Early Moderate Fluid Restriction and the Risk of Delayed Hyponatremia Following Transsphenoidal Surgery
Authors: Blount Sydney L , Hwang Jenie Y , Williams Kelley , Fong Brendan , Yuan Jane , Kim Albert H , Silverstein Julie M 
Published: May 2021

Abstract
Background: The most common cause for readmission after transsphenoidal surgery (TSS) is hyponatremia (hypoNa). Delayed hypoNa, defined as hypoNa occurring 3 to 14 days post TSS, occurs in up to 35% of patients and, if severe, can be life-threatening. We conducted a preliminary prospective study comparing two approaches of postoperative fluid management and hypothesized that patients treated with early postoperative fluid restriction would have decreased rates of delayed hypoNa.
Methods: Patients scheduled for TSS were randomly assigned to the control (CON, n=65) or fluid restriction group (Total FR (EXP 1 + EXP 2), n=57). Patients with chronic kidney disease stage III or greater, diabetes insipidus, chronic hyponatremia, or untreated adrenal insufficiency or hypothyroidism were excluded. All patients were started on postoperative weight-based intravenous fluids until postoperative day (POD) 1 and allowed to drink freely. Patients in the EXP 1 group (n=39) were fluid restricted to 1.8 liters/day (2 liters/day if weight &gt; 100 kg) from POD 3 through POD 14. The fluid restriction was changed to 1 liter/day (1.2 liters/day if weight &gt; 100 kg) (EXP 2, n=18) during the study due to interim analysis suggesting a trend toward a reduction in the incidence of hypoNa with fluid restriction. Patients in the CON group were instructed to drink ad lib. Serum sodium (Na) levels were checked every 8 hours in the hospital and on POD 3, 7, 10, and 14. Average and nadir Na between POD 3 and POD 14, incidence of mild (130-134 mEq/L), moderate (125-129 mEq/L), and severe (&lt; 125 mEq/L) hypoNa, and readmission for hypoNa were evaluated. Mann-Whitney U test, Fischer’s exact test, Pearson’s chi-square, and T-test were used for statistical analysis.
Results: Nadir Na was lower in CON compared to EXP 2 (135.1 ± 5.8 vs 138.4 ± 2.8, p=0.024). There was a trend toward a decreased incidence of hypoNa in EXP 2 (11%) compared to CON (30%) (p=0.133). Although there was no significant difference in the incidence of hypoNa (p=0.323) between CON and the EXP 1 and EXP 2 groups combined (Total FR), there was a trend toward a lower nadir Na (135.1 ±5.8 vs 137 ± 4.6, p=0.082) and average Na (138.8 ± 3.1 vs139.8 ± 2.5, p=0.140) in CON versus Total FR group, respectively. There was no statistically significant difference in average Na or incidence of hypoNa in CON compared to EXP 1. The incidence of mild, moderate, and severe hyponatremia was similar among groups, except in EXP 2 which had a lower, although not statistically significant, incidence of severe hyponatremia (0% vs 7.7%) and readmission for hyponatremia (5.6% vs 17.5%) compared to CON. There was no difference in the incidence of acute kidney injury or hypernatremia between groups.
Conclusion: Preliminary results suggest early moderate fluid restriction after TSS may reduce the incidence of delayed hyponatremia as compared to mild or no fluid restriction. Further analysis with more participants is needed.