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The Cochrane Database of Systematic... Oct 2014Respiratory distress syndrome (RDS) is caused by a deficiency of pulmonary surfactant (an active agent that keeps pulmonary alveoli open and facilitates the entry of air... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Respiratory distress syndrome (RDS) is caused by a deficiency of pulmonary surfactant (an active agent that keeps pulmonary alveoli open and facilitates the entry of air to the lungs, thus improving the oxygenation of the newborn).A number of interventions such as pulmonary surfactant and prenatal corticosteroids are used to prevent RDS. Ambroxol has been studied as a potential agent to prevent RDS, but effectiveness and safety has yet to be evaluated.
OBJECTIVES
To evaluate the efficacy and safety of giving ambroxol to pregnant women who are at risk of preterm birth, for preventing neonatal RDS.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (29 November 2013), CENTRAL (The Cochrane Library 2013, Issue 11),Embase (1988 to November 2013), MEDLINE (PubMed 1970 to November 2013), LILACS (1982 to November 2013), the WHO International Clinical Trials Registry Platform (ICTRP) (November 2013) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing the administration of ambroxol given to pregnant women at risk of preterm birth versus placebo, antenatal corticosteroids (betamethasone or dexamethasone), or no treatment.We did not identify any trials comparing ambroxol with dexamethasone (corticosteroid) in this review. Nor did we identify any trials comparing ambroxol combined with corticosteroid versus corticosteroid alone, or placebo/no treatment.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and trial quality. Two review authors independently extracted data. Data were checked for accuracy.
MAIN RESULTS
We included 14 studies (in 18 trial reports), involving 1047 pregnant women at risk of preterm birth with 1077 newborns. However, three of the included studies did not report on this review's outcomes of interest. We carried out two main comparisons: ambroxol versus antenatal corticosteroids (betamethasone); and ambroxol versus placebo or no treatment. Seven RCTs provided data for our comparison of ambroxol versus corticosteroid (betamethasone) and two trials contributed data to our comparison of ambroxol compared to placebo or no treatment.The included studies were generally judged as having either 'low' risk of bias or 'unclear' risk of bias (because the trial reports provided insufficient details about methods of sequence generation, allocation concealment and blinding). Primary outcomesThere was no clear evidence of a difference in the incidence of RDS among newborns born to women who received ambroxol when compared to newborns of women who were given the corticosteroid, betamethasone (risk ratio (RR) 0.79, 95% confidence interval (CI) 0.59 to 1.07, seven RCTs, 728 women/758 newborns, moderate quality evidence) or placebo/no treatment (average RR 0.74; 95% CI 0.46 to 1.20, two studies, 204 women/204 newborns,T2= 0.07; I(2)= 53%, low-quality evidence). Results were imprecise and consistent with appreciable benefit as well as negligible effect.Similarly, there was no clear evidence of a difference in the rates of perinatal mortality between the group of women who received ambroxol and women in the corticosteroid (betamethasone) group (RR 0.51, 95% CI 0.23 to 1.12, six studies, 648 women/657 newborns, moderate quality evidence) or the placebo/no treatment group (RR 0.61; 95% CI 0.19 to 1.98, one study, 116 women/116 newborns, low-quality evidence).In terms of maternal adverse effects, there was no clear differences (in nausea or vomiting) between those women who received ambroxol compared to either those women who received corticosteroids (betamethasone) (average RR 3.45; 95% CI 0.34 to 35.51, three studies, 305 women, T(2)= 2.82; I(2)= 67%, very low-quality evidence), or women who received placebo or no treatment (RR 1.79; 95% CI 0.45 to 7.13, one study, 116 women, low-quality evidence). No other adverse effects (e.g. diarrhoea, gastric irritation and headache) were reported in the included studies. Secondary outcomesFor the review's secondary outcomes, none of the included studies reported on the incidence of bronchopulmonary dysplasia, periventricular haemorrhage, necrotising enterocolitis or rate of maternal mortality.One small trial (involving 88 women) comparing ambroxol with placebo or no treatment, reported no difference between groups in terms of the need for mechanical ventilation in the neonate (RR 0.94; 95% CI 0.73 to 1.21, 88 women/88 babies, low-quality evidence) or the administration of pulmonary surfactant (RR 1.19; 95% CI 0.61 to 2.30, one RCT, 88 women/88 babies, low-quality evidence).
AUTHORS' CONCLUSIONS
This review is based on very low to moderate quality evidence from 14 small trials (many are published in the form of conference abstracts with minimal methodological details provided). There is insufficient evidence to support or refute the practice of giving ambroxol to women at risk of preterm birth for preventing neonatal RDS, perinatal mortality and adverse effects. More research is needed in order to fully evaluate the benefits and risks of this intervention.
Topics: Adrenal Cortex Hormones; Ambroxol; Betamethasone; Expectorants; Female; Humans; Infant, Newborn; Pregnancy; Premature Birth; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome, Newborn
PubMed: 25361381
DOI: 10.1002/14651858.CD009708.pub2 -
Canadian Respiratory Journal 2016To assess whether noninvasive ventilation with Heliox reduces the need for endotracheal ventilation and subsequent complications in preterm infants with respiratory... (Meta-Analysis)
Meta-Analysis Review
To assess whether noninvasive ventilation with Heliox reduces the need for endotracheal ventilation and subsequent complications in preterm infants with respiratory distress syndrome (RDS). A search of major electronic databases, including MEDLINE and the Cochrane Central Register of Controlled Trials, for randomized or quasi-randomized controlled trials that compared noninvasive ventilation with Heliox versus noninvasive ventilation with standard gas for preterm infants with RDS was performed. The primary outcome was the incidence of intubation. The secondary outcomes were the level of PaCO, the use of surfactant, and other complications. Two randomized and one quasi-randomized controlled trials including 123 preterm infants were assessed. Heliox was found to significantly decrease the incidence of intubation (RR: 0.42; 95% CI: 0.23 to 0.78), the level of PaCO (MD: -9.61; 95% CI: -15.76 to -03.45), and the use of surfactant (RR: 0.25; 95% CI: 0.10 to 0.61) as compared with standard gas. No significant differences were found in other secondary outcomes. Noninvasive ventilation with Heliox decreases the incidence of intubation in preterm infants suffering from RDS. However, data on clinical outcomes are limited. Larger trials are needed to verify the beneficial effects.
Topics: Carbon Dioxide; Helium; Humans; Infant, Newborn; Intubation, Intratracheal; Noninvasive Ventilation; Oxygen; Partial Pressure; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Treatment Outcome
PubMed: 27994493
DOI: 10.1155/2016/9092871 -
The Cochrane Database of Systematic... Jan 2010Early surfactant reduces mortality and pulmonary complications in preterm infants with respiratory distress syndrome. However, current surfactant administration... (Review)
Review
BACKGROUND
Early surfactant reduces mortality and pulmonary complications in preterm infants with respiratory distress syndrome. However, current surfactant administration strategies require endotracheal intubation with or without continued mechanical ventilation. Bronchopulmonary dysplasia and chronic lung disease (CLD) are associated with mechanical ventilation and potentially life-long effects. Non-invasive methods of surfactant administration including intra-amniotic surfactant may avoid endotracheal intubation and mechanical ventilation, potentially preventing development of CLD.
OBJECTIVES
To determine if intra-amniotic instillation of surfactant for women at risk of preterm birth, compared to placebo or no treatment or post-delivery tracheal surfactant instillation, reduces morbidity or mortality, or both, in preterm infants. If intra-amniotic instillation is effective, in subgroup analysis to determine the effect of 1) gestational age; 2) type of surfactant; 3) dose; 4) timing; 5) indication; and 6) multiple pregnancy.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (August 2009), MEDLINE (1950-August 2009), handsearched the Proceedings of Pediatric Academic Societies (American Pediatric Society, Society for Pediatric Research and European Society for Pediatric Research) from 1990-2009 in Pediatric Research Journal and Abstracts online and the Proceedings of Perinatal Society of Australia and New Zealand (PSANZ) (1996-2009). We also searched the Science Citation Index (Web of Science) (August 2009) and checked reference lists of identified studies. We contacted Abbott Laboratories, Inc for unpublished studies.
SELECTION CRITERIA
Published, unpublished and ongoing randomised controlled, cluster-randomised or quasi-randomised trials of intra-amniotic instillation of surfactant for women at risk of preterm birth, compared to placebo or no treatment or post-delivery tracheal surfactant instillation.
DATA COLLECTION AND ANALYSIS
Three review authors independently assessed study eligibility and quality.
MAIN RESULTS
We found no trials were found met the inclusion criteria for this review.
AUTHORS' CONCLUSIONS
We identified no randomised trials that evaluated the effect of intra-amniotic instillation of surfactant for women at risk of preterm birth. Evidence from animal and observational human studies suggest that intra-amniotic surfactant administration is potentially safe, feasible and effective. Well designed trials of intra-amniotic instillation of surfactant for women at risk of preterm birth are needed.
Topics: Amnion; Female; Humans; Infant, Newborn; Injections; Pregnancy; Premature Birth; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn
PubMed: 20091659
DOI: 10.1002/14651858.CD007916.pub2 -
The Cochrane Database of Systematic... Oct 2006Acquired Antithrombin (AT) deficiency is a common and prognostically important finding in sick preterm infants with respiratory distress syndrome (RDS). It has been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acquired Antithrombin (AT) deficiency is a common and prognostically important finding in sick preterm infants with respiratory distress syndrome (RDS). It has been hypothesised that AT concentrate may improve clinical outcomes in preterm infants with RDS.
OBJECTIVES
To determine whether the administration of AT concentrate decreases mortality in preterm infants with RDS compared with placebo or no treatment.
SEARCH STRATEGY
An electronic literature search in the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE in August 2006 was performed. No language restriction was applied. References from identified studies were cross-checked for possible additional studies. Experts in the field and pharmaceutical companies were contacted for unpublished data. Abstracts of the American Society of Pediatric Research and European Society of Pediatric Research meetings (1983-2005) were searched and authors of relevant studies were contacted to obtain additional information.
SELECTION CRITERIA
Randomized controlled trials comparing any dose and duration of AT therapy with placebo or no treatment in preterm infants with RDS.
DATA COLLECTION AND ANALYSIS
Two reviewers independently extracted data from included studies regarding mortality, intraventricular hemorrhage, mechanical ventilation, and other reported events in the clinical course of the patients. Data for similar outcomes were combined where appropriate, using a fixed-effects model in MetaView 4.2 (Update Software).
MAIN RESULTS
Two trials consisting of 182 preterm infants, fulfilled the inclusion criteria. Mean gestational age of patients included was 28 weeks. In one trial, patients had to be intubated and ventilated for RDS to be eligible for the study. In the other trial, RDS was not mentioned as an inclusion criteria, however the vast majority of infants in the study received surfactant. No individual trial showed a significant difference in mortality. One of the trials was stopped early because of an increase in deaths in the AT group. The pooled analysis for mortality within the first week of life showed a typical relative risk of 2.67 (95% CI 0.72-9.83) in favour of the control group. Only the trial that was stopped early followed the infants long enough to report neonatal mortality. This trial reported 7 deaths (11.5%) in the AT group and two deaths (3.3%) in the placebo group within 28 days of life. Secondary outcomes included days of mechanical ventilation and supplemental oxygen which were only reported in 1 trial. Both outcomes were in favour of the control group and statistically significant (p < 0.05).
AUTHORS' CONCLUSIONS
Preterm infants with RDS are unlikely to benefit from AT treatment and may be harmed.
Topics: Anticoagulants; Antithrombin III; Antithrombins; Humans; Infant, Newborn; Infant, Premature; Pulmonary Surfactants; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome, Newborn
PubMed: 17054254
DOI: 10.1002/14651858.CD005383.pub2 -
The Cochrane Database of Systematic... Jan 2010Viral bronchiolitis is a common cause of respiratory failure in infants and children, and accounts for a significant portion of intensive care unit (ICU) admissions... (Review)
Review
BACKGROUND
Viral bronchiolitis is a common cause of respiratory failure in infants and children, and accounts for a significant portion of intensive care unit (ICU) admissions during seasonal epidemics. Currently there is no evidence to support the use of anything but supportive care for this disease. Surfactant is a potentially promising therapy; alterations in its composition have been described in bronchiolitis, and it may play a role in the host immunity for this disease.
OBJECTIVES
To assess the efficacy of exogenous surfactant for the treatment of bronchiolitis in mechanically ventilated infants and children.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2006, issue 1) which contains the Acute Respiratory Infections Group's Specialized Register; MEDLINE (1966 to Week 1, February 2006); and EMBASE (1990 to September 2005).
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing surfactant with placebo or surfactant with no surfactant in mechanically ventilated infants and children with viral bronchiolitis.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed trial quality. Unpublished data were requested from trial authors when necessary.
MAIN RESULTS
Three trials containing a total of 79 patients met the inclusion criteria. No mortality or adverse effects associated with surfactant administration were reported in any of these trials. In the three trials, use of surfactant was associated with a decrease in duration of mechanical ventilation by 2.6 days (95% confidence interval (CI) -5.34 to 0.18 days; P value 0.07) and a decrease in ICU length of stay by 3.3 days (95% CI -6.38 to -0.23 days; P value 0.04). In two studies with 59 patients, in which duration of mechanical ventilation in the control groups was more comparable, surfactant was associated with a decrease in ventilator days by 1.21 days (95% CI 0.75 to 1.67 days) and a decrease in ICU stay by 1.81 days (95% CI 1.19 days to 2.42 days). Individually the studies reported some short term benefit of surfactant on pulmonary mechanics and gas exchange.
AUTHORS' CONCLUSIONS
Available data on surfactant were not sufficient to provide reliable estimates of its effects in mechanically ventilated infants and children with bronchiolitis. Future studies should be adequately powered and will need to address unresolved questions regarding which surfactant preparation may be best suited for the treatment of bronchiolitis, the appropriate dose and administration interval, and how the choice of ventilator strategy may modify its effects.
Topics: Bronchiolitis, Viral; Child, Preschool; Critical Illness; Humans; Infant; Pulmonary Surfactants; Randomized Controlled Trials as Topic; Respiratory Syncytial Virus Infections
PubMed: 20091572
DOI: 10.1002/14651858.CD005150.pub3 -
Paediatric Respiratory Reviews Jun 2024Extreme preterm (EP) birth, denoting delivery before the onset of the third trimester, interrupts intrauterine development and causes significant early-life pulmonary... (Meta-Analysis)
Meta-Analysis Review
Extreme preterm (EP) birth, denoting delivery before the onset of the third trimester, interrupts intrauterine development and causes significant early-life pulmonary trauma, thereby posing a lifelong risk to respiratory health. We conducted a systematic review and meta-analysis to investigate adult lung function following EP birth (gestational age <28 weeks); comparing forced expiratory volume in first second (FEV), forced vital capacity (FVC), and FEV/FVC to reference values. Subgroup differences were explored based on timing of birth relative to surfactant use (1991) and bronchopulmonary dysplasia (BPD) status. Systematic searches were performed in Medline, EMBASE, Web of Science and Cochrane Central. Quality assessments were carried out using a modified Newcastle-Ottawa Scale for cohort studies. Sixteen studies encompassing 1036 EP-born adults were included, with 14 studies (n = 787) reporting data as %predicted, and 11 (n = 879) as z-score (not mutually exclusive). Overall mean [95 % confidence interval (CI)] %FEV was 85.30 (82.51; 88.09), %FVC was 94.33 (91.74; 96.91), and FEV/FVC was 79.54 (77.71 to 81.38), all three with high heterogeneity. Overall mean (95 %CI) zFEV was -1.05 (-1.21; -0.90) and zFVC was. -0.45 (-0.59; -0.31), both with moderate heterogeneity. Subgroup analyses revealed no difference in FEV before versus after widespread use of surfactant, but more impairments after neonatal BPD. This meta-analysis revealed significant airflow limitation in EP-born adults, mostly explained by those with neonatal BPD. FEV was more reduced than FVC, and FEV/FVC was at the lower limit of normal. Although at a group level, most adult EP-born individuals do not meet COPD criteria, these findings are concerning.
Topics: Humans; Infant, Extremely Premature; Forced Expiratory Volume; Bronchopulmonary Dysplasia; Vital Capacity; Infant, Newborn; Adult; Pulmonary Surfactants
PubMed: 38490917
DOI: 10.1016/j.prrv.2024.02.002 -
Neonatology 2021Prematurely born infants regularly develop respiratory distress syndrome and require assisted ventilation. Ventilation may injure the premature lung and increase the...
INTRODUCTION
Prematurely born infants regularly develop respiratory distress syndrome and require assisted ventilation. Ventilation may injure the premature lung and increase the risk of bronchopulmonary dysplasia. Continuous positive airway pressure (CPAP), a form of noninvasive ventilation, is commonly used in modern neonatology. Limited clinical data are available on the acute and long-term effect of neonatal exposure to CPAP on the lung. Given the restricted clinical data, newborn animal models have been used to study the influence of CPAP on lung structure and function. The findings of animal studies can guide neonatal care and improve the use of CPAP.
METHODS
A systematic review of electronic databases (Medline, Embase, and Cinahl) was performed using the medical subject heading terms, "CPAP" or "continuous positive airway pressure" and "animals" and "newborn." Abstracts were screened for inclusion using predetermined eligibility criteria.
RESULTS
In total, 235 abstracts were identified and screened for inclusion. Of these, 21 papers were included. Large (N = 18) and small (N = 3) animal models investigated the effects of CPAP. Pulmonary outcomes included gas exchange, lung structure and function, surfactant metabolism, lung inflammation and injury, and the effect of intrapulmonary therapy. Compared to mechanical ventilation, CPAP improves lung function, evokes less lung injury, and does not disrupt alveolar development. Surfactant administration combined with CPAP further improves respiratory outcomes. Of concern are findings that CPAP may increase airway reactivity.
DISCUSSION/CONCLUSION
CPAP offers numerous advantages over mechanical ventilation for the immature lung. The combination of CPAP and exogenous surfactant administration offers further pulmonary benefit.
Topics: Animals; Animals, Newborn; Continuous Positive Airway Pressure; Humans; Infant, Newborn; Infant, Premature; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn
PubMed: 33091899
DOI: 10.1159/000511086 -
The Cochrane Database of Systematic... Jul 2015Respiratory distress syndrome (RDS) is the single most important cause of morbidity and mortality in preterm infants. In infants with progressive respiratory... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Respiratory distress syndrome (RDS) is the single most important cause of morbidity and mortality in preterm infants. In infants with progressive respiratory insufficiency, intermittent positive pressure ventilation (IPPV) with surfactant is the standard treatment for the condition, but it is invasive, potentially resulting in airway and lung injury. Continuous distending pressure (CDP) has been used for the prevention and treatment of RDS, as well as for the prevention of apnoea, and in weaning from IPPV. Its use in the treatment of RDS might reduce the need for IPPV and its sequelae.
OBJECTIVES
To determine the effect of continuous distending pressure (CDP) on the need for IPPV and associated morbidity in spontaneously breathing preterm infants with respiratory distress.Subgroup analyses were planned on the basis of birth weight (> or < 1000 or 1500 g), gestational age (groups divided at about 28 weeks and 32 weeks), methods of application of CDP (i.e. CPAP and CNP), application early versus late in the course of respiratory distress and high versus low pressure CDP and application of CDP in tertiary compared with non-tertiary hospitals, with the need for sensitivity analysis determined by trial quality.At the 2008 update, the objectives were modified to include preterm infants with respiratory failure.
SEARCH METHODS
We used the standard search strategy of the Neonatal Review Group. This included searches of the Oxford Database of Perinatal Trials, the Cochrane Central Register of Controlled Trials (CENTRAL, 2015 Issue 4), MEDLINE (1966 to 30 April 2015) and EMBASE (1980 to 30 April 2015) with no language restriction, as well as controlled-trials.com, clinicaltrials.gov and the International Clinical Trials Registry Platform of the World Health Organization (WHO).
SELECTION CRITERIA
All random or quasi-random trials of preterm infants with respiratory distress were eligible. Interventions were continuous distending pressure including continuous positive airway pressure (CPAP) by mask, nasal prong, nasopharyngeal tube or endotracheal tube, or continuous negative pressure (CNP) via a chamber enclosing the thorax and the lower body, compared with spontaneous breathing with oxygen added as necessary.
DATA COLLECTION AND ANALYSIS
We used standard methods of The Cochrane Collaboration and its Neonatal Review Group, including independent assessment of trial quality and extraction of data by each review author.
MAIN RESULTS
We included six studies involving 355 infants - two using face mask CPAP, two CNP, one nasal CPAP and one both CNP (for less ill babies) and endotracheal CPAP (for sicker babies). For this update, we included no new trials.Continuous distending pressure (CDP) is associated with lower risk of treatment failure (death or use of assisted ventilation) (typical risk ratio (RR) 0.65, 95% confidence interval (CI) 0.52 to 0.81; typical risk difference (RD) -0.20, 95% CI -0.29 to -0.10; number needed to treat for an additional beneficial outcome (NNTB) 5, 95% CI 4 to 10; six studies; 355 infants), lower overall mortality (typical RR 0.52, 95% CI 0.32 to 0.87; typical RD -0.15, 95% CI -0.26 to -0.04; NNTB 7, 95% CI 4 to 25; six studies; 355 infants) and lower mortality in infants with birth weight above 1500 g (typical RR 0.24, 95% CI 0.07 to 0.84; typical RD -0.28, 95% CI -0.48 to -0.08; NNTB 4, 95% CI 2.00 to 13.00; two studies; 60 infants). Use of CDP is associated with increased risk of pneumothorax (typical RR 2.64, 95% CI 1.39 to 5.04; typical RD 0.10, 95% CI 0.04 to 0.17; number needed to treat for an additional harmful outcome (NNTH) 17, 95% CI 17.00 to 25.00; six studies; 355 infants). We found no difference in bronchopulmonary dysplasia (BPD), defined as oxygen dependency at 28 days (three studies, 260 infants), as well as no difference in outcome at nine to 14 years (one study, 37 infants).
AUTHORS' CONCLUSIONS
In preterm infants with respiratory distress, the application of CDP as CPAP or CNP is associated with reduced respiratory failure and mortality and an increased rate of pneumothorax. Four out of six of these trials were done in the 1970s. Therefore, the applicability of these results to current practice is difficult to assess. Further research is required to determine the best mode of administration.
Topics: Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Intermittent Positive-Pressure Ventilation; Outcome Assessment, Health Care; Pneumothorax; Positive-Pressure Respiration; Pulmonary Surfactants; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome, Newborn; Selection Bias
PubMed: 26141572
DOI: 10.1002/14651858.CD002271.pub2 -
Pediatric Critical Care Medicine : a... Sep 2004Viral bronchiolitis is the leading cause of respiratory failure among infants in the United States. Currently, the mainstay of treatment is supportive care. The... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Viral bronchiolitis is the leading cause of respiratory failure among infants in the United States. Currently, the mainstay of treatment is supportive care. The effectiveness of treatments used for mechanically ventilated infants with bronchiolitis is unclear.
OBJECTIVE
To evaluate the strength of the evidence supporting the use of currently available treatments for critically ill infants with bronchiolitis.
DATA SOURCE
We searched PubMed, citations of relevant articles, personal files, and conference proceedings, and we contacted experts in the field.
STUDY SELECTION
Randomized, controlled trials evaluating any therapy for bronchiolitis that included children in an intensive care unit.
DATA EXTRACTION
Two reviewers independently extracted data and assessed methodologic quality.
DATA SYNTHESIS
A total of 2,319 citations were screened, and 16 randomized, controlled trials were included. There were three trials of surfactant, three of ribavirin, three of immune globulin, three of systemic corticosteroids, and one each of vitamin A, interferon, erythropoietin, and heliox. A meta-analysis of the three surfactant studies showed a strong trend toward a decrease in duration of mechanical ventilation of 2.58 days (95% confidence interval, -5.34 to 0.18 days; p =.07) and a significant decrease of 3.3 intensive care unit days (95% confidence interval, -6.38 to -0.23 days; p =.04). A meta-analysis of the three systemic corticosteroid studies showed no overall effect on duration of mechanical ventilation when all three trials were combined (-0.62 day; 95% confidence interval, -2.78 to 1.53 days; p =.57). We identified one published meta-analysis of three ribavirin studies showing a significant decrease in ventilator days with ribavirin (-1.2 days; 95% confidence interval, -0.2 to -3.4 days; p =.2).
CONCLUSIONS
Currently, there are no clearly effective interventions available to improve the outcome of critically ill infants with bronchiolitis. Surfactant seems to be a promising intervention, and corticosteroids or ribavirin may also be beneficial.
Topics: Bronchiolitis; Combined Modality Therapy; Critical Illness; Female; Follow-Up Studies; Humans; Immunoglobulins; Infant; Infant, Newborn; Intensive Care Units, Neonatal; Male; Pulmonary Surfactants; Randomized Controlled Trials as Topic; Respiration, Artificial; Respiratory Insufficiency; Risk Assessment; Steroids; Survival Analysis; Treatment Outcome
PubMed: 15329166
DOI: 10.1097/01.pcc.0000128891.54799.67 -
The Cochrane Database of Systematic... Jul 2009Pulmonary disease is a major cause of mortality and morbidity in term and near term infants. Conventional ventilation (CV) has been used for many years but may lead to... (Comparative Study)
Comparative Study Review
BACKGROUND
Pulmonary disease is a major cause of mortality and morbidity in term and near term infants. Conventional ventilation (CV) has been used for many years but may lead to lung injury, require the subsequent use of more invasive treatment such as extracorporeal membrane oxygenation (ECMO), or result in death. There are some observational studies indicating that high frequency oscillatory ventilation (HFOV) may be more effective in these infants as compared to CV.
OBJECTIVES
To determine the effect of HFOV as compared with CV on mortality and morbidity in infants born at 35 weeks gestational age or more with severe respiratory failure requiring mechanical ventilation.
SEARCH STRATEGY
Standard search methods of the Cochrane Neonatal Review group were used. These included searches in January 2009 of The Cochrane Library, MEDLINE, EMBASE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, and journal hand searching by the Cochrane Collaboration.
SELECTION CRITERIA
Randomized or quasi-randomized trials comparing HFOV and CV in term or near term infants with intractable respiratory failure were included in this review.
DATA COLLECTION AND ANALYSIS
The standard methods of the Cochrane Neonatal Review Group were used. The investigators separately extracted, assessed and coded all data for each study. Any disagreement was resolved by discussion. Data were synthesized using risk ratio [RR with (95% confidence intervals, CI)] and mean difference (with standard deviation, SD).
MAIN RESULTS
Two trials met the inclusion criteria. One trial involving the "elective" use of HFOV randomized 118 infants at the start of CV. The other trial of "rescue" HFOV randomized 81 infants with later respiratory failure on CV. Neither trial showed evidence of a reduction in mortality at 28 days or in failed therapy on the assigned mode of ventilation requiring cross-over to the other mode. Neither study reported significant differences in the risk of pulmonary air leak, chronic lung disease (28 days or more in oxygen) or intracranial injury. In the study of elective HFOV, there was no difference noted in days on a ventilator or days in hospital. In the one rescue study, there was no difference in the risk of needing extracorporeal membrane oxygenation.
AUTHORS' CONCLUSIONS
There are no data from randomized controlled trials supporting the use of rescue HFOV in term or near term infants with severe pulmonary dysfunction. The area is complicated by diverse pathology in such infants and by the occurrence of other interventions (surfactant, inhaled nitric oxide, inotropes). Randomized controlled trials are needed to establish the role of elective or rescue HFOV in near term and term infants with pulmonary dysfunction before widespread use of this mode of ventilation in such infants.
Topics: High-Frequency Ventilation; Humans; Infant, Newborn; Lung Diseases; Randomized Controlled Trials as Topic; Respiration, Artificial; Salvage Therapy; Term Birth; Treatment Outcome
PubMed: 19588337
DOI: 10.1002/14651858.CD002974.pub2