Articles140 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
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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2022, Journal of Critical CareCitation Excerpt :Some advocate the use of hypotonic fluids since an isotonic maintenance fluid strategy contains much more sodium than humans usually ingest through a healthy diet [8]. Opponents of a hypotonic maintenance fluid strategy point out the dangers of hyponatremia [9]. Recently, we published two studies that focused on the sodium content of maintenance fluid therapy: the MIHMoSA crossover experiment (Metabolism of Isotonic versus Hypotonic Maintenance Solutions in Adults) in healthy volunteers and the randomized controlled TOPMAST trial (Tonicity of Perioperative Maintenance SoluTions) in patients undergoing major thoracic surgery before being admitted to the intensive care unit (ICU) [10,11].
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