Inhaled nitric oxide inhibits the release of matrix metalloproteinase-2, but not platelet activation, during extracorporeal membrane oxygenation in adult rabbits.

BACKGROUND/PURPOSE: In neonates receiving extracorporeal membrane oxygenation (ECMO), platelet activation and dysfunction occur with the release of matrix metalloproteinase (MMP)-2, which stimulates platelet aggregation. Because inhaled nitric oxide (NO) reduces pulmonary hypertension and inhibits platelet aggregation, the authors examined the effects of inhaled NO on platelet activation induced by ECMO. METHODS: Ten adult white New Zealand rabbits were instrumented for ECMO and assigned randomly to receive either inhaled NO at 40 ppm or 30% oxygen for 1 hour before ECMO and continued for 4 hours after starting ECMO. Platelet counts, collagen-induced platelet aggregation ex vivo, plasma MMP-2, and MMP-9 activities were measured. RESULTS: (1) ECMO caused thrombocytopenia, decreased platelet aggregation, and increased plasma MMP-2 and MMP-9 activities in controls. (2) Inhaled NO inhibited platelet aggregation before ECMO but did not affect the ECMO-induced thrombocytopenia and platelet activation. (3) Inhaled NO significantly abolished the ECMO-induced increase in plasma MMP-2 but not MMP-9 activities. CONCLUSIONS: Although inhaled NO did not inhibit the platelet activation during ECMO in adult rabbits, it attenuated the increase in plasma MMP-2 activity that may be important for neonates treated with ECMO.

Isolated mental developmental delay in very low birth weight infants: association with prolonged doxapram therapy for apnea.

OBJECTIVE: We investigated factors associated with isolated mental delay in infants weighing < 1250 g at birth. STUDY DESIGN: With a case-control design, matching variables for 40 cases included gestation, birth weight, sex, grade of intraventricular hemorrhage, and socioeconomic status. Case subjects had a mental developmental index < 70, and controls had a mental developmental index > or = 85, according to the Bayley Scales of Infant Development II at 18 months' corrected age. RESULTS: There were no differences between the case and control subjects for neonatal complications and antenatal or postnatal steroid use. There was a marked difference in the cumulative dosage and duration of doxapram therapy used for apnea of prematurity (total dose 2233 +/- 1927 mg vs 615 +/- 767 mg, P < .001; duration 45.2 +/- 32.5 days vs 19.4 +/- 23.4 days, P < .001 for case subjects and control subjects, respectively). Multivariate analysis did not identify additive predictive variables. CONCLUSION: Isolated mental delay in infants weighing < 1250 g at birth was associated with the total dosage and duration of doxapram therapy for severe apnea. Although this may be a marker for cerebral dysfunction manifesting as apnea of prematurity, possible adverse effects of doxapram or its preservative, benzyl alcohol, on the developing brain deserve further study.

The western Canadian experience with congenital diaphragmatic hernia: perinatal factors predictive of extracorporeal membrane oxygenation and death.

This study documents how congenital diaphragmatic hernia (CDH) is managed in level III neonatal intensive care units (NICUs) in western Canada and examines perinatal factors predictive of the need for extracorporeal membrane oxygenation (ECMO). Information was obtained retrospectively from all level III NICUs in western Canada about the management of infants with CDH between 1992 and 1996; 91 infants with isolated CDH were identified. A prenatal diagnosis was made in 42 cases (46%). Surfactant was used in 53%, high-frequency oscillation (HFO) in 29%, and nitric oxide (NO) in 27%. Of the 69 infants born in referral centers, 29 (42%) were referred for possible ECMO; 17 (59%) of those required ECMO, with 65% survival. The overall requirement for ECMO was 30%. Death or ECMO occurred in 40% of cases overall. Overall survival was 82%. Survival in those needing ECMO was 74%, and in those not needing ECMO 86%. Significant predictors of death or ECMO were: prenatal diagnosis (P < 0.05), maximum postductal arterial partial pressure of oxygen (PaO2) < 100 mmHg (P < 0.001), and an oxygenation index (OI) at 6 h > 15 (P < 0.001). In cases where there is a prenatal diagnosis of CDH the mother should deliver at an ECMO center. Alternatively, an OI of > 15 at 6 h and PaO2 < 100 mmHg should prompt referral to an ECMO center.

Net cost of palivizumab for respiratory syncytial virus prophylaxis during the 1998/99 season in northern Alberta.

OBJECTIVE: Palivizumab has been shown to decrease respiratory syncytial virus (RSV) hospitalization rates in preterm infants and infants with chronic lung disease. The objective of the present study was to determine whether the use of palivizumab during the 1998/99 RSV season would have resulted in a cost-saving in infants discharged from Edmonton hospitals. DESIGN: A retrospective study of RSV hospitalizations was performed by contacting parents and reviewing hospital lists. The net cost of using palivizumab was determined by comparing the cost of giving the drug from November 1, 1998 to April 1, 1999 with the cost of potentially averted medical transports and hospitalizations. POPULATION: One hundred fifty-nine infants discharged from Edmonton hospitals who met the Canadian Paediatric Society's criteria for receiving palivizumab during the 1998/99 RSV season were studied. RESULTS: The cost of using palivizumab in these 159 study infants would have been $753,300. The infants had 21 RSV hospitalizations and required four medical transports. The estimated cost of RSV hospital-based care for these infants was $168,888. Assuming a drug efficacy of 39% in infants with chronic lung disease and 78% in infants born before 33 weeks' gestation with no chronic lung disease, $121,147 of these costs could have been averted if palivizumab had been used. CONCLUSIONS: The net cost to the health care system of using palivizumab, as recommended in the Canadian Paediatric Society guidelines, in study infants in northern Alberta during the 1998/99 RSV season would have been $632,153.

The mechanisms of platelet dysfunction during extracorporeal membrane oxygenation in critically ill neonates.

OBJECTIVE: Although bleeding associated with thrombocytopenia often complicates extracorporeal membrane oxygenation (ECMO), the mechanisms of platelet dysfunction during ECMO remain poorly understood. We investigated the role of matrix metalloproteinase (MMP)-2, which recently has been shown to mediate a novel pathway of platelet aggregation, in the platelet dysfunction induced by ECMO. DESIGN: Prospective longitudinal case study. SETTING: Level III neonatal intensive care unit. PATIENTS: Ten neonates treated with ECMO. INTERVENTION: ECMO procedure. MEASUREMENTS: Platelet counts and collagen-induced platelet aggregation ex vivo; plasma markers of platelet (soluble P-selectin) and endothelial (soluble E-selectin and total nitrite/nitrate) activation; plasma MMP-2 and MMP-9 activities; and concentrations of tissue inhibitors of MMPs. MAIN RESULTS: During ECMO, time-dependent platelet activation, as evidenced by thrombocytopenia, decreased platelet aggregation, and increased plasma soluble P-selectin concentrations were found in the absence of endothelial activation, as shown by normal plasma concentrations of soluble E-selectin and nitric oxide metabolites (nitrite/nitrate). There was a time-dependent increase in plasma MMP-2 but not MMP-9 activity; tissue inhibitors of MMPs were not detected. Plasma soluble P-selectin concentrations significantly correlated with simultaneous plasma MMP-2 (r2 = .37, p < .0001) but not with MMP-9 activities. Platelet dysfunction persisted despite repeated platelet transfusions to maintain platelet counts >100 x 10(9)/L. CONCLUSIONS: ECMO resulted in the activation of platelets but not endothelial cells. During ECMO, platelet dysfunction persisted despite platelet transfusions. MMP-2 may play a role in the development of platelet dysfunction caused by ECMO.

The hemodynamic effects of inhaled nitric oxide and endogenous nitric oxide synthesis blockade in newborn piglets during infusion of heat-killed group B streptococci.

OBJECTIVE: To determine the effects of therapy with inhaled nitric oxide (NO) gas and partial or complete blockade of endogenous NO synthesis with N(omega)nitro-L-arginine (L-NA) on the hemodynamic responses to group B streptococci infusion in newborn piglets. DESIGN: Randomized, acute intervention study. SETTING: Animal research laboratory. SUBJECTS: Twenty-five anesthetized piglets younger than 3 days of age divided into five groups. INTERVENTIONS: Heat-killed group B streptococci (GBS) were infused systemically until a 50% increase in pulmonary artery pressure (PAP) was obtained, and the infusion was continued for another 2 hrs. The five groups were designed as follows: group 1, sepsis control: continuous GBS infusion, with two brief trials (10 mins) of inhaled NO given after the initial development of pulmonary hypertension and again 2 hrs later; group 2, continuous inhaled NO: NO was given at 40 ppm for 2 hrs during GBS infusion; group 3, high-dose L-NA pretreatment: 10 mg/kg L-NA bolus followed by 1 mg/kg/min before, and continuing throughout, GBS infusion; group 4, high-dose L-NA: same dose as in group 3, but given after the start of the GBS infusion with continuous inhaled NO at 40 ppm; and group 5, low-dose L-NA: 3 mg/kg bolus given after start of GBS infusion with continuous inhaled NO at 40 ppm. MEASUREMENTS AND MAIN RESULTS: The sepsis controls, group 1, had an increase in PAP, which took 15-45 mins to develop, from a mean of 3.4 (SD 0.7) to 5.9 (1.9) kPa (p < .05), at which time the cardiac index had decreased from 169 (28) to 146 (46) mL/kg/min (p < .05). Brief inhaled NO during the early phase decreased PAP to normal. Two hours later, PAP had increased to 6.1 (0.2) kPa and cardiac index had decreased to 88 (31) mL/kg/min. Inhaled NO after 2 hrs decreased PAP to 3.2 (0.5) kPa and increased cardiac index to 106 (44) ml/kg/min (p < .05). Continuous inhaled NO (group 2) ameliorated the deterioration in cardiac index, which at 2 hrs was 140 (30) mL/kg/min (significantly greater than in the sepsis controls) (p < .05). The L-NA-pretreated animals (group 3) had a greater increase in PAP and pulmonary vascular resistance index when GBS infusion was started. PAP increased from 3.0 (0.7) to 7.3 (1.5) kPa within 15 mins, and cardiac index simultaneously decreased to 68 (20) mL/kg/min. Cardiac index subsequently rapidly deteriorated to 48 (21) mL/kg/min, and only one of five animals survived for 2 hrs. Group 4 animals also developed a rapid deterioration in cardiac output, and only two of five survived for 2 hrs. Group 5 animals had results indistinguishable from group 2 animals. CONCLUSION: Pulmonary hypertension and shock resulting from GBS infusion in newborn piglets are much worse if endogenous NO production is completely inhibited. Continuous inhaled NO with or without low-dose L-NA inhibits the decrease in cardiac output.

A cost-effectiveness analysis of the application of nitric oxide versus oxygen gas for near-term newborns with respiratory failure: results from a Canadian randomized clinical trial.

OBJECTIVE: To conduct a cost-effectiveness analysis of the use of inhaled nitric oxide (NO) vs. oxygen administered to near-term (gestational age > or =34 wks) newborns with severe respiratory illness that were referred for consideration of extracorporeal membrane oxygenation (ECMO). DESIGN: The cost-effectiveness analysis is based on outcome and utilization data from two multicentered randomized clinical trials conducted by the Canadian Inhaled Nitric Oxide Study group, one for patients with congenital diaphragmatic hernia (CDH) and one for patients without CDH. Data from the western Canadian ECMO center were used to establish costs. SETTING: Patients were cared for in Canadian regional neonatal intensive care units, including two ECMO centers. Air transport was used for transporting patients between centers. PATIENTS: Term and near-term newborns with severe respiratory illness who were receiving maximum conventional therapy and whose oxygenation index was >40. INTERVENTIONS: Patients randomly received NO or oxygen. If their conditions deteriorated, they qualified for ECMO. Not all that qualified for ECMO received it because of individual parent/ physician preferences. MEASUREMENTS AND MAIN RESULTS: The cost-effectiveness ratio was the ratio of net cost (including neonatal intensive care, ECMO, and transport) to net outcome (survival) for the two interventions. For non-CDH cases, the cost-effectiveness ratio was $36,613 (Canadian) per life saved; the confidence intervals were wide and the results were not statistically significant. For CDH patients, the death rate was lower for oxygen and the oxygen patients cost less; the results were not statistically significant. CONCLUSIONS: The small numbers of patients in the trials precluded significant results. Further, our results have a short-term time horizon (discharge to home or death). Thus, for non-CDH patients, the favorable ratio provides very qualified evidence in favor of NO.

Partial liquid ventilation with and without inhaled nitric oxide in a newborn piglet model of meconium aspiration.

The object of this study was to determine the effects of partial liquid ventilation (PLV) with and without inhaled nitric oxide (NO) over a 4-h period on lung mechanics, gas exchange, and hemodynamics in an animal model of meconium aspiration syndrome (MAS). Twenty-four fentanyl-anesthetized piglets were instrumented and administered a slurry of human meconium to create a model with hypoxia, hypercarbia, acidosis, and pulmonary hypertension. They were then randomly assigned to conventional ventilation, conventional ventilation plus inhaled NO at 40 ppm, PLV using perfluorodecalin, or PLV plus inhaled NO. The perfluorocarbon was added until a meniscus was visible in the endotracheal tube during expiration. Hemodynamics, lung mechanics, and gas exchange were monitored for 4 h, and then the animals were killed. The conventionally ventilated animals continued to deteriorate, and three of the six died prior to 4 h. All the animals in the remaining groups survived. Oxygenation improved significantly immediately with the start of inhaled NO (from 43.8 SD 10.3 to 62.6 SD 11.7 mm Hg after 30 min) and stayed elevated compared with the control group for the remainder of the study (62.4 SD 21.8 mm Hg at 4 h compared with 44.9 SD 1.6 mm Hg for the control group, p < 0.05). Oxygenation improved more slowly in the PLV alone group, being slightly less than control at 30 min (p = NS) but increasing to 104 SD 34.9 after 4 h (p < 0.01 compared with the control group), at which time it was also greater than inhaled NO alone (p < 0.05). The combined group had an acute increase in oxygenation indistinguishable from the NO alone group and maintained this until the end of the study. Lung compliance was unaffected in the inhaled NO group. In both the liquid ventilation groups the lung compliance improved with the instillation of perfluorodecalin (from 0.46 SD 0.18 to 0.62 SD 0.09 ml/cm H(2)O/kg in the PLV alone group at 1 h, p < 0.05 compared with the control group) and remained stable for the remainder of the study. Cardiac output and pulmonary vascular resistance were not significantly affected by any of the treatments. It was concluded that in this animal model of MAS, inhaled NO led to an acute improvement in gas exchange and prolonged survival compared with conventional therapy. PLV improved lung mechanics, which was maintained over the course of the study. The combination of PLV and inhaled NO produced both effects, acutely improving both gas exchange and lung mechanics. Combined therapy with PLV and inhaled NO may have benefits in the MAS.

The Edmonton experience with venovenous extracorporeal membrane oxygenation.

BACKGROUND/PURPOSE: Despite the proven effectiveness of venovenous extracorporeal membrane oxygenation (VV ECMO) in the treatment of neonates with severe respiratory failure, this technique is not widely used. The purpose of this study was to assess the authors' policy of preferred use of VV ECMO with a cephalad catheter and to compare the results with those of the Extracorporeal Life Support Organization (ELSO) Registry. METHODS: Charts of neonatal ECMO candidates were reviewed retrospectively. Data were collected for gestational age, birth weight, and diagnosis. Severity of illness was assessed by oxygenation index, lactate levels, and inotropic requirements before cannulation. Patients were divided into three groups: venovenous (VV), venoarterial (VA), and VV to VA ECMO. A cephalad catheter was inserted in the distal part of the jugular vein. RESULTS: Sixty-five neonates were supported with ECMO. Cannulation with a double lumen venovenous (VVDL) catheter was attempted in 63 neonates and successfully accomplished in 57. A survival rate of 86% was observed in neonates initially placed on VV ECMO. Five neonates initially placed on VV ECMO underwent conversion to VA ECMO. CONCLUSIONS: This study showed that the authors' preferred policy of VV ECMO did not result in an increase in mortality rate based on a comparison with ELSO data. VV ECMO with a cephalad catheter provides adequate support for unstable neonates with respiratory failure.

Congenital diaphragmatic hernia: developing a protocolized approach.

BACKGROUND/PURPOSE: The purpose of this study was to evaluate the evolving outcome of newborns who have congenital diaphragmatic hernia (CDH) using a protocolized approach to management, which includes extracorporeal membrane oxygenation (ECMO) and to present the details of such a management protocol. METHODS: A retrospective chart review was conducted of the neonatal outcome of near-term (>34 weeks' gestation) newborns with CDH all referred to the Royal Alexandra Hospital either before or after delivery. A protocol was developed that included antenatal assessment, the use of antenatal steroids, planned delivery, use of prophylactic surfactant, pressure limited gentle ventilation, permissive hypercarbia and hypoxia, and venovenous ECMO, if indicated. RESULTS: Sixty-five infants with CDH were treated from February 1989 through August 1996. Twenty-three infants were inborn, 20 of whom were antenatal referrals. Overall, 51 of the 65 infants survived (78%). Thirteen of the 23 inborn infants survived with conservative management, and 10 required ECMO, of whom, eight were long-term survivors. Thirty-eight infants required ECMO, and 26 survived (68%), whereas there were only two deaths among the 27 conservatively treated infants. Eighteen of 20 inborn infants with an antenatal diagnosis survived, compared with 13 of 21 (62%) outborn infants. An antenatal diagnosis before 25 weeks' gestation was associated with a 60% survival rate. Sixty-three percent of infants whose best postductal PaO2 value before ECMO was less than 100 torr survived, and 7 of 11 infants with a best postductal PaO2 value of less than 50 torr before ECMO survived (64%). The average age at surgery progressively increased over time both for infants who did not require ECMO (1.3 days to 5.8 days; P = .01) and for infants who received ECMO (1.9 days to 8.2 days; P = .016). CONCLUSIONS: The use of a protocolized management for infants with CDH has been associated with improving outcome in a population at high risk. The components (either separately or combined) of these protocolized approaches need to be tested in prospective trials to determine their true benefit. In addition, there is a need to evaluate prospectively the outcomes of infants with CDH born in ECMO centers compared with those infants born in other tertiary care neonatal units to determine the most appropriate management of the fetus with CDH.

Before viability: a geographically based outcome study of infants weighing 500 grams or less at birth.

OBJECTIVE: The primary objective of this study was to determine the likelihood of long-term survival and avoidance of disabilities in a geographically based population of infants born at 20 weeks gestation or more and weighing 500 g or less at birth. STUDY DESIGN: This was a 12-year historical cohort follow-up study of all infants born in this gestational age and birth weight category in the Province of Alberta, Canada, between 1983 and 1994. Data were collected from certificates of live births or stillbirths, death certificates, hospital records, and longitudinal multidisciplinary follow-up examinations. RESULTS: One thousand one hundred ninety-three infants were of 20 weeks gestation or more, weighed 500 g or less, and were born between 1983 and 1994. Eight hundred eleven (68.0%) were stillborn and 382 (32.0%) were born alive. Among the latter, neonatal intensive care was provided in 113 (29.6%) and withheld in 269 (70.4%). The infants receiving intensive care were of heavier birth weight, later gestational age, higher antenatal risk scores, were more likely to be born in a level III center, to have received antenatal steroids, and to have been delivered by cesarean section. Of the infants receiving intensive care, 95 (84. 1%) died and 18 (15.9%) were discharged alive, but 5 of these died after discharge because of respiratory complications. The infants discharged alive had later gestational age, were more likely to be small for gestational age, singletons, treated with antenatal steroids, and to have been delivered by cesarean section. Maternal indications were described in the majority of cesarean sections done for live-born infants. The 13 infants who were long-term survivors were followed at ages 12 and 36 months adjusted age. Four had no serious disabilities, 4 had one disability (cerebral palsy or mental retardation), and 5 had multiple disabilities (cerebral palsy plus mental retardation with blindness in 2 cases and deafness in 1 case). CONCLUSION: The majority of infants born at gestational age 20 weeks or more weighing <500 g were stillborn. Among live births, neonatal intensive care was withheld in 70% and initiated in 30%. Of the latter, 11% survived to 36 months of age, and of these, 4 infants (31%), most of whom are small for gestational age, female infants, avoided major disabilities but 9 (69%) had one or more major disabilities. Survivors are prone to rehospitalizations early in life, slow growth, feeding problems, and minor visual difficulties; rates of learning-related and behavioral problems at school age are not yet known. Implications. Parents and caregivers faced with the impending delivery of an infant in this gestational age/birth weight category should understand that survival without multiple major disabilities is possible but rare. They should be made aware of local population-based results and not just isolated reports.

Inhaled nitric oxide improves oxygenation in piglets with meconium aspiration.

We hypothesized that nitric oxide (NO) inhalation in a model of meconium aspiration in newborn piglets would decrease pulmonary vascular resistance. Seven neonatal piglets were obtained at less than 48 hr of age and instrumented under fentanyl anesthesia. Inhaled NO (40 parts per million) was administered during normoxia and again after hypoxia was induced by reducing FiO2 to 0.13. During normoxia NO inhalation caused a fall in pulmonary artery pressure from a mean of 3.15 (SD 0.8) kPa to 2.84 (SD 0.7) kPa (P < 0.01). Hypoxia (mean arterial O2 saturation 35%) increased PA pressures to a mean of 5.4 (SD 1.6) kPa and NO administration during hypoxia decreased PA pressures to 3.6 (SD 1.2) kPa (P < 0.001). In order to determine the effects of NO in a model of meconium aspiration, 6 to 7 mL/kg of 20% human meconium in normal saline was instilled into the trachea. This procedure induced hypoxemia (mean SaO2 43.4%, SD 19), respiratory acidosis, (mean PaCO2 12.1 kPa, SD 0.5; mean pH 7.04, SD 0.03), and pulmonary arterial hypertension (mean pulmonary artery pressure 6.0 kPa, SD 1.3) despite ventilation with 90% oxygen. Inhaled NO was then administered in concentrations of 5, 10, 20, 30, 40, 60, and 80 parts per million in random order according to a Latin square design.(ABSTRACT TRUNCATED AT 250 WORDS)

Province-based study of neurologic disability of children weighing 500 through 1249 grams at birth in relation to neonatal cerebral ultrasound findings.

BACKGROUND: Adverse neurodevelopmental outcome in premature infants is more common in the presence of certain ultrasonographically detectable intracranial lesions. Present nomenclature and classifications of parenchymal changes in preterm infants of varying gestations have led to some confusion. Descriptive definitions may be clinically useful. Regionalized perinatal and neonatal care enables population-based studies of these lesions and subsequent outcomes. METHODS: Two- to 3-year outcomes of neonates weighing 500 through 1249 g born in Alberta to Alberta residents during 1987 through 1990 were reviewed in relation to neonatal cerebral ultrasound lesions. Odds ratios and confidence limits for disability were calculated. RESULTS: Of 960 live births in this weight group, 669 (70%) survived to 1 year adjusted age; 646 (96.6%) were assessed at follow-up, and 80 (12.4%) of these were disabled: cerebral palsy, 8.7%; vision loss, 2.9%; hearing loss, 1.3%; epilepsy, 0.6%; mental retardation, 4.8%; more than one disability per child, 3.6%; and projected dependent disability, 1.4%. Lesions considered to be predictive of disability on ultrasound (excluding germinal layer hemorrhage) were found in 79 (11.8%), parenchymal lesions in 63 (9.4%) of 1-year survivors: intraventricular hemorrhage (IVH) (n = 59), persistent or transient cerebral ventriculomegaly (n = 50), persistent or transient intraparenchymal periventricular echodensity (n = 29), and cystic periventricular leukomalacia (n = 7). All lesions except isolated IVH were associated with adverse outcome; 37% of disabled children, 61% of multiply disabled children, and all children projected to become dependently disabled had parenchymal lesions with or without IVH. Triple lesions of IVH, cerebral ventriculomegaly, and intraparenchymal periventricular echodensity gave an odds ratio for disability of 50. Transient lesions had significant risk. CONCLUSIONS: This province-based study provides a descriptive scheme of serial neonatal cerebral ultrasound lesions and outcome considered useful for clinicians caring for newborns of lowest gestational ages. The overall incidence of parenchymal lesions was lower than frequently reported. Combinations of lesions were linked to increased incidence, complexity, and severity of childhood disability.

Congenital diaphragmatic hernia: associated malformations--cystic adenomatoid malformation, extralobular sequestration, and laryngotracheoesophageal cleft: two case reports.

Two infants with unusual bronchopulmonary malformations associated with congenital diaphragmatic hernia (CDH) are presented. One infant had extralobular sequestration and cystic adenomatoid malformation of the lower lobe, in addition to a left-sided CDH. The second infant had a laryngotracheoesophageal cleft extending to the carina (type III) in addition to a left-sided CDH. These associated malformations can have major implications in terms of diagnosis, resuscitation, and surgical management of infants with CDH.

Inhaled nitric oxide for premature infants after prolonged rupture of the membranes.

We evaluated the use of inhaled nitric oxide in eight premature infants (520 to 1440 gm, 24 to 31 weeks of gestation) who failed to respond to conventional management and who had prolonged rupture of the membranes and oligohydramnios. All infants had a significant improvement in oxygenation and a fall in mean airway pressure with inhaled nitric oxide. Further studies are required to determine the safety and efficacy of this form of therapy.