119: Marine Envenomations

Human contact with venomous marine creatures is common and may result in serious harm from biological toxins or mechanical injury inflicted by the stinging apparatus. Significant morbidity results from envenomation by spiny fish, cone snails, octopi, sea snakes, and several species of jellyfish. Despite advances in basic science research regarding the biochemical nature of marine toxins and their mechanisms of action, our knowledge of the pathophysiology related to clinical syndromes in humans and the optimal therapies for human envenomation remain limited. Evidence for effective treatment is primarily derived from in vitro and in vivo animal research without the benefit of controlled human trials. However, current research in toxinology coupled with clinical observations allows the development of cogent treatment guidelines for victims of marine envenomation.

Cnidaria

The phylum Cnidaria (formerly Coelenterata) includes more than 9000 species, of which approximately 100 are known to injure humans. They are commonly referred to as jellyfish; however, their phylogenetic designations separate “true jellyfish” and other organisms into distinct classes (Table 119–1; Fig. 119–1A). All species possess microscopic cnidae (the Greek knide means nettle), which are highly specialized organelles consisting of an encapsulated hollow barbed thread bathed in venom. Thousands of these stinging organelles, called nematocysts (or cnidoblasts), are distributed along tentacles. A trigger mechanism called a cnidocil regulates nematocyst discharge. Pressure from contact with a victim’s skin, or chemical triggers such as osmotic change, stimulates discharge of the thread and toxin from its casing. Penetration of flesh leads to intradermal venom delivery. Nematocysts of most Cnidaria are incapable of penetrating human skin, rendering them harmless. Cnidaria causing human envenomation, such as the box jellyfish, discharge threads capable of penetrating into the papillary dermis.¹³⁶

Cubozoa.

Members of the class Cubozoa are not true jellyfish. Animals in the Cubomedusae order have a cube-shaped bell with four corners, each supporting between 1 and 15 tentacles. Species from this order produce the greatest morbidity and mortality of all Cnidaria. The order has two main families of toxicologic importance: Chirodropidae and Carybdeidae.

The Chirodropidae family is well known for the box jellyfish Chironex fleckeri (Greek cheiro means hand, Latin nex means murderer; therefore, “assassin’s hand”). When full grown, its bell measures 25 to 30 cm in diameter and 15 tentacles are attached at each “corner” of the bell. These tentacles may extend up to 3 m in length. Another member of this family is Chiropsalmus quadrigatus, the sea wasp. Its pale blue color makes detection in water nearly impossible.

The Carybdeidae family is most notable for Carukia barnesi, the Irukandji jellyfish.⁶¹ Its small size, with a bell diameter of only 2.5 cm, limits detection in open waters.

Hydrozoa.

Members of the Hydrozoa class are also not true jellyfish. The order Siphonophora (Physaliidae family) includes two unusual creatures of toxicologic concern: Physalia physalis, the Portuguese man-of-war, and its smaller counterpart, Physalia utriculus, the bluebottle. They are pelagic (floating) colonial Hydrozoa, meaning they exist as a colony of multiple hydroids in a formed mass. The easily recognizable blue sail that floats above the surface of the water is filled with nitrogen and carbon monoxide. Tentacles of P. physalis may reach lengths exceeding 30 m and contain more than 750,000 nematocysts in each of its numerous tentacles (up to 40). P. utriculus has only one tentacle that measures up to 15 m.

The Milleporina order includes the sessile Millepora alcicornis (fire coral) that exists as a fixed colony of hydroids. It appears much like true coral and has a white to yellow-green lime carbonate exoskeleton. Small tentacles protrude through minute surface gastropores. The overall structure ranges from 10 cm to 2 m.

Scyphozoa.

True jellyfish belong to the class Scyphozoa and are extremely diverse in size, shape, and color. Common varieties known to envenomate humans are Cyanea capillata (lion’s mane or hair jelly), Chrysaora quinquecirrha (sea nettle), and Pelagia noctiluca (mauve stinger). The mauve stinger is easily recognized; it appears pink in daylight and phosphorescent at night. Larvae of Linuche unguiculata cause sea bather’s eruption (SBE). The larvae are pinhead sized and are seen only when they are grouped in large numbers near the surface of the water.

Anthozoa.

The Anthozoa class has a diverse membership, including true corals, soft corals, and anemones. Only the anemones are of toxicologic importance. They are common inhabitants of reefs and tide pools and attach themselves to rock or coral. Armed with modified nematocysts known as sporocysts located on their tentacles, they produce stings similar to those of organisms from other Cnidaria classes.

History and Epidemiology.

Stings from Cnidaria represent the overwhelming majority of marine envenomations. In Australia, approximately 10,000 stings per year are recorded from Physalia spp alone.⁵⁶ Most Cnidaria stings occur during the warmer months of the year. Stings occur with greatest frequency on hotter-than-average days with low winds, particularly during times of low precipitation. “Stinger nets” are used in high-risk areas of the Australian coastline; however, one study reported that 63% of stings requiring medical attention occurred within netted waters.⁸⁸ Each stinger season, the Royal Darwin Hospital in Australia treats approximately 40 patients with stings.⁴² A prospective evaluation of stings presenting to that hospital during a 12-month period from 1999 to 2000 revealed that 70% resulted from the box jellyfish. The remaining 30% involved other Cubozoa such as C. barnesi.¹⁰⁹ Although this finding may indicate a predominance of box jellyfish as the cause of stings, it also suggests that stings from box jellyfish are more severe and require medical attention with greater frequency than stings from other species of Cnidaria.

Stings from C. barnesi, the organism originally identified as the cause of Irukandji syndrome, were initially considered unique to Australia. However, an unidentified species produced three cases of an Irukandjilike syndrome in the Florida Keys.⁶⁹ More recent reports identify an Irukandjilike syndrome north of Australian waters in the Torres Strait,¹⁰⁰ suggesting a more diverse geographical distribution and possibly more than one responsible organism.

Cases of SBE, a stinging rash evoked by contact with Cnidaria larvae, occur in clusters. Variation in intensity and frequency occurs from year to year as exemplified by a 25-year hiatus during which no cases were reported in Florida.¹⁴⁴ In 1992, more than 10,000 cases of SBE occurred in south Florida, with similar peaks in the 1940s and 1960s. Cases of SBE also are reported in Cuba, Mexico, the Caribbean, and occasionally as far north as New York.

Cnidaria common to the United States include the Portuguese man-of-war and sea nettle. Other species are widely distributed throughout the tropical and temperate waters of the globe (Table 119–1). Locations with documented Cnidaria-related deaths include the United States (Florida, North Carolina, Texas), Australia, the Indo-Pacific region (Malaysia, Langkawi Islands, Philippines, Solomon Islands, Papua New Guinea), and the coast of China.^{12,23,56,87,135} Since 1884, approximately 70 deaths in Australia are attributed to C. fleckeri. An estimated two to three deaths per year occur in Malaysia from an unknown species. Approximately 20 to 40 deaths are reported yearly in the Philippines from an unidentified species of the Chirodropidae family. Three deaths are well documented from P. physalis in the United States (Florida, North Carolina). One death from Chiropsalmus quadrumanus occurred along the coast of Texas. Eight fatalities in the Bohai waters of China (Yellow Sea) are reported from Stomolophus nomurai. Although Chirodropidae are found off the western coast of Africa, no fatalities in that region are documented in the medical literature.

Pathophysiology.

Cnidaria venoms contain a variety of components that may induce dermatonecrosis, myonecrosis, hemolysis, or cardiotoxicity, depending on the particular species. In rats, C. fleckeri venom evokes transient hypertension, followed by hypotension and cardiovascular collapse within minutes.¹¹⁶ Cardiac effects in animals include negative inotropy, conduction delay, ventricular tachycardia, and decreased coronary artery blood flow.⁴² However, experiments using the purest venom extracts without contamination from tentacle material demonstrate cardiovascular collapse without electrocardiographic changes.¹¹⁶ C. fleckeri venom also possesses dermatonecrotic and hemolytic fractions, although hemolysis is not documented in humans.⁹ Two myotoxins from C. fleckeri cause powerful sustained muscle contractions in isolated muscle fibers.⁴⁶ Isolated heart models using C. fleckeri venom suggest its mechanism of action is nonspecific enhancement of cation conductance leading to increased Na⁺ and Ca²⁺ entry into cells.¹⁰⁵ Other in vitro work confirms increased Na⁺ permeability in cardiac tissue.⁶³

C. barnesi, the Irukandji jelly, likely induces its dramatic vasopressor effects via catecholamine release. In rats, the venom produces a pressor response that is blocked by α₁-adrenergic antagonism.¹¹⁵ The pressor response is not dose dependent; therefore, catecholamines in the venom are an unlikely cause. In vitro experiments suggest a Na⁺ channel modulator effect leading to massive catecholamine release.¹⁵⁷ No electrocardiographic abnormalities occurred in envenomated rats.

Venom from Physalia spp blocks neural impulses in isolated frog sciatic nerve⁸² and produces ventricular ectopy, cardiovascular collapse, hyperkalemia, and hemolysis in dogs.⁷² Physalia spp venom inhibits Ca²⁺ entry into the sarcoplasmic reticulum.⁸² Similar mechanisms are proposed for Chrysaora, Chiropsalmus, and Stomolophus. C. quinquecirrha venom, which contain a 150-kDa polypeptide that induces atrioventricular block¹⁹ and produces myocardial ischemia, hypertension, dysrhythmias, and nerve conduction block,^24,25 as well as hepatic and renal necrosis.¹⁰⁴ C. quinquecirrha–induced hepatotoxicity is believed to be a direct toxin effect not mediated by pore formation or Ca²⁺ channel effects.⁷⁴ Equinatoxin II (EqtII), found in the venom of the anemone Actinia equina, creates pores in cell membranes leading to hemolysis.¹ This protein belongs to a group of anemone lysins known as actinoporins that bind to cell membranes and form pores via oligimerization.⁹³

An immune-mediated response to venom may explain some sting-related symptoms. Elevated serum anti–sea nettle immunoglobulin IgM, IgG, and IgE may persist for years in patients with exaggerated reactions to stings compared with controls.²⁰ A direct correlation between titers against Chrysaora and Physalia and severity of a visible skin reaction to envenomation strongly suggests an allergic component.¹²⁶ Elevated IgG titers were demonstrated in one death from P. physalis.¹³⁵ Dermatonecrosis from C. fleckeri may involve the release of leukotrienes and other arachidonic acid derivatives as well as direct toxin-mediated cell damage.⁴³ Postenvenomation syndromes may result from an exaggerated, prolonged, aberrant T-cell response.^26,27 Erythema nodosum following a sting from P. physalis lends further support to an immunologic component.⁵ SBE displays a characteristic delay in onset of symptoms and can be effectively treated with steroids, suggesting a primary immune-mediated process. This is further supported by histopathology revealing the presence of perivascular and interstitial infiltrates with lymphocytes, neutrophils, and eosinophils.¹⁵⁸

Clinical Manifestations.

Most patients with stings are treated beachside and never require hospitalization. The vast majority of patients with stings who seek medical care do so because of severe pain without evidence of systemic poisoning.⁴² However, severe systemic manifestations may develop following stings from C. fleckeri, C. barnesi, P. physalis, and a few other Cnidaria.

Envenomation by C. fleckeri inflicts the most severe pain and is frequently associated with systemic toxicity. Common symptoms include immediate severe pain, followed by an erythematous whiplike linear rash with a “frosted ladder” appearance. The pain often is excruciating and may require parenteral analgesia. Systemic symptoms include nausea, vomiting, muscle spasms, headache, malaise, fever, and chills. Pain generally abates over several hours, although the rash may persist for days. In a prospective series of C. fleckeri stings, 58% manifested delayed hypersensitivity reactions in the form of an itchy maculopapular rash at 7 to 14 days.¹⁰⁹ Most resolved spontaneously; some were treated with antihistamines and topical corticosteroids.

Fatality is documented to occur with only 4 m of tentacle markings.¹³⁶ Death is rapid, preventing many victims from reaching medical care, or even the shore.⁸⁶ Cardiac arrest and pulmonary edema may develop in young, healthy patients without prior cardiopulmonary disease.^78,92,156 Survival is possible with immediate cardiopulmonary resuscitation (CPR).¹⁵⁵ C. quadrumanus, a close relative of the box jellyfish, induces symptoms that are similar to C. fleckeri stings, including pulmonary edema and death.¹²

Previous reports suggesting a 15% to 20% fatality rate¹²² following C. fleckeri envenomation likely represent a gross overestimation given the low number of documented fatalities in the context of the extraordinary number of yearly stings. A prospective study of stings from Cubozoa over one year in Australia revealed no dysrhythmias, pulmonary edema, or death.¹⁰⁹ No patient received antivenom, and analgesia was the only pharmacotherapy implemented. Hospital admission was not required for any victim. Although most victims suffer only local severe pain, serious systemic toxicity occurs occasionally, and may include vertigo, ataxia, paralysis, delirium, syncope, respiratory distress, pulmonary edema, hypotension, and dysrhythmias. In a series of 10 reported deaths from C. fleckeri, all occurred in children, suggesting vulnerability due to lower body mass and thinner dermis.⁴²

Irukandji syndrome is a severe form of envenomation following Cubozoa stings from C. barnesi.⁷⁵ Individuals afflicted often notice a mild sting while they are in the water; however, skin findings typically are absent. Severe systemic symptoms develop within 30 minutes and mimic a catecholamine surge including tachycardia, palpitations, hyperpnea, headache, pallor, restlessness, apprehension, sweating, and a sense of impending doom. A prominent feature is severe whole-body muscle spasms that come in waves and preferentially affect the back. Spasms are described as unbearable and frequently require parenteral analgesia. Symptoms generally abate over several hours. Admission rates in patients presenting to medical care can exceed 50%.⁸⁸ Hypertension is universal and may be severe, with systolic blood pressures well over 200 mm Hg. Two fatalities are described involving severe hypertension (systolic 280/150 mm Hg and 230/90 mm Hg) resulting in intracranial hemorrhage.^52,75 Hypotension frequently follows, requiring vasopressor support. Pulmonary edema can develop within hours. Echocardiograms consistently reveal global ventricular dysfunction.^90,95 Restored cardiac function typically returns after several days.⁸⁹ A retrospective review of 116 cases of Irukandji presenting to Cairns Base Hospital identified elevated troponin I measurements in 22% of patients.⁷⁵ Electrocardiographic changes are described as nonspecific.

P. physalis envenomation typically induces severe pain, bullae, and skin necrosis (Fig. 119–1B). Systemic symptoms include weakness, numbness, anxiety, headache, abdominal and back spasms, lacrimation, nasal discharge, diaphoresis, vertigo, hemolysis, cyanosis, acute kidney injury, shock, and, rarely, death. Some patients experience local numbness and paralysis of the affected extremity that resolves spontaneously.⁷⁶ As with serious C. fleckeri stings, cardiovascular collapse and death can occur within minutes of envenomation.²³ However, fatalities can be delayed several days following envenomation and relate to complications such as myocardial infarction and aspiration pneumonitis.¹³⁵ An unusual presentation is reported of a 4 year-old child who was stung along the North Carolina coast and developed massive hemolysis requiring transfusions, followed by acute kidney failure necessitating temporary hemodialysis.⁷⁰ In contrast to P. physalis, P. utriculus stings typically are mild, although systemic toxicity occasionally develops.⁵⁸

M. alcicornis (fire coral) is a common cause of stings in southern United States and Caribbean waters. While a member of the same phylogenetic class as P. physalis, it produces far less significant injuries. It is a nuisance to divers who touch the coral and suffer moderate burning pain for hours. Untreated pain generally lessens within 90 minutes, with skin wheals flattening at 24 hours and resolving within one week. Hyperpigmentation may persist for up to 8 weeks.¹⁶ The feather hydroid is the most numerous of the Hydrozoa and produces only mild stings.⁹⁷

True jellyfish typically are less harmful to humans than Cubozoa or Hydrozoa. However, systemic toxicity and occasional deaths are reported from certain species such as S. nomurai, C. capillata, C. quinquecirrha, and P. noctiluca. Stomolophus meleagris is a common cause of stings; however, its weak venom produces only minor injury.⁴

Larvae of Linuche unguiculata are the primary cause of a pruritic papular eruption on the skin of sea bathers in Florida, occurring mostly in areas covered by a bathing suit as a result of larvae trapped under the garments. Cases were first noted in 1949 and dubbed SBE.¹²⁷ The larvae appear as pin-sized brown to green-brown spheres in the upper 2 inches of the water and are typically unnoticed. In a retrospective review, 50% of people reported a stinging sensation while they were in the water, and 25% reported itching upon exiting the water.¹⁵⁸ The remainder of patients developed symptoms within 11 hours. Skin lesions develop within hours of itching and appear as discrete, closely spaced papules, with pustules, vesicles, and urticaria. Most lesions occur in areas covered by the bathing suit where the larvae accumulate; however, folds of skin such as the axilla, breasts, and neck may be affected. Itching often is severe and prevents sleep. New lesions may continue to develop over 72 hours. The average duration of symptoms is just under 2 weeks, and a small percentage of patients experience a recurrence of lesions several days later. Systemic symptoms such as chills, headache, nausea, vomiting, and malaise may occur.

Following stings from sea anemones, victims may develop either immediate or delayed pain. Skin findings range from mild erythema and itching to ulceration. A review of 55 stings from Anemonia sulcata presenting to a hospital in Yugoslavia (Adriatic Sea) revealed that, in addition to the local skin findings, many patients suffered nausea, vomiting, muscle aches, and dizziness.⁹⁴ Larvae of the anemone Edwardsiella lineata also cause SBE among ocean swimmers in Long Island, New York. The hell’s fire anemone Actinodendron plumosum is native to the South Pacific and produces significant local pain. One death occurred in the Virgin Islands following envenomation from an unknown species described as a “white anemone with blue tips.” The onset of hepatic and renal failure was rapid and required transplantation, after which the patient died.⁶⁵ Nonfatal elevation of hepatic enzyme concentrations following anemone sting also is reported.¹⁷

Diagnostic Testing.

Laboratory evaluation may be warranted in patients suffering systemic toxicity following Cnidaria envenomation. Serial measurement of serum cardiac markers should be obtained from victims of Irukandji stings or others with consequential cardiovascular toxicity. Following severe stings from a variety of Cnidaria, urinalysis, hematocrit, and serum creatinine measurements should be considered to detect the presence of hemolysis and subsequent kidney injury. Chest radiography is indicated for complaints of dyspnea or abnormalities in oxygenation. Venom assays are not available, and serum antibody titers are not clinically useful.

Management.

Initial interventions after Cnidaria envenomation are directed toward stabilization of cardiopulmonary abnormalities in cases of severe envenomation. Secondary measures are directed toward the prevention of further nematocyst discharge, which could intensify pain and enhance toxicity. Many topical therapies have been used for this purpose, including sea water, vinegar, a commercial solution known as Stingose, methylated spirits, ethanol, isopropyl alcohol, dilute ammonium hydroxide, urine, sodium bicarbonate, papain, shaving cream, and sand.

Vinegar is a common first-line treatment for topical application following Cnidaria stings. In vitro trials with C. fleckeri tentacles demonstrate complete irreversible inhibition of nematocyst discharge following a 30-second application.⁷¹ Additional study findings include massive nematocyst discharge with application of urine or ethanol, and no effect on discharge with use of sodium bicarbonate. Follow-up in vivo experiments demonstrate that vinegar is effective for other Cubozoa, including Morbakka (large Cubozoan in Australia),⁵¹ Carybdea rastoni,⁵⁴ and C. barnesi.⁵⁵ Although massive nematocyst discharge occurs when vinegar is applied to C. capillata tentacles in vitro, clinical exacerbation following this treatment is not reported in humans.⁵⁰ Massive discharge also occurs with C. quinquecirrha.⁵⁸ A smaller degree of discharge (30%) occurs with P. physalis,⁵⁸ whereas nematocysts of P. utriculus are unaffected by application of vinegar.⁷¹

Stingose is a commercially available product designed to counteract venom of insects, bees, stinging plants, and marine stingers. It is an aqueous solution of 20% aluminum sulfate and 1.1% surfactant. Its purported mechanism of action is denaturing of proteins and long-chain polysaccharides via interactions with the Al³⁺ ion, as well as osmotic removal of venom. A human volunteer trial involving stings from live tentacles of C. fleckeri demonstrated pain relief within 5 seconds of Stingose application.⁷³ Similar results were achieved following treatment of stings from C. quinquecirrha. Further investigation involved beachside evaluation of 17 C. fleckeri and 150 P. utriculus sting victims treated with Stingose immediately following injury. All victims reported rapid relief. However, placebo or alternative therapies were not used in this case series. The efficacy of treatment with vinegar, Stingose, methylated spirits, and salt water was measured in human volunteers following forearm application of P. physalis tentacles.¹⁴⁷ Vinegar demonstrated superior pain control compared with Stingose, whereas methylated spirits increased pain. The study assessed pain relief only and did not investigate the effects of the treatments on nematocyst discharge or systemic toxicity. A small volunteer study utilizing topical lidocaine reported successful treatment of stings via topical analgesia and reduced nematocyst discharge.¹³

In many cases the identity of the “jellyfish” causing injury is unknown. In those cases, therapy must be guided by geographic location. In the United States, where P. physalis and C. quinquecirrha are of greatest consequence, sea water should be used to aid in tentacle removal given that vinegar enhances nematocyst discharge in those species. In the Indo-Pacific region, where C. fleckeri and C. barnesi are of greatest concern, vinegar application confers greater advantage. Following a 30-second application, adherent tentacles must be carefully removed. This can be accomplished with a gloved or towel-covered hand, or with sand and gentle scraping with a credit card or other blunt, straight-edged tool.

In a nonrandomized trial, ice packs provided rapid, effective relief for patients with mild to moderate pain from Cnidaria stings in Australia.⁴⁷ Patients with severe pain were less likely to benefit from ice packs. Many Cnidaria venoms are heat labile and may be neutralized at 122°F (50°C) for 20 minutes leading some clinicians to recommend treating stings with hot water immersion (HWI). However, availability of hot water at the beach and the high temperature needed to neutralize venom limits implementation of this therapy. Some authors suggest that the use of heat is not only ineffective for venom neutralization, but that it also increases pain.¹⁸ However, recent controlled trials designed to address this controversy highlight the efficacy of HWI in lieu of cold packs for the treatment of stings from Carybdea alata and Physalia spp.^{58,91,107,142,152,161} This finding may relate more to gate control theory of pain and modulation of pain signals rather than venom destruction. HWI therapy for treatment of C. fleckeri stings has not been rigorously evaluated.

Pressure immobilization bandaging is a technique that applies sufficient pressure to a wound to impede lymphatic drainage and prevent the entrance of venom into systemic circulation. Its application for snakebites is commonplace outside the United States, while its role following Cnidaria stings has sparked controversy. Given the rapid onset of symptoms, the utility of a technique that impedes lymphatic drainage is unlikely to provide benefit. Although the technique would be used only after tentacle removal, some microscopic nematocysts remain adherent to the skin after visible tentacles are removed. In vitro data investigating the effect of pressure on discharged nematocysts demonstrate not only that discharged nematocysts still contain venom, but that applying pressure forces more venom down the hollow tube.¹¹² This finding is correlated clinically as patients can deteriorate following pressure immobilization bandaging.⁵⁷ Given the lack of evidence suggesting benefit, coupled with clear in vitro evidence of increased venom delivery with this technique, it should not be implemented for treatment of Cnidaria stings.

Box jellyfish antivenom is sheep-derived whole IgG raised against the “milked” venom of C. fleckeri. It has been available in Australia since 1970. Combining C. fleckeri venom with box jellyfish antivenom prior to injection into pigs prevents all toxicity.¹⁴³ An isolated chick muscle experiment demonstrates that box jellyfish antivenom prevents the neurotoxicity and myotoxicity from C. fleckeri following pretreatment; however, there is no “rescue effect in this research.”¹¹³ Given that antivenom in humans is always used as a rescue therapy, the research raises concerns regarding efficacy in the clinical setting. Pretreatment of rats with box jellyfish antivenom prevented cardiovascular collapse in 40%, but did not blunt the initial hypertensive effect.¹¹⁴ In vitro data demonstrate that box jellyfish antivenom neutralizes the dermatonecrotic, hemolytic, and lethal fractions of venom from Chiropsalmus spp; however, the venom of P. physalis and C. quinquecirrha were not neutralized.¹⁰ Other in vitro and in vivo data demonstrate incomplete neutralization of Chiropsalmus spp venom.^10,113

There are no controlled studies in humans evaluating the efficacy of box jellyfish antivenom in the treatment of C. fleckeri envenomations, nor is there convincing evidence that its administration has saved human lives. Despite the frequency of hospital visits for stings from C. fleckeri in Australia, the use of box jellyfish antivenom is rare.⁴² Evidence for its efficacy stems from case reports suggesting that pain abates rapidly after administration.^15,156 Although box jellyfish antivenom may improve pain control, patients still may require parenteral opioids for analgesia following antivenom administration.¹¹ Significant morbidity and mortality still occur despite antivenom use.^41,92,136 Case reports of box jellyfish antivenom use for C. barnesi stings demonstrate no apparent benefit.⁴⁹

Many serious stings occur in the Northern Territory of Australia, where stinger nets are not commonly used. Distance from medical care limits the ability to obtain antivenom in a timely fashion.⁴² Although box jellyfish antivenom can be administered by paramedics via intramuscular (IM) injection,⁵⁷ poor IM absorption and incomplete venom neutralization with antivenoms, as well as delayed peak serum concentrations, limit the utility of this approach.¹²¹ The amount of antivenom required to neutralize twice the lethal dose in humans is estimated at 12 vials.⁴² The manufacturer recommends treating initially with one ampule intravenously (IV) diluted 1:10 with saline or three undiluted ampules (1.5–4 mL each) IM at three separate sites, if IV access is unavailable. Some authors who have treated multiple patients with antivenom suggest treating coma, dysrhythmia, or respiratory depression with one ampule IV, titrating up to three ampules with continuation of CPR in patients with refractory dysrhythmias until a total of six ampules have been administered.¹⁰⁹ For less serious envenomations, clinicians may consider administering one ampule if ice packs and parenteral analgesia prove ineffective.¹⁰⁹ Serious adverse events or delayed sequelae following the use of IV antivenom are uncommon, although allergic reactions are a consideration.¹³⁷

Verapamil was evaluated as a treatment for C. fleckeri stings based on evidence that Ca²⁺ entry into cells represents an important mechanism of toxicity. One animal model demonstrated synergy with use of verapamil in combination with box jellyfish antivenom,²⁸ whereas another showed verapamil pretreatment as well as rescue prolonged survival.²¹ This is in contrast to other models demonstrating that verapamil negates the benefits of antivenom¹¹⁴ and increases mortality.¹⁴³ Verapamil administration to animals with C. quinquecirrha envenomation demonstrated no benefit.¹⁰⁴ Interestingly, addition of magnesium to antivenom for treatment of C. fleckeri envenomation in rats prevented cardiovascular collapse in 100%, suggesting that magnesium may have a role in the treatment of stings from this species.¹¹⁴ Given that animal data are inconsistent with regard to verapamil and that hypotension may develop with severe envenomation, use of calcium channel blockers is not currently recommended for treatment of C. fleckeri stings.

Treatment for Irukandji syndrome should focus on analgesia and blood pressure control. Several modalities for control of severe hypertension have been suggested and include phentolamine, IV magnesium sulfate, and nitroglycerin.^40,53 Dosing guidelines and efficacy following magnesium infusion for this indication are not established. Whereas hypotension may occur in late stages of toxicity, clinicians should also consider short-acting titratable agents such as esmolol, nitroprusside, or nicardipine.

Mollusca

The phylum Mollusca (Latin mollis meaning soft) includes the classes Cephalopoda (octopus, squid, and cuttlefish) and Gastropoda (cone snails). Cephalopod species of toxicologic concern are limited to the blue-ringed octopus Hapalochlaena maculosa and the greater blue-ringed octopus Hapalochlaena lunulata. The blue-ringed and greater blue-ringed octopi are found in the Indo-Pacific region, primarily in Australian waters (Fig. 119–2). Of the 400 species of cone snails that belong to the genus Conus, 18 are implicated in human envenomations.

History and Epidemiology.

The blue-ringed octopus normally displays a yellow-brown color, but develops iridescent blue rings when threatened. The species is not aggressive and only bites humans when handled. A 1983 review of reported octopus envenomations uncovered a total of 14 cases, all of which occurred in Australia.¹⁴⁹ There were two deaths⁶² and four serious envenomations. Other reviews suggest that up to seven deaths may have occurred prior to 1969, some outside Australia.⁴⁵

Estimates of reported cone snail envenomations suggest only 15 human deaths have occurred worldwide.⁴⁸ Conus geographicus (fish hunting cone) is the most common species implicated, although Conus textile may also cause death in humans. Cone snails predominantly inhabit the Indo-Pacific, including all parts of Australia, New Guinea, Solomon Islands, and the Philippines. Two deaths from C. geographicus occurred in Guam.⁸⁵

Pathophysiology.

The salivary gland of the blue ringed octopus secretes a toxin originally designated maculotoxin and later identified as tetrodotoxin.¹³¹ The beak of the octopus creates small punctures in human skin through which venom is introduced. Tetrodotoxin blocks Na⁺ conductance in neurons, leading to paralysis. Venom also contains serotonin (5-HT), hyaluronidase, tyramine, histamine, tryptamine, octopine, taurine, acetylcholine, and dopamine.¹³⁸ Rabbits subjected to bites develop rapid flaccid paralysis without cardiotoxicity and die from asphyxia. Other animal models using venom gland extract demonstrate rapid onset of respiratory muscle paralysis and severe hypotension.⁶⁰ Death occurs despite artificial respiration and results from hypotension.

Cone snails have a hollow proboscis that contains a tooth bathed in venom. Envenomations occur when the shells are handled. The proboscis can extend the length of its shell, thereby envenomating the hand of someone touching the opposite end of the shell. Any Conus species contains approximately 100 peptides or conotoxins in its venom along with hyaluronidases that aid in local tissue breakdown.¹⁴⁸ Targets include voltage- and ligand-gated ion channels as well as G-protein–linked receptors (Table 119–2).^84,110,141 Many of these peptides are used extensively in laboratory research for their ability to selectively target a variety of specific Ca²⁺ channel subtypes. Venom from Conus imperialis (worm hunter) contains a substantial amount of 5-HT, a component not found in any other Conus venom tested thus far.⁹⁹ This species also contains a vasopressinlike peptide.¹⁰⁶ The neuropeptide omega-conotoxin, isolated from Conus magnus, is valued for its antinociceptive properties that arise from blockade of the N-type voltage-sensitive Ca²⁺ channel in spinal cord afferents.⁹⁸ The Food and Drug Administration approved ziconotide (Prialt, Elan Pharmaceuticals) in 2004 for intrathecal (IT) infusion in patients with severe chronic pain that require IT therapy, and in whom other treatment modalities such as IT morphine are not tolerated or ineffective. Patients reported modest improvements in pain with long-term treatment.¹⁵¹ Frequent side effects such as dizziness, nausea, confusion, and memory impairment limit the broad application of this therapy.

Clinical Manifestations.

The blue-ringed octopus creates one or two puncture wounds with its chitinous jaws, inflicting only minor discomfort. A wheal may develop with erythema, tenderness, and pruritus. Tetrodotoxin exerts a curarelike effect characterized by paralysis without depressing mental status. Symptoms include perioral and intraoral paresthesias, diplopia, aphonia, dysphagia, ataxia, weakness, nausea, vomiting, flaccid muscle paralysis, respiratory failure, and death. Detailed case reports describe rapid onset of symptoms.^32,149 Complete paralysis requiring intubation with findings of fixed and dilated pupils is followed within 24 to 48 hours by near-complete recovery of neuromuscular function. In one reported death, a young man placed the octopus on his shoulder. He subsequently noted a small puncture wound, developed dry mouth, dyspnea, inability to swallow, and became apneic. Asystole occurred 30 minutes after arrival at the hospital despite mechanical ventilation.⁶² Another similar bite resulted in symptom onset at 10 minutes, followed by death at 90 minutes, despite bystander CPR.¹³⁸ With less severe envenomations, cerebellar signs may arise without paralysis. Near-total paralysis with intact mentation resolving over 24 hours is described in humans.¹³⁸

Cone snail envenomation results from careless handling of the animal or rummaging through sand. Cone snails are nocturnal feeders, so they may present more of a hazard to night divers. Localized symptoms range from a slight sting to excruciating pain, tissue ischemia, cyanosis, and numbness. Systemic symptoms include weakness, diaphoresis, diplopia, blurred vision, aphonia, dysphagia, generalized muscle paralysis, respiratory failure, cardiovascular collapse, and coma. Death is rapid and occurs within 2 hours. Based on military medical records of more than 30 cases predating 1970, the mortality rate approaches 25%, with C. geographicus causing the most deaths.⁸⁵ Other estimates suggest that, without medical care, mortality may reach 70%.¹⁶⁰ Given the rarity of severe human envenomations from cone snails, the manner of death, whether purely from respiratory insufficiency or direct cardiovascular toxicity, remains unknown.

Diagnostic Testing.

Laboratory testing following envenomation from octopi or cone snails should be directed by clinical findings. Although not a widely available assay, tetrodotoxin can be detected in the urine or serum using high-performance liquid chromatography with subsequent fluorescence detection.¹⁰⁸

Management.

Primary interventions include maintenance of airway, breathing, and circulation. Some authors recommend hot water (113°–122°F, 45°–50°C,) following cone snail stings for pain relief.⁸⁵ Unlike Cnidaria envenomations, where nematocysts full of venom can persist on the skin and lead to continued venom delivery, stings from the octopus and cone snail mirror those of snakebites, where venom delivery is an immediate and finite event. Therefore, pressure immobilization bandaging may blunt toxin distribution by decreasing lymphatic spread.⁴⁸ Additional measures include local wound care and tetanus prophylaxis. Antivenom is not available for octopus or cone snail venoms.

Echinodermata, Annelida, and Porifera

The Echinodermata phylum includes sea stars, brittle stars, sea urchins, sand dollars, and sea cucumbers. Annelida are segmented worms that include the Polychaetae family of bristle worms. Sponges are classified in the Porifera phylum. One feature that all three phyla share is the passive envenomation of people who mistakenly handle or step on the animals. Most stings from these creatures are mild.

History and Epidemiology.

Echinoderms, annelids, and sponges are ubiquitous ocean inhabitants. The crown-of-thorns Acanthaster planci is found in the warmest waters of Polynesia to the Red Sea and is a particularly venomous species because of its sharp spines that easily puncture human skin. Sea urchins inhabit all oceans of the world. Bristle worms such as Hermodice carunculata typically inhabit tropical waters such as those of Florida and the Caribbean. However, some species thrive in the frigid waters of Antarctica. The fire sponge Tedania ignis is a brilliant yellow-orange sponge identified in large numbers off the coast of Hawaii and in the Florida Keys. Other common American sponges are Neofibularia nolitangere (poison-bun sponge or touch-me-not sponge) and Microciona prolifera (red sponge). Neofibularia mordens (Australian stinging sponge) is a common Southern Australian variety. In the Mediterranean, sponges are often colonized with sea anemones that may inflict severe stings.¹⁶

Pathophysiology.

Sea urchins are covered in spines and pedicellariae. The pedicellariae are pincerlike appendages used for feeding, cleaning, and defense. They generally contain more venom than the spines and are more difficult to remove from wounds. Urchins laden with pedicellariae can evoke more severe stings than urchins with less pedicellariae. Venom contained within the spines consists of steroid glycosides, serotonin, hemolysin, protease, and acetylcholinelike substances. Some species harbor neurotoxins. The most venomous are species of Diadema, Echinothrix, and Asthenosoma. Sea stars are less noxious because they generally have short, blunt spiny projections. The crown-of-thorns is the exception with its longer, sharp spines containing toxic saponins with hemolytic and anticoagulant effects as well as histaminelike substances.¹³⁹ Sea cucumbers excrete holothurin, a sulfated triterpenoid oligoglycoside, from the anus (organs of Cuvier) as a defense. The toxin inhibits neural conduction in fish, leading to paralysis. Some sea cucumbers eat Cnidaria and subsequently secrete their venom.

Bristle worms have many parapodia that have the appearance, but not the function, of legs. Several bristles extend from each parapodium giving the family (Polychaeta) its name (poly means many, chaetae means bristles). The bristles may penetrate human skin, leading to envenomation with an unknown substance.

Sponges have an elastic skeleton with spicules of silicon dioxide or calcium carbonate. They attach to the sea floor or coral beds. Toxins include halitoxin, odadaic acid, and subcritine, the nature of which is uncertain.²² Dried sponges are nontoxic; however, on rewetting they may produce toxicity even after several years.¹³⁴

Clinical Manifestations.

Most injuries from sea urchins are caused by inadvertently stepping on the spines or attempting to handle the animal. An intense burning with local tissue reaction occurs, including edema and erythema. Rarely, with multiple punctures, lightheadedness, numbness, paralysis, bronchospasm, and hypotension may reportedly occur, although this is not documented in the peer-reviewed medical literature.³ Reports of death are not well substantiated. The Pacific urchin Tripneustes has a neurotoxin with a predilection for cranial nerves.¹⁶ Mild elevations of hepatic enzymes are reported in one patient with foot cellulitis from an urchin sting.¹⁵⁹ Small cuts on the skin from handling starfish may allow venom to penetrate, leading to contact dermatitis. The crown-of-thorns may cause severe pain, nausea, vomiting, and muscular paralysis.⁹⁷ Cutaneous, scleral, or corneal exposure to sea cucumbers triggers contact dermatitis, intense corneal inflammation, and even blindness. Bristle worms are shrouded with bristles that can produce a reddened urticarial rash. Symptoms typically are mild and resolve over several hours to days.

Contact with the fire sponge, poison-bun sponge, or red-moss sponge causes erythema, papules, vesicles, and bullae that generally subside within 3 to 7 days. Victims may develop fever, chills, and muscle cramps. Skin desquamation occurs at 10 days to 2 months,⁴ with chronic skin changes lasting several months.²² Erythema multiforme and anaphylaxis are uncommon complications associated with Neofibularia spp exposure.¹⁶ Contact with sponges that are colonized with Cnidaria can lead to dermatitis with skin necrosis, referred to as sponge diver’s disease.

Management.

The primary objective following envenomation from sea urchins and crown-of-thorns starfish is analgesia. Submersion of the affected extremity in hot water (105°–115°F, 40.6°–46.1°C) and administration of oral analgesics often is sufficient.^48,97 Puncture wounds require radiographic evaluation to locate potential foreign bodies. Spines frequently crumble with attempted extraction. Intraarticular spines necessitate surgical removal. Decisions regarding spines in other locations should be influenced by ease of removal, presence of infection, and persistent pain. Tetanus immune status must be addressed. Decisions regarding antibiotic prophylaxis should be based on degree of injury and patient factors such as diabetes or other comorbidities. Although most infections likely are secondary to human skin flora, marine flora such as Mycobacterium marinum and Vibrio parahaemolyticus are potential wound contaminants. Treatment of sponge exposures usually requires only removal of spicules using adhesive tape or the edge of a credit card. Antihistamines and topical corticosteroids often provide no relief from stinging sponges.²²

Snakes

Sea snakes are members of the class Reptilia and are divided into two subfamilies: Hydrophiinae and Laticaudinae. They are close relatives of the cobra and krait. Length typically does not exceed 1 m. Their tails are flattened, and their bodies often are brightly colored. Distinction from eels is made by the presence of scales and the absence of fins and gills. All 52 species of sea snakes are venomous and at least six species are implicated in human fatalities. The most common species cited in human envenomation are Enhydrina schistosa, the beaked sea snake, and Pelamis platurus, the yellow-bellied sea snake.

History and Epidemiology.

Sea snakes are common to the tropical and temperate Indian and Pacific Oceans, but they are also found along the eastern Pacific Coast of Central and South America and the Gulf of California. In the eastern Pacific region, the yellow-bellied sea snake is the only species known. There are no sea snakes in the Atlantic Ocean. The majority of envenomations occur along the coasts of Southeast Asia, the Persian Gulf, and the Malay Archipelago (Malaysia). Snakes tend to inhabit the turbid coastlines and deeper reefs of these regions.

The true incidence of sea snake envenomation is unknown because many bites are not recorded. Worldwide the number of deaths per year may approach 150, with an overall mortality rate estimated at 3%.⁴⁸ In a review of 120 documented bites, 51.7% of victims were fishermen handling nets.¹¹⁸ The remainder of victims were wading or swimming along the coastline. In a review of 101 bites occurring from 1957 to 1964 in Northwest Malaysia, more than 50% of bites were from the beaked sea snake, including seven of the eight fatal bites in that series, bringing the mortality to 8% prior to the availability of antivenom.¹²⁰ However, 31 “dry bites” were excluded, suggesting that the overall mortality is somewhat lower. Among the 20% of patients in that series suffering “serious envenomation,” half died despite supportive care. A follow-up series of patients after the introduction of antivenom described 2 deaths out of 11 “serious envenomations,” suggesting a decreased mortality resulting from this intervention. These were all retrospective reviews of published or personally communicated cases.

Pathophysiology.

All sea snakes have small front fangs. Their venom is neurotoxic, myotoxic, nephrotoxic, and hemolytic. Known components of the venom include acetylcholinesterase, hyaluronidase, leucine aminopeptidase, 5'-nucleotidase, phosphodiesterase, and phospholipase A. The neurotoxin is a highly stable 6000- to 8000-Da protein similar to that of cobra and krait venom. In mice, beaked sea snake venom is four to five times more potent than cobra venom based on a μg/kg ratio; however, cobra venom yield is greater.³¹ Venom homology exists across many species.⁷⁷ The neurotoxin targets postsynaptic acetylcholine (ACh) receptors creating a blockade at the neuromuscular junction.¹⁴⁰ Presynaptic effects include initial enhanced ACh release and subsequent inhibition of ACh release.^103,120,150 In vitro research confirms direct nephrotoxicity of crude venom and may partially explain the nephrotoxicity described clinically.¹³⁰ Rhabdomyolysis likely contributes to this clinical finding.

Clinical Manifestations.

Sea snakes generally are docile, except when provoked, or during the mating season. Bites typically are painless or inflict minimal discomfort. Between one and four fang marks are common; however, up to 20 fang marks are possible as a result of multiple bites. The diagnosis can be obscured because victims may not associate the slight prick following the bite with later onset of ascending paralysis. Symptoms may progress within minutes, although a delay of up to 6 hours is possible. Neurotoxin-induced paralysis occurs in conjunction with muscle destruction stemming from myotoxic fractions. Painful muscular rigidity and myoglobinuria are hallmarks of sea snake myotoxicity. Myoglobinuria develops between 30 minutes and 8 hours after the bite. Other classic symptoms include ascending flaccid paralysis, dysphagia, trismus, ptosis, aphonia, nausea, vomiting, fasciculations, and ultimately respiratory insufficiency, seizures, and coma.

Diagnostic Testing.

Laboratory diagnostics are directed toward identifying hemolysis, myonecrosis, hyperkalemia, and acute kidney injury. Serum electrolytes, creatinine, and creatine phosphokinase, as well as hematocrit and urinalysis, should be obtained. Elevated concentrations of hepatic enzymes may indicate severe envenomation. Serial measurement of these parameters is recommended.

Management.

Prehospital management of sea snakebites mirrors treatment of terrestrial snakebites (Chap.122) and includes immobilization of the extremity and consideration of a pressure immobilization bandage to impede lymphatic drainage. Currently no data regarding the efficacy of this technique for sea snake envenomations are available. Tourniquets that impede venous or arterial flow are not recommended and may be detrimental.Airway and respiratory effort require close monitoring because paralysis can develop rapidly.

The most commonly used antivenoms for sea snakes are equine IgG Fab fragments produced using the venom of beaked sea snake (E. schistosa) or terrestrial tiger snake (Notechis scutatus) (Table 119–3). In vitro experiments demonstrate that sea snake antivenom is effective for neutralizing all species of sea snakes tested (Praescutata viperina in Thailand, P. platurus in Central America, Laticauda semifasciata in the Philippines, Laticauda laticaudata in Japan, Hydrophis cyanocinctus, Lapemis hardwickii).¹⁴⁶ Optimal neutralization occurs within the subfamily Hydrophiinae, which contains E. schistosa; however, effective neutralization is demonstrated within the subfamily Laticaudinae. Terrestrial tiger snake antivenom also can neutralize sea snake venom in vitro. Based on the volume of antivenom required, tiger snake antivenom was superior for neutralization of all sea snake venoms tested except that of the beaked sea snake, for which sea snake antivenom was more effective.⁷ This finding is expected because sea snake antivenom is raised against beaked sea snake venom. In contrast to volume comparisons, measurements of unit dosing demonstrate sea snake antivenom is more effective for all venoms tested. Another in vitro study comparing tiger snake and sea snake antivenom against venom E. schistosa demonstrated tiger snake antivenom was 10 times more effective in terms of milligram of venom neutralized per milliliter of antivenom.¹⁰² In the same study, the use of 17 different types of elapid antivenom resulted in poor neutralization of beaked sea snake venom.

In rescue experiments with mice using 11 sea snake venoms and 4 different antivenoms (E. schistosa, E. schistosa-N. scutatus, N. scutatus, and polyvalent sea snake L. hardwickii, L. semifasciata, H. cyanocinctus), tiger snake antivenom was superior to all others with respect to volume amount required to prevent death.^2,8,64 Another finding of the study was improved efficacy with early administration of antivenom.

No controlled human trials have evaluated the efficacy of sea snake antivenom, although case reports suggest improved outcomes and more rapid recovery with its use.^101,120 Anecdotal experience in Malaysia using sea snake antivenom suggests slow recovery from myalgias and weakness over 48 hours, compared with resolution over 2 weeks without antivenom (two cases, one control).¹¹⁹

Based on in vitro and in vivo research, selection of the optimal antivenom for treatment of sea snakebites is unclear. Both sea snake and tiger snake antivenom are effective in neutralizing a wide variety of sea snake venoms. Therefore, the most readily available antivenom should be used when needed. Commonwealth Serum Laboratories manufactures both monovalent sea snake and tiger snake antivenom for use in Australia. However, there is limited distribution to aquariums and zoos outside Australia. The manufacturer’s guidelines for use of monovalent sea snake antivenom recommend administration of one ampule (1000 units) for systemic symptoms. However, because symptoms may be delayed and early administration is more likely to result in venom neutralization, any evidence of envenomation should prompt the administration of antivenom. The antivenom requires a 1:10 dilution with 0.9% sodium chloride solution followed by administered IV over 30 minutes. A 1:5 dilution can be used for small children. Skin testing is not recommended. Epinephrine and antihistamines should be readily available. No upper limit is suggested for the number of vials to administer, although larger amounts are more likely to result in serum sickness. Patients have received up to 7000 units without adverse effect directly attributable to the antivenom.¹⁰¹ One ampule (3000 units) of tiger snake antivenom can be used as an alternative if sea snake antivenom is unavailable. Other treatments should focus on wound care, tetanus prophylaxis, analgesia, and fluid administration to minimize nephrotoxicity from myoglobinuria.

Fish

Stingrays are members of the class Chondrichthyes (order Rajiformes: skates and rays). Families include Dasyatidae (whip ray or sting ray), Urolophidae (round ray), Myliobatidae (batfish or eagle ray), Gymnuridae (butterfly ray), and Potamotrygonidae (river ray, freshwater).

Spiny fish of the family Scorpaenidae include a variety of venomous creatures (Table 119–4). Fish of the genus Pterois are commonly called lionfish (P. volitans and P. lunulata). Stonefish are grouped under the genus Synanceja and include S. trachynis (Australian estuarine stonefish), S. horrida (Indian stonefish), and S. verrucosa (reef stonefish). They are unattractively disguised to blend in with the rocky sea bottom (Fig. 119–3). Scorpionfish have a similar appearance and belong to the genus Scorpaena (eg, S. guttata: California sculpin). Other Scorpaenidae include Notesthes robusta (bullrout) and Gymnapistes marmoratus (cobbler). The European weeverfish produce toxicity similar to members of Scorpaenidae and are classified under the family Trachinidae. This includes Trachinus vipera (lesser weever) and Trachinus draco (greater weever, aka adderpike, stingfish, seacat). These bottom dwellers are smaller and have fewer spines than Scorpaenidae and are much less ghoulish in appearance. Catfish also may envenomate humans. Although most live in freshwater, marine catfish such as Plotosus lineatus can inflict injury. Other venomous spiny fish include rabbitfish, stargazers, toadfish, ratfish, and even some sharks that have spines on their dorsal fins (Port Jackson shark, dogfish shark).

History and Epidemiology.

There are 11 different species of stingrays in US coastal waters (seven in the Atlantic, four in the Pacific). In the southeastern United States, Dasyatis americana is a common inhabitant. Urolophus halleri is the most common species on the western coast of the United States. Some estimates suggest 1500 to 2000 stingray injuries occur yearly in the United States. Most envenomations occur when the animal is inadvertently stepped on. In one review a total of 17 fatalities resulting from trunk wounds, hemorrhage, or tetanus were identified worldwide.⁴⁸ Another review of 603 cases of stingray injuries identified two deaths resulting from intraabdominal trauma.¹²⁴

Three populations are at highest risk for spiny fish envenomation: fishermen sorting the catch from nets, waders, and aquarium enthusiasts. Only five deaths from Scorpaenidae have been reported; all resulted from stonefish and are poorly documented.^39,48 No deaths from stonefish are reported in Australia, a country where they are commonly found in coastal waters.⁴² The incidence of weeverfish stings is unknown, but they are a common occurrence in the summertime among Italian coastal towns.^30,133 Scorpaenidae inhabit waters throughout the tropical and temperate oceans. They exist as far north as the Gulf of Oman and Southern Japan and extend south beyond New Zealand. In the United States, Scorpaenidae stings occur in the Florida Keys, in the Gulf of Mexico, off the coast of California, and in Hawaii. Lionfish (genus Pterois) (Fig. 119–4) are common to home aquariums and account for most poison center calls involving spiny fish envenomation in the United States. The bullrout inhabits the eastern coast of Australia, along with the cobbler, which is found only in Australia. Weeverfish inhabit shallow temperate waters with sandy or muddy bottoms in the eastern Atlantic and Mediterranean, including the European Coast extending to the southern tip of Norway.²⁹ The marine catfish lives in the tropical Indo-Pacific waters.

Pathophysiology.

Tapered, bilaterally retroserrated spines covered by an integumentary sheath emanate from the stingray tail. The ventrolateral groove contains venom glands that saturate the spine with venom and mucus. The venom contains several amino acids, serotonin, 5'-nucleotidase, and phosphodiesterase.⁴ In animal models, venom induces local vasoconstriction, bradydysrhythmias, atrioventricular nodal block, subendocardial ischemia, seizures, coma, cardiovascular collapse, and death.^3,124 A rabbit model demonstrates initial vasodilation followed by vasoconstriction and cardiac standstill, suggesting a direct cardiac effect.¹²⁵ Wound specimens reveal necrotic muscle and neutrophilic infiltrates.⁶ Other reports show central hemorrhagic necrosis with surrounding lymphoid and eosinophilic infiltrates indicating an immune-mediated cause of delayed wound healing.⁶⁷

Scorpaenidae have 12 to 13 dorsal, 2 pelvic, and 3 anal spines that are covered with an integumentary sheath. Glands at the base contain 5 to 10 mg of venom each. Ornate pectoral fins are not venomous. Venom can remain stable for 24 to 48 hours after the fish dies.⁹⁶ Three main toxins have been isolated from various species of stonefish: stonustoxin (SNTX), verrucotoxin (VTX), and trachynilysin (TLY). SNTX, from S. horrida,⁶⁸ has two subunits, α and β (71,000 and 79,000 Da, respectively). It induces formation of hydrophilic pores in cell membranes.³³ Toxicity in animals includes hemolysis, local edema, vascular permeability, platelet aggregation, endothelium-dependent vasodilation, and hypotension. Decreased myocardial contractility occurs in rabbits.¹²⁸ Heating stonefish venom to 122°F (50°C) for 5 minutes prevents wound necrosis and hypotension in animal models.¹⁵³ VTX, isolated from S. verrucosa, shares homology with SNTX in that both block cardiac Ca²⁺ channels.⁶⁶ TLY, isolated from S. trachynis, is a 159-kDa protein that forms pores in cell membranes. It allows Ca²⁺ entry and causes Ca²⁺-dependent release of ACh from nerve endings at motor end plates and increased catecholamine release.^81,111,129 S. trachynis venom causes endothelium-dependent vasodilation and cardiovascular collapse in rats, which appears to be mediated by muscarinic and adrenergic receptors.³⁴ Hemolysis is demonstrated in animals but does not occur in humans.⁸⁰ Other venoms of Scorpaenidae include hyaluronidase, proteinase, phosphodiesterase, alkaline phosphomonoesterase, arginine esterase, arginine amidinase, 5'-nucleotidase, acetylcholinesterase, and biogenic amines. Crude venom from G. marmoratus, P. volitans, and S. trachynis leads to increased intracellular Ca²⁺ and muscle contracture in vivo.³⁷ Toxins from other spiny fish include dracotoxin (T. draco), trachinine (T. vipera), and nocitoxin (N. robusta).³⁶ Effects mirror those of Scorpaenidae toxins.¹³²

Clinical Manifestations.

Stepping on the body of a stingray causes a reflexive whip of the tail leading to wounds in the lower extremity. Intense pain out of proportion to the appearance of the wound is characteristic. Symptoms peak 30 to 90 minutes after injury and may persist for 48 hours. Local edema, cyanosis, erythema, and petechiae may follow rapidly and may lead to necrosis and ulceration. Systemic symptoms include weakness, nausea, vomiting, diarrhea, vertigo, headache, syncope, seizures, muscle cramps, fasciculations, hypotension, and dysrhythmias. Chest and abdominal wounds, as well as tetanus, have caused death.¹¹⁷

Stings from stonefish produce immediate, severe pain with rapid wound cyanosis and edema that may progress up the injured extremity. Pain reaches a maximum after 30 to 90 minutes and usually resolves over 6 to 12 hours, although pain may persist for days. Headache, vomiting, abdominal pain, delirium, seizures, limb paralysis, hypertension, respiratory distress, dysrhythmias, congestive heart failure, and hypotension characterize systemic toxicity.⁸³ Wound healing may require months.

A poison center case series from 1979 to 1988 identified 23 cases of P. volitans envenomation.¹⁴⁵ Reported symptoms included pain, swelling, nausea, numbness, joint pain, anxiety, headache, dizziness, and cellulitis. Another Poison Center series identified 51 Scorpaenidae stings (45 P. pterois, 6 S. guttata).⁷⁹ Intense pain was reported in 98%, extension of pain to the limb in 22%, swelling in 58%, and systemic signs (nausea, diaphoresis, dyspnea, chest pain, abdominal pain, weakness, hypotension, and syncope) in 13%. Thirteen percent of patients in the series developed wound infection; one patient’s wound healing was delayed several weeks. Stings from weeverfish are similar to Scorpaenidae envenomation and rarely result in death.¹⁴ Injury from catfish stings is comparable to that of other stinging fish.⁴⁴

Management.

Wounds inflicted by stingrays and spiny fish should be carefully examined for imbedded foreign material. Radiographs may uncover retained spines. Stingray wounds can be extensive and require surgical attention for vascular or tendonous disruption. Tetanus immune status should be addressed. Prophylactic antibiotics may decrease rates of wound infection.³⁸ In a series of 51 stings from P. pterois and S. guttata, 80% of patients had complete relief of local pain with hot water immersion.⁷⁹ Hot water produces similar relief for pain from weeverfish stings.¹²³ A review of 119 stingray envenomations demonstrates comparable efficacy with hot water immersion.³⁸ Although patients occasionally required a single dose of oral or parenteral analgesia, clinicians rarely prescribed analgesics upon discharge. In a human volunteer study in which subjects received a subcutaneous injection of stingray venom, severe pain developed immediately, and was alleviated with water heated to 122°F (50°C).¹²⁴ Pain increased with application of cold water. Local lidocaine infiltration provides an alternate modality for pain control.⁵⁹

Stonefish antivenom, an equine-derived IgG Fab fragment, is raised against the venom of S. trachynis. Each ampule contains 2000 units and neutralizes 20 mg venom. Between 1965 and 1981, antivenom was used in at least 267 cases.⁴² Anecdotal reports suggest it provides effective relief from pain.^42,154 In a review of 26 documented cases in Australia where antivenom was administered IM, no acute adverse effects were identified.¹³⁷ Two of 15 patients who had follow-up visits suffered serum sickness. Rash may develop several days postinjection.¹⁵⁴ In vitro and in vivo research with the anti­venom demonstrates neutralization of venom from G. marmoratus³⁵ and P. volitans³⁶; however, the application for human therapy remains untested.

The manufacturer recommends IM administration of stonefish antivenom, although IV administration may be considered. Administration is indicated for systemic toxicity or refractory pain. The number of puncture wounds guides therapy: one vial for one to two punctures, two vials for three to four punctures, and three vials for five or more punctures. Epinephrine and diphenhydramine should be readily available for treatment of anaphylactic reactions.

• Fatalities from marine envenomations are rare. However, significant morbidity may result from bites and stings, including severe pain, retained foreign bodies, infection, respiratory compromise, hemodynamic instability, and a variety of other end organ toxicities.

• Special attention is required when treating envenomations inflicted by box jellyfish or sea snakes. These injuries are not uncommon and may result in serious harm or even death. Knowledge of the clinical manifestations and available antidotes may reduce morbidity.

• A thorough understanding of the mechanisms of toxicity and expected clinical course following envenomations from marine creatures will provide clinicians with the ability to manage these injuries effectively.

• Interventions should focus on patient comfort and recognition of potential complications.

• Hot water immersion (HWI) may provide adequate analgesia from a number of different species of Cnidaria, as well as stings from a variety of spiny fish.

References