重组人粒细胞集落刺激因子对早产儿早发型败血症合并中性粒细胞减少症的辅助治疗效果
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摘要
目的研究重组人粒细胞集落刺激因子(rhG-CSF)对早产儿早发型败血症(NEOS)合并粒细胞减少症的辅助治疗效果。方法选取新生儿早发型败血症合并中性粒细胞减少症的早产儿为研究对象,随机分为对照组和治疗组。对照组给予抗菌药物及其他支持治疗,治疗组在对照组治疗的基础上加用rhG-CSF,5μg·kg~(-1)·d~(-1),皮下注射。观察治疗后2组患儿抗菌药物使用疗程、发生黄疸持续、粒细胞恢复、实验室检查、并发症以及不良反应等指标。结果 rhG-CSF辅助治疗可提高抗感染疗效,肌张力改变、血压降低、体温异常及黄疸持续与对照组比较差异有统计学意义(P<0.05);炎性指标降钙素原和C-反应蛋白水平与对照组比较差异有统计学意义(P<0.05);感染相关治疗,如住院、抗菌药物使用疗程、呼吸机的使用时间、治疗7 d危重症评分与对照组比较差异有统计学意义(P<0.05)。治疗组在治疗3和7 d后白细胞计数和中性粒细胞计数均显著升高(P<0.05)。结论 rhG-CSF辅助治疗NEOS合并中性粒细胞减少症可有效提高抗感染疗效,降低并发症发生率,明显提高白细胞与中性粒细胞计数水平,且无明显不良反应发生。
Objective To study the effect of adjunctive therapy with recombinant human granulocyte colony-stimulating factor(rhG-CSF) on the outcome of neonatal early-onset septicemia(NEOS).Methods The neonates who met the early-onset sepsis clinical diagnostic criteria and associated with neutropenia syndrome were selected and randomly divided into control group and treatment group.The control group was treated with anti-infection and supportive treatment and the rhG-CSF treatment group was received extra rhG-CSF,5 μg·kg~(-1)·d~(-1).After treatment,the course of antibiotics,continuous time of jaundice,duration of ventilator days,neutrophil recovery time,laboratory tests,incidence of side effects,white blood cell count and the absolute neutrophil count were observed and the treatment effect of the adjuvant treatment was evaluated.Results The rhG-CSF adjunctive therapy may improve the efficacy of anti-infection:there were significant differences in the four aspects of muscle tone change,lower blood pressure,abnormal body temperature and duration of jaundice between the rhG-CSF group and the control group(P<0.05); The procalcitonin(PCT) and C-reactive protein(CRP) level between the rhG-CSF group and the control group had significant differences(P<0.05).The rhG-CSF treatment group showed a significant increase in white blood cell count and neutrophil count after 3 and 7 d treatment when compared with the control group(P<0.05).Conclusion The rhG-CSF adjunctive treatment can improve the anti-infection effect,reduce the incidence of complications and significantly improve the level of leukocyte and neutrophil count,and no significant side effect was observed.
Objective To study the effect of adjunctive therapy with recombinant human granulocyte colony-stimulating factor(rhG-CSF) on the outcome of neonatal early-onset septicemia(NEOS).Methods The neonates who met the early-onset sepsis clinical diagnostic criteria and associated with neutropenia syndrome were selected and randomly divided into control group and treatment group.The control group was treated with anti-infection and supportive treatment and the rhG-CSF treatment group was received extra rhG-CSF,5 μg·kg~(-1)·d~(-1).After treatment,the course of antibiotics,continuous time of jaundice,duration of ventilator days,neutrophil recovery time,laboratory tests,incidence of side effects,white blood cell count and the absolute neutrophil count were observed and the treatment effect of the adjuvant treatment was evaluated.Results The rhG-CSF adjunctive therapy may improve the efficacy of anti-infection:there were significant differences in the four aspects of muscle tone change,lower blood pressure,abnormal body temperature and duration of jaundice between the rhG-CSF group and the control group(P<0.05); The procalcitonin(PCT) and C-reactive protein(CRP) level between the rhG-CSF group and the control group had significant differences(P<0.05).The rhG-CSF treatment group showed a significant increase in white blood cell count and neutrophil count after 3 and 7 d treatment when compared with the control group(P<0.05).Conclusion The rhG-CSF adjunctive treatment can improve the anti-infection effect,reduce the incidence of complications and significantly improve the level of leukocyte and neutrophil count,and no significant side effect was observed.
引文
[1] 吴丽华,王志国.早产儿中性粒细胞减少症的发病率及其影响因素探讨[J].临床儿科杂志,2001,19(2):76-77.
[2] 王江涛,张璋,熊虹.重组人粒细胞生成素在早产儿感染合并粒细胞减少症中的应用[J].中国医学创新,2011,8(11):155-156.
[3] 邵肖梅,叶鸿瑁,丘小汕.实用新生儿学 [M].4 版.北京:人民卫生出版社,2011:338-342.
[4] Kuhn P,Messer J,Espaqne S,et al.A multicenter,randomized,placebo-controlled trial of prophylactic recombinant granulocyte-colony stimulating factor in preterm neonates with neutropenia[J].J Pediatr,2009,155(3):324-330.
[5] Bernstein H M,Calhoun D A,Christensen R D.Use of myeloid colony-stimulating factors in neonates with septicemia[J].Curr Opin Pediatri,2002,14(1):91-94.
[6] 何凤莲,赵大海,杨进,等.PCT与CRP在社区获得性肺炎中的诊断价值[J].临床肺科杂志,2014,19(4):607-609.
[7] Kücük?dük S,Sezer T,Yildiran A,et al.Randomized,double-blinded,placebo-controlled trial of early administration of recombinant human granulocyte colony-stimulating factor to non-neutropenic preterm newborns between 33 and 36 weeks with presumed sepsis[J].Scand J Infect Dis,2002,34(12):893-897.
[8] Marshall J C.The effects of granulocyte colony-stimulating factor in preclinical models of infection and acute inflammation[J].Shock,2005,24 (Suppl 1):120-129.
[9] Bo L,Wang F,Zhu J,et al.Granulocyte-colony stimulating factor (G-CSF) and granulocyte macrophage colony stimulating factor (GM-CSF) for sepsis:a Meta-analysis[J].Crit Care,2011,15(1):R58.
[10] 吴琳琳.粒细胞集落刺激因子对早产儿败血症合并中性粒细胞减少症辅助治疗效果研究及作用机制探讨[D].福州:福建医科大学,2012:1-112.
[11] Cohen-Wolkowiez M,Benjamin D K Jr,Capparelli E.Immunotherapy in neonatal sepsis:advances in treatment and prophylaxis[J].Curr Opin Pediatr,2009,21(2):177-181.
[12] Kocheerlakota P,La Gamma E F.Human granulocyte colony-stimulating factor may improve outcome attributable to neonatal sepsis complicated by neutropenia[J].Pediatrics,1997,100(1):E6.
[13] 华瑛,曹舫.重组人粒细胞集落刺激因子治疗恶性肿瘤大剂量联合化疗后白细胞减少症103例临床观察[J].西北药学杂志,2013,28(5):522-523.
[14] 金珊.重组人粒细胞集落刺激因子治疗化疗后Ⅳ度骨髓抑制疗效观察[J].贵州医药,2009,33(5):439-440.
[15] 符一岚,曹丽芝,龚倩,等.肿瘤患者应用重组人粒细胞集落刺激因子致严重不良反应13例临床分析[J].肿瘤药学,2018,8(1):108-111,116.
[16] Karageorgopoulos D E,Wang R,Yu X H,et al.Fosfomycin:evaluation of the published evidence on the emergence of antimicrobial resistance in Gram-negative pathogens[J].J Antimicrob Chemother,2012,67(2):255-268.
[17] Brink A J,Bizos D,Boffard K D,et al.Guideline:appropriate use of tigecycline[J].S Afr Med J,2010,100(6 Pt 2):388-394.
[18] Bernstein H M,Pollock B H,Calhoun D A,et al.Administration of recombinant granulocyte colony-stimulating factor to neonates with septicemia:a Meta-analysis[J].J Pediatr,2001,138(6):917-920.
[19] Molloy E J,O′neill A J,Grantham J J,et al.Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor have differential effects on neonatal and adult neutrophil survival and function[J].Pediatr Res,57(6):806-812.
[20] Rosenthal J,Healey T,Ellis R,et al.A two-year follow-up of neonates with presumed sepsis treated with recombinant human granulocyte colony-stimulating factor during the first week of life[J].J Pediatr,1996,128(1):135-137.
[2] 王江涛,张璋,熊虹.重组人粒细胞生成素在早产儿感染合并粒细胞减少症中的应用[J].中国医学创新,2011,8(11):155-156.
[3] 邵肖梅,叶鸿瑁,丘小汕.实用新生儿学 [M].4 版.北京:人民卫生出版社,2011:338-342.
[4] Kuhn P,Messer J,Espaqne S,et al.A multicenter,randomized,placebo-controlled trial of prophylactic recombinant granulocyte-colony stimulating factor in preterm neonates with neutropenia[J].J Pediatr,2009,155(3):324-330.
[5] Bernstein H M,Calhoun D A,Christensen R D.Use of myeloid colony-stimulating factors in neonates with septicemia[J].Curr Opin Pediatri,2002,14(1):91-94.
[6] 何凤莲,赵大海,杨进,等.PCT与CRP在社区获得性肺炎中的诊断价值[J].临床肺科杂志,2014,19(4):607-609.
[7] Kücük?dük S,Sezer T,Yildiran A,et al.Randomized,double-blinded,placebo-controlled trial of early administration of recombinant human granulocyte colony-stimulating factor to non-neutropenic preterm newborns between 33 and 36 weeks with presumed sepsis[J].Scand J Infect Dis,2002,34(12):893-897.
[8] Marshall J C.The effects of granulocyte colony-stimulating factor in preclinical models of infection and acute inflammation[J].Shock,2005,24 (Suppl 1):120-129.
[9] Bo L,Wang F,Zhu J,et al.Granulocyte-colony stimulating factor (G-CSF) and granulocyte macrophage colony stimulating factor (GM-CSF) for sepsis:a Meta-analysis[J].Crit Care,2011,15(1):R58.
[10] 吴琳琳.粒细胞集落刺激因子对早产儿败血症合并中性粒细胞减少症辅助治疗效果研究及作用机制探讨[D].福州:福建医科大学,2012:1-112.
[11] Cohen-Wolkowiez M,Benjamin D K Jr,Capparelli E.Immunotherapy in neonatal sepsis:advances in treatment and prophylaxis[J].Curr Opin Pediatr,2009,21(2):177-181.
[12] Kocheerlakota P,La Gamma E F.Human granulocyte colony-stimulating factor may improve outcome attributable to neonatal sepsis complicated by neutropenia[J].Pediatrics,1997,100(1):E6.
[13] 华瑛,曹舫.重组人粒细胞集落刺激因子治疗恶性肿瘤大剂量联合化疗后白细胞减少症103例临床观察[J].西北药学杂志,2013,28(5):522-523.
[14] 金珊.重组人粒细胞集落刺激因子治疗化疗后Ⅳ度骨髓抑制疗效观察[J].贵州医药,2009,33(5):439-440.
[15] 符一岚,曹丽芝,龚倩,等.肿瘤患者应用重组人粒细胞集落刺激因子致严重不良反应13例临床分析[J].肿瘤药学,2018,8(1):108-111,116.
[16] Karageorgopoulos D E,Wang R,Yu X H,et al.Fosfomycin:evaluation of the published evidence on the emergence of antimicrobial resistance in Gram-negative pathogens[J].J Antimicrob Chemother,2012,67(2):255-268.
[17] Brink A J,Bizos D,Boffard K D,et al.Guideline:appropriate use of tigecycline[J].S Afr Med J,2010,100(6 Pt 2):388-394.
[18] Bernstein H M,Pollock B H,Calhoun D A,et al.Administration of recombinant granulocyte colony-stimulating factor to neonates with septicemia:a Meta-analysis[J].J Pediatr,2001,138(6):917-920.
[19] Molloy E J,O′neill A J,Grantham J J,et al.Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor have differential effects on neonatal and adult neutrophil survival and function[J].Pediatr Res,57(6):806-812.
[20] Rosenthal J,Healey T,Ellis R,et al.A two-year follow-up of neonates with presumed sepsis treated with recombinant human granulocyte colony-stimulating factor during the first week of life[J].J Pediatr,1996,128(1):135-137.