aintenance intravenous fluids are an integral
part of care in acutely ill hospitalized children, the main objective
being to compensate for the renal and insensible losses.The fluid
calculation is based on the five decade old Holliday and Segar formula
derived from calorie expenditures of healthy children . However,
accumulating evidence over the years has challenged this traditional
approach. The hypotonic formulae extrapolated from healthy children tend
to overestimate fluid needs in sick children as their endogenous
metabolism and calorie expenditure are reduced. Additionally,
non-hemodynamic stimuli for Arginine Vasopressin (AVP) impairs the
kidney’s ability to excrete free water thus adding ‘fuel to the fire,
thereby increasing the risk of hyponatremia. It is believed that
virtually every hospitalized patient requiring intravenous fluids has a
potential stimulus for AVP excess and should be considered to be at risk
This physiological phenomenon has been amply
supported by evidence that suggest that hypotonic fluids are the primary
factor leading to hospital-acquired hyponatremia. A recent meta analysis
 of 10 randomized controlled trials involving 855 subjects concluded
that hypotonic intravenous fluids significantly increased the risk of
hyponatremia in hospitalized children. In this issue of Indian
Pediatrics, Shamim, et al.  have reported a randomized
controlled trial comparing reduced maintenance volume (60%) isotonic
versus standard maintenance volume hypotonic maintenance fluids, and
concluded that the former resulted in fewer hyponatremic episodes during
the first 48 hours of fluid therapy. The incidence of hyponatremia in
the hypotonic versus isotonic saline group was 70% and 33.3%,
respectively, thus echoing the previous observations on this issue.
Also, the incidence was much higher than the previously reported range
of 1.4% to 45% , possibly due to higher proportion of central nervous
system and respiratory illnesses representing 71.6% of the total study
population. It is well known that children with meningitis,
encephalitis, bronchiolitis, gastroenteritis, and head injury are at an
increased risk for hyponatremia . However, what is intriguing is the
higher incidence of hyponatremia in the isotonic group (33.3%). Most of
the studies comparing the two regimens have reported incidence of
hyponatremia in isotonic group to the tune of 1.7-16% [5-7]. This brings
us to an important question – can hyponatremia be commonly seen even
with isotonic maintenance fluids? The answer is yes, again throwing the
spotlight on the role of kidneys in excreting hypertonic urine and
generating electrolyte free water (EFW). Expansion of intravascular
volume following isotonic fluids triggers partial secondary desalination
resulting in hypertonic urine due to disproportionately more sodium than
water loss. The excess EFW thus formed is retained in presence of
non-osmotic AVP effect. The other mechanism to explain hyponatremia with
isotonic fluids is the intracellular shift and redistribution of sodium
due to increased membrane permeability known as translocational
hyponatremia or sick cell hyponatremia . This was the postulate put
forward by authors of a prospective observational study where the fall
in serum sodium levels in critically ill children could not be explained
solely by EFW excess or natriuresis . The above findings suggest that
hyponatremia in this study cohort was possibly multifactorial.
Alternative mechanisms of secondary desalination and trans-locational
hyponatremia may need further exploration. Urine output measurements,
urinary electrolytes, and AVP estimation would have been invaluable and
thrown more light on this issue.
The other question the current study raises but does
not answer is that of rate of administration versus tonicity of
fluids. This debate has been addressed by a few investigators. The
opponents of isotonic fluid use argue that if the most important
determinant of hyponatremia is excess EFW then why not counter it with
restricted fluids rather than increased salt? This argument finds favor
in the observations reported in susceptible euvolemic patients, in whom
both isotonic and hypotonic maintenance fluids resulted in net sodium
increase when fluid restriction countered the AVP-induced ‘secondary
desalination’ . On the contrary, Yung, et al.  in their
double-blind randomized controlled trial concluded that fluid type
rather than rate had a greater effect on sodium concentration even
though the pre-admission fluids received by the patients were not
recorded. Kannan, et al. , in their randomized controlled
trial demonstrated that incidence of hyponatremia was reduced in the
group receiving 0.9% saline in 5% dextrose at standard maintenance
volume. Similar observations were reported by Coulthard, et al.
, where post operative administration of one-third normal saline at
two-thirds of standard rate caused hyponatremia in 37% of patients.
As of now, the body of evidence is largely tilted in
favor of isotonic maintenance fluids in sick children. However before a
‘one size fits all’ strategy becomes applicable across the board, we
need more answers on alternative mechanisms for hyponatremia. To put the
fluid type versus rate debate to rest, further robust studies
with multiple arms for different fluid tonicity and volumes along with
measurement of urinary electrolytes, osmolality and plasma AVP levels
are needed. Until then we need to tailor individual fluid needs, based
on clinical scenario and strict serum sodium monitoring.
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