Clinical Toxicology Case Clinical Toxicology Case PresentationPresentation

By Dr. Kevin Go,UCH.By Dr. Kevin Go,UCH.

A woman presenting with numbness A woman presenting with numbness and hypotension after taking herbal and hypotension after taking herbal

medicine.medicine.

HistoryHistory

F/ 44F/ 44 History of right knee & thigh pain for 2 yearsHistory of right knee & thigh pain for 2 years Attended a herbalist on 21/12/2004Attended a herbalist on 21/12/2004 Took some herbal broth in the eveningTook some herbal broth in the evening Develop perioral numbness, abdominal Develop perioral numbness, abdominal

pain ,watery diarrhea and generalised pain ,watery diarrhea and generalised weakness 3 hrs after herbal brothweakness 3 hrs after herbal broth

In AEDIn AED

c/o palpitation and dizzinessc/o palpitation and dizziness BP : 85/49 BP : 85/49 P: 48/min.,irregularP: 48/min.,irregular Temp: 36.5Temp: 36.5 H’stix : 6.5 mmol/LH’stix : 6.5 mmol/L

Physical ExaminationPhysical Examination

ConsciousConscious Chest clearChest clear HS dualHS dual Abd : soft, non tenderAbd : soft, non tender Muscle power : 5/5 both sidesMuscle power : 5/5 both sides Jerks were normal Jerks were normal No nystagmus /past-pointingNo nystagmus /past-pointing Neck softNeck soft

ECGECG

InvestigationInvestigation

ECG : freq ventricular ectopic beats with coupletsECG : freq ventricular ectopic beats with couplets PR : 0.11 secPR : 0.11 sec QRS : 0.075 secQRS : 0.075 sec QTc : 0.448 secQTc : 0.448 sec

Na : 143.2 mmol/LNa : 143.2 mmol/L K : 4.03 mmol/LK : 4.03 mmol/L Venous pH: 7.36Venous pH: 7.36

Management in AED.Management in AED.

Oxygen givenOxygen given IV NS 500ml FR givenIV NS 500ml FR given Put on cardiac monitorPut on cardiac monitor CCU was consulted CCU was consulted Possibility of herbal medicine poisoning , the Possibility of herbal medicine poisoning , the

prescription tracedprescription traced

PrescriptionPrescription

Which is the responsible toxic Which is the responsible toxic ingredient?ingredient?

草烏 草烏 ( ( Caowu) or aconitineCaowu) or aconitine

ProgressProgress

After admission to CCU, BP :108/70After admission to CCU, BP :108/70 Put on IVF and cardiac monitorPut on IVF and cardiac monitor Repeated ECG showed SR with no more vent Repeated ECG showed SR with no more vent

ectopic 7 hrs after admissionectopic 7 hrs after admission No antiarrhymic drugs givenNo antiarrhymic drugs given Transfer to cardiac ward next day morning Transfer to cardiac ward next day morning

(22/12/04) with symptoms subsided(22/12/04) with symptoms subsided Remained uneventfulRemained uneventful

Investigation:Investigation:

Hb :11 g/dLHb :11 g/dL L/RFT essentially normalL/RFT essentially normal Troponin I :not raisedTroponin I :not raised Blood gas : normalBlood gas : normal Bedside echocardiogram : satisfactory LV Bedside echocardiogram : satisfactory LV

functionfunction Blood and urine was sent to TRL : aconitine Blood and urine was sent to TRL : aconitine

and deoxyaconitine was detected in the urine and deoxyaconitine was detected in the urine compatible with aconitine poisoningcompatible with aconitine poisoning

AconitineAconitine

Aconitine:Aconitine: Highly poisonous C-19 diterpenoid-ester alkaloid.Highly poisonous C-19 diterpenoid-ester alkaloid. Derived from aconite rootstock.Derived from aconite rootstock. 川烏 川烏 ,, 草烏草烏 , , 附子附子 , , 雪上一枝蒿 雪上一枝蒿 in herbal medicine contains in herbal medicine contains

aconitine alkaloidsaconitine alkaloids Possess anti-inflammatory, analgesic and cardiotonic effect.Possess anti-inflammatory, analgesic and cardiotonic effect. Treatment:Treatment:

RheumatismRheumatism NeuralgiaNeuralgia FeverFever Cardiac complaint.Cardiac complaint.

Raw aconite roots:Raw aconite roots: Generally toxic Generally toxic Need possessing before useNeed possessing before use

Possessing :Possessing : Soaked in water or saturated lime water and boiled Soaked in water or saturated lime water and boiled

until the aconitine white core disappearsuntil the aconitine white core disappears Boiling : hydrolysis of aconitine to less toxic Boiling : hydrolysis of aconitine to less toxic

benzylaconine and aconine derivativebenzylaconine and aconine derivative

Aconite alkaloid : very narrow therapueutic Aconite alkaloid : very narrow therapueutic indexindex

Poisoning can be due to:Poisoning can be due to: Inadequate possessingInadequate possessing Overdose Overdose Inappropriate preparation methodsInappropriate preparation methods

Toxicity of aconitine.Toxicity of aconitine.

MechanismMechanism Activate the voltage sensitive Na channels in the Activate the voltage sensitive Na channels in the

heart , nerves and muscles heart , nerves and muscles Enhance inward Na current during the plateau Enhance inward Na current during the plateau

phase of action potentialphase of action potential Prolong the repolarizationProlong the repolarization Premature excitation of cardiac myocitesPremature excitation of cardiac myocites

Both cardiotoxin and neurotoxinBoth cardiotoxin and neurotoxin

Symptoms of poisoningSymptoms of poisoning

DizzinessDizziness Nausea and vomitingNausea and vomiting Parasthesia Parasthesia Muscle weakness ( interfere neuromuscular transmission)Muscle weakness ( interfere neuromuscular transmission) Hypotension and bradyarrhythmia ( muscarinic effect)Hypotension and bradyarrhythmia ( muscarinic effect) Supravent /vent tachyarrhythmia ( premature excitation)Supravent /vent tachyarrhythmia ( premature excitation) Death usually due to ventricular arrhythmiaDeath usually due to ventricular arrhythmia Symptoms onset :a few minutes to 2 hrsSymptoms onset :a few minutes to 2 hrs

Management of aconitine poisoning .Management of aconitine poisoning .

Clinical experience remained limitedClinical experience remained limited No antidote availableNo antidote available Rx mainly supportiveRx mainly supportive Gut decontamination by activated charcoal Gut decontamination by activated charcoal

may reduce absorption of aconitinemay reduce absorption of aconitine For hypotension: IVF and inotropes For hypotension: IVF and inotropes

Treatment of ventricular Treatment of ventricular arrhythmia due to aconitine arrhythmia due to aconitine

Remained a challengeRemained a challenge Cardioversion and cardiac pacing :probably Cardioversion and cardiac pacing :probably

not effectivenot effective Lignocaine not usefulLignocaine not useful Amiodarone and flecainide may be reasonable Amiodarone and flecainide may be reasonable

drugs of first choicedrugs of first choice

Cardiotoxicity after accidental herb induced Cardiotoxicity after accidental herb induced aconite poisoning .aconite poisoning .

Y.T.Tai et alY.T.Tai et alLancet 1992; 340: 1254-56.Lancet 1992; 340: 1254-56.

17 17 patients with aconitine induced cardiotoxicity during 1989-1991 were patients with aconitine induced cardiotoxicity during 1989-1991 were treatedtreated

All patients Chinese. Median age :56. Only 1 had hx of MI.All patients Chinese. Median age :56. Only 1 had hx of MI. 2 had VF2 had VF 13 got VT (sustained and polymorphic)13 got VT (sustained and polymorphic) 2 had freq VEB2 had freq VEB DC cardioversion :unsuccessful in 10 patientsDC cardioversion :unsuccessful in 10 patients No single antiarrythmic drugs uniformly effectiveNo single antiarrythmic drugs uniformly effective Lignocaine :unsuccessful in all patientsLignocaine :unsuccessful in all patients Suppression of VT eventually susccessful in 9 patients with amiodarone Suppression of VT eventually susccessful in 9 patients with amiodarone

(5), flecainide (2), procainamide (1), and mexiletine (1)(5), flecainide (2), procainamide (1), and mexiletine (1) 2 patients died from refractory VF within 6 hrs of admission2 patients died from refractory VF within 6 hrs of admission Remaining 15 stabilized within 24 hrRemaining 15 stabilized within 24 hr

Other case report.Other case report.

61 61 yr man with aconitine induced refractory yr man with aconitine induced refractory VEB successfully treated with amiodarone VEB successfully treated with amiodarone (150mg loading ,then 1300mg in 36 hrs) after (150mg loading ,then 1300mg in 36 hrs) after failure of lignocainefailure of lignocaine

DF Yeih, FT Chiang Heart 2000; 84(4): E8 DF Yeih, FT Chiang Heart 2000; 84(4): E8

Other treatment option:Other treatment option:

Charcoal haemoperfusion for 4hrsCharcoal haemoperfusion for 4hrs Clinical Features and management of herbs induced Clinical Features and management of herbs induced

aconitine poisoning. aconitine poisoning.

Lin CC et al Annals of Emerg Med 2004 ;43(5):574-9Lin CC et al Annals of Emerg Med 2004 ;43(5):574-9

Cardiopulmonary bypass.Cardiopulmonary bypass.Ohuchi S. Kyobu Geka 2000;53:541-544Ohuchi S. Kyobu Geka 2000;53:541-544

Thank you.Thank you.

Summary + CommentsSummary + Comments

Use of TCM is common in Hong KongUse of TCM is common in Hong Kong Aconitine poisoning is most commonly reportedAconitine poisoning is most commonly reported Consider aconitine poisoning as DDx in patients Consider aconitine poisoning as DDx in patients

presenting with paresthesia ,muscle weakness , presenting with paresthesia ,muscle weakness , hypotension and vent .dysrrhythmia.hypotension and vent .dysrrhythmia.

Treatment is mainly supportiveTreatment is mainly supportive IVF + Inotropes for hypotensionIVF + Inotropes for hypotension Amiodarone for tachyarrthymiaAmiodarone for tachyarrthymia

Symptoms usually subside within 24 hoursSymptoms usually subside within 24 hours