Postoperative Fluid Restriction to Prevent Delayed Hyponatremia

Background: Readmission following endoscopic endonasal transsphenoidal surgery (EETS) for a pituitary adenoma is most commonly due to delayed hyponatremia and affects up to 35% of patients. Some institutions have empirically adopted postoperative fluid restriction (FR) protocols based on retrospective studies that suggest a decrease in the incidence of hyponatremia and related readmissions. However, these interventions are often associated with additional modifications in postoperative management, making it difficult to establish a clear causal relationship between FR and hyponatremia. We present the results of the first prospective randomized controlled study to evaluate the clinical impact of post-EETS fluid management.

Methods: A total of 300 participants scheduled for EETS (2016–2023) at a single institution were included. Exclusion criteria included patients with CKD, CHF, arginine vasopressin deficiency on postoperative day (POD) 3, chronic hyponatremia, and untreated adrenal insufficiency or hypothyroidism. In the original study design, patients were randomly assigned to control group (n = 94) or moderate FR group (n = 39). Participants in the control group were instructed to drink ad-lib. Participants in moderate FR were fluid-restricted to 1.8 L per day (2 L per day if weight > 100 kg) from POD 3 to 14. Based on interim analysis suggesting a trend toward reduced hyponatremia, FR was changed to strict FR (n = 62) of 1 L per day (1.2 L per day if weight > 100 kg). Serum sodium (Na) level was monitored. Incidence of hyponatremia (Na level < 135 mEq/L), moderate hyponatremia (Na level 125–129 mEq/L), and severe hyponatremia (Na level < 125 mEq/L), as well as readmissions for hyponatremia were evaluated. Fluid intake and thirst were assessed.

Results: In the control, moderate FR, and strict FR groups, the incidences of overall hyponatremia were 31.9, 28.2, and 21.0%; the incidences of moderate hyponatremia were 5.3, 5.1, and 4.8%; and the incidences of severe hyponatremia were 7.4, 5.1, and 0%, respectively. Readmission for hyponatremia occurred in 6.4% (n = 6) in the control group, 7.7% (n = 3) in moderate FR, and 1.6% (n = 1) in strict FR. Severe hyponatremia occurred significantly less frequently in the strict FR compared to the control group (95% CI: 0.00–1.02; p = 0.04). Nadir Na level was significantly higher in strict FR compared to the control group (1.81 mEq/L higher; 95% CI, 0.34–3.27; p = 0.02), and in the combined FR group (moderate + strict) compared to the control group (1.64 mEq/L higher; 95% CI: 0.24–3.04; p = 0.02). Although mean thirst scores were similar among groups, an individual’s thirst score was significantly associated with compliance with the assigned FR protocol.

Conclusion: Results of this randomized control study show a reduced rate of severe hyponatremia and readmission for hyponatremia in patients on FR from POD 3 to 14 after EETS compared to patients instructed to drink ad-lib. These results provide compelling evidence that postoperative FR after EETS decreases the rate of delayed hyponatremia and related readmission. The degree of thirst did not significantly differ in patients undergoing FR. Further studies are needed to assess the optimal amount and duration of FR after EETS.

Publication History

Article published online:
07 February 2025