Contact Us    Contact Us     |     Feedback
MOBILE VIEW  | 

PLANTS-CNS DEPRESSANTS

Export To Excel

Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) This management deals generally with plants that produce an altered level of consciousness. Other symptoms may also occur with many of these plants, as noted in the clinical effects section.
    B) The following is a list of individual plant managements for species or groups that may cause an altered level of consciousness:
    1) KAVA
    2) NICOTINE
    3) PLANTS-ANTICHOLINERGIC
    4) PLANTS-ACONITUM
    5) PLANTS-ACKEE
    6) PLANTS-ARECA CATECHU
    7) PLANTS-CYTISINE
    8) PLANTS-DRYOPTERIS
    9) PLANTS-GRAYANOTOXINS
    10) PLANTS-LANTANA
    11) PLANTS-LUPINE
    12) PLANTS-SOLANINE
    13) PLANTS-VERATRUM ALKALOIDS

Specific Substances

    1) Depressant Plants
    2) Plants that produce CNS depression

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Exposure to plants that effect the CNS can cause a wide variety of presenting symptoms. Patients may exhibit a range of consciousness from comatose to hallucinations to agitation. The symptoms are dependent on the nature of a plant exposure. Onset is highly variable. Pathophysiology is also diverse. Symptomatology can be due to primary CNS effects or secondary to end organ effects of the toxin. Secondary causes of a change in mental status may include: hypoglycemia, hepatic failure, and sympathetic response. Plant toxins can sometimes be included in larger classes of toxins, such as anticholinergics and sympathomimetics. Mental status changes can range from agitation to coma and are dependent on the toxin type and dose. The following is a list of individual plant managements for species or groups that may cause an altered level of consciousness: KAVA, NICOTINE, PLANTS-ANTICHOLINERGIC, PLANTS-ACONITUM, PLANTS-ACKEE, PLANTS-ARECA CATECHU, PLANTS-CYTISINE, PLANTS-DRYOPTERIS, PLANTS-GRAYANOTOXINS, PLANTS-LANTANA, PLANTS-LUPINE, PLANTS-SOLANINE and PLANTS-VERATRUM ALKALOIDS.

Laboratory Monitoring

    A) Obtain serum electrolytes, glucose, renal function tests and hepatic enzymes in patients with unexplained changes in mental status to evaluate for metabolic causes.
    B) Serum testing for plant alkaloids (other than digoxin) is not available in the hospital setting.
    C) A urine drug screen may be a useful adjunct in the altered patient to rule out exposure from other pharmacologic agents.
    D) A head CT and lumbar puncture may be useful to evaluate for other causes of altered mentation.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) The vast majority of plant poisonings require only supportive care. For those patients with significant CNS depression or other symptoms, adequate observation of vital signs and hydration state should be done in an Emergency Department observation unit. No specific antidote exists. HYPOTENSION: Resuscitation with intravenous crystalloid is the first-line treatment as it may be related to dehydration. Hypotension that is refractory to fluids may require vasopressors. TACHYCARDIA: If tachycardia is secondary to dehydration, treat with intravenous crystalloids. Treat tachycardia secondary to agitation with benzodiazepines. DELIRIUM: Sedation with benzodiazepines may be beneficial.
    2) DERMAL EXPOSURE: Remove contaminated clothing and wash exposed area thoroughly with soap and water. A physician may need to examine the area if irritation or pain persists after washing.
    3) EYE EXPOSURE: Remove contact lens 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, the patient should be seen in a healthcare facility.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Support respiratory and cardiovascular function. Treat symptoms of anaphylaxis with epinephrine, steroids, and antihistamines. Treat seizures with benzodiazepines.
    C) DECONTAMINATION
    1) PREHOSPITAL: Exploratory plant ingestions by children rarely cause significant toxicity. Prehospital gastrointestinal decontamination is generally not recommended because of the potential for CNS depression and subsequent aspiration.
    2) HOSPITAL: Exploratory plant ingestions by children rarely cause significant toxicity. Gastrointestinal decontamination is generally not warranted. Recommend against the use of gastric lavage or whole bowel irrigation given the risk of CNS depression and aspiration. Consider activated charcoal following large ingestions, if the overdose is recent, the patient is not vomiting, and is able to maintain airway.
    D) AIRWAY MANAGEMENT
    1) Monitor airway in the setting of CNS depression. Recommend the use of end tidal CO2 monitoring for evaluation of ventilation status. Use pulse oximetry to evaluate oxygenation. Endotracheal intubation may be necessary if the patient is unable to protect their airway.
    E) ANTIDOTE
    1) No specific antidote exists. Varies by individual plant exposure.
    F) ENHANCED ELIMINATION
    1) Enhanced elimination is unlikely to be necessary in most plant exposures; the vast majority of patients do well with supportive care.
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: Anyone with an intentional ingestion, symptoms other than vomiting, or children who have ingested more than a "taste" amount of potentially toxic plant material should be evaluated in a healthcare facility.
    2) ADMISSION CRITERIA: Patients with persistent vital sign abnormalities, seizures, altered mental status, CNS depression, or muscle weakness should be admitted.
    3) OBSERVATION CRITERIA: Patients who are asymptomatic after 4 to 6 hours following an oral ingestion of plant material can be discharged.
    4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing severe poisonings or following a significant plant ingestion by a child.
    H) DIFFERENTIAL DIAGNOSIS
    1) Differential diagnosis for CNS altering plants is broad. Consider medications that may induce an anticholinergic or sympathicomimetic toxidrome. Consider other mind altering substances such as hallucinogens, serotoninergic agents, or sedative-hypnotics. Other herbal remedies which may be cardiotoxic should be considered and can include: dioxin-like cardioactive steroids (Ch'an Su), anticholinergics (Jimson Weed), and stimulants (Ephedra, Khat). Also, consider hypoglycemia, hypoxia, hypercarbia, CNS or systemic infections, severe endocrinopathies (eg, myxedema, thyroid storm, Addison's crisis), liver failure, Reye's syndrome or withdrawal states.
    0.4.4) EYE EXPOSURE
    A) SUMMARY
    1) See ORAL overview for further information.
    B) DECONTAMINATION
    1) Remove contact lens 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, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) SUMMARY
    a) See ORAL overview for further information.
    2) DECONTAMINATION
    a) Remove contaminated clothing and wash exposed area thoroughly with soap and water. A physician may need to examine the area if irritation or pain persists after washing.

Range Of Toxicity

    A) TOXICITY can range from mild to severe, and depends on the specific compound and the dose of exposure. In general, most plant exposures result in relatively minor clinical effects, especially those involving exploratory ingestions in children. There are few or no guidelines available for predicting toxicity based on an amount ingested.

Clinical Effects

Summary Of Exposure

    A) Exposure to plants that effect the CNS can cause a wide variety of presenting symptoms. Patients may exhibit a range of consciousness from comatose to hallucinations to agitation. The symptoms are dependent on the nature of a plant exposure. Onset is highly variable. Pathophysiology is also diverse. Symptomatology can be due to primary CNS effects or secondary to end organ effects of the toxin. Secondary causes of a change in mental status may include: hypoglycemia, hepatic failure, and sympathetic response. Plant toxins can sometimes be included in larger classes of toxins, such as anticholinergics and sympathomimetics. Mental status changes can range from agitation to coma and are dependent on the toxin type and dose. The following is a list of individual plant managements for species or groups that may cause an altered level of consciousness: KAVA, NICOTINE, PLANTS-ANTICHOLINERGIC, PLANTS-ACONITUM, PLANTS-ACKEE, PLANTS-ARECA CATECHU, PLANTS-CYTISINE, PLANTS-DRYOPTERIS, PLANTS-GRAYANOTOXINS, PLANTS-LANTANA, PLANTS-LUPINE, PLANTS-SOLANINE and PLANTS-VERATRUM ALKALOIDS.

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM DEFICIT
    1) WITH POISONING/EXPOSURE
    a) Alteration of consciousness may occur in various forms with differing onset, severity and duration. Some of the different types of CNS depression, as caused by different types of plants, are listed below. Some of these have more specific managements which should be consulted for additional information.
    b) ANTICHOLINERGICS: Species such a Datura stramonium (jimson weed), Atropa belladonna, Hyoscyamus niger (henbane), and Solandra spp (ie, chalice vine) contain anticholinergic toxins that when ingested or inhaled can produce the typical toxidrome: dry mucous membranes, decreased bowel sounds, flushed skin, hyperthermia, urinary retention, and altered mental status. Drowsiness often accompanies the syndrome, but a paradoxical reaction can occur in which the patient is agitated and hallucinating. See PLANTS-ANTICHOLINERGIC management.
    c) SYMPATHOMIMETICS: Species in the geni of Aconitum (monkshood), Veratrum (hellebore), Nicotinia (tobacco) can mimic increased sympathetic outflow. Agitation and hallucinations can accompany dysrhythmias, tachycardia and hypertension. See PLANTS-ACONITUM, PLANTS-VERATRUM ALKALOIDS, and NICOTINE managements as appropriate.
    d) HYPOGLYCEMIA: Ingestion of unripened Ackee fruit (from the species Blighia sapida) can result in a drop in serum glucose. The hypoglycemia can cause confusion, drowsiness, and coma. See PLANTS-ACKEE management.
    e) DELAYED DEPRESSION: Unconsciousness is a late, and usually ominous sign, in poisoning by the ackee (Blighia sapida); nicotine-, anabasine-, or cytisine-containing plants, such as cultivated and native tobacco plants (Nicotiana species), or cytisine (or similar quinolizidine alkaloid) containing plants such as golden chain (Laburnum anagyroides) and perhaps large quantities of mescal bean (Sophora secundiflora) or Golden Banner (Thermopsis species). Ingestion of the unripe fruit of the lantana (Lantana camara) may also present this type of depression. See PLANTS-ACKEE , PLANTS-CYTISINE, PLANTS-LANTANA, PLANTS-LUPINE, and NICOTINE managements as appropriate.

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) HEPATIC COMA
    1) WITH POISONING/EXPOSURE
    a) Hepatic failure can result from the ingestion of some plants that contain pyrrolizidine alkaloids. As the liver damage progresses, the accumulation of body toxins usually cleared by the liver can cause encephalopathy, which manifests as confusion and can progress to coma.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Obtain serum electrolytes, glucose, renal function tests and hepatic enzymes in patients with unexplained changes in mental status to evaluate for metabolic causes.
    B) Serum testing for plant alkaloids (other than digoxin) is not available in the hospital setting.
    C) A urine drug screen may be a useful adjunct in the altered patient to rule out exposure from other pharmacologic agents.
    D) A head CT and lumbar puncture may be useful to evaluate for other causes of altered mentation.

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) Patients with persistent vital sign abnormalities, seizures, altered mental status, CNS depression, or muscle weakness should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Anyone with an intentional ingestion, symptoms other than vomiting, or children who have ingested more than a "taste" amount of potentially toxic plant material should be evaluated in a healthcare facility.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a poison center or medical toxicologist for assistance in managing severe poisonings or following a significant plant ingestion by a child.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients who are asymptomatic after 4 to 6 hours following an oral ingestion of plant material can be discharged.

Monitoring

    A) Obtain serum electrolytes, glucose, renal function tests and hepatic enzymes in patients with unexplained changes in mental status to evaluate for metabolic causes.
    B) Serum testing for plant alkaloids (other than digoxin) is not available in the hospital setting.
    C) A urine drug screen may be a useful adjunct in the altered patient to rule out exposure from other pharmacologic agents.
    D) A head CT and lumbar puncture may be useful to evaluate for other causes of altered mentation.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Exploratory plant ingestions by children rarely cause significant toxicity. Prehospital gastrointestinal decontamination is generally not recommended because of the potential for CNS depression and subsequent aspiration.
    6.5.2) PREVENTION OF ABSORPTION
    A) Exploratory plant ingestions by children rarely cause significant toxicity. Gastrointestinal decontamination is generally not warranted. Recommend against the use of gastric lavage or whole bowel irrigation given the risk of CNS depression and aspiration. Consider activated charcoal following large ingestions, if the overdose is recent, the patient is not vomiting, and is able to maintain airway.
    B) 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) SUPPORT
    1) MANAGEMENT OF MILD TO MODERATE TOXICITY: The vast majority of plant poisonings require only supportive care. For those patients with significant CNS depression or other symptoms, adequate observation of vital signs and hydration state should be done in an Emergency Department observation unit. No specific antidote exists. HYPOTENSION: Resuscitation with intravenous crystalloid is the first-line treatment as it may be related to dehydration. Hypotension that is refractory to fluids may require vasopressors. TACHYCARDIA: If tachycardia is secondary to dehydration, treat with intravenous crystalloids. Treat tachycardia secondary to agitation with benzodiazepines. DELIRIUM: Sedation with benzodiazepines may be beneficial.
    2) MANAGEMENT OF SEVERE TOXICITY: Support respiratory and cardiovascular function. Treat symptoms of anaphylaxis with epinephrine, steroids, and antihistamines. Treat seizures with benzodiazepines.
    B) MONITORING OF PATIENT
    1) Obtain serum electrolytes, glucose, renal function tests and hepatic enzymes in patients with unexplained changes in mental status to evaluate for metabolic causes.
    2) Serum testing for plant alkaloids (other than digoxin) is not available in the hospital setting.
    3) A urine drug screen may be a useful adjunct in the altered patient to rule out exposure from other pharmacologic agents.
    4) A head CT and lumbar puncture may be useful to evaluate for other causes of altered mentation.
    C) AIRWAY MANAGEMENT
    1) Monitor airway in the setting of CNS depression. Recommend the use of end tidal CO2 monitoring for evaluation of ventilation status. Use pulse oximetry to evaluate oxygenation.
    2) Endotracheal intubation may be necessary if the patient is unable to protect their airway.
    D) HYPOTENSIVE EPISODE
    1) Resuscitation with intravenous crystalloid is the first-line treatment as it may be related to dehydration. Hypotension that is refractory to fluids may require vasopressors.
    a) SUMMARY
    1) 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.
    b) DOPAMINE
    1) 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).
    2) 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).
    c) NOREPINEPHRINE
    1) 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).
    2) DOSE
    a) 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).
    b) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    c) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
    E) 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, 2010; 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).
    F) TACHYCARDIA
    1) If tachycardia is secondary to dehydration treat with intravenous crystalloids. Treat tachycardia secondary to agitation with benzodiazepines.
    G) DELIRIUM
    1) Sedation with benzodiazepines may be beneficial.

Enhanced Elimination

    A) SUMMARY
    1) Enhanced elimination is unlikely to be necessary in most plant exposures; the vast majority of patients do well with supportive care.

Abstracts

Case Reports

    A) BETEL NUT: Chewing betel nut (Areca catechu) typically causes a mild sense of stimulation followed by a short period of depression. The effects have been likened to those of alcohol. If large amounts are chewed, the user may become excited, ataxic, glassy-eyed, uninhibited, tremulous, and occasionally truculent. The above symptoms are generally present on the day the nuts are chewed, but within 24 hours the subject becomes dull, slow in comprehension, apathetic, and slow of motor response (Cawte, 1985).
    B) KAVA: An intoxicating drink made from Piper methysticum and widely used in the Southern Pacific area for social and ceremonial occasions. Kava usage may produce reversible anesthesia of the mouth and skin, euphoria, sedation, muscle weakness, ataxia, and intoxication (Mathews et al, 1988). One of Kava's ingredients (dihydromethysticin) is an active, mild tranquilizer of the meprobamate type (Cawte, 1988). When used chronically, patients using 500 mg/day developed exfoliative dermatitis (Cawte, 1988).
    C) NEEM OIL (extra of neem tree (Azadirachta Indica A Juss): INFANT: A healthy 3-month old presented with unconsciousness (Glasgow coma score 10) after being given 5 mL of neem oil orally for reported indigestion. He was noted to have tachycardia and tachypnea with a normal blood pressure and adequate oxygen perfusion. However, he developed metabolic acidosis (pH 7.21, bicarbonate 14, base deficit -10). Blood sugar and other laboratory studies were normal. He was started on oxygen, IV fluids, and antibiotics. The infant became more alert and metabolic acidosis started improving about 18 to 24 hours after admission and was discharged after 48 hours. He remained well at 3 month follow-up (Kumar & Kumar, 2014).
    D) POLYPODIUM VULGARE: Studies using an aqueous extract of the root of polypodium vulgare reported a number of pharmacological effects in animals. Polypodium vulgare, produced CNS depression, a decrease in spontaneous motor activity, decrease in body temperature, increased reaction time to painful stimuli, and a fall in blood pressure which was rapid in onset and short in duration in laboratory animals (Mannan et al, 1989).
    E) VALERIAN: There has been little work done on the CNS depressant effects of valerian, however, in one study valerian aqueous extraction doses of 450 to 900 mg were tested against placebo in a double blind study, and found that when tested on insomniacs, valerian decreased sleep latency. There was no difference in the effects between the 2 doses (Leathwood & Chauffard, 1985).

Range Of Toxicity

Summary

    A) TOXICITY can range from mild to severe, and depends on the specific compound and the dose of exposure. In general, most plant exposures result in relatively minor clinical effects, especially those involving exploratory ingestions in children. There are few or no guidelines available for predicting toxicity based on an amount ingested.

Minimum Lethal Exposure

    A) SUMMARY
    1) TOXICITY can range from mild to severe, and depends on the specific compound and the dose of exposure. In general, most plant exposures result in relatively minor clinical effects, especially those involving exploratory ingestions in children. There are few or no guidelines available for predicting toxicity based on an amount ingested.

Pharmacology Toxicology

Toxicologic Mechanism

    A) ACKEE FRUIT: The natural toxin found in unripe ackee fruit is hypoglycin A (a water-soluble liver toxin). Concentrations can be 100 times higher than those in ripe fruit. Hypoglycin A and its major metabolite, methylenecyclopropylacetic acid (MCPA), are potent hypoglycemic agents with the underlying mechanism being a decrease in the rate of fatty acid beta oxidation, likely due to inhibition of acyl dehydrogenase flavin-dependent oxidation (Barennes et al, 2004; Meda et al, 1999) . The metabolism of hypoglycin leads to hypoglycemia in humans (Joskow et al, 2006).
    1) Coma often develops in serious poisonings (Hill, 1952; CDC, 1992).
    B) KAVA-KAVA: It contains several alkaloids, methysticin, dihydromethysticin, kawain, dihydrokawin, and demethoxyyangonin, which produces drowsiness (Brown & Malone, 1978). The effect is not usually pronounced, and has been seen more as an effect in animal experimentation (Cawte, 1985; Buckley et al, 1967).
    1) Marked sedation may occur following ingestion of large doses of kava (Bone, 1994).
    C) PASSIFLORA: The exact mechanism of action of Passiflora incarnata extract has NOT yet been determined. Neuropharmacological studies in animals have shown a complex activity on the CNS, inducing dose-dependent stimulation and depression. The extract causes a rise in the nociceptive threshold which may be due to motor impairment induced by the extract. In rats, locomotor activity was significantly affected, as was pentobarbital-induced sleeping time, which was prolonged. Rats were protected from the convulsive effects of pentylenetetrazole. Further studies are needed to assess possible relationships with CNS neurotransmitters (Speroni & Minghetti, 1988). The plant flavonoids may act on central benzodiazepine receptors (Bourin et al, 1997). After fractionating and testing in mice, the active constituent remains unidentified, but appears to be a benzoflavone moiety (Dhawan et al, 2001b).
    1) The herbal extract is a sedative with depressant actions (Duke et al, 2002; Speroni & Minghetti, 1988; Aoyagi et al, 1974). Although significant human toxicity is uncommon, it might be expected that large doses would result in CNS depression (Solbakken et al, 1997).

References

General Bibliography

    1) AMA Department of DrugsAMA Department of Drugs: AMA Evaluations Subscription, American Medical Association, Chicago, IL, 1992.
    2) Aoyagi N, Kimura R, & Murata T: Studies on Passiflora incarnata dry extract. I. Isolation of maltol and pharmacological action of maltol and ethyl maltol. Chem Pharm Bull (Tokyo) 1974; 22:1008-1013.
    3) Barennes H, Valea I, Boudat AM, et al: Early glucose and methylene blue are effective against unripe ackee apple (Blighia sapida) poisoning in mice. Food Chem Toxicol 2004; 42:809-815.
    4) Bone K: Kava-a safe herbal treatment for anxiety.. Br J Phytother 1994; 3:147-153 .
    5) Bourin M, Bougerol T, & Guitton B: A combination of plant extracts in the treatment of outpatients with adjustment disorder with anxious mood: controlled study versus placebo. Fundam Clin Pharmacol 1997; 11:127-132.
    6) Brophy GM, Bell R, Claassen J, et al: Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012; 17(1):3-23.
    7) Brown JL & Malone MH: Legal highs-constituents activity, toxicology, and herbal folklore. Clin Toxicol 1978; 12:1.
    8) Buckley JP, Furgiuele AR, & O'Hara M: Pharmacology of kava, in Efron DH Holmstedt EH & Kline NS (eds): Ethnopharmacologic Search for Psychoactive Drugs, Raven Press, New York, NY, 1967.
    9) CDC: Toxic hypoglycemic syndrome - Jamaica, 1989-1991. CDC: MMWR 1992; 41:53-55.
    10) Cawte J: Macabre effects of a "cult" for Kava. Med J Aust 1988; 148:545-546.
    11) Cawte J: Psychoactive substances of the south seas: betel, kava and pituri. Aust New Zealand J Psychiatry 1985; 19:83-87.
    12) Chamberlain JM, Altieri MA, & Futterman C: A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children. Ped Emerg Care 1997; 13:92-94.
    13) Chin RF , Neville BG , Peckham C , et al: Treatment of community-onset, childhood convulsive status epilepticus: a prospective, population-based study. Lancet Neurol 2008; 7(8):696-703.
    14) Choonara IA & Rane A: Therapeutic drug monitoring of anticonvulsants state of the art. Clin Pharmacokinet 1990; 18:318-328.
    15) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    16) Dhawan K, Kumar S, & Sharma A: Anti-anxiety studies on extracts of Passiflora incarnata Linneaus. J Ethnopharmacol 2001b; 78:165-170.
    17) Duke JA, Bogenschutz-Godwin MJ, & duCellier J: Passionflower, in: Handbook of Medicinal Herbs, 2nd edition, CRC Press, Boca Raton, FL, 2002.
    18) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
    19) FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.
    20) Golej J, Boigner H, Burda G, et al: Severe respiratory failure following charcoal application in a toddler. Resuscitation 2001; 49:315-318.
    21) Graff GR, Stark J, & Berkenbosch JW: Chronic lung disease after activated charcoal aspiration. Pediatrics 2002; 109:959-961.
    22) Harris CR & Filandrinos D: Accidental administration of activated charcoal into the lung: aspiration by proxy. Ann Emerg Med 1993; 22:1470-1473.
    23) Hegenbarth MA & American Academy of Pediatrics Committee on Drugs: Preparing for pediatric emergencies: drugs to consider. Pediatrics 2008; 121(2):433-443.
    24) Hill KR: The vomiting sickness of Jamaica. A review. West Ind Med J 1952; 1:243-264.
    25) Hvidberg EF & Dam M: Clinical pharmacokinetics of anticonvulsants. Clin Pharmacokinet 1976; 1:161.
    26) Joskow R, Belson M, Vesper H, et al: Ackee fruit poisoning: an outbreak investigation in Haiti 2000-2001, and review of the literature. Clin Toxicol (Phila) 2006; 44(3):267-273.
    27) Kleinman ME, Chameides L, Schexnayder SM, et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Part 14: pediatric advanced life support. Circulation 2010; 122(18 Suppl.3):S876-S908.
    28) Kumar S & Kumar N: Neem oil poisoning as a cause of toxic encephalopathy in an infant. Indian J Pediatr 2014; 81(9):955.
    29) Leathwood PD & Chauffard F: Aqueous extract of valerian reduces latency to fall asleep in man. Planta Medica 1985; 51:144-148.
    30) Loddenkemper T & Goodkin HP: Treatment of Pediatric Status Epilepticus. Curr Treat Options Neurol 2011; Epub:Epub.
    31) Mannan A, Khan RA, & Asif M: Pharmacodynamic studies on polypodium vulgare (Linn). Indian J Exp Biol 1989; 27:556-560.
    32) Manno EM: New management strategies in the treatment of status epilepticus. Mayo Clin Proc 2003; 78(4):508-518.
    33) Mathews JD, Riley MD, & Fejo L: Effect of the heavy usage of Kava on physical health: summary of a pilot survey in an Aboriginal community. Med J Aust 1988; 148:548-555.
    34) Meda HA, Diallo B, & Buchet JP: Epidemic of fatal encephalopathy in preschool children in burkina faso and consumption of unripe ackee (Blighia sapida) fruit. Lancet 1999; 353:536-540.
    35) None Listed: Position paper: cathartics. J Toxicol Clin Toxicol 2004; 42(3):243-253.
    36) Peberdy MA , Callaway CW , Neumar RW , et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care science. Part 9: post–cardiac arrest care. Circulation 2010; 122(18 Suppl 3):S768-S786.
    37) Pollack MM, Dunbar BS, & Holbrook PR: Aspiration of activated charcoal and gastric contents. Ann Emerg Med 1981; 10:528-529.
    38) Product Information: diazepam IM, IV injection, diazepam IM, IV injection. Hospira, Inc (per Manufacturer), Lake Forest, IL, 2008.
    39) Product Information: dopamine hcl, 5% dextrose IV injection, dopamine hcl, 5% dextrose IV injection. Hospira,Inc, Lake Forest, IL, 2004.
    40) Product Information: lorazepam IM, IV injection, lorazepam IM, IV injection. Akorn, Inc, Lake Forest, IL, 2008.
    41) Product Information: norepinephrine bitartrate injection, norepinephrine bitartrate injection. Sicor Pharmaceuticals,Inc, Irvine, CA, 2005.
    42) Rau NR, Nagaraj MV, Prakash PS, et al: Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988; 297:918-919.
    43) Scott R, Besag FMC, & Neville BGR: Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomized trial. Lancet 1999; 353:623-626.
    44) Solbakken AM, Rorbakken G, & Gundersen T: An herbal product used for intoxication. Tidsskr Nor Loegeforen 1997; 117:1140-1141.
    45) Speroni E & Minghetti A: Neuropharmacological activity of extracts from Passiflora incarnata. Planta Med 1988; 54:488-491.
    46) Sreenath TG, Gupta P, Sharma KK, et al: Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children: A randomized controlled trial. Eur J Paediatr Neurol 2010; 14(2):162-168.