Effect of Protein Supplementation and Fluid Restriction on Plasma Sodium Levels in Patients Undergoing Pituitary Surgery

Disturbances in water balance, often due to disturbed arginine vasopressin (AVP) secretion from pituitary stalk and/or posterior lobe damage/manipulation, are common complications following pituitary surgery. This can result in either AVP deficiency, causing polyuria and polydipsia, or AVP excess, leading to water retention and dilutional hyponatremia (syndrome of inappropriate antidiuresis, SIAD). SIAD affects up to 30% of patients, typically developing between days 4 and 14 post-surgery, with a peak around day 7. While usually mild, severe hyponatremia is a leading cause of hospital readmission. Management includes fluid restriction, oral urea, or, in severe cases, hypertonic saline and AVP receptor antagonists.

Non-medicinal preventive strategies, such as prophylactic fluid restriction, have demonstrated efficacy in reducing SIAD incidence and hospital readmissions, but the optimal protocol remains unestablished. Dietary protein supplementation has recently emerged as a potential novel intervention, leveraging osmotic diuresis from increased endogenous urea production derived from the physiological amino-acid metabolism to raise plasma sodium levels. However, no data in the postoperative setting are available

This study aims to compare protein supplementation and fluid restriction to standard care (no specific intervention) in preventing post-pituitary surgery hyponatremia. From days 4 to 9 post-surgery, participants will receive one of the three treatments: Treatment A: Patients will limit their total daily fluid intake to a maximum of 1000 ml Treatment B: Patients will consume an additional 80 grams of protein daily through two 150 ml protein drinks (40 grams of protein each, MOLTEIN PURE Drink, OMANDA) in various flavors. Treatment C: Patients will not receive specific instructions. They will follow standard post-operative care and serve as a control group.

Inclusion criteria

• Adult patients (aged 18 or older) undergoing trans-sphenoidal or trans-cranial surgery for sellar / suprasellar pathology
• No pre-existing AVP-deficiency and SIAD or other causes of hyponatremia

Exclusion criteria

• AVP deficiency diagnosed before surgery based on established criteria
• Other type of neurosurgery / intracranial pathology / pre-existing spontaneous CSF -rhinorrhea
• Traumatic brain injury or intracranial hemorrhage
• Systemic infection or other causes for systemic stress
• Lactose intolerance, milk protein allergy, soy allergy, nuts allergy or known hypersensitivity or allergy to one of the components of the protein supplementation
• Inborn metabolic disorders implying carbohydrate, lipid, or protein metabolism
• Severe hepatic impairment (ALAT/ASAT >3x upper limit) or advanced symptomatic liver disease defined as past or current hepatic encephalopathy, liver cirrhosis Child C, or decompensated (bleeding, jaundice, hepatorenal syndrome)
• Reduction of eGFR <45 mL/min/1.73m² (KDIGO G3b, G4 and G5) or end stage renal disease (dialysis)
• Recently initiated (within the last 5 days) SGLT2 inhibitors, vaptans, or oral urea therapy
• Pregnancy or breastfeeding
• Lack of capacity or other reason preventing from giving informed consent or following study procedures.

Post-Inclusion Exclusion criteria (day 3 post-surgery, i.e.,time of randomization): - AVP deficiency diagnosed on post-operative day 3