SYSTEMIC HYPERTENSION

Diuretic-Induced Hypokalemia in Uncomplicated
Systemic Hypertension: Effect of Plasma Potassium
   Correction on Cardiac Arrhythmias

VASILIOS PAPADEMETRIOU, MD, ROSS FLETCHER, MD, IMBRAHIM M. KHATRI, MD and
                 EDWARD D. FREIS, MD

Sixteen patients with diuretic-induced hypokalemia
underwent 24-hour ambulatory electrocardiographic
monitoring during and after correction of hypoka-
lemia. Plasma potassium averaged 2.83 f 0.08
mEq/liter before and 3.73 f 0.06 mEq/liter after
correction with potassium chloride, triamterene or
both. Premature atrial contractions decreased in 6
patients, increased in 6 and remained unchanged
in 4. There was no improvement in ventricular ec-
topic activity after plasma potassium correction.

Ventricular ectopic activity improved in 5 patients,
worsened in 10 and remained unchanged in 1.
Ventricular tachycardia was not observed in either
phase. Plasma magnesium remained normal
throughout. The investigators conclude that in pa-
tients with uncomplicated hypertension, correction
of diuretic-induced hypokalemia does not signifi-
cantly reduce the occurrence of spontaneous atrial
or ventricular ectopic activity.

(Am J Cardiol 1983;52:1017-1022)

Of all patients who receive a thiazide diuretic for the
treatment of essential hypertension, in 20 to 40%
hypokalemia will develop.lp2 Because of side effects
associated with hypokalemia, potassium chloride or
potassium-sparing diuretics are often administered to
patients who receive diuretic therapy. Considering the
number of patients who receive diuretic therapy, it is
not surprising that the amount of potassium chloride
prescribed annually is estimated to be 20 to 30 billion
milliequivalents." This practice has been maintained
despite several recent reports that question the need for
routine potassium replacement therapy and even point
out the potential risk of such treatment.3-5

An increase in cardiac arrhythmias is considered one
of the major risks associated with hypokalemia. The
increased susceptibility to digitalis-related arrhythmias
in hypokalemic patients has been well documented6,7
and is widely accepted. However, in patients with hy-
pertension uncomplicated by cardiac disease, an asso-
ciation between thiazide-induced hypokalemia and an

From the Veterans Administration Medical Center, Washington, DC.
Manuscript received April 12, 1983; revised manuscript received July
8, 1983, accepted July 12, 1983.
Address for reprints:- Vasilios Papademetriou, MD, Veterans Ad-
ministration Medical Center (151E), 50 Irving Street, NW, Washington,
DC 20422.

increased incidence of arrhythmias has not been es-
tablished, and the subject remains controversial. Ex-
amining routine electrocardiograms retrospectively,
Pick8 concluded that a potassium deficit by itself can
only exceptionally affect the formation and conduction
of normal impulses, whereas Davidson et a19 suggested
that patients with hypokalemia without heart disease
who do not take digitalis had an increased incidence of
ectopic beats. However, examination of routine elec-
trocardiograms is a poor indicator of cardiac ectopic
activity, and conclusions drawn from these studies
cannot be considered representative or reliable.

The present study investigates prospectively the ef-
fect of correction of hypokalemia on cardiac arrhyth-
mias in patients with uncomplicated hypertension and
hypokalemia secondary to long-term diuretic therapy.
Twenty-four-hour ambulatory electrocardiographic
recording was selected as the most reliable method of
identifying cardiac arrhythmias.lcJl

Methods

Patients: Twenty-one hypertensive patients entered the
study; all of them had a serum potassium level 13.2 mEq/liter
while receiving diuretic treatment. Patients were excluded
from the study if they had a history of myocardial infarction,
angina pectoris, congestive heart failure, renal insufficiency
(creatine 12.0 mg/dl), active peptic ulcer, significant mental

1017


1018   HYPOKALEMIA AND CARDIAC ARRHYTHMIAS

TABLE I Patient Characteristics

                          Hypokalemic Phase       Normokalemic Phase      Daily Dose of
                      Anti-HTN
Pt    Race   Age (yr)    Medication*      PK      PW        PK      PMS    KCI (mEq) Triam (mg)

P, M, HCTZ
M. HY. HCTZ
HCTZ
M, HCTZ
P, HCTZ
P, CH
CL. HY. HCTZ
R, CH
HCTZ
P, CH
HCTZ
HCTZ
HCTZ
CL, CH
HCTZ
HCTZ

5:;
3.2

2.8
2.9

f::

2.9
2.5
3.2
8::
3.0

2.6
2.3
3.0

1.6
1.5
1.3
1.4
1.5
:::
1.4
1.3
1.6
1.2
1.2
1.6
-

G

3.5
3.5
3.9
3.8
3.5
3.5
4.1

3.8
3.8
3.9
3.7
3.6
3.7
3.6
4.3
3.5

1.6
1.7
1.4
1.4
::t
1.6
1.7
1.4
1.4
1.7
2.0
1.8

-

G

       150
72      200

;:
       200
72
72
4:      200
       200
48

       200
       100
96

::       200
48

Mean f SEM       52.75 f 2.3             2.83 f 0.08   1.49 f 0.06   3.73 f 0.06   1.59 f 0.06

CH = chlorthalidone; CL = clonidine; HCTZ = hydrochlorothiazide; HTN = hypertension; HY = hydralazine; KCI = potassium chloride; M =
methyldopa; P = propranolol; PK = plasma potassium; PMg = plasma magnesium; R = reserpine; Triam = triamterene.

illness, digitalis therapy for any reason or peripheral edema
of any origin. Five patients were terminated from the trial: 3
because of noncompliance, 1 patient because he developed
depression while receiving reserpine and chlorthalidone and
left the study and 1 because he developed overt hyperglycemia
that required insulin treatment. Of the 16 patients who
completed the study, 14 were black and 2 were white. They
were 29 to 69 years old (mean f standard error of the mean
[SEMI 53 f 2). Twelve of the 16 patients had normal elec-
trocardiograms, 2 had left ventricular hypertrophy by voltage
criteria only and 2 had nonspecific changes in leads III and
aVF. All patients had been receiving treatment for essential
hypertension that included diuretic therapy for 4 to 48 months
(mean 17 f 3) before entering the study. Twelve patients were
taking hydrochlorothiazide, 50 mg twice daily, and 4 were
taking chlorthalidone, 50 mg once daily. Hypertension was
controlled with hydrochlorothiazide alone in 7 patients and
9 required regimens of 2 or 3 drugs that included methyldopa,
propranolol, clonidine, reserpine or hydralazine in addition
to the diuretic (Table I). The antihypertensive regimen did
not change throughout the study. All patients required po-
tassium chloride supplement or a potassium-sparing diuretic
to maintain near-normal serum potassium levels before the
study.

No specific dietary instructions were given other than to
observe moderate salt restriction; that is, to avoid heavily
salted foods and to add no salt at the table.

Study protocol: All patients were seen every 2 weeks. At
each visit throughout the study, sitting blood pressure, heart
rate, body weight and plasma creatine, sodium, potassium,
chloride and magnesium concentrations were determined.
Blood samples were collected in sterilized lo-ml tubes that
contained 143 units of lithium heparin and were analyzed
within 30 minutes.

Phase l-Screening phase: Potassium chloride or potas-
sium-sparing diuretic therapy was discontinued and patients
were seen every 2 weeks. Antihypertensive therapy was con-
tinued. Only patients whose plasma potassium level was re-
duced to 53.2 mEq/liter during any 1 of a possible 4 successive
visits were included in the study. Once hypokalemia was
confirmed by this criterion (plasma potassium 53.2 mEq/
liter), additional tests, including 12-lead electrocardiography
and arterial blood pH and gas determinations were performed.
Twenty-four-hour ambulatory electrocardiographic moni-

toring was initiated within 2 hours after hypokalemia was
confirmed and completed before replacement therapy with
potassium chloride was begun.

Phase 2-Potassium chloride replacement therapy: After
baseline studies described under phase 1 in all patients with
plasma potassium 13.2 mEq/liter, replacement therapy was
initiated with 3 tablets of 8 mEq of potassium chloride in a
wax matrix ("Slow-K") 2 times daily (48 mEq/day). The dose
of potassium chloride was increased every 2 weeks until hy-
pokalemia was successfully corrected or the maximum dose
of 96 mEq/day was given. Successful correction of hypokale-
mia was considered to have been achieved when the plasma
potassium was 23.5 mEq/liter and was at least 0.5 mEq/liter
higher than the unsupplemented baseline value. In patients
who achieved correction of hypokalemia, 24-hour ambulatory
electrocardiographic monitoring, 12-lead electrocardiography
and arterial blood gases and pH were obtained on the same
visit that the correction of plasma potassium became mani-
fest.

Phase 3-Triamterene alone or with potassium chloride:
All patients who completed phase 2 entered phase 3. Potas-
sium chloride therapy was discontinued and hypokalemia
(plasma potassium (3.2 mEq/hter) was allowed to recur after
which triamterene, 50 mg twice daily, was begun. The dose of
triamterene was increased every 2 weeks until hypokalemia
was successfully corrected or the maximum dose of 200 mg/
day had been given. In patients whose hypokalemia had not
been corrected with the maximum dose of either potassium
chloride or triamterene, a combination therapy of triamterene
and potassium chloride was instituted. Again on the same visit
that plasma potassium was found normalized, 24-hour am-
bulatory electrocardiographic monitoring and 12-lead elec-
trocardiography were performed and arterial blood gas was
obtained from patients whose hypokalemia was not corrected
in phase 2 but was corrected in phase 3. Arterial blood samples
were taken before and after correction of hypokalemia from
12 patients. The 4 other patients refused sampling.

Ambulatory electrocardiographic monitoring: Am-
bulatory electrocardiographic monitoring was carried out for
24 hours using a double-channel model 425 Avionics recorder,
and analysis was performed on a model 660A Avionics 2
channel electrocardioscanner. Analysis of all tapes was carried
out by an experienced technician. For quality control, 80% of
the tapes were also analyzed by a second technician. Minimal


November 1, 1983 THE AMERICAN JOURNAL OF CARDIOLOGY Volume 52

1019

0      Before      Diuretic     Diuretic +

         l&tic      Only     K+ Repletion
FIGURE 1. Plasma potassium (Kf) levels before any diuretic therapy,
on diuretic therapy alone and after correction with potassium chloride
triamterene or both. o p <O.OOOl. SEM = standard error of the
mean.

interobserver variability was found. In addition, samples from
each hour of recording, including the important arrhythmias,
were printed on hard copies, in real time, and were reviewed
by 1 of the investigators.

Cardiac arrhythmias were tabulated for convenience under
subgroups as follows: (1) supraventricular-premature atria1
contractions (PACs) 1 to 9,lO to 49 or 250 per hour. Supra-
ventricular tachycardia, atria1 flutter or fibrillation and
atrioventricular disturbances were reported as separate
events. (2) Ventricular arrhythmias-premature ventricular
contractions (PVCs) unifocal 1 to 9, 210 per hour, multifocal
1 to 9, ZlO/hour, PVCs in couplets and ventricular tachy-
cardia.

Statistical analysis of the results was performed where
appropriate using Student's t test for paired observations.
Fisher's exact probability test was used to determine statis-
tical significance between patients with couplets before and
after correction of hypokalemia.12

Results

The 16 patients who constituted the study group were
known to have had hypokalemia in the past and had
been receiving potassium chloride or a potassium-
sparing diuretic. Review of the charts of 14 of these
patients for which pretreatment data could be found
revealed that they had normal serum potassium levels
(4.20 f 0.09, mean f SEM) before diuretic therapy for
hypertension. In all except 1 patient, the plasma po-
tassium was reduced to 13.2 mEq/liter within the first
2 weeks after the potassium chloride or the potas-
sium-sparing diuretic was discontinued. In the 14 pa-
tients with prediuretic serum potassium of 4.20 f 0.09
mEq/liter, the unsupplemented plasma potassium was
reduced to 2.83 f 0.08 mEq/liter (range 2.20 to 3.20)
(Fig. 1).

After correcting hypokalemia with either potassium
chloride alone, triamterene alone or a combination, the
plasma potassium was increased to 3.73 f 0.06 mEq/
liter (range 3.50 to 4.30) (p <O.OOOl). Of the 16 patients,
only 8 were corrected with potassium chloride alone in

TABLE II  Changes in Acid Base Balance (n = 12)

              During       After K
            Hypokalemia    Repletion   p Value
Arterial blood pH    7.43 f 0.01    7.41 f 0.01    NS
Arterial PaGO*      43 f 2       40f 1
Arterial HCOs       28f 1       24f 1   ON:2
Urine pH         6.42 f 0.34    5.83 f 0.21   ti3
K = potassium; NS = not significant.

doses up to 96 mEq/day. Of the remaining 8, 4 were
corrected with triamterene alone in doses up to 200
mg/day and 4 required the combination of triamterene
200 mg plus potassium chloride in doses of 48 to 72
mEq/day.

The mean plasma magnesium was 1.49 f 0.06 mEq/
liter during the hypokalemic phase and 1.59 f 0.06
mEq/liter after potassium repletion (Table I). This
difference was not statistically significant. Although
several patients had low borderline plasma magnesium
levels of 1.2 or 1.3 mEq/liter (normal range 1.3 to 2.1),
there was no correlation between plasma magnesium
levels and the occurrence of cardiac arrhythmias.

The mean arterial blood pH, COz, HC03 and urinary
pH were examined in 12 patients before and after cor-
rection of hypokalemia (Table II). Although the mean
values were within normal limits, values for individual
patients indicated mild metabolic alkalosis during the
hypokalemic phase. Although no significant change
occurred in pH or PaCOz after correction of hypokale-
mia, a significant (p <0.02) reduction in HC03 con-
centration was observed, indicating a shift to a less al-
kaline state. No change was observed in the acidity of
the urine. However, these changes in the acid-base
balance between the 2 phases were mild and it is very
unlikely that they significantly affected the ratio of
intracellular to extracellular potassium.

Table III shows the occurrence of cardiac arrhythmias
during hypokalemia and after potassium repletion in
all 16 patients individually. With respect to supraven-
tricular arrhythmias, 9 patients were free of PACs for
the total 24-hour monitoring during the hypokalemic
phase, compared with 7 patients after potassium re-
pletion. The number of PACs decreased in 6 patients
after hypokalemia was corrected. However, in 6 other
patients the occurrence of PACs increased. In the re-
maining 4 there was no change. In addition to PACs
during the hypokalemic phase, 3 patients had supra-
ventricular tachycardia for 2 to 14 seconds. After po-
tassium repletion 1 patient had supraventricular
tachycardia for 4 seconds. One patient had atrioven-
tricular dissociation with junctional rhythm during both
phases, which occurred during sleep in both monitorings
and was associated with a slow atria1 rate.

Ventricular ectopic activity decreased in 5 patients
after potassium repletion. However, in 10 patients,
ventricular ectopic activity increased after potassium
repletion as compared with that in the hypokalemic
phase. Patient 6 showed no change between the 2
phases. Comparing ventricular arrhythmias that oc-
curred during the hypokalemic phase with those after


1020   HYPOKALEMIA AND CARDIAC ARRHYTHMIAS

TABLE Ill  Changes in Cardiac Arrhythmias Before and After Correction of Hypokalemia (Number of Hours Per 24-Hour
     Monitoring)

            Supraventricular Arrhythmias                    Ventricular Arrhythmias
                      PACs                       Unifocal PVCs    Multifocal PVCs
                                  SVT    A-VD
R   PK 0    1-9/h   10-49/h   250/h (s)    U-4 0    1-9/h   LlO/h   1-9/h   LlO/h   Couplets VT

. .
6
7

. . .
. .

.
. .
. . .

. . .
.
. . .
'ii
. . .
2
. . .
. .
.
. . .
. . .
. .
4
10
. .
. .
. . .
. . .
. . .
. . .
. . .
. .
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. . .
. . .
. . .
. . .
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.
.
. . .

. . .
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. . .
. . .
. . .
. .
. . .
. .
. . .
. .
. . .
. . .
. . .
. . .
. .
. . .
. . .
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. . .
. . .
. . .
. .
.
.
. . .
. .
.
. . .
. .
. . .
i

21
10
13
2

. .

3
11
10
20

.

. .
. .
. .
1
. .
. .
. .




.
1
. . .
5
7
. .
. .
.
1
. .

. . .
.
.
1:
9

. . .
1

1   2.9
   3.5
2   2.2
   3.5
3   3.2
   3.9
4   2.8
   3.8
5   2.9
   3.5
6   2.9
   3.5
7   2.9
   4.1
8   2.9
   3.8
9   2.5
   3.8
10 3.2
   3.9
11   3.2
   3.7
12   2.7
   3.6
13   3.0
   3.7
14 2.6
   3.6
15   2.3
   4.3
16 3.0
   3.5

24
:;
24
1
2;
::
%:
f i

21
24
1
20

2
;4
20
%4
23
z
24
19

. . .
s
2

. . .
23
15

. . .
8
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1:
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4
1
:
1

.
1:
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3

. . .
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15
2

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. . .
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5
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3

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2.1
3

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3

4
1;
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'12
5
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5

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3

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1
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1

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. .
5

.

A-VD = atrioventricular dissociation; PAC = premature atrial contractions; PK = plasma potassium; PVC = premature ventricular contractions;
SVT = supraventricular tachycardia; VT = ventricular tachycardia.

potassium repletion, there was no improvement in the
group as a whole. In fact, the mean number of hours per
monitoring during which each group of arrhythmias was
observed was slightly greater after potassium repletion
in all groups of ventricular arrhythmias than it was
before (Table IV).

Figure 2 shows the distribution of patients according
to the most severe or complex types of arrhythmias.
There was a trend toward more complex types of ar-
rhythmias after potassium repletion. For example, al-
though only 1 patient had couplets during the hypo-
kalemic phase, 6 patients had couplets after potassium
repletion. However, this change was not statistically
significant.

            Discussion
The major objective of this study was to determine
whether correction of hypokalemia in patients with
otherwise uncomplicated hypertension results in a de-
crease of cardiac arrhythmias. Only patients with overt
hypokalemia (plasma potassium 53.2 mEq/liter) were
selected. Long-term diuretic treatment was considered
essential for the purpose of the study, and no attempt
was made to discontinue diuretic treatment at any
time.

The results provided no evidence that correction of
hypokalemia would reduce the incidence of cardiac
arrhythmias. These results are in contrast to those re-
cently reported by Holland et a1.r3 The 2 studies were
similar in that both dealt with patients with uncom-
plicated hypertension with diuretic-induced hypoka-
lemia who were of similar age (29 to 64 years in Hol-
land's study and 29 to 68 years in ours). However, sev-
eral differences in the design of the studies may account
for the different outcomes. In Holland's study, diuretic
treatment was discontinued and the serum potassium
levels were allowed to increase to normal. Patients with
more than minimal ventricular ectopic activity during
the prediuretic phase were excluded. By selecting only
patients without significant arrhythmias during the
normokalemic phase, there was little or no possibility
of improvement of ventricular ectopic activity by chance
when hypokalemia was present. Several investigators
have shown considerable day-to-day spontaneous
variability of ventricular arrhythmias detected by
long-term electrocardiographic recording.14J5 Thus, the
association of the arrhythmias observed during the di-
uretic phase with low plasma potassium is not justi-
fied.

Of the 21 patients who entered their study, 7 devel-
oped complex ventricular ectopic activity during


November 1, 1983 THE AMERICAN JOURNAL OF CARDIOLOGY Volume 52    1021

TABLE IV  Number of Hours Per 24-Hour Monitoring that
      Each Group of Arrhythmias Was Observed

VEA          Hyookalemic Phase  K Reoletion Phase

0                  17.31 f 1.62      14.06 f 2.05
Unifocal PVCs; 1-9/h      3.75 f 0.87      4.50 f 1.33
Unifocal PVCs: 2 10/h     0.13 f 0.09      0.50 f 0.33
Multifocal PVCs; 1-9/h     1.19 f 0.44      1.75 f 0.58
Multifocal PVCs; 110/h     1.38 f 1.13      2.00 f 1.39
Couplets              0.25 f 0.25      0.63 f 0.24
VT                      0              0

Values are mean & standard error of the mean,
K = potassium; PVC = premature ventricular contractions; VEA =
ventricular ectopic activity; VT = ventricular tachycardia.

hypokalemia, and of those, 1 patient had runs of ven-
tricular tachycardia. Only these 7 patients received
spironolactone for hypokalemia correction and they
showed an improvement in ventricular ectopic activity
after plasma potassium was restored. Again, selecting
only the patients with increased ventricular ectopic
activity for potassium repletion favors the possibility
of improvement of ventricular ectopic activity by chance
and diminishes the possibility of worsening of ventric-
ular ectopic activity. It is not known what might have
happened to the 14 patients who had minimal ventric-
ular ectopic activity during hypokalemia had they re-
ceived potassium-correcting therapy. By chance, their
ventricular ectopy might have increased after plasma
potassium correction, blunting the results of the group
as a whole. Finally, in Holland's study hydrochlorothi-
aside was either decreased or discontinued in all 7 pa-
tients who received spironolactone for potassium re-
pletion. Therefore, it is difficult to correlate changes in
ventricular ectopic activity with plasma potassium
concentrations because there was not only a changed
plasma potassium level, but also, at the same time, a
reduction or elimination of hydrochlorothiazide.

In our study, patients were selected by only 2 criteria:
evidence of diuretic-induced hypokalemia and freedom
from known heart disease. All medication, including the
diuretic, remained unchanged throughout the study.
Antihypertensive therapy was maintained, because
some of our patients had severe hypertension that re-
quired up to 3 drugs to be controlled. It is unlikely that
continuation of antihypertensive agents prevented any
cardiac arrhythmias from appearing. In both the study
of Holland et al and our study, approximately one third
of the patients presented with more than minimal
ventricular ectopic activity during the hypokalemic
phase. In this study, all patients had treatment to cor-
rect plasma potassium, and 3 patients (Patients 1,7 and
14) with minimal ventricular ectopic activity during
hypokalemia developed couplets after plasma potassi-
um correction. Although this may have been due to
chance, obviously it adversely affects the average re-
sponse of the entire group to potassium repletion.

The issue of the arrhythmogenic potential of hypo-
kalemia was addressed in a recent editorial by Har-
rington et a&l6 who reviewed the literature and con-
cluded that the published experience discloses no evi-
dence that fatal ventricular ectopic activity results from
hypokalemia per se. Others,17 in agreement with our

10

touring Hypokalemir

m After K+ Repletion

al   unlfocal   multbfocal  multifocal   COUplets
   310     1-9     310

Frequency of PVC's Per Hour

FIGURE 2. Distribution of patients according to the most severe or
complex type of ventricular arrhythmia during hypokalemia and after
plasma potassium (K+) correction. Changes are not statistically sig-
nificant. PVCs = premature ventricular contractions.

study, found no change in ventricular ectopic activity
in hypertensive patients without known heart disease,
during hypokalemia or after hypokalemia correction
compared with the prediuretic period.

Recent reports implicate magnesium depletion as a
cause of cardiac arrhythmias. Dyckner and Wester1s20
studied ventricular arrhythmias in a group of hypo-
kalemic patients with congestive heart failure, hyper-
tension or liver disease. They observed no significant
change in the frequency or type of ventricular ar-
rhythmias after correction of serum potassium. Intra-
cellular potassium also remained unchanged, whereas
serum potassium increased from 3.40 to 4.27 mEq/
liter.i* In contrast, magnesium infusion led to an in-
crease in cellular potassium content and a concomitant
decrease in the frequency of PVCS.~O In the present
study it seems unlikely that magnesium played an im-
portant role in the persistence of cardiac arrhythmias
before and after plasma potassium correction. Plasma
magnesium was within the normal range (1.3 to 2.1
mEq/liter) averaging 1.49 f 0.06 mEq/liter before and
1.59 f 0.06 mEq/liter after correction of hypokalemia
and did not correlate with cardiac arrhythmias. Al-
though unlikely, the possibility of having intracellular
magnesium depletion despite normal plasma values
cannot be ruled out. Other investigators21 believe that
magnesium can only induce experimental arrhythmias
at concentrations that are unphysiologic and even in-
compatible with life.

Why cardiac arrhythmias should persist after cor-
rection of hypokalemia is not clear. We suggest 2 hy-
potheses. The first is that the arrhythmias observed in
this study may have had no relation to potassium deficit
or hypokalemia. If so, correction of plasma potassium
levels would not decrease the incidence of such ar-
rhythmias. Ventricular arrhythmias may occur in pa-
tients without cardiovascular disease. Brodsky et a122
found that 50% of 50 male medical students without
cardiovascular disease and with normal echocardio-
grams had PVCs on ambulatory electrocardiographic


1022   HYPOKALEMIA AND CARDIAC ARRHYTHMIAS

recordings, but only 1 had more than 50 in 24 hours. One
medical student had ventricular couplets and 1 had a
short episode of ventricular tachycardia. Clarke et a123
performed 2 consecutive 24-hour recordings in 86
subjects, aged 16 to 65 years, who had no clinical evi-
dence of cardiovascular disease. Ventricular ectopic
beats were seen in 63 subjects, 7 of whom averaged more
than 5 per hour. Thirteen subjects had multiform ven-
tricular ectopic beats, 3 bigeminy, 2 R-on-T phenome-
non and 2 brief episodes of ventricular tachycardia.
Arrhythmias were more frequent in the older patients.
In our patients also, older patients tended to have more
cardiac arrhythmias during both monitorings (Tables
I and III).

The second hypothesis is that the arrhythmias indeed
were related to potassium depletion, but they failed to
respond to the correction of plasma potassium levels
because there was no concomitant change in intracel-
lular potassium. Although electrophysiologic events on
the myocardial cell are influenced by cations like cal-
cium, sodium or magnesium, under clinical conditions,
the resting membrane potential is determined primarily
by the concentration gradient for potassium across the
membrane.24 Changes in the ratio between intracellular
and extracellular potassium will have an impact on the
resting membrane potential, according to the formu-
la1s20: resting membrane potential = -61.5 log intra-
cellular potassium/extracellular potassium. A relative
decrease in intracellular potassium or an increase in
extracellular potassium leads to a less negative resting
membrane potential; the cell approaches the threshold
of excitation and the conduction is slowed in the ven-
tricle, promoting reentrant circuits.18~20,21

Whether diuretic therapy results in depletion of total
body potassium stores is controversial,4y2L27 but several
investigators have shown that there is no increase in
intracellular potassium with potassium supplements
in patients treated with a diuretic.25,28v2g

The moderate, but not significant, shift of our pa-
tients toward more complex arrhythmias and the in-
crease in the number of patients with couplets after
correction of plasma potassium are not necessarily as-
sociated with correction of hypokalemia because this
shift can be attributed to the spontaneous variation that
may occur in consecutive 24-hour ambulatory electro-
cardiographic monitorings.i4J5

Acknowledgment: We are indebted to Barbara Lynn
Davis, CVT, and to Aldo Notargiacomo, BS, for excellent
technical assistance.

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