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Continuous distending pressure for respiratory distress in preterm infants

RHL Commentary by Deorari A

1. INTRODUCTION

Nearly 6%–10% of newborn infants suffer from respiratory disease due to pneumonia, delayed adaptation, meconium aspiration syndrome, respiratory distress syndrome and apnea (1). Respiratory distress syndrome (RDS) is an important cause of morbidity and mortality in premature infants. Use of antenatal steroids, surfactant replacement therapy and intermittent positive pressure ventilation (IPPV) has greatly improved outcomes for neonates with RDS (2).

IPPV is currently regarded as the standard of treatment for neonates with RDS. However, IPPV is invasive and has the potential to damage the lungs of neonates. Continuous distending pressure (CDP), when applied to premature babies with RDS, re-expands the collapsed alveoli, splints the airways, reduces effort of breathing and improves pattern and regularity of respiration, leading to improved blood oxygenation, lower carbon dioxide concentrations and improved pH. Compared with IPPV, CDP has been associated with lesser lung injury and lower incidence of chronic lung disease (3, 4, 5). CDP is gaining popularity even in developing countries (6, 7).

The present Cochrane review sought to determine the effect of CDP "on the need for IPPV and associated morbidity in spontaneously breathing preterm infants with respiratory distress" (8).

2. METHODS OF THE REVIEW

The review includes randomized or quasi-randomized studies on preterm babies with respiratory failure where CDP (including continuous positive airway pressure using mask, prongs, nasopharyngeal prongs or endotracheal tube or continuous negative pressure using a chamber applied on thorax and lower body) was compared with standard care consisting of oxygen therapy by hood. The primary outcome was treatment failure as defined by death or respiratory failure based on use of assisted ventilation, blood gas criteria, or transfer to a neonatal intensive care unit. The secondary outcomes studied were pulmonary air leak, chronic lung disease (defined as oxygen dependency at 28 days of life), use of surfactant and abnormal neurosonogram.

The authors employed the standard comprehensive search strategy recommended by the Neonatal Cochrane Group, which includes search of electronic databases, conference proceedings, cross-references, and journal hand-searching. Included trials were assessed for presence of risk of bias and heterogeneity. Most of the trials included in the meta-analysis were done in 1970s, when practices were markedly different as compared to the present day.

3. RESULTS OF THE REVIEW

Six trials involving 355 preterm neonates were included in this review. In addition to most trials being from 1970s, when relatively heavier (mean birth weight between 1700 g and 2000 g) infants were included in trials, limitations identified by the review authors included: small number of neonates; use of varied nasal interfaces; delayed start of treatment (more than 10 h after birth in all except one study); and lack of proper blinding and outcome assessment. Pooled analysis of included trials showed that continuous distending pressure use reduced the overall mortality rate [relative risk (RR) 0.52, 95% confidence interval (CI) 0.32–0.87; risk difference (RD) −0.15, 95% CI −0.26 to −0.04; number needed to treat (NNT) 7 (95% CI 4–25)] and the rate of treatment failure (death or assisted ventilation) (RR 0.65, 95% CI 0.52–0.81; RD −0.20, 95% CI −0.29 to −0.10; NNT 5, 95% CI 4–10). However, use of CDP was associated with an increased risk of pneumothorax [RR 2.64 (95% CI 1.39, 5.04); RD 0.10, 95% CI 0.04–0.23; number needed to harm 7, 95% CI 4–24). No difference was observed in the need to use surfactant (reported in one trial) or chronic lung disease at 28 days (reported in three trials). This lack of significance may be due to the small number of neonates enrolled in the trials.

A similar degree of benefit was observed in a subgroup analysis comparing early use of CDP with standard care (RR for treatment failure 0.59, 95% CI 0.44–0.79). Moreover, there is experimental and clinical literature to suggest that early CDP conserves the neonate’s own surfactant stores and minimizes the stimulation of inflammatory cascade. Another review (9) comparing early versus delayed initiation of CDP in RDS has observed reduced subsequent use of intermittent mandatory ventilation (RR 0.55, 95% CI 0.32–0.96) and reduced duration of ventilator assistance (mean difference 33.7 hours) if CDP is started early when fraction of inspired oxygen (FiO2) requirement is >0.3.

4. DISCUSSION

4.1 Applicability of the results

Most of the randomized trials evaluating CDP against head box oxygen were conducted in pre-surfactant, pre-antenatal steroid era on more mature infants using a variety of patient interfaces and with limited respiratory support for sick neonates. Unfortunately, now to generate further evidence is impossible as it would be unethical to deny CDP to a control group. However, applicability of CDP in the present-day scenario in developing countries is enhanced by the fact that the largest number of neonates in the meta-analysis in this review was contributed by a recent trial conducted in non-tertiary care centers in a developed country. Despite improvements of newborn care in health facilities in developing countries, this low-cost effective intervention lacks widespread use due to lack of trained health-care professionals, compromised care at birth and delay at institution of intervention, which may result in poor outcomes.

4.2 Implementation of the intervention

CDP should be initiated at the earliest signs of respiratory distress in neonates at risk for RDS. Some arbitrary criteria can be Silverman score of ≥ 4 or FiO2 requirement ≥ 0.3. CDP can be initiated even in the delivery room if delay in shifting to a neonatal intensive care unit is anticipated, rather than withholding any form of respiratory support for that much duration. For secondary and tertiary care hospitals, training of health-care professionals in CDP application, monitoring and weaning should be done on a priority basis. For making the intervention operational, availability of low-cost machines with affordable patient interfaces, along with a source of air–oxygen blender, should be addressed as a priority.

4.3 Implications for research

There is an urgent need to develop low-cost continuous positive airway pressure machines and patient interfaces that are safe, reliable and effective. Studies are needed to define the criteria for initiating and stopping CDP and optimum pressure, pressure sources and ideal methods for delivering CDP (10).

Acknowledgement: Dr Deepak Chawla, Neonatologist, Department of Pediatrics, Government Medical College, Chandigarh, India.

References

• National Neonatal Perinatal Database Network: report 2002-2003. New Delhi: National Neonatology Forum of India; 2004.
• Avery ME, Tooley WH, Keller JB, Hurd SS, Bryan MH, Cotton RB, et al. Is chronic lung disease in low birth weight infants preventable? A survey of eight centers. Pediatrics 1987;79:26-30.
• Morley CJ, Davis PG, Doyle LW, Brion LP, Hascoet JM, Carlin JB; COIN Trial Investigators. Nasal CPAP or intubation at birth for very preterm infants. New England Journal of Medicine 2008;358:700-8.
• Aly H, Milner JD, Patel K, El-Mohandes AA. Does the experience with the use of nasal continuous positive airway pressure improve over time in extremely low birth weight infants? Pediatrics 2004;114:697-702.
• Finer NN, Carlo WA, Duara S, Fanaroff AA, Donovan EF, Wright LL, et al. Delivery room continuous positive airway pressure/positive end-expiratory pressure in extremely low birth weight infants: a feasibility trial. Pediatrics 2004;1143:651-7
• Koti J, Murki S, Gaddam P, Reddy A, Reddy MD. Bubble CPAP for respiratory distress syndrome in preterm infants. Indian Pediatrics 2009.pii:S097475590800567-1.
• Urs PS, Khan F, Maiya PP. Bubble CPAP - a primary respiratory support for respiratory distress syndrome in newborns. Indian Pediatrics 2009;46:409-11.
• Ho JJ, Subramaniam P, Henderson-Smart DJ, Davis PG. Continuous distending pressure for respiratory distress in preterm infants. Cochrane Database of Systematic Reviews 2009;Issue 2. Art. No.: CD002271;. DOI: 10.1002/14651858.CD002271.
• Ho JJ, Henderson-Smart DJ, Davis PG. Early versus delayed initiation of continuous distending pressure for respiratory distress syndrome in preterm infants. Cochrane Database of Systematic Reviews 2002;Issue 2. Art. No.: CD002975; DOI: 10.1002/14651858.CD002975.
• De Paoli AG, Davis PG, Faber B, Morley CJ. Devices and pressure sources for administration of nasal continuous positive airway pressure (NCPAP) in preterm neonates. Cochrane Database of Systematic Reviews 2008;Issue 1. Art. No.: CD002977; DOI: 10.1002/14651858.CD002977.pub2.

This document should be cited as: Deorari A. Continuous distending pressure for respiratory distress in preterm infants: RHL commentary (last revised: 1 January 2010). The WHO Reproductive Health Library; Geneva: World Health Organization.