Michael J Antunes

Psychological Aspects of Parenting Critically Ill Neonates

This study was designed to objectively examine depression and distress levels in parents of ill versus parents of healthy neonates by utilizing two well-validated questionnaires, the Beck Depression Inventory (BDI) and Kellner Symptom Questionnaire (KSQ). In addition, morbidity of infants was assessed by the Minde-Whitelaw Neonatal Morbidity Scale, and parents completed a socioeconomic questionnaire. Analysis of mean BDI and KSQ scores revealed significant differences between parents of ill neonates and parents of healthy neonates in BDI, total KSQ scores, KSQ anxiety, and depression scale scores. Within these groups, respondents whose scores fell into moderate to severe ranges of distress on either questionnaire were referred for counseling. The BDI and KSQ, can be tools for better understanding about distress levels in parents of ill and healthy neonates.

The Clinical Value of Screening Chest Radiography in the Neonate With Lung Disease

To examine the role of routine chest radiography in the management of the critically ill neonate with pulmonary disease, 41 term and preterm infants with lung diseases were prospectively evaluated. Seventy radiographs (35%) were obtained for clinical indications and 128 (65%) for prospective screening. Studies were compared with each infants most recent previous study, if available. Every exam was designated Level I, if the radiograph identified a new finding that required clinical intervention; Level II, if an abnormality or interval change was observed that did not require immediate intervention; or Level III, if there was no interval change since the previous radiograph. Thirty-three (47%) indication radiographs and 63 (49%) screening radiographs showed significant changes since the previous study. Twenty-four (34%) of the indication radiographs and 42 (33 % ) of the screening radiographs had Level I abnormalities (P = NS). Nine ( 13 % ) of the indication radiographs and 21 (16%) of the screening radiographs had Level II abnormalities (P= NS). Results suggest that routine screening chest radiographic studies are an important adjunct of care in critically ill newborns with respiratory disease and may identify potential problems before they are reflected in a change in clinical status.

Infant thoracic surgery: Procedure-dependent pulmonary response

Respiratory insufficiency is a common complication of thoracic surgery in infants. To better define this dysfunction, pulmonary compliance (CL) and resistance (R) were measured for 17 infants who underwent common thoracic procedures: Blalock-Taussing shunting (n = 7) repair of congenital coarctation of the aorta (n = 10). Measurements were obtained preoperatively and 0, 1, and 3 days postoperatively. Preoperatively, CL was lower and R was similar for the two groups. Both groups had decreased CL and increased R on postoperative day 0; infants with coarctation had recovery to preoperative values by postoperative day 1 for CL, and day 3 for R. CL and R did not return to the preoperative values by postoperative day 3 in infants with a shunt procedure. The changes in R were greater than those in CL for both groups in the postoperative period. These data indicate that such thoracic procedures are associated with pulmonary morbidity that is airway-predominant, and that the degree of compromise and the time until recovery are, in part, procedure-specific.

Neurodevelopment and Medical Follow-up of Infants Treated with Inhaled Nitric Oxide (NO). † 1250

Neurodevelopment and Medical Follow-up of Infants Treated with Inhaled Nitric Oxide (NO). † 1250

MECONIUM INDUCED INJURY IN THE RAT ALTERS SURFACTANT DISTRIBUTION AND COMPOSITION. † 1197

Meconium aspiration syndrome (MAS) remains a common cause of respiratory failure in neonates resulting from lung injury with surfactant inhibition. In this study we examined the effect of meconium injury on alveolar surfactant phospholipids (PL) and proteins over 72 hours in spontaneously breathing animals. Twenty two adult rats were given 4.5 mg dry weight human meconium as a 20% slurry after endotracheal intubation. Rats were mechanically ventilated in room air briefly (5-10 minutes) and extubated to spontaneously breathe room air. They were sacrificed at 16 (n=5), 24 (n=6), 48 (n=7) and 72 hrs (n=4). Healthy control animals (n=7) received no meconium. Lavages (BAL) were obtained from excised lungs and sequentially centrifuged for isolation of cells (Cell Ct × 106), then large (Lag) and small (Sag) surfactant aggregates. The mean ± SE for BAL total protein (mg), total PL (mg), and Dipalmitoylphosphatidylcholine (DPPC, mg) in Lag and Sag were:Table Western blot and immunoblot analysis demonstrated semi-quantitative increases in surfactant proteins A and B compared to controls at 16 and 24 hours. This suggests that meconium injury may have differential effects on surfactant PL and proteins. In this model, meconium instillation resulted in reversible injury with exudative changes preceding alterations in surfactant composition. We speculate that surfactant inhibition in MAS may be partially attributed to exudative lung injury resulting in accelerated surfactant PL metabolism.

SUPEROXIDE DISMUTASE AND SURFACTANT THERAPY IN A RAT MODEL OF MECONIUM INJURY. † 1969

Meconium aspiration syndrome (MAS) is related, in part, to exudative lung injury causing surfactant inhibition and pulmonary dysfunction. We evaluated the effect of intratracheal (IT) surfactant replacement (Survanta, Ross Laboratories) and recombinant human Cu-Zn superoxide dismutase (SOD) in a rat model of meconium (mec) injury. Intubated adult rats (400-500gm), ventilated with room air, received IT mec (.625ml/kg of 60mg/ml, n=5) or saline(1.6ml/kg, n=6). Three groups received mec then either 100mg/kg Survanta(Surv) after 15 min (n=4), or 5mg/kg SOD after 35min (n=5) or both Surv then SOD (n=3). All groups were ventilated for 60min, extubated to room air and at 24 hours (correlating with maximal injury) dynamic lung compliance (Cdyn, ml/cmH2O/kg) was measured and bronchoalveolar lavage (BAL) obtained. The mean±SE of BAL total protein (Protein, ug/ml), surfactant phospholipid (PL,ug/ml) and surfactant protein (SP-A, B, ratio to saline group) by immuno dot-blot and Western analysis were:Table Compared to saline animals, mec animals demonstrated lower Cdyn (1.2±33 vs..74±.17, respectively, p<0.05), which did not improve with Surv or SOD. In this model, Surv or SOD, alone or in combination, did not prevent exudative lung injury, or improve pulmonary mechanics. Surv alone increased PL and SP-A, while Surv with SOD resulted in even greater increases. We speculate that Surv therapy after mec injury may increase alveolar surfactant, and this effect may be accentuated by combined therapy with SOD.

MECONIUM INJURY RESULTS IN ALTERED LUNG ELASTIC FORCES INDEPENDENT OF SURFACTANT FUNCTION. † 1137

Increased surface tension (ST) forces at the gas-liquid interface are responsible, in part, for the pulmonary dysfunction associated with aspiration of meconium (Mec). Parenchymal lung injury from Mec, however, may alter elastic lung properties and compromise mechanics independent of ST forces. To investigate the pathophysiology of Mec injury, we instilled 32mg dry weight of human Mec in 0.5 ml saline (NS), or NS intratracheally in 400-450 gm adult rats, followed by 30 minutes of mechanical ventilation with room air. Following extubation, the animals spontaneously breathed room air for 16 hours, a period we previously demonstrated to concur with maximal exudative lung injury. After 16 hours, dynamic compliance (Cdyn, ml/cmH2O/kg) and total pulmonary resistance (cmH2O/l/s) were measured using an esophageal balloon and pnuemotachography. Excised, degassed lungs were then inflated with NS, to generate static liquid filled pressure-volume curves(Cstat, ml/cmH2O/kg). Separate Mec and NS animals had lungs excised and lavaged (BAL) with NS. Total protein (Protein, μg/ml) and electrophoresis(PAGE) were performed on cell free lavage fluid. The mean±SE values were: Table PAGE demonstrated a predominance of serum proteins in BAL, confirming endothelial dysfunction. Even with the elimination of ST forces by liquid filling, injured lungs demonstrated heightened elastic forces and lung compliance remained decreased. These results indicate airway and parenchymal dysfunction associated with meconium induced lung injury. This suggests that in Mec injury, surfactant inhibition accounts for only part of the diminished mechanics, and that interstitial lung changes may significantly and independently affect lung mechanics.

PARTIAL LIQUID VENTILATION FOR INFANTS FAILING ON EXTRACORPOREAL MEMBRANE OXYGENATION (ECMO). † 1251

A trial of partial liquid ventilation (PLV) with sterile perflubron(LiquiVent©; Alliance Pharmaceutical, San Diego CA.) is being conducted for infants with severe respiratory failure requiring ECMO support. Infants are enrolled, following informed parental consent, if they have been on ECMO for at least 48 hours, and are not responding to therapy. The lungs are filled with an FRC of perflubron and the infant is maintained on ECMO support and conventional ventilation. Evaporative losses of perflubron are replaced. PLV is continued for up to 96 hours if improvement is noted. To assess the effect of PLV on lung function, compliance (CL, ml/cmH2O/kg,) is determined by airway manometry and pneumotachography. Six infants (ARDS = 4, CDH = 2) have been studied (Mean ± SE age 3 ± 1.6 months) following prolonged periods of ECMO without improvement (mean ± SE 13± 3.3 days on ECMO, range 5 to 21 days). The infants tolerated PLV well, with volume recruitment observed on chest radiograph, and debris removal occurring on suctioning. The total amount of perflubron instilled varied with each infant (mean ± SE 64 ± 19 ml/kg, range 16 to 125 ml/kg). Compared to pre-PLV, all infants demonstrated improvements in Cl during PLV, ranging from 24 to 344% increase (Mean ± SE 186 ± 51%). Four of 6 infants weaned from ECMO to conventional ventilation for at least 3 days. One infant with CDH died of respiratory failure and one infant died from generalized Herpes soon after ECMO was withdrawn. Two infants died at 4 and 68 days post-PLV, and two are long term survivors. None of the deaths were related to PLV. These data demonstrate that PLV recruits lung volume and improves CL in critically ill infants on ECMO. The impact of PLV on long term outcome in these critically ill infants, however, will need to be evaluated. Supported in part by NIH MO1RR00240.