Page 1747 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

1216 PART 11: Special Problems in Critical Care

Seizures should be treated with intravenous diazepam or lorazepam. digitalis sensitivity. Such factors include hypokalemia, hypomagnese-
Phenytoin may be administered cautiously in refractory cases. Paralysis mia, myocardial disease, old age, hypothyroidism, and a variety of other
with continuous EEG monitoring may be indicated when seizures are metabolic disturbances (hypoxemia, acid-base abnormalities, hypercal-
refractory (as may be seen in amoxapine overdose) to control tempera- cemia, and hypernatremia).
ture and limit muscle breakdown. The clinical manifestations of digitalis intoxication include fatigue,
Gastric lavage may be considered during the first hour after a life- gastrointestinal symptoms (anorexia, nausea, vomiting, diarrhea, and
threatening ingestion. Single-dose AC is effective and should be consid- abdominal pain), neurologic disturbances (blurred vision, visual color
ered if the airway is protected. Because these drugs are lipid soluble and changes, headache, dizziness, and delirium), and cardiac arrhythmias
protein bound, dialysis and hemoperfusion are not effective. (including many types, but classically supraventricular tachycardia with
There has been a single case reported in the literature on the use of intra- AV block). Massive digoxin overdose also causes hyperkalemia, because
venous lipid emulsion (discussed in the section on β-blocker toxicity) of inhibition of cellular Na-K-ATPase function. Plasma digoxin levels
in severe tricyclic antidepressant toxicity with hypotension that was not correlate generally with therapeutic and toxic effects, but variability in
responsive to vasopressors and sodium bicarbonate. 277 response to a particular level is common. 280,281
Digoxin levels should be measured at steady state. This occurs after
■ DIGOXIN approximately 1 week when renal function is normal, and to allow time
for distribution a blood level should be obtained at least 6 hours after
Digitalis is a cardiac glycoside clinically used for treatment of systolic the last dose. Based on data demonstrating benefit of low serum digoxin
myocardial dysfunction and supraventricular arrhythmias. The most concentrations in heart failure, many laboratories have lowered the
282
commonly prescribed cardiac glycoside in the United States is digoxin, therapeutic range for digoxin to 0.5 to 1.0 ng/mL.
although natural glycosides (eg, oleander, lily of the valley, and foxglove) Gastrointestinal decontamination including gastric lavage and
produce a similar clinical presentation in overdose. Digoxin is exten- activated charcoal may be considered within an hour of acute inges-
sively tissue bound (mostly in muscle), resulting in a massive apparent tion. Additional decontamination modalities including MDAC and
volume of distribution (4-7 L/kg). Many sources divide digoxin toxic- cholestyramine, although used in the past, have insufficient evidence
ity into three types: acute, acute-on-chronic, and chronic. Diminished to support their routine use if digoxin-specific Fab fragments are
clearance because of kidney disease, which often increases half-life to available. Hemodialysis or hemoperfusion remove only small amounts
80 to 180 hours, is the most common precipitant of acute-on-chronic of total body digitalis (because of large volume of distribution), but HD
episodes. Drug interactions also elevate digoxin levels by impairing renal may still be indicated for correction of hyperkalemia or other acid-base
excretion (eg, verapamil, other calcium-channel blockers, quinidine, derangements in renally impaired patients. Fortunately, immunotherapy
and cyclosporine) or hepatic biotransformation (eg, cyclosporine, vera- with digoxin-specific antibody Fab fragments is widely available. These
pamil, other calcium-channel blockers, or amiodarone), or decreasing sheep-derived antibodies bind intravascular digoxin, also competitively
digoxin tissue binding and Vd (eg, quinidine). Finally, increased oral removing digoxin bound to cellular Na-K-ATPase sites. 283,284 Indications
bioavailability because of antibiotic-induced sterilization of digoxin- and protocol for Fab therapy are contained in Table 124-23. Following
metabolizing gut flora may also precipitate digoxin toxicity. Digitalis intravenous administration of Fab, digoxin levels and toxic effects
278
may also be ingested in toxic amounts as an unsuspected component of (hyperkalemia and arrhythmias) decrease almost immediately, and the
herbal preparations or as a deliberate self-overdose, although these Fab fragments and bound digoxin are eliminated by glomerular filtra-
279
forms of acute overdose are much less common than acute-on-chronic tion. Standard total plasma digoxin levels can be misleading after treat-
overdoses. Several factors aside from excess total body digoxin can pre- ment, as the digoxin bound to Fab fragments will continue to contribute
cipitate toxicity, even in the therapeutic range, by increasing myocardial to total levels. Fab fragments have also been successfully used to treat

TABLE 124-23 Indications and Protocol for Digoxin Immune Fab Therapy (Digibind)
Dose Estimate (# Vials) Based on Serum Steady State Approximate Digibind Dose for Treatment of a Single
Indications Digoxin Levels a Large Ingestion b
1. Severe ventricular arrhythmias # Vials = (serum digoxin level in ng/mL) (weight in kg)/100 # Vials = (total digitalis body load in mg)/(0.5 mg digitalis bound/vial) c
2. Progressive, atropine unresponsive bradyarrhythmias

Examples: for a 70-kg adult: Serum concentration Examples: Quantity of 0.25-mg tabs ingested
3. Ingestion of >10 mg of digoxin in adults (ng/mL) #Vials
1 1 (80% bioavailable) #Vials
4. Steady-state concentration >10 mg/mL 2 2 25 10
4 3 50 20
5. Progressive potassium elevation or potassium >5 mEq/L 8 6 75 30
12 9 100 40
16 11
20 14
a Six vials are usually adequate to reverse most cases of chronic toxicity.
b Twenty vials are usually adequate to treat acute ingestions of unknown quantity.
c Each vial of Digibind contains 38 mg of purified digoxin-specific Fab fragments which will bind 0.5 mg of digoxin or digitoxin.
Data from the Physicians’ Desk Reference. Montvale, NJ: Medical Economics; 1996.

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