医学资料甲基强的松龙在脊柱非创伤性疾病治疗中的应用北京大学第三医院骨科孙宇

甲基强的松龙在脊柱非创伤甲基强的松龙在脊柱非创伤性疾病治疗中的应用性疾病治疗中的应用Methylprednisolone Usein Orthopedic Conditions(Non-traumatic Spinal Diseases)北京大学第三医院骨科 孙宇Yu Sun,MDProfessor of Orthopaedic SurgeryPeking University Third HospitalBeijing,Peoples Republic of ChinaMPMP的药理作用的药理作用 Pharmacologic Effect of MP in SCI(Hall 1981-85)抑制SCI后脂质过氧化的程度减轻SCI后损伤部位脊髓血流量下降的程度提高SCI后Na+-K+ATP酶的活性支持SCI后的能量代谢1.Inhibits lipid peroxidation 2.Increases blood flow to site of injury3.Stimulates Na+-K+ATPase activity4.Promotes energy metabolismMP的药理作用 Pharmacologic Effect of MP in SCI(Hall 1981-85)5.减少局部乳酸含量，提高丙酮酸含量6.抑制Ca+内流，减轻纤维蛋白的降解7.抑制中性粒细胞和巨噬细胞向损伤部位的浸润8.抑制损伤后炎症介质及炎症性细胞因子的产生5.Reduces local lactic acid content,increasing pyruvic acid content6.Suppresses Ca+influx,reducing fibrin degradation7.Inhibits neutrophil and macrophage infiltration into the injured site8.Depresses the production of inflammatory mediators and cytokines after injury1、减轻脊髓和神经根细胞膜水肿2、抑制神经细胞膜和轴突、树突的脂质过氧化进程3、抑制一般性炎症反应和作用Relieving edema of cell membranes of spinal cord and nerve rootsInhibiting lipid peroxidation of nerve cell membrane,axons and dendrites 1.Suppressing general inflammatory reactionMPMP在脊柱非创伤性疾患中应用的理论依据在脊柱非创伤性疾患中应用的理论依据Theoretical Support for MP in Treating Non-traumatic Spinal Diseases4、间接改善局部血液循环5、抑制细胞的凋亡6、减轻再灌注损伤4.Indirectly improving local blood circulation5.Inhibiting apoptosis6.Relieving reperfusion injury MPMP在脊柱非创伤性疾患中应用的理论依据在脊柱非创伤性疾患中应用的理论依据Theoretical Support for MP in Treating Non-traumatic Spinal DiseasesMPMP应用现状及方法应用现状及方法Current Use of MP方法：1.术中或术后可疑有神经系统损伤时，按照NASCIS II方案应用MP冲击疗法。2.其他情况时，应用剂量无统一认识。Methods1.MP therapy as per NASCIS II proposal can be applied in cases of suspected nerve injury during or after the operation 2.No consensus on the dosage in other situations 脊柱外科疾病（颈椎）脊柱外科疾病（颈椎）Surgical Treatment of Spine Diseases(cervical spine)临床常见疾病及治疗方法1.颈椎骨折脱位切开复位内固定2.颈椎病前路、后路减压、固定、融合3.颈椎肿瘤切除Common diseases and treatments1.Open reduction and internal fixation of fracture-dislocation of cervical spine2.Anterior or posterior decompression,fixation and fusion for cervical spondylosis3.Resection of cervical spinal tumors脊柱外科疾病（颈椎）脊柱外科疾病（颈椎）Diseases of Spine Surgery(cervical spine)车祸伤 左侧C6神经根损伤 Car crash injury Neurologically deficit of C6 nerve root on left side碎骨片Small piece of bone graft小关节交锁Locked facet joint椎间盘碎片Disc fragment后路切开复位，经椎弓根螺钉内固定Posterior approach for ORIF and trans-pedicle screw fixation前路椎间盘切除、植骨、内固定Anterior ACDF and plating脊髓型颈椎病，发育性颈椎管狭窄,C4-5椎间盘突出Cervical spondylotic myelopathy,Developmental cervical Spinal stenosis,C4-5 disc protrusion脊柱外科疾病（颈椎）脊柱外科疾病（颈椎）Diseases of Spine Surgery(cervical spine)脊柱外科疾病（颈椎）脊柱外科疾病（颈椎）Diseases of Spine Surgery(cervical spine)后路C3-7椎管成形术+前路C4-5椎间盘切除+CAGE植入Posterior C3-7 laminoplasty+Anterior C4-5 discectomy +CAGE implantation颈椎管内肿瘤，压迫脊髓Cervical intraspinal tumor,compressed spinal cord脊柱外科疾病（颈椎）脊柱外科疾病（颈椎）Diseases of Spine Surgery(cervical spine)脊柱外科疾病（颈椎）脊柱外科疾病（颈椎）Surgical Treatment of Spine Diseases(cervical spine)4.颈椎后纵韧带骨化、黄韧带骨化减压手术5.颈椎畸形的矫正6.颈椎结核病灶清除术4.Decompression of ossification of posterior longitudinal ligament and ligamenta flava of cervical spine5.Correction of cervical spine malformation/deformity6.Focus clearance of tuberculosis of cervical spine颈椎后纵韧带骨化，脊髓严重受压,单开门术后Ossification of posterior longitudinal ligament of cervical spine,severely compressed spinal cord，post-open door laminoplasty脊柱外科疾病（颈椎）脊柱外科疾病（颈椎）Diseases of Spine Surgery(cervical spine)颈椎结核，椎管内脓肿Tuberculosis of cervical spine,intraspinal abscess脊柱外科疾病（颈椎）脊柱外科疾病（颈椎）Diseases of Spine Surgery(cervical spine)颈椎椎板切除术后后凸畸形Post-laminectomy cervical Kyphosis 脊柱外科疾病（颈椎）脊柱外科疾病（颈椎）Diseases of Spine Surgery(cervical spine)颈椎前路松解+后路松解+前后路固定、矫正、融合Combined anterior and posterior release,fixation,correction and fusion 脊柱外科疾病（颈椎）脊柱外科疾病（颈椎）Diseases of Spine Surgery(cervical spine)手术常见并发症*喉上神经、喉返神经水肿*神经根牵拉损伤*反应性脊髓水肿*脊髓损伤Common complicationsEdema of superior laryngeal nerve and recurrent laryngeal nerve Stretch injury of nerve rootsResponsive edema of spinal cordSpinal cord injury 脊柱外科疾病（颈椎）脊柱外科疾病（颈椎）Surgical Treatment of Spine Diseases(cervical spine)甲强龙对颈前路术后耳鼻喉并发症的影响甲强龙对颈前路术后耳鼻喉并发症的影响 Effects of MP on ENT Complications After Anterior Cervical Decompression给药方法 分别于术后即刻，术后12小时，24小时按1mg/kg的剂量静脉注射MPMedication:1mg/kg MP is administered intravenously at the end of operation,12hr,and 24hr after operation separately Eur-Spine-J 2003 12(1)84-90甲强龙对颈前路术后耳鼻喉并发症的影响甲强龙对颈前路术后耳鼻喉并发症的影响 Effects of MP on ENT Complications After Anterior Cervical Decompression评价指标:-客观指标:根据内窥镜评价咽、喉黏膜 受损的范围 -主观指标:患者自觉手术对吞咽的影响Evaluation indicators:Objective indicators:Accessing the range of throat mucous membrane lesion according to endoscope Subjective indicators:Patients perceptions about the influence of operation on swallowingEur-Spine-J 2003 12(1)84-90甲强龙对颈前路术后耳鼻喉并发症的影响甲强龙对颈前路术后耳鼻喉并发症的影响 Effects of MP on ENT Complications After Anterior Cervical Decompression结论：甲强龙可减轻颈前路术后咽、喉黏膜受损的程度、减少呼吸系统并发症的发生。Conclusions:MP can relieve the damage of throat mucous membrane after anterior cervical decompression and reduce the complications of respiratory systemEur-Spine-J 2003 12(1)84-90北医三院的治疗方案北医三院的治疗方案Regimens in Peking University Third Hospital甲强龙用法:(1)未发生急性脊髓损伤 120mg,静脉输入，小壶给药 持续3-5天 不需要逐渐减量 Treatment with MP(1)No acute spinal cord injury120mg,intravenous injection,administered via Act-o-VialOnce per day for 3 to 5 daysNeed not gradually decrease the dosage 北医三院的治疗方案北医三院的治疗方案Regimens in Peking University Third Hospital甲强龙用法:(2)术中发生急性脊髓损伤 按照急性脊髓损伤治疗方案 30mg/kg（冲击量），静注，持续20分钟 5.4mg/kg/小时（持续量），静注，持续23小时 Treatment with MP(2)In case of acute spinal cord injury occurred during OPAccording to the regimens of MP for ASCI30mg/kg（bolus),iv,for 20min.5.4mg/kg/hr(infusion),iv,for 23hr.解放军总医院骨科应用解放军总医院骨科应用MPMP于颈椎病的外科治疗于颈椎病的外科治疗Use of MP in the Surgical Treatment of Cervical Spondylosis in Department of Orthopaedics,General Hospital of PLA*入选标准：年龄60岁 确诊为脊髓型颈椎病 手术方式为颈前路减压固定Inclusion Criteria:Age 60 years old Final diagnosis is cervical spondylotic myelopathy Treatment:anterior cervical decompression and fixation*Peoples Liberation Army排除标准：有脑部疾患者有胸、腰段脊髓或神经根病变合并神经根型颈椎病或OPLL先天性颈椎管狭窄MRI T2加权像有高信号Exclusion Criteria:Those who haveBrain diseaseThoracic and lumbar myelopathy or radiculopathyCervicalspondylotic radiculopathy or OPLLSimultaneous congenital cervical spinal stenosisHigh signal intensity at MRI T2WI 解放军总医院骨科应用解放军总医院骨科应用MPMP于颈椎病的外科治疗于颈椎病的外科治疗Use of MP in the Surgical Treatment of Cervical Spondylosis in Department of Orthopaedics,General Hospital of PLA*病例资料：A组（N=22)小剂量。MP80-240mg/次，每天2次，术后应用持续5-7天。Data of the cases:Group A(N=22)Low dose,MP 80-240mg,b.i.d,5-7days after operation 解放军总医院骨科应用解放军总医院骨科应用MPMP于颈椎病的外科治疗于颈椎病的外科治疗Use of MP in the Surgical Treatment of Cervical Spondylosis in Department of Orthopaedics,General Hospital of PLA*B组（N=25)：大剂量。MP首剂1000mg，术中减压前30min应用，术后每日递减200mg，共5天Group B(N=25)High dose,initial dose of 1000mg MP,administered 30 min before decompression;decrease progressively 200mg/d after operation;total 5 days 解放军总医院骨科应用解放军总医院骨科应用MPMP于颈椎病的外科治疗于颈椎病的外科治疗Use of MP in the Surgical Treatment of Cervical Spondylosis in Department of Orthopaedics,General Hospital of PLA*C组（N=24)：大剂量。MP首剂1000mg，术后当天应用，术后每日递减200mg，共5天。Group C(N=24)High dose,initial dose of 1000mg MP,administered immediately after operation;decrease progressively 200mg/d;total 5 days解放军总医院骨科应用解放军总医院骨科应用MPMP于颈椎病的外科治疗于颈椎病的外科治疗Use of MP in the Surgical Treatment of Cervical Spondylosis in Department of Orthopaedics,General Hospital of PLA*病例资料：D组（N=16)对照组，未用MPData of the cases:Group D(N=16)Control;no MP解放军总医院骨科应用解放军总医院骨科应用MPMP于颈椎病的外科治疗于颈椎病的外科治疗Use of MP in the Surgical Treatment of Cervical Spondylosis in Department of Orthopaedics,General Hospital of PLA*Neurological function score after operation Group A Group B Group C Group D Near-term(1 week)39.713.6 53.814.6 56.615.3 41.716.6 Long-term(6 months)51.414.4 74.816.2 76.814.8 53.118.2 The recovery of function after operationof Group B and C is significantly better than that of Group A and D解放军总医院骨科应用解放军总医院骨科应用MPMP于颈椎病的外科治疗于颈椎病的外科治疗Use of MP in the Surgical Treatment of Cervical Spondylosis in Department of Orthopaedics,General Hospital of PLA*术后神经功能评分恢复率 A组组 B组组 C组组 D组组 近期（近期（1 1周）周）39.739.713.6 53.813.6 53.814.6 56.614.6 56.615.3 41.715.3 41.716.616.6 远期远期(半年半年)51.4)51.414.4 74.814.4 74.816.2 76.816.2 76.814.8 53.114.8 53.118.218.2 B组和C组术后神经功能的改善明显优于A组及D组 结论：大剂量MP应用于颈椎病患者有助于术后神经功能改善Conclusions:High-dose MP improves recovery of neurological function in patients with cervical spondylosis after the operation解放军总医院骨科应用解放军总医院骨科应用MPMP于颈椎病的外科治疗于颈椎病的外科治疗Use of MP in the Surgical Treatment of Cervical Spondylosis in Department of Orthopaedics,General Hospital of PLA*疾病类型：胸椎骨折、脱位 胸椎管狭窄 胸椎畸形（侧凸、后凸）Diseases:Fracture-dislocation of thoracic spine Stenosis of thoracic spinal canal Deformity of thoracic spine (scoliosis,kyphosis)脊柱外科疾病（胸椎）脊柱外科疾病（胸椎）Surgical Treatment of Spine Diseases(thoracic spine)胸椎后纵韧带骨化、黄韧带骨化 胸椎椎管内肿瘤 胸椎结核 Ossification of posterior longitudinal ligament and ligamenta flava of thoracic spine Intraspinal tumors of thoracic spine Tuberculosis of thoracic spine脊柱外科疾病（胸椎）脊柱外科疾病（胸椎）Surgical Treatment of Spine Diseases(thoracic spine)疾病类型：腰椎间盘突出症 腰椎骨折、脱位 腰椎管狭窄Diseases:Lumber disc protrusion Fracture-dislocation of lumber spine Stenosis of lumber spinal canal脊柱外科疾病（腰椎）脊柱外科疾病（腰椎）Surgical Treatment of Spine Diseases(thoracic spine)疾病类型：腰椎畸形（侧凸、后凸）腰椎椎管内肿瘤 腰椎结核Diseases:Deformity of lumber spine(scoliosis,kyphosis)Intraspinal tumors of lumber spine Tuberculosis of lumber spine脊柱外科疾病（腰椎）脊柱外科疾病（腰椎）Surgical Treatment of Spine Diseases(lumber spine)MPMP在腰间盘突出症手术治疗中在腰间盘突出症手术治疗中的应用的应用Use of MP in Surgery for Lumbar Disc Protrusion Mechanical and chemical stimulation of outer layers of annulus fibrosus and sinuovertebral nerve in posterior longitudinal ligament by protruded nucleus pulposus beck painMechanical and chemical stimulation of nerve roots by protruded nucleus pulposus and its inflammatory reactionsciatica突出的髓核对纤维环外层及后纵韧带上的窦椎神经的机械性、化学性刺激腰痛突出的髓核及其引起的炎症反应对神经根的机械性、化学性刺激坐骨神经痛神经根性疼痛产生的原因神经根性疼痛产生的原因Causes of Nerve Root Pain正常的神经根对于压迫和牵拉有一定的耐受性。髓核突出后的病理生理改变：Normal nerve roots have some tolerance to compression and stretch.Pathophysiological changes in nucleus pulposus protrusion:神经根性疼痛产生的原因神经根性疼痛产生的原因Causes of Nerve Root PainMcCarron(1967)髓核可以引起硬膜外的炎症反应Saal(1990)腰椎间盘突出症的患者间盘组织内PLA2活性增高Byrod G（2000）硬膜外放置髓核组织可引发局部炎症反应，增加神经根血管的通透性McCarron(1967)Nucleus pulposus could cause epidural inflammatory reactionSaal(1990)PLA2 activity increasing in intervertebral disc of patients with lumbar disc protrusionByrod G(2000)Nucleus pulposus placed epidurally could cause local inflammatory reaction and increase vascular permeability of nerve roots.神经根性疼痛产生的原因神经根性疼痛产生的原因Causes of Nerve Root Pain 炎症反应的存在可降低神经根对机械性作用的耐受性。Inflammatory reaction could reduce the tolerance of nerve roots to mechanical forces Murphy,et al.Clin Neurosurg.1997;15:343-351.间盘组织产生化学性物质的刺激及自身免疫反应使神经根产生炎症。Stimulation of chemical substance produced by intervertebral disc and autoimmune reaction cause inflammatory reaction of nerve roots.Surgery.WU Zaide.Eds.Peoples Medical Publishing House,2000.神经根性疼痛产生的原因神经根性疼痛产生的原因Causes of Nerve Root Pain突出的髓核压迫或牵张已有炎症的神经根，使其静脉回流受阻，进一步增加水肿，从而对疼痛的敏感性增高。受压的神经根缺血。Protruded nucleus pulposus compress or stretch inflamed nerve roots,result in the obstruction of venous return,further aggravate edema,and increase the sensitivity to pain.Ischemia of compressed nerve roots Surgery.WU Zaide.Eds.Peoples Medical Publishing House,2000.神经根性疼痛产生的原因神经根性疼痛产生的原因Causes of Nerve Root Pain Inclusion Criteria 入选标准入选标准Acute episodeSingle level protrusionInefficiency of 6 weeks conservative therapy Having operation within 6 months after episodeFinal diagnosis dependent on CT and MRI scan急性发作单一节段间盘突出保守治疗6周无效发作后6个月内接受手术治疗确诊依赖CT及MRI检查手术方法：单侧椎板间开窗，髓核摘除 Surgical procedures:Single level laminotomy,removal of nucleus pulposusMPMP在腰椎间盘突出症手术治疗中的应用在腰椎间盘突出症手术治疗中的应用Use of MP in Surgery for Lumbar Disc ProtrusionJ Neurosurg.1993 Mar;78(3):383-7.剔除病例剔除病例Exclusion Criteria 病史超过6个月 多节段间盘突出 椎管狭窄 症状与影像学表现不符 有过椎管内手术史More than 6 months history Multiplelevel protrusion Stenosis of spinal canal Symptoms not consistent with image manifestation Having history of intraspinal operation手术方法：单侧椎板间开窗，髓核摘除 Surgical procedures:Single level laminotomy,removal of nucleus pulposusMPMP在腰椎间盘突出症手术治疗中的应用在腰椎间盘突出症手术治疗中的应用Use of MP in Surgery for Lumbar Disc ProtrusionJ Neurosurg.1993 Mar;78(3):383-7.手术开始时At the beginning of operation 手术结束时At the end of operation第一组Group 1250mg MP 静脉注射160mg MPA 肌肉注射 30ml0.25%普鲁卡因皮下及肌肉注射250mg MP IV160mg MPA IM 30ml 0.25%procaine subcutaneous injection and IM30ml0.25%普鲁卡因皮下及肌肉注射浸泡有80mgMPA的脂肪覆盖神经根30ml 0.25%procaine subcutaneous injection and IMFat marinated with 80mg MPA covering nerve roots 第二组Group 230ml0.25%普鲁卡因皮下及肌肉注射30ml 0.25%procaine subcutaneous injection and IM30ml0.25%普鲁卡因皮下及肌肉注射30ml 0.25%procaine subcutaneous injection and IM第三组Group 310ml0.5%利多卡因皮下及肌肉注射10ml 0.5%procaine subcutaneous injection and IMJ Neurosurg.1993 Mar;78(3):383-7MPMP在腰椎间盘突出症手术治疗中的应用在腰椎间盘突出症手术治疗中的应用Use of MP in Surgery for Lumbar Disc Protrusion Complete remission of nerve root pain after operation01234567891 day 1 week 1 month Group 1Group 2Group 3J Neurosurg.1993 Mar;78(3):383-7.术后神经根性疼痛完全缓解情况 Nerve Root Pain Relief After OP术后时间Time of Post-OP结论 腰椎间盘突出症手术中应用MP可缩短腰间盘突出症病人的住院时间，减少术后止痛药的应用，更快的缓解根性疼痛症状Conclusions MP administration during surgery for lumbar disc protrusion shortened hospitalization,reduced the use of analgesia,and relieves the symptoms of nerve root pain faster.MPMP在腰椎间盘突出症手术治疗中的应用在腰椎间盘突出症手术治疗中的应用Use of MP in Surgery for Lumbar Disc Protrusion大剂量MP在脊柱手术后的应用Use of High-dose MP After Spinal Surgery用药方法：用药方法：MP组：术后1小时甲强龙按30mg/kg加入0.9%生理盐水1小时内滴注，以后23小时按5.4mg/kg维持滴注。Treatment:MP Group30mg/kg MP added in 0.9%normal saline intravenous drip for the first hour after surgery,5.4mg/kg continuous infusion in subsequent 23hr 陈旸 颈腰痛杂志2003年第24卷第1期35-36Chen Yang,2003MP methylprednisolone;DX dexamethasone大剂量MP在脊柱手术后的应用Use of High-dose MP After Spinal Surgery DX组：组：术后地塞米松10mg 加入20%甘露醇250ml。每日两次，持续一周 DX GroupDX 10mg added in 20%mannitol 250ml intravenous drip after peraton,bid,lasting for 1 week 陈旸 颈腰痛杂志2003年第24卷第1期35-36Chen Yang,2003MP methylprednisolone;DX dexamethasone大剂量MP在脊柱手术后的应用Use of High-dose MP After Spinal SurgeryMP methylprednisolone;DX dexamethasone脊柱侧弯Scoliosis脊柱滑脱Spondylolisthesis腰间盘突出Lumbar disc protrusion腰椎管狭窄Stenosis of lumbar spineMP组MP group021613DX 组DX group161211病例资料：Cases：陈旸 颈腰痛杂志2003年第24卷第1期35-36Chen Yang,2003结果：结果：术后1天、2周、3个月 感觉运动评分及患者自主满意度评估。Results:Time frame:1 day,2 weeks and 3 months post-OPEndpoints:Sensory motor score and self-satisfaction evaluation大剂量MP在脊柱手术后的应用Use of High-dose MP After Spinal Surgery结果：术后1天：MP组症状改善或消失占90%，DX组73.3%，术后2周及3个月：无差异。Results:1 day after operation:90%of patients with symptoms relieved or vanishedin MP group,versus 73.3%in DX group.There were no differences between the two groups at 2 weeks and 3 months after the surgery.大剂量MP在脊柱手术后的应用Use of High-dose MP After Spinal SurgeryMPMP在非创伤性脊柱疾患手术后的应用存在问题在非创伤性脊柱疾患手术后的应用存在问题Post-surgical Problems in Use of MP for Non-traumatic Spinal Diseases After Operation 适应症？药物剂量的确定？用药方法？可能的并发症的防治？Indications?Determination of drug dosage?Methods of drug administration?Prevention and treatment of possible complications?需要多中心双盲对照研究需要多中心双盲对照研究!Multi-center,double blind,casecontrol studies are needed!谢 谢