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Case Study 2: Symptomatic Bradycardia. Robert S. Hoffman, MD Director New York City Poison Center. Objectives. Understand the differential diagnosis of drug-induced bradycardia Explain the use of the laboratory in cases of unknown bradycardia

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case study 2 symptomatic bradycardia

Case Study 2: Symptomatic Bradycardia

Robert S. Hoffman, MD

Director

New York City Poison Center

objectives
Objectives
  • Understand the differential diagnosis of drug-induced bradycardia
  • Explain the use of the laboratory in cases of unknown bradycardia
  • Discuss the treatment of patients with known and unknown causes of bradycardia
differential diagnosis
Differential Diagnosis
  • A 42 year old man presents to the hospital complaining of weakness and dizziness following an intentional drug overdose
    • He is pale and diaphoretic appearing but awake
    • Blood pressure 62/30 mm Hg
    • Pulse 40/minute; slightly irregular
    • Physical examination otherwise normal
slide5

EAPCCT

Investigation of the Poisoned Patient-Case Studies

Bordeaux, May 2010

question 1
Question 1
  • The most likely etiology of this patient’s toxicity is:
    • A. Digoxin
    • B. Calcium channel blocker
    • C. Beta blocker
    • D. Clonidine
    • E. Organophosphate
answer 1
Answer 1
  • You can not be certain at this point:
    • A. Digoxin
    • B. Calcium channel blocker
    • C. Beta blocker
    • D. Clonidine
      • Sedation
    • E. Organophosphate
      • Muscarinic and nicotinic findings
slide14

EAPCCT

Investigation of the Poisoned Patient-Case Studies

Bordeaux, May 2010

question 2
Question 2
  • Which laboratory tests might be useful to help narrow the differential diagnosis
    • A. Glucose
    • B. Calcium
    • C. Potassium
    • D. Sodium
    • E. Both A and C
answer 2
Answer 2
  • Which laboratory tests might be useful to help narrow the differential diagnosis
    • A. Glucose
    • B. Calcium
    • C. Potassium
    • D. Sodium
    • E. Both A and C
diagnosis and prognosis
Diagnosis and Prognosis

Bismuth C, et al: Clin Toxicol 1973; 6:153-162

slide18

Composite endpoints

  • Death
  • Vasoactive drugs (epinephrine, etc)
  • Pacemaker
slide21

EAPCCT

Investigation of the Poisoned Patient-Case Studies

Bordeaux, May 2010

question 3
Question 3
  • Which ECG finding is MOST characteristic of digoxin toxicity:
    • A. Scooped ST segment
    • B. Sinus bradycardia
    • C. Atrial tachycardia with high degree A-V block
    • D. Bidirectional ventricular tachycardia
    • E. Slow atrial fibrillation
answer 3
Answer 3
  • Which ECG finding is MOST characteristic of digoxin toxicity:
    • A. Scooped ST segment
    • B. Sinus bradycardia
    • C. Atrial tachycardia with high degree A-V block
    • D. Bidirectional ventricular tachycardia
    • E. Slow atrial fibrillation
slide29

EAPCCT

Investigation of the Poisoned Patient-Case Studies

Bordeaux, May 2010

question 4
Question 4
  • Which rhythm is inconsistent with digoxin toxicity
    • A. Sinus tachycardia
    • B. Rapid atrial fibrillation
    • C. Supraventricular tachycardia at 150/min
    • D. Multifocal atrial tachycardia
    • E. All of the above
answer 4
Answer 4
  • Which rhythm is inconsistent with digoxin toxicity
    • A. Sinus tachycardia
    • B. Rapid atrial fibrillation
    • C. Supraventricular tachycardia at 150/min
    • D. Multifocal atrial tachycardia
    • E. All of the above
more case information
More Case Information
  • ECG: As shown previously
  • Glucose: 300 mg/dL (16.16 mmol/L)
  • Serum potassium: 4.8 mmol/L
  • A fluid bolus of 1L of saline is given without response
    • Blood pressure 72/40 mm Hg
    • Pulse 45/min
slide33

EAPCCT

Investigation of the Poisoned Patient-Case Studies

Bordeaux, May 2010

question 5
Question 5
  • Which of the following therapies is most appropriate at this point?
    • A. Digoxin antibodies
    • B. Epinephrine
    • C. Glucagon
    • D. Calcium
    • E. Milrinone
answer 5
Answer 5
  • Which of the following therapies is most appropriate at this point?
    • A. Digoxin antibodies
    • B. Epinephrine
    • C. Glucagon
    • D. Calcium
    • E. Milrinone
slide37

Kline JA, Tomaszewski CA, Schroeder JD, Raymond RM: Insulin is a superior antidote for cardiovascular toxicity induced by verapamil in the anesthetized canine. J Pharmacol Exp Ther 1993;267:744-50

more case information38
More Case Information
  • A serum digoxin concentration is reported as non-detectable.
  • The patient is given the following with little improvement:
    • 3 grams of calcium chloride
    • Escalating doses of glucagon (up to 10 mg)
    • Amrinone
    • Dopamine continuous infusion
slide39

EAPCCT

Investigation of the Poisoned Patient-Case Studies

Bordeaux, May 2010

question 6
Question 6
  • Which therapies might be indicated next:
    • A. Hemodialysis/hemoperfusion
    • B. Pacemaker
    • C. Intra-aortic balloon pump
    • D. High-dose insulin euglycemia therapy
    • E. Intravenous fat emulsion
answer 6
Answer 6
  • Which therapies might be indicated next:
    • A. Hemodialysis/hemoperfusion
    • B. Pacemaker
    • C. Intra-aortic balloon pump
    • D. High-dose insulin euglycemia therapy
    • E. Intravenous fat emulsion
cardiac energy dynamics
Cardiac Energy Dynamics
  • Normal Function
  • Preferred Substrate
    • Fatty Acids
      • High energy
      • Stable pool
cardiac energy dynamics43
Cardiac Energy Dynamics
  • Sick hearts
  • Convert to glucose
    • Immediate energy
    • Limited availability
    • Large swings
    • Basis for:
      • Tight glucose control
      • High dose insulin/euglycemia therapy
slide44

Kline JA, Tomaszewski CA, Schroeder JD, Raymond RM: Insulin is a superior antidote for cardiovascular toxicity induced by verapamil in the anesthetized canine. J Pharmacol Exp Ther 1993;267:744-50

slide46

Yuan TH, et al: Insulin-glucose as adjunctive therapy for severe calcium channel antagonist poisoning. J Toxicol Clin Toxicol 1999;37:463-474

technique
Technique
  • Bolus 1 unit/kg of regular insulin
  • Follow with a continuous infusion
    • 0.5-2.0 units/kg/hour of regular insulin
  • Add glucose as necessary
    • 0.5-1 gm/kg/hr
  • Allow mild hypokalemia (only mild)
lipid emulsion therapy
Lipid Emulsion Therapy
  • Mechanism of action
  • 2 Prevailing hypotheses
    • “Lipid sink theory”
    • Bioenergetic theory
lipid emulsion therapy49
Lipid Emulsion Therapy
  • Lipid sink theory
    • Intralipid partitions the drug into a lipid phase creating a concentration gradient for removal of the drug from the target organ

Weinberg GL: Reg Anesth Pain. 2006;31:296

slide50

Tebutt S: Intralipid prolongs survival in a rat model of verapamil toxicity. Acad Emerg Med 2006;13:134

methods
Methods
  • 14 dogs instrumented extensively
  • Verapamil toxicity, defined as a 50% decrease in MAP
  • All dogs got atropine and calcium chloride (15 mg/kg q 5min)
  • Randomized
    • IFE (7 mg/kg of 20%) IV
    • Or equivalent volumes of 0.9% normal saline
methods56
Methods
  • 30 sedated and ventilated clomipramine poisoned rabbits
  • At 50% MAP given
    • 0.9% NaCl 12 mL/kg
    • OR 8.4% sodium bicarbonate 3 mL/kg
    • OR 20% Intralipid 12 mL/kg
human case reports
Human Case Reports
  • Bupivacaine, Levobupivacaine, Ropivacaine, Mepivacaine
  • Bupropion and lamotrigine
  • Beta blockers
  • Haloperidol and other antipsychotics
  • Calcium channel blockers
  • Tricyclic antidepressants
lipid emulsion
Lipid Emulsion
  • Weinberg Protocol
  • Bolus
    • 1.5 mL/kg over one minute
    • Repeat every 3-5 minutes
    • Maximum 8 mL/kg
  • Infusion
    • 0.25 mL/kg/min until hemodynamic recovery
    • Can increase to 0.5 mL/kg/min if needed
indications for digibind in acute overdose
Indications For Digibind In Acute Overdose
  • Serum potassium over 5.0 mEq/L
  • Any life-threatening dysrhythmia
    • Redefine for digoxin
  • A digoxin level over 10-15 ng/mL
  • Need for prolonged ICU observation
  • Mixed overdose with calcium calcium channel blocker
slide61

EAPCCT

Investigation of the Poisoned Patient-Case Studies

Bordeaux, May 2010

question 7
Question 7
  • What is the correct dose of digoxin-specific Fab in an adult patient with an acute overdose and severe toxicity?
    • A. 1 vial
    • B. 2 vials
    • C. 5 vials
    • D. 10 vials
    • E. 20 vials
answer 7
Answer 7
  • What is the correct dose of digoxin-specific Fab in an adult patient with an acute overdose and severe toxicity?
    • A. 1 vial
    • B. 2 vials
    • C. 5 vials
    • D. 10 vials
    • E. 20 vials
digibind dosing
Digibind Dosing
  • Empiric dose
    • 10 to 20 vials in acute overdose
  • Amount ingested known
    • Each vial binds 0.5 mg of digoxin
    • Assume 100% bioavailability
    • Divide:

mg ingested

0.5 mg/vial

digibind dosing65
Digibind dosing
  • Level known: [ ]=d/Vd; d=[ ] X Vd

level (ng/mL) X Wt (Kg) X 5.6 L/kg

0.5 mg/vial X 1000

level (ng/mL) X wt (kg)

~

100

summary
Summary
  • Understand the physiology
  • Understand the toxicology
  • Define the physiology
    • Labs
    • ECG
    • Clinical status
  • Tailor the antidotes to the physiology and toxicology
clinical clues
Clinical Clues
  • Blood pressure
    • Preserved with digoxin
  • Mental status
    • Preserved with CCB
  • Electrolytes
    • K+ increased with digoxin, less so with beta blockers
    • Glucose increased with calcium channel blockers