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PARALYTIC SHELLFISH

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Paralytic shellfish poisoning is produced by dinoflagellates (unicellular algae) Pyrodinium, Prorocentrum, Gymnodinium and Alexandrium (LaBarbera-Sanchez et al, 2004; Goldfrank et al, 2002; Chen & Chou, 2001; Durborow, 1999; de Carvalho et al, 1998) .
    B) PSP toxins are a group of 21 structurally related neurotoxins, and are among the most common and deadly phycotoxins (van den Top et al, 2001; Chen & Chou, 2001). Because dinoflagellates can occur in tropical and moderate climate zones, shellfish can accumulate these toxins worldwide. These toxins effect the central nervous system and can produce muscular nerve block (HSDB , 2002).
    C) Saxitoxins are a family of water-soluble neurotoxins, and are the best-known component of the PSP toxin group. In general, most toxic shellfish contain a mixture of several saxitoxins, which are dependent on the species of algae, geographic area and type of marine animal involved (Lehane, 2001).
    D) NOTE: Neurotoxin shellfish poisoning is similar to, but less severe than paralytic shellfish poisoning. Paralysis is usually not seen (Dembert et al, 1981).
    E) Paralytic shellfish poisoning is often associated with "red tide" blooms, but may occur with or without the red tide (Lehane, 2001). These algal blooms are a natural phenomena triggered by a series of events, which can include human pollution. Over 300 phytoplankton species produce "red tides", but only 60 to 70 species are actually harmful (Velez et al, 2001).

Specific Substances

    A) Shellfish associated with paralytic shellfish poisoning
    1) Alaskan butter clam
    2) Atlantic thorny oyster (paralytic shellfish poisoning)
    3) Aulacomya ater (Chilean bivalve ribbed mussel)
    4) Australian xanthid crab (Eriphia sebana)
    5) Clam (paralytic shellfish poisoning)
    6) Clinocardium nuttalli (cockles)
    7) Cockles (paralytic shellfish poisoning)
    8) Fish poisoning, paralytic shellfish
    9) Gtx iv
    10) Littleneck clams
    11) Mussels (paralytic shellfish poisoning)
    12) Mytilus californianus (Californian sea mussel)
    13) Mytilus edulis (toxic mussel)
    14) Nassarius papillosus (gastropod)
    15) Oyster (paralytic shellfish poisoning)
    16) Placopecten magellanicus (sea scallop)
    17) Protothaca staminea (littleneck clam)
    18) Pufferfish (southeastern US Atlantic coast; paralytic shellfish poisoning)
    19) Razor clams
    20) Sand crabs
    21) Saxidomus gigantus (Alaskan butterclam)
    22) Scallop (paralytic shellfish poisoning)
    23) Siliqua patula (razor clam)
    24) Top shells
    25) Turban shells
    26) Univalve mollusks
    27) Xanthid crabs
    28) Whelks
    Dinoflagellates associated with paralytic shellfish poisoning
    1) Alexandrium tamarense (dinoflagellate)
    2) Gymnodinium catenatum (dinoflagellate)
    3) Gonyaulax
    4) Gonyaulax acatenella
    5) Gonyaulax catenella
    6) Gonyaulax tamarensis
    7) Prorocentrum gracile (dinoflagellate)
    8) Protogonyaulax
    9) Pyrodinium bahamense
    10) Pyrodinium bahamense var. compressa
    11) Pyrodinium phoneus
    Freshwater cyanobacteria associated with paralytic shellfish poisoning
    1) Aphanizomenon (freshwater cyanobacteria)
    2) Aphanizomenon gracile (freshwater cyanobacteria)
    3) Aphanizomenon issatscnkoi (Europe; freshwater cyanobacteria)
    4) Anabena circinalis (Australia; freshwater cyanobacteria)
    5) Lyngbya wollei (U.S.; freshwater cyanobacteria)
    Saxitoxin
    1) STX
    2) Mussel poison dihydrochloride
    3) Clam poison dihydrochloride
    4) Gonyaulax toxic dihydrochloride
    5) Paralytic shellfish poison
    6) Paralytic shellfish poisoning
    7) PSP (Paralytic Shellfish Poisoning)
    8) Shellfish, paralytic poisoning
    9) Mytil otoxin
    Gonyautoxin I
    1) GTX I
    2) 11-hydroxy saxitoxin sulfate
    Gonyautoxin II
    1) GTX II
    2) 11-hydroxy saxitoxin sulfate (beta epimer)
    Gonyautoxin III
    1) GTX III
    2) 11-hydroxy neosaxitoxin sulfate
    Gonyautoxin IV
    1) GTX IV; 11-hydroxy
    2) 11-hydroxy neosaxitoxin sulfate (beta epimer)
    Neosaxitoxin
    1) neo-STX
    2) 1-hydroxysaxitoxin

Available Forms Sources

    A) SOURCES
    1) Dinoflagellates are the major food source for molluscs. When toxic dinoflagellates increase in number and are ingested by molluscs, the neurotoxins (saxitoxin, gonyautoxin, neosaxitoxin, and its derivatives) are concentrated in their tissues, but the molluscs are unaffected. As dinoflagellates proliferate ("bloom"), they often impart a reddish-brown discoloration to the water, ie "red tide". However, "red tide" can be caused by nontoxic dinoflagellate species; and shellfish may become toxic in the absence of "red tide". Ingestion of shellfish contaminated by dinoflagellates or algae may cause paralytic, neurotoxic , and amnestic symptoms. The toxins are water soluble and heat stable. The toxins may be absorbed through mucous membranes and small intestine (Evans, 1972; Henderson et al, 1973) .
    2) PSP results from the consumption of mussels, clams and oysters that have consumed toxic dinoflagellates. Dinoflagellates are plankton that are used as food for a large number of marine animals (LaBarbera-Sanchez et al, 2004; Lehane, 2001; Louzao et al, 2001; van den Top et al, 2001; Morse, 1977).
    3) The toxins (e.g., saxitoxin) are concentrated in the digestive glands of bivalve shellfish (i.e., mussels, oysters and clams) (Morse, 1977; Lehane, 2001). In abalone the toxins are also concentrated in the epipodial fringe. Scrubbing can remove significant amounts of toxin in abalone because it removes epithelium where the toxins appear to be concentrated (Pitcher et al, 2001).
    4) Species infected by the dinoflagellate include: mussels, clams, oysters, scallops, univalve mollusks, starfish, limpets, sand crabs, whelks, turban shells, top shells, xanthid crabs, and various fish. When toxic dinoflagellates increase in number and are ingested by bivalve molluscs, the neurotoxins are concentrated in their tissues, but the molluscs are unaffected. Ingestion of shellfish contaminated by dinoflagellates or algae may cause paralytic, neurotoxic, and amnestic symptoms (LaBarbera-Sanchez et al, 2004; de Carvalho et al, 1998; Morse, 1977; Anon, 1984). In addition, predators of bivalve molluscs, such as scavenging shellfish, crabs, lobsters, and fish may also be saxitoxin vectors (Lehane, 2001).
    5) In most countries, the permitted content for PSP toxins in bivalve molluscs is 80 micrograms/100 grams (van den Top et al, 2001; Louzao et al, 2001).
    6) PUFFERFISH: PSP toxins have been responsible for outbreaks of illness following pufferfish ingestion world wide (e.g., the United States, Bangladesh and the Philippines) (Landsberg et al, 2006; CDC, 2002; Sato et al, 2000; Mahmud et al, 2000) .
    a) Although most pufferfish caught in US waters are not known to be toxic, several of the approximately 100 species of pufferfish contain neurotoxins. Since January 2002, 10 cases (5 from Florida, 3 from New Jersey, and 2 from Virginia) of PSP have been reported after the ingestion of pufferfish from the Titusville, Florida area. Pufferfish are known to eat molluscs, which might result in an accumulation of the neurotoxin. All cases recovered (CDC, 2002).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) WITH POISONING/EXPOSURE
    1) CDC CASE DEFINITIONS
    a) BACKGROUND
    1) Harmful algal blooms are fast growing algae that are found worldwide, which can have a negative impact on the environment, as well as the health and safety of humans and animals. As part of the ongoing efforts by the Centers for Disease Control and Prevention (CDC), the Harmful Algal Bloom-related Illness Surveillance System (HABISS) collects data on the effects to human and animal health due to the potential environmental impact of HABs. It has developed case definitions for harmful algal bloom (HABs) toxin-related diseases as part of their national surveillance efforts to support public health decision-making. The following has been created to identify pertinent information related to a potential exposure to HABs. For further information regarding the reporting of suspected human illness due to HABs, please contact: Lorraine C. Backer, PhD, MPH, Senior Scientist and Team Lead, National Center for Environmental Health, CDC, Atlanta, GA at lfb9@cdc.gov or Rebecca LePrell, MPH, HABISS Coordinator, National Center for Environmental Health, CDC, at gla7@cdcd.gov.
    b) ACUTE SYMPTOMS
    1) HEENT: Nystagmus (eye muscle twitch, can be indicator of vestibular nerve damage), temporary blindness, iridoplegia, jaw and facial muscle incoordination or paralysis, loss of gag reflex, immobilization of the tongue, dysphagia and difficulty speaking. All of these are typically late findings in poisoning.
    2) CARDIOVASCULAR: Tachycardia, occasionally hypertension or hypotension, and chest pain.
    3) RESPIRATORY: Respiratory distress and death due to respiratory paralysis may occur within the first 12 hours.
    4) NEUROLOGIC: Initially, paresthesias ("pins and needles") and numbness of lips, tongue, face, neck, and extremities may occur. Other symptoms reported may include ataxia, flaccid paralysis, headaches, dizziness, giddiness, drowsiness, and sensation of lightness.
    5) PUFFERFISH exposure: Symptoms include nausea and vomiting.
    c) CHRONIC SYMPTOMS (Greater than 3 months)
    1) Muscle weakness may last for weeks.
    d) FATALITY RATE
    1) 1% to 14%. NOTE: Fatality rate is dependent on access to advanced medical care (primarily cardiopulmonary support).
    e) TIME TO ONSET OF SYMPTOMS
    1) Minutes to hours (less than 24) after eating contaminated food.
    f) DURATION
    1) May last days. Some symptoms (eg, generalized weakness, muscle incoordination) from pufferfish poisoning may last for weeks.
    g) CAUSATIVE ORGANISMS
    1) "Red tide" dinoflagellate, but not the same "red tide" as the Florida red tide.
    2) Marine Dinoflagellates: Gymnodimium catenatum, Pyrodinium bahamense, Pyrodinium bahamense var. compressum, Pyrodinium spp, Alexandrium spp, and Gonyaulax spp.
    3) Cyanobacteria from fresh water: Aphanizomenon sp (US), Aphanizomenon gracile, Aphanizomenon issatscnkoi (Europe), Anabena circinalis (Australia), and Lyngbya wollei (US).
    h) TOXIN
    1) The following toxins have been associated with paralytic shellfish poisoning: Saxitoxins (18 + congeners)(STX); Saxitoxin dihydrochloride; Neosaxitoxin; a group of 21 structurally related neurotoxins; Mussel poison dihydrochloride; Clam poison dihydrochloride; Gonyaulax toxic dihydrochloride; Mytil otoxin; Gonyautoxin I (11-hydroxy saxitoxin sulfate); GII (11-hydroxy saxitoxins sulfate-beta epimer); GIII (11-hydroxy neosaxitoxin sulfate); GIV (11-hydroxy neosaxitoxin sulfate - beta epimer); Neosaxitoxin; Neo STX; 1-hydroxysaxitoxin
    i) ROUTE OF EXPOSURE
    1) Eating contaminated shellfish. Can also be found in Tetraodontidae species, such as the pufferfish. Paralytic shellfish poisoning has also been described in the blue-ringed octopus, as well as the eggs of the horseshoe crab.
    j) VECTOR
    1) Bivalve shellfish, including scallops (Placopecten magellanicus), mussels (Mytilus califonianus, M. edulis), clams (Alaskan butter clam, Saxidomus gigantus), oysters, cockles, univalve mollusks (eg, top shells, turban shells), whelks Pufferfish from southeastern US Atlantic coast (particularly Indian River Lagoon in Florida).
    2) NOTE: Saxitoxins have been found in herbivorous fish and crabs, Atlantic thorny lobster, Australian xanthid crab (Eriphia sebana).
    3) NOTE: Pufferfish can bioaccumulate high concentrations in their bodies through their diet, which includes small bivalves. In addition, the toxin appears to remain in pufferfish tissues for a long time, even during preparation.
    k) DOSE
    1) Mouse LD50 10 to 30 mcg/kg
    l) MECHANISM
    1) Sodium channel blocker that is similar to tetrodotoxin. It blocks action potentials in nerves by binding to the pores of the voltage-gated, fast sodium channels in nerve cell membranes, essentially preventing any affected nerve cells from firing by blocking the channels used in the process.
    m) LIKELY GEOGRAPHIC DISTRIBUTION
    1) Temperate marine areas worldwide, including east and west coasts of the US and Canada, the area around Japan, Taiwan, area from southern Norway to Spain, Australia, British Columbia, South Africa (abalone), Patagonia and Guatemala.
    2) Temperate freshwaters, Southeastern US coast
    3) Geographic distribution of the relevant HABs can be found at the "Woods Hole Oceanographic Institution" website.
    n) DIFFERENTIAL DIAGNOSIS
    1) Other marine toxin poisonings (eg, neurotoxic, diarrheic, amnesic, or azaspiracid shellfish poisoning; pectenotoxin poisoning), scombroid fish poisoning, pesticide poisoning including organophosphate poisoning, cholinesterase inhibitor poisoning, microbial food poisonings and food allergies.
    o) DIAGNOSIS
    1) Usually based on characteristic symptoms and a recent history of eating bivalve mollusks. Confirmation of the suspected food source by a variety of methods generally provides supportive evidence of exposure. NOTE: Saxitoxin is water-soluble and may be difficult to detect.
    p) SUSPECT CASE
    1) History of recent consumption of fish or shellfish and rapid onset of neurologic symptoms with or without accompanying gastrointestinal symptoms.
    q) CONFIRMED CASES
    1) Suspect cases along with confirmation of toxin in fish or shellfish or clinical symptoms.
    r) ANIMAL SENTINEL DATA
    1) Fish kills, cetaceans
    s) REFERENCE
    1) (HABISS Work-Group et al, Jan 12, 2009)

Laboratory Monitoring

    A) There are no specific laboratory tests that are useful in the diagnosis of paralytic shellfish poisoning.
    1) In patients who are symptomatic, careful attention to hemodynamics as well as respiratory status should be instituted. A chemistry panel as well as monitoring of urine output may be considered if the patient has had nausea/emesis where electrolytes may be a concern.
    B) Confirmation of the suspected food source by a variety of methods generally provides supportive evidence of exposure; however, it does not contribute to the immediate care of the patient, but may be obtained for epidemiologic purposes.
    C) EMG may show marked prolongation of distal motor and sensory latencies, decreased conduction velocities, and reduced motor and sensory amplitudes.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) The use of gastrointestinal decontamination often are of limited utility with paralytic shellfish poisoning. Patients often present with symptoms much later after their ingestion. A dose of activated charcoal may be considered if there are no contraindications (ie, altered mental status, respiratory failure), along with early presentation.
    B) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    C) Maintain hydration with normal saline with a target urine output of 1 to 2 milliliters/kilogram/hour.
    D) In symptomatic patients, their serum electrolytes, BUN, creatinine, calcium, magnesium, phosphorous, urine output, CPK, ECG, pulse oximetry, cardiac rhythm should be monitored closely.
    E) HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine (5 to 20 mcg/kg/min) or norepinephrine (ADULT: begin infusion at 0.5 to 1 mcg/min; CHILD: begin infusion at 0.1 mcg/kg/min); titrate to desired response.
    F) DYSRHYTHMIAS OR CONDUCTION ABNORMALITIES
    1) Seizures may occur, typically from hypoxia and not from the toxin. A benzodiazepine should be considered first-line in the event of a seizure.
    2) Lidocaine should be considered in cases of dysrhythmias and ventricular conduction delays (ADULT - 1 to 1.5 mg/kg IV push followed by maintenance infusion of 1 to 4 mg/min; CHILD - 1 mg/kg IV bolus followed by a continuous infusion of 20 to 50 mcg/kg/min).
    G) Most patients recover with supportive care alone. Monitor for respiratory depression, patients with significant neurotoxicity may need endotracheal intubation and mechanical ventilation.

Range Of Toxicity

    A) The toxic and lethal doses for humans are represented by various authors as follows: (1) mild case can be caused by ingesting 1 mg of toxin (equivalent to five poisonous mussels or clams weighting about 150 g each); (2) 2 mg of toxin causes moderate illness; and (3) 3 mg causes severe symptoms. Four milligrams could be lethal if no treatment were provided, although this is based on only history and case reports.
    B) An estimated lethal dose is 500 mcg, but patients have survived ingesting meat contaminated with 43 mg of paralytic shellfish poison/100 g of meat.
    C) Toxicity has been reported with intake estimated to be as low as 124 mcg.

Clinical Effects

Summary Of Exposure

    A) WITH POISONING/EXPOSURE
    1) CDC CASE DEFINITIONS
    a) BACKGROUND
    1) Harmful algal blooms are fast growing algae that are found worldwide, which can have a negative impact on the environment, as well as the health and safety of humans and animals. As part of the ongoing efforts by the Centers for Disease Control and Prevention (CDC), the Harmful Algal Bloom-related Illness Surveillance System (HABISS) collects data on the effects to human and animal health due to the potential environmental impact of HABs. It has developed case definitions for harmful algal bloom (HABs) toxin-related diseases as part of their national surveillance efforts to support public health decision-making. The following has been created to identify pertinent information related to a potential exposure to HABs. For further information regarding the reporting of suspected human illness due to HABs, please contact: Lorraine C. Backer, PhD, MPH, Senior Scientist and Team Lead, National Center for Environmental Health, CDC, Atlanta, GA at lfb9@cdc.gov or Rebecca LePrell, MPH, HABISS Coordinator, National Center for Environmental Health, CDC, at gla7@cdcd.gov.
    b) ACUTE SYMPTOMS
    1) HEENT: Nystagmus (eye muscle twitch, can be indicator of vestibular nerve damage), temporary blindness, iridoplegia, jaw and facial muscle incoordination or paralysis, loss of gag reflex, immobilization of the tongue, dysphagia and difficulty speaking. All of these are typically late findings in poisoning.
    2) CARDIOVASCULAR: Tachycardia, occasionally hypertension or hypotension, and chest pain.
    3) RESPIRATORY: Respiratory distress and death due to respiratory paralysis may occur within the first 12 hours.
    4) NEUROLOGIC: Initially, paresthesias ("pins and needles") and numbness of lips, tongue, face, neck, and extremities may occur. Other symptoms reported may include ataxia, flaccid paralysis, headaches, dizziness, giddiness, drowsiness, and sensation of lightness.
    5) PUFFERFISH exposure: Symptoms include nausea and vomiting.
    c) CHRONIC SYMPTOMS (Greater than 3 months)
    1) Muscle weakness may last for weeks.
    d) FATALITY RATE
    1) 1% to 14%. NOTE: Fatality rate is dependent on access to advanced medical care (primarily cardiopulmonary support).
    e) TIME TO ONSET OF SYMPTOMS
    1) Minutes to hours (less than 24) after eating contaminated food.
    f) DURATION
    1) May last days. Some symptoms (eg, generalized weakness, muscle incoordination) from pufferfish poisoning may last for weeks.
    g) CAUSATIVE ORGANISMS
    1) "Red tide" dinoflagellate, but not the same "red tide" as the Florida red tide.
    2) Marine Dinoflagellates: Gymnodimium catenatum, Pyrodinium bahamense, Pyrodinium bahamense var. compressum, Pyrodinium spp, Alexandrium spp, and Gonyaulax spp.
    3) Cyanobacteria from fresh water: Aphanizomenon sp (US), Aphanizomenon gracile, Aphanizomenon issatscnkoi (Europe), Anabena circinalis (Australia), and Lyngbya wollei (US).
    h) TOXIN
    1) The following toxins have been associated with paralytic shellfish poisoning: Saxitoxins (18 + congeners)(STX); Saxitoxin dihydrochloride; Neosaxitoxin; a group of 21 structurally related neurotoxins; Mussel poison dihydrochloride; Clam poison dihydrochloride; Gonyaulax toxic dihydrochloride; Mytil otoxin; Gonyautoxin I (11-hydroxy saxitoxin sulfate); GII (11-hydroxy saxitoxins sulfate-beta epimer); GIII (11-hydroxy neosaxitoxin sulfate); GIV (11-hydroxy neosaxitoxin sulfate - beta epimer); Neosaxitoxin; Neo STX; 1-hydroxysaxitoxin
    i) ROUTE OF EXPOSURE
    1) Eating contaminated shellfish. Can also be found in Tetraodontidae species, such as the pufferfish. Paralytic shellfish poisoning has also been described in the blue-ringed octopus, as well as the eggs of the horseshoe crab.
    j) VECTOR
    1) Bivalve shellfish, including scallops (Placopecten magellanicus), mussels (Mytilus califonianus, M. edulis), clams (Alaskan butter clam, Saxidomus gigantus), oysters, cockles, univalve mollusks (eg, top shells, turban shells), whelks Pufferfish from southeastern US Atlantic coast (particularly Indian River Lagoon in Florida).
    2) NOTE: Saxitoxins have been found in herbivorous fish and crabs, Atlantic thorny lobster, Australian xanthid crab (Eriphia sebana).
    3) NOTE: Pufferfish can bioaccumulate high concentrations in their bodies through their diet, which includes small bivalves. In addition, the toxin appears to remain in pufferfish tissues for a long time, even during preparation.
    k) DOSE
    1) Mouse LD50 10 to 30 mcg/kg
    l) MECHANISM
    1) Sodium channel blocker that is similar to tetrodotoxin. It blocks action potentials in nerves by binding to the pores of the voltage-gated, fast sodium channels in nerve cell membranes, essentially preventing any affected nerve cells from firing by blocking the channels used in the process.
    m) LIKELY GEOGRAPHIC DISTRIBUTION
    1) Temperate marine areas worldwide, including east and west coasts of the US and Canada, the area around Japan, Taiwan, area from southern Norway to Spain, Australia, British Columbia, South Africa (abalone), Patagonia and Guatemala.
    2) Temperate freshwaters, Southeastern US coast
    3) Geographic distribution of the relevant HABs can be found at the "Woods Hole Oceanographic Institution" website.
    n) DIFFERENTIAL DIAGNOSIS
    1) Other marine toxin poisonings (eg, neurotoxic, diarrheic, amnesic, or azaspiracid shellfish poisoning; pectenotoxin poisoning), scombroid fish poisoning, pesticide poisoning including organophosphate poisoning, cholinesterase inhibitor poisoning, microbial food poisonings and food allergies.
    o) DIAGNOSIS
    1) Usually based on characteristic symptoms and a recent history of eating bivalve mollusks. Confirmation of the suspected food source by a variety of methods generally provides supportive evidence of exposure. NOTE: Saxitoxin is water-soluble and may be difficult to detect.
    p) SUSPECT CASE
    1) History of recent consumption of fish or shellfish and rapid onset of neurologic symptoms with or without accompanying gastrointestinal symptoms.
    q) CONFIRMED CASES
    1) Suspect cases along with confirmation of toxin in fish or shellfish or clinical symptoms.
    r) ANIMAL SENTINEL DATA
    1) Fish kills, cetaceans
    s) REFERENCE
    1) (HABISS Work-Group et al, Jan 12, 2009)

Vital Signs

    3.3.3) TEMPERATURE
    A) WITH POISONING/EXPOSURE
    1) Fever has been associated with PSP in some cases (HSDB , 2002).

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) BLINDNESS: Temporary blindness has been reported with PSP (Sakamoto et al, 1987; Rodrigue et al, 1990; Lehane, 2001).
    2) NYSTAGMUS: May be seen with PSP (de Carvalho et al, 1998; Sakamoto et al, 1987).
    3) OPHTHALMOPLEGIA and iridoplegia may be seen after PSP ingestion (Long et al, 1990).
    3.4.6) THROAT
    A) WITH POISONING/EXPOSURE
    1) MUSCLE INCOORDINATION OR PARALYSIS: May make swallowing or speech difficult (pp 1-2; Sakamoto et al, 1987).
    2) Jaw and facial muscle paralysis, loss of gag reflex, and immobilization of the tongue has been seen after PSP exposure (Long et al, 1990; MMWR, 1991).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) TACHYARRHYTHMIA
    1) WITH POISONING/EXPOSURE
    a) Tachycardia has been reported in PSP cases (Sakamoto et al, 1987; CDC, 2002).
    B) ELECTROCARDIOGRAM ABNORMAL
    1) WITH POISONING/EXPOSURE
    a) T-wave changes have been seen in the ECGs of PSP patients (Sakamoto et al, 1987). Often nonspecific and not typically associated with cardiac ischemia.
    C) HYPERTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) Hypertension may occur after PSP (Gessner & Middaugh, 1995; Lehane, 2001; CDC, 2002).
    b) CASE REPORT: A 65-year-old woman developed hypertension (bpm 160/70) after PSP that was associated with eating a contaminated pufferfish (CDC, 2002).
    c) CASE REPORT: A 28-year-old man developed severe hypertension that peaked at 244/131 mmHg approximately 11 to 12 hours after ingesting mussels contaminated with PSP toxins (Gessner et al, 1997).
    D) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) Hypotension may occur from either central or peripheral causes. The hypotension appears to be less severe and more transitory than with tetrodotoxin (Anon, 1984).
    b) CASE REPORTS: Four men presented with oral paresthesias and vomiting approximately 5 minutes after ingesting two raw ribbed mussels contaminated with PSP toxins, later identified as Gonyautoxins. Over the next 40 minutes, the patients developed hypotension and progressive respiratory failure, necessitating mechanical ventilation. Approximately 4 hours after beginning treatment with hydration, dobutamine, furosemide, and ranitidine, the clinical status of all four patients improved, with resolution of signs and symptoms approximately 12 hours after onset (Garcia et al, 2005).
    E) CHEST PAIN
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 65-year-old woman developed chest pain and mild tachycardia after PSP that was associated with eating a contaminated pufferfish (CDC, 2002).
    3.5.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) CARDIAC FAILURE
    a) In studies conducted on frogs, the PSP toxin had a direct effect on the heart and its conduction system. It produced a slight decrease in heart rate and contractile force with severe bradycardia and bundle branch block or complete cardiac failure. The poison also provoked prompt, but reversible depression in the contractility of isolated cat papillary muscle (Klaassen et al, 1996).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) ACUTE RESPIRATORY INSUFFICIENCY
    1) WITH POISONING/EXPOSURE
    a) Respiratory failure may be seen due to paralysis of the respiratory muscle (Acres & Gray, 1978; Long et al, 1990).
    b) INCIDENCE: In a series of 117 patients with paralytic shellfish poisoning, 4 patients required endotracheal intubation (Gessner & Middaugh, 1995).
    c) CASE REPORT: Approximately 4 to 6 hours after PSP, a 65-year-old woman developed an ascending muscular paralysis. Respiratory function indicated carbon dioxide retention along with a rapid decrease in vital capacity. The patient was electively intubated and ventilated. Over the next day, reflexes and voluntary movement returned. The patient was successfully extubated at 72 hours and discharged to home (CDC, 2002).
    d) CASE REPORT: A 28-year-old man developed paresthesias, nausea and vomiting an hour or two after eating a meal of PSP contaminated muscles. He then developed a severe headache, dysarthria, dysphagia, ataxia and hypertension (172/110). Fifteen minutes after presentation to an emergency department he abruptly became apneic, with dilated sluggishly reactive pupils, no response to pain or voice and no deep tendon reflexes. Hypertension persisted and he remained completely unresponsive for approximately 4 hours. He gradually regained strength and movement and was extubated, and by 32 hours after presentation was complaining only of weakness (Gessner et al, 1997).
    e) CASE REPORTS: Four men presented with oral paresthesias and vomiting approximately 5 minutes after ingesting two raw ribbed mussels contaminated with PSP toxins, later identified as Gonyautoxins. Over the next 40 minutes, the patients developed hypotension and progressive respiratory failure, necessitating mechanical ventilation. Approximately 4 hours after beginning treatment with hydration, dobutamine, furosemide, and ranitidine, the clinical status of all four patients improved, with resolution of signs and symptoms approximately 12 hours after onset (Garcia et al, 2005).
    f) CASE REPORT: A man developed paresthesia of hands, feet, face and tongue about 20 minutes after ingesting 12 fresh cooked wild mussels (Mytilus galloprovincialis). He presented to a healthcare facility within 3 hours of ingesting the mussels with paresthesias, clumsiness, limb muscle weakness, vertigo, and slurred speech. Physical examination revealed decreased lung air entry (a peak expiratory flow rate of 210 L/min and arterial oxygen saturation of 96% on room air) and bilateral wheezing, diplopia with gaze to his left, mildly reduced power bilaterally in flexion of his elbows and fingers, and signs of cerebellar dysfunction (bilateral hypermetria and dysdiadochokinesis). His symptoms gradually improved and he was discharged 31 hours postingestion (Turnbull et al, 2013).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM FINDING
    1) WITH POISONING/EXPOSURE
    a) Giddiness, dizziness, drowsiness, impaired consciousness, incoherent speech, aphasia and a feeling of lightness (ie, floating sensation) have been described after PSP (Garcia et al, 2005; HSDB , 2002; Lehane, 2001). Symptoms can begin with 30 minutes of shellfish ingestion (Lehane, 2001).
    b) CASE REPORT: A man developed paresthesia of hands, feet, face and tongue about 20 minutes after ingesting 12 fresh cooked wild mussels (Mytilus galloprovincialis). He presented to a healthcare facility within 3 hours of ingesting the mussels with paresthesias, clumsiness, limb muscle weakness, vertigo, and slurred speech. Physical examination revealed decreased lung air entry (a peak expiratory flow rate of 210 L/min and arterial oxygen saturation of 96% on room air) and bilateral wheezing, diplopia with gaze to his left, mildly reduced power bilaterally in flexion of his elbows and fingers, and signs of cerebellar dysfunction (bilateral hypermetria and dysdiadochokinesis). His symptoms gradually improved and he was discharged 31 hours postingestion (Turnbull et al, 2013).
    B) PARESTHESIA
    1) WITH POISONING/EXPOSURE
    a) Paresthesias and a "pins and needles" feeling may be felt (de Carvalho et al, 1998; Anon, 1976; Long et al, 1990; MMWR, 1991). Numbness of the lips, tongue, and throat may occur within minutes. This may spread to the fingertips, legs, arms, and neck (Acres & Gray, 1978; Rodrigue et al, 1990; MMWR, 1991).
    b) CASE REPORT: A man developed paresthesia of hands, feet, face and tongue about 20 minutes after ingesting 12 fresh cooked wild mussels (Mytilus galloprovincialis). He presented to a healthcare facility within 3 hours of ingesting the mussels with paresthesias, clumsiness, limb muscle weakness, vertigo, and slurred speech. Physical examination revealed decreased lung air entry (a peak expiratory flow rate of 210 L/min and arterial oxygen saturation of 96% on room air) and bilateral wheezing, diplopia with gaze to his left, mildly reduced power bilaterally in flexion of his elbows and fingers, and signs of cerebellar dysfunction (bilateral hypermetria and dysdiadochokinesis). His symptoms gradually improved and he was discharged 31 hours postingestion (Turnbull et al, 2013).
    c) CASE SERIES: Of 10 cases of PSP associated with pufferfish ingestion that originated from the Titusville, Florida region, all cases experienced symptoms of tingling in the mouth and lips or fingertips and numbness. Mouth numbness was reported for over 2 weeks in a 50-year-old male (CDC, 2002).
    d) INCIDENCE: In a series of 117 patients with paralytic shellfish poisoning, 113 (97%) had paresthesias, 64 (55%) had perioral numbness, 61 (52%) had perioral tingling, and 43 (37%) had extremity tingling (Gessner & Middaugh, 1995).
    e) Two fisherman, who ingested 7 to 9 ribbed mussels (Aulacomya ater), developed nausea, paresthesia, muscular weakness, and paralysis, and died 3 to 4 hours post-ingestion. Postmortem analysis of tissues and body fluids identified PSP toxins, including saxitoxin, neo-saxitoxin, and gonyautoxins (Garcia et al, 2004).
    f) CASE REPORTS: Four men presented with oral paresthesias and vomiting approximately 5 minutes after ingesting 2 raw ribbed mussels contaminated with PSP toxins, later identified as Gonyautoxins. Over the next 40 minutes, the patients developed hypotension and progressive respiratory failure, necessitating mechanical ventilation. Approximately 4 hours after beginning treatment with hydration, dobutamine, furosemide, and ranitidine, the clinical status of all four patients improved, with resolution of signs and symptoms approximately 12 hours after onset (Garcia et al, 2005).
    C) ATAXIA
    1) WITH POISONING/EXPOSURE
    a) Incoordination may progress to ataxia and dysmetria (de Carvalho et al, 1998; Acres & Gray, 1978).
    b) INCIDENCE: In a series of 117 patients with paralytic shellfish poisoning, 32 (27%) had ataxia (Gessner & Middaugh, 1995).
    D) NEUROPATHY
    1) WITH POISONING/EXPOSURE
    a) Marked prolongation of distal motor and sensory latencies, decreased conduction velocities, and reduced motor and sensory amplitudes have been seen following saxitoxin exposure (Long et al, 1990).
    b) CASE SERIES: Of 10 cases of PSP associated with pufferfish ingestion that originated from the Titusville, Florida region, all cases experienced peripheral neuropathy (CDC, 2002).
    E) HEADACHE
    1) WITH POISONING/EXPOSURE
    a) Headache may occur in cases of PSP (Garcia et al, 2005; Lehane, 2001; Gessner et al, 1997; Rodrigue et al, 1990; pp 1-2) .
    F) ASTHENIA
    1) WITH POISONING/EXPOSURE
    a) Weakness is common and may progress to paralysis in severe cases (Garcia et al, 2005; Gessner et al, 1997; Acres & Gray, 1978)
    b) INCIDENCE: In a series of 117 patients with paralytic shellfish poisoning, 33 (28%) developed weakness and 4 developed limb paralysis (Gessner & Middaugh, 1995).
    c) Two fisherman, who ingested 7 to 9 ribbed mussels (Aulacomya ater), developed nausea, paresthesia, muscular weakness, and paralysis, and died 3 to 4 hours post-ingestion. Postmortem analysis of tissues and body fluids identified PSP toxins, including saxitoxin, neo-saxitoxin, and gonyautoxins (Garcia et al, 2004).
    G) CRANIAL NERVE DISORDER
    1) WITH POISONING/EXPOSURE
    a) Dysarthria, diplopia, dysphagia, fixed dilated pupils, and absent ciliary reflex, can develop (Gessner et al, 1997; de Carvalho et al, 1998). In severe cases, the patient may appear to be brain dead (Gessner et al, 1997).
    b) INCIDENCE: In a series of 117 patients with paralytic shellfish poisoning, 19 (16%) had diplopia, 16 (14%) had dysarthria, and 6 had dysphagia (Gessner & Middaugh, 1995).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH POISONING/EXPOSURE
    a) Although nausea and vomiting may occur after ingestion (Garcia et al, 2005; Garcia et al, 2004; CDC, 2002; Akaeda et al, 1998; MMWR, 1991; Long et al, 1990; Anon, 1983) , symptoms may not occur in all cases of PSP (Lehane, 2001).
    b) INCIDENCE: In a series of 117 patients with paralytic shellfish poisoning, 45 (38%) had nausea and 34 (29%) had vomiting (Gessner & Middaugh, 1995).
    B) DIARRHEA
    1) WITH POISONING/EXPOSURE
    a) Diarrhea may occur with exposure (CDC, 2002; Anon, 1983).
    b) INCIDENCE: In a series of 117 patients with paralytic shellfish poisoning, 10 (9%) had diarrhea (Gessner & Middaugh, 1995).
    C) ABDOMINAL PAIN
    1) WITH POISONING/EXPOSURE
    a) Abdominal pain was reported following ingestion of ribbed mussels (Aulacomya ater) contaminated with paralytic shellfish toxins (Garcia et al, 2005).
    D) EXCESSIVE SALIVATION
    1) WITH POISONING/EXPOSURE
    a) Hypersalivation has been reported following PSP (Lehane, 2001).
    E) APTYALISM
    1) WITH POISONING/EXPOSURE
    a) INCIDENCE: In a series of 117 patients with paralytic shellfish poisoning, 23 (20%) had dry mouth (Gessner & Middaugh, 1995).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) ITCHING OF SKIN
    1) WITH POISONING/EXPOSURE
    a) Swimming in the "red tide" may produce pruritus and skin irritation. Warm fluids may feel like "cold rain" on the skin.
    B) ERUPTION
    1) WITH POISONING/EXPOSURE
    a) Rash has been reported with PSP (HSDB , 2002).
    C) EXCESSIVE SWEATING
    1) WITH POISONING/EXPOSURE
    a) Diaphoresis may occur with exposure (Lehane, 2001).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) BACKACHE
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: Lower back pain occurred in 6 out of 6 fishermen approximately 24 hours after eating mussels with saxitoxin concentrations of 24,400 mcg/100 g of raw mussel and 4280 mcg/100 g of cooked mussels. Lower back pain persisted for approximately 3.3 days (MMWR, 1991).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) There are no specific laboratory tests that are useful in the diagnosis of paralytic shellfish poisoning.
    1) In patients who are symptomatic, careful attention to hemodynamics as well as respiratory status should be instituted. A chemistry panel as well as monitoring of urine output may be considered if the patient has had nausea/emesis where electrolytes may be a concern.
    B) Confirmation of the suspected food source by a variety of methods generally provides supportive evidence of exposure; however, it does not contribute to the immediate care of the patient, but may be obtained for epidemiologic purposes.
    C) EMG may show marked prolongation of distal motor and sensory latencies, decreased conduction velocities, and reduced motor and sensory amplitudes.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) There are no specific laboratory tests that are useful in the diagnosis of paralytic shellfish poisoning. Diagnosis is based on characteristic symptoms, along with testing suspected contaminated seafood to support the diagnosis.
    a) In symptomatic patients, closely monitor serum electrolytes, BUN, creatinine, calcium, magnesium, phosphorus, urine output, and CPK.
    4.1.4) OTHER
    A) OTHER
    1) EMG
    a) EMG may show marked prolongation of distal motor and sensory latencies, decreased conduction velocities, and reduced motor and sensory amplitudes.
    2) MONITORING
    a) In patients who are symptomatic, careful attention to hemodynamics as well as respiratory status should be instituted. A chemistry panel as well as monitoring of urine output may be considered if the patient has had nausea/emesis where electrolytes may be a concern.

Methods

    A) MULTIPLE ANALYTICAL METHODS
    1) SUMMARY: Samples from suspected contaminated seafood may be tested with a variety of methods.
    2) Saxitoxin can be separable from neosaxitoxin by careful gradient ion-exchange chromatography (Oshima et al, 1977). HPLC, liquid chromatography-mass spectrometry, immunoaffinity chromatography (IAC) or capillary electrophoresis methods have also been developed to evaluate seafood and environmental samples (Garcia et al, 2004; Louzao et al, 2001; Usleber et al, 2001; Jaime et al, 2001; CDC, 2002; Garthwaite, 2000; Laycock et al, 1994).
    3) In one study, hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) with positive electrospray ionization (ESI) methods were used to quantitatively determine PSP toxins in sea foods (Zhuo et al, 2013).
    4) Lawrence & Niedzwiadek (2001) described the use of prechromatographic oxidation and liquid chromatography with fluorescence detection for the quantitative determination of selected PSP toxins in shellfish samples. This method is designed to evaluate seafood products based on regulatory guidelines (Lawrence & Niedzwiadek, 2001).
    5) The combination of a fluorescent assay, Folin-Ciocalteau reagent assay, and a linear gradient elution from a strong cation-exchange mini-column will allow identification of STX, GTX-1, GTX-2, GTX-3, GTX-4, and neoSTX from crude extract (Mosley et al, 1985).
    B) BIOASSAY
    1) MOUSE BIOASSAY: Most countries have either established or proposed regulatory limits for PSP toxins as they occur in seafood products. The standard AOAC (Association of Official Analytical Chemists) mouse bioassay is an approved method for determination of shellfish toxicity. More reliable and less costly methods have been used in recent years (Louzao et al, 2001).
    2) Powell & Doucette (1999) described the use of a receptor binding assay for PSP toxins using microplate scintillation technology. The test is based on a high affinity interaction between the toxins and their pharmacologic target, the voltage-gated sodium channel. The results agreed closely with the standard mouse bioassay (Powell & Doucette, 1999).
    a) The receptor assay can not be used to determine which saxitoxin congeners are present in a sample, but it can be an efficient means of assessing PSP-like toxicity. It can accommodate a diversity of sample types ranging from algal extracts to human fluids. The authors suggested that it could be an effective screening tool for use by public health officials in suspected cases of PSP exposure.
    3) Cell bioassay confirmed the presence of a sodium channel-blocking toxin that was consistent with the presence of saxitoxin in a recent outbreak of PSP (CDC, 2002).
    C) IMMUNOASSAY
    1) ENZYME IMMMUNOASSAY (EIA) is a simple and rapid test procedure that can be used as a screening tool with shellfish and other seafood (Usleber et al, 2001).
    2) COMMERCIAL QUALITATIVE ASSAY: A commercial antibody-based rapid qualitative test (MIST Alert(TM) for PSP) is available, and can be used as a screening tool for detection of PSP toxins in bivalve molluscs. The tool may also have application for use in shellfish management, and end-product testing by nonscientific personnel (Mackintosh et al, 2002).
    3) Kawatsu et al (2002) describe an enzyme immunoassay based on a monoclonal antibody against gonyautoxin that can be used for mass monitoring of shellfish.
    D) FLUOROMETRIC ASSAY
    1) Louzao et al (2001) described a fluorometric assay method that was specific, sensitive, rapid and reliable in monitoring PSP toxin levels in samples of seafood products and toxic algae. This method allows quantitation of toxins by detecting membrane potential changes in human excitable cells. Toxins bind to sodium channels with an affinity proportional to their intrinsic toxic potency. Results were found to be comparable to those of the mouse bioassay (Louzao et al, 2001).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) In one study of 150 patients, 30% were hospitalized, primarily to assure adequate airway and provide assisted ventilation (Montebruno, 1993).

Monitoring

    A) There are no specific laboratory tests that are useful in the diagnosis of paralytic shellfish poisoning.
    1) In patients who are symptomatic, careful attention to hemodynamics as well as respiratory status should be instituted. A chemistry panel as well as monitoring of urine output may be considered if the patient has had nausea/emesis where electrolytes may be a concern.
    B) Confirmation of the suspected food source by a variety of methods generally provides supportive evidence of exposure; however, it does not contribute to the immediate care of the patient, but may be obtained for epidemiologic purposes.
    C) EMG may show marked prolongation of distal motor and sensory latencies, decreased conduction velocities, and reduced motor and sensory amplitudes.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) In general, gastrointestinal decontamination is limited utility with paralytic shellfish poisoning. Patients usually present with symptoms late after their ingestion, and many patients have spontaneous vomiting. A dose of activated charcoal may be considered if there are no contraindications (ie, altered mental status, respiratory failure), and the patients presents soon after ingestion.
    B) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) In general, gastrointestinal decontamination is limited utility with paralytic shellfish poisoning. Patients usually present with symptoms late after their ingestion, and many patients have spontaneous vomiting. A dose of activated charcoal may be considered if there are no contraindications (ie, altered mental status, respiratory failure), and the patients presents soon after ingestion.
    B) ACTIVATED CHARCOAL
    1) SUMMARY - Activated charcoal has generally been recommended to block further absorption of the toxins associated with PSP (Lehane, 2001).
    2) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    3) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) There is no specific antidote. For the treatment of paralytic shellfish poisoning (PSP), management consists of early recognition as well as supportive care. Patients may be paralyzed, but are often fully conscious(Lehane, 2001).
    2) Most patients recover with supportive care alone. Monitor for respiratory depression, patients with significant neurotoxicity may need endotracheal intubation and mechanical ventilation.
    B) FLUID/ELECTROLYTE BALANCE REGULATION
    1) Replace fluid and electrolyte deficits and maintain hydration with a target urine output of 1 to 2 milliliters/kilogram/hour.
    2) Since the saxitoxin is excreted via the urine (CDC, 2002), fluid therapy can enhance renal excretion (Lehane, 2001).
    C) HYPOTENSIVE EPISODE
    1) SUMMARY
    a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
    2) DOPAMINE
    a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    3) NOREPINEPHRINE
    a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
    b) DOSE
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
    D) MONITORING OF PATIENT
    1) SUMMARY: In symptomatic patients, their hemodynamic status, acid-base, serum electrolytes, BUN, creatinine, calcium, magnesium, phosphorous, urine output, CPK, ECG, pulse oximetry, cardiac rhythm should be monitored closely.
    2) Monitor blood gases as indicated to ensure adequate oxygenation and ventilation. Lactic acidosis has been reported in experimental animals exposed to saxitoxins (Lehane, 2001).
    E) CONDUCTION DISORDER OF THE HEART
    1) LIDOCAINE
    a) LIDOCAINE/DOSE
    1) ADULT: 1 to 1.5 milligrams/kilogram via intravenous push. For refractory VT/VF an additional bolus of 0.5 to 0.75 milligram/kilogram can be given at 5 to 10 minute intervals to a maximum dose of 3 milligrams/kilogram (Neumar et al, 2010). Only bolus therapy is recommended during cardiac arrest.
    a) Once circulation has been restored begin a maintenance infusion of 1 to 4 milligrams per minute. If dysrhythmias recur during infusion repeat 0.5 milligram/kilogram bolus and increase the infusion rate incrementally (maximal infusion rate is 4 milligrams/minute) (Neumar et al, 2010).
    2) CHILD: 1 milligram/kilogram initial bolus IV/IO; followed by a continuous infusion of 20 to 50 micrograms/kilogram/minute (de Caen et al, 2015).
    b) LIDOCAINE/MAJOR ADVERSE REACTIONS
    1) Paresthesias; muscle twitching; confusion; slurred speech; seizures; respiratory depression or arrest; bradycardia; coma. May cause significant AV block or worsen pre-existing block. Prophylactic pacemaker may be required in the face of bifascicular, second degree, or third degree heart block (Prod Info Lidocaine HCl intravenous injection solution, 2006; Neumar et al, 2010).
    c) LIDOCAINE/MONITORING PARAMETERS
    1) Monitor ECG continuously; plasma concentrations as indicated (Prod Info Lidocaine HCl intravenous injection solution, 2006).

Enhanced Elimination

    A) HEMODIALYSIS
    1) Hemodialysis was reported in 2 cases. In one it appeared to aid recovery, in the other it did not (Acres & Gray, 1978). Not enough data exists to conclude whether hemodialysis is effective. Generally speaking, supportive care with focus on respiratory support is the mainstay of treatment. Based on the evidence as well as use of supportive care, extracorporeal removal cannot be recommended at this time.

Abstracts

Case Reports

    A) ADVERSE EFFECTS
    1) Typical cases may be classified into mild, moderate and severe (Anon, 1984).
    2) MILD: Paresthesias and numbness of lips, tongue, face, and neck, spreading to the fingertips and toes. Nausea, dizziness, and headache may be seen.
    3) MODERATE: Difficulty with speech; arms and legs becoming numb and tingling, then stiff and uncoordinated. There is general weakness, a feeling of lightness, rapid pulse, and some breathing difficulty.
    4) SEVERE: Muscles become paralyzed, there is severe respiratory difficulty, and a choking sensation.

Range Of Toxicity

Summary

    A) The toxic and lethal doses for humans are represented by various authors as follows: (1) mild case can be caused by ingesting 1 mg of toxin (equivalent to five poisonous mussels or clams weighting about 150 g each); (2) 2 mg of toxin causes moderate illness; and (3) 3 mg causes severe symptoms. Four milligrams could be lethal if no treatment were provided, although this is based on only history and case reports.
    B) An estimated lethal dose is 500 mcg, but patients have survived ingesting meat contaminated with 43 mg of paralytic shellfish poison/100 g of meat.
    C) Toxicity has been reported with intake estimated to be as low as 124 mcg.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) 0.5 mg is considered potentially lethal (Acres & Gray, 1978).
    2) Severe intoxications or fatalities have been reported after ingestions of 456 mcg to 1060 mcg paralytic shellfish toxin per person (Turnbull et al, 2013; Hale, 1981; Anon, 1972).
    B) CASE REPORTS
    1) An outbreak of PSP in Guatemala resulted in a 50 percent (8/16) mortality rate among children less than 6 years old. The minimum lethal dose for 1 child was 140 mouse units of toxin/kilogram body weight. (A mouse unit is about 0.18 microgram/gram of saxitoxin). Children may have been more sensitive to saxitoxin than adults or the lack of advanced life support contributed to the high fatality rate (Morse, 1977; Rodrigue et al, 1990).
    2) A native Alaskan man died of cardiopulmonary arrest 2 hours after consuming 25 to 30 steamed butter clams and 2 teaspoons of butter clam broth. Gastric contents contained 370 micrograms/100 grams of PSP toxin and the clam broth contained 2650 micrograms/100 grams of PSP toxin (MMWR, 1991).
    3) Two fisherman, who ingested 7 to 9 ribbed mussels (Aulacomya ater), developed nausea, paresthesia, muscular weakness, and paralysis, and died 3 to 4 hours post-ingestion. Post-mortem analysis of tissues and body fluids identified PSP toxins, including saxitoxin, neo-saxitoxin, and gonyautoxins (Garcia et al, 2004).

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) The toxic and lethal doses for humans are represented by various studies as follows: (1) a mild case can be caused by ingesting 1 milligram of toxin (equivalent to five poisonous mussels or clams weighing about 150 grams each); (2) 2 milligrams causes moderate illness; and (3) 3 milligrams can produce severe illness. Four milligrams could be lethal if no treatment were provided. All of these are estimates and susceptible to biologic variation (Klaassen et al, 1996).
    2) The lowest reported doses that have caused mild symptoms of paralytic shellfish poisonings are 120 and 304 mcg paralytic shellfish toxin (PST) per person (Turnbull et al, 2013).
    3) The National Shellfish Sanitation Program (NSSP) closes shellfish beds when the meats of raw shellfish contain 80 mcg of toxin per 100 grams of the edible portion of the shellfish (Hughes et al, 1977).
    B) CASE REPORTS
    1) Two brothers survived eating mussels containing 43 mg of PSP/100 grams. Good supportive care including respiratory support was required (Acres & Gray, 1978).
    2) A man developed paresthesia of hands, feet, face and tongue about 20 minutes after ingesting 12 fresh cooked wild mussels (Mytilus galloprovincialis). He presented to a healthcare facility within 3 hours of ingesting the mussels with paresthesias, clumsiness, limb muscle weakness, vertigo, and slurred speech. Physical examination revealed decreased lung air entry (a peak expiratory flow rate of 210 L/min and arterial oxygen saturation of 96% on room air) and bilateral wheezing, diplopia with gaze to his left, mildly reduced power bilaterally in flexion of his elbows and fingers, and signs of cerebellar dysfunction (bilateral hypermetria and dysdiadochokinesis). His symptoms gradually improved and he was discharged 31 hours postingestion. It was determined that the paralytic shellfish toxin intake was between 1218 and 2688 mcg with the PST concentrations of about 7.25 to 16 mg/kg, based on the estimated 168 grams of meat from 12 mussels (Turnbull et al, 2013).
    3) Severe symptoms have occurred with as little as 124 mcg of toxin (Hale, 1981; Anon, 1972).
    4) A 53-year-old woman survived eating soft-shell clams containing saxitoxin levels ranging from 2,100 to 5,300 micrograms/100 grams of clam tissue. With supportive care all neurologic deficits resolved over 5 days (Long et al, 1990).
    5) PUFFERFISH: Ten cases of PSP were associated with the ingestion of pufferfish from Titusville, Florida. All patients developed some degree of neurologic dysfunction, but complete recovery was reported in all cases (CDC, 2002).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) SAXITOXIN DIHYDROCHLORIDE
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 8 mcg/kg (RTECS , 2002)
    2) LD50- (ORAL)MOUSE:
    a) 263 mcg/kg (RTECS , 2002)

Pharmacology Toxicology

Toxicologic Mechanism

    A) Dinoflagellates are the major food source for molluscs. When toxic dinoflagellates increase in number and are ingested by molluscs, the neurotoxins (saxitoxin, gonyautoxin, neosaxitoxin, and its derivatives) are concentrated in their tissues, but the molluscs are unaffected. As dinoflagellates proliferate ("bloom"), they often impart a reddish-brown discoloration to the water e.g. "red tide." However, "red tide" can be caused by nontoxic dinoflagellate species; and shellfish may become toxic in the absence of "red tide." Ingestion of shellfish contaminated by dinoflagellates or algae may cause paralytic, neurotoxic, and amnestic symptoms. The toxins are water soluble and heat stable. The toxins may be absorbed through mucous membranes and small intestine (Evans, 1972; Henderson et al, 1973).
    B) Although each toxin exhibits a different potency, the mechanism of action remains the same. Paralytic shellfish act by blocking neuromuscular transmission by binding to the voltage-gated sodium channel, which inhibits the influx of sodium ions and prevents nerve cells from producing action potentials. This results in blockade of nerve conduction and muscle contraction. Action on sodium is reversible and results in no damage to the nerve or muscle (Evans, 1972; Henderson et al, 1973; Louzao et al, 2001). In high concentrations, cardiac muscle and smooth muscle will be inhibited (Willis & Wright, 1980).
    C) Saxitoxins are a family of water-soluble neurotoxins and are among the extremely potent (Lehane, 2001). The toxin produces neuromuscular weakness without hypotension and lacks the emetic and hypothermic action of tetrodotoxin (Klaassen et al, 1996). Saxitoxin may suppress conduction at the A-V node and inhibits the respiratory center (Acres & Gray, 1978).
    D) Saxitoxin may induce hypotension directly by action on the vascular smooth muscle, or by blocking vasomotor nerves (Kao, 1972).
    E) Respiratory depression and paralysis may be a central action, or a result of action on the peripheral nerves (Evans, 1970; Sakamoto et al, 1987).

Physicochemical

Physical Characteristics

    A) Saxitoxin is a white solid, that is tasteless and colorless. It is water soluble and heat stable, but boiling 3 to 4 hours at pH 3 causes loss of activity.
    B) Saxitoxin can not be destroyed by normal cooking or freezing methods (CDC, 2002).

Ph

    A) Saxitoxin is quite basic, having 2 titratable groups, one with a pKA of 8.24, the other 11.5 (Anon, 1984; HSDB , 2002).

Molecular Weight

    A) Saxitoxin dihydrochloride - 372.26 (HSDB , 2002)

Animal Toxicology

Clinical Effects

    11.1.1) AVIAN/BIRD
    A) Shags, terns, and cormorants developed inflammation of the gastrointestinal tract, hemorrhages in the base of the brain, and other hemorrhages (Anon, 1984).

Range Of Toxicity

    11.3.2) MINIMAL TOXIC DOSE
    A) FISH
    1) The LD50 of PSP toxin in herring, pollock, flounder, salmon, and cod range from 400 to 755 mcg/kg (Anon, 1984).

References

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