1. No category

ORIGINAL CONTRIBUTION
Treatment of Chronically Digoxin-Poisoned Patients
With a Newer Digoxin Immune Fab—A Retrospective Study
Tammi H. Schaeffer, DO; Sara L. Mlynarchek, MPH; Christopher F. Stanford, MA; João Delgado, MD;
Christopher P. Holstege, MD; Dean Olsen, DO; and Gregory M. Bogdan, PhD
Context: Digoxin is used in the treatment of patients with
cardiac dysfunction, though toxicity sometimes results from
the use of this medication. In 1986, the US Food and Drug
Administration (FDA) approved a digoxin immune Fab for the
treatment of such patients. In 2001, the FDA approved a
newer digoxin immune Fab, a digoxin-specific antibody
(DSAb) known as DigiFab (Protherics Inc, Brentwood, Tennessee), though minimal literature exists on the clinical effects
of this DSAb.
Objectives: To characterize a cohort of patients presenting
with chronic digoxin toxicity and to describe the clinical course
of these patients with the use of DSAb.
Methods: A retrospective study included patients with lifethreatening cardiotoxicity and serum digoxin level greater
than 2 ng/mL who were treated at two US hospitals from 2003
to 2006. Trained investigators abstracted data from patients’
medical records and assessed changes in clinical and laboratory parameters at regular intervals (0-4, >4-12, >12-24, and
>24-72 hours) after treatment with DSAb. An expert panel
reviewed electrocardiogram results to identify life-threatening manifestations of digoxin toxicity before and after DSAb
treatment. Efficacy of treatment was assessed as rates of
improvement in clinical parameters and cardiotoxic effects.
From the Rocky Vista University College of Osteopathic Medicine in Parker,
Colorado (Dr Schaeffer); University of Colorado Denver School of Medicine
(Dr Schaeffer) and School of Pharmacy (Dr Bogdan); Rocky Mountain Poison
and Drug Center—Denver Health (Dr Schaeffer, Ms Mlynarchek, Mr Stanford,
and Dr Bogdan); University of Connecticut School of Medicine in Farmington
and Hartford Hospital in Connecticut (Dr Delgado); University of Virginia
School of Medicine in Charlottesville (Dr Holstege); and St Barnabas Medical
Center in New York City and New York City Poison Center (Dr Olsen). Mr Stanford’s MA is in biomechanics.
Financial Disclosures: Rocky Mountain Poison and Drug Center—Denver
Health (Dr Schaeffer, Ms Mlynarchek, Mr Stanford, Dr Bogdan) received
financial compensation from Protherics Inc (the manufacturer of DigiFab)
for this clinical research project. Staff members of Rocky Mountain Poison and
Drug Center received only their regular salary for participation, with no compensation from Protherics Inc. Authors who were members of the consensus
panel (Drs Schaeffer, Delgado, Holstege, Olsen) received honoraria as compensation for the time it took to review and evaluate electrocardiogram
results.
Address correspondence to Tammi H. Schaeffer, DO, Rocky Mountain
Poison and Drug Center, 777 Bannock St, MC 0180, Denver, CO 80204-4507.
E-mail: [email protected]
Submitted July 10, 2009; revision received January 7, 2010; accepted April 15,
2010.
Schaeffer et al • Original Contribution
Rates of adverse drug reactions were used to characterize
safety. All data were analyzed with descriptive statistics.
Results: Fourteen patients (mean [SD] age, 71.3 [10.4] years)
were treated for chronic digoxin toxicity. At presentation, 12
patients had a heart rate of less than 45 beats per minute, 1 had
third-degree heart block, and 1 had asystole. Mean serum
digoxin level was 3.6 ng/mL. Eleven patients had abnormal
renal function. After administration of DSAb, clinical parameters improved in all patients. Within 24 hours, cardiotoxicity
resolved in 7 of 9 evaluable patients. Two adverse drug reactions possibly related to DigiFab occurred, both of which
resolved with conventional measures. Two patients died from
conditions unrelated to treatment.
Conclusion: The newer DSAb appears to be a safe and effective treatment for resolving digoxin toxicity in adults, as indicated by electrocardiogram and clinical assessments. Because
patients with multiple comorbidities may be at greater risk for
digoxin toxicity, they should be closely monitored during
treatment with digoxin.
J Am Osteopath Assoc. 2010;110(10):587-592
espite its inherent toxicity, digoxin continues to be
widely used in the treatment of patients with cardiac
dysfunction, including congestive heart failure (CHF) and
cardiac arrhythmias. Although the use of digoxin for CHF has
declined in recent years, the incidence of toxicity from digoxin
has remained steady.1 The reported incidence of signs and
symptoms consistent with digoxin toxicity ranges from 1%
to 30% of patients using digoxin, depending on the criteria for
toxicity and the specific cohort studied.2-5
The evaluation and treatment of patients with digoxin
toxicity are often categorized by the chronicity of the ingestion.
Early studies on the treatment of patients with symptomatic
digoxin toxicity included more acute poisonings than chronic
poisonings.6,7 More recently, Lapostolle et al8 reviewed medical records from 20 hospitals in France and found that 86% of
patients presenting with digoxin toxicity were chronically
intoxicated. This percentage may represent a change toward
increased chronicity in digoxin-poisoned patients.
Chronic digoxin toxicity is manifested in elderly patients
and in patients taking medications that affect electrolyte levels
and renal function.9 Although such patients are known to be
predisposed to toxicity, further characterization of sensitive
D
JAOA • Vol 110 • No 10 • October 2010 • 587
ORIGINAL CONTRIBUTION
populations could allow for identification of variables predicting toxicity. Improved understanding of these variables
could lead to reductions in the considerable healthcare costs
associated with managing digoxin toxicity.10
The use of antibody treatment has resulted in substantial
improvement in the treatment of patients with serious digoxin
toxicity.6,7,11,12 The majority of existing reports on the safety and
efficacy of antibody treatment concern Digibind (digoxin
immune Fab [ovine] [DIFab]; GlaxoSmithKline plc, Brentford,
England), which, in 1986, became the first digoxin-specific
Fab to be approved by the US Food and Drug Administration
(FDA). In 2001, the FDA approved DigiFab (digoxin immune
Fab [ovine] [DSAb]; Protherics Inc, Brentwood, Tennessee), a
digoxin-specific antibody targeted for use by patients with
life-threatening digoxin toxicity.
Although both DIFab and DSAb have been shown to
possess similar pharmacokinetic properties13 and are clinically interchangeable, minimal literature exists on the clinical
use of DSAb to date.
The present report has two main objectives: (1) to characterize a cohort of patients presenting with chronic digoxin
toxicity, and (2) to describe the clinical course associated with
the use of the newer antibody treatment, DSAb, in these
patients.
Methods
Investigators from two hospitals (Hartford Hospital in Connecticut, University of Virginia Medical Center in Charlottesville) reviewed medical records of patients who were
treated with DSAb for life-threatening effects of digoxin toxicity. Records were identified from queries of the hospital
pharmacy databases for patients for whom DSAb was dispensed. Only records of patients treated between January 2003
and July 2006 were included. Before accessing the records,
institutional review board approval, with a waiver of informed
consent, was obtained by the investigator from each site.
Medical records were initially reviewed to evaluate study
entrance criteria. Patients of any age and either sex with lifethreatening cardiotoxicity, a history of digoxin ingestion (either
chronic or acute), and a serum digoxin level of at least 2 ng/mL
before DSAb treatment were included. Life-threatening cardiotoxicity was defined as the presence of one or more of the
following rhythm disturbances, as revealed by electrocardiogram (ECG) results within 6 hours before initiation of DSAb
treatment: asystole, ventricular tachycardia or fibrillation,
second- or third-degree heart block, or a ventricular rate of
less than 45 beats per minute (bpm).
Patients’ ECG results (ie, ECG charts and rhythm strips)—
with all protected health information removed—were submitted to, and reviewed by, an expert consensus panel consisting of two site investigators (J.D., C.P.H.) and two other
physicians (T.H.S., D.O.). All panel members were experienced board-certified emergency department physicians and
medical toxicologists. To eliminate potential reviewer bias, no
588 • JAOA • Vol 110 • No 10 • October 2010
panel member reviewed any record of a patient who was
treated at his or her own institution. Thus, ECG results from
each patient were reviewed by three panelists.
Unanimous or majority vote by the consensus panel was
required for a patient’s record to meet the inclusion criterion
of life-threatening cardiotoxicity. Any patient without lifethreatening cardiotoxicity was excluded from the study. Other
exclusion criteria were known or suspected ingestion of a digitalis-containing compound other than digoxin (eg, digitoxin,
purple foxglove) and known cardiac pacing at baseline.
Data from each eligible medical record were collected by
the site investigator using a standardized case report form.
Before collection of study data, investigators completed a
training process to facilitate accuracy and consistency of data
collection. The training process included a trainer (C.F.S.)
instructing the four panel members in abstraction of a sample
medical record, followed by feedback to correct any errors
and to reinforce adherence to study definitions.
Study data included demographic characteristics of
patients; details of digoxin exposure; medical and medication
history; baseline findings (eg, blood urea nitrogen [BUN]/creatinine ratio, cardiac abnormalities, serum digoxin level, serum
potassium level); details of treatment (including concomitant
therapies); posttreatment response (as revealed by ECG and
clinical assessments); and drug-related adverse events. Investigators evaluated patients’ responses to treatment as changes
in ECG results at regular intervals after the end of DSAb treatment (0-4, >4-12, >12-24, >24-72 hours), relative to baseline
and as permitted by available data. At each posttreatment
time interval, each investigator assigned a value of improved (no
or lesser life-threatening effect compared to baseline), worsened (greater life-threatening effect compared to baseline), not
improved (same life-threatening effect compared to baseline), or
no data (no recording available with which to compare to baseline) to ECG results.
Copies of all ECG charts and rhythm strips recorded up
to 72 hours after the end of DSAb were de-identified, randomly ordered, and submitted for consensus panel review.
Randomization was performed to prevent panel reviewers
from identifying abnormalities based on relative comparisons
among serial recordings for a single patient.
Reviewers identified the presence or absence of specific
life-threatening cardiotoxic effects on each posttreatment ECG
recording by using the same criteria and procedures that were
followed during baseline ECG review. At each posttreatment
interval, results for each patient were reviewed, and one of the
four designations describing cardiac response relative to baseline (ie, improved, worsened, not improved, no data) was
assigned to the results. Heart rate and blood pressure measurements were used to assess cardiac response for time intervals during which no ECG rhythm strips were made.
The extent of clinical efficacy of DSAb was characterized
by rates of improvement over time in life-threatening cardiotoxic effects. Drug safety was characterized by rates of
Schaeffer et al • Original Contribution
ORIGINAL CONTRIBUTION
serious (eg, life-threatening, requiring inpatient hospitalization) and nonserious drug-related adverse events.
All data were analyzed with descriptive statistics. Continuous variables were analyzed using means, and categorical
variables were analyzed using medians. Categorical variables
were sex and ethnicity. All other variables were continuous. Statistical analyses were performed using SPSS software (version 15.0; SPSS Inc, Chicago, Illinois).
Results
A total of 49 medical records were screened for DSAb administration (Figure). Of these records, 21 were excluded for not
meeting entrance criteria. These excluded records were from
patients who had serum digoxin levels less than 2 ng/mL, an
implanted pacemaker, or no baseline ECG. Of the 28 patients
who met initial entrance criteria, 14 were excluded after ECG
evaluation revealed no electrocardiographic abnormality. This
exclusion left 14 charts in the study.
Demographic characteristics of the included patients are
presented in Table 1. The majority of patients were elderly
white adults (mean [SD] age, 71.3 [10.4] years), though age
ranged from 47 to 90 years. There was an equal distribution of
patients by sex.
All 14 included patients were taking digoxin for a prescribed indication before the DSAb treatment of the present
study. Reported indications for digoxin were atrial fibrillation (9 patients), CHF (2 patients), or both of these conditions
(3 patients). All patients had digoxin toxicity related to accidental or unintentional chronic exposure (ie, ingestion of a
prescribed dose that, because of the inability to excrete digoxin,
accumulated over a period greater than 24 hours). No patient
in the present study was identified as having acute or acuteon-chronic toxicity. Patients reported a mean of 6.1 (range, 39) for the number of body systems affected by comorbid conditions in their medical history.
Table 2 shows presenting values for cardiac abnormalities,
serum digoxin levels, and BUN/creatinine ratios. Life-threatening cardiac rhythm abnormalities present before DSAb treatment included slow ventricular rate (<45 bpm) in 12 patients,
third-degree (ie, complete) heart block in 1 patient, and asystole in 1 patient.
The mean presenting serum digoxin level of patients was
3.6 ng/mL. At baseline, 13 patients had renal function data
available, and 11 of these patients had abnormal renal function,
as denoted by elevated serum creatinine levels (Table 2).
Although there was poor correlation between serum creatinine
and serum digoxin levels (correlation coefficient for bivariate
analysis [r] = 0.1), 8 of the 13 patients had dehydration, as
defined by a BUN/creatinine ratio of greater than or equal to
20:1. Five of these 8 patients were being treated with diuretics.
The mean presenting potassium level of patients was
5.4 mmol/L. During the assessment intervals, there was a
general progression toward normalization of potassium level,
with a mean potassium level of 4.3 mmol/L by the final interval
(>24-72 hours).
Patients were prescribed a mean of 10.4 outpatient medications, including digoxin. Cardiovascular drugs were the
most commonly prescribed medication (ie, mean of 5.1 car-
Patient Charts Reviewed (n=49)
Did Not Meet Study Entrance Criteria
(n=21):
◾ Serum digoxin level <2 ng/mL (n=11)
◾ No baseline ECG (n=9)
◾ Implanted pacemaker (n=1)
ECG Performed Within 6 Hours Before DSAb
Administration (n=28)
Did Not Meet Study Entrance Criteria
(ECG Showed No Abnormality; n=14)
Patients Included in Study (N=14)
Figure. Algorithm depicting review of patient charts for inclusion in a retrospective study on the use of the
digoxin-specific antibody DigiFab (digoxin immune Fab [ovine]; Protherics Inc, Brentwood, Tennessee) for the
treatment of chronically digoxin-poisoned patients. Abbreviations: DSAb, digoxin-specific antibody; ECG, electrocardiogram.
Schaeffer et al • Original Contribution
JAOA • Vol 110 • No 10 • October 2010 • 589
ORIGINAL CONTRIBUTION
diovascular medications, including means of 1.4 anti-arrhythmics and 0.7 diuretics). Endocrine medications were the second
most commonly prescribed medication (mean, 2.9 medications).
All patients received at least one intravenous dose of
Characteristic
Value
DSAb. Thirteen patients received a single dose, and 1 patient
◾ Age, y
received a second dose 28.5 hours after the first dose. The
◽ Mean (SD)
71.3 (10.4)
number of vials of DSAb ranged from 1 to 7 per dose (median,
◽ Range
47-90
2 vials).
◾ Sex, No.
Table 3 lists characteristics of concomitant treatments (eg,
7
◽ Men
atropine, glucose/insulin, vasopressor) provided to each
◽ Women
7
patient before, during, and up to 72 hours after the end of
◾ Race, No.
DSAb treatment. Eleven patients received one or more con◽ Black
1
comitant treatments before, during, and/or after DSAb.
◽ White
11
Table 4 shows results of cardiac assessments at each post◽ Unknown
2
treatment
time interval, including a general progression toward
†
◾ Height, cm
improvement
over time in patients with evaluable data.
◽ Mean (SD)
164.3 (14.6)
◾ Weight, kg‡
Although 14 patients were studied, not all patients had evalu◽ Mean (SD)
79.5 (20.1)
able data at all time intervals.
At the first posttreatment interval (0-4 hours), 3 of 7 evalu* DSAb indicates the digoxin-specific antibody DigiFab (digoxin immune Fab
able
patients showed improvement based on ECG findings.
[ovine]; Protherics Inc, Brentwood, Tennessee).
Within
the >4-to-12-hour interval, 4 of 6 evaluable patients
† Height of 2 patients was unknown (n=12).
‡ Weight of 1 patient was unknown (n=13).
demonstrated improvement. Within the >12-to-24-hour
interval, improvement was found in 7 of 9 evaluable patients.
By 72 hours after the end of DSAb treatment, improvement occurred in 11 of 11 evaluable patients. Worsening
Table 2
of cardiac abnormalities was not detected in any patient
Presenting ECG and Laboratory Values for Participants
at any posttreatment time interval.
in Retrospective Study of DSAb* (N=14)
The remaining 3 patients did not have sufficient data
with
which to determine DSAb efficacy by 72 hours
Cardiac
Serum Digoxin,
BUN/Creatinine,
posttreatment. Patient 8 and patient 11 did not have
Patient
Abnormality
ng/mL
mg/dL (Ratio)
evaluable data available for any posttreatment time
1
VR†
4.8
46/2.8 (16.4)
interval. Although these individuals met entrance criteria
2
VR
5.2
51/1.3 (39.2)‡
and were entered into the study, they were unable to be
‡
3
VR
3.4
55/2.7 (20.4)
†
‡
evaluated in final assessment. Patient 14 did not show
4
VR
6.5
63/3.1 (20.3)
correction of slow ventricular rate (<45 bpm) during
5
VR†
6.5
23/1.2 (19.2)
2.2
19/1.3 (14.6)
6
VR†
the first two posttreatment intervals and had no data
7
HB3
2.7
52/8.6 (6.0)§
with which to assess improvement during the last two
8
VR
3.3
86/2.6 (33.1)‡
intervals. This patient had advanced metastatic lung
9
VR†
2.2
22/1.4 (15.7)
cancer and, within 24 hours after hospital admission,
10
VR
3.4
...
she began to be treated with “comfort measures only” (ie,
11
VR†
2.3
41/1.3 (31.5)‡
hospice
care).
12
VR†
3.1
102/3.5 (29.1)‡
A
total
of 14 adverse events were reported in 10
13
A†
2.2
27/1.0 (27.0)‡
†
‡
patients.
Two
adverse events (hypotension and tachy14
VR
3.2
30/0.7 (42.9)
cardia) were deemed possibly related to DSAb administration. Both of these adverse events were nonserious,
* DSAb indicates the digoxin-specific antibody DigiFab (digoxin immune Fab [ovine];
Protherics Inc, Brentwood, Tennessee).
requiring only conventional treatment (eg, fluids,
† Electrocardiogram recording from previous, routine hospital visit (ie, prebaseline)
oxygen).
The remaining 12 adverse events were deterwas available in patient’s medical record. No life-threatening rhythm abnormality
was present in that recording.
mined to not be related to DSAb administration. Of
‡ Dehydration defined by BUN/creatinine ratio 20:1.
these 12 events, 2 were serious—cardiac arrest and res§ Patient 7 had end-stage renal failure and was on hemodialysis.
piratory failure—and 10 were nonserious—abdominal
Abbreviations: A, asystole; BUN, blood urea nitrogen; ECG, electrocardiogram; HB3,
pain, anorexia (2 events), anxiety, bronchospasm, fatigue,
third-degree heart block; VR, ventricular rate <45 beats per minute; ... indicates no
data.
fever, hypotension, presyncope, and tachycardia.
Two deaths (patient 4 and patient 14) were reported
Table 1
Baseline Characteristics of Participants
in Retrospective Study of DSAb* (N=14)
590 • JAOA • Vol 110 • No 10 • October 2010
Schaeffer et al • Original Contribution
ORIGINAL CONTRIBUTION
Table 3
Concomitant Treatments Administered to Participants
in Retrospective Study of DSAb* (N=14)
Concomitant Treatments
Patient
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Before DSAb
During DSAb
After DSAb
Atr, GI, F
Atr, F
Atr, GI, V
GI, V
F, Mg
F
E
GI
None
F
None
V
None
Atr
None
None
V
None
None
None
None
None
None
None
None
V
None
None
None
GI, Mg
V
E
Mg
None
E
P, F
None
E, F
None
GI, V
None
None
* DSAb indicates the digoxin-specific antibody DigiFab (digoxin immune Fab
[ovine]; Protherics Inc, Brentwood, Tennessee).
Abbreviations: Atr, atropine; E, enhanced elimination (ie, hemodialysishemoperfusion); F, fluid resuscitation; GI, glucose-insulin; Mg, magnesium;
P, pacemaker; V, vasopressor(s).
during the study period. Both deaths occurred more than 5
days after the end of DSAb treatment, and neither death was
deemed related to DSAb administration.
Patient 4 was a man, aged 65 years, in whom overwhelming sepsis developed from gallstone pancreatitis and
cholecystitis. His slow ventricular rate responded favorably to
DSAb, but his underlying condition worsened during the next
several weeks. He died from respiratory failure 6 weeks after
receiving DSAb.
Patient 14 (referred to previously) was a woman, aged
67 years, with advanced, end-stage lung cancer. She was
admitted to the hospital with the intention of managing her
pain and “easily correctable” problems. However, within 24
hours after admission and administration of DSAb, treatment
orders were changed to “comfort measures only.” This patient
was subsequently discharged, and she died 1 week after completion of DSAb treatment.
Comment
Despite reports involving a high proportion of patients with
acute digoxin toxicity when antibody treatment first became
available,6,7,11,12 the population of the present study had predominantly chronic digoxin toxicity, which is consistent with
other reports in recent years.8 This chronic pattern of digoxin
toxicity likely reflects the most current clinical experience with
digoxin poisoning in the United States.
The present study found a generally beneficial response
to the newer digoxin immune Fab, DSAb, though study
Schaeffer et al • Original Contribution
patients did not respond as rapidly as those reported in earlier
studies of the previously approved digoxin immune Fab,
DIFab.6,12,14 This difference may be a reflection of the change
from acute to chronic ingestions and/or the presence of other
illnesses and comorbidities in our cohort, including the cardiovascular disease that prompted the use of digoxin.
Although only 3 of 7 patients with evaluable data demonstrated cardiac improvement by 4 hours after DSAb administration, it is important to recognize that 3 patients had no
chance of demonstrating improvement in cardiac abnormalities within this interval because they did not have posttreatment ECG results available until after 12 hours. As secondary
endpoints, heart rate and blood pressure—possibly indirect
markers of improvement—trended toward the normal range
in most patients during the assessment period. However, it is
difficult to know if the overall improvement in patients was
caused by DSAb, management of the underlying disease, or
both. Because other metabolic processes often precipitate
chronic digoxin toxicity, symptomatic and supportive care
concomitant with the use of DSAb should be continued.
Dehydration associated with elevated creatinine levels
was prevalent within the cohort of the present study. Diuretics
Table 4
Changes in Cardiac Abnormalities in Digoxin-Poisoned Patients
After Treatment With DSAb,* Relative to Baseline (N=14)
Hours After DSAb Treatment
Patient†
1
2
3
4
5‡
6
7
9
10
12
13
14§
Patients Showing
Improvement, No.//
0-4
⬎4-12
⬎12-24
⬎24-72
U
U
I
I
...
...
...
U
...
I
...
U
3
I
...
I
I
U
...
...
I
...
...
...
U
4
I
U
I
I
U
...
I
I
I
I
...
...
7
I
I
I
I
I
I
I
I
I
I
I
...
11
* DSAb indicates the digoxin-specific antibody DigiFab (digoxin immune Fab
[ovine]; Protherics Inc, Brentwood, Tennessee).
† Patient 8 and patient 11 did not have evaluable data for any
posttreatment time interval.
‡ Patient 5 received a second dose of DSAb 28.5 hours after the end of the
first dose.
§ Patient 14 did not show correction of slow ventricular rate during the first
two posttreatment intervals and had no data with which to assess
improvement during the last two intervals. She had advanced metastatic
lung cancer and died 1 week after completion of DSAb treatment.
// Improvement ratings based on electrocardiogram and clinical (ie, blood
pressure, heart rate) assessments of cardiac abnormalities of patients for
whom data were available (see Table 2).
Abbreviations: I, improved; U, unchanged; ... indicates no data.
JAOA • Vol 110 • No 10 • October 2010 • 591
ORIGINAL CONTRIBUTION
are a common medication, in addition to digoxin, taken by
patients with CHF. Loss of fluids can precipitate dehydration,
with resultant decreases in glomerular filtration rate and clearance of drugs, including digoxin. This clearance decrease can
predispose patients to toxicity, even when taking their usual,
prescribed doses. The hydration status of patients with CHF
should be closely monitored to balance these dehydration
effects with the fluid overload commonly seen in this patient
population.
Hydration status is also associated with various electrolyte abnormalities. Although potassium levels improved
over time in evaluated patients, presenting potassium levels are
more clinically relevant for prognosticating acute digoxin
overdose.15 In patients with chronic digoxin toxicity, by contrast, changes in potassium levels could be related to other
factors, such as hydration status and concomitant medications other than digoxin.
Hussain et al1 reported increases in the incidence of
digoxin toxicity and in the use of DSAb—despite an overall
decrease in use of digoxin for CHF. Because their study used
a CHF registry, however, patients taking digoxin for atrial
fibrillation were not captured.1 It is unclear whether the
increased digoxin toxicity and increased use of DSAb reported
by Hussain et al1 are results of an increase in recommendations
to use DSAb by poison centers. Furthermore, the finding of
decreased use of digoxin for CHF1 may be associated with an
increased use of digoxin for heart rate control.
The present study found that DSAb has a favorable safety
profile, as evidenced by few drug-related adverse events.
Interestingly, we found that 14 of 28 patients initially screened
for inclusion were treated with DSAb in the absence of relevant
ECG findings. This use of DSAb suggests a comfort level
among healthcare providers with administering DSAb—
almost as a diagnostic tool (eg, to remove the possibility of
digoxin toxicity from differential diagnosis)—in cases with
no clear ECG evidence of digoxin toxicity.
Limitations
Initially, we attempted to include additional hospitals in our
analysis besides the two that were included. However, when
we contacted those hospital pharmacies and evaluated their
records, we found there was no way to know whether the
drug product used was DIFab or DSAb. In those hospitals, the
pharmacy stock was intermixed without documentation
regarding which product was actually dispensed. Thus, we
were able to include only two hospitals.
Our analysis was open to pediatric patients, as well as
adult patients. However, we found no pediatric charts that
met entrance criteria. The lack of these young patients in our
analysis may limit the generalizability of the results. The ability
to generalize our results for all cases of digoxin toxicity is also
limited by the small sample size of the present study.
We found no evidence of serum sickness in any patient.
However, the length of hospitalization (median, 4.6 days) may
592 • JAOA • Vol 110 • No 10 • October 2010
have been too brief to sufficiently detect the manifestation of
signs or symptoms associated with that condition. Finally, the
present study was a retrospective chart review, and it has the
expected limitations inherent in any study with that design.
Conclusion
DigiFab appears to be a well-tolerated and effective treatment
for adults who have ECG changes consistent with chronic,
life-threatening digoxin toxicity. Older patients with multiple
comorbidities may be more at risk for digoxin toxicity. Thus,
these patients should be closely monitored during treatment
with digoxin, especially in regard to concomitant medications
and renal status.
References
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the post-DIG trial era. J Card Fail. 2006;12(5):343-346.
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1971;284(18):989-997.
3. Koch-Weser J, Duhme DW, Greenblatt DJ. Influence of serum digoxin concentration measurements on frequency of digitoxicity. Clin Pharmacol Ther.
1974;16(1):284-287.
4. Mahdyoon H, Battilana G, Rosman H, Goldstein S, Gheorghiade M. The
evolving pattern of digoxin intoxication: observations at a large urban hospital from 1980 to 1988. Am Heart J. 1990;120(5):1189-1194.
5. Steiner JF, Robbins LJ, Hammermeister KE, Roth SC, Hammond WS. Incidence
of digoxin toxicity in outpatients. West J Med. 1994;161(5):474-478.
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6. 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;81
(6):1744-1752. http://circ.ahajournals.org/cgi/reprint/81/6/1744. Accessed August
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