Isotonic fluids – are they better than hypotonic fluids for children? Journal Club Thursday 16 th April 2015 Charlotte Elder.

Isotonic fluids – are they better than

hypotonic fluids for children?

Journal Club

Thursday 16th April 2015

Charlotte Elder

The maintenance need for water in parenteral fluid therapy

Holliday and SegarPediatrics 1957

0.9%

0.45%0.18%

HypernatraemiaHyperchloraemic acidosisFluid overload

HyponatraemiaDehydration

The Clinical Question

Population In children requiring intravenous fluid

Intervention Isotonic fluid (Na140)

Comparison Hypotonic fluid (Na77)

Outcome Reduce hyponatraemia

Design Randomised, double-bind, placebo controlled trial

50% - 150% maintenance

Recruited from ED and pre-ops

Na >150 mmol/LNa <130 mmol/L

IVI < 6 hours

LOT OF exclusions – basically any condidtion in which “standard fluid” may not be given DI, neuro surg, meningitis,

• 1:1 NA140:Na77

• Stratified by baseline Na

• >135, 135-145, >145

• All HCP

• Fluid bags A-H

• Identical looking

Normal saline: 154 mEq/L sodium and 154 mEq/L chloride.

Methods• Serum Na within 4 hours

• Post-op – serum Na end of procedure

• Rate determined by clinicians

• Study fluid for 72 hrs or <50% maintenance

• Study fluid stopped if:

– Na <130

– Na >150

– With Δ baseline 3+ mmol/L

– Clincian decided not in pt’s best interest

– Intention to treat data

Methods• Serum electrolytes

– 6, 24, 48, 72

– Na, K, Cl, HCO3, U, Cr, Gl

• Blood gas analyser OR Vitros lab assay

• Urine electrolytes at ~24 hours

• Clinical team monitored fluid status:

– Standardised hydration assessment – if indicated and when fluid

stopped

• SAEs recorded e.g. ITU admissions

Outcome measures• Primary

– Occurrance of hyponatraemia within 72 hours

• Na <135 mmol/L with ≥3 mmol/L

• Secondary

– Severe hyponatraemia <130 mmol/L

– Hypernatraemia >145 mmolL

– Severe hypernatraemia >150 mmolL

– Hyperchloraemia >110 mmol/L

– Hypermagnesaemia >1.2 mmol/L

– Hypercarbia >30 mmol/L

– Mean serum Na and wt at 6, 24, 48, 72 hours

– Others: fits, CO, coma, recannulation, hydration changes

Stats• Sample size: 320 per arm

– Reduction of hyponatraemia from 10% Na77 to 4% Na140

– Power: 80%

• Intention to treat analysis

• OR – measure of association between an exposure and an outcome– Odds of hyponatraemia occurring with Na77

– >1 is association

• Sensitivity and subgroup analyses– Age, total fluid, ITU/surgery, contaminated samples,

Study flow chart

http://www.casp-uk.net/

Hyponatraemia 4% vs 11%

Significant difference

0.16-0.61

p=0.001

Limitations

• Blood gas vs lab assay

• Not a trial of 0.9% fluid

• Not powered for symptomatic hyponatraemia

• Multiple exclusions

Summary and Conclusion

Very well designed study

CLINICAL BOTTOM LINE

– Don’t use IV fluids unless clinically indicated

– Watch for signs of hypoNa EARLY - within first 6 hrs

– Consider use of isotonic fluids as routine?