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Administration of hypotonic solutions vs. isotonic solutions in hospitalized children.

The Evidence Summarized and Leveled

Study 1. Findings from a meta-analysis that included 6 randomized controlled trials indicated that hypotonic solutions (less than 0.9% NS) significantly increased the risk of developing acute hyponatraemia over isotonic (0.9% NS or Ringers Lactate) solutions. Overall treatment effect--Odds of hyponatremia after hypotoninc solution are 17.2 times greater than with isotonic fluid (95% CI 8.67 to 34.2), and result in greater patient morbidity. Six studies met inclusion criteria in this meta-analysis. Limitations--The 6 studies had heterogeneous designs, small samples of variable quality (only 2 RCTs), and did not consider confounding factors, such as mixed populations (included surgical and non-surgical, majority are postoperative) (Level 1) (Choong, Kho, Menon, & Bohn, 2006). Nonetheless, systematic reviews are the strongest to guide practice.

Study 2. Hospitalized children who developed hyponatremia received more electrolyte-free water and had a higher positive water balance than those who did not develop hyponatremia. This group also received fluid amounts that were above recommended maintenance requirements. This retrospective, case-control study with a convenience sample (N = 40) did not have an adequate sample size to enable statistical judgments that are accurate and reliable (the study did not have adequate power). It included surgical and non-surgical patients. Cases were matched on age, gender, and weight, but not diagnosis, which may be a factor in the outcome of interest (case-control, observational with inadequate power) (Level IV) (Hoorn, Geary, Robb, Halperin, & Bohn, 2004).

Study 3. Children hospitalized in an intensive care unit (N = 122) were randomized to receive isotonic or hypotonic fluids. After 24 hours of fluid therapy, hyponatremia was present in 20.6% in the hypotonic group versus 5.1% in the isotonic group (p = 0.02). Other than hyponatremia, no differences in number of adverse events was observed (Level 11) (Montanana et al., 2008).

Study 4. Post-operative use of isotonic fluid in children undergoing surgical correction of scoliosis (N = 24) helps prevent hyponatremia. Few patients (n = 4) received isotonic, and there was no statistical comparison between groups, only within groups looking at decrease in sodium (observational cohort study with inadequate power) (Level IV) (Burrows, Shutack, & Crone, 1983).

Study 5. There was no difference in the incidence of moderate or severe hyponatremia in children who received hypotonic or isotonic fluids (a trend was noted toward increased incidence of hyponatremia in those receiving hypotonic fluids postoperatively). Retrospective study in children undergoing surgery (excluding cardiac, neurosurgical, renal) admitted to the pediatric intensive care unit (N = 145); isotonic fluid was administered to fewer children (20% of sample); small sample size limited statistical power (Level IV) (Au et al., 2008).

Study 6. While all 3 studies that met inclusion criteria for this systematic review advised against routine use of hypotonic IV fluids for maintenance, results were inconclusive. Also, administration of hyptonic fluids did not always account for the development of hyponatremia (systematic review with only 3 observational studies, some with weak designs, no randomized trials) (Level IV) (Beck, 2007).

Study 7. Hospitalized patients have excess arginine vasopressin (AVP) production that increases their risk for developing hyponatremia. Administration of hypotonic fluid when excess AVP present results in hyponatremia. Use of 0.9% NS can prevent hyponatremia with no neurological complications reported from use of 0.9% NS. Patients with free water losses (for example, from renal concentrating defects or secondary to diarrhea or fever) likely require more hypotonic fluid (Level VII) (Moritz & Ayus, 2007).

Study 8. Hypovolemia often causes the non-osmotic stimulation of antidiuretic hormone in acutely ill children. Rapid expansion of extracellular fluid with isotonic saline and then oral or 1V maintenance should be tailored to half maintenance or maintenance based on the child's response. Other factors that stimulate antidiuretic' hormone (ADH) production, such as vomiting, anesthesia, and medications, must also be considered. Use of isotonic saline for maintenance therapy may impose comparable consequences to those of free water load, as argued by Mortiz and Ayus (2007) (Level VII) (Holliday, Ray, & Friedman, 2007).

Implications for Practice

* The systemic review (Study 1) gives the strongest evidence that is also supported by Study 3.

* The demonstration of the benefits of isotonic fluids over hypotonic fluids warrants more research.

* Fluid administration must be individualized. Both hyponatremia and hypernatremia have negative consequences.

* The potential for hospitalized children who are receiving parenteral fluids must be considered, particularly in the post-operative period, to be at risk for developing hyponatremia or hypernatremia. Blood pressure, neurological status, daily weights, fluid balance, and serum sodium concentration should be closely monitored and other signs of hyponatremia and hypernatremia assessed.

* Hypotonic fluid should not be administered to children who have a serum sodium less than 138 mmol/L (Hoorn et al., 2004).

* There are currently no practice guidelines available.

Additional Readings

Armon, K., Riordan, A., Playfor, S., Millman, G., Khader, A., & the Paediatric Research Society. (2008). Hyponatraemia and hypokalaemia during intravenous fluid administration. Archives of Disease in Childhood, 93(4), 285-287.

Playfor, S.D. (2004). Hypotonic intravenous solutions in children. Expert Opinion on Drug Safety, 3(1), 67-73.


Au, A.K., Ray, RE., McBryde, K.D., Newman, K.D., Weinstein, S.L., &

Bell, M.J. (2008). Incidence of postoperative hyponatremia and complications in critically-ill children treated with hypotonic and normotonic solutions. Journal of Pediatrics, 152(1), 33-38.

Beck, C.E. (2007). Hypotonic versus isotonic maintenance intravenous fluid therapy in hospitalized children: A systematic review. Clinical Pediatrics, 46(9), 764-770.

Burrows, RA., Shutack, J.G., & Crone, R.K. (1983). Inappropriate secretion of antidiuretic hormone in a postsurgical pediatric population. Critical Care Medicine, 11(7), 527-531.

Choong, K., Kho, ME., Menon, K., & Bohn, D. (2006). Hypotonic versus isotonic saline in hospitalised children: A systematic review. Archives of Disease in Childhood, 91(10), 828-835.

Holliday, M.A., Ray, RE., & Friedman, A.L. (2007). Fluid therapy for children: Facts, fashions and questions. Archives of Disease in Childhood, 92(6), 546-550.

Hoorn, E.J., Geary, D., Robb, M., Halperin, M.L., & Bohn, D. (2004). Acute hyponatremia related to intravenous fluid administration in hospitalized children: An observational study. Pediatrics, 113(1), 1279-1284.

Melnyk, B.M., & Fineout-Overholt, E. (2005). Evidence-based practice in nursing and healthcare. Philadelphia: Lippincott Williams & Wilkins.

Montanana, RA., Modesto, I., Alapont, V., Ocon, A.R, Lopez, RO., Lopez Prats, J.L., et al. (2008). The use of isotonic fluid as maintenance therapy prevents iatrogenic hyponatremia in pediatrics: A randomized, controlled open study. Pediatric Critical Care Medicine, 9(6), 589-597.

Mortiz, M.L., & Ayus, J.C. (2007) Hospital-acquired hyponatremia Why are hypotonic parenteral fluids still being used? Nature Clinical Practice. Nephrology, 3(7), 374-382.

To develop a spirit of inquiry and support implementation of evidence-based practice, this new column provides an overview of available evidence on selected clinical practice issues. Readers are invited to submit clinical questions for review. The population, intervention, comparison, and outcome (PICO) method is used to phrase the clinical question, provide an overview of the available evidence, and offer implications for clinical practice based on the evidence. Evidence is categorized by level based on Melnyk and Fineout-Overholt's (2005) rating system for the hierarchy of evidence (see Figure 1), with Level I providing more credible results. Conclusions should not be considered official recommendations for care nor serve as an official position statement of this journal or any nursing organization.

Note: It is important to note that the level of evidence plus the quality of evidence leads to confidence to act and change practice. To contact the column editors with your clinical questions or comments, email or

Cindy Smith Greenberg, DNSc, RN, CPNP, is an Assistant Professor and Chair, Department of Nursing, California State University, Fullerton, CA.

Vicky R. Bowden, DNSc, RN, is Director of the Honors Program and Professor, School of Nursing, Azusa Pacific University, Azusa, CA.
Figure 1. Rating System for the Hierarchy of Evidence

Level I     Evidence for a systematic review or meta-analysis of
            all relevant RCTs or evidence-based clinical practice
            guidelines based on systematic reviews of RCTs.
Level II    I Evidence obtained from at least one well-designed RCT.
Level III   Evidence obtained from well-designed controlled
            trials without randomization.
Level IV    Evidence from well-designed case-control and cohort
Level V     Evidence from systematic reviews of descriptive and
            qualitative studies.
Level VI    Evidence from a single descriptive or qualitative study.
Level VII   Evidence from the opinion of authorities and/or
            reports of expert committees.

Source: Melnyk & Fineout-Overholt, 2005.
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Title Annotation:To Question: Leading Us to The Answer
Author:Greenberg, Cindy Smith; Bowden, Vicky R.
Publication:Pediatric Nursing
Article Type:Report
Geographic Code:1USA
Date:Jan 1, 2009
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