Document 6479269

Hypermagnesemia*
A Potential
Complication
Theophyfline
Intoxication
Charcoal
Charles’
During Treatment
with
Oral
Activated
and Magnesium-Containing
A. Weber,
It!. D. t
and
Rafael
Al.
of
Cathartics
Santiago,
M. D.
Toxic reaction
to theophylline
compounds
is common.
Oral
activated
charcoal
(OAC) is a widely
accepted
mode of
therapy
for management
of moderate
to severe cases of
theophylline
toxicity. Magnesium-containing
cathartics
are
generally
recommended
in conjunction
with OAC in the
treatment
of drug or toxin ingestions.
We report two cases
of hypermagnesemia
complicating
the treatment
of theo-
,
F. C. C. P
phylline
patients,
toxicity with OAC and magnesium
citrate.
In both
the hypermagnesemia
contributed
significantly
to
morbidity
or mortality.
In light of these cases and after
review of the literature,
we suggest that sorbitol
be considered the cathartic
agent
of choice
in the treatment
of
theophylline
toxicity with OAC. (Chest 1989; 95:56-59)
= oral
OAC
activated
charcoal
MAT
multifocal
atrial
tachy-
cardia
T
heophvlliiie
toxicity
remains
a common
occurrence
recently
been
.
clearance
rate
fully
utilized
of several
drugs
and
in the
management
Oral
shown
intoxicated
work
n”2
by
adsorbing
gastrointestinal
absorption.3
Activated
the
charcoal
remaining
a concentration
gradient
agent
along
generally
recommended
decrease
the
through
adsorbed
gradient
with
.
transit
time
of the
charcoal
theoretically
activated
common
efficacy
use,
as
of theophylline
it
A 61-year
is
charcoal
toxicity
unaware
applies
or of their
for
treatment
to the
April
bated
Hall
USAF
Medical
Center
admitted
in
which
tachycardia
arrival
in the
tube,
also
given
pam,
1edicine,
Texas.
tFellov;
Staff,
Pulmonary
and
Wilford
Pulmonary
Pulmonary
Hall
Critical
USAF
Care
Division,
During
Medical
Center,
Disease
Service.
Disease
Service,
and
Medicine,
Uniformed
Services
University
The
opinions
expressed
are
those
of
necessarily
represent
official
USAF
plicy.
Manuscript
Reprint
Texas
received
requests:
March
Dr
24;
Santiago,
revision
[TSAF
Lackland
Assistant
Professor
of
AFB,
artery
occlusion
sq
and
of the Health
Sciences.
the
authors
and
do not
accepted
Hospital,
78236-5.300
56
Downloaded From: http://publications.chestnet.org/ on 09/09/2014
May
23.
Lackland
AFB,
fell
therapy
pressure
of2O
blood
rate
and
mm
level
artery
was
found
to be 6.9
serum
creatinine
was
0.6
after
admission.
The
patient
well
as
six
enterally,
for a total
of 55 g of magnesium
pressure
remained
low
various
left
vasopressor
ventricle
with
agents.
with
diffuse
relative
An
1.8
Hg,
IJmin!
dynes’s
associated
admission,
however,
had
was
pulmonary
Initial
BUN
2 g of
of magnesium
over
an 8-h
echocardiogram
revealed
A
Hypermagnesemia
head
citrate
period.
while
CT
(Webe
a
was
oliguria
received
bradycardia
hypokinesis.
catheter
after
mg/dl;
doses
charcoal!
dopamine
of
mm
mg/dl.
soon
as
the
of 2,431
hours
and
IV
index
90/60
Several
Serum
hemoperfusion
mean
index
occurred
sulfate
after
IV diaze-
(PA)
Hg,
cardiac
6 mg/dl,
magnesium
Soon
and
mm
Hg,
pressure
was
were
requiring
resistance
of 80 beats/mm.
magnesium
each
sulfate
control.
anticonvulsants
of 31/25
vascular
citrate,
MAT
for
for
30 g via a
required
phenobarbital
A pulmonary
a PA pressure
a systemic
a sinus
and
magne-
Treatment
of IV magnesium
ensued,
hypoafter
serum
charcoal,
to 24. 1 p.g/ml,
with
was
of multifocal
g) of magnesium
hypotension
p.gfkg/min.
Systemic
with
serum
of
30
at
revealing
m,
and
mixture,
initial
which
a
intu-
Shortly
mg/dl).
activated
on
an admission
The
(8.7
was
patient
reported
developed,
quickly
She
beat/mm.
hypomagnesemia
epilepticus
levels
150
with
ml
diphenylhydantoin,
theophylline
following
1.8 to 2.4
1-g boluses
of
status
placed
Department
150
because
admission,
of
p.g/ml.
begun
2 h. Two
Center
arrest
findings
laboratory
(normal,
was
and
every
the
of 42.4
mg/dl
1.5
toxicity
repeated
at a rate
EGG
On
Medical
The
and
3-
captopril.
activity.
ventilation.
and
inhaled
and
Hall
seizure
pulse
ICU,
level
was
nasogastric
mcm’.
the
*From
or
outpatient
therapy,
daily,
a respiratory
irregular
(MAT)
Her
oxygen
twice
at Wilford
mechanical
theophylline
level
Room
medical
was deferred.
of
ca-
of hypertension
disease.
of generalized
a rapid,
atrial
orally
experienced
received
theophylline
to Wilford
treatment
she
a history
home
mg
Emergency
with
had
pulmonary
ofcontinuous
period
and
support
recently
magnesium
REPORTS
woman
300
1987,
questionable
sium
pro-
white
TheoDur
arrival
10
and
hypermagnesemia,
to the morbidity
involved.
obstructive
magnesium
ducing
hypermagnesemia.
We present
two cases
patients
consisted
agonists,
serum
of any data on
to the treatment
potential
old
chronic
tensive
agents,
magnesium
citrate
are commonly
used
in the
of drug
toxicities.
Despite
we are
specifically
of the
CASE
severe
the
OAC
1
the
lumen
of the
to charcoal
the use of a
activated
agents
with
in iatrogenic
significantly
to
systemic
of thefrom
toxicity
resulted
contributed
mortality
the gut,
prevent
reabsorption
of charcoaldrug,
and help
maintain
a concentration
across
the gut wall that favors
further
drug
excretion.
Among
cathartic
and magnesium
sulfate
management
of a variety
their
their
the
These
thartics
which
CASE
within
further
movement
intestinal
mucosal
circulation
into the
gut.4
Since
the binding
of theophylline
within
the gut is potentially
reversible,5
cathartic
appears
drug
,
down
theophylline
has
the
has been
successof theophylline-
(CI) tract
preventing
and by promoting
the
ophylline
clinical
activated
charcoal
(OAC)
to enhance
significantly
Blood
receiving
a dilated
scan
was
Santiago)
unremarkable.
Intravenous
apparent
creatinine
on
4 of
magnesium
level
level
and
to
Following
variables.
The
cardiac
CASE
24
36
index
lowering
improved
changes
h
patient
the
During
ranged
remains
hospitalized
first
from
1 .8 to
magnesium
to values
of 2.9
other
six
was
the
serum
of
a
serum
magnesium
ofthe
index
the
serum
agents.
cardiac
and
cognitive
to
the
with
performed
lower
the
significant
patient
to moderate
next
the
without
to
without
lov;
was
attempt
vasopressor
dialysis
normal,
m
mild
all
of hospitalization,
m.
Hemodialysis
an
the
from
were
remained
hemodialysis,
over
weaned
Limin!sq
was
Following
decreased,
days
in
boluses
output
of < 10 ml!min.
level.
LJsq
chloride
Urine
hospitalization
successfully
2.2
benefit.
clearance
day
four
calcium
hemodynamic
to
3.6
later
A 77-year
admitted
Medical
old woman
with
to the Medical
Center
prolonged
on
29 May
hospital
congestive
Eventually
course
day
serum
cellulitus,
was
extubated
and
52,
theophylline
level
charcoal
300-ml
dose
of magnesium
patient
was
blood
pressure
found
dopamine
and
trates
on chest
Laboratory
3.1
mm,
glucose,
304
7.8
mg/dl
albumin,
1.6
magnesium
BUN,
g/dl.
of 2.0
Llmin,
mg/dl,
occlusion
with
broad-spectrum
namic
response
to
patients
the
hemodynamic
pursued.
The
theophylline
diffuse
cultures
grew
and
died
within
An autopsy
alveolar
dopamine
patient
was
Blood
recognized,
no
study
of
revealed
damage,
Staphylococcus
h
and
hemody-
to this
was
not
recognition
evidence
of
of charcoal
tubular
by hypoactive
sepsis,
course.
in the
the
myocardial
made
the
failure,9
bowel
and
bradycardia,
paralysis
CN S depression,
muscle
with
secondary
respiratory
kidneys
are responsible
homeostasis.
Seventy-five
plasma
is unbound
and
and
refractory
hypocalcemia.6”#{176}
for maintaining
magnesium
percent
of magnesium
freely
filtered
at the level
intracranial
effectively
excluded.
following
hemodialysis
level
further
in our
1)atients
pattern
as clear,
played
As
with
and clinical
course
but suggests
that
a significant
the
first
patient,
was present
susceptible
role
iii
the
underlying
and
may have
to the effects
of
our knowledge
only
two previously
reported
describe
symptomatic
hypermagiiesemia
as a
result
of treatment
with OAC and magnesium-containing cathartics.9,16
Both
of those
cases
occurred
in
patients
The
in
of
without
renal
disease
and
resulted
in either
respiratory
failure
or prolongation
of ventilatory
support.
In one case,
diminished
bowel
function
due to
tricyclic
overdose
may have contributed
to magnesium
toxicity.
16
CHEST
Downloaded From: http://publications.chestnet.org/ on 09/09/2014
elevated
were
absorpproblem.
signifiand sinus
in partic-
To
profound
hypomotility,
and
toxicity
dysfunction
patient
more
cases
include
sounds
magnesium
course.
The
may
bowel
of serum
hypermagnesia
hypermagnesemia.
be
rate
been
was the dominant
cause
for hypotension.
it is
difficult
to determine
to what extent
hypermagnesemia contributed
to the refractory
hypotension
ohserved
in this case.
However,
with serum
magnesiuni
levels greater
than 10 mg/dl,
it is reasonable
to assume
dis-
can
disease
role ofmagnesiuin
The hemodynamic
second
case is not
an iatrogenic
hypotension,7’8
weakness
and
infarction,
hypovolemia,
of hypotensiori
normalization
supports
order
resulting
from the use of magnesium-containing
medications
in the setting
of renal
impairment.6
effects
renal
glomerular
filtration
the magnesium
had
to absent
myocardial
pressure
and
The resolution
patient’s
aureus.
is frequently
preexisting
effective
zero after
and
hypotension
with
associated
derenal perfusion
and oliguria
had ensued.
patients
developed
diminished
bowel
activity
judged
that
necrosis.
DISCUSSION
Hypermagnesemia
or
‘#{176} ‘
sepsis
were
rod.
the
acute
was
cultures
hemodialysis
48
occur
excretory
hypermagof normal
absence
of stools)
shortly
into their
courses.
While
likely multifactoral
in etiology,
hypermagnesemia
was
probably
a contributing
factor.
Further,
the absence
of
and
of 900
with
by hypermagnesemia
was
and
cardiac
Hg,
a Gram-negative
contribution
status
patient
toxicity.
aspiration,
aureus
possible
mg/dl,
revealed
the
There
gluconate.
renal
ular
of
a serum
resistance
and
antibiotics.
calcium
for Staphylococcus
Although
persisted,
renal function.9
cases we described,
the
and symptomatic
in the setting
normal
creatiniiie
large
serum
had
10 mm
infusions
6 g/day),
the
Moreover,
serum
and
1.5
vascular
when
clear-
ofa
serum
measurement
during
may
near-normal
In the
(as
occurs
nil/ruin.
overcome
nesemia
creased
Both
setting
mg/dl);
had
of
may
(about
creatiniiie
iii
(in the
magnesium
intake)
falls below
30
the
levels and,
of parathyroid
mEq/L;
count
creatinine,
mg/dl;
creatinine,
a systemic
taken
IV
3.3
to decreases
even
reabvaries
Serum
inagnesiu
in levels
in a physiologic
range,
l)ut
to excrete
a magnesium
load
hypermagnesemia
loads
is then
of Inagilesium
in serum
magnesium
with the effects
capacity
administered
of which
catharsis
may have led to further
magnesium
tion from the gut, thereby
compounding
the
In case 1 it appears
that hypermagneseinia
cantly
contributed
to refractory
hypotension
bradycardia.
Other
causes
for hypotension,
infil-
ventilated.
10.3
pressure
re-
bilateral
patient
catheter
and
ensued
a WBC
5.3
the
the
to the
44 mg/dl;
to
serum
artery
Hypotension
treated
transferred
potassium,
before
later
administration
BUN,
increasing
was
a systolic
mechanically
phosphate,
and
levarterenol).
positive
serum
(later
week
hours
values:
shift;
A
by a single
developed
and
On
patient
with
was
following
left
serum
the
followed
fluid
subsequently
(measurement
5)
Lung
and
was absent,
but
likely approached
nausea.
tachyarrhythmias
the
artery
of 3.5
(desscm
to
Pulmonary
pulmonary
output
patient
was intubated
One
level
24 mg/dl.
a mean
and
mWdl;
and
A
a day.
and
g). Several
The
mg/dl;
twice
tachycardic
responded
a marked
mg/dl;
7.6
(17.5
and
Hg.
included
magnesium,
calcium,
tube
film,
with
orally
noted
She
x-ray
Maintenance
anorexia
Supraventricular
data
7,200/cu
p.g/ml
citrate
cardioversion.
pneumotho-
to a ward.
was
mm
failure.
by right
dependence.
30 g via an enteral
initially
infusion.
quiring
of44
respiratory
ventilator
mg
developed
unresponsive
of 65
ICU
and
300
patient
activated
acute
moved
TheoDur,
the
given
Medical
with
pulmonary
disease
Unit at Wilford
Hall
complicated
failure,
included
hospital
1987
ensued
heart
she
medications
chronic
obstructive
Intensive
Care
majority
excretn)n
proportionally
magnesium
2
rax,
falls
dietary
clearance
with
deficits.
the
fractional
changes
extent,
hormone
and
are normally
maintained
the ability
ofthe
kidneys
ance,
hemodynamic
months
glomerulus,
sorbed.
The
greatly
with
to a minimal
I 95
I 1 I JANUARY,
1989
57
There
is little
ing the
OAC.’7”
ticularly
ingestions,
practice.
ages
evidence
the literature
iii
demonstratof
par-
in
the
setting
of sustained-release
tablet
and it will likely continue
to be a common
While
firm guidelines
delineating
the dos-
of these
cathartics
amount
of magnesium
in case
1 exceeded
limit.
magnesium
developed
‘
have
not been
established,
citrate
received
by the
the generally
The
second
magnesium
of 17.5
dosage
recommended
patient,
after
which
intoxication
g of magnesium
recommendations.
citrate,
the
patient
In a study
of normal
charcoal,
sulfate
sorbitol
was
or magnesium
transit
time
Goldberg
combination
OAC alone
and
a single
is within
in
Studies
on
to be effective
balance
We
are
and
marked
We
nesemia
in this setting
may occur
of regularity,
but may go unrecognized
with
to the
serum
toxicity
of the ingested
magnesium
levels are
Review
regarding
of the clinical
and
the use of cathartic
with OAC leads
sorbitol
should
us to conclude,
be considered
choice
in the treatment
including
those caused
not
recom-
degree
of the
associated
many
attributed
drug
or toxin because
routinely
obtained.
as have others,’24
that
the cathartic
agent
of
of drug toxicities
compounds.
If
58
Downloaded From: http://publications.chestnet.org/ on 09/09/2014
Cooper
of theophylline
Crit
Jf
KR.
Care
J
Treatment
Chest
Med
1984;
J
Pediatr
clearance
Med
1982;
94:314-16
drugs
with
activated
307:676-78
Cliii
WE.
87:325-29
of theophylline
1979;
of
pharinacokinetics
\Vacker
of theophylline
1985;
M. Inhibition
charcoal.
intoxications.
JR
Swartz
of oral
Pharmacokinet
Excess
R, Arky
ofrefractory
Bourgeois
activated
1982;
magnesium.
BA.
char-
7:465-89
Pharmacol
Extreme
Ann
hypotension.
FJ,
Thaigarajah
hypotetision
1986;
9 Fassler
CA,
Rev
hyperinagnesensia
Med
Intern
tioii.
as
1975;
83:657-
11
Med
1985;
FR
Magnesium
1981.
BS,
Coburn
RE,
jW
J
Med
Cohen
in renal
I
15
Pollack
WJ,
and
deficiency
Spray
JJ.
Marini
hypoventila-
and
the
CC,
excess.
Annu
mimic/antagonist
Rossmeisl
Intern
C,
and
HH.
Stone
Med
Oh
T.
EC.
1964;
Hart
J
Br Med
1984;
Hyperinag-
61:73-87
C,
hypophosphatemia
Aspiration
of
310:1253-54
Ann
Bhagat
sulfate.
1986;
DB,
Magnesium,
MD,
Hyperinagnesemia
14 Harsch
Obstet
145:1604-96
1984;
failure.
Garcia-Webb
magnesium
J
32:245-59
N Engl
Randall
C. Profound
Am
of hypotension
Singer
Levine
Med
Badesch
a cause
Intern
nesernia
13
as
RK,
calcium.
12
RM,
toxicity
Med
DiFazio
therapy.
154:919-20
Arch
Rude
GM,
Harbert
magnesium
Rodriguez
Magnesium
10
S.
complicating
Gynecol
Thompson
after
W
ingestion
of
288(6149):759
ofactivated
charcoal
[Letter].
J
N Engl
314:318
MM,
of activated
Dunbar
BS,
Holbrook
charcoal
and
gastric
PR,
Fields
contents.
Al.
Ann
Aspiration
Emerg
Med
1981; 10:528-29
J,
16 Jones
Heiselman
magnesium
Med
17
D,
1986;
18
Effects
of
tract
Toxicol
Clin
Van
Graaff
de
Eddy
overdose
A. Cathartic-induced
management.
Ann
Emerg
15:1214-18
JJ.
Stewart
J,
Dougherty
during
toxicity
gastrointestinal
Leickly
F,
enteral
drug
emetic
and
Toxicol
1983;
WB,
and
the
H.
of
agents
toxic
on
the
J
ingestion.
20:199-253
Thompson
Dayton
cathartic
treatment
WL,
J
absorption.
Sunshine
and
Adsorbent
Pharmacol
1, Fretthold
cathartic
Exp
D,
of
inhibition
Ther
1982;
221:656-
63
19
experimental
literature
agents
in conjunction
of a variety
by theophylline
to
58
8
hypermag-
some
because
nonspecific
nature
of symptoms
and signs
with elevated
magnesium
levels.
Furthermore,
of the clinical
findings
may be incorrectly
due
29:273-300
Rev
The
that
occur
Treatment
charcoal.
PJ. Clinical
in acute
a cause
of
suspension
were
toxicity
resulting
CK.
L, Weinberger
N Engi
7 Mordes
two
when
FL,
Gastrointestinal
6 Mordes
hypernatremia.
suspect
not
charcoal.
activated
by activated
C.
1978;
ofonly’
oral
C, Hendeles
coal
the
thais
sus-
Mahutte
activated
Clauser
5 Neuvonen
CI
oral
with
charcoal.
mean
JM,
CN,
absorption
to
of the san#{236}e
charcoal
dosage
(1 gfkg) mixed
in 4.3 ml!
kg body weight
of35
percent
sorbitol.2
We described
two cases
in which
the treatment
of
theophylline
intoxication
with OAC and magnesiumcontaining
cathartics
resulted
in or contributed
to
hypotension.
does
also
are
14
3 Sintek
mended
dosage
in adults
is 1 g/kg ofactivated
charcoal
in 4.3 mI/kg body weight
of 70 percent
sorbitol
every
four hours.
The recommendation
in children
consists
refractory
catharsis
Berman
toxicity
Furthermore,
a prerequisite.2
should
agents
toxicity
function.
with
2 Sessler
adults
show activated
charcoal-sorbitol
and safe, although
appropriate
attention
is still
in the
REFERENCES
RJ,
12:113’
activated
aware
use
magnesium-containing
but
bowel
1 rrue
magnesium
fullowing
administration
in pediatric
patients
of charcoal-sorbitol
treatment
of drug
for
dehydration
to fluid
receiving
to either
in reducing
their
Magnesium
when
administered
dose
the
charcoal
2
efkcts
occurred
doses
severe
volunteers
superior
citrate
theophylline.
administered
toxicity.
4 Levy
inducing
reports
of’ adverse
sorbitol.2’
2.5 Both
excessive
activated
employed,
30-g
however,
and
colleagues
demonstrated
that
ofsorbitol
and OAC is more effective
in
enhanciiig
elimination
of ingested
tamed-release
magnesium
be anticipated
toxicity
It can be mixed
with
a more palatable
slurry
ingestion.
are
hemodynainically
unstable,
intoxicated
patient
should
be judicious,
with close
monitoring
of serum
magnesium
levels
and observation
for clinical
evidence
of
decreased
A therapeutic
alternative
to magnesium-containing
cathartics
is the use of soi’bitol,
a poorly
absorbed
sugar
which
acts as an effective
osmotic
agent following
produce
cathartics
magnesium
efficacy
of adding
a cathartic
to a regimen
Nonetheless,
their
use appears
logical,
Flomenbauin
N,
toxicologic
Schwartz
CR,
ed.
Philadelphia:
20
21
Krenzelok
EP
of cathartics
1985;
14:1152-55
TA.
Severe
L,
Saunders
Keller
Roberts
: evaluation
and practice
Principle
WB
times
Farley
Goldfrank
presentations
R,
Go,
hypernatremic
Selected
clinical
1986:1699
Stewart
combined
JR.
and management.
In:
ofemergency
medicine.
RD.
with
Gastrointestinal
charcoal.
dehydration
Hypermagnesemia
Ann
transit
Emerg
after
(Webei
Med
use
of an
Santiago)
activated
charcoal-sorbitol
J
suspension.
Pediatr
1986;
activated
109:719-
Toxicol
22
22
Goldberg
effect
MJ,
of sorbitol
concentrations
Ther
23
Minocha
1987;
Spector
and
after
R,
Park
GD,
activated
Johnson
charcoal
slow-release
GF,
on
Roberts
serum
theophylline.
P The
24
theophylline
Clin
Herold
A,
Bruns
DE,
Spyker
DA.
Effect
Krenzelok
for activated
25 McCord
DA,
in 70%
sorbitol
in healthy
individuals.
Clin
22:529-36
EI
Spyker
DA.
charcoal-sorbitol
Dosage
treatment
recommendaClin
Toxicol
1985;
23:579-87
Pharmacol
41:108-11
A,
Minocha
tions
charcoal
1984-85;
of
Pediatr
M. Toxicity
1987;
of sorbitol-charcoal
suspension.
[Letter].
J
111:307-08
Plan to Attend
55th Annual Scientific AssemblyXVI World Congress on Diseases of the Chest
Boston
.
October
30-November
2, 1989
CHEST
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