EBM Review: The Pediatric Intravenous Maintenance Solution study (PIMS): a randomised controlled double-blind trial.

McNab S, Duke T, South M, et al. 140 mmol/L of sodium versus 77 mmol/L of sodium in maintenance intravenous fluid therapy for children in hospital (PIMS): a randomised controlled double-blind trial. Lancet. 2014 Nov 28.

BACKGROUND: Use of hypotonic intravenous fluid to maintain hydration in children in hospital has been associated with hyponatraemia, leading to neurological morbidity and mortality. We aimed to assess whether use of fluid solutions with a higher sodium concentration reduced the risk of hyponatraemia compared with use of hypotonic solutions.

METHODS: We did a randomised controlled double-blind trial of children admitted to The Royal Children’s Hospital (Melbourne, VIC, Australia) who needed intravenous maintenance hydration for 6 h or longer. With an online randomisation system that used unequal block sizes, we randomly assigned patients (1:1) to receive either isotonic intravenous fluid containing 140 mmol/L of sodium (Na140) or hypotonic fluid containing 77 mmol/L of sodium (Na77) for 72 h or until their intravenous fluid rate decreased to lower than 50% of the standard maintenance rate. We stratified assignment by baseline sodium concentrations. Study investigators, treating clinicians, nurses, and patients were masked to treatment assignment. The primary outcome was occurrence of hyponatraemia (serum sodium concentration <135 mmol/L with a decrease of at least 3 mmol/L from baseline) during the treatment period, analysed by intention to treat. The trial was registered with the Australian New Zealand Clinical Trials Registry, number ACTRN1260900924257.

FINDINGS: Between Feb 2, 2010, and Jan 29, 2013, we randomly assigned 690 patients. Of these patients, primary outcome data were available for 319 who received Na140 and 322 who received Na77. Fewer patients given Na140 than those given Na77 developed hyponatraemia (12 patients [4%] vs 35 [11%]; odds ratio [OR] 0·31, 95% CI 0·16-0·61; p=0·001). No clinically apparent cerebral oedema occurred in either group. Eight patients in the Na140 group (two potentially related to intravenous fluid) and four in the Na77 group (none related to intravenous fluid) developed serious adverse events during the treatment period. One patient in the Na140 had seizures during the treatment period compared with seven who received Na77.

INTERPRETATION: Use of isotonic intravenous fluid with a sodium concentration of 140 mmol/L had a lower risk of hyponatraemia without an increase in adverse effects than did fluid containing 77 mmol/L of sodium. An isotonic fluid should be used as intravenous fluid for maintenance hydration in children.

Reviewed by:

Farida Kwaji Farida Kwaji, MD

Diane (Isaacson) Charles Diane Charles, MD

Background

  • In 1957 an historical study by Holliday and Segar provided electrolyte and fluid calculations for fluid rehydration by age group that are still used till this day.
  • Since this time there has been significant debate regarding the appropriate electrolyte composition to be used for inpatient iv fluid hydration.
  • The majority of fluids currently in use are hypotonic in comparison to plasma and potentially can lead to hyponatremia and its subsequent complications.
  • Given the concern for the association between hypotonic IV fluids and hyponatremia previous studies have advocated for the increased in sodium concentration from 30mmol/L to 75mmol/L.
  • However even with this change hyponatremia has continued to be a concern and there were no large heterogeneous pediatric inpatient population studies.

EBM iv fluids

Study Methods

  • 3 year randomised double blind control trial.
  • Heterogeneous population of children at The Royal Children’s Hospital in Melbourne Australia.
  • Goal: to establish whether an isotonic fluid Na140 reduced risk of hyponatremia compared with hypotonic fluid Na77 without an increase in adverse effects.

Results

  • Primary outcome: Occurrence of hyponatremia
    • < 135mmol/L or < 3mmol/L from baseline
  • Secondary outcomes:
    • Hypernatremia (>145mmol/L and > 3mmol/L from baseline)
    • Severe hyponatremia ( <130 mmol/L and < 3mmol/L from baseline)
    • Severe Hypernatremia (>150mmol/L and > 3mmol/l from baseline)
    • Hypercholremia (>110 mmol/L)
    • Hypermagnesemia ( > 1.2 mmol/L)
    • Increased serum bicarbonate ( >30mmol/L)
    • Mean serum Na
    • Mean change in weight
    • Overhydration
    • Dehydration
    • Need for replacement IV
    • Seizures
    • Clinically apparent cerebral edema

Discussion and Conclusion

  • The risk for hyponatremia was notable in the first 6 hrs in the Na140 group but persisted past 6hrs in Na77 group.
  • Availability of isotonic fluids in facilities?
  • Possible inclusion of other conditions affecting ADH secretion.
  • Given study findings of less hyponatremia with isotonic fluids, what about normal saline? Cost effective?
  • IV fluid preferences for infants < 3mo?
  • Adverse effects were not specified.
  • Underlying seizure population in the study groups was not evaluated.
  • There is no specification in IVF resuscitation was used prior to study enrollment.
    • Would this change study results?
  • What is the optimal schedule to recheck Na with IVF hydration?

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