Elsevier

The Lancet

Volume 385, Issue 9974, 28 March–3 April 2015, Pages 1190-1197
The Lancet

Articles
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

https://doi.org/10.1016/S0140-6736(14)61459-8Get rights and content

Summary

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.

Funding

National Health and Medical Research Council, Murdoch Childrens Research Institute, The Royal Children's Hospital, and the Australian and New Zealand College of Anaesthetists.

Introduction

The appropriate sodium concentration of intravenous fluid used to maintain hydration in children in hospital has generated much debate.1, 2, 3, 4, 5 Traditionally, these fluids have contained sodium concentrations as low as 30 mmol/L—much less than the sodium concentration in plasma. The use of such hypotonic fluid in children has been reported to be a cause of hyponatraemia, with some children having severe outcomes such as seizures, cerebral oedema, and death.6, 7, 8, 9, 10 Antidiuretic hormone contributes to the development of hyponatraemia through reduction in excretion of water, reducing the body's capacity to compensate for increased water loads. Common indications for children to be admitted into hospital, including febrile and infectious illnesses11, 12, 13, 14, 15 and surgical procedures,16, 17 have been associated with increased antidiuretic hormone concentrations, suggesting that more children are at risk of hyponatraemia and associated complications than were previously thought.

Recognition of the association between hyponatraemia and intravenous fluid has increased and some authorities have recommended use of the sodium concentration of 75 mmol/L in maintenance fluid therapy, much higher than was previously used18 but cases of hyponatraemia continue to be noted.19 Randomised trials of intravenous fluid in specific subpopulations, particularly those involving postoperative and intensive care patients, have suggested that use of an isotonic fluid with a similar sodium concentration to plasma might reduce risk of hyponatraemia.20, 21, 22, 23, 24, 25, 26, 27, 28 However, evidence from large heterogeneous populations of children in hospital is scarce.19 Additionally, some investigators have raised concerns about potential adverse outcomes from widespread use of isotonic intravenous fluids, including hypernatraemia,29, 30 fluid overload,2 and hyperchloraemic acidosis.31, 32

In the Paediatric Intravenous Maintenance Solution (PIMS) study, we did a randomised controlled trial in a heterogeneous population of children admitted to one hospital to establish whether an isotonic fluid (140 mmol/L of sodium [Na140]) reduced the risk of hyponatraemia compared with a hypotonic fluid (77 mmol/L of sodium [Na77]) without an increase in adverse effects.

Section snippets

Study design and patients

We did a randomised, double-blind trial at The Royal Children's Hospital, Melbourne, VIC, Australia, a tertiary paediatric teaching hospital and specialist referral centre. Eligible participants were children aged between 3 months and 18 years that needed intravenous maintenance fluid. We chose 3 months as the lower age limit because infants younger than this age might be at greater risk of hypernatraemia because of their reduced renal concentrating ability, and might need more than 5% glucose.

Results

Between Feb 2, 2010, to Jan 29, 2013, 1109 children needing intravenous maintenance fluid were referred to the study team (figure 1). Of the 690 children randomly assigned, 13 were randomised in error and one withdrew consent for any data to be used, resulting in 676 patients available for analysis (338 in each treatment group). These patients were used in all analyses when possible. However, 35 patients (5%) did not have a blood test done after starting study fluid, resulting in missing data

Discussion

Our findings show that children given an isotonic fluid with 140 mmol/L of sodium had a lower risk of developing hyponatraemia than did those given fluid containing 77 mmol/L of sodium. Despite previous concerns for isotonic maintenance solutions,30, 35 we noted no evidence for a difference in the proportion of patients with hypernatraemia between the two treatment groups. The rate and type of adverse outcomes, including overhydration and intravenous line reinsertion, were also similar between

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