Positive end-expiratory pressure for resuscitation of newborn infants at birth

O'Donnell C, Davis P, Morley C

Background - Methods - Results - References

Cover sheet

Title

Reviewers

O'Donnell C, Davis P, Morley C

Dates

Date edited: 13/08/2004
Date of last substantive update: 19/03/2003
Date of last minor update: 25/05/2004
Date next stage expected / /
Protocol first published: Issue 3, 2003
Review first published: Issue 4, 2004

Contact reviewer

Dr Colm P.F. O'Donnell
Fellow in Neonatal Paediatrics
Division of Newborn Services
Royal Women's Hospital Melbourne
132 Grattan Street
Carlton
Victoria AUSTRALIA
3053
Telephone 1: +61 3 9344 2000 extension: 3141
Facsimile: +61 3 9344 2185
E-mail: colm.odonnell@rwh.org.au
Secondary contact person's name: Peter Davis

Contribution of reviewers

Dr. O'Donnell and Dr. Davis performed the literature search. Dr. O'Donnell wrote the manuscript, which was reviewed by Dr. Davis and Prof. Morley.

Internal sources of support

Royal Women's Hospital, Melbourne, AUSTRALIA
Murdoch Children's Research Institute, AUSTRALIA
University of Melbourne, AUSTRALIA

External sources of support

National Health and Medical Research Council, AUSTRALIA

What's new

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: / /
Date reviewers' conclusions section amended: / /
Date comment/criticism added: / /
Date response to comment/criticisms added: / /

Text of review

Synopsis

Synopsis pending.

Abstract

Background

Effective ventilation is the key to successful neonatal resuscitation. Positive pressure ventilation is initiated with manual ventilation devices which may or not deliver positive end-expiratory pressure (PEEP). PEEP is known to have beneficial effects in preterm animal models and its use is ubiquitous in mechanical ventilation in neonatal intensive care.

Objectives

To determine whether the use of PEEP during positive pressure ventilation at neonatal resuscitation reduces mortality or morbidity.

Search strategy

The standard search strategy of the Cochrane Neonatal Review Group was used. Pub Med (1966 to May 2004) was searched using the MeSH headings Infant, Newborn, Resuscitation, Positive Pressure Respiration and the text words Positive End-Expiratory Pressure or PEEP. The Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2004) was searched using text words Newborn and Resuscitation. No language restrictions were applied. The abstracts of the Society for Pediatric Research and the European Society for Pediatric Research, were searched from 1995-May 2004. Abstracts were also searched in Anaesthesiology, Canadian Journal of Anaesthesia, British Journal of Anaesthesia, Anaesthesia and Intensive Care and Anaesthesia and Analgesia.

Selection criteria

Randomised and quasi-randomised controlled trials comparing ventilation devices providing PEEP with those not providing PEEP in the resuscitation of infants at birth.

Data collection & analysis

Assessment of methodology regarding blinding of randomisation, intervention and outcome measurements as well as completeness of follow-up was planned. We planned to evaluate the treatment effect using a fixed effects model using relative risk (RR), relative risk reduction, risk difference (RD) and number needed to treat (NNT) for categorical data and using mean, standard deviation and weighted mean difference (WMD) for continuous data. We planned an evaluation of heterogeneity to help determine the suitability of pooling results.

Main results

No studies were found meeting the criteria for inclusion in this review.

Reviewers' conclusions

There is insufficient evidence to determine the efficacy and safety of PEEP during positive pressure ventilation at neonatal resuscitation. Randomised clinical trials comparing positive pressure ventilation with and without PEEP at neonatal resuscitation are warranted.

Background

A small but important proportion (3 to 5%) of newborn babies require resuscitation at birth (Saugstad 1998). Problems may begin primarily in the mother, the placenta or the fetus but present in the infant as ineffective or absent breathing efforts immediately after birth. If uncorrected, lack of oxygen and acidosis occur and eventually lead to damage of vital organs. The mainstay of resuscitation is oxygenation of the vital organs through the provision of assisted breathing, i.e. ventilation. Ventilation may be delivered via a face mask or an endotracheal tube. The choice of interface depends on the experience of the operator and the severity of the infant's condition. Though ventilation of these babies is the most important aspect of their care, at present little evidence exists to guide clinicians how best to provide ventilatory support. Since intubation and positive pressure ventilation were first recommended in 1928, a pattern of resuscitation has evolved based on extrapolation and assumption rather than on clinical measurement (Milner 1991).

A role for positive end expiratory pressure (PEEP) in resuscitation?
A range of devices are available to provide assisted ventilation in the delivery room. Some provide no PEEP (e.g. Laerdal self inflating bag); some provide variable but measured PEEP (e.g. flow inflating or anaesthesia bags) and some provide a predetermined and measured level of PEEP (e.g. the Neopuff Infant Resuscitator). PEEP may be delivered to babies resuscitated with a face mask or with an endotracheal tube. The function of PEEP is to keep the lungs of ventilated infants partially expanded at the end of expiration, thereby preventing their complete deflation. PEEP is important for establishing and maintaining functional residual capacity (FRC) (Vilstrup 1992; Thome 1998). In preterm infants there is a strong association between absence of FRC and subsequent hyaline membrane disease requiring ventilation (Upton 1991). In very preterm lambs, the application of PEEP during resuscitation halves the oxygen requirements within ten minutes (Probyn 2002). The use of PEEP from the initiation of ventilation has been shown to reduce hyaline membrane formation (Argiras 1987), preserve surfactant function (Michna 1999) and reduce the expression of inflammatory markers (Naik 2001) in the lungs of preterm animal models. Probyn 2002 found that responses of a lamb model varied according to the level of PEEP, with optimal oxygenation without adverse effects being seen at cm water. If PEEP were provided during resuscitation of human infants this may lead to more rapid correction of oxygen and carbon dioxide levels and less damage to the lungs, particularly in preterm infants.

While PEEP is always used during intermittent positive pressure ventilation (IPPV) in the intensive care setting, there are no current recommendations about the use of PEEP in resuscitation of the newborn. Twelve years ago it was noted that it is "possible that a resuscitation device that delivered positive end expiratory pressure would be of benefit to preterm infants … such a device would certainly warrant serious investigation" (Upton 1991).

Current international recommendations on the resuscitation of newborn infants outline the central role of IPPV and describe the use of self-inflating and flow-inflating bags at resuscitation (ILCOR 2000). They make no mention of other resuscitation devices nor recommendation regarding the use of PEEP during neonatal resuscitation.

Objectives

In newly born infants receiving resuscitation with intermittent positive pressure ventilation, does resuscitation using devices providing positive end-expiratory pressure (PEEP) compared to devices not providing PEEP reduce mortality and morbidity?

Further analysis was planned to determine the effects of PEEP during resuscitation in the following subgroups:

term infants (37 weeks gestation and above), preterm infants (less than 37 weeks)
the type of ventilation device used (e.g. self-inflating bag, flow-inflating, T-pieces)

Criteria for considering studies for this review

Types of studies

All randomised and quasi-randomised controlled trials were to be included.

Types of participants

Term and preterm infants resuscitated using positive pressure ventilation at birth.

Types of interventions

Resuscitation using devices providing PEEP versus those not providing PEEP. For the purposes of this review we define PEEP as an end-expiratory pressure applied during intermittent positive pressure ventilation via a face mask or an endotracheal tube. Studies comparing these interventions alongside others in the delivery room (e.g.. surfactant, nasal continuous positive airways pressure) were considered eligible for inclusion.

Types of outcome measures

Death in the delivery room
Death during hospitalisation or to latest follow-up
Apgar scores at one and five minutes
Heart rate at five minutes
Endotracheal intubation in the delivery room
Endotracheal intubation during hospitalisation
Duration of respiratory support i.e.. nasal continuous airway pressure and ventilation via an endotracheal tube considered separately and in total
Duration of supplemental oxygen requirement
Chronic lung disease

the need for supplemental oxygen at 28 days of life
the need for supplemental oxygen at 36 weeks gestational age

Air leaks: pneumothorax, pneumomediastinum, pneumopericardium, pulmonary interstitial emphysema
Seizures including clinical and electroencephalographic
Hypoxic ischaemic encephalopathy (Sarnat classification - Sarnat 1976)
Cranial ultrasound abnormalities: any intraventricular haemorrhage (IVH), grade 3 or 4 (IVH) according to Papile classification (Papile 1978) and cystic periventricular leukomalacia
Long term neurodevelopmental outcome

Search strategy for identification of studies

The standard search strategy of the Cochrane Neonatal Review Group was used. Pub Med (1966 to May 2004) was searched using the MeSH headings Infant, Newborn, Resuscitation, Positive Pressure Respiration and the text words Positive End-Expiratory Pressure or PEEP. The Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2004) was searched using text words Newborn and Resuscitation. No language restrictions were applied. The abstracts of the Society for Pediatric Research and the European Society for Pediatric Research were searched from 1996-May 2004. Abstracts of the proceedings of the following annual meetings and journals were also hand-searched:

American Society of Critical Care Anesthesiologists and Society for Obstetric Anesthesia and Perinatology in Anesthesiology (1999-May 2004)
Canadian Journal of Anaesthesia (1999-May 2004)
Anaesthetic Research Society in British Journal of Anaesthesia (1999-May 2004)
Australian Society of Anaesthetists, Australian and New Zealand Intensive Care Society, Australian and New Zealand College of Anaesthetists Faculty of Intensive Care in Anaesthesia and Intensive Care (1996-May 2004).

Methods of the review

The standard methods of the Neonatal Review Group of the Cochrane Collaboration were employed. Trial searches, assessments of methodology and extraction of data were performed independently by each reviewer with comparison and resolution of any differences found at each stage. Assessment of methodology regarding blinding of randomisation, intervention and outcome measurements as well as completeness of follow-up was planned. We planned to evaluate the treatment effect using a fixed effects model as follows:

categorical data using relative risk (RR), relative risk reduction, risk difference (RD) and number needed to treat (NNT)
continuous data using mean, standard deviation and weighted mean difference (WMD)
the 95% confidence intervals for each measure of effect
an evaluation of heterogeneity using the I² statistic to help determine the suitability of pooling results.

Description of studies

No studies were found meeting the criteria for inclusion in this review

Excluded study
A case series of 30 infants resuscitated using a rebreathing (i.e. flow-inflating (anaesthesia) bag) which provided PEEP was described by Upton 1991. Comparisons were made by the investigators between this group and historical controls they had previously resuscitated using a self-inflating bag. PEEP appeared beneficial in establishing a functional residual capacity (FRC). In the 22 preterm infants studied, a strong association between absence of FRC and the development of hyaline membrane disease requiring ventilation was noted. This study was excluded because there were no contemporaneous controls and no randomisation.

Study awaiting assessment
A study comparing resuscitation with end-expiratory pressure versus resuscitation without end-expiratory pressure was performed by Finer 2003 as a pilot for a larger study comparing respiratory support using continuous positive airways pressure (CPAP) to intubation and intermittent positive pressure ventilation (IPPV) for extremely preterm infants at delivery. All infants were resuscitated using a T-piece device which could deliver PEEP. Infants were only to be intubated for resuscitation; no infants were intubated for surfactant administration. Infants were randomised to receive end-expiratory pressure at resuscitation - i.e. CPAP by face mask, or IPPV with PEEP via a face mask or endotracheal tube (ETT) - or no end-expiratory pressure - i.e. free-flow oxygen or IPPV without PEEP via a face mask or ETT. A full report of this study is awaited.

Methodological quality of included studies

No studies were found meeting the criteria for inclusion in this review

Results

No studies were found meeting the criteria for inclusion in this review

Discussion

We found no randomised controlled trials addressing the use of PEEP during neonatal resuscitation, thus this systematic review does not establish whether its use reduces mortality and morbidity or results in harm. We conclude that the widespread use of PEEP in this context (Graham 2001; O'Donnell(a) 2004; O'Donnell(b) 2004) is based only on evidence derived from animal models and observational studies. Future studies should enrol both term and preterm infants who require positive pressure ventilation for resuscitation at delivery. Suitable designs may include randomised comparisons of single manual ventilation devices with which PEEP may be delivered (e.g.. anaesthetic bags or T-pieces) used with and without PEEP. A more practical approach may be to compare devices which do not deliver PEEP (e.g. self-inflating bag) with ones which do. Important outcomes would include those specified in our criteria for considering studies for this review.

Reviewers' conclusions

Implications for practice

There is insufficient evidence to determine the safety and efficacy of PEEP during positive pressure ventilation at neonatal resuscitation.

Implications for research

Although there exists biological plausibility for the use of PEEP and many clinicians are using devices providing PEEP to resuscitate newborn infants, randomised clinical trials comparing positive pressure ventilation with and without PEEP at neonatal resuscitation are warranted.

Acknowledgements

Potential conflict of interest

None

Characteristics of excluded studies

Study	Reason for exclusion
Upton 1991	A cohort of 30 infants resuscitated using a rebreathing (i.e. flow-inflating (anaesthesia) bag which provided PEEP, compared with infants previously resuscitated with a self-inflating bag (historical controls). This study was excluded because there were no contemporaneous controls and no randomisation.

References to studies

References to excluded studies

Upton 1991 {published data only}

Upton CJ, Milner AD. Endotracheal resuscitation of neonates using a rebreathing bag. Archives of Disease in Childhood 1991;66:39-42.

References to studies awaiting assessment

Finer 2003 {published data only}

Finer N, Carlo W, Duara S, Fanaroff A, Donovan E for the NICHD Neonatal Network. Randomized pilot trial of delivery room CPAP in the ELBW infant. In: "Late breaker" abstract (LB-10) at Pediatric Academic Societies' Annual Meeting May 2003 (http://www.pas-meeting.org/2003Seattle/Abstracts/LBFullAbs.htm - accessed 28th May2004). May 2003.

* indicates the primary reference for the study

Other references

Additional references

Argiras 1987

Argiras EP, Blakely CR, Dunnill MS, Otremski S, Sykes MK. High PEEP decreases hyaline membrane formation in surfactant deficient lungs. British Journal of Anaesthesia 1987;59:1278-85.

Bjorklund 1997

Bjorklund LJ, Ingimarsson J, Custedt T, John J, Robertson B, Werner O, Vilstrup CT. Manual ventilation with a few large breaths at birth compromises the therapeutic effect of subsequent surfactant replacement in immature lambs. Pediatric Research 1997;42:348-55.

Graham 2001

Graham AN, Finer NN. The use of continuous positive airways pressure and positive end-expiratory pressure in the delivery room (abstract). Pediatric Research 2001;49:400A (2299).

ILCOR 2000

International Liaison Committee on Resuscitation. International guidelines for neonatal resuscitation: An Excerpt from the Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care: International Consensus on Science. Pediatrics 2000;106:E29.

Jobe 2002

Jobe AH, Kramer BW, Moss TJ, Newnham JP, Ikegami M. Decreased indicators of lung injury with continuous positive expiratory pressure in preterm lambs. Pediatric Research 2002;52:387-92.

Michna 1999

Michna J, Jobe AH, Ikegami M. Positive end-expiratory pressure preserves surfactant function in preterm lambs. American Journal of Respiratory and Critical Care Medicine 1999;160:634-9.

Milner 1991

Milner AD. Resuscitation of the newborn. Archives of Disease in Childhood 1991;66:66-9.

Naik 2001

Naik AS, Kallapur SG, Bachurski CJ, Jobe AH, Michna J, Kramer BW, Ikegami M. Effects of ventilation with different positive end-expiratory pressures on cytokine expression in the preterm lamb lung. American Journal of Respiratory and Critical Care Medicine 2001;164:494-8.

O'Donnell(a) 2004

O'Donnell CPF, Davis PG, Morley CJ. Neonatal resuscitation: review of ventilation equipment and survey of practice in Australia and New Zealand. Journal of Paediatrics and Child Health 2004;40:208-12.

O'Donnell(b) 2004

O'Donnell CPF, Davis PG, Morley CJ. Positive pressure ventilation at neonatal resuscitation: review of equipment and international survey of practice. Acta Paediatrica 2004;93:583-8.

Papile 1978

Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. Journal of Pediatrics 1978;92:529-34.

Probyn 2002

Probyn ME, Hooper S, Morley CJ. Reduction in oxygen requirement using positive end-expiratory pressure in a preterm lamb model of hyaline membrane disease (abstract). Pediatric Research 2002;51:A1954.

Sandhar 1988

Sandhar BK, Niblett DJ, Argiras EP, Dunnill MS, Sykes MK. Effects of positive end-expiratory pressure on hyaline membrane formation in a rabbit model of the neonatal respiratory distress syndrome. Intensive Care Medicine 1988;14:538-46.

Sarnat 1976

Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress: a clinical and electroencephalographic study. Archives of Neurology 1976;33:696-705.

Saugstad 1998

Saugstad OD. Practical aspects of resuscitating asphyxiated newborn infants. European Journal of Pediatrics 1998;157:S11-S15.

Thome 1998

Thome U, Topfer A, Schaller P, Pohlandt F. The effect of positive end expiratory pressure, peak inspiratory pressure and inspiratory time on functional residual capacity in mechanically ventilated preterm infants. European Journal of Pediatrics 1998;157:831-7.

Vilstrup 1992

Vilstrup CT, Bjorklund LJ, Larrson A, Lachmann B, Werner O. Functional residual capacity and ventilation homogeneity in mechanically ventilated small neonates. Journal of Applied Physiology 1992;73:276-83.

Notes

Published notes

Amended sections

Cover sheet
Synopsis
Abstract
Background
Objectives
Criteria for considering studies for this review
Search strategy for identification of studies
Methods of the review
Description of studies
Methodological quality of included studies
Results
Discussion
Reviewers' conclusions
Potential conflict of interest
References to studies
Other references
Characteristics of excluded studies
Characteristics of ongoing studies

Contact details for co-reviewers

Dr Peter G Davis, MD, MBBS
Consultant Paediatrician
Division of Paediatrics
Royal Women's Hospital
132 Grattan St
Melbourne
Victoria AUSTRALIA
3053
Telephone 1: +61 3 93442000 extension: 2130
Facsimile: +61 3 93471761
E-mail: pgd@unimelb.edu.au

Prof Colin J Morley, MA DCH MD FRCP FRCPCH FRACP
Professore / Divisional Director
Division of Neonatal Services
Royal Women's Hospital
132 Grattan St
Carlton
Victoria AUSTRALIA
3053
Telephone 1: +61 3 93442000 extension: 2527
E-mail: morleyc@cryptic.rch.unimelb.edu.au

This review is published as a Cochrane review in The Cochrane Library, Issue 4, 2004 (see http://www.thecochranelibrary.com/ for information). Cochrane reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and The Cochrane Library should be consulted for the most recent version of the Review.