No substantive change in the review update was made in June 2004 as no new trials were identified after a thorough literature search.
Nasal intermittent positive pressure ventilation (NIPPV) is a potentially beneficial treatment for apnea in premature babies, but more research is needed to confirm effectiveness and safety.
Recurrent spells of apnea (pause in breathing greater than 20 seconds) are almost universal in babies born before 34 weeks gestation. Nasal continuous positive airway pressure (NCPAP), delivered via small prongs inserted in the baby's nose, offers breathing support and is a useful treatment for apnea, but not all babies respond. Some infants fail and require a breathing tube inserted into their trachea (windpipe), which has potential complications (infection, injuries to the vocal cords). This review of two small trials suggests that nasal intermittent positive pressure ventilation (NIPPV), also delivered via nasal prongs, may be more effective than NCPAP alone in preterm babies whose apneas are frequent or severe. Further research is needed to confirm effectiveness and safety, as few babies have been studied so far.
Types of outcome measures:
- failure of therapy as defined by apnea that is frequent or severe requiring additional ventilatory support
- rates of endotracheal intubation
- rates of apnea and bradycardia expressed as events per hour
- gastrointestinal complications i.e. abdominal distension requiring cessation of feeds, or GI perforation
Implications for practice: NIPPV may be a useful method of augmenting the beneficial effects of NCPAP in preterm infants with apnea that is frequent or severe. Its use appears to reduce the frequency of apneas more effectively than NCPAP. Additional safety and efficacy data are required before recommending NIPPV as standard therapy for apnea.
Implications for research: Future trials with sufficient power should assess the efficacy (reduction in failure of therapy) and safety (GI complications) of NIPPV. Outcomes should be assessed throughout the entire period during which the infant requires assisted ventilation. The recent ability to synchronise NIPPV with an infant's spontaneous respirations is a promising development requiring further assessment.
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 hypoventilation and oxygen saturation levels have been described.
Miller 1985 reported a case series of 10 very small newborn infants with intractable apnea of prematurity who were treated with IPPV administered via nasal prongs. A survival rate of 50% was found, but there was no comparison with a control group. A more recent case series reported that 5 of 7 infants failing NCPAP because of intractable apnea were managed without intubation and mechanical ventilation using nasal IPPV, with only minor side effects (Derleth 1992). NIPPV in various forms was reported to be used by 53% of Canadian tertiary care nurseries in the mid 1980s (Ryan 1989). 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). The 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.
Until recently, NIPPV was not synchronized with the infant's breathing. It is possible that gastrointestinal side-effects might be reduced if ventilator breaths were delivered in synchrony with laryngeal opening.
1. In preterm infants with recurrent apnea, does treatment with NIPPV
reduce the rate of failure of therapy (frequent or severe apneas requiring
additional ventilatory support or use of endotracheal intubation) as compared
with treatment with NCPAP?
2. Does NIPPV lead to more GI complications i.e. gastric distension
requiring cessation of feeds, or GI perforation, as compared to NCPAP?
Subgroup analyses were planned on the basis of:
- method of NIPPV delivery (nasal prongs or nasopharyngeal tube)
- methylxanthine usage
- characteristics of participants: birth weight and corrected age at
time of intervention, eg with cut-offs at 1000g and 28 weeks
Secondary outcome measures:
1. a) Rates of apnea and bradycardia expressed as events per hour
b) Differences in rates of apnea (before-after treatment) expressed as events per hour
- this outcome was identified after examining the available trials
2. C02 levels (mm Hg) after 4 to 6h of treatment - this outcome was identified after examining the available trials
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. Data were extracted independently by the 3 reviewers, then compared and differences resolved. Categorical data (proportion requiring intubation) were analysed using relative risk, risk difference and number needed to treat. Continuous data (frequency of apneas, C02 levels) were analysed using means and weighted mean difference. Additional information was sought from the authors: Lin 1998 generously provided individual patient data from which it was possible to calculate differences in apnea rates, i.e. rate before intervention minus that after intervention. The mean and standard deviation of the difference in apnea rate was then calculated. The fixed effects model was used. The crossover trial of Ryan (Ryan 1989) was handled in accordance with the methods of the Cochrane Neonatal Review Group - ie the effect and variance estimators from analysis of both periods combined were 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).
Blinding of randomisation: The two studies met this criterion.
Blinding of intervention: This was not attempted by either study.
Complete follow-up: Achieved in both trials.
Blinding of outcome measurement: This was attempted only by Lin 1998. In this study, the primary outcomes, rates of apnea and bradycardia, were determined from printouts of cardiorespiratory traces assessed by observers blinded to treatment allocation.
1. Failure of therapy: need for additional ventilatory support during the 4 to 6 hour period of the study
No infants were "rescued" by the alternative mode of treatment, ie any
infant requiring additional support received endotracheal intubation. Both
trials (n=74 observations) reported this outcome, but only 1 infant (randomised
to NCPAP) needed intubation {RR 0.30 (0.01, 6.84), RD -0.029 (-0.120, 0.062)}.
2. Rates of apnea (events/hour):
Ryan (1989) (40 observations) reported no significant decrease in rate
of apnea with NIPPV as compared to NCPAP: WMD -0.10 (-0.53, 0.33).
3. Change in rates of apnea (events/hour):
Lin (1998)(n=34) showed a statistically significantly greater reduction
in the rate of apnea in the NIPPV group: WMD -1.19 (-2.31, -0.07).
4. pC02 (mmHg) at 4 to 6h:
The final pCO2 value reported in each trial was used, at 4 hours for
Lin and 6 hours for Ryan. The meta-analysis showed no significant difference
in pCO2 values {WMD 0.95 (-3.05, 4.94)}.
Planned subgroup analyses could not be performed. Both trials used
NIPPV that was not synchronised and both used aminophylline in all patients.
Ryan (1989) used both nasal prongs and nasopharyngeal tubes but did not
report results based on mode of CPAP delivery. Lin's patients were all treated
with Hudson prongs.
NIPPV is a potentially useful way of augmenting NCPAP. The relatively recent ability to synchronise ventilator breaths with the infant's own respiratory cycle has led to renewed interest in this mode of ventilatory support. For many reasons including trauma to the airway, barotrauma and infection, it appears desirable to minimise the usage and duration of endotracheal intubation of preterm infants and the results of this review suggest that NIPPV may assist in achieving this aim.
The question of whether NIPPV should be used for infants experiencing
troublesome apnea has considerable overlap with that relating to postextubation
care, given that one of the most common causes of extubation failure is recurrent
apnea. Recent RCTs (Barrington 1999, Friedlich 1999) have shown that NIPPV
is superior to CPAP in preventing extubation failure without major side effects
(GI perforation or significant feeding intolerance leading to cessation of
feeds).
The authors acknowledge the extra information provided by Dr Lin and thank Prof David Henderson-Smart for his help in the preparation of this review.
Study | Methods | Participants | Interventions | Outcomes | Notes | Allocation concealment |
Lin 1998 | Blinding of randomisation: Yes - sealed envelope Blinding of intervention: no Complete followup: Yes Blinding of outcome assessment: No | Included: premature infants not receiving ventilatory support, having > 2 apneas per hour over preceding 4 hours and failing to respond to tactile stimulation and oxygen supplementation and aminophylline. Excluded: infants with apnea related to IVH, sepsis, electrolyte imbalance of congenital anomalies. | Experimental group (n=18): non-synchronised, NIPPV with PIP of 12-20 delivered via nasal prongs. Control group (n=16): 4-5 cm H20 CPAP via Hudson prongs. Both groups had orogastric tube in situ and were not fed during the study. Infants were kept in the supine position and the mandible held with a strap to prevent air leakage. | Primary outcome: frequencies of apneic and bradycardic episodes before and after the intervention. Printouts of cardiorespiratory monitoring were reviewed by a blinded observer. Secondary outcomes: blood gas analyses before and after intervention. | A | |
Ryan 1989 | Blinding of randomisation: Yes - computer generated randomisation schedule. Blinding of intervention: No Complete followup: Yes Blind outcome assessment: Yes for bradycardia and apnea. | Included: Stable infants < 32 weeks being treated with nasal CPAP for apnea of prematurity and receiving aminophylline. Excluded: infants with known causes of apnea. | 20 infants enrolled in the trial: 10 randomized to NIPPV (not synchronised) with PIP of 20, PEEP of 4 and rate of 20 delivered by nasal prongs or nasopharyngeal tubes; 10 randomised to NCPAP of 4. Each group crossed over to the other treatment after 6 hours. | Primary outcomes: rates of apnea (>15 sec with fall in transcutaneous p02 of >5 mm Hg and/or drop in heart rate of > 20%) and bradycardia (>20% drop in baseline geart rate). Both expressed as events per hour. Secondary: arterial blood gases taken at 0, 2 and 6 hours of each treatment. | Crossover study: randomised, 2-period crossover | A |
Lin CH, Wang ST, Lin YJ, Yeh TF. Efficacy of nasal intermittent positive pressure ventilation in treating apnea of prematurity. Pediatric Pulmonology 1998;26:349-53.
Ryan 1989 {published data only}
Ryan CA, Finer NN, Peters KL. Nasal intermittent positive-pressure ventilation offers no advantages over nasal continuous positive airway pressure in apnea of prematurity. American Journal of Diseases of Children 1989;143:1196-8.
* indicates the primary reference for the study
Andréasson B, Lindroth M, Svenningsen NW, Jonson B.. Effects on respiration of CPAP immediately after extubation in the very preterm infant. Pediatric Pulmonology 1988;4:213-8.
Barrington KJ, Finer NN. The natural history of the appearance of apnea of prematurity. Pediatric Research 1991;29:372-5.
Barrington KJ, Bull D, Finer NN. Randomized controlled trial of nasal synchronized intermittent mandatory ventilation after extubation of very low birth weight infants. Pediatric Research 1999;45:184A.
Bott J, Carroll MP, Conway JH, Keitly 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;341:1555-7.
Derleth DP. Clinical experience with low rate mechanical ventilation via nasal prongs for intractable apnea of prematurity. Pediatric Research 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;94:811-5.
Friedlich P, Lecart C, Posen R, Ramicone E, Chan L, Ramanathan R. A randomized trial of nasopharyngeal synchronized intermittent mandatory ventilation versus nasopharyngeal continuous positive airway pressure in very low birth weight infants after extubation. Journal of Perinatology 1999;19:413-8.
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;76:406-10.
Henderson-Smart D, Steer P. Methylxanthine treatment for apnea in preterm infants (Cochrane Review). In: Cochrane Library, Issue 4, 1999. Oxford: Update Software.
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. Pediatric Pulmonology 1998;25:175-81.
Miller MJ, Carlo WA, Martin RJ. Continuous positive airway pressure selectively reduces obstructive apnea in preterm infants. Journal of Pediatrics 1985;106:91-4.
Moretti C, Marzetti G, Agostino R, Panero A, Picece BS, Mendicini M et al. Prolonged intermittent positive pressure ventilation by nasal prongs in intractable apnea of prematurity. Acta Paediatrica Scandinavica 1981;70:211-6.
Nelson NM. Members of the task force on prolonged apnea of the American Academy of Pediatrics. Pediatrics 1978;61:651-2.
Piper AJ, Parker S, Torzillo PJ, Sullivan CA, Bye PT. Nocturnal nasal IPPV stabilizes patients with cystic fibrosis and hypercapnic respiratory failure. Chest 1992;102:846-50.
Ruggins NR. Pathophysiology of apnea in preterm infants. Archives of Disease in Childhood 1991;66:70-3.
Schmidt BK. Methylxanthine therapy in premature infants: Sound practice, disaster, or fruitless byway? Journal of Pediatrics 1999;135:526-8.
Lemyre B, Davis PG, De Paoli AG. Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for apnea of prematurity (Cochrane Review). In: The Cochrane Library, Issue 3, 2000. Oxford: Update Software.
Lemyre B, Davis PG, De Paoli AG. Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for apnea of prematurity (Cochrane Review). In: The Cochrane Library, Issue 1, 2002. Oxford: Update Software.
Lemyre B, Davis PG, De Paoli AG. Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for apnea of prematurity (Cochrane Review). In: The Cochrane Library, Issue 3, 2003. Oxford: Update Software.
01.01 Failure of therapy: intubation
01.02 Rate of apnea (events/hr)
01.03 Change in rate of apnea (events/hr)
01.04 pC02 at 4-6h (mmHg)
Comparison or outcome | Studies | Participants | Statistical method | Effect size |
---|---|---|---|---|
01 NIPPV vs NCPAP | ||||
01 Failure of therapy: intubation | 1 | 74 | RR (fixed), 95% CI | 0.30 [0.01, 6.84] |
02 Rate of apnea (events/hr) | 1 | 40 | WMD (fixed), 95% CI | -0.10 [-0.53, 0.33] |
03 Change in rate of apnea (events/hr) | 1 | 34 | WMD (fixed), 95% CI | -1.19 [-2.31, -0.07] |
04 pC02 at 4-6h (mmHg) | 2 | 74 | WMD (fixed), 95% CI | 0.95 [-3.04, 4.94] |
Antonio G De Paoli, Dr
Neonatal Fellow
Neonatal Unit
Royal Women's Hospital
132 Grattan St
Carlton, Melbourne
Victoria AUSTRALIA
3053
Telephone 1: +61 3 93442000 extension: 2472
E-mail: depaolitony@netscape.net
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. |