Hypoxemia with atelectasis during clazosentan therapy after subarachnoid hemorrhage: a potential effect of suppressed hypoxic pulmonary vasoconstriction.

Clazosentan, a selective endothelin-A (ET-A) receptor antagonist, is used to prevent cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). Although pulmonary edema and fluid retention are recognized adverse effects, hypoxemia associated with atelectasis has not been described. Endothelin-1 contributes to hypoxic pulmonary vasoconstriction (HPV), which preserves ventilation-perfusion (V/Q) matching by diverting blood flow from poorly ventilated regions; pharmacologic ET-A blockade may attenuate HPV, increasing intrapulmonary shunt and impairing oxygenation. We report a man in his 60s with aneurysmal SAH (World Federation of Neurosurgical Societies [WFNS] I, Fisher 3) who underwent clipping surgery and postoperative clazosentan infusion (10 mg/h, standard Japanese dosage). On day 7 of infusion, hypoxemia (SpO2 < 90% room air) developed; on day 8, arterial blood gas showed PaO2 62.5 mmHg with a PaO2/FiO2 (P/F) ratio of 109. Chest computed tomography (CT) demonstrated right lower-lobe atelectasis without pulmonary edema or pleural effusion, and echocardiography showed normal cardiac function. Clazosentan was discontinued and corticosteroid therapy initiated, after which oxygenation improved and the atelectasis resolved. The patient was extubated on day 18 and discharged with good neurological recovery. This case illustrates a plausible mechanism whereby ET-A receptor blockade suppresses HPV, exacerbating V/Q mismatch in the presence of segmental atelectasis. Improvement after drug withdrawal supports this association. Clinicians should recognize that hypoxemia during clazosentan therapy may occur independently of fluid overload and warrants early respiratory evaluation.