右美托咪定剂量对老年脊柱手术患者术后认知功能障碍发生率及Aβ和细胞因子水平的影响:120例随机对照试验

Effects of dexmedetomidine doses on postoperative cognitive dysfunction and serumβ-amyloid and cytokine levels in elderly patients after spine surgery:a randomized controlled trial

目的探讨右美托咪定(DEX)预防老年脊柱手术患者术后认知功能障碍(POCD)发生率的免疫调节机制及合理剂量。方法选择行择期脊柱手术患者120例,随机分为4组:S组(n=30,0.2μg·kg^(-1)·h^(-1)DEX),M组(n=30,0.5μg·kg^(-1)·h^(-1)DEX),L组(n=30,0.8μg·kg^(-1)·h^(-1)DEX),C组(n=30,等容量生理盐水);S组、M组、L组麻醉诱导前使用0.3μg/kg负荷量DEX泵注10 min,C组则使用等容量生理盐水泵注;全身麻醉诱导气管插管后对S组、M组、L组分别静脉泵注DEX 0.2、0.5、0.8μg·kg^(-1)·h^(-1)至手术结束前40 min,记录苏醒时间和低血压、窦性心动过缓的发生,术前(D0)及术后1 d(D1)、3 d(D2)、7 d(D_(3))评估患者MMSE评分及检测Aβ、TNF-α、IL-1β和IL-6的血清浓度。结果与DO比较,4组患者术后D1时间点的Aβ、TNF-α、IL-1β和IL-6血清水平明显升高(P<0.05);M组、L组Aβ血清水平D_(3)时间点下降至术前水平(P>0.05),而C组、S组仍较高水平;M组、L组的TNF-α、IL-1β和IL-6的血清水平在D2时间点恢复术前水平(P>0.05),而C组、S组D3时间点才恢复。与C组比较,M组、L组的POCD发生率显著减少(P<0.05),但M组、L组两组之间没有显著差异。L组患者低血压和心动过缓的发生率最高(P<0.01),苏醒时间(Tw)也比其他3组长(P<0.05)。结论围术期使用DEX0.3μg/kg负荷剂量泵注10 min后,持续泵注0.5μg·kg^(-1)·h^(-1)DEX可控制Aβ和促炎性细胞因子血清水平,有效预防老年脊柱手术患者POCD发生。

Objective To explore the immunomodulatory mechanism and optimal dose of dexmedetomidine(DEX)for preventing postoperative cognitive dysfunction(POCD)in elderly patients undergoing spinal surgery.Methods A total of 120 elderly patients undergoing elective spinal surgery with general anesthesia were randomized into 4 groups to receive a loading dose of 0.3μg/kg DEX for 10 min before anesthesia induction followed by maintenance doses of 0.2,0.5,and 0.8μg·kg^(-1)·h^(-1)(low-,medium-,and high-dose DEX groups,respectively)or an equal volume of normal saline(control group).DEX and saline was discontinued 40 min before the end of the surgery.Before induction(D0)and on day 1(D_(1)),day 3(D2)and day 7(D3)after the operation,the cognitive function of the patients was assessed using the MMSE scale and their serum levels ofβ-amyloid(Aβ),TNF-α,IL-1βand IL-6 were measured.The occurrence of adverse effects including bradycardia and hypotension and the recovery time of the patients were recorded.Results Compared with those on D0,serum levels of Aβ,IL-1β,IL-6,and TNF-αon D_(1) were markedly increased in all the groups(P<0.05);the levels of Aβdecreased to the baseline level on D3 in medium-and high-dose DEX groups(P>0.05)but remained high in the other two groups.On D_(2),TNF-α,L-1βand IL-6 recovered their baseline levels in medium-and high-dose DEX groups(P>0.05)but remained elevated in the other two groups.The incidences of POCD in medium-and high-dose DEX groups were comparable but significantly lower than that in the control group(P<0.05).The incidences of hypotension and bradycardia were the highest in high-dose DEX group(P<0.01),which also had longer recovery time than the other 3 groups(P<0.05).Conclusion With a loading dose of 0.3μg/kg followed by a maintenance doses of 0.5μg·kg-1·h-1,DEX can effectively reduce the incidence of POCD in elderly patients undergoing spinal surgery by inhibiting the production of Aβand pro-inflammatory cytokines.