常频机械通气对极低和超低出生体重儿脑损伤影响的临床研究
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摘要
目的
探讨机械通气对极低和超低出生体重儿脑损伤的影响及机械通气下极低和超
低出生体重儿脑损伤发生或加重的高危因素。
方法
回顾分析中国医科大学盛京医院新生儿病房于2007年3月至2009年12月收治的需行机械通气治疗的极低和超低出生体重儿82例,并随机选取同期住院的82例未行机械通气极低和超低出生体重儿的临床及影像学资料,比较两组脑损伤的发生率；同时将机械通气患儿按脑损伤形式分为非脑实质出血组、脑白质损伤组及非脑损伤组,对三组患儿在呼吸机参数(最高PIP、最高PEEP、RR)、血气指标(最高Pa02、最低Pa02、最高PaC02、最低PaC02)、通气时间等指标作比较,探讨机械通气对极低和超低出生体重儿脑损伤的影响因素。
结果
机械通气组患儿脑损伤总的发生率、非脑实质出血发生率及脑白质损伤发生率分别为71.95%、45.12%(重度颅内出血的发生率为9.76%)、26.82%；非机械通气组患儿脑损伤总的发生率、非脑实质出血发生率及脑白质损伤发生率分别为37.80%、25.61%(重度颅内出血的发生率为2.44%)、12.20%；机械通气条件下三组极低出生体重儿在最高PIP、最高PEEP、最高Pa02、最低Pa02、呼吸频率、上机时间等方面无统计学意义(P>0.05),但非脑实质出血组与非脑损伤组最高PaCO2及平均动脉压有统计学意义(P<0.05)；脑白质损伤组与非脑损伤组在最低二氧化碳分压方面有统计学意义(P<0.05)。
结论
机械通气组极低和超低出生体重儿脑损伤的发生率明显高于非机械通气组；机械通气下极低和超低出生体重儿脑损伤仍以非脑实质出血为主,其次为脑白质损伤；机械通气时所致的高碳酸血症及低碳酸血症可能是极低和超低出生体重儿脑损伤发生或加重的高危因素。
Objective
To explore the influence of mechanical ventilation on brain injury in very low and extremely low birth weight(VLBW and ELBW) infant and risk factors related brain damage in VLBW and ELBW infants with mechanical ventilation.
Methods
The study was prospectively performed on 82 VLBW and ELBW infants with mechanical ventilation and 82 VLBW and ELBW infants without mechanical ventilation at the same period from March 2007 to December 2009 at the neonatal intensive care unit of the Shengjing Hospital of China Medical University. Detailed clinical and imaging data of all subjects were analyzed,the rate of brain injury between the two groups was compared. The 82 VLBW and ELBW infants with mechanical ventilation were divided into three groups:non-cerebral hemorrhage group (37)、and white matter damage(WMD) group (22)and non-injury group (23). The highest and lowest values of PaCO2、PaO、the highest values of PIP, PEEP, respiratory rate and days of ventilation were compared in the three groups.
Results
The rate of total brain injury、non-cerebral hemorrhage and WMD in VLBW and ELBW infants with mechanical ventilation was respectively 71.95%、45.12%(severe IVH 9.76%) and 26.82%; The rate of total brain injury、non-cerebral hemorrhage and WMD in control group was respectively 37.80%、25.61%(severe IVH 2.44%) and 12.20%; The rate of total brain injury、IVH and WMD in VLBW and ELBW infants with mechanical ventilation significantly higher and the degree was more serious than that of control group.In the mechanical ventilation group, there was no significant difference in the highest and lowest values of PaO2、the highest values of PIP, PEEP, respiratory rate and days of ventilation in non-cerebral hemorrhage group、WMD-group and non-injury group. The difference in the highest values of PaCO2 between non-cerebral hemorrhage group and non-injury group were considered statistically significant, and there was also significant difference in the lowest values of PaCO2 between WMD-group and non-injury group.
Conclusion
The incidence of brain injury significantly higher than non-mechanical ventilation group in VLBW and ELBW infants; The form of brain damage is in mechanical ventilation infants is still mainly non-cerebral hemorrhage, followed by white matter damage. Hypercapnia. hypocapnia and hypotension generated in mechanical ventilation may induce or aggravate brain injury in VLBW and ELBW infants.
探讨机械通气对极低和超低出生体重儿脑损伤的影响及机械通气下极低和超
低出生体重儿脑损伤发生或加重的高危因素。
方法
回顾分析中国医科大学盛京医院新生儿病房于2007年3月至2009年12月收治的需行机械通气治疗的极低和超低出生体重儿82例,并随机选取同期住院的82例未行机械通气极低和超低出生体重儿的临床及影像学资料,比较两组脑损伤的发生率；同时将机械通气患儿按脑损伤形式分为非脑实质出血组、脑白质损伤组及非脑损伤组,对三组患儿在呼吸机参数(最高PIP、最高PEEP、RR)、血气指标(最高Pa02、最低Pa02、最高PaC02、最低PaC02)、通气时间等指标作比较,探讨机械通气对极低和超低出生体重儿脑损伤的影响因素。
结果
机械通气组患儿脑损伤总的发生率、非脑实质出血发生率及脑白质损伤发生率分别为71.95%、45.12%(重度颅内出血的发生率为9.76%)、26.82%；非机械通气组患儿脑损伤总的发生率、非脑实质出血发生率及脑白质损伤发生率分别为37.80%、25.61%(重度颅内出血的发生率为2.44%)、12.20%；机械通气条件下三组极低出生体重儿在最高PIP、最高PEEP、最高Pa02、最低Pa02、呼吸频率、上机时间等方面无统计学意义(P>0.05),但非脑实质出血组与非脑损伤组最高PaCO2及平均动脉压有统计学意义(P<0.05)；脑白质损伤组与非脑损伤组在最低二氧化碳分压方面有统计学意义(P<0.05)。
结论
机械通气组极低和超低出生体重儿脑损伤的发生率明显高于非机械通气组；机械通气下极低和超低出生体重儿脑损伤仍以非脑实质出血为主,其次为脑白质损伤；机械通气时所致的高碳酸血症及低碳酸血症可能是极低和超低出生体重儿脑损伤发生或加重的高危因素。
Objective
To explore the influence of mechanical ventilation on brain injury in very low and extremely low birth weight(VLBW and ELBW) infant and risk factors related brain damage in VLBW and ELBW infants with mechanical ventilation.
Methods
The study was prospectively performed on 82 VLBW and ELBW infants with mechanical ventilation and 82 VLBW and ELBW infants without mechanical ventilation at the same period from March 2007 to December 2009 at the neonatal intensive care unit of the Shengjing Hospital of China Medical University. Detailed clinical and imaging data of all subjects were analyzed,the rate of brain injury between the two groups was compared. The 82 VLBW and ELBW infants with mechanical ventilation were divided into three groups:non-cerebral hemorrhage group (37)、and white matter damage(WMD) group (22)and non-injury group (23). The highest and lowest values of PaCO2、PaO、the highest values of PIP, PEEP, respiratory rate and days of ventilation were compared in the three groups.
Results
The rate of total brain injury、non-cerebral hemorrhage and WMD in VLBW and ELBW infants with mechanical ventilation was respectively 71.95%、45.12%(severe IVH 9.76%) and 26.82%; The rate of total brain injury、non-cerebral hemorrhage and WMD in control group was respectively 37.80%、25.61%(severe IVH 2.44%) and 12.20%; The rate of total brain injury、IVH and WMD in VLBW and ELBW infants with mechanical ventilation significantly higher and the degree was more serious than that of control group.In the mechanical ventilation group, there was no significant difference in the highest and lowest values of PaO2、the highest values of PIP, PEEP, respiratory rate and days of ventilation in non-cerebral hemorrhage group、WMD-group and non-injury group. The difference in the highest values of PaCO2 between non-cerebral hemorrhage group and non-injury group were considered statistically significant, and there was also significant difference in the lowest values of PaCO2 between WMD-group and non-injury group.
Conclusion
The incidence of brain injury significantly higher than non-mechanical ventilation group in VLBW and ELBW infants; The form of brain damage is in mechanical ventilation infants is still mainly non-cerebral hemorrhage, followed by white matter damage. Hypercapnia. hypocapnia and hypotension generated in mechanical ventilation may induce or aggravate brain injury in VLBW and ELBW infants.
引文
1 Paneth N, Pmdelli R, Kazam E, et al. Brain damage in preterm infant [M]. London:Mackeith Press.1994,99-118.
2 Papile LA, Burstein, Burstein R, et al. Incidence and evaluation of subependymal and intraventricul hemorrhage:a study of infants with birth weight less than 1500g[J]. Pediatr, 1978,92:529.
3 Owens R. Intraventricular hemorrhage in the p remature neonate.[J]. Neonatal Netw,2005,24(3):55-71.
4 Antoniuk S, da Silva RV. Periventricular and intraventricular hemorrhage in the premature infants.[J]. Rev Neurol,2000,31 (3):238-243.
5 陈惠金,我国早产儿脑室内出血的早期诊断和防治现状.临床儿科杂志,2004,22(1)：3
6 Hassan Kadri, Alhakam A. Mawla, Jehad Kazah. The incidence, timing, and predisposing factors of germinal matrix and intraventricular hemorrhage (GMH/IVH) in preterm neonates. Childs Nerv Syst,2006,22:1086-1090.
7 Vural M,Yilmaz I,Ilikkan B, et al.Intraventricular hemorrhage in preterm newborns:Risk factors and results from a University Hospital in Istanbul,8 years after.Pediatrics International, 2007,49:341-344.
8 吴香兰,卢光进,叶贞志等,机械通气下极低出生体重儿颅内出血相关因素分析.中国妇幼保健,2006,21：1951-1953
9 Kaise JR,Gauss CH, Pont MM, et al. Hypercspnia during the first 3 days of life is associated with severe intraventricular hemorrhage in very low birth weight infants. J Perinatol,2006, 26:279-285.
10 Burgess GH,Oh W.Effects of phenobarbital on cerebral blood flow velocity after endotracheal suctioning in premature neonates.Arch Pediatr Adolesc Med,2001,155:723-727.
11 Fabres J, Carlo WA, Phillips V, Howard G, Ambalavanan N.Both extremes of arterial carbon dioxide pressure and the magnitude of fluctuations in arterial carbon dioxide pressure are associated with severe intraventricular hemorrhage in preterm infants. Pediatrics. 2007,119:299-305.
12 Woodgate PG, Davies M W. Perm issive hypercapnia for the prevention of m orbidity and m ortality in m echanically ventilated newborn infants. Cochrane Database Syst Rev,2001, (2):CD0O2O61.
13 陈惠金.早产儿脑室周围白质软化的研究进展[J].实用儿科临床杂志,2004,19：83-86.
14 Silveira RC, Procianoy RS, Dill JC, da Costa CS. Periventricular leukomalacia in very low birth weight preterm neonates with high risk for neonatal sepsis. J Pediatr.2008,84:211-216.
15 Greisen G, Vannueei RC. Is periventrieular leucom alacia a result of hypoxic-isehaemie injury? Hypocapnia and the preterm brain. Biol Neonate,2001,79:194-200.
16 Christina Giannakopoulou, Eftichia Korakaki, Antonia Manoura,et al. Significance of hypocarbia in the development of periventricular leukomalacia in preterm infants.Pediatrics international,2004,46:268-273.
17 Fujimoto S, Togari H。 Yamaguchi N, et al. Hypocarbia and cystic eriventricular leukomalaeia in preterm infants [J]. Arch Dis Child.1994,71:1F107-110.
18 MuraseM, Ishida A. Early hypocarbia of p reterm infants:its relationship to periventricular leukomalacia and cerebral palsy, and its perinatal risk factors[J]. Acta Paedia,2005, 94(1):85-91.
19 Christina Giannakopoulou, Eftichia Korakaki, Antonia Manoura,et al. Significance of hypocarbia in the development of periventricular leukomalacia in preterm infants.Pediatrics international,2004,46:268-273.
20 刁敬军,明秀芬,张军等,机械通气早产儿脑室周围白质软化危险因素分析.中国当代儿科杂志,2005,7(2)：174-175
1 Thomas DB, Burnard ED.Prevention of intraventricular haemorrhage in babies receiving artificial ventilation.Med J Aust.1973 May 12,1:933-936.
2 Welin AK, SandbergM, Lindblom A, et al. White matter injury following prolonged free radical formation in the 0.65 gestation fetal sheepbrain[J]. Pediatr Res,2005,58:100-105.
3 Ollins MP,Lorenz JM,Jetton JR, et al. Hypocaapnia and other ventilation-related risk factors for cerebral palsy in loe birth weight infants.Pediatr Res,2001,50:712-719.
4 Luyt K,Wright D,Baumer JH,Randomised study comparing extent of hypocarbia in preterm infants during conventional and patient triggered.Arch Dis Child Fetal Neonatal ED,1996,74:F63-69.
5 Greisen G, Vannueei RC. Is periventrieular leucom alacia a result of hypoxic-isehaemie injury? Hypocapnia and the preterm brain. Biol Neonate,2001,79:194-200.
6 Vannucci RC, Towfighi J, Heitjan DF, Brucklacher RM.Carbon dioxide protects the perinatal brain from hypoxicischemic damage:an experimental study in the immature rat. Pediatrics 1995,95:868-874.
7 Fritz KI,Ashraf QM,Mishra OP,et al.Effect of moderate hypocapnic ventilation on nuclear DNA fragmentation and energy metabolism in the cerebral cortex of new piglets.Pediat Res,2001,50:586-589.
8 Klinger G, Beyene J, Shah P, et al. Do hyperoxaemia and hypocapnia add to the risk of brain injury after intrapartum asphyxia? ArchDis Child Fetal Neonatal Ed,2005,90:49-52.
9 Gleason CA, Short BL. Jones MD. Cerebral blood flow and metabo lism during and after prolonged hypocapnia in newborn lamb.J Pediatr,1989,115:309-314.
10 Graziani LJ, Spitzer AR, Mitchell DG, Mechanical ventilation in preterm infants: neurosonographic and developmental studies. Pediatrics.1992;90:515-522
11 Fujimoto S, Togari H。Yamaguchi N, et al. Hypocarbia and cystic eriventricular leukomalaeia in preterm infants [J]. Arch Dis Child.1994,71:1F107-110.
12 陈惠金.早产儿脑室周围白质软化的研究进展[J].实用儿科临床杂志,2004,19：83-86.
13 Murase M,Ishida A. Early hypocarbia of preterm infants:Its relationship to periventricular leukomalacia and cerebral palsy, and its perinatal risk factors. Acta P(?)diatrica,2005,94:85-91.
14 Silveira RC, Procianoy RS, Dill JC, da Costa CS. Periventricular leukomalacia in very low birth weight preterm neonates with high risk for neonatal sepsis. J Pediatr.2008,84:211-216.
15 Christina Giannakopoulou, Eftichia Korakaki, Antonia Manoura,et al. Significance of hypocarbia in the development of periventricular leukomalacia in preterm infants.Pediatrics international,2004,46:268-273.
16 Erickson SJ, Grauaug A, Gurrin L, et al. Hypocarbia in the ventilated preterm infant and its
effect on intraventricular haemorrhageand bronchopulmonary dysplasia. J Paediatr Child Health,2002,38:560-562.
17 Okumura A, Hayakawa F, Kato T, et al. Hypocarbia in preterminfant s with perivent ricular leukomalacia:the relation between hypocarbia and mechanical ventilation. Pediatrics,2001,107:469-475.
18 Ohyu J, Endo A, Itoh M, et al. Hypocapnia under hypoten sion in duces apo ptotic neuronal cell death in the hlppocampus of newborn rabbits. Pediatr Res,2000,48:24-29.
19 Marron MJ,Crisafi MA,Driscoll JM, et al. Hearing and neurodevelopmental outcome in survivors of persistent pulmonary hypertensionof the newborn. Pediatrics,1992,90:392-396.
20 Ambalavan an N. Ca rlo WA. Hypocapnia and hypercapnia in respiratory management of newbolTl infants[J]. Clin Perinatol,2001,28:517-530.
21 Hassan Kadri, Alhakam A. Mawla, Jehad Kazah. The incidence, timing, and predisposing factors of germinal matrix and intraventricular hemorrhage (GMH/IVH) in preterm neonates. Childs Nerv Syst,2006,22:1086-1090.
22 Vural M,Yilmaz I,Ilikkan B, et al.Intraventricular hemorrhage in preterm newborns:Risk factors and results from a University Hospital in Istanbul,8 years after.Pediatrics Iternational,2007,49:341-344.
23 Gleissner M, J orch G, Avenarius S. Risk factors for intravent ricular hemorrhage in a birth cohort of 3721 premature infants. J Perinat Med,2000,28:104-110.
24 Cools F, Offringa M. Meta-analysis of elective highfrequency ventilation in preterm infants with respiratory distress syndrome.Arch Dis Child Fe t al Neonat al Ed,1999,80:F15-20.
25 Burgess GH,Oh W.Effects of phenobarbital on cerebral blood flow velocity after endotracheal suctioning in premature neonates.Arch Pediatr Adolesc Med,2001,155:723-727.
26 Kaiser JR, Gauss CH, Pont MM, Williams DK. Hypercapnia during the first 3 days of life is associated with severe intraventricular hemorrhage in very low birth weight infants. J Perinatol. 2006,26:279-285.
27 Fabres J, Carlo WA, Phillips V, Howard G, Ambalavanan N.Both extremes of arterial carbon dioxide pressure and the magnitude of fluctuations in arterial carbon dioxide pressure are associated with severe intraventricular hemorrhage in preterm infants. Pediatrics. 2007,119:299-305.
28 Kaiser JR, Gauss CH, Williams DK. The effect s of hypercapnia on cerebral autoregulation in ventilated very low birth weight infants. Pediatr Res,2005,58:931-935.
29 Kaise JR,Gauss CH, Pont MM, et al. Hypercspnia during the first 3 days of life is associated with severe intraventricular hemorrhage in very low birth weight infants. J Perinatol,2006, 26:279-285.
30 Erika W. Hagen, PhDa, Mona Sadek-Badawi,et al. Permissive Hypercapnia and Risk for Brain Injury and Developmental Impairment. Pediatrics.2008,1016.
31 Carlo WA, Stark AR, Wright LL, et al. Minimal ventilation to prevent bronchopulmonary dysplasia in extremely-low-birthweight infants. J Pediatr.2002,141:370-374.
32 Thome UH, Carroll W, Wu TJ, et al. Outcome of extremely preterm infants randomized at birth to different PaCO2 targets during the first seven days of life. Biol Neonate.2006,90:218-225.
33 Hemphill JC 3rd, Neck T, Carhuapo ma JR, et al.Is neurointenaive care really optional for comprehensive stroke careStroke,2005,36:2344-2345.
34 Donn SM,Roloff DW,Goldstein GW.Prevention of intraventricular haemorrhage in preterm infants by phenobarbitone:a controlled trial,Lancet,1981,2:215-217.
35 Postnatal Changes in Cerebral Oxygen Extraction in the Preterm Infant Are Associated with Intraventricular Hemorrhage and Hemorrhagic Parenchymal Infarction but Not Periventricular Leukomalacia Pediatr Res 2004,56:111-116.
36 Perry EH,Bada HS,Ray JD,et al.Blood pressure increases birth-weight-dependent stability boundary,and Intraventricular hemorrhage. Pediatrics,1990,85:727-732.
37 黄海娟 邵肖梅 早产儿脑血流自主调节功能的研究。新生儿科杂志,2003,18：156-159.
38 Roloff, DW.Hyperoxemia and increased mortality in prematures. Pediatr Res,1977,11:578.
39 N ijima S, Sho rtland DB, L eveneM I, et al. Arch Dis Child,1988; 63:1126-1130.
40 Brus F, Van O, Okken A, et al. Number and activation of circulating polymorphonuclear leukocytes and platelets are associated with neonatal respiratory distress syndrome severity.Pediatrics,1997,99:672-680.
41 Koheltet D, Perlman M, Hanna G, et al.Reduced platelet counts in neonatal respiratorydistress syndrome. Biol Neonate,1990,39:456-463.
42 Kohlhauser C,Bernert G,Hermn M,et al.Effect of endotracheal suctioning in high-frequency oscillatory and conventionally ventilated low birth weight neonates on cerebral hemodynamics observd by near infrared spectroscopy (NIRS).pediatr Pulmonol.2000,29:270-275.
2 Papile LA, Burstein, Burstein R, et al. Incidence and evaluation of subependymal and intraventricul hemorrhage:a study of infants with birth weight less than 1500g[J]. Pediatr, 1978,92:529.
3 Owens R. Intraventricular hemorrhage in the p remature neonate.[J]. Neonatal Netw,2005,24(3):55-71.
4 Antoniuk S, da Silva RV. Periventricular and intraventricular hemorrhage in the premature infants.[J]. Rev Neurol,2000,31 (3):238-243.
5 陈惠金,我国早产儿脑室内出血的早期诊断和防治现状.临床儿科杂志,2004,22(1)：3
6 Hassan Kadri, Alhakam A. Mawla, Jehad Kazah. The incidence, timing, and predisposing factors of germinal matrix and intraventricular hemorrhage (GMH/IVH) in preterm neonates. Childs Nerv Syst,2006,22:1086-1090.
7 Vural M,Yilmaz I,Ilikkan B, et al.Intraventricular hemorrhage in preterm newborns:Risk factors and results from a University Hospital in Istanbul,8 years after.Pediatrics International, 2007,49:341-344.
8 吴香兰,卢光进,叶贞志等,机械通气下极低出生体重儿颅内出血相关因素分析.中国妇幼保健,2006,21：1951-1953
9 Kaise JR,Gauss CH, Pont MM, et al. Hypercspnia during the first 3 days of life is associated with severe intraventricular hemorrhage in very low birth weight infants. J Perinatol,2006, 26:279-285.
10 Burgess GH,Oh W.Effects of phenobarbital on cerebral blood flow velocity after endotracheal suctioning in premature neonates.Arch Pediatr Adolesc Med,2001,155:723-727.
11 Fabres J, Carlo WA, Phillips V, Howard G, Ambalavanan N.Both extremes of arterial carbon dioxide pressure and the magnitude of fluctuations in arterial carbon dioxide pressure are associated with severe intraventricular hemorrhage in preterm infants. Pediatrics. 2007,119:299-305.
12 Woodgate PG, Davies M W. Perm issive hypercapnia for the prevention of m orbidity and m ortality in m echanically ventilated newborn infants. Cochrane Database Syst Rev,2001, (2):CD0O2O61.
13 陈惠金.早产儿脑室周围白质软化的研究进展[J].实用儿科临床杂志,2004,19：83-86.
14 Silveira RC, Procianoy RS, Dill JC, da Costa CS. Periventricular leukomalacia in very low birth weight preterm neonates with high risk for neonatal sepsis. J Pediatr.2008,84:211-216.
15 Greisen G, Vannueei RC. Is periventrieular leucom alacia a result of hypoxic-isehaemie injury? Hypocapnia and the preterm brain. Biol Neonate,2001,79:194-200.
16 Christina Giannakopoulou, Eftichia Korakaki, Antonia Manoura,et al. Significance of hypocarbia in the development of periventricular leukomalacia in preterm infants.Pediatrics international,2004,46:268-273.
17 Fujimoto S, Togari H。 Yamaguchi N, et al. Hypocarbia and cystic eriventricular leukomalaeia in preterm infants [J]. Arch Dis Child.1994,71:1F107-110.
18 MuraseM, Ishida A. Early hypocarbia of p reterm infants:its relationship to periventricular leukomalacia and cerebral palsy, and its perinatal risk factors[J]. Acta Paedia,2005, 94(1):85-91.
19 Christina Giannakopoulou, Eftichia Korakaki, Antonia Manoura,et al. Significance of hypocarbia in the development of periventricular leukomalacia in preterm infants.Pediatrics international,2004,46:268-273.
20 刁敬军,明秀芬,张军等,机械通气早产儿脑室周围白质软化危险因素分析.中国当代儿科杂志,2005,7(2)：174-175
1 Thomas DB, Burnard ED.Prevention of intraventricular haemorrhage in babies receiving artificial ventilation.Med J Aust.1973 May 12,1:933-936.
2 Welin AK, SandbergM, Lindblom A, et al. White matter injury following prolonged free radical formation in the 0.65 gestation fetal sheepbrain[J]. Pediatr Res,2005,58:100-105.
3 Ollins MP,Lorenz JM,Jetton JR, et al. Hypocaapnia and other ventilation-related risk factors for cerebral palsy in loe birth weight infants.Pediatr Res,2001,50:712-719.
4 Luyt K,Wright D,Baumer JH,Randomised study comparing extent of hypocarbia in preterm infants during conventional and patient triggered.Arch Dis Child Fetal Neonatal ED,1996,74:F63-69.
5 Greisen G, Vannueei RC. Is periventrieular leucom alacia a result of hypoxic-isehaemie injury? Hypocapnia and the preterm brain. Biol Neonate,2001,79:194-200.
6 Vannucci RC, Towfighi J, Heitjan DF, Brucklacher RM.Carbon dioxide protects the perinatal brain from hypoxicischemic damage:an experimental study in the immature rat. Pediatrics 1995,95:868-874.
7 Fritz KI,Ashraf QM,Mishra OP,et al.Effect of moderate hypocapnic ventilation on nuclear DNA fragmentation and energy metabolism in the cerebral cortex of new piglets.Pediat Res,2001,50:586-589.
8 Klinger G, Beyene J, Shah P, et al. Do hyperoxaemia and hypocapnia add to the risk of brain injury after intrapartum asphyxia? ArchDis Child Fetal Neonatal Ed,2005,90:49-52.
9 Gleason CA, Short BL. Jones MD. Cerebral blood flow and metabo lism during and after prolonged hypocapnia in newborn lamb.J Pediatr,1989,115:309-314.
10 Graziani LJ, Spitzer AR, Mitchell DG, Mechanical ventilation in preterm infants: neurosonographic and developmental studies. Pediatrics.1992;90:515-522
11 Fujimoto S, Togari H。Yamaguchi N, et al. Hypocarbia and cystic eriventricular leukomalaeia in preterm infants [J]. Arch Dis Child.1994,71:1F107-110.
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