Вы находитесь на странице: 1из 4

Clin. Cardiol.

14, 165-168 (1991)

Cardiac Conduction Defects Associated with Hyponatremia

M.D., Y . SHEMESH, M.D..* M.D.. R. PAUZNER, M.D.,
Departments of Internal Medicine E, and *Cardiology, Chaim Sheba Medical Center, Tel Hashomer and Sackler School of
Medicine, Tel Aviv University, Tel Aviv, Israel

Summary: Cardiac conduction defects have not been previ- logical basis for these is serum hypo-osmolality which in
ously described in association with hyponatremia, although turn causes neuronal cell swelling and dysfunction.*
in patients with congestive heart failure the frequency of Clinical cardiac toxicity associated with hyponatremia
ventricular premature beats was found to correlate to the has not been described, although in patients with conges-
severity of' hyponatremia. We describe three patients with tive heart failure it was shown that the number of ventric-
second-degree or complete atrioventricular (AV) block ular premature beats (VPBs) correlated to the same degree
which occurred during or shortly after an episode of se- with the severity of either hyponatremia or hypokalemia.
vere hyponatremia. The first had thiazide-induced In this report we describe three patients who developed
hyponatremia while on amiodamne. In the second, definite reversible cardiac conduction defects temporally associated
etiology for hyponatremia which was associated with long- with hyponatremia or its correction.
standing polydipsia could not be established. The third had
ischemic heart disease and intermittent conversion of his
first-degree to second-degree AV block while hyponatremic Patient 1
after diuretics use. Although it is usually difficult to single
out hyponatremia as the cause of conduction defects which A 75-year-old woman with hypertension and paroxys-
usually occur in the presence of cardiac disease, potent mal atrial fibrillation was treated by digoxin 0.25 mg and
medications or other electrolyte abnormalities, we suggest amiodarone 200 mg daily. One week prior to admission
that hyponatremia may play a role in the pathogenesis of Kaluril (hydrochlorothiazide 50 mg, amiloride 5 mg) was
conduction defects in the diseased heart. started. She was admitted because of progressive weak-
ness. On examination she was oriented. The pulse was
regular at 68/min, and blood pressure was 130/90 mmHg.
Key wards: heart block, hyponatremia
Cardiac examination was unremarkable and the rest of the
physical examination was normal. Electrocardiogram
Introduction showed first-degree atrioventricular (AV) block with P-
R interval of 0.24 s and complete left bundle-branch block
Hyponatremia, the most common electrolyte disorder (CLBBB). A few hours later she became confused. Blood
in hospitalized patients is usually asymptomatic. I When pressure was unchanged and on ECG complete AV block
clinical manifestations of hyponatremia do occur they are appeared, requiring insertion of a temporary pacemaker.
usually related to central nervous system dysfunction: con- Pacemaker insertion did not alter mental status. Serum so-
fusion, convulsions, coma, and death. The pathophysio- dium concentration at that time was 120 mmol/l and potas-
sium was 5 mmol/l (Table I). When serum sodium reached
126 mmol/l, the patient became oriented and the ECG
showed 2: 1 AV block. A day later ECG showed normal
sinus rhythm and CLBBB. The CLBBB disappeared when
serum sodium level rose above 130 mmol/l. There was
Address for reprints: no electrocardiographic or enzymatic evidence of my-
Zvi Farlel, M.D.
ocardial infarction. Serum digoxin concentration on ad-
Department of Internal Medicine E mission was 0.3 ng/ml.
Sheba Medical Center
Tel Hashomer 5262 I Comment
Received: April 2, 1990 The patient presents a case of thiazide-induced
Accepted with revision: July I , 1990 hyponatremia, which typically occurs in elderly women
166 Clin. Cardiol. Vol. 14. Fcbruary 1991

TABLEI Coursc of electrolyte and electrocardiographic changes in two patients

Hospitalization Serum sodium Serum potassium Serum

day (mmol/l) (mmol/l) bicarbonate (minol/l) ECC

Patient I
1 CLBBB, and first-degree
A V block (P-R 0.24S )
I 120 5 .O Completc AV block
2 117 5.3 18 Complete A V block
alternating with CLBBB
3 126 4.8 24 2:l A V block. CLBBB
4 131 5.1 22 Normal sinus rhythm
5 128 5.I Normal sinus rhythm
6 137 4.9 24 Normal sinus rhythm
7 14 I 5.3 Normal sinus rhythm
Patient 2
I 108 4.1 First-degree A V block
(P-R 0.44 S )
I29 4.7 20 P-R 0.34s
134 4.2 20 Wcnkebach type AV block
I39 4.2 16 Normal sinus rhythm
147 4.1 14 Nomial sinus rhythm
142 4.0 Normal sinus rhythm
140 4.2 20 Normal sinus rhythm
Ahbreviutions: CLBBB=complete left bundle-branch block, AV =atrioventricular.

a few days after thiazide therapy is ~ t a r t e d . The

~ unusual sodium, blood pressure, and body temperature wcrc all
appearance of conduction defects could not be explained normal. Wenkebach type second-dcgrce AV block ap-
solely by a diseased conduction system, myocardial ische- peared on ECG. This electrocardiographic abnormality as
mia, or by amiodarone or digoxin therapy. The close tem- well as the sinus bradycardia and the first-degree AV block
poral association between the totally reversible conduc- spontaneously disappeared after 24 h (Table I). His con-
tion defect and hyponatremia strongly suggests that fusion lasted a few more days until complete recovcry ot
hyponatremia played a role in the pathogenesis of the con- mental function. Serum cortisol and thyroxine concentra-
duction defect. tions as well a5 chest x-rays were normal. The EECi
showed diffuse abnormality compatible with the severe
electrolyte disturbance. Cerebral computerized tomogra-
Patient 2 phy and examination of the ccrebrospinal fluid were nor-
mal. Thus, no definite cause for the hyponatrcniia could
A 33-year-old man was admitted because of confusion. be established. It was attributed partially at least to cx-
The patient sustained traumatic quadriplegia at age 20, cessive drinking.'j
and because of an indwelling permanent urinary catheter
he used to drink large quantities of water. Five days prior Comments
to admission he developed diffuse abdominal pains,
nausea, vomiting, and diarrhea, and later became drowsy The cause of the hyponatremia in this paticnt was not
and dysarthric. On admission he was confused, his rectal definitively established. Theoretically, a viral disease
temperature was 33"C, blood pressure was 110/60 mmHg, could account for most or all clinical manifestations: my-
pulse rate was 52 beatdmin, hemoglobin concentration ocarditis, encephalitis, and concomitantly and indirectly-
was 90 g/l and serum sodium concentration was 108 hyponatremia.' No known virus could be dernonstratcd
mmol/l. ECG showed sinus bradycardia with first-degree in blood or cerebro spinal fluid (CSF) and thc EEG find-
A V block, P-R interval of0.44 s, and J waves. Hyponatre- ings argue against herpes encephalitis. Alternativcly, thc
mia was corrected by hypertonic saline, and serum sodi- hypothermia observed could have contributed to the ECG
um concentration of 129 mmol/l was measured after 22 changes. Hypothermia-associated ECG abnormalitics in-
h (Table I). The patient became more oriented, his tem- clude bradycardia, atrial fibrillation, prolonged Q-T in-
perature rose to 36"C, and the P-R intcrval shortened (0.34 terval, first-degree AV block, and the pathognomonic J
s), however, 8 h later he became confused again. Serum waves. 8 . 9 However, these changes are usually associatcd
M. Mouallem et d . : Cardiac conduction defects and hyponatremia I67

with prolonged and profound hypothermia ( <30°C),and development of second-degree AV block. This defect was
to the best of our knowledge second-degree AV block has not documented in previous hospitalizations when he was
never been associated with the mild degree of hypother- not hyponatremic, or in the last weeks of his life, when
mia observed in our patient. It is more plausible, there- he was only mildly hyponatremic. It is interesting that dur-
fore, that hyponatremia was involved in the conduction ing the period of moderate to severe hyponatremia, the
system abnormalities, since the latter were noted on ad- second-degree AV block was only intermittent. This may
mission and improved upon correction of hyponatremia. further indicate that hyponatremia was not the only ab-
The delayed appearance of Wenkebach type AV block is normality responsible for the conduction defect.
interesting, since it may represent a delayed type of dys-
function, analogous to the cerebral dysfunction encoun-
tered after correction of hyponatremia. l o Discussion

Two of the patients described (Nos. 1 and 3) had com-

Patient 3 plete or second-degree AV block during hyponatremia.
Both patients had either a diseased heart (Patient 3) or were
A 60-year-old man with ankylosing spondylitis, diabetes receiving antiarrhythmic agents (Patient 1). In one patient
mellitus, and ischemic cardiomyopathy (LVEF= 15%) who did not have a known heart disease (Patient 2),
was known to have first-degree AV block, with P-R in- hyponatremia was associated with a first-degree AV block,
terval of 0.28 s. His therapeutic regimen consisted of and only after correction of hyponatremia second-degree
furosemide, spironolactone, and digoxin 0.25 mg daily. AV block was observed. In all three cases hyponatremia
Five weeks before the last admission, he was hospital- was severe, with serum sodium concentration of 108-
ized because of right heart failure with no evidence of I17 mmol/l. Serum potassium concentrations and acid
acute myocardial infarction. At that time ECG showed base indices were both normal in all patients.
P-R interval of 0.36 s and signs of old anterior myocardi- Hyponatremia has not previously been associated with
al infarction. Serum digoxin concentration was 0.9 ng/ml, cardiac conduction defects, although co-occurrence of
serum sodium was 132 mmol/l, potassium 4.7 mmol/l, hyponatremia and sinoatrial block was described in one
and glucose 16.5 mmol/l. Digoxin was discontinued, and patient. I I In that patient both abnormalities may have been
chlorothiazide 0.5 g daily was added to the therapeutic independently induced by carbamazepine therapy which
regime. One month later he was hospitalized because of is known to cause both hyponatremia'* and cardiac con-
progressive weakness. There were no physical signs of duction defects. l 3
heart failure except for cachexia. Serum sodium was 116 Theoretically, reduction of the extracellular concentra-
mmolil, potassium 4.7 mmol/l, and glucose 18 mmol/l. tion of sodium should slow cardiac pacemaker activity.
ECG showed P-R interval of 0.28 s and signs of old an- In animal experiments, only severe reduction of the sodi-
terior myocardial infarction. Next day, at serum sodium um concentration in the fluid perfusing the isolated heart
concentration of 1 18 mmol/l and potassium 5 mmol/l, caused reduction in its contraction rate as well as in its
ECG showcd Mobitz type 2 second-degree AV block. Di- excitability and conduction velocity. l4 When dogs were
uretics were discontinued and fluid intake was restricted induced to develop wide QRS complexes, either through
to 1,000 ml/day. During the next 14 days serum sodium hyperkalemia or quinidine administration (a situation ap-
concentration ranged from 115 to 128 mmol/l. During parently simulating a diseased myocardial conduction sys-
these days ECG showed Mobitz type 2 alternating with tem), infusion of sodium salt solution resulted in a decrease
Wenkcbitch type second-degree AV block. However, there in the duration of the QRS complex.15 In the turtle, iso-
were days in which only first-degree AV block was record- lated heart perfusion with low sodium solution made the
ed. During the rest of his hospital stay, when serum sodi- heart more sensitive to the myocardial effects of hyper-
um concentrations were between 125-133 mmol/l, no kalemia as shown on electrocardiography. I 6 These obser-
second-degree AV block was recorded. Reappearance of vations raise the possibility that low sodium concentra-
severe heart failure demanded reinstitution of diuretics. tions can affect the diseased human heart, a condition that
Multiorgan failure developed and the patient died 34 days cannot be accurately simulated by an animal model.
after admission. Permission to autopsy was not granted. Documentation of the effects of various sodium con-
centrations on the human myocardial conduction system
Comment are scarce. Garcia-Palmieri described four patients with
hyperkalemia and hyponatremia who had wide QRS com-
This patient had severe ischemic cardiomyopathy and plexes. Three of the patients also had a moderate to se-
ankylosing spondylitis, each of which can potentially cause vere metabolic acidosis. The patients received hyperton-
conduction abnormalities. Evidently, this patient had a dis- ic saline with reversal of the ECG changes. This effect
eased conduction system, however, it is highly probable can be either attributed to a change in serum potassium,
that appearance of hyponatremia worsened the function o r to a modification of the cardiac effects of the hyper-
of the discascd conduction system and contributed to the kalemia. This observation may provide further evidence
I68 Clin. Cardiol. Vol. 14, February 1991

that hyponatremia may aggravate or cause cardiac con- 5 . Friedman E, Shadel M , Halkin H, Farfel Z:Thiazidc-induced
duction defects in a diseased heart. hyponatremia: Reproducibility by single dose rcchallenge in-
cluding an analysis of pathogenesis. Ann Intcwi Mrd 110. 24
In the specific hyponatremic patient, ascribing conduc-
( 1989)
tion defect to hyponatremia is usually complicated by other 6. Leehey DJ, Picache AA, Robertson GL: Hyponatremia in quad-
coexisting conditions which may have a direct deleteri- riplegic patients. CIin Sci 75, 441 (1988)
ous effect on the conduction system: primary cardiac dis- 7. Mouallem M, Friedman E, Rubinstein E: Inappropriate antidi-
ease, diuretic and antiarrhythmic drugs, or other electro- uretic hormone secretion with infectious mononucleosis (let-
lyte abnormalities (mainly hypokalemia and hyperkale- ter). N Engl J Med 3 II, 262 ( 1984)
mia). The clinical course of the three patients herein 8. Clements SD, Hurst JW: Diagnostic value of electrocardio-
graphic abnormalities in subjects accidentally exposed t o cold.
described suggests that hyponatremia may play a role in Am J Cardiol 29, 729 (1972)
the pathogenesis of the observed atrioventricular conduc- 9. Trevino A, Razi B, Beller BM: The characteristic electrocardi-
tion defects. ogram of accidental hypothermia. Arch Intern Mod 127. 470
The association between cardiac conduction defects and (1971)
hyponatremia is far from established. Future clinical ex- 10. Arieff A I: Hyponatremia, convulsions, respiratory arrest, and
perience with increased index of suspicion will help to permanent brain damage after elective surgery in healthy woni-
en. N Engl J Med 314, 1529 (1986)
establish the relation between these abnormalities further,
II. Johannessen AC, Nielsen OA: Sino-atrial block, hyponatrae-
and to understand the mechanism of this phenomenon niia and urticaria caused by carbamazepinc. 0go.c.kr LUryyr 149,
better. 376 (1987)
12. Ashton MG. Ball SG, Thomas TH, Lee MR: Water intoxicn-
tion associated with carbamazepine treatment. Br M e d J I, I134
References ( 1977)
13. Boesen F, Andersen EB. Jensen EK, Ladefogcd SD: Cardiac
conduction disturbances during carbamazepine therapy. k t o
I. Anderson RJ, Chung H, Kluge R, Schrier RW: Hyponatreniia:
Nrurol Sccmd 68, 49 (1983)
A prospective analysis of its epidemiology and the pathogenetic
role of vasopressin. Ann Intern Mrd 102, 164 (1985) 14. Trautwein W: Generation and conduction of impulses in the
2. Norenberg MD, Leslie KO, Robertson AS: Association between heart as affected by drugs. Phartnucol Rrv 15, 277 (1963)
rise in seturn sodium and central pontine niyelinolysis. Ann Neu- 15. Surawicz B: Relationship between electrocardiogram and elec-
rol II, 128 (1982) trolytes. An1 Heirrt J 73, 814 (1967)
3. Dargie HJ, Cleland JGF, Leckie BJ, lnglih CG, East BW, Ford 16. Butcher WA, Wakim KC, Essex HE, Pruitt RD. Burchell HR:
I: Relation of arrhythmias and electrolyte abnormalities to sur- The effect of changes in concentration of cations o n the clcc-
vival in patients with severe chronic heart failure. Circulution trocardiogram of the isolated perfused heart. Atn Hetrrt J 4 I,
75 (suppl IV), 98 (1987) 801 (1952)
4. Abramow M, Cogan E: Clinical aspects and pathophysiology 17. Garcia-Palmieri MR: Reversal of hyperkalemic cardiotoxicity
of diuretic induced hyponatremia. Ad\' Nc,plirol 13. I (1984) with hypertonic saline. Am Hrurt J 64, 483 (1962)