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Biomedical subjects

Michael D Schreiber

Publications and source records attributed to Michael D Schreiber.

11 recordsLinked to original sources
PubMed2005

Neurodevelopmental outcomes of premature infants treated with inhaled nitric oxide.

BACKGROUND: Chronic lung disease and severe intraventricular hemorrhage or periventricular leukomalacia in premature infants are associated with abnormal neurodevelopmental outcomes. In a previous randomized, controlled, single-center trial of premature infants with the respiratory distress syndrome, inhaled nitric oxide decreased the risk of death or chronic lung disease as well as severe intraventricular hemorrhage and periventricular leukomalacia. We hypothesized that infants treated with inhaled nitric oxide would also have improved neurodevelopmental outcomes. METHODS: We conducted a prospective, longitudinal follow-up study of premature infants who had received inhaled nitric oxide or placebo to investigate neurodevelopmental outcomes at two years of corrected age. Neurologic examination, neurodevelopmental assessment, and anthropometric measurements were made by examiners who were unaware of the children's original treatment assignment. RESULTS: A total of 138 children (82 percent of survivors) were evaluated. In the group given inhaled nitric oxide, 17 of 70 children (24 percent) had abnormal neurodevelopmental outcomes, defined as either disability (cerebral palsy, bilateral blindness, or bilateral hearing loss) or delay (no disability, but one score of less than 70 on the Bayley Scales of Infant Development II), as compared with 31 of 68 children (46 percent) in the placebo group (relative risk, 0.53; 95 percent confidence interval, 0.33 to 0.87; P=0.01). This effect persisted after adjustment for birth weight and sex, as well as for the presence or absence of chronic lung disease and severe intraventricular hemorrhage or periventricular leukomalacia. The improvement in neurodevelopmental outcome in the group given inhaled nitric oxide was primarily due to a 47 percent decrease in the risk of cognitive impairment (defined by a score of less than 70 on the Bayley Mental Developmental Index) (P=0.03). CONCLUSIONS: Premature infants treated with inhaled nitric oxide have improved neurodevelopmental outcomes at two years of age.

Administration, Inhalation↗
PubMed2004

Interleukin (IL)-1 beta in tracheal aspirates from premature infants induces airway epithelial cell IL-8 expression via an NF-kappa B dependent pathway.

Tracheal aspirate IL-8 concentration and airway epithelial cell IL-8 expression are each increased in premature infants undergoing mechanical ventilation. We sought to determine the cytokines responsible for IL-8 expression in this context. Tracheal aspirates were collected from 18 mechanically ventilated premature infants. IL-8 protein abundance was high in tracheal aspirates from ventilated premature infants (mean, 5806 +/- 4923 pg/mL). IL-1 alpha (mean, 20 +/- 6 pg/mL), IL-1 beta (mean 67 +/- 46 pg/mL), and tumor necrosis factor (TNF)-alpha (mean, 8 +/- 2 pg/mL) were also found. Incubation of tracheal aspirates with 16HBE14o- human bronchial epithelial cells increased IL-8 protein in both cell lysates and supernatants, as well as transcription from the IL-8 promoter. Aspirates also induced nuclear factor (NF)-kappa B activation. Mutation of the IL-8 promoter NF-kappa B site abolished aspirate-induced IL-8 transcription. Endotoxin concentrations in the tracheal aspirates were negligible and incapable of inducing IL-8 promoter activity. Finally, incubation of tracheal aspirates with a neutralizing antibody against IL-1 beta reduced epithelial cell IL-8 production, whereas neutralizing antibodies against IL-1 alpha and TNF-alpha had no effect. We conclude that airway fluid from mechanically ventilated premature infants contains soluble factors capable of inducing airway epithelial cell IL-8 expression via a NF-kappa B-dependent pathway, and that IL-1 beta plays a specific role in this process.

Cells, Cultured↗
PubMed2003

Inhaled nitric oxide in premature infants with the respiratory distress syndrome.

BACKGROUND: Inhaled nitric oxide improves gas exchange, decreases pulmonary vascular lability, and reduces pulmonary inflammation. We hypothesized that the use of inhaled nitric oxide would decrease the incidence of chronic lung disease and death in premature infants with the respiratory distress syndrome. METHODS: We conducted a randomized, double-blind, placebo-controlled study of the effect of inhaled nitric oxide during the first week of life on the incidence of chronic lung disease and death in premature infants (less than 34 weeks' gestation) who were undergoing mechanical ventilation for the respiratory distress syndrome. Infants were randomly assigned to receive inhaled nitric oxide (10 ppm on day 1, followed by 5 ppm for six days) or inhaled oxygen placebo for seven days. We further randomly assigned the infants in each group to receive intermittent mandatory or high-frequency oscillatory ventilation. RESULTS: A total of 207 premature infants were enrolled. In the group given inhaled nitric oxide, 51 infants (48.6 percent) died or had chronic lung disease, as compared with 65 infants (63.7 percent) in the placebo group (relative risk, 0.76; 95 percent confidence interval, 0.60 to 0.97; P=0.03). There was no significant difference between the nitric oxide and placebo groups in the overall incidence of intraventricular hemorrhage and periventricular leukomalacia (33.3 percent and 38.2 percent, respectively), but the group given inhaled nitric oxide had a lower incidence of severe intraventricular hemorrhage and periventricular leukomalacia (12.4 percent vs. 23.5 percent; relative risk, 0.53; 95 percent confidence interval, 0.28 to 0.98; P=0.04). The type of ventilation had no significant effect on the outcome. CONCLUSIONS: The use of inhaled nitric oxide in premature infants with the respiratory distress syndrome decreases the incidence of chronic lung disease and death.

Administration, Inhalation↗
PubMed2003

Cardiopulmonary effects of nebulized sodium nitroprusside in term infants with hypoxic respiratory failure.

OBJECTIVE: To study whether nebulized nitroprusside (neb-NP) improves oxygenation in term infants with hypoxic respiratory failure (HRF). STUDY DESIGN: We studied 22 newborn term infants (gestational age, 39.7+/-0.4 weeks [mean+/-SEM]; birth weight, 3.6+/-0.1 kg) with hypoxia (Pao2<100 mm Hg) during mechanical ventilation (Fio2=1.0). Sodium nitroprusside (5 mg followed by 25 mg) was nebulized into the inspiratory arm of the ventilator circuit. Vital signs and arterial blood gas values were recorded after 20 minutes at each dose and before and after initiation of inhaled nitric oxide (iNO). RESULTS: Pao2 increased significantly with 5 mg neb-NP (from 64.6+/-5.6 to 90.1+/-15.3 mm Hg, P=.04) and with 25 mg neb-NP (113.2+/-20.4 mm Hg, P=.009). Differences between mean Pao2 at 5 mg versus 25 mg neb-NP were also statistically significant (P=.03). When comparing the effect of neb-NP to iNO, the treatment-induced increases in Pao2 were similar (52.1+/-18.7 vs 62.2+/-18.2 mm Hg, respectively, P=not significant). CONCLUSIONS: Neb-NP causes a dose-dependent increase in oxygenation in term infants with HRF, similar in magnitude to iNO* Neb-NP may be beneficial in infants with HRF when iNO is not readily available.

Administration, Inhalation↗
PubMed2003

Predictive power of initial severity of pulmonary disease for subsequent development of bronchopulmonary dysplasia.

Using retrospectively acquired data from 138 mechanically ventilated premature infants, logistic regression was used to determine the relationships between the risk of bronchopulmonary dysplasia (BPD) and indices of initial respiratory disease severity [oxygen index (OI) and alveolar-arterial pO(2) difference (A-a DO(2))]. Indices were calculated from the first arterial blood gas analysis after initial surfactant administration. Infants were also classified as having mild [OI <4 cm H(2)O x mm Hg(-1), A-a DO(2) <150 mm Hg (20 kPa)] or severe [OI >or=10 cm H(2)O x mm Hg(-1), A-a DO(2) >or=300 mm Hg (40 kPa)] respiratory disease, and the ability of this classification to predict subsequent BPD risk was calculated. OI and A-a DO(2) were significantly higher in the BPD group. Logistic regression analysis showed that BPD risk increased linearly with both OI (9%/cm H(2)O x mm Hg(-1)) and A-a DO(2) [16%/50 mm Hg (16%/6.7 kPa)]. However, the predictive power (receiver-operator characteristic) of these models was modest. Unexpectedly, 29% of infants with mild initial disease developed BPD. These data suggest that, while BPD prediction in infants with severe disease is straightforward, the identification of those few infants with mild to moderate disease destined to develop BPD remains problematic.

Bronchopulmonary Dysplasia↗
PubMed2002

Direct comparison of the effects of nebulized nitroprusside versus inhaled nitric oxide on pulmonary and systemic hemodynamics during hypoxia-induced pulmonary hypertension in piglets.

OBJECTIVE: To test the hypothesis that nebulized nitroprusside and inhaled nitric oxide would not differ in producing selective pulmonary vasodilation during hypoxia-induced pulmonary hypertension in piglets. SETTING: University laboratory. SUBJECTS: Five piglets. INTERVENTIONS: Piglets (n = 5) were anesthetized and instrumented to monitor systemic arterial pressure, pulmonary artery pressure, and cardiac output continuously. Hypoxia was induced (DeltaFio2 from 0.5 to 0.08), and either nebulized nitroprusside (5 mg/mL at 4 L/min flow; total dose 25 mg) or inhaled nitric oxide (20 ppm) was introduced into the ventilator circuit for 15 mins. Normoxia was then restored, and a repeat cycle of hypoxia followed by the alternate vasodilator treatment was initiated. MEASUREMENTS AND MAIN RESULTS: Hypoxia significantly reduced Pao2 (from 206 to 30 torr) and elevated pulmonary artery pressure (from 18 to 33 torr) while not significantly affecting systemic arterial pressure or cardiac output. During hypoxia, inhaled nitric oxide reduced pulmonary artery pressure from 33 to 21 torr (p <.01), whereas systemic arterial pressure and cardiac output were unchanged. During hypoxia, nebulized nitroprusside also reduced pulmonary artery pressure from 33 to 23 mm Hg (p <.01; p = nonsignificant vs. inhaled nitric oxide), whereas systemic arterial pressure and cardiac output again remained constant. The time course of the reduction in pulmonary artery pressure during inhaled nitric oxide was roughly ten-fold more rapid (<5 secs) than during nebulized nitroprusside ( approximately 1 min). Neither inhaled nitric oxide nor nebulized nitroprusside altered pH, Pao2, or Paco2. CONCLUSION: Both inhaled nitric oxide and nebulized nitroprusside produced prompt, significant, selective reduction of pulmonary artery pressure and pulmonary vascular resistance in piglets with hypoxia-induced pulmonary hypertension, without apparent effects on systemic hemodynamics or pulmonary gas exchange. The equivalence of the two effects in this animal model suggests that cautious extrapolation of the use of nebulized nitroprusside as a convenient bridge to inhaled nitric oxide in selected clinical contexts for human infants may be warranted.

Analysis of Variance↗
PubMed2002

Inhaled nitric oxide therapy in premature infants with mild to moderate respiratory distress syndrome.

Inhaled nitric oxide (iNO) therapy has been demonstrated to acutely improve oxygenation in preterm infants with severe pulmonary disease. Administration of iNO to the premature infants with less severe pulmonary illness has not yet been studied extensively. Therefore, the authors performed a pilot study enrolling thirty-four premature infants with respiratory distress syndrome (RDS) within 72 hours of age, birth weight between 500-2,000 g, whose oxygenation indexes exceeded our birthweight-specific criteria. Infants were randomly assigned to either treatment with (iNO group; n = 16) or without (control group; n = 18) iNO. Inhaled NO was started at 20 ppm and weaned to 5 ppm over 24-48 hours. Routine cranial ultrasonography was performed and the occurrence of intraventricular hemorrhage (IVH) was interpreted by an attending pediatric radiologist unaware of the treatment group assignment. The study showed that the two groups were of similar birth weight (mean+/-SEM): control 901+/-73 g vs iNO 874+/-70 g; and gestational age: control 27.2+/-0.5 wk vs iNO 26.8+/-0.5 wk. Other baseline parameters between the two groups were also similar. The mean ages of the infants at the time of entry were 11.7+/-2.2 and 8.3+/-0.9 hours in the controls and iNO group. The entry oxygenation index (OI) did not differ between the two groups: control 11.9+/-2.2 vs iNO 10.8+/-1.50. After 30 minutes of iNO therapy, there was a 50 per cent increase in partial pressure of oxygen tension (PaO2) and 15 per cent reduction in OI, (p = 0.02 and p = 0.04 vs baseline, respectively). No statistical difference in the incidence of significant IVH (Grade III and IV) was detected: control 27.8 per cent; iNO 25.0 per cent. The incidence of other acute complications as well as early neonatal death, were comparable between the groups. The mean methemoglobin concentration was 1.2+/-0.5 per cent. In conclusion, these preliminary data suggest that iNO, as used in this protocol, acutely improves oxygenation without increasing significant IVH in premature infants with mild to moderate RDS. These important findings serve to justify further study of the efficacy of iNO on long term pulmonary outcome and mortality in this group of infants.

Administration, Inhalation↗
PubMedDate not supplied

Hyperbaric oxygen therapy for a neurologically devastated child: whose decision is it?

A recent case highlights one of the on-going and unresolved controversies in pediatric ethics: who makes treatment decisions for children. Children, by definition, do not have the maturity to make medical choices. Those decisions must be made for them. The issue remains by whom and on what standard those choices should be made.

Decision Making↗