限制性液体复苏策略对儿童脓毒性休克失代偿期患儿的临床疗效

Clinical efficacy of limited fluid resuscitation strategy in treatment of children with septic shock in decompensation stage

目的探讨限制性液体复苏(LFR)策略对儿童脓毒性休克(SS)失代偿期患儿的临床疗效。方法选取2017年1月至2019年12月,在广西壮族自治区妇幼保健院新阳院区和厢竹院区儿童重症监护病房(PICU)收治的60例SS失代偿期患儿为研究对象。采用信封法,将其随机分为观察组(n=30)和对照组(n=30)。对2组患儿均给予规范抗休克治疗。观察组采取LFR及血管活性药物维持患儿收缩压>同年龄段儿童正常收缩压下限(第5百分位数);而对照组患儿采取积极液体复苏(AFR)维持收缩压在同年龄段典型收缩压范围(第50百分位数);2组患儿均维持舒张压为收缩压的2/3。采用重复测量资料的方差分析或成组t检验,对2组患儿年龄、动脉血乳酸浓度、复苏血压、心率、尿量、氧合指数(OI)、乳酸清除率(LCR)、输液量、血管活性药物剂量、机械通气时间、PICU住院时间等进行统计学分析。采用χ~2检验,对2组患儿的性别、液体过负荷发生率、连续血液净化(CBP)实施率及28 d病死率等进行统计学分析。本研究遵循的程序符合广西壮族自治区妇幼保健院伦理委员会所制定的医学伦理学标准,并得到该委员会批准[审批文号:(2017-1)4-16号],并且本研究与患儿监护人均签署临床研究知情同意书。结果 (1)2组患儿的性别、年龄、入院时动脉血乳酸浓度、合并重症肺炎/小儿急性呼吸窘迫综合征(PARDS)、合并心肌抑制、小儿危重病例评分(PCIS)等临床资料分别比较,差异均无统计学意义(P>0.05)。(2)观察组患儿的复苏时收缩压为(77±3) mmHg(1 mmHg=0.133 kPa),明显低于对照组的(93±4) mmHg,2组比较,差异有统计学意义(t=18.441,P<0.001)。(3)观察组患儿复苏后6、24 h输液量分别为(69±16)mL/kg和(120±20) mL/kg,显著低于对照组的(95±17) mL/kg和(166±19) mL/kg,2组比较,差异均有统计学意义(t=-5.716、—9.112,P<0.001)。观察组患儿复苏后24 h肾上腺素、甲肾上腺素用量分别为(151±26)μg/kg和(158±23)μg/kg,低于对照组的(201±35)μg/kg和(196±39)μg/kg,2组分别比较,差异亦有统计学意义(t=—6.210、—4.633,P<0.001)。(4) 2组患儿复苏后6、24 h尿量、动脉血乳酸浓度及LCR比较,差异均无统计学差意义(P>0.05)。(5) 2组患儿复苏时及复苏后1、6、12、24 h的OI和心率,经重复测量资料的方差分析结果显示,对于OI,不同处理措施与时间因素有交互效应(F_(处理×时间)=20.821、P<0.001);对于心率,不同处理措施与时间因素无交互效应(F_(处理×时间)=0.525、P=0.717)。进一步固定时间因素进行分析的结果显示,观察组患儿复苏后12、24 h的OI均明显高于对照组患儿,组间比较,差异均有统计学意义(t=2.084、2.090,P=0.042、0.041);而2组患儿各时间点心率比较,差异均无统计学意义(P>0.05)。进一步固定处理措施因素的分析结果为,观察组组内OI和心率总体比较,差异均有统计学意义(OI:F=1.675,P=0.014;心率:F=2.854,P<0.001),对照组组内总体比较,差异亦有统计学意义(OI:F=1.642,P=0.016;心率:F=3.695,P<0.001)。(6)观察组患儿液体过负荷者发生率、机械通气时间和PICU住院时间分别为13.3%(4/30),(8.2±0.8) d和(8.2±0.8) d,均显著低于或短于对照组的36.7%(11/30)、(6.8±1.2) d和(10.2±1.7) d,2组分别比较,差异均有统计学意义(χ~2=4.356、t=—4.933、—5.407,P=0.037、<0.001、<0.001)。结论 LFR能快速改善SS失代偿期患儿的氧合状态,缩短机械通气时间和PICU住院时间,并且对28 d病死率无明显影响。因本研究纳入样本量较小,且为单中心研究,仍需大样本、多中心的随机对照试验进一步研究、证实。

Objective To investigate clinical efficacy of limited fluid resuscitation(LFR)in the treatment of children with septic shock(SS)in decompensation stage.Methods From January 2017 to December 2019,a total of 60 children with SS in decompensation stage admitted to Pediatric Intensive Care Unit(PICU)of Maternity and Child Health Care Hospital of Guangxi Zhuang Autonomous Region were selected into this study.They were randomly divided into observation group(n=30)and control group(n=30)by envelope method.Children in both group were given standardized anti-shock treatment.Patients in observation group were adopted LFR measure and vasoactive drugs to maintain systolic blood pressure above lower limit of normal systolic blood pressure of children at the same age(5th percentile).Meanwhile,patients in control group were adopted active liquid resuscitation(AFR)measure and maintained systolic blood pressure within the typical systolic blood pressure range of the same age(50th percentile).The diastolic blood pressure of patients was maintained at 2/3 of systolic blood pressure in both groups.The arterial blood lactate acid concentration,blood pressure,heart rate,urine volume,oxygenation index(OI),lactate clearance rate(LCR),infusion volume,vasoactive drug dose,mechanical ventilation time,and hospital stay in PICU were statistically analyzed by ANOVA of repeated measurement data and independent-samples t test.Chi-square test was used to analyze age,gender,incidence of fluid overload,continuous blood purification(CBP)implementation rate and 28 d mortality of two groups.The procedure followed in this study conformed to the medical ethics standards in Maternity and Child Health Hospital of Guangxi Zhuang Autonomous Region has been approved by the ethics committee[Approval No.(2017-1)4-16].Informed consent was obtain from each participant.Results①There were no significant difference between two groups in gender,age,arterial blood lactate concentration at admission,severe pneumonia/pediatric acute respiratory distress syndrome(PARDS),myocardial depression and pediatric critical illness score(PCIS)(P>0.05).②The resuscitation blood pressure in observation group was(77±3)mmHg(1 mmHg=0.133 kPa),significantly lower than that of control group(93±4)mmHg,and the difference between two groups was statistical significance(t=18.441,P<0.001).③The infusion volume at 6 and 24 hours after resuscitation in observation group were(69±16)mL/kg and(120±20)mL/kg,respectively,which were significantly lower than those of(95±17)mL/kg and(166±19)mL/kg in control group,and the differences between two groups were statistical significance(t=—5.716,—9.112;P<0.001,<0.001).And dosage of epinephrine and norepinephrine at 24 h after resuscitation in observation group were(151±26)μg/kg and(158±23)μg/kg,respectively,which were lower than those of(201±35)μg/kg and(196±39)μg/kg in control group.There were also significant difference between two groups(t=—6.210,—4.633;P<0.001,<0.001).④There were no significant differences between two groups in urine volume,arterial blood lactate acid concentration and LCR at 6 and 24 h after resuscitation between two groups(P>0.05).⑤The OI and heart rate at resuscitation and 1,6,12,and 24 h after resuscitation in two groups showed that,for OI,there was an interaction effect between different treatment measures and time factors(F treatment×time=20.821,P<0.001);for heart rate,there was no interaction effect between different treatment measures and time factors(F treatment×time=0.525,P=0.717).The results of further analysis by fixing time factor showed that OI at 12,24 h after resuscitation in observation group were significantly higher than those in control group,and the differences were statistical significance(t=2.084,2.090;P=0.042,0.041);while the difference of heart rate at each time point between two groups had no statistical significance(P>0.05).The results of further analysis by fixing treatment measures showed that there were significant differences in the overall comparison of OI and heart rate within the observation group(OI:F=1.675,P=0.014;heart rate:F=2.854,P<0.001),and there were also significant differences in the overall comparison within control group(OI:F=1.642,P=0.016;heart rate:F=3.695,P<0.001).⑥The incidence rate of fluid overload,duration of mechanical ventilation and hospital stay in PICU in observation group were 13.3%(4/30),(8.2±0.8)d and(8.2±0.8)d,respectively,which were significantly lower than those of 36.7%(11/30),(6.8±1.2)d and(10.2±1.7)d in control group,and the differences between two groups were statistical significance(χ2=4.356,t=—4.933,—5.407;P=0.037,<0.001,<0.001).Conclusions LFR can rapidly improve the oxygenation of children with SS in decompensation stage,shorten mechanical ventilation duration and hospital stay in PICU,and have no significant affect on 28 d mortality.Because sample size in this study is relatively small,and it is a single-center study,it still needs to be further confirmed by large-sample,multicenter,randomized controlled trials.