Comparative Study Of Tolvaptan And Furosemide In The Treatment Of Hyponatremia Caused By SIADH After Pituitary Adenoma Surgery

ObjectiveHyponatremia after the endonasal endoscopic pituitary adenoma resection is a common complication,which was often caused by syndrome of abnormal antidiuretic hormone secretion(SIADH).There were many treatment options for this kind of hyponatremia.The traditional treatment methods included fluid restriction,loop diuretics and hypertonic saline.To our knowledge,furosemide was used in combination with hypertonic saline to compensate for the loss of sodium from the urine.In recent years,the application of selective vasopressin V2 receptor antagonists has been widely concerned.In addition,there were some less used therapies,such as urea,lithium and demeclocycline.Nevertheless,there were a few studies about the efficacy of traditional and novel methods in the treatment of hyponatremia caused by SIADH.Therefore,this study aimed to compare the efficacy and safety of tolvaptan and furosemide in the treatment of hyponatremia caused by SIADH after pituitary surgery.MethodThis study retrospectively analyzed the patients who were hospitalized and diagnosed with pituitary adenoma in Qilu Hospital of Shandong University from December 2018 to December 2020.A total of 34 patients with hyponatremia after pituitary surgery were collected(16 cases in tolvaptan group and 18 cases in furosemide group).Patients with hyponatremia were treated with tolvaptan or furosemide respectively after meeting the diagnostic criteria of SIADH.It should be pointed out that furosemide was used in combination with hypertonic saline according to the pharmacological properties of loop diuretics.The basic information,imaging findings,preoperative and postoperative hematological examination results,neurological symptoms of hyponatremia,pathological types and side effects of drugs were analyzed.Categorical variables were analyzed by Chi-square test and numerical variable were analyzed by independent sample t test or Mann-Whitney U test.ResultsA total of 34 patients with hyponatremia after pituitary surgery were collected(16 cases in tolvaptan group and 18 cases in furosemide group).There were no significant differences in preoperative clinical data,laboratory examination,imaging findings and postoperative pathology between the two groups.All patients in two groups with hyponatremia met the diagnostic criteria of SIADH.The mean onset time of hyponatremia in all patients was day 6.7±0.9 after surgery,and the serum sodium concentration reached the lowest point on postoperative day 7.8±1.0.The mean minimum serum sodium concentration was 125.1+5.0mmol/L.As for neurological symptoms of hyponatremia,18 cases(53%)had no obvious symptoms,13 cases(38%)had mental depression,9 cases(26%)had nausea and vomiting,and 11 cases(32%)showed fatigue.There were no significant differences between the two groups in the onset time,the time of the lowest serum sodium concentration,the minimum blood sodium concentration,the number of cases with different serum sodium concentration gradients and neurological symptoms.the mean nadir of the serum sodium concentration before treatment did not differ between the both groups.On the second to fourth day after treatment,the serum sodium concentration in tolvaptan group was higher than that in furosemide group(P=0.022 on the second day;P=0.001 on the third day;P=0.012 on the fourth day).The duration of hyponatremia in tolvaptan group were 2.1±0.8 days.The duration of hyponatremia in furosemide group were 3.2±1.5 days.There was significant difference in the duration of hyponatremia between the two groups(P=0.030).The side effect of drugs included thirst,hypokalemia and rapid correction of serum sodium concentration.In tolvaptan group,there were 4 cases(25%)with thirst and 5 cases(31%)with rapid correction of serum sodium concentration.Of note,no cases developed hypokalemia in tolvaptan group.There were 6 cases(33%)with thirst,4 cases(22%)with hypokalemia and 3 patients 17%)with rapid correction of serum sodium concentration in furosemide group.There was no significant difference between the two groups in the number of patients with thirst and rapid correction of serum sodium concentration,but the number of patients with hypokalemia in furosemide group was significantly higher than that in tolvaptan group(P=0.045).ConclusionTolvaptan was more effective than frusemide in the treatment of hyponatremia which was produced by SIADH after the endonasal endoscopic pituitary adenoma resection.As for the side effect,furosemide was more likely to cause hypokalemia than tolvaptan.However,both groups resulted in a high incidence of rapid correction of serum sodium concentration.It is necessary to closely monitor the change of serum sodium concentration during the treatment.