Administration of Digoxin

Administration of Digoxin Roger W. Jelliffe Dis Chest 1969;56;56-60 DOI 10.1378/chest.56.1.56 The online version of this article, along with updated information and services can be found online on the World Wide Web at: http://chestjournal.chestpubs.org/content/56/1/56

Dis Chest is the official journal of the American College of Chest Physicians. It has been published monthly since 1935. Copyright1969by the American College of Chest Physicians, 3300 Dundee Road, Northbrook, IL 60062. All rights reserved. No part of this article or PDF may be reproduced or distributed without the prior written permission of the copyright holder. (http://chestjournal.chestpubs.org/site/misc/reprints.xhtml) ISSN:0096-0217

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THERAPEUTIC

GUIDELINES

Administration Roger

W.

Jelliffe,

factors

talis sympathetic

affect

therapy. support

a patient’s

Ischemia, to the

myocardium

total amount the patient’s tors

M.D.#{176}#{176}

INTRODUCTION

M any of the

of Digoxin*

electrolyte myocardium,

to respond

or concentration body are some

which

response

may

affect

to

digi-

and

a patient’s

response

The

therapeutic

approach

to digoxin

described

help that

of glycoside is presently

in the intended

roid

in

electrolyte

no

obvious

absorption. ance upon under

normal

abnormality

The this

influence therapeutic

em-

to clarify one of these of the total amount or

concentration This approach patients

here

of

the

total

amount

this,

a certain

the

body

initial

is lost

dose

time

the

dose

been

lost

certain raises

the

total

proportional

body.

Because

amount

to

present

trations,

chemically with

at death,

when

sets

total

is given,

a certain

body

various

by

again

new

total

approximately is lost

per

the day,

same

has

if renal

function

of

a

tient’s

endogenous

creatinine

percent correlated clearance.3’4

of total with

Medicine, *eASsOCiate

the

University Los Angeles, Professor of

of

Southern

California,

School

from

shown

in

concenare

highly

digoxin

stores

as milligram

per

i

digoxin

clinical judgment, the patient’s weight body

he desires

stores get

If not,

this

than

tained

of

cachectic by

the

stores

rising

and

he

per

physician

therapy. whether

are

close

a

He can or not

or falling can,

on his

using

now adjust and renal

a creatinine make

you

think

estimate

his

digoxin function

to

any

serum

1 mg/

100

creatinine

saying

his until

a stable

or

clearance

tradosto

selected

ml,

that

initial

creatinine you

obtain

creatinine

a dialysis creatinine

56


in

is, a true

clearance. level

rough

a very

paesti-

clearance

can

creatinine

clearance

on

on your

a reasonable

endogenous

of

have

gives

reasonably

so.

of what use

digoxin

for his patient.

can

do

measurement

not

California. Medicine.

stores program,

in

19 of toxicity

(milligrams

to digoxin confidence

ditional age to

greater

of

thus

shown

Discussion). body

concentrations

patients

with

as

59 patients, of digitalis

(see total

dosage

level

on

evidence

body

keep

correlated

digoxin,

data

programs

total

If you

highly of

to calculate in

estimate *From

share As

body

in

myo-

at autopsy,

also

present

mate

hod-#{149} a paThus

body

the

digoxin

expressed

from

and useful guide with reasonable

tient,

remains

is

new know

and that the is highly

are

and

If you

the

stable. It has been shown digoxin lost per day

usual body.

total

concentrations

ability

kilograms)

and

percent

they

treatment

of

for the

percent

measured calculated

2, obtained had developed

(milligrams)

body

routes,

its

can

amount determines as

myocardial

toxicity

body

to

of digoxi’-

of that dose, adjusted as shown later. By

up

in the

of

he

total

toxicity,

take

example,

correlated

on other

percent still remains. The next dose given total body digoxin stores to a new level, and

once

1, for

Figure whom

day.

a patient

percent

dose,

cumulated

and

amount

Digitalis

electrolyte balis currently

are

the

each

given

at the level absorption

from

in

of the

digoxin stores gastrointestinal next

body

present

percent

in a patient’s The

from

the

It is this total cumulated body that essentially

appears

The losses

and each

patient’s

the

study.

Digoxin

his

effect

total

given

between

cardium

total

who

gastrointestinal

of altered approach

doses lost

kilogram.5

patient’s body.14 for adult euthybalance

daily

calculate

Figure

ploys methods which important parameters,

the amount

pharmacologic

i” fac-

therapy.

have

total

digoxin stores. the patient’s

the

of digitalis present of many important

knows

the serially

imbalance, the ability

to digitalis,

one

which but

patients

program clearance

who

can

is

simple are

be

ob-

=

100

ADMINISTRATION

OF

DIGOXIN

57 able the

.3O/1/

/I

Adjusting proximately

///

I-

to assume that average, reaches

tive

I/i

///

,

the

the

tient

/O//

//

0.319,

daily

dose

a steady

(1)

5

/

o

/

/

find

that

patients

.10

are

taking

oral

doses

are

body total

amounts oral loading

(2) 1

/

.05

total

oral

about

1 LL

.004

.012

CALC.

J

.020

BODY

,0

DIGOXIN

.030

CONC

(uq/m)

1. Correlation between myocardial digoxin concentration (chemically measured at autopsy) and computed body digoxin concentrations at time of death.5 These body concentrations were comptited from serial data of digoxin dosage and blood urea nitrogen.4 These patients had not been treated by the method described here. The two patients shown by circled crosses had died with unequivocal evidence of digoxin toxicity. They had the highest FIGURE

myocardial total body

digoxin digoxin

(circled dots, of toxicity.

x (1/serum

concentrations concentrations.

including

five

time,

urine

and

the

The

control

highest

other

patients)

the

losses

determine

If possible,

specimen

since

digoxin

Let

pa-

had

us begin

by

(creatinine

clearance

the

state

steady

doses

of

0.25,

data

no

define

the

most

patients

what

0.375,

the and

percent method

to

amounts normal mI/mm)

105

common 0.5

of digoxin renal function who are in

fixed

oral

of

digoxin

mg

doses

CHEST,

mg

respectively, dose.

be

felt,

daily re-

is

fully

absorbed.

VOL.

56,

NO.

1,

JULY

These

amounts

loading

normal

will

not

optimal with that

in

for most

patients.

loading

dose

may of

loading

adequate

oral

or

six

the

effects

doses

in

this

of

therapeutic

given

in

or

par-

depending In

This

evaluate

range

orally

about

apart. to

such

are notably rhythm. It is

situation.

hours

op-

Objective

absorption)

dose

time

achieve

degrees be

for

urgency

five

are

daily

patient.

digitalization regular sinus

reasonable

(adjusting

the

single

loading

effect

doses

for

who

common

necessarily

in any

however,

allow

to

required

function

the

from

appear

dose

renal on

range

above.

result

general,

try

three

divided

should

usually

relatively

rapid

rate

in atrial

as ventricular

fibrillation, and yet it lets you get the loading dose in, titrated to that response, at least, within 12 hours so that significant excretion can be neglected for practical purposes. If the patient requires more, continue reasonable curs.

However, passes access reason-

1.5 mg.

should

the

by

Reasonable

thus

with

amounts

give

respectively. should

of the

of truly in patients

upon

these

achieved

doses

digitalization

criteria lacking

Since

effective,

100% mg

maintained

These timal

in such

________________ Oral Loading Dose

=

1.42

described

If ber digoxin dose

this stepwise response or

Subsequent

dosage digoxmn

only about 80 to 90 percent of oral digoxin the portal and hepatic circulation and gains to the rest of the body.6’7 It thus appears DIS.

stores

daily

should

ranges

responding

spectively.

Parenteral

1.22 oral

digoxiii doses of

and

subsequently

to

DOSE

with =

on

daily

that

a

crea-

clearance.4

LOADING

asking

use

serum

of

using

creatinine

in patients

however,

a fasting

obtained

endogenous

present

and

subsequent

were

THE

are

and fixed

85 percent

0.7 to about

The

creatinine).

hour

100%

about

loading

enterally

24

only

1.06,

daily percent

35

Amt

85%

/

tients evidence

0.91,

of

equal =

digoxin

Amt, or Parenteral Loading_Dose

or 0.71,

/

measured computed

body

the

/

/

/

(%)

total

0.61,

after

respectively.

(see The Maintenformula for the pa-

=

losses

peak

just

mg

losses

stores the

Dose

Daily we

doses for apgives effec-

losses

daily

on

state

Effective

/ /

O

0.425

daily

=

/ /

z

and

state

body digoxmn below). Using

in such

of oral digoxin, circulation.

common oral oral absorption

steady

of the total ance Dose,

/7/

.20’-

of 0.213,

in

intake, I

the above 85 percent

doses

Since

/7/I

85 percent the general

methods

have the that

been

patient even may

(and

biological evidence

previously has regular though a

be present thus

of

in

his

in

his

titration until a of overdosage ocdealing

with

over-

discussed.4 sinus rhythm, rememreasonable amount of body

myocardium),

1969


from

the it takes

loading time

58

ROGER at Figure

100

daily PTS. E

TOXICITY

4 or

centrations

90

one

day

cent

70

z

uJ

60

U-

50

the

of

total and

The

maintenance normal

renal will

mainly

(3)

20

where ance

10 I

.03

.04

BODY 2

FIGURE toxic

Relationship

and

glycoside

patients

computations ment programs, toxicity.

in

to have

a good

statistics

of

Figure

mg

give

52 patients, 19 of whom

diuresis.

total

who

computed

one

evaluate

Lost

creatinine

is

creatinine (or the

cleargraph),

(CC/5)

endogenous this equation

50/5,

it equa-

is

14+

=

If

empirical

clearance

mI/mm

is 50

or approximately

24 percent

I

ORAL-

/

PARENTERAL----

the

those

versus

When

body

the

been

previously

does

not

to

of

to

mg/kg

in

from

approximately with toxicity

of data

this

try

to

evaluate

concentration

If the

slower about

approximately

clinical

approach, 0.013

in and

elective,

a body

of subsehave

then

it seems

(this

value

of

patients

with

toxicity), again parts. Remember

dividing the loading dose that parenteral loading

into three and main-

tenance

are

their

doses

only

85

percent

of

I

situation

mg/kg

9 percent

‘U

a 160-lb

the

5 percent respectively.

is relatively

discussed.4

1.5

concentrations

0.0175

to

of 0.75

first, if possible. Methods for body digoxin stores, if desired,

permit

reasonable includes

glycoside

response

mg/kg raising

doses

concentrations,

situation

patient’s

loading

body

Figure 2, include 29 percent of patients

oral

counterparts.

BODY THE

MAINTENANCE

FIGURE

DOSE

achieve

After

routes. the

of

total

must

response

0.0085

These

0.0085 quently

percent

body is derived from 59 such had received other treathad evidence of digitalis

Here

3, oral

approximately

the

graph

(crea-

14 percent

E

will

adult.

patient only

=

body

07

.

cumulated

various

Data

satisfactory

toxicity. As in

this

total

(mg/kg)

the

at

concentrations.

.05

CONC.

between

nontoxic

14 plus

lose

axis,

A patient

Y

.02

.01

whose

lose

anuric

pa-

clearance

hepatobiliary

CC represents (mI/mm). Using

a patient

will

an

per-

vertical

of his

at a graph,

describes Percent

the

will

the from clearance.

(creatinine

while

by

day

losses.4

35 percent

zero)

to look

which

30

function

on daily

dose

given.

creatinine

shown

lose

=

been

each

con-

this

between

lost

such

day,

clearance day,

tion

LI

dose,

in one

has

proper

digoxin

Start

relationship

to replace

cumbersome

4C

0

dose

JELLIFFE the

body

endogenous

ml/min)

to find

level.

digoxin

their

105

per

#{149}1

the

with

tinine

desired

body

tients

(3)

to sustain

loading

4 shows

digoxmn 0

your

after

is designed

‘I, I.-

equation dose

at

Figure 80

use

maintenance

W.

the

total

loading

dose

has

been

given,

look

3. Graph of body digoxin

oral

WEIGHT

and

(lb.)

parenteral

concentrations

of

loading 0.0085,

doses 0.013,

to and

0.0175 mg/kg.

DIS.

CHEST,

VOL.


56,

NO.

1,

JULY

1969

ADMINISTRATION

OF

DIGOXIN

59

4. Relationship

FIGURE

daily

percent

maintenance pressed

digoxin per day, daily maintenance

cent

of the

if the

loading

loading

you

well suffered may

on

given

was

felt

WITH

CHANGING

with

known

If a patient doing then

dose

dose

PATIENTS

for example, dose would

a certain a sudden

daily reduction

renal

of endogenous

creatinine

tomorrow’s creatinine

Adjust

digoxin

stores

viously

doing

renal

constant well

function

level

digoxin

oral

with

86

provides

the

closely the

This

im-

output. and

easiest

size

slide

can

be

for

example.

only in physician would

0.125,

to reach

selected

dose.

Tablets

are

and

calculated

desire

having

for

to have

to

of 0.216

0.25,

has

culated

much

a dose

patient,

pills

cut

reasonable

be mg

can

only

VOL.

56,

NO.

he into

hope 1,

this

of dig-

therapy

of

the

provide

0.215 elixir

Moreover,

of

to achieve

such

the

form

elixir

dosage

form

absorption

therapy

produces rule

by were

then

halves

JULY

that

is and

of the pharma-

body with

perform

who

up

do

digoxin

serial

terminals

computations and give the

puter which prints past glycoside concentrations

renal enters and

and

is. To

this

glycosides

data of dosage and phone. The operator

however,

calculations

stores

concentration

other

A pocket-

this,

concen-

of past historical or hosa patient’s present cal-

to extend

computer such

call

digoxin and

Even

must

body

arithmetic.

errors.

helpful.

if one total

problem

requires

arithmetical

is most

laborious

time-shared

at present

approximations

One

desired

0.5 mg sizes. the oral dose he

his

tablet,

ml

of pediatric

way the

mg

4.3

would use

of gastrointestinal

method

of cumulated

adjust

DIcoxIN

OF

a 0.25

mg/

example,

DIScUSSION

pre-

often

cardiac

frequently

leave

for

out

approximates data

(0.05

mg,

of

that

precision.

most

0.216

which

in dosage

digoxin

measure

appears

same

creati-

range of color-

accuracy of

percent

a syringe,

(extotal

clearance.4

of

easily

It currently

which

the

given

endogenous

present

dose

give more

by

dose

and

elixir

most body

he was will

improving

to give

mouth,

CHEST,

an than

dose the

route),

trations over a long period pital data to find out what

quarters

DIS.

For

Arithmetic

clearance

wishes

with

ml).

may

of

obtained.6’7

dose to his to keep total

that

PREPARATIONS

by

pediatric

therapeutic

measurements

at the

preparations

available After the

the

of digoxin

stores. period

with.4 by

creatinine accordingly.

one

use

elixir

clearance.

digoxin clearance,

remember

Current

ideally

of digoxmn and in renal function,

daily)

as well. way to improve

rather

digoxin percent

will provide a greater in the future, perhaps

is to

one

function. (preferably

In addition,

faced

dose

was

total body digoxin stores through his

frequent

recent

oxin

FUNCTION

clearance

companies tablets

coded One

route, one.

mg.

of altered

when

same

then:

3. Get

Check dosage

the

ceutical convenient

his proper be 24 per-

a proper

creatinine

Calculate his previous 2. Try to preserve these

prove

by to be RENAL

1.

4.

and thus

as

loading nine

of his single

between or daily

losses

approach

as well,

operators

in central rapidly operator function this data


to of

areas

can

for physicians the pertinent over into

present cumulated which the calling

1969

alleviate

basic

the the

telecombody physi-

ROGER

60 cian

can

ent

clinical

compare

tell

the

with

operator

tration

he

operator

gested

dose

wishes,

his

total

wishes this, and

and

proper The

adjusted

in

to of

concen-

his

clearglycosides,

such

calls

were

to

control

though If other

digitalis given,

leaf

and the

but

available

data

one

glycoside

by

terminal)

protox-

made

required

lanatoside situation

permit

tral

is available

by

in

an increased such as dig-

C have more

is

with

rate

at

proper

another

JELLIFFE

ventricular

probably preparations

also been complex,

replacement

of

a different

excretion if creatinine clearance easy access to computers (such

from

treatment of digitalis

be

itoxin, recently

physician’s

2 is derived

icity

before

atrial fibrillation, risk of toxicity.

have. The prints a sug-

other

Figure on other evidence

shortly

may

then

creatinine

59 calls on 52 patients grams, 19 of whom had at or

to

and

replacement data

pres-

glycoside

patient computer

weight

and may

past

physician

body

his the

program, patient’s

if present.8

patient’s The

what

now

enters

ance,

his

performance.

W.

rate

of

is known3 and as a time-shared

a telephone

call

if

to

a cen-

mit

Herz-

facility.8’0

by REFERENCES

physicians

in the

suggested

dose

described factory

Los

here, clinical showed

Thirty-seven involved

cent) of

50

on

of 52

the

manifestation

(or 71 patients or

or

reported

with

less.

of

while

19

satiseight

2 3

4

clearances

results

will

be

1. 6 SUMMARY

described

Gun.

to

requires

the

type

clinical

of

Med.,

patient

judgment

108:531,

plus

tiated

careful

adjustment

function

and

of dosage

body

weight.

concentrations

of

appear

reasonable

to give

many patients. proximately patients

0.0085,

if

patient’s

and

toxicity. possible.

Start

digoxin

0.0175

mg/kg

include respectively

apof lower

ascetic

that

worthy

of

upon

its

elevate by could tian

he the

was,

beauty. and

saw.

painter.

possessor

pure

did

the

But

by The

see they

splendor grim, harsh

exclaimed

name

humanity

full

that Such

clear leaving

Venetians with

could

not

only

their vision

recognize

was

as his imposed

inescapable enriched

and

physical

Titian

gift

a

and it

of Titian’s maold Florentine

duty and fellow

to

Amer.

G.K.:

MITCHELL,

subjects,

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subjects

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intravenous

ad-

1962. for

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lofts’

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skill color

of

and and

digItalis Fed.

dos-

Proc.,

27:

digitalis

27:248, Dr.

dosage

pro-

1969.

Jelliffe,

Zonal

2025

Los

Avenue,

vision

spiritual the

common

perceiving.

without

ran eye

far and

above

and

mind,

his

beyond marvelous

indefatigable labor fixed forever in glowing luminous themes all his fellow men had seen He

did

his

duty

to

his

genius

and

mankind.

Riggs,

Italians

everything

fiuorometric

autopsy,

COLORS

to

ennobled

ther-

1968.

Reprint Angeles

IN

A

at

AND

human

Computer

Amer.

grams,

concentrations

SYMPHONY When he studied the turer work, Michaelangelo,

9

digoxin

R.G.:

W.H.,

human

telephone

348,

of

digoxin

in

AND in

R.W.:

age-a

for

the

digoxin

JELLIFFE,

func-

1961.

ministration, 8

response

with

Greater

renal

body

therapeutic concentrations 29 percent

digitalis

concentrations

the

0.013,

These 9 and

5,

with

to Calculated

digitalis

renal

1969.

studies

J.E.,

7 DOHERTY,

method

STEPHENSON,

PERKINS,

J.E., digoxin

of

reduced

1968.

myocardial

51:347,

DOHERTY,

and

improved

AND

dosage

1967.

69:703,

of

Path.,

Tritiated

of digoxin here

R.W.,

determination

drug

analysis

normal 1:305,

An

mt. Med.,

Ann.

of

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Inathematical with

R.W.:

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theory

13:212,

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5 JELLIFFE,

more

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apy,

A

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Formal

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tion,

32:945,

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J. Theor.

JELLIFFE.

zur

Wschr.,

KRUGER-THIEMER,

kinetics

per-

Quantitatives

Kim.

regimens,

dose clear-

36

A.:

AUGSBERGEH, glycosiden,

digitalis

(or

creatinine

These

1

method

percent) of these with creatinine

less,

patients

ml/min

fully

some

ml/min

involved 25

based

date,

47 of 48 were associated with response, while only four (or

toxicity. programs of

area.#{176}To

programs

percent)

ances

Angeles

and

Ti-

New

its significance.

DIS.

CHEST,

A. Venice

S.:

York,

1946

VOL.

56,


Titian

of His

the

Day,

NO.

Magnificent

Bobbs-Merrill,

1,

JULY

1969

Administration of Digoxin Roger W. Jelliffe Dis Chest 1969;56; 56-60 DOI 10.1378/chest.56.1.56 This information is current as of July 14, 2011 Updated Information & Services Updated Information and services can be found at: http://chestjournal.chestpubs.org/content/56/1/56 Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.chestpubs.org/site/misc/reprints.xhtml Reprints Information about ordering reprints can be found online: http://www.chestpubs.org/site/misc/reprints.xhtml Citation Alerts Receive free e-mail alerts when new articles cite this article. To sign up, select the "Services" link to the right of the online article. Images in PowerPoint format Figures that appear in CHEST articles can be downloaded for teaching purposes in PowerPoint slide format. See any online figure for directions.
