亚低温对新生儿缺氧缺血性脑病的疗效
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摘要
目的观察全身亚低温对新生儿缺氧缺血性脑病(HIE)的疗效和安全性。方法50例中、重度HIE新生儿分为两组。常温组23例,采用常规治疗;亚低温组27例,在常规治疗的基础上加用72 h的全身亚低温治疗。监测两组患儿的RR、HR、BP、血气分析、血电解质、血常规、凝血功能和肝肾功能。出生后14 d评估两组患儿吸吮吞咽原始反射的恢复情况。出生后28 d行新生儿行为神经测定(NBNA),出生后6、12和18个月分别行Bayley婴儿发育量表检查。结果亚低温组治疗24～72 h的HR较常温组减慢(P<0.05),复温后HR恢复正常。两组患儿均出现低钙血症和纤维蛋白原降低,但亚低温组治疗24～96 h血钙和纤维蛋白原浓度均高于常温组(P<0.05)。两组吸吮吞咽原始反射评分无统计学差异(P>0.05)。亚低温组NBNA评分和各时点Bayley婴儿发育量表评分均高于常温组(P<0.05),病死和严重伤残发生率低于常温组(18.5%vs.47.8%)(P<0.05)。结论全身亚低温治疗对新生儿HIE具有近期和远期的神经保护作用。
Objective To observe the efficacy and safety of systemic therapeutic mild hypothermia for neonatal hypoxic-ischemic encephalopathy(HIE).Methods Fifty asphyxiated newborns with moderate and severe HIE were divided into two groups.Group C(23 cases) received routine treatment and group A(27 cases) was given additional systemic therapeutic mild hypothermia for 72 hours.Respiratory rate,heart rate,blood pressure,blood gas analysis,blood electrolytes,blood routine,coagulation function and liver and kidney functions were monitored during treatment.The rehabilitation of original reflex(sucking and swallowing reflex) was assessed on the 14~(th) day after birth and neonatal behavioral neurological assessment(NBNA) was performed on the 28~(th) day after birth.The long-term effect was evaluated by Bayley scales of infant development in the 6~(th),12~(th) and 18~(th) month after birth.Results Heat rate in 24 to 72 hours after systemic therapeutic hypothermia in group A was lower than that in group C(P<0.05),which returned to normal after rewarming.Hypocalcemia and fibrinogenopenia occurred in two groups,while the blood levels of calcium and fibrinogen were higher in group A than those in group C in 24 to 96 hours after systemic therapeutic mild hypothermia(P<0.05).There was no significant difference in the original reflex scores of sucking and swallowing between two groups(P>0.05).The scores of NBNA and Bayley scales of infant development were higher,while the mortality and incidence of severe disability were lower in group A than those in group C(18.5% vs.47.8%)(P<0.05).Conclusion Systemic therapeutic mild hypothermia has obvious short-and longer-term neuroprotective effects.
Objective To observe the efficacy and safety of systemic therapeutic mild hypothermia for neonatal hypoxic-ischemic encephalopathy(HIE).Methods Fifty asphyxiated newborns with moderate and severe HIE were divided into two groups.Group C(23 cases) received routine treatment and group A(27 cases) was given additional systemic therapeutic mild hypothermia for 72 hours.Respiratory rate,heart rate,blood pressure,blood gas analysis,blood electrolytes,blood routine,coagulation function and liver and kidney functions were monitored during treatment.The rehabilitation of original reflex(sucking and swallowing reflex) was assessed on the 14~(th) day after birth and neonatal behavioral neurological assessment(NBNA) was performed on the 28~(th) day after birth.The long-term effect was evaluated by Bayley scales of infant development in the 6~(th),12~(th) and 18~(th) month after birth.Results Heat rate in 24 to 72 hours after systemic therapeutic hypothermia in group A was lower than that in group C(P<0.05),which returned to normal after rewarming.Hypocalcemia and fibrinogenopenia occurred in two groups,while the blood levels of calcium and fibrinogen were higher in group A than those in group C in 24 to 96 hours after systemic therapeutic mild hypothermia(P<0.05).There was no significant difference in the original reflex scores of sucking and swallowing between two groups(P>0.05).The scores of NBNA and Bayley scales of infant development were higher,while the mortality and incidence of severe disability were lower in group A than those in group C(18.5% vs.47.8%)(P<0.05).Conclusion Systemic therapeutic mild hypothermia has obvious short-and longer-term neuroprotective effects.
引文
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[11] 王来栓. 脑损伤后的内源性神经再生机制[M]//邵肖梅,周文浩. 胎儿和新生儿脑损伤.2版.上海:上海科技教育出版社,2017:44-51.
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[13] 卫生部新生儿疾病重点实验室,复旦大学附属儿科医院.亚低温治疗新生儿缺氧缺血性脑病方案(2011)[J]. 中国循证儿科杂志,2011,6(5):337-339.
[14] 中国医师协会新生儿专业委员会. 早产儿脑损伤诊断与防治专家共识[J]. 中国当代儿科杂志,2012,14(12):883-884.
[15] 邓明英,吴晓华,陈凯星,等. 早期干预对早产儿脑损伤及脑发育的影响[J]. 中国妇幼保健,2011,26(17):2609-2610.
[16] 卫生部新生儿疾病重点实验室,复旦大学附属儿科医院,《中国循证儿科杂志》编辑部,等.足月儿缺氧缺血性脑病循证治疗指南(2011-标准版)[J].中国循证儿科杂志,2011,6(5):336.
[17] 葛娅,邹敏书,余健. 全身亚低温治疗对缺氧缺血性脑病新生儿的影响[J]. 华南国防医学杂志,2008,22(2):42-43.
[18] Edwards AD, Brocklehurst P, Gunn AJ, et al. Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data[J]. BMJ,2010,340:c363.
[19] Liu CL, Siesj? BK, Hu BR. Pathogenesis of hippocampal neuronal death after hypoxia-ischemia changes during brain development[J]. Neuroscience,2004,127(1):113-123.
[20] Fleiss B,Gressens P. Tertiary mechanisms of brain damage: a new hope for treatment of cerebral palsy[J]? Lancet Neurol,2012,11(6):556-566.
[21] Zhu C,Xu F,Wang X,et al.Different apoptotic mechanisms are activated in male and female brains after neonatal hypoxia-ischemia[J].J Neurochem,2006,96(4):1016-1027.
[22] 贾雯.不同时间窗亚低温治疗新生儿缺氧缺血性脑病的对比研究[D]. 泸州: 四川医科大学,2015:1-63.
[23] Akisu M,Huseyinoy A,Yalaz M,et al. Selective head cooling with hypothermia suppresses the generation of platelet-activating factor in cerebrospinal fluid of newborn infants with perinatal asphyxia[J].Prostaglandins Leukot Essent Fatty Acids,2003,69(1):45-50.
[24] 陈树斌,徐树生,李绍臣,等. 围术期轻度低温对神经外科手术患者血小板功能的影响[J]. 中国全科医学,2009,12(6):443-445.
[25] Speer M,Perlman JM. Modest hypothermia as a neuroprotective strategy in high-risk term infants[J]. Clin Perinatol,2006,33(1):169-182.
[26] Gluckman PD,Wyatt JS,Azzopardi D,et al.Selective head cooling with mild systemic hypothermia after neonatal encephalopathy:multicentre randomised trial[J].Lancet,2005,365(9460):663-670.
[27] 李钢,徐如祥,柯以铨,等. 重型颅脑创伤急性期D-dimer动态变化对预后的价值[J].中华神经外科杂志,2008,24(7):543-545.
[28] 李钢,史克珊,曹作为,等. 亚低温治疗重型颅脑损伤病人纤维蛋白原和D-二聚体的变化及临床意义[J]. 中国微侵袭神经外科杂志,2008,13(10):445-447.
[29] Band RA,Abella BS. Hypothermia and cardiac arrest:the promise of intra-arrest cooling[J].Crit Care,2008,12(2):138.
[30] 陈桃英,王晓蕾,李雅雯,等.亚低温联合促红细胞生成素治疗中重度新生儿缺氧缺血性脑病的疗效[J].江苏医药,2014,40(1):47-49.
[2] Olsen SL,DeJonge M,Kline A,et al. Optimizing therapeutic hypothermia for neonatal encephalopathy[J]. Pediatrics,2013,131(2):e591-e603.
[3] Azzopardi D,Strohm B,Linsell L,et al. Implementation and conduct of therapeutic hypothermia for perinatal asphyxial encephalopathy in the UK——analysis of national data[J].PLoS ONE,2012,7(6):e38504.
[4] Hagmann CF,Brotschi B,Bernet V,et al. Hypothermia for perinatal asphyxial encephalopathy[J].Swiss Med Wkly,2011,141:w13145.
[5] 郭晓燕,朱长连,程秀永,等. 亚低温与促红细胞生成素联合治疗新生儿缺氧缺血性脑损伤的效果[J]. 实用儿科临床杂志,2008,23(2):111-113.
[6] Landau Y,Berger I,Marom R,et al. Therapeutic hypothermia for asphyxiated newborns:experience of an Israeli tertiary center[J].Isr Med Assoc J,2011,13(1):29-33.
[7] Rutherford M,Ramenghi LA,Edwards AD,et al. Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy:a nested substudy of a randomised controlled trial[J]. Lancet Neurol,2010,9(1):39-45.
[8] 孙金峤,陈燕琳,周文浩,等. 亚低温治疗新生儿缺氧缺血性脑病临床效果的Meta分析[J]. 中国循证儿科杂志,2009,4(4):340-348.
[9] Brines M,Ceram A. Discovering erythropoietin's extra-hematopoietic functions: biology and clinical promise[J]. Kidney Int,2006,70(2):246-250.
[10] 朱长连,孙慧清. 促红细胞生成素治疗新生儿脑病研究进展[M]//邵肖梅,周文浩. 胎儿和新生儿脑损伤.2版.上海:上海科技教育出版社,2017:114-117.
[11] 王来栓. 脑损伤后的内源性神经再生机制[M]//邵肖梅,周文浩. 胎儿和新生儿脑损伤.2版.上海:上海科技教育出版社,2017:44-51.
[12] 中华医学会儿科学分会新生儿学组. 新生儿缺氧缺血性脑病诊断标准[J]. 中华儿科杂志,2005,43(8):584.
[13] 卫生部新生儿疾病重点实验室,复旦大学附属儿科医院.亚低温治疗新生儿缺氧缺血性脑病方案(2011)[J]. 中国循证儿科杂志,2011,6(5):337-339.
[14] 中国医师协会新生儿专业委员会. 早产儿脑损伤诊断与防治专家共识[J]. 中国当代儿科杂志,2012,14(12):883-884.
[15] 邓明英,吴晓华,陈凯星,等. 早期干预对早产儿脑损伤及脑发育的影响[J]. 中国妇幼保健,2011,26(17):2609-2610.
[16] 卫生部新生儿疾病重点实验室,复旦大学附属儿科医院,《中国循证儿科杂志》编辑部,等.足月儿缺氧缺血性脑病循证治疗指南(2011-标准版)[J].中国循证儿科杂志,2011,6(5):336.
[17] 葛娅,邹敏书,余健. 全身亚低温治疗对缺氧缺血性脑病新生儿的影响[J]. 华南国防医学杂志,2008,22(2):42-43.
[18] Edwards AD, Brocklehurst P, Gunn AJ, et al. Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data[J]. BMJ,2010,340:c363.
[19] Liu CL, Siesj? BK, Hu BR. Pathogenesis of hippocampal neuronal death after hypoxia-ischemia changes during brain development[J]. Neuroscience,2004,127(1):113-123.
[20] Fleiss B,Gressens P. Tertiary mechanisms of brain damage: a new hope for treatment of cerebral palsy[J]? Lancet Neurol,2012,11(6):556-566.
[21] Zhu C,Xu F,Wang X,et al.Different apoptotic mechanisms are activated in male and female brains after neonatal hypoxia-ischemia[J].J Neurochem,2006,96(4):1016-1027.
[22] 贾雯.不同时间窗亚低温治疗新生儿缺氧缺血性脑病的对比研究[D]. 泸州: 四川医科大学,2015:1-63.
[23] Akisu M,Huseyinoy A,Yalaz M,et al. Selective head cooling with hypothermia suppresses the generation of platelet-activating factor in cerebrospinal fluid of newborn infants with perinatal asphyxia[J].Prostaglandins Leukot Essent Fatty Acids,2003,69(1):45-50.
[24] 陈树斌,徐树生,李绍臣,等. 围术期轻度低温对神经外科手术患者血小板功能的影响[J]. 中国全科医学,2009,12(6):443-445.
[25] Speer M,Perlman JM. Modest hypothermia as a neuroprotective strategy in high-risk term infants[J]. Clin Perinatol,2006,33(1):169-182.
[26] Gluckman PD,Wyatt JS,Azzopardi D,et al.Selective head cooling with mild systemic hypothermia after neonatal encephalopathy:multicentre randomised trial[J].Lancet,2005,365(9460):663-670.
[27] 李钢,徐如祥,柯以铨,等. 重型颅脑创伤急性期D-dimer动态变化对预后的价值[J].中华神经外科杂志,2008,24(7):543-545.
[28] 李钢,史克珊,曹作为,等. 亚低温治疗重型颅脑损伤病人纤维蛋白原和D-二聚体的变化及临床意义[J]. 中国微侵袭神经外科杂志,2008,13(10):445-447.
[29] Band RA,Abella BS. Hypothermia and cardiac arrest:the promise of intra-arrest cooling[J].Crit Care,2008,12(2):138.
[30] 陈桃英,王晓蕾,李雅雯,等.亚低温联合促红细胞生成素治疗中重度新生儿缺氧缺血性脑病的疗效[J].江苏医药,2014,40(1):47-49.