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Tracheal gas insufflation for the prevention of morbidity and mortality in mechanically ventilated newborn infants

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Authors

Mark W Davies1, Paul G Woodgate2

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


1Grantley Stable Neonatal Unit, Royal Brisbane and Women's Hospital, Department of Paediatrics & Child Health, The University of Queensland, Brisbane, Australia [top]
2Dept of Neonatology, Mater Mothers' Hospital, South Brisbane, Australia [top]

Citation example: Davies MW, Woodgate PG. Tracheal gas insufflation for the prevention of morbidity and mortality in mechanically ventilated newborn infants. Cochrane Database of Systematic Reviews 2002, Issue 2. Art. No.: CD002973. DOI: 10.1002/14651858.CD002973.

Contact person

Mark W Davies

Grantley Stable Neonatal Unit, Royal Brisbane and Women's Hospital
Department of Paediatrics & Child Health, The University of Queensland
Butterfield St
Herston
Brisbane
Queensland
4029
Australia

E-mail: Mark_Davies@health.qld.gov.au

Dates

Assessed as Up-to-date: 12 March 2010
Date of Search: 17 December 2009
Next Stage Expected: 12 March 2012
Protocol First Published: Issue 1, 2001
Review First Published: Issue 2, 2002
Last Citation Issue: Issue 2, 2002

What's new

Date / Event Description
12 March 2010
Updated

This updates the existing review "Tracheal gas insufflation for the prevention of morbidity and mortality in mechanically ventilated newborn infants" published in the Cochrane Database of Systematic Reviews (Davies 2002).

Updated search found no new trials.

No changes to conclusions.

History

Date / Event Description
22 October 2008
Amended

Converted to new review format.

28 December 2001
New citation: conclusions changed

Substantive amendment

Abstract

Background

Tracheal gas insufflation (TGI) is a technique where a continuous flow of gas is instilled into the lower trachea during conventional mechanical ventilation. TGI can improve carbon dioxide removal with lower ventilation pressures and smaller tidal volumes, potentially decreasing secondary lung injury and chronic lung disease (CLD).

Objectives

To assess whether, in mechanically ventilated neonates, the use of tracheal gas insufflation reduces mortality, CLD and other adverse clinical outcomes without significant side effects.

Search methods

Searches were made of MEDLINE 1966 to December 2001, CINAHL 1982 to December 2001, the Cochrane Controlled Trials Register (Cochrane Library, Issue 4, 2001) and conference and symposia proceedings.

This search was updated in December 2009.

Selection criteria

Randomised controlled trials (RCT) that include newborn infants who are mechanically ventilated, and compare TGI during conventional mechanical ventilation (CMV) with CMV alone. Primary outcomes - mortality, CLD and neurodevelopmental outcome; secondary outcomes - air leak, intraventricular haemorrhage, periventricular leukomalacia, duration of mechanical ventilation, duration of respiratory support, duration of oxygen therapy, duration of hospital stay, retinopathy of prematurity, immediate adverse effects.

Data collection and analysis

Each reviewer assessed eligibility, trial quality and extracted data separately. Study authors were contacted for additional information if necessary.

Results

Only one small study was found to be eligible. This study found no evidence of effect on mortality, CLD or age at first extubation. The total duration of ventilation was 9.3 days shorter in the TGI group (95% CI from 15.7 to 2.9 days shorter). The age at complete weaning from ventilation was 26 days shorter in the TGI group (95% CI from 46 to 6 days shorter). There was no evidence of effect on the total duration of respiratory support, oxygen therapy or hospital stay.

Authors' conclusions

There is evidence from a single RCT that TGI may reduce the duration of mechanical ventilation in preterm infants - although the data from this small study do not give sufficient evidence to support the introduction of TGI into clinical practice. The technical requirements for performing TGI (as performed in the single included study) are great. There is no statistically significant reduction in the total duration of respiratory support or hospital stay. TGI cannot be recommended for general use at this time.

Plain language summary

Tracheal gas insufflation for the prevention of morbidity and mortality in mechanically ventilated newborn infants

Tracheal gas insufflation (TGI) is a new technique to supplement mechanical ventilation in neonatal intensive care, but benefit and safety have not been proven. Tracheal gas insufflation (TGI - also called 'dead space washout') is a new add-on technique for mechanical ventilation (machine-assisted breathing) for babies in neonatal intensive care. It requires new and expensive specialised equipment and skills. TGI involves sending a continuing flow of air/oxygen into the lower part of a baby's trachea (windpipe). The review found only one trial of TGI, which showed it might reduce the length of time babies need mechanical ventilation, but not necessarily reduce the time on oxygen therapy or the stay in hospital. More research is needed to establish if this technology is safe and beneficial.

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Background

Description of the condition

Preterm infants have a very high dead space to tidal volume ratio which can limit the amount of CO2 clearance possible with conventional mechanical ventilation (Dassieu 1998). This high dead space to tidal volume ratio leads to a relatively greater amount of CO2 trapped in the dead space in the smallest of infants (e.g. extremely low birth weight infants who are most at risk of developing chronic lung disease). Increased CO2 clearance may only be possible by increasing tidal volume, with possible adverse effects such as volutrauma, acute lung injury and chronic lung disease. In this situation washing CO2 out of the trachea may be of particular benefit.

Description of the intervention

Tracheal gas insufflation (TGI), or dead space washout, is a technique where, in addition to conventional mechanical ventilation (CMV), a continuous flow of gas (air/oxygen) is instilled into the lower trachea. This additional flow, or insufflation, of gas can occur throughout the ventilator cycle or only during expiration, with or without the addition of active aspiration of gas from the trachea during expiration (De Robertis 1999). TGI can be achieved with the insufflation of gas via extra lumens in the endotracheal tube (ETT) or a catheter placed down the primary lumen of an ETT.

TGI has been demonstrated to increase carbon dioxide (CO2) removal and lower arterial carbon dioxide (PaCO2) in animal studies (Bernath 1997, De Robertis 1999), and in uncontrolled studies in human adults (Richecoeur 1999) and preterm neonates (Danan 1996, Dassieu 1998). It allows the use of lower peak inspiratory pressures and smaller tidal volumes to achieve similar PaCO2s, potentially decreasing volu- and baro-trauma, and secondary lung injury (Bernath 1997, De Robertis 1999, Richecoeur 1999). In neonates this could potentially lead to decreased chronic lung disease (CLD).

How the intervention might work

Two reports in the literature describe the use of TGI in preterm neonates (Danan 1996, Dassieu 1998). Both studies were uncontrolled and investigated short-term respiratory outcomes only. They both confirmed that TGI increases CO2 removal and allows the use of smaller tidal volumes and lower peak inspiratory pressures, but neither assessed the effect on the incidence of CLD.

The response to, or benefit from, TGI may not be the same for all neonates but may vary according to birth weight and/or gestational age. Furthermore, there may be variation in effect dependent upon the strategy used: 1) TGI administered throughout the respiratory cycle or only during expiration, 2) tracheal gas aspiration used simultaneously with TGI or TGI used alone, 3) TGI used as an elective procedure or as rescue treatment.

Potential side effects relate to the smaller internal diameter of the endo-tracheal tubes required for the technique or the use of intra-luminal ETT catheters, possibly increasing the incidence of ETT tube obstruction; increased ETT handling, possibly increasing the incidence of accidental extubation; and uncontrolled manipulations of minute ventilation, possibly resulting in fluctuations in PaCO2 and altered haemodynamics, cerebral blood flow or oxygenation with consequent adverse neurological sequelae.

Objectives

The primary objective was to assess whether, in mechanically ventilated neonates, the use of tracheal gas insufflation reduces mortality, duration of respiratory support, chronic lung disease, adverse neurodevelopmental outcome, and other adverse clinical outcomes.

A secondary objective was to assess whether the use of tracheal gas insufflation is associated with significant side effects.

Subgroup analyses were planned to determine whether the results differ by:

Population:

  1. gestational age
  2. birth weight

Intervention:

  1. tracheal gas insufflation throughout the respiratory cycle or only during expiration
  2. tracheal gas aspiration simultaneously with tracheal gas insufflation or tracheal gas insufflation alone
  3. whether used as elective or rescue treatment

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Methods

Criteria for considering studies for this review

Types of studies

Randomised controlled trials. Crossover studies will be excluded.

Types of participants

Newborn infants who are mechanically ventilated.

Types of interventions

Tracheal gas insufflation during conventional mechanical ventilation compared with conventional mechanical ventilation alone.

Types of outcome measures

One or more of the following outcomes must be reported:

  • mortality (neonatal and/or before discharge)
  • chronic lung disease (requirement for respiratory support and/or oxygen at 28 days of age and at 36 weeks corrected gestational age with or without changes on the chest x-
  • ray)
  • neurodevelopmental outcome (cerebral palsy, sensorineural hearing loss, visual impairment and/or developmental delay) at 1, 2, 3, 5 or 7 years.
  • air leak
  • intraventricular haemorrhage (any, grade 3-4)
  • periventricular leukomalacia
  • duration of mechanical ventilation (IPPV)
  • duration of respiratory support (IPPV or CPAP)
  • duration of oxygen therapy
  • duration of hospital stay
  • retinopathy of prematurity (any, stage 3 or greater)

Immediate adverse effects such as:

  • endo-tracheal tube obstruction
  • re-intubation whilst still ventilated
  • altered haemodynamics, cerebral blood flow or oxygenation, including hypotension, bradycardia, tachycardia, increased cerebral blood flow, decreased cerebral blood flow, periods of decreased arterial oxygen saturation (duration and severity)
  • severe hypocapnia (PaCO2 < 25mmHg)
  • severe hypercapnia (PaCO2 >70mmHg)

Search methods for identification of studies

Electronic searches

Using textword search terms 'tracheal gas insufflation', 'dead space washout', 'expiratory washout' and the MeSH search term 'exp infant, newborn' searches were made of MEDLINE 1966 to December 2001, CINAHL 1982 to December 2001, the Cochrane Controlled Trials Register (Issue 4, 2001). There were no limits on the search with respect to language or whether published data or not.

In December 2009, we updated the search as follows: MEDLINE (search via PubMed), CINAHL, EMBASE and CENTRAL (The Cochrane Library) were searched from 2001 to December 2009. Search terms: 'tracheal gas insufflation' OR 'dead space washout' OR 'expiratory washout'. Limits: human, newborn infant and clinical trial. No language restrictions were applied.

Searching other resources

In addition, we searched for trials by contacting expert informants and hand searching journals mainly in the English language, searching previous reviews including cross references, abstracts, and conference and symposia proceedings published in Pediatric Research from 1990 to 1994.

Data collection and analysis

The standard methods of the Cochrane Neonatal Review Group Guidelines were employed.

Selection of studies

All randomised and quasi-randomized controlled trials fulfilling the selection criteria described in the previous section were included. Both investigators reviewed the results of the search and separately selected the studies for inclusion. The review authors resolved any disagreement by discussion.

Data extraction and management

Data were extracted independently by the reviewers. Differences were resolved by discussion and consensus of the reviewers. Study investigators were contacted for additional information or data.

Assessment of risk of bias in included studies

Criteria and methods used to assess the methodological quality of the trials: standard method of the Cochrane Collaboration and its Neonatal Review Group were used.

The two reviewers worked independently to search for and assess trials for inclusion and methodological quality. Studies were assessed using the following key criteria: allocation concealment (blinding of randomisation), blinding of intervention, completeness of follow-up, and blinding of outcome measurement/assessment. For each criterion, assessment was yes, no, can't tell. Two review authors separately assessed each study. Any disagreement was resolved by discussion. This information was added to the Characteristics of Included Studies Table.

In addition, for the update in 2010, the following issues were evaluated and entered into the Risk of Bias Table:

  1. Sequence generation (checking for possible selection bias). Was the allocation sequence adequately generated?
    For each included study, we categorized the method used to generate the allocation sequence as:
    • adequate (any truly random process e.g. random number table; computer random number generator);
    • inadequate (any non random process e.g. odd or even date of birth; hospital or clinic record number);
    • unclear.
  2. Allocation concealment (checking for possible selection bias). Was allocation adequately concealed?
    For each included study, we categorized the method used to conceal the allocation sequence as:
    • adequate (e.g. telephone or central randomisation; consecutively numbered sealed opaque envelopes);
    • inadequate (open random allocation; unsealed or non-opaque envelopes, alternation; date of birth);
    • unclear.
  3. Blinding (checking for possible performance bias). Was knowledge of the allocated intervention adequately prevented during the study? At study entry? At the time of outcome assessment?
    For each included study, we categorized the methods used to blind study participants and personnel from knowledge of which intervention a participant received. Blinding was assessed separately for different outcomes or classes of outcomes. We categorized the methods as:
    • adequate, inadequate or unclear for participants;
    • adequate, inadequate or unclear for personnel;
    • adequate, inadequate or unclear for outcome assessors.
    In some situations there may be partial blinding e.g. where outcomes are self-reported by unblinded participants but they are recorded by blinded personnel without knowledge of group assignment. Where needed “partial” was added to the list of options for assessing quality of blinding.
  4. Incomplete outcome data (checking for possible attrition bias through withdrawals, dropouts, protocol deviations). Were incomplete outcome data adequately addressed?
    For each included study and for each outcome, we described the completeness of data including attrition and exclusions from the analysis. We noted whether attrition and exclusions were reported, the numbers included in the analysis at each stage (compared with the total randomised participants), reasons for attrition or exclusion where reported, and whether missing data were balanced across groups or were related to outcomes.Where sufficient information was reported or supplied by the trial authors, we re-included missing data in the analyses. We categorized the methods as:
    • adequate (< 20% missing data);
    • inadequate (greater than/or equal to 20% missing data):
    • unclear.
  5. Selective reporting bias. Are reports of the study free of suggestion of selective outcome reporting?
    For each included study, we described how we investigated the possibility of selective outcome reporting bias and what we found. We assessed the methods as:
    • adequate (where it is clear that all of the study’s pre-specified outcomes and all expected outcomes of interest to the review have been reported);
    • inadequate (where not all the study’s pre-specified outcomes have been reported; one or more reported primary outcomes were not pre-specified; outcomes of interest are reported incompletely and so cannot be used; study fails to include results of a key outcome that would have been expected to have been reported);
    • unclear.
  6. Other sources of bias. Was the study apparently free of other problems that could put it at a high risk of bias?
    For each included study, we described any important concerns we had about other possible sources of bias (for example, whether there was a potential source of bias related to the specific study design or whether the trial was stopped early due to some data-dependent process). We assessed whether each study was free of other problems that could put it at risk of bias as:
    • yes;no;or unclear.

If needed, we planned to explore the impact of the level of bias through undertaking sensitivity analyses.

Measures of treatment effect

Statistical analyses were performed using Review Manager software. For individual trials, where possible, mean differences (and 95% confidence intervals) were reported for continuous variables such as duration of oxygen therapy. For categorical outcomes such as mortality, the relative risk and risk difference (and 95% confidence intervals) were reported.

Assessment of heterogeneity

We planned to evaluate the heterogeneity between trials by inspecting the forest plots and quantifying the impact of heterogeneity using the I2statistic.

Data synthesis

If multiple trials were identified, we planned to perform meta-analysis using Review Manager software (RevMan 5) supplied by the Cochrane Collaboration. For estimates of typical relative risk and risk difference, we planned to use the Mantel-Haenszel method. For measured quantities, we planned to use the inverse variance method. All meta-analyses were planned to be done using the fixed effect model.

Subgroup analysis and investigation of heterogeneity

Subgroup analyses were planned to determine whether the results differ by:
Population:
  1. gestational age
  2. birth weight
Intervention:
  1. tracheal gas insufflation throughout the respiratory cycle or only during expiration
  2. tracheal gas aspiration simultaneously with tracheal gas insufflation or tracheal gas insufflation alone
  3. whether used as elective or rescue treatment

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Results

Description of studies

Only one study was identified and found eligible for inclusion in this review. Dassieu et al (Dassieu 2000) performed a randomised, controlled trial comparing conventional pressure-controlled ventilation and continuous tracheal gas insufflation with conventional pressure-controlled ventilation alone in preterm infants. The trial included infants < 30 weeks gestational age who were ventilated for hyaline membrane disease and had received surfactant. Included infants had to be randomised by six hours of age. Forty-one infants were randomised and after seven post-randomisation exclusions 34 infants were studied - 15 TGI and 19 control. The mean (SD) gestational age was 27.8 (1.3) weeks and the mean (SD) weight was 965 (202) grams. Babies were randomised at a mean (SD) age of 226 (81) minutes and at a mean (SD) interval of 50 (42) minutes after surfactant administration. The primary outcomes of the study were the ventilatory pressures required and oxygenation status during ventilation. Secondary outcomes included mortality, chronic lung disease and duration of mechanical ventilation.

In the experimental group TGI was achieved via a specially constructed ETT with eight secondary lumens in the wall of the ETT. The secondary lumens allow continuous gas flow of 0.5 L/min to produce TGI (6 lumens) and pressure monitoring (1 lumen) - one lumen is left free to use for the introduction of surfactant. A pump is required to draw warmed humidified gases from the inspiratory line for TGI. A separate computerised monitoring system is also needed to monitor pressure at the distal ETT to enable emergency cut-off of the TGI flow with any abnormal rise in intratracheal pressure (to prevent dangerous lung hyperinflation). TGI was used in this group of infants until extubation. TGI was discontinued during any periods of high-frequency ventilation. In both groups conventional mechanical ventilation (with or without TGI) was continued if the oxygenation index remained within the range of two to 12. An oxygenation index of >12 resulted in a switch to high-frequency ventilation. Infants were weaned from ventilation when the ventilatory rate was below 30 breaths per minute and the oxygenation index was less than two.

In response to our request, the study investigators provided unpublished data for some outcomes not included in the primary report (Dassieu 2000) including the total duration of respiratory support, oxygen therapy and hospital stay. They also provided data on neurodevelopmental outcomes (cerebral palsy, sensorineural hearing loss, visual impairment and/or developmental delay); however, the details of exact definitions and timing of assessments are not clear and these outcomes have not been included in this review. Other data were published as medians and the study investigators have provided the data as means and standard deviations.

Risk of bias in included studies

In Dassieu et al's study (Dassieu 2000):

  1. treatment allocation was randomised (exact method not stated);
  2. treatment allocation was concealed using 'sealed envelopes';
  3. treatment was not blinded - however in both groups ventilation settings were adjusted according to a predefined protocol to target set oxygen saturation and PCO2; and there were predefined criteria for weaning ventilation and extubation;
  4. follow-up was not complete - 41 patients were randomised and there were seven (17%) post-randomisation exclusions. Three of these exclusions were because of technical difficulties with the equipment which prevented commencement of TGI; therefore, analysis is not an 'intention to treat' analysis. Follow-up rates for the remaining 34 infants were generally better than 90% (except for ROP and occurrence of severe hypo- or hypercapnia);
  5. most of the published outcomes were not assessed by blinded evaluators.

Effects of interventions

The results of this review are based on one eligible study with small numbers.

Mortality (neonatal and/or before discharge):

There was no statistically significant difference between groups.

Chronic lung disease (requirement for respiratory support and/or oxygen at 28 days of age and at 36 weeks corrected gestational age:

There was no statistically significant difference between groups.

Neurodevelopmental outcome (cerebral palsy, sensorineural hearing loss, visual impairment and/or developmental delay):

No data available.

Air leak:

There was no statistically significant difference between groups.

IVH:

There was no statistically significant difference between groups.

PVL:

There was no statistically significant difference between groups.

Duration of mechanical ventilation:

The duration of mechanical ventilation was measured and reported as three different variables:

  1. the age (in days) at first extubation - this was not significantly different between groups.
  2. total duration of ventilation (defined as the sum of the periods of ventilation until the infant remains extubated for seven consecutive days post-extubation) was 9.3 days shorter in the TGI group (95% CI from 15.7 to 2.9 days shorter).
  3. age at complete weaning from ventilation was 26 days shorter in the TGI group (95% CI from 46 to 6 days shorter).

Duration of respiratory support (IPPV or CPAP):

There was no statistically significant difference between groups. However, this was six days longer in the treatment group (mean difference 6 days, 95% CI -6.4 to 18.4) and the 95% confidence interval is wide.

Duration of oxygen therapy:

There was no statistically significant difference between groups.

Duration of hospital stay:

There was no statistically significant difference between groups. However this was 10 days shorter in the treatment group (mean difference -10 days, 95% CI -30 to 10) and the 95% confidence interval is wide.

ROP:

There was no statistically significant difference between groups.

Endo-tracheal tube obstruction:

There was no statistically significant difference between groups.

Re-intubation whilst still ventilated:

There was no statistically significant difference between groups.

Altered haemodynamics, cerebral blood flow or oxygenation, including hypotension, bradycardia, tachycardia, increased cerebral blood flow, decreased cerebral blood flow, periods of decreased arterial oxygen saturation (duration and severity):

No data available.

Severe hypocapnia (PaCO2 < 25mmHg):

There was no statistically significant difference between groups.

Severe hypercapnia (PaCO2 >70mmHg):

There was no statistically significant difference between groups.

Discussion

This review is limited in its scope given that only one study was identified which met the inclusion criteria. The single included study (Dassieu 2000) was a well conducted randomised controlled trial with only one moderately worrisome methodological shortcoming - the post-randomisation exclusions (although the proportion is < 20% of those randomised). The study was a small study with only 34 subjects randomised and followed-up. Therefore, whilst most of the comparisons favour the treatment group, only two outcomes, both related to duration of mechanical ventilation, reached statistical significance. The potential for type 2 error is considerable and the 95% confidence intervals are wide.

Nevertheless this study provides some evidence that TGI may be useful in reducing the duration of mechanical ventilation for infants < 30 weeks gestation with hyaline membrane disease. It is important to note, however, that the total duration of respiratory support (i.e. conventional ventilation, high frequency ventilation and continuous positive airway pressure) was six days longer in the treatment group although this difference was not statistically significant. The duration of hospital stay was reduced in the treatment group by 10 days but this also did not reach statistical significance. Much larger studies would be required to determine whether the advantage of a reduction in the duration of mechanical ventilation is not lost by an increased total duration of respiratory support, or augmented by a reduction in hospital stay. Benefits also need to be weighed against an intervention that is technically demanding, requires additional specialised equipment and may add considerably to the cost of ventilation.

Authors' conclusions

Implications for practice

There is evidence from a single small RCT that TGI may reduce the duration of mechanical ventilation in preterm infants - although the data from this single small study do not give sufficient evidence to support the introduction of TGI into clinical practice. The technical requirements for performing TGI (as performed in the single included study) are great, and there is no statistically significant reduction in the total duration of respiratory support or hospital stay. TGI cannot be recommended for general use at this time.

Implications for research

Appropriately sized RCTs are required to determine whether the advantage of TGI in reducing the duration of mechanical ventilation is not lost by an increased total duration of respiratory support, or augmented by a reduction in hospital stay. Future studies should also investigate the effects on long term neuro-developmental outcomes (i.e. cerebral palsy, sensorineural hearing loss, visual impairment and/or developmental delay) to determine that any short term gains are not lost with an increased incidence of disability in survivors.

Acknowledgements

We would like to thank Prof Claude Danan, from the Service de Reanimation Neonatale, Hopital Intercommunal de Creteil, for providing extra data from Dassieu et al's study (Dassieu 2000).

The Cochrane Neonatal Review Group has been funded in part with Federal funds from the Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Department of Health and Human Services, USA, under Contract No. HHSN267200603418C.

Contributions of authors

MWD - instigated the review, wrote the protocol, searched for studies, extracted data from included studies, entered data into RevMan, wrote the review.

PGW - wrote the protocol, searched for studies, extracted data from included studies, wrote the review.

The March 2010 update was conducted centrally by the Cochrane Neonatal Review Group staff (Yolanda Montagne, Diane Haughton, and Roger Soll). This update was reviewed and approved by MWD.

Potential conflict of interest

  • None noted.

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Characteristics of studies

Characteristics of Included Studies

Dassieu 2000

Methods

RCT
(sealed envelopes).

Randomised within 6 hours of birth.

Randomised - YES (exact method of sequence generation not stated).
Blindness of randomisation (allocation) - YES (sealed envelopes, although not stated whether envelopes were opaque).
Blindness of intervention - NO.
Completeness of follow up - NO.
Blinding of outcome measurement - NOT ALL.

Participants

Newborn infants < 30 weeks gestational age.
Ventilated for hyaline membrane disease and had received surfactant.

Exclusions

  1. HIE
  2. refractory hypotension
  3. lethal malformations
  4. congenital malformations with pulmonary consequences.
Interventions

Experimental group - conventional pressure-controlled ventilation with continuous tracheal gas insufflation. (Number randomised = 19) TGI was used in this group of infants until extubation. TGI was discontinued during any periods of high-frequency ventilation.

Control group - conventional pressure-controlled ventilation alone. (Number randomised = 22)

Treatment was not blinded - however in both groups ventilation settings were adjusted according to a predefined protocol to target set oxygen saturation and PCO2; and there were predefined criteria for weaning ventilation and extubation.

In both groups conventional mechanical ventilation (with or without TGI) was continued if the oxygenation index remained within the range of 2 to 12. An oxygenation index of >12 resulted in a switch to high-frequency ventilation. Infants were weaned from ventilation when the ventilatory rate was below 30 breaths per minute and the oxygenation index was < 2.

Outcomes

Published - primary

  • ventilatory pressures
  • oxygenation status

Published - secondary

  • mortality at 28 days
  • mortality at discharge
  • oxygen at 28 days
  • oxygen at 36 weeks
  • pneumothorax
  • ETT obstruction
  • IVH any
  • IVH grade 3+
  • PVL
  • need for HFOV (OI >12)
  • death or CLD at 28 days
  • death or CLD at 36 weeks
  • days to first extubation
  • total duration IPPV

Unpublished (as at September 2001)

  • pneumothorax
  • emphysema
  • need for re-intubation whilst ventilated (plug)
  • need for re-intubation whilst ventilated (other)
  • severe hypocapnia (< 25) even once
  • severe hypercapnia (>70) even once
  • age of complete weaning from ventilatory support IPPV or HFO
  • age of complete weaning from nasal ventilation
  • age of complete weaning from oxygen
  • retinopathy (any)
  • retinopathy (stage 3 or greater)
  • duration of hospital stay (NICU + general)
  • cerebral palsy
  • sensorineural hearing loss
  • visual impairment
  • developmental delay
Notes

There were 7 post-randomisation exclusions, 4 from the experimental group and 3 from the control group. These exclusions were because of:
technical difficulties with equipment so that TGI could not be commenced (3);
post-randomisation withdrawal of consent (2);
no consent obtained (1);
oxygenation index >12 at the time of randomisation (1).
In the case of the last 3 reasons for exclusion, it is not clear from which group the exclusions occurred.

Risk of bias table
Item Judgement Description
Adequate sequence generation? Unclear

RCT using sealed envelopes. Randomised within 6 hours of birth. Exact method of sequence generation not stated

Allocation concealment? Yes

Blindness of randomisation (allocation) - Yes (sealed envelopes, although not stated whether envelopes were opaque)

Blinding? No

Blindness of intervention - No
Blinding of outcome measurement - Not all

Incomplete outcome data addressed? No

Completeness of follow-up - No

Free of selective reporting? Unclear
Free of other bias? Unclear

Characteristics of excluded studies

Wald 2005

Reason for exclusion

Not a study of tracheal gas insufflation (i.e., wrong intervention).

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References to studies

Included studies

Dassieu 2000

Dassieu G, Brochard L, Benani M, Avenel S, Danan C. Continuous tracheal gas insufflation in preterm infants with hyaline membrane disease. American Journal of Respiratory and Critical Care Medicine 2000;162:826-31.

Excluded studies

Wald 2005

Wald M, Kalous P, Lawrenz K, Jeitler V, Weninger M, Kirchner L. Dead-space washout by split-flow ventilation. A new method to reduce ventilation needs in premature infants. Intensive Care Medicine 2005;31:674.

Studies awaiting classification

  • None noted.

Ongoing studies

  • None noted.

Other references

Additional references

Bernath 1997

Bernath MA, Henning R. Tracheal gas insufflation reduces requirements for mechanical ventilation in a rabbit model of respiratory distress syndrome. Anaesthesia and Intensive Care 1997;25:15-22.

Danan 1996

Danan C, Dassieu G, Janaud J-C, Brochard L. Efficacy of dead-space washout in mechanically ventilated premature newborns. American Journal of Respiratory and Critical Care Medicine 1996;153:1571-6.

Dassieu 1998

Dassieu G, Brochard L, Agudze E, Patkai J, Janaud J-C, Danan C. Continuous tracheal gas insufflation enables a volume reduction strategy in hyaline membrane disease: technical aspects and clinical results. Intensive Care Medicine 1998;24:1076-82.

De Robertis 1999

De Robertis E, Sigurdsson SE, Drefeldt B, Jonson B. Aspiration of airway dead space. A new method to enhance CO2 elimination. American Journal of Respiratory and Critical Care Medicine 1999;159:728-32.

Richecoeur 1999

Richecoeur J, Lu Q, Vieira SRR, Puybasset L, Kalfon P, Coriat P, Rouby J-J. Expiratory washout versus optimization of mechanical ventilation during permissive hypercapnia in patients with severe acute respiratory distress syndrome. American Journal of Respiratory and Critical Care Medicine 1999;160:77-85.

Other published versions of this review

Davies 2002

Davies MW, Woodgate PG. Tracheal gas insufflation for the prevention of morbidity and mortality in mechanically ventilated newborn infants. Cochrane Database of Systematic Reviews 2002, Issue 2. Art. No.: CD002973. DOI: 10.1002/14651858.CD002973.

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Data and analyses

1 Continuous TGI during conventional mechanical ventilation (CMV) vs CMV alone

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
1.1 Mortality before day 28 1 34 Risk Ratio (M-H, Fixed, 95% CI) 0.25 [0.01, 4.85]
1.2 Mortality before discharge 1 34 Risk Ratio (M-H, Fixed, 95% CI) 0.32 [0.04, 2.55]
1.3 In oxygen at day 28 in survivors to 28 days 1 32 Risk Ratio (M-H, Fixed, 95% CI) 0.38 [0.09, 1.60]
1.4 In oxygen at 36 weeks corrected GA in survivors to 36 weeks corrected GA 1 29 Risk Ratio (M-H, Fixed, 95% CI) 0.54 [0.21, 1.39]
1.5 Death or CLD at 28 days 1 34 Risk Ratio (M-H, Fixed, 95% CI) 0.32 [0.08, 1.28]
1.6 Death or CLD at 36 weeks corrected GA 1 34 Risk Ratio (M-H, Fixed, 95% CI) 0.53 [0.24, 1.17]
1.7 Pneumothorax 1 34 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
1.8 Endotracheal tube obstruction 1 34 Risk Ratio (M-H, Fixed, 95% CI) 3.75 [0.16, 85.98]
1.9 Intraventricular haemorrhage (any) in survivors to 28 days 1 32 Risk Ratio (M-H, Fixed, 95% CI) 0.57 [0.12, 2.67]
1.10 Intraventricular haemorrhage (grade 3+) in survivors to 28 days 1 32 Risk Ratio (M-H, Fixed, 95% CI) 0.16 [0.01, 2.88]
1.11 Periventricular leukomalacia in survivors to 28 days 1 32 Risk Ratio (M-H, Fixed, 95% CI) 0.23 [0.01, 4.35]
1.12 Pulmonary interstitial emphysema among babies examined 1 28 Risk Ratio (M-H, Fixed, 95% CI) 0.33 [0.04, 2.83]
1.13 Retinopathy of prematurity (any) among babies examined 1 19 Risk Ratio (M-H, Fixed, 95% CI) 0.73 [0.05, 9.97]
1.14 Retinopathy of prematurity (grade 3+) among babies examined 1 19 Risk Ratio (M-H, Fixed, 95% CI) Not estimable
1.15 Need for re-intubation because of ETT obstruction in babies where data are available 1 29 Risk Ratio (M-H, Fixed, 95% CI) 3.20 [0.14, 72.62]
1.16 Need for re-intubation for any reason other than ETT obstruction in babies where data are available 1 27 Risk Ratio (M-H, Fixed, 95% CI) 0.13 [0.01, 2.36]
1.17 One or more episodes of severe hypocapnia (PaCO2 < 25 mmHg) in babies where data are available 1 25 Risk Ratio (M-H, Fixed, 95% CI) 2.17 [0.22, 20.94]
1.18 One or more episodes of severe hypercapnia (PaCO2 >70 mmHg) in babies where data are available 1 25 Risk Ratio (M-H, Fixed, 95% CI) 1.08 [0.08, 15.46]
1.19 Time to first extubation (days) in survivors to 28 days 1 32 Mean Difference (IV, Fixed, 95% CI) -6.60 [-13.91, 0.71]
1.20 Total duration of ventilation until remains extubated for 7 consecutive days (days) in survivors to 28 days 1 32 Mean Difference (IV, Fixed, 95% CI) -9.30 [-15.60, -3.00]
1.21 Age at complete weaning from ventilation - IPPV or HFO (days) in survivors to discharge 1 29 Mean Difference (IV, Fixed, 95% CI) -26.00 [-46.11, -5.89]
1.22 Age at complete weaning from respiratory support - ventilation or CPAP (days) in survivors to discharge 1 29 Mean Difference (IV, Fixed, 95% CI) 6.00 [-6.38, 18.38]
1.23 Age at complete weaning from oxygen (days) in survivors to discharge 1 29 Mean Difference (IV, Fixed, 95% CI) -21.00 [-47.03, 5.03]
1.24 Duration of hospital stay (days) in survivors to discharge 1 29 Mean Difference (IV, Fixed, 95% CI) -10.00 [-30.29, 10.29]

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Sources of support

Internal sources

  • Grantley Stable Neonatal Unit, Royal Women's Hospital, Brisbane, Australia
  • Perinatal Research Centre, Royal Women's Hospital, Brisbane, Australia
  • Dept of Paediatrics and Child Health, University of Queensland, Brisbane, Australia
  • Centre for Clinical Studies, Mater Hospital, Brisbane, Australia
  • Cochrane Perinatal Team, Brisbane, Australia
  • Royal Children's Hospital Foundation, Brisbane, Australia

External sources

  • No sources of support provided.

This review is published as a Cochrane review in The Cochrane Library, Issue 4, 2010 (see http://www.thecochranelibrary.com External Web Site Policy 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 recent version of the review.