Abstract 41: Mixed Vasopressin Antagonism as a Directed Therapy for Cerebral Edema in Acute Stroke Patients
Introduction: Conivaptan, a mixed vasopressin receptor (V1a and V2) antagonist approved by FDA for use in hypervolemic/euvolemic hyponatremia, reduces early cerebral edema in experimental stroke models through regulation of plasma osmolality and AQ-4/GFAP modulation
Hypothesis: To evaluate the safety and effectiveness of conivaptan in reducing midline shift, brain volume, and neurological deficits in acute stroke patients.
Methods: We analyzed clinical and radiological data collected from a prospective protocol. Patients (n=8) with acute stroke who demonstrated neurological deficits secondary to cerebral edema and demonstrated lack of improvement with hypertonic saline and serum sodium of 145 mmol or greater were included. Intravenous conivaptan 40 mg per day was administered and daily CT scans obtained for 3 days. Daily GCS score, fluid input/output, net brain volume, pineal shift and septum pellucidum shift were ascertained to assess the effectiveness of conivaptan. Since brain edema is maximum at 3-4 days of stroke onset, subgroup analysis of stroke patients (n=4) in whom time interval between symptom onset and conivaptan administration was in that range was undertaken.
Results: Analysis revealed mean age 56 ± 15 years and gender ratio of 1 with average pineal shift increase from 2.42mm to 2.87mm, decrease in average septum pellucidum shift from 4.17mm to 3.29mm and improvement in mean GCS score from 7.25 to 9.12. Subgroup analysis of 4 patients who received conivaptan within 4 days demonstrated a decrease in the average pineal shift from 2.32mm to 2.02mm; average septum pellucidum shift decrease from 2.68mm to 2.48mm. Average GCS score of patients improved from 5.75 to 9.25. No significant changes were noted in the overall net brain volume.
Conclusions: We observed clinical and radiological improvement after early administration (<4 days) of conivaptan in acute stroke patients as evidenced by reduction in the mean pineal gland and septum pellucidum shift and significant improvement in GCS. Further clinical safety trials are underway to study the efficacy of conivaptan in treatment of brain edema in acute ischemic and hemorrhagic stroke.
Author Disclosures: V.S. Hedna: None. M.H. Qureshi: None. N.S.Y. Mohammad: None. A.I. Qureshi: None.
- © 2015 by American Heart Association, Inc.