Gettin

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Gettin Digi Wit it

• Digoxin Overdose
• Core Rounds March 6, 2003
• A.F. Chad, MD, CCFP
• Randall Berlin, MD

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The Fresh Prince

• After years of getting jiggy, Will Smith develops
  CHF and is Rx Digoxin
• He presents to the FHH feeling not jiggy
• What should you do?

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Wild Wild West

• Digoxin is a cardiac glycoside from Foxglove
  plant
• Other cardiac glycosides from oleander, foxglove,
  and lily-of-the-valley
• Used in ancient Roman as cardiac med
• Physicians first studied 18th C
• Digoxin toxicity 1st described in 1785

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Gettin Jiggy

• Inotropic effects via inhibition Na/K ATPase pump
  -gt incr myocardial Ca -gt more forceful
  contraction
• Increases automaticity in atrial and ventricular
  tissue
• Slows conduction through AV node (via
  parasympathomimetic tone)

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Gettin Jiggy ECG Effects

• Downward scooping of ST segment
• Inverted T waves
• Reduced T wave amplitude
• Short QT interval
• U waves
• Prolonged PR interval
• Does NOT affect QRS duration

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Gettin Jiggy

• Onset 5-30 mins IV, peak 1-4 hrs
• Onset 30-120 mins po, peak 2-6 hrs
• N levels 0.6-2.6 nmol/L, most reliable 6 hrs
  post ingestion
• Narrow therapeutic window
• Large Vd (5.6L/Kg)
• Crosses BBB, placenta
• Hepatic degredation (15), excreted in urine
  (85)
• T1/2 30-40hrs (4-6d in RF)

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So Fresh

• USA
• 0.4 hospital admissions
• 1.1 of outpatients on digoxin
• 10-18 nursing home patients
• Internationally
• 2.1 of inpatients on digoxin
• 0.3 of admissions

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Yes, Yes, Yall ?Not that common?

• Williamson, KM, et al. Digoxin ToxicityAn
  Evaluation in Current Clinical Practice. Arch
  Intern Med. 19981582444-2449
• 5 hospitals, dig levels taken in 3434, 2009 gt2.6
  nmol/L, only 83 (4.1) clinical tox, 16 had
  levels lt 6hrs

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Men in Black

• Morbidity 4.6-10
• 50 if digoxin level gt 7.7nmol/L

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Not So Fresh Prince

• Will Smith My breathin is ill G, I gots me
  some palpitations, my guts be groovin like DJ
  Jazzy Jeff, and I be seein yellow-green, like
  them aliens in Men in Black.
• Does this sound like hes digi wit it?

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Nod Ya Head

• Constitutional symptoms
• (weakness, fatigue)
• CVS
• (Palpitations, Syncope, Dyspnea)
• CNS
• (Confusion and somnolence, Dizziness w/o vertigo,
  Agitation, delirium, hallucinations, h/a,
  Paresthesias, neuropathic pain, Seizures
  (extremely rare)

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Nod Ya Head

• Ocular
• (Disturbances color vision with tendency to
  yellow-green , Blurring, diplopia, Halos,
  scotomas, Photophobia)
• GI
• (NVD, anorexia, Abdo pain (uncommon))

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Nod Ya Head

• Acute
• Mainly Cardiac ad GI
• Chronic
• Can have any of the Symptoms

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Big Willie Style

• ANY arrhythmia
• Classically paroxysmal atrial tachycardia 21
  block, accelerated jnc, bidirectional VT, TdP
• Typically combo of increased ectopy or
  automaticity with block
• Acute or healthy heart more typical to have
  bradyarrhythmias and blocks
• Chronic or diseased hearts enhanced automaticity
  impaired conduction

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Big Willie Style

• Hemodynamic instability -gt arrhythmia or CHF
• PVCs most common arrhythmia
• Sinus brad bradyarrhythmias very common Slow
  a.fib with little variation in ventricular rate
  (regularization of the R-R interval)
• Heart block
• Rapid a.fib or flutter is rare
• VT
• Cardiac arrest from asystole or VF usually fatal

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Big Willie Style

• GI symptoms common, abdo exam nonspecific.
• Neurological findings related to changes in
  sensorium or mental status
• Lateralizing findings usually indicate another
  disease process.
• Visual changes occur, pupils are spared,
  objective findings few
• Drug-induced fever does not occur

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Not So Fresh Prince

• Will Smith Dr Dre, my beat physician put me on
  lasix, spironolactone, ibuprofen, amiodarone, and
  propafenone.
• Is tryin to do me like Biggie?

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Yall Know

• Drug interactions most common cause
• directly increase plasma levels, alter renal
  excretion, induce electrolyte abnormalities.

• Amiloride
• Amiodarone
• Calcium channel blockers
• Propafenone
• Quinidine
• Quinine
• Indomethacin
• Spironolactone
• Hydrochlorothiazide
• Other loop diuretics
• Triamterene
• Amphotericin B

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Yall Know

• Hypokalemia, hyperkalemia, hypernatremia increase
  the toxic CVS effects of digoxin re effects on
  NA/K ATPase pump.
• Digoxin toxicity does not cause hypokalemia, but
  hypokalemia can worsen digoxin toxicity.
• Hyperkalemia is usual lyte abnormality ppt by
  digoxin toxicity, esp acute

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Yall Know

• Hypomagnesemia
• increases myocardial digoxin uptake and decreases
  cellular NaK ATPase activity
• makes correcting hypokalemia very difficult
• Acidosis depresses Na/K ATPase pump and may
  cause digoxin toxicity
• Dehydration

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Yall Know

• Ischemia suppresses Na/K ATPase pump and
  independently alters automaticity
• Hypothyroid re decreased renal excretion, smaller
  volume of distribution.
• Bioavailability varies depending on formulation
• Toxicity may occur by increasing bioavailability.

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Yall Know

• Deteriorating renal function, dehydration, lytes,
  ischemia precipitate chronic toxicity.
• Acute overdose or accidental exposure to plants
  containing cardiac glycosides may cause acute
  toxicity.

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Yall Know

• Complex interaction between digoxin and various
  lyte renal abnormalities
• normal digoxin levels (0.6-2.6 nmol/L) renal
  insufficiency or severe hypokalemia may have more
  serious cardiotoxicity than patient with high
  digoxin levels and no renal or electrolyte
  disturbances

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Not So Fresh Prince

• Will Smith If yall help me out, Ill put yo on
  my next album you can bust rhymes with me
  Puffy.
• After a Mic check, What tests should you do?

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Tests for the Willenium

• Digoxin level
• Electrolytes, Mg, Ca, Renal Fnc tests
• ECG
• CXR
• ?Echo
• ?Cath

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Tests for the Willenium

• Acute toxicity, repeat the dig level q 2-4 hours
• Levels do not necessarily correlate with
  toxicity, esp acute ingestion.
• Acutely digoxin levels do not equilibrate quickly
  re variable absorption and tissue distribution.

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Tests for the Willenium

• Toxicity related to intracellular levels, not
  serum
• Digoxin level drawn lt4 hrs of acute ingestion may
  be incredibly high with no apparent toxicity.
• Rx guided by digoxin level and serum K and
  patient's clinical and ECG

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Not So Fresh Prince 1

• Big Willie all of a sudden becomes less jiggy and
  hypotensive
• Monitor shows a bradysrhythmia
• Now What?
• Should I pace him (to the beat of Wild Wild West)?

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Not So Fresh Prince 2

• Big Willie all of a sudden becomes less jiggy and
  hypotensive,
• Monitor shows a tachydysrhythmia
• Now What?
• Should I cardiovert him (like a glock to the
  chest)?

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Not So Fresh Prince 3

• Big Willie all of a sudden becomes less jiggy and
  hypotensive,
• Monitor shows peaked Ts, widened QRS.
• K comes back _at_ 7mmol/L
• Should I give him Ca?

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Not So Fresh Prince 4

• Big Willie all of a sudden becomes less jiggy and
  hypotensive
• Your Rx to date have done nothing (including your
  attempt at rappin Parents Just Dont Understand)
• Is there anything else you could use?

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Just the two of Us

• ABCD!!!!
• IVs, Monitors
• Consider AC Lavage if acute
• Anti-arrhythmics
• Lyte Abn
• Digibind

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Black Suits Coming CVS

• ANY Arrhythmia!!!
• Unstable digibind
• Brady atropine, ?pacing (lowers Fib threshold)?

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Black Suits Coming CVS

• Stable VT / Ventricular arrhythmias
• digibind, dilantin, lido, Mg, avoid cardioversion
• Lido, dilantin 1st line antiarrhythmic, case /
  dog studies, decrease ventricular ectopy w/o
  slowing nodal activity
• Unstable VT or VF
• digibind cardioversion, defibrillate vfib
• Do not cardiovert SVTs

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Black Suits Coming CVS

• Ca BAD
• increase dig effects?, contractions?, tetany?
• Cardioversion / defib relatively contraindicated
  re ventricular ectopy -gt safe if not toxic
• Ditchey RV, Curtis GP. Effects of apparently
  nontoxic doses of digoxin on ventricular ectopy
  after direct-current electrical shocks in dogs. J
  Pharmacol Exp Ther 1981 Jul218(1)212-6.
• Ditchey RV, Karliner JS. Safety of electrical
  cardioversion in patients without digitalis
  toxicity. Ann Intern Med. 1981 Dec95(6)676-9.
• N21

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Black Suits Coming Pacing?

• Taboulet, P, et al. Acute Digitalis Intoxication
  - Is pacing Still Appropriate? Clin Tox, 31(2),
  261-273 (1993).
• ?No?
• N92
• 41 Rx Lavage, AC, /- atropine -gt all survived
• 51 Rx, as above, but pace vs FAB vs both
• 23 paced, 12 FAB, 16 both
• 9 / 39 paced -gt 7 VF, 2 VA 2 to pacer use (7
  prior to FAB), also infxn, pacer malfnc
• 3 / 28 FAB -gt 2 in VF / VA prior -gt died, one
  died later of VF 100 hrs later

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Will 2K

• Usual Rx
• Insulin glucose, B2 ags, Kayexelate, NaHCO3 /
  correct acidosis, dialysis
• Avoid Ca -gt ppt ventricular dysrrhythmias
• Caution with digibind if using other means to
  correct hyperkalemia prior to digibind Rx-gt will
  result in markedly decreased K!!!

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Block Party When Digibind

• Arrhythmias associated with hemodynamic
  instability
• Altered LOC attributed to digoxin toxicity
• Hyperkalemia K gt 5 mEq/L
• Digoxin level gt 10 nmol/L in adults at steady
  state (ie, 6-8 h postingestion)
• Ingestion gt 10 mg in adults (40 X 0.25 mg
  tablets) or gt 0.3 mg/kg in children
• Hypotension not responsive to fluids

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Block Party Digibind

• Digoxin-FAB fragments
• From IgG of Sheep
• Excreted renally
• Each vial contains 40mg
• Each Vial binds 0.5mg digoxin
• 4121 Cn for 10 vials
• 10 vials accute, 5 chronic

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Block Party Digibind

• Chronic toxicity number of vials digoxin level
  (ng/mL) X weight (kg)/100
• Acute overdose number of vials total amount
  ingested (mg) X 0.8 / 0.5
• Give IV over 30 mins
• Effect by then, peak in 4 hrs
• Check levels in 4-6 hrs
• Levels post digibind will be markedly elevated
  and are uninterpretable unless you are able to
  get free digoxin levels

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Block Party Digibind

• Saluk, S et al. Treatment of severe digitalis
  intoxication with digoxin-specific antibody
  fragments A clinical review. Crit Care Med June
  198816, 6 629-635.
• 20 papers, N255, mainly case reports
• FAB is GREAT and safe!

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Block Party Digibind

• Hickey, et al. Digoxin-Specific FAB, Expanded
  Data on Safety. JACC Vol 17, No.3, March 1,
  1991590-8.
• N717, form filled out if FAB used, F/U form post
  Rx
• 357 responded, 172 partially, 89 none
• No response usually incorrect Dx or inadequate
  dosing
• No deaths attributed to FAB, 6 allergic responses

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Block Party Digibind

• Smith, TW, et al. Treatment of life-threatening
  digitalis intoxication with digoxin-specific Fab
  antibody fragments experience in 26 cases. NEJM.
  1982, 3071357-1361.

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Block Party Digibind

• Antman EM, et al. Treatment of 150 cases of
  life-threatening digitalis intoxication with
  digoxin-specific Fab antibody fragments final
  report of a multicentre trial. Circulation
  1990811744-1752.

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Block Party Digibind

• N150
• 75 long term, 15 accidental, 59 suicidal, 1 fetal
• 148 responses documented, 80 resolved, 10
  improved, 10 no response
• Median time to response 19 mins, 75 response
  lt60 mins
• 14 adverse effects (hypoK, CHF)
• Poor / non-response-gt CAD, wrong Dx, inadequate
  dose, pts moribund

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Miami

• ABCDs
• Monitors, IVs
• Lytes, dig level, ECG
• If toxic
• Supportive Rx
• Rx hyperkalemia
• Rx Digibind FAB if unstable

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Residents DO just Understand!

• Thanks to Dr Ber(lin), he doper than Dre
• You, for keepin it real
• My hommies back in tha projects in East Saskatoon
• Biggie Tupac
• Peace Out