CARDIAC ARREST FROM OVERDOSE

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CARDIAC ARREST FROM OVERDOSE

• All patients should have
• DECONTAMINATION of the GIT
• CORRECTION of ELECTROLYTES abnormalities
• CARDIOVERSION when appropriate
• OXYGENATION and protection of airway
• CONSULTATION WITH THE CLINICAL PHARMACOLOGIST
• Successful resuscitation has been well documented
  after 8 hours of CPR

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CARDIAC ARREST FROM OVERDOSE

• Overdose patients may have
• a reversible cause for their arrest
• good general health
• novel treatments for arrhythmias
• cerebral protection

3
CARDIAC ARREST FROM OVERDOSE

• The major causes of cardiac arrhythmia in our
  area are
• QUINIDINE-LIKE DRUGS
• SYMPATHOMIMETIC DRUGS
• CALCIUM CHANNEL BLOCKERS
• BETA BLOCKERS
• DIGITALIS
• CHLOROQUINE
• Arrhythmias may also be secondary to
  metabolic/electrolyte abnormalities eg
• salicylates, methanol, ethylene glycol

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QUINIDINE-LIKE DRUGS

• TRICYCLIC ANTIDEPRESSANTS
• PHENOTHIAZINES
• QUINIDINE
• PROCAINAMIDE
• DISOPYRAMIDE
• QUININE

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SYMPATHOMIMETIC DRUGS

• INCREASED SENSITIVITY TO CATECHOLAMINES
• CHLORAL HYDRATE
• THEOPHYLLINE
• INCREASED CATECHOLAMINES
• AMPHETAMINES
• COCAINE
• THEOPHYLLINE
• BETA AGONISTS
• Arrhythmias normally respond to beta blockade
  (propranolol)

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CHLORAL HYDRATE OVERDOSE

• Grandfather drug hypnotic 1869
• 1890 review of the first 44 deaths
• death tricyclics
• Prodrug with enhanced formation of active
  tichloroethanol by alcohol
• Rapid absorption with peak levels 0.5-1 hour
• Deaths as little as 2-3 grams in adults (5-10
  grams more commonly)
• Recreational and inappropriate use
• Trichloroethanol T1/2 between 8 to 35 hours
  sensitises myocardium to catecholamines.

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CALCIUM CHANNEL BLOCKERS

• HYPOTENSION
• Peripheral vasodilatation myocardial depression
• Volume expansion (normal saline)
• Calcium gluconate (1-4 ampoules)
• BRADYARRHYTHMIA
• Ca (4-8 ampoules)
• Adrenaline, isoprenaline, dopamine infusion
• Correct acidosis if pHgt7.2
• Pacemaker if 2nd degree heart block or above

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CHLOROQUINE

• Features of toxicity may develop within 30
  minutes
• death may occur within 3-4 hours
• myocardial depression
• arrhythmia.
• TOXICOKINETICS
• RAPIDLY ABSORBED
• DOSE DEPENDENT KINETICS

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CHLOROQUINE - RISK FACTORS FOR SUDDEN DEATH

• Ingested gt 50 mg/kg of chloroquine base
• Systolic BP lt 90 mmHg
• QRS of gt 110 msecs
• Major complications
• deteriorating level of consciousness
• seizure
• any cardiac arrhythmia.

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CHLOROQUINE - TREATMENT

• Elective intubation and ventilation.
• Diazepam 2 mg/kg over 30 minutes followed by 1-2
  mg/kg/day infusion.
• Adrenaline 0.25 micg/kg/hr by continuous infusion
• systolic BP gt 100 mmHg.
• Gastric lavage followed by activated charcoal.

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DIGOXIN - TOXICCOKINETICS

• Vd 5-7L/kg
• T1/2 30-45h
• peak effect 3-6h
• absorption 50-80
• urinary excretion 60-80
• therapeutic level 0.6-2.0 ng/ml

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DIGOXIN - PATHOPHYSIOLOGY

• Inhibits Na K ATPase
• increased automaticity and excitability
• extrasystoles
• tachyarrhythmias
• increased refractoriness at AV node decreased
  conduction velocity throughout conduction system
• AV block
• bradycardia
• prolonged PR interval

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DIGOXIN - PREDISPOSING FACTORS

• DRUG INTERACTIONS
• Quinidine
• Calcium channel blockers
• Amiodarone
• Spironolactone
• NSAIDs (decreased renal clearance)
• Diuretics (K Mg Na HCO3)

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DIGOXIN - PREDISPOSING FACTORS

• DISEASE STATES
• electrolyte imbalance
• renal failure
• myocardial infarct
• cor pulmonale
• hypothyroidism
• cardiac failure
• hypoxia

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INDICATIONS FOR DIG Fab USE

• hyperkalaemia
• tachyarrhythmias (60-65 mortality)
• high grade AV block
• digoxin level gt 15ng/ml
• DOSE
• equimolar 1 vial (40mg) neutralises 0.6mg
  digoxin

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BETA BLOCKER POISONING - Mechanism of Toxicity

• Block betas
• hypotension
• bradycardia
• cardiac failure
• insulin release
• hypoglycaemia
• bronchoconstriction (beta 2)

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BETA BLOCKER POISONING - Mechanism of Toxicity

• Stimulate beta adrenoreceptors (partial agonist)
• tachycardia
• hypertension
• Membrane stabilising (quinidine like)
• QRS widening
• cardiac conduction block, asystole

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BETA BLOCKER POISONING - Mechanism of Toxicity

• Central Nervous system effects
• coma
• seizures
• Class III antiarrhythmic activity (sotalol)
• QT prolongation
• Torsade de pointes

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CARDIAC CASE 1

• 18 y o woman admitted 3 hours after overdose of
• 3.5gms of slow release verapamil
• 6gms of paracetamol
• tetracycline 4500mg
• 1000 mg of pseudoephedrine
• vomited before arrival

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CARDIAC CASE - EXAMINATION

• On arrival in casualty
• P 120, BP 110/80, RR 20, afebrile
• Drowsy but oriented and cooperative
• Other examination NAD
• Lavaged with green tablets (colour of Isoptin SR)
  returned
• 50gms of charcoal with sorbitol.

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CARDIAC CASE - INITIAL INVESTIGATIONS

• ECG - sinus tachycardia with normal QRS width
• admitted to ICU for monitoring
• 4 hour serum paracetamol level was 38 nmol/L
• (significant risk of hepatotoxicity gt 1300nmol/L
  at 4 hours)
• Further 50gm dose of charcoal 4 hours later

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CARDIAC CASE - LATER ON

• 16 hours post overdose
• BP fell to 70/40 and then 50/30.
• P 50
• oxygen saturation dropped to 75
• ECG
• absent P waves
• prominent U waves
• normal QRS duration and QT interval

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CARDIAC CASE - TREATMENT

• IV atropine 0.6mgs - no response
• IV calcium gluconate
• 6gms over 20 minutes
• further 6gms over the next hour
• Following the calcium bolus
• P60 sinus rhythm, BP 100/80
• oxygen saturation gt 95
• Infusion of 10 calcium gluconate at 2gms an hour
  continued for 10 hours (total calcium gluconate
  dose of 30gms)
• She was also given 2.5L IV fluids.

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CARDIAC CASE - OUTCOME

• Twenty four hours post admission
• Largely recovered
• sinus rhythm P 60, BP 115/70
• Calcium was ceased
• No further hypotension or bradycardia
• Peak serum Ca was 4.8 (NR2.18 - 2.47mmol/L)
• Serial Verapamil levels at 6, 18, 22 and 46 hours
  were 616, 2374, 2518 and 1006 ng/ml
• (range during usual therapy - 100-300 ng/ml)
• Non cardiogenic pulmonary oedema