Treatment of patent ductus arteriosus: indomethacin or ibuprofen?

Persistent patent ductus arteriosus (PDA) in preterm infants can result in serious hemodynamic changes causing respiratory, gastrointestinal and renal morbidities if not treated within the first week of life. The treatment options available are a conservative approach, pharmacological treatment with cyclo-oxygenase (COX) inhibitors and surgical ligation. The COX inhibitors approved for use in the United States are indomethacin and ibuprofen lysine. Both of these drugs are equally effective in closing the PDA. Subtle differences exist between these two preparations. Indomethacin has a protective effect on the incidence of intraventricular hemorrhage (IVH) but reduces the blood flow to the kidneys and the brain. Ibuprofen is less toxic but has no effect on IVH. Efficacy of pharmacological treatment is influenced by timing of initiation of therapy. Surgical treatment is the only option when pharmacological treatment fails to close the PDA in symptomatic infants. Long-term neurological and respiratory morbidities are associated with surgical ligation. This paper reviews these medical considerations in the treatment options for PDA in premature infants.

Microphonic versus end-tidal carbon dioxide nasal airflow detection in neonates with apnea.

Impedance pneumography in combination with expired CO2 monitoring are commonly used techniques for detecting central and obstructive apnea in infants. In this investigation an American Telephone and Telegraph StarSet-1 3000-ohm self-actuating microphone connected to the end of an infant cannula was used to monitor neonatal nasal airflow to detect breaths and apnea. The microphone was placed in a soundproof container to eliminate environmental sound artifacts. Analyses of 100 breaths from five patient samples during active and quiet sleep showed that there was no significant difference between microphone and expired CO2 recording of respiration. The techniques were 98% and 96% sensitive, respectively. Microphonic detection of nasal airflow identified 27 of the 32 episodes of upper airway obstruction (84.2%) registered by end-tidal CO2 recording. Inspiratory and expiratory events could also be well documented. Microphonic recording of nasal airflow is a reliable and inexpensive technique to detect apnea.

Sleep apnea and hypoxemia in recently weaned premature infants with and without bronchopulmonary dysplasia.

Infants with bronchopulmonary dysplasia (BPD) experience significant hypoxemia. Apnea indices and oxygen saturation levels of ten infants with BPD were compared to ten healthy premature infants who were evaluated to rule out apnea or bradycardia prior to discharge from the hospital. Infants with BPD who had been recently (less than 7 days) weaned from supplemental oxygen were evaluated on and off supplemental oxygen. Premature controls had never received oxygen nor ventilation assistance. Infants with BPD were born significantly more prematurely (28.1 +/- 1.0 vs. 33.0 +/- 3.9 weeks; P = 0.0012) while chronologic ages at the time of evaluation, adjusted for prematurity, were equal (37.1 +/- 3.1 vs. 38.0 +/- 2.7 weeks). Comparisons of apnea densities (expressed as percent of sleep time) between BPD and non-BPD prematures revealed the following: neither the average obstructive apnea (0.15 +/- 0.36 vs. 0.14 +/- 0.31) nor periodic breathing densities (6.0 +/- 8.56 vs. 10.2 +/- 5.84) were different. Infants with BPD experienced significantly more central apnea (0.62 +/- 0.34 vs. 0.16 +/- 0.11; P = 0.003) than did non-BPD prematures. Average oxygen saturation levels were significantly less among BPD vs. non-BPD prematures (90.0 +/- 10.18% vs. 95.7 +/- 4.33%; P = 0.033). When supplemented with oxygen, BPD prematures had significantly higher saturation (X = 94.5%) than when breathing room air (X = 90.0%). Both central apnea and periodic breathing densities declined significantly with this improvement in saturation (0.64 vs. 0.04% and 6.0 vs. 1.4%, respectively). These data suggest that saturation status may indicate central respiratory stability in chronic lung disease.

Prediction of the acute response to surfactant therapy by pulmonary function testing.

We tested the hypothesis that pretreatment pulmonary function values would be predictive of the response to the synthetic pulmonary surfactant, Exosurf (Burroughs Wellcome Co.) treatment of infants with respiratory distress syndrome (RDS). Pulmonary compliance and resistance were measured prior to Exosurf treatment in 40 infants with severe RDS. In 36 patients who survived for at least 24 hr the acute response to therapy was quantitated by calculated post-treatment/pretreatment ratios of ventilator efficiency index (VEI) and arterial/alveolar oxygen tension ratios [Pa/AO2]. The values of these calculated response ratios 24 and 48 hr after treatment varied widely among individual patients. The magnitude of the response was not related to birthweight, gestational age, age at treatment, pretreatment VEI, pretreatment Pa/AO2, or pretreatment pulmonary compliance. However, the response to Exosurf as measured by improvements in Pa/AO2 at 24 and 48 hr was related to pretreatment pulmonary resistance (r = -0.34, P less than 0.05 and r = -0.60, P less than 0.001), high pretreatment pulmonary resistance was associated with a poor response to Exosurf 24 and 48 hr after treatment.

Renal function during the first 72 hours of life in sick infants with birthweight less than 1250 grams.

Renal function was evaluated by inulin clearance (Cin) in infants weighing less than 1250 g (N = 16) during the first 72 hours of life. Their mean +/- SD gestational age (GA) was 28.5 +/- 2.2 weeks and the birthweight (BW) was 990 +/- 158 g. Eleven studies were performed on day 1, 9 on day 2, and 11 on day 3. Mean Cin were 0.27 +/- 0.23, 0.37 +/- 0.13, and 0.46 +/- 0.44 mL/kg/min on days 1, 2, and 3, respectively, but the changes were not significant. Individual Cin values ranged from 0.039 to 1.54 mL/kg/min. The Cin was lower than that observed in larger and more mature infants. There was no correlation between Cin and fractional sodium excretion (FeNa), GA, BW, or fluid intake. Fe Na did not correlate with serum sodium or sodium intake.

Apnea in subsequent asymptomatic siblings of infants who had an apparent life-threatening event.

Infants experiencing apparent life-threatening events (ALTE) have been reported to have elevated frequencies of periodic breathing and obstructive apnea when compared to presumably normal control groups. Whether these characteristics extend to the siblings of ALTE infants remains unknown. This study compared, retrospectively, the apnea indices of 13 first-born infants experiencing an ALTE with their subsequent asymptomatic siblings who had undergone polygraphic sleep apnea evaluations (including electrocardiogram, chest wall movements, expired CO2, and transcutaneous pulse oximetry). Gestation, birthweight, age at study, apnea and periodic breathing indices, and oxygen desaturations were compared. Regression analyses revealed that adjustments for gestational and postnatal age eliminated differences in apnea indices. ALTE infants and their subsequent siblings experienced similar rates of apnea. Neither group had elevated rates of prolonged central apneas (greater than 10 seconds duration) or periodic breathing (greater than 5% sleep time). Neither group had subsequent severe apneas. The use of polygraphic study and cardiac/apnea monitors in subsequent siblings of ALTE are unnecessary and should be considered only when there is parental disagreement.

Cerebrocostomandibular syndrome. Case report and literature review.

Cerebrocostomandibular syndrome (CCM) is characterized by micrognathia, cleft palate, rib defects, and frequently, mental deficiency. Death from respiratory complications occurs in 40 percent of cases before they reach 1 year of age. We describe a case of CCM with the previously unreported findings of large for gestational age at birth, radiologic evidence of bilaterally displaced radial heads, and development of brachycephaly.

Rapid determination of glomerular filtration rate in infants using Tc-99m DTPA.

Glomerular filtration rate obtained by using Tc-99m DTPA was compared with that obtained from Schwartz's formula using serum creatinine and length in 21 infants (age range, 3 to 348 days). The GFR (mean +/- SD) obtained by Tc-99m DTPA was 76 +/- 37 ml/min per 1.73m2 and by the Schwartz formula was 83 +/- 49 ml/min per 1.73m2. GFR by Tc-99m DTPA method overestimated GFR by 3.6% compared to the Schwartz method. The imaging technique and the advantages are discussed.

Nasal intermittent positive pressure ventilation after surfactant treatment for respiratory distress syndrome in preterm infants <30 weeks' gestation: a randomized, controlled trial.

OBJECTIVE: To compare the effect of early extubation to nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) on the need for mechanical ventilation via endotracheal tube (MVET) at 7 days of age in preterm infants <30 weeks' gestation requiring intubation and surfactant for respiratory distress syndrome (RDS) within 60 min of delivery. STUDY DESIGN: Multicenter, randomized, controlled trial. A total of 57 infants were randomized within 120 min of birth to NCPAP (BW 1099 g and GA 27.8 weeks) and 53 infants to NIPPV (BW 1052 g, and GA 27.8 weeks). Infants were stabilized on NCPAP at birth and were given poractant alfa combined with MVET within 60 min of age. When stabilized on MVET, they were extubated within the next hours or days to NCPAP or NIPPV. RESULT: A total of 42% [corrected] of infants needed MVET at 7 days of age in the NCPAP group compared with 17% in the NIPPV group (OR: 3.6; 95% CI: 1.5, 8.7). Days on MVET were 12 ± 11 days in NCPAP group compared with 7.5 ± 12 days in the NIPPV group (median 1 vs 7 days; P=0.006). Clinical bronchopulmonary dysplasia (BPD) was 39% in the NCPAP group compared to 21% in the NIPPV group (OR: 2.4; 95% CI: 1.02, 5.6). Physiological BPD was 46% in the NCPAP group compared with 11% in the NIPPV group (OR: 6.6, 95% CI: 2.4, 17.8; P=0.001). There were no differences in any other outcomes between the two groups. CONCLUSION: NIPPV compared with NCPAP reduced the need for MVET in the first week, duration of MVET, and clinical as well as physiological BPD in preterm infants receiving early surfactant for RDS.

Iatrogenic complications in the neonatal intensive care unit.

With the introduction of novel technologies and approaches in neonatal care and the lack of appropriately designed and well-executed randomized clinical trials to investigate the impact of these interventions, iatrogenic complications have been increasingly seen in the neonatal intensive care unit. In addition, increased awareness and the introduction of more appropriate quality control measures have resulted in higher levels of suspicion about and increased recognition of complications associated with delivery of care. The incidence of complications also rises with the increased length of hospital stay and level of immaturity. Approximately half of the iatrogenic complications are related to medication errors. The other complications are due to nosocomial infections, insertion of invasive catheters, prolonged mechanical ventilation, administration of parenteral nutrition solution, skin damage and environmental complications. Adopting newer technologies and preventive measures might decrease these complications and improve outcomes. Quality improvement projects targeting areas for improvement are expected to build team spirit and further improve the outcomes. In addition, participation in national reporting systems will enhance education and provide an opportunity to compare outcomes with peer institutions.

To tube or not to tube babies with respiratory distress syndrome.

The use of mechanical ventilation in premature infants with respiratory distress syndrome (RDS) and respiratory failure often results in barotrauma, volutrauma and chronic lung disease (CLD). Research indicates that early surfactant therapy and initiation of nasal continuous positive airway pressure (CPAP) for these infants significantly reduces the need for mechanical ventilation and the incidence of CLD. Different CPAP delivery systems exist, each with some practical and clinical advantages and disadvantages. Clinical trials indicate that optimal management of neonatal RDS could be improved by early surfactant treatment followed immediately by extubation and stabilization on CPAP. Evidence suggests a synergistic effect between early surfactant administration (within 2 h of birth) and rapid extubation to nasal CPAP with a significant reduction in the need for mechanical ventilation and its associated morbidities.

Fetal and newborn lambs differ in their cardiopulmonary responsiveness to adenosine agonists.

We investigated cardiorespiratory responses to adenosine analogs in the pre- and postnatal periods in an unanesthetized chronic animal preparation. Heart rate, blood pressure, breathing movements and blood gases were measured in 8 fetal lambs (117-130 days gestation) and 9 newborn lambs (4-30 days). Various doses of analogs were given by intravenous infusion. L-N6-5'-Phenylisopropyladenosine (L-PIA), 5-N-ethyl carboxamidoadenosine (NECA) and cyclohexyladenosine (CHA) were studied. All analogs produced dose-dependent bradycardia and hypotension in the fetus. However, in the newborn, NECA produced a dose-dependent tachycardia, whereas PIA and CHA produced a dose-dependent bradycardia. Fetal breathing movements were interrupted by all the analogs, but they did not produce apnea in the newborn. No changes in blood gases were observed. The actions of the adenosine agonists were blocked by caffeine.

Respiratory abnormalities in infants of substance-abusing mothers: role of prematurity.

It is a current hypothesis that maternal history of drug addiction during pregnancy and detection of drugs in the urine of the newborn are associated with increased incidence of apnea. To test this hypothesis, we reviewed polygraphic studies of respiration in two groups of infants who had been exposed in utero to cocaine (and other drugs). The first group was composed of 20 term infants (39.1 +/- 0.8 weeks gestation), and premature infants (35.4 +/- 0.8 weeks gestation). None of the infants were on methylxanthines. These infants were matched with 15 term and 15 preterm infants of similar gestational age. Variables studied were: heart rate, respiration, chest impedance pneumography, nasal airflow and oxygen saturation (pulse oximetry). Apnea indices for central and obstructive events of short and long duration as well as periodic breathing and oxygen saturation were obtained. Term drug-exposed infants had less central apnea and a higher rate of periodic breathing compared to term controls, whereas drug-exposed premature infants had more obstructive apnea and less periodic breathing compared to premature controls. These observed differences within groups were subtle and clinically insignificant. Other parameters studied were not different. When term and preterm infants were compared, preterm infants had significantly higher central apnea, obstructive apnea and periodic breathing rates. These differences appeared to be related to gestational age differences, not to drug exposure. There was no evidence that exposure to cocaine and other drugs actually inhibited respiration.