/or,
  • relieving to some extent (or, preferably, eliminating) one or more additional symptoms associated with the sting, such as, but not limited to redness, swelling, formation of whelps, blisters, and/or hives, and itching.

Proposed treatments for jellyfish envenomation include dilute acetic acid (vinegar), warm urine and ammonia, hot water, sodium bicarbonate (baking soda), and meat tenderizer (papain or bromelain). More recently, dilute solutions of local anesthetics (eg, benzocaine, lidocaine) have been recommended as treatment to relieve the pain of jellyfish stings. The rationale for these remedies has been based on the prevention of further envenomation and the inhibition of pain or further tissue destruction.

Current treatments for jellyfish envenomation demonstrate however variable response, with conflicting results between studies and species. A treatment beneficial for one species may in fact worsen an envenomation from another. This contributes to considerable confusion about what treatment is best for stings whether the species is known or unknown.

The American Heart Association–American Red Cross International Consensus on First Aid Science With Treatment Recommendations currently advocates vinegar or baking soda slurry followed by the application of heat (or an ice pack if heat is not available) for all jellyfish stings in North America and
Hawaii. As with other box jellyfish, vinegar will deactivate unfired nematocysts on the skin but has no effect on the venom already in the body. Acetic acid solutions like vinegar have been shown to render the stinging cells harmless, preventing them from firing more toxins into your body. Some works however suggests that vinegar may not be an ideal agent because it causes pain exacerbation or nematocyst discharge in some species.

The table 1 below collects ad summarizes the results of some of the published trial on the treatment of jellyfish envenomation.

Nicholas T Ward et al. Evidence based treatment of jellyfish stings in North America and Hawaii, 2012

Current recommended treatments of stings involve 2 distinct yet ideally simultaneous strategies. One is to reverse the pain and tissue damage from the venom itself.
The second is to prevent further discharge of venom-laden nematocysts to allow their eventual removal intact.
Some therapies might be successful at the former but fail or worsen effects with regard to the latter. Different effects across different classes or species of jellyfish may occur.
The perfect agent would be readily available, cheap, capable of inactivating venom and applicable across multiple species of jellyfish and would block further release.

Reasonable assumption is that removal of any remaining tentacles would prevent further discharge and would be an important element in the treatment of envenomation. The method of such removal, however, remains ill defined. Attempted removal may itself cause discharge, with further envenomation and potential worsening of symptoms.

Considering the conflicting results between different studies, it’s not clear yet what treatment is the best for jellyfish stings. I summarize below some of the most recent studies and their conclusions.

Studies by Hartwick et al suggest that vinegar provides relief from jellyfish stings by preventing further nematocyst discharge or through inactivation of the toxin. These experiments were conducted on the Australian box jellyfish Chironex fleckeri. Two additional studies support prevention of nematocyte discharge with vinegar. However, vinegar may cause nematocyst discharge in other North American jellyfish, including Atlantic Ocean Physalia spp, Pelagia noctiluca, Lytocarpus philippinus, and Cyanea capillata.

Burnett et al recommended a baking soda slurry to decrease further nematocyst release. Alcohol, acids, and urea, however, were found to cause nematocyst discharge in several common species of jellyfish.

Pereira et al evaluated the use of pressure immobilization bandages in the prevention of nematocyst discharge. Pressure immobilization bandages have been demonstrated to increase the release of venoms. Theoretically, bandages block systemic absorption of toxin and thus may be beneficial even if more venom is extruded.

Evidence supports using aluminum sulfate because it may significantly reduce pain in Physalia physalis stings, but no or incomplete resolution of pain was found for Carybdea alata. It is unclear whether aluminum sulfate mixtures inhibit further envenomation, have direct effects on the venom, or inhibit pain sensation. Observed positive effects may be species dependent.

In their characterization of the venom of Chironex fleckeri, Baxter and Marr showed that heat, formalin, and Ethylenediaminetetraacetic acid reduced all activities of the venom. This study provides a theoretical basis for hot water immersion therapy. Experimental evidence for North American and Hawaiian species supports this concept.

LOCAL ANESTHETICS AND LIDOCAINE

Several studies show as lidocaine could be considered a good treatment. In fact it has been shown to provide relief from jellyfish stings by acting both as an anesthetic and by preventing further discharge of nematocysts from tentacles which remain on the skin.

A series of tests were carried out in 2010 with chemicals traditionally used to treat jellyfish stings (e.g. acetic acid, ammonia, meat tenderizer, baking soda and urea) to determine if these chemicals stimulated or inhibited nematocyst discharge and if they brought relief to testers who were exposed to jellyfish tentacles. It was found that many of the chemicals traditionally used to treat jellyfish stings stimulated nematocyst discharge and did not relieve the pain. However there was immediate relief when a common anesthetic lidocaine was sprayed on the skin of testers in contact with jellyfish tentacles.

Laura Birsa et al. Evaluation of the effects of various chemicals on discharge of and pain caused by jellyfish nematocysts, 2010

Lidocaine hydrochloride solutions reduced the pain associated with the jellyfish stings and reduced the amount of swelling and redness associated with jellyfish exposure. Lidocaine concentrations of 10 and 15% produced immediate relief from the stinging sensation. The 4 and 5% solutions produced relief after approximately 1 min while 1, 2 and 3% solutions required 10 to 20 min before there was any noticeable relief [see tables below].

What is lidocaine and how does it work?

Lidocaine, xylocaine or lignocaine are common local anesthetic and antiarrhythmic drugs.
Local anesthetics gain access to their blocking site on the sodium channel by diffusing into or through the cell membrane. These anesthetics block sodium channels and thereby the excitability of all neurons, including sensory neurons: it alters signal conduction in neurons by blocking the fast voltage gated sodium (Na+) channels in the neuronal cell membrane that are responsible for signal propagation. With sufficient blockage the membrane of the postsynaptic neuron will not depolarize and will thus fail to transmit an action potential. This creates the anaesthetic effect by not merely preventing pain signals from propagating to the brain but by stopping them before they begin. Careful titration allows for a high degree of selectivity in the blockage of sensory neurons, whereas higher concentrations will also affect other modalities of neuron signaling.

Lidocaine acts as an aesthetic by blocking sodium ion channels in nerves that sense pain, thus preventing these nerves from transmitting pain signals to the brain [Binshtok et al., 2007].
Initial exposure of tentacle suspensions to lidocaine prevented the nematocyst discharge by subsequent exposure to acetic acid, ethanol, ammonia or bromelain [see figure below].
Thus lidocaine in addition to acting as an anesthetic on skin in contact with jellyfish tentacles inhibited nematocyst discharge possibly by blocking sodium and/or calcium channels of the nematocytes.
The action of lidocaine to inhibit discharge of nematocysts is likely due to blockage of the chemoreceptors and mechanoreceptors that are responsible for the discharge of nematocysts from the nematocytes. This blockage by lidocaine may be due to the action of lidocaine on sodium ion channels in nematocyst membranes. There is evidence that nematocyst discharge is initiated by an increase in the osmotic pressure of nematocyte fluid which is brought about by removal of bound calcium ions. Thus, lidocaine may also have some effect on calcium ion channels in nematocyst membranes.

Hydrophilic anesthetics, e.g. lidocaine hydrochloride, act on the hydrophilic region of the nerve membrane which is different from the hydrophobic regions of the membrane acted on by hydrophobic anesthetics, e.g. benzocaine. The nematocyst thread, which can be up to 1 mm long, can penetrate the skin epidermis to the dermal capillaries while lidocaine can penetrate and act down to 5 mm below the skin surface. Benzocaine while providing some relief from the pain of jellyfish stings was slower acting than lidocaine and also did not prevent the appearance of areas of redness on the skin.

CONCLUSION

Even though jellyfish are among the major sources of marine envenomation today and even though jellyfish stings are a common health hazard for beach vacationers, an effective treatment is still unknown.

Current treatments for jellyfish envenomation demonstrate variable responses, with conflicting results between studies and species. This contributes to considerable confusion about what treatment is best.
Chemicals traditionally used to treat skin in contact with jellyfish, i.e. ethanol, meat tenderizer, ammonia, acetic acid, were found to stimulate nematocyst discharge and provided little or no relief from the pain and stinging sensation resulting from jellyfish contact.

The American Heart Association–American Red Cross International Consensus on First Aid Science with Treatment Recommendations currently advocates vinegar or baking soda slurry followed by the application of heat (or an ice pack if heat is not available) for jellyfish stings. Several studies, however, suggest vinegar may not be an ideal agent because it causes pain exacerbation or nematocyst discharge in most species, except Physalia.

Lidocaine, an amino amide, appears to provide relief from jellyfish stings by acting both as an anesthetic and by preventing further discharge of nematocysts from tentacles which remain on the skin.
Unfortunately, they may be difficult to obtain at the site of envenomation, such as the beach or diving sites. In these instances, removing the nematocysts and washing the area with saltwater may be considered.
Additional studies need to be performed to delineate the best treatment.

Link
Evidence-based treatment of jellyfish stings in North America and Hawaii, 2012
First aid treatment of jellyfish stings in Australia, 1993
Management of Marine Stings and Scrapes, 1989
Hot Water, Lidocaine Best for Easing Some Jellyfish Stings, 2012
Vinegar: Medicinal Uses, 2006
More about jellyfish anatomy
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