Permissive hypercapnia to decrease lung injury in ventilated preterm neonates

Lung injury in ventilated premature infants occurs primarily through the mechanism of volutrauma, often due to the combination of high tidal volumes in association with a high end-inspiratory volume and occasionally end-expiratory alveolar collapse. Tolerating a higher level of arterial partial pressure of carbon dioxide (PaCO2) is considered as 'permissive hypercapnia' and when combined with the use of low tidal volumes may reduce volutrauma and lead to improved pulmonary outcomes. Permissive hypercapnia may also protect against hypocapnia-induced brain hypoperfusion and subsequent periventricular leukomalacia. However, extreme hypercapnia may be associated with an increased risk of intracranial hemorrhage. It may therefore be important to avoid large fluctuations in PaCO2 values. Recent randomized clinical trials in preterm infants have demonstrated that mild permissive hypercapnia is safe, but clinical benefits are modest. The optimal PaCO2 goal in clinical practice has not been determined, and the available evidence does not currently support a general recommendation for permissive hypercapnia in preterm infants.     

Permissive hypercapnia in protective lung ventilatory strategies

Hypercapnia has traditionally been avoided in paediatric critical illness; indeed, traditional approaches advocated hypocapnia in a number of disease states. However, recent advances in understanding of the role of excessive tidal stretch has prompted clinicians to avoid high tidal volumes or plateau pressures, and to tolerate the resulting ‘permissive’ hypercapnia. Advances in understanding of the biology of hypercapnia have led to consideration of an active role for hypercapnia in the pathogenesis of inflammation and tissue injury. Newer data suggest that elevated CO₂ may be protective, but in some experimental situations can cause harm. This review assesses the role of ventilatory strategies involving permissive hypercapnia in the management of neonates and children with acute severe respiratory failure. The physiological effects of hypercapnia on the lung and systemic organs are discussed, and evidence from laboratory models of lung and systemic organ injury is considered, demonstrating the potential for hypercapnia to modulate the injury process. The role of permissive hypercapnia in various clinical settings relevant to neonatal and paediatric practice, and the risks and benefits of hypercapnia in specific clinical situations are also considered.     

允许性高碳酸血症通气法治疗急性呼吸窘迫综合征的临床研究

目的 探讨允许性高碳酸血症通气法（PHV）治疗急性呼吸窘迫综合征（ARDS）中的价值。方法 1996年3月～2005年12月收住PICU，符合1994年欧美制订的ARDS诊断标准确诊为ARDS的患儿27例，分为治疗组12例，采用PHV通气，维持PaCO2在45～55mmHg（1mmHg=0．133kPa）之间；对照组15例，常规通气方式。监测机械通气24、48h的呼吸机参数、血气值和氧合指数（PaO2／FiO2，OI），比较两组机械通气时间、并发症、死亡例数。结果 （1）治疗24、48h后，治疗组PIP、PEEP、MAP值显著低于对照组（P〈0．05）；OI、pH及PaO2差异无显著性（P〉0．05），治疗组PaCO2较对照组显著高（P〈0．01）。（2）治疗组机械通气时间较对照组显著减少（P〈0．01）；对照组5例发生气漏较治疗组差异有显著性（P〈0．05）；两组病死率差异无显著性（25％比26．7％，P〉0．05）。结论 PIV法治疗ARDS较传统通气方式可减低并发症、缩短通气时间，病死率无明显降低。     

允许性高碳酸血症通气法治疗新生儿呼吸窘迫综合征

目的探讨允许性高碳酸血症通气法(PHV)在治疗新生儿呼吸窘迫综合征(NRDS)中的价值.方法随机选择两组需机械通气治疗的NRDS病人,对照组(n=25)以传统通气方式治疗,PHV组(n=31)降低PIP、PEEP、MAP等通气条件,允许血气中PaCO2超过正常值,在45～55 mmHg之间,比较两组通气条件、通气过程中血气值及并发症、病死率.结果两组在通气过程中,PaCO2/FiO2及PaCO2无显著性差异(P均＞0.05),而pH值、PaCO2有显著性差异(P＜0.05和P＜0.01),同时PHV组上机时间显著减少(P＜0.05),气漏发生率和病人死亡率均降低(0/12%和12.9%/24%).结论PHV法在治疗NRDS中较传统通气方式能降低并发症的发生率及病死率,具有推广价值.     

Modifiable risk factors for preterm brain injury

In the last decade preterm birth rates have continued to rise hand in hand with improving neonatal care. Unfortunately rates of severe disability have remained static. National benchmarking of key outcomes shows significant variations in adaptation of best practices across United Kingdom (UK). While emerging technologies give us a glimpse of fascinating possibilities, widespread adoption of evidence-based interventions should remain a priority. In this article we have attempted to outline mechanisms of preterm brain injury and identify the most promising strategies currently available to minimize it. Quality improvement strategies (QI) that can help perinatal teams adopt best practices and promising new therapies are discussed.     

Modifiable risk factors for preterm brain injury

The prevalence of preterm birth is increasing globally and it is a leading cause of neurodevelopmental impairment in childhood. Preterm brain injury consists predominantly of: white matter disease, which may be diffuse or cystic and is usually accompanied by grey matter alterations; and haemorrhagic lesions (germinal matrix haemorrhage–intraventricular haemorrhage).The evidence base for neuroprotective strategies has grown in recent years. Antenatal interventions include the use of corticosteroids and magnesium sulphate, and organisation of maternity services so that early postnatal transfer is avoided. Postnatal interventions associated with improved neurological outcome include delayed clamping of the umbilical cord, respiratory management strategies that reduce the incidence of pneumothorax and bronchopulmonary dysplasia, avoidance of hypotension and hypocarbia, feeding practices that promote human milk intake, caffeine therapy, avoidance of early relatively high dose postnatal dexamethasone, and minimising the incidence of postnatal sepsis. In this review, we describe the predominant forms of preterm brain injury in the current era and consider the evidence base for clinical practices designed to reduce brain injury and adverse outcome after preterm birth.     

Inflicted traumatic brain injury: relationship of developmental outcome to severity of injury

Inflicted traumatic brain injury (TBI) is a frequent consequence of physical child abuse in infants and children. Twenty-eight children who were 2-42 months of age when hospitalized for moderate to severe TBI were enrolled in a prospective, longitudinal study of neurobehavioral outcome following acquired brain injury. Relative to a comparison group, the children with inflicted TBI had significant deficits in cognitive, motor and behavioral domains when assessed with the Bayley Scales of Infant Development-II 1 and 3 months after the injury. Nearly half of the injured children showed persisting deficits in attention/arousal, emotional regulation and motor coordination. Greater injury severity, as indicated by lower coma scale scores, longer periods of unconsciousness and the presence of edema/cerebral infarctions was associated with poorer outcomes in all domains.     

Investigating developmental delay/impairment

Pre-school children presenting to developmental paediatric services because of concerns that they are not peer-equivalent is a well recognised clinical scenario, and yet the approach to investigation varies widely. Evaluation depends on thorough history taking, careful clinical examination and astute observation of social and play skills. An investigative pathway needs to be evidence-based but also pragmatic; tailored to the child whilst acknowledging the benefit of validated screening tests. Although the overall positive yield is small, it must not be forgotten that negative test results also have value. Both clinician and parents will be reassured by the exclusion of genetic, metabolic and structural aetiologies in their search for answers. It is increasingly acknowledged that there are more subtle presentations of recognised disorders and the new generation of genetic tests and neurological imaging is allowing earlier and more accurate diagnosis. This may afford opportunities for amelioration of the condition in the affected child, together with more accurate genetic counselling for the family and indeed the child themselves. The search for an answer should never stop.     

早产儿404例脑损伤发生率及相关因素分析

目的 调查我院住院早产儿脑损伤发生率及影响因素.方法 对2003年8月至2005年10月我院收治的404例早产儿应用ABR4000S/L B超诊断仪在生后3～7 d内常规进行床边头颅B超检查.结果 150例早产儿存在脑损伤,平均胎龄为(33.27±1.99)周;平均出生体重(1 993±505)g.总的脑室内出血发生率35.2%(142/404),脑室周围白质软化的发生率3.5%(14/404),轻度脑损伤发生率23.5%(95/404),重度脑损伤发生率13.6%(55/404).胎龄越小,体重越低,脑损伤发生率越高,但与颅内出血程度无关.妊高征、宫内窘迫、胎龄、高频振荡通气治疗、出生时窒息、出生体重可使早产儿脑损伤发生率增高.结论 早产儿脑损伤的发生及严重程度与多因素有关,头颅B超可对早产儿脑损伤作出早期诊断,为早期干预提供依据.     

早产儿404例脑损伤发生率及相关因素分析

目的调查我院住院早产儿脑损伤发生率及影响因素。方法对2003年8月至2005年10月我院收治的404例早产儿应用ABR4000S/L B超诊断仪在生后3~7d内常规进行床边头颅B超检查。结果150例早产儿存在脑损伤,平均胎龄为(33·27±1·99)周;平均出生体重(1993±505)g。总的脑室内出血发生率35·2%(142/404),脑室周围白质软化的发生率3·5%(14/404),轻度脑损伤发生率23·5%(95/404),重度脑损伤发生率13·6%(55/404)。胎龄越小,体重越低,脑损伤发生率越高,但与颅内出血程度无关。妊高征、宫内窘迫、胎龄、高频振荡通气治疗、出生时窒息、出生体重可使早产儿脑损伤发生率增高。结论早产儿脑损伤的发生及严重程度与多因素有关,头颅B超可对早产儿脑损伤作出早期诊断,为早期干预提供依据。     

Newborns at high risk for brain injury: the role of the amplitude-integrated electroencephalography

ObjectiveAmplitude-integrated electroencephalography (aEEG) is a simplified bedside neurophysiology tool that has been implemented in the neonatal intensive care unit and studied in an extensive range of clinical applications in the past decade. This critical review aimed to evaluate a variety of clinical applications of aEEG monitoring in diagnosis, clinical management, and prognosis assessment in critically ill neonates.SourcesThe databases of Pubmed, SciELO, Lilacs, and Cochrane, books, and other online resources were consulted, as well as sources of professional experiences.Summary of findingsThe clinical use of aEEG to access real-time brain function, background activity, and utility in seizures detection has been described. A critical review was realized considering the authors’ professional experience. Newborns with hypoxic-ischemic encephalopathy and seizures screening represent the most common studied population. However, several studies have shown interesting applications on preterm infants, newborns with congenital heart disease, and other clinical situations of high risk of injury to the developing brain.ConclusionThe aEEG has shown to be a useful non-invasive bedside monitor that aids in evaluating brain function, background activity, and cyclicity. aEEG findings have also demonstrated good prognostic value in a group of critically ill neonates. The aEEG seizure diagnosis capability has limitations, which have been already well established. The use of neonatal brain monitoring such as aEEG was shown to give valuable information in several high-risk clinical situations.     

Pyruvate administered to newborn rats with insulin-induced hypoglycemic brain injury reduces neuronal death and cognitive impairment

Based on previous studies, we had made a try to administer sodium pyruvate to newborn Wistar rats suffering repetitive and profound hypoglycemia, which can induce brain injury. Fluoro-Jade B was used to marked degenerative neurons 1 day after the third hypoglycemic insult, and Morris water navigation task was performed to assess cognitive function when the rats were 6 weeks old. We found that administration of sodium pyruvate to those rats whose hypoglycemia was terminated by dextrose can reduce neurodegeneration induced by hypoglycemia and improve the cognitive function. Supplementing sodium pyruvate with glucose to terminate severe neonatal hypoglycemia is an effective intervention.     

Prognosis, rehabilitation and outcome after inflicted brain injury in children--a case of professional developmental delay

Reported outcomes after child brain injury are variable, creating difficulties for predicting individual needs and service provision. In the UK, prognosis for children surviving early brain injury is characteristically optimistic. Communication between hospital and community agencies is poor. There is little regard for facilitating optimal recovery, and even less for supporting the child's further learning and development. The problem persists in spite of accumulating clinical and scientific evidence over the last 100 years. The consequences are wide-ranging and detrimental to the physical and mental health of the child and family. The disabled child becomes a progressively handicapped adult. Long-term outcome in old age may be unnecessarily compromised. The social and economic costs will be correspondingly and unnecessarily high.     

Growth impairment in children treated for brain tumours.

Growth and growth hormone (GH) secretion were studied in 14 children with brain tumours before radiation and chemotherapy and at various time intervals afterwards. The peak GH response to hypoglycaemia was normal in all patients before radiation. In 6 patients the peak GH response was impaired 1 year after radiation, and in a seventh it was normal at 1 year but impaired 2 years after radiation. In 12 of 13 patients the growth velocity during the first year of chemotherapy was below the 3rd centile, although none of these had an initial standing height below the 3rd centile. Thus it appears that poor growth in such children occurs irrespective of whether radiation-induced GH deficiency develops. The cause of this impaired growth is unknown.