Perioperative sodium overload is associated with the occurrence of pulmonary complications related to clazosentan in patients with subarachnoid hemorrhage followed by obliterative management for ruptured aneurysm: A retrospective observational study

Clazosentan, selective endothelin A receptor (ET_A) antagonist, has effectively prevented vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (aSAH). However, pulmonary complications are recognized adverse events, and predictive factors remain unclear.

Between April 2022 and June 2024, 66 patients with aSAH were treated at our institution. The patients who underwent obliterative intervention for ruptured aneurysm and received clazosentan were included. Patients were stratified into those who developed pulmonary complications related to clazosentan (PCrC) and those who did not (non-PCrC). Relevant demographic, laboratory, and radiographical data were analyzed.

Of the 51 patients analyzed, PCrC occurred in 10 patients, and a median onset interval of 3 days post-administration. The mean age of the PCrC group was significantly higher than that of the non-PCrC group (p = 0.049). Additionally, serum sodium levels (p = 0.023), brain natriuretic peptide concentration (p = 0.010) and cardiothoracic ratio (p = 0.002) on admission were significantly elevated in the PCrC group.

The plausible mechanism underlying PCrC involves the selective inhibition of ET_A receptors by clazosentan, and inverse activation of ET_B receptors. This activation may disrupt sodium equilibrium in alveoli, contributing to PCrC. Patients with preexisting conditions such as subclinical heart failure or relative hypernatremia may be particularly susceptible to PCrC.