Background: Nimodipine can block the influx of calcium into the vascular smooth muscle cell and prevent secondary ischemia in patients with aneurysmal subarachnoid hemorrhage. However, the reduction of blood pressure after long-term intravenous administration of nimodipine has been associated with neurological deterioration. Yet, no effective solutions have been suggested to address this phenomenon. The use of neuroprotective drug combinations may reduce the risk of sudden blood pressure loss. This prospective, randomized, controlled trial was performed to evaluate the nimodipine-sparing effect of perioperative dexmedetomidine infusion during aneurysmal subarachnoid hemorrhage. Methods: One hundred nine patients who underwent aneurysm embolization were divided into three groups: group C (n = 35, infused with 0.9% sodium chloride at the same rate as other two groups), group D1 (n = 38, dexmedetomidine infusion at 0.5 μg·kg-1 for 10 min, then adjusted to 0.2 μg·kg-1·h-1), and group D2 (n = 36, dexmedetomidine infusion at 0.5 μg·kg-1 for 10 min, then adjusted to 0.4 μg·kg-1·h-1). Patient-controlled analgesia was given for 48 h after surgery. The primary outcome measure was the total consumption of nimodipine during the first 48 h after surgery. The secondary outcome measures were recovery time at post-anesthesia care unit (PACU), postoperative pain intensity scores, dexmedetomidine and sufentanil consumption, hemodynamic, satisfaction of patients and neurosurgeon, neurologic examination (Glasgow Coma Scale, GCS), Bruggemann comfort scale, and adverse effects. Intraoperative hemodynamics were recorded at the following time-points: arrival at the operating room (T1); before intubation (T2); intubation (T3); 5 min (T4), 10 min (T5), and 15 min (T6) after intubation; suturing of femoral artery (T7); end of surgery (T8); extubation (T9); and 5 min (T10), 10 min (T11), and 15 min (T12) after arrival at the PACU. The level of sedation was recorded at 15 min, 30 min, 1 h, and 2 h after extubation. We also recorded the incidence of symptomatic cerebral vasospasm during 7 days after surgery, Glasgow Outcome Score (GOS) at 3 months, and incidence of cerebral infarction 30 days after surgery. Results: The consumption of nimodipine during the first 48 h after surgery was significantly lower in group D2 (P < 0.05). Compared with group C, HR and MAP were significantly decreased from T2 to T12 in group D1 and D2 (P < 0.05). Patients in group D2 showed a significantly decreased MAP from T5 to T9 compared with group D1 (P < 0.05). The consumption of sevoflurane, remifentanil, dexmedetomidine, and nimodipine were all significantly reduced in groups D1 and D2 during surgery (P < 0.05). Compared with group C, MAP was significantly decreased in groups D1 and D2 during the first 48 h after surgery (P < 0.05). Compared with group C, consumption of sufentanil and dexmedetomidine at 1 h, pain intensity at 1 h, and 8 h after surgery were significantly decreased in groups D1 and D2 (P < 0.05). FAS was significantly higher in group D2 at 8 h, 16 h, and 24 h after surgery. LOS was significantly lower only in group D2 at 0.5 h after surgery (P < 0.05). Compared with group C, BCS was significantly higher group D2 at 4 h and 8 h after surgery (P < 0.05). There were no significant differences among the three groups in consumption of propofol, cisatracurium, fentanyl, and vasoactive drugs during operation, recovery time at PACU, satisfaction of patients and neurosurgeon, and number of applied urapidil and GCS during the first 48 h after surgery. The incidence of symptomatic cerebral vasospasm during 7 days after surgery, GOS of 3 months, and cerebral infarction after 30 days were also comparable among the three groups. Conclusions: Dexmedetomidine (infusion at 0.5 μg·kg-1 for 10 min, then adjusted to 0.4 μg·kg-1·h-1 during the surgery) significantly reduced the total consumption of nimodipine during the first 48 h after surgery and promoted early rehabilitation of patients although the incidences of symptomatic cerebral vasospasm, GOS, and cerebral infarction were not reduced.
Ren, C., Gao, J., Xu, G. jun, Xu, H., Liu, G., Liu, L., … Zhang, Z. (2019). The nimodipine-sparing effect of perioperative dexmedetomidine infusion during aneurysmal subarachnoid hemorrhage: A prospective, randomized, controlled trial. Frontiers in Pharmacology, 10(JULY). https://doi.org/10.3389/fphar.2019.00858