Impact of perioperative dexamethasone on postoperative.ppt

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Company Logo,Impact of,perioperative,dexamethasone,on postoperative,analgesia and side-effects:systematic review,andmeta,-analysis,围手术期地塞米松对术后镇痛影响和副作用,:,系统性回顾和荟萃分析,British Journal of,Anaesthesia,110(2):191200(2013),Backgroud,研究背景,Company Logo,Backgroud,Glucocorticoids,have,been used to reduce,in?ammation,and,tissue damage in a,variety of conditions,including,in?ammatory,bowel disease,rheumatoid arthritis,and some malignancies.,Glucocorticoids,have,potent,immunomodulatory,effects,and are used in,the treatment of acute,allograft rejection.,They also have,antiemetic properties,and,dexamethasone,is,commonly used for the,prevention of,postoperative nausea,and vomiting(PONV),糖皮质激素在多数情况下,被用来减少炎症和组织,损伤下，包括炎症性肠病、,风湿性关节炎、和一些,恶性肿瘤。糖皮质激素具,有强大的免疫调节作用,用于治疗急性同种异体排,斥反应，同时也有止,吐作用，例如地塞米松常,常被用来预防术后恶心,呕吐,Company Logo,Backgroud,The efficacy of,glucocorticoids,for,reducing pain and,infiammation,after,surgery has recently,been explored.Early,studiesin,patients,undergoing dental,procedures showed,that,glucocorticoids,were effective in,reducing postoperative,pain,andoedema,.,A number of recent,studies have,investigated,the potential analgesic,bene?t,of a single,perioperative,dose,of,dexamethasone,but,H,ave,inconsistentfindings,.,最近有关于糖皮质激素对,减少手术后的疼痛和炎症,反应的疗效的研究。之前,有研究显示在接受牙科手,术的患者使用糖皮质激素,有效地减少术后疼痛和水,肿,.,最近有不少关于单次,使用的围手术期剂量地塞,米松潜在的止痛效果的研,究调查，但具有不一致的,结果,Company Logo,Backgroud,Long-,termtreatment,withglucocorticoids,is,A,ssociated with many,side-effects.,However,it is unclear,if a single,perioperative,dose of,dexamethasone,increases the risk of,these adverse effects.,This is due to many of,the published studies,being underpowered,to detect clinically,relevant,sideeffects,and many studies also,excluded patients at,thehighest,risk of,glucocorticoid,-related,adverse effects.,长期使用糖皮质激素治疗,具有许多相关副作用。但,是单次围手术期剂量的地,塞米松是否增加这些副作,用并不清楚。这是由于许,多已出版研究并没有足够,的动力对此临床相关副反,应进行检测，同时也是由,于很多研究将具有糖皮质,激素相关副反应的高风险,患者排除在研究之外的原,因,Company Logo,Backgroud,We therefore,performed this,systematic review to,determine if a single,perioperative,dose of,dexamethasone,in,adult surgical patients,undergoing surgery,under general,anaesthesia,has a,useful analgesic effect,in the postoperative,period.We also,investigated whether,the use of,dexamethasone,increases the risk of,postoperative adverse,effects.,因此我们进行这个系统性,回顾来确定单次使用的围,手术期剂量地塞米松在成,年外科病人手术全身麻醉,下是否存在一个有效的术,后镇痛效果，同时我们还,研究了地塞米松的使用是,否会增加术后不良反应的,风险,Company Logo,Methods,研究方法,Company Logo,Methods,We followed the,recommendations of the,PRISMA,S,tatement in,creating this,review.The,databases of MEDLINE,(19662011),EMBASE,CINAHL,and the Cochrane,Register of Controlled Trials,were searched,without language restrictions,to identify full reports of,randomized,controlled trials,I,n whicha single,i.v,.dose of,dexamethasone,was given,perioperatively,to adult,patients undergoing surgery,U,nder general,anaesthesia,and was compared with,either placebo,or another antiemetic agent.,我们的回顾性分析以,MEDLINE(1966,2011)EMBASE,，,CINAHL,数据库中具有询,证医学控制的随机、对照,试验完整报告为对象。在,这些研究中，成年外科病,人手术全身麻醉将单次使,用的围手术期剂量地塞米,松与安慰剂或其他止吐剂,相比,Company Logo,Methods,Keywords used in the search,included,dexamethasone,s,teroids,corticosteroids,glu,cocorticoids,pain,postope,rativepain,nausea,vomitin,g,postoperative,nausea and,vomiting,and,surgery.In,addition,the references of,included studies and,related systematic reviews,were manually searched for,additional,R,elevant studies.,Trials were required to,report pain outcomes,S,uch as pain scores,analgesic consumption,administration of rescue,analgesics,or time to first,dose of analgesic.Trials,were included if they,measured pain as either a,primary or,secondary outcome.,查找关键字包括“地塞米松”、,“类固醇”、“皮质类固醇”、“糖,皮质激素”、“疼痛”、“术后疼,痛”、“恶心”、“呕吐”“术后恶,心呕吐”，“手术”，此外相关综,述也被手工搜索出来进行参考，,包括内容有疼痛评分，止痛药使,用剂量，止痛药使用管理，或者,止痛药首次使用剂量，以及如何,判断疼痛是原发还是继发性疼痛,Company Logo,Methods,Studies in which,patients received,intrathecal,or epidural,local,anaesthetics,or,opioids,were,excluded.In addition,studies using high,doses of,dexamethasone,(20,mg)were excluded.,We also excluded,studies involving,dental/endodontic,procedures,as there is,a recently published,review on this subject.,Data from abstracts,letters to the editor,retrospective trials,and,casereports,were,not included.,那些患者接受鞘内或硬膜,外局部麻醉药或阿片类药,物的研究被排除在本次分,析之外。此外,使用高剂量,的地塞米松（,20,毫克,),的,研究被排除在外。也排除,涉及牙科,/,牙髓手术的研,究，因为近期已经有相关,回顾性分析。那些从摘,要，致编辑信，回顾性实,验及个案报告中的数据未,给予采用,Company Logo,Methods,The data were entered into a,data collection form that,included the following:(i),type of surgery,(ii)number,ofpatients,(iii),dose(s,)of,dexamethasone,(iv),comparator(s),(v,)timing of,administration,(vi)primary,outcome measure of study,(PONV,vs,postoperative,pain),(vii)outcome,measures including pain,scores,analgesic,consumption,need,for rescue analgesia,time,tofirst analgesic request,andtime,in post-,anaesthesia,care unit(PACU),and(viii),sideeffects,related to,dexamethasone,administration,including,wound infection,delayed,wound,healing,hyperglycaemia,and,perineal,pruritus,.,分析收集的数据内容包括：,1.,手术类型，,2.,病人数量，,3.,地,塞米松用量，,4.,对比药物使用,剂量,5.,止痛药使用管理，,6.,首,次评估（术后恶心呕吐和术后疼,痛）,7.,评估内容包括疼痛评,分，止痛药使用剂量，是否需要,紧急止痛药物，首次止痛药使用,时间，在,pacu,停留时间，伤口,愈合延迟，高血糖以及会阴部是,否出现瘙痒,Company Logo,Methods,In studies evaluating,different doses of,dexamethasone,or,more than one comparator,the data from all doses and,comparators were pooled for,analysis.Pain scores,documented at the early(2 h,after the end of surgery)and,late(24,48,and 72 h after,the end of surgery),postoperative periods were,included for analysis.When,pain scores were reported at,different time points,those,reported within 1 h of our,D,efined time points were,included in the analysis.Pain,intensityscores,were,assumed to be at rest unless,otherwise,noted.Pain,scores,reported using the 0100,mm visual,analoguescale,(VAS)were converted to the,11-point(010;0,no pain,and 10,worst possible pain),scale.,在收集的研究中，因各自使用的,地塞米松剂量及其对比的药物均,有不同，因此我们将,对比药物,合,并进行分析。疼痛评分分为早期,（术后,2,小时）和晚期（术后,24,，,48,，,72,小时）的研究被,列入分析，当疼痛评分所记录的,时间段不同时，那些记录时间与,我们要求时间点相差,1,小时之内,的研究同样被列为分析目标。疼,痛评分使用,0100mm VAS,的将被转换为,11,分测量评分,（,010,，,0,分为无痛，,10,分,为最痛）,Company Logo,Methods,All postoperative,opioid,consumption was converted,T,o morphine equivalents,using the table included in,Supplementary Appendix S1.,In addition,ketorolac,dosages were converted to,morphine equivalents.,Opioid,consumption was,analysed,for the early(2 h),and late(24 h)postoperative,periods.When,opioid,consumption was reported at,D,ifferent time points,reported data within 1 h of,our defined time,points were included in the,analysis.One study reported,mean,opioid,consumption in,milligrams per kilogram.,This was converted to total,milligrams using 70 kg as the,patientsaverage weight,based upon data from,the,NationalPublic,Health,Institute of Finland,所有使用了镇痛药物的患者根据,量表（,Supplementary,Appendix S1,）换算成为吗啡,用量进行统计，当吗啡使用时间,与我们分析的时间点有所不同，,那么偏差在,1,小时之内的研究同,样被列入分析。当有研究使用的,吗啡剂量以毫克,/,公斤计算时则,根据,National Public,Health Institute of,Finland,数据换算成标准体重,的,70,公斤患者所使用的药物的,毫克数,Company Logo,Methods,where this study was,performed.pers,using the,median,range,or both as,A,measure of central,tendency,an attempt,was made to contact the,author and secure group,data as mean,andstandard,deviation.,When this was not,possible,the median,range,or both were,converted to the mean,standard deviation,or,both.,当研究统计使用中位数,范,围,或两者集中趋势进行度,量，我们会尝试联系作者,取得平均数及标准差的数,值，如果不成功，我们会,将这些中位数,范围,或两者,集中趋势进行度量转换成,为均数及标准差,Company Logo,Meta-analysis,数据分析,Company Logo,Meta-analysis,Analyses were performed using,the Review Manager,(,RevMan,)Software Version 5.1,(The Nordic Cochrane Centre,The Cochrane Collaboration,Copenhagen,Denmark,2008),and Comprehensive Meta Analysis,software(Version2.2.050).For,continuous data,mean,differences(MD)with,95%,con?dence,interval(CI),were calculated.If the 95%CI,included 0,we assumed that the,difference between,dexamethasone,and control was,not statistically,signi?cant,.,Dichotomous data were,analysed,using relative risk(RR),with95%CI.If the 95%CI,around the RR did not include 1.0,we assumed that the difference,between the,dexamethasone,and,the control groups was,statistically significant.,数据分析使用,RevMan,5.1,及,广泛,Meta,分析软件（,2.2.050,）,进行,针对连续资料数据，平均差,的,95%,置信区间被计算出来，,假如,95%,置信区间包括,0,，则,我们认为地塞米松与对照药物之,前的差异无统计学意义。,针对二分变量数据,使用相对,危险度同,95%,置信区间，假如,围绕相对危险度的,95%,置信区,间不包括,1.0,，我们认为地塞米,松与对照药物之前的差异具有统,计学意义,Company Logo,Meta-analysis,In addition to the main,analysis(,dexamethasone,vs,control),a number of,sensitivity analyses were,performed,onthe,primary,outcomes of 24 h pain scores,and,opioid,consumption.,Data were,analysed,according to the primary,outcome of included studies,(pain,vs,PONV),procedure,T,ype(laparoscopic,vs,open,abdominal,vs,middle ear),and control group(saline,vs,other,antiemetics,).We also,performed a subgroup,analysis comparing,preoperative,vs,I,ntraoperative,administration of,dexamethasone,.,此外，针对主要分析（地塞米松与对照组），对,24h,首次的疼痛评分及阿片类药物的使用情况进行一些敏感度分析。数据分析根据,1.,所收集研究中主要分析对象（疼痛与术后恶心呕吐），,2.,手术类型（腹腔镜手术，开腹手术，中耳手术）,2.,对照组（使用盐水和其他止吐剂）,我们同时对术前和术中使用地塞米松所产生的效果进行了亚分析,Company Logo,Meta-analysis,To assess whether there was,doseresponse for the,analgesic,ef?cacy,of,dexamethasone,we,performed a random effects,meta-regression in which the,outcome variables were the,MD in 24 h morphine,consumption or 24 h pain,scores with the predictor,variable being,dexamethasone,dose in both,analyses.To further assess,for a doseresponse,relationship,we,performed a,subgroup analysis comparing,24 h,opioid,consumption and,24 h pain scores with doses,of 45 and 810mg.,Subgroup analyses were,performed using a Q-test for,heterogeneity across,subgroup,为了评估地塞米松的止痛效果是否存在剂量效应，我们对那些使用了地塞米松的研究中结果变量在,24,小时内吗啡使用量的中位数以及,24,小时内疼痛评分预测变量使用了随机模型回归分析。,为了更远的评估剂量效应，我们使用了地塞米松,45,毫克与,810,毫克用量的亚组分析观察它们,24,小时使用吗啡剂量及,24,小时疼痛评分，该亚组分析因其不均匀性而使用了,q,检验,Company Logo,Results,结果,Company Logo,Results,A total of 308 publications,were identified.Of those,45,studies were included in this,review giving a total of 5796,patients(2997 who received,dexamethasone,and 2799,who did not).,Dexamethasone,alone or in,combination with a serotonin,(5-HT3)receptor antagonist,haloperidol,metoclopramide,or,midazolam,was,considered the study,drug.Doses,of,dexamethasone,ranged from,1.25 to 20 mg,with 8 mg,being the most common dose,used.,我们总共搜索到,308,篇文献，,其中,45,篇被本次分析采用,包括,5796,病例,(2997,人使用了地,塞米松，而,2799,人未使用）。,单独使用地塞米松或者联合使用,5-,羟色胺受体拮抗剂，氟哌啶,醇，胃复安或者咪达唑仑这经过,深思熟虑所采用的研究药物。地,塞米松使用剂量范围为,1.2520mg,其中,8mg,为最,常用剂量,Company Logo,Results,Five studies included multiple,doses of,dexamethasone,and,38,studies had at least one group,that received only,dexamethasone,.,Nine studies had at least one,group that received,dexamethasone,in combination,with a serotonin(5-HT3)receptor,antagonist.Two studies included,a group that received,dexamethasone,and,midazolam,one study included a group that,receivedboth,metoclopramide,and,dexamethasone,and,another,included a group that received,both haloperidol and,dexamethasone.Dexamethasone,was given before operation in 28,studiesand,intraoperatively,in 18.,One,studyrandomized,patients to,receive,dexamethasone,either,before operation or,intraoperatively,.,5,篇报道使用了大剂量的地塞米,松，,38,篇报道中至少有一组只,使用了地塞米松，,9,篇报道中至,少有一组使用了地塞米松结合使,用,5-,羟色胺受体拮抗剂，,2,篇报,道中有一组使用了地塞米松和咪,达唑仑，,1,篇报道中有一组使用,地塞米松和胃复安而另外一组使,用了氟哌啶醇和地塞米松。在,28,篇报道中地塞米松为术前给,药，而,18,篇为术中给药，而有,篇报道则是将病人随机化分组为,术前和术中给药,Company Logo,Results,For the purpose of this analysis,normal saline,serotonin,(5-HT3)receptor antagonists,butyrophenones,and,metoclopramide,were categorized,as the control(comparator)group.,Of the included studies,31,compared,dexamethasone,with a,placebo group,while 21 studies,included a comparator other than,saline including 5-HT3,antagonists,droperidol,metoclopramide,midazolam,andhaloperidol.Seven,studies had,pain as their primary outcome,while 35 studies had PONV as the,primary outcome.In,twostudies,both pain and PONV were primary,outcomes.One,study used another,measure(a global quality of,recoveryscale,)as its primary,outcome.There,was considerable,variation in the method of,opioid,administration betweenstudies.Of the 19,studiesin,which,opioid,analgesic requirement was,quanti?ed,at either 2 or 24 h after,operation,approximately half,(10 studies)usedPRNanalgesic,patient-controlled analgesia.,为了进行这次分析,我们将生理,盐水，,5-,羟色胺受体拮抗剂，,丁酰苯和胃复安作为对照组。在,选入的报道中,有,31,篇将地塞米,松与安慰剂组进行对照，,21,篇,与生理盐水，,5-,羟色胺受体拮,抗剂，胃复安或者咪达唑仑进行,对照，,7,篇以疼痛为主要研究对,象，而,35,篇以术后恶心呕吐为,主要研究对象，,2,篇同时以疼痛,和术后恶心呕吐为研究对象。,1,篇一其他研究指标为研究对象,19,篇报道阿片类药物在术后,2,小时或,24,小时给药,Company Logo,Results,Pain scores,Nineteen studies(2040,patients)recorded VAS pain,scores,atrest,2 h after,operationPatients,receiving,dexamethasone,had,significantlylower,VAS pain,scores at rest at 2 h MD,0.49(95%CI:-0.83,-0.15,P=0.005)(I2=94%).,Two studies(125 patients),recorded VAS pain scores,withmovement,2 h after,operation.There,was no,significantreduction,in pain,scores in patients receiving,dexamethasoneMD,-0.15,(95%CI:-0.95,0.64,P=0.70)(I2=60%),疼痛评分,19,篇报道（,2040,病例）记,录了术后安静状态下,2,小时的,VAS,疼痛评分，使用了地塞米,松的患者评分显著降低,（,P=0.005,）,2,篇报道（,125,病例）提示,术后活动状态下,2,小时的,VAS,疼,痛评分，使用了地塞米松的患者,并没有明显下降,(P=0.70),Company Logo,Results,Pain scores,Twenty-eight studies,(3781 patients)recorded,VAS,painscores,at 24 h after,operation(Fig.2).,Patients receiving,D,examethasone,had,significantly lower VAS pain,scores at 24 h MD-0.48,(95%CI:-0.62,-0.35,P,0.00001)(I2=97%).,There was evidence of dose,responsiveness with respect,to the 24 h pain scores.,When,thetwo,studies using,dexamethasone,20 mg were,removed,there,was no,further evidence of dose,responsivenessP,=0.139.,Subgroup analysis of 24 hpain scores also showed no,D,ifference,etween,doses of 45,and 810 mg(P=0.12).,疼痛评分,28,篇报道（,3781,病例）记录,了使用了地塞米松的患者术后,24h,的,VAS,疼痛评分显著下降,(P=0.00001),而且有证据证明剂量效应对,24,小时疼痛评分具有影响,(P=0.026),，而当两篇使用了,20mg,地塞米松报道被剔除以,后，药物的剂量效应影响并没有,统计学意义（,P=0.139,）,24,小时疼痛评分的,45,和,810,mg,亚组分析同样认为无剂量相,关性,(P=0.12),Company Logo,Results,Pain scores,Patients who received,dexamethasone,reported,signicantly,lower VAS pain,scores at 24 h after,laparoscopic,surgery(P=0.001),but not,after open abdominal,surgery(P,=0.08)or middle,ear surgery,(P=0.64).Subgroup analysis,showed a statistically,signicant,difference,between preoperative and,intraoperative,administration,of,dexamethasone,(P=0.03).,The reduction in 24 h VAS,scores,wasgreater,when,dexamethasone,was given,before operation,（,P=0.00001)compared,with,intraoperatively,(P=0.002),疼痛评分,接受了地塞米松注射的患者在腔,镜手术后的,VAS,评分明显降低,(P=0.001),，但是在开腹手术,(P=0.08),或者中耳手术,(P=0.64),后并无降低,亚组分析显示术前与术中使用地,塞米松的结果有显著不同，当术,前使用（,P=0.00001)VAS,评,分相对术中使用,(P=0.002),具,有显著降低,Company Logo,Results,Pain scores,Four studies(465 patients),recorded VAS with,movement at 24 h after,surgery.Patients receiving,dexamethasone,had,signicantly,lower VAS pain,scores (P=0.007),Six studies(393 patients),recorded VAS pain scores at,48,hafter,operation.,Patients receiving,dexamethasone,had,signicantly,lower VAS pain,scores at 48 h(P=0.00001),疼痛评分,4,篇报道（,465,例）记录了术后,24h,活动患者的,VAS,使用地,塞米松的患者具有明显低的,VAS,评分（,p=0.007,），,6,篇,报道（,393,例）记录了术后,48h,患者的,VAS,使用地塞米松,的患者具有明显低的,VAS,评分,(P=0.00001),Company Logo,Results,Opioid,us