Constructing a relevant decision aid for parents of children with bronchopulmonary dysplasia.

BACKGROUND: To develop and test a decision aid for counseling parents of children with bronchopulmonary dysplasia (BPD).Local problem:Parental education about complex conditions is not standardized and communication and understanding may not be adequate. METHODS: Semi-structured interviews were conducted with 33 neonatal clinicians and 12 parents of children with BPD using a qualitative research design. The interviews were used to identify education topics that were felt to be important in BPD education. These topics were then used to create a visual decision aid to be used in counseling sessions with parents. The decision aid was then used in mock counseling sessions with 15 'experienced' participants and 7 'naïve' participants to assess its efficacy. The participants completed a pre and post test to assess change in knowledge as well as an 11-question Likert style acceptability survey. INTERVENTION: Implementation of a decision aid while educating parents about BPD. RESULTS: Topics identified during the interviews were used to create eight educational cards which included pictures, pictographs and statistics. Overall, participants thought the decision aid contained an appropriate amount of information, were easy to understand and improved their knowledge about BPD. Testing demonstrated a significant increase in knowledge in both the 'experienced' (P<0.0001) and 'naïve' group (P=0.0064). CONCLUSION: A decision aid for parents of children with BPD may improve understanding of the condition and help facilitate communication between parents and doctors.

Delivery room interventions to prevent bronchopulmonary dysplasia in extremely preterm infants.

Bronchopulmonary dysplasia (BPD) is the most common chronic respiratory complication of preterm birth. Preterm infants are at risk for acute lung injury immediately after birth, which predisposes to BPD. In this article, we review the current evidence for interventions applied during neonatal transition (delivery room and first postnatal hours of life) to prevent BPD in extremely preterm infants: continuous positive airway pressure (CPAP), sustained lung inflation, supplemental oxygen use during neonatal resuscitation, and surfactant therapy including less-invasive surfactant administration. Preterm infants should be stabilized with CPAP in the delivery room, reserving invasive mechanical ventilation for infants who fail non-invasive respiratory support. For infants who require endotracheal intubation and mechanical ventilation soon after birth, surfactant should be given early (<2 h of life). We recommend prudent titration of supplemental oxygen in the delivery room to achieve targeted oxygen saturations. Promising interventions that may further reduce BPD, such as sustained inflation and non-invasive surfactant administration, are currently under investigation.

Benefits of non invasive ventilation.

Mechanical ventilation of the newborn infant has increased neonatal survival. However, this increased survival has come at the expense of increased morbidity, in the form of bronchopulmonary dysplasia, and at the cost of an expensive technology. Continuous positive airway pressure (CPAP) is accepted as conferring clinical benefit in supporting the recently extubated preterm infant and in the management of apnea of prematurity. Attention is now being drawn to physiologic and clinical evidence to support CPAP use, with or without early surfactant, as a primary treatment of hyaline membrane disease. The purpose of this review is to explore these proposed benefits of non invasive ventilation and place them in the context of current clinical evidence.

Pulmonary fluorodeoxyglucose uptake in infants of very low birth weight with and without intrauterine inflammation.

OBJECTIVE: We compared early pulmonary (18)fluorodeoxyglucose ((18)FDG) uptake in infants who had very low birth weight with and without exposure to intrauterine inflammation by using positron emission tomography (PET). A secondary goal was to correlate (18)FDG uptake with later death or bronchopulmonary dysplasia. METHODS: Within 72 hours of birth, 22 singleton infants between 25 and 30 weeks of gestation had a thoracic PET scan after intravenous (18)FDG. Influx constants (K(i)) for (18)FDG were determined. Placental histology assessed exposure to intrauterine inflammation. RESULTS: Chorioamnionitis was found in 13 infants. Seven of these infants also had evidence of funisitis. No inflammation was detected in the remaining nine infants. Median (minimum, maximum) thoracic K(I) was 0.008 (0.006, 0.011) mL/min/mL in infants with funisitis, 0.006 (0.002, 0.008) in infants with chorioamnionitis only, and 0.006 (0.001, 0.015) in infants with no evidence of intrauterine inflammation (P=.16). No relation was found between K(i) and later death or bronchopulmonary dysplasia. Cord blood interleukin-6 was elevated in newborns with placental inflammation (P=.014). CONCLUSION: Early thoracic PET scanning for metabolically active inflammatory cells does not differ between infants with and without exposure to intrauterine inflammation. Evidence of early intrapulmonary sequestration of inflammatory cells in some infants without chorioamnionitis points to the complex etiology of postnatal inflammation.

Pulmonary deposition of salbutamol aerosol delivered by metered dose inhaler, jet nebulizer, and ultrasonic nebulizer in mechanically ventilated rabbits.

The deposition efficiency of three methods of aerosol delivery of salbutamol into lungs of ventilated rabbits was compared: 1) metered dose inhaler (MDI) with holding chamber (HC), 2) jet nebulizer (JN), and 3) ultrasonic (US) nebulizer. The latter system was tested using two different sized medication reservoirs, a large (20 mL) cup (US20) and a small (10 mL) cup (US10). After delivery of technetium-99m-labeled salbutamol aerosol, deposition in the lungs, trachea, and ventilator circuit were estimated by a gamma counter. Total pulmonary deposition [mean(SEM)] as a percentage of the prescribed drug was: MDI + HC 0.22(0.05)%; JN 0.48(0.05)%; US20 0.90(0.13)%; US10 3.05(0.49)%. Only the deposition from the US10 was statistically significantly higher than the other modes (p < 0.05). Dynamic scintigraphy showed that, among the nebulizers, the US10 continued to deliver medication for longer than either the JN or the US20. We conclude that the US10 appears to be more efficient in delivering aerosol to the lung in this rabbit model and merits further evaluation for clinical efficiency.

[18F]fluorodeoxyglucose uptake in neonatal acute lung injury measured by positron emission tomography.

The objective of this study was to evaluate positron emission tomography (PET) of [18F]fluorodexoyglucose (18FDG) uptake as a measure of neonatal acute lung injury. Inasmuch as intrapulmonary sequestration of neutrophils is a hallmark of acute lung injury, quantification of neutrophil activity using 18FDG may offer a novel, in vivo technique to examine the progression and resolution of this disease. Ten newborn piglets were studied: six received bronchoalveolar lavage followed by 4 h of high pressure ventilation of create acute lung injury. Four healthy piglets served as controls. 18FDG (0.8 mCi/kg; 29.6 MBq) was given i.v. and PET (ECAT 953/31, Siemens) was performed for 90 min. During PET, all animals were sedated, paralyzed, and ventilated to maintain normal blood gases. The time course of radioactivity in lung regions and in plasma was used to calculate the rate constant for the metabolic trapping of 18FDG in tissue according to the method of C. S. Patlak. Median 18FDG influx constants were significantly higher in injured piglets (0.0187 min-1) than in control piglets (0.0052 min-1) (p < 0.01). Moreover, consistent with the 18FDG uptake data, injured piglets had moderate to severe injury on lung histology whereas control piglets had only slight and focal histologic changes. We conclude that PET of 18FDG uptake is an accurate, readily repeatable in vivo measure of neonatal acute lung injury.

Efficiency of aerosol medication delivery from a metered dose inhaler versus jet nebulizer in infants with bronchopulmonary dysplasia.

The best means for optimal delivery of drugs into lungs of infants with bronchopulmonary dysplasia (BPD) is uncertain. We aimed to measure radio-aerosol deposition of salbutamol by jet nebulizer and metered dose inhalers (MDI) in ventilated and non-ventilated BPD infants. In a randomized, crossover sequence, salbutamol lung deposition was measured using an MDI (2 puffs or 200 micrograms) or sidestream jet nebulizer (5 minutes of nebulization with 100 micrograms/kg) in 10 ventilated (mean birthweight, 1,101 g) and 13 non-ventilated (mean birthweight, 1,093 g) prematurely born infants. Non-ventilated infants inhaled aerosol through a face mask, connected to a nebulizer or an MDI and spacer (Aerochamber). Ventilated infants received aerosol from an MDI + MV15 Aerochamber or a nebulizer inserted in the ventilator circuit. Lung deposition by both methods was low: mean (SEM) from the MDI was 0.67 (0.17)% of the actuated dose, and from the nebulizer it was 1.74 (0.21)% and 0.28 (0.04)% of the nebulized and initial reservoir doses, respectively. Corresponding figures for the ventilated infants were 0.98 (0.19)% from the MDI and 0.95 (0.23)% and 0.22 (0.08)% from the nebulizer. In both groups, and for both methods of delivery, there was marked inter-subject variability in lung deposition and a tendency for the aerosol to be distributed to the central lung regions.

Cytokine expression by neutrophils and macrophages in vivo: endotoxin induces tumor necrosis factor-alpha, macrophage inflammatory protein-2, interleukin-1 beta, and interleukin-6 but not RANTES or transforming growth factor-beta 1 mRNA expression in acute lung inflammation.

Using a rat model of acute lung inflammation induced by intratracheal instillation of lipopolysaccharide (LPS), we investigated the kinetics of mRNA expression and the potential cellular sources of tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2), interleukin (IL)-1 beta, IL-6, RANTES, and transforming growth factor-beta 1 (TGF-beta 1). By Northern blot analysis, TNF-alpha and MIP-2 mRNAs in total lung tissue increased markedly by 30 min and peaked by 1 h after LPS exposure, whereas expression of IL-1 beta and IL-6 was not detected until 1 h and peaked within 6 h. In contrast, neither RANTES nor TGF-beta 1 mRNA was induced by LPS throughout 72 h, although a basal expression was detected in both saline- and LPS-treated lung tissues. At 1 h after LPS, the bronchoalveolar lavage (BAL) fluid contained about 98% alveolar macrophages (AM), whereas by 6 or 12 h, 88% of BAL cells were polymorphonuclear neutrophils (PMN). Upon extraction of total RNA after separation of AM from PMN in BAL, Northern analysis showed that at 1 h, AM expressed pronounced signals for TNF-alpha, MIP-2, IL-1 beta, and IL-6. At 6 and 12 h, however, while cytokine transcripts decreased in AM, PMN exhibited strong signals for these cytokines. A low basal noninducible signal for TGF-beta 1 but not RANTES was detected in both AM and PMN. Finally, by in situ hybridization techniques, PMN in the lung tissue, particularly those located in the vicinity of the bronchiole and vasculature, were demonstrated to localize MIP-2 mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Polymorphonuclear leukocytes as a significant source of tumor necrosis factor-alpha in endotoxin-challenged lung tissue.

The kinetic expression and potential cellular source of tumor necrosis factor-alpha (TNF-alpha) in lipopolysaccharide-(LPS) induced acute lung inflammation was investigated using a rat model by Northern blot analysis, in situ hybridization and immunohistochemistry. LPS induced a polymorphonuclear leukocyte infiltrate in the lung that peaked between 6 and 24 hours. TNF-alpha messenger (m)RNA was strongly induced by LPS in whole lung tissues shown by Northern analysis. Both alveolar macrophages and polymorphonuclear leukocytes (PMNs), purified from bronchoalveolar lavage fluids of LPS-treated rats, were shown to express TNF-alpha mRNA by Northern analysis. However, PMNs displayed several times more TNF-alpha mRNA, relative to actin mRNA, than alveolar macrophages at 6 and 12 hours. By in situ hybridization, most of the cells positive for TNF-alpha mRNA at 6 and 12 hours seemed to be PMNs located within the tissue near bronchioles or vessels. By immunohistochemistry, TNF-alpha protein was localized mainly to alveolar macrophages at early times (1 to 3 hours) after LPS challenge, and thereafter, PMNs seemed to be the predominant source of TNF-alpha protein as more than 90% of total intraalveolar positive cells at 6 and 12 hours were PMN. Thus, our data provide the first in vivo evidence that PMNs can serve as a significant source of TNF-alpha at sites of acute inflammation.

Respiratory response and pharmacokinetics of intravenous salbutamol in infants with bronchopulmonary dysplasia.

The effects of iv salbutamol on respiratory mechanics were studied in six infants with bronchopulmonary dysplasia. Salbutamol was infused at a dose of 30 micrograms/kg over 30 min in five infants; a sixth infant received 66.7 micrograms/kg over 4 min. Salbutamol caused improvement in total respiratory system compliance and in airflow resistance. There was no correlation between salbutamol serum concentration and pulmonary function. Elimination half-time appears to be dictated in these infants more by the distribution volume (Vd) than by clearance (Cl). The area under concentration-time curve of salbutamol correlated inversely to the change in heart rate (HR). There was a significant positive correlation between Vd and percent HR change. These data provide evidence that preterm infants have measurable activity of bronchiolar beta 2 receptor responsive to salbutamol.

Widened subarachnoid space in pre-discharge cranial ultrasound: evidence of cerebral atrophy in immature infants?

The authors examined the incidence of widened subarachnoid spaces (SAS) among 75 infants with birthweights less than or equal to 1250g, and their significance in developmental outcome. Nine of 30 infants with gestations less than or equal to 27 weeks had widened SAS in their pre-discharge ultrasound scans. Three of the nine, including two with periventricular leukomalacia (PVL), had late-onset ventricular enlargement, unrelated to intraventricular haemorrhage (IVH): all three were developmentally impaired. The other six infants without ventricular enlargement developed normally, including one with IVH. Five of the remaining 21 infants with gestations less than or equal to 27 weeks and without widened SAS were developmentally impaired. Widened SAS was not associated with a significantly increased risk of developmental impairment; ventricular enlargement and PVL were the only significant factors. The authors conclude that an isolated finding of widened SAS is not predictive of impairment in immature infants.

High-frequency oscillation in the rescue of infants with persistent pulmonary hypertension.

High-frequency oscillatory ventilation (HFOV) was used to treat 41 infants with persistent pulmonary hypertension of the newborn (PPHN). Of the 37 patients who showed early improvement on HFOV, three died. The remaining 34 patients demonstrated, within one hour of the switchover to HFOV, a rise in mean arterial/alveolar oxygen tension ratio (PaO2/PaO2) from 0.093 +/- 0.041 (SD) to 0.132 +/- 0.051 (p less than .001), and a fall in mean PaCO2 from 42 +/- 10 to 34 +/- torr 9 (p less than .01). Mean airway pressure (Paw) fell significantly (p less than .01) within 12 h. The mean duration of conventional mechanical ventilation before starting HFOV was longer in 13 patients who developed bronchopulmonary dysplasia (BPD) than in 21 non-BPD patients (44.7 +/- 32.3 vs. 19.1 +/- 15.6 h, p less than .002), as was the duration of exposure to Paw greater than 15 cm H2O during that treatment mode (31.8 +/- 21.3 vs. 9.5 +/- 6.0 h, p less than .001). HFOV is often effective in the treatment of patients with PPHN, and early initiation of this type of mechanical ventilation may be associated with a reduced incidence of BPD.

Comparison of the digitalis receptor in erythrocytes from preterm infants and adults.

We compared 86rubidium by erythrocytes of preterm infants and adults as a measurement of their Na+, K+, ATPase enzyme system. In neonates, total uptake (0.92 +/- 0.13 micrograms/10(6) cells) and specific uptake (0.64 +/- 0.076 micrograms/10(6) cells) were significantly higher than in adults (0.52 +/- 0.1 and 0.29 +/- 0.06 micrograms/10(6) cells, respectively; p less than 0.025). The percentage of specific uptake from total uptake was higher in infants (73.3 +/- 2.3%) than in adults (57.9 +/- 4.6%) (p less than 0.005). No differences were found in the affinity constant of 86Rb uptake between infants (4.35 +/- 0.48 ng/ml) and adults (4.85 +/- 0.48 ng/ml). Stratification of infants according to their serum K+ concentrations revealed that levels above 5.4 mEq/liter were associated with a higher specific uptake (0.79 +/- 0.107 micrograms/10(6) cells) than in normokalemic infants (0.54 +/- 0.09 micrograms/10(6) cells) or adults (0.304 +/- 0.061 micrograms/10(6) cells) (p less than 0.05). The difference between hyperkalemic and normokalemic infants persisted after excluding those who received adult packed cells (0.88 +/- 0.1 and 0.6 +/- 0.12 micrograms/10(6) cells, respectively) (p less than 0.05). Infants with serum K+ greater than 5.8 mEq/liter received on average significantly more K+ in previous days (2.46 +/- 0.49 versus 1.13 + 0.34 mEq/kg.day; p less than 0.025). The different K+ level could not be attributed to different creatinine clearance in the two groups.

Diagnosis and therapy of necrotizing tracheobronchitis in ventilated neonates.

From January 1983 to September 1984 our neonatal ICU (NICU) treated eight endotracheally intubated infants who had suspected airway obstruction characterized by hypercarbia dissonant with severity of lung disease and difficulty in ventilation with lack of chest movement, both on conventional intermittent mandatory ventilation and high-frequency oscillation. Bronchoscopic removal of necrotic tissue was possible in six infants, two of whom survived. Bronchoscopy showed desquamation of epithelial surfaces, leaving encrusted exudations considered to be characteristic of necrotizing tracheobronchitis (NTB). The four nonsurvivors of bronchoscopy and one of the infants not submitted to bronchoscopy had NTB confirmed at autopsy. NTB was not associated with any specific lung disease, humidifier, or ventilator. The autopsy frequency of NTB during this period was 5 per 160 NICU admissions. A separate chart review of unselected autopsied cases in 1981 and 1982 showed that 12 of 284 neonates admitted to the NICU had NTB. NTB appears to be a rediscovered condition related to endotracheal intubation and mechanical ventilation using high mean airway pressures.