Aconitum Alkaloid Poisoning Review of Cases
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