Hypotonic IV Fluid May Raise Hyponatremia Risk in Children

Veronica Hackethal, MD

December 31, 2013

Hospitalized children who receive hypotonic maintenance intravenous (IV) fluids are at higher risk of developing hyponatremia than those receiving isotonic IV fluids, according to a recent meta-analysis published online December 30 in Pediatrics.

"Isotonic fluids are safer than hypotonic fluids in hospitalized children requiring maintenance IV fluid therapy in terms of [plasma sodium concentration (pNA)]," the authors write. They mention the possibility for hypotonic maintenance IV fluids to increase severe complications of hyponatremia, such as death and hyponatremic encephalopathy. The authors note, however, that the sample size of this meta-analysis may have been too small to capture and draw conclusions about such rare events.

Following longstanding tradition, the authors explain, hospitalized children who need maintenance IV fluids most commonly receive hypotonic fluids, a practice recommended in guidelines and text books. However, according to the authors, hospitalized children under physiological stress often secrete antidiuretic hormone, promoting water retention and making them prone to hyponatremia. Receiving hypotonic IV fluids may further exacerbate illness-related hyponatremia.

The authors searched PubMed, Embase, Cochrane Library, and clinicaltrials.gov for randomized clinical trials published before April 11 that compared hypotonic with isotonic IV fluid maintenance therapy in hospitalized children aged 1 month to 17 years. They extracted data from identified the trials using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standardized form. They analyzed the trials for pooled relative risk of developing hyponatremia (pNA <136 mmol/L), severe hyponatremia (pNa <130 mmol/L), hypernatremia (pNA >145 mmol/L), pNA changes after initiating IV fluid therapy, and adverse events. They also assessed for risk for bias using the Cochrane risk-of-bias tool.

They identified 10 randomized controlled trials covering 855 patients that met the inclusion criteria. Hypotonic IV fluids were significantly associated with higher risk for hyponatremia (relative risk [RR], 2.24; 95% confidence interval [CI], 1.52 - 3.31; P < .0001; I 2, 14%) and for severe hyponatremia (RR, 5.29; 95% CI, 1.74 - 16.06; P < .003; I 2, 0%).

In addition, children receiving hypotonic IV fluids showed significantly greater decreases in pNA (−3.49 mmol/L; 95% CI, −5.63 to −1.35; P = .001; I 2, 87%). There were no significant differences between the 2 fluids and the risk for hypernatremia (RR, 0.73; 95% CI, 0.22 - 2.48; P = .62; I 2, 0%). Adverse effects included 1 death in the setting of respiratory distress syndrome and normal pNA, 1 case of hyponatremic encephalopathy with stupor and seizure in a child receiving hypotonic IV fluids, and new-onset hypertension in 2 children receiving hypotonic fluids.

Study limitations included differences between patients regarding variables such as fluid types (eg, 0.45% saline vs 0.18% saline), differences in fluid duration and administration rate, and study quality. The inclusion of only published studies could also have introduced publication bias. Finally, most of the included studies had small sample sizes.

The authors conclude that isotonic IV maintenance fluids are safer than hypotonic fluids in hospitalized children. However, they emphasize the need for pNA monitoring, noting that no IV fluid is ideal for all children because of differing compositions and rates and duration of administration. "At present," they note, "isotonic fluids may be a better choice than the traditional recommendations."

The authors have disclosed no relevant financial relationships.

Pediatrics. Published online December 30, 2013. Abstract

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