右美托咪定联合乌司他丁对心肺转流下瓣膜置换术病人的脑保护作用

    Brain protective effect of dexmetomidine combined with ulinastatin on patients undergoing valve replacement under cardiopulmonary bypass

    • 摘要:
      目的研究右美托咪定联合乌司他丁对心肺转流下瓣膜置换术病人的脑保护作用。
      方法择期行心脏瓣膜置换术的病人80例,随机分为对照(N)组、右美托咪定(D)组、乌司他丁(U)组、右美托咪定复合乌司他丁(U+D)组。D组病人诱导前予以1.0 μg/kg右美托咪定静脉泵入15 min,之后以0.4 μg·kg-1·h-1持续输注至术毕,U组诱导后给予乌司他丁20 000 U/kg,D+U组右美托咪定和乌司他丁使用方法同上,N组等量0.9%氯化钠溶液。在4组病人体外循环前(T1)、升主动脉开放(T2)、停机(T3)、术毕6 h(T4)行血气分析检测颈内静脉血氧饱和度(SjvO2)、动脉-颈内静脉血氧含量差(Da-jvO2)、脑氧摄取率(CERO2),并记录局部脑氧饱和度(rSO2),同时于T1~T4、术毕24 h(T5)时间点采用ELISA法测定血清白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、S-100β蛋白、神经元特异性烯醇化酶(NSE)含量。最后于术前1 d(T0)、术后第7天(T6)评定术后神经认知,统计术后1周内谵妄的发生情况。
      结果T2~T3时,与N组相比,D组、U组、D+U组的SjvO2明显升高,Da-jvO2、CERO2明显降低;与D组、U组相比,D+U组的SjvO2明显升高,而Da-jvO2、CERO2明显降低(P < 0.05~P < 0.01)。T2时,与N组相比,D组、U组、D+U组的rSO2明显升高;与D组、U组相比,D+U组的rSO2明显升高(P < 0.05~P < 0.01)。T2~T4时,与N组相比,D组、U组、D+U组的NSE、S-100β、IL-6、TNF-α水平显著降低;与D组、U组相比,D+U组的NSE、S-100β、IL-6、TNF-α水平显著降低(P < 0.05~P < 0.01)。T6时,与N组相比,D组、U组、D+U组MMSE评分增高;与D组相比,D+U组MMSE评分增高(P < 0.01),与U组相比,D+U组MMSE评分增高,差异有统计学意义(P < 0.01)。T6时,与N组相比,D组和U组谵妄发生率差异无统计学意义,而D+U组术后1周内谵妄发生率降低(P < 0.01);与D组相比,D+U组谵妄发生率降低(P < 0.05)。
      结论右美托咪定联合乌司他丁可进一步抑制心瓣膜病病人瓣膜置换手术CPB期间的交感神经活性及炎症反应,显著改善病人围术期脑氧代谢,减轻脑损伤,具有一定的脑保护作用。

       

      Abstract:
      ObjectiveTo investigate the brain protective effect of dexmedetomidine combined with ulinastatin on patients undergoing valve replacement under cardiopulmonary bypass.
      MethodsEighty patients undergoing elective cardiac valve replacement were randomly divided into control group (group N), dexmedetomidine group (group D), ulinastatin group (group U), and dexmedetomidine combined with ulinastatin group (group U+D).Group D was pumped 1.0 μg/kg for 15 minutes before induction, and then 0.4 μg·kg-1·h-1 until the end of the operation.Group U was given 20 000 U/kg intravenously immediately after induction.The usage of dexmetomidine and ulinastatin in group U+D was the same as above, and group N had the same amount of 0.9% sodium chloride solution.Before cardiopulmonary bypass (T1), ascending aorta opening (T2), shutdown (T3), and 6 hours after surgery (T4), blood gas analysis was performed to detect internal jugular vein oxygen saturation (SjvO2), arterial internal jugular vein oxygen content difference (Da-jvO2), and cerebral oxygen uptake rate (CERO2) in four groups of patients, and local cerebral oxygen saturation (rSO2) was recorded.Serum interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), S-100 β, and neuron specific enolase (NSE) were measured by ELISA at the time point T1 to T4 and 24 hours after surgery (T5).Finally, postoperative neurocognition was assessed on the first day before surgery (T0) and the seventh day after surgery (T6), and the incidence of delirium within one week after surgery was statistically analyzed.
      ResultsAt T2-T3, compared with group N, the levels of SjvO2 were remarkably raised in other three groups, while the leves of Da-jvO2 and CERO2 were remarkably descend; compared with group D and group U, the levels of SjvO2 were remarkably raised in group D+U, while the levels of Da-jvO2 and CERO2 was remarkably descend (P < 0.05 to P < 0.01).At T2, compared with group N, the levels of rSO2 was remarkably raised in other three groups; compared with group D and group U, the levels of rSO2 were remarkably raised in group D+U (P < 0.05 to P < 0.01).At T2-T4, compared with group N, the concentration of NSE, S100β, IL-6 and TNF-α was lower in group D, group U and group D+U; compared with group D and group U, the concentration of NSE, S100β, IL-6 and TNF-α was lower in Group D+U (P < 0.05 to P < 0.01).At T6, compared with group N, the MMSE score of others three groups raised; compared with group D, the MMSE score of group D+U increased (P < 0.01), compared with group U, the MMSE score of group D+U increased, there was significant difference (P < 0.01).At T6, compared with group N, there was no significant difference in the incidence of delirium in group D and group U, but the incidence of delirium in group D+U was decreased within one week after operation (P < 0.01), and the incidence of delirium in group D+U was lower than that in group D (P < 0.05).
      ConclusionsDexmetomidine combined with ulinastatin can further inhibit the sympathetic activity and inflammatory reaction of patients with rheumatic valvular disease during CPB, significantly improve perioperative cerebral oxygen metabolism, reduce brain injury, and have a certain brain protective effect.

       

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