1. Copyright restrictions may apply JAMA Pediatrics Journal Club Slides: Intravenous Maintenance Fluids Friedman JN, Beck CE, DeGroot J, Geary DF, Sklansky DJ, Freedman SB. Comparison of isotonic and hypotonic intravenous maintenance fluids: a randomized clinical trial. JAMA Pediatr. Published online March 9, 2015. doi:10.1001/jamapediatrics.2014.3809.

2. Copyright restrictions may apply Background –Hyponatremia is a recognized cause of morbidity and mortality in hospitalized children. –Evidence suggests that hypotonic intravenous (IV) maintenance fluid administration in hospitalized children increases their risk of developing hyponatremia. –IV fluid tonicity has not been well studied in nonsurgical hospitalized children outside the intensive care unit setting. –Concerns regarding isotonic fluid use (hypernatremia, fluid overload) have also not been addressed in this population. Study Objective –To compare isotonic (sodium chloride, 0.9%, and dextrose, 5%) with hypotonic (sodium chloride, 0.45%, and dextrose, 5%) IV maintenance fluids in a hospitalized general pediatric population. Introduction

3. Copyright restrictions may apply Study Design –Double-blind randomized clinical trial. –154 mEq/L of sodium (sodium chloride, 0.9%, and dextrose, 5%) vs 77 mEq/L of sodium (sodium chloride, 0.45%, and dextrose, 5%). –Potassium added per the responsible physician. –Oral fluids considered in total fluid intake. –Monitoring until 48 hours or earlier per termination criteria. Setting –General pediatric unit of a freestanding tertiary care children’s hospital. Patients –Admitted children aged 1 month to 18 years with a normal baseline serum sodium level, requirement for IV fluid administration at 80% to 120% of maintenance, and anticipated IV fluid requirement of ≥48 hours. –Children with diagnoses that required specific fluid tonicity and volumes were excluded. Methods

4. Copyright restrictions may apply Methods Outcomes –Primary: mean serum sodium level 48 hours after initiation of therapy. –Secondary: Mean serum sodium level 24 hours after initiation of therapy. Development of hyponatremia (sodium <135 mEq/L plus a decrease of ≥4 mEq/L from baseline). Development of hypernatremia (sodium >145 mEq/L plus an increase of ≥4 mEq/L from baseline). Signs of fluid overload (weight gain, hypertension, edema). Limitations –Not powered to detect statistical differences in secondary outcomes. –Findings cannot be generalized to excluded children with specific IV fluid requirements (eg, those requiring rehydration or replacement fluids) or to postoperative children or those admitted to an intensive care unit.

5. Copyright restrictions may apply Results Study Profile

6. Copyright restrictions may apply Results Participants –Median age, 4.5 years. –Most common diagnoses: pneumonia, sickle cell disease, infections, asthma, vomiting. –No differences in baseline variables. –Groups received similar total volumes of IV and oral fluids. Primary and Secondary Outcomes –No statistically significant differences between the groups. –Two patients in the hypotonic group developed hyponatremia. –One patient in each group developed hypernatremia. Adverse Events –None attributed to study intervention.

7. Copyright restrictions may apply Results Primary and Secondary Outcomes a

8. Copyright restrictions may apply Comment In a population of general pediatric patients outside the intensive care unit, there was no significant difference in mean serum sodium levels at 24 and 48 hours between those in the isotonic and hypotonic IV maintenance fluid groups. 2 of 56 patients in the hypotonic group developed hyponatremia (vs nil in the isotonic group). –Their participation in the study was terminated at 24 hours; it is unknown how low their 48-hour sodium level would have been had they continued to receive hypotonic fluids. No increase in clinically relevant hypernatremia or fluid overload occurred in the children receiving isotonic fluids.

9. Copyright restrictions may apply Conclusions The study results support the notion that isotonic maintenance fluid administration is safe in general pediatric patients and may result in fewer cases of hyponatremia.

10. Copyright restrictions may apply If you have questions, please contact the corresponding author: –Jeremy N. Friedman, MBChB, FRCP, Department of Paediatrics, Paediatric Outcomes Research Team, The Hospital for Sick Children, 555 University Ave, Toronto, ON M5G 1X8, Canada (jeremy.friedman@sickkids.ca). Funding/Support This study was supported by grants from Physicians’ Services Incorporated Foundation and Department of Paediatrics, The Hospital for Sick Children. Conflict of Interest Disclosures None reported. Contact Information