University of Michigan
Department of Pediatrics
Evidence-Based Pediatrics Web Site

Question

• Among hospitalized children with dehydration, does the use of isotonic intravenous fluid result in less adverse outcomes?

Clinical Bottom Lines

1. There is potential harm with hypotonic intravenous solutions in children related to hyponatremia and complications of hyponatremia.
2. Isotonic intravenous solutions can protect against and in some cases correct hyponatremia.
3. Neither isotonic nor hypertonic solutions were associated with significant hypernatermia.

Summary of Key Evidence

1. Children ages 6 months to 14 years with a presumptive diagnosis of gastroenteritis were eligible for the study only after a decision to treat with intravenous fluids had been made.  Children were excluded from the study if they had a known abnormality of ADH secretion, nephrogenic diabetes insipidis, renal disease, acute or chronic lung disease, or were receiving drugs known to stimulate ADH secretion.¹  
2. At enrollment, children were prospectively randomized to receive 0.45% saline + 2.5% dextrose (N/2) or 0.9% saline + 2.5% dextrose (NS).  The treating physician was told which fluid had been selected.  The rate of infusion was not randomized, but was determined by the treating physician according to one of two clinical protocols, the “rapid replacement protocol” (RRP) or the “slow replacement protocol” (SRP).  Blood samples were collected before and 4 hours after the start of IV fluids.
3. There were no differences in the historical, clinical, or biochemical characteristics at presentation or the fluid rate received comparing the 51 children who received N/2 with the 51 who received NS.
4. The short-term response of plasma and urinary electrolytes and osmolarity to treatment with either fluid choice was analyzed according to whether the children were hyponatremic or normonatremic at time 0.  Data from 51 in each group was analyzed 4 hours after rehydration.
5. After four hours of rehydration with N/2, the mean plasma sodium had not changed in the hyponatremic children (p = 0.32) but had decreased significantly in the normonatremic group (p< 0.001). In the normonatremic group, plasma Na decreased by at least 2mmol/L in 51% compared with 13% in the hyponatremic group (p< 0.001).
6. After four hours of rehydration with NS, there was a mean increase in plasma Na of 2.4 mmol/L in children who were initially hyponatremic (p< 0.001) compared with no significant change in the normonatremic group (p = 0.08).  13% of the normonatremic group and none of the hyponatremic group experienced a plasma Na decrease of at least 2mmol/L.
7. The infusion rate (RRP versus SRP) was not a determinant of the change in plasma sodium in either treatment arm.
8. Additionally, 42 children (22 N/2 and 20 NS) received IV fluids for greater than 4 hours.  5 of the 22 children treated with N/2 but none treated with NS (p = 0.03) had persistent significant hyponatremia.
9. Neither solution was associated with significant hypernatremia.

Additional Comments

• Formal study of randomized participants only followed for 4 hours past initiation of therapy. Further data collection would be helpful from a longer RCT.
• Study participants and caregivers were not blinded.

Citation

1. Neville KA, Verge CF, Rosenberg AR, O'Meara MW, Walker JL  Isotonic is better than hypotonic saline for intravenous rehydration of children with gastroenteritis: a prospective randomised study. Arch Dis Child 2006;91:226-32.
2. Choong K, Kho ME, Menon K, Bohn D.  Hypotonic versus isotonic saline in hospitalized children: a systematic review. Arch Dis Child 2006;91:828-35.

CAT Author: Amanda Long, MD

CAT Appraisers: Beth Tarini, MD

Date appraised: April 18, 2007