Hypotonic versus Isotonic Fluids in Hospitalized Children: A Systematic Review and Meta-Analysis

doi:10.1016/j.jpeds.2014.01.040

The Journal of Pediatrics

Volume 165, Issue 1, July 2014, Pages 163-169.e2

https://doi.org/10.1016/j.jpeds.2014.01.040 Get rights and content

Objective

To determine whether the use of hypotonic vs isotonic maintenance fluids confers an increased risk of hyponatremia in hospitalized children.

Study design

A search of MEDLINE (1946 to January 2013), the Cochrane Central Registry (1991 to December 2012), Cumulative Index for Nursing and Allied Health Literature (1990 to December 2012), and Pediatric Academic Societies (2000-2012) abstracts was conducted using the terms “hypotonic fluids/saline/solutions” and “isotonic fluids/saline/solutions,” and citations were reviewed using a predefined protocol. Data on the primary and secondary outcomes were extracted from original articles by 2 authors independently. Meta-analyses of the primary and secondary outcomes were performed when possible.

Results

A total of 1634 citations were screened. Ten studies (n = 893) identified as independent randomized controlled trials were included. Five studies examined subjects in the intensive care unit setting, including 4 on regular wards and 1 in a mixed setting. In hospitalized children receiving maintenance intravenous fluids, hyponatremia was seen more often in those receiving hypotonic fluids than in those receiving isotonic fluids, with an overall relative risk of 2.37 (95% CI, 1.72-3.26). Receipt of hypotonic fluids was associated with a relative risk of moderate hyponatremia (<130 mmol/L) of 6.1 (95% CI, 2.2-17.3). A subgroup analysis of hypotonic fluids with half-normal saline found a relative risk of hyponatremia of 2.42 (95% CI, 1.32-4.45).

Conclusion

In hospitalized children in intensive care and postoperative settings, the administration of hypotonic maintenance fluids increases the risk of hyponatremia when compared with administration of isotonic fluids. For patients on general wards, insufficient data are available based on the reviewed studies, and individual risk factors must be assessed.

Section snippets

Methods

We developed a detailed protocol for the selection of studies (available on request from the authors). Studies eligible for inclusion were clinical trials that enrolled hospitalized children aged 1 month to 18 years and compared isotonic and hypotonic IV fluids. Studies were excluded if they did not have a comparison group or only studied patients with diabetes insipidus, diabetic ketoacidosis, burns, or shock, because the former is known to involve sodium dysregulation and the latter 3 require

Results

Our initial search identified 1634 articles, which, after cross-reference and initial screening, we narrowed to 85 abstracts and full text articles. After final review and discussion, we selected 22 full text articles (Figure 1; available at www.jpeds.com). Eleven articles were identified as randomized controlled trials from which data were extracted (Table II).16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26 One article was excluded because complete results were not available, given that the article

Discussion

We found a significantly increased risk of hyponatremia in hospitalized patients receiving hypotonic fluids at maintenance rates. This risk was consistent looking at change in serum sodium and moderate hyponatremia, as well as in the subset of trials using 0.5 normal 0.45% saline as the comparison fluid. This review adds to the previous systematic review¹³ by including 8 additional randomized controlled trials with 777 additional subjects; the majority of these subjects were in an ICU or

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Acute electrolyte and acid-base imbalance is experienced by many children following kidney transplant. This is partly because doctors give very large volumes of artificial fluids to keep the new kidney working. When severe, fluid imbalance can lead to seizures, cerebral edema and death. In this pragmatic, open-label, randomized controlled trial, we randomly assigned (1:1) pediatric kidney transplant recipients to Plasma-Lyte-148 or standard of care perioperative intravenous fluids (predominantly 0.45% sodium chloride and 0.9% sodium chloride solutions). We then compared clinically significant electrolyte and acid-base abnormalities in the first 72 hours post-transplant. The primary outcome, acute hyponatremia, was experienced by 53% of 68 participants in the Plasma-Lyte-148 group and 58% of 69 participants in the standard fluids group (odds ratio 0·77 (0·34 - 1·75)). Five of 16 secondary outcomes differed with Plasma-Lyte-148: hypernatremia was significantly more frequent (odds ratio 3·5 (1·1 – 10·8)), significantly fewer changes to fluid prescriptions were made (rate ratio 0·52 (0·40-0·67)), and significantly fewer participants experienced hyperchloremia (odds ratio 0·17 (0·07 – 0·40)), acidosis (odds ratio 0·09 (0·04 - 0·22)) and hypomagnesemia (odds ratio 0·21 (0·08 – 0·50)). No other secondary outcomes differed between groups. Serious adverse events were reported in 9% of participants randomized to Plasma-Lyte-148 and 7% of participants randomized to standard fluids. Thus, perioperative Plasma-Lyte-148 did not change the proportion of children who experienced acute hyponatremia compared to standard fluids. However fewer fluid prescription changes were made with Plasma-Lyte-148, while hyperchloremia and acidosis were less common.
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Citation Excerpt :
4 Concerns over iatrogenic hyponatremia and associated morbidity and mortality led to several studies and meta-analyses that largely supported the increased risk of clinically significant hyponatremia in children receiving hypotonic mIVF.4 –6 One proposed model for this phenomenon involves free water physiology in ill children.
The long-standing use of hypotonic fluids in pediatric maintenance fluids has been challenged in recent years due to concerns over iatrogenic hyponatremia causing morbidity and mortality. Newer research has highlighted the safety of isotonic fluid alternatives. The American Academy of Pediatrics published an evidenced-based Clinical Practice Guideline in December of 2018 (Feld et al., 2018) to support the routine use of isotonic solutions in pediatric maintenance fluids. This article will also highlight relevant history, current practice, and a quality improvement project to standardize isotonic fluid use in the inpatient pediatric setting.
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: B.F. is a scholar of the Research to Advance Community Health Center. The authors declare no conflicts of interest.

: Portions of this study were presented as an abstract, which received the 2013 Abstract Research Award from the American Academy of Pediatrics, Section of Hospital Medicine at the AAP National Conference & Exhibition in Orlando, FL, October 26-29, 2013.

View full text

Original ArticleHypotonic versus Isotonic Fluids in Hospitalized Children: A Systematic Review and Meta-Analysis

Objective

Study design

Results

Conclusion

Section snippets

Methods

Results

Discussion

J Pediatr

Homeostatic limits to safe parenteral fluid therapy

N Engl J Med

The maintenance need for water in parenteral fluid therapy

Pediatrics

Arginine vasopressin and renin in acutely ill children: implication for fluid therapy

Acta Paediatr

Hospital-acquired hyponatremia: why are hypotonic parenteral fluids still being used?

Nat Clin Pract Nephrol

Fluid therapy for children: facts, fashions and questions

Arch Dis Child

Hospital-acquired hyponatremia: why are there still deaths?

Pediatrics

Prevention of hospital-acquired hyponatremia: a case for using isotonic saline

Pediatrics

Maintenance intravenous fluid prescribing practices among paediatric residents

Acta Paediatr

Hyponatraemia and death or permanent brain damage in healthy children

BMJ

Hypotonic versus isotonic saline in hospitalized children: a systematic review

Arch Dis Child

RevMan version 5.2

A randomised controlled trial of Hartmann's solution versus half normal saline in postoperative paediatric spinal instrumentation and craniotomy patients

Arch Dis Child

Hypotonic versus isotonic maintenance fluids in critically ill children: a multicenter prospective randomized study

Acta Paediatr

Randomised controlled trial of intravenous maintenance fluids

J Paediatr Child Health

The use of isotonic fluid as maintenance therapy prevents iatrogenic hyponatremia in pediatrics: a randomized, controlled open study

Pediatr Crit Care Med

Original Article
Hypotonic versus Isotonic Fluids in Hospitalized Children: A Systematic Review and Meta-Analysis