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远程缺血预处理对脊髓型颈椎病减压术后脊髓缺血再灌注损伤保护作用研究

Effect of Remote Ischemic Preconditioning on Spinal Cord Ischemia-reperfusion Injury after Elective Cervical Decompression Surgery

【作者】 胡胜

【导师】 熊利泽; 董海龙;

【作者基本信息】 第四军医大学 , 麻醉学, 2009, 博士

【副题名】随机对照临床试验研究

【摘要】 背景脊髓型颈椎病是颈椎病最严重的类型,也是导致成年人出现脊髓功能障碍最常见的原因。治疗方法包括非手术治疗和手术治疗。手术减压被认为是治疗的金标准。手术治疗的主要目的是充分解除对脊髓的压迫和维持脊柱的稳定性。恰当的手术治疗可以使大部分患者神经功能得到满意的恢复。然而,减压手术可导致脊髓缺血再灌注损伤。脊髓缺血再灌注损伤常可导致不同程度脊髓功能障碍,严重影响脊髓型颈椎病患者术后生存质量,甚至危及生命。许多动物实验研究已证实远程缺血预处理具有减轻心、脑、肝、肾、脊髓、胃等器官的缺血再灌注损伤作用。最近一些临床随机对照试验研究证实,肢体远程缺血预处理可减轻心脑血管手术时心肌和脑的缺血再灌注损伤。肢体远程缺血预处理具有安全、效果确切、价格低廉、无创伤且临床操作简便易行等优点。设计本研究旨在探讨肢体远程缺血预处理对脊髓型颈椎病患者术后脊髓缺血再灌注损伤的保护作用,为将来其临床应用提供科学依据。目的研究肢体缺血预处理对脊髓型颈椎病减压术后脊髓缺血再灌注损伤的保护作用。方法40例择期行脊髓减压手术的脊髓型颈椎病患者在麻醉诱导前随机分成两组:肢体远程缺血预处理组和对照组,每组各20例。肢体远程缺血预处理参照文献使用充气式止血带对右上肢实施3次5分钟缺血5分钟再灌注,充气压力为200mmHg。检测麻醉诱导前、减压前、减压后及术后1、3、5、7天血清S-100B和神经元特异性烯醇化酶(NSE)的浓度。在围术期采用正中神经体感诱发电位(SEPs)仪监测脊髓功能。术前及术后7天、1、3、6个月神经功能状况评估采用国际标准的日本骨科学会脊髓型颈椎病评分法(JOA score),并计算出相应各时间点的恢复率(Recovery Rate, RR)。结果1.对血清生化指标的影响。肢体远程缺血预处理可使术后6小时、术后1天S-100B及术后6小时、术后1、3、5天NSE的释放明显减少(P<0.05)。2.体感诱发电位的变化。预处理组和对照组各时间点诱发电位的监测指标及术中显著变化的发生率无显著性差异(P>0.05)。3.神经功能的情况。两组术后7天及术后1、3个月神经功能恢复率具有显著性差异(P<0.05)。结论本研究结果证实,肢体缺血预处理对脊髓型颈椎病术后脊髓缺血再灌注损伤具有保护作用,对术后患者的预后有益。这些新的研究结果为将来肢体缺血预处理在脊髓型颈椎病减压手术中开展多中心临床试验研究提供了一定的科学依据。

【Abstract】 Background:Cervical spondylotic myelopathy is the most serious condition of cervical spondylosis and a leading cause of spinal cord dysfunction in the adult population. Treatment options include operative and non-operative treatments. Surgical decompression is considered the gold standard of treatment. The objective of operative treatment is to adequately decompress the spinal cord and to maintain the stability of the spinal column. Appropriate operative treatment of cervical spondylotic myelopathy will result in satisfactory recovery from myelopathy in most cases. However, elective cervical decompression surgery is associated with spinal cord ischemia-reperfusion injury. Spinal cord ischemia-reperfusion injury after surgical decompression often leads to neurological deficits which seriously influence the quality of life after surgery and even threaten the survival of patients with cervical spondylotic myelopathy. Remote ischemic preconditioning (RIPC) reduces injury caused by ischemia-reperfusion in distant organs. RIPC has been proved to be protective against ischemia-reperfusion injury in brain, heart, liver, kidney, spinal cord, gut, and etc in many animal studies. Quite a few clinical trials have recently reported that remote ischemic preconditioning reduces myocardial and cerebral injury after major cardiovascular and neurovascular surgery. Remote ischemic preconditioning is a safe, effective, noninvasive, and cost-effective strategy for reducing ischemia-reperfusion injury in clinical settings. This study was designed to investigate whether limb remote ischemic preconditioning is beneficial to surgical outcome in patients with cervical spondylotic myelopathy, and to provide scientific basis for its clinical application in the future.ObjectiveTo investigate the effect of remote ischemic preconditioning on spinal cord ischemia-reperfusion injury in patients with cervical spondylotic myelopathy undergoing cervical decompression surgery. MethodsForty adult myelopathic patients undergoing elective cervical decompression surgery were randomly assigned to either a remote ischemic preconditioning group (n=20) or a control group (n=20) before induction of anesthesia. Limb remote ischemic preconditioning consisted of three 5-min cycles of right upper limb ischemia, induced by an automated cuff-inflator placed on the upper arm and inflated to 200 mmHg, with an intervening 5 min of reperfusion during which the cuff was deflated. Serum samples for measurements of S-100B and neuron-specific enolase (NSE) concentrations were drawn before the induction of anesthesia, before decompression, after decompression and at 6h, 1, 3, 5, 7days after surgery. Median nerve somatosensory evoked potentials (SEPs) were measured before, during and after surgery. Preoperative and postoperative neurological functional status was evaluated using a Japanese Orthopaedic Association (JOA) scale, and the recovery rate (RR) was calculated. Assessment was done before the operation, at 7 days and 1 month, 3 months, 6 months after surgery.Results1.Biochemical markers: Remote ischemic preconditioning significantly reduced serum S-100B release at 6 h, 1day after surgery and NSE release at 6h, 1, 3, 5days after surgery (P<0.05).2.Somatosensory evoked potentials: No differences in SEPs measurements at either time point and in the incidences of significant SEPs changes between Control group and RIPC group during the surgery were observed (P>0.05).3.The recovery rate: There were significant differences in the RR at 7 days and 1 month, 3 months after surgery between the two groups (P<0.05). ConclusionsThe present study demonstrates that adult myelopathic patients undergoing elective cervical decompression surgery at a single center could benefit from remote ischemic preconditioning, using transient upper limb ischemia. These novel data support the need for a larger multi-center clinical study of RIPC in patients undergoing elective cervical decompression surgery for cervical spondylotic myelopathy (CSM).

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