Things We Do For No Reason: The Default Use of Hypotonic Maintenance Intravenous Fluids in Pediatrics

Why Isotonic Maintenance IV Fluids Are Usually The Right Choice For Children

General recommendations for hypotonic IV fluids are primarily based on theoretical calculations from the fluid and electrolyte requirements of healthy individuals, and studies have not validated the use of hypotonic IV fluids in clinical practice.¹ Acutely ill patients are at risk for excessive levels of ADH from numerous causes (see Table 2).² As a result, nearly every hospitalized patient is at risk for excess ADH release, thus making them vulnerable to the development of hyponatremia. The syndrome of inappropriate secretion of ADH (SIADH) occurs when nonosmotic/nonhemodynamic stimuli trigger ADH release, which leads to excessive free-water retention and resultant hyponatremia. Schwartz and Bartter reported the first two cases of SIADH in 1957 when hyponatremia developed in the setting of bronchogenic carcinoma.⁴ Although the publication by Holliday and Seger did acknowledge the potential for water intoxication, it was written before this report and before the effects of ADH on the sodium levels of hospitalized patients were clearly understood.² SIADH is now recognized as one of the most common causes of hyponatremia in hospitalized patients.^{5, 6}

Numerous studies have demonstrated that patients who receive hypotonic IV fluids have a significantly higher risk of developing hyponatremia than patients who receive isotonic IV fluids.^7,8 An infrequent, yet serious, complication of iatrogenic hyponatremia is hyponatremic encephalopathy, which carries a high rate of morbidity or mortality.⁹ The prevention of hyponatremia is essential as the early symptoms of hyponatremic encephalopathy are nonspecific and can be easily missed.²

More than 15 prospective randomized controlled trials (RCTs) involving over 2,000 children have demonstrated that isotonic IV fluids are more effective in preventing hospital-acquired hyponatremia than hypotonic IV fluids and are not associated with the development of fluid overload or hypernatremia. A 2014 metaanalysis comprising 10 RCTs and involving over 800 children found that when compared with isotonic IV fluids, hypotonic IV fluids present a relative risk of 2.37 for sodium levels to drop below 135 mEq/L and a relative risk of 6.1 for levels to drop below 130 mEq/L. The numbers needed to treat (NNT) with isotonic IV fluids to prevent hyponatremia in each group were 6 and 17, respectively.⁷ A Cochrane review published in 2014 presented comparable findings, demonstrating that hypotonic IV fluids had a 34% risk of causing hyponatremia; by comparison, isotonic IV fluids had a 17% risk of causing hyponatremia and a NNT of six to prevent hyponatremia.⁸ In a large RCT conducted in 2015 with 676 pediatric patients, McNabb et al. found that when compared with patients receiving isotonic IV fluids, those receiving hypotonic IV fluids had a higher incidence of developing hyponatremia (10.9% versus 3.8%) with a NNT of 15 to prevent hyponatremia with the use of isotonic fluids.¹⁰ Published trials have likely been underpowered to detect a difference in the infrequent adverse hyponatremia outcomes of seizures and mortality.

On the basis of these data, patient safety alerts have recommended the avoidance of hypotonic IV fluids in the United Kingdom (UK) and Australia, and the 2015 UK guidelines for children now recommend isotonic IV fluids for maintenance needs.¹¹ Although many of the aforementioned studies included predominantly critically ill or surgical pediatric patients, the risk of hyponatremia with hypotonic IV fluids seems similarly increased in nonsurgical and noncritically ill pediatric patients.¹⁰

For patients at risk for excess ADH release, some have supported the use of hypotonic IV fluids at a lower than maintenance rate to theoretically decrease the risk of hyponatremia, but this practice has not been effective in preventing hyponatremia.^2,12 Unless a patient is in a fluid overload state, such as in congestive heart failure, cirrhosis, or renal failure; isotonic maintenance IV fluids should not result in fluid overload.³ Available evidence for guiding maintenance IV fluid choice in neonates or young infants is limited. Nevertheless, given the aforementioned reasons, we generally recommend the prescription of isotonic IV fluids for most in this population.