Synchronized mechanical ventilation for respiratory support in newborn infants

Greenough A, Dimitriou G, Prendergast M, Milner AD

Background - Methods - Results - Characteristics of Included Studies - References - Data Tables and Graphs

Dates

Date edited: 13/11/2007
Date of last substantive update: 31/08/2007
Date of last minor update: / /
Date next stage expected 15/09/2009
Protocol first published: Issue 1, 1998
Review first published: Issue 1, 1998

Contact reviewer

Prof Anne Greenough
Professor of Clinical Respiratory Physiology
Dept of Child Health
King's College School of Medicine and Dentistry
Bessemer Road
London
UK
SE5 9PJ
Telephone 1: +44 20 3299 3037
Facsimile: +44 20 3299 8284
E-mail: anne.greenough@kcl.ac.uk

Contribution of reviewers

Professor Anne Greenough and Professor Anthony Milner have coauthored all issues of this review.

Professor Gabriel Dimitriou coauthored the inital review of this subject (1998) and the review updates (2001 and 2004).

Dr. Michael Prendergast coauthored this 2007 review update.

Internal sources of support

None

External sources of support

None

What's new

This review updates the existing review of "Synchronized mechanical ventilation for respiratory support in newborn infants" published in The Cochrane Library, Issue 3, 2004 (Greenough 2004).

Two additional studies were identified as eligible for inclusion and additional studies were designated as "excluded studies". Two further triggered modes are included: pressure support and pressure regulated volume control ventilation have been included

Dates

Date review re-formatted: / /
Date new studies sought but none found: / /
Date new studies found but not yet included/excluded: / /
Date new studies found and included/excluded: 31/07/2007
Date reviewers' conclusions section amended: 31/08/2007
Date comment/criticism added: / /
Date response to comment/criticisms added: / /

Text of review

Synopsis

High frequency positive pressure ventilation and triggered ventilation may reduce air leaks and duration of ventilation respectively in newborns needing mechanical assistance to breathe properly.

The majority of newborn babies in need of mechanical assistance to support their breathing, also breathe on their own to some degree. If the baby's attempts to breathe are synchronized with the mechanical breaths from the ventilator, less pressure may be needed. This could reduce the chance of air leak or variations in blood flow to the brain. The review of trials found, when compared to conventional mechanical ventilation (CMV), high frequency positive pressure ventilation (HFPPV) reduced the risk of air leak and triggered ventilation was associated with a shorter duration of ventilation. Newer forms of triggered ventilation have only been evaluated in small randomised trials and have not been demonstrated to have advantages in important clinical outcomes.

Abstract

Background

During synchronized mechanical ventilation, positive airway pressure and spontaneous inspiration coincide. If synchronous ventilation is provoked, adequate gas exchange should be achieved at lower peak airway pressures, potentially reducing baro/volutrauma, air leak and bronchopulmonary dysplasia. Synchronous ventilation can potentially be achieved by manipulation of rate and inspiratory time during conventional ventilation and employment of patient triggered ventilation.

Objectives

To compare the efficacy of:
(i) synchronized mechanical ventilation, delivered as high frequency positive pressure ventilation (HFPPV) or patient triggered ventilation - assist control ventilation (ACV) or synchronous intermittent mandatory ventilation (SIMV)) with conventional ventilation (CMV)
(ii) different types of triggered ventilation (ACV, SIMV, pressure regulated volume control ventilation (PRVCV) and SIMV plus pressure support (PS)

Search strategy

Searches from 1985-2007 of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2007),
Oxford Database of Perinatal Trials, MEDLINE, previous reviews, abstracts and symposia proceedings; hand searches of journals in the English language and contact with expert informants.

Selection criteria

Randomised or quasi-randomised clinical trials comparing synchronized ventilation delivered as high frequency positive pressure ventilation (HFPPV) or triggered ventilation (ACV/SIMV) to conventional mechanical ventilation (CMV) in neonates. Randomised trials comparing different triggered ventilation modes (ACV, SIMV, SIMV plus PS and PRVCV) in neonates.

Data collection & analysis

Data regarding clinical outcomes including mortality, air leaks (pneumothorax or pulmonary interstitial emphysema (PIE)), severe intraventricular haemorrhage (grades 3 and 4), bronchopulmonary dysplasia (BPD) (oxygen dependency beyond 28 days), moderate/severe BPD (oxygen/respiratory support dependency beyond 36 weeks postmenstrual age (PMA) and duration of weaning/ventilation.

Four comparisons were made: (i) HFPPV vs. CMV; (ii)ACV/SIMV vs. CMV; (iii) ACV vs. SIMV or PRVCV vs. SIMV (iv) SIMV plus PS vs. SIMV. Data analysis was conducted using relative risk for categorical outcomes, weighted mean difference for outcomes measured on a continuous scale.

Main results

Fourteen studies were eligible for inclusion. The meta-analysis demonstrates that HFPPV compared to CMV was associated with a reduction in the risk of air leak (typical relative risk for pneumothorax was 0.69, 95% CI 0.51, 0.93). ACV/SIMV compared to CMV was associated with a shorter duration of ventilation (weighted mean difference -34.8 hours, 95% CI -62.1, -7.4). ACV compared to SIMV was associated with a trend to a shorter duration of weaning (weighted mean difference -42.4 hours, 95% CI -94.4, 9.6). Neither HFPPV nor triggered ventilation was associated with a significant reduction in the incidence of BPD. There was a non-significant trend towards a lower mortality rate using HFPPV vs. CMV and a non-significant trend towards a higher mortality rate using triggered ventilation vs. CMV. No disadvantage of HFPPV or triggered ventilation was noted regarding other outcomes. Since the last review, two new patient triggered modes have been included: pressure regulated volume control ventilation (PRVCV) and SIMV plus pressure support. Each of these methods of ventilation has only been tested in single randomised trials with no significant advantages in important outcomes.

Reviewers' conclusions

Compared to conventional ventilation, benefit is demonstrated for both HFPPV and triggered ventilation with regard to a reduction in air leak and a shorter duration of ventilation, respectively. In none of the trials was complex respiratory monitoring undertaken and thus it is not possible to conclude that the mechanism of producing those benefits is by provocation of synchronized ventilation. Further trials are needed to determine whether synchronized ventilation is associated with other benefits, but optimisation of trigger and ventilator design with respect to respiratory diagnosis is encouraged before embarking on further trials. It is essential newer forms of triggered ventilation are tested in adequately powered randomised trials with long-term outcomes before they are incorporated into routine clinical practice.

Background

The majority of neonates breathe during mechanical ventilation. Those that actively exhale against positive pressure inflation develop pneumothoraces, whereas, if positive pressure inflation and spontaneous inspiration coincide (synchrony) oxygenation and carbon dioxide elimination improve. If synchrony occurs, it should be possible to achieve adequate gas exchange at lower inflating pressures, reducing barotrauma, a known risk factor for bronchopulmonary dysplasia. Active expiration is more common if infants have non-compliant lungs and are ventilated with long inspiratory times and/or relatively slow ventilator rates (30-40 bpm). Increasing ventilator rate and reducing inspiratory time, mimicking more closely the preterm infant's respiratory pattern, has been shown in a proportion of infants to stop them actively expiring. Such a ventilation protocol, called high frequency positive pressure ventilation (HFPPV), is also more likely to be associated with synchronous ventilation. An alternative method of promoting synchronous ventilation is to allow the patient to trigger the ventilator; that is their inspiratory efforts trigger positive pressure inflations. Theoretically, by causing synchronous ventilations, either HFPPV or patient triggered modes of ventilation should improve tidal volume exchange and blood gases, reduce blood pressure and cerebral blood flow velocity fluctuations and thus in the longer term reduce air leaks and associated intraventricular haemorrhage and BPD. Indeed, 'triggered ventilation' compared to conventional mechanical ventilation (CMV) has been shown to improve tidal volume (Jarreau 1996) and oxygenation (Cleary 1995) and reduce blood pressure fluctuations (Hummler 1996). The aim of this review was to determine whether HFPPV and/or triggered ventilation are associated with the expected longer term benefits and if these advantageous outcomes are explained by synchronized ventilation. This review updates the existing review of synchronized ventilation which was published in Cochrane Library Issue 3, 2004 (Greenough 2004).

Objectives

To compare the efficacy of:
(i) synchronized mechanical ventilation, delivered as high frequency positive pressure ventilation (HFPPV) or patient triggered ventilation (assist control ventilation, ACV) and synchronous intermittent mandatory ventilation (SIMV)), with conventional ventilation
(ii) different types of triggered ventilation (ACV, SIMV, pressure regulated volume control ventilation (PRVCV)) and SIMV with pressure support (PS))

Criteria for considering studies for this review

Types of studies

Randomised or quasi-randomised clinical trials comparing the use of synchronized ventilation (HFPPV or patient triggered ventilation) to conventional ventilation and randomised trials of different modes of triggered ventilation in neonates were considered for this review.

Types of participants

Neonates (less than four weeks of age) requiring assisted ventilation

Types of interventions

Two forms of ventilation likely to induce synchrony were considered:
High frequency positive pressure ventilation (HFPPV, ventilator rates ≥ 60 bpm) and triggered ventilation.
Triggered ventilation was divided into:
- assist control ventilation (ACV), otherwise known as synchronous intermittent positive pressure ventilation (SIPPV), the infant being able to trigger a positive pressure inflation with each breath,
- synchronized intermittent mandatory ventilation (SIMV), the infant being able to trigger only a pre-set number of positive pressure inflations,
- pressure regulated volume control ventilation (PRVCV), a synchronized pressure-limited assist control mode that sequentially varies the delivered pressure to approximate a target inspiratory tidal volume
- SIMV with pressure support (PS), PS assists every spontaneous breath by providing an inspiratory pressure boost

For the purposes of this review, conventional ventilation (CMV) is defined as pressure pre-set, time limited ventilation delivered at rates of < 60 bpm.
Infants were randomly allocated to receive one or other forms of ventilation (except in the study of Heicher when alternate allocation was used):
HFPPV vs. CMV
ACV or SIMV vs. CMV
ACV vs. SIMV or PRVCV vs. SIMV
SIMV plus PS vs. SIMV

Types of outcome measures

Data regarding clinical outcomes included mortality, air leaks (pneumothorax or pulmonary interstitial emphysema (PIE)), severe intraventricular haemorrhage (grades 3 and 4), bronchopulmonary dysplasia (BPD) (oxygen dependency beyond 28 days), moderate/severe BPD (oxygen dependency and/or respiratory support dependency at 36 weeks PMA) and duration of weaning/ventilation.

Search strategy for identification of studies

See: Cochrane Neonatal Group methods used in reviews.
Searches were made of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2007), Oxford Database of Perinatal Trials; MEDLINE from 1966-2007 and EMBASE 1996-2007 (MeSH terms: mechanical ventilation; triggered ventilation; artificial respiration; newborn infant); previous reviews, abstracts, symposia proceedings; hand searches of journals in the English language and contact with expert informants.

Methods of the review

Two of the review authors (MP, AG) identified trials that might be included. Each trial was then assessed independently by each review author who completed data collection forms that the review authors had both previously agreed upon. The results were then compared and if there was disagreement a third review author (ADM) assessed the results independently. For each included trial, information was collected regarding the method of randomizations, blinding, stratification, number of centres participating in the study, trial inclusion and exclusion criteria and sample size. Demographic data of the trial participants was also collected (e.g. gestational age, birthweight, postnatal age, primary diagnosis). Information on clinical outcomes was analysed including death, air leaks, intraventricular haemorrhage, chronic lung disease, duration of ventilation or weaning, ventilation mode failure and extubation failure. The denominator for each outcome was the number randomised. In the meta-analyses involving comparison with CMV, either HFPPV or ACV/SIMV was designated the experimental therapy. In the meta-analysis of ACV or PRVCV vs. SIMV, ACV or PRVCV was designated the experimental therapy. In the meta-analysis of SIMV with PS vs. SIMV, SIMV with PS was designated the experimental therapy.

Description of studies

The review includes the following studies:
1. HFPPV vs. CMV
Heicher 1981, OCTAVE 1991, Pohlandt 1992.

2. ACV /SIMV vs. CMV
Chan 1993 (ACV vs. CMV), Donn 1994 (SIMV vs. CMV), Bernstein 1996 (SIMV vs. CMV), Chen 1997 (SIMV vs. CMV), Baumer 2000 (ACV vs. CMV), Beresford 2000 (ACV vs CMV).

3. ACV vs. SIMV
Chan 1994; Dimitriou 1995

4. PRVCV vs. SIMV
Reyes 2006

5. SIMV plus PS vs. SIMV
D'Angio 2005

The trials of Pohlandt 1992; Chan 1993; Chan 1994; Dimitriou 1995; Baumer 2000 and Beresford 2000 included only preterm infants. The study of Donn 1994 included preterm infants with BW 1100-1500 g. The study of Reyes 2006 included preterm infants with birthweight 500 -1000 g. The study of D'Angio 2005 included preterm infants with birthweight 500 - 1249 g. The trials of Bernstein 1996; Heicher 1981 and OCTAVE 1991 studied mainly premature neonates. The study of Chen 1997 included term and preterm infants but analysed the groups separately; only the results from the 62 infants with RDS are included in the meta-analysis. Information regarding use of antenatal steroids was given only in the trials of Baumer 2000; Beresford 2000; Reyes 2006 and D'Angio 2005. Data regarding surfactant usage were available in the trials of Donn 1994; Chan 1994; Dimitriou 1995; Bernstein 1996; Chen 1997; Baumer 2000; Beresford 2000; D'Angio 2005 and Reyes 2006. In the Baumer 2000 study, 423 of the infants randomised to PTV and 422 infants randomised to CMV had cranial ultrasound examinations. The age at entry varied between studies; the trials of Chan 1993; Chan 1994; Dimitriou 1995; Reyes 2006 were weaning studies. Data for the duration of ventilation or weaning were obtained by personal communication with the investigators for Baumer 2000; Beresford 2000; Chan 1993; Chan 1994 and Dimitriou 1995 studies.

Sixty-one additional studies were detected, but were found to be not eligible for inclusion in this review (see Table, Characteristics of Excluded Studies).

Methodological quality of included studies

All the studies, but one, were randomised; Heicher 1981 used alternate allocation. The method of randomization is reported in all but one trial (Chen 1997). Certain outcomes were only available in some of the trials and therefore only presented for the subgroups in which they were reported for at least two trials, except for the trials assessing PRVCV and SIMV plus PS.

HFPPV vs. CMV
In the studies of Heicher 1981 and OCTAVE 1991 analysis was by intention to treat, but in Pohlandt 1992 infants not ventilated strictly according to the technique to which they were randomised were excluded from the analysis.

SIMV/ACV vs. CMV
Analysis was according to intention to treat in Chan 1993 and Baumer 2000; in the study of Bernstein 1996 6%of infants erroneously randomised because of problems including seizures, non-viability and birthweight <500 g were excluded from the analysis.

ACV vs. SIMV
Dimitriou 1995 is presented as two studies (Dimitriou 1995a; Dimitriou 1995b), as two separate consecutive randomised trials were performed in which PTV was compared to two different methods of delivering SIMV.
In Chan 1994 and Dimitriou 1995 weaning failure was defined as no reduction in ventilator settings over a 24 or 48 hour period respectively; extubation failure was requirement for re-intubation using standardized criteria within a 48 hour period.

PRVCV vs. SIMV
In the study of D'Angio 2005 analysis was by intention to treat, one infant did not receive the allocated intervention.

SIMV plus PS vs. SIMV
In the study of Reyes 2006 analysis was by intention to treat, five infants who were randomised met exclusion criteria, their results were not included in the analysis.

Results

HFPPV VS. CMV (COMPARISON 01):
Death (Outcome 01.01):
Three trials (Heicher 1981; OCTAVE 1991; Pohlandt 1992) reported this outcome. None demonstrated a significant effect. The meta-analysis indicates a trend towards reduction in death rate using HFPPV but this does not reach statistical significance (typical relative risk 0.80, 95% CI 0.62, 1.03).

Air leaks (Outcome 01.02):
Three trials (Heicher 1981; OCTAVE 1991; Pohlandt 1992) reported pneumothorax as an outcome; one trial (Heicher 1981) reported a significant effect, with a lower rate of pneumothorax in the HFPPV group. The meta-analysis supports a significant reduction in the risk of pneumothorax (typical relative risk for pneumothorax was 0.69, 95% CI 0.51, 0.93). The number needed to treat with HFPPV to prevent one pneumothorax is 11. In addition, Pohlandt 1992 et al reported a significant reduction in PIE in the HFPPV group.

BPD (oxygen dependency at 28 days) (Outcome 01.03):
Three trials (Heicher 1981; OCTAVE 1991; Pohlandt 1992) reported this outcome. None demonstrated a significant effect. The meta-analysis found no evidence of effect.

Other outcomes:
The incidence of PDA post randomizations was given in two trials (Heicher 1981; Pohlandt 1992); in neither did it differ significantly.

ACV/SIMV VS. CMV (COMPARISON 02):
Death (Outcome 02.01):
Five trials (Baumer 2000; Beresford 2000; Bernstein 1996; Chen 1997; Donn 1994) reported this outcome. None demonstrated a significant effect. The meta-analysis indicates a trend towards an increase in death rate using ACV/SIMV but this does not reach statistical significance (typical relative risk 1.19, 95% CI 0.95, 1.49).

Air leaks (Outcome 02.02):
Six trials (Baumer 2000; Beresford 2000; Bernstein 1996; Chan 1993; Chen 1997; Donn 1994) reported this outcome. None demonstrated a significant effect. The meta-analysis found no evidence of effect.

Duration of ventilation (hours) (Outcome 02.03):
Four trials (Baumer 2000; Beresford 2000; Chen 1997; Donn 1994) reported this outcome. Bernstein 1996 also reported the duration of ventilation, but as the median and 95% confidence intervals (SIMV 103 hours, 94 - 118 vs. CMV 120 hours, 101-142) and his results are therefore not presented in the relevant Outcome (02.03). A significantly shorter duration of ventilation was noted in Chen's study (Chen 1997) and Donn's study (Donn 1994). The meta-analysis of the four studies supported a significant reduction in ventilation duration (WMD -34.8 hours, 95% CI -62.1, -7.4). Chan 1993 reported the duration of weaning: ACV mean 39 hours, SD 45 vs. CMV mean 65 hours, SD 75 (the results are not presented in Outcome 02.03).

Extubation failure (Outcome 02.04):
Four trials (Baumer 2000; Chan 1993; Chen 1997; Donn 1994) reported this outcome. One trial (Chen 1997) reported a significant effect in favour of ACV/SIMV. The meta-analysis of the results of the four trials, however, did not demonstrate a significant effect, the typical relative risk being 0.93 (95% CI 0.68, 1.28).

Severe IVH (Outcome 02.05):
Five trials (Baumer 2000; Beresford 2000; Bernstein 1996; Chen 1997; Donn 1994) reported this outcome. None demonstrated a significant effect. The meta-analysis found no evidence of effect.

BPD (oxygen dependency at 28 days) (Outcome 02.06):
Four trials (Baumer 2000; Bernstein 1996; Chen 1997; Donn 1994) reported this outcome. None demonstrated a significant effect. The meta-analysis found no evidence of effect.

Moderate/severe BPD (Oxygen dependency at 36 weeks PMA) (Outcome 02.07):
Two trials (Baumer 2000; Beresford 2000) reported this outcome. Neither demonstrated a significant effect. The meta-analysis found no evidence of effect.

Other outcomes:
In two trials (Chen 1997; Beresford 2000) the incidence of PDA is given post randomizations. In one trial only (Beresford 2000) the incidence of PDA requiring indomethacin and/or ligation was higher in the conventional group for both survivors (p < 0.05) and the whole population of infants (p < 0.05).

ACV VS. SIMV and PRVCV VS. SIMV (COMPARISON 03):
Duration of weaning (hours) (Outcome 03.01):
Three trials of ACV vs. SIMV (Chan 1994; Dimitriou 1995a; Dimitriou 1995b) reported this outcome. None demonstrated a significant effect. In all three, however the duration of weaning tended to be shorter in infants supported by ACV rather than SIMV. The meta-analysis supported a trend in this direction which, however, did not reach statistical significance. The PRVCV vs. SIMV trial (D'Angio 2005) reported the median duration of mechanical ventilation (24 days vs. 33 days respectively), the difference was not statistically significant.

Weaning failure (Outcome 03.02):
Three trials of ACV vs. SIMV (Chan 1994; Dimitriou 1995a; Dimitriou 1995b) reported this outcome. None demonstrated a significant effect. The meta-analysis found no evidence of effect.

Extubation failure (Outcome 03.03):
Three trials of ACV vs. SIMV (Chan 1994; Dimitriou 1995a; Dimitriou 1995b) reported this outcome. None demonstrated a significant effect. The meta-analysis found no evidence of effect. The PRVCV vs. SIMV trial (D'Angio 2005) reported the proportion of infants alive and extubated at 14 days (41% vs. 37% respectively), this was not statistically significant

Air leaks (Outcome 03.04):
Three trials of ACV vs. SIMV (Chan 1994; Dimitriou 1995a; Dimitriou 1995b) reported this outcome. None demonstrated a significant effect. The meta-analysis found no evidence of effect. In the PRVCV vs. SIMV trial (D'Angio 2005) there were no significant effects with regard to either pneumothorax or PIE.

Death (Outcome 03.05):
One trial of PRVCV vs. SIMV examined this outcome, there was no significant difference

Severe IVH (Outcome 03.06):
There was one trial (PRVCV vs. SIMV). There was no significant effect.

Moderate/severe BPD (Outcome 03.07):
One trial PRVCV vs. SIMS examined this outcome, there was no significant effect.

SIMV plus PS VS. SIMV (Reyes 2006) (COMPARISON 04):
Death (Outcome 04.01):
There was no significant effect with regard to death at 28 days or death prior to discharge.

Air leaks (Outcome 04.02):
The occurrence of PIE and pneumothorax are reported separately, there were no significant differences in either outcome.

BPD, oxygen dependency at 28 days (Outcome 04.03):
There was no significant effect.

Moderate/severe BPD, oxygen dependency at 36 weeks PMA (Outcome 04.03):
There was no overall significant effect.

Severe IVH (Grade III and IV) (Outcome 04.04):
There was no significant effect

Other outcomes:
There was no significant effect re PDA. Days on mechanical ventilation and supplementary oxygen did not differ by ventilation status, but in the subgroup of infants with birthweight 700 - 1000 g, the days of supplementary oxygen were lower in the SIMV plus PS group (p = 0.034).

Discussion

Physiological studies have demonstrated in prematurely born neonates that both high frequency positive pressure ventilation and triggered ventilation are more likely to provoke a synchronous respiratory interaction that is the infant's inspiratory efforts coincide with positive pressure inflations. When compared to CMV, those ventilation modes were shown to be associated with improved ventilation. Unfortunately, in none of the subsequent randomised trials is it reported whether synchronous ventilation was achieved and few outcome measures are consistently reported in all relevant trials. Nevertheless, the meta-analyses demonstrate a significant decrease in air leak and a shorter duration of ventilation with HFPPV and triggered ventilation respectively. However, no significant effect on the incidence of BPD or death has been shown using either HFPPV or ACV/SIMV. No deleterious effects of those two ventilatory modes were highlighted. Some positive effects have been demonstrated of the newer triggered modes PRVCV and SIMV plus PS, but both modes have each only been examined in one randomised trial, further trials are required which incorporate long-term outcomes.

Reviewers' conclusions

Implications for practice

Comparative trials demonstrate that, compared to CMV, HFPPV is associated with a reduced risk of air leak and triggered ventilation with a shorter duration of ventilation. Thus, on clinical grounds, those ventilatory modes would seem preferable for preterm neonates to 'conventional' ventilation delivered at rates of less than 60 bpm. Comparative trials demonstrated that in preterm infants in the recovery stage of respiratory distress, ACV compared to SIMV is associated with a shorter duration of ventilation; thus, ACV would seem the more desirable mode of weaning for preterm neonates. There are insufficient randomised trials of PRVCV or pressure support vs. SIMV to make any conclusions to their efficacy with regard to long term efficacy.

Implications for research

Further trials are encouraged to assess whether ventilation modes likely to provoke synchronous ventilation will have other benefits and whether the mechanism of such effects is by provoking synchrony. Optimisation of trigger and ventilator performance with respect to respiratory diagnosis is essential. Randomised trials of the newer triggered modes with long-term outcomes are essential to determining their efficacy.

Acknowledgements

Dr Dimitriou was supported by the Children Nationwide Medical Research Fund.

Potential conflict of interest

Professor Anne Greenough and Professor Anthony Milner have held grants and/or been an invited speaker for several of the companies who manufacture/sell ventilators (SLE, Draeger, Bearcub, EME, Sechrist).

Characteristics of included studies

Study	Methods	Participants	Interventions	Outcomes	Notes	Allocation concealment
Baumer 2000	Randomized. Multicenter trial. Randomization method: randomly allocation by telephone. Stratified by centre. Within each centre, randomisation in blocks to ensure a similar distribution of babies in each arm of the study. Blinding of randomization: yes Blinding of intervention:no Complete follow up:no Blinding of outcome measurement:no	Gestational age <32 weeks. Assisted ventilation within 72 hours of birth. Not ventilated for more than 6 hours at randomisation. RDS. Exclusion: major congenital malformation or inhalational pneumonitis Sample size 924 PTV: 465 CMV: 459	PTV vs CMV	Primary: Hospital mortality or need for oxygen treatment at 36 weeks of gestation; pneumothorax; cerebral ultrasound abnormality nearest to 36 weeks of gestation; duration of ventilation in survivors.	Ventilator types: PTV: SLE 2000 (airway pressure trigger), Draeger babylog 8000 (airway flow trigger). CMV: SLE 2000, Draeger Babylog, Sechrist. 423 of those randomized to PTV and 422 infants randomized to CMV had cranial ultrasound examination.	A
Beresford 2000	Randomized. Multicenter trial Randomization method: computer generated sequence hidden in sequentially numbered, opaque envelopes. Stratified by BW. Blinding of randomization:yes Blinding of intervention:no Complete follow up:no Blinding of outcome measurement:no	Birthweight 1000-2000 gm. Assisted ventilation within 24 hours of birth. RDS. Exclusion: major malformations, congenital heart disease, MAS. Sample size 386 PTV:193 CMV:193	PTV vs CMV	Primary: Incidence of CLD Secondary: Death. Pneumothorax IVH Cystic PVL Shunt insertion.	Ventilator types: SLE 2000 (airway pressure trigger).	A
Bernstein 1996	Randomized. Multicenter trial Intention-to-treat basis Randomization method: sealed, opaque envelopes .Stratified by BW. Blinding of randomization:yes Blinding of intervention:no Complete follow up:no Blinding of outcome measurement:no	Birthweight >500gm. Assisted ventilation. Age <36hrs. RDS, congenital pneumonia, MAS. CxR with abnormal lung parenchyma, FiO2>0.4(all BW) and MAP>7 cmH2O (for infants with BW >1250 gm). Duration of CMV prior randomization <12 hrs, spontaneous breathing rate >20 bpm and indwelling arterial line. Exclusion: infants with air leak, seizures, IVH grade III or IV, neuromuscular disease affecting respiration, major malformations including chromosomal abnormalities, CDH, CHD (except PDA), lung hypoplasia, septic shock or severe skin disease. Sample size 350* SIMV:178 (167 analyzed) CMV:172 (160 analyzed) *23 excluded post randomization	SIMV vs CMV	Primary: Acute effect on oxygenation Sedative/analgesic drug requirements Duration of ventilation. Air leaks Secondary: Severe IVH Death. Need for pharmacological paralysis, ECMO or long term supplemental oxygen The age at which infants undergoing long-term ventilation (>14 days) regained their BW	Ventilator types: Infant Star with Star Sync module (abdominal movement monitor)	A
Chan 1993	Randomized. Single centre trial. Randomization method: sealed, opaque envelopes. Blinding of randomization:yes Blinding of intervention:no Complete follow up:no Blinding of outcome measurement:no	Gestational age <36 weeks. Age: 1-21 days. RDS. In the recovery stage of the respiratory disease (at 40bpm). Sample size 40 PTV:20 CMV:20	PTV vs CMV	Primary: Hours of ventilation from entering the study until first extubation (weaning). Secondary: Number of infants failed weaning. Number of infants failed extubation	Ventilator types: SLE 2000 (airway pressure trigger), Sechrist IV-100B	A
Chan 1994	Randomized. Single centre trial Randomization method: sealed, opaque envelopes. Blinding of randomization:yes Blinding of intervention:no Complete follow up:no Blinding of outcome measurement:no	GA<35 weeks Age < 1-23 days Weaning -loaded with aminophylline Exclusion: apnoea, failure to trigger Sample size 40 SIMV:20 CMV:20	PTV vs SIMV	Primary: Duration of weaning Secondary: Number of infants who failed weaning Number of infants who failed extubation	Ventilator types: SLE 2000 (airway pressure trigger) CMV	A
Chen 1997	Randomized. Single centre trial Blinding of randomization: not stated Blinding of intervention:no Complete follow up:no Blinding of outcome measurement:no	BW<1.75 kg,GA <34 w and RDS. Assisted ventilation. Exclusion: congenital malformation, inherited metabolic abnormalities, sepsis, treatment with muscle relaxants. Sample size 77 SIMV:38 CMV:39 RDS sample size:62 SIMV:31 CMV:31 MAS sample size:15 SIMV:7 CMV:8 Term infants (MAS) excluded from the analysis.	SIMV vs CMV	Primary: Duration of ventilation. Need of reintubation. Air leaks, PDA, IVH. Secondary: BPD, ROP Death.	Ventilator types: Infant star with Star sync module (airflow trigger) (CMV) Bear-Cub	B
D'Angio 2005	Randomized Single centre trial Randomization method: block randomization scheme by one of the investigators Blinding of randomization: yes Blinding of intervention: no Complete follow up: no Blinding of outcome measurement: no	Ventilated infants BW of 500-1249 gm Less than six hours of age Gestational age > 24 weeks Sample size 212 PRVCV 104 SIMV 108	PRVCV vs SIMV	Primary: Proportion of infants alive and extubated at 14 days Secondary: Death Moderate/severe BPD Airleaks Severe IVH (grades 3 and 4)	Ventilator type: Servo 300, infants who required slow rates > 40 bpm (maximum for the Servo 300) were transferred to the BIRD VIP ventilator	A
Dimitriou 1995a	Randomized. Single centre trial Randomization method: sealed, opaque envelopes. Blinding of randomization:yes Blinding of intervention:no Complete follow up:no Blinding of outcome measurement:no	GA<35 weeks Age <15 days Weaning -loaded with aminophylline Exclusion: apnoea, failure to trigger Sample size 40 PTV:20 SIMV:20	PTV vs SIMV	Primary: Duration of weaning Secondary: Number of infants failed weaning Number of infants who failed extubation	Ventilator types: SLE 2000 (airway pressure trigger)	A
Dimitriou 1995b	Randomized. Single centre trial Randomization method: sealed, opaque envelopes. Blinding of randomization:yes Blinding of intervention:no Complete follow up:no Blinding of outcome measurement:no	GA <35 weeks Age <15 days Weaning - loaded with aminophylline Exclusion: apnoea, failure to trigger Sample size 40 PTV:20 SIMV:20	PTV vs SIMV	Primary: Duration of weaning Secondary: Number of infants who failed weaning Number of infants who failed extubation	Ventilator types: SLE 2000 (airway pressure trigger)	A
Donn 1994	Randomized Single centre trial Randomization method:lottery (sampling without replacement) Blinding of randomization : not reported Blinding of intervention:no Complete follow up:no Blinding of outcome measurement:no	Preterm infants. BW between 1.1-1.5 kg, RDS, SRT Sample size 30 PTV:15 CMV:15	PTV vs CMV	Primary: Duration of ventilation Secondary: Airleaks IVH CLD	Ventilator types: PTV V.I.P. BIRD (airflow trigger) CMV Sechrist IV-100B, V.I.P BIRD	B
Heicher 1981	Quasi-randomised. Single center trial. Patients alternatively assigned to one of the two study ventilatory modes Blinding of randomization:no Blinding of intervention:no Complete follow up:no Blinding of outcome measurement:no	Birthweight > 750 gm. No gross anomalies. Abnormal lung fields on chest radiograph. Respiratory distress syndrome, pneumonia Exclusion: infants with chromosomal abnormalities or meconium aspiration Sample size 102 Rapid rates:51 Slow rates:51	HFPPV. Rapid rates (60bpm) with IT: 0.5 sec versus slow rates (20-40 bpm) with IT:1sec	Clinical improvement. Need for pharmacological paralysis. Hours of assisted ventilation. Hours of FiO2> 0.6. CLD. Mortality.	Ventilator types: Baby Bird, Bird Co.	C
OCTAVE 1991	Randomized Multicenter trial Randomization method: sealed, opaque envelopes. Blinding of randomization:yes Blinding of intervention:no Complete follow up:yes Blinding of outcome measurement:no	Age<72 hrs. Assisted ventilation. Exclusion: meconium aspiration Sample size 346 HFPPV : 174 LFPPV : 172	HFPPV (60bpm) versus LFPPV (20-40 bpm)	Incidence of pneumothorax. Incidence and severity of CLD. Mortality. Neurodevelopmental outcome.	Ventilator type: Sechrist IV 100B	A
Pohlandt 1992	Randomized (with stratification for gestational age). Method of randomization: random number table. Blinding of randomization : not reported Blinding of intervention:no Complete follow up:no Blinding of outcome measurement:no	Gestational age <32 weeks. Assisted ventilation. Supplemental FiO2 >0.4. Sample size 181 HFPPV : 91 LFPPV : 90	HFPPV (60 bpm with IT:0.3 sec) vs LFPPV ( 30-40 bpm with IT:1 sec)	Incidence of extra-alveolar air leaks. Mortality.	Ventilator types: AIV Loosco MKII, Biomed MVP 10, Babylog-Draeger, Sechrist IV-100B, Siemens Servo -B and Servo-C, Stephan. 181 infants were enrolled into the study, but only 137 fulfilled the criteria and their results were analyzed.	B
Reyes 2006	Randomized Single centre Randomization method: sequential Sealed opaque envelopes from a computer generated randomized list Blinding of randomization : no Complete follow up: yes Blinding of outcome measurement: no	Birthweight 500-1000 gm appropriate birthweight for gestational age Mechanical ventilation requirement < 12 hours after birth until 7 days Exclusion: congenital anomalies; neuromuscular disease; lung hypoplasia; congenital heart disease; hypotension requiring intravenous medication; PIE or pneumothorax; required HFOV > 24 hours; received sedation or muscle relaxation Sample size: 107 53 SIMV plus PS 54 SIMV	SIMV plus PS versus SIMV	Primary: Proportion of infants requiring supplementary oxygen at 28 days Secondary: Death Airleaks BPD IVH (Grades III and IV) (Grade III and IVH)	Ventilator type: Pressure limited flow triggered VIP ventilator	C

HFPPV:high frequency positive pressure ventilation
RDS:respiratory distress syndrome
CLD: chronic lung disease
SIMV: synchronized intermittent mandatory ventilation
PS: pressure support
PTV: patient triggered ventilation
CDH: congenital diaphragmatic hernia
CHD: congenital heart disease
CMV: conventional mechanical ventilation
BPD: bronchopulmonary dysplasia
ROP: retinopathy of prematurity
IVH: intraventricular haemorrhage
SRT:surfactant replacement therapy
IT: inspiratory time
PRVCV: pressure-regulated volume control ventilation
ACV: assist control ventilation

Characteristics of excluded studies

Study	Reason for exclusion
Abd El-Moneim 2005	Short term cross over study
Abubakar 2005	Randomised short term cross over study
Amitay 1993	Not assigned respiratory support mode by randomization
Bernstein 1993	Not assigned respiratory support mode by randomization
Chan 1993b	Not assigned respiratory support mode by randomization
Cheema 2001	Short term comparison of volume guarantee synchronized ventilation to PTV or SIMV
Cleary 1995	Acute effects of synchronized ventilation
Courtney 2002	Randomised comparison of HFOV to SIMV
Craft 2003	Randomised comparison of SIMV to High Frequency Flow Interrupter
Dani 2006	Short term randomized comparison of PSV with VG to HFOV
deBoer 1993	Not assigned respiratory support mode by randomization
Dimitriou 1998	Comparison of triggering devices
Durand 2001	Randomised pilot study comparing HFOV to SIMV
Firme 2005	Randomised short term cross over study
Friedlich 1999	Nasopharyngeal SIMV versus CPAP
Greenough 1986	Not assigned respiratory support mode by randomization
Greenough 1987a	Not assigned respiratory support mode by randomization
Greenough 1987b	Not assigned respiratory support mode by randomization
Greenough 1988a	Not assigned respiratory support mode by randomization
Greenough 1988b	Not assigned respiratory support mode by randomization
Greenough 1991	Not assigned respiratory support mode by randomization
Guthrie 2005	Randomised short term comparison of SIMV and mandatory minute volume
Herrera 2002	Acute effects of volume-guaranteed SIMV
Hird 1990a	Not assigned respiratory support mode by randomization
Hird 1990b	Not assigned respiratory support mode by randomization
Hird 1991a	Not assigned respiratory support mode by randomization
Hird 1991b	Not assigned respiratory support mode by randomization
Hird 1991c	Not assigned respiratory support mode by randomization
Hird 1991d	Not assigned respiratory support mode by randomization
Hummler 1996	Acute effects of synchronized ventilation
Hummler 1997	Acute effects of mechanical ventilation
Hummler 2006	Randomised short term cross over study
Jaber 2005	Randomised short term cross over comparison of PSV and volume support ventilation
Jarreau 1996	Acute outcome of synchronized ventilation
John 1994	Comparison of triggering devices
Kapasi 1999	Short term randomized comparison of ventilation modes
Keszler 2004	Short term randomised comparison of ventilation modes with ACV with or without volume guarantee
Laubscher 1997	Comparison of triggering devices
Lista 2006	Acute effects of different levels of volume targetting during synchronised intermittent positive pressure ventilation with the context of a randomised trial
Luyt 2001	Acute effects of PTV and conventional ventilation compared within the context of a randomised trial
Migliori 2003	Non randomised comparison of pressure support synchronized ventilation and SIMV
Mitchell 1989	Not assigned respiratory support mode by randomization
Mizuno 1994a	Not assigned respiratory support mode by randomization
Mizuno 1994b	Not assigned respiratory support mode by randomization
Moretti 1999	Nasal SIPPV to nasal CPAP
Mrozek 2000	Randomised comparison (short-term) of volume-targeted synchronized ventilation and CMV
Nafday 2005	Randomised comparison (short term) of pressure support with volume guarantee
Nakae 1998	Comparison of triggering devices
Nikischin 1996	Comparison of triggering devices
Nishimura 1995	Comparison of triggering devices
Olsen 2002	Cross over trial comparing pressure support with volume guarantee synchronized ventilation to SIMV
Osorio 2005	Cross over short term comparison of SIMV with or without pressure support
Polimeni 2006	Short term cross over study
Servant 1992	Not assigned respiratory support mode by randomization
Smith 1997	Acute outcome of synchronized ventilation
Takeuchi 1994	Not assigned respiratory support mode by randomization
Tanaka 1995	Not assigned respiratory support mode by randomization
Thiagarajan 2004	Comparison of triggering devices
Upton 1990	Not assigned respiratory support mode by randomization
Vishveshwara 1991	Not assigned respiratory support mode by randomization

References to studies

References to included studies

Baumer 2000 {published data only}

Baumer JH. International randomised controlled trial of patient triggered ventilation in neonatal respiratory distress syndrome. Archives of Disease in Childhood 2000;82:F5-F10.

Beresford 2000 {published data only}

Beresford MW, Shaw NJ, Manning D. Randomised controlled trial of patient triggered and conventional fast rate ventilation in neonatal respiratory distress syndrome. Archives of Disease in Childhood 2000;82:F14-18.

Bernstein 1996 {published data only}

Bernstein G, Mannino FL, Heldt GP, Callahan JD, Bull DH, Sola A, Ariagno RL, Hoffman GL, Frantz ID, Troche BI, Roberts JL, Dela Cruz TV, Costa E. Randomized multicenter trial comparing synchronized and conventional intermittent mandatory ventilation in neonates. Journal of Pediatrics 1996;128:453-63.

Chan 1993 {published data only}

Chan V, Greenough A. Randomised controlled trial of weaning by patient triggered ventilation or conventional ventilation. European Journal of Pediatrics 1993;152:51-4.

Chan 1994 {published data only}

Chan V, Greenough A. Comparison of weaning by patient triggered ventilation or synchronous mandatory intermittent ventilation. Acta Paediatrica 1994;83:335-7.

Chen 1997 {published data only}

Chen J-Y, Ling U-P, Chen J-H. Comparison of synchronized and conventional intermittent mandatory ventilation in neonates. Acta Paediatrica Japonica 1997;39:578-83.

D'Angio 2005 {published data only}

D'Angio CT, Chess PR, Kovacs SJ, Sinkin RA, Phelps DL, Kendig JW et al. Pressure-regulated volume control ventilation vs synchronized intermittent mandatory ventilation for very low birthweight infants. Archives of Pediatric and Adolescent Medicine 2005;159:868-75.

Dimitriou 1995a {published data only}

Dimitriou G, Greenough A, Giffin FJ, Chan V. Synchronous intermittent mandatory ventilation modes versus patient triggered ventilation during weaning. Archives of Disease in Childhood 1995;72:F188-90.

Dimitriou 1995b {published data only}

Donn 1994 {published data only}

Donn SM, Nicks JJ, Becker MA. Flow-synchronized ventilation of preterm infants with respiratory distress syndrome. Journal of Perinatology 1994;14:90-4.

Heicher 1981 {published data only}

Heicher DA, Kasting DS, Harrod JR. Prospective clinical comparison of two methods for mechanical ventilation of neonates: rapid rate and short inspiratory time versus slow rate and long inspiratory time. Journal of Pediatrics 1981;98:957-61.

OCTAVE 1991 {published data only}

Oxford Region Controlled Trial of Artificial Ventilation (OCTAVE) Study Group. Multicentre randomised controlled trial of high against low frequency positive pressure ventilation. Archives of Disease in Childhood 1991;66:770-5.

Pohlandt 1992 {published data only}

Pohlandt F, Saule H, Schrîder H, Leonhardt A, Hîrnchen H, Wolff C, Bernsau U, Oppermann H-C. Decreased incidence of extra-alveolar air leakage or death prior to air leakage in high versus low rate positive pressure ventilation: results of a randomised seven-centre trial in preterm infants. European Journal of Pediatrics 1992;151:904-9.

Reyes 2006 {published data only}

Reyes ZC, Claure N, Tauscher MK, D'Ugard C, Vanbuskirk S, Bancalari E. Randomized, controlled trial comparing synchronized intermittent mandatory ventilation and synchronized intermittent mandatory ventilation plus pressure support in preterm infants. Pediatrics 2006;118:1409-17.

References to excluded studies

Abd El-Moneim 2005 {published data only}

Abd El-Moneim ES, Fuerste HO, Krueger M, Elmagd AA, Brandis M, Schulte-Moenting J, Hentschel R. Pressure support ventilation combined with volume guarantee versus synchronized intermittent mandatory ventilation: a pilot crossover trial in premature infants in their weaning phase. Critical Care Medicine 2005;6:286-92.

Abubakar 2005 {published data only}

Abubakar K, Keszler M. Effect of volume guarantee combined with assist/control vs synchronized intermittent mandatory ventilation. Journal of Perinatology 2005;25:638-42.

Amitay 1993 {published data only}

Amitay M, Etches PC, Finer NN, Maidens JM. Synchronous mechanical ventilation of the neonate with respiratory disease. Critical Care Medicine 1993;21:118-24.

Bernstein 1993 {published data only}

Bernstein G, Cleary JP, Heldt GP, Rosas JF, Schellenberg l, Mannino FL. Response time and reliability of three neonatal patient triggered ventilators. American Review of Respiratory Disease 1993;148:358-64.

Chan 1993b {published data only}

Chan V, Greenough A. Neonatal patient triggered ventilators. Performance in acute and chronic lung disease. Br J Int Care 1993;3:216-9.

Cheema 2001 {published data only}

Cheema IU, Ahluwalia JS. Feasibility of tidal volume-guided ventilation in newborn infants: a randomized, crossover trial using the volume guarantee modality. Pediatrics 2001;107:1323-8.

Cleary 1995 {published data only}

Cleary JP, Bernstein G, Mannino FL, Heldt BP. Improved oxygenation during synchronized intermittent mandatory ventilation in neonates with respiratory distress syndrome: a randomized, crossover study. Journal of Pediatrics 1995;126:407-11.

Courtney 2002 {published data only}

Courtney SE, Durand DJ, Asselin JM, Hudak ML, Aschner JL, Shoemaker CT. High-Frequency Oscillatory ventilation versus convetional mechanical ventilation for very-low birth-weight infants. New England Journal of Medicine 2002;347:643-52.

Craft 2003 {published data only}

Craft AP, Bhandari V, Finer NN. The sy-fi study: a randomized prospective trial of synchronized intermittent mandatory ventilation versus a high-frequency flow interrupter in infants less than 1000 g. Journal of Perinatology 2003;23:14-9.

Dani 2006 {published data only}

Dani C, Bertini G, Pezzati M, Filippi L, Pratesi S, Caviglioli C, Rubaltelli FF. Effects of pressure support ventilation plus volume guarantee vs high-frequency oscillatory ventilation on lung inflammation in preterm infants. Pediatric Pulmonology 2006;41:242-9.

deBoer 1993 {published data only}

de Boer RC, Jones A, Ward PS, Baumer JH. Long term trigger ventilation in neonatal respiratory distress syndrome. Archives of Disease in Childhood 1993;68:308-11.

Dimitriou 1998 {published data only}

Dimitriou G, Greenough A, Lauscher B, Yamaguchi N. Comparison of airway pressure triggered and airflow triggered ventilation in immature infants. Acta Paediatrica 1998;87:1256-60.

Durand 2001 {published data only}

Durand DJ, Asselin JM, Hudak ML, Aschner JL, McArtor RD, Cleary JP, VanMeurs KP, Stewart DL, Shoemaker CT, Wiswell TE, Courtney SE. Early high-frequency oscillatory ventilation versus synchronized intermittent mandatory ventilation in very low birth weight infants: a pilot study of two ventilation protocols. Journal of Perinatology 2001;21:221-9.

Firme 2005 {published data only}

Firme SR, McEvoy CT, Alconcel C, Tanner J, Durand M. Episodes of hypoxemia during synchronized intermittent mandatory ventilation in ventilator-dependent very low birth weight infants. Pediatric Pulmonology 2005;40:9-14.

Friedlich 1999 {published data only}

Friedlich P, Lecart C, Posen R, Ramicone E, Chan L, Ramanathan R. A randomized trial of nasopharyngeal synchronized interittent mandatory ventilation versus nasopharyngeal continuous positive airway pressure in very low birthweight infants after extubation. Journal of Perinatology 1999;19:413-18.

Greenough 1986 {published data only}

Greenough A, Morley CJ, Pool J. Fighting the ventilator - are fast rates an effective alternative to paralysis? Early Human Development 1986;13:189-94.

Greenough 1987a {published data only}

Greenough A, Pool J, Greenall F, Morley CJ, Gamsu H. Comparison of different rates of artificial ventilation in preterm neonates with the respiratory distress syndrome. Acta Paediatrica Scandinavica 1987;76:706-12.

Greenough 1987b {published data only}

Greenough A, Greenall F, Gamsu H. Synchronous respiration - which ventilator rate is best? Acta Paediatrica Scandinavica 1987;76:713-18.

Greenough 1988a {published data only}

Greenough A, Greenall F. Patient triggered ventilation in premature neonates. Archives of Disease in Childhood 1988;63:77-8.

Greenough 1988b {published data only}

Greenough A, Pool J. Neonatal patient triggered ventilation. Archives of Disease in Childhood 1988;63:394-7.

Greenough 1991 {published data only}

Greenough A, Hird MF, Chan V. Airway pressure triggered ventilation for preterm neonates. Journal of Perinatal Medicine 1991;19:471-6.

Guthrie 2005 {published data only}

Guthrie SO, Lynn C, Lafleur BJ, Donn SM, Walsh WF. A crossover analysis of mandatory minute ventilation compared to synchronized intermittent mandatory ventilation in neonates. Journal of Perinatology 2005;25:643-6.

Herrera 2002 {published data only}

Herrera CM, Gerhardt T, Claure N, Everett R, Musante G, Thomas C, Bancalari E. Effects of volume-guaranteed synchronized intermittent mandatory ventilation in preterm infants recovering from respiratory failure. Pediatrics 2002;110:529-33.

Hird 1990a {published data only}

Hird MF, Greenough A. Causes of failure of neonatal patient triggered ventilation. Early Human Development 1990;23:101-8.

Hird 1990b {published data only}

Hird MF, Greenough A. Gestational age: an important influence on the success of patient triggered ventilation. Clinical Physics and Physiological Measurement 1990;11:307-12.

Hird 1991a {published data only}

Hird MF, Greenough A. Randomised trial of patient triggered ventilation versus high frequency positive pressure ventilation in acute respiratory distress. Journal of Perinatal Medicine 1991;19:379-84 (listed in Wallach EE (ed) Current Opinion in Obstetrics & Gynecology, February 1993).

Hird 1991b {published data only}

Hird MF, Greenough A. Patient triggered ventilation in chronically ventilator-dependent infants. European Journal of Pediatrics 1991;150:732-4.

Hird 1991c {published data only}

Hird MF, Greenough A. Patient triggered ventilation using a flow triggered system. Archives of Disease in Childhood 1991;66:1140-3.

Hird 1991d {published data only}

Hird MF, Greenough A. Comparison of triggering systems for neonatal patient triggered ventilation. Archives of Disease in Childhood 1991;66:426-8 (abstracted in Clinical Digest Series - Pediatrics/Neonatology, Northbrook IL, USA).

Hummler 1996 {published data only}

Hummler H, Gerhardt T, Gonzalez A, Claure N, Everett R, Bancalari E. Influence of different methods of synchronized mechanical ventilation on ventilation, gas exchange, patient effort and blood pressure fluctuations in premature neonates. Pediatric Pulmonology 1996;22:305-13.

Hummler 1997 {published data only}

Hummler H, Gerhardt T, Gonzalez A, Claure N, Everett R, Bancalari E. Increased incidence of sighs (augmented inspiratory eforts) during synchronized intermittent mandatory ventilation (SIMV) in preterm neonates. Pediatric Pulmonology 1997;24:195-203.

Hummler 2006 {published data only}

Hummler H, Engelmann A, Pohlandt F, Franz AR. Volume-controlled intermittent mandatory ventilation in preterm infants with hypoxemic episodes. Intensive Care Medicine 2006;32:577-84.

Jaber 2005 {published data only}

Jaber S, Delay JM, Matecki S, Sebbane M, Eledjam JJ, Brochard L. Volume-guaranteed pressure-support ventilation facing acute changes in ventilatory demand. Intensive Care Medicine 2005;31:1181-8.

Jarreau 1996 {published data only}

Jarreau P-H, Moriette G, Mussat P, Mariette C, Mohanna A, Harf A, Lorino H. Patient-triggered ventilation decreases the work of breathing in neonates. American Journal of Respiratory and Critical Care Medicine 1996;153:1176-81.

John 1994 {published data only}

John J, Bjîrklung LJ, Svenningsen NW, Jonson B. Airway and body surface sensors for triggering in neonatal ventilation. Acta Paediatrica 1994;83:903-9.

Kapasi 1999 {published data only}

Kapasi M, Fujino Y, Kirmse M et al. Effort and work of breathing in neonates during assisted patient triggered ventilation. Pediatric Research 1999;45:306A.

Keszler 2004 {published data only}

Keszler M, Abubakar K. Volume guarantee: stability of tidal volume and incidence of hypocarbia. Pediatric Pulmonology 2004;38:240-5.

Laubscher 1997 {published data only}

Laubscher B Greenough A, Kavadia V. Comparison of body surface and airway triggered ventilation in extremely premature infants. Acta Paediatrica 1997;86:102-4.

Lista 2006 {published data only}

Lista G, Castoldi F, Fontana P, Reali R, Reggiani A, Bianchi S, Compagnoni G. Lung inflammation in preterm infants with respiratory distress syndrome: effects of ventilation with different tidal volumes. Pediatric Pulmonology 2006;41:357-63.

Luyt 2001 {published data only}

Luyt K, Wright D, Baumer JH. Randomised study comparing extent of hypocarbia in preterm infants during conventional and patient triggered ventilation. Archives of Disease in Childhood. Fetal and Neonatal edition 2001;84:F14-7.

Migliori 2003 {published data only}

Migliori C, Cavazza A, Motta M, Chirico G. Effect on respiratory function of pressure support ventilation versus synchronised intermittent mandatory ventilation in preterm infants. Pediatric Pulmonology 2003;35:364-7.

Mitchell 1989 {published data only}

Mitchell A, Greenough A, Hird MF. Limitations of neonatal patient triggered ventilation. Archives of Disease in Childhood 1989;64:924-9.

Mizuno 1994a {published data only}

Mizuno K, Takeuchi T, Itabashi K, Okuyama K. Efficacy of synchronized IMV on weaning neonates from the ventilator. Acta Paediatrica Japonica 1994;36:162-6.

Mizuno 1994b {published data only}

Mizuno K, Kako Y, Ito H, Hasegawa M, Endo T, Imai Y, Hayashi T, Takeuchi T, Itabashi K, Okuyama K. Efficacy of abdominal expansion triggered synchronized IMV in newborns. J Jap Neonat Assoc 1994;30:278.

Moretti 1999 {published data only}

Moretti C, Gizzi C, Papoff P, Lampariello S, Capoferri M, Calcagnini G, Bucci G. Comparing the effects of nasal synchronized intermittent positive pressure ventilation (nSIPPV) and nasal continuous positive airway pressure (nCPAP) after extubation in very low birth weight infants. Early Human Development 1999;56:167-77.

Mrozek 2000 {published data only}

Mrozek JD, Bendel-Stenzel EM, Meyers PA, Bing DR, Connett JE, Mammel MC. Randomized controlled trial of volume-targeted synchronized ventilation and conventional intermittent mandatory ventilation following initial exogenous surfactant therapy. Pediatric Pulmonology 2000;29:11-8.

Nafday 2005 {published data only}

Nafday SM, Green RS, Lin J, Brion LP, Ochshorn I, Holzman IR. Is there an advantage of using pressure support ventilation with volume guarantee in the initial management of preterm infants with respiratory distress syndrome? A pilot study. Journal of Perinatology 2005;25:193-7.

Nakae 1998 {published data only}

Nakae Y, Yamakage M, Horikawa D, Aimono M, Tamiya K, Namiki A. Triggering delay time and work of breathing in three paediatric patient triggered ventilators. Canadian Journal of Anaesthesia 1998;45:261-5.

Nikischin 1996 {published data only}

Nikischin W, Gerhardt T, Everett R, Gonzalez A, Hummler H, Bancalari E. Patient triggered ventilation: a comparison of tidal volume and chest wall and abdominal motion as trigger signals. Pediatric Pulmonology 1996;22:28-34.

Nishimura 1995 {published data only}

Nishimura M, Hess D, Kacmarek RM. The response of flow-triggered infant ventilators. American Journal of Respiratory and Critical Care Medicine 1995;152:1901-9.

Olsen 2002 {published data only}

Olsen SL, Thibeault DW, Truog WE. Crossover trial comparing pressure support with synchronized intermittent mandatory ventilation. Journal of Perinatology 2002;22:461-6.

Osorio 2005 {published data only}

Osorio W, Claure N, D'Ugard C, Athavale K, Bancalari E. Effects of pressure support during an acute reduction of synchronized intermittent mandatory ventilation in preterm infants. Journal of Perinatology 2005;25:412-6.

Polimeni 2006 {published data only}

Polimeni V, Claure N, D'Ugard C, Bancalari E. Effects of volume-targeted synchronized intermittent mandatory ventilation on spontaneous episodes of hypoxemia in preterm infants. Biology of the Neonate 2006;89:50-5.

Servant 1992 {published data only}

Servant GM, Nicks JJ, Donn SM, Bandy KP, Lathrop C, Dechert RE. Feasibility of applying flow-synchronized ventilation to very low birthweight infants. Respiratory Care 1992;37:249-53.

Smith 1997 {published data only}

Smith KM, Walig TM, Bing DR, Georgieff MK, Boros SJ, Mammel MC. Lower respiratory rates without decreases in oxygen consumption during neonatal synchronized intermittent mandatory ventilation. Intensive Care Medicine 1997;23:463-8.

Takeuchi 1994 {published data only}

Takeuchi MK, Itabashi K, Okuyama K. Efficacy of synchronized IMV on weaning neonates from the ventilator. Acta Paediatrica Japonica 1994;36:162-6.

Tanaka 1995 {published data only}

Tanaka D, Takeuchi T, Kako Y, Imai Y, Hayashi T, Itahashi K, Okuyama K. The energy expenditure of the newborn infants during SIMV. J Jap Neonat Assoc 1995;31:333.

Thiagarajan 2004 {published data only}

Thiagarajan RR, Coleman DM, Bratton SL, Watson RS, Martin LD. Inspiratory work of breathing is not decreased by flow-triggered sensing during spontaneous breathing in children receiving mechanical ventilation: a preliminary report. Pediatric Critical Care Medicine 2004;5:375-8.

Upton 1990 {published data only}

Upton CJ, Milner AD, Stokes GM. The effect of changes in inspiratory time on neonatal triggered ventilation. European Journal of Pediatrics 1990;149:648-50.

Vishveshwara 1991 {published data only}

Vishveshwara N, Freeman B, Peck M, Caliwag N, Shook S, Rajani KB. Patient triggered synchronized assisted ventilation of newborns: report of a preliminary study and three years' experience. Journal of Perinatology 1991;11:347-54.

* indicates the primary reference for the study

Other references

Other published versions of this review

Greenough 1998

Greenough A, Milner AD, Dimitriou G. Synchronized mechanical ventilation for respiratory support in newborn infants. In: Cochrane Database of Systematic Reviews, Issue 1, 1998.

Greenough 2001

Greenough A, Milner AD, Dimitriou G. Synchronized mechanical ventilation for respiratory support in newborn infants. In: Cochrane Database of Systematic Reviews, Issue 1, 2001.

Greenough 2004

Greenough A, Milner AD, Dimitriou G. Synchronized mechanical ventilation for respiratory support in newborn infants. In: Cochrane Database of Systematic Reviews, Issue 3, 2004.

Comparisons and data

Comparison or outcome	Studies	Participants	Statistical method	Effect size
01 HFPPV vs CMV
01 Death	3	585	RR (fixed), 95% CI	0.80 [0.62, 1.03]
02 Air leaks			RR (fixed), 95% CI	Subtotals only
03 BPD (oxygen dependency at 28 days)	3	585	RR (fixed), 95% CI	1.09 [0.78, 1.51]
02 ACV / SIMV vs CMV
01 Death	5	1729	RR (fixed), 95% CI	1.19 [0.95, 1.49]
02 Airleaks	6	1769	RR (fixed), 95% CI	1.03 [0.80, 1.34]
03 Duration of ventilation (hours)	4	1402	WMD (fixed), 95% CI	-34.78 [-62.11, -7.44]
04 Extubation failure	4	1056	RR (fixed), 95% CI	0.93 [0.68, 1.28]
05 Severe IVH	5	1729	RR (fixed), 95% CI	1.03 [0.74, 1.43]
06 BPD (oxygen dependency at 28 days)	4	805	RR (fixed), 95% CI	0.91 [0.75, 1.12]
07 Moderate/Severe BPD (oxygen dependent at 36 weeks PCA)	2	1310	RR (fixed), 95% CI	0.90 [0.75, 1.08]
03 ACV or PRVCV vs SIMV
01 Duration of weaning (hours)	3	120	WMD (fixed), 95% CI	-42.38 [-94.35, 9.60]
02 Weaning failure	3	120	RR (fixed), 95% CI	0.78 [0.31, 1.93]
03 Extubation failure	3	120	RR (fixed), 95% CI	1.00 [0.37, 2.67]
04 Air leaks	3	120	RR (fixed), 95% CI	0.80 [0.23, 2.83]
05 Death	1	211	RR (fixed), 95% CI	1.03 [0.50, 2.11]
06 Severe IVH (grade III and IV)	1	203	RR (fixed), 95% CI	0.67 [0.29, 1.58]
07 Moderate/Severe BPD	1	185	RR (fixed), 95% CI	0.83 [0.55, 1.27]
04 PS + SIMV versus SIMV
01 Death	2	214	RR (fixed), 95% CI	0.68 [0.29, 1.59]
02 Air leaks			RR (fixed), 95% CI	Subtotals only
03 BPD	2	214	RR (fixed), 95% CI	0.91 [0.74, 1.12]
04 Severe IVH (grade III and IV)	1	107	RR (fixed), 95% CI	0.92 [0.41, 2.08]

01 HFPPV vs CMV

01.01 Death

01.02 Air leaks

01.02.01 Pneumothorax

01.02.02 Pulmonary interstitial emphysema

01.03 BPD (oxygen dependency at 28 days)

02 ACV / SIMV vs CMV

02.01 Death

02.02 Airleaks

02.03 Duration of ventilation (hours)

02.04 Extubation failure

02.05 Severe IVH

02.06 BPD (oxygen dependency at 28 days)

02.07 Moderate/Severe BPD (oxygen dependent at 36 weeks PCA)

03 ACV or PRVCV vs SIMV

03.01 Duration of weaning (hours)

03.02 Weaning failure

03.03 Extubation failure

03.04 Air leaks

03.04.01 Total air leaks

03.05 Death

03.05.01 Death prior to discharge

03.06 Severe IVH (grade III and IV)

03.07 Moderate/Severe BPD

03.07.01 Moderate/Severe BPD (oxygen dependency in survivors at 36 weeks PMA)

04 PS + SIMV versus SIMV

04.01 Death

04.01.01 Death during first 28 days

04.01.02 Death prior to discharge

04.02 Air leaks

04.02.01 Pneumothorax

04.02.02 Pulmonary interstitial emphysema

04.03 BPD

04.03.01 BPD (oxygen dependency at 28 days)

04.03.02 Moderate/Severe BPD (oxygen dependency at 36 weeks PMA)

04.04 Severe IVH (grade III and IV)

Contact details for co-reviewers

Dr Gabriel Dimitriou
University General Hospital of Patras
RIO 26504
Patras
GREECE
Telephone 1: 0030 2610999856
Facsimile: 0030 2610994683
E-mail: gdimitriou@med.upatras.gr

Prof Anthony D Milner
Emeritus Professor of Neonatology
Department of Child Health
King's College London School of Medicine and Dentistry
Neonatal Intensive Care Unit
King's College London School of Medicine
Bessemer Road
London UK
SE5 9RS
Telephone 1: 0044 20 3299 3037
Facsimile: 0044 20 3299 8284
E-mail: anthony.milner@kcl.ac.uk

Michael Prendergast
UCLA Drug Abuse Research Center
Neuropsychiatric Institute, University of California
11050 Santa Monica Blvd, Suite 150, Los Angeles, CA 90025
Los Angeles
California USA
90025
E-mail: mlp@ucla.edu

This review is published as a Cochrane review in The Cochrane Library, Issue 1, 2008 (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.