A case report on Liu Shen Wan (六神丸 )Poisoning

History

A 26 year old man Accidentally taken 100 tablets of

LiushenwanHe got mild upper respiratory tract

infectionTook the pills as remedy

Symptoms started 1 hour laterFelt dizzy and nauseatedPalpitation, chest discomfort and limb

weaknessNo vomitingNo epigastric pain

Physical Examination

Vitals were stableBP 145/79Pulse 77/minAfebrile Cold extremitiesGCS 15/15

Abdomen soft and nontenderBowel sound sluggishChest clear, equal AEHeart sound dual, no murmurNo focal neurological signs

H’stix: normalECG : sinus rhythm, no ischemic changesCXR : normalAdmit to medical ward subsequently

CBPR/LFTAmylaseParacetamol, Salicylate level: normalSymptoms subsided quicklyDischarge the next day after admission

Liu Sheng Wan 六神丸Well known Chinese composite herbal

medicationSix ingredients: Niu Huang 牛黃 ,

SheXiang 麝香 , CianSu 蟾酥 , BingPiang冰片 , Xiong Huang 雄黃 , Pearl 珍珠

Indications: URTI, apthous ulcer, otitis media, gingivitis, cellulitis

Different brands of Liu Shen Wan

Used for over 100 years in China4 major brands: Lui’s, Yeung’s, Ji’s and Leung’s

Packing: 6 bottles in 1 pack, 10 pills per bottle

Dosage ：for adults 10 pills 3 times a day

Route of administration:OralAs lozenges

Composition (Lui’s) ： Pearl 珍珠 28% SheXiang 麝香 20% NiuHuang 牛黃 22% Xiansu 蟾酥 24%

Others 6%

CianSu 蟾酥

Milky venomous secretion from Toad’s parotid glands

Methical beliefs: analgesic, anesthetic, detoxifying and heart strengthening effect

Used in febrile convulsion, heart disease, gum bleeding and anxiety

Chemical composition: cardioactive steroids: bufalin, cinobufagin, resibufogenin and epinephrine

Chemical structure similar to digoxinOnset time : 20min – 2 hrToxic reaction can begin after 12 hours of

ingestionSymptoms of intoxication are nausea,

vomiting, headache, dizziness, limb numbness and even convulsion

Suggested approach for treating Ciansu poisoning

Breif rapid triage with history taking and clinical assessment

Basic laboratory investigations including measurement of serum potassium and digoxin concentrations

Surface ECG and telemetry monitoringReporting to and consult with the local

poison control centreGeneral life supportive measures

Treatment with digoxin specific Fab fragments

No calcium administration for hyperkalaemia

retention of sample for investigation

Xiong Huang 雄黃

Arsenic sulfide

Methical beliefs: antibacterial, detoxifying action

Acute overdose: GI: nausea, vomiting, diarrhoea CVS: hypotension, tachycardia, shock and

death Neurological: lethargy, agitation, delirium,

seizure, sensorimotor axonal peripheral neuropathy

Hematological: pancytopenia, relative eosinophillia, basophilic stippling

Dermatologic: delayed effect desquamation, periorbital edema, diffuse

maculopapular rash Transverse white striae

Long term uses: chronic arsenic poisoning Fatigue, malaise Gastroenteritis, leukopenia, anemia, sensory

predominant peripheral neuropathy, hepatic transaminase elevation, noncirrhotic portal hypertension, and peripheral vascular insufficiency.

Skin disorder: rain-drop pigmentation, hyperkeratotic changes, neuropathy, anemia

Lung, bladder, skin cancer

Treatment

DecontaminationEnhanced eliminationChelating agents:

Unithiol (DMPS) Dimercaprol (BAL) Oral succimer (DMSA)

NiuHuang 牛黃

Cow’s gall stoneMythical beliefs: strengthen heart,

tranquilizing, detoxifying and antipyreticUsed in heart disease, anemia, sepsis and

alcoholic intoxicationToxic effect: hypotensive, gastroparesis,

increase prolactin secretion in rats

SheXiang 麝香

Known as muskSecretion from gland between the

umbilicus and genitals of a deer living in Himalayas

Methical beliefs: tranquilizing, antiepileptic and heart strengthening effect

Used in anxiety and epilepsyToxic effects: uterine contraction,

antiplatelet, hypotensive

BingPiang 冰片

BorneolDerivative of the stem in Dipterocarp

(tropical tree). Ingredients of turpentine and camphorAnalgesic, anti-inflammatoryUsed in conjunctivitis, pharyngitis, cellulitis

and skin ulcerToxic effect: uterine contraction in second

and third trimester of gestation in rats

Zhen Zhu 珍珠

Tranquilizing and anti-inflammatoryUsed in insomnia, pharyngitis, cough

suppressing, skin healing and body strengthening.

Toxic effects: diuretic, decreased gastric acidity

Literature search

Chan HM. 41 cases of adverse effect caused by Liushenwan. Journal of Hubei institute for Nationalities (medical edition): 2003 Vol. 20 No.3 P.57

41 cases searched from 21 journals over 5 years

Epidemiology

Age: 8 days – 60 years oldMale : 22 cases (53.7%)Female: 19 cases (46.3%)Time of onset: 20 min – 2 hrSymptom onset: after 1 dose or multiple

repeated doses

Distribution of adverse reactions

Type of reactions

No.of cases

% Clinical manifestation

Toxidrome 23 56.1 Nausea, vomiting, milk regurgitation, dyspnea, chest pain, bradycardia, dysrhythmia, confusion, irritability, dizziness, epistaxis

Allergic response

13 31.7 skin rash, angioedema, anaphylactic shock and death

Other reactions 5 12.2 Preterm labor, priapism, skin pigmentation, keratosis

Toxidromes Enteric :

nausea, vomiting, diarrhoea, neonatal regurgitation Circulation:

cold peripheries, cyanosis, weak pulses bradycardia, dysrhythmia, atrioventricular block shock and death

Respiratory reactions: chest pain, dyspnea, tachypnea shallow breathing respiratory failure and death

Hematological system: cyanosis, epistaxis

Most of the toxic symptoms are accountable by Arsenic and Ciansu

Arsenic: Gastrointestinal upset, oral and gastric mucosa edema,

hemorrhage and necrosis. Long term use: liver and renal damage, skin

pigmentation Ciansu

Digoxin like effect blocking AV conduction pathways, causing cardiovascular and respiratory compromise in severe intoxication.

Hu M.C. Discussions on adverse reaction of LiuShenWan. Journal of Combined Chinese and Western Medicine. 1991, Vol.11, No.9, P563-4.

28 cases reported 14 cases of intoxication 8 neonates, 4 infants, 2 adults Symptom onset : 0.5-12 hrs Mortality: 5 (4 neonates); Discharged: 8; no data

available: 1 Fatal cases:

lip cyanosis, facial flushing 3rd degree atrioventricular block T wave changes, epistaxis circulatory failure

12 cases of allergy:8: allergic drug rash4: scarletiform drug rash1: eczematous drug rash1: drug rash with fixed pattern1: purpuric drug rash1: anaphylatic shock1: laryngeal edema

2 idiosyncratic responses

Discussion

Mild intoxication Symptoms correspond to ciansu and arsenic

sulphide poisoning Many brands of Liushenwan available over the

counter Mortality reported mainly in neonatal intoxication Should prohibit use of the drug in neonates Legistration required for prescription

Most fatal cases has cardiovascular manifestations including 3 degree AV block, bradycardia, circulatory shock

Atropine, adrenaline used for resuscitation Digoxin like effects Multiple atrial ectopics reported in a patient on

digoxin therapy taking the recommended dose of LiuShenWan

Synergistic effects with digoxin Treatment according to digoxin toxicity