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 by LCMS – Suggestive of 云南烏頭 • No herbal residue for inspection • 3 rd 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 2 nd pack but not the 1 st /3 rd 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 1 st 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 • 1 st pack (herbal residue): yunaconitine • 2 nd 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