Normal saline infusion for stroke after intravenous thrombolysis: a randomized controlled phase II trial

The intravenous administration of abundant normal saline is an easy-to-use strategy commonly employed to expand the blood volume. This study aimed to evaluate the efficacy and safety of the early administration of an abundant normal saline infusion after intravenous thrombolysis for promoting functional independence in patients with acute ischemic stroke. This multicenter randomized open-label blinded-outcome trial included 241 patients aged 18–80 years who underwent intravenous thrombolysis within 4.5 h of acute ischemic stroke onset in China. Eligible patients were randomized to receive either an abundant intravenous infusion of normal saline (2,000 mL administered at a rate of 200 mL/h; normal saline group) or a small intravenous infusion of normal saline (200–400 mL administered at a rate of 200 mL/h; control group) immediately following intravenous thrombolysis. The primary outcome was a functional independence (90-day modified Rankin Scale score of 0–2). The safety outcomes included the mortality and left ventricular ejection fraction. At 90 days, 106 (88.3%) patients in the normal saline group and 93 (78.2%) patients in the control group had a favorable outcome (unadjusted risk ratio = 1.13; 95% confidence interval [CI], 1.01 to 1.27; P = 0.04; adjusted risk ratio = 1.15; 95% CI, 1.03 to 1.28; adjusted P = 0.01). The death rate and 72-hour left ventricular ejection fraction were not significantly different between the two groups (normal saline versus control group, mortality, 1.7% versus 4.2%, P = 0.28; left ventricular ejection fraction, 63.0 [62.0 to 64.0] versus 63.0 [60.0 to 64.0], P = 0.06). The early intravenous administration of abundant normal saline to acute ischemic stroke patients treated by intravenous thrombolysis exhibited improved 90-day outcomes without increasing the risk of death or impairment of cardiac systolic function. This simple and cost-effective means has potential to enhance thrombolytic therapy, particularly in resource-limited settings. These hypothesis-generating findings warrant confirmation in future trials. URL: https://www.clinicaltrials . gov; Unique identifier: NCT05993078.