依达拉奉联合尼莫地平治疗创伤性蛛网膜下腔出血的临床疗效及对脑微循环和血清白介素6、肿瘤坏死因子α、S100β蛋白水平的影响
|
摘要
目的观察依达拉奉联合尼莫地平治疗创伤性蛛网膜下腔出血(tSAH)的临床疗效,探讨其对脑微循环和血清白介素6(IL-6)、肿瘤坏死因子α(TNF-α)、S100β蛋白水平的影响。方法选取2015年3月—2017年4月攀枝花市第二人民医院收治的tSAH患者88例,采用随机数字表法分为对照组与观察组,每组44例。在常规治疗基础上,对照组患者给予尼莫地平治疗,观察组患者在对照组基础上给予依达拉奉治疗;两组患者均连续治疗14 d。比较两组患者临床疗效,治疗前及治疗后7、14 d颅内压、格拉斯哥昏迷量表(GCS)评分及血清IL-6、TNF-α、S100β蛋白水平,治疗前及治疗后14 d脑微循环指标,治疗后3个月预后。结果观察组患者临床疗效优于对照组(P<0.01)。治疗前两组患者颅内压、GCS评分比较,差异无统计学意义(P>0.05);治疗后7、14 d观察组患者颅内压低于对照组,GCS评分高于对照组(P<0.05)。治疗前两组患者脑血容量(CBV)、脑血流量(CBF)及平均通过时间(MTT)比较,差异无统计学意义(P>0.05);治疗后14 d观察组患者CBV大于对照组,CBF快于对照组,MTT短于对照组(P<0.05)。治疗前两组患者血清IL-6、TNF-α、S100β蛋白水平比较,差异无统计学意义(P>0.05);治疗后7、14 d观察组患者血清IL-6、TNF-α、S100β蛋白水平低于对照组(P<0.05)。治疗后3个月观察组患者预后良好率高于对照组(P<0.05)。结论依达拉奉联合尼莫地平治疗tSAH的临床疗效确切,可有效降低患者颅内压及血清IL-6、TNF-α、S100β蛋白水平,减轻患者昏迷、意识障碍程度,改善患者脑微循环及预后。
Objective To observe the clinical effect of edaravone combined with nimodipine on traumatic subarachnoid hemorrhage(tSAH),to investigate the impact on cerebral microcirculation,serum levels of IL-6,TNF-α and S100β protein. Methods A total of 88 patients with tSAH were selected in the Second People's Hospital of Panzhihua from March 2015 to April 2017,and they were divided into control group and observation group according to random number table,each of 44 cases. Based on conventional treatment,patients in control group received nimodipine,while patients in observation group received edaravone combined with nimodipine;both groups continuously treated for 14 days. Clinical effect,intracranial pressure,GCS score,serum levels of IL-6,TNF-α,S100β protein before treatment,7 and 14 days after treatment,index of cerebral microcirculation before treatment and 14 days after treatment,and prognosis 3 months after treatment were compared between the two groups. Results Clinical effect in observation group was statistically significantly better than that in control group(P<0.01). No statistically significant differences of intracranial pressure or GCS score was found between the two groups before treatment(P>0.05);7 and 14 days after treatment,intracranial pressure in observation group was statistically significantly lower than that in control group,respectively,while GCS score was statistically significantly higher than that in control group,respectively(P<0.05). No statistically significant differences of CBV,CBF or MTT was found between the two groups before treatment(P>0.05);14 days after treatment,CBV in observation group was statistically significantly larger than that in control group,CBF in observation group was statistically significantly faster than that in control group,and MTT in observation group was statistically significantly shorter than that in control group(P<0.05). No statistically significant differences of serum level of IL-6,TNF-α or S100β protein was found between the two groups(P>0.05),while serum levels of IL-6,TNF-α and S100β protein in observation group were statistically significantly lower than those in control group 7 and 14 days after treatment(P<0.05). Proportion of patients with good prognosis in observation group was statistically significantly higher than that in control group 3 months after treatment. Conclusion Edaravone combined with nimodipine has certain clinical effect in treating tSAH,can effectively reduce the intracranial pressure,serum levels of IL-6,TNF-α and S100β protein,reduce the severity of coma and conscious disturbance,improve the cerebral microcirculation and prognosis.
Objective To observe the clinical effect of edaravone combined with nimodipine on traumatic subarachnoid hemorrhage(tSAH),to investigate the impact on cerebral microcirculation,serum levels of IL-6,TNF-α and S100β protein. Methods A total of 88 patients with tSAH were selected in the Second People's Hospital of Panzhihua from March 2015 to April 2017,and they were divided into control group and observation group according to random number table,each of 44 cases. Based on conventional treatment,patients in control group received nimodipine,while patients in observation group received edaravone combined with nimodipine;both groups continuously treated for 14 days. Clinical effect,intracranial pressure,GCS score,serum levels of IL-6,TNF-α,S100β protein before treatment,7 and 14 days after treatment,index of cerebral microcirculation before treatment and 14 days after treatment,and prognosis 3 months after treatment were compared between the two groups. Results Clinical effect in observation group was statistically significantly better than that in control group(P<0.01). No statistically significant differences of intracranial pressure or GCS score was found between the two groups before treatment(P>0.05);7 and 14 days after treatment,intracranial pressure in observation group was statistically significantly lower than that in control group,respectively,while GCS score was statistically significantly higher than that in control group,respectively(P<0.05). No statistically significant differences of CBV,CBF or MTT was found between the two groups before treatment(P>0.05);14 days after treatment,CBV in observation group was statistically significantly larger than that in control group,CBF in observation group was statistically significantly faster than that in control group,and MTT in observation group was statistically significantly shorter than that in control group(P<0.05). No statistically significant differences of serum level of IL-6,TNF-α or S100β protein was found between the two groups(P>0.05),while serum levels of IL-6,TNF-α and S100β protein in observation group were statistically significantly lower than those in control group 7 and 14 days after treatment(P<0.05). Proportion of patients with good prognosis in observation group was statistically significantly higher than that in control group 3 months after treatment. Conclusion Edaravone combined with nimodipine has certain clinical effect in treating tSAH,can effectively reduce the intracranial pressure,serum levels of IL-6,TNF-α and S100β protein,reduce the severity of coma and conscious disturbance,improve the cerebral microcirculation and prognosis.
引文
[1]OH J,LEE W,JANG J Y,et al.Delayed Traumatic Subarachnoid Hemorrhage in a Polytraumatized Patient with Disseminated Intravascular Coagulation[J].Korean J Crit Care Med,2015,30(4):336-342.DOI:10.4266/kjccm.2015.30.4.336.
[2]KURAMATSU J B,KOLLMAR R,GERNER S T,et al.Is Hypothermia Helpful in Severe Subarachnoid Hemorrhage?An Exploratory Study on Macro Vascular Spasm,Delayed Cerebral Infarction and Functional Outcome after Prolonged Hypothermia[J].Cerebrovasc Dis,2015,40(5/6):228-235.DOI:10.1159/000439178.
[3]吴琼,李晓凤,王大路,等.尼莫地平治疗蛛网膜下腔出血后脑血管痉挛的临床观察[J].中国医药导刊,2017,19(2):155-156.DOI:10.3969/j.issn.1009-0959.2017.02.022.
[4]纪祥辉,刘莉,冯仰柏.依达拉奉联合尼莫地平治疗蛛网膜下腔出血后脑血管痉挛的临床疗效观察[J].实用心脑肺血管病杂志,2015,23(5):64-66.DOI:10.3969/j.issn.1008-5971.2015.05.019.
[5]黄其军,陈宏刚.尼莫地平联合依达拉奉治疗蛛网膜下腔出血的疗效观察及其对S100蛋白的影响[J].海南医学,2013,24(1):13-15.DOI:10.3969/j.issn.1003-6350.2013.01.0006.
[6]SIASIOS I,KAPSALAKI E Z,FOUNTAS K N,et al.Cerebral vasospasm pharmacological treatment:an update[J].Neurol Res Int,2013,2013(11):571328.DOI:10.1155/2013/571328.
[7]WASHINGTON C W,DERDEYN C P,DHAR R,et al.A Phase I proof-of-concept and safety trial of sildenafil to treat cerebral vasospasm following subarachnoid hemorrhage[J].J Neurosurg,2016,124(2):318-327.DOI:10.3171/2015.2.JNS142752.
[8]SHIMAMURA N,OHKUMA H.Phenotypic transformation of smooth muscle in vasospasm after aneurysmal subarachnoid hemorrhage[J].Transl Strike Res,2014,5(3):357-364.DOI:10.1007/s12975-013-0310-1.
[9]BUDOHOSKI K P,CZOSNYKA M,KIRKPATRICK P J,et al.Bilateral failure of cerebral autoregulation is related to unfavorable outcome after subarachnoid hemorrhage[J].Neurocrit Care,2015,22(1):65-73.DOI:10.1007/s12028-014-0032-6.
[10]杨彬源,陈桂增,王本艳,等.马来酸桂哌齐特联合尼莫地平治疗动脉瘤性蛛网膜下腔出血后脑血管痉挛疗效观察[J].海南医学,2017,28(6):971-973.DOI:10.3969/j.issn.1003-6350.2017.06.037.
[11]吴静芳,马志强,丁翔,等.尼莫地平对动脉瘤性蛛网膜下腔出血脑血管痉挛的临床疗效研究[J].现代生物医学进展,2014,14(17):3319-3321.DOI:10.13241/j.cnki.pmb.2014.17.031.
[12]斯良楠,孙晓川,张晓冬.经动脉灌注尼莫地平治疗蛛网膜下腔出血后脑血管痉挛[J].中国介入影像与治疗学,2015,12(9):527-531.DOI:10.13929/j.1672-8475.2015.09.003.
[13]DE LIMA OLIVEIRA M D L,KAIRALLA A C,FONOFF E T,et al.Cerebral microdialysis in traumatic brain injury and subarachnoid hemorrhage:state of the art[J].Neurocrit Care,2014,21(1):152-162.DOI:10.1007/s12028-013-9884-4.
[14]张哲英,唐勇,甄玲玲,等.尼莫地平治疗外伤性蛛网膜下腔出血疗效的系统评价[J].重庆医学,2014,43(18):2291-2293,2296.DOI:10.3969/j.issn.1671-8348.2014.18.011.
[15]郎胜坤,马铁柱,郝芊芊,等.依达拉奉联合尼莫地平治疗蛛网膜下腔出血的疗效观察及其对患者血清CRP、S100水平的影响分析[J].标记免疫分析与临床,2016,23(4):385-388.DOI:10.11748/bjmy.issn.1006-1703.2016.04.009.
[16]冯怡墨,孙晓川,张晓冬,等.依达拉奉联合马来酸桂哌齐特治疗动脉瘤性蛛网膜下腔出血后脑血管痉挛的临床观察[J].中国药房,2017,28(2):230-232.DOI:10.6039/j.issn.1001-0408.2017.02.24.
[17]KAMOGAWA E,SUEISHI Y.A multiple free-radical scavenging(MULTIS)study on the antioxidant capacity of a neuroprotective drug,edaravone as compared with uric acid,glutathione,and trolox[J].Bioorg Med Chem Lett,2014,24(5):1376-1379.DOI:10.1016/j.bmcl.2014.01.045.
[18]MIYAJI Y,YOSHIMURA S,SAKAI N,et al.Effect of edaravone on favorable outcome in patients with acute cerebral large vessel occlusion:subanalysis of RESCUE-Japan Registry[J].Neurol Med Chir(Tokyo),2015,55(3):241-247.DOI:10.2176/nmc.ra.2014-0219.
[19]MARDER C P,NARLA V,FINK J R,et al.Subarachnoid hemorrhage:beyond aneurysms[J].AJR Am J Roentgenol,2014,202(1):25-37.DOI:10.2214/AJR.12.9749.
[20]SERVADEI F,PICETTI E.Traumatic subarachnoid hemorrhage[J].World neurosurgery,2014,82(5):e597-598.DOI:10.1016/j.wneu.2014.08.034.
[21]ERSAHIN M,OZSAVCI D,SENER A,et al.Obestatin alleviates subarachnoid haemorrhage-induced oxidative injury in rats via its anti-apoptotic and antioxidant effects[J].Brain Inj,2013,27(10):1181-1189.DOI:10.3109/02699052.2013.804199.
[22]刘华桥.急性创伤性颅脑损伤患者血浆S100B蛋白动态变化水平及临床意义[J].河北医药,2015,37(21):3209-3211.DOI:10.3969/j.issn.1002-7386.2015.21.002.
[23]高明明,梁维邦,徐武,等.尼莫地平联合丁基苯酞对外伤性蛛网膜下腔出血患者脑微循环的影响[J].现代生物医学进展,2016,16(28):5451-5454.DOI:10.13241/j.cnki.pmb.2016.28.013.
[2]KURAMATSU J B,KOLLMAR R,GERNER S T,et al.Is Hypothermia Helpful in Severe Subarachnoid Hemorrhage?An Exploratory Study on Macro Vascular Spasm,Delayed Cerebral Infarction and Functional Outcome after Prolonged Hypothermia[J].Cerebrovasc Dis,2015,40(5/6):228-235.DOI:10.1159/000439178.
[3]吴琼,李晓凤,王大路,等.尼莫地平治疗蛛网膜下腔出血后脑血管痉挛的临床观察[J].中国医药导刊,2017,19(2):155-156.DOI:10.3969/j.issn.1009-0959.2017.02.022.
[4]纪祥辉,刘莉,冯仰柏.依达拉奉联合尼莫地平治疗蛛网膜下腔出血后脑血管痉挛的临床疗效观察[J].实用心脑肺血管病杂志,2015,23(5):64-66.DOI:10.3969/j.issn.1008-5971.2015.05.019.
[5]黄其军,陈宏刚.尼莫地平联合依达拉奉治疗蛛网膜下腔出血的疗效观察及其对S100蛋白的影响[J].海南医学,2013,24(1):13-15.DOI:10.3969/j.issn.1003-6350.2013.01.0006.
[6]SIASIOS I,KAPSALAKI E Z,FOUNTAS K N,et al.Cerebral vasospasm pharmacological treatment:an update[J].Neurol Res Int,2013,2013(11):571328.DOI:10.1155/2013/571328.
[7]WASHINGTON C W,DERDEYN C P,DHAR R,et al.A Phase I proof-of-concept and safety trial of sildenafil to treat cerebral vasospasm following subarachnoid hemorrhage[J].J Neurosurg,2016,124(2):318-327.DOI:10.3171/2015.2.JNS142752.
[8]SHIMAMURA N,OHKUMA H.Phenotypic transformation of smooth muscle in vasospasm after aneurysmal subarachnoid hemorrhage[J].Transl Strike Res,2014,5(3):357-364.DOI:10.1007/s12975-013-0310-1.
[9]BUDOHOSKI K P,CZOSNYKA M,KIRKPATRICK P J,et al.Bilateral failure of cerebral autoregulation is related to unfavorable outcome after subarachnoid hemorrhage[J].Neurocrit Care,2015,22(1):65-73.DOI:10.1007/s12028-014-0032-6.
[10]杨彬源,陈桂增,王本艳,等.马来酸桂哌齐特联合尼莫地平治疗动脉瘤性蛛网膜下腔出血后脑血管痉挛疗效观察[J].海南医学,2017,28(6):971-973.DOI:10.3969/j.issn.1003-6350.2017.06.037.
[11]吴静芳,马志强,丁翔,等.尼莫地平对动脉瘤性蛛网膜下腔出血脑血管痉挛的临床疗效研究[J].现代生物医学进展,2014,14(17):3319-3321.DOI:10.13241/j.cnki.pmb.2014.17.031.
[12]斯良楠,孙晓川,张晓冬.经动脉灌注尼莫地平治疗蛛网膜下腔出血后脑血管痉挛[J].中国介入影像与治疗学,2015,12(9):527-531.DOI:10.13929/j.1672-8475.2015.09.003.
[13]DE LIMA OLIVEIRA M D L,KAIRALLA A C,FONOFF E T,et al.Cerebral microdialysis in traumatic brain injury and subarachnoid hemorrhage:state of the art[J].Neurocrit Care,2014,21(1):152-162.DOI:10.1007/s12028-013-9884-4.
[14]张哲英,唐勇,甄玲玲,等.尼莫地平治疗外伤性蛛网膜下腔出血疗效的系统评价[J].重庆医学,2014,43(18):2291-2293,2296.DOI:10.3969/j.issn.1671-8348.2014.18.011.
[15]郎胜坤,马铁柱,郝芊芊,等.依达拉奉联合尼莫地平治疗蛛网膜下腔出血的疗效观察及其对患者血清CRP、S100水平的影响分析[J].标记免疫分析与临床,2016,23(4):385-388.DOI:10.11748/bjmy.issn.1006-1703.2016.04.009.
[16]冯怡墨,孙晓川,张晓冬,等.依达拉奉联合马来酸桂哌齐特治疗动脉瘤性蛛网膜下腔出血后脑血管痉挛的临床观察[J].中国药房,2017,28(2):230-232.DOI:10.6039/j.issn.1001-0408.2017.02.24.
[17]KAMOGAWA E,SUEISHI Y.A multiple free-radical scavenging(MULTIS)study on the antioxidant capacity of a neuroprotective drug,edaravone as compared with uric acid,glutathione,and trolox[J].Bioorg Med Chem Lett,2014,24(5):1376-1379.DOI:10.1016/j.bmcl.2014.01.045.
[18]MIYAJI Y,YOSHIMURA S,SAKAI N,et al.Effect of edaravone on favorable outcome in patients with acute cerebral large vessel occlusion:subanalysis of RESCUE-Japan Registry[J].Neurol Med Chir(Tokyo),2015,55(3):241-247.DOI:10.2176/nmc.ra.2014-0219.
[19]MARDER C P,NARLA V,FINK J R,et al.Subarachnoid hemorrhage:beyond aneurysms[J].AJR Am J Roentgenol,2014,202(1):25-37.DOI:10.2214/AJR.12.9749.
[20]SERVADEI F,PICETTI E.Traumatic subarachnoid hemorrhage[J].World neurosurgery,2014,82(5):e597-598.DOI:10.1016/j.wneu.2014.08.034.
[21]ERSAHIN M,OZSAVCI D,SENER A,et al.Obestatin alleviates subarachnoid haemorrhage-induced oxidative injury in rats via its anti-apoptotic and antioxidant effects[J].Brain Inj,2013,27(10):1181-1189.DOI:10.3109/02699052.2013.804199.
[22]刘华桥.急性创伤性颅脑损伤患者血浆S100B蛋白动态变化水平及临床意义[J].河北医药,2015,37(21):3209-3211.DOI:10.3969/j.issn.1002-7386.2015.21.002.
[23]高明明,梁维邦,徐武,等.尼莫地平联合丁基苯酞对外伤性蛛网膜下腔出血患者脑微循环的影响[J].现代生物医学进展,2016,16(28):5451-5454.DOI:10.13241/j.cnki.pmb.2016.28.013.