The low-salt syndromes in congestive heart failure

The Low-Salt

Syndromes Heart ALFRED

in Congestive

Failure* VOGL, M.D., F.A.C.C

New York, New York

N

years ago Schroeder

INE

dition which

treated

intensively

He described

reported

he had observed for congestive

on a con-

heart

it as characterized

clinically

responsiveness creasing

to mercurial

diuretics,

azotemia.

He named

by

Reports

on similar

ness under

and bio-

outcome

and in-

created

in rapid

of different

the impression

portant,

fairly

of the existence

well defined

DEPLETION

that called for the close attention profession.

These

a period punctuated popularity

by two events:

which employed

of daily mercurial congestive

injections

appeared

which

was regarded

the administration

of

seemed to be the logical remedy physiologic

and thereby

In addition, lowering

of the

establish

electrolyte

experience,

clear that the original

interpretation

ture of the low-salt syndrome plified and was applicable

trary,

few patients.

cardiacs gestive

solute.

On the conhigher

than

(e.g. 65 meq/kg of sodium in con-

failure,

41

meq/kg

dium retained

in

nonedematous

in edematous

patients

of toof so-

was in ex-

cess of the retained volume of water. In patients with low serum sodium concentrations

to

this excess quantity

of sodium cannot possibly be

replenish the presumably depleted salt stores often not only proved to be futile but were ac-

present in the hypotonic

tually followed

must

by an aggravation

in the

subjects) and simultaneous determination tal body water revealed that the quantity

number

attempts

concentrations

has been found markedly

of the na-

had been oversim-

Moreover,

through

heart failure

the total body sodium in decompensated

in the normal

of cases only, and that the therapeutic measures based on that concept proved effective only in relatively

that in congestive

of the electrolyte

it became

to a limited

it has been demonstrated

body stores of the respective

to re-

concentrations

however,

to that of the

serum does not as a rule signify depletion of the total

restore the response to mercurials.

wider

in

rela-

(hyponatremia).

isotope technics

as

of salt in a sufficient

quantity

level is lowered

tion is depressed out of proportion

of this

the cause

states are not uncommon

the serum chloride

tively more than that of sodium (hypochloremia), or in which the serum sodium concentra-

series

self-evident :

and of ra-

facts became

drop in serum sodium concentration.

In fact, pathologic

chloride

measures for the correction

syndrome”

salt depletion

With

with

in the treatment

the following

A fall in serum chloride does not necessarily indicate

the rising

prolonged

technics,

a corresponding

heart failure.

Appropriate

trouble,

coincided

IN CONGESTIVE

evident:

disorder

of salt-free diets and a vogue of a di-

uretic routine

“low-salt

dioisotope

of the medical

publications

events.

With the aid of flame photometry

and

of an im-

iatrogenic

pathogenetic

ill-

and as the

FAILURE

by various

succession

in par-

as a biochemical phe-

a variety of circumstances

ELECTROLYTE

this condition

occurrences

appeared

of serum

hyponatremia

nomenon that can occur spontaneously in protracted

the low-salt syndrome. investigators

the lowering

concentrations,

ticular, has been recognized

and un-

by a fall in serum chloride

Furthermore,

electrolyte

failure.

rapid physical and mental deterioration chemically

failure.

in patients

of congestive

therefore

* From the Third Medical Division of Bellevue Hospital, and the Department College of Medicine, New York, N. Y. 192

THE

be

extracellular

assumed

that

fluid.

sodium

It has

of Medicine, New York University

AMERICAN

JOURNAL

OF CARDIOLOGY

___ Vogl

with a 20 per cent decrease tration,

resulting

(4) Predominant

Example:

in chloride

Fall

in Sodium

a 35 per cent

concentration,

resulting

,m

tration,

d‘0

10

a CI

in sodium

in a level of 100 meq,“l, in chloride

concen-

resulting in a level of 80 meq/l.

Loss of electrolytes

.. ..

-20

Concentration:

decrease

with a 20 per cent decrease

.x-i

conccn-

in a chloride level of 80 meq,‘l.

in excess of loss of water

can produce patterns exemplified at the right.

by the columns

The same figures will, however,

result from dilution

of these electrolytes,

or from

Which

one of

a combination

of both factors.

these conditions

prevails in a given case could be

decided

beyond

estimation

question

only by a concurrent

of the total body water and the total

body electrolytes. It seems, however, currently Fig. 1. Typical electrolyte patterns chronic congestive heart failure.

encountered

in

available

partly

the

(potassium

depleted

and

cellular

elements.

Another

part

into

overhydrated)

of the sodium appears to have entered pots (bone, become

cartilage,

bound

connective

tissue)

to polyelectronic

such as mucoproteins.

solid deor has

constituents,

In such cases the lower-

ing of the serum sodium concentration

is obvi-

ously not the result of a real sodium deficiency but is due to dilution tracellular

of the sodium

fluid, a state therefore

in the ex-

commonly

re-

ferred to as dilution hyponatremia. The

diagram

terns of serum tions

(Fig. sodium

as encountered

1) shows four typical patand chloride in patients

concentra-

in congestive

heart failure :

(1) Sodium

probably

the Xormal Range: patients

Chloride

Concentrations

This pattern

within

is seen in treated

in whom loss of water and of electro-

lytes from the extracellular

fluid has occurred

in

their physiologic proportions. (2) Proportionate Fall in Both Sodium and Chloride Concentration:

Example:

crease of the concentration sodium concentration ride concentration (3) Predominant Example: centration, FEBRUARY,

a 20 per cent deof both, resulting

in a

of 118 meq/l and a chlo-

of 80 meq/l. Fall in Chloride Concentration:

a 10 per cent decrease in sodium conresulting 1959

in a level

of 125 meq/l,

in

the result of electrolyte in cardiac

edema

rapidly

patients

during

patients

a low-salt

syndrome)

dilution.

Con-

diuretic

treat-

of hyponatremia

(and of

is in all likelihood

chiefly

due to true electrolyte Under

depletion.

these circumstances

it is understand-

able, that it has been suggested to abandon term

“low-salt

syndrome”

both inaccurate

altogether

and misleading.

clearly

of the cases,

between

the continued,

has

the biochemi-

and any well-defined

However,

not low

and no relationship

been established

cal findings drome.

the

as being

After all, the

salt stores of the body are admittedly in most

in

this is

who have lost their

vigorous

ment, the development

clinical

syn-

it may be claimed in favor of

though

temporary,

retention

of

the name that it has served as a useful catchword which dramatically

and

to infer from

that

whom edema coexists with hyponatremia versely,

moved

permissible data,

consequences

cal use of potent precise

names

on a convincing with certain

brought diuretic

as a collective

but uncriti-

agents.

Until

are introduced

which

correlation

of clinical

electrolyte

salt syndromes”

changes,

more

are based pictures

the term “low-

may still serve a useful purpose designation

cal and biochemical Types

into focus the dire

of an overenthusiastic

for a group of clini-

complexes.

of “Low-Salt

Syndromes:”

Among

the

syndromes encountered in congestive failure which are associated with lowered serum electrolytes,

two main types have to be kept apart

for practical

purposes :

194

Low-Salt

(1) An during

acute

or subacute

intensive

diuretic

(2) A chronic

form developing

treatment;

form occurring

Syndromes to be found vigorous

in untreated

as

after days or weeks of continued

treatment.

companying

well as in treated patients, therefore evidently not

distinctive

attributable

misinterpreted

to excessive diuresis.

down-hill

THE ACUTE LOW-SALT SYNDROME The acute “low-salt

The

syndrome,” when appearing

in the course of a vigorous diuretic regimen, manifest

itself predominantly or

hyponatremia

as dehydration,

as

It may de-

as hybochloremia.

velop immediately

may

after the first profuse diuresis

or only later after a series of copious therapeutic The

diureses.

symptomatology

types is not distinctive ferentiation

of

the

three

enough to permit

on clinical

grounds.

vere cases are marked

a dif-

The more se-

by thirst, anorexia, and lethargy,

nau-

however,

(2) effect

after

a single

ensue.

excessive

of sodium

sometimes

ceptionally

sensitive to the diuretic Multiple,

mercurial. cramps

patient who is ex-

very

action of the

painful

are often the most distressing

In elderly

muscle

symptom.

people the sudden increase

in blood

viscosity may cause arterial or venous thrombosis. As long as water proportions

and solutes are lost in the

in which they exist in the extracellu-

lar fluid, serum

electrolyte

determinations

not reveal any definite deviations mal.

The

teins,

however,

changes If

rise in hematocrit

will

from the nor-

and plasma

will give an indication

pro-

of the

hyponatremia exceeds Hence

the

patient

has

adequate

extravascular

sodium

loss during

plasma

space

concentration.

In

will

plasma the

soon volume

more

re-esand

severely

excess of sodium quires

during

the excretion

gree of potassium potassium

deficiency

affects

in the

saline adsituations

only or for patients who are unable to take fluids by mouth. Alterations attributable

in the serum electrolyte concentrations to diuretic therapy are more likely

diuresis

cations, invariably

of the potassium (i.e.,

predominantly

accomThe reveal

concentra-

hypokalemia),

the

re-

some de-

of hypochloremia.

serum

cellular

as it

potassium

concentration. (3) vailing

is less likely to be produced

Hyponatremia diuretic

trend

therapy,

towards

Hyponatremia

with varying

unless

depression

of the supervening

is very doubtful

whether

is effec-

chloride med-

is frequently

degrees of acidosis,

of the predominant

the pre-

hypochloremia

by ammonium

tremia complicating ascribed exclusively

Parenteral

diuretics

does not necessarily

itself in a depression tions

mercurial

depletion

lon) is usually sufficient.

in emergency

mercurial

of other

panies the development

or because

is required

diuresis. bound to

whose salt intake is

receives

dehydrated patient, however, oral administration of salt and water (e.g., in the form of bouilministration

mercurial

or even daily, and continues to reSince the chloride excreted in spond to them.

ication.

intravascular

than

loss consistently

frequently

into

a more physiologic

more

as a side

is virtually

a patient

restricted,

tively counteracted

the

sodium

treatment

chloride

depletion

fluid stores a shift of fluid from the interstitial tablish

Lab-

concentration

the

mercurial

since

chloride

by intensive

that have taken place.

as a

state.

is more common

Hypochloremia of prolonged

sharply

no edema or to an edematous

of a possi-

as well as chloride

affecting

develop whenever

with little or

; it should,

distribution

in serum chloride

diuresis usually results when a full dose of a merto a patient

development

tests may then reveal either a predomi-

curial

is given either

re-

may, of course, also

than the chloride.

calf mus-

Acute dehydration

failure.

satisfactory

factor for this refractory

or a depression

prostration

(1)

diuretic

of electrolyte

nant reduction

a fall in blood pressure and a tend-

and some degree of renal failure frequently

congestive

always arouse the suspicion

causative

ac-

has no

and can easily be

of a previously

ble disturbance

levels,

picture

changes

features

course of advanced

cessation

oratory

clinical

as being due to the anticipated

be part of this inevitable

cle cramps,

Oliguria

diagnostic

sponse to mercurial

sea, striking

ency to syncope in the erect position.

The

these biochemical

associated

either

because

of the fixed base renal failure.

It

any case of hypona-

congestive failure to therapeutically

can be caused

In fact, it is now known electrolyte depletion. that in many cases of this kind there is no real lack of sodium but just dilution of it in an excess of extracellular water. Such patients, although THE

AMERICAN

JOURNAL

OF CARDIOLOGY

Vogl they

may

have

electrolyte

excreted

during

large

diuresis,

lost a corresponding

quantities

evidently

amount

have

of not

of water from the

extracellular compartment. The combination of salt

restriction

with

However,

in many

of the

patients

in

whom hy-ponatremia

is discovered in the course it has probably been treatment,

of diuretic present retic

even before

regimen.

In other

found following

electrolyte

depletion

distribution

indication deficit.

apparently

in

congestive

heart

and water also

nature is not well understood.

infections. Its It appears, how-

should when

A correct greatly

and a corThis, in

osmolarity.

turn, induces a shift of sodium into the cells and an adjustment

of the extracellular

hypotonicity-

of the intracellular

adjustment

requires

necessarily body

tenance

fluid to the This

contents. of

results in an expansion

fluid v,olume.

dition

retention The

creation

of such a new and relatively of the body

homeostasis

fluids

involves

water

and

of the total and main-

congestive

assessment

potassium,

mation

hematocrit Secured

at

FEBRUARY,

1959

in congespitres-

This suggests that activation hormone, of this disin

connotes

nitro-

obtained

the

at

this inforseverity- of factors.

More

important

help to

avoid

uncertainty

still, it will materially and

errors

later on, if and when attempts diac

compensation

should

encounter

and

to

in management to establish produce

unexpected

car-

diuresis

difficulties.

It

will then be easier to decide to what extent

Treatment

ex-

for the

of the state of refractoriness. of Dilution

Chronic

Hyponatremia:

dilution hyponatremia is not known to produce any characteristic symptoms. It represents a encountered Since specific

at the correction

of the chemical

are

not available,

limited

with increasing

estimations

more routinely.

therapeutic

are

measures efforts

will

illness and of complicating

of salt restriction;

(2)

be

of the

disorders.

Any plan of treatment should, however, iably include the following rules: (1) tinuation

done aimed

changes as such

to the best possible management

underlying is interested

this particular condition : (1) The presence of hyponatremia

be

this stage,

will aid in evaluating

as electrolyte

order. For two reasons the clinician

of sodium, urea

cessive diuresis may have been responsible

long-acting

of ADH, the pituitary antidiuretic may play a major role in the causation

and/or prolonged

development

and the

is

the disease and the role of complicating

frequency

sin preparations.

a situation

estimation should

“dilution

in patients

disturb-

determination

bicarbonates,

finding

by administering

of such

an

treatment,

chloride,

of the practi-

prior to the institution of a At least in those patients who

laboratory

hyponatremia”

edema.

by the routine

osmoreceptor regulations of the body. Experimentally it is possible to produce typical tive failure

failure,

stable con-

mechanisms

fluid

congestive

changes

in

lead

heart failure?

intensive

and evidently requires modifications

in the volume-controlling

inevitably

electrolyte

are likely to require

outset.

the loss of potassium,

sodium hy-pona-

of the extracellular

diuretic

the

fall in cellular

would

be the attitude

regimen.

of cellular

tion of water,

dilution

of the

of serum electrolytes diuretic

and

which leads to the libera-

sodium

the apparent

encountering

facilitated

gen,

responding

serum

as a therapeutic

SYNDROMES”

ever, that the disorder begins with a disturbance metabolism

efforts cardiocir-

MANAGEMENT OF THE “LOW-SALT

develops not rarely

chronic

expansion

to aggravation

ances in chronic

wasting diseases, in malnu-

severe

for replenishing

to further and

of lowered

be misconstrued

such attempts

tremia,”

tioner

which is now known to occur

and

finding

In cases of “chronic

What

with advanced

in other protracted trition

The

long stand-

It is a disorder of electrolyte

failure.

(2)

levels might

super-

CHRONIC DILUTION HYPONATREMIA Hyponatremia

well-planned

not only the basic

culatory disorder, but also possible complications, such as malnutrition or infections.

hyponatremia.”

in connection

requiring

treating

possibly with acute pulmonary

words, hyponatremia

upon a mild, pre-existent,

ing “dilution

of the diu-

illness

towards

excessive diuresis is most likely

the result of acute imposed

the institution

serious

a

liberal fluid intake may well contribute to the development of hypotonicity of the extracellular fluid.

195

invar-

Conlimitation of

196 the

Low-Salt fluid

intake

administration potassium increase

to about

(or of potassium the chloride

the ever-present

chloride)

of refractory

likely to succeed

this

and repeatedly are indispensable

It

of large

to identify

of

(Dia-

expected

jections

choice

administration cedure

contains The

chloride

is being continued.

results in satisfactory

produced sodium.

ammonium

chloride

net effect

If this pro-

diuresis, far

in

ployed as a means of reviving

be

of total

and,

con-

has been em-

responsiveness

to

dicated. chloride

Not

more

than

ammonia

level

approaches

of little

at this point, the injection

is given

was ineffective

genesis of dilution

hyponatremia.

lar

osmolarity

sodium

from

Administra-

(5 to 6 g potassium

day) may not only promote but the

restoration

also induce cells

into

a satisfactory

deficiency

in the patho-

the

the

chloride

a

of cellureturn

of

extracellular

Thus the pathologic process is reversed space. with which the chain of events started which had led to hypotonicity of the extracellular fluid. For the reasons already discussed, the administration of sodium chloride is clearly contraindicated in the dilution type of hyponatremia. Treatment of Electrolyte Depletion: In contrast to the uncertainties and difficulties with which the

management

of chronic

dilution

hypona-

urea

depends.

until the serum

normal.

While,

as

does not set in spontaneously

peutic measures discussed are apparently

tion of potassium

into

a rule, diuresis

chloride

the detoxifying

of the liver upon which the conversion

thera-

potassium

or

4 g of ammonium

The

of the

inadvisable

infusions of a 1 or

by vein in order not to overtax

lasting effect unless proper consideration to the correction

The

capsules

than in enteric-coated appears

These doses should be repeated

which seems to be a basic element

for the

per hour or 10 g/day should be given

of the liberated

D&iency:

of

Oral

adequate

milieu

action.

chloride.

well tolerated.

a more favorable

Correction of Potassium

hypochloremic

2 per cent solution in 5 per cent glucose are in-

by initiating for mercurial

can

syndrome”

is the drug

the deficient

slow intravenous

capacity

a rise in serum sodium concentra-

of

or to

results

of the drug in gelatine

mercurials. It is conceivable that this method may benefit patients with dilution hyponatremia tion and thus creating

with

If oral intake

impossible,

present

best

chloride

ensures better absorption tablets.

the course

“low-salt

in general,

To at

grounds alone.

doses of 4 to 8 g are usually administration

to

the

associated

to supply

and in

since it is impossible

The

Acidosis:

Ammonium

excess

rise in the concentra-

gestive failure a course of cortisone

to

acidosis.

purpose

tion of the serum sodium. Cortisone: In certain cases of intractable

during

of disorder

when

the urine

is diminution

body fluid with a relative

the type

Hypochloremic be

symp-

situation,

determinations

gauge the progress on clinical

doses

Furnishing the amounts is

response to diuretics.

electrolyte

treatment

acetazolamide

while

serial

in

causative

the clinical

the chemical

the start

proves

given

adequate

in relieving

an adequate

end

mox) . When a high serum chloride concentration has been produced, a series of mercurial inis

in

A special

of a hyperchloremic

and

electrolyte

et al. for the

Acidosis:

administration chloride

deficient

interim.

essential

factor, is much more promising.

restoring

the

of those conditions

is the

depletion

long to permit

cases of this type.

starts with the production by

salt

toms, in improving

during

Production of Hyperchloremic

ammonium

is beset, treatment

which

deficiency;

method has been devised by Rubin

acidosis

tremia

of

or other potent

sufficiently

adaptations

management

(3)

and

in order to

potassium

of mercurials

at intervals

homeostatic

cc/day;

chloride

stores and to counteract

cellular

(4) administration diuretics

1,200

of ammonium

Syndromes

before

of a mercurial

which

is now likely to produce

diuresis.

Hyponatremia: When hyponatremia is present, and either the clinical course or serial electrolyte determinations rivation

suggest that dietary

combined

with

sodium dep-

a significant

sodium

loss plays a major causative role in the respective case, an attempt should be made to replenish the apparently depleted sodium stores. It will be indicated associated

especially

if the hyponatremia

with acidosis.

Hypertonic

of sodium chloride or lactate cent) are used for this purpose.

is

solutions

(usually

5 per

The amount of sodium needed to raise the existent sodium level to normal can be calculated by a formula which takes the estimated sideration.

total

body fluid into con-

Such calculations THE AMERICAN

are, however,

JOURNAL

for

OF CARDIOLOGY

several reasons not of much practical the first place,

administration

In

value.

of sodium

to a

patient with hyponatremia is always to be regarded as an experiment with an unpredictable It is therefore

outcome. administer

clearly

inadvisable

to

the total calculated quantity of soMoreover, clinical improvedium at one time. ment and restoration

of the response

to mercu-

most

cases there

ferent

empirical

treatment

level.

largely

and must be guided by clinical

as well

and

is more

chloride

fluid intake

day- by slow intravenous

of potassium.

evaluated

drip while restricting The result should be

by determining

serum

sodium

from day to day as well as by watching

levels

the body

ployed.

the

treatment

clinical

picture.

If no progress

made or if signs of increasing develop,

the experiment

congestive

is

failure

must be considered

a

failure and discontinued promptly. In hyponatremia as well as in hypochloremia, however,

to a limited

to a considerable

extent,

tassium medication. routinely

chloride

of potassium

po-

be given

In

acetate,

and bicarbonate

hyponatremia

it may be advisable

the

administration

of

centration

or improving administration

hypertonic

in

uncertain

to start treatment

of potassium

alone.

If this measure by itself, after a fair trial, not succeed in raising the serum sodium cautious

as

and in acidosis as a mixture

citrate,

juices.

etiology with

and,

in such cases, in alkalosis preferably

potassium fruit

fluid intake

on simultaneous

Potassium.should

the

clinical

of small

does con-

picture,

quantities

of

saline should be the next step. S~JMMARY

The dromes”

current

concept

and their

marized as follows: (1) The low-salt either clinically

of the

“low-salt

management syndrome

may

syn-

be sum-

is not an entity

or biochemically

but represents

a group of loosely related disorders. (2) The finding of a low concentration

of so-

dium and chloride in the serum can connote either electrolyte loss or water retention. (3)

The

differentiation

states is made largely FEBRUARY, 1959

between

on clinical

these

grounds.

be

achieved

to furnishing

includes

the

and the concurrent

if

sodium

restriction

of

administration

It can,

by and large,

is individualized,

the diuretic

procedures

be avoided

if

and if the effect of

is critically

evaluated

from day to day. BIBLIOGRAPHY

success appears to depend on the con-

tinued adherence

but

to

con-

(6) The iatrogenic production of a “lowsalt syndrome ” is not an inevitable risk whenever a low-salt diet and potent diuretics are em-

vveight, the urine output and, last but not least, entire

likely

is not limited

more than 200 to 300 cc of 5 per cent saline per oral fluid intake sharply.

types,

remains

as by laboratory observation. Correction of the altered electrolyte (5) centrations

of

are dif-

and the dilution

but in a given case treatment

rials has been found to occur before the serum had reached a normal probably wise to give not

a combination

of management

for the depletion

sodium

concentration It is therefore

is probably

both factors. (4) The principles

two In

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