Alerts, Notices, and Case Reports - Fatal Salicylate Toxicity From

637

Alerts,

Notices,

and

Case

Reports

Fatal

Salicylate

Toxicity

From

Bismuth

Subsalicylate

STEVEN

J.

SAINSBURY,

MD

Templeton,

Califomia

FATAL

SALICYLATE

INGESTION

usually

results

from

concen-

trated

formulations

of

salicylates

found

in

analgesics,

cold

and

sinus

medications,

and

aspirin-containing

topical

com-

pounds.

I

describe

a

case

of

salicylate

toxicity

leading

to

death

secondary

to

the

abuse

of

Pepto-Bismol,

whose

active

and

toxic

ingredient

is

bismuth

subsalicylate.

Report

of

a

Case

The

patient,

an

82-year-old

previously

healthy

woman,

presented

to

the

Riverside

(California)

Community

Hospital

Emergency

Department

with

an

altered

level

of

conscious-

ness,

according

to

her

son

with

whom

she

was

living.

In

the

previous

24

hours,

she

had

exhibited

slurred

speech,

leth-

argy,

and

a

decreased

oral

intake.

Her

son

also

reported

that

for

several

days

she

had

complained

of

an

exacerbation

of

her

chronic

abdominal

pain.

As

a

result,

she

had

been

ingesting

large

amounts

of

Pepto-Bismol

tablets

daily,

including

66

tablets

in

the

24

hours

before

admission.

There

was

no

his-

tory

of

nausea

or

vomiting.

Stools

had

been

watery

and

black

for

several

days.

Her

medical

history

was

significant

for

chronic

abdomi-

nal

pain

that

remained

undiagnosed

despite

extensive

evalua-

tions

in

the

past.

She

had

not

seen a

physician

in

several

years.

Current

medications

included

only

Pepto-Bismol.

She

was

allergic

to

codeine.

On

her

initial

examination,

this

frail,

small-of-stature

el-

derly

woman

was

confused

and

lethargic.

Her

supine

blood

pressure

was

118/70

mm

of

mercury

with

a

pulse

rate

of

70

per

minute,

a

respiratory

rate

of

20,

and

a

temperature

of

37°C

(98.6°F);

she

weighed

36

kg

(79

lb).

Her

skin

was

warm

and

dry

with

tenting.

Mucous

membranes

were

dry.

Auscultation

of

her

lungs

revealed

rales

at

the

left

base.

The

abdomen

displayed

no

palpable

mass,

rebound,

guarding,

or

organomegaly.

On

rectal

examination,

the

stool

was

dark

brown

and

guaiac-negative.

On

neurologic

examination,

she

was

disoriented

in

all

spheres

and

lethargic.

The

following

laboratory

values

were

obtained:

hemoglo-

bin

I

1 1

grams

per

liter

(1

1.

1

grams

per

dl);

hematocrit

0.32;

leukocyte

count

11.2

x

109

per

liter

(11,200

per

11),

with

0.87

neutrophils,

0.06

bands,

and

0.06

lymphocytes;

sodium

143,

potassium

3.5,

chloride

108,

and

carbon

dioxide

con-

tent

16

mmol

per

liter;

blood

urea

nitrogen

1.0

mmol

per

liter

(28

mg

per

dl);

creatinine

97

ltmol

per

liter

(1.1

mg

per

dl);

prothrombin

time

15.5

seconds

(control

11

to

13);

partial

prothrombin

time

30.2

seconds

(control

20

to

30);

and

glu-

cose

level

6.0

mmol

per

liter

(108

mg

per

dl).

Arterial

blood

(Sainsbury

SJ:

Fatal

salicylate

toxicity

from

bismuth

subsalicylate.

West

J

Med

1991

Dec;

155:637-639)

From

the

Emergency

Department,

Twin

Cities

Community

Hospital,

Templeton,

Califomia.

Reprint

requests

to

Steven

J.

Sainsbury,

MD,

Emergency

Department,

Twin

Cities

Community

Hospital,

1100

Las

Tablas,

Templeton,

CA

93465.

gas

determinations

with

the

patient

receiving

2

liters

of

oxy-

gen

showed

a

pH

of

7.55,

a

Pco2

of

14

mm

of

mercury,

and

a

P12

of

160

mm

of

mercury,

consistent

with

a

mixed

respira-

tory

alkalosis

and

metabolic

acidosis.

A

salicylate

level

was

46

mg

per

dl.

Other

studies

included

a

normal

electrocardiogram

and

upright

chest

radiograph.

A

plain

film

of

the

abdomen

re-

vealed

pronounced

densities

in

the

bowel,

consistent

with

"barium

or

some

other

radio-opaque

substance,"

according

to

the

radiologist's

interpretation

(Figure

1).

Computed

to-

mography

of

the

head

showed

diffuse

cortical

atrophy.

The

patient

was

admitted

to

the

care

of

her

family

practi-

tioner

with

a

diagnosis

of

dehydration,

encephalopathy,

and

salicylate

toxicity

due

to

Pepto-Bismol

abuse.

Despite

hydra-

tion

and

urinary

alkalinization

over

the

next

two

days,

her

condition

continued

to

deteriorate,

and

she

had

progressively

lower

hematocrits,

higher

leukocyte

counts,

and

steady

sali-

cylate

levels

and

anion

gaps.

A

gastroscopy

revealed

mild

generalized

intestinal

inflammation

but

no

focal

bleeding.

Three

days

after

admission,

her

hematocrit

was

0.19,

a

sali-

cylate

level

was

20

mg

per

dl,

and

the

anion

gap

was

24.

She

died

of

pulmonary

edema

on

the

same

day.

Discussion

As

a

result

of

safety

packaging

and

the

rise

of

acet-

aminophen

use

as

an

antipyretic

in

chiildren,

there

has

been

a

dramatic

decrease

in

the

incidence

of

salicylate

deaths

in

children

over

the

past

several

years.

I

Yet,

aspirin

remains

as

a

relatively

common

source

of

poisoning

in

adults.

Integrated

into

more

than

200

different

formulations

(probably

more

than

any

other

drug),

salicylates

are

commonly

overlooked

by

patients

and

physicians

alike

as

a

source

of

potential

toxic-

ity

(Table

1).2-4

Figure

1.-A

plain

film

of

the

abdomen

shows

pronounced

densities

in

the

bowel.

ALERTS,

NOTICES,

AND

CASE

REPORTS

The

elderly

in

particular

are

at

high

risk

for

both

acciden-

tal

and

chronic

salicylate

poisoning.5

Presenting

frequently

with

an

altered

sensorium,

they

can

prompt

a

fruitless

search

for

a

primary

neurologic

cause,

delaying

critical

treatment

of

their

toxic

syndrome.

Even

when

salicylates

are

identified

as

the

source

of

a

patient's

illness,

determining

the

degree

of

toxicity

is

difficult.

The

usefulness

of

the

Done

nomogram

is

currently

unclear,

and

it

is

certainly

invalid

in

cases

of

chronic

toxicity,

with

the

use

of

enteric-coated

preparations,

and

when

there

is

delayed

gastric

emptying

or

salicylate

con-

cretions.4,6

Salicylates

uncouple

oxidative

phosphorylation

and

in-

hibit

dehydrogenases

and

aminotransferases,

leading

to

a

rise

in

organic

anions

and

metabolic

acidosis.

They

also

stimulate

the

respiratory

system,

resulting

in

hyperventilation

and

re-

spiratory

alkalosis.

This

in

turn

leads

to

the

renal

excretion

of

bicarbonate

and

potassium.

Larger

doses

can

depress

respi-

rations.

Hypothrombinemia

and

platelet

dysfunction

are

common

complications

of

salicylate

toxicity,

producing

pro-

longed

bleeding

times.

Other

effects

are

diaphoresis

and

hy-

perthermia,

each

worsening

dehydration.

1.4

The

clinical

features

of

salicylate

toxicity

are

hyperpnea,

confusion,

lethargy,

tinnitus,

vomiting,

and

abdominal

pain.

Signs

include

fever

(particularly

in

children),

diaphoresis,

dehydration,

and

hyperventilation.

Coma

indicates

a

poor

prognosis.

1'4,7

The

treatment

of

salicylate

poisoning

is

challenging.

De-

spite

their

dehydration,

many

patients

are

predisposed

to

noncardiogenic

pulmonary

edema.

Forced

alkaline

diuresis,

the

cornerstone

of

emergency

department

therapy,

can

worsen

this

condition.

Excessive

bicarbonate

administration

to

increase

the

renal

excretion

of

salicylates

or

to

correct

the

salicylate-induced

metabolic

acidosis

can

lead

to

equally

dangerous

alkalinemia.

Hemodialysis

can

be

effective

in

eliminating

salicylates,

but

its

use

should

be

reserved

for

severely

poisoned

patients.

4'8

The

patient

in

this

report

had

most

of

the

classic

features

of

salicylate

poisoning.

She

presented

with

dehydration

and

central

nervous

system

dysfunction.

Examination

revealed

acid-base

and

clotting

disorders,

with

progressive

central

nervous

system

depression,

anemia,

pulmonary

edema,

and

eventually

death.

Because

of

long-term

salicylate

use,

in

the

form

of

enteric-coated

tablets,

the

salicylate

level

underesti-

mated

both

the

degree

and

likelihood

of

the

progression

of

toxicity.

What

is

atypical

is

the

source

of

the

salicylate:

Pepto-

Bismol

tablets,

each

of

which

contains

262

mg

of

bismuth

subsalicylate

and

102

mg

of

available

salicylate.9

The

recom-

mended

dosing

schedule-2

tablets

orally

four

times

a

day-

would

deliver

11.6

mg

of

salicylate

per

kilogram

per

day

in

a

70-kg

adult,

less

than

3

mg

per

kg

per

dose.

In

this

case

study,

the

ingestion

of

66

tablets

by

a

36-kg

patient

resulted

in

a

dose

of

187

mg

per

kg-taken

in

conjunction

with

probable

under-

lying

long-term

salicylate

abuse.

Although

mentioned

fre-

quently

in

the

literature

as

a

source

of

absorbable

salicylate,

Pepto-Bismol

use

has

not

been

reported

in

an

actual

death

from

salicylate

toxicity.9-"1

The

key

to

effective

intervention

in

salicylate

toxicity

remains

the

prompt

recognition

of

its

existence,

whether

it

be

accidental,

suicidal,

or

iatrogenic.

REFERENCES

1.

Haddad

L:

Salicylates,

In

Tintinalli

JE,

Rothstein

RJ,

Krome

RL

(Eds):

Emer-

gency

Medicine:

A

Study

Guide.

New

York,

NY,

McGraw-Hill,

1985

2.

Leist

E,

Banwell

J:

Products

containing

aspirin.

N

Engl

J

Med

1974;

291:710-

712

3.

Bryson

P:

Salicylates,

In

Comprehensive

Review

in

Toxicology.

Rockville,

Md,

Aspen

Publishers,

1989

4.

Sullivan

JB,

Lander

DH:

Planning

an

effective

strategy

in

salicylate

poisoning,

In

Egherman

W

(Ed):

Emergency

Medicine

Reports,

Vol

7,

San

Francisco,

Calif,

American

Medical

Reports,

1986,

pp

89-96

5.

Anderson

RJ,

Potts

DE,

Gabow

PA,

et

al:

Unrecognized

adult

salicylate

intoxi-

cation.

Ann

Intem

Med

1976;

85:745-748

6.

Todd

PJ,

Sills

JA,

Harris

F,

Cowen

JM:

Problems

with

overdoses of

sustained-

release

aspirin

(Letter).

Lancet

1981;

1:777

7.

Hill

JB:

Salicylate

intoxication.

N

Engl

J

Med

1973;

288:1110-1113

8.

Heffner

J,

Starkey

T,

Anthony

P:

Salicylate-induced

noncardiogenic

pulmonary

edema.

West

J

Med

1979;

130:263-266

TABLE

1.-Common

Sources

of

Salicylates

Selected

Formulations

(Manufacturer)

Generic

and

Chemical

Name

Prescription

Darvon

Compound

(Eli

Lilly

and

Co)

..

..................

Propoxyphene

HCI,

aspirin,

and

caffeine

Empirin

with

Codeine

(Burroughs

Wellcome)

.............

Aspirin

and

codeine

phosphate

Fiorinal

(Sandoz)

.Bail

...........

.......

..

M

U,aspirin,

and

caffeine

Percodan

(DuPont)

.Oxyc

..o.

..................

O*y0done

HCI,

oxycodone

terephthalate,

and

aspirin

Over-the-Counter

Aspirin

tablets

and

suppositories

(numerous

preparations)

...

--

Alka-Seltzer

(Miles

Inc)

.............

Aspirin,

sodium

bicarbonate,

citric

acid,

sodiu'm

citrate,

and

sodium

salicylate

Ascriptin

(Rhone-Poulenc

Rorer)

.......................Aspirin,

magnesium

hydroxide,

dried

aluminum

hydroxide

gel,

and

calcium

carbonate

Aspercreme

(Thompson

Medical)

......................

Topical

cream

containing

trolamine

salicylate

Ben-Gay

External

Analgesic

(Pfizer)

.....................

Topical

cream

containing

methyl

salicylate

and

menthol

Bufferin

(Bristol-Myers)

.

..................

Aspirin,

calcium

carbonate,

magnesium

oxide,

and

magnesium

carbonate

Cope

(Glenbrook)

..................

Aspirin

and

caffeine

Dristan

(Whitehall)

..................

Phenylephrine

HCI,

chlorpheniramine

maleate,

and

acetaminophen

Ecotrin

(SmithKline

Beecham)

.

....................

Entericcoated

aspirin

Excedrin

(Bristol-Myers)

.....

........Ac........

Ataminophen,

aspirin,

and

caffeine

Midol

(Glenbrook).

.........................

Acetaminophen,

pamabrom,

and

pyrilamine

maleate

Oil

Of

wintergreen.Mty

.l...

........

Mt

salicylate

Pepto-Bismol

(Procter

&

Gamble).Bismuth

subsaliclate

Sine-Aid

(McNeil)

.A

...........................e..

A&taminophen

and

pseudoephedrine

HCI

Triaminicin

(Sandoz)

...........

Phenylpropanalamine

HCI

and

chlorpheniramine.maleate

Vanquish

(Glenbrook)

............

..................

Aspirin,

acetaminophen,

caffeine,

dried

aluminum

hydroxide

gel,

and

magnesium

hydroxide

HCI

-

hydrochloride

638

9.

Bierer

DW:

Bismuth

subsalicylate:

History,

chemistry,

and

safety.

Rev

Infect

Dis

1990;

12(Suppl):S3-8

10.

Salicylate

in

Pepto-Bismol.

Med

Lett

Drugs

Ther

1980;

22:63

11.

Pickering

LK,

Feldman

S,

Ericsson

CD,

Cleary

TG:

Absorption

of

salicylate

and

bismuth

from

a

bismuth

subsalicylate-containing

compound

(Pepto-Bismol).

J

Pediatr

1981;

99:654-656

Ciguatera

Fish

Poisoning

in

San

Francisco,

California,

Caused

by

Imported

Barracuda

RICHARD

J.

GELLER,

MD

Fresno,

Califomia

KENT

R.

OLSON,

MD

PIERRE

E.

SENECAL,

MD

San

Francisco,

California

CIGUATERA

FISH

POISONING

is

endemic

to

tropical

waters,

where

reef-dwelling

fish

ingest

toxins

produced

by

the

dino-

flagellate

Gambierdiscus

toxicus.

The

disease,

which

is

caused

by

the

ingestion

of

fish

contaminated

with

ciguatera

toxins,

produces

gastrointestinal

and

neurologic

symptoms.

These

consist

of

an

early

gastrointestinal

phase

(abdominal

pain,

vomiting,

diarrhea)

followed

by

a

neurologic

or

consti-

tutional

phase

(pruritus,

muscle

pain,

weakness,

"burning

tongue,"

blurred

vision,

dizziness,

headache,

and

hot-cold

reversal).

We

report

an

outbreak

of

ciguatera

poisoning

that

occurred

in

1989

in

San

Francisco,

California,

caused

by

barracuda

(Sphyraena

species)

imported

from

Florida.

This

disease

is

rare

in

California,

having

previously

been

reported

in

Monterey,

California

(caused

by

mullet

imported

from

Florida),

and

in

the

San

Francisco

Bay

Area

(jack

fish

from

Midway

Island).l

Reports

of

Cases

Four

members

of

a

Vietnamese-American

family

became

ill

after

sharing

a

meal.

The

family

included

a

54-year-old

man,

a

53-year-old

woman,

their

21-year-old

daughter,

and

24-year-old

son.

All

patients

were

in

good

health

before

the

meal,

which

consisted

of

fresh

corn

on

the

cob,

commer-

cially

canned

mushrooms,

and

steamed

fish.

Only

the

fish

was

eaten

by

all

four

people.

No

shellfish

had

been

ingested.

The

fish

was

said

to

be

a

"nhong"

fish,

described

as

1.2

m

(4

ft)

long

with

a

pointed

snout.

It

was

purchased

from

an

open-air

farmers'

market

in

San

Francisco.

The

family

pur-

chased

and

ate

only

the

head

of

the

fish,

which

they

said

was

large

and

contained

abundant

flesh.

Investigation

by

the

county

health

department

determined

that

the

fish

eaten

was

from

a

shipment

of

frozen

barracuda

flown

in

from

Fort

Pierce,

Florida,

and

apparently

sold

to

several

Asian-Ameri-

can

families.

(Geller

RJ,

Olson

KR,

Sendcal

PE:

Ciguatera

fish

poisoning

in

San

Fran-

cisco,

California,

caused

by

imported

barracuda.

West

J

Med

1991

Dec;

155:639-642)

From

the

San

Francisco

Bay

Area

Regional

Poison

Control

Center,

San

Francisco

General

Hospital

Medical

Center

(Drs

Olson

and

Senedcal),

the

Fresno

Regional

Poison

Control

Center,

Fresno

Community

Hospital

and

Medical

Center

(Dr

Geller),

and

University

of

Califomia,

San

Francisco,

School

of

Medicine.

Dr

Senedcal

is

a

Clinical

Pharmacology

and

Toxicology

Fellow

of

the

Fonds

de

la

recherche

en

sante

du

Quedbec.

Reprint

requests

to

Richard

Geller,

MD,

Fresno

Regional

Poison

Control

Center,

Fresno

Community

Hospital

and

Medical

Center,

PO

Box

1232,

Fresno,

CA

93715.

Case

1

At

five

hours,

the

father

complained

of

weakness,

burn-

ing

of

the

tongue,

and

blurred

vision.

He

became

profoundly

weak

and

by

eight

hours

could

not

get

up

off

the

floor.

He

had

no

nausea,

vomiting,

or

diarrhea.

Paramedics

found

the

pa-

tient

prostrate

with

a

pulse

of

40

beats

per

minute

and

a

systolic

pressure

of

80

mm

of

mercury.

He

did

not

have

chest

pain,

and

there

were

no

signs

of

heart

failure.

Atropine

sul-

fate,

0.5

mg,

was

administered

intravenously

(IV).

Twenty

minutes

later,

his

blood

pressure

was

132/52

mm

of

mercury,

and

his

pulse

was

88

beats

per

minute.

In

the

Emergency

Department

at

San

Francisco

General

Hospital,

he

had

numbness

to

the

face

and

extremities,

weak-

ness,

and

periumbilical

abdominal

pain.

His

blood

pressure

was

144/90

mm

of

mercury,

pulse

rate

84

beats

per

minute,

and

he

was

afebrile.

Initial

laboratory

values

included

a

leu-

kocyte

count

of

9.0

x

109

per

liter

(9,000

per

II),

hemoglo-

bin

120

grams

per

liter

(12.0

grams

per

dl),

and

hematocrit

0.37

(37%).

The

serum

glucose

level

was

12.7

mmol

per

liter

(229

mg

per

dl),

blood

urea

nitrogen

7.9

mmol

per

liter

(22

mg

per

dl),

and

creatinine

106.1

iLmol

per

liter

(1.2

mg

per

dl).

Serum

sodium

was

139,

potassium

3.3,

chloride

103,

and

bicarbonate

27

mmol

per

liter.

Arterial

blood

gas

deter-

minations

with

the

patient

receiving

supplemental

oxygen

showed

a

Po2

of

344

mm

of

mercury,

a

Pco2

of

44.8

mm

of

mercury,

and

pH

7.35.

Because

of

abdominal

pain,

a

surgical

evaluation

was

done.

Bradycardia

and

hypotension

recurred,

but

additional

atropine

was

not

given.

Instead,

fluid

administration

was

begun.

After

six

hours,

he

had

received

4,000

ml

of

fluid

IV

and

his

systolic

blood

pressure

had

still

fallen

to

70

mm

of

mercury,

with

a

pulse

of

54

beats

per

minute.

An

abdominal

x-ray

series

was

initially

read

as

showing

free

air

under

the

diaphragm.

A

subsequent

exploratory

laparotomy

revealed

no

intra-abdominal

disease,

His

hospital

course

was

remarkable

for

persistent

weak-

ness,

recurrent

bradycardia,

and

hypotension.

His

pulse

rate

stayed

between

45

and

55

beats

per

minute

with

systolic

blood

pressures

in

the

range

of

80

to

90

mm

of

mercury.

He

tolerated

these

values

generally

without

symptoms

and

was

discharged

after

nine

days.

Two

days

later,

he

was

readmitted

with

severe

pruritus

unresponsive

to

the

administration

of

diphenhydramine

hydrochloride,

which

had

led

to

a

significant

cellulitis

around

his

buttocks

and

presacral

area

due

to

excoriation.

Mild

orthostatic

changes

in

pulse

and

blood

pressure

were

noted

but

did

not

cause

symptoms.

Case

2

At

12

hours,

the

mother

became

ill

in

the

emergency

department

while

waiting

for

her

husband.

She

complained

of

fatigue,

nausea,

and

chest

pain.

Initially

her

pulse

rate

was

68

beats

per

minute

and

her

blood

pressure

was

132/90

mm

of

mercury.

At

18

hours,

she

had

nausea

and

vomiting

and

complained

that

her

face

and

throat

felt

swollen.

Her

blood

pressure

was

then

noted

to

be

80/38

mm

of

mercury,

and

her

pulse

was

60

beats

per

minute.

Thereafter,

her

pulse

and

blood

pressure

remained

low.

Initial

laboratory

tests

revealed

a

leukocyte

count

of

11.6

x

109

per

liter

(11,600

per

1d),

with

0.69

granulocytes

and

0.27

lymphocytes;

hemoglobin

122

grams

per

liter;

and

hematocrit

0.375.

Serum

sodium

was

141,

potassium

3.8,

THE

WESTERN

JOURNAL

OF

MEDICINE

o

DECEMBER

1991

o

155

9

6

639