- Email: [email protected]
Management of infants with chronic lung disease of prematurity in the United Kingdom
Early Human Development (2005) 81, 165 — 170
www.elsevier.com/locate/earlhumdev
Management of infants with chronic lung disease of prematurity in the United Kingdom N.J. Shawa,1, Sailesh Kotechab,* a
Liverpool Womens Hospital Crown Street L8 7SS, United Kingdom Division of Child Health, University of Leicester, Leicester LE2 7LX, United Kingdom
b
KEYWORDS Chronic lung disease of prematurity; Bronchopulmonary dysplasia; Oxygen therapy; Oxygen saturations; Diuretics; Corticosteroids
Abstract The management of chronic lung disease of prematurity (CLD) is challenging for the neonatologist. There are few well-powered randomised controlled trials to inform practice and longer-term outcomes of some interventions have only recently been identified (for example the possible association between the use of corticosteroids and neurodevelopmental abnormalities). As a result, many neonatologists rely on empirical management derived from the evidence available. We describe, in this article, our own approach to the management of CLD, and acknowledge that practice may vary between units within the United Kingdom. D 2004 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Chronic lung disease of prematurity (CLD) has now become one of the major adverse outcomes of prematurity. In the last decade or so, its incidence and prevalence have increased owing to a greater number of extremely preterm infants surviving than ever before. This article will be concerned with a number of issues related to the management of babies developing or with established chronic lung disease, namely oxygen therapy, the place of drug therapy, the use of domiciliary oxygen and follow up procedures.
* Corresponding author. Tel.: +44 116 252 5881; fax: +44 116 258 5502/252 3282. E-mail addresses: [email protected] (N.J. Shaw)8 [email protected] (S. Kotecha). 1 Tel.: +44 151 708 9988; fax: +44 151 702 4313.
2. The use of oxygen in acute respiratory disease Hypoxia may injure tissues by not providing adequate oxygen to allow normal cellular function and may also contribute to pulmonary hypertension which is an important component of neonatal lung diseases. Hyperoxia has been implicated as an etiological factor in the development of some cases of retinopathy of prematurity in vulnerable infants and may also play a role in the pathogenesis of other free radical diseases (bronchopulmonary dysplasia and periventricular leucomalacia). There is no clear definition as to what constitutes adequate oxygenation in babies receiving intensive care. The gold standard measurement of systemic oxygenation is the partial pressure of oxygen in the arterial blood (PaO2) and the acceptable range of PaO2 in babies has been suggested as being 45 mm Hg to 75 mm Hg (6—10 KPa) [1]. Pulse oximetry allows continuous
0378-3782/$ - see front matter D 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.earlhumdev.2004.12.008
166 measurement of arterial oxygenation non-invasively and was originally used in neonatal units to detect acute episodes of reduced oxygenation. The rapid response time of the technology in pulse oximeters makes it ideally suited to this task. SpO2 is usually accurate to within + or 2% of SaO2. Because of this small inaccuracy and the complex nature of the relationship between SaO2 and PaO2, it is not possible to estimate PaO2 accurately from SpO2 values. SpO2 however can be used for monitoring to avoid hypoxia and hyperoxia. Using the suggested range of 6—10 KPa it has been shown that in premature babies, hyperoxia does not occur if SpO2 is maintained below 95% using an Ohmeda oximeter [2]. Identification of hypoxia is more difficult using pulse oximetry. Most healthy babies spend less than 5% of the time with SpO2 less than 89% [3] although an SpO2 cut-off of 90% only identifies 55% of hypoxic episodes in sick babies [4]. A complicating factor in using pulse oximetry to assess oxygenation is that Nellcor oximeters read approximately 2% above Ohmeda oximeters. Our practice in babies at risk of retinopathy of prematurity (b31 weeks or b1500 g) is to ensure that SpO2 does not go above 95% when supplemental oxygen is being administered. The lower limit for oximetry is initially set at 89% but is often adjusted individually if the PaO2 measurements are below 45 mm Hg with bacceptableQ SpO2 levels. In babies with a low risk of retinopathy (above 32 weeks) we do not use an upper limit for saturation and try and maintain oxygen saturations at 94% and above (see below).
3. Oxygen therapy and monitoring in chronic respiratory disease Chronic hypoxia may predispose an infant with chronic lung disease to acute life-threatening events, pulmonary hypertension and right heart failure. Concerns were raised from the STOP-ROP study that maintaining high oxygen saturations could predispose the infants to a worse pulmonary status [5]. However the adverse pulmonary outcomes in this study were not well defined. The more recent BOOST study showed that maintaining higher oxygen saturations resulted in more babies being discharged receiving home oxygen therapy and longer oxygen dependency [6]. There was, however, no positive effect of maintaining higher oxygen saturations on growth or neurodevelopmental outcome after 1 year and no adverse effect on the quality of life of the parents or the family. In another study it has also been reported that in units
N.J. Shaw, S. Kotecha where there is a more liberal use of home oxygen, there is no increase in the overall financial burden of sending more babies home receiving oxygen therapy [7]. Our practice is to aim for a normal oxygen saturation in infants with chronic lung disease particularly when the risk of hyperoxia contributing to the development of retinopathy of prematurity is negligible. In infants over 32 weeks post-menstrual age, to allow a reasonable margin of safety, oxygen is administered to maintain oxygen saturations at 94% or above when using Ohmeda oximeters. Using Nellcor oximeters the saturation may need to be maintained at a higher level. In practical terms, infants requiring more than 40% of inspired oxygen are likely to require oxygen administered via a headbox. We generally do not offer these infants oral feeds by breast or bottle as this may produce restlessness, hypoxia and deterioration. If the infant appears restless for no specific reason, a pacifier or occasionally a few millilitres of comfort feed is offered. Infants who require supplemental oxygen who are clinically stable and who still require orogastric tube feeds have oxygen saturation monitoring performed on a weekly basis for at least 4 h whilst awake, sleeping and feeding to assess the amount of oxygen required. Once the infant is established on full oral feeds, monitoring is performed to assess the amount of supplemental oxygen required in preparation for home. We feel it is more practical and possibly safer to recommend supplemental home oxygen therapy continuously even if infants drop their saturations only during sleep or episodes of feeding.
4. The use of drugs 4.1. Corticosteroids A number of studies have reported the use of postnatal steroids in acute and chronic neonatal respiratory disease, in particular aiming to reduce the risk of chronic lung disease or length of oxygen dependency. Overall they suggest that systemic steroids may aid in weaning from the mechanical ventilator but not necessarily alter outcome in terms of mortality or chronic lung disease. Metaanalyses have been performed which suggest a beneficial effect in terms of a reduction in the combined incidence of chronic lung disease or death whenever steroids are given postnatally [8,9,10]. This effect appears to be most striking when steroids are given between 7 and 14 days of
Management of infant with chronic lung disease age. However there are concerns regarding both short-term side effects (hypertension, hyperglycaemia and septic episodes) and long-term side effects (neurodevelopmental impairment and impaired growth) of systemic steroid use in the neonate. Concern regarding neurodevelopmental adverse outcome has been linked to dexamethasone containing the sulphite moiety. Sulphite free dexamethasone however can be obtained readily. In our practice, steroids are not given to babies with respiratory distress syndrome under 7 days of age because of concerns that acute side effects outweigh the benefits. At 7—14 days of age, infants weighing less than 2000 g who are ventilator dependent, who are receiving high concentrations of inspired oxygen and in whom the consultant feels there is little prospect of clinical improvement, may receive 0.25 mg/kg 12 hourly of dexamethasone. This dose is halved after 3 days and stopped after 6 days although if a clinical response is seen the dose may be reduced earlier. Prior to starting treatment, full discussion takes place with the parents regarding the rationale for treatment and potential side effects. Contraindications to this therapy may include sepsis, gastrointestinal bleeding, major malformation, hypertension, severe intraventricular haemorrhage and severe haemodynamic instability. Patent ductus arteriosus as a cause of ventilator dependency should be excluded. At present there is no strong evidence that prolonged courses of systemic steroids in ventilator dependent infants are beneficial. After 14 days, steroids are considered for those babies who are ventilator dependent in high concentrations of oxygen. However they are not given to babies and infants requiring headbox oxygen alone. Occasionally if the infants respiratory status rebounds significantly after stopping steroids, a second course of dexamethasone may be considered with slower tapering of the dose. Inhaled steroids have shown to be no better than systemic steroids at weaning babies from the ventilator [11,12]. Inhaled steroids started prophylactically to try and prevent respiratory symptoms of airway’s obstruction later on have not, in a small study, been shown to be more effective than placebo [13]. Once the child is discharged home, he or she is prone to recurrent respiratory illness in particular episodes of acute airways obstruction associated with wheezing. Generally oral steroids may be given for an acute attack (prednisolone 2 mg/kg for 3 days) and inhaled steroids may be commenced if recurrent wheezing is a problem, particularly where there is a strong family history of atopy. In the absence of randomised trials or any other evidence to support
167 this approach, treatment is administered according to the British Thoracic Society asthma guidelines for the under fives [14].
4.2. Bronchodilators Bronchodilators have been shown to reduce airways resistance acutely in the ventilated baby with respiratory distress syndrome. However, there is no evidence for their benefits in the long term. It is the author’s practice to use these in acute wheezing episodes in the infant with chronic lung disease. The evidence concerning whether a beta2 agonist or an anti-cholinergic is most effective is weak and often either of these agents is used empirically.
4.3. Diuretics The association between chronic lung disease, high fluid intakes and patent ductus arteriosus has led to the belief that pulmonary oedema may play an important role in the pathogenesis of chronic lung disease. Pulmonary interstitial oedema is one of the characteristic pathological changes seen in infants with chronic lung disease and may result in reduced lung compliance and increased airways resistance. Several randomised controlled trials in preterm infants with chronic lung disease have demonstrated short- to medium-term improvements in pulmonary function with a reduction in airways resistance and lung compliance with both Frusemide and Thiazide diuretics. These changes were associated with a reduction in oxygen and ventilator requirements after 1 week of treatment [15,16]. Two randomised controlled trials [17,18] have investigated the effects of long-term oral therapy with thiazide diuretics in infants with developing or established chronic lung disease. One study of ventilator dependent infants with severe chronic lung disease demonstrated a significant and clinically important (number needed to treat=3), reduction in mortality prior to discharge from hospital in infants treated with an 8 week course of hydrochlorothiazide and spironolactone [17]. The other study showed a reduction in supplemental oxygen requirements in non-ventilated infants treated with 4 weeks of chlorothiazide and Spironolactone [18]. However there was no evidence of a benefit in total duration of respiratory support or hospital stay with diuretic therapy in either study although a large proportion of control infants in both studies received extra doses of frusemide. Babies treated with long-term thiazide therapy received less extra doses of fruse-
168 mide. There is virtually no information from randomised controlled trials about the long-term safety and efficacy of frusemide therapy in infants with chronic lung disease. Uncontrolled series have suggested a number of potential complications with diuretic therapy including electrolyte disturbance, deranged calcium and phosphate metabolism, nephrotoxicity and ototoxicity. In particular treatment with frusemide is associated with hypercalcuria and nephrocalcinosis. However there is no evidence from individual randomised controlled trials of an excess of significant adverse effects (e.g. nephrocalcinosis, hearing loss and growth) with diuretic therapy, although this may reflect the small number of infants studied. One small randomised controlled trial evaluating the efficacy of adding spironolactone to a thiazide diuretic did not demonstrate any benefits in terms of efficacy or electrolyte balance [19]. The authors’ practice is to consider ventilator dependent preterm infants with developing or established chronic lung disease for long-term diuretic therapy with regular oral hydrochlorothiazide and spironolactone. Diuretics are not used routinely in non-ventilated preterm infants with chronic lung disease, however on occasions treatment with either hydrochlorothiazide and spironolactone or IV frusemide in non-ventilated infants requiring high fraction inspired oxygen concentrations is considered particularly where there is excessive weight gain. Cardiac failure, which is extremely rare in chronic lung disease, is also an indication for diuretics. Babies receiving diuretics are monitored for electrolyte disturbance.
4.4. Domiciliary oxygen Babies are considered for home oxygen therapy once they are not having any major acute events whilst receiving supplemental oxygen therapy on the Neonatal Unit. These babies usually are tolerating full oral feeds although on occasions babies have been discharged home receiving tube feeds. The parents should be willing to take the child home receiving supplemental oxygen therapy and the social situation is assessed for the presence of extended support for the family. A number of oxygen delivery systems are available which will not be discussed in detail here [20]. Basically, oxygen can be provided via an oxygen concentrator installed into the home together with portable cylinders for ambulatory use and back-up cylinders in case of electricity failure, a system whereby oxygen is delivered by a large non-portable and smaller portable cylinders or via a liquid oxygen system (the latter may be more practical and cost-
N.J. Shaw, S. Kotecha effective if the baby is receiving high-flow oxygen). Oxygen may be delivered via single nasal cannula or nasal specs (the authors favour the latter as it appears to be less irritant). Prior to discharge the parents are taught basic resuscitation on the Neonatal Unit, and given an information book on chronic lung disease. They also receive a visit from the home oxygen nurse who discusses and gives training to the parents in the use of home oxygen. Babies, once discharged are given the contact number of the home oxygen nurse and are able to have open access to a designated ward at the Children’s Hospital, the staff of whom are experienced in dealing with oxygen dependent babies. Once the decision has been made to discharge the infant home on supplemental oxygen, the baby remains on the same oxygen flow pending their outpatients review. Prior to discharge, ECG monitoring will have been discontinued and oxygen saturation monitoring will be intermittent. On discharge, the GP and health visitor are informed. The preterm community midwifery team visit in the first week after discharge and an early outpatient appointment is made within 10 days of discharge. At that stage the care of the baby is handed over to the personnel in the chronic lung disease clinic (Consultant Respiratory Paediatrician, Oxygen Dependency Nurse). At the clinic a dietician is present. She gives advice on weaning to solids, reviews the child’s weight gain and may suggest intervention with high protein, high calorie formula. Feeding problems are not uncommon in children at follow up and the clinic staff give advice on these. On occasions formal speech therapy referral and educational psychology intervention is appropriate for these difficulties.
4.5. Vaccination Babies are offered triple vaccination and it is recommended to the general practitioner that influenza vaccination be given. At present pneumococcal vaccine is not routinely offered. There is uncertainty about the threshold for offering passive immunisation with immunoglobulin against RSV. At present the authors offer babies Palivizumab at the beginning of the RSV season to all babies receiving continuous oxygen therapy.
4.6. Follow up Follow up of these infants involves a multidisciplinary approach which may involve the neonatologist or respiratory paediatrician, respiratory nurse,
% Total time spent below SpO2 value
Management of infant with chronic lung disease 100
169
References
80 60 40 20 0 <86
<88
<90
<92
<94
<96
<98
<100
SpO2 concentration
Figure 1
SpO2 profiles in healthy preterm infants.
health visitor, general practitioner, dietician, speech therapist and other agencies when appropriate. Babies are followed up monthly alternately in the home and in clinic. During this, any general concerns are addressed and an assessment of the child’s respiratory status, feeding and growth is made. Oxygen saturation measurements are performed. If all is well and the child’s bspotQ oxygen saturation is above 94% using an Ohmeda oximeter or higher using a Nellcor, the parents are asked to take the child out of oxygen for 2 h a day in the first instance. This time off oxygen is incrementally increased over the next 2—3 months, after which a continuous overnight oxygen saturation study is performed. If the child maintains acceptable saturations according the normal range of oxygen saturation for age, (Fig. 1) then the child is taken out of oxygen overnight. We have found this incremental approach to be more acceptable to parents who have come to depend on the oxygen and also the approach makes it easier to put the child back into oxygen if they should have an intercurrent respiratory illness causing hypoxia. Oxygen equipment is usually left in the home for a further 2 months after stopping oxygen treatment altogether. There is little evidence to guide the correct way of withdrawing oxygen therapy from a child and the authors accept that there may be a wide range of safe practices currently in use.
4.7. Financial implications Although the costs associated with the management of infants with chronic lung disease are large, these are borne by the National Health Service of the UK and do not involve additional costs to the parents. Electrical costs associated with the use of the oxygen concentrator are reimbursed to the parents and most infants are entitled to Disability Living Allowance.
[1] Anonymous RA. Development of audit measures and guidelines in the management of neonatal respiratory distress syndrome. Report of a joint working group of the British Association of Perinatal Medicine and the Research Unit of the Royal College of Physicians. Arch Dis Child 1992;67: 1221 – 7. [2] Cochran DP, Shaw NJ. The use of pulse oximetry in the prevention of hyperoxia in preterm infants. Eur J Pediatr 1995;154:222 – 4. [3] Ng A, Subhedar NV, Primhak RA, Shaw NJ. Arterial oxygen saturation profiles in healthy preterm infants. Arch Dis Child 1998;79:F64 – 6. [4] Gupta R, Yoxall CW, Subhedar NV, Shaw NJ. Individualised pulse oximetry limits in neonatal intensive care. Arch Dis Child 1999;F194 – 6. [5] The STOP-ROP Multicenter Study Group. Supplemental Therapeutic Oxygen for Prethreshold Retinopathy Of Prematurity (STOP-ROP), a randomized, controlled trial: I. Primary outcomes. Pediatrics 2000 (Feb.);105(2):295 – 310. [6] Askie LM, Henderson-Smart DJ, Irwig L, Simpson JM. Oxygen-saturation targets and outcomes in extremely preterm infants. N Engl J Med 2003;349:959 – 67. [7] Greenough A., Alexander J., Burgess S., Chetcuti P.A.J., Cox S., Lenney W., et al. High versus restricted use of home oxygen therapy, health care utilisation and the cost of care in CLD infants. Eur J Pediatr 2004;163(6):292 – 6. [8] Halliday HL, Ehrenkranz RA, Doyle LW. Early postnatal (b96 hours) corticosteroids for preventing chronic lung disease in preterm infants (Cochrane Review). The Cochrane Library, Issue, vol. 3. Chichester, UK7 John Wiley & Sons, 2004. [9] Halliday HL, Ehrenkranz RA, Doyle LW. Delayed (N3 weeks) postnatal corticosteroids for chronic lung disease in preterm infants (Cochrane Review). The Cochrane Library, Issue, vol. 3. Chichester, UK7 John Wiley & Sons, 2004. [10] Halliday HL, Ehrenkranz RA, Doyle LW. Moderately early (7—14 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants (Cochrane Review). The Cochrane Library, Issue, vol. 3. Chichester, UK7 John Wiley & Sons, 2004. [11] Shah V, Ohlsson A, Halliday HL, Dunn MS. Early administration of inhaled corticosteroids for preventing chronic lung disease in ventilated very low birth weight preterm neonates (Cochrane Review). The Cochrane Library, Issue, vol. 3. Chichester, UK7 John Wiley & Sons, 2004. [12] Shah SS, Ohlsson A, Halliday H, Shah VS. Inhaled versus systemic corticosteroids for preventing chronic lung disease in ventilated very low birth weight preterm neonates (Cochrane Review). The Cochrane Library, Issue, vol. 3. Chichester, UK7 John Wiley & Sons, 2004. [13] Beresford MW, Primhak R, Subhedar NV, Shaw NJ. Randomised double blind placebo controlled trial of inhaled fluticasone propionate in infants with chronic lung disease. Arch Dis Child Fetal Neonatal Ed 2002;87(1):F62 – 3. [14] The British Thoracic Society Scottish Intercollegiate Guidelines Network. Thorax 2003;58(Suppl. I):i1 – 92. [15] Brion LP, Primhak RA, Ambrosio-Perez I. Diuretics acting on the distal renal tubule for preterm infants with (or developing) chronic lung disease (Cochrane Review). The Cochrane Library, Issue, vol. 3. Chichester, UK7 John Wiley & Sons, 2004. [16] Brion LP, Primhak RA. Intravenous or enteral loop diuretics for preterm infants with (or developing) chronic lung disease (Cochrane Review). The Cochrane Library, Issue, vol. 3. Chichester, UK7 John Wiley & Sons, 2004.
170 [17] Kao LC, Durand DJ, McCrea RC. Randomised trial of long-term diuretic therapy for infants with oxygen dependent bronchopulmonary dysplasia. J Pediatr 1994; 124:772 – 81. [18] Albersheim SG, Solimano AJ, Sharma AK. Randomised double blind controlled trial of long term diuretic therapy for bronchopulmonary dysplasia. J Pediatr 1989; 115:615 – 20.
N.J. Shaw, S. Kotecha [19] Hoffman DJ, Gerdes JS, Abbasi S. Pulmonary function and electrolyte balance following spironolactone treatment in preterm infants with chronic lung disease: a double-blind, placebo-controlled randomised trial. J Perinatol 2000; 20:41 – 5. [20] Dunbar H, Kotecha S. Domiciliary oxygen for infants with chronic lung disease of prematurity. Care Crit Ill 2000; 16(3):90 – 3.
www.elsevier.com/locate/earlhumdev
Management of infants with chronic lung disease of prematurity in the United Kingdom N.J. Shawa,1, Sailesh Kotechab,* a
Liverpool Womens Hospital Crown Street L8 7SS, United Kingdom Division of Child Health, University of Leicester, Leicester LE2 7LX, United Kingdom
b
KEYWORDS Chronic lung disease of prematurity; Bronchopulmonary dysplasia; Oxygen therapy; Oxygen saturations; Diuretics; Corticosteroids
Abstract The management of chronic lung disease of prematurity (CLD) is challenging for the neonatologist. There are few well-powered randomised controlled trials to inform practice and longer-term outcomes of some interventions have only recently been identified (for example the possible association between the use of corticosteroids and neurodevelopmental abnormalities). As a result, many neonatologists rely on empirical management derived from the evidence available. We describe, in this article, our own approach to the management of CLD, and acknowledge that practice may vary between units within the United Kingdom. D 2004 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Chronic lung disease of prematurity (CLD) has now become one of the major adverse outcomes of prematurity. In the last decade or so, its incidence and prevalence have increased owing to a greater number of extremely preterm infants surviving than ever before. This article will be concerned with a number of issues related to the management of babies developing or with established chronic lung disease, namely oxygen therapy, the place of drug therapy, the use of domiciliary oxygen and follow up procedures.
* Corresponding author. Tel.: +44 116 252 5881; fax: +44 116 258 5502/252 3282. E-mail addresses: [email protected] (N.J. Shaw)8 [email protected] (S. Kotecha). 1 Tel.: +44 151 708 9988; fax: +44 151 702 4313.
2. The use of oxygen in acute respiratory disease Hypoxia may injure tissues by not providing adequate oxygen to allow normal cellular function and may also contribute to pulmonary hypertension which is an important component of neonatal lung diseases. Hyperoxia has been implicated as an etiological factor in the development of some cases of retinopathy of prematurity in vulnerable infants and may also play a role in the pathogenesis of other free radical diseases (bronchopulmonary dysplasia and periventricular leucomalacia). There is no clear definition as to what constitutes adequate oxygenation in babies receiving intensive care. The gold standard measurement of systemic oxygenation is the partial pressure of oxygen in the arterial blood (PaO2) and the acceptable range of PaO2 in babies has been suggested as being 45 mm Hg to 75 mm Hg (6—10 KPa) [1]. Pulse oximetry allows continuous
0378-3782/$ - see front matter D 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.earlhumdev.2004.12.008
166 measurement of arterial oxygenation non-invasively and was originally used in neonatal units to detect acute episodes of reduced oxygenation. The rapid response time of the technology in pulse oximeters makes it ideally suited to this task. SpO2 is usually accurate to within + or 2% of SaO2. Because of this small inaccuracy and the complex nature of the relationship between SaO2 and PaO2, it is not possible to estimate PaO2 accurately from SpO2 values. SpO2 however can be used for monitoring to avoid hypoxia and hyperoxia. Using the suggested range of 6—10 KPa it has been shown that in premature babies, hyperoxia does not occur if SpO2 is maintained below 95% using an Ohmeda oximeter [2]. Identification of hypoxia is more difficult using pulse oximetry. Most healthy babies spend less than 5% of the time with SpO2 less than 89% [3] although an SpO2 cut-off of 90% only identifies 55% of hypoxic episodes in sick babies [4]. A complicating factor in using pulse oximetry to assess oxygenation is that Nellcor oximeters read approximately 2% above Ohmeda oximeters. Our practice in babies at risk of retinopathy of prematurity (b31 weeks or b1500 g) is to ensure that SpO2 does not go above 95% when supplemental oxygen is being administered. The lower limit for oximetry is initially set at 89% but is often adjusted individually if the PaO2 measurements are below 45 mm Hg with bacceptableQ SpO2 levels. In babies with a low risk of retinopathy (above 32 weeks) we do not use an upper limit for saturation and try and maintain oxygen saturations at 94% and above (see below).
3. Oxygen therapy and monitoring in chronic respiratory disease Chronic hypoxia may predispose an infant with chronic lung disease to acute life-threatening events, pulmonary hypertension and right heart failure. Concerns were raised from the STOP-ROP study that maintaining high oxygen saturations could predispose the infants to a worse pulmonary status [5]. However the adverse pulmonary outcomes in this study were not well defined. The more recent BOOST study showed that maintaining higher oxygen saturations resulted in more babies being discharged receiving home oxygen therapy and longer oxygen dependency [6]. There was, however, no positive effect of maintaining higher oxygen saturations on growth or neurodevelopmental outcome after 1 year and no adverse effect on the quality of life of the parents or the family. In another study it has also been reported that in units
N.J. Shaw, S. Kotecha where there is a more liberal use of home oxygen, there is no increase in the overall financial burden of sending more babies home receiving oxygen therapy [7]. Our practice is to aim for a normal oxygen saturation in infants with chronic lung disease particularly when the risk of hyperoxia contributing to the development of retinopathy of prematurity is negligible. In infants over 32 weeks post-menstrual age, to allow a reasonable margin of safety, oxygen is administered to maintain oxygen saturations at 94% or above when using Ohmeda oximeters. Using Nellcor oximeters the saturation may need to be maintained at a higher level. In practical terms, infants requiring more than 40% of inspired oxygen are likely to require oxygen administered via a headbox. We generally do not offer these infants oral feeds by breast or bottle as this may produce restlessness, hypoxia and deterioration. If the infant appears restless for no specific reason, a pacifier or occasionally a few millilitres of comfort feed is offered. Infants who require supplemental oxygen who are clinically stable and who still require orogastric tube feeds have oxygen saturation monitoring performed on a weekly basis for at least 4 h whilst awake, sleeping and feeding to assess the amount of oxygen required. Once the infant is established on full oral feeds, monitoring is performed to assess the amount of supplemental oxygen required in preparation for home. We feel it is more practical and possibly safer to recommend supplemental home oxygen therapy continuously even if infants drop their saturations only during sleep or episodes of feeding.
4. The use of drugs 4.1. Corticosteroids A number of studies have reported the use of postnatal steroids in acute and chronic neonatal respiratory disease, in particular aiming to reduce the risk of chronic lung disease or length of oxygen dependency. Overall they suggest that systemic steroids may aid in weaning from the mechanical ventilator but not necessarily alter outcome in terms of mortality or chronic lung disease. Metaanalyses have been performed which suggest a beneficial effect in terms of a reduction in the combined incidence of chronic lung disease or death whenever steroids are given postnatally [8,9,10]. This effect appears to be most striking when steroids are given between 7 and 14 days of
Management of infant with chronic lung disease age. However there are concerns regarding both short-term side effects (hypertension, hyperglycaemia and septic episodes) and long-term side effects (neurodevelopmental impairment and impaired growth) of systemic steroid use in the neonate. Concern regarding neurodevelopmental adverse outcome has been linked to dexamethasone containing the sulphite moiety. Sulphite free dexamethasone however can be obtained readily. In our practice, steroids are not given to babies with respiratory distress syndrome under 7 days of age because of concerns that acute side effects outweigh the benefits. At 7—14 days of age, infants weighing less than 2000 g who are ventilator dependent, who are receiving high concentrations of inspired oxygen and in whom the consultant feels there is little prospect of clinical improvement, may receive 0.25 mg/kg 12 hourly of dexamethasone. This dose is halved after 3 days and stopped after 6 days although if a clinical response is seen the dose may be reduced earlier. Prior to starting treatment, full discussion takes place with the parents regarding the rationale for treatment and potential side effects. Contraindications to this therapy may include sepsis, gastrointestinal bleeding, major malformation, hypertension, severe intraventricular haemorrhage and severe haemodynamic instability. Patent ductus arteriosus as a cause of ventilator dependency should be excluded. At present there is no strong evidence that prolonged courses of systemic steroids in ventilator dependent infants are beneficial. After 14 days, steroids are considered for those babies who are ventilator dependent in high concentrations of oxygen. However they are not given to babies and infants requiring headbox oxygen alone. Occasionally if the infants respiratory status rebounds significantly after stopping steroids, a second course of dexamethasone may be considered with slower tapering of the dose. Inhaled steroids have shown to be no better than systemic steroids at weaning babies from the ventilator [11,12]. Inhaled steroids started prophylactically to try and prevent respiratory symptoms of airway’s obstruction later on have not, in a small study, been shown to be more effective than placebo [13]. Once the child is discharged home, he or she is prone to recurrent respiratory illness in particular episodes of acute airways obstruction associated with wheezing. Generally oral steroids may be given for an acute attack (prednisolone 2 mg/kg for 3 days) and inhaled steroids may be commenced if recurrent wheezing is a problem, particularly where there is a strong family history of atopy. In the absence of randomised trials or any other evidence to support
167 this approach, treatment is administered according to the British Thoracic Society asthma guidelines for the under fives [14].
4.2. Bronchodilators Bronchodilators have been shown to reduce airways resistance acutely in the ventilated baby with respiratory distress syndrome. However, there is no evidence for their benefits in the long term. It is the author’s practice to use these in acute wheezing episodes in the infant with chronic lung disease. The evidence concerning whether a beta2 agonist or an anti-cholinergic is most effective is weak and often either of these agents is used empirically.
4.3. Diuretics The association between chronic lung disease, high fluid intakes and patent ductus arteriosus has led to the belief that pulmonary oedema may play an important role in the pathogenesis of chronic lung disease. Pulmonary interstitial oedema is one of the characteristic pathological changes seen in infants with chronic lung disease and may result in reduced lung compliance and increased airways resistance. Several randomised controlled trials in preterm infants with chronic lung disease have demonstrated short- to medium-term improvements in pulmonary function with a reduction in airways resistance and lung compliance with both Frusemide and Thiazide diuretics. These changes were associated with a reduction in oxygen and ventilator requirements after 1 week of treatment [15,16]. Two randomised controlled trials [17,18] have investigated the effects of long-term oral therapy with thiazide diuretics in infants with developing or established chronic lung disease. One study of ventilator dependent infants with severe chronic lung disease demonstrated a significant and clinically important (number needed to treat=3), reduction in mortality prior to discharge from hospital in infants treated with an 8 week course of hydrochlorothiazide and spironolactone [17]. The other study showed a reduction in supplemental oxygen requirements in non-ventilated infants treated with 4 weeks of chlorothiazide and Spironolactone [18]. However there was no evidence of a benefit in total duration of respiratory support or hospital stay with diuretic therapy in either study although a large proportion of control infants in both studies received extra doses of frusemide. Babies treated with long-term thiazide therapy received less extra doses of fruse-
168 mide. There is virtually no information from randomised controlled trials about the long-term safety and efficacy of frusemide therapy in infants with chronic lung disease. Uncontrolled series have suggested a number of potential complications with diuretic therapy including electrolyte disturbance, deranged calcium and phosphate metabolism, nephrotoxicity and ototoxicity. In particular treatment with frusemide is associated with hypercalcuria and nephrocalcinosis. However there is no evidence from individual randomised controlled trials of an excess of significant adverse effects (e.g. nephrocalcinosis, hearing loss and growth) with diuretic therapy, although this may reflect the small number of infants studied. One small randomised controlled trial evaluating the efficacy of adding spironolactone to a thiazide diuretic did not demonstrate any benefits in terms of efficacy or electrolyte balance [19]. The authors’ practice is to consider ventilator dependent preterm infants with developing or established chronic lung disease for long-term diuretic therapy with regular oral hydrochlorothiazide and spironolactone. Diuretics are not used routinely in non-ventilated preterm infants with chronic lung disease, however on occasions treatment with either hydrochlorothiazide and spironolactone or IV frusemide in non-ventilated infants requiring high fraction inspired oxygen concentrations is considered particularly where there is excessive weight gain. Cardiac failure, which is extremely rare in chronic lung disease, is also an indication for diuretics. Babies receiving diuretics are monitored for electrolyte disturbance.
4.4. Domiciliary oxygen Babies are considered for home oxygen therapy once they are not having any major acute events whilst receiving supplemental oxygen therapy on the Neonatal Unit. These babies usually are tolerating full oral feeds although on occasions babies have been discharged home receiving tube feeds. The parents should be willing to take the child home receiving supplemental oxygen therapy and the social situation is assessed for the presence of extended support for the family. A number of oxygen delivery systems are available which will not be discussed in detail here [20]. Basically, oxygen can be provided via an oxygen concentrator installed into the home together with portable cylinders for ambulatory use and back-up cylinders in case of electricity failure, a system whereby oxygen is delivered by a large non-portable and smaller portable cylinders or via a liquid oxygen system (the latter may be more practical and cost-
N.J. Shaw, S. Kotecha effective if the baby is receiving high-flow oxygen). Oxygen may be delivered via single nasal cannula or nasal specs (the authors favour the latter as it appears to be less irritant). Prior to discharge the parents are taught basic resuscitation on the Neonatal Unit, and given an information book on chronic lung disease. They also receive a visit from the home oxygen nurse who discusses and gives training to the parents in the use of home oxygen. Babies, once discharged are given the contact number of the home oxygen nurse and are able to have open access to a designated ward at the Children’s Hospital, the staff of whom are experienced in dealing with oxygen dependent babies. Once the decision has been made to discharge the infant home on supplemental oxygen, the baby remains on the same oxygen flow pending their outpatients review. Prior to discharge, ECG monitoring will have been discontinued and oxygen saturation monitoring will be intermittent. On discharge, the GP and health visitor are informed. The preterm community midwifery team visit in the first week after discharge and an early outpatient appointment is made within 10 days of discharge. At that stage the care of the baby is handed over to the personnel in the chronic lung disease clinic (Consultant Respiratory Paediatrician, Oxygen Dependency Nurse). At the clinic a dietician is present. She gives advice on weaning to solids, reviews the child’s weight gain and may suggest intervention with high protein, high calorie formula. Feeding problems are not uncommon in children at follow up and the clinic staff give advice on these. On occasions formal speech therapy referral and educational psychology intervention is appropriate for these difficulties.
4.5. Vaccination Babies are offered triple vaccination and it is recommended to the general practitioner that influenza vaccination be given. At present pneumococcal vaccine is not routinely offered. There is uncertainty about the threshold for offering passive immunisation with immunoglobulin against RSV. At present the authors offer babies Palivizumab at the beginning of the RSV season to all babies receiving continuous oxygen therapy.
4.6. Follow up Follow up of these infants involves a multidisciplinary approach which may involve the neonatologist or respiratory paediatrician, respiratory nurse,
% Total time spent below SpO2 value
Management of infant with chronic lung disease 100
169
References
80 60 40 20 0 <86
<88
<90
<92
<94
<96
<98
<100
SpO2 concentration
Figure 1
SpO2 profiles in healthy preterm infants.
health visitor, general practitioner, dietician, speech therapist and other agencies when appropriate. Babies are followed up monthly alternately in the home and in clinic. During this, any general concerns are addressed and an assessment of the child’s respiratory status, feeding and growth is made. Oxygen saturation measurements are performed. If all is well and the child’s bspotQ oxygen saturation is above 94% using an Ohmeda oximeter or higher using a Nellcor, the parents are asked to take the child out of oxygen for 2 h a day in the first instance. This time off oxygen is incrementally increased over the next 2—3 months, after which a continuous overnight oxygen saturation study is performed. If the child maintains acceptable saturations according the normal range of oxygen saturation for age, (Fig. 1) then the child is taken out of oxygen overnight. We have found this incremental approach to be more acceptable to parents who have come to depend on the oxygen and also the approach makes it easier to put the child back into oxygen if they should have an intercurrent respiratory illness causing hypoxia. Oxygen equipment is usually left in the home for a further 2 months after stopping oxygen treatment altogether. There is little evidence to guide the correct way of withdrawing oxygen therapy from a child and the authors accept that there may be a wide range of safe practices currently in use.
4.7. Financial implications Although the costs associated with the management of infants with chronic lung disease are large, these are borne by the National Health Service of the UK and do not involve additional costs to the parents. Electrical costs associated with the use of the oxygen concentrator are reimbursed to the parents and most infants are entitled to Disability Living Allowance.
[1] Anonymous RA. Development of audit measures and guidelines in the management of neonatal respiratory distress syndrome. Report of a joint working group of the British Association of Perinatal Medicine and the Research Unit of the Royal College of Physicians. Arch Dis Child 1992;67: 1221 – 7. [2] Cochran DP, Shaw NJ. The use of pulse oximetry in the prevention of hyperoxia in preterm infants. Eur J Pediatr 1995;154:222 – 4. [3] Ng A, Subhedar NV, Primhak RA, Shaw NJ. Arterial oxygen saturation profiles in healthy preterm infants. Arch Dis Child 1998;79:F64 – 6. [4] Gupta R, Yoxall CW, Subhedar NV, Shaw NJ. Individualised pulse oximetry limits in neonatal intensive care. Arch Dis Child 1999;F194 – 6. [5] The STOP-ROP Multicenter Study Group. Supplemental Therapeutic Oxygen for Prethreshold Retinopathy Of Prematurity (STOP-ROP), a randomized, controlled trial: I. Primary outcomes. Pediatrics 2000 (Feb.);105(2):295 – 310. [6] Askie LM, Henderson-Smart DJ, Irwig L, Simpson JM. Oxygen-saturation targets and outcomes in extremely preterm infants. N Engl J Med 2003;349:959 – 67. [7] Greenough A., Alexander J., Burgess S., Chetcuti P.A.J., Cox S., Lenney W., et al. High versus restricted use of home oxygen therapy, health care utilisation and the cost of care in CLD infants. Eur J Pediatr 2004;163(6):292 – 6. [8] Halliday HL, Ehrenkranz RA, Doyle LW. Early postnatal (b96 hours) corticosteroids for preventing chronic lung disease in preterm infants (Cochrane Review). The Cochrane Library, Issue, vol. 3. Chichester, UK7 John Wiley & Sons, 2004. [9] Halliday HL, Ehrenkranz RA, Doyle LW. Delayed (N3 weeks) postnatal corticosteroids for chronic lung disease in preterm infants (Cochrane Review). The Cochrane Library, Issue, vol. 3. Chichester, UK7 John Wiley & Sons, 2004. [10] Halliday HL, Ehrenkranz RA, Doyle LW. Moderately early (7—14 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants (Cochrane Review). The Cochrane Library, Issue, vol. 3. Chichester, UK7 John Wiley & Sons, 2004. [11] Shah V, Ohlsson A, Halliday HL, Dunn MS. Early administration of inhaled corticosteroids for preventing chronic lung disease in ventilated very low birth weight preterm neonates (Cochrane Review). The Cochrane Library, Issue, vol. 3. Chichester, UK7 John Wiley & Sons, 2004. [12] Shah SS, Ohlsson A, Halliday H, Shah VS. Inhaled versus systemic corticosteroids for preventing chronic lung disease in ventilated very low birth weight preterm neonates (Cochrane Review). The Cochrane Library, Issue, vol. 3. Chichester, UK7 John Wiley & Sons, 2004. [13] Beresford MW, Primhak R, Subhedar NV, Shaw NJ. Randomised double blind placebo controlled trial of inhaled fluticasone propionate in infants with chronic lung disease. Arch Dis Child Fetal Neonatal Ed 2002;87(1):F62 – 3. [14] The British Thoracic Society Scottish Intercollegiate Guidelines Network. Thorax 2003;58(Suppl. I):i1 – 92. [15] Brion LP, Primhak RA, Ambrosio-Perez I. Diuretics acting on the distal renal tubule for preterm infants with (or developing) chronic lung disease (Cochrane Review). The Cochrane Library, Issue, vol. 3. Chichester, UK7 John Wiley & Sons, 2004. [16] Brion LP, Primhak RA. Intravenous or enteral loop diuretics for preterm infants with (or developing) chronic lung disease (Cochrane Review). The Cochrane Library, Issue, vol. 3. Chichester, UK7 John Wiley & Sons, 2004.
170 [17] Kao LC, Durand DJ, McCrea RC. Randomised trial of long-term diuretic therapy for infants with oxygen dependent bronchopulmonary dysplasia. J Pediatr 1994; 124:772 – 81. [18] Albersheim SG, Solimano AJ, Sharma AK. Randomised double blind controlled trial of long term diuretic therapy for bronchopulmonary dysplasia. J Pediatr 1989; 115:615 – 20.
N.J. Shaw, S. Kotecha [19] Hoffman DJ, Gerdes JS, Abbasi S. Pulmonary function and electrolyte balance following spironolactone treatment in preterm infants with chronic lung disease: a double-blind, placebo-controlled randomised trial. J Perinatol 2000; 20:41 – 5. [20] Dunbar H, Kotecha S. Domiciliary oxygen for infants with chronic lung disease of prematurity. Care Crit Ill 2000; 16(3):90 – 3.