Nelson Claure

Changing trends in the epidemiology and pathogenesis of neonatal chronic lung disease

OBJECTIVE To assess the role of specific risk factors that may predispose preterm infants with mild or no initial respiratory distress syndrome to the development of chronic lung disease (CLD). STUDY DESIGN Clinical data were collected prospectively from 119 ventilator-supported preterm infants with birth weights between 500 and 1000 gm, who survived more than 28 days and required fewer than 3 days of treatment with fraction of inspired oxygen > 25% during the first 5 days of life. Logistic regression analysis was used in a multivariate assessment of risk factors for CLD. RESULTS Chronic lung disease occurred in 44 of the patients (37%). The analysis showed that low birth weight, patent ductus arteriosus (PDA), and sepsis were significant risk factors for CLD. The corresponding odds ratios for CLD and their 95% confidence intervals (CI) were as follows: 2.9 per 100 gm birth weight decrement (CI, 1.7 to 4.8); 6.2 (CI, 2.1 to 18.4) for PDA; and 4.4 (CI, 1.3 to 14.5) for sepsis. When sepsis and PDA occurred simultaneously, the odds ratio for CLD increased to 48.3 (CI, 6.3 to > 100) in comparison with infants without these conditions. Episodes of PDA were categorized as either early (occurring during the first week of life) or late (after the first week), and the respective odds ratios for CLD were 2.8 (CI, 0.8 to 9.4) and 21.1 (CI, 5.6 to 80) in comparison with infants without PDA. For the duration of symptomatic PDA, the odds ratio for CLD was 3.5 per week that the PDA remained open (CI, 1.9 to 6.5). CONCLUSION CLD is a frequent sequela in very low birth weight infants with mild or no respiratory distress syndrome. In this population, the development of late episodes of PDA, usually in association with a nosocomial infection, seems to play a primary role in the pathogenesis of CLD.

Bronchopulmonary dysplasia: changes in pathogenesis, epidemiology and definition.

Bronchopulmonary dysplasia (BPD) continues to be one of the most common long-term complications associated with preterm birth. Its incidence is increasing as the survival of extreme premature infants improves, but its clinical presentation is milder than the original description of Northway and collaborators. In contrast to the classic BPD that was strongly related to mechanical injury and oxygen toxicity, current forms of the condition are more related to immaturity, perinatal infection and inflammation, persistent ductus arteriosus and disrupted alveolar and capillary development. Many different definitions of BPD have been proposed, most of which are based on the duration of supplemental oxygen requirement. The different definitions can produce strikingly different incidence figures, which may account for the wide variations in the condition reported in the literature. Some of the limitations of the criteria most commonly used to diagnose BPD are discussed in this article.

Influence of infection on patent ductus arteriosus and chronic lung disease in premature infants weighing 1000 grams or less

OBJECTIVES To test the hypotheses that (1) infection increases ductal dilatory prostaglandins and inflammatory mediators that may influence the closure of a patent ductus arteriosus (PDA), increasing the incidence of late episodes of PDA (after 7 days) and the rate of closure failures, and (2) the concurrence of PDA and infection increases the risk of chronic lung disease (CLD). METHODS One hundred fourteen premature infants (birth weight, 500 to 1000 gm) were prospectively assessed for PDA and infection. Serum levels of 6-ketoprostaglandin F1 alpha and tumor necrosis factor alpha were measured routinely in all infants and when PDA or infection was present. Multivariate assessment of risk factors for PDA closure failure and for CLD was done by logistic regression, and expressed as an odds ratio and as 95% confidence intervals. RESULTS Late PDA episodes were more frequent in infants with infection than in those without infection. A temporally related infection (<5 days between both diagnoses) was associated with an increased risk of PDA closure failure (odds ratio, 19.1 (confidence interval, 4 to 90)). In addition to birth weight and the severity of initial respiratory failure, PDA and infection increased the risk of CLD (odds ratio, 11.7 (confidence interval, 1.7 to 81) for PDA; odds ration, 3.1 (confidence interval, 1 to 11) for infection). Furthermore, when both factors were temporally related, they further increased the risk of CLD (odds ratio, 29.6 (confidence interval, 4.5 to >100)). Infants with infection and those with PDA had higher levels of 6-ketoprostaglandin F1 alpha than did control subjects. Levels of tumor necrosis factor alpha were also elevated in infants with infection and in those with late PDA. CONCLUSIONS Infection adversely influences PDA outcome by increasing the risk of late ductal reopening and PDA closure failures. Increased levels of prostaglandins and tumor necrosis factor alpha in infants with infection may explain the poor PDA outcome. The concurrence of PDA and infection potentiates their negative effects on the risk of CLD.

Necrotizing Enterocolitis in Full-Term or Near-Term Infants: Risk Factors

A retrospective case-control study of necrotizing enterocolitis (NEC) affecting infants weighing > 2,000 g at birth was performed to determine those factors which could contribute to the development of NEC. Twenty-four infants met the criteria of definite NEC. For each case the next 2 healthy newborns were matched as controls. When compared with the control group, NEC infants had a significantly higher frequency of prolonged rupture of membranes, chorioamnionitis, Apgar score < 7 at 1 and 5 min, respiratory problems, congenital heart disease, hypoglycemia, and exchange transfusions. Only 3 infants with NEC were healthy newborns with an unremarkable perinatal course before NEC. There were no differences in the frequency of preeclampsia, maternal diabetes, maternal drug abuse, meconium-stained amniotic fluid and polycythemia. These results indicate that most of these more mature infants have a predisposing factor before developing NEC.

Proportional assist ventilation in low birth weight infants with acute respiratory disease: A comparison to assist/control and conventional mechanical ventilation ☆ ☆☆ ★

OBJECTIVES To compare the physiologic efficacy and safety aspects of proportional assist (PA), assist/control (A/C), and intermittent mandatory ventilation (IMV) in very low birth weight infants with acute respiratory illness and to test the hypothesis that ventilatory pressure requirements are lower and arterial oxygenation is improved during PA when compared with IMV or A/C at an equivalent inspired oxygen fraction. STUDY DESIGN Randomized, 3-period, crossover design. METHODS Thirty-six infants were stratified by birth weight (600 to 750, 751 to 900, and 901 to 1200 g) and exposed to consecutive 45-minute epochs of the 3 modalities in a sequence chosen at random. Tidal volumes of 4 to 6 mL/kg were targeted during A/C and IMV. The IMV rate was matched to the rate during an A/C test period. PA was adjusted to unload the resistance of the endotracheal tube and the disease-related increase in lung elastic recoil. RESULTS Compared with A/C and IMV, PA maintained similar arterial oxygenation with lower airway and transpulmonary pressures (15% to 44% reduction depending on the index variable). The oxygenation index decreased by 28% during PA. No adverse events were observed. The number and severity of apneic episodes and periods of arterial oxygen desaturations were similar with the 3 modes. Similar results were obtained within each birth weight subgroup. CONCLUSIONS PA safely maintains gas exchange with smaller transpulmonary pressure changes compared with A/C and IMV. It may therefore offer a way of reducing the incidence of chronic lung disease in low birth weight infants.

Mechanisms for episodes of hypoxemia in preterm infants undergoing mechanical ventilation

OBJECTIVE To ascertain possible mechanisms implicated in the development of transient episodes of hypoxemia (oxygen saturation < 85%) frequently observed in preterm infants undergoing mechanical ventilation, even after the acute phase of respiratory failure has passed. STUDY DESIGN Tidal flow, airway and esophageal pressure, and oxygen saturation were continuously recorded in 10 infants (mean +/- SD, birth weight 733 +/- 149 gm, gestational age 25.5 +/- 2.2 weeks, age 26.3 +/- 11.9 days) who had repeated episodes of hypoxemia without any evident cause. Measurements of minute ventilation (VE) inspiratory compliance (Ci), and inspiratory resistance (Ri) were compared before and during episodes of hypoxemia. RESULTS All episodes of hypoxemia were preceded by an active exhalation that produced a mean decrease in end-expiratory lung volume of 6.4 +/- 2.8 ml/kg. The reduction in lung volume was immediately followed by a sudden decrease in tidal flow and volume, despite continuation of mechanical ventilation at the same rate and peak pressure. The resulting hypoventilation was associated with a drop in Ci to approximately one half and an increase in Ri to more than double the baseline values. Approximately 30 seconds after the beginning of hypoventilation, the arterial oxygen saturation reached a hypoxemic level (oxygen saturation < 85%)> CONCLUSION Most hypoxemic episodes were triggered by an expiratory effort that produced a large decrease in lung volume. This reduction in lung volume probably leads to closure of small airways and the development of intrapulmonary shunts, which would explain the rapid development of hypoxemia.

Patent Ductus Arteriosus and Respiratory Outcome in Premature Infants

A persistent ductus arteriosus is a common event in preterm infants. The systemic-to-pulmonary shunting that occurs as the pulmonary vascular resistance decreases after birth can have significant cardiovascular and respiratory consequences. Acute pulmonary effects include pulmonary edema and hemorrhage, worsened lung mechanics and deterioration in gas exchange with hypoxemia and hypercapnia. The increased pulmonary blood flow can also produce damage to the capillary endothelium and trigger an inflammatory cascade. This, plus the need for longer and more aggressive mechanical ventilation, can explain the association between patent ductus arteriosus and an increased risk for bronchopulmonary dysplasia in extremely premature infants.

Multicenter Crossover Study of Automated Control of Inspired Oxygen in Ventilated Preterm Infants

OBJECTIVE: To determine the efficacy and safety of automated adjustment of the fraction of inspired oxygen (Fio2) adjustment in maintaining arterial oxygen saturation (Spo2) within an intended range for mechanically ventilated preterm infants with frequent episodes of decreased Spo2. METHODS: Thirty-two infants (gestational age [median and interquartile range]: 25 weeks [24–27 weeks]; age: 27 days [17–36 days]) were studied during 2 consecutive 24-hour periods, one with Fio2 adjusted by clinical staff members (manual) and the other by an automated system (automated), in random sequence. RESULTS: Time with Spo2 within the intended range (87%–93%) increased significantly during the automated period, compared with the manual period (40% ± 14% vs 32% ± 13% [mean ± SD]). Times with Spo2 of >93% or >98% were significantly reduced during the automated period (21% ± 20% vs 37% ± 12% and 0.7% vs 5.6% [interquartile ranges: 0.1%–7.2% and 2.7%–11.2%], respectively). Time with Spo2 of <87% increased significantly during the automated period (32% ± 12% vs 23% ± 9%), with more-frequent episodes with Spo2 between 80% and 86%, whereas times with Spo2 of <80% or <75% did not differ between periods. Hourly median Fio2 values throughout the automated period were lower and there were substantially fewer manual Fio2 changes (10 ± 9 vs 112 ± 59 changes per 24 hours; P < .001), compared with the manual period. CONCLUSIONS: In infants with fluctuations in Spo2, automated Fio2 adjustment improved maintenance of the intended Spo2 range led to reduced time with high Spo2 and more-frequent episodes with Spo2 between 80% and 86%.

Influence of different methods of synchronized mechanical ventilation on ventilation, gas exchange, patient effort, and blood pressure fluctuations in premature neonates

We studied the effects of two methods of synchronized mechanical ventilation [synchronized intermittent mandatory ventilation (SIMV) and assist/control (A/C)] on ventilation, gas exchange, patient effort, and arterial blood pressure (ABP) fluctuations. SIMV and A/C were applied in random order in 12 preterm neonates (gestational age, 29.7 ± 2.3 weeks; birth weight, 1,217 ± 402 g). We measured total (Vetot) and mechanical (Vemech) minute ventilation, spontaneous (Vtspont) and ventilator supported (Vtmech) tidal volume, transcutaneous oxygen saturation (SpO2), transculaneous PO2 (TcPO2), and PCO2, (TcPCO2), mean airway pressure (Paw), phasic esophageal pressure deflections (Pe) as an estimate of inspiratory effort, mean arterial blood pressure (ABP), and beat‐to‐beat ABP fluctuations. The measurements obtained during conventional intermittent mandatory ventilation (IMV) were compared with the recordings during SIMV and A/C. To make the measurement conditions comparable and to prevent hyperventilation, peak inspiratory pressure was reduced during the A/C mode so that Vetot remained in the same range as during the IMV mode. Whereas Vetot was similar in all three conditions by study design, Vemech was larger during SIMV and A/C than during IMV. Vtmech increased during SIMV and by study design was smaller during A/C than during IMV. Pe decreased during SIMV and A/C compared with IMV, and Paw was higher during A/C than during IMV or SIMV. Beat‐to‐beat ABP fluctuations were reduced during SIMV and A/C compared with IMV and showed a close positive correlation with Pe changes. We conclude that SIMV increases Vemech and reduces Pe compared with IMV, resulting in smaller intrathoracic and ABP fluctuations. During A/C, a substantial portion of the spontaneous respiratory effort is shifted to the ventilator, resulting in a further decrease in Pe and ABP fluctuations Pediatr Pulmonol. 1996; 22:305–313.

Effects of Synchronization During Nasal Ventilation in Clinically Stable Preterm Infants

Nasal ventilation is increasingly used to reduce invasive ventilation in preterm infants. The effects of nasal ventilation and the advantages of synchronized nasal ventilation have not been fully evaluated. The objective was to compare the short-term effects of nasal intermittent mandatory ventilation (NIMV) and synchronized NIMV (S-NIMV) with nasal continuous positive airway pressure (NCPAP) on ventilation, gas exchange, and infant-ventilator interaction. Sixteen clinically stable preterm infants requiring NCPAP (GA, 27.6 ± 2.3 wk; birthweight (BW), 993 ± 248 g; and age, 15 ± 14 d) were exposed to NCPAP, NIMV at 20/min, NIMV at 40/min, S-NIMV at 20/min, and S-NIMV at 40/min for 1 h each (Infant-Star ventilator), in random order. Tidal volume, minute ventilation, and gas exchange did not differ significantly between NCPAP, NIMV, and S-NIMV. Inspiratory effort decreased during S-NIMV compared with NCPAP and NIMV, whereas inspiratory effort during NIMV did not differ from NCPAP. Active expiratory effort and expiratory duration increased during NIMV. Chest wall distortion, apnea and hypoxemia spells, abdominal girth, and comfort did not differ. In conclusion, there were no short-term benefits on ventilation and gas exchange of nasal ventilation compared with NCPAP in clinically stable preterm infants. However, synchronized nasal ventilation reduced breathing effort and resulted in better infant-ventilator interaction than nonsynchronized nasal ventilation.