孕酮治疗急性颅脑损伤有效性和安全性的Meta分析
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摘要
目的:系统评价孕酮治疗急性颅脑损伤的有效性和安全性,为临床治疗提供参考。方法:计算机检索Cochrane图书馆、ClinicalTrials、Web of Science、PubMed、Embase、中国生物医学文献数据库、中国知网数据库和万方数据库,收集孕酮(试验组)对比安慰剂或空白对照(对照组)治疗急性颅脑损伤的随机对照试验(RCT),筛选文献、提取资料并采用Cochrane系统评价员手册5.1.0提供的偏倚风险评估工具评价文献质量后,采用RevMan 5.3软件进行Meta分析。结果:共纳入10项RCT,共计2 652例患者。Meta分析结果显示,两组患者病死率[RR=0.77,95%CI(0.56,1.07),P=0.12]、败血症发生率[RR=1.11,95%CI(0.77,1.60),P=0.59]、肝酶升高发生率[RR=1.30,95%CI(0.68,2.50),P=0.43]比较,差异均无统计学意义;试验组神经功能预后良好患者例数显著多于对照组[RR=1.23,95%CI(1.05,1.43),P=0.008]。病死率亚组分析结果显示,两组GCS≤8分患者病死率[RR=0.79,95%CI(0.57,1.10),P=0.16]、GCS≤12分患者病死率[RR=0.69,95%CI(0.23,2.10),P=0.52]、GCS 9～12分患者病死率[RR=0.78,95%CI(0.26,2.35),P=0.65]比较,差异均无统计学意义。神经功能预后亚组分析结果显示,两组GCS≤8分神经功能预后良好患者例数[RR=1.18,95%CI(0.98,1.43),P=0.09]、GCS≤12分神经功能预后良好患者例数[RR=1.15,95%CI(0.87,1.51),P=0.32]、GCS 9～12分神经功能预后良好患者例数[RR=2.07,95%CI(0.24,17.71),P=0.51]比较,差异均无统计学意义。结论:孕酮可改善急性重度颅脑损伤患者的神经功能预后,安全性较好,但不能降低病死率。
OBJECTIVE:To evaluate the efficacy and safety of progesterone in the treatment of acute traumatic brain injury systematically,and to provide reference for clinical use. METHODS:Retrieved from Cochrane library,ClinicalTrials,Web of Science,PubMed,Embase,CBM,CNKI and Wanfang database,randomized controlled trial(RCTs) about progesterone(trial group) versus placebo or blank control(control group) in the treatment of acute traumatic brain injury were collected. After literature screening,data extraction and quality evaluation by risk bias evalution tool of Cochrane systematic evaluator manual 5.1.0,Meta-analysis was performed by using Rev Man 5.3 statistical software. RESULTS:A total of 10 RCTs were included,involving 2 652 patients. Results of Meta-analysis showed that there was no statistical significance in mortality[RR=0.77,95%CI(0.56,1.07),P=0.12],the incidence of septicemia [RR=1.11,95%CI(0.77,1.60),P=0.59] or elevated liver enzymes[RR=1.30,95%CI(0.68,2.50),P=0.43]. The number of patients with favorable neurological outcome[RR=1.23,95%CI(1.05,1.43),P=0.008] in trial group was significantly more than control group. Results of subgroup analysis of mortality showed that there was no statistical significance in the mortality of patient's GCS≤8 [RR=0.79,95%CI(0.57,1.10),P=0.16],that of patient's GCS≤12[RR=0.69,95%CI(0.23,2.10),P=0.52] or that of patient's GCS ranging from 9 to 12 [RR=0.78,95%CI(0.26,2.35),P=0.65]between 2 groups. Results of subgroup analysis of neurological outcome showed that there was no statistical significance in the number of favorable neurological outcome of patient's GCS≤8 [RR=1.18,95% CI(0.98,1.43),P=0.09],the number of favorable outcome of patient's GCS≤12[RR=1.15,95% CI(0.87,1.51),P=0.32] and the number of favorable neurological outcome of patient's GCS ranging from 9 to 12[RR=2.07,95% CI(0.24,17.71),P=0.51]. CONCLUSIONS:Progesterone can improve the prognosis of neurological function in patients with acute traumatic brain injury with good safety but cannot reduce mortality.
OBJECTIVE:To evaluate the efficacy and safety of progesterone in the treatment of acute traumatic brain injury systematically,and to provide reference for clinical use. METHODS:Retrieved from Cochrane library,ClinicalTrials,Web of Science,PubMed,Embase,CBM,CNKI and Wanfang database,randomized controlled trial(RCTs) about progesterone(trial group) versus placebo or blank control(control group) in the treatment of acute traumatic brain injury were collected. After literature screening,data extraction and quality evaluation by risk bias evalution tool of Cochrane systematic evaluator manual 5.1.0,Meta-analysis was performed by using Rev Man 5.3 statistical software. RESULTS:A total of 10 RCTs were included,involving 2 652 patients. Results of Meta-analysis showed that there was no statistical significance in mortality[RR=0.77,95%CI(0.56,1.07),P=0.12],the incidence of septicemia [RR=1.11,95%CI(0.77,1.60),P=0.59] or elevated liver enzymes[RR=1.30,95%CI(0.68,2.50),P=0.43]. The number of patients with favorable neurological outcome[RR=1.23,95%CI(1.05,1.43),P=0.008] in trial group was significantly more than control group. Results of subgroup analysis of mortality showed that there was no statistical significance in the mortality of patient's GCS≤8 [RR=0.79,95%CI(0.57,1.10),P=0.16],that of patient's GCS≤12[RR=0.69,95%CI(0.23,2.10),P=0.52] or that of patient's GCS ranging from 9 to 12 [RR=0.78,95%CI(0.26,2.35),P=0.65]between 2 groups. Results of subgroup analysis of neurological outcome showed that there was no statistical significance in the number of favorable neurological outcome of patient's GCS≤8 [RR=1.18,95% CI(0.98,1.43),P=0.09],the number of favorable outcome of patient's GCS≤12[RR=1.15,95% CI(0.87,1.51),P=0.32] and the number of favorable neurological outcome of patient's GCS ranging from 9 to 12[RR=2.07,95% CI(0.24,17.71),P=0.51]. CONCLUSIONS:Progesterone can improve the prognosis of neurological function in patients with acute traumatic brain injury with good safety but cannot reduce mortality.
引文
[1]丁涟沭.创伤性脑损伤后标志物的研究进展[J/CD].中华神经创伤外科电子杂志,2015,1(1):42-44.
[2]MAAS AIR,MENON DK,ADELSON PD,et al.Traumatic brain injury:integrated approaches to improve prevention,clinical care,and research[J].Lancet Neurol,2017,16(12):987-1048.
[3]康德智,孙炜,魏俊吉,等.加强多学科协作,推动重型颅脑创伤患者的早期康复治疗[J].中华医学杂志,2017,97(21):1602-1603.
[4]江基尧.中国颅脑创伤的发展方向[J].中华创伤杂志,2015,31(9):774-776.
[5]MORGANTI-KOSSMANN MC,RANCAN M,OTTO VI,et al.Role of cerebral inflammation after traumatic brain injury:a revisited concept[J].Shock,2001,16(3):165-177.
[6]蒋天伟,杭春华.创伤性脑损伤中孕酮的应用研究进展[J].中华实验外科杂志,2016,33(3):851-854.
[7]ANDERSON GD,FARIN FM,BAMMLER TK,et al.The effect of progesterone dose on gene expression after traumatic brain injury[J].J Neurotrauma,2011,28(9):1827-1843.
[8]WRIGHT DW,KELLERMANN AL,HERTZBERG VS,et al.ProTECT:a randomized clinical trial of progesterone for acute traumatic brain injury[J].Ann Emerq Med,2007,49(4):391-402.
[9]SKOLNICK BE,MAAS AI,NARAYAN RK,et al.A clinical trial of progesterone for severe traumatic brain injury[J].N Engl J Med,2014,371(26):2467-2476.
[10]WRIGHT DW,YEATTS SD,SILBERGLEIT R,et al.Very early administration of progesterone for acute traumatic brain injury[J].N Engl J Med,2014,371(26):2457-2466.
[11]XIAO G,WEI J,YAN W,et al.Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury:a randomized controlled trial[J].Crit Care,2008.DOI:10.1186/cc6887.
[12]SOLTANI Z,SHAHROKHI N,KARAMOUZIAN S,et al.Does progesterone improve outcome in diffuse axonal injury?[J].Brain Inj,2017,31(1):16-23.
[13]MOFID B,SOLTANI Z,KHAKSARI M,et al.What are the progesterone-induced changes of the outcome and the serum markers of injury,oxidant activity and inflammation in diffuse axonal injury patients?[J].Int Immunopharmacol,2016.DOI:10.1016/j.intimp.2016.01.015.
[14]XIAO GM,WEI J,WU ZH,et al.Clinical study on the therapeutic effects and mechanism of progesterone in the treatment for acute severe head injury[J].Zhonghua Wai Ke Za Zhi,2007,45(2):106-108.
[15]AMINMANSOUR B,NIKBAKHT H,GHORBANI A,et al.Comparison of the administration of progesterone versus progesterone and vitamin D in improvement of outcomes in patients with traumatic brain injury:a randomized clinical trial with placebo group[J].Adv Biomed Res,2012.DOI:10.4103/2277-9175.100176.
[16]SHAKERI M,BOUSTANI MR,PAK N,et al.Effect of progesterone administration on prognosis of patients with diffuse axonal injury due to severe head trauma[J].Clin Neurol Neurosurg,2013,115(10):2019-2022.
[17]ABOUKHABAR H,ABOUELELA A,MOUSA S,et al.Impact of progesterone administration on outcome of patients with severe traumatic brain injury[J].Res Opi Anesth Intensive Care,2017.DOI:10.4103/roaic.roaic_106_16.
[18]傅西安,王旭阳.创伤性脑损伤的研究热点问题[J].国际外科学杂志,2013,40(11):729-731.
[19]CUTLER SM,CEKIC M,MILLER DM,et al.Progesterone improves acute recovery after traumatic brain injury in the aged rat[J].J Neurotrauma,2007,24(9):1475-1486.
[20]WRIGHT DW,BAUER ME,HOFFMAN SW,et al.Serum progesterone levels correlate with decreased cerebral edema after traumatic brain injury in male rats[J].J Neurotrauma,2001,18(9):901-909.
[21]王冬梅,常杰,白云贤,等.急性颅脑损伤血清性激素水平变化与预后的研究[J].中华神经外科杂志,2014,30(7):715-717.
[2]MAAS AIR,MENON DK,ADELSON PD,et al.Traumatic brain injury:integrated approaches to improve prevention,clinical care,and research[J].Lancet Neurol,2017,16(12):987-1048.
[3]康德智,孙炜,魏俊吉,等.加强多学科协作,推动重型颅脑创伤患者的早期康复治疗[J].中华医学杂志,2017,97(21):1602-1603.
[4]江基尧.中国颅脑创伤的发展方向[J].中华创伤杂志,2015,31(9):774-776.
[5]MORGANTI-KOSSMANN MC,RANCAN M,OTTO VI,et al.Role of cerebral inflammation after traumatic brain injury:a revisited concept[J].Shock,2001,16(3):165-177.
[6]蒋天伟,杭春华.创伤性脑损伤中孕酮的应用研究进展[J].中华实验外科杂志,2016,33(3):851-854.
[7]ANDERSON GD,FARIN FM,BAMMLER TK,et al.The effect of progesterone dose on gene expression after traumatic brain injury[J].J Neurotrauma,2011,28(9):1827-1843.
[8]WRIGHT DW,KELLERMANN AL,HERTZBERG VS,et al.ProTECT:a randomized clinical trial of progesterone for acute traumatic brain injury[J].Ann Emerq Med,2007,49(4):391-402.
[9]SKOLNICK BE,MAAS AI,NARAYAN RK,et al.A clinical trial of progesterone for severe traumatic brain injury[J].N Engl J Med,2014,371(26):2467-2476.
[10]WRIGHT DW,YEATTS SD,SILBERGLEIT R,et al.Very early administration of progesterone for acute traumatic brain injury[J].N Engl J Med,2014,371(26):2457-2466.
[11]XIAO G,WEI J,YAN W,et al.Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury:a randomized controlled trial[J].Crit Care,2008.DOI:10.1186/cc6887.
[12]SOLTANI Z,SHAHROKHI N,KARAMOUZIAN S,et al.Does progesterone improve outcome in diffuse axonal injury?[J].Brain Inj,2017,31(1):16-23.
[13]MOFID B,SOLTANI Z,KHAKSARI M,et al.What are the progesterone-induced changes of the outcome and the serum markers of injury,oxidant activity and inflammation in diffuse axonal injury patients?[J].Int Immunopharmacol,2016.DOI:10.1016/j.intimp.2016.01.015.
[14]XIAO GM,WEI J,WU ZH,et al.Clinical study on the therapeutic effects and mechanism of progesterone in the treatment for acute severe head injury[J].Zhonghua Wai Ke Za Zhi,2007,45(2):106-108.
[15]AMINMANSOUR B,NIKBAKHT H,GHORBANI A,et al.Comparison of the administration of progesterone versus progesterone and vitamin D in improvement of outcomes in patients with traumatic brain injury:a randomized clinical trial with placebo group[J].Adv Biomed Res,2012.DOI:10.4103/2277-9175.100176.
[16]SHAKERI M,BOUSTANI MR,PAK N,et al.Effect of progesterone administration on prognosis of patients with diffuse axonal injury due to severe head trauma[J].Clin Neurol Neurosurg,2013,115(10):2019-2022.
[17]ABOUKHABAR H,ABOUELELA A,MOUSA S,et al.Impact of progesterone administration on outcome of patients with severe traumatic brain injury[J].Res Opi Anesth Intensive Care,2017.DOI:10.4103/roaic.roaic_106_16.
[18]傅西安,王旭阳.创伤性脑损伤的研究热点问题[J].国际外科学杂志,2013,40(11):729-731.
[19]CUTLER SM,CEKIC M,MILLER DM,et al.Progesterone improves acute recovery after traumatic brain injury in the aged rat[J].J Neurotrauma,2007,24(9):1475-1486.
[20]WRIGHT DW,BAUER ME,HOFFMAN SW,et al.Serum progesterone levels correlate with decreased cerebral edema after traumatic brain injury in male rats[J].J Neurotrauma,2001,18(9):901-909.
[21]王冬梅,常杰,白云贤,等.急性颅脑损伤血清性激素水平变化与预后的研究[J].中华神经外科杂志,2014,30(7):715-717.