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PLANTS-OENANTHE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) The primary toxic plant in this group in Oenanthe crocata which is a member of the Umbelliferae family. Although poisonings from this plant are relatively uncommon (in one study only 13 since 1900, mostly in children) the mortality has been nearly 70% (Mitchell & Routledge, 1978). The roots gathered in spring and winter contain the highest concentrations. Although the toxins are detoxified in air, they remain stable while inside the fleshy root (Frohne & Pfander, 1983).

Specific Substances

    A) Oenanthe aquatica
    1) Fineleaf water dropwort
    2) Water-fennel
    Oenanthe crocata
    1) Hemlock Water Dropwort
    2) Dead Men's Fingers (roots)
    3) Five-fingered root (roots)
    Oenanthe javanica (Bl.) DC.
    1) Shuiqin
    Oenanthe sarmentosa
    1) Water celery
    2) Water fennel
    Oenanthetoxin
    1) OETX

Available Forms Sources

    A) FORMS
    1) OENANTHE CROCATA: Highly toxic, contains oenanthotoxin in its underground portions (Dubois & Schneider, 1981).
    a) King et al (1985) isolated 20 mg of oenanthotoxin from 200 grams of tubers. A sample gathered in Britain contained 0.06 percent oenanthotoxin.
    b) Anet et al (1953) found that the concentration of oenanthotoxin was highest in the winter and early spring.
    2) Cicutoxin (from water hemlock) is an isomer of oenanthotoxin (Mitchell & Routledge, 1978).
    3) The roots of these plants have been mistaken for the edible sweet flag (Iris species), parsnips, celery, and pig-nut (Conopodium jajus) (Mitchell & Routledge, 1978) O'Mahony et al, 1987).
    a) O.californicum: Unknown if toxic
    b) O. filiformus: Unknown if toxic
    c) O. fistulous is thought to contain agents similar in action to oenanthotoxin, called oenanthine (Goodrich & Lynn, 1928).
    d) O. javanica (Bl.) DC. extract has been tested as an anti-arrhythmic agent in rats. Intravenous injection of 3 mg/kg of the extract antagonized the arrhythmias induced by calcium chloride and aconitine (Ji et al, 1990). The plant is known to contain several glycosides, phenylpropanoids, and polyacetylenes (Fujita et al, 1995).
    e) O. lachenallii: Unknown if toxic
    f) O. Phellandrium (Lam) is thought to be toxic. The fruits may create gastritis, circulatory failure, cerebral disturbances, vertigo, intoxication, seizures, and CNS depressant effects such as coma. Ingestions may be fatal. The fruits contain 1 to 1.25% essential oil, the majority (80%) of which is phellandrene (Duke, 1985). The agent responsible for its toxicity is unknown. It is used in various parts of the world as a medical herb.
    g) O. pimpenoides: Thought to poison cattle, causing a CNS depressant type poisoning not leading to seizures (Forsyth, 1966).
    h) O. sarmentosa: The raw plant material (leaves, rhizomes, and stems) were extracted using a number of different solvents. After evaporation of the solvents, the extracts were fed to white rats and guinea pigs with no apparent toxic effect (Goodrich & Lynn, 1928).
    i) Lampe & McCann (1985) report that it is unknown if toxic.
    j) O. silaifolia has been implicated in poisoning of cattle in Greece, causing a CNS depressant type of poisoning (Aspiotis et al, 1960).
    k) O. stolonoferia has been tested as an anti-arrhythmic agent. A methanolic extract from this plant (100 mg/kg IV) was used in rats with cardiac ischemia. It reduced arrhythmias and myocardial infarct size (Zhang et al, 1995). It has not been used in humans.
    l) O. tirefolia: Unknown if toxic
    B) USES
    1) The fruits of Oenanthe aquatica (L), a herbaceous water plant found in Europe, has been shown to contain a series of C15 oxygenated polyacetylenes (Vincieri et al, 1985). This plant has been recommended for use in herbal medications for treatment of obstinate ulcers, dyspepsia, occasional fever, and chronic pectoral aliments (Guenter, 1965; Negri, 1979). Oenanthotoxin-type poisoning has not been mentioned, but this plant is suspected of causing cattle poisoning in Greece. Symptoms were of CNS depression not proceeding to seizures (Miedzobrodzki, 1960).

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) The earliest signs in humans are nausea and vomiting and hypersalivation. These may be followed by malaise, tremors, generalized seizures, and cardiopulmonary arrest. One individual experienced visual hallucinations following a grand mal seizure after ingesting O. crocata
    0.2.4) HEENT
    A) Mydriasis has been seen in some cases of poisonings.
    0.2.5) CARDIOVASCULAR
    A) Hypotension has been seen in some cases. Cardiopulmonary arrest may occur in later stages of intoxication.
    0.2.6) RESPIRATORY
    A) Respiratory arrest may be seen, and in serious cases respiratory support may be required for hours. Hyperventilation initially may lead to respiratory alkalosis.
    0.2.7) NEUROLOGIC
    A) CNS stimulation starting with tremors and leading to seizures is a hallmark of poisoning. Malaise and confusion may be seen either before or following seizures.
    0.2.8) GASTROINTESTINAL
    A) Various gastrointestinal effects may be seen, including nausea, epigastric pain and vomiting.
    0.2.10) GENITOURINARY
    A) Hematuria has rarely been observed.
    0.2.11) ACID-BASE
    A) Patients may have a respiratory alkalosis early, or be acidotic due to anoxia after respiratory arrest.
    0.2.14) DERMATOLOGIC
    A) Flushing was seen in two poisoned children.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

Laboratory Monitoring

    A) No specific laboratory measures are indicated. Patients have occasionally demonstrated elevated CPK, LDH or aldolase.
    B) Patients have rarely experienced hematuria or glycosuria.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Emesis is NOT recommended due to the rapid onset of vomiting and seizures.
    B) GASTRIC LAVAGE: Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in the head down left lateral decubitus position or by endotracheal intubation. Control any seizures first.
    1) CONTRAINDICATIONS: Loss of airway protective reflexes or decreased level of consciousness in unintubated patients; following ingestion of corrosives; hydrocarbons (high aspiration potential); patients at risk of hemorrhage or gastrointestinal perforation; and trivial or non-toxic ingestion.
    C) 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.
    D) 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.
    E) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue).
    1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
    2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.
    F) REFRACTORY SEIZURES: Consider continuous infusion of midazolam, propofol, and/or pentobarbital. Hyperthermia, lactic acidosis and muscle destruction may necessitate use of neuromuscular blocking agents with continuous EEG monitoring.

Range Of Toxicity

    A) No specific toxic amount has been determined. Below are several representative cases with amounts and primary symptoms. In many cases the amount ingested is unknown, being represented as "a meal". Often the patient has been found dead and not able to answer questions as to quantity.
    1) One tuber eaten raw, two others cooked: Vomiting, seizures, survived with anticonvulsants.
    2) "A plant bulb" caused vomiting, seizures, cardiopulmonary arrest. She survived with supportive care.
    3) Oenanthotoxin is not stable, and drying or cooking may destroy the toxin.

Clinical Effects

Summary Of Exposure

    A) WITH POISONING/EXPOSURE
    1) The earliest signs in humans are nausea and vomiting and hypersalivation. These may be followed by malaise, tremors, generalized seizures, and cardiopulmonary arrest. One individual experienced visual hallucinations following a grand mal seizure after ingesting O. crocata

Heent

    3.4.1) SUMMARY
    A) Mydriasis has been seen in some cases of poisonings.
    3.4.3) EYES
    A) MYDRIASIS has been noted in patients after ingestion of O. crocata (Egdahl, 1911, Pallares et al, 1985). In one case, the patient had been seizing and had a cardiopulmonary arrest prior to the mydriasis being noted, so the cause of this sign is somewhat unclear (Pallares et al, 1985). Mydriasis was also observed in another adult following a grand mal seizure after inadvertently ingesting O. crocata (Downs et al, 2002).
    B) MIOSIS was reported in one poisoning case, and has been observed in some animal poisonings (Mitchell & Routledge, 1978).
    C) Pupil reaction in 40 rabbits poisoned by oenanthotoxin was not consistent (Grundy & Howarth, 1956).

Cardiovascular

    3.5.1) SUMMARY
    A) Hypotension has been seen in some cases. Cardiopulmonary arrest may occur in later stages of intoxication.
    3.5.2) CLINICAL EFFECTS
    A) CARDIAC ARREST
    1) Cardiopulmonary arrest was seen in one patient who had multiple seizure episodes (Pallares et al, 1985).
    B) HYPOTENSIVE EPISODE
    1) Hypotension was noted in children who were exposed to this plant (Robson, 1965).
    3.5.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HYPOTENSION
    a) Fatally poisoned animals developed hypotension first, which progressed to severe hypertension. The hypotensive phase varied in both degree and duration. Only hypotension developed in animals that had their central nervous system destroyed (Grundy & Howarth, 1956).

Respiratory

    3.6.1) SUMMARY
    A) Respiratory arrest may be seen, and in serious cases respiratory support may be required for hours. Hyperventilation initially may lead to respiratory alkalosis.
    3.6.2) CLINICAL EFFECTS
    A) APNEA
    1) Respiratory arrest may be seen in seriously poisoned patients. Respiratory support has been required for as long as 16 hours (Pallares et al, 1985).
    B) HYPERVENTILATION
    1) Hyperventilation may occur in human poisonings and lead to an initial respiratory alkalosis (Mitchell & Routledge, 1978).
    C) ATELECTASIS
    1) Autopsies done on a human fatality who died after a period of seizures showed hemorrhages of the brain and/or the complete collapse of both lungs.

Neurologic

    3.7.1) SUMMARY
    A) CNS stimulation starting with tremors and leading to seizures is a hallmark of poisoning. Malaise and confusion may be seen either before or following seizures.
    3.7.2) CLINICAL EFFECTS
    A) SEIZURE
    1) Seizures have been seen in both humans and animals (Downs et al, 2002; Mitchell & Routledge, 1978; Thomas, 1937). Within a few minutes of an IP injection of oenanthotoxin, test animals develop either local or general tremors which advance to seizures and eventually death (Clarke et al, 1949; Grundy & Howarth, 1956).
    a) CASE REPORTS - A group of 8 adults ate what they thought was water parsnips (later determined to be Oenanthe crocata {"hemlock water dropwort"}) and, approximately 10 hours after eating, one individual had a witnessed grand mal seizure lasting about 5 minutes. Another individual in the group, also developed a grand mal seizure lasting about 3 minutes after eating a second portion of the meal containing the root on the following day. The patients recovered completely with supportive care (Downs et al, 2002).
    b) Over 500 cases of human poisoning were reported in the late 1800's and the early 1900's, with a death rate of approximately 26% to 44%. In one series of cases, 70% of those who developed seizures died (Grundy & Howarth, 1956).
    2) Most seizures occur WITHIN 30 to 60 minutes of ingestion, and are tonic or clonic muscle spasms accompanied by trismus (Mitchell & Routledge, 1978; Anger et al, 1976). In one individual, seizures did not develop until 10 hours after exposure (Downs et al, 2002).
    3) Pallares et al (1985) relate a case where 6 episodes of tonic-clonic seizures, each lasting about 2 minutes, were seen in a patient who ingested just one bulb. This patient did not lose sphincter control, or consciousness.
    B) MALAISE
    1) A generalized malaise has been noted, often prior to the onset of seizures (Pallares et al, 1985). Weakness of the lower limbs has also been reported after ingestion of a few tubers (Mitchell & Routledge, 1977).
    C) PARESTHESIA
    1) CASE REPORT - Paresthesias of the fingers was noted in one patient who had ingested one raw and two other rootlets (Mitchell & Routledge, 1977).
    D) CLOUDED CONSCIOUSNESS
    1) CASE REPORT - Slurred speech and confusion was noted in a patient who ingested 3 portions of a root (Mitchell & Routledge, 1977).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) SEIZURES
    a) Within a few minutes of an IP injection of oenanthotoxin, test animals develop either local or general tremors which advance to seizures and eventually death (Clarke et al, 1949; Grundy & Howarth, 1956).

Gastrointestinal

    3.8.1) SUMMARY
    A) Various gastrointestinal effects may be seen, including nausea, epigastric pain and vomiting.
    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) Nausea, leading to epigastric pain and vomiting, has been seen in human cases, and is often one of the early signs (Downs et al, 2002)j(Pallares et al, 1985; King et al, 1985).
    2) CASE REPORTS - A group of 8 adults ate what they thought was water parsnips (later determined to be Oenanthe crocata {"hemlock water dropwort"}), and approximately 14 hours after eating, several individuals complained of nausea and vomiting. One patient had repeated episodes of vomiting. The remainder of the group all had varying degrees of nausea and vomiting, with the severity of the symptoms dependent on the amount ingested. All cases recovered completely (Downs et al, 2002).
    B) EXCESSIVE SALIVATION
    1) Hypersalivation combined with oral damage due to seizures, may result in blood stained frothing at the mouth (King et al, 1985; Pallares et al, 1985; Thomas, 1937).

Genitourinary

    3.10.1) SUMMARY
    A) Hematuria has rarely been observed.
    3.10.2) CLINICAL EFFECTS
    A) BLOOD IN URINE
    1) Transient hematuria and glycosuria were noted in one poisoned patient (Mitchell & Routledge, 1977).

Acid-Base

    3.11.1) SUMMARY
    A) Patients may have a respiratory alkalosis early, or be acidotic due to anoxia after respiratory arrest.
    3.11.2) CLINICAL EFFECTS
    A) ACIDOSIS
    1) Patients may become acidotic secondary to respiratory failure (Pallares et al, 1985).
    2) Severe metabolic acidosis was reported in one patient who had prolonged seizures and respiratory distress (Ball et al, 1987).

Dermatologic

    3.14.1) SUMMARY
    A) Flushing was seen in two poisoned children.
    3.14.2) CLINICAL EFFECTS
    A) EXCESSIVE SWEATING
    1) Increased sweating has been noted in both human and animal exposures (Downs et al, 2002; Mitchell & Routledge, 1977).
    B) FLUSHING
    1) Flushing was noted in children poisoned by this plant (Robson, 1965).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) RHABDOMYOLYSIS
    1) Elevated CK, LDH, and aldolase has been reported in patients who developed repeated seizures (Pellares et al, 1985). The CPK in one patient who had a seizure was 11.2 uKat/L (O'Mahony et al, 1987).
    B) INCREASED MUSCLE TONE
    1) Muscular spasms and weakness have been reported in human poisonings (Mitchell & Routledge, 1978).

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    B) ANIMAL STUDIES
    1) Grundy & Howarth (1956) reported the birth of a normal live litter of rabbits one day after intentional poisoning with water dropwort and subsequent treatment with pentobarbital for seizure control. There were no birth problems reported and there was no subsequent follow-up of the litter.

Carcinogenicity

    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the carcinogenic or mutagenic potential of this agent.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No specific laboratory measures are indicated. Patients have occasionally demonstrated elevated CPK, LDH or aldolase.
    B) Patients have rarely experienced hematuria or glycosuria.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) No specific laboratory measures are indicated. Patients have occasionally demonstrated elevated CPK, LDH or aldolase (Pellares et al, 1985).
    4.1.3) URINE
    A) URINALYSIS
    1) Patients have rarely experienced hematuria or glycosuria (Mitchell & Routledge, 1977).

Methods

    A) MULTIPLE ANALYTICAL METHODS
    1) Various methods of identifying oenanthotoxin from plant material or gastric contents are discussed by King et al (1985). These include thin-layer chromatography, high performance liquid chromatography, UV absorption spectra, and mass spectrometry. They were unable to identify or isolate oenanthotoxin from body organs provided by autopsy. Del Castiloo et al (1980) determined oenanthotoxin, in vitro, using a fluorometric method.
    2) High performance liquid chromatography (HPLC) was used to identify oenanthotoxin in gastric aspirate (Ball et al, 1987).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) No specific laboratory measures are indicated. Patients have occasionally demonstrated elevated CPK, LDH or aldolase.
    B) Patients have rarely experienced hematuria or glycosuria.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) EMESIS/NOT RECOMMENDED -
    1) Is not recommended due to the rapid onset of vomiting and seizures (30-60 minutes).
    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) EMESIS/NOT RECOMMENDED
    1) Is not recommended due to the rapid onset of vomiting and seizures (30-60 minutes).
    B) GASTRIC LAVAGE
    1) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).
    a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.
    2) PRECAUTIONS:
    a) SEIZURE CONTROL: Is mandatory prior to gastric lavage.
    b) AIRWAY PROTECTION: Place patients in the head down left lateral decubitus position, with suction available. Patients with depressed mental status should be intubated with a cuffed endotracheal tube prior to lavage.
    3) LAVAGE FLUID:
    a) Use small aliquots of liquid. Lavage with 200 to 300 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in older children or adults) and 10 milliliters/kilogram body weight of normal saline in young children(Vale et al, 2004) and repeat until lavage return is clear.
    b) The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
    c) CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.
    4) COMPLICATIONS:
    a) Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications (Caravati et al, 2001).
    b) Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).
    5) CONTRAINDICATIONS:
    a) Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.
    C) ACTIVATED CHARCOAL
    1) 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.
    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).
    6.5.3) TREATMENT
    A) SEIZURE
    1) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    2) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    3) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    4) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).
    5) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    6) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    7) PHENYTOIN/FOSPHENYTOIN
    a) Benzodiazepines and/or barbiturates are preferred to phenytoin or fosphenytoin in the treatment of drug or withdrawal induced seizures (Wallace, 2005).
    b) PHENYTOIN
    1) PHENYTOIN INTRAVENOUS PUSH VERSUS INTRAVENOUS INFUSION
    a) Administer phenytoin undiluted, by very slow intravenous push or dilute 50 mg/mL solution in 50 to 100 mL of 0.9% saline.
    b) ADULT DOSE: A loading dose of 20 mg/kg IV; may administer an additional 5 to 10 mg/kg dose 10 minutes after loading dose. Rate of administration should not exceed 50 mg/minute (Brophy et al, 2012).
    c) PEDIATRIC DOSE: A loading dose of 20 mg/kg, at a rate not exceeding 1 to 3 mg/kg/min or 50 mg/min, whichever is slower (Loddenkemper & Goodkin, 2011; Prod Info Dilantin(R) intravenous injection, intramuscular injection, 2013).
    d) CAUTIONS: Administer phenytoin while monitoring ECG. Stop or slow infusion if dysrhythmias or hypotension occur. Be careful not to extravasate. Follow each injection with injection of sterile saline through the same needle (Prod Info Dilantin(R) intravenous injection, intramuscular injection, 2013).
    e) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over next 12 to 24 hours for maintenance of therapeutic concentrations. Therapeutic concentrations of 10 to 20 mcg/mL have been reported (Prod Info Dilantin(R) intravenous injection, intramuscular injection, 2013).
    c) FOSPHENYTOIN
    1) ADULT DOSE: A loading dose of 20 mg phenytoin equivalent/kg IV, at a rate not exceeding 150 mg phenytoin equivalent/minute; may give additional dose of 5 mg/kg 10 minutes after the loading infusion (Brophy et al, 2012).
    2) CHILD DOSE: 20 mg phenytoin equivalent/kg IV, at a rate of 3 mg phenytoin equivalent/kg/minute, up to a maximum of 150 mg phenytoin equivalent/minute (Loddenkemper & Goodkin, 2011).
    3) CAUTIONS: Perform continuous monitoring of ECG, respiratory function, and blood pressure throughout the period where maximal serum phenytoin concentrations occur (about 10 to 20 minutes after the end of fosphenytoin infusion) (Prod Info CEREBYX(R) intravenous injection, 2014).
    4) SERUM CONCENTRATION MONITORING: Monitor serum phenytoin concentrations over the next 12 to 24 hours; therapeutic levels 10 to 20 mcg/mL. Do not obtain serum phenytoin concentrations until at least 2 hours after infusion is complete to allow for conversion of fosphenytoin to phenytoin (Prod Info CEREBYX(R) intravenous injection, 2014).
    8) RECURRING SEIZURES
    a) If seizures are not controlled by the above measures, patients will require endotracheal intubation, mechanical ventilation, continuous EEG monitoring, a continuous infusion of an anticonvulsant, and may require neuromuscular paralysis and vasopressor support. Consider continuous infusions of the following agents:
    1) MIDAZOLAM: ADULT DOSE: An initial dose of 0.2 mg/kg slow bolus, at an infusion rate of 2 mg/minute; maintenance doses of 0.05 to 2 mg/kg/hour continuous infusion dosing, titrated to EEG (Brophy et al, 2012). PEDIATRIC DOSE: 0.1 to 0.3 mg/kg followed by a continuous infusion starting at 1 mcg/kg/minute, titrated upwards every 5 minutes as needed (Loddenkemper & Goodkin, 2011).
    2) PROPOFOL: ADULT DOSE: Start at 20 mcg/kg/min with 1 to 2 mg/kg loading dose; maintenance doses of 30 to 200 mcg/kg/minute continuous infusion dosing, titrated to EEG; caution with high doses greater than 80 mcg/kg/minute in adults for extended periods of time (ie, longer than 48 hours) (Brophy et al, 2012); PEDIATRIC DOSE: IV loading dose of up to 2 mg/kg; maintenance doses of 2 to 5 mg/kg/hour may be used in older adolescents; avoid doses of 5 mg/kg/hour over prolonged periods because of propofol infusion syndrome (Loddenkemper & Goodkin, 2011); caution with high doses greater than 65 mcg/kg/min in children for extended periods of time; contraindicated in small children (Brophy et al, 2012).
    3) PENTOBARBITAL: ADULT DOSE: A loading dose of 5 to 15 mg/kg at an infusion rate of 50 mg/minute or lower; may administer additional 5 to 10 mg/kg. Maintenance dose of 0.5 to 5 mg/kg/hour continuous infusion dosing, titrated to EEG (Brophy et al, 2012). PEDIATRIC DOSE: A loading dose of 3 to 15 mg/kg followed by a maintenance dose of 1 to 5 mg/kg/hour (Loddenkemper & Goodkin, 2011).
    4) THIOPENTAL: ADULT DOSE: 2 to 7 mg/kg, at an infusion rate of 50 mg/minute or lower. Maintenance dose of 0.5 to 5 mg/kg/hour continuous infusing dosing, titrated to EEG (Brophy et al, 2012)
    b) Endotracheal intubation, mechanical ventilation, and vasopressors will be required (Brophy et al, 2012) and consultation with a neurologist is strongly advised.
    c) Neuromuscular paralysis (eg, rocuronium bromide, a short-acting nondepolarizing agent) may be required to avoid hyperthermia, severe acidosis, and rhabdomyolysis. If rhabdomyolysis is possible, avoid succinylcholine chloride, because of the risk of hyperkalemic-induced cardiac dysrhythmias. Continuous EEG monitoring is mandatory if neuromuscular paralysis is used (Manno, 2003).
    B) 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).
    4) Animals experienced both an initial hypotension, then hypertension. Blood pressure should be monitored carefully, since the duration and extent of the hypotensive phase may be erratic (Grundy & Howarth, 1956).
    C) DRUG THERAPY FINDING
    1) Various treatments have been tried to combat the CNS stimulant effects. These include morphine, chloral hydrate, chloroform, and various barbiturates. (McGraph, 1937; (Starreveld & Hope, 1975; Robson, 1965) The most effective treatment agents when a benzodiazepine has failed, were the barbiturates (Mitchell & Routledge, 1978).

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    6.9.2) TREATMENT
    A) GENERAL TREATMENT
    1) No treatment is required.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

    A) SUMMARY
    1) No studies have addressed the utilization of extracorporeal elimination techniques in poisoning with this agent.

Abstracts

Case Reports

    A) ADULT
    1) A 54-year-old woman ingested a plant bulb she thought was edible, but was later identified as O. crocata. Within 15 minutes she developed sweating, nausea, epigastric pain, vomiting and generalized malaise. Shortly thereafter she experienced two-minute long periods of tonic-clonic seizures with frothing at the mouth. She did not lose consciousness or sphincter control. There were six such attacks prior to being admitted to the hospital. She was admitted in cardiopulmonary arrest, and was given resuscitative measures. The peripheral pulse reappeared, and mydriasis with light response was noted. Since the arterial blood pH on admission was 6.89, this was corrected with intravenous bicarbonate. After resuscitation, her blood pressure was 90/50 mmHg with a heart rate of 110 beats/minute. Her admission electrocardiogram showed atrial fibrillation which changed to sinus rhythm within a few hours. She was connected to a volumetric ventilator for 16 hours. Eight hours post admission she regained consciousness. Laboratory noted an increase in CPK, LDH, and aldolase, which normalized after 10 days. Oenanthetoxin was confirmed by analysis of blood, urine, and gastric juice. She was discharged without sequelae on the 6th day postingestion, and followed as an outpatient (Pallares et al, 1985).

Range Of Toxicity

Summary

    A) No specific toxic amount has been determined. Below are several representative cases with amounts and primary symptoms. In many cases the amount ingested is unknown, being represented as "a meal". Often the patient has been found dead and not able to answer questions as to quantity.
    1) One tuber eaten raw, two others cooked: Vomiting, seizures, survived with anticonvulsants.
    2) "A plant bulb" caused vomiting, seizures, cardiopulmonary arrest. She survived with supportive care.
    3) Oenanthotoxin is not stable, and drying or cooking may destroy the toxin.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) King et al (1985) extracted 20 milligrams of oenanathotoxin from 200 grams of tubers. A sample they gathered in Britian, in the winter contained 0.06% oenanthotoxin.

Maximum Tolerated Exposure

    A) CASE REPORTS
    1) SUMMARY - No specific toxic amount has been determined. Below are several representative cases with amounts and primary symptoms. In many cases the amount ingested is unknown, being represented as "a meal". Often the patient has been found dead and not able to answer questions as to quantity.
    a) One tuber eaten raw, two others cooked: Vomiting, seizures, survived with anticonvulsants (Mitchell & Routledge, 1977).
    b) "A plant bulb" caused vomiting, seizures, cardiopulmonary arrest. She survived with supportive care (Pallares et al, 1985).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) CASE REPORTS
    a) Three fatal cases are described by King et al (1985). The amounts ingested were generally not known but consisted of the tubers being include in a meal or casserole. Plant material was often found in the victims' stomach, showing rapid onset of symptoms.

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (INTRAPERITONEAL)MOUSE:
    1) 1.2 mg/kg (Grundy & Howarth, 1956)
    B) LD50- (ORAL)MOUSE:
    1) 7-8 mg/kg (Grundy & Howarth, 1956)

Pharmacology Toxicology

Toxicologic Mechanism

    A) Oenanthetoxin, the toxic substance in O. crocata, has several functions, one of which is autonomous nervous system dysfunction, with the attack coming at the brainstem level (Grundy & Howarth, 1956; Starreveld & Hope, 1975). The clinical presentation is also characterized by muscarinic side effects (Pellares et al, 1985).
    B) Oenanthetoxin is a neutral ethylenic and acetanilid diol (Dubois & Schneider, 1981; Clarke et al, 1949). Anet et al (1953) discovered three major components of oenanthotoxin, a trans-heptadeca-2,8,10-triene- 4-diyne-1,14-diol, oenanthetol (C14-deoxyoenanthotoxin), and oenanthetone (C14-ketone of C1-deoxyoenanthotoxin). All of these have the same carbon skeleton, and represent a different portion of oenanthotoxin depending on the time of year. The oenanthetol and oenanthetone appear to have very low toxicity (King et al, 1985). All in all, over 30 related compounds have been isolated by Bohlmann & Roe (1968).
    C) In frog myelinated nerve fibres at concentrations of 0.1 mm, oenanthotoxin blocked the action potential and the sodium potassium and displacement currents (Dubois & Schneider, 1981).

Physicochemical

Molecular Weight

    A) Varies

Animal Toxicology

Clinical Effects

    11.1.2) BOVINE/CATTLE
    A) Oenanthe crocata: Symptom onset may be rapid, causing "sudden death". Symptom presentation may be as follows: The animal is at first displeased with the taste of the ingested material, and there is mouthing and salivating. The pupils become dilated and the animal becomes increasingly uncoordinated. This may lead to respiratory difficulty and seizures. Arterial blood may appear at the nares (Van Inzen & Gunn, 1989). Deaths have been noted in cattle. The postmortem examination of two poisoned cows showed hemorrhages on the rumen wall, extensive blood staining in the trachea and pulmonary hemorrhages (Van Inzen & Gunn, 1989).
    B) Oenanthe phellandrium: Cattle that ingest the fresh leaves may develop paralysis (Grieve, 1974).
    C) A CNS depressant type toxicity which does not lead to seizure has been attributed to the poisoning of cattle by O. pimpinelloides, O. aquatica, and O. silaifolia (Forsyth, 1966; Aspiotis et al, 1960) Miedzobrodzki, 1960).
    11.1.5) EQUINE/HORSE
    A) Symptoms include salivation, dilated pupils, and seizures which may be terminal (Cooper & Johnson, 1984).
    11.1.9) OVINE/SHEEP
    A) Sheep are less susceptible to the effects. At least half of an exposed group may recover. After the usual acute poisoning symptoms, the sheep may develop diarrhea for 48 hours then gradually normalize (Cooper & Johnson, 1984).
    11.1.10) PORCINE/SWINE
    A) After ingestion pigs may vomit for a short time, then die suddenly without other signs (Cooper & Johnson, 1984).

Treatment

    11.2.2) LIFE SUPPORT
    A) GENERAL
    1) MAINTAIN VITAL FUNCTIONS: Secure airway, supply oxygen, and begin supportive fluid therapy if necessary.
    11.2.5) TREATMENT
    A) CATTLE
    1) CASE REPORTS
    a) In one case, large doses of sedative and anesthetic agents were used. Xylazine, acepromazine maleate, and pentobarbitone sodium given so as to induce anesthesia worked best. Four animals who were treated within a few minutes of exhibiting the initial signs were saved (Van Inzen & Gunn, 1989).

Range Of Toxicity

    11.3.2) MINIMAL TOXIC DOSE
    A) SPECIFIC TOXIN
    1) The oenanthetoxin is not detoxified by drying or storage (Cooper & Johnson, 1984), but exposure to air will destroy the material (Mitchell & Routledge, 1978).

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