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The Cochrane Database of Systematic... 2000This section is under preparation and will be included in the next issue. (Review)
Review
BACKGROUND
This section is under preparation and will be included in the next issue.
OBJECTIVES
To assess the effect of intratracheal administration of synthetic surfactant in premature newborns with established respiratory distress syndrome (RDS).
SEARCH STRATEGY
Searches were made of the Oxford Database of Perinatal Trials, Medline (MeSH terms: pulmonary surfactants; limits: age groups, newborn infant; publication types, clinical trial), previous reviews including cross references, abstracts, conference and symposia proceedings, expert informants, and journal handsearching in the English language.
SELECTION CRITERIA
Randomized controlled trials which compared the effect of synthetic surfactant treatment to routine management in the treatment of preterm infants with respiratory distress syndrome.
DATA COLLECTION AND ANALYSIS
Data regarding clinical outcome including the incidence of pneumothorax, pulmonary interstitial emphysema, pulmonary hemorrhage, patent ductus arteriosus, necrotizing enterocolitis, apnea of prematurity, intraventricular hemorrhage (any grade, and severe intraventricular hemorrhage), bronchopulmonary dysplasia, neonatal mortality, bronchopulmonary dysplasia or death, retinopathy of prematurity (any retinopathy, and retinopathy greater than Stage 3), mortality at hospital discharge, mortality to one year of age, and cerebral palsy (any, and moderate/severe cerebral palsy) was excerpted from the report of the clinical trials by the reviewer. Data were analyzed according to the standards of the Cochrane Neonatal Review Group.
MAIN RESULTS
Six randomized controlled trials of synthetic surfactant treatment of established respiratory distress syndrome were identified. Five of the studies used Exosurf Neonatal (a synthetic surfactant composed of dipalmitoylphosphatidylcholine, hexadecanol and tyloxapol); one small study utilized a mixture of dipalmitoylphosphatidylcholine (DPPC) and phosphatidylglycerol (PG). Treatment with intratracheal Exosurf Neonatal in premature infants with established respiratory distress syndrome improves pulmonary gas exchange and decreases the requirement for ventilatory support. In individual trials, the use of Exosurf Neonatal resulted in a statistically significant reduction in pneumothorax, patent ductus arteriosus, bronchopulmonary dysplasia (BPD), BPD or death at 28 days, and mortality. Similar results are seen when these large trials of Exosurf Neonatal are analyzed in conjunction with the smaller trial of dry powdered DPPC and phosphatidylglycerol (PG). The meta-analysis supports a decrease in the risk of pneumothorax (typical relative risk 0.64, 95% CI 0.55, 0.76, typical risk difference -0.09, 95% CI -0.12,-0.06), a decrease in the risk of pulmonary interstitial emphysema (typical relative risk 0.62, 95% CI 0.54, 0.71, typical risk difference -0.12, 95% CI -0.16, -0.09), a decrease in the risk of patent ductus arteriosus (typical relative risk 0.90, 95% CI 0.84, 0.97; typical risk difference -0.06 95% CI -0.10, -0.02), a decrease in the risk of intraventricular hemorrhage (typical relative risk 0.88, 95% CI 0.77, 0.99; typical risk difference -0.04, 95% CI -0.08, -0.00), a decrease in the risk of bronchopulmonary dysplasia (typical relative risk 0.75, 95% CI 0.61, 0.92; typical risk difference -0.04, 95% CI -0.06, -0.01), a decrease in the risk of neonatal mortality (typical relative risk 0. 73, 95% CI 0.61, 0.88; typical risk difference -0.05, 95% CI -0.07, -0.02), a decrease in the risk of bronchopulmonary dysplasia or death at 28 days (typical relative risk 0.73, 95% CI 0.65, 0.83; typical risk difference -0.06, 95% CI -0.11, -0.05), a decrease in the risk of mortality prior to hospital discharge (typical relative risk 0.79, 95% CI 0.68, 0.92; typical risk difference -0.05, 95% CI -0.07, -0.02) and a decrease in the risk of mortality during the first year of life (typical relative risk 0.80, 95% CI 0.69, 0.94; typical risk difference -0.04, 95% CI -0.07, -0.01). (ABS
Topics: Humans; Infant, Newborn; Infant, Premature; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn
PubMed: 10796417
DOI: 10.1002/14651858.CD001149 -
The Cochrane Database of Systematic... Jul 2015At birth, infants' lungs are fluid-filled; this fluid must be replaced by air to allow for effective breathing. Some infants are judged to have inadequate breathing at... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
At birth, infants' lungs are fluid-filled; this fluid must be replaced by air to allow for effective breathing. Some infants are judged to have inadequate breathing at birth and are resuscitated with positive pressure ventilation (PPV). Giving prolonged (sustained) inflations at the start of PPV may help clear lung fluid and establish gas volume in the lungs.
OBJECTIVES
To assess the efficacy of initial sustained (> one second duration) lung inflation compared to standard inflations (≤ one second) in newly born infants receiving resuscitation with intermittent PPV.
SEARCH METHODS
We searched on PubMed (1966 to 1 February 2015), EMBASE (1980 to 1 February 2015) and the Cochrane Central Register of Controlled Trials (the Cochrane Library 2015). No language restrictions were applied. We searched the abstracts of the Pediatric Academic Societies (PAS) from 2000 to 2014.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs comparing giving initial sustained lung inflations (SLI) vs. standard inflations to infants receiving resuscitation with PPV at birth.
DATA COLLECTION AND ANALYSIS
We assessed methodological quality of the included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomisation, blinding, loss to follow-up and handling of outcome data). We evaluated the treatment effect using a fixed-effect model using risk ratio for categorical data and using mean, standard deviation (SD) and weighted mean difference (WMD) for continuous data.
MAIN RESULTS
Two trials enrolling 352 infants met our inclusion criteria. There were no differences in the rates of mortality during hospitalisation (RR 1.59, 95% CI 0.81 to 3.10; two trials, 352 infants), intubation in the first three days of life (RR 0.85, 95% CI 0.72 to 1.02; two trials, 352 infants) or chronic lung disease (RR 1.06, 95% CI 0.79 to 1.42; two trials, 349 infants) between infants who received sustained versus standard inflations. The rate of patent ductus arteriosus (reported as need for pharmacological treatment) was higher in the sustained inflation group (RR 1.27, 95% CI 1.03 to 1.56; two trials, 352 infants).
AUTHORS' CONCLUSIONS
At present there is insufficient evidence from clinical trials to determine the efficacy and safety of initial sustained lung inflation for newborn infants resuscitated with PPV. RCTs comparing PPV with and without sustained inflations at neonatal resuscitation are warranted.
Topics: Ductus Arteriosus, Patent; Hospital Mortality; Humans; Infant, Newborn; Intubation, Intratracheal; Positive-Pressure Respiration; Pulmonary Surfactants; Randomized Controlled Trials as Topic; Resuscitation; Time Factors
PubMed: 26132716
DOI: 10.1002/14651858.CD004953.pub2 -
The Cochrane Database of Systematic... May 2024Respiratory distress occurs in up to 7% of newborns, with respiratory support (RS) provided invasively via an endotracheal (ET) tube or non-invasively via a nasal... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Respiratory distress occurs in up to 7% of newborns, with respiratory support (RS) provided invasively via an endotracheal (ET) tube or non-invasively via a nasal interface. Invasive ventilation increases the risk of lung injury and chronic lung disease (CLD). Using non-invasive strategies, with or without minimally invasive surfactant, may reduce the need for mechanical ventilation and the risk of lung damage in newborn infants with respiratory distress.
OBJECTIVES
To evaluate the benefits and harms of nasal high-frequency ventilation (nHFV) compared to invasive ventilation via an ET tube or other non-invasive ventilation methods on morbidity and mortality in preterm and term infants with or at risk of respiratory distress.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL and three trial registries in April 2023.
SELECTION CRITERIA
Randomised controlled trials (RCTs), cluster- or quasi-RCTs of nHFV in newborn infants with respiratory distress compared to invasive or non-invasive ventilation.
DATA COLLECTION AND ANALYSIS
Two authors independently selected the trials for inclusion, extracted data, assessed the risk of bias, and undertook GRADE assessment.
MAIN RESULTS
We identified 33 studies, mostly in low- to middle-income settings, that investigated this therapy in 5068 preterm and 46 term infants. nHFV compared to invasive respiratory therapy for initial RS We are very uncertain whether nHFV reduces mortality before hospital discharge (RR 0.67, 95% CI 0.20 to 2.18; 1 study, 80 infants) or the incidence of CLD (RR 0.38, 95% CI 0.09 to 1.59; 2 studies, 180 infants), both very low-certainty. ET intubation, death or CLD, severe intraventricular haemorrhage (IVH) and neurodevelopmental disability (ND) were not reported. nHFV vs nasal continuous positive airway pressure (nCPAP) used for initial RS We are very uncertain whether nHFV reduces mortality before hospital discharge (RR 1.00, 95% CI 0.41 to 2.41; 4 studies, 531 infants; very low-certainty). nHFV may reduce ET intubation (RR 0.52, 95% CI 0.33 to 0.82; 5 studies, 571 infants), but there may be little or no difference in CLD (RR 1.35, 95% CI 0.80 to 2.27; 4 studies, 481 infants); death or CLD (RR 2.50, 95% CI 0.52 to 12.01; 1 study, 68 participants); or severe IVH (RR 1.17, 95% CI 0.36 to 3.78; 4 studies, 531 infants), all low-certainty evidence. ND was not reported. nHFV vs nasal intermittent positive-pressure ventilation (nIPPV) used for initial RS nHFV may result in little to no difference in mortality before hospital discharge (RR 1.86, 95% CI 0.90 to 3.83; 2 studies, 84 infants; low-certainty). nHFV may have little or no effect in reducing ET intubation (RR 1.33, 95% CI 0.76 to 2.34; 5 studies, 228 infants; low-certainty). There may be a reduction in CLD (RR 0.63, 95% CI 0.42 to 0.95; 5 studies, 307 infants; low-certainty). A single study (36 infants) reported no events for severe IVH. Death or CLD and ND were not reported. nHFV vs high-flow nasal cannula (HFNC) used for initial RS We are very uncertain whether nHFV reduces ET intubation (RR 2.94, 95% CI 0.65 to 13.27; 1 study, 37 infants) or reduces CLD (RR 1.18, 95% CI 0.46 to 2.98; 1 study, 37 participants), both very low-certainty. There were no mortality events before hospital discharge or severe IVH. Other deaths, CLD and ND, were not reported. nHFV vs nCPAP used for RS following planned extubation nHFV probably results in little or no difference in mortality before hospital discharge (RR 0.92, 95% CI 0.52 to 1.64; 6 studies, 1472 infants; moderate-certainty). nHFV may result in a reduction in ET reintubation (RR 0.42, 95% CI 0.35 to 0.51; 11 studies, 1897 infants) and CLD (RR 0.78, 95% CI 0.67 to 0.91; 10 studies, 1829 infants), both low-certainty. nHFV probably has little or no effect on death or CLD (RR 0.90, 95% CI 0.77 to 1.06; 2 studies, 966 infants) and severe IVH (RR 0.80, 95% CI 0.57 to 1.13; 3 studies, 1117 infants), both moderate-certainty. We are very uncertain whether nHFV reduces ND (RR 0.92, 95% CI 0.37 to 2.29; 1 study, 74 infants; very low-certainty). nHFV versus nIPPV used for RS following planned extubation nHFV may have little or no effect on mortality before hospital discharge (RR 1.83, 95% CI 0.70 to 4.79; 2 studies, 984 infants; low-certainty). There is probably a reduction in ET reintubation (RR 0.69, 95% CI 0.54 to 0.89; 6 studies, 1364 infants), but little or no effect on CLD (RR 0.88, 95% CI 0.75 to 1.04; 4 studies, 1236 infants); death or CLD (RR 0.92, 95% CI 0.79 to 1.08; 3 studies, 1070 infants); or severe IVH (RR 0.78, 95% CI 0.55 to 1.10; 4 studies, 1162 infants), all moderate-certainty. One study reported there might be no difference in ND (RR 0.88, 95% CI 0.35 to 2.16; 1 study, 72 infants; low-certainty). nHFV versus nIPPV following initial non-invasive RS failure nHFV may have little or no effect on mortality before hospital discharge (RR 1.44, 95% CI 0.10 to 21.33); or ET intubation (RR 1.23, 95% CI 0.51 to 2.98); or CLD (RR 1.01, 95% CI 0.70 to 1.47); or severe IVH (RR 0.47, 95% CI 0.02 to 10.87); 1 study, 39 participants, all low- or very low-certainty. Other deaths or CLD and ND were not reported.
AUTHORS' CONCLUSIONS
For initial RS, we are very uncertain if using nHFV compared to invasive respiratory therapy affects clinical outcomes. However, nHFV may reduce intubation when compared to nCPAP. For planned extubation, nHFV may reduce the risk of reintubation compared to nCPAP and nIPPV. nHFV may reduce the risk of CLD when compared to nCPAP. Following initial non-invasive respiratory support failure, nHFV when compared to nIPPV may result in little to no difference in intubation. Large trials, particularly in high-income settings, are needed to determine the role of nHFV in initial RS and following the failure of other non-invasive respiratory support. Also, the optimal settings of nHVF require further investigation.
Topics: Humans; Infant, Newborn; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome, Newborn; Noninvasive Ventilation; High-Frequency Ventilation; Infant, Premature; Bias; Intubation, Intratracheal; Pulmonary Surfactants
PubMed: 38695628
DOI: 10.1002/14651858.CD012712.pub2 -
Medicine Nov 2020Pulmonary surfactant (PS) is commonly used for the treatment of neonatal respiratory distress syndrome (NRDS), several randomized controlled trials (RCTs) have evaluated... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pulmonary surfactant (PS) is commonly used for the treatment of neonatal respiratory distress syndrome (NRDS), several randomized controlled trials (RCTs) have evaluated the role of nebulized versus invasively delivered PS, yet the results remained inconsistent. Therefore, we aimed to conduct this meta-analysis to evaluate the effects and safety of nebulized versus invasively delivered PS in the treatment of NRDS.
METHODS
We searched PubMed et al databases from inception date to May 15, 2020 for RCTs that compared nebulized vs invasively delivered PS. Two authors independently screened the studies and extracted data from the published articles. Summary odd ratios (OR) or mean differences (MDs) with 95% confidence intervals (CIs) were calculated for each outcome by means of fixed- or random-effects model.
RESULTS
Two RCTs with a total of 95 preterm neonates were identified, with 48 neonates received PS nebulization and 47 neonates undergone invasive PS administration. There was no significant difference in the SpO2 level (MD = -0.44, 95% CI -6.01 to 5.12) and the A/APaO2 level (MD = 0.01, 95% CI -0.02 to 0.05) 1 hour after treatment among 2 groups. But the duration of mechanical ventilation in the nebulization groups was significantly less than that of invasive group (MD = -30.70, 95% CI -41.45 to 19.95).
CONCLUSIONS
Given the limited evidences, the effects and safety of nebulized versus invasively delivered PS still need further verification.
Topics: Administration, Inhalation; Humans; Infant, Newborn; Infusions, Intravenous; Nebulizers and Vaporizers; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Treatment Outcome
PubMed: 33235071
DOI: 10.1097/MD.0000000000023113 -
Clinics (Sao Paulo, Brazil) 2019The relationship between surfactant-associated protein D polymorphisms and chronic obstructive pulmonary disease risk remains controversial. This article is the first to... (Meta-Analysis)
Meta-Analysis
The relationship between surfactant-associated protein D polymorphisms and chronic obstructive pulmonary disease risk remains controversial. This article is the first to systematically evaluate this relationship. A comprehensive worldwide search was conducted for relevant literature on surfactant-associated protein D gene mutations and chronic obstructive pulmonary disease risk prediction. Study quality was evaluated using the Newcastle-Ottawa scale. After four genetic models (the allele, additive, recessive, and dominant models) were identified, odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were applied in this meta-analysis. The meta-analysis included 659 individuals in the case group and 597 in the control group. In the Asian population, none of the four genetic models revealed any significant association between rs2243639 genotype and the risk of chronic obstructive pulmonary disease. In Caucasians, however, the recessive model exhibited significant risk associated with rs2243639. Furthermore, there was a significant association between rs721917 genotype and the risk of chronic obstructive pulmonary disease in the Asian population. In contrast, none of the four gene models revealed any significant risk associated with this gene in the Caucasian population. This meta-analysis suggests that rs2243639 is not related to the risk of chronic obstructive pulmonary disease in the Asian population but is related to this risk in the Caucasian population. Regarding rs721917, the T allele may increase the risk of chronic obstructive pulmonary disease in the Asian population.
Topics: Alleles; Genetic Association Studies; Humans; Linear Models; Polymorphism, Single Nucleotide; Pulmonary Disease, Chronic Obstructive; Pulmonary Surfactant-Associated Protein D; Risk Factors
PubMed: 31116231
DOI: 10.6061/clinics/2019/e855 -
The Cochrane Database of Systematic... Dec 2015Animal-derived surfactants have been shown to have several advantages over the first generation synthetic surfactants and are the most commonly used surfactant... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Animal-derived surfactants have been shown to have several advantages over the first generation synthetic surfactants and are the most commonly used surfactant preparations. The animal-derived surfactants in clinical use are minced or lavaged and modified or purified from bovine or porcine lungs. It is unclear whether significant differences in clinical outcome exist among the available bovine (modified minced or lavage) and porcine (minced or lavage) surfactant extracts.
OBJECTIVES
To compare the effect of administration of different animal-derived surfactant extracts on the risk of mortality, chronic lung disease, and other morbidities associated with prematurity in preterm infants at risk for or having respiratory distress syndrome (RDS).
SEARCH METHODS
We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 7), MEDLINE via PubMed (1966 to July 31, 2015), EMBASE (1980 to July 31, 2015), and CINAHL (1982 to July 31, 2015). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials.
SELECTION CRITERIA
Randomized or quasi-randomized controlled trials that compared the effect of animal-derived surfactant extract treatment administered to preterm infants at risk for or having RDS to prevent complications of prematurity and mortality.
DATA COLLECTION AND ANALYSIS
Data regarding clinical outcomes were excerpted from the reports of the clinical trials by the review authors. Subgroup analyses were performed based on gestational age, surfactant dosing and schedule, treatment severity and treatment strategy. Data analysis was performed in accordance with the standards of the Cochrane Neonatal Review Group.
MAIN RESULTS
Sixteen randomized controlled trials were included in the analysis. Bovine lung lavage surfactant extract to modified bovine minced lung surfactant extract: Seven treatment studies and two prevention studies compared bovine lung lavage surfactant extract to modified bovine minced lung surfactant extract. The meta-analysis did not demonstrate any significant differences in death or chronic lung disease in the prevention trials (typical RR 1.02, 95% CI 0.89 to 1.17; typical RD 0.01, 95% CI -0.05 to 0.06; 2 studies and 1123 infants; high quality evidence) or treatment trials (typical RR 0.95, 95% CI 0.86 to 1.06; typical RD -0.02 , 95% CI -0.06 to 0.02; 3 studies and 2009 infants; high quality evidence) Modified bovine minced lung surfactant extract compared with porcine minced lung surfactant extract: Nine treatment studies compared modified bovine minced lung surfactant extract to porcine minced lung surfactant extract. Meta-analysis of these trials demonstrate a significant increase in the risk of mortality prior to hospital discharge (typical RR 1.44, 95% CI 1.04 to 2.00; typical RD 0.05, 95% CI 0.01 to 0.10; NNTH 20, 95% CI 10 to 100; 9 studies and 901 infants; moderate quality evidence), death or oxygen requirement at 36 weeks' postmenstrual age (typical RR 1.30, 95% CI 1.04 to 1.64; typical RD 0.11, 95% CI 0.02 to 0.20; NNTH 9, 95% CI 5 to 50; 3 studies and 448 infants; moderate quality evidence), receiving more than one dose of surfactant (typical RR 1.57, 95% CI 1.29 to 1.92; typical RD 0.14, 95% CI 0.08 to 0.20; NNTH 7, 95% CI 5 to 13; 6 studies and 786 infants), and patent ductus arteriosus (PDA) requiring treatment (typical RR 1.86, 95% CI 1.28 to 2.70; typical RD 0.28, 95% CI 0.13 to 0.43; NNTH 4, 95% CI 2 to 8; 3 studies and 137 infants) in infants treated with modified bovine minced lung surfactant extract compared with porcine minced lung surfactant extract. In the subgroup analysis based on initial dose of surfactant, improvement in mortality prior to discharge (typical RR 1.62, 95% CI 1.11 to 2.38; typical RD 0.06, 95% CI 0.01 to 0.11; NNTH 16, 95% CI 9 to 100) and risk of death or oxygen requirement at 36 weeks' postmenstrual age (typical RR 1.39, 95% CI 1.08 to 1.79; typical RD 0.13, 95% 0.03 to 0.23; NNTH 7, 95% CI 4 to 33) was limited to higher initial dose of porcine minced lung surfactant (> 100 mg/kg). Other comparisons: No difference in outcome was noted between bovine lung lavage surfactant extract versus porcine minced lung surfactant extract. There were no studies comparing bovine lung lavage surfactant extract versus porcine lung lavage surfactant; or porcine minced lung surfactant extract versus porcine lung lavage surfactant.
AUTHORS' CONCLUSIONS
Significant differences in clinical outcome were noted in the comparison trials of modified minced lung surfactant extract (beractant) compared with porcine minced lung surfactant extract (poractant alfa) including a significant increase in the risk of mortality prior to discharge, death or oxygen requirement at 36 weeks' postmenstrual age, PDA requiring treatment and "receiving > 1 dose of surfactant" in infants treated with modified bovine minced lung surfactant extract compared with porcine minced lung surfactant extract. The difference in these outcomes was limited to studies using a higher initial dose of porcine minced lung surfactant extract. It is uncertain whether the observed differences are from differences in dose or from source of extraction (porcine vs. bovine) because of the lack of dose-equivalent comparison groups with appropriate sample size. No differences in clinical outcomes were observed in comparative trials between bovine lung lavage surfactant and modified bovine minced lung surfactants.
Topics: Animals; Cattle; Humans; Infant, Newborn; Infant, Premature; Oxygen Inhalation Therapy; Pulmonary Surfactants; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome, Newborn; Swine
PubMed: 26690260
DOI: 10.1002/14651858.CD010249.pub2 -
The Cochrane Database of Systematic... Oct 2017This is an update of a review published in 2012. A related review "Inhaled versus systemic corticosteroids for preventing bronchopulmonary dysplasia in ventilated very... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of a review published in 2012. A related review "Inhaled versus systemic corticosteroids for preventing bronchopulmonary dysplasia in ventilated very low birth weight preterm neonates" has been updated as well. Bronchopulmonary dysplasia (BPD) is a serious and common problem among very low birth weight infants, despite the use of antenatal steroids and postnatal surfactant therapy to decrease the incidence and severity of respiratory distress syndrome. Due to their anti-inflammatory properties, corticosteroids have been widely used to treat or prevent BPD. However, the use of systemic steroids has been associated with serious short- and long-term adverse effects. Administration of corticosteroids topically through the respiratory tract may result in beneficial effects on the pulmonary system with fewer undesirable systemic side effects.
OBJECTIVES
To compare the effectiveness of inhaled versus systemic corticosteroids administered to ventilator-dependent preterm neonates with birth weight ≤ 1500 g or gestational age ≤ 32 weeks after 7 days of life on the incidence of death or BPD at 36 weeks' postmenstrual age.
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 1), MEDLINE via PubMed (1966 to 23 February 2017), Embase (1980 to 23 February 2017), and CINAHL (1982 to 23 February 2017). We also searched clinical trials registers, conference proceedings and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials comparing inhaled versus systemic corticosteroid therapy (irrespective of dose and duration) starting after the first week of life in ventilator-dependent very low birth weight infants.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by the Cochrane Collaboration.
MAIN RESULTS
We included three trials that involved a total of 431 participants which compared inhaled versus systemic corticosteroids to treat BPD. No new trials were included for the 2017 update.Although one study randomised infants at < 72 hours (N = 292), treatment started when infants were aged > 15 days. In this larger study, deaths were included from the point of randomisation and before treatment started. Two studies (N = 139) randomised and started treatment at 12 to 21 days.Two trials reported non-significant differences between groups for the primary outcome: incidence of death or BPD at 36 weeks' postmenstrual age among all randomised infants. Estimates for the largest trial were Relative risk (RR) 1.04 (95% Confidence interval (CI) 0.86 to 1.26), Risk difference (RD) 0.03 (95% CI -0.09 to 0.15); (moderate-quality evidence). Estimates for the other trial reporting the primary outcome were RR 0.94 (95% CI 0.83 to 1.05), RD -0.06 (95% CI -0.17 to 0.05); (low-quality evidence).Secondary outcomes that included data from all three trials showed no significant differences in the duration of mechanical ventilation or supplemental oxygen, length of hospital stay, or the incidence of hyperglycaemia, hypertension, necrotising enterocolitis, gastrointestinal bleed, retinopathy of prematurity or culture-proven sepsis moderate- to low-quality evidence).In a subset of 75 surviving infants who were enrolled from the United Kingdom and Ireland, there were no significant differences in developmental outcomes at seven years of age between groups (moderate-quality evidence). One study received grant support and the industry provided aerochambers and metered dose inhalers of budesonide and placebo for the same study. No conflict of interest was identified.
AUTHORS' CONCLUSIONS
We found no evidence that inhaled corticosteroids confer net advantages over systemic corticosteroids in the management of ventilator-dependent preterm infants. There was no evidence of difference in effectiveness or adverse event profiles for inhaled versus systemic steroids.A better delivery system guaranteeing selective delivery of inhaled steroids to the alveoli might result in beneficial clinical effects without increasing adverse events.To resolve this issue, studies are needed to identify the risk/benefit ratio of different delivery techniques and dosing schedules for administration of these medications. The long-term effects of inhaled steroids, with particular attention to neurodevelopmental outcomes, should be addressed in future studies.
Topics: Administration, Inhalation; Beclomethasone; Bronchopulmonary Dysplasia; Chronic Disease; Dexamethasone; Glucocorticoids; Humans; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Randomized Controlled Trials as Topic; Respiration, Artificial; Respiratory System Agents
PubMed: 29035425
DOI: 10.1002/14651858.CD002057.pub4 -
The Cochrane Database of Systematic... Oct 2004Multiple pharmacologic treatments have been studied for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple pharmacologic treatments have been studied for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).
OBJECTIVES
Our objective was to determine the effects of pharmacologic treatments on clinical outcomes in adults with ALI or ARDS.
SEARCH STRATEGY
We searched OVID versions of CENTRAL (The Cochrane Library Issue 3, 2003), MEDLINE (1966 to week 2, January 2004), EMBASE (1980 to week 4, 2004), CINAHL (1982 to week 2, January 2004), and HEALTHSTAR (1995 to December 2003); proceedings from four conferences (1994 to 2003); and bibliographies of review articles and included studies.
SELECTION CRITERIA
Randomized controlled trials of pharmacologic treatments compared to no therapy or placebo for established ALI or ARDS in adults admitted to an intensive care unit, with measurement of early mortality (primary outcome), late mortality, duration of mechanical ventilation, ventilator-free days to day 28, or adverse events. We excluded trials of nitric oxide, partial liquid ventilation, fluid and nutritional interventions, oxygen, and trials in other populations reporting outcomes in subgroups of patients with ALI or ARDS.
DATA COLLECTION AND ANALYSIS
Two reviewers independently screened titles and abstracts, rated studies for inclusion, extracted data and assessed methodologic quality of included studies. Disagreements were resolved by consensus in consultation with a third reviewer. For each pharmacologic therapy, we quantitatively pooled the results of studies using random effects models where permitted by the available data. We contacted study authors when clarification of the primary outcome was required.
MAIN RESULTS
Thirty three trials randomizing 3272 patients met our inclusion criteria. Pooling of results showed no effect on early mortality of prostaglandin E1 (seven trials randomizing 697 patients; relative risk [RR] 0.95, 95% confidence interval [CI] 0.77 to 1.17), N-acetylcysteine (five trials randomizing 239 patients; RR 0.89, 95% CI 0.65 to 1.21), early high-dose corticosteroids (two trials randomizing 187 patients; RR 1.12, 95% CI 0.72 to 1.74), or surfactant (nine trials randomizing 1441 patients; RR 0.93, 95% CI 0.77 to 1.12). Two interventions were beneficial in single small trials; corticosteroids given for late phase ARDS reduced hospital mortality (24 patients; RR 0.20, 95% CI 0.05 to 0.81), and pentoxifylline reduced one-month mortality (RR 0.67, 95% CI 0.47 to 0.95) in 30 patients with metastatic cancer and ARDS. Individual trials of nine additional interventions failed to show a beneficial effect on prespecified outcomes.
REVIEWERS' CONCLUSIONS
Effective pharmacotherapy for ALI and ARDS is extremely limited, with insufficient evidence to support any specific intervention.
Topics: Acetylcysteine; Adrenal Cortex Hormones; Alprostadil; Humans; Pulmonary Surfactants; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome
PubMed: 15495113
DOI: 10.1002/14651858.CD004477.pub2 -
The Cochrane Database of Systematic... Jul 2017At birth, infants' lungs are fluid-filled. For newborns to have a successful transition, this fluid must be replaced by air to enable effective breathing. Some infants... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
At birth, infants' lungs are fluid-filled. For newborns to have a successful transition, this fluid must be replaced by air to enable effective breathing. Some infants are judged to have inadequate breathing at birth and are resuscitated with positive pressure ventilation (PPV). Giving prolonged (sustained) inflations at the start of PPV may help clear lung fluid and establish gas volume within the lungs.
OBJECTIVES
To assess the efficacy of an initial sustained (> 1 second duration) lung inflation versus standard inflations (≤ 1 second) in newly born infants receiving resuscitation with intermittent PPV.
SEARCH METHODS
We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1), MEDLINE via PubMed (1966 to 17 February 2017), Embase (1980 to 17 February 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 17 February 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles to identify randomised controlled trials and quasi-randomised trials.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs comparing initial sustained lung inflation (SLI) versus standard inflations given to infants receiving resuscitation with PPV at birth.
DATA COLLECTION AND ANALYSIS
We assessed the methodological quality of included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomisation, blinding, loss to follow-up, and handling of outcome data). We evaluated treatment effects using a fixed-effect model with risk ratio (RR) for categorical data and mean, standard deviation (SD), and weighted mean difference (WMD) for continuous data. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.
MAIN RESULTS
Eight trials enrolling 941 infants met our inclusion criteria. Investigators in seven trials (932 infants) administered sustained inflation with no chest compressions. Use of sustained inflation had no impact on the primary outcomes of this review - mortality in the delivery room (typical RR 2.66, 95% confidence interval (CI) 0.11 to 63.40; participants = 479; studies = 5; I² not applicable) and mortality during hospitalisation (typical RR 1.01, 95% CI 0.67 to 1.51; participants = 932; studies = 7; I² = 19%); the quality of the evidence was low for death in the delivery room (limitations in study design and imprecision of estimates) and was moderate for death before discharge (limitations in study design of most included trials). Amongst secondary outcomes, duration of mechanical ventilation was shorter in the SLI group (mean difference (MD) -5.37 days, 95% CI -6.31 to -4.43; participants = 524; studies = 5; I² = 95%; low-quality evidence). Heterogeneity, statistical significance, and magnitude of effects of this outcome are largely influenced by a single study: When this study was removed from the analysis, the effect was largely reduced (MD -1.71 days, 95% CI -3.04 to -0.39, I² = 0%). Results revealed no differences in any of the other secondary outcomes (e.g. rate of endotracheal intubation outside the delivery room by 72 hours of age (typical RR 0.93, 95% CI 0.79 to 1.09; participants = 811; studies = 5; I² = 0%); need for surfactant administration during hospital admission (typical RR 0.97, 95% CI 0.86 to 1.10; participants = 932; studies = 7; I² = 0%); rate of chronic lung disease (typical RR 0.95, 95% CI 0.74 to 1.22; participants = 683; studies = 5; I² = 47%); pneumothorax (typical RR 1.44, 95% CI 0.76 to 2.72; studies = 6, 851 infants; I² = 26%); or rate of patent ductus arteriosus requiring pharmacological treatment (typical RR 1.08, 95% CI 0.90 to 1.30; studies = 6, 745 infants; I² = 36%). The quality of evidence for these secondary outcomes was moderate (limitations in study design of most included trials - GRADE) except for pneumothorax (low quality: limitations in study design and imprecision of estimates - GRADE).
AUTHORS' CONCLUSIONS
Sustained inflation was not better than intermittent ventilation for reducing mortality in the delivery room and during hospitalisation. The number of events across trials was limited, so differences cannot be excluded. When considering secondary outcomes, such as need for intubation, need for or duration of respiratory support, or bronchopulmonary dysplasia, we found no evidence of relevant benefit for sustained inflation over intermittent ventilation. The duration of mechanical ventilation was shortened in the SLI group. This result should be interpreted cautiously, as it can be influenced by study characteristics other than the intervention. Future RCTs should aim to enrol infants who are at higher risk of morbidity and mortality, should stratify participants by gestational age, and should provide more detailed monitoring of the procedure, including measurements of lung volume and presence of apnoea before or during the SLI.
Topics: Ductus Arteriosus, Patent; Hospital Mortality; Humans; Infant, Newborn; Intubation, Intratracheal; Positive-Pressure Respiration; Pulmonary Surfactants; Randomized Controlled Trials as Topic; Respiration, Artificial; Resuscitation; Time Factors
PubMed: 28707404
DOI: 10.1002/14651858.CD004953.pub3 -
The Cochrane Database of Systematic... Mar 2015Respiratory failure due to lung immaturity is a major cause of mortality in preterm infants. Although the use of intermittent positive pressure ventilation (IPPV) in... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Respiratory failure due to lung immaturity is a major cause of mortality in preterm infants. Although the use of intermittent positive pressure ventilation (IPPV) in neonates with respiratory failure saves lives, its use is associated with lung injury and chronic lung disease. A newer form of ventilation called high frequency oscillatory ventilation has been shown in experimental studies to result in less lung injury.
OBJECTIVES
The objective of this review was to determine the effect of the elective use of high frequency oscillatory ventilation (HFOV) as compared to conventional ventilation (CV) on the incidence of chronic lung disease (CLD), mortality and other complications associated with prematurity and assisted ventilation in preterm infants who were mechanically ventilated for respiratory distress syndrome (RDS).
SEARCH METHODS
Searches were made of the Oxford Database of Perinatal Trials, MEDLINE, EMBASE, previous reviews including cross references, abstracts, conference and symposia proceedings; and from expert informants and handsearching of journals by The Cochrane Collaboration, mainly in the English language. The search was updated in January 2009 and again in November 2014.
SELECTION CRITERIA
Randomised controlled trials comparing HFOV and CV in preterm or low birth weight infants with pulmonary dysfunction, mainly due to RDS, who required assisted ventilation. Randomisation and commencement of treatment needed to be as soon as possible after the start of CV and usually in the first 12 hours of life.
DATA COLLECTION AND ANALYSIS
The methodological quality of each trial was independently reviewed by the review authors. The standard effect measures were relative risk (RR) and risk difference (RD). From 1/RD the number needed to benefit (NNTB) to produce one outcome was calculated. For all measures of effect, 95% confidence intervals (CIs) were used. For interpretation of subgroup analyses, a P value for subgroup differences as well as the I(2) statistic for between-subgroup heterogeneity were calculated. Meta-analysis was performed using both a fixed-effect and a random-effects model. Where heterogeneity was over 50%, the random-effects model RR was also reported.
MAIN RESULTS
Nineteen eligible studies involving 4096 infants were included. Meta-analysis comparing HFOV with CV revealed no evidence of effect on mortality at 28 to 30 days of age or at approximately term equivalent age. These results were consistent across studies and in subgroup analyses. The risk of CLD in survivors at term equivalent gestational age was significantly reduced with the use of HFOV but this effect was inconsistent across studies, even after the meta-analysis was restricted to studies that applied a high lung volume strategy with HFOV. Subgroup analysis by HFOV strategy showed a similar effect in trials with a more strict lung volume recruitment strategy, targeting a very low fraction of inspired oxygen (FiO2), and trials with a less strict lung volume recruitment strategy and with a somewhat higher or unspecified target FiO2. Subgroup analyses by age at randomisation, routine surfactant use or not, type of high frequency ventilator (oscillator versus flow interrupter), inspiratory to expiratory (I:E) ratio of high frequency ventilator (1:1 versus 1:2) and CV strategy (lung protective or not) could not sufficiently explain the heterogeneity. Pulmonary air leaks, defined as gross air leaks or pulmonary interstitial emphysema, occurred more frequently in the HFOV group, whereas the risk of severe retinopathy of prematurity was significantly reduced.Although in some studies an increased risk of severe grade intracranial haemorrhage and periventricular leukomalacia was found, the overall meta-analysis revealed no significant differences in effect between HFOV and CV. The short-term neurological morbidity with HFOV was only found in the subgroup of two trials not using a high volume strategy with HFOV. Most trials did not find a significant difference in long-term neurodevelopmental outcome, although one recent trial showed a significant reduction in the risk of cerebral palsy and poor mental development.
AUTHORS' CONCLUSIONS
There is evidence that the use of elective HFOV compared with CV results in a small reduction in the risk of CLD, but the evidence is weakened by the inconsistency of this effect across trials. Probably many factors, both related to the intervention itself as well as to the individual patient, interact in complex ways. In addition, the benefit could be counteracted by an increased risk of acute air leak. Adverse effects on short-term neurological outcomes have been observed in some studies but these effects are not significant overall. Most trials reporting long-term outcome have not identified any difference.
Topics: Chronic Disease; High-Frequency Ventilation; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lung Diseases; Lung Injury; Randomized Controlled Trials as Topic; Respiration, Artificial; Respiratory Distress Syndrome, Newborn
PubMed: 25785789
DOI: 10.1002/14651858.CD000104.pub4