Clinical Guideline Highlights for the Hospitalist: Maintenance Intravenous Fluids in Infants and Children

Hospitalized children with inadequate fluid intake are often administered maintenance intravenous fluids (IVFs) to support metabolic needs and sensible losses. Historically, hypotonic IVFs have been the standard, based on theoretical water and electrolyte requirements for estimated energy expenditure.¹ However, when combined with increased levels of arginine vasopressin (AVP) seen in acutely ill children which impairs free-water excretion,² hypotonic IVF can result in hyponatremia. The recently published guideline by the American Academy of Pediatrics (AAP)³ is the first to provide an evidence-based recommendation on the use of maintenance IVF therapy in children.

Patients between the ages of 28 days and 18 years should receive isotonic solutions with appropriate potassium chloride and dextrose for maintenance IVFs (evidence quality: high; recommendation strength: strong)

Isotonic fluids, such as 0.9% NaCl (normal saline), Hartmann solution and PlasmaLyte, contain a sodium concentration similar to that of plasma (135-144 mEq/L). Lactated Ringer solution (LR) is near-isotonic (sodium 130 mEq/L), but was not used in any of the reviewed studies and therefore not included in the recommendation. Excluded are patients with neurosurgical disorders, congenital or acquired cardiac disease, hepatic disease, cancer, renal dysfunction, diabetes insipidus, voluminous watery diarrhea, severe burns, or patients in the neonatal intensive care unit.

The primary benefit of the AAP recommendation is the reduced risk of iatrogenic hyponatremia and its associated sequelae, including complications or impact on cost of care. The number needed to treat with isotonic fluids was 7.5 to prevent any hyponatremia and 27.8 to prevent moderate hyponatremia (<130 mEq/L). Increases in readmission rates, length of stay, and cost of hospitalization have been reported in a recent meta-analysis reviewing the economic burden of hyponatremia in both adults and children.⁴

Potential harms from the use of isotonic fluids include hypernatremia, hyperchloremic metabolic acidosis, and fluid overload, although available data have not demonstrated an increased risk of these complications. In light of a recent normal saline (NS) shortage in the United States, limited availability is also a consideration. Plasmalyte is more costly than NS and is currently incompatible with the addition of dextrose.

Methods in Preparing Guideline

The guideline development committee included broad representation by pediatric experts in primary care, hospital medicine, emergency medicine, critical care medicine, nephrology, anesthesiology, surgery and quality improvement, as well as a guideline methodologist/informatician and epidemiologist.

Search strategies from recently published systematic reviews of clinical trials comparing isotonic with hypotonic maintenance IVFs were used to identify studies eligible for inclusion. A total of 17 studies with 2,455 total patients were initially identified and included. One additional study meeting inclusion criteria was found after the committee convened and excluded from the guideline.⁵ Three reviewers from the subcommittee performed a structured critical appraisal of each article. The methods of each trial were assessed for risk-of-bias in multiple domains, including randomization, allocation concealment, performance, detection, attrition and reporting. Forest plots were generated using random-effects models and Mantel-Haenzel statistics with the outcome of hyponatremia. The guideline underwent review by various stakeholders including AAP councils, committees, and sections, and individuals considered experts in the field.

A strength of the guideline is the high quality of the evidence and the consistent findings. All of the included studies were randomized clinical trials and the number of included patients was large. Of the 17 included studies, 16 reported a risk ratio favoring isotonic fluids over hypotonic fluids in the prevention of developing hyponatremia; the results of the study that favored hypotonic fluids were not statistically significant on their own. A sensitivity analysis was performed to exclude one study with a 20% weight, determined by multiple factors such as sample size, confidence interval, and an unusually high rate of hyponatremia in the isotonic and hypotonic fluids groups (33.3 % and 70%, respectively).⁶ After exclusion, there was no change in the overall estimated risk in hypotonic fluids leading to hyponatremia. Only one trial had two sources of high risk of bias (allocation concealment, attrition) and the remaining had only low or unclear risk of biases in the various domains.

The study that was excluded due to its late identification similarly shows increased risk of hyponatremia in groups administered hypotonic fluids (risk ratio 6.5-8.5), and would likely not affect the estimated risk.⁵

Despite differences in types of patients enrolled, rate of administered fluids, type of IVF, frequency of lab testing, and study duration, the I² (degree of heterogeneity) of the forest plot of all included studies remained low at 14% and the increased risk of hyponatremia from hypotonic fluids remained consistent.

Due to study design differences, a limitation of the guideline is that no recommendation is made regarding the type of isotonic fluids and the rate of IVF administration. Additionally, due to the low frequency of clinically significant sequelae of hyponatremia, such as hyponatremic encephalopathy, it remains uncertain how many patients would need to be treated with isotonic fluids to prevent a rare but potentially devastating event.