Aerosolized PGE1: a selective pulmonary vasodilator in neonatal hypoxemic respiratory failure results of a Phase I/II open label clinical trial

Twenty term/near term neonates with hypoxemic respiratory failure and oxygenation index >/=20 were enrolled in a Phase I/II feasibility, safety and dose escalation study of inhaled PGE(1) (IPGE(1)). Incremental doses of IPGE(1), delivered by a jet nebulizer over a 2-h period, followed by weaning over 1 h, were given to 13 patients before receiving inhaled nitric oxide (INO) (Group I), and to seven patients, who failed to respond to INO (Group II). Response was defined as an increase in P(a)O(2) of either >/= 25 (full) or 10-25 (partial) torr. Exit criteria included an acute deterioration in oxygenation status, a persistent oxygenation index above 35 in Group I, or the availability of extracorporeal membrane oxygenation (ECMO) in Group II. The mean (SD) increase in P(a)O(2) at the end of IPGE(1) administration was 63 (62.3) in Group I (p = 0.024), and 40 (62.1) in Group II (p > 0.05). In Group I, 8 of 13 neonates had a full response, but 4 deteriorated following discontinuation of IPGE(1). Of these four, two responded to INO and two were placed on ECMO. Five patients deteriorated before or during IPGE(1,) and none of them responded to INO. In Group II, three of seven patients had a full response to IPGE(1). One patient with a partial response and all patients exiting before or during IPGE(1) administration were placed on ECMO. The results of our study indicate that IPGE(1) may be a safe, selective pulmonary vasodilator in neonatal hypoxemic respiratory failure.     

Inhaled nitric oxide improves oxygenation in very premature infants with low pulmonary blood flow

AIM: Inhaled nitric oxide (iNO) is used to reduce right-to-left extrapulmonary shunting by decreasing pulmonary vascular resistance in term or near-term infants. The objectives of this study were to determine, first, the pulmonary blood flow status of very preterm infants with hypoxaemic respiratory failure, then the response of oxygenation to iNO therapy according to pulmonary blood flow (PBF) and, finally, to verify the lack of adverse side effects of iNO on the ductus arteriosus. METHODS: Infants below 32 wk gestational age (GA) with hypoxic respiratory failure and aAO2 < 0.22 were randomized as the control or iNO group. PBF was evaluated by pulsed Doppler measurement of mean pulmonary blood flow velocity (MPBFV) in the left pulmonary artery. Low PBF (LPBF) was defined as MPBFV < 0.2 m/s. RESULTS: Seventy infants of 23 to 31 wk GA with hypoxic respiratory failure were randomized either to receive or not to receive 5 ppm iNO in addition to optimal care. Twenty-eight infants were diagnosed with LPBF (11/35 in iNO vs 17/35 in the control groups). Thirty minutes after receiving iNO the number of LPBF infants dropped to 8/35. In the iNO group, aAO2 increased significantly from 0.14 +/- 0.05 to 0.24 +/- 0.08 after iNO, but only in the LPBF infants (mean +/- SD; p = 0.027). CONCLUSION: In infants below 32 wk GA with hypoxic respiratory failure, Doppler echocardiographic assessment of LPBF seems to be able to determine which patients are likely to benefit from iNO therapy on systemic oxygenation.     

Effect of initial nitric oxide concentration on outcome in infants with persistent pulmonary hypertension of the newborn

A randomized nonblinded comparison of two treatment groups was performed to determine whether treatment of infants with persistent pulmonary hypertension of the newborn using a continuous 6-ppm dose of inhaled nitric oxide (iNO) changes the likelihood of death or utilization of extracorporeal membrane oxygenation (ECMO) when compared to infants treated with 20 ppm iNO for 4 h followed by 6 ppm. Twenty-nine infants with a gestational age >/=34 weeks and a diagnosis of persistent pulmonary hypertension of the newborn were enrolled during the 3- year study period. The relative risk (20/6 vs. 6 ppm) for treatment with ECMO was 3.11 (p = 0.02), for death it was 2.80 (p = 0.32), and for either death or ECMO it was 3.42 (p = 0. 006). There was no apparent advantage of treatment with a higher dosage of iNO at the initiation of therapy in the reduction of death or utilization of ECMO. These data suggest that a continuous lower dose of iNO results in a comparable improvement in oxygenation as a short exposure of higher dose iNO at the initiation of therapy.     

The safety and efficacy of nitric oxide therapy in premature infants

OBJECTIVES: To assess the safety-efficacy balance of low-dose inhaled nitric oxide (iNO) in hypoxemic premature infants because no sustained beneficial effect has been demonstrated clearly and there are concerns about side effects. STUDY DESIGN: Eight hundred and sixty infants <32 weeks were randomized at birth to receive 5 ppm iNO or placebo when they presented with hypoxemic respiratory failure (HRF) defined by a requirement for mechanical ventilation, fraction of inspired oxygen (FIO 2 ) >40%, and arterio-alveolar ratio in oxygen (aAO 2 ) <0.22. The primary end point was intact survival at 28 days of age. RESULTS: Sixty-one of 415 infants presented with HRF and were compared with 84 of 445 controls who presented with HRF. There was no difference in the primary end point (61.4% in infants [23% with HRF who were treated with iNO] vs 61.1% in controls [21.4% in controls with HRF]; P = .943). For the infants with HRF who were treated with iNO, there was no significant difference from controls for intraventricular hemorrhage (IVH) (6% vs 7%), necrotizing enterocolitis (8% vs 6 %), or patent ductus arteriosus (PDA) (34% vs 37%). Compared with nonhypoxemic infants, the risk of bronchopulmonary displasia (BPD) increased significantly in HRF controls (OR = 3.264 [CI 1.461-7.292]) but not in infants with HRF who were treated with iNO (OR = 1.626 [CI 0.633-4.178]). CONCLUSIONS: iNO appears to be safe in premature infants but did not lead to a significant improvement in intact survival on day 28.     

Low-dose inhaled nitric oxide for neonates with pulmonary hypertension

Objective : Inhaled nitric oxide (iNO) has been shown to cause selective pulmonary vasodilatation and improve ventilation-perfusion matching and may be an important therapeutic option for the treatment of persistent pulmonary hypertension of the newborn (PPHN). We report our experience on the use of iNO in neonates with severe PPHN.
Methodology : Inhaled NO was administered to 10 infants with PPHN and persistent hypoxaemia (meconium aspiration syndrome, n = 9; pneumonia, n = 1) after failure of conventional therapy to improve oxygenation. With the exception of one infant, iNO was commenced at 10 ppm.
Results : After 30 min exposure to iNO, the arterial oxygen tension (PaO₂) rose from a median of 49 mmHg (6.5 kPa) [range 12-82 mmHg (1.6-10.9 kPa)] to 75 mmHg (10 kPa) [range 17-450 mmHg (2.3-60 kPa)] ( P = 0.005), while the median oxygenation index fell (pre-iNO of 37 vs post-iNO 20) ( P = 0.005) and median systemic arterial pressure rose (pre-iNO 46.5 mmHg (6.2 kPa) [range 32-63 mmHg (4.3 to 8.4 kPa vs post-iNO 54.5 mmHg (7.3 kPa) [range 36-74 kPa]) P = 0.005). All infants subsequently continued to receive iNO with the duration of exposure to iNO ranging from 12 to 168 h (median duration 100 h). Three infants died despite showing an initial beneficial response to iNO. The mean duration of intubation for survivors was 11.9 ± 2.6 days. Methaemoglobinaemia and toxic levels of nitrogen dioxide were not seen during iNO administration. Of the seven survivors, 12 month follow up in two infants and 4 month follow up in four infants showed age-appropriate neurodevelopmental skills, with one infant having very mild hearing loss.
Conclusions : Inhaled NO reduces the oxygenation index by improving the PaO₂ and decreasing ventilation pressures, and appears to be clinically useful in severely hypoxaemic infants with PPHN refractory to conventional treatment.     

Disease-related response to inhaled nitric oxide in newborns with severe hypoxaemic respiratory failure

Inhaled nitric oxide (iNO) has been shown to improve oxygenation in severe persistent pulmonary hypertension of the newborn (PPHN). However, PPHN is often associated with various lung diseases. Thus, response to iNO may depend upon the aetiology of neonatal acute respiratory failure. A total of 150 (29 preterm and 121 term) newborns with PPHN were prospectively enrolled on the basis of oxygenation index (OI) higher than 30 and 40, respectively. NO dosage was stepwise increased (10–80 ppm) during conventional mechanical or high-frequency oscillatory ventilation while monitoring the oxygenation. Effective dosages ranged from 5 to 20 ppm in the responders, whereas iNO levels were unsuccessfully increased up to 80 ppm in the nonresponders. Within 30 min of iNO therapy, OI was significantly reduced in either preterm neonates (51 ± 21 vs 23 ± 17, P < .0001) or term infants with idiopathic or acute respiratory distress syndrome (45 ± 20 vs 20 ± 17, P < .0001), `idiopathic' PPHN (39 ± 14 vs 14 ± 9, P < .0001), and sepsis (55 ± 25 vs 26 ± 20, P < .0001) provided there was no associated refractory shock. Improvement in oxygenation was less significant and sustained (OI = 41 ± 16 vs 28 ± 18, P < .001) in term neonates with meconium aspiration syndrome and much less (OI = 58 ± 25 vs 46 ± 32, P < .01) in those with congenital diaphragmatic hernia. Only 21 of the 129 term newborns (16%) required extracorporeal membrane oxygenation (57% survival). Survival was significantly associated with the magnitude in the reduction in OI at 30 min of iNO therapy, a gestational age ≥34 weeks, and associated diagnosis other than congenital diaphragmatic hernia. Conclusion, iNO improves the oxygenation in most newborns with severe hypoxaemic respiratory failure including preterm neonates. However, response to iNO is disease-specific. Furthermore, iNO when combined with adequate alveolar recruitment and limited barotrauma using exogenous surfactant and HFOV may obviate the need for extracorporeal membrane oxygenation in many term infants. Received: 24 April 1997 / Accepted in revised form 3 January 1998     

Respiratory syncytial virus immune globulin treatment of RSV lower respiratory tract infection in previously healthy children

OBJECTIVE: To evaluate the efficacy of high titer respiratory syncytial virus (RSV) immune globulin (RSVIG) in the treatment of previously healthy children hospitalized with proven RSV lower tract infection (LRI). METHOD: Infants and young children /=2. 5 were enrolled. RESULTS: One hundred and one previously healthy children hospitalized with RSV LRI received either 1500 mg/kg of RSVIG (RespiGam, MedImmune Inc, Gaithersburg, MD) or albumin placebo in a randomized, double-blind, placebo-controlled trial. Forty-six RSVIG and 52 recipients of placebo met all eligibility criteria. Demographic characteristics of the two groups were similar. More RSVIG recipients (46% vs 29%) had an SaO2 /=3.0) had 1.6 fewer hospital days and 2.7 days less ICU stays. CONCLUSION: RSVIG infusions seemed safe and generally well tolerated. Although some beneficial effect trends were seen for those with more severe disease who were treated there was no evidence that treatment with RSVIG resulted in reduced hospitalization and reduced ICU stays in all children with RSV disease.     

Use of inhaled nitric oxide in the new born period: results from the European inhaled nitric oxide registry

Aims: The aim of this study was to present data relating to the use of inhaled nitric oxide (iNO) in newborn infants included in the European Inhaled Nitric Oxide Registry. Methods: Demographic, clinical and therapeutic data from seven European centres are reported. Univariate analyses were performed to identify factors associated with acute response to iNO and survival without extra corporeal membrane oxygenation (ECMO). Results: A total of 112 newborn infants received iNO, with 40% being less than 34 weeks gestational age. The commonest indication for iNO was secondary pulmonary hypertension. Acute response to iNO was more common in infants with a higher oxygenation index (median OI 32.7 vs 22.6, p = 0.040), although acute response did not predict survival without ECMO. Infants who survived without ECMO had a lower OI prior to therapy (median OI 24 vs 43, p = 0.009), were commenced on a higher starting dose (median dose 20 ppm vs 10 ppm p = 0.013) and received a lower maintenance dose (median dose 10 vs 17 ppm, p = 0.027) than those who died or received ECMO. Conclusion: Collating and reporting data about iNO therapy in neonates across a number of European centres using a web‐based system is feasible. These data may be used to monitor the clinical use of iNO, identify adverse effects, generate research hypotheses and promote high standards in the clinical use of iNO.     

Nocturnal hypoglycemia detected with the Continuous Glucose Monitoring System in pediatric patients with type 1 diabetes

OBJECTIVE: To use the Continuous Glucose Monitoring System (CGMS, MiniMed, Sylmar, Calif) to determine if bedtime blood glucose levels were associated with the occurrence of nocturnal hypoglycemia. STUDY DESIGN: Patients (n = 47, 18 boys, mean age 11.8 +/- 4.6 years) with type 1 diabetes used CGMS for 167 nights. Data were analyzed for glucose 100 mg/dL and 150 mg/dL. RESULTS: A glucose value of 100 mg/dL, P = NS), and no bedtime glucose value between 110 and 300 mg/dL decreased the incidence of nocturnal hypoglycemia to 相似文献   

Oxygen saturation during the first 24 hours of life

AIM: To determine normative data for arterial oxygen saturation, measured by pulse oximetry (SpO2), in healthy full term infants throughout their first 24 hours of life. METHODS: Long term recordings of SpO2, pulse waveform, and breathing movements were made on 90 infants. Recordings were analysed for baseline SpO(2), episodes of desaturation (SpO2 /= four seconds, and periodic apnoea (>/= three apnoeic pauses, each separated by /= 20 seconds) were identified in six recordings. Four desaturations fell to 相似文献   

吸入一氧化氮治疗足月或近足月儿低氧性呼吸衰竭的循证医学证据

目的：通过对吸入一氧化氮（iNO）治疗足月或近足月儿低氧性呼吸衰竭（HRF）的临床研究进行循证分析,综合评价iNO治疗足月或近足月儿HRF的临床效果,为临床应用提供指导。方法：制定原始文献的纳入标准、排除标准及检索策略,检索PubMed、EMBASE、Ovid、Springer和中国期刊全文数据库等,获得iNO治疗足月或近足月儿HRF的临床文献。使用国际Cochrane中心推荐的方法进行文献质量评估后,采用Review Manager 4.2软件对满足纳入标准的有关iNO治疗足月或近足月儿HRF的随机对照试验（RCT）研究进行Meta分析。结果：共检索出162篇文献,对符合标准的15篇RCT研究进行Meta分析,其中11篇为多中心研究,4篇为单中心研究。 结果表明经过iNO的治疗,能够在30 min到60 min显著降低患儿的氧合指数(OI) (P<0.05)、升高动脉血氧分压（PaO2）(P<0.05),减少使用体外膜肺 (P<0.05),长期神经系统的发育随访和对照组比较没有统计学差异(P>0.05);先天性膈疝患儿经过iNO的治疗不能改善患儿的氧合和减少死亡率(P>0.05)。结论：经用Meta分析认为对于患有HRF的足月或近足月儿,除了先天性膈疝外,当OI＞25或吸入FiO2达到100％,PaO2<13.3 kPa时,可以进行iNO的治疗,但对患儿长期神经系统发育的影响还需要进行随访。     

Inhaled nitric oxide use in newborns

Inhaled nitric oxide (iNO) is a pulmonary vasodilator that plays a major role in regulating vascular muscle tone. It has emerged as a treatment for hypoxemic respiratory failure in newly born infants that is associated with persistent high pulmonary vascular pressure and resultant right-to-left shunting of blood (persistent pulmonary hypertension of the newborn). Current evidence shows that iNO improves oxygenation and decreases the combined outcome of death or need for extracorporeal membrane oxygenation in infants ≥35 weeks’ gestational age at birth. Its role in managing preterm infants <35 weeks’ gestational age is not yet established. iNO is safe when administered in tertiary care settings using strict protocols and monitoring. The recommended starting dose is 20 ppm with gradual reduction of the dose following improvement in oxygenation.     

A critical appraisal of a systematic review: Sokol J, Jacob SE, Bohn D: Inhaled nitric oxide for acute hypoxemic respiratory failure in children and adults. Cochrane Database Syst Rev 2003 (1): CD002787.

OBJECTIVE: To review the findings and discuss the implications of the use of inhaled nitric oxide for acute hypoxemic respiratory failure in patients beyond the neonatal period. DESIGN: A critical appraisal of a systematic review. Findings: The authors conducted a systematic review with meta-analysis to determine the effect of inhaled nitric oxide on clinical outcomes of patients with acute hypoxemic respiratory failure. The outcomes included mortality, changes in oxygenation, ventilator-free days, duration of intensive care and hospital stays, and adverse effects. It was a high-quality systematic review provided with strict entry criteria, an extensive literature search, and thorough critical appraisals. Only five trials (n = 623) met entry criteria. Inhaled nitric oxide had no effect on mortality in studies without crossover of treatment failures to open-label inhaled nitric oxide (relative risk, 0.98; 95% confidence interval, 0.66-1.44). A statistically significant improvement in oxygenation was observed in one study. The effect, however, was observed only in the first 4 days of treatment and was not clinically significant. The heterogeneity in study findings precluded meta-analyses of other clinical outcomes and adverse effects in the selected studies. CONCLUSIONS: There is insufficient evidence to determine whether inhaled nitric oxide is beneficial or harmful for acute hypoxemic respiratory failure in children and adults. While awaiting further studies to prove its benefit, inhaled nitric oxide should not either be recommended as a standard management or excluded for the treatment of acute hypoxemic respiratory failure.     

Pathophysiology-directed therapy for acute hypoxemic respiratory failure in acute myeloid leukemia with hyperleukocytosis

A 17-year-old with acute myeloid leukemia M4 and hyperleukocytosis developed fulminant hypoxemic respiratory failure at presentation. After failing to respond to conventional mechanical ventilation and leukapheresis, he was started on inhaled nitric oxide (iNO) with dramatic improvement in oxygenation. Following graduated chemotherapy, his pulmonary status again deteriorated coincident with tumor lysis. After failing to respond to increases in iNO, he was placed in prone position with immediate improvement. The patient was successfully extubated. Patients with myelomonocytic leukemias are at risk for early death due to pulmonary complications. The use of adjuvant therapies directed by specific pathophysiology might decrease this risk.     

Inhalation therapy with nitric oxide in pulmonary hypertension: Comparison of preterm infants versus newborn infants

BACKGROUND: Inhaled nitric oxide (iNO) is used as a vasodilator in pulmonary hypertension (PH) of the newborn infant. PATIENTS AND METHODS: Retrospective analysis of patients, who were treated at our department with iNO in the period from 1994-2001. Response was defined as an increase of the paO (2)/FiO (2) Ratio > or = 20 % and/or a decrease of the oxygenation index (OI) >/= 20 % after 2 h (early response), and consecutively after 24 h (late response). The patients were divided into a) primary persistent pulmonary hypertension of the newbom (PPHN), or b) pulmonary hypertension secondary to meconium aspiration syndrome (MAS), sepsis or congenital diaphragmatic hernia (CDH). RESULTS: Between 1994 and 2001 we treated 47 patients with iNO at our neonatal intensive care unit. We included 16 (35 %) preterm infants (GA 34,5 [25 - 37] weeks, GG 2061 [680 - 3410] g) (Median/Range) and 31 (65 %) newbom (GA 40 [38 - 42] weeks, GG 3510 [2550 - 4560] g). 18 (38 %) patients suffered from primary PPHN, 29 (62 %) from secondary PPHN (14 MAS [30 %], 8 sepsis [17 %], 4 CDH [8 %]). 8 (50 %) preterm and 20 (64 %) term infants showed a positive iNO response after 2 h, again 8 (50 %) preterm and 20 (64%) term infants showed a positive iNO response after 24 h. There was neither a significant difference between term and preterm infants at 2 h, nor at 24 h. Between 2 h and 24 h 10 patients changed in their response to iNO. 5 (18 %) patients with early response showed a significant degradation after 24 h, whereas 5 (26 %) of the patients without early response showed a significant improvement of the oxygenation alter 24 h. Alltogether 13 (72 %) patients with PPHN, 8 (57 %) with MAS, 2 (50 %) with CDH, 4 (50 %) with sepsis showed a positive iNO response after 24 h. In regard to the oxygenation parameters at start of iNO-therapy, the patients with early response did not differ from the patient without response (median OI: 20,0 versus 21,8, median paO (2)/FiO (2) Ratio: 59,3 versus 55,0 mmHg at the start of the iNO therapy). CONCLUSION: In regard to iNO response, there was no significant difference between term and preterm infants. Due to the changing response, a positive iNO-response after 2 h had no predictive value for the further prognosis of the oxygenation situation under iNO therapy.     

Inhaled nitric oxide therapy for acute respiratory distress syndrome in children

The aim of this study was to evaluate the effects of inhaled nitric oxide (iNO) therapy on oxygenation and mortality in children with acute respiratory distress syndrome (ARDS). Thirty-three children with ARDS and an arterial SatO2 <88% despite mechanical ventilation were analyzed. Patients in the iNO group were prospectively enrolled and treated with conventional therapy plus iNO. The control group consisted of retrospectively analyzed patients treated only with conventional therapy. A significant increase in PaO2/FiO2 ratio (25.6%) and decrease in oxygenation index (19.5%) was observed after 4 h of iNO treatment, when compared to baseline values. A positive response to iNO was detected in 69% of patients, and there was no difference between pulmonary and extrapulmonary ARDS. There was no difference in mortality and duration of mechanical ventilation between iNO and control group.     

Innovative neonatal ventilation and meconium aspiration syndrome

Respiratory failure remains a major cause of morbidity and mortality in the neonatal population. Infants with hypoxemic respiratory failure because of meconium aspiration syndrome (MAS), persistent pulmonary hypertension of the newborn (PPHN), and pneumonia/sepsis have a potential for increased survival with extracorporeal membrane oxygenation (ECMO). Other treatment options previously limited to inotropic support, conventional ventilatory management, respiratory alkalosis, paralysis and intravenous vasodilators have been replaced by high-frequency oscillatory ventilation (HFOV), surfactant, and inhaled nitric oxide (iNO). HFOV has been advocated for use to improve lung inflation while potentially decreasing lung injury through volutrauma. Other reports describe enhanced efficacy of HFOV when combined with iNO. Subsequent to studies reporting surfactant deficiency or inactivation may contribute to neonatal respiratory failure exogenous surfactant therapy has been implemented with apparent success. Recent studies have shown that iNO therapy in the neonate with hypoxemic respiratory failure can result in improved oxygenation and decreased need for ECMO. In this article, the authors place in context of a system-based strategy the prenatal, natal and postnatal management of babies delivered through meconium stained amniotic fluid (MSAF) so that adverse outcomes are minimized, and the least number of babies require innovative ventilatory support. At Pennsylvania Hospital, over a six-year period (1995 to 2000), 14.5% (3370/23,175 of live births babies were delivered with MSAF. These data show that 4.6% (155/3370) of babies with MSAF sustained MAS. Overall, 26% (40/155) of babies with MAS needed ventilatory support or 0.17% of all live-births); of these only 20% (8/40 or 0.035% of live births) needed innovative ventilatory support. None died or needed ECMO. These data describe the impact of a system-based approach to prevent and manage adverse outcomes related to MSAF at regional Level III perinatal center.     

高频振荡通气、肺表面活性物质联合一氧化氮吸入治疗新生儿低氧性呼吸衰竭的临床研究

目的 探讨用高频振荡通气（HFOV）、肺表面活性物质（PS）联合一氧化氮吸入（iNO）治疗新生儿低氧性呼吸衰竭（HRF）的疗效。方法 116例HRF患儿随机分为三联组和二联组,各58例。三联组采用HFOV、PS联合iNO治疗;二联组采用HFOV 联合iNO治疗。观察两组患儿治疗前及治疗后24 h、48 h的血气分析、PaO2/FiO2（P/F）、OI值和肺动脉压力（PA）的变化,比较不同P/F值、OI值和是否合并PPHN患儿的治疗结局。结果 三联组的上机时间和iNO治疗时间均短于二联组（P<0.01）,且治疗后24 h、48 h的血气指标PaO2 、PaCO2均优于二联组（P<0.01）。三联组合并PPHN的患儿治疗后24 h、48 h的PA值均较二联组下降明显（P<0.01）。在P/F值≤50的病例中,三联组的治愈率优于二联组（P<0.05）;两组死亡者的P/F值均低于存活者（P<0.01）。在OI值≥40的病例中,三联组的治愈率优于二联组（P<0.05）;两组死亡者的OI值均高于存活者（P<0.01）。三联组合并PPHN患儿治愈率优于二联组（P<0.05）。三联组住院时间较二联组缩短（P<0.01）。三联组总治愈率高于二联组（P<0.05）。两组患儿并发症发生率比较差异无统计学意义（P >0.05）。治疗中两组均未监测到严重不良反应。结论 HFOV、PS和iNO三联治疗较HFOV和iNO二联治疗新生儿HRF更为有效,可显著改善氧合,提高患儿的存活率,尤其是为患严重肺部疾病合并PPHN,且P/F值≤50或OI值≥40的病情极危重患儿提供了一个新的治疗手段。     

Nitric oxide inhalation therapy in very low-birthweight infants with hypoplastic lung due to oligohydramnios

BACKGROUND: Although nitric oxide inhalation (iNO) therapy improves arterial oxygenation and reduces the rate of extracorporeal membrane oxygenation in term neonates, the efficacy of this therapy in premature infants is controversial. The objective of the present study was to determine whether iNO therapy improves the survival of very low-birthweight infants with pulmonary hypoplasia due to prolonged rupture of membrane. METHODS: A retrospective comparative study of very low-birthweight infants with pulmonary hypoplasia due to oligohydramnios who had or had not been treated with iNO therapy, was performed (iNO-treated group, eight infants; control group, 10 infants). A neonate was considered to have pulmonary hypoplasia due to oligohydramnios if the following conditions were satisfied: (i) artificial surfactant treatment did not improve the respiratory distress; (ii) prolonged rupture of membrane (PROM) continued for more than 5 days with oligohydramnios; and (iii) sufficient arterial oxygenation did not occur even after giving 100% oxygen, and more than 8 cm H(2)O of mean airway pressure was needed to maintain arterial oxygenation. RESULTS: Nitric oxide inhalation improved arterial oxygenation rapidly and consistently in all eight infants with pulmonary hypoplasia. All eight iNO-treated infants survived longer than 28 days, while five of the 10 control infants died within 24 h of birth (P < 0.05). Before starting iNO, seven of the eight treated infants had shown persistent pulmonary hypertension, which was confirmed by echocardiography. No iNO-treated infant had IVH greater than grade 1, while one control infant had grade 2 IVH. All six long-term survivors in the iNO-treated group are developing normally, while only two of the control infants are developing normally as of February 2002. CONCLUSIONS: The majority of the infants with pulmonary hypoplasia due to oligohydramnios had persistent pulmonary hypertension. iNO improved the arterial oxygenation and significantly improved the survival rate. A controlled study to determine whether iNO therapy improves the survival rate of preterm infants with pulmonary hypoplasia due to oligohydramnios is necessary.