72 Electrolyte & Blood Pressure 4:72-76, 2006

3)

Hyponatremia : Management Errors

Jang Won Seo, M.D., and Tae Jin Park, M.D.

Department of Internal Medicine, Hallym University College of Medicine, Chunchon, Korea

Rapid correction of hyponatremia is frequently associated with increased morbidity and mortality.
Therefore, it is important to estimate the proper volume and type of infusate required to increase the
serum sodium concentration predictably. The major common management errors during the treatment of
hyponatremia are inadequate investigation, treatment with fluid restriction for diuretic-induced
hyponatremia and treatment with fluid restriction plus intravenous isotonic saline simultaneously. We
present two cases of management errors. One is about the problem of rapid correction of hyponatremia
in a patient with sepsis and acute renal failure during continuous renal replacement therapy in the
intensive care unit. The other is the case of hypothyroidism in which hyponatremia was aggravated by
intravenous infusion of dextrose water and isotonic saline infusion was erroneously used to increase
serum sodium concentration.

Key Words : Hyponatremia, Management errors, Fluid restriction, Hypothyroidism

treatment of hyponatremia are as follows3):

Introduction
1) Inadequate investigation, which could have
changed management
Hyponatremia is the most common electrolyte dis-
2) Treatment with fluid restriction for diuretic-
turbance encountered in clinical practice, with a
induced hyponatremia
1)
prevalence up to 15% in a general hospital population .
3) Treatment with fluid restriction plus intravenous
Hyponatremia in critically ill patients can cause signi-
saline simultaneously
ficant morbidity and mortality. Inappropriate treatment
4) Continuing the use of thiazide despite of the
of hyponatremia can make the matters worse. The
probable cause of hyponatremia is thiazide-induced
diagnosis and management of salt and water abnor-
hyponatremia
malities in critically ill patients is often challenging. A
5) “Blind” intravenous saline for modest (>125
systematic approach by clinicians, using a detailed
mmol/L) hyponatremia in a non-critical situation
history, physical examination, and relevant diagnostic
6) Iatrogenic causes secondary to intravenous dex-
tests, will assist in efficient management of salt and
trose
2)
water problems . The management of hyponatremia is
In this report, we present two cases of management
not a simple theme because of the difficulty of the
errors that occur commonly in our clinical practice.
assessment of each patient's volume status evaluation.
One is about the rapid correction of severe hypona-
Clinical judgment and laboratory investigations are
tremia in a patient admitted to the intensive care unit.
important to help elucidate a diagnosis.
The other case is about the unreasonable use of
The major common management errors during the
isotonic saline and hypertonic saline infusion in a
hypothyroid patient who needs fluid restriction and
Correspondence author : Jang Won Seo, M.D.
Department of Internal Medicine, Hallym University College of thyroid hormone replacement.
Medicine, Chunchon, Korea
Tel : 02)2639-5786, Fax : 02)2677-9756
E-mail : [email protected]
 JW Seo : Hyponatremia : Management Errors 73

admitted to the neurosurgery department due to the

Case second lumbar vertebra burst fracture caused by fall
down injury. When he was admitted to the hospital,
Case 1 laboratory findings were as follows: blood urea nitro-
A 87-year-old woman presented to the emergency gen 19 mg/dL, creatinine 0.8 mg/dL, serum sodium
department complaining of progressive weakness, fe- 137 mmol/L, serum potassium 4.0 mmol/L, and serum
ver, and myalgia over the past 5 days. Her mental total CO2 22 mmol/L. The serum sodium decreased to
status was alert but sometimes confused. She had 129 mmol/L 12 days after his admission. His serum
moderate tenderness in her both costovertebral angles. sodium concentrations were in the range of 122-132
Vital signs on admission revealed : blood pressure mmol/L for 12 days, and the final serum sodium level
100/70 mmHg, body temperature 36.9℃, pulse 72 bpm, was 129 mmol/L when the consultation was done.
and respiratory rate 20/min. Laboratory findings were Physical examination revealed no evidence of volume
as follows : blood urea nitrogen 60 mg/dL, creatinine depletion. His mental status was alert and well
3.5 mg/dL, serum sodium 117 mmol/L, serum potas- oriented. Vital signs on the consultation day showed:
sium 3.8 mmol/L, serum total CO2 14.6 mmol/L, and blood pressure 120-140/70-80 mmHg, body tempera-
ionized calcium 1.02 mmol/L. The patient was pre- ture 36.9℃, pulse 72 bpm, and respiratory rate 20/min.
sumed to have acute renal failure associated with Daily intake/output were 3,250/1,800 mL, 3,100/1,850
urosepsis and managed with continuous renal replace- mL and 2,260/2,200 mL during the consecutive 3 days
ment therapy. After admission to the intensive care before the consultation. He was taking soft diet and
unit, her serum sodium increased to 130 mmol/L after fluids ad lib. The main fluids infused during the last
7 hours later with normal saline infusion of 1,600 mL. 12 days were intravenous dextrose water and isotonic
Even though there were no immediate complications saline. On the consultation day, hypertonic saline (3%
associated with rapid correction of hyponatremia in saline) was infused without notifying the nephrologist.
this patient, the total increment of serum sodium was The hypertonic saline was stopped immediately.
21 mmol/L (from 117 mmol/L to 138 mmol/L) during Thereafter, oral fluid restriction (<urine output＋es-
the duration of 22 hr 30 min. The results of thyroid timated insensible loss) was done and the saline
and adrenal function test were within normal limits. infusion was held simultaneously. The thyroid function
Two days later, the continuous renal replacement test revealed that he had hypothyroidism: T3 47.4
therapy was stopped because of the increase in urine ng/dL (reference values : 60-181), TSH 58.1 uIU/mL
output. Thereafter, she was recovered from acute renal (0.35-5.5), and free T4 0.30 ng/dL (0.89-1.76). The
failure associated with urosepsis and her serum results of adrenal function test were within normal
sodium levels were stable without any further de- limits. His serum sodium levels slowly returned to
terioration. Until now, for about 6 weeks after rapid normal after oral fluid restriction and thyroxine admi-
correction of her hyponatremia, no neurologic changes nistration without any further infusion of intravenous
were present suggestive of the development of the fluids.
osmotic demyelination syndrome (ODS).
Discussion
Case 2
A 55-year-old man consulted with the nephrology The first case was about the problem of rapid
division about the evaluation and management of correction of hyponatremia with continuous renal re-
persistent hyponatremia over the past 7 days. He was placement therapy in a patient with urosepsis-
74 JW Seo : Hyponatremia : Management Errors

associated acute renal failure. In this case, the mental hyponatremic neurologic symptoms included lethargy
status of the 87-year-old woman was not altered. If (33.3%), confusion with drowsy mentality (33.3%),
sepsis is combined in a patient with severe hypona- dizziness (18.6%), and semicoma (7.4%). At a single
tremia, we usually have a difficulty in assessing the medical center they retrospectively analyzed the clini-
mental status. Thus, it is tempted for us to use cal course of 27 consecutive patients who presented
hypertonic saline for correction of hyponatremia. It with neurologic hyponatremic symptoms and with
＋ 6)
should be more complex when we apply the con- plasma Na concentrations less than 125 mmol/L .
tinuous renal replacement therapy for the management Severe symptomatic hyponatremia should be treated
of acute renal failure accompanying hyponatremia in with hypertonic saline, and the plasma Na＋ concen-
the intensive care unit. In the first case, we should tration should be raised by 1 to 2 mmol/L per hour for
＋
have checked the plasma Na concentration more the first 3 to 4 h or until the seizures subside. In other
＋
frequently but, plasma Na concentration was checked words, the plasma Na＋ concentration should probably
after 1600 mL of isotonic saline was infused over 7 be raised by no more than 12 mmol/L during the first
＋
hours. Meanwhile, the plasma Na concentration in- 24 h. In volume-contracted states, the treatment of
creased by 13 mmol/L (from 117 mmol/L to 130 choice is to increase the serum Na＋ concentration by
mmol/L) during the first 7 hours. It is a kind of very 10 mmol/L or to levels of 120 to 125 mmol/L over 6
common management error that frequently occurs in hours by administering hypertonic 3 to 5% saline5).
our clinical practice. In this case, even though we did Hyponatremia in critically ill patients can cause sig-
not use hypertonic saline, we had to consider the nificant morbidity and mortality. Inappropriate treat-
effect of continuous renal replacement therapy (CRRT) ment of hyponatremia can make the matters worse. As
＋
on the level of plasma Na concentration and had to in the study by Huda et al.3), the main treatments
＋
check the plasma Na concentration at least every two given for hyponatremic patients were fluid restriction,
4)
hours or so. In the report by Ji et al. , continuous intravenous saline, simultaneous fluid restriction and
veno-venous hemofiltration (CVVH) was effective in intravenous saline, and diuretic stopped/reduced. In
the treatment of acute severe hyponatremia. They their analysis, overall 34 cases (33%) were considered
suggested that CVVH could be considered as a treat- to have significant management errors. Out of these,
ment option because of its slow and continuous nature. 14 patients died (41%). The cohort that was felt to be
For the adequate rate of correction of hyponatremia managed appropriately, however had a mortality of 14
when we use CRRT, they recommended that the of 70 (20%).
serum sodium concentration be corrected at an av- Rapid correction of hyponatremia is frequently
erage rate of 2.5±0.14 mmol/L/h at 6 h, 1.2±0.1 mmol/ associated with increased morbidity and mortality.
L/h at 24 h and 0.82±0.1 mmol/L/h at 48 h. Therefore, it is important to estimate the proper
The rate of correction of hyponatremia depends on volume and type of infusate required to change the
whether neurologic dysfunction is present. In asymp- serum sodium concentration predictably. Recently,
＋
tomatic patients, the plasma Na concentration should Adrogue and Madias proposed a new formula for the
be raised by no more than 0.5 to 1.0 mmol/L per h management of both hyponatremia and hyperna-
and by less than 10 to 12 mmol/L over the first 24 h. traemia. According to this formula, the anticipated
＋
Acute or severe hyponatremia (plasma Na concen- change in the patient's serum sodium concentration as
tration <110 to 115 mmol/L) tends to present with a result of administration of 1 L of any infusate can
altered mental status and/or seizures and requires be calculated by equation (1):
5)
more rapid correction . Park et al. reported that
 JW Seo : Hyponatremia : Management Errors 75

＋ ＋ ＋
△[Na ] = ([Na ]inf - [Na ]s)/(TBW＋1) (1) tible to the development of ODS, since their brain cell

where [Na＋], [Na＋]inf and [Na＋]s represent the ex- volume has returned to near normal as a result of the

pected change in the patient's serum sodium concen- osmotic adaptive mechanisms. Therefore, administra-

tration, the sodium concentration of the infusate and tion of hypertonic saline to these individuals can cause

the sodium concentration of the patient's serum, sudden osmotic shrinkage of brain cells5). The review

respectively, expressed in mEq/L, and TBW represents of the reported cases in which initial transient

the patient's estimated total body water, expressed in neurologic recovery by the initial rapid correction of

liters. When the administered solution contains potas- hyponatremia, then was followed by delayed deteriora-

sium chloride also, the equation (1) is converted as tion of ODS (biphasic course) suggests that clinicians

follows: treating the patients with severe symptomatic hypo-

＋ ＋ ＋ ＋
natremia should be aware of the possibility of delayed
△[Na ]={([Na ]inf＋[K ]inf)-[Na ]s}/(TBW＋1) (2)
neurologic sequelae despite the initial recovery of
＋ 9)
where [K ]inf represents the potassium concen- neurologic status .
tration of the infusate. The second case was about the erroneous manage-
This formula that has been proposed by Adrogue ment with isotonic saline and dextrose water infusion
and Madias predicted with relatively accuracy the instead of fluid restriction and thyroxin administration
changes in serum sodium concentration in almost all in a patient with hypothyroidism-induced hypona-
patients. Thus, it should be considered as a very tremia. For the long term correction of asymptomatic,
useful tool for the management of dysnatremias. non-volume-depleted hyponatremia, the general rule is
However, special attention should be paid when this to restrict electrolyte-free water intake. Fluid intake
equation is used in patients with hyponatremia due to should be coupled with high dietary salt intake.
extracellular volume depletion after euvolemia's resto- Isotonic saline infusion with a loop diuretics are some-
ration and primary polydipsia in order to avoid rapid times prescribed. In this case, diuretic induces urinary
7)
correction of hyponatremia . salt loss and reduces the risk of ECF volume ex-
Under normal conditions, total body water is 50 or pansion. For the patient with hyponatremia which is
60% of lean body weight in women or men, respec- iatrogenically induced by intravenous dextrose and
tively. Therefore, to raise the plasma Na＋ concentra- isotonic saline infusions, fluid restriction is the main-
tion from 105 to 115 mmol/L in a 65-kg man requires stay of treatment. Water restriction is also a com-
＋
390 mmol [(115-105)×65×0.6] of Na . It is suggested ponent of the therapeutic approach to hyponatremia
that if one cannot remember this formula, a useful associated with primary polydipsia, renal failure and
practice is to administer 250 mL of either 3 or 5% syndrome of inappropriate antidiuretic hormone secre-
8)
saline over 4 to 6 hours . tion (SIADH). Water restriction is not usually used for
The risk of correcting hyponatremia too rapidly is the diuretic-induced hyponatremia or hypovolemic
the development of the osmotic demyelination syn- hyponatremia. If hypothyroidism is a possible cause of
drome (ODS). This is a neurologic disorder charac- hyponatremia such as in our case, giving thyroxine is
terized by flaccid paralysis, dysarthria, and dysphagia. the most important step for the management of
The diagnosis is suspected clinically and can be hyponatremia associated with hypothyroidism. In our
confirmed by appropriate neuroimaging studies. There patient, the hyponatremia was resolved by oral fluid
is no specific treatment for the disorder, which is restriction and thyroxine replacement therapy. Further
associated with significant morbidity and mortality. intravenous fluid infusion was not required any more.
Patients with chronic hyponatremia are most suscep- Disorders of sodium and water balance can be
76 JW Seo : Hyponatremia : Management Errors

approached by following a few basic steps: Thorough tremia in a general hospital population. Clin Nephrol
22:72-76, 1984
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includes serum electrolytes, osmolality, urine osmo- Med 18:3-8, 2003
3) Huda MS, Boyd A, Skagen K, Wile D, van
lality, and urine sodium concentration are usually all
Heyningen C, Watson I, Wong S, Gill G : Investi-
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4) Ji DX, Gong DH, Xu B, Tao J, Ren B, Zhang YD,
sodium concentration often to ensure adequate treat-
Liu Y, Hu WX, Li LS : Continuous veno-venous
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in management of both hyponatremia and hyper- tremia: a report of 6 cases. Zhonghua Nei Ke Za
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natremia10).
5) Singer GG, Brenner BM, Robertson GL :
The development of severe hyponatraemia in hos- Hyponatremia. In : Harrison's Principles of Internal
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