Iatrogenic Hyponatremia

Hyponatremia (serum sodium less than 135 mmol/L) and hypokalemia (serum potassium less
than 3.5 mmol/L) are common in hospitalized patients. However, both electrolyte disorders are
often unrecognized by clinicians owing to various reasons such as the absence of lab facility,
cost and awareness. Iatrogenic hyponatremia is generally caused by giving too much hypotonic
maintenance solutions or parenteral nutrition solutions which contain low or no sodium.
Typical maintenance solutions have been available in the market for many years which are
indicated to treat moderate dehydration or insufficient water intake. They contain potassium to
fulfill minimum requirement of potassium and aimed at preventing hypokalemia in patients
with insufficient food intake. The amount of sodium in traditional maintenance solution has
been devised to fulfil daily requirement of sodium and generally they are hypotonic. Recently ,
there is increasing evidence that hypotonic maintenance solution could trigger or predispose
iatrogenic hyponatremia. Hospital-acquired acute hyponatremia is increasingly recognized as a
cause of morbidity and mortality in children.
The routine practice of providing hypotonic maintenance IV solutions, usually containing 20
mmol/L to 30 mmol/L of Na, is based on Holliday and Segars seminal paper(13) published in
1957 and translates to the use of 0.2% NaCl/dextrose 5%. These recommendations were based
on caloric expenditure in healthy children, and electrolyte composition was derived from that
of human and cows milk. Branded maintenance solutions are promoted by emphasizing the
potassium content rather than the sodium content.

Isotonic saline solution added with potassium as maintenance intravenous fluid therapy can
prevent acquired hyponatremia in hospitalized children.
Current Findings
Reports of clinical studies in pediatric patients which confirmed iatrogenic hyponatremia
induced by hypotonic maintenance solutions
No Investigators Design Results
1 Montaana PA, Modesto A randomized 122 ICU At 24 h, 20.6% of patients in the
i Alapont V, Ocn AP, et al patients to receive isotonic hypotonic group were
or hypotonic fluids.(21 hyponatremic versus 5.1% in the
isotonic group (P=0.02).
2 Yung M, Keeley S. randomized 50 ICU The type of fluid (P=0.006) but
patients to receive isotonic not the rate (P=0.12) was significantly
fluids (normal saline) or associated with the degree
hypotonic fluids (0.18% of fall in serum Na
NaCl/4% dextrose), at
either the traditional
maintenance
rate or two-thirds of that
rate.
 3 Rey C, Los-Arcos M, 125 children from
Hernndez A, Snchez A, three paediatric ICUs in
Daz JJ, Lpez-Herce J. Spain. After adjusting for
age, weight and
Na at admission, those
receiving hypotonic fluids
(Na 50 mmol/L
to 70 mmol/L) versus
isotonic maintenance fluid
Hypotonic solutions resulted in a
decrease in Na of 3.2 mmol/L with a
5.8-fold
increased risk of hyponatremia
compared with patients receiving
isotonic maintenance fluids.(23

4 Kannan L, Lodha R, 167 hospitalized Fourteen per cent (8 of 56) of patients

Vivekanandhan S, Bagga children.(24) Fourteen per
A, Kabra SK, Kabra cent (8 of 56) of patients
M. randomized to
. receive hypotonic IV
maintenance fluids (0.18%
NaCl/5% dextrose) or
isotonic IV fluid (0.9%
NaCl/5% dextrose)
(P=0.014).
5 Choong K, Arora S, 258 children enrolled at
Cheng J, et al. the time of surgery in
Hamilton, Ontario,
Choong et al(25)
randomized to
receive hypotonic IV maintenance
fluids (developed a plasma Na <130
mmol/L versus 1.7% (1 of 58) in the
group randomized to receive isotonic
IV fluid (P=0.014). Eight patients
developed hypernatremia (plasma
Na >150 mEq/L), none of whom were
reported to be clinically symptomatic,
and only two of whom had received
isotonic fluids
showed that isotonic fluids
were significantly safer than hypotonic
fluids in protecting against
acute postoperative hyponatremia.
Isotonic fluids did not increase
the risk of hypernatremia

Several parenteral solutions available in the Indonesian market are shown in the following
table:
Composition
Product Size Carbohydrate Total Osmolarity
Electrolytes (mmol/L) (g/L) calorie (mOsm/L)
Na+ K+ Cl- Ca++ Lactate
-
Glucose (kcal/L)
0.9$ NaCl 500 ml 154 154 308
Ringers Lactate 500 ml 130 4 108 1.5 28 272.5
KAEN 3B 500 ml 50 20 50 20 27 108 290
KAEN 3A 500 ml 60 10 50 20 27 108 290
KAEN MG3 500 ml 50 20 50 20 100 400 695
WIDA KDN-1 500 ml 77 20 97 27.5 93.5 333
WIDA KDN-2 500 ml 77 40 117 27.5 93.5 373
WIDA KN-1 500 ml 154 20 174 348
WIDA KN-2 500 ml 154 40 194 388
From this table it is obvious that WIDA KN-1 and WIDA KN-2 have sufficient sodium with the
minimum risk of causing hyponatremia.
Therefore, the selection of maintenance fluids need to be reconsidered especially in pediatric
patients.
In conclusion, clinicians should avoid indiscriminate use of maintenance solutions. The goal of
giving isotonic potassium containing solutions is to prevent hypokalemia without the risk of
hyponatremia.

References:

1. Montaana PA, Modestoi Alapont V, Ocn AP, et al. Pediatr Crit Care Med 2008;9(6):589-97

2. Yung M, Keeley S. Randomised controlled trial of intravenous maintenance fluids. J Paediatr

Child Health 2009;45(1-2):9-14

3. Rey C, Los-Arcos M,Hernndez A, Snchez A, Daz JJ, Lpez-Herce J. Hypotonic versus isotonic
maintenance fluids in critically ill children: A multicenter prospective randomized study. Acta
Paediatrica 2011;100(8):1138-43

4. Kannan L, Lodha R, Vivekanandhan S, Bagga A, Kabra SK, Kabra M. Intravenous fluid regimen
and hyponatremia among children: A randomized controlled trial. Pediatr Nephrol
2010;25(11):2303-9.

5. Choong K, Arora S, Cheng J, et al. Hypotonic versus isotonic maintenance fluids after surgery
in children: A randomized controlled trial. Pediatrics 2011;128(5):857-66