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Meta-Analysis
. 2017 Oct 17;10(10):CD003666.
doi: 10.1002/14651858.CD003666.pub4.

Volume-targeted versus pressure-limited ventilation in neonates

Claus Klingenberg  1 , Kevin I Wheeler, Naomi McCallion, Colin J Morley, Peter G Davis
Affiliations
Meta-Analysis

Volume-targeted versus pressure-limited ventilation in neonates

Claus Klingenberg et al. Cochrane Database Syst Rev. .

Abstract

Background: Damage caused by lung overdistension (volutrauma) has been implicated in the development of bronchopulmonary dysplasia (BPD). Modern neonatal ventilation modes can target a set tidal volume as an alternative to traditional pressure-limited ventilation (PLV) using a fixed inflation pressure. Volume-targeted ventilation (VTV) aims to produce a more stable tidal volume in order to reduce lung damage and stabilise the partial pressure of carbon dioxide (pCO2).

Objectives: To determine whether VTV compared with PLV leads to reduced rates of death and death or BPD in newborn infants and to determine whether use of VTV affected outcomes including air leak, cranial ultrasound findings and neurodevelopment.

Search methods: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 12), MEDLINE via PubMed (1966 to 13 January 2017), Embase (1980 to 13 January 2017) and CINAHL (1982 to 13 January 2017). We also searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We contacted the principal investigators of studies to obtain supplementary information.

Selection criteria: Randomised and quasi-randomised trials comparing VTV versus PLV in infants of less than 44 weeks' postmenstrual age and reporting clinically relevant outcomes.

Data collection and analysis: We assessed risk of bias for each trial using Cochrane methodology. We evaluated quality of evidence for each outcome using GRADE criteria. We tabulated mortality, rates of BPD, short-term clinical outcomes and long-term developmental outcomes.

Statistics: for categorical outcomes, we calculated typical estimates for risk ratios (RR), risk differences (RD) and number needed to treat for an additional beneficial outcome (NNTB). For continuous variables, we calculated typical estimates for mean differences (MD). We used 95% confidence intervals (CI) and assumed a fixed-effect model for meta-analysis.

Main results: Twenty randomised trials met our inclusion criteria; 16 parallel trials (977 infants) and four cross-over trials (88 infants). No studies were blinded and the quality of evidence for outcomes assessed varied from moderate to low.We found no difference in the primary outcome, death before hospital discharge, between VTV modes versus PLV modes (typical RR 0.75, 95% CI 0.53 to 1.07; low quality evidence). However, there was moderate quality evidence that the use of VTV modes resulted in a reduction in the primary outcome, death or BPD at 36 weeks' gestation (typical RR 0.73, 95% CI 0.59 to 0.89; typical NNTB 8, 95% CI 5 to 20) and the following secondary outcomes: rates of pneumothorax (typical RR 0.52, 95% CI 0.31 to 0.87; typical NNTB 20, 95% CI 11 to 100), mean days of mechanical ventilation (MD -1.35 days, 95% CI -1.83 to -0.86), rates of hypocarbia (typical RR 0.49, 95% CI 0.33 to 0.72; typical NNTB 3, 95% CI 2 to 5), rates of grade 3 or 4 intraventricular haemorrhage (typical RR 0.53, 95% CI 0.37 to 0.77; typical NNTB 11, 95% CI 7 to 25) and the combined outcome of periventricular leukomalacia with or without grade 3 or 4 intraventricular haemorrhage (typical RR 0.47, 95% CI 0.27 to 0.80; typical NNTB 11, 95% CI 7 to 33). VTV modes were not associated with any increased adverse outcomes.

Authors' conclusions: Infants ventilated using VTV modes had reduced rates of death or BPD, pneumothoraces, hypocarbia, severe cranial ultrasound pathologies and duration of ventilation compared with infants ventilated using PLV modes. Further studies are needed to identify whether VTV modes improve neurodevelopmental outcomes and to compare and refine VTV strategies.

PubMed Disclaimer

Conflict of interest statement

CJM: has acted as a consultant to Drager Medical and Acutronic Medical Instruments, both manufacturers of neonatal ventilators. The companies had no involvement with the funding, design or conduct of this review.

CK: None

KIW: None

PGD: None

NMC: None

Figures

1
1
Study flow diagram: review update. PLV: pressure‐limited ventilation; VTV: volume‐targeted ventilation.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ subgroup by mode of ventilation, Outcome 1 Death before discharge from hospital.
1.2
1.2. Analysis
Comparison 1 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ subgroup by mode of ventilation, Outcome 2 Death or bronchopulmonary dysplasia (BPD) (36 weeks).
1.3
1.3. Analysis
Comparison 1 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ subgroup by mode of ventilation, Outcome 3 Failure of mode of ventilation.
1.4
1.4. Analysis
Comparison 1 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ subgroup by mode of ventilation, Outcome 4 Addition of neuromuscular paralysis where previously not paralysed.
1.5
1.5. Analysis
Comparison 1 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ subgroup by mode of ventilation, Outcome 5 Duration of positive pressure ventilation (days, survivors).
1.6
1.6. Analysis
Comparison 1 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ subgroup by mode of ventilation, Outcome 6 Duration of positive pressure ventilation (log data, survivors).
1.7
1.7. Analysis
Comparison 1 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ subgroup by mode of ventilation, Outcome 7 Inspired oxygen concentration % (study definition).
1.8
1.8. Analysis
Comparison 1 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ subgroup by mode of ventilation, Outcome 8 Any pH < 7.25.
1.9
1.9. Analysis
Comparison 1 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ subgroup by mode of ventilation, Outcome 9 Hypocarbia partial pressure of carbon dioxide (pCO2) < 35 mmHg/4.7 kPa.
1.10
1.10. Analysis
Comparison 1 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ subgroup by mode of ventilation, Outcome 10 Respiratory acidosis; pH < 7.25 and pCO2 > 8 kPa.
1.11
1.11. Analysis
Comparison 1 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ subgroup by mode of ventilation, Outcome 11 Incidence of hypocarbia or respiratory acidosis.
1.12
1.12. Analysis
Comparison 1 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ subgroup by mode of ventilation, Outcome 12 Patent ductus arteriosus.
1.13
1.13. Analysis
Comparison 1 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ subgroup by mode of ventilation, Outcome 13 Air leak (any).
1.14
1.14. Analysis
Comparison 1 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ subgroup by mode of ventilation, Outcome 14 Pneumothorax.
1.15
1.15. Analysis
Comparison 1 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ subgroup by mode of ventilation, Outcome 15 Pulmonary interstitial emphysema.
1.16
1.16. Analysis
Comparison 1 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ subgroup by mode of ventilation, Outcome 16 Any intraventricular haemorrhage (IVH).
1.17
1.17. Analysis
Comparison 1 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ subgroup by mode of ventilation, Outcome 17 Periventricular leukomalacia (PVL).
1.18
1.18. Analysis
Comparison 1 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ subgroup by mode of ventilation, Outcome 18 IVH grade 3‐4.
1.19
1.19. Analysis
Comparison 1 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ subgroup by mode of ventilation, Outcome 19 Any IVH or PVL.
1.20
1.20. Analysis
Comparison 1 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ subgroup by mode of ventilation, Outcome 20 IVH grade 3‐4 or PVL.
1.21
1.21. Analysis
Comparison 1 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ subgroup by mode of ventilation, Outcome 21 BPD (supplemental oxygen in survivors at 36 weeks only).
2.1
2.1. Analysis
Comparison 2 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ infants weighing less than 1000 g, Outcome 1 Death in hospital.
2.2
2.2. Analysis
Comparison 2 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ infants weighing less than 1000 g, Outcome 2 Death or bronchopulmonary dysplasia (BPD) (36 weeks).
2.3
2.3. Analysis
Comparison 2 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ infants weighing less than 1000 g, Outcome 3 Duration of positive pressure ventilation (days, survivors).
2.4
2.4. Analysis
Comparison 2 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ infants weighing less than 1000 g, Outcome 4 Duration of positive pressure ventilation (log data, survivors).
2.5
2.5. Analysis
Comparison 2 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ infants weighing less than 1000 g, Outcome 5 Any pH < 7.25.
2.6
2.6. Analysis
Comparison 2 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ infants weighing less than 1000 g, Outcome 6 Hypocarbia partial pressure of carbon dioxide (pCO2) < 35 mmHg/4.7 kPa.
2.7
2.7. Analysis
Comparison 2 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ infants weighing less than 1000 g, Outcome 7 Respiratory acidosis pH < 7.25 and pCO2 > 60 mmHg/8 kPa.
2.8
2.8. Analysis
Comparison 2 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ infants weighing less than 1000 g, Outcome 8 Hypocarbia or respiratory acidosis.
2.9
2.9. Analysis
Comparison 2 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ infants weighing less than 1000 g, Outcome 9 Patent ductus arteriosus.
2.10
2.10. Analysis
Comparison 2 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ infants weighing less than 1000 g, Outcome 10 Air leak (any).
2.11
2.11. Analysis
Comparison 2 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ infants weighing less than 1000 g, Outcome 11 Pneumothorax.
2.12
2.12. Analysis
Comparison 2 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ infants weighing less than 1000 g, Outcome 12 Pulmonary interstitial emphysema.
2.13
2.13. Analysis
Comparison 2 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ infants weighing less than 1000 g, Outcome 13 Any intraventricular haemorrhage (IVH).
2.14
2.14. Analysis
Comparison 2 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ infants weighing less than 1000 g, Outcome 14 IVH grade 3‐4.
2.15
2.15. Analysis
Comparison 2 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ infants weighing less than 1000 g, Outcome 15 Periventricular leukomalacia (PVL).
2.16
2.16. Analysis
Comparison 2 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ infants weighing less than 1000 g, Outcome 16 Any IVH or PVL.
2.17
2.17. Analysis
Comparison 2 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ infants weighing less than 1000 g, Outcome 17 IVH grade 3‐4 or PVL.
2.18
2.18. Analysis
Comparison 2 Volume‐targeted ventilation (VTV) versus pressure‐limited ventilation (PLV) ‐ infants weighing less than 1000 g, Outcome 18 BPD (supplemental oxygen in survivors at 36 weeks).
3.1
3.1. Analysis
Comparison 3 Miscellaneous post hoc analyses, Outcome 1 Severe disability (any definition).
3.2
3.2. Analysis
Comparison 3 Miscellaneous post hoc analyses, Outcome 2 Severe disability (any definition) or death.
3.3
3.3. Analysis
Comparison 3 Miscellaneous post hoc analyses, Outcome 3 Gross motor developmental issue (any definition).
3.4
3.4. Analysis
Comparison 3 Miscellaneous post hoc analyses, Outcome 4 Steroids for bronchopulmonary dysplasia.
3.5
3.5. Analysis
Comparison 3 Miscellaneous post hoc analyses, Outcome 5 Need for home oxygen (survivors).
3.6
3.6. Analysis
Comparison 3 Miscellaneous post hoc analyses, Outcome 6 Need for home oxygen (survivors weighing < 1000 g).
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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D'Angio 2005 {published and unpublished data}
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Duman 2012 {published and unpublished data}
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Erdemir 2014 {published data only}
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Guven 2013 {published and unpublished data}
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Herrera 2002 {published data only}
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Hummler 2006 {published data only (unpublished sought but not used)}
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Jain 2016 {published and unpublished data}
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Keszler 2004a {published and unpublished data}
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Nafday 2005 {published and unpublished data}
    1. 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 premature infants with respiratory distress syndrome? A pilot study. Journal of Perinatology 2005;25(3):193‐7. [DOI: 10.1038/sj.jp.7211233; PUBMED: 15674409] - DOI - PubMed
Piotrowski 1997 {published and unpublished data}
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Piotrowski 2007 {published and unpublished data}
    1. Piotrowski A, Bernas S, Fendler W. A randomised trial comparing two synchronised ventilation modes in neonates with respiratory distress syndrome. Anestezjologia Intensywna Terapia 2007;39(2):58‐63. [EMBASE: 2007370596]
Polimeni 2006 {published and unpublished data}
    1. 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(1):50‐5. [DOI: 10.1159/000088198; PUBMED: 16155386] - DOI - PubMed
Singh 2006 {published and unpublished data}
    1. Singh J, Sinha SK, Alsop E, Gupta S, Misra A, Donn SM. Long term follow‐up of very low birthweight infants from a neonatal volume versus pressure mechanical ventilation trial. Archives of Disease in Childhood. Fetal and Neonatal Edition 2009;94(5):F360‐2. [DOI: 10.1136/adc.2008.150938; PUBMED: 19321507] - DOI - PubMed
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Sinha 1997 {published data only}
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Zhou 2007 {published data only (unpublished sought but not used)}
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References to studies excluded from this review

Abd El‐Moneim 2005 {published data only}
    1. Abd El‐Moneim ES, Fuerste HO, Krueger M, Elmagd AA, Brandis M, Schulte‐Moenting J, et al. Pressure support ventilation combined with volume guarantee versus synchronized intermittent mandatory ventilation: a pilot crossover trial in premature infants in their weaning phase. Pediatric Critical Care Medicine 2005;6(3):286‐92. [DOI: 10.1097/01.PCC.0000161071.47031.61; PUBMED: 15857526 ] - DOI - PubMed
Abubakar 2001 {published data only}
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Abubakar 2006 {published data only}
    1. Abubakar KM, Montazami S, Keszler M. Volume guarantee accelerates recovery from endotracheal tube suctioning in ventilated preterm infants. Pediatric Academic Societies Annual Meeting; 2006 April 29‐May 2; San Francisco (CA) 2006. [E‐PAS2006:5560.343]
Cheema 2001 {published data only}
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Colnaghi 2006 {published data only}
    1. Colnaghi M, Weissmann G, Ciralli F, Matassa PG, Condo V, Messina D, et al. Volume‐targeted ventilation and lung inflammatory injury in preterm infants with RDS. Pediatric Academic Societies Annual Meeting; 2006 April 29‐May 2; San Francisco (CA) 2006. [E‐PAS2006:5506.340]
Dotta 2004 {published data only}
    1. Dotta A, Crescenzi F, Braguglia A, Campi F, Rechichi J, Orzalesi M. Cerebral haemodynamics in preterm infants during synchronized intermittent mandatory ventilation (SIMV) and synchronized intermittent positive pressure ventilation (SIPPV), with and without volume guarantee (VG). Pediatric Academic Societies' Annual Meeting; 2004 May 1‐4; San Francisco (CA). 2004. [PAS2004:3061]
Keszler 2004b {published data only}
    1. Keszler M, Abubakar KM. Volume guarantee accelerates recovery from forced exhalation episodes. Pediatric Academic Societies' Annual Meeting; 2004 May 1‐4, 2004; San Francisco (CA). 2004. [PAS2004:3092]
Lista 2000 {published data only}
    1. Lista G, Marangione P, Azzali A, Castoldi F, Pogliani L, Compagnoni G. The "guaranteed volume" in pressure support ventilation reduces the risk of barotrauma in premature children with severe respiratory syndrome. Acta Bio‐medica de l'Ateneo Parmense 2000;71(Suppl 1):453‐6. [PUBMED: 11424787] - PubMed
NCT00157989 {unpublished data only}
    1. NCT00157989. Study to assess safety and feasibility of resuscitation of preterm infants with controlled volume of air/oxygen. clinicaltrials.gov/show/NCT00157989 Date first received: 8 September 2005.
NCT00295230 {published and unpublished data}
    1. NCT00295230. Effects of volume guarantee with pressure supported vs. synchronized intermittent mandatory ventilation in VLBW infants. clinicaltrials.gov/show/NCT00295230 Date first received: 21 February 2006.
Olsen 2002 {published data only}
    1. Olsen SL, Thibeault DW, Truog WE. Crossover trial comparing pressure support with synchronized intermittent ventilation. Journal of Perinatology 2002;22(6):461‐6. [DOI: 10.1038/sj.jp.7210772; PUBMED: 12168123] - DOI - PubMed
Ramirez‐Del Valle 2006 {published data only}
    1. Ramirez‐Del Valle JO, Villa‐Guillen M, Reyes A, Murguia‐de Sierra T. Tidal volume (VT) delivery and stability of different ventilatory parameters during synchronized mechanical ventilation with or without volume guarantee (VG). Is VT stability always associated to peak inspiratory changes?. Pediatric Academic Societies Annual Meeting; 2006 April 29‐May 2; San Francisco (CA). 2006. [E‐PAS2006:4843.186]
Shah 2013 {published data only}
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Sinha 2008 {published data only}
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Stefanescu 2015 {published data only}
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Unal 2014 {unpublished data only}
    1. Unal S, Ergenekon E, Aktas S, Altuntas N, Beken S, Kazanci E, et al. Evaluation of ventilatory parameters, short and long term morbidities in preterms ventilated with either PSV+VG or SIMV+VG. 5th Congress of the European Academy of Paediatric Societies; 2014 Oct 17‐21 October; Barcelona (Spain) 2014. [NCT01514331]
Wach 2003 {published data only}
    1. Wach RA, Osiovich HC. Can assist control plus volume guarantee (AC+VG) avoid large tidal volumes (TV) in ventilated spontaneously breathing infants with BPD?. Pediatric Academic Societies' Annual Meeting; 2003 May 3‐6; Seattle (Washington). 2003. [PAS2003:2896]

References to studies awaiting assessment

Liu 2016 {unpublished data only}
    1. Liu CZ, Huang BY, Tan BY, Guan HF, Xu XH, Guo QY. Efficacy of volume‐targeted ventilation for the treatment of neonatal respiratory distress syndrome. Zhongguo Dang Dai Er Ke za Zhi [Chinese Journal of Contemporary Pediatrics] 2016;18(1):6‐9. [PUBMED: 26781404] - PMC - PubMed
Miracle 2016 {published data only}
    1. Miracle X, Salvia MD, Figueras J, Rodriguez JM, Carbonell X. Effects of pressure support plus volume guarantee ventilation versus synchronized intermittent mandatory ventilation in extremely low birth weight infants with respiratory distress syndrome: a prospective, randomized study. Journal of Maternal‐Fetal and Neonatal Medicine 2016;29(Supple 1):236‐7. [DOI: 10.1080/14767058.2016.1191212; PUBMED: 27633796] - DOI - PubMed

References to ongoing studies

ACTRN12609000986279 {unpublished data only}
    1. ACTRN12609000986279. A randomized controlled trial of modes of ventilatory support in preterm babies from point of delivery to the neonatal intensive care unit. www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=308342&isRe... Date first received: 9 July 2009.
Salvia 2006 {published and unpublished data}
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References to other published versions of this review

McCallion 2005
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