选择性头部亚低温治疗新生儿缺氧缺血性脑病临床多中心研究疗效阶段性分析

目的：通过临床多中心随机对照研究观察选择性头部亚低温治疗新生儿HIE的有效性。方法：收集2002年5月至2004年11月30日之前入选的至今已经完成18个月随访的新生儿HIE患儿共187（低温组104例，对照组83例）例进行初步疗效分析。低温组生后6h以内开始选择性头部低温联合全身轻度低温治疗，维持鼻咽部温度34±0.2℃，直肠温度维持在34.5℃以上；持续72h，然后自然复温。常温组维持直肠温度在36～37.5℃之间。生后 18个月进行神经发育评估（Gesell，s Development Diagnosis），主要观察严重伤残的发生率和死亡率。患儿存在脑瘫或智力发育迟滞中的任何一项定义为严重伤残。结果：187例中共失访30例（16％），实际有效病例157例（低温组88例，常温组69例）。低温组和常温组死亡和严重伤残的联合发生率分别为31.8％和50.7％（odds ratio：0.45，95％ CI 0.23－0.86，P=0.02）；其中死亡率分别为20.5％和31.9％（odds ratio：0.54，95％ CI 0.26－1.11，P=0.10）；严重伤残率分别为14.3％和27.7％（odda ratio：0.43，95％ CI 0.17－1.11，P=0.07）。进一步分析亚低温对不同严重程度的HIE的治疗效果，在中度HIE患儿中，低温治疗组死亡和严重伤残的联合发生率为24.2％，较对照组（52％）显著降低，(odds ratia:0.29,95% CI 0.10-0.9, P=0.03)；重度HIE患儿低温组和对照组的死亡和严重伤残的联合发生率分别为为55.6％和73.3％（P=0.13）。结论：选择性头部低温联合全身轻度低温72小时，可以显著降低HIE新生儿严重伤残率的发生,尤其是中度HIE患儿。     

选择性头部亚低温治疗新生儿缺氧缺血性脑病临床研究

目的 研究选择性头部亚低温(SHC)治疗新生儿缺氧缺血性脑病(HIE)的安全性及临床疗效.方法 收集新生儿重度HIE共54例,至入院96h有效病例41例,随机分为SHC组(n=21)和对照组(n=20).SHC组患儿生后6 h内开始给予SHC治疗,鼻咽部温度维持在(34.0±0.2)℃,直肠温度维持>34.5℃,持续72 h,然后自然复温;对照组患儿直肠温度维持36.0～37.5℃.两组均进行心电图、血压、经皮氧饱和度、鼻咽部温度和直肠温度监测.观察主要不良反应包括:严重心律失常、静脉血栓或出血、难以纠正的低血压.疗效观察指标包括:18个月时严重伤残发生率和病死率,智能测验运动发育指数及认知发育指数.结果 两组均未出现严重心律失常、低血压和肾功能衰竭.至生后18个月随访,共失访6例(14.6%),其中SHC组和对照组的失访率分别为14.3%(3/21)和15.0%(3/20),差异无显著性(P>0.05),实际有效病例SHC组为18例,对照组为17例.SHC组和对照组的死亡和严重伤残联合发生率分别为22.2%(4/18)、52.9%(9/17),差异有显著性(P<0.05).结论 SHC持续72 h治疗新生儿HIE是可行和安全的,可降低神经系统后遗症发生率及严重伤残率.     

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

目的 探讨亚低温联合促红细胞生成素(EPO)对缺氧缺血性脑损伤(HIBD)新生儿的疗效.方法 窒息新生儿65例随机分为联合组(16例)、低温组(24例)及常规组(25例).3组均常规治疗,低温组实施72 h的全身亚低温治疗,联合组在亚低温治疗的同时加用EPO[300 IU/(kg·次),隔日1次,连用6次].并对各组早期(治疗0、12、24、48、72与80 h)的新生儿神经学评分,生后7、14、28 d 的新生儿行为神经测定(NBNA),生后3、6个月智能发育评估(CDCC)及6个月的随访情况进行分析.并对检测结果进行方差分析.结果 联合组治疗24、48、72 与80 h的神经学评分较常规组及治疗前、治疗12 h均显著降低(Pa﹤0.05);生后14、28 d时联合组、低温组NBNA评分均明显高于常规组(Pa﹤0.05);联合与低温组3个月与6个月智力发育指数(MDI)、心理运动发育指数(PDI)均明显高于常规组(Pa﹤0.05);但联合与低温组之间各指标均无显著性差异(Pa >0.05). 结论全身亚低温与EPO的联合应用对HIBD可发挥明显的短期和较长期的保护作用,但与单纯亚低温相比无明显的协同效应.     

Cooling in the real world: Therapeutic hypothermia in hypoxic-ischemic encephalopathy

Background and aimThe benefits of therapeutic hypothermia have not been assessed from the perspective of the neurology clinic. We aimed to report the impact of the implementation of a local regional therapeutic hypothermia program on the neurodevelopmental outcomes of surviving hypoxic-ischemic encephalopathy (HIE) infants who were followed in the neonatal neurology clinic.MethodsRetrospective analysis of term infants referred to the neonatal neurology clinic after having been diagnosed with HIE and meeting eligibility criteria for therapeutic hypothermia between March 1999 and June 2010. Therapeutic hypothermia was implemented in September 2008. Outcome measures were dichotomously defined as: normal or adverse, which included cerebral palsy, global developmental delay, and epilepsy.ResultsThirty infants were included in the pre-therapeutic hypothermia group. Thirty-one infants received therapeutic hypothermia and 27 were adequately followed and included in the post-therapeutic hypothermia group. The frequency of an adverse outcome was significantly higher in the pre-therapeutic hypothermia infants (19/30 [63%] versus 4/27 [15%]; OR = 0.10; 95% CI, 0.03–0.37; P < 0.001). Neonatal clinical seizures were more frequent in the pre-therapeutic hypothermia group (P = 0.012). There were no differences regarding frequency of fetal distress, rate of caesarean sections, Apgar scores, need of resuscitation, cord/initial blood gases, and degrees of encephalopathy between the two groups.ConclusionsThe implementation of a regional therapeutic hypothermia program in our institution has vastly reduced the observed neurological morbidity of surviving HIE infants followed in our neonatal neurology clinic. A similar change in outcomes of infants with HIE can be anticipated by other centers and other clinics adopting this therapy.     

Systemic Candida infections in infants in intensive care nurseries: high incidence of central nervous system involvement

The clinical courses in 27 infants with culture or autopsy evidence of systemic candidiasis were reviewed. Twenty-two infants (group 1) had persistent signs of sepsis and clinical deterioration or died before institution of antifungal therapy. Five infants (group 2) improved markedly before culture results were reported, and recovered without systemic antifungal therapy. Fourteen infants in group 1 (64%) had central nervous system infection. Of four patients in whom CNS involvement was diagnosed only postmortem, antemortem cerebrospinal fluid from three was abnormal despite sterile cultures; no antemortem CSF was obtained in the other. In meningitis caused by susceptible organisms addition of flucytosine sterilized CSF within 5 days, although prior amphotericin monotherapy had been unsuccessful. Of 14 patients in group 1 who received systemic antifungal therapy, only one died with Candida infection. Toxicity from antifungal agents occurred in 11 of 13 successfully treated infants, but was reversible in every case except one by modifying the dosage. Our data indicate that (1) CNS infection is very common in infants with systemic candidiasis, (2) combined flucytosine-amphotericin therapy may facilitate treatment of CNS infection and should be the initial therapy for systemic candidiasis in infants, (3) Gram stains of CSF and urine enhance early diagnosis, (4) isolation of Candida from normally sterile body fluids in high-risk infants should be considered pathogenic and therapy initiated unless the clinical course strongly suggests otherwise, and (5) toxicity from antifungal agents is common but usually reversible.     

Serum S100B and neuron-specific enolase levels in normothermic and hypothermic infants after perinatal asphyxia

Aim: Serum S100B and neuron‐specific enolase (NSE) levels are elevated after perinatal asphyxia, but the influence of hypothermia on these proteins has not been previously reported. The aim of this study was to evaluate the effect of systemic hypothermia on these protein levels after perinatal asphyxia, time course, and association with perinatal factors and neurodevelopmental outcome at 2 years of age. Methods: Serum S100B and NSE levels were measured at fixed time points in asphyxiated infants treated with standard intensive care on hypothermia (HT: n = 13) or normothermia (NT: n = 11). Results: Serum S100B and NSE levels were grossly elevated in both HT and NT groups. Compared with the values at 6 h of age, S100B values decreased over time in both groups (NT: p = 0.002, HT: p = 0.04). Serum S100B values were lower in HT infants compared with those in NT infants (p = 0.047 at 48 h). Serum S100B and NSE values were significantly higher in infants who died or developed severe neurological impairment (S100B, p < 0.05 at all time points; NSE, p = 0.036 at 24 h of age). Conclusion: Both NSE and S100B levels are highly elevated following asphyxia. Serum S100B levels were lower in the HT group and strongly correlated with the neurodevelopmental outcome.     

Effects of hypothermia on NSE and S-100 protein levels in CSF in neonates following hypoxic/ischaemic brain damage

Aim: The aim of the study was to evaluate the effects of hypothermia on neuron‐specific enolase (NSE) and S‐100 protein levels in cerebrospinal fluid (CSF) in neonates with hypoxic/ischaemic encephalopathy (HIE). Methods: Fifty‐one enrolled neonates with HIE were divided into two groups: hypothermia (n = 23) and control (n = 28). NSE and S‐100 protein were measured with immunoradiometric assays. Amino acid neurotransmitters were also measured by reversed‐phase high‐performance liquid chromatography. Neurodevelopmental assessments were performed at 3 and 12 months of age. Results: Neuron‐specific enolase and S‐100 levels were lower, and neurodevelopment outcome was better in the hypothermia group compared with the control group. Among the infants who received hypothermia, CSF NSE and S‐100 were significantly higher in those who developed severe neurological impairment (mental development index or physical development index <70). There were no significant differences between the two groups in amino acid neurotransmitters. Conclusion: These results indicated that hypothermia was associated with decreased CSF NSE and S‐100 level and correlated with neurodevelopmental outcome in infants with HIE.     

Use of plastic bags to prevent hypothermia at birth in preterm infants‐do they work at lower gestations?

Background: Hypothermia at birth is strongly associated with mortality and morbidity in preterm infants. Occlusive wrapping of preterm infants during resuscitation, including polythene bags have been shown to prevent hypothermia.
Objectives: To evaluate the effectiveness of the introduction of polythene bags at resuscitation of infants born below 30 weeks gestation in a large tertiary neonatal centre.
Methods: Retrospective audit of admission temperatures of all infants born below 30 weeks gestation for two years before and two years after the introduction of polythene bags. Hypothermia was defined as admission axillary temperature < 36°C.
Results: A total of 334 eligible infants were born during the study period. Two hundred and fifty-three (75.8%) had admission temperatures recorded. The incidence of hypothermia fell from 25% to 16%(p = 0.098) for the whole group since the introduction of polythene bags. The main reduction in hypothermia was seen in infants born above 28 weeks gestation (19.4% vs. 3.9%, p = 0.017). There was no significant effect in infants born between 28 weeks and 30 weeks (29.3% vs. 24.8%, p = 0.58).
Conclusions Polythene bags are effective in reducing the incidence of hypothermia at admission in infants born below 30 weeks gestation. The benefit in infants born below 28 weeks gestation was only marginal. This is in contrast to previously published studies. This may be related to the comparatively low incidence of hypothermia at the study centre even prior to introduction of polythene bags.     

Intracranial hemorrhage in small-for-gestational-age neonates: comparison with weight-matched appropriate-for-gestational-age infants

In a comparative study of 93 small-for-gestational-age (SGA) infants against 93 weight-matched, appropriate-for-gestational-age (AGA) neonates, the SGA group exhibited a significantly lower incidence of periventricular-intraventricular type intracranial hemorrhage (ICH) at the first ultrasound scan than did the AGA neonates (9/93 vs 21/93; p less than 0.02). This apparent advantage was no longer maintained in later scans of the first week (16/93 vs 27/93; NS), despite the fact that the SGA group were 4 weeks advanced in gestational age and had fewer respiratory problems than the AGA controls. It is prudent, therefore, to follow SGA infants closely for ICH by repeat ultrasound examinations even if the first scan is negative. Evaluation of the subgroup of SGA infants with ICH against the total SGA population revealed lower admission body temperature and Apgar scores, and higher incidence of asphyxia, resuscitation, and mortality. The above observations in SGA infants with ICH and the lack of a similar trend between the AGA infants with ICH and the total AGA population suggest that SGA status, hypothermia, and ICH are interrelated. Hypothermia, therefore, can be used as a convenient marker for the possibility of ICH in low birth weight SGA infants. The authors' data is consistent with the view that hypothermia and ICH are both the consequences of perinatal asphyxia in SGA infants and probably reflect the magnitude of stormy perinatal events.     

Neuroprotection with hypothermia in the newborn with hypoxic-ischaemic encephalopathy. Standard guidelines for its clinical application

Standardisation of hypothermia as a treatment for perinatal hypoxic-ischaemic encephalopathy is supported by current scientific evidence. The following document was prepared by the authors on request of the Spanish Society of Neonatology and is intended to be a guide for the proper implementation of this therapy. We discuss the difficulties that may arise when moving from the strict framework of clinical trials to clinical daily care: early recognition of clinical encephalopathy, inclusion and exclusion criteria, hypothermia during transport, type of hypothermia (selective head or systemic cooling) and side effects of therapy. The availability of hypothermia therapy has changed the prognosis of children with hypoxic-ischaemic encephalopathy and our choices of therapeutic support. In this sense, it is especially important to be aware of the changes in the predictive value of the neurological examination and the electroencephalographic recording in cooled infants. In order to improve neuroprotection with hypothermia we need earlier recognition of to recognise earlier the infants that may benefit from cooling. Biomarkers of brain injury could help us in the selection of these patients. Every single infant treated with hypothermia must be included in a follow up program in order to assess neurodevelopmental outcome.     

Changes in laboratory parameters indicating cell necrosis and organ dysfunction in asphyxiated neonates on moderate systemic hypothermia

AIM: Asphyxia is a major cause of morbidity and mortality in term infants. In addition to cerebral injury other organs are also distressed due to hypoxic-ischaemic insult. Systemic hypothermia has a beneficial effect on brain injury. We tested the impact of hypothermia on hypoxic damage of other internal organs. METHODS: Asphyxiated term neonates (n = 21) were randomised to groups treated with hypothermia (n = 12) and normothermia (n = 9). Hypothermia (33-34 degrees C) was initiated within 6 h of life, and maintained for 72 h. We determined serum transaminase, lactate dehydrogenase, creatine kinase, uric acid, creatinine levels and diuresis during 6, 24, 48 and 72 postnatal hours. RESULTS: Area under curve values of aspartate aminotransferase (ASAT), lactate dehydrogenase (LDH), uric acid and creatinine during the investigated period and alanine aminotransferase (ALAT) value at 72 h were lower in neonates on hypothermia than in those on normothermia. Renal failure and liver impairment affected less hypothermic than normothermic neonates (3/12 vs. 7/9, p = 0.03, 3/12 vs. 6/9 p = 0.08, respectively). Four of the 12 hypothermic and 6 of the 9 normothermic neonates developed multiorgan failure. CONCLUSIONS: These results suggest that systemic hypothermia may protect against cell necrosis and tissue dysfunction of internal organs after neonatal asphyxia.     

选择性头部亚低温治疗新生儿缺氧缺血性脑病

目的探讨选择性头部亚低温对新生儿缺氧缺血性脑病（HIE）的疗效。方法50例中、重度HIE新生儿随机分为治疗组和对照组各25例。对照组予对症支持治疗，治疗组在此基础上予选择性头部亚低温，持续72h。观察治疗后二组头颅B超大脑中动脉阻力指数（RI）和生后5—7d及28dNBNA评分。结果治疗组与对照组比较总有效率48％（12／25例）vs28％（7／25例），中度HIE有效率68．75％（11／16例）vs41．18％（7／17例），重度HIE有效率11．11％（1／9例）vs0。生后3—4d头颅B超大脑中动脉RI〈0．55的患儿，治疗组与对照组比较总有效率13．33％（2／15例）vs0，R10．55～0．80的总有效率100％（10／10例）vs58．33％（7／12例）。结论选择性头部亚低温做为一种脑保护治疗可被用来治疗新生儿HIE；亚低温对中度HIE治疗可能有效。     

NEONATAL MORBIDITY OF S. G. A. INFANTS IN RELATION TO THEIR NUTRITIONAL STATUS AT BIRTH

ABSTRACT. 46 consecutively born term infants with a birthweight ≤ the 2.3 percentile for gestational age were divided into two groups according to their nutritional status at birth quantified by the ponderal index (100 × weight/length³). Though all infants had a ponderal index below the 50th percentile, those with a ponderal index below the 3rd percentile (about half of the study group) were more frequently affected by asphyxia, hypoglycaemia, hypothermia, and hyperviscosity than their more proportionally grown counterparts. On this account the identification of disproportionally grown small-for-gestational age infants by using the ponderal index as a yardstick of the nutritional status at birth, is necessary because they constitute a high-risk group among small-for-gestational age infants.     

晚期早产儿的临床回顾分析

目的 研究晚期早产儿存在的临床问题.方法 回顾性总结我院新生儿病房及新生儿监护病房2007年9月至2008年9月收治的晚期早产儿508例、足月儿1 514例的临床资料.记录低体温、呼吸窘迫、暂时性呼吸增快、低血糖、黄疸、颅内出血的发生率及临床转归.结果 与足月儿相比.晚期早产儿低体温(13.4%vs 0)、低血糖(19.9%vs 3.0%)、呼吸窘迫(38.6%vs 10.8%)、暂时性呼吸增快(31.0%vs 13.1%)、颅内出血(5.1%vs 2.3%)、黄疽(55.0%vs 33.0%)及喂养不耐受(52.4%vs 14.2%)的发生率高,差异有非常显著性(P＜0.01).晚期早产儿接受机械通气、应用肺表面活性物质和经鼻持续气道正压通气呼吸支持的比例高于足月儿(P＜0.05,P＜0.01).晚期早产儿未完成治疗的比例高于足月儿(P＜0.01).结论 晚期早产儿比足月儿存在更多的临床问题,是不应被忽视的高危人群.     

Hypothermia to treat neonatal hypoxic ischemic encephalopathy: systematic review

OBJECTIVES: To systematically review the effectiveness, as determined by survival without moderate to severe neurodevelopmental disability in infancy and childhood, and the safety of hypothermia vs normothermia in neonates with postintrapartum hypoxic-ischemic encephalopathy and to perform subgroup analyses based on severity of encephalopathy (moderate or severe), type of hypothermia (systemic or selective head cooling), and degree of hypothermia (moderate [or=33.6 degrees C]). DATA SOURCES: MEDLINE, EMBASE, CINAHL (Cumulative Index for Nursing and Allied Health Literature), the Cochrane Library, abstracts of annual meetings of the Pediatric Academic Societies, and bibliographies of identified articles. STUDY SELECTION: Randomized and quasi-randomized controlled trials without language restriction were assessed by 2 reviewers independently and discrepancies were resolved by involving a third reviewer. Quality of the trials was assessed on the basis of concealment of allocation, method of randomization, masking of outcome assessment, and completeness of follow-up. INTERVENTION: Systemic or selective head hypothermia compared with normothermia. MAIN OUTCOME MEASURE: Death or moderate to severe neurodevelopmental disability. RESULTS: Eight studies of acceptable quality were included. The combined outcome of death or neurodevelopmental disability in childhood was reduced in infants receiving hypothermia compared with control infants (4 studies including 497 infants; relative risk, 0.76, 95% confidence interval, 0.65-0.88; number needed to treat, 6; 95% confidence interval, 4-14), as were death and moderate to severe neurodevelopmental disability when analyzed separately. Cardiac arrhythmias and thrombocytopenia were more common with hypothermia; however, they were clinically benign. CONCLUSIONS: In neonates with postintrapartum asphyxial hypoxic-ischemic encephalopathy, hypothermia is effective in reducing death and moderate to severe neurodevelopmental disability either in combination or separately and is a safe intervention.     

Cerebral metabolism and regional cerebral blood flow during moderate systemic cooling in newborn piglets

BACKGROUND: Clinical trials of hypothermic therapy in asphyxiated infants have started recently. However, clinical studies have been delayed by the difficulty in selecting infants with a bad neurological prognosis and by the concern regarding adverse effects of hypothermia. The purpose of this study is to examine the effects of systemic cooling on cerebral metabolism (CMR) and the regional cerebral blood flow (rCBF) in newborn piglets. METHODS: The rCBF in the seven parts of the brain were measured with colored microspheres. The blood samples for the measurement of cerebral oxygen consumption (CMRO2) and cerebral glucose consumption (CMRglc) was collected from the umbilical artery and the superior sagittal sinus. RESULTS: Reductions of cerebral cortex temperature to 32 degrees C decreased blood flow in all brain regions. In particular, blood flow in the brainstem decreased more significantly than in any other region. The total cerebral blood flow (CBF), CMRO2 and CMRglc, respectively, decreased to 32.3+/-3.9 mL/100 g per min, 2.8+/-1.0 mLO2/100 g per min and 22+/-12 mmol/100 g per min at 32 degrees C (41, 53 and 46% of the initial value). The CBF decreased in parallel with CMRO2 and CMRglc down to 35 degrees C, but CBF decreased to a greater extent than CMRO2 and CMRglc at below 35 degrees C. CONCLUSIONS: The indication of hypothermic therapy and the degree of cooling have to be performed very carefully. Systemic cooling is especially dangerous for the total asphyxiated infants who might have damage to the brainstem because the blood flow in the brainstem has significantly decreased during hypothermia.     

Combination effect of systemic hypothermia and caspase inhibitor administration against hypoxic-ischemic brain damage in neonatal rats

Caspases are believed to play a key role in the delayed neuronal cell death observed in the rat brain after hypoxic-ischemic (HI) insult. Caspase inhibitors have been developed as antiapoptotic agents. Hippocampal damage after HI insult is strongly related to tissue temperature, and systemic hypothermia has been introduced clinically for brain protection. In this study, we examined the effects of a caspase inhibitor and systemic hypothermia on neuronal protection in the developing rat brain. Postnatal d 7 rat pups were subjected to the Rice model of hypoxia for 1 h. Systemic hypothermia was induced with a water bath at 29 degrees C. Before HI insult, a pan-caspase inhibitor, boc-aspartyl-(OMe)-fluoromethyl-ketone (BAF), was injected into the cerebral ventricle. The ipsilateral hippocampus was subjected to caspase assays and histologic assessment. The HI group at 37 degrees C (HI-37 degrees C) showed a peak of caspase-3 activity 16 h after insult. This activity was significantly reduced in the presence of BAF or hypothermia (HI-29 degrees C group, p < 0.05) or by the combination of HI-29 degrees C + BAF (p < 0.01 versus HI-37 degrees C). The number of neuronal cells in the ipsilateral hippocampal CA1 region in the HI-37 degrees C group was significantly decreased (62.9% versus control). The number of neuronal cells was maintained in the HI-37 degrees C + BAF group (82.7%), the HI-29 degrees C group (78.7%), and the combination group (95.2%) (p < 0.05 versus HI-37 degrees C). A combination of systemic hypothermia and BAF produced a strong protective effect against neuronal damage in the developing rat brain, along with a reduction in caspase-3 activity.     

Hypothermia reduces neurological damage in asphyxiated newborn infants

BACKGROUND: Perinatal asphyxia remains one of the most devastating neurologic processes. There is experimental and clinical evidence that cerebral cooling may suppress the biochemical cascades leading to delayed cerebral damage. OBJECTIVE: To determine if hypothermia started soon after delivery reduces cerebral damage in term infants. DESIGN/METHODS: Retrospective chart analysis with historical controls. Ten asphyxiated newborns treated with hypothermia between October 1998 and October 1999 were compared to 11 asphyxiated newborns admitted from September 1997 to September 1998. Characteristics at birth of infants of the two groups (control and hypothermia) were comparable. After obtaining parental consent, whole-body hypothermia was induced before the 6th hour of life by placing a cold blanket (Polar Air, Augustine Medical Inc., model 600) around the body of the patients. Rectal temperature was maintained between 32 and 34 degrees C for 72 h. Outcome was assessed by neurological evaluation at birth and every 3 months up to the 12th month. Brain MRI was performed in the 2nd month. We had no evidence of severe adverse events related to hypothermia. In the hypothermic group there was a significant (p < 0.05) reduction of major neurologic abnormalities at follow-up and abnormal MRI findings. CONCLUSIONS: Hypothermia appears to be safe. Our results on morphological damage evaluated by brain MRI and neurological outcome are encouraging: randomized controlled trials are needed to confirm this experience.     

头部亚低温对新生儿缺氧缺血性脑病氧化应激损伤和行为神经评分的影响

目的探讨选择性头部亚低温治疗新生儿缺氧缺血性脑病(HIE)对氧化应激损伤及新生儿行为神经评分(NBNA)的影响。方法选择2010年1～12月入住本院新生儿重症监护病房的中、重度HIE患儿,随机分为亚低温治疗组(观察组)和常规治疗组(对照组),分别检测治疗开始后0h、24h、48h、72h、7天外周血清中超氧化物歧化酶(SOD)和丙二醛(MDA)的浓度,比较两组患儿生后7天、14天及28天的NBNA评分。结果两组患儿治疗开始时SOD浓度和MDA浓度比较差异均无统计学意义(P>0.05)。观察组(28例)在治疗后24h、48h、72h血浆SOD浓度分别为(70.2±10.1)u/ml、(86.8±14.9)u/ml、(108.0±16.9)u/ml,明显高于对照组的(61.5±12.4)u/ml、(65.2±11.0)u/ml、(72.0±13.3)u/ml,血浆MDA浓度分别为(5.23±0.71)mmol/L、(4.40±0.62)mmol/L、(4.28±0.50)mmol/L,明显低于对照组的(6.56±0.70)mmol/L、(7.01±0.67)mmol/L、(6.52±0.66)mmol/L,差异有统计学意义(P均<0.05)。治疗7天两组SOD浓度和MDA浓度比较差异无统计学意义(P>0.05)。生后7天两组患儿NBNA评分比较差异无统计学意义(P>0.05),生后14天、28天观察组NBNA评分明显高于对照组,差异有统计学意义(P<0.05)。结论选择性头部亚低温治疗可通过抑制氧自由基的产生及脂质过氧化物反应,减轻脑缺血再灌注后的氧化应激损伤,起到神经保护作用。     

选择性头部亚低温治疗新生儿缺氧缺血性脑病安全性临床多中心研究

目的：尽管小规模的临床研究表明亚低温治疗新生儿缺氧缺血性脑病（hypoxic-ischemic，HIE）是安全的，但仍需大规模的临床多中心的研究进一步证明。本研究目的通过临床多中心研究观察选择性头部亚低温治疗新生儿HIE的安全性。方法：入选标准：生后6 h以内；胎龄 ≥36周，体重≥2 500 g；脐动脉血气分析 pH < 7.0或BE ≤-16 mmol·L-1或生后1 min Apgar评分 ≤ 3并持续到5 min仍然 ≤ 5；生后6 h内出现脑病的临床表现或EEG明显异常。排除标准：严重先天性疾病、合并感染、其他原因导致颅内损伤、严重贫血（Hb < 120 g·L-1）。从2002年5月- 2006年2月共收集246例不同严重程度的新生儿HIE，随机分为治疗组（低温治疗）134例和对照组112例。低温组和常温组各失访17例和12例，故有效病例共217例（低温组117例，对照组100例）。低温组生后6 h内开始选择性头部亚低温治疗，维持鼻咽部温度（34±0.2）℃℃，肛温维持在35℃以上,持续72 h，然后自然复温。常温组维持肛温在36～37.5oC。两组均进行心电、血压、经皮氧饱和度、鼻咽部温度和肛温监测。发现心率失常者进行EEG检测。观察主要不良反应包括：死亡率、严重心律失常、静脉血栓或出血、难以纠正的低血压。低温组72 h时检测肝、肾功能和血常规、血电解质、血糖及血气分析。观察可能出现的其他不良反应。结果：低温组和常温组的死亡率分别为17.9％和25％(P＝0.20)，死亡原因中两组均以重度脑病(低温组和对照组分别为：6.8%和7%，P＝0.96)和呼吸衰竭(低温组和对照组分别为：6.8%和6%，P＝0.8)为主；对照组有1例患者出现室性心律失常和DIC；低温组发生DIC和消化道出血患者各1例；两组均未出现难以纠正的严重低血压和大静脉血栓。低温组和常温组发生严重不良反应的概率分别为 1.7％和2％（P＝1.0）。低温治疗期间心率降低，但仅有4例(3.4%)患儿心率低于80次/分钟；两组之间血压、肝及肾功能、电介质、血生化、血气分析及血常规的变化均无显著性差异。结论：选择性头部亚低温结合全身轻度低温72 h治疗足月新生儿HIE是可行的和安全的。