South Asian Clinical Toxicology Research Collabor Management of cardiac Management of cardiac arrests due to oleander or arrests due to oleander or pharmaceutical poisoning. pharmaceutical poisoning. Andrew Dawson Program Director Sri Lanka www.sactrc.or g Wellcome Trust & Australian National Health and Medical Research Council International Collaborative Capacity Building Research Grant (GR071669MA ) Management of cardiac arrests due to oleander or pharmaceutical poisoning.
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South Asian Clinical Toxicology Research Collaboration Management of cardiac arrests due to oleander or pharmaceutical poisoning. Andrew Dawson Program.
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South Asian Clinical Toxicology Research Collaboration
Management of cardiac arrests due Management of cardiac arrests due to oleander or pharmaceutical to oleander or pharmaceutical
poisoning.poisoning.
Andrew Dawson
Program Director
Sri Lanka
www.sactrc.org
Wellcome Trust & Australian National Health and Medical Research Council International Collaborative Capacity Building Research Grant (GR071669MA )
Management of cardiac arrests due to oleander or pharmaceutical poisoning.
South Asian Clinical Toxicology Research Collaboration
Toxic Cardiac ArrestToxic Cardiac ArrestAdvanced Cardiac Life Support Advanced Cardiac Life Support
(ACLS)(ACLS)= Don’t Stop= Don’t Stop
Albertson TE, Dawson A, de Latorre F, et al TOX-ACLS: toxicologic-oriented advanced cardiac life support. Ann Emerg Med 2001 Apr;37(4 Suppl):S78-90
– www.sactrc.org
South Asian Clinical Toxicology Research Collaboration
Why did ACLS forget cardiac Why did ACLS forget cardiac glycosides?glycosides?
South Asian Clinical Toxicology Research Collaboration
The Toxic CVS mnemonicThe Toxic CVS mnemonicAtropine
Bicarbonate
Cations Calcium Mg
Diazepam
Epinephrine
Fab Digoxin Antibodies
Glucagon
Human Insulin Euglycaemia
South Asian Clinical Toxicology Research Collaboration
DRUG INDICATION DOSE
A Atropine Vagal 0.6 - 1.2mgs
Organophosphates 50-100mgs
B Bicarbonate Alkalinsation Tricyclic, Antipsychotics, Cocaine, Verapamil
1-2 meq/kg in repeated bolus doses. Target pH 7.5-7.55
C Calcium Chloride/ Gluconate Calcium Channel Blockers
1 gram bolus repeated every 3 minutes. Target calcium double normal level
D Diazepam Chloroquine Cocaine & Amphetamine
Up to 3 mgs/kg in chloroquine, unitl sedated in cocaine
E Epinephrine & Inotropics Chloroquine
F Fab Antibodies Digoxin & Cardiac Glycosides
Dose based on ingestion or concentration or titrated against effect
G Glucagon Beta Blockers,Calcium Channel Blockers
5-10 mgs IVI stat then infusion if response
H I Human Insulin Euglycaemia Calcium Channel Blockers,
Beta Blockers
0.5 us/kg plus glucose see protocol
South Asian Clinical Toxicology Research Collaboration
The CaseThe Case A 70 kg man presents on 1-2 hours following a
South Asian Clinical Toxicology Research Collaboration
Consequences of cardiac glycoside Consequences of cardiac glycoside binding 2binding 2
Decrease in conduction through the SA and AV nodes
Due to increase in vagal parasympathetic tone and by direct depression of this tissue
Seen as decrease in ventricular response to SV rhythms and PR interval prolongation
In very high dose poisoning, Ca2+ load may overwhelm the sarcoplasmic reticulum’s capacity to sequester it, resulting in systolic arrest – ‘stone heart’
South Asian Clinical Toxicology Research Collaboration
South Asian Clinical Toxicology Research Collaboration
Digoxin Fab antibodiesDigoxin Fab antibodies
Smith TW et al. N Engl J Med 1976;294:797-800– 22.5 mg of digoxin
– K+ initially 8.7 mmol/l
Fab fragments of digoxin-specific ovine antibodies
South Asian Clinical Toxicology Research Collaboration
Effect of Fab in oleander poisoning
•Eddleston M et al Lancet 2000
South Asian Clinical Toxicology Research Collaboration
Effect of anti-digoxin Fab on dysrhythmiasEffect of anti-digoxin Fab on dysrhythmias
South Asian Clinical Toxicology Research Collaboration
Effect of Fab on serum potassiumEffect of Fab on serum potassium
South Asian Clinical Toxicology Research Collaboration
de Silva (Lancet 2003)– MDAC 5/201 [2·5%] vs SDAC 16/200 [8%]– RR 0.31 (95% CI 0.12 to 0.83)
SACTRC (Lancet 2007)– MDAC 22/505 [4·4%] vs SDAC 24/505 [4.8%]– RR 0.92 (95% CI 0.52 to 1.60)
Why? Different regimen? Poor compliance?
Activated Charcoal:Activated Charcoal: two published RCTs two published RCTs
South Asian Clinical Toxicology Research Collaboration
What other treatment options are What other treatment options are available?available?
Anti-arrhythmics – lidocaine & phenytoin
Atropine & pacemakers
Correction of electrolyte abnormalities– Correction of hyperkalaemia
Glucose/Insulin
Fructose 1,6 diphosphate
Unfortunately, as yet, no RCTs to guide treatment
South Asian Clinical Toxicology Research Collaboration
Classic treatmentsClassic treatments
Phenytoin/lidocaine – depress automaticity, while not depressing AV node conduction.
Phenytoin reported to terminate digoxin-induced SVTs.
Atropine – given for bradycardias.
Temporary pacemaker – to increase heart rate, but cannot prevent ‘stone heart’. Also insertion of pacemaker may trigger VF in sensitive heart. Now not recommended where Fab is available.
South Asian Clinical Toxicology Research Collaboration
AtropineAtropine Indications (Management of Poisoning: Fernando R)
– < pulse less than 40 beats/minute– 20 Block or greater
Reality:– most patients receive it (and are atropine toxic)
No evidence that it decreases mortality Routine use may:
– Increase oleander absorption and blood levels – Decrease effectiveness of gastrointestinal
decontamination– Mask clinical deterioration
South Asian Clinical Toxicology Research Collaboration
Response of atropine-naïve oleander poisoned patients to 0.6mg of atropine
40 50 60 70 80 90 10050556065707580859095
100105110115120125130135
rate at 15minrate at 5min
baseline rate
Rat
e
South Asian Clinical Toxicology Research Collaboration
Correction of electrolyte disturbancesCorrection of electrolyte disturbances
– In shock cardiac metabolism switches from FFA to carbohydrate
– At the same time shock is associated with: inhibition of insulin release insulin resistance poor tissue perfusion impaired glycolysis and carbohydrate delivery
– CCB and beta blockers insulin lack or resistance
South Asian Clinical Toxicology Research Collaboration
0.5 – 1 Unit/kg/hr regular insulin
give 0.5 gm/kg/hr dextrose (glu > 100)
check glucose every 30 mins initially
Insulin & Glucose: DoseInsulin & Glucose: Dose
South Asian Clinical Toxicology Research Collaboration
Use of insulin/dextrose: Cardiac Use of insulin/dextrose: Cardiac glycosideglycoside
Van Deusen 2003 – single case. No effect – neither dangerous nor beneficial.
Reports from India of ‘successfully’ treating yellow oleander poisoning with insulin dextrose when no other therapies were available.
Oubaassine and colleagues 2006 – reported case of combined digoxin (17.5 mg) & insulin (50 iu) poisoning with no substantial cardiac effects and no hyperkalaemia.
Might lowering [K+] > 5.5 mmol/L be beneficial???
South Asian Clinical Toxicology Research Collaboration
Oubaassine 2006 – rat workOubaassine 2006 – rat work
Rats were infused with 0.625 mg/hr digoxin.
After 20 mins, half received high dose glucose and insulin to keep glucose between 5.5 to 6.6 mmol/L.
Time to death recorded
Thirty minutes after digoxin infusion, plasma [K+] had risen in control group compared to insulin glucose group: 6.9 ± 0.5 mmol/L vs 4.9 ± 0.3 mmol/L.
Effect on clinically important outcomes?
South Asian Clinical Toxicology Research Collaboration
Effect of insulin dextrose on survivalEffect of insulin dextrose on survival
0 30 60 90 120 150 180
0
2
4
6
8
10 Control
Insulin glucose
insulinglucose/salinestarts
digoxin starts
Time
Su
rviv
al
South Asian Clinical Toxicology Research Collaboration
Fructose 1-6 diphosphateFructose 1-6 diphosphate
Extensive human experience for a number of conditions
? Cardiac glycoside
South Asian Clinical Toxicology Research Collaboration
CaseCase 19 yo Ms R took 3 seeds of oleander 11 am Consented to the FDP phase II study 18:45
– Sinus Brady (HR 40) for over a minute– Then narrow complex tachycardia) for 30sec– Intermittent 2nd degree HB
South Asian Clinical Toxicology Research Collaboration
20:45 –– Sinus bradycardia & pulseless
Adrenaline and atropine given
– VT and VF a total of 5 DC shocks were given. Ongoing DC shocks for VF – occasionally reverting, but VF
refractory At this stage Mg 2g has been given, NaHCO3, atropine, and
dobutamine infusion
21:45 – 60mg/kg of FDP was given as a bolus over 5mins
– return of spontanous circulation BP 110/70
22:55 re arrested, 23:20hrs resuscitation ceased
South Asian Clinical Toxicology Research Collaboration
South Asian Clinical Toxicology Research Collaboration