Yunosuke Ogawa

A multicenter randomized trial of high frequency oscillatory ventilation as compared with conventional mechanical ventilation in preterm infants with respiratory failure

A multicenter randomised trial was conducted in nine neonatal centers in Japan to re-evaluate the safety and the efficacy of high frequency oscillatory ventilation using the piston type oscillator (Hummingbird) in the treatment of respiratory failure in preterm infants weighing between 750 and 2000 g at birth. A total of 92 infants were enrolled in the study. Forty-six infants were allocated to high frequency oscillatory ventilation and 46 infants to conventional mechanical ventilation. There were no differences in sex, birth weight, gestation and Apgar score between groups. The study was begun 2.0 +/- 1.6 h (mean +/- S.D.) after birth in the high frequency oscillation group and 1.7 +/- 1.5 h after birth in the conventional mechanical ventilation group. The absence of intraventricular hemorrhage was confirmed by echography in all cases before beginning ventilation. Mortality was similar in high frequency oscillatory ventilation and conventional mechanical ventilation (0 and 2%). The incidence of intraventricular hemorrhage was also similar in the high frequency and conventional mechanical ventilation groups (15 and 13% overall; 4 and 2% in grades III and IV, respectively). Nine percent of the infants in high frequency oscillatory ventilation and 13% in conventional mechanical ventilation developed bronchopulmonary dysplasia, but the difference was not significant. The frequency of air leaks was also equal in both groups. Periventricular leukomalacia was detected in 9% of infants on conventional mechanical ventilation and 2% on high frequency oscillation, but the difference was not significant. Mean airway pressure was significantly higher in the high frequency oscillatory ventilation group and the infants on high frequency oscillation showed a significantly higher arterial to alveolar oxygen tension ratio after 6 h of treatment. These results suggest that high frequency oscillatory ventilation does not increase the risk of severe complications such as air leaks, intraventricular hemorrhage or periventricular leukomalacia when it is used by experienced neonatologists. Indeed high frequency oscillatory ventilation helps provide better oxygenation with higher mean airway pressure without increasing the risk of bronchopulmonary dysplasia and severe complications such as air leaks and intraventricular hemorrhage.

Risk factors of renal involvement and significant proteinuria in Henoch-Schönlein purpura

Abstract. Risk factors of renal involvement and significant proteinuria in patients with Henoch-Schönlein purpura (HSP) were retrospectively evaluated by univariate and multivariate analyses. The analysis was performed in 134 patients with HSP. Renal involvement was found in 65 patients (49%) and 97% of the renal involvement was found within 3 months of disease onset. Moderate or severe proteinuria was recognised in 25 patients. A univariate analysis revealed that an age of more than 4 years at the onset, severe abdominal pain with gastrointestinal bleeding, persistent purpura over a month, coagulation factor XIII activity <80%, and treatment with factor XIII concentrate were associated with developing renal involvement. A multivariate analysis showed that severe abdominal symptoms, an age of more than 4 years, and persistent purpura increased the risk of renal involvement. Risk factors of moderate or severe proteinuria were also examined. The risk factors in a univariate analysis were severe abdominal symptoms, persistent purpura, decreased factor XIII activity, treatment with steroids, and treatment with factor XIII concentrate. Of those, persistent purpura, treatment with factor XIII concentrate, and factor XIII activity <80% were associated with significant proteinuria in a multivariate analysis. Among the patients with severe abdominal symptoms, factor XIII activity was significantly decreased in patients with significant proteinuria compared to other patients without significant proteinuria. Conclusion: Long-term prognosis of Henoch-Schönlein purpura is dependent on the severity of renal involvement. In those patients who have the risk factors of renal involvement, especially significant proteinuria, close attention should be paid to a urinalysis for at least 3 months from the onset of the disease.

Surfactant replacement therapy in neonatal respiratory distress syndrome

We conducted a prospective, randomized, controlled trial comparing the efficacy of two doses of a reconstituted bovine surfactant (Surfactant TA) in premature infants requiring mechanical ventilation shortly after birth for respiratory distress syndrome. Forty-six infants weighing 1000–1499 g were randomized into two groups: a low-dose group (23 infants given a single dose of 60 mg surfactant lipid/kg) and a high-dose group (23 infants given a single dose of 120 mg/kg). The mean (SD) age at which surfactant was given was 5.5 (±1.2) h in the low-dose group and 6.0 (±1.5) h in the high dose group. Both treatments improved oxygenation (increased arterial-alvcolar PO2 ratio) with decreased mean airway pressure, the high-dose surfactant having a more beneficial effect in prolonging the response. Infants in the high-dose group had significantly less (P<0.05) incidence of both intraventricular haemorrhage and bronchopulmonary dysplasia. This prospective trial documents that a greater benefit can be obtained by increasing the dose of surfactant (120 mg/kg) beyond 60 mg/kg in the treatment of premature infants with severe respiratory distress syndrome (RDS).

Treatment of meconium aspiration syndrome with surfactant lavage in an experimental rabbit model

Meconium aspiration syndrome (MAS) is a frequent cause of respiratory distress in term infants. Recent reports suggested that surfactant dysfunction contributes to the pathophysiology of MAS. In the present study, we assessed the effect of three different concentrations of surfactant suspensions in the lavage fluid of a rabbit model of MAS. Young animals were given 5 mL/kg of a 20% slurry of human meconium into the endotracheal tube and were then mechanically ventilated. The animals were divided into four groups receiving lavage fluids with either saline or surfactant suspensions (2.5 mg/mL, 5 mg/mL, and 10 mg/mL). Lavage was performed an hour after meconium instillation with one of the four solutions at 10 mL/kg in three divided doses. After lavage, the total amount of meconium recovered was measured.

Effect of surfactant lavage in a rabbit model of meconium aspiration syndrome

Meconium aspiration syndrome (MAS) is a frequent cause of respiratory distress in neonates. Recent reports have suggested that surfactant dysfunction contributes to the pathophysiology of MAS and surfactant therapy improves oxygenation of infants with MAS. We evaluated the effect of bronchial lavage with surfactant solution in a rabbit model of meconium aspiration. All animals were given 5 mL/kg of a 20% slurry of human meconium into the endotracheal tube and mechanically ventilated. The animals were then divided into saline lavage (n = 5) or surfactant lavage (n = 5). Lavage was performed an hour after meconium instillation. After the lavage the total amount of meconium recovered was measured. Blood gas was monitored during the experiment. The amount of meconium recovered by saline lavage was 14%, and by surfactant lavage was 57%. The surfactant group had a significant improvement in gas exchange, whereas the saline group had no improvement. It was concluded that the lavage with surfactant solution effectively washed out meconium and improved gas exchange in rabbit model of MAS.

Long-term prognosis of asphyxiated full-term neonates with CNS complications

Eighty-six asphyxiated full-term neonates with CNS complications such as hypoxic-ischemic encephalopathy, admitted during a 10-year period (1972-81), were studied. Sixty-three (73%) of the infants survived the neonatal period, and 55 of these, excluding one who died at 7 months, were followed for 3 to 13 years. Thirteen (24%) of these 55 children showed either major (n = 8) or minor (n = 5) abnormalities. The former had multiple significant handicaps such as cerebral palsy, epilepsy and mental retardation. The latter had mild sequelae that did not interfere with normal life. High risk factors of predictive value in infancy for the sequelae were the absence of the Moro reflex over 6 days and abnormal neurological signs on discharge (P less than 0.001, respectively). Although the neonatal mortality decreased slightly in the last four years (1978-81) compared to in the first and second three year periods (1972-74, 1975-77) (P less than 0.10), the unchanged pattern of the outcome over the 10 years might indicate the importance of more preventive and intensive care for perinatal asphyxia to reduce the incidence of handicapped children.

Pulmonary surfactant protein A in sera for assessing neonatal lung maturation

To examine whether surfactant protein A (SP-A) in postnatal serum can predict the development of respiratory distress syndrome (RDS), we analyzed the relationship between serum concentrations of SP-A and the risk of RDS using sera from neonates within 24 h after birth. A total of 104 blood samples including 23 samples from newborn infants with RDS were obtained. SP-A content in sera was measured with an enzyme-linked immunosorbent assay system consisting of a standard of native SP-A and two monoclonal antibodies against human SP-A. The level of serum SP-A increased with advancing gestation. Since the mean level of serum SP-A in patients with RDS (3.8 ng/ml) was significantly lower than those without RDS (12.0 ng/ml) (P<0.001), we calculated the diagnostic index values at various cutoff points and chose cutoff values to predict the risk of RDS. Maximum diagnostic value of 85% was obtained at a cutoff point of 3.8 ng/ml (sensitivity 57% and specificity 93%). We also chose a cutoff value of 2.1 ng/ml for definitive diagnosis of RDS, and 8.3 ng/ml for exclusive diagnosis of RDS. The adjusted odds ratios of RDS was significantly elevated when SP-A concentration in serum was under the cutoff values. The presence of SP-A in cord blood serum was also confirmed by immunoblotting analysis. We emphasize the value of SP-A examination in cord blood or postnatal serum from infants who exhibited respiratory difficulties at birth. We believe that our results are consistent with the hypothesis that SP-A is a useful serum marker in predicting the development of RDS.

Interleukin 8 and granulocyte elastase in the tracheobronchial aspirate of infants without respiratory distress syndrome or intrauterine infection and development of chronic lung disease

To elucidate the mechanism of the development of chronic lung disease (CLD) in infants without respiratory distress syndrome or intra‐uterine infection, we serially measured the concentrations of interleukin 8 (IL‐8) and granulocyte elastase α1 proteinase inhibitor complex (E‐α1 PI) and elastase activity in the tracheobronchial aspirate of very low birth weight infants without respiratory distress syndrome or intra‐uterine infection until day 28. IL‐8 concentration and elastase activity between day 21 and 28 in infants who developed CLD later were significantly higher compared with those in infants who did not develop CLD. E‐α1 PI concentration between day 25 and 28 in infants who developed CLD later was significantly higher compared with those in infants who did not develop CLD. The area under the curve of the IL‐8 and E‐α1 PI concentrations and elastase activity between day 1 and day 28 in infants with CLD was significantly higher than those in infants without CLD. These data suggest that the lung tissue injury caused by the enzymes from neutrophils accumulated and activated by IL‐8 also play an important role in the development of this type of CLD.

Increased platelet activating factor in the tracheal aspirates from neonates with patent ductus arteriosus

We investigated platelet-activating factor (PAF) in the tracheal aspirate from 3 intubated low birth weight infants with symptomatic patent ductus arteriosus (PDA). PAF increased with the onset of symptomatic PDA and decreased to the control range soon after the ductal closure. The concentration of PAF in 26 samples taken during symptomatic PDA (median 16 pg/micrograms lipid phosphorus, range 1.4-1,200 pg/micrograms lipid phosphorus) was significantly higher than that of 31 samples from the same three patients during the periods without symptomatic PDA (median 1.9 pg/micrograms lipid phosphorus, range 0-12 pg/micrograms lipid phosphorus; P < 0.001). All 3 infants later developed chronic lung disease. These results suggest that large shunting PDA provokes PAF release to the air way of the neonate and that PAF might play a role in chronic lung disease developing after symptomatic PDA.

Interleukin 8 and granulocyte elastase α1 proteinase inhibitor complex in the tracheobronchial aspirate of infants with chronic lung disease following intra-uterine infection

In order to elucidate the role of interleukin 8 (IL‐8) in the development of chronic lung disease (CLD) of neonates with intra‐uterine infection, serial and simultaneous measurements of the concentration of IL‐8 and granulocyte elastase α1 proteinase inhibitor complex (E‐α1PI) in the tracheobronchial aspirate of low birth weight infants were conducted. Infants with a high serum IgM level at birth, and who subsequently developed CLD, showed significantly high concentrations of IL‐8 and E‐α1PI in the first 48 h. It seemed that IL‐8 stimulated neutrophils to release neutrophil enzymes which, in turn, caused the lung tissue injury, resulting in the development of CLD following intra‐uterine infection.