aconitum alkaloid poisoning review of cases. aconitum l. ( 烏頭 ) 製川烏 –...

Aconitum Alkaloid Poisoning

Review of Cases

Aconitum L. ( 烏頭 )

• 製川烏– 毛茛科植物烏頭的母根的炮製品– 1.5~3g

• 製草烏– 毛茛科植物北烏頭的塊根的炮製品– 1.5~3g

• 製附子– 毛茛科植物烏頭的子根的炮製品– 3~15g

草烏• Wide variety in China market

• Source: Cultivated /Wild

• > 16 species

Aconitum alkaloids

• Aconitine ( 乌头碱 ), Hypaconitine ( 次乌头碱 ), Mesaconitine ( 新乌头碱 )

• Effective ingredients– Analgesic and anti-inflammatory actions

• Potent toxins– Cardio-toxic, neuro-toxic– voltage-gated Na(+) channel activators

Processing ( 炮製 )

• Essential to reduce toxicity– As low as 0.3g of 生草烏 is toxic

• Hydrolysis:– Aconitine Benzoylaconine Aconine

1/200 Toxic 1/2000 Toxic

• 生薑、甘草 : decrease aconite toxicity pH of herbal broth enhance hydrolysis

• 十八反 :本草明言十八反 , 半蔞貝薟芨攻烏 ,

藻戟遂芫俱戰草 , 諸參辛芍叛藜蘆 .

• 烏頭反半夏 : enhance aconite toxicity pH of herbal broth inhibit hydrolysis

Aconitum Poisoning

• Taiwan– 17 cases from 1990-99

• H.K. PWH (1989-91):– 15 patients

• DH (1/00 – 6/04):– 7 admissions with 3 requiring intensive care– All recovered– Overdose /improper decoction/ self-prescription

Case 1

• Apr 2004• M/20• Taking TCM for back pain for 2 months• Formula did not contain aconite herbs

– 牛膝 , 杜仲 , 杞子 , 知母 , 川斷 , 白芥子 , 蒼朮 , 白朮 , 防風 , 淫羊藿 , 百花蛇 , 枳殼 , 白芍 , 威靈仙 , 茯苓 , 狗脊 , 春砂仁

• Bought 3 identical packs of herbs from herbal shop• Became unwell shortly after taking second pack

– Vomiting– Drowsy

• ECG: polymorphic ventricular tachycardia

• Arrhythmia resistant to treatment

• Admitted to Cardiac care unit

• Recovered eventually

Lab Findings

• Herbal broth remains: – Aconitum alkaloids (yunaconitine, crassicauline) detected b

y LCMS– Suggestive of 云南烏頭

• No herbal residue for inspection• 3rd pack of raw herbs:

– No aconite herbs on inspection– No aconitum alkaloids detected by chemical analysis

• Urine:– Aconitum alkaloids detected + drugs given after admission

Cause of Poisoning:

• Aconite contamination– Present in the 2nd pack but not the 1st /3rd pack

Case 2

• June 2004• F/50• Inoperable kidney tumor• On TCM for pain control and tolerated• Double dosage by herself

– 熟附子 ( 五錢 ), 製川烏 ( 六錢 ), 製草烏 ( 六錢 )

– 生薑、甘草 二錢

• Presented with numbness, palpitation and dizziness

• Uneventful recovery

Lab Findings

• Urine: Hypaconitine detected

• No residue a/v

Cause of Poisoning

• Self prescription

• Exceed the recommended dose

Case 3

• July 2004• M/30• Low back pain• Took prescribed herbal broth

– 制川烏 , 制草烏 各三錢– 甘草 二錢

• 40 minutes later– Numbness, weakness, vomit, chest discomfort

• ECG: sinus bradycardia (40bpm), VEB

• Under Cardiac care unit

• Recovery

Lab Findings

• Yunaconitine detected in urine

• No herbal residue

Cause of Poisoning

• ?Improper decoction– No “ 先煎” instruction in the prescription

• Exceed recommended dose

Case 4• Sep 2004• F/83• DM, IHD, HT, AF• Chronic kidney disease

– GFR: 12.3 mL/min/1.73m2

• Admit with general malaise, decrease general condition• Found slow AF (~30bpm) on admission• To Cardiac care unit for observation• Took prescribed herbal broth

– 附子 三錢 , 甘草 二錢 , 川貝母三錢

Lab Findings

• Urine: hypaconitine detected

• No herbal residue

Cause of Poisoning

• ?Improper decoction– No “ 先煎” instruction in the prescription

• ?Underlying renal impairment

Case 5

• Dec 2004

• F/44

• Knee pain

• Took prescribed herbal broth– 制草烏 ( 二錢 )– 生薑、甘草 not added

– Prepared at herbal shop

• Numbness, weakness

• Hypotension BP 89/49

• ECG: bradycardia(48bpm), frequent VEBs

• Admitted to CCU

Lab Findings

• Urine: Aconitine, deoxyaconitine detected

Cause of Poisoning

• Exceed recommended dose

Case 6

• Jan 2005

• M/52

• Took prescribed herbal broth for LBP– 川烏 , 草烏 ( 製 ) and 附子 ( 各三錢 先煎 )– 甘草 二錢

• Numbness and weakness

• Full Recovery

Lab Findings

• Urine: yunaconitine, hypaconitine, deoxyaconitine

• Herbs sent to Govt Lab for quantitation:– Aconitum Alkaloids content <0.15%

Cause of Poisoning

• Exceed recommended dose

Case 7

• Mar 2005• M/62• Headache• Self prescribed herbal broth

– 川烏 二兩– 生薑、甘草 not added

– 五味子 added

• Numbness, weakness, dizziness, chest discomfort

• Shock on admission (BP 75/54, P105)

• ECG: multiple premature ventricular contractions

• Admitted to ICU

• Patient survived

Lab Findings

• Urine: Mesaconitine, Hypaconitine detected

• No herbal residue

Cause of Poisoning• Self prescription

• Overdose

• Improper decoction

Case 8

• Apr 2005• F/27• URTI symptoms• Prescribed 2 packs of TCM by herbalist

– No aconite herbs

• Took 1st pack numbness, weakness, chest discomfort

• Subside afterwards

• Reboil the herbal residue the next morning

• Re-develop symptoms

• Seen at A&E

• BP 104/66 P62

• ECG normal

• Discharged directly

Lab Findings

• Urine: yunaconitine

• 1st pack (herbal residue): yunaconitine

• 2nd pack (raw herb): no aconitum alkaloids

• Small piece of herb remnant that looked different from the rest was isolated and identified by microscopy to be 草烏

Cause of Poisoning

• Aconite contamination

Summary

• 4 males and 4 females• Age range from 20-83• 5 admitted to intensive/ cardiac care unit• All recovered

– Aconite contamination: 2 cases– Self prescription: 2 cases– Improper decoction: 3 cases– Exceed recommended dose: 5 cases– 生薑、甘草 not added: 2 cases

Safe Practice• Follow safety dosage

• Proper processing and decoction

• BE careful with high dosage/combined use

Other herbs reported to cause Arrhythmia

Other herbs reported to cause Arrhythmia

• 山豆根• 鴉胆子• 石榴樹皮• 藜芦

Lab investigations

• Blood/urine for toxicology screening

• Herbal broth/ remnants

• Formulas

• Raw herbs

Management

• No specific antidote• Treatment is supportive• Decontamination

– Lavage, activated charcoal

• Arrhythmia refractory to drug Rx– Atropine for bradycardia– No single anti-arrhythmic agent was uniformly

effective for arrhythmia control