Abstract: BACKGROUND: During synchronized mechanical ventilation, positive airway pressure and spontaneous inspiration coincide. If synchronous ventilation is provoked, adequate gas exchange should be achieved at lower peak airway pressures, potentially reducing baro/volutrauma, air leak and bronchopulmonary dysplasia. Synchronous ventilation can potentially be achieved by manipulation of rate and inspiratory time during conventional ventilation and employment of patient triggered ventilation. OBJECTIVES: To compare the efficacy of: (i) synchronized mechanical ventilation, delivered as high frequency positive pressure ventilation (HFPPV) or patient triggered ventilation - assist control ventilation (ACV) or synchronous intermittent mandatory ventilation (SIMV)) with conventional ventilation (CMV) (ii) different types of triggered ventilation (ACV, SIMV, pressure regulated volume control ventilation (PRVCV) and SIMV plus pressure support (PS) SEARCH STRATEGY: Searches from 1985-2007 of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2007),Oxford Database of Perinatal Trials, MEDLINE, previous reviews, abstracts and symposia proceedings; hand searches of journals in the English language and contact with expert informants. SELECTION CRITERIA: Randomised or quasi-randomised clinical trials comparing synchronized ventilation delivered as high frequency positive pressure ventilation (HFPPV) or triggered ventilation (ACV/SIMV) to conventional mechanical ventilation (CMV) in neonates. Randomised trials comparing different triggered ventilation modes (ACV, SIMV, SIMV plus PS and PRVCV) in neonates. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including mortality, air leaks (pneumothorax or pulmonary interstitial emphysema (PIE)), severe intraventricular haemorrhage (grades 3 and 4), bronchopulmonary dysplasia (BPD) (oxygen dependency beyond 28 days), moderate/severe BPD (oxygen/respiratory support dependency beyond 36 weeks postmenstrual age (PMA) and duration of weaning/ventilation.Four comparisons were made: (i) HFPPV vs. CMV; (ii) ACV/SIMV vs. CMV; (iii) ACV vs. SIMV or PRVCV vs. SIMV (iv) SIMV plus PS vs. SIMV. Data analysis was conducted using relative risk for categorical outcomes, weighted mean difference for outcomes measured on a continuous scale. MAIN RESULTS: Fourteen studies were eligible for inclusion. The meta-analysis demonstrates that HFPPV compared to CMV was associated with a reduction in the risk of air leak (typical relative risk for pneumothorax was 0.69, 95% CI 0.51, 0.93). ACV/SIMV compared to CMV was associated with a shorter duration of ventilation (weighted mean difference -34.8 hours, 95% CI -62.1, -7.4). ACV compared to SIMV was associated with a trend to a shorter duration of weaning (weighted mean difference -42.4 hours, 95% CI -94.4, 9.6). Neither HFPPV nor triggered ventilation was associated with a significant reduction in the incidence of BPD. There was a non-significant trend towards a lower mortality rate using HFPPV vs. CMV and a non-significant trend towards a higher mortality rate using triggered ventilation vs. CMV. No disadvantage of HFPPV or triggered ventilation was noted regarding other outcomes. Since the last review, two new patient triggered modes have been included: pressure regulated volume control ventilation (PRVCV) and SIMV plus pressure support. Each of these methods of ventilation has only been tested in single randomised trials with no significant advantages in important outcomes. AUTHORS' CONCLUSIONS: Compared to conventional ventilation, benefit is demonstrated for both HFPPV and triggered ventilation with regard to a reduction in air leak and a shorter duration of ventilation, respectively. In none of the trials was complex respiratory monitoring undertaken and thus it is not possible to conclude that the mechanism of producing those benefits is by provocation of synchronized ventilation. Further trials are needed to determine whether synchronized ventilation is associated with other benefits, but optimisation of trigger and ventilator design with respect to respiratory diagnosis is encouraged before embarking on further trials. It is essential newer forms of triggered ventilation are tested in adequately powered randomised trials with long-term outcomes before they are incorporated into routine clinical practice.

Abstract: This manuscript reports on two very low birth weight premature infants with respiratory distress, receiving parenteral nutrition and broad-spectrum antibiotics for about 3 weeks, who developed Candida albicans sepsis associated with fungal mycoses and endocarditis, despite treatment with Amphotericin B and Caspofungin. On days 40 and 47, respectively, antifungal therapy was modified to liposomal Amphotericin B combined with Fluconazole 6 mg/kg/day for 4 weeks, resulting in complete resolution of the mycetomas. Our observations suggest that the combination of liposomal Amphotericin B with Fluconazole is able to result in complete resolution of cardiac mycetomas in preterm infants.

Abstract: INTRODUCTION: Chronic oxygen dependency (COD) is a common adverse outcome of very premature birth. It is, therefore, important to develop an accurate and simple predictive test to facilitate targeting of interventions to prevent COD. Our aim was to determine if a simple score based on respiratory support requirements predicted COD development. METHODS: A retrospective study of 136 infants, median gestation age (GA) 28 weeks (range: 23-33 weeks) and a prospective study of 75 infants, median GA 30 weeks (range: 23-32 weeks), were performed. The score was calculated by multiplying the inspired oxygen concentration by the level of respiratory support (mechanical ventilation: 2.5; continuous positive airway pressure: 1.5; nasal cannula or head box oxygen or air: 1.0). Scores were calculated on data from days 2 and 7, and their predictive ability compared to that of the maximum inspired oxygen concentration at those ages and (retrospective study) the results of lung volume measurement. RESULTS: Infants that were oxygen dependent at 28 days and 36 weeks post-menstrual age (PMA) had higher scores on days 2 (p<0.0001, p<0.0001, respectively) and 7 (p<0.0001, p<0.0001, respectively) than the non-oxygen dependent infants in both the retrospective and prospective cohorts. Construction of receiver operator characteristic curves demonstrated the score performed better than the inspired oxygen level and lung volume measurement results. A score on day 7 >0.323 had 95% specificity and 78% sensitivity in predicting COD at 28 days, and 80% specificity and 73% sensitivity in predicting COD at 36 weeks PMA. CONCLUSION: Chronic oxygen dependency can be predicted using a simple scoring system.

Abstract: Chronic lung disease (CLD) is a common outcome of neonatal intensive care. To determine whether the results of serial exhaled nitric oxide (eNO) measurements during the perinatal period differed between infants who did and did not develop CLD. In addition, we wished to assess whether eNO results were more predictive of CLD development than lung function test results or readily available clinical data (gestational age and birthweight). The patients were 24 infants with a median gestational age of 27 (range 25-31) weeks. Measurements of eNO levels, functional residual capacity (FRC), and compliance of the respiratory system (CRS) were attempted on postnatal days 1, 3, 5, 7, 14, and 28 days. The 12 infants who developed CLD were of significantly lower birthweight and gestational age than the rest of the cohort; in addition, they had lower median FRC (P < 0.02) and CRS (P < 0.02) results, but not higher eNO levels, in the first week after birth. Construction of receiver operator characteristic (ROC) curves demonstrated that the CRS and FRC results on Day 3 were the best predictors of CLD development; the areas under the ROC curves were 0.94 and 0.91, respectively. Early lung function test results, but not eNO levels, are useful in predicting CLD development, but are not significantly better than birthweight.

Abstract: BACKGROUND/PURPOSE: The management of exomphalos is controversial with many centers in the United Kingdom and elsewhere advocating a conservative nonsurgical approach for the larger examples. Nevertheless, this approach is not without problems or complication. The aim of the study was to ascertain the outcome of all infants with an antenatally diagnosed exomphalos treated recently at our institution using a policy of aggressive abdominal wall closure. METHODS: This is a retrospective review of all infants with exomphalos treated from January 1995 to September 2002. RESULTS: There were 35 infants, all of whom underwent surgery. These were separated into 3 groups: group A (all exomphalos minor) underwent primary closure (n = 11), group B (exomphalos major) underwent primary closure (n = 13), and group C (exomphalos major) underwent staged closure involving a silo (n = 11). Infants in group C had a lower birth weight (P = .05) and were less mature (P = .06). They required longer periods of ventilation (P < .001), a longer hospital stay (P = .001), and a longer period to achieve full enteral feeds (P < .001). Overall survival was 34 (97%) of 35 infants. One premature infant who was born with a ruptured exomphalos sac (birth weight, 862 g) died of nonsurgical complications (sepsis and respiratory failure) early after the creation of a silo. CONCLUSIONS: An aggressive surgical approach in infants with exomphalos is a safe option resulting in effective abdominal wall closure. This requires a skilled multidisciplinary approach and possibly greater resources than other options.

Abstract:

Abstract: OBJECTIVES: To determine if insensible water loss (IWL) differed between infants exposed or not exposed antenatally to corticosteroids and to explore possible mechanisms for the early postnatal diuresis associated with antenatal steroid exposure. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Level three neonatal intensive care unit. PATIENTS: Ninety six infants, median gestational age 27.5 weeks (range 23-33). MAIN OUTCOME MEASURES: Comparison of the IWL, urine output and osmolality, fluid input, electrolyte imbalance, respiratory illness severity (as assessed by surfactant requirement, maximum peak inspiratory pressure, and inspired oxygen concentration), and cardiovascular status (as assessed by inotrope requirement) between infants with antenatal corticosteroid exposure and gestational age matched controls. RESULTS: The infants exposed to antenatal steroids differed significantly from the controls in having both a lower IWL (p = 0.0135) and a higher urine output (p = 0.0036) on day 1, and fewer developed hyponatraemia (p = 0.027) on day 2. Fewer of those exposed to antenatal steroids required inotropes (p = 0.06), but their respiratory status was similar to that of the controls. CONCLUSIONS: Infants exposed to antenatal corticosteroids have a lower IWL. The results suggest that greater skin maturation, but also better perfusion rather than less severe respiratory status, explains the early diuresis in infants exposed to antenatal steroids.

Abstract: "New" bronchopulmonary dysplasia (BPD) has been suggested to be a maldevelopment sequence with reduced alveolarisation of the lungs; affected infants then would be predicted to have low lung volumes. The aim of this study was to test that hypothesis by comparing the lung volumes of infants who had had mild-moderate BPD with those without BPD of similar postmenstrual age. Lung volumes of 17 infants who had mild-moderate BPD (oxygen dependent beyond 28 days, but not past term) (BPD infants) were compared to those of 17 infants without BPD (non-BPD infants). All were born at less than 33 weeks of gestation and studied at postmenstrual ages of 33 to 39 weeks. Lung volume was assessed by measurement of functional residual capacity (FRC). The BPD infants had lower lung volumes (median 19.1 ml/kg) than the non-BPD infants (median 26.5 ml/kg) (p = 0.0001). The BPD compared to the non-BPD infants were of greater postnatal age (p = 0.0003), born at a lower gestational age (p = 0.0001) and of lighter birthweight (p = 0.0001). Regression analysis, however, demonstrated that lung volume was significantly related to BPD status (p = 0.005), independently of postnatal age, birthweight and gestational age. It is concluded that the lower lung volumes of the infants who had had mild-moderate BPD support the hypothesis that new BPD is associated with poor alveolarisation.

Abstract: Our aim was to determine whether the chest radiograph appearance at 7 days predicted chronic lung disease development (oxygen dependency at 36 weeks post-menstrual age) or death before discharge and if it was a better predictor than readily available clinical data. Two consecutive studies were performed. In both, chest radiographs taken at 7 days for clinical purposes were assessed using a scoring system for the presence of fibrosis/interstitial shadows, cystic elements and hyperinflation and data were collected regarding gestational age, birth weight, use of antenatal steroids and post-natal surfactant and requirement for ventilation at 7 days. Oxygenation indices were calculated in the first study (study A) at 120 h and in the second (study B) at 168 h. In study A, there were 59 infants with a median gestational age of 26 weeks (range 24 to 28 weeks) and in study B, 40 infants with a median gestational age of 27 weeks (range 25-31 weeks). In both studies, infants who developed chronic lung disease had a significantly higher total chest radiograph score, with a higher score for fibrosis/interstitial shadowing than the rest of the cohort. Infants who died before discharge differed significantly from the rest with regard to significantly higher scores for cysts. In both studies, the areas under the receiver operator characteristic curves with regard to prediction of chronic lung disease were higher for the total chest radiograph score compared to those for readily available clinical data. CONCLUSION: In infants who require a chest radiograph for clinical purposes at 7 days, the chest radiograph appearance can facilitate prediction of outcome of infants born very prematurely.

Abstract: BACKGROUND: Infants with severe respiratory failure are frequently transferred to high volume strategy, high frequency oscillation (HFO). Mean airway pressure (MAP) is then elevated, the aim being to open up atelectatic lungs and hence improve gas exchange. AIM: To test the hypothesis that lung volume prior to transfer would predict the response to high volume strategy HFO and identify which factors related to poor outcome (death). METHODS: Lung volume was assessed by measurement of functional residual capacity (FRC) and the response to HFO determined by the change in the alveolar arterial gradient (AaDO2) on transfer from conventional mechanical ventilation (CMV) to the optimal MAP on high volume strategy HFO. PATIENTS: Forty-two infants with a median gestational age of 28 (range 23 to 40) wk were studied. RESULTS: FRC prior to transfer correlated significantly with the change in MAP necessary to optimize oxygenation (p = 0.012), but not the change in AaDO2 in response to HFO. There were no significant differences in the lung volumes of survivors and non-survivors, but those who died were more immature (p = 0.0009) and had a smaller response to HFO (p = 0.035). CONCLUSION: Lung volume prior to transfer to high volume strategy HFO might be helpful to guide oscillatory settings, but is a poor predictor of the response to high volume strategy HFO.

Abstract: Iatrogenic fetal reduction is undertaken to try and improve the outcome of multiple pregnancies by reducing the rate of severe preterm delivery. In twin pregnancies, however, spontaneous death of one of the fetuses is associated with increased risk of cerebral palsy (CP) in the survivor. The aim of this study was to determine whether iatrogenic fetal reduction might also increase the prevalence of CP. The database of a tertiary fetal medicine unit was interrogated to identify women with trichorionic triplet pregnancies who had either given birth to three live infants or two live infants following selective fetal reduction. A questionnaire was sent to the women's general practitioners asking them to report whether any of the children had CP. The results of the questionnaire revealed that the CP prevalence (13.8 per 1000) of 72 children from trichorionic triplet pregnancies reduced to twins by selective termination was similar to that of 111 children from trichorionic triplet pregnancies with no loss (18 per 1000), but the pregnancies with selective termination delivered at a later gestation (P = 0.004). CONCLUSION: a lower cerebral palsy rate might have been expected in the pregnancies with selective termination given that they were delivered at a later gestational age; these data, therefore, emphasise the importance of further investigating the impact of selective reduction on the prevalence of cerebral palsy.

Abstract: BACKGROUND: During synchronized mechanical ventilation, positive airway pressure and spontaneous inspiration coincide. Thus, if synchronous ventilation is provoked, adequate gas exchange should be achieved at lower peak airway pressures, potentially reducing barotrauma and hence airleak and chronic lung disease. Synchronous ventilation can be achieved by manipulation of rate and inspiratory time during conventional ventilation and employment of patient assisted ventilation. OBJECTIVES: To compare (i) the efficacy of synchronized mechanical ventilation, delivered as high frequency positive pressure ventilation or triggered ventilation (patient triggered ventilation (PTV) or synchronous intermittent mandatory ventilation (SIMV)) with conventional ventilation(ii) different types of triggered ventilation SEARCH STRATEGY: Searches from 1985-2004 of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2004), Oxford Database of Perinatal Trials, MEDLINE, previous reviews, abstracts and symposia proceedings; hand searches of journals in the English language and contact with expert informants. SELECTION CRITERIA: Randomized or quasi randomized clinical trials comparing synchronized ventilation delivered as high frequency positive pressure ventilation (HFPPV) or triggered ventilation (PTV/SIMV) to conventional mechanical ventilation (CMV) in neonates. Randomized trials comparing different triggered ventilation modes (PTV and SIMV) in neonates. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including mortality, airleaks (pneumothorax or pulmonary interstitial emphysema (PIE)), severe intracerebral haemorrhage (grades 3 and 4), chronic lung disease (oxygen dependency beyond 28 days) and duration of weaning/ventilation. Three comparisons were made: (i) HFPPV vs CMV; (ii) PTV/SIMV vs CMV; (iii) PTV vs SIMV. Data analysis was conducted using relative risk for categorical outcomes, weighted mean difference for outcomes measured on a continuous scale. MAIN RESULTS: Eleven studies were eligible for inclusion. The meta-analysis demonstrate that HFPPV compared to CMV was associated with a reduction in the risk of airleak (typical relative risk for pneumothorax was 0.69, 95% CI 0.51, 0.93). PTV/SIMV compared to CMV was associated with a shorter duration of ventilation (weighted mean difference -34.8 hours, 95% CI -62.1, -7.4). PTV compared to SIMV was associated with a trend to a shorter duration of weaning (weighted mean difference -42.4 hours, 95% CI -94.4, 9.6). Neither HFPPV nor triggered ventilation was associated with a significant reduction in the incidence of chronic lung disease. There was a non-significant trend towards a lower mortality rate using HFPPV versus CMV, but a non-significant trend towards a higher mortality rate using triggered ventilation versus CMV. No disadvantage of HFPPV or triggered ventilation was noted regarding other outcomes. REVIEWERS' CONCLUSIONS: Compared to conventional ventilation, benefit is demonstrated for both HFPPV and triggered ventilation with regard to a reduction in airleak and a shorter duration of ventilation, respectively. In none of the trials was complex respiratory monitoring undertaken and thus it is not possible to conclude that the mechanism of producing those benefits is by provocation of synchronized ventilation. Further trials are needed to determine whether synchronized ventilation is associated with other benefits, but optimization of trigger and ventilator design with respect to respiratory diagnosis is encouraged before embarking on further trials.

Abstract: Infant diaphragm function may be adversely affected in a variety of disorders and conditions. Key to establishing an accurate diagnosis are appropriate control data. The aim of this study was to determine the effect of maturation on diaphragm function, using a nonvolitional test. Diaphragm function was assessed by measuring the transdiaphragmatic pressure (Pdi) generated by magnetic stimulation of the phrenic nerves. Ballon catheters were positioned in the lower third of the esophagus and stomach. Esophageal (Pes) and gastric (Pgas) pressure changes were measured using differential pressure transducers. The pressure signals were amplified and displayed in real time on a computer (running Labview trade mark software) and Pdi derived by online subtraction of Pes from Pgas. Twenty-nine infants (14 born preterm), at a median gestational age of 37 (range, 25-42) weeks, were studied at a median postconceptional age (PCA) of 39 (range, 32-44) weeks. At time of measurement, none had respiratory problems or were hyperinflated (functional residual capacity ranged from 23-35 mL/kg). The preterm infants had significantly lower transdiaphragmatic pressures responses following median left (4.0, range 2.5-6.8 cmH(2)O vs. 4.8, range 2.8-7.2 cmH(2)O) and median right phrenic nerve stimulation (3.6, range 2.6-4.8 cmH(2)O vs. 4.3, range 2.7-6.8 cmH(2)O) (P < 0.05) than term infants. Following left and right phrenic nerve stimulation, Pdi correlated significantly with gestational age (r = 0.4, P < 0.05, and r = 0.4, P < 0.05, respectively) and PCA (r = 0.37, P = 0.05, and r = 0.56, P < 0.01, respectively). We conclude that gestational age at birth and postconceptional age at time of measurements must be taken into account when interpreting the results of infant diaphragm function tests.

Abstract: Infants with surgically correctable anomalies, abdominal wall defects (AWD) or congenital diaphragmatic hernia (CDH) may have poor postnatal diaphragmatic function, because the low intra-abdominal pressure experienced by such patients in utero could result in impaired diaphragmatic development. Our objective was to compare postoperative diaphragmatic function of infants with CDH or AWD to that of gestational age-matched controls. Diaphragmatic function was assessed by measurement of the transdiaphragmatic pressure and maximum inspiratory pressure at the mouth generated during crying against an occlusion. In addition, the transdiaphragmatic pressure produced by unilateral and/or bilateral magnetic stimulation of the phrenic nerves (TwPdi) was examined. Lung volume was assessed by measurement of functional residual capacity (FRC) using a helium gas dilution technique. Ten infants with CDH, 26 with AWD infants (19 gastroschisis, seven exomphalos), and 36 gestational age-matched controls were studied. Compared with their matched controls, the eight CDH infants with left-sided defects had significantly lower left (p < 0.01) and right (p < 0.05) TwPdi and FRC (p < 0.01), and the gastroschisis infants, but not those with exomphalos, had significantly lower left and right TwPdi (p < 0.05). There were no significant differences in transdiaphragmatic pressure and maximum inspiratory pressure at the mouth between the CDH or AWD infants and the controls. Diaphragmatic function postoperatively is impaired in infants with CDH or gastroschisis.

Abstract: OBJECTIVE: To identify whether the results of assessment of respiratory muscle strength or respiratory load were better predictors of extubation failure in preterm infants than readily available clinical data. PATIENTS: Thirty six infants, median gestational age 31 (range 25-36) weeks and postnatal age 3 (1-14) days; 13 were < 30 weeks of gestational age. METHODS: Respiratory muscle strength was assessed by measurement of maximum inspiratory pressure generated during airway occlusion, and inspiratory load was assessed by measurement of compliance of the respiratory system. RESULTS: Overall, seven infants failed extubation-that is, they required reintubation within 48 hours. These infants were older (p < 0.01), had a lower gestational age (p < 0.01), and generated lower maximum inspiratory pressure (p < 0.05) than the rest of the cohort. Similar results were found in the infants < 30 weeks of gestational age. Overall and in those < 30 weeks of gestational age, gestational age and postnatal age had the largest areas under the receiver operator characteristic curves. CONCLUSION: In very premature infants, low gestational age and older postnatal age are better predictors of extubation failure than assessment of respiratory muscle strength or respiratory load.

Abstract: BACKGROUND: Pediatric orthotopic liver transplantation (OLT) has a low mortality. Some children, however, have an adverse outcome defined as a prolonged ventilatory support requirement and protracted pediatric intensive care unit (PICU) stay. The aim of this study was to determine if that adverse outcome related to the child's condition pre-OLT and/or the development of a pleural effusion or diaphragmatic dysfunction. METHODS: The study included 210 children with a median age at transplantation of 45.5 months (range 0.2-252 months). Fourteen had undergone retransplantation. The duration of ventilatory support (intermittent positive pressure ventilation [IPPV]) and PICU admission and development of a pleural effusion and/or diaphragmatic dysfunction were documented for each child. The patients were divided into three groups according to whether they had acute liver failure (ALF), chronic liver disease at home (CHOM), or chronic liver failure sufficiently ill to be in the hospital awaiting transplantation (CHOSP). RESULTS: The 36 children with ALF were of similar age to the 138 CHOM and 36 CHOSP children but required longer IPPV (P<0.0001) and PICU stay (P<0.0001). Overall, 17 children developed diaphragmatic dysfunction and 138 pleural effusions; affected children required longer IPPV and PICU stay (P<0.01). Regression analysis demonstrated that diaphragmatic dysfunction, but not pleural effusion development, was associated with prolonged ventilation (P<0.01) and protracted PICU stay (P<0.05). Other risk factors were ALF (P<0.01), retransplantation (P<0.01), and young age (P<0.05). CONCLUSION: Diaphragmatic dysfunction adversely influences PICU morbidity after OLT. Early assessment of diaphragmatic function, and if necessary aggressive management, might improve outcome.

Abstract: OBJECTIVE: To determine if differences in respiratory muscle strength could explain any posture related effects on oxygenation in convalescent neonates. METHODS: Infants were examined in three postures: supine, supine with head up tilt of 45 degrees, and prone. A subsequent study was performed to determine the influence of head position in the supine posture. In each posture/head position, oxygen saturation (SaO2) was determined and respiratory muscle strength assessed by measurement of the maximum inspiratory pressure (PIMAX). Patients: Twenty infants, median gestational age 34.5 weeks (range 25-43), and 10 infants, median gestational age 33 weeks (range 30-36), were entered into the first and second study respectively. RESULTS: Oxygenation was higher in the prone and supine with 45 degrees head up tilt postures than in the supine posture (p<0.001), whereas PIMAX was higher in the supine and supine with head up tilt of 45 degrees postures than in the prone posture (p<0.001). Head position did not influence the effect of posture on PIMAX or oxygenation. CONCLUSION: Superior oxygenation in the prone posture in convalescent infants was not explained by greater respiratory muscle strength, as this was superior in the supine posture.

Abstract: BACKGROUND: High frequency oscillation (HFO) is now frequently used as rescue support, but it has been suggested that as many as one-third of survivors have abnormal neurodevelopmental findings at follow-up. OBJECTIVE: To identify risk factors for adverse neurodevelopmental outcome at 1 and 2 years in very prematurely born patients, who, because of severe neonatal respiratory failure, had required transfer to high frequency oscillation (HFO). METHODS: A case control study was performed. Controls were supported by conventional mechanical ventilation (CMV) only and matched to HFO infants for gestational age. At 1 and 2 years, neurodevelopmental status was assessed in both groups. Abnormal neurodevelopmental outcome was diagnosed if infants had impairment with or without disability or a Griffiths developmental quotient of at least two standard deviations below the mean. PATIENTS: Fifty-six infants were studied, median gestation age of 28 weeks (range 23--31). RESULTS: At 2 years of age, a greater proportion of the HFO infants compared to the controls had an abnormal outcome (p<0.05). HFO infants with an abnormal outcome compared to those with a normal outcome had poorer oxygenation prior to transfer to HFO (p=0.05), but did not have a lower initial improvement in oxygenation or longer duration of hypocarbia on HFO. Logistic regression demonstrated adverse outcomes significantly related to HFO use and gestational age in the whole study population and to gestational age in the HFO infants. CONCLUSION: An initial response to HFO does not guarantee normal neurodevelopmental outcome. Rescue HFO in very immature infants should be used cautiously.

Abstract: In very low birth weight (VLBW) infants, colloid infusion is associated with impaired perinatal lung function and increased oxygen dependency duration. The aim of this study was to determine whether perinatal colloid infusion was associated with abnormal neurodevelopmental outcome. All perinatal fluid input (crystalloid and colloid) given to VLBW infants entered into a randomised trial was recorded. At 1 and/or 2 years, the neurodevelopmental status of VLBW infants was routinely assessed. Of 131 survivors, median gestational age 27 weeks (range 23-33 weeks), 95 were seen at follow-up. Nineteen had abnormal neurodevelopmental outcome and differed significantly from the rest of the cohort with regard to their birth weight, magnitude of colloid infusion received and the proportions who had received postnatal steroids, suffered prolonged oxygen dependency or having had intracerebral haemorrhage/periventricular leucomalacia development. Regression analysis demonstrated that only colloid infusion related significantly to abnormal neurodevelopmental outcome independent of other variables. CONCLUSION: These data suggest that colloid infusion should be used with caution in the perinatal period.

Abstract: The aim of this study was to assess the frequency of new abnormalities on routine chest radiographs of ventilated, very low birth weight (VLBW) infants during the acute stage of their illness. Infants were identified who had had at least three daily routine chest radiographs. The appearance of their subsequent radiographs was compared to that obtained on the 1st day of ventilatory support and the timing of new abnormalities (malposition of the endotracheal or nasogastric tube, pulmonary interstitial emphysema, pleural effusion, pulmonary oedema, lobar collapse or consolidation) noted. A total of 100 radiographs were examined from 30 VLBW infants, median gestational age 27 weeks (range 23-32 weeks). New abnormalities were present on the radiographs of 24 infants and on 50% of the radiographs examined. The commonest abnormalities noted were pulmonary interstitial emphysema, collapse and consolidation. Conclusion. Routine daily chest radiographs in mechanically ventilated, very low birth weight infants during the acute stage of their respiratory illness can yield new information important in patient care, new abnormalities being demonstrated in 50% of radiographs examined.

Abstract: BACKGROUND: During synchronized mechanical ventilation, positive airway pressure and spontaneous inspiration coincide. Thus, if synchronous ventilation is provoked, it is likely that adequate gas exchange should be achieved at lower peak airway pressures, reducing barotrauma and hence airleak and chronic lung disease. Synchronous ventilation can be achieved by manipulation of rate and inspiratory time during conventional ventilation and employment of patient assisted ventilation. OBJECTIVES: To compare (i) the efficacy of synchronized mechanical ventilation, delivered as high frequency positive pressure ventilation or triggered ventilation (patient triggered ventilation (PTV) or synchronous intermittent mandatory ventilation (SIMV)) with conventional ventilation (ii) different types of triggered ventilation SEARCH STRATEGY: Searches were made from 1985-2000 of the Oxford Database of Perinatal Trials, Medline (MeSH terms: mechanical ventilation; triggered ventilation; newborn infant); previous reviews, abstracts, symposia proceedings, hand searching of journals in the English language and contacting expert informants. SELECTION CRITERIA: Randomized or quasi randomized clinical trials comparing synchronized ventilation delivered as high frequency positive pressure ventilation (HFPPV) or triggered ventilation (PTV/SIMV) to conventional mechanical ventilation (CMV) in neonates. Randomized trials comparing different triggered ventilation modes (PTV and SIMV) in neonates. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including mortality, airleaks (pneumothorax or pulmonary interstitial emphysema (PIE)), severe intracerebral haemorrhage (grades 3 and 4), chronic lung disease (oxygen dependency beyond 28 days) and duration of weaning/ventilation. Data subdivided into three groups: (i) HFPPV vs CMV; (ii) PTV/SIMV vs CMV; (iii) PTV vs SIMV. Data analysis was conducted according to the standards of the Neonatal Cochrane Review Group. MAIN RESULTS: The meta-analysis demonstrates that HFPPV compared to CMV was associated with a reduction in the risk of airleak (typical relative risk for pneumothorax was 0.69 (95% CI 0.51, 0.93). PTV/SIMV compared to CMV was associated with a shorter duration of ventilation (weighted mean difference -31.8 hours, 95% CI -54.1, -9.6). PTV compared to SIMV was associated with a trend to a shorter duration of weaning (weighted mean difference -42.4 hours, 95% CI -94.4, 9.6). No disadvantage to HFPPV or triggered ventilation was noted regarding other outcomes but neither ventilatory mode was associated with a significant reduction in the incidence of chronic lung disease. REVIEWER'S CONCLUSIONS: Compared to conventional ventilation, benefit is demonstrated for both HFPPV and triggered ventilation with regard to a reduction in airleak and a shorter duration of ventilation respectively. In none of the trials was complex respiratory monitoring undertaken and thus it is not possible to conclude that the mechanism of producing those benefits is by provocation of synchronized ventilation. Further trials are needed to determine whether synchronized ventilation is associated with other benefits but optimization of trigger and ventilator design with respect to respiratory diagnosis is encouraged before embarking on further trials.

Abstract:

Abstract: The performances of two triggering systems using a single neonatal ventilator type (SLE) were compared. Eight infants, gestational age 27-30 wk, were each recorded during two 1-h periods of patient-triggered ventilation (PTVs), one with airway pressure and one with airflow triggering. The airflow trigger had a shorter trigger delay (p < 0.02), higher sensitivity (p < 0.02) and lower asynchrony rate (p < 0.02). Conclusion: In immature infants with mild respiratory distress syndrome using the SLE ventilator with inflation times of 0.3 to 0.36 sec, airflow triggering is more appropriate than airway pressure triggering.

Abstract: The aim of this study was to assess if albumin infusion in hypotensive, preterm infants improved blood pressure (BP), metabolic acidosis and core peripheral temperature difference, indicating that such infants had been hypovolemic. Thirty-seven infants, median gestational age 27 weeks (range 23-34) were studied. Their mean BP, core-peripheral temperature difference, pH and base deficit prior to and post albumin infusion were compared. Albumin infusion was associated with BP elevation (p < 0.01) and a small reduction in the base deficit (p < 0.01), but no significant changes overall in the pH or peripheral core temperature difference. Similar results were seen if only 34 infants less than or equal to 4 days of age treated for their first episode of hypotension were considered, although in that group there was also a modest rise in pH (p < 0.02). These data suggest clinically relevant hypovolemia is uncommon in hypotensive, preterm ventilated infants and hence volume expanders are inappropriate routine first therapy.

Abstract: The aim of this study was to determine the effect of maturation on diaphragmatic function. In addition, we investigated whether noninvasive assessment yielded similar results to invasive measurement. Twenty-eight infants, median gestational age (GA) 35.5 wk (range, 25 to 42 wk) and postconceptional age (PCA), 37.6 wk (range, 32 to 44 wk), were examined. Diaphragmatic function was assessed by measuring the maximal transdiaphragmatic pressure during crying (cPdi) using balloon catheters in the midesophagus (Pes) and the stomach (Pgas). In 14 of the infants, a noninvasive measurement of inspiratory muscle strength, maximal inspiratory pressure (PImax), was also made. cPdi and PImax were recorded during a crying effort with the airway occluded at end-expiration. The median cPdi and Pes during crying (cPes), but not Pgas during crying (cPgas), were significantly lower in those studied at a PCA of less than term compared with those studied at an older age (p < 0.05). cPdi and cPes, but not cPgas, correlated significantly with PCA (r = 0.44, p < 0.02; r = 0.43, p < 0.03; respectively) and gestational age (r = 0.46, p < 0.02 and r = 0.56, p < 0.01; respectively). In the 14 infants, the median PImax was lower, but it correlated significantly with cPdi (r = 0.79, p < 0.01). We conclude maturation does affect diaphragm function, and PImax may provide a noninvasive index of diaphragm strength.

Abstract: Thymic hyperplasia, although not a rare condition in infancy, is usually asymptomatic. We describe an infant presenting in the perinatal period with marked tachypnoea. An enlarged thymus, demonstrated on chest radiograph and CT, was associated with small-volume, non-compliant lungs. Other causes of pulmonary malfunction and maldevelopment were excluded. CONCLUSION: Thymic enlargement is unusually associated with neonatal respiratory distress but should be considered in the differential diagnosis.

Abstract: The aim of this study was to assess if continuous positive airways pressure (CPAP) delivered by an infant flow driver (IFD) was a more effective method of improving lung function than delivering CPAP by a single nasal prong. A total of 36 infants (median gestational age 29 weeks, range 25-35 weeks) were studied, 12 who received CPAP via an IFD, 12 who received CPAP via a single nasal prong and 12 without CPAP. CPAP was administered post extubation if apnoeas and bradycardias or a respiratory acidosis developed or electively if the infant was of birth weight <1.0 kg. Lung function was assessed by the supplementary oxygen requirement and measurement of compliance of the respiratory system using an occlusion technique. Assessments were made immediately prior to and after 24 h of CPAP administration and at similar postnatal ages in the non-CPAP group. The infants who did not require CPAP had better lung function (non significant) than the other two groups before they received CPAP. After 24 h, lung function had improved in both CPAP groups to the level of the non CPAP infants. The supplementary oxygen requirements of all three groups decreased over the 24 h period, but this only reached significance in the single nasal prong group (P<0.05). Four infants supported by the IFD, but none with a single nasal prong, became hyperoxic. CONCLUSION: Continuous positive airways pressure administration via the infant flow driver appears to offer no short-term advantage over a single nasal prong system when used after extubation in preterm infants.

Abstract: The aim of this study was to compare the results of lung function measurements made before and after extubation and ventilator settings recorded immediately prior to extubation with regard to their ability to predict extubation success in mechanically ventilated, prematurely born infants. Immediately after extubation all infants were nursed in an appropriate amount of humidified oxygen bled into a headbox. Functional residual capacity, spontaneous tidal volume and compliance of the respiratory system were measured both within 4 h before and within 24 h after extubation. The peak inspiratory pressure and inspired oxygen concentration immediately prior to extubation were recorded. The results were related to extubation failure: requirement for continuous positive airways pressure or re-ventilation within 48 h of extubation. A total of 30 infants, median gestational age 29 weeks (range 25-33 weeks) were studied at a median postnatal age of 3 days (range 1-6 days). Extubation failed in ten infants, who differed significantly from the rest of the cohort with regard to their post extubation functional residual capacity (FRC) (median 23, range 15.6-28.7 ml/kg versus 28.6, range 18.1-39.2 ml/kg, P<0.01) and their requirement for a higher inspired oxygen concentration post extubation (median 0.30, range 0.21-0.40 versus 0.22, range 0.21-0.36, P<0.05). An FRC of less than 26 ml/kg post extubation had the highest positive predictive value in predicting extubation failure. CONCLUSION: A low lung volume performed best in predicting extubation failure when compared to the results of other lung function measurements and commonly used 'clinical' indices, i.e. ventilator settings. A low gestational age, however, was a better predictor of extubation failure than a low lung volume.

Abstract: The aim of this study was to determine whether fluid restriction does indeed significantly increase acute adverse effects. One-hundred-and-sixty-eight ventilated infants, median gestational age 27 wk (range 23-33) and birthweight 953 g (range 486-1500), entered into a randomized controlled trial of two fluid regimes. Infants on regime A were to be prescribed 60 ml/kg of fluids on day 1 which was gradually increased over the first week to 150 ml/kg, infants on fluid regime B were to be prescribed approximately 20% less fluid over the first week. Daily fluid input and output were recorded. Serum electrolytes, bilirubin, creatinine and urine osmolalities were measured daily. Arginine vasopressin levels were assessed on days 1, 3 and 5. Episodes of jaundice, hypoglycaemia and hypotension requiring treatment were noted. Infants on regime B actually received overall 11% and, in the first 4 days, 19% less fluid than those on regime A (p < 0.001). There were no statistically significant differences in the occurrence of episodes of jaundice, hypotension, hypoglycaemia, hypernatraemia or hyponatraemia between infants on the two regimes. Although the infants on regime B had significantly higher urine osmolalities and lower urine output for most of the perinatal period, their median creatinine and arginine vasopressin levels did not differ significantly from those on regime A. We conclude that fluid restriction to less than 90% of usual maintenance fluids is not associated with an excess of acute adverse effects.

Abstract: Chronic oxygen dependency (COD) is a common sequela to very premature birth. Steroid therapy may reduce COD if given within the first 2 weeks, but has important side effects. It is, therefore, crucial to identify an accurate predictor of COD and hence only expose high-risk infants to intervention therapy. The aim of this study was to determine if, within 48 hr of birth, abnormal lung function predicted COD and whether such results performed better than readily available clinical data. Results from 100 consecutive, very low birth-weight infants, median gestation age 28 weeks (range, 24-33), who were ventilated within 6 hr of birth and survived beyond 36 weeks postconceptional age (PCA), were analyzed. Lung volume was assessed by measurement of functional residual capacity (FRC) using a helium gas dilution technique, and compliance was measured using either a passive inflation or an occlusion technique. The maximum peak inflating pressure and inspired oxygen concentration within the first 48 hr were recorded. The infants who remained oxygen-dependent beyond 28 days (n = 58) and 36 weeks PCA (n = 24) differed from the rest in being more immature (P < 0.001), more had a patent ductus arteriosus, and they had both a lower median lung volume (P < 0.001) and lower compliance (P < 0.01) on day 2. An FRC <19 mL/kg and a low gestational age were the most accurate predictors of COD at 28 days. An FRC <19 mL/kg on day 2 remained the best predictor of COD beyond 28 days if only the 50 infants whose gestational age was < or = 28 weeks were considered. We conclude that demonstration of a low lung volume in the first 48 hr helps to identify infants who might benefit from therapy aimed at preventing COD.

Abstract: BACKGROUND/PURPOSE: Pulmonary hypoplasia is a major cause of mortality and morbidity in infants with congenital diaphragmatic hernia (CDH). Pulmonary hypoplasia is characterized by low volume lungs, and affected infants are likely to have a low lung area on their chest radiograph. The authors assessed whether, in CDH infants, computer-assisted analysis of the chest radiograph lung area gave an accurate indication of lung volume, and if a low lung area was a better predictor of poor outcome (death or oxygen dependency at 28 days) than other test results. METHODS: Comparisons were made of the radiographic lung area derived by computer-assisted analysis and lung volume, assessed by measurement of functional residual capacity (FRC) on day 1 before surgical intervention and on the first postoperative day. Compliance was measured, and the maximum and modified ventilation indices and maximum Paco2 also was noted. Twenty-five CDH infants with a median gestational age of 38 weeks were studied; 18 had FRC measurements preoperatively. RESULTS: Both preoperatively and postoperatively, the lung areas and FRCs correlated significantly (r = 0.51, P<.05; r = 0.76, P<.02, respectively). Eleven infants had a poor outcome (5 infants died without an operation); that group preoperatively differed significantly from those with a good outcome with respect to having a lower compliance (P<.02) and higher maximum ventilation index (P<.01) and maximum modified ventilation index (P<.05). Only postoperatively did infants with a poor outcome versus good outcome have a significantly lower lung area (P<.05); they also had a lower increase in lung area preoperatively to postoperatively (P<.01). Receiver operator characteristic curves were constructed; comparison of the areas under the curves showed that preoperatively, a low compliance and high ventilation index were the best predictors of poor outcome. Postoperatively, a low lung area performed as well as the ventilation indices. CONCLUSION: Computer-assisted analysis of the lung area on the chest radiograph is useful in predicting outcome in CDH infants postoperatively but not preoperatively.

Abstract: BACKGROUND: The type 4 phosphodiesterase (PDE) isoenzyme is the main isoenzyme of PDE involved in the control of adult mononuclear cell proliferation. OBJECTIVE: To establish whether PDE isoenzymes are present in umbilical cord blood mononuclear cells by the use of selective PDE inhibitors, and to identify which PDE isoenzymes are involved in controlling the proliferation of cord blood mononuclear cells. METHODS: Cord blood was obtained from normal deliveries and mononuclear cells isolated as described previously [1] with some modifications. Mononuclear cells were then stimulated to proliferate with phytohaemagglutinin (PHA) (2 microg/mL) in the presence of selective PDE inhibitors. Proliferation was measured by [3H]-thymidine incorporation. RESULTS: The type 4 PDE inhibitors (CDP840, rolipram and RO 20-1724), and the mixed PDE3/4 inhibitor, zardaverine, produced a concentration-related inhibition of PHA-stimulated cord blood mononuclear cell proliferation (P < 0.05, ANOVA). The non-selective PDE inhibitor, theophylline, also produced a concentration-related inhibition of proliferation (P < 0.05, ANOVA). In contrast, the PDE1 inhibitor, vinpocetine, the PDE3 inhibitor, siguazodan, and the PDE5 inhibitor, zaprinast, were unable to inhibit cord blood mononuclear cell proliferation. CONCLUSION: PDE4 is present in umbilical cord mononuclear cells and is involved in the control of cord blood mononuclear cell proliferation.

Abstract: Respiratory muscle strength can be assessed by measurement of maximal inspiratory (PIMAX) and maximal expiratory pressure (P(EMAX)) during crying. There are, however, relatively few data on P(IMAX) and P(EMAX) in infancy, particularly from those born preterm. Our aim was to investigate which factors influenced P(IMAX) and P(EMAX) in preterm and term infants. Forty infants, median gestational age 37 weeks (range 26-43) and birthweight 2.579 kg (range 0.956-5.180) were studied at a postconceptional age (PCA) of 38 weeks (range 32-44). None had respiratory problems. A facemask was placed firmly over the infant's mouth and nose and the infant studied during spontaneous crying. A pneumotachograph fitted snugly into the facemask and from a sideport airway pressure changes were measured. During crying, the distal end of the pneumotachograph was occluded for five breaths and at least three separate occlusions were made. The highest P(EMAX) value sustained for at least 1 s and the highest peak inspiratory pressure P(IMAX) were recorded. The mean P(IMAX) and P(EMAX) were higher in the term compared to the preterm infants (70 cmH2O +/-S.D. 19 versus 58 cmH2O +/-S.D. 17 P(IMAX) and 53 cmH2O +/-S.D. 13 versus 44 cmH2O +/-S.D. 19 P(EMAX), P< 0.05). Both P(IMAX) and P(EMAX) related significantly with postconceptional age, gestational age and weight, but not postnatal age. Stepwise regression analysis demonstrated P(IMAX) related independently with PCA and P(EMAX) with weight. These results suggest respiratory muscle strength is influenced by maturation at birth.

Abstract: BACKGROUND: Fluid restriction has been reported to improve survival of infants without chronic lung disease (CLD), but it remains unknown whether it reduces CLD in a population at high risk of CLD routinely exposed to antenatal steroids and postnatal surfactant without increasing other adverse outcomes. AIM: To investigate the impact of fluid restriction on the outcome of ventilated, very low birthweight infants. STUDY DESIGN: A randomised trial of two fluid input levels in the perinatal period was performed. A total of 168 ventilated infants (median gestational age 27 weeks (range 23-33)) were randomly assigned to receive standard volumes of fluid (60 ml/kg on day 1 progressing to 150 ml/kg on day 7) or be restricted to about 80% of standard input. RESULTS: Similar proportions of infants on the two regimens had CLD beyond 28 days (56% v 51%) and 36 weeks post conceptional age (26% v 25%), survived without oxygen dependency at 28 days (31% v 27%) and 36 weeks post conceptional age (58% v 52%), and developed acute renal failure. There were no statistically significant differences between other outcomes, except that fewer of the restricted group (19% v 43%) required postnatal steroids (p < 0.01). In the trial population overall, duration of oxygen dependency related significantly to the colloid (p < 0.01), but not crystalloid, input level; after adjustment for specified covariates, the hazard ratio was 1.07 (95% confidence interval 1.02 to 1.13). CONCLUSIONS: In ventilated, very low birthweight infants, fluid restriction in the perinatal period neither reduces CLD nor increases other adverse outcomes. Colloid infusion, however, is associated with increased duration of oxygen dependency.

Abstract: Arginine vasopressin (AVP) levels on days 1, 3 and 5 and fluid balance in the perinatal period were assessed in 60 infants, median gestational age 27 weeks (range 24-33). Fluid input and output, urine osmolality and episodes of hyponatraemia were recorded on a daily basis. Forty-one infants subsequently developed chronic lung disease (CLD), they were more immature, of lower birthweight and had higher AVP levels on days 3 and 5 (p < 0.05) than the rest of the cohort. Despite similar levels of fluid input, compared to the non-CLD infants, those who developed CLD had higher urine osmolalities on days 1, 5, 6 and 7 (p < 0.05), but there were not significant differences between the two groups regarding urine output or episodes of hyponatraemia. Logistic regression analysis revealed AVP levels on day 3 were significantly correlated with the duration of oxygen dependency independent of other factors. We conclude elevated AVP levels in the perinatal period are associated with CLD development, but our results suggest they have little functional significance.

Abstract: A nonvolitional test to assess diaphragm strength in neonates has not been previously described. Our aim was to assess the feasibility of cervical (CMS) and anterior (AMS) magnetic stimulation of the phrenic nerves in neonates. Double circular stimulating coils (90-mm) were used. For CMS, one coil was placed over the cervical spine to bilaterally stimulate the phrenic nerve roots, whereas for AMS the coils were placed on the anterolateral aspect of the neck to allow unilateral and bilateral stimulation. Diaphragm contractility was assessed as transdiaphragmatic pressure (Pdi) measured with balloon catheters positioned in the midesophagus and stomach. Stimulus supramaximality was assessed by examining diaphragm twitch Pdi (TwPdi) across a range of stimulator outputs; 85, 90, 95, and 100% of maximum. Pressure signals were measured by differential pressure transducer and displayed in real time on a computer. Patients were studied supine during sleep. CMS was performed on seven neonates (mean gestational age [GA] 38 wk, range 33 to 40 wk) and AMS on 18 neonates (mean GA 37 wk, range 32 to 41 wk). The mean (SD) TwPdi with CMS was 2.5 (0.8) cm H(2)O. CMS was not supramaximal; reducing the stimulator output below 100% caused marked reductions in TwPdi, also the shape of the pressure waveforms suggested that CMS may not have activated the diaphragm alone. Mean (SD) TwPdi with AMS was 4.5 (1.3) cm H(2)O on the left, 4.1 (0.9) cm H(2)O on the right, and 8.7 (3.9) cm H(2)O for bilateral stimulation. The shape of the pressure waveforms suggested that AMS was more specific and a plateau in TwPdi at higher stimulator outputs indicated supramaximality. We conclude that AMS may provide a useful technique to assess diaphragm function in the neonate.

Abstract: BACKGROUND: During synchronous ventilation, positive pressure ventilation and spontaneous inspiration coincide. Thus, if synchronous ventilation is provoked, it is likely that adequate gas exchange should be achieved at lower peak pressures, reducing barotrauma and hence airleak and chronic lung disease. Synchronous ventilation can be achieved by manipulation of rate and inspiratory time during conventional ventilation and employment of patient assisted ventilation. OBJECTIVES: To compare (i) the efficacy of synchronized mechanical ventilation, delivered as high frequency positive pressure ventilation or triggered ventilation (patient triggered ventilation (PTV) or synchronous intermittent mandatory ventilation (SIMV)) with conventional ventilation (ii) different types of triggered ventilation SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal Trials, Medline (MESH terms: mechanical ventilation; triggered ventilation; newborn infant); previous reviews, abstracts, symposia proceedings, hand searching of journals in the English language and contacting expert informants. SELECTION CRITERIA: Randomized or quasi randomized clinical trials comparing synchronized ventilation delivered as high frequency positive pressure ventilation (HFPPV) or triggered ventilation (PTV/SIMV) to conventional ventilation (CMV) in neonates. Randomized trials comparing different triggered ventilation modes (PTV and SIMV) in neonates. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including mortality, airleaks (pneumothorax or pulmonary interstitial emphysema (PIE)), severe intracerebral haemorrhage (grades 3 and 4), chronic lung disease (oxygen dependency beyond 28 days) and duration of weaning/ventilation. Data subdivided into three groups: (i) HFPPV vs CMV; (ii) PTV/SIMV vs CMV; (iii) PTV vs SIMV. Data analysis was conducted according to the standards of the Neonatal Cochrane Review Group. MAIN RESULTS: The meta-analysis demonstrates that HFPPV compared to CMV was associated with a reduction in the risk of airleak (typical relative risk 0.68, 95% CI 0.55, 0.68). PTV/SIMV compared to CMV was associated with a shorter duration of ventilation (Weighted mean difference -45.2 hours, 95% CI -78.3, -12.1). PTV compared to SIMV was associated with a trend to a shorter duration of weaning (Weighted mean difference 42.4 hours, 95% CI -9.6,94.4). No disadvantage to HFPPV or triggered ventilation was noted regarding other outcomes. REVIEWER'S CONCLUSIONS: Compared to conventional ventilation, benefit is demonstrated for both HFPPV and triggered ventilation with regard to a reduction in airleak and a shorter duration of ventilation respectively. In none of the trials was complex respiratory monitoring undertaken and thus it is not possible to conclude that the mechanism of producing those benefits is by provocation of synchronized ventilation. Further trials are needed to determine whether synchronized ventilation is associated with a reduction in chronic oxygen dependency.

Abstract: The aims of this study were to compare the morbidity of infants with gastroschisis (GS) with that of infants with exomphalos (EX) without lethal abnormalities and to identify factors predictive of adverse outcome: a requirement for parenteral nutrition (PN) for over 1 month and hospital admission for over 2 months. The medical records of 45 infants with anterior wall defects (32 with GS) diagnosed antenatally who consecutively received intensive care in one institution from 1993 were reviewed. Both the GS and EX infants had a median gestational age of 37 weeks, but the former were lighter at birth (P < 0.01). Fourteen infants (all with GS) were able to start feeds only after 2 weeks; 10 (8 with GS) developed liver dysfunction; and 5 (all with GS) died. The GS compared to the EX infants required a longer period of PN (median 20 vs 10 days, P < 0.01) and longer hospital admission (median 40 vs 25 days, P < 0.01). In the GS group the time to start feeding related independently to prolonged hospital stay, and the existence of structural bowel abnormalities (SBA) related independently to both measures of adverse outcome, with a positive predictive value of 100%. We conclude that infants with GS, particularly those with SBA, suffer greater morbidity than infants with EX without lethal abnormalities.

Abstract: Post-extubation chest radiographs (CXRs) are frequently requested on the neonatal intensive care unit, but it is controversial whether they generate useful information. A low lung volume assessed by measurement of functional residual capacity (FRC) post extubation has been demonstrated to predict extubation failure, which is a subsequent requirement for increased respiratory support. We have previously shown that the CXR lung area obtained by computer assisted analysis significantly correlated with FRC and, therefore, speculated that a low CXR lung area post extubation would reliably predict extubation failure. The aim of this study was to test the hypothesis by analysing CXRs from 20 infants, with median gestational age of 28 weeks (range 25-33 weeks) and postnatal age 4 days (range 1-11 days). CXRs were obtained within 4 h of extubation and were scanned and analysed using a Power Macintosh computer with a Wacom A5 Ultra pad and NIH image software. The cardiac, mediastinal and thymic shadows, and areas of perihilar and lobar consolidation were subtracted from the thoracic area to give the lung area. Seven infants failed extubation and differed significantly from the rest of the cohort only with regard to their CXR lung area, median gestational age, birth weight and postnatal age. Receiver operator characteristic (ROC) curves were constructed and the areas under each ROC curve were compared. Analysis demonstrated that a low CXR lung area and an older postnatal age were the best predictors of extubation failure. A post-extubation CXR lung area of < 8.5 cm2 had the highest specificity (100%) in predicting extubation failure. We conclude that routine post-extubation CXRs can have a useful role.

Abstract: The aim of this study was to determine whether elective use of nasal continuous positive airways pressure (CPAP) following extubation of preterm infants was well tolerated and improved short- and long-term outcomes. A randomized comparison of nasal CPAP to headbox oxygen was undertaken and a meta-analysis performed including similar randomized trials involving premature infants less than 28 days of age. A total of 150 infants (median gestational age 30 weeks, range 24-34 weeks) were randomized in two centres. Fifteen nasal CPAP infants and 25 headbox infants required increased respiratory support post-extubation and 15 nasal CPAP infants and nine headbox infants required reintubation (non significant). Eight infants became intolerant of CPAP and were changed to headbox oxygen within 48 h of extubation; 19 headbox infants developed apnoeas and respiratory acidosis requiring rescue nasal CPAP, 3 ultimately were re-intubated. Seven other trials were identified, giving a total number of 569 infants. Overall, nasal CPAP significantly reduced the need for increased respiratory support (relative risk, 0.57, 95% CI 0.43-0.73), but not for re-intubation (relative risk 0.89, 95% CI 0.68-1.17). Nasal CPAP neither influenced significantly the intraventricular haemorrhage rate reported in four studies (relative risk 1.0, 95% CI 0.55, 1.82) nor that of oxygen dependency at 28 days reported in six studies (relative risk 1.0, 95% CI 0.8, 1.25). In two studies nasal CPAP had to be discontinued in 10% of infants either because of intolerance or hyperoxia. CONCLUSION: Elective use of nasal continuous positive airways pressure post-extubation is not universally tolerated, but does reduce the need for additional support.

Abstract: The chest radiograph of very premature infants at 36 weeks post-conceptional age (PCA) was evaluated with regard to the degree of hyperinflation and cardiomegaly, and the presence of fibrosis/interstitial shadowing, cystic elements, air bronchograms and opacification. The evolution of abnormalities was assessed by comparing the radiograph appearance at 36 weeks PCA with that at 28 days post-natal age (PNA). Three scoring systems were used to determine how any abnormalities present could be best quantified to reflect disease severity as determined by chronic dependency upon supplementary oxygen status. Chest radiographs at 36 weeks PCA from 60 infants (median gestational age 26 weeks (range 24-28)) were studied. 47 infants also had radiographs at 28 days PNA. Only three infants had no chest radiograph abnormalities at 36 weeks PCA, although 24 infants were not dependent upon supplementary oxygen. The most common abnormalities were interstitial shadowing and hyperinflation, while cystic elements and cardiomegaly were rare. The radiographic appearance had deteriorated from 28 days PNA to 36 weeks PCA (p < 0.05); more infants at 36 weeks PCA were hyperinflated (p < 0.01). The chest radiograph appearances of infants who were dependent upon supplementary oxygen scored higher than those who were not (p < 0.01) using all three scoring systems. The system that assessed only the presence of interstitial shadowing, cystic elements and hyperinflation had the highest specificity in identifying oxygen dependency beyond 36 weeks PCA and had the highest area under the respective receiver operator characteristic curve. In conclusion, the majority of very immature infants have an abnormal chest radiograph appearance at 36 weeks PCA. The appearance can, however, be meaningfully scored by evaluating only three abnormalities.

Abstract: Our aim was to identify factors predictive of death in preterm infants in whom inhaled nitric oxide was administered in response to poor oxygenation (oxygenation index > or =15). Of the 23 (median gestational age 28 weeks, range 24-36) infants consecutively so treated, 15 died. Non-survival was commoner in infants with air leaks (12 of 12, P < 0.002) and/or a change in their oxygenation index of less than 30% in response to inhaled nitric oxide administration (P < 0.05). CONCLUSION: In preterm infants given inhaled nitric oxide because of poor oxygenation, a diagnosis of airleak and a lack of initial response are predictive of death.

Abstract: The aim of this study was to determine whether computer assisted analysis of lung area on the chest radiograph reliably predicted lung volume in neonates. Anteroposterior chest radiographs taken for clinical purposes were scanned and analysed using a Power Macintosh computer with a Wacom A5 Ultra Pad and NIH image software. The cardiac, mediastinal and thymic densities and areas of perihilar and lobar consolidation were subtracted from the thoracic area to give the lung area. This was compared with lung volume, assessed by measurement of functional residual capacity (FRC), within 1 h of the chest radiograph being performed. 50 infants, median gestational age 30 weeks (range 24-43) were studied. Their median lung area was 11.23 cm2 (range 0.82-28.53) and lung volume 28 ml (range 3-103). The intraobserver and interobserver coefficients of repeatability of lung area were 1.0 cm2 and 1.06 cm2, respectively. Lung area correlated significantly with FRC (r = 0.60, p < 0.0001). It is concluded that computer assisted analysis of the chest radiograph lung area is a reliable method of assessing lung volume in neonates.

Abstract: Complications of ventilatory support are more common if this assistance is prolonged. Our aim was to determine if results of respiratory function measurement on the first day of ventilation identified children who would develop prolonged ventilatory dependence (> or = 4 days) and whether such results were a more accurate predictor than readily available clinical data. Thirty three children, median age 2 years (range 0.1-13.6), who were supported by a constant flow ventilator and hence had measurements of compliance of the respiratory system (CRS) and resistance of the respiratory system (RRS) on the first day of ventilatory support, were retrospectively identified. Those who needed prolonged ventilatory support had a lower CRS on day one (p < 0.01) and required at any time during their ventilatory career both a higher maximum inspired oxygen concentration (p < 0.01) and peak inspiratory pressure (PIP) (p < 0.01). Logistic regression analysis demonstrated that only a low CRS and high maximum PIP were significantly correlated with prolonged ventilator dependence. A low CRS (<0.4 (ml/cmH2O) kg(-1)) and a high maximum PIP (>27 cmH2O) had similar sensitivities (83%) and specificities (71% and 67% respectively) in predicting prolonged ventilatory dependence. The CRS results, unlike the maximum PIP results, however, were always available on the first day of ventilatory support. We therefore conclude that respiratory function measurements have a role in identifying children who would benefit from strategies to prevent prolonged ventilator dependence.

Abstract: Neonatal chronic lung disease (CLD) is usually diagnosed if an infant remains oxygen dependent beyond 36 weeks postconceptional age (PCA). Our aim was to determine whether a shorter duration of respiratory support accurately predicted subsequent respiratory morbidity. A total of 103 infants, median gestational age 29 weeks (range 23-35), were followed prospectively for 5 years. They had a birth weight of < 1500 g or, if a birth weight of between 1500 and 2000 g, had required neonatal ventilatory support. Parents completed diary cards; their child had positive symptom status if, in any one year, they coughed and/or wheezed on at least 3 days per week for a 4-week period or for at least 3 days following each upper respiratory tract infection. Subsequent respiratory morbidity, positive symptom status in years 1 and 2 or all 5 pre-school years, was related to various definitions of prolonged respiratory support: intermittent positive pressure ventilation dependence > 7 days; oxygen dependence > 28 days and oxygen dependence > 36 weeks PCA. In years 1 and 2, 25 children were symptomatic and 22 in all 5 years. The patients with subsequent respiratory morbidity were distinguished from those without by requiring longer respiratory support (P < 0.05). Logistic regression analysis demonstrated only oxygen dependence beyond 28 days was independently related to subsequent respiratory morbidity (P < 0.01). The positive predictive values and likelihood ratios (95% confidence intervals) for positive symptom status in all 5 years were for intermittent positive pressure ventilation > 7 days 35% (16-53) and 19.5 (1.01-3.76), for oxygen dependency > 28 days 42% (23-61) and 2.20 (1.45-5.02) and for oxygen dependency >36 weeks PCA 35% (13-58) and 1.67 (0.65-4.31). CONCLUSION: Oxygen dependency at 28 days of age remains a useful criterion on which to diagnose "neonatal" chronic lung disease.

Abstract: The aim of this study was to compare gas exchange and volume delivery during high frequency oscillation at two frequently used inspiratory:expiratory (I:E) ratios: 1:2 and 1:1, other oscillatory settings being kept constant. A group of 13 infants with respiratory distress syndrome, median gestational age 28 weeks (range 23-36) and postnatal age 1 day (range 1-8) were studied. At the I:E ratio of 1:1 compared to 1:2 the median paCO(2) was lower, P < 0.05 (30 mmHg, range 22-47 vs 34 mmHg, range 27-46) and the volume delivered higher, P < 0.01 (2.6 ml/kg, range 1.2-5.6 vs 2.0 ml/kg, range 1.0-3.9). There was no significant difference in oxygenation levels at the two I:E ratios. In a related in vitro study, changing the I:E ratio from 1:2 to 1:1 increased the mean airway pressure by a median of 8.6% (range 2.9-28.1%). CONCLUSION: Routinely maintained longer expiratory than inspiratory times during high frequency oscillation should be discouraged.

Abstract:

Abstract: Inhaled nitric oxide (iNO) can be an effective vasodilator in pulmonary hypertension of the newborn (PHN). The aim of this study was to determine whether differences in arginine levels, from which endogenous NO is produced, explain the variability in response to NO and whether the arginine levels were lower in term and preterm infants with PHN than in infants without PHN (controls). We prospectively studied 30 infants (17 born preterm) with clinically diagnosed PHN and treated with iNO and 22 controls (14 born preterm). Three NO levels (10, 20, 40 ppm) were administered to the PHN infants to identify that associated with maximum oxygenation. Twenty-seven infants with PHN improved following iNO and had lower arginine levels than those infants who did not respond to iNO (p < 0. 05). No significant relationship, however, was noted between the arginine levels and either the magnitude of change in the oxygenation index in response to iNO or the NO level associated with maximum oxygenation. The median plasma arginine level prior to iNO of the PHN infants was 12.5 (range 2-53) mu mol/l, but not significantly lower than that of the controls (median 24, range 3-82 mu mol/l). We conclude that differences in plasma arginine levels are unlikely to explain the variation in response to iNO and that, although arginine levels tended to be lower in infants with PHN, this is not a consistent finding in either the term or preterm infants.

Abstract: The aim of this study was to investigate if blood pressure (BP) rhythms were present in the perinatal period in very immature infants. Twenty-two infants, median gestational age 24-28 weeks, who had indwelling arterial lines with undamped arterial BP waveforms, were studied. The infants were all receiving intensive care under constant conditions. The hourly mean, systolic and diastolic BPs on days 2 and 7 were examined. A cosinor analysis of the mean BP was performed examining period lengths of 4, 8, 12, 16, 20, and 24 h to determine whether ultradian and/or circadian rhythms existed. On day 2, but not day 7, the mean and systolic BPs showed significant variation and circadian and ultradian rhythms were demonstrated. We suggest that maternal influences may be responsible for the BP rhythms noted in very immature infants on day 2.

Abstract: Some infants, despite being born at low gestations (< 28 weeks gestational age) do not develop RDS and are not surfactant treated. The changes in lung function during the neonatal period in such infants have not been explored, hence it is unknown whether they are similar to those of surfactant treated infants with RDS of similar gestational age. Such data would facilitate assessment of the impact of surfactant administration on the lung function abnormalities of very immature infants with RDS. We, therefore, compared the results of neonatal lung function measurements from immature infants with RDS who received surfactant to those from infants with non-RDS respiratory distress not so treated and matched to the RDS infants for gestational age and within 10% of birthweight. Compliance and functional residual capacity (FRC) were measured daily for the first five days and then at 1, 2 and 4 weeks in 16 infants, median gestational age 27 weeks (range 25-27 weeks). Although exogenous surfactant administration to the immature infants with RDS was associated with improvements in lung function, the non RDS, non surfactant treated infants had both higher compliance (p < 0.05) and lung volumes (p < 0.01) throughout the perinatal period. These results demonstrate surfactant administration does not fully correct the perinatal lung function abnormalities of very immature infants with RDS.

Abstract: A case-controlled study was performed to determine whether preterm premature rupture of the membranes (PPROM), particularly if occurring in the second trimester, increased the duration of ventilatory support or hospital admission. Infants born after membrane rupture of at least 24 hours duration and prior to 37 weeks of gestation were identified. It was possible to match for gestational age and birthweight 40 PPROM infants, 15 of whom had onset of rupture of the membranes (ROM) prior to 27 weeks of gestation, with a control (an infant whose mother had not suffered PPROM). A greater proportion of the mothers of the PPROM infants had received antenatal steroids (p<0.01), had an antepartum hemorrhage (p=0.06) or delivered vaginally (p<0.02). More PPROM infants had pulmonary hypoplasia (p<0.03) or infection (p<0.01). Overall, however, and if only those matched pairs where membrane rupture had occurred prior to 27 weeks of gestation were considered, there were no statistically significant differences in the duration of ventilatory support or hospital admission. Step-wise regression analysis confirmed that in the study population overall and in the matched pairs where membrane rupture had occurred at less than 27 weeks of gestation, neither the duration of ventilation nor hospital admission significantly related to PPROM. These findings have implications when counselling parents.

Abstract: Fluid overload worsens respiratory failure; conversely, fluid restriction has been associated with a higher survival rate without chronic lung disease. We therefore hypothesised that fluid restriction in the perinatal period might improve lung function in ventilated, prematurely born infants of very low birthweight. As a consequence, we compared in a randomised trial the effect of two fluid regimes on perinatal lung function. On one regime infants were to receive 60 ml/kg on day 1, increasing to 150 ml/kg by day 7, and on the other regime approximately 25% less fluid was to be prescribed. Lung function was assessed by measurement of functional residual capacity (FRC) and compliance. Measurements were made daily on days 1 to 5 and then on day 7. Ninety infants, median gestational age 28 weeks (range 23-33), were included in the study. There were no significant differences between the two groups regarding their gestational age or birthweight, or in the proportions who received antenatal steroids or postnatal surfactant. The infants on the restricted regime received significantly less fluid (P < 0.01). The only significant differences in lung function between the two groups, however, were that the infants on the restricted regime had a higher mean compliance on day 3, but thereafter the difference was reversed. Colloid intake, however, unfavourably affected lung function, total colloid intake being negatively correlated with both the area under the curve of birth-adjusted FRC (P=0.003) and compliance (P=0.001). CONCLUSION: We conclude that early fluid restriction appears to have very little impact on perinatal lung function.

Abstract: Positive end expiratory pressure (PEEP) is routinely used when ventilating preterm infants, and high levels are recommended in those with severe respiratory distress syndrome (RDS). Elevation of PEEP increases lung volume, as does surfactant administration. We postulated that in surfactant-treated infants even modest PEEP levels could result in overdistension and (CO(2)) retention. To test that hypothesis, lung volume, compliance and arterial blood gases were measured in eight preterm infants (median gestational age 28 weeks, range 26-35 weeks) at three PEEP levels. The infants, all with RDS, were studied at a median time of 18 h, (range 12-68 h) after their last dose of surfactant. Infants were routinely nursed at 3 cmH(2)O of PEEP, the PEEP level was then raised to 6 cmH(2)O or lowered to 0 cmH(2)O in random order. The new setting was maintained for 20 min; the PEEP level was then changed to the third level (0 or 6 cmH(2)O) again for 20 min. At the end of each 20-min period, lung volume, compliance and blood gases were measured. Lung volume was assessed by measuring functional residual capacity (FRC) using a helium dilution technique. Compliance was measured by relating the volume change from a positive pressure inflation maintained until no further volume change occurred to the pressure drop (peak inflating pressure PEEP). Increasing PEEP from 0 to 3 cmH(2)O and particularly to 6 cmH(2)O resulted in increases in FRC (P < 0.05), oxygenation (ns) and paCO(2) (P < 0.02). Specific compliance (compliance/FRC) (P < 0.05) and pH (P < 0.02) fell. CONCLUSION: Following surfactant treatment, relatively low levels of positive end expiratory pressure (</=3 cmH(2)O) may be appropriate.

Abstract: AIM: To determine whether the incidence of respiratory distress syndrome (RDS) is related to ethnic origin in very premature infants (< or = 32 weeks of gestational age and birthweight < or = 2.0 kg). METHOD: A retrospective cohort study was performed to determine the incidence of respiratory disorders in African, Caribbean, and caucasian infants. An African infant was matched with two infants (one of Caribbean and one of caucasian descent) for gestational age and birth order and, if several eligible matching infants were found, for gender and approximate birth date. Fifty African infants (median gestational age 28 weeks, range 23-32) were matched with an infant of Caribbean and one of caucasian descent. RESULTS: Compared with the incidence of RDS in African infants (40%), that in caucasian infants (75%) was significantly higher (p < 0.05), while the incidence in the Caribbean infants (54%) did not differ significantly. Regression analysis showed that ethnic origin was related to the occurrence of RDS independent of gestational age, size for dates, antenatal steroids, hypertension during pregnancy, premature rupture of membranes, maternal smoking, mode of delivery and infant gender. CONCLUSION: The enhanced lung maturation found in certain ethnic groups, even when born prematurely, has implications for clinical management.

Abstract: METHODS: Daily measurements of lung volume (functional residual capacity, FRC) were made during the perinatal period in eight infants (median gestational age, 37 weeks; range, 34 to 38 weeks) with abdominal wall defects. RESULTS: On the first day of life and before surgical intervention, four infants had FRCs below the reference range; the occurrence of low lung volumes was not significantly related to gestational age or diagnosis. Lung volume was further, but only temporarily, impaired by surgical closure of the abdominal wall defect, with a reduction in the median FRC from 25 mL/kg (range, 18 to 36) preoperatively to 12 mL/kg (range, 5 to 19) on the first postoperative day (P < .02). CONCLUSION: These data are consistent with abnormal antenatal lung growth in certain infants with abdominal wall defects.

Abstract: The aim of this study was to determine the relative effects of theophylline and caffeine on neonatal respiratory function. Fifty-three preterm infants (45 infants with a median gestational age of 28 weeks, range 24-34 weeks completed the protocol) were randomized to receive either theophylline (loading dose 4 mg/kg followed by 4 mg/kg/day) or caffeine (loading dose 10 mg/kg followed by 5 mg/kg/day). Compliance of the respiratory system (CRS), strength of Hering Breuer reflex and the inspired oxygen concentration requirement were measured immediately prior to, 24 h and 7 days after commencing therapy. There was no statistically significant difference in the patient characteristics of the two groups, but only the theophylline group contained immature infants (i.e. < 26 weeks gestational age (n = 7)). At 24 h, there was a significant improvement in CRS and reduction in supplementary oxygen requirements in the caffeine group (p < 0.01), in the theophylline group no such significant effects were seen. In the study population overall, after 7 days of treatment in both the theophylline and caffeine groups there was an improvement in CRS (p < 0.05 and p < 0.01 respectively) and a reduction in the inspired oxygen concentration (p < 0.05 and p < 0.01 respectively). There was, however, a significant reduction in the strength of the Hering Breuer reflex only in the caffeine group (p < 0.05) and this was a decrease which related to the change in CRS (p < 0.05). The only statistically significant difference in the magnitude of change in CRS, reflex strength or supplementary oxygen requirements between the two groups was that the reduction in inspired oxygen requirement in the caffeine group was greater than that in the theophylline treated infants at 24 h (p < 0.05). We conclude theophylline and caffeine have similar effects on neonatal respiratory function, but our results suggest caffeine administration may be associated with an earlier onset of action.

Abstract: AIM: To examine the delivered volume during "high volume strategy" high frequency oscillation, used as rescue treatment in preterm infants; and to identify factors, other than frequency and oscillatory amplitude, influencing the magnitude of volume delivery. METHOD: Twenty infants (median gestational age 29 weeks) were studied on 45 occasions. Two oscillator types were used (SensorMedics and SLE). Delivered volume was measured under clinical conditions with the arterial blood gases within a predetermined range. A specially calibrated pneumotachograph system was used. RESULTS: Overall, the median delivered volume was 2.4 ml/kg (range 1.0 to 3.6 ml/kg); on 32 occasions the delivered volume was greater than 2.0 ml/kg and on seven greater than 3.0 ml/kg. The delivered volume related significantly to disease severity; there was an inverse correlaton between delivered volume and both the oxygenation index (OI) (r = -0.51) and AaDO2 (r = -0.54). CONCLUSION: Delivered volume during HFO may, in certain infants, exceed the anatomical dead space, permitting some direct alveolar ventilation.

Abstract: Prematurely born children frequently have respiratory problems at follow-up. A non-invasive and easily performed lung function test would greatly facilitate their evaluation and appropriate treatment. We have, therefore, assessed whether the shape of the tidal breathing expiratory flow curve would give useful information in such a population. One hundred and twenty traces were randomly selected from plethysmographic measurements of thoracic gas volume and airway resistance made during a follow-up study of a prematurely born population. The children had a median gestational age of 29 (range 23-35, interquartile range 27-31) weeks and postnatal age at the time of measurement of 11 (range 6-24, interquartile range 7-13) months. From the flow and volume signals, the mean time to reach peak tidal expiratory flow as a proportion of the total expiratory time (tPTEF : tE) was determined for each child. The median tPTEF : tE differed significantly between children who, in the neonatal period, had or had not required mechanical ventilation (p < 0.001) and had or had not had an increased inspired oxygen requirement (p < 0.01), and who were or were not symptomatic at follow-up (p < 0.001). Logistic regression analysis demonstrated that a low tPTEF : tE ratio was independently associated with symptom status. These results suggest that assessment of a tidal breathing parameter during follow-up of prematurely born children may be useful. As tPTEF : tE can be measured without sedation, relatively quickly and with simple equipment, potentially large study populations could be investigated, and this technique should now be evaluated in a non-sedated group of young prematurely born children.

Abstract:

Abstract: Infants born prematurely who develop chronic lung disease (CLD) have airways obstruction and hence may have low lung volume. The aim of this study was to test that hypothesis and ascertain whether the nature of the comparison control group influenced the results. Sixteen infants who were oxygen dependent for more than 28 days (CLD) and eight infants without CLD had measurements of functional residual capacity (FRC) at 14 and 28 days. The 16 CLD infants consisted of eight less than 27 weeks gestational age (group A) and eight greater than 26 weeks gestational age (group B). The eight infants without CLD (group C) were each matched for gestational age and gender to infants in group B. Group A compared to group C had lower FRCs both at 14 days (median 18 ml/kg vs 27 ml/kg, P < 0.01) and 28 days (median 20 ml/kg vs 26 ml/kg, P < 0.05), but group A differed from group C with respect to both gestational age (P < 0.01) and birth weight (P < 0.01). The FRC results of group B were lower than those of their matched controls (group C) only at 28 days (median 22 vs 26 ml/kg, P < 0.05). Overall, the FRC results at 14 and 28 days correlated significantly with the duration of oxygen and ventilator dependence and weakly with gestational age. CONCLUSION: These results support the hypothesis that FRC results are lower in infants with CLD compared to those without CLD when measured in the neonatal period and emphasize the importance of an appropriate control group. Measurement of lung volume may facilitate assessment of the response to therapies for CLD.

Abstract: Exogenous surfactant administration improves respiratory function. The speed of improvement appears greater if a natural rather than an artificial surfactant is used, our aim was to determine if that effect was explained by differences in fluid balance, evidenced by the timing of the diuresis onset (i.e. output greater than input). Thirty infants (median gestational age 29 weeks), 10 given an artificial surfactant (Exosurf), 10 a natural surfactant (Survanta) and 10 no surfactant (controls) were studied. During the first three days, compliance and functional residual capacity were measured daily, arginine vasopressin (AVP) levels estimated on days 1, 3 and 5 and, in 8-hourly intervals, the median arterial/alveolar ratio was calculated for each individual and urine output and fluid input recorded. Throughout the three-day period, the median arterial/alveolar ratio was always significantly higher in the control compared to the two surfactant groups (p < 0.05). On day 3 the Exosurf-treated babies had lower compliance and functional residual capacity (p < 0.05) than the other two groups. Neither the timing of diuresis onset, timing of the maximum diuresis nor the AVP levels, however, differed significantly between the groups. Only surfactant treatment and type of surfactant, but not the timing of the onset nor of the maximum diuresis, related significantly to changes in lung function. These results do not support the hypothesis that differences in fluid balance explain differences in the lung function improvement rate following natural and artificial surfactant.

Abstract: Failure of patient-triggered ventilation in very immature infants may be due to the use of inappropriate triggering systems. Two types of airflow trigger were therefore compared consecutively to an airway pressure (SLE) triggering system. Each comparison was made in 10 infants, < or =28 weeks of gestation. Comparison was made of the delivered volume, trigger performance and blood gases using each system for 1 h. Both comparisons showed that the airflow triggering systems performed better: one (Draeger Babylog 8000) had a higher sensitivity (p < 0.01) and the other (Bird VIP airflow trigger), in which inflation was terminated by sensing a reduction in inspiratory flow, had a lower degree of asynchrony (p < 0.01) and a tendency to deliver higher volumes. These results suggest that triggering systems sensing airflow changes may be superior to those sensing airway pressure changes in very immature infants. The use of a mechanism to synchronize the termination of inflation to the end of the patient's inspiration may offer further advantages.

Abstract:

Abstract: The speed of action and side-effects of systemic verus inhaled steroids was compared in infants with mild-moderate oxygen dependency. Forty infants (median gestational age 27 weeks) were randomized to receive either 10 days of dexamethasone (systemic group) or budesonide (100 micrograms qds) (inhaled group). At randomization, there was no significant difference in the gestational or postnatal age, inspired oxygen requirements or compliance of the respiratory system of the two groups. After 36 h of treatment, there were significant changes (P < 0.01) in both the inspired oxygen concentration and compliance of the respiratory system in the systemic but not the inhaled group. Only after 1 week of inhaled therapy were improvements in respiratory status noted but, even at that time, the inspired oxygen requirement was significantly lower in the systemic versus the inhaled group. In the systemic group only, however, were there significant increases in blood pressure. CONCLUSION: Systemically administered rather than inhaled steroids appear to have a faster onset of action.

Abstract: Changes in lung volume (functional residual capacity) compliance and oxygenation in the first 48 h of life in infants given surfactant replacement therapy were studied. Fourteen infants, median gestational age 30 weeks (range 26-35), who were given two doses of an artificial surfactant (Exosurf) at approximately 2 h of age and 12 h later, were examined. Compared to baseline, functional residual capacity, compliance of the respiratory system and oxygenation, significantly improved at 24 and 48 hours, but specific compliance (compliance/functional residual capacity) decreased. The greater changes, however, were experienced between baseline and 24 h. These data suggest that the elevation of FRC over the first 48 hours of life may be due to increased distension as well as recruitment of alveoli.

Abstract: BACKGROUND/PURPOSE: Infants who have congenital diaphragmatic hernia (CDH) have high mortality and morbidity. The aim of this study was to determine the relative ability of the results of serial measurements of compliance of the respiratory system (CRS) and lung volume (functional residual capacity (FRC)) to predict poor outcome: death or oxygen dependency at 28 days. In addition, the authors wished to document the evolution of any lung function abnormalities during the perioperative period. METHODS: Daily measurements of CRS and FRC were made in the first week of life and subsequently during week 2 in 16 infants who had a median gestational age of 38 weeks and birth weight of 3.2 kg. RESULTS: Seven infants had a poor outcome: five died and two others remained oxygen dependent beyond 28 days. The infants who had a poor outcome were characterized on day 1 by a significantly lower CRS, but not FRC (P < .05). In comparison with results from day 1, the median CRS of the infants overall had significantly improved only by week 2 (P < .05), there was no such significant change in FRC with increasing postnatal age. At week 2, only the CRS results differed significantly between those infants who had and who did not have poor outcome (P < .05). CONCLUSION: The results of serial measurements of CRS, rather than FRC are the more useful predictor of outcome in infants who have CDH.

Abstract: In a 9-y prospective study, the occurrence and duration of lung volume abnormalities in 21 young asthmatic children (median age at recruitment 4 y, range 3-8 y) was determined. The median functional residual capacity (FRC) at recruitment was 135% of that predicted for height (range 79-187%) and 13 children were hyperinflated. The median FRC decreased significantly after 3 y of follow-up and by 9 y only one child remained hyperinflated. We conclude that persistent elevation of lung volume in young asthmatic children appears to be uncommon.

Abstract: Lung function abnormalities, including hyperinflation, are common in young children born prematurely. The aim of this study was, in such patients, to determine factors associated with hyperinflation, that is an elevated lung volume. Lung volume was estimated by measuring functional residual capacity (FRC) before and after bronchodilator therapy in 41 5-year-old children who had been born prematurely at a median of 30 weeks gestational age. Hyperinflation was defined as an FRC greater than 120% of that predicted for height and a positive bronchodilator response as a greater than or equal to 10% change in FRC. Twelve (29%) of the children were symptomatic at 5 years, their median FRC (132%) was significantly higher than that of the asymptomatic children (109%), P < 0.01). Twelve (29%) children were hyperinflated; a greater proportion of the hyperinflated compared to the non-hyperinflated patients were symptomatic at 5 years (7 or 58% versus 5 or 17%) (P < 0.05) and responded to bronchodilator therapy (9 or 75% versus 4 or 14%) (P < 0.01). Regression analysis demonstrated that hyperinflation related significantly only to current symptom status, but not perinatal variables. Conclusion: Hyperinflation in young children born prematurely reflects current symptom status and not adverse neonatal events.

Abstract: Respiratory distress syndrome (RDS) is characterized by lungs having collapsed alveoli (atelectasis) which reduces the volume of the gas-containing spaces of the lung. It seems likely, therefore, that measurement of lung volume might discriminate between infants with severe respiratory failure due to RDS and those with minimal respiratory distress. To test this hypothesis, lung volume was measured at end expiration, that is functional residual capacity (FRC), in 40 infants (median gestational age 29 weeks, range 24-35) all mechanically ventilated from birth. FRC was measured using a helium gas dilution technique at a median of 3 h of age. The infants were divided into two groups according to their FRC results: group A (n = 29) low FRC (FRC < 24 ml kg-1) and group B (n = 11) normal FRC (FRC > or = 24 ml kg-1). The clinicians were unaware of the FRC results. There was no significant difference in the gestational age or birthweight of the two groups, but group A were characterized by a significantly greater proportion requiring surfactant replacement therapy (p < 0.01), a higher maximum peak inspiratory pressure (p < 0.01) and inspired oxygen requirement (p < 0.01). A low FRC had 79% sensitivity and 91% specificity in predicting a requirement for surfactant replacement therapy. We conclude that measurement of FRC in the first hours of life does allow discrimination of disease severity.

Abstract: To test the hypothesis that premature infants in whom extubation fails in the first 10 days of life have low volume lungs, functional residual capacity (FRC) was measured in the first hour after extubation. Once extubated, infants received the appropriate level of inspired oxygen necessary to maintain acceptable arterial oxygen saturation. After humidification, oxygen was bled into a headbox, and FRC was assessed using a helium gas dilution technique and a specially designed infant circuit. The results were related to extubation failure, which was diagnosed when the infant required nasal continuous positive airway pressure or re-intubation and ventilation within 48 hours. The latter two forms of respiratory support were instituted by the clinical team, whenever the infant developed recurrent or severe apnea or respiratory acidosis. Infants were eligible for entry into the study when born prematurely and extubated within the first 10 days of life. Twenty infants initially ventilated for respiratory distress syndrome at a median gestational age of 29 weeks (range, 26-36 weeks) were studied at a median postnatal age of 3 days (range, 1-7 days). All were receiving theophylline. Extubation failed in seven infants, who did not differ significantly from the rest of the cohort regarding gestational age, birthweight, postnatal age, or inspired oxygen concentration (F(I)O2) at extubation, but their maximum F(I)O2 during ventilation was higher than in those infants who did not require reintubation (P < 0.05). In the infants who failed extubation, the median FRC was 19 ml/kg (range, 12-27 ml/kg), which was lower than that of the infants in whom extubation was successfully accomplished (median, 28 ml/kg; range, 19-37 ml/kg; P < 0.01). An FRC of less than 26 ml/kg had a sensitivity of 71% and specificity of 77% in predicting extubation failure. These results support the hypothesis that a very low lung volume relates to extubation failure in the first 10 days of life.

Abstract: Children born prematurely and recruited into a prospective follow up study were examined at 5 years of age. Our aim was to determine aetiological associations of respiratory symptoms in such children and, in particular, to determine the importance of severe chronic lung disease (CLD, oxygen dependence beyond 36 weeks post conceptional age). Respiratory status was documented from parental history in 103 children of median gestational age 29 weeks (range 23-35), 17 of whom had suffered from severe CLD. In 90 of the 103 children lung function had been assessed at 1 year of age. Regression analysis revealed that neither severe CLD nor other perinatal variables, but only a family history of atopy, significantly related to a positive symptom status. A high airways resistance at 1 year also significantly related to positive symptom status. Conclusion: Reduction in severe CLD (oxygen dependence beyond 36 weeks postconceptional age) may make relatively little impact on respiratory morbidity in young school children born prematurely.

Abstract: Compliance of the respiratory system (CRS) was measured before and after surgical intervention in 14 infants who had anterior abdominal wall defects (AWD) (7 exomphalos, 7 gastroschisis). The median gestational age was 37 weeks (range, 34 to 40) and median birth weight was 2.38 kg (range, 1.94 to 3.45). The infants had stiff lungs before surgery (median CRS, 0.58 mL/cm H2(O)/kg). During the first and second postoperative days, the median CRS decreased to 0.33 mL/cm H2(O)/kg (P < .05). In seven cases, measurements also were obtained on the third and fourth postoperative days, which showed an increase in the median CRS (day 3, 0.47 mL/cm H2(O)/kg; P < .05). These findings show that in infants with AWD, primary surgical closure is associated with deterioration of lung function, but this effect is temporary.

Abstract: Volume delivery by positive pressure inflation was determined in 20 premature infants and 10 infants born at term on days 1 and 2. The spontaneous tidal volume, respiratory rate and inspiratory to expiratory (I:E) ratio were measured daily in the first week of life in an additional group of 20 infants born prematurely. Measurements were made using a pneumotachograph only when the infants were stable and had acceptable blood gases for at least 2 h. There was variability between individuals but the median delivered volume by positive pressure ventilation ranged between 4.9 and 6.1 ml/kg on days 1 and 2 and within the groups of different maturity. There was no significant difference in the results of infants born prematurely or at term or when studied on days 1 or 2. The median spontaneous tidal volume during the first week of life varied between 5.4 and 6.7 ml/kg; respiratory rate between 72 and 80 breaths/min and I:E ratio from 0.67 to 0.77. Postnatal age had no significant effect on the results. These results suggest volume delivery by positive pressure inflation during a stable period of ventilation is similar to the spontaneous tidal volume.

Abstract: Spontaneous respiratory activity during high frequency oscillation (HFO) and its relationship to changes in blood gases on transfer to HFO has been assessed. Eighteen infants were studied, median gestational age 27 weeks and postnatal age 1 day. Simultaneous measurements of changes in oesophageal and airway pressure, flow and volume were made during a period of conventional ventilation and then during HFO. From these recordings, the infants' spontaneous respiratory rate during the two ventilatory techniques were calculated. Arterial blood gases were measured immediately before and after a 30-min period of HFO. All the infants were breathing during conventional ventilation (median rate of 55 breaths/min). On transfer to HFO, the respiratory rate of the whole group decreased to a median of 23 breaths/min (P < 0.001), but only five infants became apnoeic. The changes in respiratory rate did not relate significantly to changes in PaCO2. Oxygenation deteriorated in four of the five apnoeic infants and in the two infants who became agitated during HFO. In the remaining 11 infants, whose median respiratory rate was 28 breaths/min (range 15-77) during HFO, oxygenation improved by a median of 12 mmHg (range 4-42). We conclude that, in the majority of infants, spontaneous respiratory activity during HFO is compatible with improvements in blood gases.

Abstract: Twelve infants, median gestational age 27 weeks and postnatal age 1 day, were examined to determine whether oxygenation improves on transfer to high frequency oscillation (HFO). Lung volume was assessed before transfer to HFO by measuring functional residual capacity (FRC) using a helium gas dilution technique and specially designed infant circuit. On transfer to HFO, the inspired oxygen was initially kept constant, but the mean airway pressure (MAP) increased until maximum oxygenation was achieved (optimal MAP). The median FRC of the 12 infants before HFO was 8.1 ml/kg (range 4.7 to 28.7) and their median alveolar-arterial oxygen gradient (A-aDO2) 484 mm Hg. On transfer to HFO, oxygenation did not improve in two infants, but, overall, the A-aDO2 fell to a median of 289 mm Hg (p < 0.05). The median optimal MAP was 18.5 cm H2O (range 10.6 to 24.4) and this had an inverse correlation with the FRC before starting HFO (p < 0.01). The median change in MAP needed to maximise oxygenation on HFO also correlated negatively with FRC (p < 0.01).

Abstract: The efficacy of combining rate and pressure reduction during weaning by synchronous intermittent mandatory ventilation (SIMV) were compared with weaning by patient triggered ventilation (PTV) (pressure reduction alone) in two randomised trials. Regardless of ventilation mode, pressure was reduced to the same level according to the size of the infant. In the first trial, the SIMV rate was also reduced progressively to a minimum of 20 breaths/minute, and in the second to five breaths/minute. Forty premature infants aged 15 days of age or less were randomly allocated into each trial. No significant differences were found in the first trial between ventilation modes in either the duration of weaning or the number of infants in whom weaning failed. In the second trial, the duration of weaning was shorter by PTV than by SIMV (median 24 hours, range 7-432 v 50 hours, range 12-500; p < 0.05); weaning failed in two infants in the PTV group and in five in the SIMV group. It is concluded that weaning by a combination of pressure and rate reduction, such as can be achieved during SIMV, offers no significant advantage over pressure reduction alone.

Abstract: Congenital diaphragmatic hernia is associated with significant mortality and morbidity. The aim of this study was to compare a series of tests with respect to prediction of outcome. Tidal volume and compliance of the respiratory system (CRS) were measured preoperatively and on the first and second postoperative days. The maximum and modified ventilation indexes and the maximum Paco2 were noted for the first 6 hours of life and the first 6 hours postoperatively. In addition, it was recorded whether the stomach was within the ipsilateral hemithorax preoperatively. Twenty infants were studied (median gestational age, 38 weeks; range, 31 to 40), six of whom had a poor outcome, ie, they died or remained oxygen-dependent after 28 days. A CRS of less than 0.18 mL/cm H2O/kg was the most accurate predictor of poor outcome, with 66% sensitivity and 100% specificity. The authors conclude that lung function measurement are useful in the assessment of infants with congenital diaphragmatic hernia.

Abstract: We have assessed whether the appearance of the chest radiograph performed within the first 2 h of birth was predictive of the response to exogenous surfactant replacement therapy (SRT), as indicated by changes in sensitive indices of disease severity, that is lung volume (functional residual capacity (FRC)) and oxygenation (a/A ratio). 18 premature infants who received two doses of a synthetic surfactant (Exosurf) were studied. The appearances of chest radiographs taken prior to the first and immediately after the second dose of SRT were scored for lung volume, degree of inflation, presence of opacification, interstitial shadows and air bronchograms. At similar times, FRC was measured and the a/A ratio calculated. Although following SRT, the chest radiograph score decreased (p < 0.01) and the FRC (p < 0.01) and a/A ratio (ns) improved, there was no significant relationship between the change in chest radiograph score and either the change in FRC or a/A ratio. In addition, only the post-SRT chest radiograph appearance correlated significantly with the respective FRC, a/A ratio and outcome (death or oxygen dependency beyond 28 days). Although the appearance of an early chest radiograph is frequently used as an indicator of the need for SRT, these results demonstrate that, unlike the post-SRT radiograph, it is a poor predictor of the response to SRT and outcome.