Positive end-expiratory pressure for resuscitation of newborn infants at birth
O'Donnell C, Davis P, Morley C
Cover sheet
Title
Positive end-expiratory pressure for resuscitation of newborn infants at birthReviewers
O'Donnell C, Davis P, Morley CDates
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 DavisContribution 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 1987Argiras
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.auProf 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.
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