LETTER TO THE EDITOR
Effect of Hypokalemia on the Clinical Impact of Hyponatremia
To the Editor:
In the March 2012 issue of The Journal of Clinical
Hypertension, Rastogi and colleagues1 published an
interesting paper about hospitalizations as a result of
thiazide-associated hyponatremia (TAH). From the
results of that study, we can conclude that concomi-
tant hypokalemia is a significant risk factor for hospi-
talization of patients with TAH.1 This further
confirms the results of the earlier study by Chow and
associates2 that showed hypokalemia as an indepen-
dent risk factor for symptomatic TAH requiring hospi-
talization. The concomitance of hypokalemia with
TAH could be merely an associated observation that is
explained by the intertwined kaliuretic and hypona-
tremic effects of thiazides; however, in the study by
Rastogi and colleagues,1 potassium supplements
indeed provided a protective effect from hospitaliza-
tion in TAH. Nevertheless, potassium supplements are
now almost never used with diuretics in clinical prac-
tice. Other drugs that elevate potassium levels with
thiazide therapy such as angiotensin-converting
enzyme inhibitors (ACE) and potassium-sparing diuret-
ics did not give the same protective effect of potassium
supplements.1 The combination of a potassium-sparing
diuretic and a thiazide may in fact increase the like-
lihood of developing TAH.1 Moreover, ACE therapy
was rather a risk factor that contributed to hospital-
ization in TAH.1 Theoretically, hypokalemia may
intensify the hyponatremia-mediated hypo-osmolality,
thus rendering the patient more prone to be symptom-
atic. However, the exact mechanism remains unclear.2
Further studies to evaluate the effect of low plasma
potassium on the clinical impact of TAH and of hypo-
natremia in general may be required.
The osmotic demyelination syndrome (ODS) is the
undesired devastating consequence of the rapid correc-
tion of chronic hyponatremia. Hypokalemia at presen-
tation may predispose patients to develop ODS
following correction of hyponatremia.3 It is also asso-
ciated with a poor outcome in patients who develop
the syndrome.4 The mechanism by which hypokalemia
contributes to both the likelihood of development and
the probability of poor outcome of ODS remains
unclear. We understand that the addition of potassium
to the infused solution increases the osmolality of that
solution.5 Therefore, if any potassium is added, it
should be calculated as an increment in the sodium
content of the given saline solution.6 Hence, we may
believe that ODS could result from the rapid rise of
osmolality due to correction of both hyponatremia
and hypokalemia in the same time.7 However, in a lit-
erature review of 66 patients with ODS who had con-
comitant hypokalemia, 20 of these cases had the serial
doi: 10.1111/j.1751-7176.2012.00643.x
656 The Journal of Clinical Hypertension Vol 14 | No 9 | September 2012
measurements of sodium and potassium available. In
no instance was the potassium level normalized prior
to the time of most rapid correction of the serum
sodium.8 In another case report, ODS developed in
spite of partially correcting severe hyponatremia only
with normal saline and in the presence of persistent
hypokalemia.9 The authors of the latter two reports
suggested that hypokalemia predisposes to the devel-
opment of ODS in hyponatremic patients and empha-
sized the priority of correcting hypokalemia before
hyponatremia in this situation. More animal or human
studies may be needed to further clarify this issue.
CONCLUSIONS
Hypokalemia may be a risk factor for patients with
TAH to be symptomatic and hospitalized. Pretreat-
ment with oral potassium supplements appears to be
protective from this effect. Other drugs that elevate
potassium levels with thiazide therapy such as ACE
and potassium-sparing diuretics did not give the same
protective effect of potassium supplements. In patients
with chronic severe symptomatic hyponatremia,
concomitant hypokalemia increases the risk of devel-
oping ODS after the rapid correction of hyponatremia.
It may be suggested that correcting hypokalemia
should be given initial priority over hyponatremia in
this situation.
Mohamed Osama Hegazi, MRCP
From the Department of Medicine, Al Adan Hospital,
Ahmadi, Kuwait
References
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Official Journal of the American Society of Hypertension, Inc.