Geraldine Ng1, Orlando da Silva2, Arne Ohlsson3
Background - Methods - Results - Characteristics of Included Studies - References - Data Tables and Graphs
1Neonatology, St Mary's Hospital (Imperial College Healthcare NHS Trust), London, UK
2Pediatrics, Universtiy of Western Ontario, London, Canada
3Departments of Paediatrics, Obstetrics and Gynaecology and Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada
Citation example: Ng G, da Silva O, Ohlsson A. Bronchodilators for the prevention and treatment of chronic lung disease in preterm infants. Cochrane Database of Systematic Reviews 2001, Issue 3. Art. No.: CD003214. DOI: 10.1002/14651858.CD003214.
Neonatology
St Mary's Hospital (Imperial College Healthcare NHS Trust)
1st Floor, The Bay's Building
Praed Street
London
London
W2 1NY
UK
E-mail: DrGYTNg@aol.com
| Assessed as Up-to-date: | 21 July 2009 |
|---|---|
| Date of Search: | 27 January 2009 |
| Next Stage Expected: | 21 July 2011 |
| Protocol First Published: | Issue 3, 1998 |
| Review First Published: | Issue 3, 2001 |
| Last Citation Issue: | Issue 3, 2001 |
| Date / Event | Description |
|---|---|
| 21 July 2009 Updated | This review updates the existing review "Bronchodilators for the prevention and treatment of chronic lung disease in preterm infants" published in the Cochrane Database of Systematic Reviews (Ng 2006). Updated search found no new trials. No changes to conclusions. |
| Date / Event | Description |
|---|---|
| 11 September 2008 Amended | Converted to new review format. |
| 30 April 2006 Updated | This review updates the existing review "Bronchodilators for the prevention and treatment of chronic lung disease in preterm infants" published in TheCochrane Library, Issue 3, 2003 (Ng 2003). |
| 07 February 2001 New citation: conclusions changed | Substantive amendment |
Chronic lung disease (CLD) occurs frequently in preterm infants. Bronchodilators have the potential effect of dilating small airways with muscle hypertrophy. Increase in compliance and tidal volume and decrease in pulmonary resistance have been documented with use of bronchodilators in studies of pulmonary mechanics in infants with CLD. Therefore, it is possible that bronchodilators might have a role in the prevention and treatment of CLD.
To determine the effect of bronchodilators given either prophylactically or as treatment for CLD on mortality and other complications of prematurity in preterm infants at risk for or having CLD.
Searches were made of MEDLINE 1966 to January 2009, EMBASE 1980 to January 2009, CINAHL 1982 to January 2009, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2009), personal files and reference lists of identified trials. No language restrictions were applied.
Randomised controlled trials involving preterm infants were eligible for inclusion. Initiation of bronchodilator therapy had to occur within two weeks of birth for prevention of CLD. For treatment of CLD, treatment had to be initiated before discharge from the neonatal unit. The intervention had to include the administration of a bronchodilator either by nebulisation, metered dose inhaler (with or without a spacer device), intravenously or orally versus placebo or no intervention. Eligible studies had to include at least one of the predefined outcomes.
We used the standard method described in the Cochrane Collaboration handbook. Two investigators extracted and assessed all data for each study. Relative risk (RR) and risk difference (RD) with 95% confidence intervals (CI) are reported for dichotomous outcomes and mean difference (WMD) for continuous data.
One eligible study was found dealing with prevention of CLD; this study used salbutamol and enrolled 173 infants. No eligible studies were found dealing with treatment of CLD. Prophylaxis with salbutamol did not show a statistically significant difference in mortality [RR 1.08 (95% CI 0.50, 2.31); RD 0.01 (95% CI -0.09, 0.11)] or CLD [RR 1.03 (95% CI 0.78, 1.37); RD 0.02 (95% CI -0.13, 0.17)]. No statistically significant differences were seen in other complications associated with CLD or preterm birth. No side effects due to salbutamol were commented on in this study.
Not enough evidence to show the effect of bronchodilators for chronic lung disease in preterm babies.
Chronic lung disease (CLD) is common in babies who are born before 34 weeks gestation. Bronchodilators are drugs that cause widening of the air passages in the lungs. They have been used for CLD because of their potential effect of dilating small airways in babies born preterm. Bronchodilators can be inhaled, taken by mouth (a puffer) or injection or by a nebulizer with a pressurized aerosol. This review of trials found that there was not enough evidence to show either positive or negative effects of bronchodilators for CLD. More research is needed.
Chronic lung disease (CLD), defined as either oxygen dependency at 28 days or at 36 weeks postmenstrual age with compatible chest radiographs, is a pulmonary disorder that occurs frequently in preterm infants (Northway 1967; Shennan 1988). It is the consequence of unresolved or abnormally repaired lung damage and has a multifactorial etiology that has been detailed extensively by previous authors. This includes exposure to high oxygen concentration, volume derived trauma, barotrauma, sepsis and inflammation (Avery 1987; Paita 1991; Rojas 1995). In the past decades, the survival rate of very low birth weight infants has increased and the prevalence of CLD remains high (Parker 1992). The incidence varies depending on the population studied, the diagnostic criteria used and variation between centre clinical management (O'Brodovich 1985; Shennan 1988; Hack 1991; Avery 1987; Lee 2000). CLD may be associated with chronic respiratory difficulties, prolonged and recurrent hospitalisation, growth restriction and death (O'Brodovich 1985; Lee 2000). The administration of antenatal corticosteroids to mothers likely to give birth preterm reduces neonatal mortality and the incidence of respiratory distress syndrome (RDS), but not the incidence of CLD (Crowley 2001). Administration of prophylactic natural surfactant extract does not reduce the incidence of CLD but reduces the combined outcome of death or CLD (Soll 2001).
Bronchodilators may be delivered orally, intravenously, by nebuliser or pressurised aerosol with or without a spacer device. With nebulisation or aerosol only 0.22 - 1.3% of the dose will reach the lung (Grigg 1992; Fok 1996). Aerosol tends to be deposited in the central lung region rather than the periphery (Fok 1996). Humidification of the gas reduces lower respiratory tract deposition of aerosol (Diot 1995). Addition of a spacer device between the nebuliser and the endotracheal tube (Harvey 1995) and synchronising nebulisation with inspiratory airflow (Diot 1995) increase deposition. There is also considerable intersubject variability in lung deposition (Fok 1996). All of these factors will modify therapeutic effects.
There are numerous available bronchodilators. Inhaled bronchodilators include non-specific beta adrenergic agents such as isoproterenol and isoetharine, and specific beta adrenergic agents such as albuterol, metaproterenol, terbutaline and isoetharine. Side effects of beta agonists include hypokalaemia, tachycardia, cardiac arrhythmias, tremor, hypertension and hyperglycaemia (Davis 1990; Farrell 1997; Sweet 2000). Inhaled anticholinergic agents include atropine and ipratropium. There are more side effects of atropine than of ipratropium as the latter is poorly absorbed. Side effects of inhaled anticholinergic agents include tachycardia, decreased gastrointestinal motility, tremor and drying of respiratory secretions (Davis 1990). Systemic bronchodilators include the methylxanthines, caffeine and theophylline, which act by blockage of adenosine receptors. Reported side effects include vomiting, diarrhoea, tachycardia, hypertension and agitation (Davis 1990; Farrell 1997; Sweet 2000).
The use of bronchodilators in CLD has been justified by their potential effect of dilating small airways having muscular hypertrophy. Increase in compliance and tidal volume and decrease in pulmonary resistance has been documented with use of bronchodilators in short-term studies of pulmonary mechanics in infants with CLD (Sosulski 1982; Cabal 1987; Kirpalani 1990; Brudno 1989, Pfenninger 1993; Gappa 1997; Fok 1998b).
This review of "Bronchodilators for the prevention and treatment of chronic lung disease in preterm infants" updates the previously published review in the Cochrane Database of Systematic Reviews (Ng 2006).
To determine the effect of bronchodilators given prophylactically or as treatment for chronic lung disease on mortality and other complications of prematurity in preterm infants at risk for or having chronic lung disease.
The intervention had to include the randomised or quasi randomised administration of a bronchodilator by nebulisation, spacer device, intravenously or orally versus placebo or no intervention. Bronchodilators include albuterol, aminophylline, atropine, caffeine, clenbuterol, cromakalim, ephedrine, epinephrine, fenoterol, hexoprenaline, ipratropium, isoetharine, isoproterenol, orciprenaline, procaterol, terbutaline, theophylline, tretoquinol. For prevention of CLD, treatment had to be initiated during the first two weeks of life with length of treatment more that seven days. For treatment, babies had to have CLD with length of treatment more that seven days. Treatment had to be initiated before discharge from the neonatal unit.
For prophylaxis: primary outcomes were mortality within the study period and CLD (defined as oxygen dependency at 28 days of life or at 36 weeks postmenstrual age with compatible chest radiograph signs).
For treatment: primary outcomes were mortality within the study period.
For prophylaxis: Secondary outcomes were number of days on oxygen, number of days on ventilator, patent ductus arteriosus (PDA), pulmonary interstitial emphysema (PIE), pneumothorax, any grade of intraventricular haemorrhage, necrotizing enterocolitis (NEC), sepsis and adverse effects of bronchodilators. Adverse effects of bronchodilators included hypokalaemia, tachycardia, cardiac arrhythmias, tremor, hypertension and hyperglycaemia.
For treatment: Secondary outcomes were number of days on oxygen, number of days on ventilator, patent ductus arteriosus (PDA), pulmonary interstitial emphysema (PIE), pneumothorax, any grade of intraventricular haemorrhage, necrotizing enterocolitis (NEC), sepsis and adverse effects of bronchodilators.
See: Collaborative Review Group search strategy. The standard search methods of the Cochrane Neonatal Review Group were employed.
The search strategy used to identify studies was according to the guidelines of the Cochrane Neonatal Review Group. Searches were made of MEDLINE 1966 to January 2009, EMBASE 1980 to January 2009, CINAHL 1982 to January 2009, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2009), personal files and reference lists of identified trials. The search strategies were adjusted to reflect the different controlled vocabularies of the databases. No language restrictions were applied.
In MEDLINE the following MeSH terms were used: bronchopulmonary dysplasia, chronic disease, lung diseases, bronchodilator agents, adrenergic agents, anticholinergic agents, albuterol, aminophylline, atropine, clenbuterol, cromakalim, ephedrine, epinephrine, fenoterol, hexoprenaline, ipratropium, isoetharine, isoproterenol, orciprenaline, procaterol, terbutaline, theophylline, tretoquinol. The following textwords were used: chronic lung disease, caffeine, salbutamol, terbutaline, albuterol, aminophylline, atropine, ipratopium, isoetharine, theophylline. Limits: newborn infant <birth to 1 month>, human, clinical trial, controlled clinical trial, meta analysis, multicenter study, randomised controlled trial.
In EMBASE the following terms were used: bronchodilating agent, adrenergic receptor stimulating agent, albuterol, clenbuterol, fenoterol, salbutamol, terbutaline, isoetharine, isoproterenol, lung dysplasia, evidence based medicine, clinical trial, multicenter study. The following textwords were used: bronchopulmonary dysplasia, clinical trial, rct, rcts, random, meta-analysis, meta analysis, multicenter, newborn, neonate, neonatal. Limits: infant < to one year >.
In CINAHL the following terms were used: bronchopulmonary dysplasia, chronic disease, lung diseases, adrenergic agents, anticholinergic agents, bronchodilator agents. The following textwords were used: albuterol, aminophylline, atropine, clenbuterol, cromakalim, ephedrine, epinephrine, fenoterol, hexoprenaline, ipratropium, isoetharine, isoproterenol, orciprenaline, procaterol, terbutaline, theophylline, tretoquinol. Limits: newborn infant < birth to 1 month >.
The standard methods of the Cochrane Neonatal Review Group were employed.
All randomised and quasi-randomised controlled trials fulfilling the selection criteria described in the previous section were included. Each of two review authors (GN, AO) reviewed the results of the search and separately selected studies for inclusion. Differences were resolved by discussion.
Each of two review authors (GN, AO) extracted data separately. Differences were resolved by discussion. For each included trial information was sought regarding the blinding of randomisation and whether the trial was single or multicentred. Information on the trial participants included birth weight, GA at birth, postnatal age, need for mechanical ventilation, and sex. Information on clinical outcomes was analysed for CLD at 28 days, CLD at 36 weeks postmenstrual age, overall mortality, IVH, NEC, air leaks, sepsis and adverse effects due to the drug. Information on hospital stay and days in oxygen or on mechanical ventilation was also sought.
The standard methods of the Cochrane Neonatal Review Group were employed. The methodological quality of each trial was reviewed independently by two review authors (GN and AO). Each identified trial was assessed for methodological quality with respect to a) masking of allocation b) masking of intervention c) completeness of follow-up d) masking of outcome assessment. This information is included in the table 'Characteristics of Included Studies'.
For the update in 2009, the risk of bias table was completed in order to address the following questions:
1. Sequence generation: Was the allocation sequence adequately generated?
2. Allocation concealment: Was allocation adequately concealed?
3. Blinding of participants, personnel and outcome assessors: Was knowledge of the allocated intervention adequately prevented during the study? At study entry? At the time of outcome assessment?
4. Incomplete outcome data: Were incomplete outcome data adequately addressed?
5. Selective outcome reporting: Are reports of the study free of suggestion of selective outcome reporting?
6. Other sources of bias: Was the study apparently free of other problems that could put it at a high risk of bias?
Statistical analyses was performed using Review Manager software. Categorical data was analysed using relative risk (RR), risk difference (RD) and the number needed to treat (NNT). Continuous data was analysed using weighted mean difference (WMD). The 95% confidence interval (CI) was reported on all estimates.
We planned to estimate the treatment effects of individual trials and examine heterogeneity between trials by inspecting the forest plots and quantifying the impact of heterogeneity using the I2 statistic. If we detected statistical heterogeneity, we planned to explore the possible causes (for example, differences in study quality, participants, intervention regimens, or outcome assessments) using post hoc sub group analyses.
The standard methods of the Neonatal Review Group were used to synthesise data using relative risk (RR), risk difference (RD) and number needed to treat (NNT) if there was a statistically significant reduction in RD and number needed to harm (NNH) if there was a statistically significant increase in the RD. Mean difference (WMD) was used for continuous variables. A fixed effect model was used for meta-analysis.
One study was identified dealing with prevention. No studies were found concerning treatment of CLD.
In the study by Denjean 1998, 173 infants needing ventilatory support in a multicentre trial in six NICUs were randomised into four groups: salbutamol + placebo, salbutamol + beclomethasone, placebo + placebo, or placebo + beclomethasone for 28 days. Randomisation was stratified by centre, GA (< 28 wks vs. 29 - 30 wks) and the type of ventilatory support. The salbutamol + placebo and salbutamol + beclomethasone groups were compared to the placebo + placebo and placebo + beclomethasone groups in this review. This comparison is unconfounded by beclomethasone as half of each group, salbutamol or placebo, will have received beclomethasone also. Salbutamol was given in a dose of 200 mcg every four hours (1200 mcg daily) via metered dose inhaler and spacer device. Beclomethasone was given in a dose of 250 mcg via metered dose inhaler and spacer device. The groups were similar with respect to the age at entry, sex, severity of the initial respiratory failure (as assessed by initial FiO2 and ventilatory index), maternal prenatal steroid therapy and multiple pregnancy. Treatment was begun on the 10th or 11th postnatal day and was given for 28 days with the dose tapering off over a period of eight days. Primary outcomes were mortality and CLD characterised at 28 days of life on the basis of clinical (oxygen dependency) and radiographic criteria. Secondary outcomes were duration of ventilatory support, duration of oxygen supplementation, ventilatory index (the product of oxygen tension and mean airway pressure) measured every week until extubation, pulmonary complications (pneumothorax, interstitial emphysema), sepsis, mandatory iv corticosteroid treatment according to the usual practice in each centre and episodes of bronchospasm treated with iv bronchodilators. Data on drug deposition were not given in this study.
The studies by Kao 1984; Kao 1987; Kao 1988; Kao 1989; Wilkie 1987; Rotschild 1989; Stefano 1991; Pfenninger 1993; Lee 1994; Gappa 1997; Nguyen 1997; Fok 1998a and Sivakumar 1999 were rejected as these studies dealt solely with pulmonary mechanics. Guimaraes 1993 was rejected as it was not a randomised controlled trial and infants were given both beclomethasone and salbutamol together.
The study by Denjean 1998 is of overall good methodological quality. A sample size calculation was included. Initial randomisation process and preparation of therapeutic units was centralized. The randomisation was blinded and stratified by center, by gestational age and by mode of ventilation used at trial entry at 10 days of age (ET IMV or IMV/CPAP)(Denjean - personal communication). The intervention was also blinded. Originally 178 infants were randomised but informed consent was either not obtained or withdrawn for five infants leaving 173 infants in the trial. Results are reported on these 173 infants. It is unclear who reported the chest radiographs for the diagnosis of CLD and whether they were blinded.
In the study by Denjean 1998 the results of the salbutamol and placebo groups were compared for the following:
Salbutamol vs placebo in the prophylaxis of CLD (Comparison 1):
Mortality (Outcome 1.1):
No significant effect was found: RR 1.08 (95% CI 0.50, 2.31); RD 0.01 (95% CI -0.09, 0.11).
CLD at 28 days (Outcome 1.2):
For overall (mild, moderate or severe) there was no significant effect: CLD RR 1.03 (95% CI 0.78, 1.37); RD 0.02 (95% CI -0.13, 0.17).
Duration of assisted ventilation (Outcome 1.3):
There was no statistically significant difference in the duration of assisted ventilation MD -1.63 days (95% CI -5.63, 2.37).
Duration of oxygen supplementation (Outcome 1.4):
There was no statistically significant difference in the duration of oxygen supplementation MD -2.82 days (95% CI -11.91, 6.27).
Mean age of weaning from ventilatory support (Outcome 1.5):
There was no statistically significant difference in weaning from respiratory support (assisted ventilation or oxygen supplementation): MD -2.87 days (95% CI -11.28, 5.54).
Need for iv dexamethasone (Outcome 01.6):
No significant effect was found: RR 0.77 (95% CI 0.49, 1.19); RD -0.08 (95% CI -0.22, 0.05). These results are not statistically significant.
Infants with one or more episodes of infection (Outcomes 1.7 and 1.8):
There was no statistically significant effect found on respiratory infections defined as increasing ventilatory requirements associated with increased serum C reactive protein and bacteria in tracheal aspirates: RR 0.61 (95% CI 0.27, 1.39); RD -0.06 (95% CI -0.16, 0.04). There was no significant effect found on sepsis defined as a positive blood culture: RR 1.06 (95% CI 0.54, 2.06); RD 0.01 (95% CI -0.10, 0.12).
The authors state that there was no difference in the secondary outcomes of pulmonary complications, weekly ventilatory index until extubation, interruptions in randomised treatment for iv salbutamol and episodes of bronchospasm treated with iv bronchodilators. However, the data are not presented in the paper. Adverse effects associated with salbutamol were not commented on in this paper.
Only one trial, Denjean 1998, was identified which dealt with prevention of CLD. No studies were found concerning treatment of CLD which assessed important clinical outcomes. The excluded studies by Kao 1984; Kao 1987; Wilkie 1987; Gappa 1997; Fok 1998a; Kao 1988; Kao 1989; Rotschild 1989; Stefano 1991; Pfenninger 1993; Lee 1994; Guimaraes 1993; Nguyen 1997 and Sivakumar 1999 found short term decreases in pulmonary resistance and increases in pulmonary compliance. However, they did not examine our primary and secondary clinical outcomes.
The study by Denjean 1998 shows no evidence that salbutamol reduces mortality or chronic lung disease at 28 days in preterm infants at risk of developing CLD. This study does not report outcomes for CLD at 36 weeks postmenstrual age which is generally regarded as the more important outcome with regards to CLD. The study does not demonstrate earlier weaning from respiratory support with salbutamol or the duration of oxygen supplementation. The study demonstrates that salbutamol does not affect need for iv dexamethasone or sepsis compared to placebo. It is possible that the use of dexamethasone varied between the six neonatal intensive care units in the study. Denjean 1998 makes no comments as to adverse effects of salbutamol in this study.
There are several possible reasons as to why salbutamol had no evidence of effect in the study by Denjean 1998. The study does not assess drug deposition which is important as this will change the therapeutic effect of the drug. The amount of drug delivered to the lung also varies with the route of administration. It is possible that the mode of delivery used in this study did not deliver enough drug to the lung. The pathophysiology of CLD is multifactorial. Since there are other mechanisms besides muscle hypertrophy in small airways, this may be another reason why salbutamol showed no evidence of effect for the prevention of CLD in this study.
The review authors were surprised at the paucity of trials which assessed clinical outcomes of bronchodilators in CLD. No randomised controlled trials could be found in an extensive search of the literature of the use of bronchodilators in the treatment of CLD.
The results of this systematic review do not provide evidence for the use of salbutamol for the prevention of CLD at the present time. We are unable to address the question as to whether bronchodilators are useful in the treatment of CLD. Future use of salbutamol and other bronchodilators in preterm infants should occur in the scenario of a placebo-controlled randomised clinical trial.
In light of the paucity of clinical trials available in this systematic review, future research should thus be directed toward addressing the question of whether bronchodilators have a preventative role in preterm infants at risk of CLD to reduce mortality, CLD at 36 weeks postmenstrual, duration of ventilatory support, duration of oxygen supplementation and long term outcomes (to 18 months corrected GA). Future researchers should also evaluate if bronchodilators have a role in preterm infants with established CLD to reduce mortality, duration of ventilatory support or duration of oxygen supplementation. It is important that future research assesses if this occurs without undue side effects. It is also important that clinical outcomes are assessed beyond short term pulmonary function. There are a wide variety of bronchodilators available and only salbutamol was assessed in this study. Future research should be directed at using different bronchodilator drugs, different drug dosages, different modes of delivery, and assessing drug deposition.
We would like to acknowledge the help of Joseph Beyene, Biostatistician, University of Toronto, Ontario, Canada and Elizabeth Uleryk, Director of the Hospital Library, the Hospital for Sick Children, Toronto.
The Cochrane Neonatal Review Group has been funded in part with Federal funds from the Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Department of Health and Human Services, USA, under Contract No. HHSN267200603418C.
G Y Ng
Literature search and identification of trials for inclusion
Evaluation of methodologic quality of included trials
Abstraction of data
Verifying and entering data into RevMan
Writing text of review
A Ohlsson
Writing protocol
Literature search and identification of trials for inclusion
Evaluation of methodologic quality of included trials
Abstraction of data
Verifying and entering data into RevMan
Revision of final review
O Da Silva
Writing Protocol
Translation of article
| Methods | Randomised prospective double-blind placebo controlled trial 1. Blinding of Randomisation - yes |
|---|---|
| Participants | Number of patients entered into the study - 87 in treatment group and 86 in control group. |
| Interventions | Metered dose inhalers were used to administer salbutamol 200 mcg every 4 hrs or the corresponding placebo. Treatment was given on the 10th or 11th postnatal day and was given for 28 days with dose tapering over a period of 8 days. |
| Outcomes | Primary outcomes were mortality and CLD at 28 days on the basis of oxygen dependency and radiographic criteria. Secondary outcomes were duration of ventilatory support, duration of oxygen supplementation, ventilatory index measured every week until extubation, pulmonary complications (pneumothorax, interstitial emphysema), mandatory iv corticosteroid treatment according to the usual practice in each centre, episodes of bronchospasm treated with iv bronchodilators - no significant differences were noted in any of the outcomes. |
| Notes | The incidence of pulmonary complications and episodes of bronchospasm were said to be the same but the data are not presented. Data for the two main groups, salbutamol and placebo, were assembled by Joseph Beyene from subgroup data in the original report for the following outcomes: duration of assisted ventilation, duration of oxygen supplementation and age at weaning from respiratory support. |
| Item | Judgement | Description |
|---|---|---|
| Adequate sequence generation? | Unclear | There is no statement regarding what methods were used to establish the sequence of allocation nor on how the allocation was performed |
| Allocation concealment? | Yes | Blinding of randomisation - yes |
| Blinding? | Unclear | 1. Blinding of randomisation - yes |
| Incomplete outcome data addressed? | Unclear | Complete follow up - originally 178 infants were randomised, but informed consent was either not obtained or withdrawn for five infants leaving 173 infants in the trial. Results are reported on all 173 infants |
| Free of selective reporting? | Yes | The authors state that initially 178 infants were randomised, but informed consent was either not obtained or withdrawn for five infants leaving 173 infants in the trial. All 178 infants are accounted for and results are reported on all 173 infants |
| Free of other bias? | Unclear | Some infants were randomised before consent was obtained |
Abbreviations:
CLD = chronic lung disease
g = grams
GA = gestational age
Bw = birthweight
wk = weeks
| Reason for exclusion | Only pulmonary mechanics were reported |
|---|
| Reason for exclusion | Only pulmonary mechanics were reported |
|---|
| Reason for exclusion | Not a randomised controlled trial. Infants were given both beclomethasone and salbutamol but not separately |
|---|
| Reason for exclusion | Not a randomised controlled trial |
|---|
| Reason for exclusion | Only pulmonary mechanics were reported |
|---|
| Reason for exclusion | Only pulmonary mechanics were reported |
|---|
| Reason for exclusion | A crossover study where each infants received placebo, metaproterenol, atropine, and combined metaproterenol and atropine. Only reported pulmonary mechanics |
|---|
| Reason for exclusion | Only pulmonary mechanics were reported |
|---|
| Reason for exclusion | Only pulmonary mechanics were reported |
|---|
| Reason for exclusion | Only pulmonary mechanics were reported |
|---|
| Reason for exclusion | Each patient was their own control subject and was randomly assigned to a placebo-salbutamol or salbutamol-placebo sequence. Only pulmonary mechanics were reported |
|---|
| Reason for exclusion | Only pulmonary mechanics were reported |
|---|
| Reason for exclusion | Only pulmonary mechanics were reported |
|---|
| Reason for exclusion | Only pulmonary mechanics were reported |
|---|
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| Outcome or Subgroup | Studies | Participants | Statistical Method | Effect Estimate |
|---|
| 1.1 Mortality | 1 | 173 | Risk Ratio (M-H, Fixed, 95% CI) | 1.08 [0.50, 2.31] |
| 1.2 CLD at 28 days | 1 | 173 | Risk Ratio (M-H, Fixed, 95% CI) | 1.03 [0.78, 1.37] |
| 1.3 Duration of assisted ventilation (days) | 1 | 173 | Mean Difference (IV, Fixed, 95% CI) | -1.63 [-5.63, 2.37] |
| 1.4 Duration of oxygen supplementation (days) | 1 | 173 | Mean Difference (IV, Fixed, 95% CI) | -2.82 [-11.91, 6.27] |
| 1.5 Age of weaning from ventilatory support (days) | 1 | 173 | Mean Difference (IV, Fixed, 95% CI) | -2.87 [-11.28, 5.54] |
| 1.6 Need for iv dexamethasone | 1 | 173 | Risk Ratio (M-H, Fixed, 95% CI) | 0.77 [0.49, 1.19] |
| 1.7 Infants with one or more episodes of respiratory infection | 1 | 173 | Risk Ratio (M-H, Fixed, 95% CI) | 0.61 [0.27, 1.39] |
| 1.8 Infants with one or more episodes of sepsis (positive blood cultures) | 1 | 173 | Risk Ratio (M-H, Fixed, 95% CI) | 1.06 [0.54, 2.06] |
This review is published as a Cochrane review in The Cochrane Library, Issue 4, 2009 (see http://www.thecochranelibrary.com for information). Cochrane reviews are regularly updated as new evidence emerges and in response to feedback. The Cochrane Library should be consulted for the most recent version of the review. |
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