Chironex fleckeri 21.Sep.2021-Expires: 7 days - Do not archive IDENTIFICATION FAMILY NAME Chirodropidae   GENUS NAME Chironex    SPECIES NAME Chironex fleckeri   COMMON NAME(S) Australian box jellyfish Box jellies Box jelly Box jellyfish Chironex box jellyfish Indringa Sea stinger Sea wasp   HABITAT Distribution These tropical jellyfish are mainly found in coastal waters in tropical areas of northern Australia. These animals frequent the shore area adjacent to mangrove creeks in which they breed, and from which they swim to feed in summer (October to May). The closer the geographical location to the equator, the greater the number of months Chironex fleckeri is found.  In Darwin, Chironex fleckeri stings have occurred for every month of the year, except for one month. When fishing for prey they favor calm water close to shore, free of snags over clear sandy bottoms, where they extend and trail their curtain of tentacles behind them.[1]   INTERVENTION CRITERIA Intervention Level Child and Adult Medical observation, preferably in an advanced care facility with Box Jellyfish Antivenom available is recommended for: - Any individual stung or suspected to have been stung by a box jellyfish   Observation Period Observation at Home All patients require medical attention.   Medical Observation Asymptomatic patients should be observed for 2 hours. If they remain asymptomatic in this time frame, the patient may be discharged into the care of a reliable observer and given instructions to return should any symptoms develop.   Stings may result in severe envenoming; symptomatic patients must not therefore be discharged until their symptoms have subsided.   Investigations Sticky tape or scalpel sampling can be performed to identify the jellyfish in question, sticky tape is applied to skin or the skin is scraped with a scalpel and then transferred to a microscope slide for examination; this allows nematocysts to be identified on the basis of morphology.[2][3]However this currently is a research tool only. A negative result does not rule out a jellyfish sting.   Admission Criteria Any patient with symptoms must be admitted to a medical facility with Box Jellyfish Antivenom and advanced life support.   TREATMENT TREATMENT SUMMARY Most stings are minor but all must be treated as potentially lethal.   In all cases retrieve and restrain the victim on the beach, prevent rubbing of attached tentacles and vigorous muscular activity. Commence and sustain cardiopulmonary resuscitation (CPR) if indicated, this always takes absolute priority.   Flush the affected area liberally with vinegar for at least 30 seconds, and only then carefully remove any adherent tentacles.[4] If the effects are minor, pain may be managed with local application of ice,[5][6] simple analgesia, and oral antihistamines; there should be early medical inspection in case of local skin damage. If pain does not respond, parenteral opioid analgesia may be required, or administration of Box Jellyfish  Antivenom which appears effective for pain relief if administered early. Antivenom is also indicated in severe envenomings to reduce life-threatening complications, and possibly reduce scarring.[7]   Cardiac dysrhythmia and arrest are particular concerns, and possibly may develop within minutes of the stinging contact. Pulmonary edema and respiratory depression/failure may subsequently evolve. Multiple vials of antivenom should be administered for these indications, but its efficacy in the management of cardiorespiratory dysfunction remains uncertain,[7] and advanced supportive care, including mechanical ventilation, is likely required to maintain such patients.   Dermonecrosis is a frequent complication of serious stings, and box jellyfish antivenom has been reported to improve both acute and long-term cutaneous damage.[8] Acute skin markings often resolve spontaneously. Thus acute dermonecrosis should be treated as a burn with specific attention to avoiding secondary bacterial infection. Delayed hypersensitivity reactions are a common late complication of stings occurring some 7 to 14 days after the event.[9] Serum sickness is a potential concern in those receiving antivenom, particularly multiple doses.   Emergency Stabilization Ensure adequate cardiorespiratory function Cardiac arrest Hypotension Flush with vinegar Emergency monitoring Decontamination Skin Irrigate Eye Irrigate immediately Antivenom(s) Box jellyfish antivenom Enhanced Elimination Not recommended Supportive Care Monitoring Neurologic Pain Anxiety Cardiovascular Cardiac dysrhythmia Respiratory Pulmonary edema Respiratory failure Hematologic Hemolysis Dermatologic Dermal necrosis Immunologic Hypersensitivity reaction Serum sickness EMERGENCY STABILIZATION Ensure Adequate Cardiopulmonary Function Airway Ensure the airway is protected if compromised (intubation may be necessary).   Immediately establish secure intravenous access.   Cardiac Arrest Cardiac dysrhythmia or arrest may occur within minutes of a sting – particularly in children. Commence and sustain cardiopulmonary resuscitation (CPR) if indicated, this takes priority over application of vinegar to neutralize tentacle stinging apparatus.   Prolonged cardiac resuscitation following standard protocols may be appropriate in selected cases as recovery with a good neurological outcome is reported in some severely poisoned patients receiving CPR for hours.[10] Artificial circulatory support interventions including veno-arterial or veno-venous extracorporeal membrane oxygenation (VA- or VV-ECMO), where available, can be considered for selected cases of severe refractory shock or severe respiratory failure due to acute respiratory distress syndrome.[10][11] There is growing experience treating poisoned patients at many ECMO-capable centers.[12][13]   Cardiopulmonary resuscitation should therefore be prolonged, and ideally not abandoned until at least 6 vials of intravenous box jellyfish antivenom have been administered.[14]   Hypotension CHILD Hypotension in children is determined by age and systolic blood pressure   Age Hypotension if Systolic Blood Pressure (mm Hg) is: 0 to 28 days < 60 1 to 12 months < 70 1 to 10 years < 70 + (age in years x 2) > 10 years < 90   Administer an isotonic crystalloid fluid 10 mL/kg IV over 5 to 10 minutes   If the systolic blood pressure does not return to the normal range, give a further 10 mL/kg body weight of the isotonic crystalloid over 5 to 10 minutes.   The intraosseous route can be used if IV access is difficult or delayed.   ADULT Administer a bolus of isotonic crystalloid fluid if systolic blood pressure is less than 100 mmHg.   Isotonic crystalloid fluid dose: 20 mL/kg IV over 5 to 10 minutes   If the systolic blood pressure does not return to the normal range, give a further 10 mL/kg body weight normal saline over 5 to 10 minutes.   The intraosseous route can be used if IV access is difficult or delayed.   Flush with Vinegar Retrieve and restrain the victim on the beach and prevent tentacle rubbing and vigorous muscular activity. Immediately douse the sting area liberally with vinegar for a minimum of 30 seconds;[15] do not attempt to remove adherent tentacles before this step, unless no vinegar is available, in which case carefully pick off the tentacles.   Pressure Bandage with Immobilization First Aid Pressure bandage with immobilization first aid was proposed to be beneficial because of its effectiveness in treating elapid snake and funnel web spider bites,[16][17] however, there is no evidence to support the use of pressure bandage with immobilization in the management of jellyfish stings.[18][19] Evidence suggests it may actually increase the amount of venom that is injected into the victim.[20] The Australian resuscitation council has announced a change in advice to a more neutral position.[21]   Emergency Monitoring If there are signs of systemic envenoming: Heart rate/rhythm Pulmonary function Level of consciousness DECONTAMINATION Skin Flush the affected area with vinegar (3 to 10 % acetic acid in water) as soon as possible,[22][23] and continue to irrigate for 30 seconds. After flushing, carefully remove any adherent tentacles.[4]   Vinegar may irritate the sting sites, but should still be applied.[24] It is not designed to relieve pain associated with jellyfish stings, but to prevent further discharge of nematocysts. Nematocyst inhibition and analgesia are two distinct and separate areas of management.   The fresh sting area should never be rubbed with sand, towels or anything else. Methylated spirits is not recommended.[4]   Eye Remove contact lenses. Irrigate immediately with water or saline for at least 30 minutes. If the eye is contaminated with solid particles, the eyelid should be completely everted and any solid material removed as quickly as possible while continuing to irrigate the eye. A topical anesthetic is recommended to enable the patient to open their eyelids sufficiently for effective irrigation.   The eye should be examined immediately following flushing with a slit-lamp microscope and fluorescein stain. Any evidence of injury requires specialist ophthalmological assessment.   ANTIVENOM Box Jellyfish Antivenom There have been conflicting studies over the efficacy of box jellyfish antivenom, its efficacy remains to be proven, particularly in relation to preventing fatalities. This is because of the dramatic nature of the sting, with death or survival usually determined within minutes.[14] Studies in animals have shown that the antivenom is largely ineffective in preventing cardiovascular collapse even when administered before envenoming;[25] this lack of effect may be due to the antivenom being unable to bind venom in sufficient time to prevent the venoms rapid effects.[25][26]   Whether the antivenom has the potential to reverse life-threatening cardiotoxicity in humans remains uncertain; the antivenom would need to be given early and in large doses (up to 6 vials) in such a scenario.[27][14] Should more than 6 vials be required contact an experienced medical toxicologist for advice. The antivenom may be beneficial if given early in the relief of severe skin pain.[8][28]   Indications Box Jellyfish Antivenom should be administered to any patient if:   - Cardiorespiratory dysfunction/arrest is apparent - Severe pain is unresponsive to other managements   Other suggested, but not uniformly accepted, indications include:   - The total sting area is greater than the area equivalent to one half of one limb (especially in children) - Cosmetic damage such as to the face is likely (the possible benefit must be carefully considered given the risks of antivenom administration)   However, these indications should be discussed with a medical toxicologist.   Dose and Administration Only administer if clearly indicated. Note the dose for a child is the same as that for an adult.   Pre-medication is not recommended although controversy exists.[29][30][31]   Prior to use of jellyfish antivenom, ensure adequate resuscitation equipment is available for the management of anaphylaxis, and that an appropriate dose of epinephrine (adrenaline) is drawn up as outlined in management of anaphylaxis. Note that anaphylaxis has not yet occurred with this antivenom and the need for early administration in severe cases may outweigh the need to be fully prepared to treat anaphylaxis.   Initial Box Jellyfish Antivenom dose   CHILD and ADULT[32]   Life threatening cardiac or respiratory failure: 1 to 3 vials IV (if cardiac arrest, consider 6 vials undiluted as rapid IV push)   Systemic envenoming (collapse, hypotension, significant cardiac dysrhythmia): 1 vial IV   Refractory pain: 1 vial IV   Preferably dilute antivenom up to 1 in 10 in an isotonic solution (e.g. normal [0.9%] saline); dilution should be less for children due to fluid load. Administer intravenously via a drip-set, commence very slowly and increase rate if there is no adverse reaction. Total dose should be given over 15 to 30 minutes.   Patients must be closely monitored for anaphylaxis during and for 30 minutes after the infusion.   Further Box Jellyfish Antivenom doses   Should cardiovascular compromise not be reversed with the initial dose, it is recommend that advice from a medical toxicologist (at the bedside or through a Poison Center) is obtained regarding whether further antivenom therapy is required.   Contra-indications There is no absolute contra-indication to this potentially life-saving intervention.   Those at increased risk of severe reaction include patients with history of: Previous reaction to antiserum Asthma Atopy   Adverse Effects Anaphylaxis The antivenom being a foreign protein could cause sensitization and, therefore, should not be given for insignificant lesions or wheals.[17]   Closely monitor the patient for indications of anaphylaxis including: Rash Erythema Pruritus Urticaria Rhinitis Conjunctivitis Vomiting Diarrhea Wheeze Dyspnea Hypotension Angioedema Shock Airways obstruction   Anaphylaxis may be managed following these (hyperlinked) recommendations.   Serum Sickness Serum sickness may occur some 4 to 14 days following antivenom administration. Patients should be made aware of the signs and symptoms of serum sickness including: Rash Fever Joint aches Pains Malaise   If high doses of antivenom have been administered prophylaxis with an oral steroid such as prednisolone may be considered, and follow-up arranged. Commence prophylaxis on day 2 to 3 post envenoming.   Prednisolone dose   CHILD 1 mg/kg (up to 50 mg) per day orally for 5 days   ADULT 50 mg per day orally for 5 days   ENHANCED ELIMINATION Enhanced Elimination Not Recommended Techniques to enhance elimination of venom following envenoming by this creature are not required.   SUPPORTIVE CARE Monitoring If there are signs of systemic envenoming:   Heart rate/rhythm Blood pressure 12 lead ECG Oxygen saturations Pulmonary function Level of consciousness   Neurologic Pain Pain following most jellyfish exposures can be managed with local application of ice, simple analgesia, and oral antihistamines.[5][6] Should this not be satisfactory there may be requirement for intravenous administration of an opioid such as morphine (0.1 mg/kg IV up to 5 mg every 10 minutes). If pain is not controlled following standard treatment administer IV magnesium sulfate and/or Box Jellyfish Antivenom;[32] antivenom may produce relief, however, this is not guaranteed in all cases, and is more likely to be successful when administered soon after the sting.   Monitor for pain   Manage pain following standard treatment protocols.   Anxiety Patients should be reassured that the majority of envenomings are not lethal and that there is an antivenom available. Effective pain management will likely contribute to reducing anxiety. Monitor patients for signs of anxiety or agitation.   For acute episodes of anxiety not responsive to non-pharmacological measures, treatment of first choice is a benzodiazepine such as diazepam:   Diazepam dose CHILD 0.1 mg orally ADULT 5 to 10 mg orally   Intravenous benzodiazepines are seldom required, but may be considered in severe cases. Monitoring of respiratory function is necessary.   Routine use of antipsychotic medication to control negative psychological reactions is not indicated. However, should such reactions be unresponsive to two or more doses of benzodiazepines, a sedating antipsychotic such as droperidol may be considered.   Cardiovascular Cardiac Dysrhythmia Severe dysrhythmia and cardiac arrest may occur and should be managed with standard protocols and with Box Jellyfish Antivenom. For life threatening cardiac decompensation or failure, intravenous magnesium sulfate should be administered alongside antivenom (0.2 mmol/kg up to 10 mmmol adult dose).[32]   Verapamil was initially advocated to treat envenoming by Chironex fleckeri,[33][34] and there is experimental evidence to suggest that verapamil significantly delayed death in experimental envenoming in mice.[33][35][36] However, in a pig model of envenoming verapamil did not prevent any effect of venom, exacerbated cardiovascular collapse, and increased mortality; it was concluded that verapamil does not prevent any of the effects of envenoming and is contra-indicated for treatment of envenoming.[37] At best it can be considered appropriate as experimental treatment for the patient with extreme envenoming. More evidence is required to determine its role.[38]   Monitor: Heart rate/rhythm Blood pressure 12 lead ECG   Manage cardiac dysrhythmia following standard treatment protocols.   Respiratory Pulmonary Edema Pulmonary edema, and possible respiratory depression may evolve during the period of envenoming. Box jellyfish antivenom may be used in management, but its efficacy is unknown. Pulmonary edema usually manifests with desaturation, tachypnea, and pulmonary crepitations. Occasionally frothy, pink sputum may be apparent.   Monitoring for this condition should include: Chest auscultation Oxygen saturation Blood gas analysis Chest x ray   Manage pulmonary edema following standard treatment protocols.   Dermatologic Necrosis Dermonecrosis is a frequent acute complication of serious stings. There are reports that Box Jellyfish Antivenom may lead to improvement in both acute and long-term cutaneous damage,[8] although the acute skin changes may resolve spontaneously. It is important to manage this jellyfish induced dermonecrosis as a burn with specific attention to avoiding secondary bacteria infection.   Examine patient for signs of developing necrosis.   Manage skin necrosis following standard treatment protocols.   Immunologic Hypersensitivity Reaction A delayed hypersensitivity reaction commonly (greater than 50% of cases) occurs 7 to 14 days following sting occurrence. A pruritic erythematous maculopapular rash develops at the tentacle contact areas and will spontaneously resolve in most, but may require oral antihistamine and topical corticosteroid cream.[9]   Closely monitor the patient for the following symptoms of a hypersensitivity reaction: Fever Shortness of breath, sore throat, or cough Nausea, vomiting, diarrhea, or abdominal pain Severe tiredness, aches, or general ill-feeling   Manage hypersensitivity reactions following standard treatment protocols.   Serum Sickness Serum sickness may occur 4 to 14 days following antivenom administration. It may therefore develop after recovery from the initial envenoming and after the patient has gone home. It is essential all patients receiving antivenom are fully informed of the possibility and symptoms of serum sickness, and instructed to return for treatment if such symptoms develop following discharge.   Patients should be made aware of the signs and symptoms of serum sickness including: Rash Fever Joint aches Pains Malaise   Serum sickness may be managed with antipyretics and analgesics, as well as anti-inflammatory agents including antihistamines and corticosteroids:   Prednisolone dose   CHILD 1 mg/kg (up to 50 mg) per day orally for 5 days   ADULT 50 mg per day orally for 5 days   Severe cases may require hospitalization.   DISCHARGE CRITERIA Patients showing signs of severe pain requiring opioid analgesia or those with systemic envenoming can be discharged once they have recovered and are asymptomatic for 6 hours.   FOLLOW UP Patients should be warned of the high (58%) incidence of delayed (Type IV) hypersensitivity reaction occurring 7 to 14 days after the initial sting. This pruritic erythematous maculopapular rash develops at the tentacle contact areas and will spontaneously resolve in most, but may require follow up for oral antihistamine and topical corticosteroid cream. Those patients receiving antivenom are at risk of developing serum sickness after 4 to 14 days, and should be made aware of the signs and symptoms of this condition including: Rash Fever Joint aches Pains Malaise All patients should be advised to return for review should signs of serum sickness occur. If there was a major envenoming, follow up should be organized. PROGNOSIS Significant life threatening symptoms can occur following a box jellyfish sting, however with prompt use of cardiopulmonary resuscitation, box jellyfish antivenom and supportive care, patients generally make a full recovery. The sting areas may be tender to the touch for weeks or months; tentacle marks may persist for substantial periods of time and permanent scarring, perhaps with pigment changes, can appear. A delayed hypersensitivity reaction may occur some 7 to 14 days after initial envenoming; this reaction is usually minor and may resolve spontaneously. SIGNS AND SYMPTOMS The Box jellyfish is one of the most dangerous venomous creatures in the world, however, most typical stings rarely require hospitalization.[14][9][6]   Following exposure, the victim may experience immediate excruciating pain which increases in mounting waves, despite removal of the tentacle. The victim may scream and become irrational.[39][40] Areas of contact appear as purple or brown lines often compared to the marks made by a whip.[39] A pattern of transverse bars is usually visible and whealing is prompt and massive. Edema, erythema, and vesiculation soon follow and when these subside patches of full thickness necrosis are revealed.[39]   Patients may develop a variety of systemic effects that include acute pulmonary edema, cardiovascular instability and dysrhythmias, hypertension, hypotension, shock, and cardiac arrest. When death occurs it is usually due to a (presumed) cardiac arrest on the beach.   Routes of Exposure Clinical effects may develop following contact with intact or dismembered jellyfish, or nets containing body parts. Exposures generally occur when people are swimming in the sea or when specimens are washed up on the beach and handled or stood on. Jellyfish do not “attack” humans and stings are usually the result of a creature drifting into humans or humans colliding into a jellyfish.   Onset/Duration of Symptoms Local effects are generally noted immediately. Victims experience intense excruciating localized skin pain, peaking at 15 minutes and waning over the subsequent 24 hours; edema, erythema and vesiculation occur initially and when these subside (after some 10 days) patches of full thickness necrosis are revealed. Death, if it occurs, is usually within 20 minutes of the sting.[14]   Severity of Envenoming Severity is dependent upon area of discharging tentacle contact. Involvement of greater than 10% skin area is potentially lethal, especially in children.[7] Death follows cardiopulmonary failure.   Mild Box Jellyfish Envenoming Moderate Box Jellyfish Envenoming Severe Box Jellyfish Envenoming Local pain Cutaneous linear marks of sting Severe local or generalized pain Nausea Vomiting Tachycardia Acute respiratory distress Dysrhythmias Shock Acute pulmonary edema Respiratory failure Cardiac arrest Death   ACUTE EFFECTS (ROUTE OF EXPOSURE) Ingestion Abdominal pain, cramping and generalized urticaria was noted after jellyfish ingestion.[41] If jellyfish are ingested it seems possible that systemic effects may occur. There have been reports of upper airway stridor developing after ingestion of jellyfish.   Eye Stings occurring on the eyeball may produce a variety of effects including: Sudden pain Blurring of vision Foreign body sensation Iritis Decreased visual acuity Elevated intraocular pressure   These symptoms may persist for 24 to 48 hours and are generally self limiting, however they do have the potential for long term sequelae.[42][43][44][45][46] Systemic symptoms following an eye exposure are unlikely.   Skin Areas of contact are linear and multiple, showing as purple or brown lines often compared to the marks made by a whip.[2] Most stings will leave a cross-hatched tentacle imprint on the skin.[47][40][39] These initial local symptoms may be followed by systemic symptoms in severe stings.   ACUTE EFFECTS (ORGAN SYSTEM) Dermatologic Wheals[28] (often prompt and massive)[39] Pain (often severe)[47][28] Edema[40] Pallor[48] Necrosis[40][39]   Cardiovascular Tachycardia[24] Dysrhythmias[49] Hypotension[24] Hypertensive crisis Cardiac arrest[48]   Respiratory Wheezing[50] Dyspnea[24] Tachypnea[47] Cyanosis[47] Acute respiratory distress[51] Acute pulmonary edema[24][47] Apnea[40] Respiratory failure[40][51]   Neurologic Weakness[52] Vertigo Headache Confusion[53] Agitation[53] Shock[24][39] Unconsciousness[48]   Musculoskeletal Muscle cramps[52] Muscle pain[47]   Gastrointestinal Nausea (Rare) Vomiting[40] (Rare) Abdominal pain (Rare)[53]   Renal Oliguria[47][50]   Hematologic Hemolytic activity has been identified in the venom of the box jellyfish[54]   Immunologic Delayed exzematous-like allergic reactions are documented in the absence of further jellyfish contact[1][9]   Pruritus Erythema Maculopapular rash Urticaria   Anaphylaxis to jellyfish venom may rarely occur[55][9]   CHRONIC EFFECTS Delayed hypersensitivity reactions may occur in patients following stings. The reaction consists of a pruritic erythematous maculopapular rash that appears at the initial tentacle contact points and occurs 7 to 14 days after envenoming. The reaction may spontaneously resolve; most recover following treatment with oral antihistamines and topical corticosteroids.[9]   TOXICITY HUMAN Acute Box jellyfish are among the most dangerous venomous creatures in the world. Over 65 deaths have been reported among swimmers in northern Australian waters. Box jellyfish is the most rapid envenoming process known, which explains the almost instantaneous onset of systemic signs and symptoms in envenomed patients. However, despite this reputation as one of the world’s most venomous creatures, the vast majority of stings are of minor consequence and not life-threatening.[5][6][9]   As with any envenoming, children are particularly susceptible. Deaths in Australia are most commonly children. It is believed that a Chironex fleckeri larger than 7 cm in diameter may be a threat to the life of a five year old child.[48]   The length and width of the wheals produced may provide a reference for gauging the severity of a sting, four metres of tentacular contact is potentially lethal and wheal widths that approach 6 mm are commonly associated with death.   There are a number of variables associated with any sting that may influence the amount of venom that is injected: - Wheal width and length (as discussed above) - Time of contact - Intimacy of contact (e.g. hairless or hairy skin) - Percentage of nematocyst on the tentacle that actually discharge - The thickness of the overlying keratin on the skin at the sting site - The venom loading of the tentacles at the time of stinging (perhaps lowered by previous feeding by the animal) - Time of year   The subsequent running and struggling on the beach, the hyperemia of the extremities from the active toxin injuring the skin, as well as towelling or rubbing of the legs may enhance the uptake of injected venom into the circulation.[48]   Any sting is considered a major sting when: - A patient has cardiovascular instability - Resuscitation was necessary - The total sting area occupies more than one half of one limb (or equivalent) (especially in children) - It is associated with impairment of consciousness   BIOLOGICAL LEVELS - TOXIC Obtaining venom blood concentrations is not practical, nor necessary for clinical management.   REPRODUCTION PREGNANCY A fetus will share the mother’s risk following systemic envenoming. It is unclear if venom crosses the placenta. There is a report of a pregnant female being stung by Chironex fleckeri, she required CPR and antivenom and successfully delivered a normal baby at term.[17]   LACTATION It is unknown if exposure to this creature results in excretion of toxic substances into breast milk.   TOXIC MECHANISM The precise mechanisms of action of chirodropid venom are unknown. It is one of the most rapidly acting and potent animal toxins known. Early animal experiments showed that the venom has hemolytic, myotoxic, dermatonecrotic and lethal factor components.[56] In humans hemolytic effects have not been shown, with skin damage and death the most important manifestations.[14]   The dermatonecrotic action of the venom may involve release of leukotrienes and other arachidonic acid derivatives in addition to direct tissue damage. Dysrhythmias are often seen with envenoming and support a primary cardiotoxic role in fatal stings. Animal studies also suggest a cardiotoxic role including impaired cardiac contractility, hypertension and hypotension, dysrhythmias such as various heart conduction blocks and ventricular tachycardia, and decreased coronary flow.[14]   Studies have also suggested that the toxin may result in abnormalities in ionic transport across membranes, specifically the toxins induce Na+ influx into the cell. The increase in intracellular Na+ will then increase intracellular Ca2+ via the Na+/Ca2+ exchange mechanism, thus producing Ca2+ overload,[57] various tissues are involved including skeletal and cardiac muscle, smooth muscle, cardiac conduction pathways and possibly central neurological pathways.   DESCRIPTION Features These tropical jellyfish are large when fully developed (up to 30 cm across the box shaped bell), and may weigh up to 6 kg. The box may have up to 15 tentacles in each corner, which may reach up to 3 metres in length. It is virtually invisible under natural conditions, even in clear sunlit water.[39][51]   All coelenterates possess stinging mechanisms in the form of a nematocyst. These structures may be present in their thousands on the tentacles or body (bell) of the jellyfish, and are used to capture prey. Each nematocyst contains a dose of sometimes very potent venom; and combines the mechanical function of a harpoon gun and an injection syringe.[1] Each normally discharges in response to mechanical or chemical stimulation.[1][58] Nematocysts from different species of jellyfish are characteristic of the respective species to which they were attached,[39][1] and can be used to identify a particular species of jellyfish on the basis of morphology.[2][3]   REFERENCES [1] Williamson J, Burnett J. Clinical toxicology of marine coelenterate injuries. In: Meier J, White J, editors. Handbook of clinical toxicology of animal venoms and poisons. Boca Raton (FL): CRC Press; 1995. p. 89-115. [2] Currie BJ, Wood YK. Identification of Chironex fleckeri envenomation by nematocyst recovery from skin. Med J Aust 1995 May 1; 162 (9): 478-80. [3] Huynh TT, Seymour J, Pereira P, Mulcahy R, Cullen P, Carrette T, Little M. Severity of Irukandji syndrome and nematocyst identification from skin scrapings. Med J Aust 2003 Jan 6; 178 (1): 38-41. [4] Hartwick R, Callanan V, Williamson J. Disarming the box-jellyfish: nematocyst inhibition in Chironex fleckeri. Med J Aust 1980 Jan 12; 1 (1): 15-20. [5] Isbister GK, Palmer DJ, Weir RL, Currie BJ. Hot water immersion v icepacks for treating the pain of Chironex fleckeri stings: a randomised controlled trial. Med J Aust 2017 Apr 3; 206 (6): 258-261. [6] Fenner PJ, Harrison SL. Irukandji and Chironex fleckeri jellyfish envenomation in tropical Australia. Wilderness Environ Med 2000 Winter; 11 (4): 233-40. [7] White J. CSL antivenom handbook. Melbourne: CSL Ltd: 2001. p. 59-61. [8] King GK. Acute analgesia and cosmetic benefits of box-jellyfish antivenom. [Letter] Med J Aust 1991 Mar 4; 154 (5): 365-6. [9] O'Reilly GM, Isbister GK, Lawrie PM, Treston GT, Currie BJ. Prospective study of jellyfish stings from tropical Australia, including the major box jellyfish Chironex fleckeri. Med J Aust 2001 Dec 3-17; 175 (11-12): 652-5. [10] Gunja N, Graudins A. Management of cardiac arrest following poisoning. Emerg Med Australas 2011 Feb; 23 (1): 16-22. [11] de Lange DW, Sikma MA, Meulenbelt J. Extracorporeal membrane oxygenation in the treatment of poisoned patients. Clin Toxicol (Phila) 2013 Jun; 51 (5): 385-93. [12] Weiner L, Mazzeffi MA, Hines EQ, Gordon D, Herr DL, Kim HK. Clinical utility of venoarterial-extracorporeal membrane oxygenation (VA-ECMO) in patients with drug-induced cardiogenic shock: a retrospective study of the Extracorporeal Life Support Organizations' ECMO case registry. Clin Toxicol (Phila) 2020; 58 (7): 705-710. [13] Ramanathan K, Tan CS, Rycus P, MacLaren G. Extracorporeal membrane oxygenation for poisoning in adult patients: outcomes and predictors of mortality. Intensive Care Med 2017 Oct; 43 (10): 1538-1539. [14] Currie BJ. Marine antivenoms. J Toxicol Clin Toxicol 2003; 41 (3): 301-8. [15] Fenner PJ, Williamson JA, Blenkin JA. Successful use of Chironex antivenom by members of the Queensland Ambulance Transport Brigade. Med J Aust 1989 Dec 4-18; 151 (11-12): 708-10. [16] Sutherland SK, Duncan AW. New first-aid measures for envenomation: with special reference to bites by the Sydney funnel-web spider (Atrax robustus). Med J Aust 1980 Apr 19; 1 (8): 378-9. [17] Williamson JA, Callanan VI, Unwin ML, Hartwick RF. Box-jellyfish venom and humans. [Letter] Med J Aust 1984 Mar 31; 140 (7): 444-5. [18] Little M. Is there a role for the use of pressure immobilization bandages in the treatment of jellyfish envenomation in Australia? Emerg Med (Fremantle) 2002 Jun; 14 (2): 171-4. 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