Substances Included Synonyms

Therapeutic Toxic Class

A)

B)

C)

Specific Substances

A)

1) Bikhroot
2) Bish
3) Bishma
4) Indian aconite
5) Visha

1) Chuanwu (the root tuber of A. carmichaeli debx)
2) Fuzi (lateral root tuber of A carmichaeli)

1) Caowu (the root tuber of A. kusnezoffii reichb.

1) Wolfbane

1) Bear's Foot
2) Cultivated aconite
3) Helmet Flower
4) Friar's Cap
5) Friar's Cowl
6) Garden Monkshood
7) Garden Wolfsbane
8) Monkshood
9) Monk's-hood
10) Mouse-Bane
11) Turk's Cap
12) Soldier's Cap
13) Wolfsbane
14) Wolf's Bane

1) Trailing Wolfsbane

1) Wolfsbane

1) Aconite
2) Aconite poisoning

Available Forms Sources

A)

1) Raw aconitine roots are highly toxic and should be processed before use. Herbal decoctions of aconite are generally prepared by soaking the roots in water or saturated lime water for up to 1 to 2 hours before boiling the herbs. This causes hydrolysis of aconite alkaloids to less toxic benzylaconine and aconine derivatives. Many variables can affect the concentration of the processed aconite root (e.g., species, place of harvest, adequacy of processing), therefore, poisoning may occur following the consumption of processed roots (Chan, 2009a; Lin et al, 2004).

B)

1) ACONITUM FEROX

a) An extract of this plant has been used as an arrow poison in India (Frohne & Pfander, 1983). It is also used as an antipyretic in Ayurvedic medicine, after "detoxification" (Mahajani et al, 1990).
b) Various other aconitum species have also been used as arrow poisons (Bisset, 1981).

2) ACONITUM NAPELLUS

a) This plant has long been know to produce toxicity and has been implicated in murder (Lewin, 1929).
b) As Tubera Aconiti, the daughter tubers were once (until the 18th century) used as a medicinal (Frohne & Pfander, 1983).
c) Poisonings have occurred when the plant has been used for a psychologic "high" (Frohne & Pfander, 1983).
d) In India, this species has been used in herbal medicines (e.g. cold preparation, antipyretic, digestive and general tonic) or to increase the intoxicating effects of alcoholic beverages (Chan, 1994). Fatalities have been reported in Indian literature related to use of tincture aconite added to liquor.

3) CHINESE HERBAL MEDICINES

a) SUMMARY: Aconitum sungpanase has been used as a sedative in China, even though it is known to be toxic (Wang & Chen, 1987). Chinese herbal medications or decoctions may contain aconites, and have been known to produce fatalities (Chan, 2010; Kelly, 1990; Fatovich, 1992; But et al, 1994; Deraemaeker et al, 1995). In Korea, aconite poisonings occurred most often after the ingestion of decoction, tincture (herbal medicinal wine) and tablets poorly prepared from crude aconite roots (Chan, 2011). In China, several patients died after consuming homemade medicated liquor (tincture) containing aconite for various ailments. Of the seven patients that died, each developed symptoms rapidly and collapsed at home before medical care could be obtained or died shortly after hospital admission. Postmortem laboratory analysis confirmed the presence of aconite in each case (Liu et al, 2011).

1) The main root of A. carmichaeli ("chuanwu") and the root of the A. kusnezoffii ("caowu") are thought to have anti-inflammatory, analgesic, and cardiotonic effects used in Chinese medicines mainly as a treatment for musculoskeletal disorders (Chan, 2002; Chan, 1994; Chan, 1994).

b) YUNACONITINE: There have been several reports of aconite poisoning following the use of herbal products containing yunaconitine, a less common acontium alkaloid, which may have been mistakenly added to various Chinese herbal formulas (Poon et al, 2006; Chan, 2011).
c) ZHANG AHEN REN SHAN FU WAN: Aconite poisoning has been reported after the use of this unregistered product that was found to contain Aconite alkaloids (Chan, 2010).
d) IMPROPER PREPARATION: The raw aconite tubers can be extremely toxic and should be processed before use. Soaking the tubers can reduce the alkaloid content (reduces the alkaloid to a less toxic benzylaconine and aconine derivatives) by up to 90%, but decoction can be variable when done by the individual (Chan, 2002).

1) It is suggested that processed aconite roots should be decocted for at least 1.5 to 2 hours before they are combined with other herbs. Fatalities have occurred when "preboiling" was too brief or the step was omitted. In many cases, the aconite roots are prescribed for musculoskeletal pain; the processed roots are usually "chauanwu" (root tuber of Aconitum carmichaeli) and "caowu" (root of tuber of A kusnezoffi) and infrequently "fuzi" (lateral root tuber of A carmichaeli). Fatalities have been reported when these roots have been poorly processed post-harvesting (Chan, 2012a).
2) CULINARY USE: There have been reports of Aconitum alkaloid poisoning after consumption of herbal soups and meals containing aconite roots. Its suggested that consumption of herbal soups and foods prepared from aconite roots may not be safe even after prolonged boiling if large quantities of the root are used and consumed. In a large cluster of cases, 19 family members all became ill within 24 hours after ingesting a pork broth containing boiled "caowu" (the root of A kusnezoffii). Symptoms appeared to be dose dependent and occurred shortly after ingestion (mean 30 minutes). An elderly patient died after ingesting 13 pieces of boiled "caowu" (Chan, 2014).

e) TINCTURE: An herbal medicinal wine produced from the aconite root and may contain a larger amount of Aconitum alkaloids (Chan, 2009a).
f) ACONITUM PSEUDO-LEAVE VAR ERECTUM: Two adults became ill with early symptoms of paraesthesia followed by hypotension and bradycardia after ingesting boiled leaves of A pseudo-leave var. erectum (not the root). Following supportive care, the couple recovered about 20 hours later and were discharged to home (Kim et al, 2009).
g) EXPOSURE: Many cases of aconite poisoning from herbal medicines have been reported in China (over 600 in 30 years) and Hong Kong (Chan, 2009a; Chan et al, 1993a; Tai et al, 1993; But et al, 1994; Deraemaeker et al, 1995).

1) In China, the primary source of aconite poisoning is due to the ingestion of a tincture (herbal medicinal wine) containing aconite root which may contain a large amount of Aconitum alkaloids due to improper preparation (Chan, 2009a).
2) In Japan, the crude drug known as "bushi" contains the aconite root and is prepared from several species of Aconitum of Chinese and Japanese origin, and used for the treatment of pain, paralysis, atonia and coldness of the extremities (Chan, 1994).

Overview

Life Support

A)

Clinical Effects

0.2.1)

A) USES: There are many different varieties of Aconitum species that are found throughout the world. Raw aconitine root and its extract are highly toxic; prolonged boiling may not significantly remove all of the toxin. Aconitum plants are used as traditional remedies, primarily in Asia, for a variety of ailments (ie, nausea and vomiting, viral illnesses, and musculoskeletal disorders) they are often prescribed for their anti-inflammatory, analgesic, sedative and cardioprotective effects. Although the root has commonly been associated with poisoning, the leaves of the aconitum pseudo-laeve var. erectum produced similar toxicity in two adults. Aconites may also cause a psychedelic "high" when used with ethanol.
B) PHARMACOLOGY: Clinical effects are caused by the c19 diterpenoid-ester alkaloids (aconitine, mesaconitine, and hypoaconitine). Yunaconitine is a less common aconitum alkaloid that has produced toxicity. Aconitine increases sodium influx through the sodium channel. Aconite may also accentuate vagal tone on the heart.
C) TOXICOLOGY: The increase in sodium channel opening causes an increase in inotropy and delays final repolarization causing premature excitation resulting in brady- or tachydysrhythmias. Accentuated vagal tone may result in bradycardia.
D) EPIDEMIOLOGY: Aconite exposure/ingestions are uncommon poisonings in the United States, but can result in serious morbidity or death. Serious exposure more commonly occurs in Asia where Aconitum species are commonly utilized in herbal preparations. Severe even fatal cases of aconite poisoning have been reported in Asia after the consumption of herbal soups and foods prepared from aconite roots. Prolonged boiling may NOT be protective if raw preparations and large quantities of aconite roots are ingested.
E) WITH THERAPEUTIC USE

1) ADVERSE EFFECTS: Paresthesias, nausea, vomiting, hypersalivation, diarrhea, skeletal muscle weakness, pain, hypotension, paralysis and dysrhythmias can develop.

F) WITH POISONING/EXPOSURE

1) OVERDOSE: Symptoms may occur minutes to hours after ingestion.
2) MILD TO MODERATE TOXICITY: Initially paresthesias of the oral mucosa can occur that may extend to the entire body along with diaphoresis and chills. This is followed by hypersalivation, nausea, vomiting, hypersalivation, diarrhea, progressive skeletal muscle weakness and severe pain.
3) SEVERE TOXICITY: Fatal brady- or tachydysrhythmias, hypotension and paralysis can develop.

0.2.3)

A) WITH POISONING/EXPOSURE

1) Hypotension and respiratory failure may occur.

0.2.4)

A) WITH POISONING/EXPOSURE

1) Miosis may be seen until the patient develops hypoxia. Mydriasis may also be seen. Diplopia and blurred vision are often experienced, as is yellow-green vision.
2) A feeling of warmth, roughness, or dryness of the mouth and throat may develop soon after the onset of poisoning. There may be a feeling of airway constriction, difficulty with speaking and difficulty with swallowing.

0.2.5)

A) WITH POISONING/EXPOSURE

1) Vagal slowing is seen in 10% to 20% of fatal intoxications. If higher concentrations are present, supraventricular tachycardia, ventricular tachycardia, torsades de pointes, and other conduction disturbances may be seen. Ventricular fibrillation may be seen, and is often the cause of death. Patients may have a severe oppressive feeling of the chest.
2) Bradycardia and hypotension are common adverse events.

0.2.6)

A) WITH POISONING/EXPOSURE

1) Respiratory paralysis is often the cause of death. Pulmonary edema may develop.

0.2.7)

A) WITH POISONING/EXPOSURE

1) An early sign of intoxication is a burning or tingling sensation in the lips, tongue, mouth, fingers and toes. This gradually extends over the entire body, but is particularly strong on the face. Patients poisoned by these plants often experience severe pain.
2) CNS depression is usually NOT seen. Patients often have severe headache, restlessness, apprehension and confusion. Muscular fasciculations may lead to tonic or clonic seizures. Incoordination is often present.

0.2.8)

A) WITH POISONING/EXPOSURE

1) Chewing on a root may cause swelling of the lips, tongue and mouth, making speech difficult.
2) Intense vomiting and a colicky-diarrhea may develop after an ingestion. A feeling of roughness or dryness of the mouth and throat may also be seen. Salivation may be increased in the early stages of intoxication.

0.2.14)

A) WITH POISONING/EXPOSURE

1) The skin may be cold and moist. Application of an ointment made from the plant to intact skin may cause itching, prickling, redness, or vesicles.
2) Dermatitis has been reported in pharmaceutical workers exposed to the plant.

0.2.15)

A) WITH POISONING/EXPOSURE

1) Muscular weakness, accompanied by generalized weakness, often occurs.
2) Initial feelings of numbness may progress to paralysis of the skeletal muscles.

0.2.20)

A) At the time of this review, no data were available to assess the teratogenic potential of this agent.
B) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

0.2.21)

A) At the time of this review, no data were available to assess the carcinogenic or mutagenic potential of this agent.

Laboratory Monitoring

A)

B)

C)

Treatment Overview

0.4.2)

A) MANAGEMENT OF MILD TO MODERATE TOXICITY

1) Symptomatic and supportive care are usually sufficient for the treatment of mild to moderate toxicity. Treat severe nausea, vomiting and diarrhea with IV fluids and antiemetics along with electrolyte repletion.

B) MANAGEMENT OF SEVERE TOXICITY

1) Treat paralysis with aggressive airway support including intubation. Treat hypotension with IV fluids and vasopressors. Atropine may be of use in treating bradycardia or hypersalivation. Ventricular dysrhythmias may be refractory to treatment. Anecdotal reports suggest that amiodarone, flecainide, lidocaine and procainamide may be useful for treating ventricular tachydysrhythmias. Consider mechanical circulatory support in patients with refractory dysrhythmias and hypotension.

C) DECONTAMINATION

1) PREHOSPITAL: Administer activated charcoal if the patient is alert, not vomiting, and able to protect the airway.
2) HOSPITAL: Administer activated charcoal if the patient is alert and can protect the airway; however, patients often have associated nausea and vomiting with ingestion.

D) AIRWAY MANAGEMENT

1) Administer !00% oxygen as needed for respiratory support. Intubate and provide assisted ventilation in patients with hemodynamic instability.

E) ANTIDOTE

1) There is no known antidote.

F) VENTRICULAR DYSRHYTHMIAS

1) Ventricular dysrhythmias may be refractory to therapy. Cardiovert unstable rhythms. An agent which blocks sodium channels would be anticipated to be most effective. Case reports have suggested that amiodarone, flecainide, lidocaine and procainamide may be useful. Mechanical circulatory support such as cardiopulmonary bypass, intra-aortic balloon pump, extracorporeal membrane oxygenation, or a left ventricular assist device should be considered early in patients with refractory dysrhythmias and hypotension to support circulation and allow the toxic alkaloids to be metabolized and excreted.

G) ENHANCED ELIMINATION

1) Unknown efficacy. Charcoal hemoperfusion has been utilized historically. A recent case reported the successful use of hemoperfusion to treat a patient with severe aconite poisoning.

H) PATIENT DISPOSITION

1) HOME CRITERIA: Asymptomatic patients may be observed at home for small exposures/unintentional ingestions.
2) OBSERVATION CRITERIA: Any patient who manifests signs of mild toxicity (ie, mild GI symptoms or oral paresthesias) after ingestion or exposure should be sent to a healthcare facility for observation. If symptoms resolve in the emergency department and the home situation permits, the patient may be discharged after psychiatric clearance if needed.
3) ADMISSION CRITERIA: Patients who present with severe symptoms (dysrhythmias, paralysis, hypotension) should be admitted to an intensive care setting. In addition, if the above mild findings persist despite treatment in the emergency department, admit the patient to the appropriate level of care.
4) CONSULT CRITERIA: Consult a medical toxicologist and cardiologist especially for patients admitted to the ICU.

I) PITFALLS

1) Failure to involve a medical toxicologist early in severe ingestions or obtain by history that an herbal agent was ingested.

J) TOXICOKINETICS

1) Rapidly absorbed orally, also absorbed through intact skin. Onset of initial symptoms is usually rapid, but can be delayed by hours.

K) DIFFERENTIAL DIAGNOSIS

1) Other herbal remedies which may be cardiotoxic should be entertained including: digoxin-like cardioactive steroids (Ch'an Su), anticholinergics (Jimson Weed), and stimulants (Ephedra, Khat).

Range Of Toxicity

A)

B)

Clinical Effects

Acid-Base

3.11.2)

A) ACIDOSIS

1) WITH POISONING/EXPOSURE

a) Metabolic acidosis developed in a patient with severe ventricular dysrhythmias following Aconitum exposure (one dose of an herbal decoction); the patient died despite aggressive treatment (But et al, 1994).

Dermatologic

3.14.1)

A) WITH POISONING/EXPOSURE

1) The skin may be cold and moist. Application of an ointment made from the plant to intact skin may cause itching, prickling, redness, or vesicles.
2) Dermatitis has been reported in pharmaceutical workers exposed to the plant.

3.14.2)

A) EXCESSIVE SWEATING

1) WITH POISONING/EXPOSURE

a) The skin may be cold and moist (Fiddes, 1958).
b) Profuse sweating has been seen after ingestion of a broth containing Aconitum species (Chan et al, 1993; Chan et al, 1993a).
c) Shortly after ingesting this material, patients may have alternating bouts of sweating and chills which eventually leads to dysesthesia (Fiddes, 1958; Frohne & Pfander, 1983).

B) ERYTHEMA

1) WITH POISONING/EXPOSURE

a) Application of an ointment made from the plant to intact skin may cause itching, prickling, redness or vesicles (Mitchell & Rook, 1979).

C) DERMATITIS

1) WITH POISONING/EXPOSURE

a) Dermatitis has been reported in pharmaceutical workers exposed to the plant (Mitchell & Rook, 1979).

D) SKIN ABSORPTION

1) WITH POISONING/EXPOSURE

a) CASE SERIES: In a review of the literature, dermal exposure to aconitum alkaloids resulted in systemic toxicity following topical application of aconite tincture. Of the 7 cases, 2 fatalities occurred following dermal application to damaged skin (ie, burn to skin and skin ulceration). The first patient was a 35-month-old child with a second-degree hot water scald over her lower limb (1.5% of the total body surface area) that was treated with aconite tincture ("caowu"). Fifteen minutes after treatment, the child collapsed with cyanosis, coma and twitching of all extremities. Despite resuscitation efforts, the child died 10 hours later. The second patient was an adult with herpes zoster and skin ulceration on the right chest and scapula that were treated with topical applications of raw "caowu" (8g) and raw "chuanwu" (8g) and other herbs. He died unexpectedly 3 days later; postmortem cardiac aconitine blood concentration was 29.9 ng/mL (Chan, 2012).

1) In the nonfatal cases, some patients developed symptoms of nausea, dizziness, and generalized paraesthesia after topical application of aconite. One patient developed hypotension and ventricular ectopy and was treated with lidocaine and magnesium. He made a complete recovery (Chan, 2012).

Musculoskeletal

3.15.1)

A) WITH POISONING/EXPOSURE

1) Muscular weakness, accompanied by generalized weakness, often occurs.
2) Initial feelings of numbness may progress to paralysis of the skeletal muscles.

3.15.2)

A) MUSCLE WEAKNESS

1) WITH POISONING/EXPOSURE

a) In a retrospective case series of 17 occurrences of aconite ingestion reported to the National Poison Center in Taiwan between 1990 and 1999, 9 of 17 patients (53%) developed generalized muscular weakness (Lin et al, 2004).
b) Muscle weakness often occurs along with a feeling of generalized lethargy (Fiddes, 1958) (Chan, 1992).
c) A 66-year-old woman developed facial and extremity paresthesias, nausea, generalized weakness, and chest pressure approximately 90 minutes after ingestion of an aconite-containing tea. At the emergency department, she developed ventricular tachycardia with varying morphologic features (monomorphic, polymorphic, and bidirectional with periods of pulselessness) refractory to both administration of adenosine and electrical cardioversion. Following supportive therapy, she converted to sinus rhythm; she was discharged as neurologically normal 4 days later (Lowe et al, 2005).

B) SPASMODIC MOVEMENT

1) WITH POISONING/EXPOSURE

a) Muscular fasciculations may lead to tonic or clonic seizures (Lampe & Fagerstrom, 1968).

C) PARALYSIS

1) WITH POISONING/EXPOSURE

a) Initial feelings of numbness may progress to paralysis of the skeletal muscles (Frohne & Pfander, 1983).

Reproductive

3.20.1)

A) At the time of this review, no data were available to assess the teratogenic potential of this agent.
B) 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)

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)

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.

Carcinogenicity

3.21.2)

A) At the time of this review, no data were available to assess the carcinogenic or mutagenic potential of this agent.

3.21.3)

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.

Summary Of Exposure

A)

B)

C)

D)

E)

1) ADVERSE EFFECTS: Paresthesias, nausea, vomiting, hypersalivation, diarrhea, skeletal muscle weakness, pain, hypotension, paralysis and dysrhythmias can develop.

F)

1) OVERDOSE: Symptoms may occur minutes to hours after ingestion.
2) MILD TO MODERATE TOXICITY: Initially paresthesias of the oral mucosa can occur that may extend to the entire body along with diaphoresis and chills. This is followed by hypersalivation, nausea, vomiting, hypersalivation, diarrhea, progressive skeletal muscle weakness and severe pain.
3) SEVERE TOXICITY: Fatal brady- or tachydysrhythmias, hypotension and paralysis can develop.

Vital Signs

3.3.1)

A) WITH POISONING/EXPOSURE

1) Hypotension and respiratory failure may occur.

3.3.2)

A) Respiratory failure may occur due to paralysis of respiratory muscles (Frohne & Pfander, 1983).

3.3.4)

A) Hypotension may be present (Munnecom et al, 2011; Merchant et al, 1963; Tomlinson et al, 1993; Chan et al, 1993a; But et al, 1994).

Heent

3.4.1)

A) WITH POISONING/EXPOSURE

1) Miosis may be seen until the patient develops hypoxia. Mydriasis may also be seen. Diplopia and blurred vision are often experienced, as is yellow-green vision.
2) A feeling of warmth, roughness, or dryness of the mouth and throat may develop soon after the onset of poisoning. There may be a feeling of airway constriction, difficulty with speaking and difficulty with swallowing.

3.4.3)

A) MIOSIS is usually seen until the patient develops hypoxia (Lampe & Fagerstrom, 1968).
B) MYDRIASIS may also be seen (Lampe & McCann, 1985).
C) DIPLOPIA and blurred vision are often experienced (Lampe & Fagerstrom, 1968; Fitzpatrick et al, 1994).
D) YELLOW-GREEN VISION may occasionally be reported (Lampe & McCann, 1985).
E) PURPLE VISION: A 21-year-old man experienced generalized paresthesias, nausea, diarrhea, vertigo, thoracic pain, dyspnea, and dyschromatopsia (purple vision) 5 hours after ingesting 3 homemade capsules containing Aconitum napellus. The patient recovered with supportive care and was discharged approximately 2 days postingestion. Analysis of one of the prepared capsules revealed that it contained 237 mg of Aconitum napellus root and 19 mcg of aconitine (Moritz et al, 2005).

3.4.6)

A) A feeling of warmth, roughness, or dryness of the mouth and throat may be seen soon after the onset of poisoning (Munnecom et al, 2011; Fiddes, 1958). There may be a feeling of airway constriction, difficulty with speaking and difficulty with swallowing (Lampe & Fagerstrom, 1968).
B) Chewing on a root may cause swelling of the lips, tongue and mouth, making speech difficult (p 1636).
C) Numbness of tongue and mouth can be an early symptom of toxicity. A young woman complained of tongue and perioral numbness shortly after drinking a tea concocted from traditional Chinese herbs that contained aconite (Boehm et al, 2011).

Cardiovascular

3.5.1)

A) WITH POISONING/EXPOSURE

1) Vagal slowing is seen in 10% to 20% of fatal intoxications. If higher concentrations are present, supraventricular tachycardia, ventricular tachycardia, torsades de pointes, and other conduction disturbances may be seen. Ventricular fibrillation may be seen, and is often the cause of death. Patients may have a severe oppressive feeling of the chest.
2) Bradycardia and hypotension are common adverse events.

3.5.2)

A) CARDIOVASCULAR FINDING

1) WITH POISONING/EXPOSURE

a) Various abnormalities have been seen, including shock, conduction delays, hypotension and dysrhythmias (Chen et al, 2015; Martens & Vandevelde, 1993).
b) Frequent cardiac complications have been seen after use of aconite containing broths (Anon, 1993).
c) In a retrospective case series of 17 occurrences of aconite ingestion reported to the National Poison Center in Taiwan between 1990 and 1999, 14 of 17 patients (82%) developed cardiovascular effects. Cardiac effects included: chest tightness (65%), palpitations (41%), sinus tachycardia, and multifocal ventricular ectopic beats. One patient had severe bradycardia requiring temporary pacemaker insertion. Four of the 17 patients (24%) developed ventricular tachycardia, but all patients recovered (Lin et al, 2004).

B) BRADYCARDIA

1) WITH POISONING/EXPOSURE

a) Vagal slowing is seen in 10% to 20% of fatal intoxications. Hartung (1930) reported bradycardia and first degree heart block in one case. Fatovich (1992) described bradycardia with heart rates as low as 30 bpm. Dysrhythmias may cause cardiac failure as early as 5 minutes or as late as 4 days postexposure (Mack, 1985).
b) CASE REPORTS/LEAVES: A couple ingested the leaves of the Aconitum pseudo-laeve var. erectum (not the root) after boiling the leaves. Within 30 minutes, they felt unwell. Hypotension and bradycardia were present on exam. They both recovered about 20 hours after exposure following supportive care (Kim et al, 2009).
c) CASE REPORT: A 58-year-old man ingested a decoction of 11 g each of 'chuanwu' (the root of A carmichaeli) and processed 'caowu' (the root of A kusnezoffi) to treat neck pain and developed persistent hypotension and bradycardia about 6 hours after ingestion. His heart rate was 45 to 68 beats/minute (mean 56.5) for approximately 36 hours. Treatment included atropine (2 doses) along with IV fluids and dopamine for hypotension. No ventricular dysrhythmias were observed. All symptoms resolved and the patient was discharged 48 hours after admission with a heart rate of 70 beats/minute (Chan, 2009).
d) CASE REPORT: A 21-year-old man experienced generalized paresthesias, nausea, diarrhea, vertigo, thoracic pain, dyspnea, and dyschromatopsia (purple vision) 5 hours after ingesting 3 homemade capsules containing Aconitum napellus. On arrival to the ED 2 hours later, his heart rate was 43 bpm. An ECG showed sinus bradycardia with polymorphic ventricular premature complexes and bigeminy. Cardiovascular abnormalities resolved 11 hours later with supportive care. Analysis of one of the prepared capsules revealed that it contained 237 mg of Aconitum napellus root and 19 mcg of aconitine (Moritz et al, 2005).

C) TACHYARRHYTHMIA

1) WITH POISONING/EXPOSURE

a) If higher concentrations are present, supraventricular tachycardia, bidirectional tachycardia (Munnecom et al, 2011; Tai et al, 1992), and other conduction disturbances may be seen (Ffrench, 1958; von Oettingen, 1958; Sollman, 1957; Agarwal et al, 1977; Kapoor & Sen, 1969).

D) VENTRICULAR ARRHYTHMIA

1) WITH POISONING/EXPOSURE

a) Multifocal premature ventricular contractions, ventricular tachycardia including monomorphic and polymorphic ventricular tachycardia, torsades de pointes and ventricular fibrillation may occur in severe poisoning (Chen et al, 2015; Chan, 2014; Dwivedi et al, 2011; Strzelecki et al, 2010; Munnecom et al, 2011; Tai et al, 1992a; Tomlinson et al, 1993; Fitzpatrick et al, 1994). Patients may have a severe oppressive feeling of the chest (Lampe & Fagerstrom, 1968).
b) CASE REPORTS

1) CASE REPORT: A 50-year-old woman ingested "chuanwu" chicken soup (500 mL) containing a piece of boiled "chuanwu" (20 g of the root of A kusnezoffii) and 2 hours later developed neurologic symptoms, dizziness, weakness and nausea. Her symptoms progressed to include sweating, palpitations, cold extremities, seizures and bowel and bladder incontinence. Upon admission, she was in shock (BP 60/40 mmHg) and had multiple episodes of ventricular tachycardia and a single episode of bradycardia. She recovered uneventfully (Chan, 2014).

a) In another case, a woman ingested a chicken soup containing "chuanwu" (15 g of the root of A. kusnezoffii) and within 10 minutes she developed neurologic symptoms, vomiting episodes, chest tightness and palpitations. Upon admission, approximately 2 hours after ingestion, the patient was in shock (BP 60/45 mmHg) and developed paroxysmal ventricular tachycardia. Following resuscitation, symptoms resolved completely within 24 hours (Chan, 2014).

2) An elderly couple (81-year-old man and 81-year-old woman) inadvertently ingested aconitum napellus (Monkshood) mistaken for another plant. The husband collapsed at home and presented to the emergency department in cardiorespiratory arrest and the ECG showed polymorphic ventricular tachycardia with alternating monomorphic ventricular tachycardia. Recurrent arrhythmias were treated for 2 hours with amiodarone, adrenaline, bicarbonate, magnesium and electrical cardioversion. The woman was treated with amiodarone and adrenaline for bidirectional ventricular tachycardia and hypotension. Both recovered completely (Munnecom et al, 2011).
3) A 54-year-old man intentionally ingested an herb and came to the emergency department about an hour later complaining of paresthesia of the mouth. Shortly after admission the patient was in polymorphic ventricular tachycardia followed by ventricular fibrillation. Despite immediate cardiopulmonary resuscitation (including direct-current cardioversion and various anti-arrhythmic agents) and mechanical ventilation, the patient died of refractory ventricular fibrillation. Two months later, laboratory analysis confirmed the presence of A napellus (whole blood concentration 24 mcg/L) in antemortem blood (Strzelecki et al, 2010).
4) A 59-year-old woman presented to the ED with palpitations, nausea, vomiting, weakness and numbness after accidentally ingesting a root thought to be Aconitum carmichaelii. An ECG showed polymorphic ventricular tachycardia, including episodes of prolonged bidirectional ventricular tachycardia with alternating left and right bundle-branch block, unresponsive to esmolol therapy. Following supportive therapy, she converted to normal sinus rhythm (Smith et al, 2005).
5) A 66-year-old woman developed facial and extremity paresthesias, nausea, generalized weakness, and chest pressure approximately 90 min after ingestion of an aconite-containing tea. At presentation to the emergency department, she had supraventricular tachycardia with hemodynamic compromise, unresponsive to adenosine and electrical cardioversion. She then developed ventricular tachycardia with varying morphologic features (monomorphic, polymorphic, and bidirectional with periods of pulselessness) refractory to electrical and unspecified pharmacologic treatment. Following supportive therapy, she converted to sinus rhythm after 4 hour and was discharged 4 days later with no sequelae (Lowe et al, 2005).
6) A 35-year-old man developed polymorphic ventricular tachycardia/torsades de pointes, following the ingestion of 3 to 4 rootstocks of Aconitum napellus. The dysrhythmias resolved after an initial bolus of magnesium (13.5 mmol) followed by an IV infusion (22.5 mmol/day) for 24 hours (Felgenhauer et al, 1999).
7) Right bundle branch block, bigeminy and hypotension (90/40 mmHg) were reported in a 31-year-old man 5 hours after ingestion of 60 blue flowers thought to be Aconitum cammarum. The patient also experienced nausea, vomiting, tremors and cold extremities. The ECG normalized within 24 hours and the patient recovered without sequelae (Pohjalainen et al, 2003).
8) A 32-year-old man applied a self-prepared aconite tincture to a chest contusion and developed palpitations, dizziness, paraesthesia and nausea and vomiting after 2 days of application. Upon admission, his blood pressure was 102/64 mmHg and heart rate was 84 to 106 beats/min. An ECG showed multi-focal ventricular ectopics and episodes of complete heart block and ventricular tachycardia. He was treated with lidocaine and magnesium and recovered completely (Chan, 2012).

c) CASE SERIES

1) CASE SERIES: During 2004 to 2008, 9 men and 6 women (aged 28 to 72 years) were admitted to the hospital after ingesting "caowu" (the root of A. kusnezoffii) cooked in pork broth. They arrived within 30 minutes to 3 hours after the onset of symptoms. The most commonly reported symptoms included seizures (n=6), irritability (n=4), and ventricular tachycardia accompanied with severe gastrointestinal symptoms (n=2). Three deaths occurred and were due to severe cardiac dysrhythmias, circulatory failure, and CNS and respiratory depression (Chan, 2014).
2) Three adults were accidentally exposed to Aconitum root with severe dysrhythmias reported in 2 of the 3 adults. A 60-year-old man developed fatal ventricular fibrillation 3 hours after exposure. The other case survived following high dose phenytoin administration (Deraemaeker et al, 1995).
3) Three adults died after aconite exposure despite aggressive resuscitation measures. Cardiac toxicity (sustained ventricular dysrhythmias, hypotension, and chest pain) occurred following single doses of herbal decoctions in 2 of 3 cases. The third patient developed similar symptoms and outcome following 5 doses of an oral decoction. Acidosis and hypokalemia were also reported (But et al, 1994).

E) VENTRICULAR FIBRILLATION

1) WITH POISONING/EXPOSURE

a) SUMMARY: Ventricular fibrillation has been observed following aconite poisoning. It has been observed in a number of fatal cases. Patients that have survived required aggressive care (Imazio et al, 2000; Dwivedi et al, 2011; Strzelecki et al, 2010; Weijters et al, 2008; McGregor et al, 2008)
b) CASE REPORT: A 39-year-old man ingested more than 100 g of an herb from his garden (thought to be celery but later identified as Aconite) and became ill within 2 hours of ingestion with severe gastrointestinal effects and a brief period of collapse. Upon presentation, he was alert with no complaints of chest pain. An ECG showed a monomorphic ventricular tachycardia with a rate of 220 bpm progressing to ventricular fibrillation. The patient required aggressive supportive care including intubation, multiple direct current cardioversions, epinephrine, magnesium and amiodarone. After one hour of resuscitation, the patient had an atrial rhythm with ongoing polymorphic ventricular complexes. Sinus rhythm returned within 4 hours and inotropic support and mechanical ventilation were stopped within 12 hours. The patient made a complete recovery (Weijters et al, 2008).
c) CASE REPORT: A 36-year-old man ingested a small amount of A. napellus and initially felt well. At presentation, he complained of perioral numbness and was hypotensive with a wide complex rhythm. Despite inotropic support and antiarrhythmic agents (magnesium, amiodarone) the patient experienced an episode of ventricular fibrillation and pulseless electrical activity. CPR was initiated. Ongoing supraventricular and ventricular dysrhythmias were eventually managed with intravenous mexiletine therapy. No permanent sequelae was observed and the patient was discharged to home (McGregor et al, 2008).

F) ELECTROCARDIOGRAM ABNORMAL

1) WITH POISONING/EXPOSURE

a) Merchant et al (1963) described 3 cases with A-V block, first-degree heart block, variable first-degree heart block (PR 0.20 to 0.28 sec), variable PR intervals (PR being 0.06 to 0.16 secs), nodal rhythm with sinus escape, ventricular fibrillation with sinus and nodal escape, bundle branch block pattern, bigeminal rhythm, and nodal and ventricular extra systoles.

G) CARDIAC ARREST

1) WITH POISONING/EXPOSURE

a) CASE REPORT: An 81-year-old man inadvertently ingested aconitum napellus (Monkshood) mistaken for another plant. He collapsed at home and presented to the emergency department in cardiorespiratory arrest and the ECG showed polymorphic ventricular tachycardia with alternating monomorphic ventricular tachycardia. Recurrent arrhythmias were treated for 2 hours with amiodarone, adrenaline, bicarbonate, magnesium and electrical cardioversion. He recovered completely within a few hours (Munnecom et al, 2011).
b) CASE REPORT: A 20-year-old man was admitted to the ED with abdominal pain and vomiting after ingesting an unknown quantity of soup made from Monkshood. He suffered a cardiac arrest shortly after arrival to the ED and resuscitation was unsuccessful (Crandon & Thompson, 2003).

H) HYPOTENSIVE EPISODE

1) WITH POISONING/EXPOSURE

a) Hypotension is likely to be present (Chen et al, 2015; Chan, 2009; Munnecom et al, 2011; Merchant et al, 1963; Tomlinson et al, 1993; Chan et al, 1993a; But et al, 1994).
b) CASE REPORTS/LEAVES: A couple ingested the leaves of the Aconitum pseudo-laeve var. erectum (not the root) after boiling the leaves. Within 30 minutes, they felt unwell. Hypotension and bradycardia were present on exam. They both recovered about 20 hours after exposure following supportive care (Kim et al, 2009).
c) CASE REPORT: A 50-year-old woman ingested "chuanwu" chicken soup (500 mL) containing a piece of boiled "chuanwu" (20 g of the root of A kusnezoffii) and 2 hours later developed neurologic symptoms, dizziness, weakness and nausea. Her symptoms progressed to include sweating, palpitations, cold extremities, seizures and bowel and bladder incontinence. Upon admission, she was in shock (BP 60/40 mmHg) and had multiple episodes of ventricular tachycardia and a single episode of bradycardia. She recovered uneventfully (Chan, 2014).

1) In another case, a woman ingested a chicken soup containing "chuanwu" (15 g of the root of A. kusnezoffii) and within 10 minutes she developed neurologic symptoms, vomiting episodes, chest tightness and palpitations. Upon admission, approximately 2 hours after ingestion, the patient was in shock (BP 60/45 mmHg) and developed paroxysmal ventricular tachycardia. Following resuscitation, symptoms resolved completely within 24 hours (Chan, 2014).

d) CASE REPORT: A 58-year-old man ingested a decoction of 11 g each of 'chuanwu' (the root of A carmichaeli) and processed 'caowu' (the root of A kusnezoffii) to treat neck pain and developed persistent hypotension and bradycardia about 6 hours after ingestion. His systolic blood pressure measurements ranged from 84 to 106 mmHg (mean 93.5) with diastolic blood pressure readings of 40 to 59 mmHg (mean 51.8). Treatment included IV fluids and dopamine. Hypotension resolved 31 hours later. The patient recovered completely and was discharged 48 hours after ingestion (Chan, 2009).
e) CASE REPORT: A 35-year-old man developed hypotension (systolic BP 60 mmHg) and dysrhythmias following the ingestion of 3 to 4 rootstocks of Aconitum napellus. The patient recovered following supportive care (Felgenhauer et al, 1999).
f) CASE SERIES: In a retrospective case series of 17 occurrences of aconite ingestion reported to the National Poison Center in Taiwan between 1990 and 1999, 7 of 17 patients (41%) developed hypotension (Lin et al, 2004).

Respiratory

3.6.1)

A) WITH POISONING/EXPOSURE

1) Respiratory paralysis is often the cause of death. Pulmonary edema may develop.

3.6.2)

A) DECREASED RESPIRATORY FUNCTION

1) WITH POISONING/EXPOSURE

a) Respiratory failure is often the cause of death (Frohne & Pfander, 1983).
b) CASE SERIES: During 2004 to 2008, 9 men and 6 women (aged 28 to 72 years) were admitted to the hospital after ingesting "caowu" (the root of A. kusnezoffii) cooked in pork broth. They arrived within 30 minutes to 3 hours after the onset of symptoms. The most commonly reported symptoms included seizures (n=6), irritability (n=4), and ventricular tachycardia accompanied with severe gastrointestinal symptoms (n=2). Three deaths occurred and were due to severe cardiac dysrhythmias, circulatory failure, and CNS and respiratory depression (Chan, 2014).

B) ACUTE LUNG INJURY

1) WITH POISONING/EXPOSURE

a) Pulmonary edema may develop (Lampe & Fagerstrom, 1968).

C) DYSPNEA

1) WITH POISONING/EXPOSURE

a) A few patients have reported difficulty with breathing after ingesting aconite containing herbals (Chan et al, 1993a; Fitzpatrick et al, 1994).
b) CASE REPORT: A 21-year-old man experienced generalized paresthesias, nausea, diarrhea, vertigo, thoracic pain, dyspnea, and dyschromatopsia (purple vision) 5 hours after ingesting 3 homemade capsules containing Aconitum napellus. The patient recovered with supportive care and was discharged approximately 2 days postingestion. Analysis of one of the prepared capsules revealed that it contained 237 mg of Aconitum napellus root and 19 mcg of aconitine (Moritz et al, 2005).

Neurologic

3.7.1)

A) WITH POISONING/EXPOSURE

1) An early sign of intoxication is a burning or tingling sensation in the lips, tongue, mouth, fingers and toes. This gradually extends over the entire body, but is particularly strong on the face. Patients poisoned by these plants often experience severe pain.
2) CNS depression is usually NOT seen. Patients often have severe headache, restlessness, apprehension and confusion. Muscular fasciculations may lead to tonic or clonic seizures. Incoordination is often present.

3.7.2)

A) PARESTHESIA

1) WITH POISONING/EXPOSURE

a) An early sign of intoxication is a burning or tingling sensation in the lips, tongue, mouth, fingers and toes. This gradually extends over the entire body, but is particularly strong on the face (Munnecom et al, 2011; Fiddes, 1958; Fatovich, 1992; Fitzpatrick et al, 1994). Following the paresthesias, the body may become numb (Yi-gu & Guang-zhao, 1988) (Chan et al, 1993).
b) CASE SERIES: In a retrospective case series of 17 occurrences of aconite ingestion reported to the National Poison Center in Taiwan between 1990 and 1999, 17 of 17 patients (100%) developed sensory or motor neurological effects. Paresthesia and numbness of the extremities occurred in 13 of 17 patients (76%), with perioral or facial numbness occurring in 8 of 17 patients (47%). Dizziness was also reported in 65% of the patients. All cases eventually recovered (Lin et al, 2004).
c) CASE REPORT: A 66-year-old woman developed facial and extremity paresthesias, nausea, generalized weakness, and chest pressure approximately 90 minutes after ingestion of an aconite-containing tea. In the emergency department, she developed ventricular tachycardia with varying morphologic features (monomorphic, polymorphic, and bidirectional with periods of pulselessness) refractory to both administration of adenosine and electrical cardioversion. Following supportive therapy, she converted to sinus rhythm; she was discharged as neurologically normal 4 days later (Lowe et al, 2005).
d) CASE REPORT: A 21-year-old man experienced generalized paresthesias, nausea, diarrhea, vertigo, thoracic pain, dyspnea, and dyschromatopsia (purple vision) 5 hours after ingesting 3 homemade capsules containing Aconitum napellus. The neurological symptoms resolved 13 hours postingestion and the patient was discharged approximately 2 days postingestion. Analysis of one of the prepared capsules revealed that it contained 237 mg of Aconitum napellus root and 19 mcg of aconitine (Moritz et al, 2005).

B) PARALYSIS

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 62-year-old woman developed limb paralysis after ingesting 150 mL of a decoction containing 3 g of dried Aconiti tuber, Uzu. It was found that the patient had ingested the solution 6 hours after dissolving it in water rather than boiling the solution to reduce it to 300 mL. Following symptomatic care the patient recovered completely (Ono et al, 2009).

C) PAIN

1) WITH POISONING/EXPOSURE

a) Patients poisoned by these plants often experience severe pain (Frohne & Pfander, 1983) (Druckrey, 1943).
b) DYSESTHESIA: Shortly after ingesting this material, patients may have alternating bouts of sweating and chills which eventually leads to a feeling of intense, icy cold (anesthesia dolorosa) (Munnecom et al, 2011; Fiddes, 1958).

D) PSYCHOMOTOR AGITATION

1) WITH POISONING/EXPOSURE

a) CNS depression is usually NOT seen. Patients are often conscious through the pain, muscle paralysis and respiratory paralysis (Frohne & Pfander, 1983). Irritability, restlessness, apprehension, and confusion are often seen (Fiddes, 1958; Lampe & Fagerstrom, 1968). Delirium has been noted in some poisonings (Merchant et al, 1963).

E) HEADACHE

1) WITH POISONING/EXPOSURE

a) Patients often have a severe headache (Lampe & Fagerstrom, 1968).

F) SEIZURE

1) WITH POISONING/EXPOSURE

a) CASE SERIES: During 2004 to 2008, 9 men and 6 women (aged 28 to 72 years) were admitted to the hospital after ingesting "caowu" (the root of A. kusnezoffii) cooked in pork broth. They arrived within 30 minutes to 3 hours after the onset of symptoms. The most commonly reported symptoms included seizures (n=6), irritability (n=4), and ventricular tachycardia accompanied with severe gastrointestinal symptoms (n=2). Three deaths occurred and were due to severe cardiac dysrhythmias, circulatory failure, and CNS and respiratory depression (Chan, 2014).
b) Muscular fasciculations may lead to tonic or clonic seizures (Merchant et al, 1963; Lampe & Fagerstrom, 1968).

G) DIZZINESS

1) WITH POISONING/EXPOSURE

a) Vertigo may be seen in intoxications (Lampe & Fagerstrom, 1968; Chan et al, 1993a).
b) CASE REPORT: A 21-year-old man experienced generalized paresthesias, nausea, diarrhea, vertigo, thoracic pain, dyspnea, and dyschromatopsia (purple vision) 5 hours after ingesting 3 homemade capsules containing Aconitum napellus. The neurological symptoms resolved 13 hours postingestion and the patient was discharged approximately 2 days postingestion. Analysis of one of the prepared capsules revealed that it contained 237 mg of Aconitum napellus root and 19 mcg of aconitine (Moritz et al, 2005).

H) COORDINATION PROBLEM

1) WITH POISONING/EXPOSURE

a) Incoordination is often present (Lampe & Fagerstrom, 1968).

Gastrointestinal

3.8.1)

A) WITH POISONING/EXPOSURE

1) Chewing on a root may cause swelling of the lips, tongue and mouth, making speech difficult.
2) Intense vomiting and a colicky-diarrhea may develop after an ingestion. A feeling of roughness or dryness of the mouth and throat may also be seen. Salivation may be increased in the early stages of intoxication.

3.8.2)

A) NAUSEA AND VOMITING

1) WITH POISONING/EXPOSURE

a) Nausea and vomiting are likely to occur after ingestion (Munnecom et al, 2011; Moritz et al, 2005; Lowe et al, 2005; Smith et al, 2005; Pohjalainen et al, 2003; Ffrench, 1958). Violent episodes of vomiting have been observed (Munnecom et al, 2011).
b) In one study of 17 patients, all had symptoms within 2 hours (Tai et al, 1992a).
c) CASE SERIES: In a retrospective case series of 17 occurrences of aconite ingestion reported to the National Poison Center in Taiwan between 1990 and 1999, 9 of 17 patients (53%) developed nausea and vomiting (Lin et al, 2004).

B) DIARRHEA

1) WITH POISONING/EXPOSURE

a) A colicky-diarrhea may be seen after ingestion (Yi-gu & Guang-zhao, 1988) (Chan et al, 1993a; Fitzpatrick et al, 1994).
b) CASE REPORT: A 21-year-old man experienced generalized paresthesias, nausea, diarrhea, vertigo, thoracic pain, dyspnea, and dyschromatopsia (purple vision) 5 hours after ingesting 3 homemade capsules containing Aconitum napellus. The patient recovered with supportive care and was discharged approximately 2 days postingestion. Analysis of one of the prepared capsules revealed that it contained 237 mg of Aconitum napellus root and 19 mcg of aconitine (Moritz et al, 2005).

C) APTYALISM

1) WITH POISONING/EXPOSURE

a) A feeling of roughness or dryness of the mouth and throat may be seen soon after the onset of poisoning (Fiddes, 1958).

D) EXCESSIVE SALIVATION

1) WITH POISONING/EXPOSURE

a) Salivation may be increased in the early stages of intoxication (Fiddes, 1958).

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) Monitor vital signs and mental status. Institute continuous cardiac monitoring and obtain an ECG.
B) Monitor serum electrolytes, including calcium and magnesium.
C) Laboratory analysis (ie, GC/MS, HPLC) may be utilized to detect aconite and confirm exposure, but is not useful to guide therapy.

4.1.2)

A) BLOOD/SERUM CHEMISTRY

1) Extensive vomiting and diarrhea may require that fluid and electrolytes be monitored and replaced as necessary.

Methods

A)

1) In a study of 7 cases of fatal aconite poisoning, various qualitative and quantitative methods including thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC) and high-performance liquid chromatography/mass spectrometry (HPLC/MS) were used to detect aconite in heart blood, liver, urine, gastric contents and the medicated liquor consumed. Aconite was confirmed in bodily fluids and/or the medicated liquor in each case (Liu et al, 2011).

B)

1) GC/MS was used to detect aconitum alkaloids from body fluids (eg, serum, urine and gastric contents), as well as the decoction solution in an individual who became ill after ingesting a Chinese herbal preparation containing 3 g of dried Aconiti tuber, Uzu, that was improperly prepared (Ono et al, 2009).

Treatment

Life Support

A)

Patient Disposition

6.3.1)

6.3.1.1) ADMISSION CRITERIA/ORAL

A) Patients who present with severe symptoms (dysrhythmias, paralysis, hypotension) should be admitted to an intensive care setting. In addition, if the above mild findings persist despite treatment in the emergency department, admit the patient to the appropriate level of care.

6.3.1.2) HOME CRITERIA/ORAL

A) Asymptomatic patients may be observed at home for small exposures/unintentional ingestions.

6.3.1.3) CONSULT CRITERIA/ORAL

A) Consult a medical toxicologist and cardiologist especially for patients admitted to the ICU.

6.3.1.5) OBSERVATION CRITERIA/ORAL

A) Any patient who manifests signs of mild toxicity (ie, mild GI symptoms or oral paresthesias) after ingestion or exposure should be sent to a healthcare facility for observation. If symptoms resolve in the emergency department and the home situation permits, the patient may be discharged after psychiatric clearance if needed.

Monitoring

A)

B)

C)

Oral Exposure

6.5.1)

A) 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)

A) 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)

A) SUPPORT

1) There is no specific antidote. Treatment is symptomatic and supportive after decontamination. Onset is rapid, and prognosis after ingestion is generally poor (Frohne & Pfander, 1983).

B) MONITORING OF PATIENT

1) Monitor vital signs and mental status. Institute continuous cardiac monitoring and obtain an ECG. Monitor serum electrolytes, including calcium and magnesium. Laboratory analysis (ie, GC/MS, HPLC) may be utilized to detect aconite and confirm exposure, but is not useful to guide therapy.

C) AIRWAY MANAGEMENT

1) Respiratory support should be available, since paralysis of respiratory muscles may occur.

D) FLUID/ELECTROLYTE BALANCE REGULATION

1) Extensive vomiting and diarrhea may require that fluid and electrolytes be monitored and replaced as necessary.

E) VENTRICULAR ARRHYTHMIA

1) ACONITE-INDUCED ventricular dysrhthymias can occur due to sodium channel activation resulting in a prolonged repolarization phase of the action potential that can promote both atrial and ventricular dysrhythmias (Munnecom et al, 2011).
2) VENTRICULAR DYSRHYTHMIAS SUMMARY

a) Obtain an ECG, institute continuous cardiac monitoring and administer oxygen. Evaluate for hypoxia, acidosis, and electrolyte disorders (particularly hypokalemia, hypocalcemia, and hypomagnesemia). Lidocaine and amiodarone are generally first line agents for stable monomorphic ventricular tachycardia, particularly in patients with underlying impaired cardiac function. Amiodarone should be used with caution if a substance that prolongs the QT interval and/or causes torsades de pointes is involved in the overdose. Unstable rhythms require immediate cardioversion.

3) Based on reports in the literature, dysrhythmias are relatively refractory to drug management.

a) CASE REPORTS: A number of different agents have been tried, including atropine, quinidine (Heistracher & Pillat, 1962), dichloroisoproterenol (Lucchesi, 1962), digitalis (Lucchesi, 1962), parasympathomimetics (Lucchesi, 1962), mexiletine (McGregor et al, 2008; Poy et al, 1986) and inorganic ions (Lucchesi, 1962; Mladoveanu et al, 1939).
b) DC cardioversion and lidocaine were not effective in a number of Hong Kong cases (Tomlinson et al, 1993; Tai et al, 1992; But et al, 1994).

4) AMIODARONE

a) AMIODARONE/INDICATIONS

1) Effective for the control of hemodynamically stable monomorphic ventricular tachycardia. Also recommended for pulseless ventricular tachycardia or ventricular fibrillation in cardiac arrest unresponsive to CPR, defibrillation and vasopressor therapy (Link et al, 2015; Neumar et al, 2010). It should be used with caution when the ingestion involves agents known to cause QTc prolongation, such as fluoroquinolones, macrolide antibiotics or azoles, and when ECG reveals QT prolongation suspected to be secondary to overdose (Prod Info Cordarone(R) oral tablets, 2015).

b) AMIODARONE/ADULT DOSE

1) For ventricular fibrillation or pulseless VT unresponsive to CPR, defibrillation, and a vasopressor therapy give an initial dose of 300 mg IV followed by 1 dose of 150 mg IV. For stable ventricular tachycardias: Infuse 150 milligrams over 10 minutes, and repeat if necessary. Follow by a 1 milligram/minute infusion for 6 hours, then a 0.5 milligram/minute. Maximum total dose over 24 hours is 2.2 grams (Neumar et al, 2010).

c) AMIODARONE/PEDIATRIC DOSE

1) Infuse 5 milligrams/kilogram as a bolus for pulseless ventricular tachycardia or ventricular fibrillation; may repeat twice up to 15 mg/kg. Infuse 5 milligrams/kilogram over 20 to 60 minutes for perfusing tachycardias. Maximum single dose is 300 mg. Routine use with other drugs that prolong the QT interval is NOT recommended (Kleinman et al, 2010).

d) ADVERSE EFFECTS

1) Hypotension and bradycardia are the most common adverse effects (Neumar et al, 2010).

5) CASE REPORTS

a) An elderly couple (81-year-old man and 81-year-old woman) inadvertently ingested aconitum napellus (Monkshood) mistaken for another plant. The husband collapsed at home and presented to the emergency department in cardiorespiratory arrest and the ECG showed polymorphic ventricular tachycardia with alternating monomorphic ventricular tachycardia. Recurrent arrhythmias were treated for 2 hours with amiodarone, adrenaline, bicarbonate, magnesium and cardioversion. The woman was treated with amiodarone and adrenaline for bidirectional ventricular tachycardia and hypotension. Both recovered completely (Munnecom et al, 2011).

6) LIDOCAINE

a) LIDOCAINE/INDICATIONS

1) Ventricular tachycardia or ventricular fibrillation (Prod Info Lidocaine HCl intravenous injection solution, 2006; Neumar et al, 2010; Vanden Hoek et al, 2010).

b) 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).

c) 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).

d) LIDOCAINE/MONITORING PARAMETERS

1) Monitor ECG continuously; plasma concentrations as indicated (Prod Info Lidocaine HCl intravenous injection solution, 2006).

7) OTHER AGENTS

a) CALCIUM

1) Begemann (1961) reported the reversal of paroxysmal supraventricular tachycardia with multiple multifocal extrasystoles by IV administration of 40 mL of calcium gluconate (10%) followed by 5 mL of magnesium sulfate (15%).
2) ANIMAL DATA: In animals, giving 10 mL/kg of a 3% solution of calcium chloride followed by 3 mL of a 12% solution of magnesium sulfate was the most successful method used to reverse arrhythmias (Mladoveanu et al, 1939).

b) MAGNESIUM

1) Magnesium was used to treat hypotension, muscarinic symptoms and arrhythmias (ventricular bigeminism, severe bradycardia (20 beats/min) and multiform premature ventricular contractions) in an elderly adult that had intentionally ingesting 5 g of crushed Aconit napel root (monkshood). Magnesium sulfate was initially administered as a 6 g loading dose followed by 3 g/day for 2 days due to the long half-life of the active metabolites; magnesium levels were monitored every 4 hours. Other therapy included IV fluid resuscitation and atropine. Clinically, the patient improved shortly after starting therapy along with normal sinus rhythm (heart rate 86 bpm) (Gottignies et al, 2009).

c) MEXILETINE

1) Mexiletine was found to be an effective agent in a patient with persistent supraventricular and ventricular dysrhythmias, which did not respond to multiple agents (including magnesium, amiodarone) and attempts at synchronized cardioversion (McGregor et al, 2008).

d) PROCAINE

1) Although Heistracher & Pillat (1962) did not find procaine particularly useful, cases of ventricular fibrillation did respond well to 0.1% procaine (as little as 50 mL) given IV (Merchant et al, 1963).

e) PHENYTOIN

1) ANIMAL DATA: Aconite-induced atrial and ventricular flutter and fibrillation were treated with intravenous phenytoin. The arrhythmias were quickly abolished, but the effects were transient (Scherf et al, 1960).

f) FLECAINIDE

1) ANIMAL DATA: In one animal study, flecainide, a sodium-channel blocker, as well as a beta blocker was an effective antiarrhythmic for aconite poisoning. The authors proposed that aconite can trigger automaticity during the plateau (phase II) of the action potential by direct, persistent activation of inward sodium channels, prolonging repolarization and inducing afterdepolarization with triggered automaticity (Gutierrez et al, 1987).

8) TORSADES DE POINTES

a) SUMMARY

1) Withdraw the causative agent. Hemodynamically unstable patients with Torsades de pointes (TdP) require electrical cardioversion. Emergent treatment with magnesium (first-line agent) or atrial overdrive pacing is indicated. Detect and correct underlying electrolyte abnormalities (ie, hypomagnesemia, hypokalemia, hypocalcemia). Correct hypoxia, if present (Drew et al, 2010; Neumar et al, 2010; Keren et al, 1981; Smith & Gallagher, 1980).
2) Polymorphic VT associated with acquired long QT syndrome may be treated with IV magnesium. Overdrive pacing or isoproterenol may be successful in terminating TdP, particularly when accompanied by bradycardia or if TdP appears to be precipitated by pauses in rhythm (Neumar et al, 2010). In patients with polymorphic VT with a normal QT interval, magnesium is unlikely to be effective (Link et al, 2015).

b) MAGNESIUM SULFATE

1) Magnesium is recommended (first-line agent) for the prevention and treatment of drug-induced torsades de pointes (TdP) even if the serum magnesium concentration is normal. QTc intervals greater than 500 milliseconds after a potential drug overdose may correlate with the development of TdP (Charlton et al, 2010; Drew et al, 2010). ADULT DOSE: No clearly established guidelines exist; an optimal dosing regimen has not been established. Administer 1 to 2 grams diluted in 10 milliliters D5W IV/IO over 15 minutes (Neumar et al, 2010). Followed if needed by a second 2 gram bolus and an infusion of 0.5 to 1 gram (4 to 8 mEq) per hour in patients not responding to the initial bolus or with recurrence of dysrhythmias (American Heart Association, 2005; Perticone et al, 1997). Rate of infusion may be increased if dysrhythmias recur. For persistent refractory dysrhythmias, a continuous infusion of up to 3 to 10 milligrams/minute in adults may be given (Charlton et al, 2010).
2) PEDIATRIC DOSE: 25 to 50 milligrams/kilogram diluted to 10 milligrams/milliliter for intravenous infusion over 5 to 15 minutes up to 2 g (Charlton et al, 2010).
3) PRECAUTIONS: Use with caution in patients with renal insufficiency.
4) MAJOR ADVERSE EFFECTS: High doses may cause hypotension, respiratory depression, and CNS toxicity (Neumar et al, 2010). Toxicity may be observed at magnesium levels of 3.5 to 4.0 mEq/L or greater (Charlton et al, 2010).
5) MONITORING PARAMETERS: Monitor heart rate and rhythm, blood pressure, respiratory rate, motor strength, deep tendon reflexes, serum magnesium, phosphorus, and calcium concentrations (Prod Info magnesium sulfate heptahydrate IV, IM injection, solution, 2009).

c) OVERDRIVE PACING

1) Institute electrical overdrive pacing at a rate of 130 to 150 beats per minute, and decrease as tolerated. Rates of 100 to 120 beats per minute may terminate torsades (American Heart Association, 2005). Pacing can be used to suppress self-limited runs of TdP that may progress to unstable or refractory TdP, or for override refractory, persistent TdP before the potential development of ventricular fibrillation (Charlton et al, 2010). In a case series overdrive pacing was successful in terminating TdP associated with bradycardia and drug-induced QT prolongation (Neumar et al, 2010).

d) POTASSIUM REPLETION

1) Potassium supplementation, even if serum potassium is normal, has been recommended by many experts (Charlton et al, 2010; American Heart Association, 2005). Supplementation to supratherapeutic potassium concentrations of 4.5 to 5 mmol/L has been suggested, although there is little evidence to determine the optimal range in dysrhythmia (Drew et al, 2010; Charlton et al, 2010).

e) ISOPROTERENOL

1) Isoproterenol has been successful in aborting torsades de pointes that was resistant to magnesium therapy in a patient in whom transvenous overdrive pacing was not an option (Charlton et al, 2010) and has been successfully used to treat torsades de pointes associated with bradycardia and drug induced QT prolongation (Keren et al, 1981; Neumar et al, 2010). Isoproterenol may have a limited role in pharmacologic overdrive pacing in select patients with drug-induced torsades de pointes and acquired long QT syndrome (Charlton et al, 2010; Neumar et al, 2010). Isoproterenol should be avoided in patients with polymorphic VT associated with familial long QT syndrome (Neumar et al, 2010).
2) DOSE: ADULT: 2 to 10 micrograms/minute via a continuous monitored intravenous infusion; titrate to heart rate and rhythm response (Neumar et al, 2010).
3) PRECAUTIONS: Correct hypovolemia before using; contraindicated in patients with acute cardiac ischemia (Prod Info Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, 2013).

a) Contraindicated in patients with preexisting dysrhythmias; tachycardia or heart block due to digitalis toxicity; ventricular dysrhythmias that require inotropic therapy; and angina. Use with caution in patients with coronary insufficiency (Prod Info Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, 2013).

4) MAJOR ADVERSE EFFECTS: Tachycardia, cardiac dysrhythmias, palpitations, hypotension or hypertension, nervousness, headache, dizziness, and dyspnea (Prod Info Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, 2013).
5) MONITORING PARAMETERS: Monitor heart rate and rhythm, blood pressure, respirations and central venous pressure to guide volume replacement (Prod Info Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, 2013).

f) OTHER DRUGS

1) Mexiletine, verapamil, propranolol, and labetalol have also been used to treat TdP, but results have been inconsistent (Khan & Gowda, 2004).

g) AVOID

1) Avoid class Ia antidysrhythmics (eg, quinidine, disopyramide, procainamide, aprindine), class Ic (eg, flecainide, encainide, propafenone) and most class III antidysrhythmics (eg, N-acetylprocainamide, sotalol) since they may further prolong the QT interval and have been associated with TdP.

F) BRADYCARDIA

1) SUMMARY

a) ATROPINE/DOSE

1) ADULT BRADYCARDIA: BOLUS: Give 0.5 milligram IV, repeat every 3 to 5 minutes, if bradycardia persists. Maximum: 3 milligrams (0.04 milligram/kilogram) intravenously is a fully vagolytic dose in most adults. Doses less than 0.5 milligram may cause paradoxical bradycardia in adults (Neumar et al, 2010).
2) PEDIATRIC DOSE: As premedication for emergency intubation in specific situations (eg, giving succinylchoine to facilitate intubation), give 0.02 milligram/kilogram intravenously or intraosseously (0.04 to 0.06 mg/kg via endotracheal tube followed by several positive pressure breaths) repeat once, if needed (de Caen et al, 2015; Kleinman et al, 2010). MAXIMUM SINGLE DOSE: Children: 0.5 milligram; adolescent: 1 mg.

a) There is no minimum dose (de Caen et al, 2015).
b) MAXIMUM TOTAL DOSE: Children: 1 milligram; adolescents: 2 milligrams (Kleinman et al, 2010).

G) 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).

H) IMPLANTATION OF VENTRICULAR ASSIST DEVICE

1) CASE REPORT: A 32-year-old man developed severe hypotension and refractory ventricular dysrhythmias after ingesting an aconite-containing herbal medication. Dysrhythmias did not respond to treatment with sotalol, amiodarone, magnesium, bretylium, epinephrine, and sodium bicarbonate. The patient was placed on cardiopulmonary bypass, received ventricular pacing, and a left ventricular assist device was placed because of severe left ventricular dysfunction. Pacing was discontinued after 12 hours and the left ventricular assist device removed after 24 hours. The patient recovered without sequelae (Fitzpatrick et al, 1994).

Enhanced Elimination

A)

1) Unknown efficacy. Charcoal hemoperfusion has been utilized historically. A recent case reported the successful use of hemoperfusion to treat a patient with severe aconite poisoning.

B)

1) CASE REPORT: A 48-year-old man ingested 30 mL of herbal wine containing caowu for low back pain and within minutes he developed paresthesia, chest discomfort and dyspnea. Upon admission, his ECG showed premature ventricular bigeminy and he was transferred to a higher level of care. A repeat ECG showed frequent premature ventricular beats, paroxysmal atrial tachycardia, polymorphic ventricular tachycardia, T-wave changes and a prolonged QTc interval. In addition, the presence of a polycystic kidney cyst (the patient had a positive family history) with hemorrhage was found. Treatment consisted of IV hydration, atropine and lidocaine (a continuous IV infusion of lidocaine at a rate of 1.7 mg/minute) to treat polymorphic ventricular premature beats and nonsustained ventricular tachycardia. The infusion was stopped due to poor prognosis. Hemoperfusion with no heparin was then started and continued for 3.5 hours. Once that was completed the patient's blood pressure decreased to 80/50 mm Hg and his consciousness remained decreased. Methylepinephrine was added to maintain his blood pressure. His arrhythmia gradually improved. By the next morning, his ECG was normal. Hemoperfusion was repeated for 2 hours (a single perfusion without heparin) and the patient had a stable blood pressure and normal urine function. A repeat abdominal CT showed polycystic kidney disease with hemorrhage, but the bleeding did not increase and his laboratory studies were normal. The patient was discharged 1 week later (Chen et al, 2015).

Abstracts

Case Reports

A)

1) A 36-year-old had an alcoholic drink containing an Aconitum preparation. Within 30 minutes lethargy occurred and the skin became swollen and numb. The patient had diarrhea, vomiting, spasms of the entire body, and an inability to speak. Death occurred 8 hours postingestion (Yi-gu & Guang-zhao, 1988).
2) A 35-year-old committed suicide by ingesting a tuber of A. brachypodium. Within 10 minutes of ingestion, nausea, abdominal pain, sweating, and unsteady gait developed. Death occurred within 1.5 hours of ingestion (Yi-gu & Guang-zhao, 1988).
3) A man ingested an estimated 5 to 10 mg of pure aconitine and immediately developed a bitter taste and a burning and tingling sensation in the tongue which progressed to numbness, tightness, and airway constriction occurred. Forty minutes after ingestion, nausea and excessive salivation developed. Seventy-five minutes after ingestion a tingling sensation all over the body was noted, but especially the face. Within 3 hours the patient vomited and salivated freely and developed weakness resulting an absence of limb movement. The patient became restless, cold, or dizzy, if movement was attempted. Symptoms persisted for 2 hours and peaked about 6 hours postingestion with gradual improvement (Fiddes, 1958).

Range Of Toxicity

Summary

A)

B)

Minimum Lethal Exposure

A)

1) The minimum lethal dose of aconitine is 3 to 6 mg (Frohne & Pfander, 1983). One gram of fresh Aconitum napellus may contain 2 to 20 mg of aconitine.
2) Fatalities have occurred with ingestion of 2 to 4 g of the root (Lampe & Fagerstrom, 1968).
3) Singh et al (1986) estimated an adult lethal dose to be 1 g of plant, 5 mL of a prepared tincture, or 2 mg of pure aconite (Singh et al, 1986).

B)

1) CULINARY USE

a) CASE SERIES: There have been reports of Aconitum alkaloid poisoning after consumption of herbal soups and meals containing aconite roots. Its suggested that consumption of herbal soups and foods prepared from aconite roots may not be safe even after prolonged boiling if large quantities of the root are used and consumed. In a large cluster of cases, 19 family members all became ill (mild cases = 12 and severe cases = 7) within 24 hours after ingesting a pork broth containing boiled "caowu" (the root of A. kusnezoffii). Symptoms appeared to be dose dependent and occurred shortly after ingestion (mean, 30 minutes). Seven individuals (aged 32 to 80 years) ingested 4 to 13 pieces of boiled " caowu" and consumed 50 to 200 mL of soup and developed mild neurological symptoms, blurred vision and palpitations and several also developed nausea and vomiting. An 80-year-old woman died after ingesting 13 pieces of boiled "caowu" and 200 mL of soup. Mild neurological symptoms that did not require clinical care developed in 12 individuals that ingested less than 3 pieces of boiled "caowu" and small amounts of soup (Chan, 2014).
b) CASE REPORT: A 39-year-old woman ingested 200 to 250 mL of "caowu" (the root of A. kusnezoffii) contained in a pig-legged soup. Her husband also drank the soup (400 to 500 mL) and awoke with neurologic symptoms and found his wife to be unarousable. Although resuscitation efforts were started in the hospital, the patient died 6 hours after ingestion. Postmortem exam found aconitine in the gastric tissues, gastric content and the liver (Chan, 2014).
c) CASE SERIES: During 2004 to 2008, 9 men and 6 women (aged 28 to 72 years) were admitted to the hospital after ingesting "caowu" (the root of A. kusnezoffii) cooked in pork broth. They arrived within 30 minutes to 3 hours after the onset of symptoms. The most commonly reported symptoms included seizures (n=6), irritability (n=4), and ventricular tachycardia accompanied with severe gastrointestinal symptoms (n=2). Three deaths occurred and were due to severe cardiac dysrhythmias, circulatory failure, and CNS and respiratory depression (Chan, 2014).

C)

1) CASE REPORTS: In a review of the literature, dermal exposure to aconitum alkaloids resulted in systemic toxicity following topical application of aconite tincture. Of the 7 cases, 2 fatalities occurred following dermal application to damaged skin (ie, burn to skin and skin ulceration). The first patient was a 35-month-old child with a second-degree hot water scald over her lower limb (1.5% of the total body surface area) that was treated with aconite tincture ("caowu"). Fifteen minutes after treatment, the child collapsed with cyanosis, coma and twitching of all extremities. Despite resuscitation efforts, the child died 10 hours later. The second patient was an adult with herpes zoster and skin ulceration on the right chest and scapula that were treated with topical applications of raw caowu (8g) and raw chuanwu (8g) and other herbs. He died unexpectedly 3 days later; postmortem cardiac blood concentration was 29.9 ng/mL (Chan, 2012).

Maximum Tolerated Exposure

A)

1) CASE SERIES: In a retrospective case series of 17 occurrences of aconite ingestion reported to the National Poison Center in Taiwan between 1990 and 1999, amounts ingested resulted in neurologic and cardiovascular toxicity, including 4 cases of ventricular tachycardia. Preparations and amounts ranged from 2 g Huo Luo Dan Chinese herbal preparation containing 0.32 g of processed A carmichaeli root and 0.33 g of processed A kusnezoffi root to 50 g of unprocessed A carmichaeli and A kusnezoffi root. Four of the patients ingested 30 to 200 mL decoctions of processed root and alcohol. All patients recovered (Lin et al, 2004).
2) CASE REPORTS: In unrelated events, 2 adults developed significant cardiotoxicity with persistent ventricular dysrhythmias including ventricular fibrillation following aconitum (A. napellus) exposure. Both required aggressive supportive care, which included inotropic and antiarrhythmic therapy. Recovery was complete in both patients (McGregor et al, 2008; Weijters et al, 2008). In one patient, the estimated exposure was more than 100 g of aconite, but serum concentrations were not obtained (Weijters et al, 2008).
3) CASE REPORT: A 58-year-old man ingested a decoction of 11 g each of 'chuanwu' (the root of A carmichaeli) and processed 'caowu' (the root of A kusnezoffi) to treat neck pain and developed persistent hypotension and bradycardia about 6 hours after ingestion. His systolic blood pressure measurements ranged from 84 to 106 mmHg (mean 93.5) with diastolic blood pressure readings of 40 to 59 mmHg (mean 51.8). Treatment included IV fluids and dopamine. Hypotension and bradycardia resolved approximately 31 and 36 hours after exposure, respectively. The patient recovered completely and was discharged 48 hours after ingestion (Chan, 2009).
4) CASE REPORTS/LEAVES: A couple ingested the leaves of the Aconitum pseudo-laeve var. erectum (not the root) after boiling the leaves. Within 30 minutes, they felt unwell. Hypotension and bradycardia were present on exam. They both recovered about 20 hours after exposure following supportive care (Kim et al, 2009).
5) CASE REPORT: A 21-year-old man experienced generalized paresthesias, nausea, diarrhea, vertigo, thoracic pain, dyspnea and dyschromatopsia (purple vision) 5 hours after ingesting 3 homemade capsules containing Aconitum napellus (he had been taking one capsule daily for several months prior to that without adverse effects). The patient recovered with supportive care and was discharged approximately 2 days postingestion. Analysis of one of the prepared capsules revealed that it contained 237 mg of Aconitum napellus root and 19 mcg of aconitine (Moritz et al, 2005).
6) CASE REPORTS: Fiddes (1958) reported 2 cases of poisoning in which 2 men took a "pinch" of pure aconitine, placed it on their hands and transferred it to their tongues. The estimated amount taken was between 5 and 10 mg. Both men became ill, but did not develop cardiac toxicity and survived the exposure. There is 0.4% to 0.8% diterpene alkaloids in A. napellus (Budavari, 1989).

Serum Plasma Blood Concentrations

7.5.2)

A) TOXIC CONCENTRATION LEVELS

1) An aconitine plasma concentration of 1.75 ng/mL was reported in a 21-year-old man 7 hours after ingesting 3 homemade capsules containing Aconitum napellus. Analysis of one of the prepared capsules revealed that it contained 237 mg of Aconitum napellus root and 19 mcg of aconitine (Moritz et al, 2005).
2) FATALITIES

a) A 54-year-old man intentionally ingested an herb and came to the emergency department about an hour later complaining of paresthesia of the mouth. Shortly after admission the patient was in polymorphic ventricular tachycardia followed by ventricular fibrillation. Despite immediate cardiopulmonary resuscitation (including direct-current cardioversion and various anti-arrhythmic agents) and mechanical ventilation, the patient died of refractory ventricular fibrillation. Two months later, laboratory analysis confirmed the presence of A napellus (whole blood concentration: 24 mcg/L) in antemortem blood (Strzelecki et al, 2010).
b) POSTMORTEM: A 25-year-old man ingested some wild flowers (later identified as A. napellus) and blackberries (Epetrium nigrum) and complained of nausea and abdominal pain. He suddenly collapsed approximately 4 hours after exposure; resuscitation was unsuccessful. Postmortem femoral blood and urine concentrations for aconitum was 3.6 mcg/L and 149 mcg/L, respectively (Pullela et al, 2008).
c) POSTMORTEM: A 60-year-old man intentionally ingested an aconite extract (A. napellus; thought to be self-cultivated), and died within 2 hours of exposure. The mean concentration in femoral blood and urine was 10.8 mcg/L and 264 mcg/L, respectively. Antemortem concentration in the urine was 334 mcg/L, and was estimated to be 6 mcg/L in the serum. The authors suggested that based on aconite's unstable nature, the concentrations may have been higher (Elliott, 2002).
d) A victim poisoned with aconitine was found to have postmortem blood levels of aconitine (29.1 ng/mL), mesaconitine (53.1 ng/mL), and hypaconitine (45.6 ng/mL). Autopsy results reported that the cause of death was acute heart failure secondary to aconite poisoning (Ohno, 1998).

3) SURVIVAL

a) In a study of 5 patients poisoned with aconite, area under the curve (AUC) was calculated. Jesaconitine (a main alkaloid) was found in 4 of the 5 cases and AUC ranged from 6.9 to 33.5 ngxhr/mL. It was noted that the patient with the most severe clinical effects (ie, ventricular tachycardia and ventricular fibrillation) also had the second highest AUC and the highest mean resistance time (reflecting time of exposure). The authors suggested that the extent of clinical effects is affected by both the amount of exposure to aconitines and the length of time of exposure (Fujita et al, 2007).

Toxicity Information

7.7.1)

A) ACONITINE

1) LD50- (INTRAPERITONEAL)MOUSE:

a) 0.328 mg/kg (Budavari, 1996)

2) LD50- (ORAL)MOUSE:

a) 1 mg/kg (Budavari, 1996)

B) ACONITUM FEROX CRUDE ROOT

1) LD50- (ORAL)MOUSE:

a) 195-210 mg/kg (Mahajani et al, 1990)

Pharmacology Toxicology

Pharmacologic Mechanism

A)

Toxicologic Mechanism

A)

B)

C)

D)

1) Aconite has a vagal action which causes a slowing of the heart. This action may be abolished by atropine (Wedd & Tenney, 1953).
2) There is also a more direct effect on the cardiac muscle which produces a spontaneous auricular rate increase, and spontaneous ventricular beating (Wedd & Tenney, 1953).
3) Atrial fibrillation is uncommon (Wedd & Tenney, 1953).
4) One study reported that aconite can trigger automaticity during the plateau (phase II) of the action potential by direct, persistent activation of inward sodium channels, prolonging repolarization and inducing afterdepolarization with triggered automaticity(Gutierrez et al, 1987).

E)

1) The roots of Aconitum carmichaeli are known to contain four glycans, aconitans A,B,C, and D, which, as a group, exhibited prominent hypoglycemic effects in normal and alloxan-produced hypoglycemic mice (Konno et al, 1985).
2) Another study, using only Aconitan A, found no changes in plasma insulin levels in either normal, glucose-loaded or alloxan-induced hyperglycemic mice, nor were there differences in cholesterol or triglyceride levels (Hikino et al, 1989).

Physicochemical

Physical Characteristics

A)

Molecular Weight

A)

Animal Toxicology

Clinical Effects

11.1.13)

A) OTHER

1) Summary: General symptoms include vomiting or attempted vomiting, colic, bloating, belching, frothy salivation, constant swallowing, bradycardia, bradypnea, muscular weakness, paralysis, and dilated pupils. Death is due to cardiopulmonary failure (Humphreys, 1988; Kingsbury, 1964).

Treatment

11.2.1)

A) GENERAL TREATMENT

1) There is no specific antidote or treatment. Heart stimulants, warmth, and rubbing the animal to increase circulation has been tried (Humphreys, 1988).

Range Of Toxicity

11.3.2)

A) DOG

1) Estimated lethal dose of aconitine is 2 to 3 milligrams in the dog (5 grams of the dried root) (Humphreys, 1988).

B) HORSE

1) Estimated lethal dose of aconitine in the horse is 10 to 12 milligrams (300 to 400 grams of the dried root) (Humphreys, 1988).

Continuing Care

11.4.1)

11.4.1.2) DECONTAMINATION/TREATMENT

A) GENERAL TREATMENT

1) There is no specific antidote or treatment. Heart stimulants, warmth, and rubbing the animal to increase circulation has been tried (Humphreys, 1988).

Sources

A)

1) Aconitine was once used in veterinary medicine as an antihypertensive (Budavari, 1989).

References

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FeedBack

PLANTS-ACONITUM

Classification | Detailed evidence-based information

Therapeutic Toxic Class

Specific Substances

Available Forms Sources

Life Support

Clinical Effects

Laboratory Monitoring

Treatment Overview

Range Of Toxicity

Acid-Base

Dermatologic

Musculoskeletal

Reproductive

Carcinogenicity

Summary Of Exposure

Vital Signs

Heent

Cardiovascular

Respiratory

Neurologic

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Monitoring Parameters Levels

Methods

Life Support

Patient Disposition

Monitoring

Oral Exposure

Enhanced Elimination

Case Reports

Summary

Minimum Lethal Exposure

Maximum Tolerated Exposure

Serum Plasma Blood Concentrations

Toxicity Information

Pharmacologic Mechanism

Toxicologic Mechanism

Physical Characteristics

Molecular Weight

Clinical Effects

Treatment

Range Of Toxicity

Continuing Care

Sources

General Bibliography