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Background: It is likely that the imbalance between the pro- and anti-inflammatory cytokines will determine the outcome in infants with severe respiratory failure receiving extracorporeal membrane oxygenation (ECMO)., Aims: We determined if there was an imbalance between pro- and anti-inflammatory cytokines in serial bronchoalveolar lavage (BAL) fluid obtained from survivors and non-survivors of ECMO., Methods: We therefore measured the cellular changes and the molar ratios of pro-inflammatory and anti-inflammatory cytokines in serial BAL fluid obtained from survivors and non-survivors of ECMO. Fifteen infants surviving ECMO (median age 1 day, range 1-120) and 7 who did not (28 days, range 1-402) were studied., Results: In the lungs of survivors, the increased proportion of airway neutrophils at presentation decreased with time and was matched by a parallel increase in percent alveolar macrophages as the infants' condition improved. The pro- and anti-inflammatory pulmonary cytokine ratios were static in the survivors. In the non-survivors, the ratio of tumour necrosis factor-alpha (TNF-alpha) against soluble TNF-receptor 1 (sTNF-R1) and soluble TNF receptor 2 (sTNF-R2) was increased at days 2-3 when compared to the survivors, but the molar ratio interleukin-1beta (IL-1beta)/soluble IL-1 receptor antagonist (sIL-1RA) was largely undetectable due to undetectable IL-1beta., Conclusions: These data suggest that the infants who survive ECMO resolve their pulmonary inflammation and that in non-survivors the ratio of TNF-alpha against its receptor antagonists is increased and is associated with a poor outcome. Furthermore, this group of infants were unable to produce significant concentrations of IL-1beta.

Background: The persistent airway neutrophilia observed in chronic lung disease of prematurity (CLD) may reflect inappropriate suppression of neutrophil apoptosis., Methods: 134 bronchoalveolar lavage (BAL) samples were obtained from 32 infants requiring mechanical ventilation for respiratory distress syndrome (RDS): 13 infants (median gestation 26 weeks, range 23 to 28) subsequently developed CLD (CLD group), and 19 infants (gestation 31 weeks, range 25 to 39) recovered fully (RDS group). A further 73 BAL samples were obtained from 20 infants (median age 2 days, range 1 to 402) receiving extracorporeal membrane oxygenation (ECMO) for severe respiratory failure., Results: Neutrophil apoptosis was increased in the RDS group (mean (SEM) neutrophil apoptosis on day 7 BAL: RDS 17.0 (8.6)% v CLD 0.7 (0.2)% (p<0.05)). BAL fluid obtained from RDS but not CLD patients was proapoptotic to neutrophils (apoptosis ratio BAL fluid/saline control: day 1, RDS 9.8 (5.5) v CLD 1.2 (0.1) (p<0.05); day 2, RDS 4.32 (2.8) v CLD 0.5 (0.4) (p<0.05)). There were similar findings in the ECMO group: survivors had proapoptotic BAL fluid compared with non-survivors (apoptosis ratio day 1, survivors 7.9 (2.1) v non-survivors 2.1 (0.7) (p<0.05))., Conclusions: Inappropriate suppression of neutrophil apoptosis may be associated with a poor outcome in newborn infants with respiratory failure.

Objectives: To determine the impact of age at repair in patients with tetralogy of Fallot on early postoperative morbidity., Methods: All patients less than 19 months of age (median age, 8 months; range, 36 days-18.5 months) who underwent complete repair of tetralogy of Fallot between January 1997 and December 1999 were reviewed. Data were analyzed on the preoperative clinical and anatomical characteristics, operative procedure and postoperative course in the intensive care unit. Independent factors associated with intensive care unit stay were sought using Cox's proportionate hazard modeling. In addition, independent factors associated with an intensive care unit stay of more than 2 days were sought in multiple logistic regression analysis., Results: Seventy-eight patients underwent surgical repair; 3 had (4%) had a previous systemic to pulmonary arterial shunt. There was no operative mortality. One late death occurred. The median intensive care unit length of stay and mechanical ventilation time were 2 days (range, 1-14) and 16.2 hours (range, 0-267), respectively. Age less than 3 months was associated with increased use of vasoactive drugs, higher postoperative fluid requirement, and a higher incidence of organ dysfunction but no patient required renal replacement therapy. The duration of ventilator support and the intensive care unit length of stay were also longer in this age group., Conclusions: Primary repair at an early age has excellent short-term outcome. Patients less than 3 months of age have an increased but transient intensive care unit morbidity.

Objective: To study the effect of carrier gas on CO(2) transport during high-frequency oscillatory ventilation in a closed model., Design: In vitro model study., Setting: Respiratory research laboratory affiliated with a tertiary center for pediatric critical care., Subject: In vitro, closed-lung model consisting of a glass tube (9.8 x 1000 mm) covered at each end with balloons., Intervention: Air or heliox (80:20) at constant pressure was oscillated inside the model, comparing the Sensormedics 3100A and Hummingbird BMO-20N oscillators at equal amplitude., Measurements and Main Results: Tracer gas (CO(2)) was injected at one end of the model, and CO(2) concentration was measured at the opposite end. Speed of CO(2) transport was expressed as the time for the CO(2) concentration to reach 63% of the final concentration (the time constant). In room air, using the Hummingbird oscillator and increasing frequency stepwise from 5 to 20 Hz, the time constant decreased from 2813 to 457 secs (p =.05). Using the Sensormedics oscillator in room air at increasing frequency from 5 to 15 Hz, the time constant decreased from 1584 to 551 secs (p =.05). In heliox, using the Hummingbird oscillator, the speed of CO(2) transport increased by 85% (p =.029) at 5 Hz and by 28% (p =.05) at 15 Hz. With the Sensormedics oscillator using heliox, the speed of CO(2) transport increased by 16% at 5 Hz (p =.009) and 52% at 15 Hz (p =.008). Proportionally, the increase in CO(2) transport with heliox was greater at 5 Hz for the Hummingbird oscillator and at 15 Hz for the Sensormedics oscillator., Conclusions: In a closed model, we showed that during high-frequency oscillatory ventilation in room air, CO(2) transport increases with increasing frequency for both ventilators. Using heliox as carrier gas significantly augmented CO(2) transport, but the increase is frequency and device dependent. The effect of heliox on oscillator performance and the clinical applicability of our findings require further study.

Background: Since few studies have assessed the repeatability of non-bronchoscopic bronchoalveolar lavage (NB-BAL), we compared cellular counts and cytokine concentrations in fluid obtained by standardised NB-BAL from each side of 20 intubated infants receiving extracorporeal membrane oxygenation (ECMO)., Methods: Total cell counts were obtained from 95 paired lavages and 77 pairs were suitable for differential counts and measurement of cytokine concentrations., Results: Moderate correlation was noted between the two sides for most cell types including total cell counts and percentages of neutrophils and macrophages (R=0.70-0.84) and for cytokine concentrations (IL-8 R=0.78, IL-6 R=0.75, TNF-alpha R=0.64, all p< or =0.001). Using Bland-Altman analysis the mean difference between the two sides approached zero for cellular constituents (total cell counts mean difference 1.7, limits of agreement -187.5 to +190.9 x 10(4)/ml; percentage neutrophils -3.9%, -41.5% to +33.6%; percentage macrophages 3.9%, -33.8% to +41.6%) but tended to be greater on the right for logarithmically transformed cytokine measurements (IL-8: left/right ratio 0.74, limits of agreement 0.12 to 5.45, IL-6: 0.93, 0.09 to 5.87, and TNF-alpha: 0.93, 0.27 to 3.16). Using linear regression with random effects to assess the variability, only the infant's age appeared to influence the cellular results but, for cytokines, only the volume retrieved affected the variability. The magnitude of the measurements, the underlying disease, the operator's experience, days on ECMO, or survival did not affect the variability., Conclusion: Measurements obtained by NB-BAL need to be interpreted with caution and strongly suggest that normalisation for the dilutional effects of saline is essential.

In muscular pulmonary atresia, major aortopulmonary collateral arteries are characteristic of pulmonary atresia with ventricular septal defect and are rarely seen in pulmonary atresia with intact ventricular septum. Two unusual cases of muscular pulmonary atresia are reported, one with an intact septum and one with a perimembranous ventricular septal defect, closed in utero by aneurysmal tricuspid tissue. In both cases the pulmonary blood supply came entirely from aortopulmonary collaterals. In case 1 a collateral artery connected the left subclavian artery and hypoplastic pulmonary arteries, and several aortopulmonary collaterals arose from the descending aorta, without overlap between these two circulations. In case 2 the pulmonary trunk and arterial duct were absent and the pulmonary blood supply came entirely from collateral arteries. The right ventricle was of normal size and tripartite with a closed perimembranous ventricular septal defect, discovered only at postmortem examination. These observations suggest right ventricular outflow tract obstruction early in fetal development, with involution of the pulmonary trunk and sixth arch derivatives, and persistence of primitive aortopulmonary connections. The morphology in case 1 is at odds with the theoretical division of pulmonary atresia with intact septum and pulmonary atresia with ventricular septal defect into two separate pathological entities that occur at different stages in fetal development.