Adrenocortical responsiveness in neonates weaned from the ventilator with dexamethasone

Adrenocortical responsiveness was assessed in eight very low birthweight neonates who had bronchopulmonary dysplasia and had been weaned from mechanical ventilation using dexamethasone. Three of the eight infants did not respond to ACTH stimulation during the first week after cessation of dexamethasone, but all three responded normally when retested at least 1 month later. The present authors have thus demonstrated that some infants have at least temporary adrenocortical unresponsiveness after prolonged courses of glucocorticoid therapy, and suggest that adrenocortical function should be assessed in all infants who are weaned from mechanical ventilation using dexamethasone.     

Dexamethasone therapy in bronchopulmonary dysplasia

Dexamethasone has recently been introduced for the treatment of bronchopulmonary dysplasia (BPD). Whereas the short-term effect of dexamethasone has been documented in previous publications, studies on the long-term effect do not appear to exist in the literature. The aim of this retrospective study was to investigate the influence of dexamethasone on respiratory parameters, the long-term efficacy, and the side-effects. Dexamethasone was given to premature babies with BPD who could not be weaned from the respirator. Twelve infants were included in this study. The gestational ages ranged from 26 to 30 weeks and the birth weights ranged from 640 to 1410 g. Dexamethasone treatment was initiated at the age of 14 to 44 days. After 6 days of dexamethasone therapy, ventilation rates and FiO2 values improved significantly. All infants were successfully weaned from mechanical ventilation and extubated at 2 to 40 days after the start of dexamethasone therapy. The follow-up for the estimation of the long-term efficacy ranged from 3 to 18 months. Ten out of twelve patients had been weaned permanently from the ventilator; one 12-months-old infant is still respirator-dependent. One patient died at 8 months from BPD. In 5 out of 12 infants we observed a leukocytosis with neither clinical signs nor microbiological signs of an infection. Septicaemia developed in one case and one patient suffered from pneumonia. Arterial hypertension was observed in one infant during dexamethasone therapy. The results suggest that dexamethasone facilitates the weaning of preterm infants with BPD from the ventilator. This treatment may prevent some infants from long-term ventilation.     

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??Postnatal glucocorticoid is an effective therapy for preventing or treating bronchopulmonary dysplasia??BPD?? among extremely preterm infants??but the side-effect profile limits its use and makes it an unacceptable option for many patients. Early low-dose hydrocortisone therapy may be beneficial to premature infants with intrauterine chorioamnionitis??but concerns remain about possible adverse effects such as gastrointestinal perforation. Late??after the first week of life?? postnatal steroids may have a better benefit-to-harm ratio than early steroids. Postnatal dexamethasone??DEX?? in 2-3 weeks after birth should mainly be reserved for infants who cannot be weaned from mechanical ventilation and the dose and duration should be kept to a minimum. However??early inhalation of budesonide or intratracheal instillation of budesonide using surfactant as a vehicle can reduce the incidence of BPD??but its safety needs further evaluation. Future studies are required to identify the preferred type??dose and timing of therapy that will provide maximal benefit with minimal side effects.     

Prolonged ventilation and intact survival in very low birth weight infants

A requirement for prolonged ventilation (>28 days) has been associated with a poor outcome in infants. We postulated that in the present population of infants who usually receive antenatal steroids and post-natal surfactant, prolonged ventilation in discrete episodes, i.e. discontinuous intermittent positive pressure ventilation (IPPV), would have a better outcome than a requirement for prolonged ventilation continuously from birth (continuous IPPV) and, in addition, that an abnormal ultrasound scan appearance would be a reliable predictor of poor outcome in infants requiring prolonged ventilation. All very low birth weight (VLBW) infants ventilated for at least 28 days (prolonged ventilation) were identified from a prospectively maintained database. At 1 year of age, neurodevelopmental status was assessed and abnormal neurodevelopmental outcome diagnosed if the infant's Griffiths developmental quotient was at least two standard deviations below the mean and/or they had impairment with disability. Of 417 VLBW infants, 41 required prolonged ventilation (30 continuous and 11 discontinuous). In the continuous IPPV group, 18 and one in the discontinuous IPPV group died or had abnormal neurodevelopmental outcome ( P<0.01). All eight infants with major cranial ultrasound abnormalities died or had abnormal outcome ( P<0.01). CONCLUSION: prolonged ventilation can be associated with intact survival, but not in very low birth weight infants with evidence of significant brain injury.     

Necrotizing tracheobronchitis: a complication of high-frequency ventilation

The tracheobronchial histopathologic findings in eight neonates who died after treatment with high-frequency jet ventilation (HFJV) were compared with those in eight similar infants who died after treatment with conventional mechanical ventilation. The HFJV and conventionally treated groups were matched as closely as possible for birth weight, gestational age, and duration of mechanical ventilation. A 4-point, nine-variable histologic scoring system was used to grade tissue changes in the trachea, carina, and mainstem bronchi. The patients who received HFJV had significantly more histologic damage in their tracheas, carinas, and right and left mainstem bronchi. At all levels of the airway examined, HFJV was associated with more inflammation, greater losses of ciliated epithelium, and more mucus within the lumen of the airway than was conventional mechanical ventilation.     

Apnoea in very low birthweight infants: Outcome at 2 years

Follow-up data to 2 years are reported for 164 of an initial cohort of 172 consecutively, surviving very low birthweight infants. The 13 infants who suffered apnoeic episodes at home were not predicted at discharge from hospital. The mean (s.d.) general developmental quotient at 2 years for the total group was 97.3(12.0), compared with 99.0 (10.2) for the 72 infants who had nil-mild apnoea in the newborn period and 96.0 (13.4) for the 92 infants with moderate-severe apnoea ( P <0.1). All six infants with general quotients <76 had sustained moderate-severe apnoea ( P <0.05). Multivariate analysis to assess the influence of confounding variables showed that the presence of chronic lung disease decreased the general quotient by 4.0 units, birthweight <1000 g 3.3 units, mechanical ventilation 2.2 units and moderate-severe apnoea only 0.1 unit. Moderate-severe apnoea occurred in six of eight babies with neurological handicap and all eight with sensory handicaps ( P <0.01). Overall, of the 12 (7.3%) handicapped children, two had no apnoea and 10 moderate-severe apnoea ( P = 0.07).
Moderate or severe apnoea occurred in 58% of very low birthweight infants and was associated with the smallest and sickest infants who had the most handicaps at 2 years. However, when correction for birthweight <1000 g, mechanical ventilation and chronic lung disease is made, apnoea per se , as it was detected and managed between 1978-80, had no additional deleterious effect on average intellectual performance though it may have been an important causative factor in functional handicap.     

Apnoea in very low birthweight infants: outcome at 2 years

Follow-up data to 2 years are reported for 164 of an initial cohort of 172 consecutively, surviving very low birth-weight infants. The 13 infants who suffered apnoeic episodes at home were not predicted at discharge from hospital. The mean (s.d.) general developmental quotient at 2 years for the total group was 97.3 (12.0), compared with 99.0 (10.2) for the 72 infants who had nil-mild apnoea in the newborn period and 96.0 (13.4) for the 92 infants with moderate-severe apnoea (P less than 0.1). All six infants with general quotients less than 76 had sustained moderate-severe apnoea (P less than 0.05). Multivariate analysis to assess the influence of confounding variables showed that the presence of chronic lung disease decreased the general quotient by 4.0 units, birthweight less than 1000 g 3.3 units, mechanical ventilation 2.2 units and moderate-severe apnoea only 0.1 unit. Moderate-severe apnoea occurred in six of eight babies with neurological handicap and all eight with sensory handicaps (P less than 0.01). Overall, of the 12 (7.3%) handicapped children, two had no apnoea and 10 moderate-severe apnoea (P = 0.07). Moderate or severe apnoea occurred in 58% of very low birthweight infants and was associated with the smallest and sickest infants who had the most handicaps at 2 years. However, when correction for birthweight less than 1000 g, mechanical ventilation and chronic lung disease is made, apnoea per se, as it was detected and managed between 1978-80, had no additional deleterious effect on average intellectual performance though it may have been an important causative factor in functional handicap.     

The use of Dexamethasone in full-term infants with severe respiratory failure and pulmonary barotrauma

Eight full-term infants (mean gestation 39.9 weeks [range 37-42] and mean birthweight 3642 g [range 3060-4200]) with severe respiratory failure (median oxygenation index 28 [range 16-65] and median arterial/alveolar PO2 ratio (a/APO2) 0.094 [range 0.038-0.165]) and pulmonary barotrauma were treated with Dexamethasone, 0.5 mg/kg per day, from the median age of 5 days (range 3-22). Six of the eight (75%) infants survived. They were weaned from mechanical ventilation and extubated a median of 2.5 days after commencing treatment with Dexamethasone. Two infants died and one of them suffered recurrent pneumothoraces. There was a significant improvement in oxygenation in the seven infants who survived the 72 h period of observation. Their median oxygenation index was 24 when Dexamethasone was commenced compared with 8 after 12 h (P less than 0.05) and 10 after 36 h (P less than 0.025). Their a/APO2 ratio was 0.095 when Dexamethasone was commenced compared with 0.289 after 12 h (P less than 0.05) and 0.207 after 36 h (P less than 0.025). There was a significant increase in the infants' arterial mean blood pressure associated with Dexamethasone therapy and one infant developed Staphylococcus aureus septicaemia. In this uncontrolled study of eight full-term infants with severe respiratory failure and pulmonary barotrauma, the use of Dexamethasone was associated with significant improvement in oxygenation and rapid weaning from mechanical ventilation.     

Unexpected hearing loss in high-risk infants

Eleven high-risk infants who had normal auditory brainstem responses at the time of discharge from the neonatal intensive care unit were found on follow-up between 13 and 48 months later to have significant sensorineural hearing loss. All 11 infants were the products of high-risk pregnancies and deliveries. Birth weights ranged from 890 to 3,700 g, but seven had birth weights of more than 1,500 g. Gestational ages ranged from 28 to 42 weeks. The length of hospitalization ranged from 45 to 167 days. All of the infants had respiratory distress, requiring prolonged mechanical ventilation with resultant chronic lung disease. All of the infants had received pancuronium, morphine, ampicillin, and gentamicin, and ten had also received furosemide and chlorothiazide. Other frequent clinical complications included abnormal CNS findings during the neonatal intensive care unit stay (ten infants), acidosis (pH less than 7.25) on the initial blood gas test (eight infants), and persistent fetal circulation in all seven infants with birth weights greater than 1,500 g. Developmentally, eight of nine children tested between 12 and 36 months of age were normal in all respects other than the hearing loss and the related language impairment. We conclude that infants who have been very ill in the newborn period, including term infants, may remain at risk for development of significant sensorineural hearing loss even though they have passed an initial auditory brainstem responses screening test in the newborn period.     

Dexamethasone effects on the hospital course of infants with bronchopulmonary dysplasia who are dependent on artificial ventilation

A randomized double-blind placebo-controlled trial was conducted to evaluate the effects of enterally administered dexamethasone on the hospital course of infants with bronchopulmonary dysplasia. A total of 23 infants with a birth weight less than 1500 g who were dependent on artificial ventilation 3 to 4 weeks of age received dexamethasone (n = 12) or saline placebo (n = 11). Dexamethasone (0.5 mg/kg per day) was given in tapering doses for 7 days followed by hydrocortisone (8 mg/kg per day) which was progressively reduced for a total of 17 days of therapy. Infants who received dexamethasone required less oxygen on days 8 and 17 (P less than .05) and were more likely to extubate 8 days after therapy than infants in the control group (respectively 8/12 vs 3/11 infants, P less than .05; P = .12 after Yates correction). The use of dexamethasone significantly shortened median duration of mechanical ventilation (4 vs 22 days, P less than .05) but had no effect on length of oxygen therapy, hospitalization, home oxygen therapy, occurrence and severity of retinopathy of prematurity, rate of growth, and mortality. No significant complications resulted from dexamethasone therapy. Measurements of plasma dexamethasone levels confirmed the absorption of drug from the gastrointestinal tract (23.7 ng/mL in dexamethasone vs 4.6 ng/mL in the control group, P less than .05). Dexamethasone administration resulted in short-term improvements in pulmonary function but did not ameliorate the hospital course of infants with bronchopulmonary dysplasia.     

Prediction of individual response to postnatal dexamethasone in ventilator dependent preterm infants

AIMS—To evaluate factors predictive of individual response to dexamethasone in preterm infants.
METHODS—A cohort of 74 preterm infants born between January 1993 and February 1996 was studied retrospectively. All of them had received dexamethasone to facilitate weaning from artificial ventilation. Demographic factors, ventilation parameters, and details of dexamethasone administration were recorded from the medical and nursing notes. Radiographs were assessed by one observer who was unaware of the clinical condition of the infant or the outcome. Outcome variables examined included change in ventilation index (VI) at 36-48 hours, the number of days to extubation from the start of dexamethasone, and death before extubation.
RESULTS—Most babies improved but changes in VI at 36-48 hours ranged from substantial deterioration to dramatic improvement. No identifiable factors were significantly associated with this range of response. The median time to extubation was 6 days. The 36 babies who extubated within the first 6 days were: significantly more mature; less likely to have pulmonary interstitial emphysema (PIE) or pneumothorax; and had significantly lower VIs in the 12 hours preceding dexamethasone treatment. The postconceptional age at extubation was the same whether babies were extubated within or after the first 6 days. Multiple linear regression confirmed a significant association between number of days to extubation and the three factors described above (adjusted R²=0.5126).
CONCLUSIONS—Individual responses to dexamethasone can be partly predicted by gestation, the presence of PIE, and the VI before dexamethasone administration.

     

Single course of antenatal steroids did not alter cortisol in preterm infants up to 18 months

Aims: To determine whether a single course of antenatal dexamethasone alters resting cortisol at 3, 8 and 18 months corrected age in preterm infants. Methods: Preterm infants born ≤32 weeks gestational age were recruited during 2001–2004 from a single neonatal intensive care unit. Resting salivary cortisol was collected at least once at 3, 8 and 18 months corrected age in a longitudinal cohort. A mixed‐effects repeated measures analysis was used to accommodate cases with less than complete follow‐up. Results: One hundred and thirty three infants were included in the present study, contributing 266 cortisol samples. Of these, 107 infants had been exposed to a single course of antenatal dexamethasone and 26 not exposed to antenatal steroids. There was no significant main effect of antenatal steroids on resting cortisol at any age. This result was not altered after adjusting for gestational age at birth, neonatal cumulative pain, morphine exposure, mechanical ventilation days and post‐natal steroid exposure. Conclusions: No effect of a single course of dexamethasone on resting salivary cortisol, an indicator of hypothalamic‐pituitary‐adrenal axis function, was found in infancy up to 18 months corrected age in infants born very preterm.     

The effects of preterm delivery and mechanical ventilation on human lung growth

The effects of preterm birth and mechanical ventilation on growth of the alveolar region of the lung were assessed by morphometric and/or quantitative biochemical methods in the lungs from 104 perinatal and infant autopsies. The lungs of 4 preterm infants who died at 4-16 weeks age without having received mechanical ventilation were large relative to body weight but showed normal alveolar number and alveolar surface area. Infants treated by mechanical ventilation for hyaline membrane disease (HMD) and who died at ages from 1 week up to 14 months showed impairment in alveolar development evidenced by low alveolar number and a low alveolar surface area. Lung volume and total lung DNA values were relatively normal. Dilated alveolar ducts were a feature at all ages with emphysematous changes apparent in the longest surviving infants. Biochemical features included a high concentration of hydroxyproline, reflecting collagen, and a high desmosine concentration, reflecting elastin, in infants dying at less than 60 weeks postconceptional age. Changes in the lungs of infants ventilated at low pressures for conditions other than HMD were of a similar nature but less severe than those seen in the HMD group. These findings indicate that preterm birth alone may have little adverse influence on lung development but that conditions necessitating mechanical ventilation may lead to permanent impairment in alveolar development. We postulate that the standard technique of applying positive pressure ventilation may itself lead to impaired alveolar growth, although the effect is enhanced by concomitant HMD and BPD.     

Rapid increase of blood pressure in extremely low birth weight infants after a single dose of dexamethasone

Blood pressure was retrospectively studied in all 22 extremely low birth weight infants (ELBW) (birth weight median 720 g, range 450–1020 g) who were admitted between July 1989 and October 1991 and received dexamethasone on days 2–25 (median 10) because of bronchopulmonary dysplasia or since lung function had not improved after installation of bovine surfactant. The average blood pressure during the 4 h before dexamethasone increased significantly (median individual increase 8 mmHg,P=0.0005) until 8–12 h thereafter. In addition to the lung disease, ten infants showed severe arterial hypotension with prolonged capillary refilling time (>3s) and oliguria and needed continuous infusion of epinephrine to increase blood pressure and urinary flow after treatment with colloids, dopamine and dobutamine had proved ineffective. Epinephrine infusion could be stopped in eight infants 8h after dexamethasone administration. In ELBW infants blood pressure rose 8–12 h after a single dose of 0.25 mg/kg dexamethasone. In ELBW infants suffering from arterial hypotension who do not respond to infusion of colloids and catecholamines, dexamethasone may represent a new therapeutic tool.     

Bronchopulmonary dysplasia and pulmonary insufficiency of prematurity. Lack of correlation of outcome with gas exchange abnormalities at 1 month of age

A review of all infants admitted to the two intensive care nurseries in Seattle from July 1, 1980, through Dec 31, 1981, was performed to evaluate the outcome of infants still requiring supplemental oxygen and/or mechanical ventilation at 1 month of age. Sixty-three infants were identified. Fifty-six infants survived to at least 2 years of age, including 11 of 13 in the subgroup of infants requiring 40% or more oxygen at 1 month of age. Eight (14%) of the 56 survivors have required prolonged rehospitalization for pneumonia or other respiratory illnesses in the first two years following birth. We conclude that the degree of gas exchange impairment assessed at 1 month of age does not predict ultimate outcome from neonatal chronic lung disease.     

Outcome at 5-6 years of prematurely born children who received morphine as neonates

AIM—To assess outcome at 5-6 years in a cohort of very preterm infants (<34 weeks of gestation) who had been randomly allocated within a controlled clinical trial to receive morphine or non-morphine treatment in the neonatal period.METHODS—Assessments were made on 87 children at 5-6 years who had been recruited in the neonatal period to two sequential controlled studies (1989-92). Infants requiring mechanical ventilation had been randomly allocated to receive either morphine (n=62) or other (n=33) solutions starting on the first day of life. Each child was seen by a single experienced observer and assessed at 5-6 years using the WPPSI-R, Movement ABC, and the Child Behaviour Checklist. The performance of children exposed to morphine was compared with that of those in the non-morphine group. Blood samples for thyroid stimulating hormone (TSH) measurement were obtained from children whose parents gave consent.RESULTS—There was no significant difference in any of the three test scales between infants in the two groups, but there was a trend towards better performance in all three tests in the morphine group. Assessment of TSH values in a subgroup of the survivors showed no difference in thyroid function between the two groups.CONCLUSION—Exposure to morphine in the neonatal period to facilitate mechanical ventilation does not seem to have any adverse effects on intelligence, motor function, or behaviour when these children are assessed at 5-6 years of age.     

小儿肺血减少性青紫型先天性心脏病呼吸衰竭时的机械通气分析

目的　 探讨小儿肺血减少性青紫型先天性心脏病 (CHD)呼吸衰竭机械通气策略。 方法 　回顾性总结我院 1992 1998年间 12例小儿肺血减少性青紫型CHD合并呼吸衰竭患儿机械通气治疗效果 ,分析通气时机、方法、参数调节及药物治疗等对转归的影响。 结果 　机械通气后SaO2 >7%9例 (占 75 %) ;<70 %3例 ,其中 2例表现通气不足。在SaO2 >85 %的 5例中 ,2例表现通气过度或气压伤。通气时间 1 5h～ 5d。结果 1例顺利撤机 ,1例急诊手术治疗 ,5例死亡。余 5例放弃治疗 ;其中 1例因复苏过晚 ,持续昏迷。 6例TOF静脉应用新福林 ,仅使用最小剂量的 1例顺利撤机。 结论 　常规供氧及药物治疗无效者 ,应及时机械通气 ;通气压力、潮气量及PEEP均不宜过大。适宜的SaO2 ,参考值为 75 %～ 85 %。新福林不宜大剂量长程使用。部分病例需外科紧急干预。     

Controlled trial of dexamethasone in respirator-dependent infants with bronchopulmonary dysplasia

A randomized trial was conducted of dexamethasone therapy in infants with bronchopulmonary dysplasia who were dependent on respirators and were not progressing clinically despite conventional treatment. Babies were admitted to the study if they had a roentgenogram and clinical diagnosis of bronchopulmonary dysplasia, were 2 to 6 weeks in age, weighed less than 1,500 g, had made no progress in weaning for the preceding five days, and were free of sepsis, patent ductus arteriosus, and congenital heart disease, and had had no intravenous fat for at least 24 hours. After parental consent was obtained, infants were randomly assigned to control or treatment groups. The study hypothesis was that with steroid treatment, babies could be weaned from the respirator within 72 hours and would show a significant improvement in lung compliance within that time. Sequential analysis exceeded criterion (P less than .05) when seven consecutive untied pairs showed weaning with dexamethasone and failure to wean in control infants. Pulmonary compliance improved by 64% in the treated group and 5% in the control group (P less than .01). No significant intergroup differences were noted in mortality, length of hospital stay, sepsis, hypertension, hyperglycemia, or electrolyte abnormalities. Study design permits the conclusion that dexamethasone can produce substantial short-term improvement in lung function, often permitting rapid weaning from the respirator, but long-term efficacy and safety must be demonstrated by further investigations.     

Randomised controlled trial of weaning by patient triggered ventilation or conventional ventilatton

A group of preterm infants (n=40) were entered into a randomised controlled trial to compare the duration and efficacy of weaning by patient triggered ventilation (PTV) or conventional ventilation. Once recovery from respiratory distress had begun, enabling the ventilator rate to be reduced to 40 breaths/min, infants were randomised to either regime. Infants randomised to PTV were weaned by reduction in ventilator pressure only, whereas infants randomised to conventional ventilation were weaned by reduction in ventilator rate only. Only one infant required re-ventilation within 24h of extubation: this infant had been weaned by conventional ventilation. Three infants, all of less than 28 weeks gestation, did not tolerate weaning by PTV and were subsequently weaned conventionally. The duration of weaning was analysed according to the original randomisation allocation and was significantly shorter in the PTV group, being a median of 30h (mean 39, range 3–186) compared to a median of 61h (mean 65, range 15–262) in the conventional group,P<0.02. We conclude PTV is the more advantageous form of weaning in preterm infants of greater than 27 weeks gestational age.     

产前地塞米松联合羊膜腔内注射肺泡表面活性物质预防早产儿呼吸窘迫综合征的效果

目的探讨地塞米松联合羊膜腔内注射肺泡表面活性物质(PS)预防新生儿呼吸窘迫综合征(NRDS)的疗效及其安全性。方法早产儿102例分为研究组42例和对照组60例,研究组其母亲产前应用地塞米松6mg肌肉注射,联合羊膜腔内注射PS预防;对照组其母亲产前地塞米松6mg肌肉注射预防。观察二组NRDS发病率、持续呼吸道正压(CPAP)使用率、并发症发生率和病死率或放弃率。结果研究和对照组性别、胎龄、出生体质量及Apgar评分比较均无显著性差异(Pa>0.05)。研究组RDS发生率、CPAP使用率、并发症发生率及病死率与对照组比较均有显著性差异(Pa<0.05)。结论产前地塞米松联合羊膜腔内注射PS可明显减少NRDS的发生率,减少CPAP的使用及并发症的发生,改善患儿预后。