Early Inhibition of Natriuresis Suppresses Symptomatic Cerebral Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage

Background: Hyponatremia is a common complication occurring in one third of patients after subarachnoid hemorrhage (SAH). One mechanism that likely mediates the development of hyponatremia in SAH is cerebral salt wasting syndrome (CSWS), which induces natriuresis and reduces total blood volume, resulting in a risk of symptomatic vasospasm (SVS). The mineral corticoid fludrocortisone acetate enhances sodium reabsorption in the renal distal tubules and may help prevent post-SAH hyponatremia. However, management with fludrocortisone acetate is ineffective if hyponatremia is advanced, because CSWS and subsequent SVS develop rapidly. Therefore, an additional earlier marker is required to predict the development of hyponatremia for the initiation of immediate treatment in select patients. However, no conclusive evidence exists showing that hyponatremia influences the risk of SVS, and no standard treatment protocol exists for treating hyponatremia in patients with SAH. This study was undertaken to evaluate whether selective early treatment of hyponatremia prevents SVS in patients with increased urinary sodium excretion in the early phase following SAH. Methods: A total of 103 patients with aneurysmal SAH were managed for a postoperative electrolyte disorder after aneurysmal clipping or coil embolization. Between 2004 and 2007 (period 1), 54 patients started treatment to correct the electrolyte disorder after hyponatremia had occurred. Between 2007 and 2011 (period 2), 49 patients were prospectively subjected to sodium replacement treatment according to their daily sodium balance, and inhibition of natriuresis with fludrocortisone acetate was initiated just after an increase in urinary sodium excretion >300 mEq/day. The occurrence of hyponatremia, SVS, and outcomes were compared between the two periods. Results: Hyponatremia was observed in 14 patients (26%) in period 1 and 7 patients (14%) in period 2. The incidence of fludrocortisone acetate administration was significantly higher, and initiation of electrolyte correction was significantly earlier, in period 2 patients. We observed a significant difference in the frequency of SVS, which occurred in 10 patients (18.5%) in period 1 and 3 patients (6.1%) in period 2. Both urinary sodium excretion and urine volume at day 7 were significantly different between the two periods. However, no significant difference was observed in overall outcome between the two periods. Conclusions: Early inhibition of natriuresis with