Digibind Antidote

Review and revised 11 July 2014

OVERVIEW

  • Digibind is the trade name for a digoxin antidote containing Digoxin-specific antibody Fab fragments
  • there is often a reluctance to give digibind due to cost and underestimating the mortality associated with digoxin toxicity, however  it is prudent to administer digibind based on a considered risk assessment and before the life-threatening manifestations of digoxin toxicity develop
  • digoxin levels cannot be accurately measured for about 3 weeks after administration of digibind, as they will be artefactually high given that most serum digoxin assays measure both free and digibind-bound digoxin in the circulation (some laboratories may be able to measure free digoxin levels specifically)
  • supplies of digibind should be available on site in the emergency department, and in severe toxicities early steps to source more may be necessary

CLASS

  • Digoxin-specific antibody Fab fragments

MECHANISM OF ACTION

  • digibind has a much higher affinity (high affinity (109–1010 L/mol) for digoxin than the Na+/K+ ATPase digoxin receptor site
  • binds to digoxin in the extracellular spaces preventing digoxin binding to the Na+/K+ ATPase
  • creates a concentration gradient that extracts digoxin from the intracellular space
  • bound digoxin is then renally eliminated with digibind

PHARMACEUTICS

  • powder
  • contains 38mg of digoxin-specific Fab fragments
  • reconstitute with sterile water

DOSE

  • each 38mg vial will bind about 0.5mg of digoxin
  • give over 30min or bolus if in an arrest
  • improvement in symptoms usually within 30 min, with maximal effect by 4 hours

Acute digoxin toxicity

  • Known dose:
    • number of vials = Ingested dose (mg) x 0.8 (bioavailability) x 2 (note that 0.8 represents the 80% oral bioavailability of digoxin)
  • Unknown dose:
  • Give 5 vials initially if the patient is hemodynamically stable
  • Give 10 vials initially if the patient is hemodynamically unstable
  • Repeat doses of 5 ampoules should be given every 30 minutes until reversal of digoxin toxicity is achieved
  • In cardiac arrest give 20 vials (760 mg), or as many vials as are available if <20 stocked

Chronic digoxin toxicity

  • Known level: number of vials required = (serum digoxin concentration – ng/L) x (weight – kg) ÷ 100
  • empiric dosing: give 2 ampoules and observe for clinical response, if toxicity remains after 30 minutes give a further 2 ampoules
  • a source of confusion is the units of measurement used by laboratories: many laboratories measurs serum digoxin levels in nmols/L. The conversion factor is ng/ml x 1.28 = nmols/L

Endpoints

  • resolution of nausa and vomiting
  • resolution of dysrhythmia
  • complete binding of total body digoxin is usually not necessary to control digoxin toxicity

INDICATIONS

Acute digoxin toxicity

  •  cardiac arrest
  • life-threatening dysrhythmia
  • K >5mM
  • >10mg ingested (adult), >4mg ingested (child)
  • >15 nM level (>12ng/mL)

Chronic digoxin toxicity

  •  cardiac arrest
  • life-threatening dysrhythmia
  • dysrhythmia or increased automaticity unlikely to be tolerated for a prolonged period
  • significant gastrointestinal symptoms
  • symptoms of digoxin toxicity and coexistent renal failure

Other life-threatening cardiac glycoside toxicities:

  • oleander poisoning
  • cane toad poisoning (bufotoxin)
  • Chinese medicines (e.g. Chan Su, Dan Shen and Lu-Shen-Wan)

No absolute contraindications

ADVERSE EFFECTS

  • anaphylaxis (rare)
  • effects from withdrawal of digoxin: AF, heart failure (negative inotropy), hypokalemia

PHARMACOKINETICS

  • Absorption – IV administration, from the end of infusion  initial response is 20 minutes (0 to 60 min) and maximal response is at 90 minutes (30-360 min)
  • Distribution – large Vd
  • Metabolism – nil
  • Elimination – urinary, t ½ = 11 hrs; bound digoxin has an elimination t1/2 of 16-30h

References

LITFL

Journal articles and textbooks

  • Antman EM, Wenger TL, Butler VP Jr, Haber E, Smith TW. Treatment of 150 cases of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments. Final report of a multicenter study. Circulation. 1990 Jun;81(6):1744-52. PubMed PMID: 2188752. [Free Full Text]
  • Ip D, Syed H, Cohen M. Digoxin specific antibody fragments (Digibind) in digoxin toxicity. BMJ. 2009 Sep 3;339:b2884. doi: 10.1136/bmj.b2884. PubMed PMID: 19729422. [Free Full Text]
  • Murray L, Daly FFS, Little M, and Cadogan M. Toxicology Handbook (2nd edition), Elsevier Australia 2011. [Google Books Preview]
  • McMillin GA, Owen WE, Lambert TL, De BK, Frank EL, Bach PR, Annesley TM, Roberts WL. Comparable effects of DIGIBIND and DigiFab in thirteen digoxin immunoassays. Clin Chem. 2002 Sep;48(9):1580-4. PubMed PMID: 12194938. [Free Full Text]

CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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