Nitric oxide for respiratory failure in infants born at or near term.
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ABSTRACT:
SUBMITTER: Barrington KJ
PROVIDER: S-EPMC6464941 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesTo characterize contemporary use of inhaled nitric oxide in pediatric acute respiratory failure and to assess relationships between clinical variables and outcomes. We sought to study the relationship of inhaled nitric oxide response to patient characteristics including right ventricular dysfunction and clinician responsiveness to improved oxygenation. We hypothesize that prompt clinician responsiveness to minimize hyperoxia would be associated with improved outcomes.DesignAn observational cohort study.SettingEight sites of the Collaborative Pediatric Critical Care Research Network.PatientsOne hundred fifty-one patients who received inhaled nitric oxide for a primary respiratory indication.Measurements and main resultsClinical data were abstracted from the medical record beginning at inhaled nitric oxide initiation and continuing until the earliest of 28 days, ICU discharge, or death. Ventilator-free days, oxygenation index, and Functional Status Scale were calculated. Echocardiographic reports were abstracted assessing for pulmonary hypertension, right ventricular dysfunction, and other cardiovascular parameters. Clinician responsiveness to improved oxygenation was determined. One hundred thirty patients (86%) who received inhaled nitric oxide had improved oxygenation by 24 hours. PICU mortality was 29.8%, while a new morbidity was identified in 19.8% of survivors. Among patients who had echocardiograms, 27.9% had evidence of pulmonary hypertension, 23.1% had right ventricular systolic dysfunction, and 22.1% had an atrial communication. Moderate or severe right ventricular dysfunction was associated with higher mortality. Clinicians responded to an improvement in oxygenation by decreasing FIO2 to less than 0.6 within 24 hours in 71% of patients. Timely clinician responsiveness to improved oxygenation with inhaled nitric oxide was associated with more ventilator-free days but not less cardiac arrests, mortality, or additional morbidity.ConclusionsClinician responsiveness to improved oxygenation was associated with less ventilator days. Algorithms to standardize ventilator management may improve signal to noise ratios in future trials enabling better assessment of the effect of inhaled nitric oxide on patient outcomes. Additionally, confining studies to more selective patient populations such as those with right ventricular dysfunction may be required.
| S-EPMC7416469 | biostudies-literature
Project description:ObjectivesWe hypothesized that inhaled nitric oxide (iNO) would not decrease death or neurodevelopmental impairment (NDI) in infants enrolled in the National Institute of Child Health and Human Development Preemie iNO Trial (PiNO) trial, nor improve neurodevelopmental outcomes in the follow-up group.Study designInfants <34 weeks of age, weighing <1500 g, with severe respiratory failure were enrolled in the multicenter, randomized, controlled trial. NDI at 18 to 22 months corrected age was defined as: moderate to severe cerebral palsy (CP; Mental Developmental Index or Psychomotor score Developmental Index <70), blindness, or deafness.ResultsOf 420 patients enrolled, 109 who received iNO (52%) and 98 who received placebo (47%) died. The follow-up rate in survivors was 90%. iNO did not reduce death or NDI (78% versus 73%; relative risk [RR], 1.07; 95% CI, 0.95-1.19), or NDI or Mental Developmental Index <70 in the follow-up group. Moderate-severe CP was slightly higher with iNO (RR, 2.41; 95% CI, 1.01-5.75), as was death or CP in infants weighing <1000 g (RR, 1.22; 95% CI, 1.05-1.43).ConclusionsIn this extremely ill cohort, iNO did not reduce death or NDI or improve neurodevelopmental outcomes. Routine iNO use in premature infants should be limited to research settings until further data are available.
| S-EPMC2770191 | biostudies-literature
Project description:We conducted a post-hoc analysis of early inhaled nitric oxide (iNO)-randomized controlled trial data to identify associations pertinent to the management of moderate hypoxic respiratory failure in term/late preterm infants.Univariate and multivariate logistic regression analyses were used to determine risk factors for the progression of respiratory failure and extracorporeal membrane oxygenation (ECMO)/death.Among the 299 enrolled infants, oxygenation index (OI) <20 at enrollment (odds ratio 0.52, confidence interval (CI) 0.27 to 0.97) and surfactant use before randomization (odds ratio 0.47, CI 0.24 to 0.91) were associated with decreased ECMO/death rates. Early surfactant use for respiratory distress syndrome, perinatal aspiration syndrome and pneumonia/sepsis was associated with lower risk of ECMO/death (P<0.001). Early iNO (OI 15 to 25) decreased the progression of respiratory failure to OI >30 (P=0.002) and to composite outcome of OI >30 or ECMO/death (P=0.02).This post-hoc analysis suggests that early use of surfactant and iNO in moderate respiratory failure is associated with improved outcomes.
| S-EPMC3841912 | biostudies-literature
Project description:BackgroundThe inhaled vasodilators nitric oxide and epoprostenol may be initiated to improve oxygenation in mechanically ventilated patients with severe acute respiratory failure (ARF); however, practice patterns and head-to-head comparisons of effectiveness are unclear.Research questionWhat are the practice patterns and comparative effectiveness for inhaled nitric oxide and epoprostenol in severe ARF?Study design and methodsUsing a large US database (Premier Healthcare Database), we identified adult patients with ARF or ARDS who were mechanically ventilated and started on inhaled nitric oxide, epoprostenol, or both. Leveraging large hospital variation in the choice of initial inhaled vasodilator, we compared the effectiveness of inhaled nitric oxide with that of epoprostenol by limiting analysis to patients admitted to hospitals that exclusively used either inhaled nitric oxide or epoprostenol. The primary outcome of successful extubation was modeled using multivariate Fine-Grey competing risk (death or hospice discharge) time-to-event models.ResultsAmong 11,200 patients (303 hospitals), 6,366 patients (56.8%) received inhaled nitric oxide first, 4,720 patients (42.1%) received inhaled epoprostenol first, and 114 patients (1.0%) received both therapies on the same day. One hundred four hospitals (34.3%; 1,666 patients) exclusively used nitric oxide and 118 hospitals (38.9%; 1,812 patients) exclusively used epoprostenol. No differences were found in the likelihood of successful extubation between patients admitted to nitric oxide-only hospitals vs those admitted to epoprostenol-only hospitals (subdistribution hazard ratio, 0.97; 95% CI, 0.80-1.18). Also no differences were found in total hospital costs or death. Results were robust to multiple sensitivity analyses.InterpretationLarge variation exists in the use of initial inhaled vasodilator for respiratory failure across US hospitals. Comparative effectiveness analyses identified no differences in outcomes based on inhaled vasodilator type.
| S-EPMC9899639 | biostudies-literature
Project description:There is solid evidence of the beneficial effect of photobiomodulation (PBM) with low-power near-infrared (NIR) light in the NIR-I window in increasing bioavailable nitric oxide (NO). However, it is not established whether this effect can be extended to NIR-II light, limiting broader applications of this therapeutic modality. Since we have demonstrated PBM with NIR laser in the NIR-II window, we determined the causal relationship between NIR-II irradiation and its specific biological effects on NO bioavailability. We analyzed the impact of NIR-II irradiation on NO release in cultured human endothelial cells using a NO-sensitive fluorescence probe and single-cell live imaging. Two distinct wavelengths of NIR-II laser (1064 and 1270 nm) and NIR-I (808 nm) at an irradiance of 10 mW/cm2 induced NO release from endothelial cells. These lasers also enhanced Akt phosphorylation at Ser 473, endothelial nitric oxide synthase (eNOS) phosphorylation at Ser 1177, and endothelial cell migration. Moreover, the NO release and phosphorylation of eNOS were abolished by inhibiting mitochondrial respiration, suggesting that Akt activation caused by NIR-II laser exposure involves mitochondrial retrograde signaling. Other inhibitors that inhibit known Akt activation pathways, including a specific inhibitor of PI3K, Src family PKC, did not affect this response. These two wavelengths of NIR-II laser induced no appreciable NO generation in cultured neuronal cells expressing neuronal NOS (nNOS). In short, NIR-II laser enhances bioavailable NO in endothelial cells. Since a hallmark of endothelial dysfunction is suppressed eNOS with concomitant NO deficiency, NIR-II laser technology could be broadly used to restore endothelial NO and treat or prevent cardiovascular diseases.
| S-EPMC9382775 | biostudies-literature
Project description:ObjectiveThis study aims to assess delayed versus early umbilical cord clamping in preeclamptic mothers undergoing scheduled caesarean delivery regarding the maternal intra-operative blood loss and neonatal outcomes.MethodsA clinical trial was conducted on 62 near-term preeclamptic mothers (36-38+6 weeks) who were planned for caesarean delivery. They were randomly assigned into two groups. The first group was the early cord clamping (ECC) group (n= 31), in which clamping the umbilical cord was within 15 seconds, while the second group was the delayed cord clamping (DCC) group (n= 31), in which clamping the umbilical cord was at 60 seconds. All patients were assessed for intra-operative blood loss and incidence of primary postpartum haemorrhage (PPH). Otherwise, all neonates were assessed for APGAR scores, the need for the neonatal intensive care unit (NICU) admission due to jaundice, and blood tests (haemoglobin, haematocrit. and serum bilirubin).ResultsThere was not any significant difference between the two groups regarding the maternal estimated blood loss (P=0.673), the rates of PPH (P=0.1), post-delivery haemoglobin (P=0.154), and haematocrit values (P=0.092). Neonatal outcomes also were showing no significant difference regarding APGAR scores at the first minute (P=1) and after 5 minutes (P=0.114), day 1 serum bilirubin (P=0.561), day 3 serum bilirubin (P=0.676), and the rate of NICU admission (P=0.671). However, haemoglobin and haematocrit values were significantly higher in the DCC group than in the ECC group (P<0.001).ConclusionThere is no significant difference between DCC and ECC regarding maternal blood loss. However, DCC has the advantage of significantly higher neonatal haemoglobin.Trial registrationIt was first registered at ClinicalTrials.gov on 10/12/2019 with registration number NCT04193345.
| S-EPMC9233844 | biostudies-literature
Project description:Neuronal nitric oxide synthase (nNOS) and nitric oxide (NO) are implicated in neuronal injury following acute hypoxia-ischemia (HI). Our hypothesis was that NO from nNOS is responsible for ongoing mitochondrial dysfunction in near-term fetal HI. Recently, we synthesized new selective nNOS inhibitors that prevent the cerebral palsy phenotype in our animal model. We tested the efficacy of a selective nNOS inhibitor (JI-8) in fetal brains after in utero HI in our rabbit model. Brain slices at 29 days gestation were obtained after in utero HI, and immediately cultured in medium containing JI-8 or saline for 3-6 days. Mitochondrial membrane integrity and function were determined by flow cytometry using rhodamine 123 and JC-1, and cell death by using propidium iodide. JI-8 decreased NO production in brain slices and also showed significant preservation of mitochondrial function at both 3 and 6 days (p < 0.05) when compared with saline and inducible NOS inhibitor 1400W. There was no difference in cell death. In conclusion, nNOS is involved in ongoing mitochondrial dysfunction after in utero HI. The subacute brain slice model could be a tool for studying the mechanisms involved in ongoing neuronal injury, and for rapidly assessing potential neuroprotectants.
| S-EPMC3225249 | biostudies-literature
Project description:ObjectiveTo identify whether inhaled nitric oxide treatment decreased indicators of long-term pulmonary morbidities after discharge from the neonatal intensive care unit.Study designThe Nitric Oxide (to Prevent) Chronic Lung Disease trial enrolled preterm infants (<1250 g) between 7 to 21 days of age who were ventilated and at high risk for bronchopulmonary dysplasia. Follow-up occurred at 12 +/- 3 months of age adjusted for prematurity; long-term pulmonary morbidity and other outcomes were reported by parents during structured blinded interviews.ResultsA total of 456 infants (85%) were seen at 1 year. Compared with control infants, infants randomized to inhaled nitric oxide received significantly less bronchodilators (odds ratio [OR] 0.53 [95% confidence interval 0.36-0.78]), inhaled steroids (OR 0.50 [0.32-0.77]), systemic steroids (OR 0.56 [0.32-0.97]), diuretics (OR 0.54 [0.34-0.85]), and supplemental oxygen (OR 0.65 [0.44-0.95]) after discharge from the neonatal intensive care unit. There were no significant differences between parental report of rehospitalizations (OR 0.83 [0.57-1.21]) or wheezing or whistling in the chest (OR 0.70 [0.48-1.03]).ConclusionsInfants treated with inhaled nitric oxide received fewer outpatient respiratory medications than the control group. However, any decision to institute routine use of this dosing regimen should also take into account the results of the 24-month neurodevelopmental assessment.
| S-EPMC2745607 | biostudies-literature
Project description:BackgroundRespiratory syncytial virus (RSV) is a major cause of hospitalisation in infants. The burden of RSV infection in healthy term infants has not yet been established. Accurate health-care burden data in healthy infants are necessary to determine RSV immunisation policy when RSV immunisation becomes available.MethodsWe performed a multicentre, prospective, observational birth cohort study in healthy term-born infants (≥37 weeks of gestation) in five sites located in different European countries to determine the health-care burden of RSV. The incidence of RSV-associated hospitalisations in the first year of life was determined by parental questionnaires and hospital chart reviews. We performed active RSV surveillance in a nested cohort to determine the incidence of medically attended RSV infections. The study is registered with ClinicalTrials.gov, NCT03627572.FindingsIn total, 9154 infants born between July 1, 2017, and April 1, 2020, were followed up during the first year of life and 993 participated in the nested active surveillance cohort. The incidence of RSV-associated hospitalisations in the total cohort was 1·8% (95% CI 1·6-2·1). There were eight paediatric intensive care unit admissions, corresponding to 5·5% of 145 RSV-associated hospitalisations and 0·09% of the total cohort. Incidence of RSV infection in the active surveillance cohort confirmed by any diagnostic assay was 26·2% (24·0-28·6) and that of medically attended RSV infection was 14·1% (12·3-16·0).InterpretationRSV-associated acute respiratory infection causes substantial morbidity, leading to the hospitalisation of one in every 56 healthy term-born infants in high-income settings. Immunisation of pregnant women or healthy term-born infants during their first winter season could have a major effect on the health-care burden caused by RSV infections.FundingInnovative Medicines Initiative 2 Joint Undertaking, with support from the EU's Horizon 2020 research and innovation programme and European Federation of Pharmaceutical Industries and Associations.
| S-EPMC9764871 | biostudies-literature
Project description:Infants born very preterm (PT), prior to 32 weeks gestation, are at increased risk of developing cerebral palsy. Children with spastic cerebral palsy have impaired selective leg joint movement, which contributes to lifelong walking limitations. We investigated whether infants born PT generated more selective hip-knee joint movement (e.g., hip flexes as knee extends) while participating in a scaffolded mobile task. Infants born PT and infants born full-term (FT) at 4 months corrected age participated in a scaffolded mobile task for 2-3 consecutive days. The scaffolded mobile task required infants to raise their legs vertically over a virtual threshold. Three threshold heights (low, middle, and high) were used to test whether the middle and high heights encourage infants to move their legs more selectively. Fifteen infants born FT learned the task and showed more selective hip-knee movement at each of the three threshold heights on the day that they learned, compared with their baseline spontaneous kicking. Thirteen infants born PT learned the task and showed more selective hip-knee movement on their learning day, but only when the middle and high thresholds were used. The results show that the scaffolded mobile task effectively encouraged infants to generate more selective hip-knee joint movement.
| S-EPMC8349863 | biostudies-literature