RESPIRATORY DISEASES

Health Evidence Bulletins - Wales
Team Leader: Dr Michael Burr Date of completion: 13/8/97

The contents of this bulletin are likely to be valid for approximately one year, by which time significantly new research evidence may become available


2. Respiratory disease in the newborn

(Users are advised to consult the supporting evidence for a consideration of all the implications of a recommendation)

This chapter has been taken from the Maternal & Early Child Health Bulletin (Chapter 20: Neonatal respiratory support)i.
i. Health Evidence Bulletins - Wales. Maternal & Early Child Health. Cardiff: Welsh Office, March 1998
Neonatal respiratory support may be required for immature infants, for mature babies following asphyxia and/or infection and for those with a variety of congenital anomalies.

 

The Statements The Evidence
2.1 Respiratory Support  
2.1a. Prophylactic post-extubation continuous positive airways pressure (CPAP) for pre-term babies is effective in preventing failure of extubation and in reducing oxygen use. Further definition is needed of the gestational age and weight groups to whom these results applyi.
(Health gain notation - 2 "likely to be beneficial")
i. Davis PG, Henderson-Smart DJ. Prophylactic post-extubation CPAP in preterm infants. Cochrane database of systematic reviews. Cochrane Library 1998 Issue 1
(Type I evidence - systematic review)
2.1b. There is no evidence of the effectiveness of elective endotracheal intubation for very low birth weight infants (= 1500g) showing no signs of respiratory distress or depression, because of the associated risksi.
(Health gain notation - 4 "unknown")
i. Enkin M, Keirse MJNC, Renfrew M, Neilson J. A guide to effective care in pregnancy and childbirth. 2nd ed. Oxford: Oxford University Press, 1995. p.335
(Type II evidence - single, flawed, trial. See p.27 in Sinclair JC, Bracken MB (eds.) Effective care of the newborn infant. Oxford: Oxford University Press, 1992)
2.1c. The use of exogenous surfactant therapy in the newborn has proved the greatest advance in the care of preterm babies in the last decade. A 40% reduction in mortality and 50% reduction in pneumothorax has been reported in babies of less than 30 weeksi. Most studies suggest that prophylactic early treatment (as early as possible, and preferably within 2 hours) has a greater beneficial effect than later administration i,ii,iii
(Health gain notation - 1 "beneficial")
although optimum regimes have been subjected to limited trial i,ii.
i. Hennes HM, Lee MB, Rimm AA, Shapiro DL. Surfactant replacement therapy in respiratory distress syndrome: Meta-analysis of clinical trials of single-dose surfactant extracts. American Journal of Diseases of Children 1991;145:102-4
(Type I evidence - meta-analysis);
ii. The OSIRIS Collaborative Group. Early versus delayed neonatal administration of a synthetic surfactant - the judgement of OSIRIS. Lancet 1992; 340:1363-1369
(Type II evidence - randomised controlled trial of 6757 infants);
iii. British Association of Perinatal Medicine Working Party. The use of exogenous surfactants in newborn infants. London: British Association of Perinatal Medicine, 1994
(Type V evidence - expert opinion)

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2.1d. Natural surfactant extract and synthetic surfactant in the treatment of established respiratory distress are both effective.
Natural surfactant has a more rapid onseti,ii.
(Health gain notation - 2 "likely to be beneficial")
i. Soll RF. Natural surfactant extract vs synthetic surfactant in the treatment of established respiratory distress syndrome. Cochrane database of systematic reviews. Cochrane Library 1998 Issue 1
(Type I evidence - meta-analysis);
ii. Halliday HL. Overview of clinical trials comparing natural and synthetic surfactants. Biology of the Neonate 1995; 67(suppl.1): 32-47
(Type I evidence - meta-analysis)
2.1e. Expert guidance is that two doses of surfactant should be given, 12 hours apart via the endotracheal tube. There is no additional benefit observed with the routine use of 3 or more doses i.
(Health gain notation - 2 "likely to be beneficial")
i. British Association of Perinatal Medicine Working Party. The use of exogenous surfactants in newborn infants. London: British Association of Perinatal Medicine. 1994
(Type V evidence - expert opinion)
2.1f. Neonatal extracorporeal membrane oxygenation (ECMO) is a complex and expensive technique. However, preliminary results demonstrate the clinical effectiveness of a well staffed and organised neonatal ECMO service when compared to conventional management in a similar tertiary centre for mature newborn infants (>= 35 weeks gestation and >=2 kg) with severe respiratory failurei.
(Health gain notation - 2 "likely to be beneficial")
caveat: Infants who develop signs of intractable respiratory failure outside a tertiary unit (ie outside a unit suitably equipped and staffed for the intensive care of neonates) should be moved to such a unit at the earliest opportunity. Access to specialist care (with or without ECMO - which is currently only available in a few centres) is the most important consideration for these babiesii.
(Health gain notation - 1 "beneficial")
i. UK Collaborative ECMO Trial Group. UK collaborative randomised trial of neonatal extracorporeal membrane oxygenation. Lancet 1996; 348: 75-82
(Type II evidence - randomised controlled trial of 185 neonates);
ii. Internal Review Group of the Maternal & Early Child Health Bulletin in this series (Contact the Project Office).
(Type V evidence - expert opinion and current good practice)

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2.1g. Nitric oxide (NO) inhalation improves oxygenation in some infants with persistent pulmonary hypertension (PPHN) i,ii. In one trial, systemic oxygenation was doubled in 53% of the nitric oxide group but only 7% of the control group although the number of deaths was similar in both groupsii. Research is currently under way to determine which infants are most likely to benefit from NO and whether it is appropriate in pre-term, as well as term, infantsiii.
caveat: NO exposure may be significant in terms of toxicity, including human cancer riskii.
i. Mariani G, Barefield ES, Carlo WA. The role of nitric oxide in the treatment of neonatal pulmonary hypertension. Current Opinion in Pediatrics 1996; 8(2):118-125
(Type I evidence - systematic review);
ii. Roberts JD, Jeffrey R, Morin FC et al. Inhaled nitric oxide and persistent pulmonary hypertension of the newborn. New England Journal of Medicine 1997; 336(9): 605-610
(Type II evidence - randomised controlled trial of 58 full-term infants);
iii. The INNOVO Trial. A multicentre randomized controlled trial currently in progress. Funded by the Medical Research Council.
(Trial in progress)
2.1h. Nitric oxide inhalation during conventional mechanical ventilation for respiratory failure reduced the use of extracorporeal membrane oxygenation (46% versus 64% dying or needing ECMO in the control group)i but had no apparent effect on mortality in full or nearly full term infantsi,ii and the effect may be slightly worsened for infants with diaphragmatic herniaii. A full evaluation, with longer term follow-up, is under wayiii.
(Health gain notation - 4 "unknown")
i. The Inhaled Nitric Oxide Study Group. Ehrenkranz RA, Stork E, Gorjanc E,  et al. Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure. New England Journal of Medicine 1997; 336(9): 597-604
(Type II evidence - randomised controlled trial of 135 infants of >=34 weeks);
ii. Finer NN, Barrington KJ. Nitric oxide in respiratory failure in the newborn infant. Cochrane database of systematic reviews. Cochrane Library 1998 Issue 1.
(Type I evidence - systematic review);
iii. The INNOVO Trial. A multicentre randomized controlled trial currently in progress. Funded by the Medical Research Council
(Trial in progress)
2.2 Prevention of Chronic lung disease  
2.2a. A meta-analysis of randomised controlled trials of early (< 72 hours), moderately early (7-14 days) and late (>3 weeks) corticosteroid treatment showed that early or moderately early steroids facilitate weaning from the ventilator and increase survival without chronic lung disease (CLD), without affecting neonatal mortality. Risks of pulmonary air leak and patent ductus arteriosus were reduced although hypertension, hyperglycaaemia and gastrointestinal bleeding were increased. Late steroids also facilitated weaning from the ventilator but did not reduce neonatal mortalityi.
(Health gain notation - 3 "trade off between beneficial and adverse effects")
i. Halliday HL. A review of postnatal corticosteroids for treatment and prevention of chronic lung disease in the preterm infant. Prenatal and Neonatal Medicine 1997; 2: 1-12
(Type I evidence - systematic review)

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2.2b. Meta-analysis of four studies suggests that there is no difference in mortality and chronic lung disease (CLD) between the routine use of High Frequency Oscillatory Ventilation (HFOV) and conventional ventilation in preterm infants with acute pulmonary dysfunction but there were trends towards an increase in intraventricular haemorrhage (IVH) or periventricular leucomalacia (PVL). In the subgroup of trials where a high volume strategy was used there was a significant reduction in CLD (Odds Ratio, OR = 0.39) and a similar effect was noted when surfactant was used (OR=0.43). For these subgroups, there were no differences in the odds of having IVH or PVLi. Further study is clearly indicated.
(Health gain notation - 3 "trade-off between beneficial and adverse effects")
caveat: The value of HFOV for ‘rescue’ therapy has not been subjected to trial ii.
i. Bhuta T, Henderson-Smart DJ. Elective high frequency oscillatory ventilation vs conventional ventilation in preterm infants with acute pulmonary dysfunction. Cochrane database of systematic reviews. Cochrane Library. 1998 Issue 1.
(Type I evidence - meta-analysis)
2.3 Bronchopulmonary dysplasia  
2.3a. The value of steroids in producing short-term improvement in lung function during the treatment of bronchopulmonary dysplasia is established (pulmonary compliance improved in 64% of the treated group and 5% of the control group)i although long term efficacy and safety has yet to be demonstratedi,ii.
(Health gain notation -1 "beneficial")
i. Avery GB, Fletcher AB, Kaplan M, Brudno DS. Controlled trial of dexamethasone in respirator-dependent infants with bronchopulmonary dysplasia. Paediatrics 1985; 75(1): 106-111
(Type II evidence - randomised controlled trial of 16 infants weighing <1500g);
ii. Ehrenkranz RA, Mercurio MR. Bronchopulmonary dysplasia. Chapter 18 in Sinclair JC, Bracken MB (eds.) Effective care of the newborn infant. Oxford: Oxford University Press, 1992
(Type I evidence - systematic review)
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Health Evidence Bulletins: Wales, Duthie Library, UWCM, Cardiff CF14 4XN. e-mail: weightmanal@cardiff.ac.uk