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

Abstract

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).

Keywords: electrolytes; fluid therapy; water-electrolyte balance.

© The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia.

Figures

Fig 1

Cumulative urine volume (primary end point) and fluid balance over the course of each study period. Black lines are individual observations per subject. Coloured lines are the marginal means estimated using the mixed effects model; the shaded areas represent 95% confidence intervals. Dashed lines are predicted values at 48 h (t48). §Outlier with exaggerated natriuresis; see text for details. The positive fluid balance at t0 is attributable to oral fluid intake (see Table 1).

Fig 2

Physiological factors involved in the regulation of effective circulating volume. In-graph P-values are for the difference between the two fluids. #Significantly different from t0 on a fluid-specific level (P<0.05). Coloured lines indicate the median value at t0 for each fluid. For representational purposes, urinary sodium and osmolality are the raw data shown as fractional polynomial prediction plots; shaded areas represent 95% confidence intervals.

Fig 3

Physiological factors involved in osmoregulation. In-graph P-values are for difference between fluids. #Significantly different from t0 on a fluid-specific level (P<0.05). Coloured lines indicate median value at t0 for each fluid.

Fig 4

Serum concentration of various electrolytes and strong ion difference (SID) over the course of both study periods. In-graph P-values are for the difference between the two fluids. #Significantly different from t0 on a fluid-specific level (P<0.05). Black dashed lines represent the normal range of the electrolytes. Coloured lines indicate the median value at t0 for each fluid.