A repeat literature search showed no new trials eligible for inclusion and there have been no substantive changes to the review.
Some evidence that nasal intermittent positive pressure ventilation (NIPPV) increases the effectiveness of nasal continuous positive airways pressure (NCPAP) in preterm babies who no longer need an endotracheal tube (tube in the wind pipe)
Preterm babies with breathing problems often require help from a machine (ventilator) that provides regular breaths through a tube in the windpipe. The process of extubation or removal of this tube does not always go smoothly and the tube may need to go back if the baby can't manage by him/herself. NCPAP and NIPPV are ways of supporting babies breathing in a less invasive way - the tubes are shorter and go only to the back of the nose and therefore cause less damage. NCPAP and NIPPV may be used after extubation to reduce the number of babies needing to go back onto the long endotracheal tube. NCPAP provides steady pressure to the back of the nose which is transmitted to the lungs, helping them to work better. NIPPV provides the same support but also adds some breaths from the ventilator. The three studies that have compared NCPAP and NIPPV each show that NIPPV reduces the need for the endotracheal tube to go back in. Further work to make sure NIPPV is safe is required.
Preterm infants may experience difficulty with spontaneous, unassisted breathing for a variety of reasons including lung immaturity, chest wall instability, upper airway obstruction and poor central respiratory drive. Historically, the primary method of support for these infants has been endotracheal intubation and intermittent positive pressure ventilation. While this method is effective, it is accompanied by unwanted complications (upper airway damage, bronchopulmonary dysplasia, sepsis) and considerable economic cost. Minimising the duration of endotracheal intubation or avoiding it completely has been a goal of neonatal intensive care. Nasal continuous positive airway pressure is a less invasive way of providing respiratory support to neonates at risk of, or actually experiencing respiratory failure. A systematic review of trials comparing nasal continuous airway pressure (NCPAP) with treatment with oxyhood concluded that NCPAP commenced immediately following a period of endotracheal intubation reduces the rate of adverse events (apnea, respiratory acidosis, and increased oxygen requirements) leading to reintubation (Davis 1999). In this systematic review approximately a quarter of all preterm infants allocated to NCPAP failed extubation and therefore the opportunity exists to further improve outcomes for infants thought to no longer require an endotracheal tube.
Adults and older children with acute or chronic ventilatory failure of various etiologies, including chronic obstructive pulmonary disease (Bott 1993), severe kyphoscoliosis (Ellis 1988) and pre-lung transplantation cystic fibrosis (Piper 1992) have been treated with intermittent positive pressure ventilation delivered via a nasal interface. Improvements in respiratory function have been described.
Nasal intermittent positive pressure ventilation has been applied to neonates for a variety of indications and was reported as being used by 53% of Canadian tertiary care nurseries in the mid 1980s (Ryan 1989). The physiological benefits of the technique have been evaluated. NIPPV has been shown to reduce asynchronous thoracoabdominal motion perhaps as a result of reducing tube resistance and/or better stabilisation of the chest wall (Kiciman 1998). Its use improves tidal and minute volumes and decreases the inspiratory effort required by neonates compared with NCPAP (Moretti 1999). This technique has not been without problems in neonates. Garland 1985 reported an association between the use of ventilation via nasal prongs and increased risk of gastrointestinal perforation. In the past, the lack of high quality evidence has led to variability in practice between neonatal intensive care units with respect to this potentially useful method of respiratory support.
In preterm infants having their endotracheal tube removed following a period of intermittent positive pressure ventilation (IPPV), does management with nasal intermittent positive pressure ventilation (NIPPV) lead to a decreased proportion requiring additional ventilatory support, compared to extubation to continuous positive airway pressure (NCPAP)?
In addition we aimed to compare the rates of endotracheal reintubation, gastric distension and gastrointestinal perforation, chronic lung disease, duration of hospitalisation and rates of apnea between the two groups.
A sensitivity analysis including only truly randomised trials was planned if any quasi-randomised trials were identified.
Subgroup analyses were planned to determine whether responses differed according to different methods of NIPPV delivery (synchronised or not, nasal or nasopharyngeal). Subgroup analysis was planned to determine whether the use (or not) of methylxanthines alters responses.
All randomised and quasi-randomised trials were included
Preterm infants (ie those born before 37 completed weeks gestation) being extubated following a period of endotracheal intubation
Intermittent positive pressure ventilation administered via the nasal route either by short nasal prongs or nasopharyngeal tubes vs nasal CPAP delivered by the same methods.
Primary outcome: Respiratory failure defined by respiratory acidosis, increased oxygen requirement or apnea that is frequent or severe leading to additional ventilatory support during the week post extubation
Secondary outcomes
1. Endotracheal reintubation during the week post extubation
2. Rates of abdominal distension requiring cessation of feeds
3. Rates of gastrointestinal perforation diagnosed radiologically or
at operation
4. Rates of chronic lung disease defined as 1) requirement for supplemental
oxygen at 28 days of life or 2) requirement for supplemental oxygen at
36 weeks corrected age
5. Duration of hospitalisation
6. Rates of apnea and bradycardia expressed as events per hour
See: Collaborative Review Group search strategy.
MEDLINE (1966 - April 14, 2003) was searched using the MeSH terms: Infant,
Newborn (exp) and Positive-pressure respiration (exp). Other sources included
the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane
Library, Issue 1, 2003), CINAHL using search terms: Infant newborn and
intermittent positive pressure ventilation, expert informants, previous
reviews including cross-references and conference and symposia proceedings
were used.
Criteria and methods used to assess the methodological quality of the trials: standard method of the Cochrane Collaboration and its Neonatal Group were used.
The three reviewers independently assessed the quality of studies using the following criteria: blinding of randomisation, blinding of intervention, completeness of followup and blinding of outcome measurement. Additional information was sought from the authors when required. Data were extracted independently by the 3 reviewers, then compared and differences resolved. Categorical data (proportion requiring reintubation) were analysed using relative risk, risk difference and number needed to treat. Continuous data (frequency of apneas) were analysed using weighted mean difference. The fixed effects model was used.
Subgroup analyses were planned, using the same methods, to determine whether responses differed according to methods of NIPPV delivery and whether or not methylxanthines were used concurrently. Subgroup analyses based on characteristics of participants were planned: birth weight (eg infants < 1000g) and corrected age at time of intervention (eg infants < 28 weeks).
Three trials meeting the inclusion criteria of the review were identified - Barrington 2001, Friedlich 1999, Khalaf 2000. Details are included in the table Characteristics of Included Studies. Rescue NIPPV was permitted for infants failing NCPAP in all three studies but the primary outcome was analysed on an intention to treat basis. The criteria for offering rescue treatment appeared to be at clinicians' discretion and the proportions offered rescue NIPPV varied between the three trials. Therefore the outcome "endotracheal reintubation", although available for each of the trials, assumed a different meaning in each.
The inclusion criteria varied somewhat between trials but broadly they enrolled very low birth weight (VLBW) infants, ie those at moderate risk of requiring endotracheal reintubation. In two trials (Khalaf 2000 and Barrington 2001) the use of methylxanthines was mandatory and in the third (Friedlich 1999) extensively prescribed (86%). Infants were extubated from low levels of ventilator support ( ventilator rates < 25 breaths per minute and oxygen concentrations <40%). The differences in these settings between the studies were small. An interesting variation in ventilatory strategies was noted between the centres: In spite of little variation seen in enrolment criteria, Khalaf 2000 and Barrington 2001 extubated their infants at a median age of less than one week, whereas infants in the Friedlich 1999 study were extubated at a median age of 18.5 and 21 days in the two groups.
NIPPV delivery was synchronised in all trials using the Infant Star ventilator with Star Synch abdominal capsule. Ventilator settings applied after extubation varied - rates between 10 and 25 per minute, PIP from that used pre-extubation to 2 to 4 cm water above that used pre-extubation. The levels to be used in the NCPAP groups also varied between studies - Barrington 2001 set a level of 6 cm water and Friedlich 1999 and Khalaf 2000 prescribed a range between 4 and 6 cm water. No attempt was made to match NIPPV and NCPAP groups with respect to mean airway pressure delivered. Devices used to deliver NCPAP/NIPPV also varied. Barrington 2001 used binasal, short Hudson Prongs, Friedlich 1999 used binasal, nasopharyngeal tubes and Khalaf 2000 used Argyle prongs. The primary outcome was assessed over the 72 hours post-extubation by Barrington 2001 and Khalaf 2000 and over 48 hours by Friedlich 1999.
Methodological quality was assessed using the criteria of the Neonatal Cochrane Review Group.
Blinding of randomisation: All three included trials met this criterion.
Blinding of intervention: This was not attempted by any study.
Complete followup: Achieved in all trials.
Blinding of outcome measurement: This was not attempted by any study.
After discussion between the three reviewers, there was no disagreement regarding quality assessment and data extraction from the three identified trials.
All three studies used synchronised NIPPV, therefore no subgroup analysis was performed to examine whether this is an important factor in successful delivery of NIPPV. Likewise almost all infants received methylxanthines prior to extubation so the planned subgroup analysis was not performed. Two trials used short binasal prongs (Barrington 2001, Khalaf 2000) and the other binasopharyngeal prongs (Friedlich 1999). Both were effective and the question of which is superior remains unanswered.
Comparisons of NIPPV with NCPAP in both studies are potentially confounded by differences in mean airway pressure (MAP) between the groups. None of the authors present data on MAP in the NIPPV group but this may have been higher than the CPAP level in the other group. Differences in outcomes may be due simply to a higher mean airway pressure in the NIPPV group.
The 3 trials identified in this review have no major methodological limitations. Because of the nature of the interventions, it has been impossible to blind caregivers and the possibility exists that bias could have arisen through uneven use of cointerventions. Potential confounders such as methylxanthine usage and weaning strategies have been dealt with by having management protocols in place, and the use of objective failure criteria in the extubation trials enhances confidence in their findings.
NIPPV is a potentially useful way of augmenting NCPAP. The relatively
recent ability to synchronise the ventilator breaths with the infant's
own respiratory cycle has led to renewed interest in this mode of ventilatory
support. For the reasons outlined in the Background it appears desirable
to minimise the duration of endotracheal intubation of preterm infants
and the results of this review suggest that NIPPV may assist in achieving
this aim by lowering the rate of respiratory failure after extubation.
Infants being extubated following a period of endotracheal intubation
have a reduced incidence of symptoms leading to reintubation, in particular
respiratory acidosis and apnea. However it is also apparent that, within
the small population studied, infants "failing" NCPAP may be rescued by
a course of NIPPV. Individual neonatal intensive care units may interpret
these results differently. The provision of synchronised NIPPV requires
a ventilator capable of delivering this mode of support. Less expensive
methods of NCPAP delivery exist and issues of resource allocation may be
important in some hospitals where synchronised NIPPV may be reserved for
infants who "earn" it. Alternatively, well equipped units may elect to
"prophylactically" use synchronised NIPPV to ensure stability of their
infants.
NIPPV is a useful method of augmenting the beneficial effects of NCPAP in preterm infants. Its use reduces the incidence of symptoms of extubation failure when compared with NCPAP. Within the limits of the small numbers of infants randomised to NIPPV there is a reassuring absence of the gastrointestinal side-effects that were reported in previous case series.
Future trials should enrol sufficient infants to detect differences in important outcomes such as chronic lung disease and gastrointestinal perforation. The impact of synchronisation of NIPPV on the technique's safety and efficacy should be established in future trials. Such trials may consider matching the MAP rather than PEEP level in NIPPV infants to the CPAP level in the NCPAP group.
The authors acknowledge the generosity of Drs Friedlich, Barrington and Bhandari who supplied "preprints" of their manuscripts and additional information for this review.
None
| Study | Methods | Participants | Interventions | Outcomes | Notes | Allocation concealment |
| Barrington 2001 | Blinding of randomisation: Yes - sequentially numbered sealed
opaque envelopes. Blinding of intervention: No Complete followup: Yes Blind outcome assessment: No |
Included infants < 1250g birth weight (mean 831 +/- 193g) , <6 weeks of age (mean 7.6 +/- 9.7 days), requiring < 35% oxygen and <18 breaths per minute on synchronised intermittent mechanical ventilation. All infants loaded with aminophylline before extubation. | Experimental group - synchronised NIPPV = nSIMV: R of 12 and
PIP of 16, PEEP of 6, PIP increased to achieve measured pressure of at
least 12. Used Grasby capsule, Infant Star ventilator and Hudson nasal
prongs. Control: Nasal CPAP of 6. |
Primary: failure of extubation by 72 hours because of either
pCO2 >70, oxygen requirement of >70% or severe or recurrent apnea
(defined). Secondary: rates of reintubation, abdominal distension, feeding intolerance and chronic lung disease. |
Power calculation performed. 54 infants enrolled - 27 in each group. Most infants failing NCPAP tried on NIPPV before reintubation. |
A |
| Friedlich 1999 | Blinding of randomisation: Yes - sealed randomisation cards. Blinding of intervention: No Complete follow up: Yes Blind outcome assessment: No |
Included: infants with birthweight 500 -1500g (means 963+/-
57g and 944 +/- 43g) considered by attending ready for extubation (SIMV rate
< 12, peak pressure <23, end expiratory pressure <6, oxygen requirement
< 40%. Aminophylline not mandated but given in ~ 85% of infants. Extubated
at 26.3 +/- 6.1 and 19.9 +/-3.8 days of life. Excluded: infants with sepsis, necrotising enterocolitis, symptomatic PDA, congenital anomalies. |
Experimental group - nasopharyngeal 3 Fr gauge tube, Infant
Star ventilator, synchronised NIPPV = nSIMV with rate of 10, PIP = that before
extubation, PEEP 4-6, IT = 0.6. Control: nasopharyngeal CPAP to desired level of attending. |
Primary: failure of extubation by 48 hours because either pH
< 7.25, pCO2 increased by 25%, oxygen requirement greater than 60%,
SIMV rate > 20 (in NIPPV group), PIP > 26 or PEEP > 8 in NIPPV
group, apnea requiring bag and mask ventilation. Secondary: endotracheal reintubation, abdominal distension, perforation or NEC, feeding delay (not defined) and nasal bleeding. |
Power calculation performed. Study closed early after interim
analysis (stopping rule not specified). 41 infants enrolled - 22 NIPPV and 19 NCPAP. Most infants failing NCPAP tried on NIPPV before reintubation. |
A |
| Khalaf 2000 | Blinding of randomisation: Yes - sealed envelopes Blinding of intervention: No Complete followup: Yes Blinding of outcome assessment: No |
Included: infants with gestational age (GA) < 34 weeks with respiratory distress syndrome ventilated using an endotracheal tube. Mean birthweights 1088g and 1032g and mean GAs of 28 weeks. Ventilator settings PIP<or=16 cm water, PEEP<or=5, R 15-25/minute and <35% oxygen. All had a therapeutic blood level of aminophylline and hematocrit > 40%. | Experimental group - synchronised NIPPV via Argyle prongs,
Infant Star ventilator at PEEP level less than or equal to 5 cm water, rate
of 15 to 25 per minute and PIP set 2 to 4 cm water above that used pre-extubation.
Gas flow set at 8-10 l/minute in both groups. Conrol group had NCPAP delivered by Argyle prongs from a Bear Cub or Infant Star ventilator at level of 4 to 6 cm water. |
Primary: failure of extubation by 72 hours because pH<7.25
or pCO2>60 mm Hg, single episode of severe apnea requiring bag and mask
ventilation or frequent apnea or desaturations (defined). Secondary outcomes included chronic lung disease defined as supplemental oxygen requirement at 36 weeks corrected age, days of ventilation and hospitalisation. Data on rates of feeding intolerance provided by authors. |
Power calculation performed. 64 infants enrolled - 34 NIPPV
and 30 NCPAP. Two infants failing NCPAP tried on NIPPV (successfully) before reintubation. For the outcome "abdominal distension causing cessation of feeds" the denominators are the numbers offered enteral feeds during the 72 hour study period ie 21(NIPPV) and 20 (NCPAP). |
A |
| Study | Reason for exclusion |
| Moretti 1999 | Randomised cross-over trial. Each infant (n=11, mean BW=1141g) received NIPPV and NCPAP in random order for a period of 1 hour. Outcomes were respiratory rates and pulmonary function tests, ie not those outcome criteria specified in the protocol |
Barrington KJ, Finer NN, Bull D. Randomised controlled trial of nasal synchronized intermittent mandatory ventilation compared with continuous positive airway pressure after extubation of very low birth weight infants. Pediatrics 2001;107:638-641.
Friedlich 1999 {published data only}
Friedlich P, Lecart C, Posen R, Ramicone E, Chan L, Ramanathan R. A randomized trial of nasopharyngeal-synchronised intermittent mandatory ventilation versus nasopharyngeal continuous positive airway pressure in very low birth weight infants following extubation. J Perinatol 1999;19:413-418.
Khalaf 2000 {published and unpublished data}
Khalaf MN, Brodsky N, Hurley J, Bhandari V. A prospective randomised controlled trial comparing synchronized nasal intermittent positive pressure ventilation (SNIPPV) versus nasal continuous positive airway pressure (NCPAP) as mode of extubation. Pediatr Res 1999;45:204a.
Moretti C, Gizzi C, Papoff P, Lampariello S, Capoferri M, Calcagnini G, Bucci G. Comparing the effects of nasal synchronized intermittent positive pressure ventilation (nSIPPV) and nasal continuous positive airway pressure (nCPAP) after extubation in very low birth weight infants. Early Hum Dev 1999;56:166-177.
* indicates the primary reference for the study
Bott J, Carroll MP, Conway JH, Keilty SE, Ward EM, Brown AM, et al. Randomised controlled trial of nasal ventilation in acute ventilatory failure due to chronic obstructive airways disease. Lancet 1993;341:1555-1557.
Davis PG, Henderson-Smart DJ. Nasal continuous positive airways pressure immediately after extubation for preventing morbidity in preterm infants (Cochrane Review). In: The Cochrane Library, Issue 2, 1999.
Derleth DP. Clinical experience with low rate mechanical ventilation via nasal prongs for intractable apnea of prematurity. Pediatr Res 1992;32:200A.
Ellis ER, Grunstein RR, Chan S, Bye PT, Sullivan CE. Noninvasive ventilatory support during sleep improves respiratory failure in kyphoscoliosis. Chest 1988;94:811-815.
Garland JS, Nelson DB, Rice T, Neu J. Increased risk of gastrointestinal perforations in neonates mechanically ventilated with either face mask or nasal prongs. Pediatrics 1985;76:406-410.
Kiciman NM, Andréasson B, Bernstein G, Mannino FL, Rich W, Henderson C, Heldt GP. Thoracoabdominal motion in newborns during ventilation delivered by endotracheal tube or nasal prongs. Pediatr Pulmonol 1998;25:175-181.
Piper AJ, Parker S, Torzillo PJ, Sullivan CE, Bye PT. Nocturnal nasal IPPV stabilizes patients with cystic fibrosis and hypercapnic respiratory failure. Chest 1992;102:846-850.
Ryan CA, Finer NN, Peters KL. Nasal intermittent positive-pressure ventilation offers no advantages over nasal continuous positive airway pressure in apnea of prematurity. Am J Dis Child 1989;143:1196-1198.
Davis PG, Lemyre B, De Paoli AG. Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation (Cochrane Review). In: The Cochrane Library, Issue 3, 2001. Oxford: Update Software.
01.01 Respiratory failure post-extubation
01.02 Endotracheal reintubation
01.03 Abdominal distension causing cessation of feeds
01.04 Gastrointestinal perforation
01.05 Chronic lung disease (oxygen supplementation at 36 weeks)
01.06 Duration of hospitalisation (days)
01.07 Rates of apnea (episodes/24 hours)
| Comparison or outcome | Studies | Participants | Statistical method | Effect size |
|---|---|---|---|---|
| 01 NIPPV vs NCPAP to prevent extubation failure | ||||
| 01 Respiratory failure post-extubation | 3 | 159 | RR (fixed), 95% CI | 0.21 [0.10, 0.45] |
| 02 Endotracheal reintubation | 3 | 159 | RR (fixed), 95% CI | 0.39 [0.16, 0.97] |
| 03 Abdominal distension causing cessation of feeds | 2 | 136 | RR (fixed), 95% CI | 1.76 [0.77, 4.05] |
| 04 Gastrointestinal perforation | 0 | 0 | RR (fixed), 95% CI | No numeric data |
| 05 Chronic lung disease (oxygen supplementation at 36 weeks) | 2 | 118 | RR (fixed), 95% CI | 0.73 [0.49, 1.07] |
| 06 Duration of hospitalisation (days) | 2 | 118 | WMD (fixed), 95% CI | -5.48 [-16.76, 5.79] |
| 07 Rates of apnea (episodes/24 hours) | 1 | 54 | WMD (fixed), 95% CI | -3.10 [-7.92, 1.72] |
Brigitte Lemyre
Division of Neonatology
Children's Hospital of Eastern Ontario
401 Smyth Road
Ottawa
Ontario CANADA
KlH 8L1
Telephone 1: 1 613 737 2415
Facsimile: 1 613 738 4847
E-mail: blemyre@ottawahospital.on.ca
| This review is published as a Cochrane review
in The Cochrane Library 2003, Issue 3, 2003 (see www.CochraneLibrary.net
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. |
