Search

Background: Population and study design heterogeneity has confounded previous meta-analyses, leading to uncertainty about effectiveness and safety of elective high-frequency oscillatory ventilation (HFOV) in preterm infants. We assessed effectiveness of elective HFOV versus conventional ventilation in this group., Methods: We did a systematic review and meta-analysis of individual patients' data from 3229 participants in ten randomised controlled trials, with the primary outcomes of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age, death or severe adverse neurological event, or any of these outcomes., Findings: For infants ventilated with HFOV, the relative risk of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age was 0.95 (95% CI 0.88-1.03), of death or severe adverse neurological event 1.00 (0.88-1.13), or any of these outcomes 0.98 (0.91-1.05). No subgroup of infants (eg, gestational age, birthweight for gestation, initial lung disease severity, or exposure to antenatal corticosteroids) benefited more or less from HFOV. Ventilator type or ventilation strategy did not change the overall treatment effect., Interpretation: HFOV seems equally effective to conventional ventilation in preterm infants. Our results do not support selection of preterm infants for HFOV on the basis of gestational age, birthweight for gestation, initial lung disease severity, or exposure to antenatal corticosteroids., Funding: Nestlé Belgium, Belgian Red Cross, and Dräger International.

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 (CLD). A newer form of ventilation called high frequency oscillatory ventilation (HFOV) has been shown to result in less lung injury in experimental studies., Objectives: The objective of this review is 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, mortality and other complications associated with prematurity and assisted ventilation in preterm infants who are mechanically ventilated for respiratory distress syndrome (RDS)., Search Strategy: Searches were made of the Oxford Database of Perinatal Trials, MEDLINE, EMBASE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal hand searching by the Cochrane Collaboration, mainly in the English language. The search was updated in January 2009., 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 various authors. The standard effect measures are relative risk (RR) and risk difference (RD). From 1/RD the number needed to treat (NNT) to produce one outcome were calculated. For all measures of effect, 95% confidence intervals were used. In subgroup analyses the 99% CIs are also given for summary RRs in the text. Meta-analysis was performed using a fixed effects model. Where heterogeneity was over 50%, the random effects RR is also given., Main Results: Seventeen eligible studies of 3,652 infants were included. Meta-analysis comparing HFOV with CV revealed no evidence of effect on mortality at 28 - 30 days of age or at approximately term equivalent age. These results were consistent across studies and in subgroup analyses. The effect of HFOV on CLD in survivors at term equivalent gestational age was inconsistent across studies and the reduction was of borderline significance overall. The effect was similar in trials with a high lung volume strategy for HFOV targeting at very low FiO(2) and trials with a high lung volume strategy with somewhat higher or unspecified target FiO(2). Subgroups of trials showed a significant reduction in CLD with HFOV when no surfactant was used, when piston oscillators were used for HFOV, when lung protective strategies for CV were not used, when randomisation occurred at two to six hours of age, and when inspiratory:expiratory ratio of 1:2 was used for HFOV. In the meta-analysis of all trials, pulmonary air leaks occurred more frequently in the HFOV group.In some studies, short-term neurological morbidity with HFOV was found, but this effect was not statistically significant overall. The subgroup of two trials not using a high volume strategy with HFOV found increased rates of Grade 3 or 4 intraventricular haemorrhage and of periventricular leukomalacia. An adverse effect of HFOV on long-term neurodevelopment was found in one large trial but not in the five other trials that reported this outcome. The rate of retinopathy of prematurity is reduced overall in the HFOV group., Authors' Conclusions: There is no clear evidence that elective HFOV offers important advantages over CV when used as the initial ventilation strategy to treat preterm infants with acute pulmonary dysfunction. There may be a small reduction in the rate of CLD with HFOV use, but the evidence is weakened by the inconsistency of this effect across trials and the overall borderline significance. Future trials on elective HFOV should target those infants who are at most risk of CLD (extremely preterm infants), compare different strategies for generating HFOV and CV, and report important long-term neurodevelopmental outcomes.

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.

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 (CLD). Conventional IPPV is provided at 30-80 breaths per minute, while a newer form of ventilation called high frequency oscillatory ventilation (HFOV) provides 'breaths' at 10 - 15 cycles per second. This has been shown to result in less lung injury in experimental studies., Objectives: The objective of this review is to determine the effect of the elective use of high frequency oscillatory ventilation (HFOV) as compared to conventional ventilation (CV) in preterm infants who are mechanically ventilated for respiratory distress syndrome (RDS), on the incidence of chronic lung disease, mortality and other complications associated with prematurity and assisted ventilation., Search Strategy: Searches were made of the Oxford Database of Perinatal Trials, MEDLINE, EMBASE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal hand searching by the Cochrane Collaboration, mainly in the English language. The search was updated in April 2007., Selection Criteria: Randomised controlled trials comparing HFOV and CV in preterm or low birth weight infants with pulmonary dysfunction, mainly due to RDS, who were given IPPV. Randomisation and commencement of treatment needed to be as soon as possible after the start of IPPV and usually in the first 12 hours of life., Data Collection and Analysis: The methodological quality of each trial was independently reviewed by the various authors. The standard effect measures are relative risk (RR) and risk difference (RD). From 1/RD the number needed to treat (NNT) to produce one outcome were calculated. For all measures of effect, 95% confidence intervals were used. In subgroup analyses the 99% CIs are also given for summary RRs in the text. Meta-analysis was performed using a fixed effects model. Where heterogeneity was over 50%, the random effects RR is also given., Main Results: Fifteen eligible studies of 3,585 infants were included. Meta-analysis comparing HFOV with CV revealed no evidence of effect on mortality at 28 - 30 days of age or at approximately term equivalent age. These results were consistent across studies and in subgroup analyses. The effect of HFOV on CLD in survivors at term equivalent gestational age was inconsistent across studies and the reduction was of borderline significance overall. Subgroups of trials showed a significant reduction in CLD with HFOV when high volume strategy for HFOV was used, when piston oscillators were used for HFOV, when lung protective strategies for CV were not used, when randomisation occurred at two to six hours of age, and when inspiratory:expiratory ratio of 1:2 was used for HFOV. In the meta-analysis of all trials, pulmonary air leaks occurred more frequently in the HFOV group. In some studies, short-term neurological morbidity with HFOV was found, but this effect was not statistically significant overall. The subgroup of two trials not using a high volume strategy with HFOV found increased rates of Grade 3 or 4 intraventricular haemorrhage and of periventricular leukomalacia. An adverse effect of HFOV on long-term neurodevelopment was found in one large trial but not in the five other trials that reported this outcome. The rate of retinopathy of prematurity is reduced overall in the HFOV group., Authors' Conclusions: There is no clear evidence that elective HFOV offers important advantages over CV when used as the initial ventilation strategy to treat preterm infants with acute pulmonary dysfunction. There may be a small reduction in the rate of CLD with HFOV use, but the evidence is weakened by the inconsistency of this effect across trials and the overall borderline significance. Future trials on elective HFOV should target those infants who are at most risk of CLD (extremely preterm infants), compare different strategies for generating HFOV and CV, and report important long-term neurodevelopmental outcomes.

Background: Respiratory failure due to lung immaturity is a major cause of mortality in preterm infants. Although intermittent positive pressure ventilation (IPPV) saves lives, lung distortion during its use is associated with lung injury and chronic lung disease (CLD). Conventional IPPV is provided at 30-80 breaths per minute while a newer form of ventilation called high frequency oscillatory ventilation (HFOV) provides 'breaths' at 10-15 cycles per second. This has been shown to result in less lung injury in experimental studies., Objectives: The objective of this review is to determine whether the elective use of high frequency oscillatory ventilation as compared to conventional ventilation (CV) in preterm infants who are mechanically ventilated for the respiratory distress syndrome decreases the incidence of chronic lung disease, without adverse effects., Search Strategy: Searches were made of the Oxford Database of Perinatal Trials, MEDLINE, EMBASE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal hand searching by the Cochrane Collaboration, mainly in the English language. The search was updated in May 2003., Selection Criteria: Randomized controlled trials comparing HFOV and CV in preterm or low birth weight infants with pulmonary dysfunction, mainly due to RDS, who are to be given IPPV. Randomization and commencement of treatment should have been as soon as possible after the start of IPPV and usually in the first 12 hours of life., Data Collection and Analysis: The methodological quality of each trial was independently reviewed by the various authors. Each author extracted data separately; they were compared and differences were resolved. Treatment effects were expressed using relative risk (RR) and risk difference (RD). From 1/RD the number needed to treat (NNT) to produce one outcome were calculated. Ninety five percent confidence intervals were used for all measures of effect., Main Results: Eleven eligible studies on 3,275 infants were included. Meta-analysis comparing HFOV with CV revealed no evidence of effect on mortality at 28-30 days of age or at approximately term equivalent age. These results were consistent across studies. The effect of HFOV on CLD in survivors at term equivalent GA was inconsistent across studies and not significant overall. Pre-specified subgroup analyses according to use of a high volume strategy, or use of surfactant, did not identify subgroups in which there was evidence of effect on death, or in which the size of effect on CLD was substantially increased, or in which heterogeneity of treatment effect on CLD was removed. Short term neurological morbidity caused by HFOV was found in some studies, but this effect was not statistically significant overall. The subgroup of two trials not using a high volume strategy with HFOV found increased rates of Grade 3 or 4 IVH and of periventricular leukomalacia. An adverse effect of HFOV on longer term neurodevelopment was found in one large trial but not in two other small trials which reported this outcome., Reviewer's Conclusions: There is no clear evidence from this systematic review that elective HFOV, as compared with CV, offers important advantages when used as the initial ventilation strategy to treat preterm babies with acute pulmonary dysfunction. There is no evidence of a reduction in death rate. There may be a small reduction in the rate of CLD with HFOV use but the evidence is weakened by the inconsistency of this effect across trials and is not significant overall. Adverse effects on short term neurological outcomes have been observed in some studies but these effects are not significant overall. Information about effects on long term outcome is not adequate overall. Any future trials on elective HFOV should target those infants who are at most risk of CLD (extremely preterm), compare different strategies for generating HFOV and CV, and report important long term pulmonary and neurodevelopmental outcomes. Economic analysis should also be incorporated.

Background: Respiratory failure due to lung immaturity is a major cause of mortality in preterm infants. Although intermittent positive pressure ventilation (IPPV) saves lives, lung distortion during its use is associated with lung injury and chronic lung disease (CLD). Conventional IPPV is provided at 30-80 breaths per minute while a newer form of ventilation called high frequency oscillatory ventilation (HFOV) provides 'breaths' at 10-15 cycles per second. This has been shown to result in less lung injury in experimental studies., Objectives: The objective of this review is to determine whether the elective use of high frequency oscillatory ventilation as compared to conventional ventilation (CV) in preterm infants who are mechanically ventilated for the respiratory distress syndrome decreases the incidence of chronic lung disease, without adverse effects., Search Strategy: Searches were made of the Oxford Database of Perinatal Trials, MEDLINE, EMBASE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal hand searching by the Cochrane Collaboration, mainly in the English language. The search was updated in October 2002., Selection Criteria: Randomized controlled trials comparing HFOV and CV in preterm or low birth weight infants with pulmonary dysfunction, mainly due to RDS, who are to be given IPPV. Randomization and commencement of treatment should have been as soon as possible after the start of IPPV and usually in the first 12 hours of life., Data Collection and Analysis: The methodological quality of each trial was independently reviewed by the various authors. Each author extracted data separately; they were compared and differences were resolved. Treatment effects were expressed using relative risk (RR) and risk difference (RD). From 1/RD the number needed to treat (NNT) for benefits, and number needed to harm (NNH) for adverse effects, were calculated. 95% confidence intervals were used., Main Results: Meta-analysis of the ten eligible studies comparing HFOV with CV revealed no evidence of effect on mortality at 28-30 days of age or at approximately term equivalent age. These results were consistent across studies. HFOV caused a significant reduction in CLD in survivors at term equivalent GA. However, the effect was not large in absolute terms [NNT 17 (10, 50)], and was inconsistent across studies. HFOV caused a significant reduction in the aggregated outcome, death or CLD at term equivalent GA. Again, however, the effect was not large [(NNT 20 (11, 100)] and was not consistent across studies. Pre-specified subgroup analyses according to use of a high volume strategy, or use of surfactant, did not identify subgroups in which there was evidence of effect on death, or in which the size of effect on CLD was substantially increased, or in which heterogeneity of treatment effect on CLD was removed. Short term neurological morbidity caused by HFOV was found in some studies, but this effect was not statistically significant overall. The subgroup of two trials not using a high volume strategy with HFOV found increased rates of Grade 3 or 4 IVH and of periventricular leukomalacia. An adverse effect of HFOV on longer term neurodevelopment was found in one large trial but not in two other small trials which reported this outcome., Reviewer's Conclusions: There is strong evidence that HFOV had no significant effect on death as this result was consistent across trials. Although HFOV caused a modest reduction in CLD, this evidence is weaker, because of inconsistencies across trials in this effect. In general, subgroup analyses according to use of high volume strategy, or surfactant, did not remove this heterogeneity, which therefore remains largely unexplained. Any future trials on elective HFOV should target those infants who are at most risk of CLD (extremely preterm), compare different strategies for generating HFOV and report important long term pulmonary and neurodevelopmental outcomes. Economic analysis should also be incorporated.

Background: Respiratory failure due to lung immaturity is a major cause of mortality in preterm infants. Although intermittent positive pressure ventilation (IPPV) saves lives, lung distortion during its use is associated with lung injury and chronic lung disease (CLD). Conventional IPPV is provided at 30-80 breaths per minute while a newer form of ventilation called high frequency oscillatory ventilation (HFOV) provides 'breaths' at 10-15 cycles per second. This has been shown to result in less lung injury in experimental studies., Objectives: The objective of this review is to determine whether the elective use of high frequency oscillatory ventilation (HFOV) as compared to conventional ventilation (CV) in preterm infants who are mechanically ventilated for the respiratory distress syndrome decreases the incidence of chronic lung disease (CLD) without adverse effects., Search Strategy: Searches were made of the Oxford Database of Perinatal Trials, MEDLINE, EMBASE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal hand searching by the Cochrane Collaboration, mainly in the English language., Selection Criteria: Randomized controlled trials comparing HFOV and CV in preterm or low birth weight infants with pulmonary dysfunction, mainly due to RDS, who are to be given IPPV. Randomization and commencement of treatment should have been as soon as possible after the start of IPPV and usually in the first 12 hours of life., Data Collection and Analysis: The methodological quality of each trial was independently reviewed by the various authors. Each author extracted data separately; they were compared and differences were resolved. The standard method of the Cochrane Neonatal Review Group was used to synthesize the data using relative risk (RR) and risk difference (RD). From 1/RD the number needed to treat (NNT) for benefits, and number needed to harm (NNH) for adverse effects, were calculated. 95% confidence intervals were used., Main Results: Meta-analysis of the eight eligible studies comparing HFOV with CV revealed that there is no difference in mortality. There are trends toward decreases in CLD in survivors at 28-30 days, 'death or CLD at 28-30 days' and a significant reduction in CLD in survivors at 36-37 weeks postmenstrual age or discharge in the HFOV group (six trials, summary RR 0.73 (0.57, 0.93). There is a significant increase in severe (grades 3 & 4) intraventricular hemorrhage (IVH) and in any pulmonary air leak syndrome [summary RR 1.19 (1.03, 1.38)] in the HFOV group. Only 2 trials have included neurodevelopmental follow up and more survivors in the HFOV group are abnormal [summary RR 1.26 (1.01, 1.58)]. In the subgroup of six trials where a high volume strategy (HVS) was used for HFOV, this is associated with significantly lower rates of CLD in survivors at 28-30 days [three trials, summary RR 0.53 (0.36, 0.76)], of 'death or CLD at 28-30 days' [three trials, summary RR 0.56 (0.40, 0.77) and oxygen use at 36-37 weeks postmenstrual age or discharge [five trials, summary RR 0.72 (0.56, 0.93)]. There were no overall differences in the rates of IVH or PVL. One trial suggests that HFOV may reduce the cost of in-hospital care. In this group of trials HFOV is associated with a strong trend for an increased rate of gross pulmonary ALS (four trials, summary RR 1.54 (0.98, 2.42)] In the subgroup of two trials (HIFI 1989, Rettwitz-Volk 1998) not using a HVS there is no effect of HFOV on the rate of CLD; however, there is an increase in the rate of periventricular leukomalacia (PVL) [summary RR 1.64 (1.02, 2.64)., Reviewer's Conclusions: Benefits of HFOV in terms of CLD appear to be outweighed by concerns about increased rates of pulmonary air leak and severe IVH. Until these issues are resolved HFOV cannot be recommended as the routine method of giving mechanical ventilation to preterm infants with RDS. Future trials should target very preterm infants who are at most risk of CLD and infants should be randomized in gestational age strata. Important long term pulmonary and neurodevelopmental outcomes should be measured and reported. Economic effects should be assessed.

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 extra corporeal membrane oxygenation (ECMO), or result in death. There are some studies indicating that high frequency oscillatory ventilation (HFOV) may be more effective in these infants as compared to CV., Objectives: The objective of this review is to determine if HFOV, as compared to conventional ventilation, reduces mortality and morbidity in term or near term infants with intractable lung disease without an increase in adverse effects., Search Strategy: Standard search methods of the Cochrane Neonatal Review group were used. These included searches of the Oxford Database of Perinatal Trials, 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 relative risk (RR) and risk difference (RD)., Main Results: Only one trial met the inclusion criteria. This rescue trial of 81 infants showed no evidence of a reduction in mortality at 28 days [RR 0.51 (0.05, 5.43)] or in failed therapy on the assigned mode of ventilation requiring cross-over to the other mode [RR 0.73 (0.47, 1.13)]. There were no significant differences in the numbers of patients requiring extracorporeal membrane oxygenation [RR 2.05 (0.85, 4.92)], days on a ventilator, days in oxygen or days in hospital., Reviewer's Conclusions: There are no data from randomized controlled trials supporting the routine 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 rescue HFOV in near term and term infants with pulmonary dysfunction before widespread use of this mode of ventilation in such infants.

Background: This section is under preparation and will be included in the next issue., Objectives: Experimental studies suggest that high frequency oscillatory ventilation (HFOV) reduces pulmonary injury during mechanical ventilation. The main objective of this review is to test the hypothesis that by use of HFOV as compared to conventional ventilation (CV) it may be possible to rescue preterm infants with very severe lung disease and so at high risk of pulmonary air leak (PAL), without adverse effects., Search Strategy: A search was carried out for all randomized controlled trials from MEDLINE using the MeSH and text terms, "high frequency ventilation", "high frequency oscillatory ventilation", " oscillatory ventilation" from the years 1980 to 1997. EMBASE, the Oxford Database of Perinatal Trials and trials identified by the Neonatal Review Group of the Cochrane Collaboration were also reviewed. Information was also sought from experts in the field, cross references from studies and proceedings of recent meetings., Selection Criteria: Randomized controlled trials of HFOV vs CV as rescue therapy in preterm infants with severe pulmonary dysfunction., Data Collection and Analysis: The standard review method of the Neonatal Review Group was used. This includes independent quality assessment and data extraction by the second author. Relative risk (RR), risk difference (RD) and number needed to treat (NNT) were used., Main Results: Only one trial was found and this showed a reduction in any new pulmonary air leak (PAL) [RR 0.73 (0.55,0.96), RD -0.174 (-0.321,-0.027)]. The number of infants that need to be treated (NNT) to prevent one infant having any PAL is six (95% CI 3, 37). There is no difference in the rate of PIE or of gross pulmonary air leak, such as pneumomediastinum or pneumothorax. Mortality and the use of IPPV at 30 days was similar in the HFOV and CV groups. The rate of intraventricular hemorrhage (IVH) of any grade is increased in infants treated with HFOV, RR 1.77 (1.06,2.96), RD 0.156 (0.020, 0. 291). Thus for every six infants (95% CI 3, 50) given rescue HFOV, one IVH of any grade is caused. There is a stronger but non-significant trend towards an increase in the more severe grades 3 or 4 IVH., Reviewer's Conclusions: There is insufficient information on the use of rescue HFOV to make recommendations for practice. The small amount of data that exists suggest that harm might outweigh any benefit. Any future use of HFOV as rescue therapy for preterm infants with severe RDS should be within randomized controlled trials and address important outcomes such as longer term pulmonary and neurological function.

Background: This section is under preparation and will be included in the next issue., Objectives: The objective of this review was to determine whether the elective (commencing soon after initiation of mechanical ventilation) use of high frequency jet ventilation (HFJV), as compared to conventional ventilation (CV) in preterm infants with respiratory distress syndrome (RDS), would decrease the incidence of chronic lung disease (CLD) without adverse effects., Search Strategy: Randomized trials from MEDLINE were identified by means of MeSH and text words 'high frequency ventilation', 'high frequency jet ventilation', 'jet ventilation' from the years 1980 to 1997. The EMBASE database, the Oxford Database of Perinatal Trials, the Neonatal Trials Register of the Neonatal Review Group of the Cochrane Collaboration and the Cochrane library were also accessed. Proceedings of recent SPR/APS meetings were hand searched. Information was obtained from experts in the field, and cross references were checked., Selection Criteria: All randomized controlled trials of elective high frequency jet ventilation versus conventional ventilation in preterm infants born at less than 35 weeks GA or with a birth weight less than 2000 gms with respiratory distress were included in the systematic review. Trials which used HFJV to 'rescue' preterm infants due to severe respiratory distress usually beyond 24 hours, and trials that used HFJV for a mandatory time period and then switched back to CV, were not included in this review., Data Collection and Analysis: The standard methods of the Neonatal Cochrane Review Group were used, including independent trial assessment and data extraction. Data were analysed using relative risk (RR) and risk difference (RD). From 1/RD the number needed to treat (NNT) for benefits and number needed to harm (NNH) for adverse outcomes were calculated., Main Results: Overall analysis of the three trials showed that HFJV is associated with a reduction in CLD at 36 weeks postmenstrual age in survivors [RR 0.58 (0.34, 0. 98), RD -0.138 (-0.268, -0.007), NNT 7 (4, 90)]. The use of home oxygen therapy was evaluated in only one study (Keszler 1997) and a lower rate was found in the HFJV group [RR 0.24 (0.07, 0.79), RD -0. 176 (-0.306, -0.047), NNT 5 (3, 21)]. Overall there was a trend towards an increase in the risk of PVL in the HFJV group, which was not significant. Subgroup analyses shows a significant increase in risk of PVL in the trial by Wiswell 1996 [RR 5.0 (1.19, 21.04), RD 0.250 (0.069, 0.431), NNH 4.0 (2.3,14.5)] where a 'low volume strategy' was the standard protocol for HFJV. In the other trial by Keszler 1997, where the intention was to use a 'high volume strategy', there was no significant difference in the incidence of PVL, RR 0.42 (0.14, 1.30). In the overall analysis, there were no significant differences in the incidence of neonatal mortality, IVH all grades or in grades 3 or 4 IVH. In the subgroup where 'low volume strategy' was used there was a non-significant trend toward an increase in risk of IVH all grades and grades 3 or 4 IVH., Reviewer's Conclusions: The overall analysis shows a benefit in pulmonary outcomes in the group electively ventilated with HFJV. Of concern is the significant increase in acute brain injury in one trial which used lower mean airway pressures when ventilating with HFJV. There are as yet no long term pulmonary or neurodevelopmental outcomes from any of the trials. Until further studies ascertain the most appropriate strategy to routinely ventilate premature infants with HFJV safely, ventilation with HFJV cannot be recommended for preterm infants with RDS.

Background: Respiratory failure due to lung immaturity is a major cause of mortality in preterm infants. Although intermittent positive pressure ventilation (IPPV) saves lives, lung distortion during its use is associated with lung injury and chronic lung disease (CLD). Conventional IPPV is provided at 30-80 breaths per minute while a newer form of ventilation called high frequency oscillatory ventilation (HFOV) provides 'breaths' at 10-15 seconds. This has been shown to result in less lung injury in experimental studies., Objectives: The objective of this review is to determine whether the elective use of high frequency oscillatory ventilation (HFOV) as compared to conventional ventilation in preterm infants who are mechanically ventilated for the respiratory distress syndrome decreases the incidence of chronic lung disease (CLD) without adverse effects., Search Strategy: Searches were made of the Oxford Database of Perinatal Trials, MEDLINE, EMBASE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal handsearching by the Cochrane Collaboration, mainly in the English language. Expert informant's search in the Japanese language was made by Prof. Y. Ogawa., Selection Criteria: Randomized controlled trials comparing HFOV and CV in preterm or low birth weight infants with pulmonary dysfunction, mainly due to RDS, who are to be given IPPV. Randomization and commencement of treatment should have been as soon as possible after the start of IPPV and usually in the first 12 hours of life., Data Collection and Analysis: The methodological quality of each trial was independently reviewed by the various authors. Each author extracted data separately; they were compared and differences were resolved. The standard method of the Cochrane Neonatal Review Group was used to synthesize the data using relative risk (RR) and risk difference (RD). From 1/RD the number needed to treat (NNT) for benefits, and number needed to harm (NNH) for adverse effects, were calculated., Main Results: Meta-analysis of the six eligible studies comparing HFOV with CV revealed that there is no difference in mortality. There are trends toward decreases in CLD in survivors at 28-30 days, 'death or CLD at 28-30 days' and CLD in survivors at 36-37 weeks postmenstrual age or discharge in the HFOV group. However, there are trends towards increases in severe (grades 3 & 4) intraventricular hemorrhage (IVH) and in periventricular leukomalacia (PVL) in the HFOV group. HFOV results in a small increase in any air leak syndrome (ALS), [summary RR 1.20 (1.03, 1.39)]. Only 2 trials have included neurodevelopmental follow up and more survivors in the HFOV group are abnormal [summary RR 1.26 (1.01, 1.58)]. In the subgroup of four trials where a high volume strategy (HVS) was used, HFOV results in more favourable pulmonary outcomes. There are significantly lower rates of CLD in survivors at 28-30 days [summary RR 0.53 (0.36, 0.76)] and of 'death or CLD at 28-30 days' [summary RR 0.56 (0.40, 0.77) with a non-significant trend towards a reduction in oxygen use at 36-37 weeks postmenstrual age or discharge [summary RR 0.74 (0.55, 1.01)]. There were no differences in the rates of IVH or PVL. Of the four trials in the subgroup using surfactant routinely, three also used the HVS. The trends in results were similar with surfactant to those for the HVS subgroup analysis. One trial suggests that HFOV may reduce the cost of in-hospital care. In the subgroup of two trials (HIFI 1989, Rettwitz-Volk 1998) not using a HVS there is no effect of HFOV on the rate of CLD; however, there is an increase in the rate of PVL [summary RR 1.64 (1.02, 2.64)., Reviewer's Conclusions: The overall meta-analyses is dominated by the large HIFI study which did not use the HVS recommended on the basis of animal studies, and in which surfactant was not available. Studies which used HVS have shown some benefits in short term measures of CLD without an in

Objectives: To systematically review the evidence to determine whether the routine use of high-frequency oscillatory ventilation (HFOV) as compared with conventional ventilation (CV) is beneficial or harmful in preterm infants requiring mechanical ventilation for pulmonary failure principally due to respiratory distress syndrome., Methods: All randomized controlled trials of elective HFOV versus CV in preterm infants <36 weeks' gestation with respiratory failure mainly attributable to respiratory distress syndrome were identified from the literature through a search of MEDLINE, EMBASE, Oxford database of Perinatal trials, and previous reviews including cross-references and abstracts. Meta-analyses using event rate ratios (ERR), event rate difference, and if significant, number needed-to-treat were calculated (95% confidence limits were used for all analyses). Two prespecified subgroup analyses were performed., Results: Four published trials were included. Meta-analyses revealed the following ERR (95% confidence intervals) for HFOV versus CV: mortality at 28 to 30 days, 1.02 (0.76, 1.39); chronic lung disease (CLD) at 28 days, 0.86 (0.73, 1.01); mortality or CLD, 0.9 (0.80, 1. 01); air-leak syndromes, 1.13 (0.97, 1.33); mechanical ventilation at 28 days, 1.06 (0.84, 1.33); supplemental oxygen at discharge, 0. 59 (0.37, 0.92); intraventricular hemorrhage (IVH) all grades, 1.11 (0.95, 1.29); IVH (grades 3 or 4), 1.32 (1.01, 1.72); and periventricular leukomalacia, 1.39 (0.91, 2.13). In the subgroup of trials in which a high volume strategy (HVS) was used the ERR for CLD was 0.53 (0.36, 0.78); mortality or CLD, 0.56 (0.40, 0.77); supplemental oxygen at discharge, 0.57 (0.36, 0.92); IVH (all grades), 0.90 (0.61, 1.33); and IVH (grades 3 or 4), 0.84 (0.39, 1. 84). Results were similar to these for the trials using surfactant. One recent trial suggests that HFOV may reduce the cost of in-hospital care., Conclusions: The overall meta-analysis is dominated by the HIFI study, which was criticized for its methodology and surfactant was not used. Subsequent studies, most of which used HVS and/or surfactant, have shown benefits in measures of CLD without an increase in rates of IVH. Caution is warranted in interpreting these results because: 1) the treatment is not blinded and this could affect some outcomes; 2) except for one small trial postneonatal survival, lung function, and neurodevelopment have not been reported from HVS trials; and 3) the benefits and disadvantages have not been reported in infants born at different gestational ages or different birth weights. Importantly, results from groups experienced in the use of HFOV may not be readily generalizable.