Preemptive Low-Dose Norepinephrine Infusion for Reducing Hemodynamic Instability During Craniotomy for Brain Tumor Resection Under Propofol–Remifentanil Total Intravenous Anesthesia: A Randomized Controlled Trial

Background: Previous trials of prophylactic norepinephrine have compared it with volume loading or non-norepinephrine vasopressors. Thus, it remains unclear whether a preemptive norepinephrine strategy provides incremental benefit over conventional management permitting reactive norepinephrine use. We evaluated whether preemptive low-dose norepinephrine infusion reduces hemodynamic instability during craniotomy for brain tumor resection under propofol–remifentanil total intravenous anesthesia (TIVA). Methods: Adult patients undergoing craniotomy for brain tumor resection under propofol–remifentanil TIVA were randomized to preemptive continuous infusion of norepinephrine (CINE; started at 0.02 µg/kg/min and titrated to remain below 0.05 µg/kg/min) or conventional management, in which norepinephrine was administered at the anesthesiologist’s discretion in response to hypotension. The primary endpoint was moderate or severe hemodynamic instability, defined as mean arterial pressure outside 80–120% and 70–130% of baseline, respectively. Secondary endpoints included rescue medication use, postoperative complications, and safety. Results: Compared with conventional management, the CINE group showed less moderate hemodynamic instability, both in the number of episodes per patient (median [interquartile range]: 6 [3–11] vs. 9 [5–13], p = 0.045) and in the proportion of anesthesia time affected (7.4% [3.6–12.4] vs. 12.2% [6.8–21.4], p = 0.017), but not less severe instability. Rescue medication was required less frequently in the CINE group (16.7% vs. 100%, p < 0.001). Complication rates were similar between the groups, and no adverse drug reactions occurred. Conclusions: Preemptive low-dose norepinephrine infusion reduced moderate hemodynamic instability during propofol–remifentanil TIVA for brain tumor resection, even against a control group receiving conventional management with reactive norepinephrine use, suggesting potential hemodynamic benefit that warrants confirmation in larger trials.