Conference Review – Cardiac Tox

Thanks to Justin Carroll for writing this week’s conference review!

Digitalis toxicity

  • MOA by inhibiting the Na+/K+ channel resulting in change in increase in intracellular Na+ and extracellular K+. This affects the functioning of the Ca2+/Na+ exchanger resulting in an increase in intracellular Ca2+.
    • Increased inotropy
      • Side effect: Decreased refractory period, Delayed after depolarizations (lower threshold for dysrhythmias)
    • Decreased excitation of cell (increased vagal tone)
      • Decreased AV nod conduction (bradyarrhythmias)
    • Narrow therapeutic index
      • Severity of toxicity better correlated to severity of hyperK+ rather than Dig level (see below)
    • Acute toxicity
      • Usually by intentional/accidental ingestion (asymptomatic for several hours
        • p/w dizzy, h/a, n/v, confusion, coma
        • Xanthopsia (yellow-green halos)
        • Bradyarrhythmia, SV tachyarrhythmia w/ AV block
        • Hyper K+ with acute ingestion.
        • Dig level inaccurate due to slow absorbs and large Vd (falsely elevated in first hrs).
      • Chronic toxicity
        • Often elderly with near or w/in therapeutic window and 2/2 to comorbidities such as renal failure, drug-drug interactions (i.e. diuretic, clarithromycin)
        • p/w n/v, GI pain, diarrhea
        • more likely to have CNS manifestations (fatigue, weakness, confusion, delirium, coma)
        • Ventricular and SV dysrhythmias (V tach very common)
        • Normal to low K+, hypo Mg2+
      • Dx
        • Regular dose usually (125 – 250 mcg). Toxicity usually d/ 1-2 mg, with fatal doses of 10 mg (adult) and 4 mg (child)
        • Toxic Dig level usually >2.5 ng/mL (levels no reliable until >6hrs)
          • Digoxin-like immuno-reactive substances (DLIS) – falsely elevated dig level 9 neonates, 3rd trimester, SAH, renal/hepatic failure, plant based steroids
        • EKG changes are important findings (4 findings)
          • T-wave flattening/inversion
          • QT shortening
          • ST scooping
          • Increased U wave amplitude
        • Dysrhythmias most commonly seen are PVC’s. Also will see SVT w/ AV block or junctional escape rhythms.
        • Bidirectional VT (alternating QRS) – specific of Dig
        • Labs:
          • Acute: K+ level for hyperkalemia and dig level (Therapeutic 0.-2.0)
          • Chronic: Not very helpful. Normal to low K+. Mildly elevated dig level
        • Tx
          • Asymptomatic pt
            • Cardiac monitor, IV access, GI decontamination (charcoal), reeval
          • Symptomatic (life-threatening dysrhythmia)
            • Digoxin-Fab
              • Indications: K+ > 6.0, life threatening dysrhythmia
              • Give 80 mg (two vials) bolus and reassess. Repeat q30-60 min until hyperkalemia or dysrhythmia resolved. (Calculation usually over estimates amount needed.
              • Chronic – give 40 mg (1 vial) q1 until asymptomatic
                • Tx may unmask other conditions (A-fib) or reported cardiac arrest, or cause hypersensitivity rxn.
              • Correct symptoms – hypoxia, hypoglycemia, hypovolemia, electrolyte abnormalities.
              • IV Mg2+
              • Atropine and/or transvenous pacer
            • Dispo f/u
              • Monitor:
                • Asymptomatic – observe until dig levels begin to decrease
                • Symptomatic – admit (ICU for 6-12 hrs. if Fab given)

BB Toxicity

  • Acute presentation
    • Cardiac symptoms include hypotension, bradycardia, ventricular dysrhythmias, AV block and delays, decreased contractility and asystole. CNS symptoms include decreased mental status, seizures, psychosis and coma. Pulmonary findings include bronchospasm.
    • Severe toxicity – bradycardia leading to shock
  • Dx
    • Clinical diagnosis based on presentation and history.
  • Tx
    • No signs of toxicity, bradycardia or hypotension:
      • Cardiac monitor, IV access, GI decontamination (w/in 6 hrs.) and observation.
        • Observation 6-8 hrs. If sustained release 12-24 hrs. Peds – 24 hrs.
      • +Toxicity, bradycardia or hypotension:
        • Patients at high risk for CV collapse. Treat to improve contractility and HR.
        • IV, O2 monitor, GI decontamination
        • Supportive care including IVF, atropine, glucagon bolus 2-10 mg IV (Peds: 50-150 mcg/kg), insulin, calcium, bicarb (if wide QRS intervals).
          • Glucagon MOA: Bypass B-adrenergic receptor to stimulate cAMP w/in cardiac myocyte improving excitation.
        • If refractory consider pacer, hemodialysis, lipid emulsion therapy and ECMO.


CCB Toxicity

  • Dihydropyridines – L-type calcium channel selectivity in peripheral vasculature.
  • Non-didydropyridines (verapamil and diltiazem) – selectively block L-type Ca2+ in myocardium
  • Pathophysiology
    • Calcium channel block leads to vascular smooth muscle relaxation, decreased contractility and conduction.
  • Dx:
    • Similar presentation of myocardial depression with peripheral vasodilation
    • Hypotension, bradycardia, varying AV blocks (PVC’s most frequent) with complete heart block in severe overdose.
    • Diagnosis per clinical presentation and varying dysrhythmias on EKG.
  • Tx:
    • IV, O2 monitor, GI decontamination
    • Supportive care including IVF, atropine, CaCl 10% 10-20 mL IV (Peds: 0.2 mL/kg) or Ca gluconate 10% 30-60mL (peds 0.6 ml/kg) IV. May repeat q 10-20 min. Consider infusion 0.4 mL/kg/hr with serial Ca2+ q1-2hrs. High dose insulin therapy (CCB inhibits beta cells), consider glucagon, bicarb (if wide QRS intervals).
    • If refractory consider pacer, hemodialysis, lipid emulsion therapy and ECMO.


Other Antihypertensives:

  • Diuretics: excessive diuresis with tachycardia, hypotension, and electrolyte abnormalities specifically hyperkalemia.
    • Tx: IVF (volume repletion) and electrolyte correction
  • Alpha-agonist: Clonidine is most common cause. Present with bradycardia and hypotension with possible opiate syndrome (coma, miosis, and respiratory depression).
  • ACE-I/ARBs: cough and angioedema
  • Hydralazine: can present with DILE (drug induced lupus erythematosus)

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