Effect of isotonic versus hypotonic maintenance fluid therapy on urine output, fluid balance, and electrolyte homeostasis: a crossover study in fasting adult volunteers

Background. Daily and globally, millions of adult hospitalized patients are exposed to maintenance i.v. fluid solutions supported by limited scientific evidence. In particular, it remains unclear whether fluid tonicity contributes to the recently established detrimental effects of fluid, sodium, and chloride overload. Methods. This crossover study consisted of two 48 h study periods, during which 12 fasting healthy adults were treated with a frequently prescribed solution (NaCl 0.9% in glucose 5% supplemented by 40 mmol litre(−1) of potassium chloride) and a premixed hypotonic fluid (NaCl 0.32% in glucose 5% containing 26 mmol litre(−1) of potassium) at a daily rate of 25 ml kg(−1) of body weight. The primary end point was cumulative urine volume; fluid balance was thus calculated. We also explored the physiological mechanisms behind our findings and assessed electrolyte concentrations. Results. After 48 h, 595 ml (95% CI: 454–735) less urine was voided with isotonic fluids than hypotonic fluids (P<0.001), or 803 ml (95% CI: 692–915) after excluding an outlier with ‘exaggerated natriuresis of hypertension’. The isotonic treatment was characterized by a significant decrease in aldosterone (P<0.001). Sodium concentrations were higher in the isotonic arm (P<0.001), but all measurements remained within the normal range. Potassium concentrations did not differ between the two solutions (P=0.45). Chloride concentrations were higher with the isotonic treatment (P<0.001), even causing hyperchloraemia. Conclusions. Even at maintenance rate, isotonic solutions caused lower urine output, characterized by decreased aldosterone concentrations indicating (unintentional) volume expansion, than hypotonic solutions and were associated with hyperchloraemia. Despite their lower sodium and potassium content, hypotonic fluids were not associated with hyponatraemia or hypokalaemia. Clinical trial registration. ClinicalTrials.gov (NCT02822898) and EudraCT (2016-001846-24).