Download Sodium channel blockade

Sodium channel blockade
Sophie Gosselin. MD
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Objectives
Role of Na channel in cardiovascular physiology
Manifestations of sodium channel antagonism
Toxins with sodium channel antagonism properties
Treatment for sodium channel toxicity
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Physiology
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Physiology
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Physiology
Source: Goldfrank Toxicologic Emergencies 9th edition. Fig 63.1
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Physiology
•Toxins bind to open or inactivated channels
•Fast heart rate (anticholinergic) increase sodium blockade
because more channels become open and are then bound
•Sodium blockade slows recovery
•Too much blockade wide QRS: bradycardia to asystoly
Source: Goldfrank Toxicologic Emergencies 9th edition. Fig 63.1
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Physiology
Source: Goldfrank Toxicologic Emergencies 9th edition.
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Predicting Toxicity
QRS > 100 ms limb lead

Bailey et al J Tox ClinTox 2004
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Predicting Toxicity
QRS > 100 ms limb lead
Ventricular arrhythmia
Sensitivity 0.79
Specificity 0.46
Seizures
Sensitivity 0.69
Specificity 0.69

Bailey et al J Tox ClinTox 2004
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Predicting Toxicity
QRS > 100 ms 30% risk of seizures
QRS > 160 ms 50% risk of seizures

Bailey et al J Tox ClinTox 2004
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Predicting Toxicity
R aVR > 3 mm
R/S aVR > 0.7
Right side conduction preferentially impaired
Hypothesis that is related to difference Na channel
structure, density or distribution (not much evidence)
Normal
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Culprits
Antidepressants
TCA
1A phase 0 fast Na channel (quinidine)
Antidysrhythmics Class 1 1B fast onset, offset (lidocaine) more effect in tachycardia
1C phase 0 (flecainide, encainide, propafenone) potent
Antihistamines
Local anesthetics
diphenhydramine, chlorpheniramine
bupivacaine, lidocaine, ropivacaine
Antimalarials
chloroquine, hydroxychloroquine
Analgesics
dextropropoxyphene
Beta-blockers
propanolol
Anticonvulsants
carbamazepine, topiramate, lamotrigine
Natural toxins
tetrodotoxin, saxitoxin, aconitine, ciguatoxin, veratridine,
batrachotoxin (keep channel open)
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Treatment - AIRWAYS
Respiratory Acidosis is BAD
BVM
Hyperventilate
Peri-intubation
Modified RSI
Sellick and BVM
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Treatment
•
Acidosis
Increases free drug concentration by decreasing protein binding
More free drug, more drug binding to the Na channel.
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Acidosis
CBF varies with PaCO2
High PaCO2
vasodilation= hypotension
Too low PaCO2
vasoconstriction = ischemia
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Treatment CIRCULATION
sodium bicarbonate
Restore “normal” conduction
Competition at the channel
Sodium load
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How much sodium bicarbonate
Depends on how big your “amp” is
1mEq/mL
1o mL
50 mL
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Treatment CIRCULATION
sodium bicarbonate
Intermittent bolus
No shock: 1-3mEq/kg IV (70 kg= 2-4 amps)
Shock: 3-6 mEq/Kg IV (70 kg= 5-8 amps)
Goal: reversal of clinical toxic effect
Until QRS narrows, arrhythmias stop.
Initially don’t worry about high pH.
AFTER with infusion keep pH 7.50-7.55
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Effect of pH
pH 7.1
pH 7.40
200 mEq NaHCO3
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Treatment- Circulation
More Sodium competition
Still more or less experimental
Hypertonic saline
10 mL/kg of 7,5% NaCL (15mEq/kg NaCL) had greater
efficacy than alkalinisation in swine model
McCabe. Ann Emerg Med .1998;32:329-333.
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Treatment
Hypotension
Na channel toxins are also alpha adrenergic blocker
Vasodilatation
Fluids fluid fluids
Phenylephrine peripherally
Norepinephrine with central line
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Treatment
Seizures
Toxicity of Na channels in brain
Sodium bicarbonate
Benzos
No phenytoin
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Case 1: Patient come in after snorting cocaine at party,
he is agitated, BP: 170/80, HR 120 sinus.
 Hoffman
R.S. BCPJ 2008
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Case 2: Patient presents after a seizure of an over the
counter medication taken in suicidal ingestion.
 Levine
and LoVecchio. Resuscitation 2010
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Diphenhydramine
induced Brugada
 Levine
J-point elevation 2mm
Slow descending ST
Masked negative T-wave
and LoVecchio. Resuscitation 2010
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After NaHCO3
 Levine
and LoVecchio. Resuscitation 2010
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Case 3 : Patient with AFiB, new medication and AKI
 Timberley
et al. BMC Emergency Medicine 2005
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After Treatment
 Timberley
et al. BMC Emergency Medicine 2005
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Summary
Intoxications:
wide QRS,
hypotension
seizures
dysrhythmias
Main treatment is NaHCO3 and airways
Refractory situations
hypertonic saline
lipid emulsion
ECMO only if available in your centre.
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Summary
Many drugs have sodium channel affinity
Produce similar cardiac toxicity
Recognize the ECG pattern
Treatment is the same
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