【作者】 刘波；

【导师】 左云霞；

【作者基本信息】 四川大学 ， 麻醉学（专业学位）， 2022， 硕士

【摘要】 背景:随着人类文明的进步,女性在生产时经历产痛的状况,得到了社会越来越多的重视。人类尝试了各种方式以减轻产痛,但都未取得令人满意的效果。直到椎管内阻滞技术应用于分娩镇痛,才使得产痛得到了极大程度的缓解。椎管内分娩镇痛是目前国际公认的,最有效且安全的分娩镇痛方式。1989年,Fusi第一次提出硬膜外分娩镇痛可能引起产时发热率升高。随后,各种回顾性及前瞻性研究都证实了硬膜外分娩镇痛与产时发热率升高相关。由于伦理限制,我们无法随机将产妇分为硬膜外分娩镇痛组与不接受任何镇痛措施组,因此目前我们无法得出硬膜外分娩镇痛将会导致产时发热率升高的结论。但根据目前大量研究看来,硬膜外分娩镇痛与产时发热之间确实存在一定的相关性。硬膜外分娩镇痛存在起效较慢,有时存在阻滞不全等情况,腰-硬联合分娩镇痛因其起效快、效果确切等优点逐渐在临床广泛应用。但关于腰-硬联合分娩镇痛与产时发热的相关性研究甚少,国内甚至没有。在国家大力推进开展分娩镇痛的情况下,我们有必要了解椎管内分娩镇痛与产时发热的关系。因此我们首先进行了一项回顾性研究,研究产时发热与腰-硬联合分娩镇痛的关联性问题,分析产时发热的危险因素以及对临床的影响。在验证产时发热与腰-硬联合分娩镇痛的关联性后,我们进行了一项双中心前瞻性队列研究,采用无线体温探头,对接受分娩镇痛孕妇进行连续体温监测,探究硬膜外分娩镇痛与腰-硬联合分娩镇痛方式对产时发热的影响。方法:首先进行单中心回顾性研究,研究方案得到成都市锦江区妇幼保健院伦理委员会批准(审批号:2018年审(93)号)。纳入标准:阴道试产产妇、胎位头位、ASAⅠ～Ⅱ级、孕37～42周、年龄18～35岁,新生儿体重2500～4000g。排除标准:产前诊断为感染性疾病、有长期类固醇药物或产前非甾体类解热镇痛药服用史、产前体温大于37.2℃以及临床资料不完整者。在电子病历系统中以关键词“顺产”和“顺产中转剖宫产”查询符合条件的产妇住院号,根据住院号进入电子病历,查阅产妇的病程记录、产程记录和分娩镇痛记录等,收集产妇的一般基本资料、生产前及产程中的临床管理以及产妇和胎儿的临床结局等信息,由双人查对并录入电脑,完成病例原始数据表的填写。根据产程记录中水银温度计所测产妇的腋窝最高温度值,将产妇分为发热组(T≥37.5℃)与未发热组(T<37.5℃)。主要研究指标为产时发热与腰-硬联合分娩镇痛的关联性,次要研究指标为产时发热的危险因素、产时发热对临床结局的影响等。然后进行双中心前瞻性队列研究,研究方案得到四川省人民医院伦理委员会批准(方案号:2020356)及成都市锦江区妇幼保健院伦理委员会批准(审批号:2021伦审(第10号),临床试验注册号为:Chi CTR2000037802。此研究在四川省人民医院及成都市锦江区妇幼保健院进行。本研究连续招募2020年9月1日—2021年9月1日期间,在四川省人民医院及成都市锦江区妇幼保健院拟自然分娩并自愿接受分娩镇痛的产妇。纳入标准:拟经阴道自然分娩并自愿接受分娩镇痛的产妇、年龄18～40岁、美国麻醉师协会(ASA)分级:Ⅰ～Ⅱ级、初产妇、单胎、入产房时,体温≤37.2℃,同意参加本试验并自愿签署知情同意书。排除标准:产前诊断为感染性疾病,有长期类固醇药物或产前非甾体类解热镇痛药服用史者。退出标准:因医疗情况,而在分娩镇痛前转为剖宫产的产妇,因各种原因连续体温数据中断时间≥30min者。随机将孕妇分为硬膜外分娩镇痛(ELA)组与腰-硬联合分娩镇痛(SELA)组。主要研究指标为两组的产时发热率,次要研究指标包括温度变化特点以及对临床结局的影响。结果:一、回顾性研究回顾性研究收集到阴道试产产妇2656例,因临床资料缺失、产前发热以及产前感染共排除50例,最终对2606例产妇进行数据分析。2606例产妇中,自然分娩2070例,剖宫产536例,接受腰-硬联合分娩镇痛1987例,总体产时发热率为16.85%(439/2606),分娩镇痛产妇产时发热率为22.09%(423/1987),非分娩镇痛产妇产时发热率为2.58%(16/619)。按分娩过程是否发热分为发热组439例,未发热组2167例。1.产时发热与腰-硬联合分娩镇痛的关联性:未发热组分娩镇痛率为72.17%,发热组分娩镇痛率为96.36%,差异具有统计学意义(P<0.05)。多因素Logistic回归分析显示行腰-硬联合分娩镇痛产妇发生产时发热的危险度为自然分娩产妇4倍以上[OR=4.444(95%CI:2.611,7.565)]。2.产时发热危险因素:多因素Logistic回归分析显示,年龄[OR=1.046(95%CI:1.008,1.086)]、BMI[OR=1.061(95%CI:1.021,1.103)]、腰-硬联合分娩镇痛[OR=4.444(95%CI:2.611,7.565)]、初产妇[OR=4.139(95%CI:2.497,6.862)]以及产程时长[OR=1.002(95%CI:1.001,1.002)]均为产时发热的危险因素。分娩镇痛时长[OR=1.002(95%CI:1.001,1.003)]为接受腰-硬联合分娩镇痛产妇的产时发热危险因素3.产时发热对产妇的影响:未发热组与发热组产妇的剖宫产率(17.90%VS33.71%)、抗生素使用率(47.07%VS 82.23%)、产后大出血发生率(5.31%VS8.43%)、平均住院费用(7172.15元VS 9069.70元)以及住院时间(3.44天VS4.23天)相比,差异具有统计学意义(P<0.05),发热组高于未发热组。两组产妇器械助产率相比(3.84%VS 4.81%),差异无统计学意义(P>0.05)。4.产时发热对新生儿的影响:未发热组新生儿NICU住院率为16.61%,发热组为36.90%,差异具有统计学意义(P<0.05)。新生儿第1分钟及第5分钟Apgar评分小于9分的比例(3.65%VS 4.56%;0.09%VS 0.46%),两组间差异无统计学意义(P>0.05)。5.产时发热的可能原因:亚组分析中,二次分娩镇痛[OR=1.256(95%CI:0.696,2.268)]并非产时发热的独立危险因素。因此推测椎管内操作引发无菌性炎症这一假说存疑,发生机制仍然不清楚。二、前瞻性队列研究前瞻性队列研究纳入自愿接受分娩镇痛的拟自然分娩孕妇259例,因分娩镇痛前中转剖宫产及分娩镇痛前体温>37.2℃排除13例,因体温监测中断≥30min,退出3例。最终纳入243例孕妇,其中ELA组136例,SELA组107例。1.腰-硬联合分娩镇痛与硬膜外分娩镇痛对产时发热的影响:SELA组产时发热率为28.97%,ELA组产时发热率18.69%,差异具有统计学意义(P<0.05),SELA组产时发热率更高。2.腰-硬联合分娩镇痛与硬膜外分娩镇痛产时发热特点:SELA组发热产妇与ELA组发热产妇相比,分娩镇痛至产时发热时间(6.85h[4.97,10.58]vs6.48h[4.68,7.47])、发热持续时间(106.00min[39.00,161.00]vs67.50min[36.00,135.00])以及发热曲线下面积(14.08℃*min[3.12,24.62]vs8.11℃*min[2.51,34.43])均无明显差异。3.腰-硬联合分娩镇痛与硬膜外分娩镇痛对产妇及新生儿的临床影响:腰-硬联合分娩镇痛相较于硬膜外分娩镇痛,产妇的剖宫产率(23.36%vs 13.24%)更高;抗生素使用率(63.55%vs 61.76%)、器械助产率(3.66%vs 6.78%)、产时出血>500ml比例(3.66%vs 8.47%)及产后2h出血>500ml(1.22%vs 0.00%)比例相比,两组并无明显差异;新生儿的NIUC住院率(23.36%vs 20.59%)、Apgar评分(9.97 vs 9.99),辅助通气率(5.61%vs 4.41%)两组并无明显差异。结论:(1)产时发热与腰-硬联合分娩镇痛具有明显关联性。(2)年龄、BMI、腰-硬联合分娩镇痛、产程时长及初产妇均为产时发热独立危险因素。(3)在接受腰-硬联合分娩镇痛的产妇中,年龄、BMI、初产妇以及腰-硬联合分娩镇痛时长均为产时发热危险因素。产时发热与产妇剖宫产率、抗生素使用率以及新生儿NICU住院率升高相关,增加分娩相关医疗费用。(4)行腰-硬联合分娩镇痛的产妇与硬膜外分娩镇痛相比,产时发热率更高,更推荐产妇行硬膜外分娩镇痛。(5)行腰-硬联合分娩镇痛的产妇与硬膜外分娩镇痛相比,剖宫产率更高,新生儿临床结局方面并没有明显差异。更多还原

【Abstract】 Background:With the progress of human civilization,the labor pain experienced by women during childbirth are gaining more and more attention by the society.Human beings tried various ways to reduce labor pain,but none of them achieved satisfactory results.Until the application of intrathecal anaesthesia in labor analgesia,labor pain was greatly relieved.Currently,intrathecal labor analgesia is internationally recognized as the most effective and safe form of labor analgesia.Since Fusi first raised the issue that epidural labor analgesia might increase the incidence of intrapartum fever in 1989,various retrospective,prospective studies have confirmed the correlation between epidural labor analgesia and intrapartum fever.Due to ethical constraints,parturients cannot be randomly divided into epidural labor analgesia group and no analgesia group.Therefore,at present,we can not draw the conclusion that epidural labor analgesia will lead to the increase of intrapartum fever rate.However,according to a great number of studies,there is a certain correlation between epidural labor analgesia and intrapartum fever.Epidural labor analgesia has slow onset and sometimes provide inadequate analgesia.Therefore,spinal-epidural labor analgesia has been widely used because of its fast onset and excellent analgesia effect,but there is little research on the correlation between spinal-epidural labor analgesia and intrapartum fever.Since labor analgesia is vigorously promoted in our country,it is necessary for us to understand the relationship between intrathecal labor analgesia and intrapartum fever.Therefore,we first conducted a retrospective study to study the association of intrapartum fever with spinal-epidural labor analgesia and analyze the risk factors for intrapartum fever.After verifying the association of intrapartum fever with spinal-epidural labor in the first part,we carried out a prospective study which continuously monitor the temperature by using an wireless temperature probe for parturients receiving labor analgesia,and explore the effects of epidural and spinal-epidural analgesia on intrapartum fever.Methods:First,a single center retrospective study was conducted.The research scheme was approved by the ethics committee of Chengdu Jinjiang Maternity and Child Health Hospital(approval No: 2018(93)).Inclusion criteria: parturients intended to have vaginal delivery fetal position as head position,ASA grade I ～ II,pregnancy 37～ 42 weeks,age 18 ～ 35 years,4000 g > neonatal weight ≥ 2500 g.Exclusion criteria:prenatal diagnosis of infectious diseases,long-term steroid drugs or prenatal non steroidal antipyretic analgesics,prenatal temperature greater than 37.2℃ and incomplete clinical data.In the hospital information system,we queried the qualified maternal hospitalization number with the keywords " normal vaginal delivery " and " normal vaginal delivery to cesarean section",entered the electronic medical record according to the hospitalization number,consulted the maternal health records,labor process records,labor analgesia records,and collect the general basic data of the maternal,The clinical management before and during delivery and the clinical outcome of parturient and fetus.The information was checked by two persons and entered into the computer to complete case report form.According to the maximum axillary temperature measured by mercury thermometer in the labor process record,the parturients were divided into fever group(T≥ 37.5 ℃)and non-Fever group(T <37.5℃).The primary outcome was the association of intrapartum fever and a spinal-epidural labor analgesia.The secondary outcomes included risk factors for intrapartum fever and the impact of intrapartum fever on clinical outcomes.Then a double-center prospective cohort study was conducted.The study protocol was approved by the ethics committee of Sichuan Provincial People’s Hospital(protocol No: 2020356)and the ethics committee of Chengdu Jinjiang Maternity and Child Health Hospital(approval No: 2021(93).The clinical trial registration number is Chictr20000037802.The study was conducted in Sichuan Provincial People’s Hospital and Chengdu Jinjiang Maternity and Child Health Hospital.This study continuously recruited parturients who planned to give birth naturally and voluntarily accepted labor analgesia from September 1,2020 to September 1,2021.Inclusion criteria: the parturients who intend to give birth naturally through vagina and voluntarily accept labor analgesia,age 18 ～ 40 years,ASA grade I ～ II,primipara,singleton,when entering the delivery room,the body temperature is ≤37.2 ℃.They agree to participate in the trial and voluntarily sign the informed consent form.Exclusion criteria: prenatal diagnosis of infectious diseases,long-term taking steroid drugs or non steroid antipyretic analgesics.Withdrawal criteria: parturients who have changed to cesarean section before labor analgesia due to changes in medical conditions during labor,and the interruption time of continuous body temperature was ≥ 30 min.Parturients were randomly divided into epidural labor analgesia(ELA)group and spinal-epidural labor analgesia(SELA)group.The primary outcome was the incidence of intrapartum fever.The secondary outcome included the characteristics of temperature change and clinical impact.Results:Retrospective studyThe retrospective study included 2656 parturients with vaginal delivery as primary plan and 50 cases were excluded due to lack of case data,prenatal fever and prenatal infection.Finally,2606 cases were included in the statistical analysis,including 439 cases in fever group and 2167 cases in non-fever group.Among the2606 parturients,2070 cases had natural delivery,536 cases had cesarean section and 1987 cases received spinal-epidural labor analgesia.The overall intrapartum fever incidence was 16.85%(439/2606),the intrapartum fever incidence for labor analgesia was 22.09%(423/1987),and the intrapartum fever incidence for non-labor analgesia was 2.58%(16/619).1.Association of intrapartum fever with spinal-epidural labor analgesia: There were 72.17% who acceped the labor analgesia in non-fever group and 96.36% in the fever group,the difference was statistically significant(P<0.05).Multivariate logistic regression analysis showed that the risk of intrapartum fever in women undergoing spinal-epidural labor analgesia was more than 4 times higher than that in women with no labor analgesia[OR=4.444(95%CI: 2.611,7.565)].2.The risk factors of intrapartum fever: multivariate logistic regression analysis showed that age [OR = 1.046(95% CI: 1.008,1.086)],BMI [OR = 1.061(95% CI:1.021,1.103)],spinal-epidural labor analgesia [OR = 4.444(95% CI: 2.611,7.565)],primipara [OR = 4.139(95% CI: 2.497,6.862)] and duration of labor [OR = 1.002(95% CI: 1.001,1.002)] were risk factors of intrapartum fever.The duration of spinal-epidural labor analgesia[OR=1.002(95%CI: 1.001,1.003)] was a risk factor for intrapartum fever in women receiving spinal-epidural labor analgesia.3.Effect of intrapartum fever on Parturients: the cesarean section percentage(17.90% vs 33.71%),the antibiotics treatment rate(47.07% vs 82.23%),the incidence of postpartum hemorrhage(5.31% vs 8.43%),the average hospitalization cost(7172.15 rmb vs 9069.70 rmb)and the length of hospital stay(3.44 days vs 4.23days)were significantly higher in the fever group(P<0.05).There was no statistically significant differences in the incidence of instrumental delivery between the two groups(3.54%vs 4.81%)(P>0.05).4.The effect of intrapartum fever on newborns: The NICU admission in non-fever group was 16.61%,and that in fever group was 36.90%,the difference was statistically significant(P<0.05).There were no significant differences between the non-fever group and fever group in percentage of Apgar score less than 9 at the first and fifth minutes(3.65% vs 4.56%;0.09% vs 0.46%)(P > 0.05).5.Possible causes of intrapartum fever: In subgroup analysis,secondary labor analgesia[OR=1.256(95%CI:0.696,2.268)] was not an independent risk factor for intrapartum fever.Therefore,labor analgesia itself is unlikely to be the cause of aseptic inflammation,and the mechanism of intrapartum fever needs more exploration.Prospective cohort study256 parturients who planned to give birth naturally and voluntarily accepted labor analgesia were included in the prospective cohort study.13 cases were excluded due to the conversion to cesarean section before labor analgesia and the body temperature before labor analgesia > 37.2 ℃,and 3 cases were withdrawn due to the interruption of body temperature monitoring ≥ 30 min.243 parturients were finally included,including 136 in ELA group and 107 in SELA group.1.The effect of spinal-epidural labor analgesia and epidural labor analgesia on intrapartum fever: The incidence of intrapartum fever was 28.97% in SELA group and 18.69% in ELA group(P < 0.05).2.Characteristics of intrapartum fever caused by spinal-epidural labor analgesia and epidural labor analgesia: The time course of intrapartum fever occurred in SELA group and ELA group were analyzed.Compared with ELA group,the onset of intrapartum fever from labor analgesia(6.85h[4.97,10.58]vs 6.48h[4.68,7.47]),the intrapartum fever duration.(106.00min[39.00,161.00]vs 67.50min[36.00,135.00])and area under fever curve(14.08℃*min[3.12,24.62]vs8.11℃*min[2.51,34.43])had no significant differences in two cohorts.3.Clinical Effects of spinal-epidural labor analgesia and epidural labor analgesia on parturients and newborns: compared with epidural labor analgesia,the rate of cesarean section(23.36% vs 13.24%)was higher in the SELA group.There were no significant differences between the two cohorts in the percentage of antibiotic application(63.55% vs 61.76%),the rate of instrumental midwifery(3.66% vs6.78%),the proportion of intrapartum hemorrhage > 500ml(3.66% vs 8.47%)and the proportion of postpartum 2h hemorrhage > 500ml(1.22% vs 0.00%);There were no significant differences in the incidence of neonatal NICU admission(23.36%vs 20.59%),Apgar score(9.97 vs 9.99),and auxiliary ventilation(5.61% vs 4.41%).Conclusion:(1)There was a significant association of intrapartum fever with spinal-epidural labor analgesia.(2)Age,BMI,spinal-epidural labor analgesia,labor duration and primipara were independent risk factors for intrapartum fever.(3)Among the parturients receiving spinal-epidural labor analgesia,age,BMI,primipara and the duration of spinal-epidural labor analgesia were the risk factors of intrapartum fever.Intrapartum fever was associated with the increase of cesarean section,the use of antibiotics and the hospitalization rate of neonatal NICU,and the medical expenses related to delivery.(4)Compared with epidural labor analgesia,parturients received spinal-epidural labor analgesia had a higher rate of Intrapartum fever.Epidural labor analgesia is better than combined spinal epidural labor analgesia(5)Compared with epidural labor analgesia,parturients received spinal-epidural labor analgesia had a higher rate of cesarean section.The neonatal clinical outcomes were similar in both spinal-epidural group and epidural group.更多还原