Systematic Review of Hypotonic Versus Isotonic Intravenous Fluids

Sunday, October 27, 2013
Regency Ballroom S (Hyatt Regency Orlando, formerly the Peabody)
Byron A Foster, MD, MPH, Dina Tom, MD and Vanessa L Hill, MD, University of Texas Health Science Center at San Antonio, San Antonio, TX


Intravenous fluids are a mainstay of inpatient pediatric care. The goal is to provide the requisite amount of water, electrolytes and glucose without disturbing physiologic equilibrium. Controversy has emerged over the appropriate amount of electrolytes these fluids should contain, namely whether they should be isotonic to blood or hypotonic. The purpose of this systematic review was to address the question of whether hypotonic fluids or isotonic fluids at maintenance rates confer an increased risk of developing hyponatremia in hospitalized, pediatric patients.



A search of Medline (1946-Jan2013), the Cochrane Central Registry (1991-Dec2012), CIANHL (1990-Dec2012) and PAS abstracts (2000-2012) was completed. Terms used in the search were ‘hypotonic fluids/saline/solutions,' ‘isotonic fluids/saline/solutions' with the restrictions of children and clinical trial. Data were extracted using a standardized form and reviewed independently by two authors with discrepancies resolved through discussion. A systematic assessment of bias was done using Cochrane Review methodology. A meta-analysis of the randomized controlled trials was completed using RevMan 5.2 with hyponatremia as the primary outcome, defined as a serum sodium <135mmol/L.


The initial search identified 1634 articles which, after cross-reference and initial screen, were narrowed to 85 abstracts and full-text articles for further review. After final review and discussion, 22 full text articles were selected. Ten articles were identified as independent randomized controlled trials and data extracted. We found an overall relative risk of 2.28 (1.73-3.00) of hyponatremia (serum sodium <135mmol/L) in the subjects who received hypotonic fluids as compared to isotonic fluids. Doing the analysis for risk difference, we found a risk difference for hyponatremia of 0.19 (95% CI: 0.11-0.26) between the two groups giving a number needed to harm of 5.26 (95% CI: 3.85-9.09) when using hypotonic fluids. For the post-hoc sub-group analysis of hypotonic fluids using at least half-normal saline as the comparison, we found similar results to the overall analysis with a relative risk of 2.42 (CI: 1.32-4.45). 


Hypotonic fluids used at maintenance rates in hospitalized pediatric patients confer an increased risk of iatrogenic hyponatremia versus isotonic fluids. Most studies primarily enrolled post-operative surgical patients, though the studies evaluating medical patients showed similar findings. Hypotonic fluids should not routinely be used in hospitalized children, and serum sodium levels should be monitored to avoid the potential morbidity associated with intravenous fluids.