688 National University Children’s Hospital between 1 January 1990 and 31 May 2005, were reviewed retrospectively. Four infants who were admitted after the neonatal period, two neonates with chromosomal abnormalities or multiple mal- formations, and one neonate who succumbed to septic shock were excluded. A total of 48 neonates were included in this study and were divided into two groups according to the time point of admission, i.e., prior to or after the introduc- tion of iNO therapy. Seventeen neonates were admitted dur- ing the period I (P1; January 1990 to May 1998; before the introduction of iNO therapy), and 31 neonates during the period II (P2; June 1998 to May 2005; after the introduc- tion of iNO therapy). Data on patients’ clinical characteris- tics and outcomes were collected and analyzed retrospectively. A flow diagram showing the course and outcome of all CDH patients enrolled in this study is presented in Fig. 1. The study was approved by the institutional research ethics committee. Respiratory management To treat neonates with CDH showing respiratory distress, a conventional ventilator (CV) was generally started as the primary ventilation mode for inborn patients or on admis- sion for outborn patients as follows; mean airway pressure (MAP), 5-10 mmHg; fraction of inspired O2 (FiO2), 0.4-1.0; and frequency, 40-60/min. If preoperative stabilization was not achieved using a CV (pH <7.25, PaCO2 >65 mmHg, and PaO2 <50 mmHg at MAP ≥10 mmHg, frequency ≥ 60/min, and FiO2 ≥0.6), HFOV was applied. Initial HFOV settings were as follows: FiO2, 0.6-1.0; frequency, 15 Hz; stroke volume, 10-15 mL; MAP, 2-3 cmH2O above the CV setting. In some patients, depending on the clinical state, HFOV was started as the primary ventilation mode. At our institution, an iNO delivery system (Metran Massmixer, Me- tran Co., Kawaguchi, Japan) and a high-frequency oscillato- Period I (n=17) Enrolled patients (n=55) Study patients (n=48) D.-H. Kim, J.D. Park, H.-S. Kim, et al. ry ventilator (Humming V, Metran Co., Kawaguchi, Japan) were first introduced in June 1998 and in August 1996, respectively. During P2, iNO was administered in addition to HFOV when PPH (right-to-left shunt on echocardiogram, difference between preductal and postductal saturation of oxygen >10%) or refractory preductal hypoxemia (pH <7.25, PaO2 <50 mmHg, and SaO2 <85% at MAP ≥15 mmHg and FiO2 ≥0.6) developed despite HFOV. The concentra- tion of iNO was initiated at 5-20 ppm and increased to a maximum of 80 ppm. Reduction of the oxygenation index (OI=[MAP×FiO2×100]/PaO2) to 30% or more within 24 hr was defined as a clinical response, and a reduction of OI to under 30% or increase of OI within 24 hr was defined as a clinical no-response (8). Respiratory management data were collected and analyzed. During P1 and P2, a CDH repair operation was performed when clinical conditions had been stabilized to some degree (pH ≥7.25, OI <12, and stable vital signs). The operation was not performed when clinical conditions had not stabilized (pH <7.25, OI ≥12, and un- stable vital signs). Postoperative respiratory management was performed as described for the preoperative protocol. Statistics Data were presented as means±standard deviations. Con- tinuous variables were compared using the Mann-Whitney U test. Categorical variables were compared using the chi- square and Fishers exact tests. p values of less than 0.05 were considered significant. Survival analysis was based on 7 days of survival data. Survival curves were constructed using the Kaplan-Meier method. Cox regression analysis was used to determine whether the survival rates of the periods were dif- ferent and independent of initial clinical characteristics. Sta- tistical analysis was performed using SPSS version 12.0. Exclusion criteria 1. Admission to NICU after neonatal period (n=4) 2. Chromosomal abnormality (n=1) 3. Multiple malformations (n=1) 4. Cause of death: septic shock (n=1) Period II (n=31) Operation (n=13) Survival (n=9) Death (n=4) No-operation (n=4) Death (n=4) Operation (n=24) Survival (n=24) No-operation (n=7) Death (n=7) Fig. 1. Flow diagram showing the courses and outcomes of the 55 patients with congenital diaphragmatic hernia (CDH) enrolled in this study. NICU, neonatal intensive care unit.