Fatal cardiac glycoside poisoning due to mistaking foxglove for comfrey


Wu, I-Lin.; Yu, J-Hao.; Lin, C-Chuan.; Seak, C-June.; Olson, K.R.; Chen, H-Yi.

Clinical Toxicology 55(7): 670-673

2017


Accidental ingestion of foxglove (Digitalis purpurea) can cause significant cardiac toxicity. We report a patient who ingested foxglove mistaking it for comfrey and developed refractory ventricular arrhythmias. The patient died despite treatment with digoxin-specific antibody fragments (DSFab) and veno-arterial extracorporeal membrane oxygenation (VA-ECMO). A 55-year-old woman presented to the emergency department with nausea, vomiting and generalized weakness eight hours after drinking "comfrey" tea. She had bradycardia (54 beats/min) and hyperkalemia (7.6 mEq/L). Electrocardiogram revealed a first-degree atrioventricular conduction block with premature atrial contractions, followed by polymorphic ventricular tachycardia three hours after arrival. A serum digoxin level was 151.2 ng/mL. The patient developed ventricular fibrillation while waiting for Digibind infusion. Resuscitation was performed and an emergent VA-ECMO was set up. A total of eight vials of Digibind were given over the next 16 hours. She temporarily regained consciousness, but remained hemodynamically unstable and subsequently developed lower limb ischemia and multiple organ failure, and she expired on hospital day seven. A botanist confirmed that the plant was foxglove. The diagnosis of cardiac glycoside plant poisoning can be difficult in the absence of an accurate exposure history. In facilities where DSFab is unavailable or insufficient, early VA-ECMO might be considered in severely cardiotoxic patients unresponsive to conventional therapy.

CLINICAL
TOXICOLOGY,
2017
http://dx.doi.org/10.1080/15563650.2017.1317350
Taylor
&
Francis
Taylor
&
Francis
Group
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Fatal
cardiac
glycoside
poisoning
due
to
mistaking
foxglove
for
comfrey
1-Lin
Wu
a
'
b
,
Jiun-Hao
Yu
b
",
Chih-Chuan
Lin
t
'',
Chen-June
Seak
b
",
Kent
R.
Olson
d
and
Hsien-Yi
Chen
b
'
'Department
of
Emergency
Medicine,
Taoyuan
Armed
Forces
General
Hospital,
Taoyuan,
Taiwan;
b
Department
of
Emergency
Medicine,
Chang
Gung
Memorial
Hospital,
Linkou
Branch,
Taoyuan,
Taiwan;
`College
of
Medicine,
Chang
Gung
University,
Taoyuan,
Taiwan;
d
California
Poison
Control
System-San
Francisco
Division,
University
of
California,
San
Francisco,
CA,
USA
ABSTRACT
Context:
Accidental
ingestion
of
foxglove
(Digitalis
purpurea)
can
cause
significant
cardiac
toxicity.
We
report
a
patient
who
ingested
foxglove
mistaking
it
for
comfrey
and
developed
refractory
ventricular
arrhythmias.
The
patient
died
despite
treatment
with
digoxin-specific
antibody
fragments
(DSFab)
and
veno-arterial
extracorporeal
membrane
oxygenation
(VA-ECMO).
Case
details:
A
55-year-old
woman
presented
to
the
emergency
department
with
nausea,
vomiting
and
generalized
weakness
eight
hours
after
drinking
"comfrey"
tea.
She
had
bradycardia
(54
beats/min)
and
hyperkalemia
(7.6
mEq/L).
Electrocardiogram
revealed
a
first-degree
atrioventricular
conduction
block
with
premature
atrial
contractions,
followed
by
polymorphic
ventricular
tachycardia
three
hours
after
arrival.
A
serum
digoxin
level
was
151.2
ng/mL.
The
patient
developed
ventricular
fibrillation
while
waiting
for
Digibind
infusion.
Resuscitation
was
performed
and
an
emergent
VA-ECMO
was
set
up.
A
total
of
eight
vials
of
Digibind
were
given
over
the
next
16
hours.
She
temporarily
regained
con-
sciousness,
but
remained
hemodynamically
unstable
and
subsequently
developed
lower
limb
ischemia
and
multiple
organ
failure,
and
she
expired
on
hospital
day
seven.
A
botanist
confirmed
that
the
plant
was
foxglove.
Conclusions:
The
diagnosis
of
cardiac
glycoside
plant
poisoning
can
be
difficult
in
the
absence
of
an
accurate
exposure
history.
In
facilities
where
DSFab
is
unavailable
or
insufficient,
early
VA-ECMO
might
be
considered
in
severely
cardiotoxic
patients
unresponsive
to
conventional
therapy.
ARTICLE
HISTORY
Received
13
January
2017
Revised
3
April
2017
Accepted
4
April
2017
Published
online
28
April
2017
Digitalis
poisoning;
foxglove;
comfrey;
digoxin-
specific
antibody
fragment;
extracorporeal
membrane
oxygenation
Introduction
Foxglove
(Digitalis
purpurea)
contains
several
potent
cardiac
glycosides
(CG),
which
may
lead
to
significant
cardiac
toxicity
following
ingestion.
Only
a
few
human
poisonings
due
to
mistaking
foxglove
leaves
for
comfrey
leaves
have
been
reported,
and
all
recovered
[1,2].
We
present
the
first
report
of
a
fatality
from
ingestion
of
foxglove
mistaking
it
for
com-
frey.
The
patient
developed
refractory
ventricular
arrhythmias
and
underwent
prolonged
resuscitation.
Insufficient
doses
of
anti-digoxin
antibodies
were
given
due
to
a
pharmacy
stock-
ing
shortage.
The
patient
eventually
died
despite
aggressive
treatment
including
veno-arterial
extracorporeal
membrane
oxygenation
(VA-ECMO).
Cast.
details
A
55-year-old
woman
presented
to
our
emergency
depart-
ment
(ED)
with
nausea,
vomiting,
generalized
weakness
and
lightheadedness
eight
hours
after
drinking
"comfrey"
herbal
tea.
She
had
blended
one
to
two
bunches
of
the
raw
plant
(mostly
leaves)
into
juice
and
drank
it.
Approximately
four
hours
after
ingestion,
she
presented
to
a
rural
hospital
due
to
nausea
and
vomiting,
and
was
discharged
home
after
symptomatic
treatment.
She
then
came
to
our
ED
because
of
continuing
symptoms.
Her
vital
signs
on
arrival
were:
blood
pressure
139/65
mmHg;
heart
rate
54
beats/min;
respiratory
rate
18
times/min;
and
body
temperature
36
°C.
She
had
nor-
mal
mental
status.
Physical
examination
did
not
reveal
any
abnormal
findings.
Laboratory
studies
showed
white
blood
cell
count
10,000/4,
hemoglobin
15.5
g/dL,
sodium
134
mEq/L,
potas-
sium
7.6
mEq/L,
calcium
9.9
mg/dL
(reference
range:
7.9-9.9
mg/dL),
magnesium
2.0
mEq/L
(1.3-2.1
mEq/L),
BUN
12.3
mg/dL,
creatinine
0.69
mg/dL
(0.44-1.03
mg/dL),
aspar-
tate
aminotransferase
29
U/L,
alanine
aminotransferase
21
U/L
and
troponin-I
0.018
ng/mL
(10%
CV:
0.06
ng/mL).
Arterial
blood
gases
disclosed
pH
7.315,
PCO
2
48.9
mmHg,
P0
2
78.4
mmHg
and
bicarbonate
24.3
mmol/L.
The
initial
electro-
cardiogram
(ECG)
revealed
a
first-degree
atrioventricular
con-
duction
block
with
interatrial
conduction
delay
and
premature
atrial
contractions
(Figure
1).
Chest
radiograph
showed
mild
bilateral
pulmonary
congestion.
Initial
therapy
for
hyperkalemia
included
intravenous
calcium
gluconate,
insulin,
dextrose
and
sodium
bicarbonate.
She
developed
progressive
bradycardia
and
hypotension
and
she
was
treated
with
fluid
resuscitation,
dopamine
infu-
sion
and
transcutaneous
pacing.
Three
hours
after
arrival,
ECG
showed
polymorphic
ventricular
tachycardia
(Figure
2).
Hsien-Yi
Chen
lO
Department
of
Emergency
Medicine,
Chang
Gung
Memorial
Hospital,
No.
5,
Fuxing
St.,
Guishan
Dist.,
Taoyuan
City
333,
Taiwan
©
2017
Informa
UK
Limited,
trading
as
Taylor
&
Francis
Group
aN,
j\i'V\AA
111
1
I
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v
1
1
"
k
2
0
I.-L
WU
ETAL
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1
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Figure
1.
Electrocardiogram
on
arrival
(8
hours
after
ingestion).
-
Electrocardiogram
before
hemodialysis
(11
hours
after
ingestion).
The
serum
potassium
level
at
this
time
was
6.7
mEq/L,
and
emergent
hemodialysis
was
performed.
Based
on
her
gastrointestinal
symptoms,
cardiac
dysrhyth-
mias
and
hyperkalemia,
we
suspected
ingestion
of
a
CG-con-
taining
plant.
A
serum
digoxin
level
was
requested
and
was
reported
as
151.2
ng/mL
(therapeutic
range:
0.8-2.0
ng/mL)
five
hours
after
arrival.
Hemodialysis
was
stopped
(only
two
hours
of
hemodialysis
was
performed)
and
two
vials
of
Digibind
TM
were
given
(our
hospital
only
had
two
vials
in
stock).
Serum
potassium
level
after
dialysis
was
4.6
meg/L.
However,
prior
to
starting
the
Digibind
TM
infusion,
the
patient
collapsed
with
a
rhythm
of
polymorphic
ventricular
tachycardia
followed
by
ventricular
fibrillation.
Cardiopulmonary
resuscitation
(CPR)
was
initiated.
The
patient
had
intermittent
temporary
return
of
spontaneous
cir-
culation
(ROSC)
during
the
CPCR.
Emergent
VA-ECMO
was
organized
and
it
was
started
approximately
60
minutes
after
her
collapse.
She
was
admitted
to
the
intensive
care
unit
where
an
additional
six
vials
of
Digibind
TM
(gathered
from
other
hospitals)
were
given
over
the
next
16
hours.
CLINICAL
TOXICOLOGY
0
3
The
patient
remained
in
asystole
over
the
first
30
hours
fol-
lowing
the
initiation
of
ECMO,
and
then
she
regained
a
spon-
taneous
rhythm
with
atrial
fibrillation
(ventricular
rate
of
60-120/min).
The
serum
troponin-I
level
peaked
at
51.54
ng/ml
on
hospital
day
two.
A
bedside
echocardiogram
revealed
poor
cardiac
contractility,
which
was
ascribed
to
extensive
myocardial
injury
associated
with
the
ventricular
dysrhyth-
mias
and
prolonged
CPCR.
The
patient
temporarily
regained
consciousness
and
could
follow
simple
command
but
remained
hemodynamically
unstable
and
was
unable
to
be
weaned
from
the
VA-ECMO
and
inotropic
agents.
She
subse-
quently
developed
lower
limb
ischemia,
acute
kidney
injury,
multiple
organ
failure
and
died
on
hospital
day
seven.
The
patient's
husband
brought
us
a
sample
of
the
alleged
"comfrey".
We
sent
it
to
a
botanist
for
identification
and
he
confirmed
that
the
plant
was
Digitalis
purpurea.
Discussio
'
Cardiac
glycosides
have
been
used
for
medicinal
purposes
for
more
than
200
years.
Despite
a
relative
decline
in
their
use
over
the
last
few
decades,
CGs
still
account
for
a
consid-
erable
number
of
poisonings
[3].
The
diagnosis
of
CG
poison-
ing
is
usually
based
on
the
exposure
history,
typical
clinical
presentations
and
the
interpretation
of
the
serum
digoxin
level.
Comfrey
(Symphytum
officinale)
leaves
resemble
those
of
foxglove
(Digitalis
purpurea)
when
the
plant
is
not
in
bloom.
CG
poisoning
from
accidentally
mistaking
foxglove
for
comfrey
or
other
plants
can
lead
to
a
delayed
diagnosis
in
the
absence
of
accurate
exposure
history
[2].
Hyperkalemia
is
the
most
common
electrolyte
abnormality
in
acute
CG
intoxication,
and
is
strongly
associated
with
mor-
tality
[4].
Acute
CG
poisoning
with
a
serum
potassium
more
than
5
mEq/L
is
an
indication
for
digoxin-specific
antibody
fragment
(DSFab)
treatment
[5].
Hyperkalemia
usually
resolves
within
hours
of
administration
of
DSFab
as
N-K-
ATPase
activity
is
restored
and
potassium
is
redistributed
back
into
cells.
While
hyperkalemia
causes
impaired
pace-
maker
activity
and
AV
nodal
conduction,
experimental
stud-
ies
suggest
that
a
mildly
elevated
serum
potassium
level
may
partially
antagonize
the
physiological
effects
of
increased
intracellular
calcium
and
may
provide
some
protection
against
ventricular
tachyarryhthmias
associated
with
CG
intoxication
[6,7].
It
is
unclear
if
treating
CG-induced
hyperka-
lemia
with
traditional
therapy
such
as
intravenous
calcium,
insulin
plus
dextrose
and
sodium
bicarbonate
affect
outcome,
although
there
is
no
evidence
that
treatment
with
calcium
is
harmful
[8].
Although
it
did
not
occur
in
our
case,
hypokal-
emia
may
occur
after
the
administration
of
DSFab
in
patients
who
previously
received
potassium-lowering
agents,
so
close
monitoring
of
potassium
levels
is
important.
Based
on
our
patient's
ECGs
and
clinical
course,
her
cardiac
arrest
was
mainly
due
to
severe
digitalis
poisoning
rather
than
hyperka-
lemia
itself.
Aggressive
correction
of
hyperkalemia
failed
to
prevent
a
fatal
dysrhythmia.
The
role
of
DSFab
in
the
treatment
of
acute
botanic
CG
poisonings
is
not
well
established.
The
main
CGs
in
Digitalis
purpurea
leaves
are
digitoxin,
gitoxin,
gitaloxin
[9].
It
is
recognized
that
there
is
incomplete
or
inconsistent
cross-
reactivity
between
the
antibodies
and
glycosides
other
than
digoxin,
and
therefore
standard
dose
calculations
based
on
the
digoxin
level
do
not
apply.
Far
greater
amounts
of
DSFab
may
be
required,
and
it
has
been
recommended
to
give
10-20
vials
of
DSFab
empirically
in
severe
cases
(life-threat-
ening
cardiac
dysrhythmia,
hemodynamically
unstable,
serum
potassium
more
than
5
mEq/L)
[5].
However,
the
high
cost
of
DSFab
leads
to
insufficient
stocking
in
developing
countries,
and
sometimes
even
in
developed
countries
[10,11].
In
facili-
ties
without
access
to
DSFab,
supportive
treatment
as
well
as
aggressive
cardiopulmonary
support
is
crucial
to
patients'
recovery.
ECMO
has
been
reported
to
successfully
treat
patients
with
severe
cardiotoxicity
caused
by
various
drugs
or
toxins,
but
has
rarely
been
utilized
in
acute
CG
poisoning
[12].
As
the
clinical
impact
of
the
intoxication
is
often
temporary,
ECMO
might
be
used
as
a
"bridge
to
recovery"
or
a
"bridge
to
antidote"
in
patients
with
severe
poisoning
[13].
In
a
retro-
spective
study
including
62
critically
ill
poisoned
patients
who
suffered
from
cardiac
arrest
or
profound
shock,
those
who
received
VA-ECMO
had
better
outcomes
(survival
rate:
86%)
than
those
who
received
conventional
treatment
only
(survival
rate:
48%)
[14].
Although
human
data
are
limited,
and
our
case
was
unsuccessful
and
her
death
may
have
been
partly
due
to
ECMO
complications,
VA-ECMO
may
be
a
rea-
sonable
choice
in
severe
CG
poisonings
when
the
patient
is
poorly
responsive
to
DSFab
therapy,
or
when
the
antidote
is
unavailable.
In
conclusion,
the
diagnosis
of
CG
plant
poisoning
can
be
difficult
in
the
absence
of
an
accurate
exposure
history.
Gastrointestinal
symptoms,
cardiac
dysrhythmias
and
hyper-
kalemia
are
highly
suggestive.
In
the
not
uncommon
circum-
stance
where
DSFab
is
not
available
or
only
in
small
quantities,
early
VA-ECMO
might
be
considered
in
severely
cardiotoxic
patients
who
do
not
response
to
traditional
sup-
portive
care.
Disclosure
statement
The
authors
report
no
conflicts
of
interest.
The
authors
alone
are
respon-
sible
for
the
content
and
writing
of
this
article.
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[12]
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