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Bronchopulmonary Dysplasia

• Summary
• Introduction
• Risk Factors
• Clinical Features
• Management of BPD in Level 3 Units
• Respiratory Criteria for Transfer to a Level 2 Hospital
• Management in the Level 2 SCN
• Oxygen
• Home oxygen
• Follow up

Summary

• the most severely affected babies are the most premature, particularly 23-26 week gestation babies
  
  
• diuretics and corticosteroids are effective in achieving short-term improvement in the status of ventilator dependant babies. Safety issues of steroid use are unresolved. There is no place for long term therapy with diuretics in level 2 SCN's
  
  
• there is no consensus on how to wean oxygen in babies with BPD
  
  
• the transition from a tertiary hospital nursery to a level 2 SCN is a difficult time for parents as they adjust to different staff and practices

Introduction

In line with the recommendations from a recent workshop in North America the term bronchopulmonary dysplasia (BPD) will be used in this chapter rather than Chronic Lung Disease. The definition is complicated, however in  this chapter BPD refers to a premature baby who has been in oxygen for > 28 days.

Over the past decade the clinical definition of BPD has evolved from oxygen dependency at 28 days of age to  oxygen dependency at 36 weeks corrected gestational age.

The National Institute for Health in the USA has further divided this definition into mild (in supplemental oxygen at 28 days of age, but in air by 36 weeks corrected age), moderate (requiring <30% supplemental oxygen at 36 weeks corrected age and severe (in >30% supplemental oxygen and/or requiring positive pressure support, CPAP or ventilation, at 36 weeks corrected age).

BPD is the single most important factor determining length of stay in babies born at less than 29 weeks. The most severely affected babies are the most premature, particularly 23 - 26 week gestation babies.

Risk Factors

• prematurity 
• peripartum inflammation/infection associated with preterm labour and/or clinical or subclinical chorioamnionitis
• postnatal lung Injury due to volutrauma, barotrauma,oxygen toxicity, hypocarbia or infection

Clinical Features

Tertiary unit babies with BPD (actual or evolving) fall into three broad groups

• babies dependant on endotracheal mechanical ventilation (MV)
• babies dependant of Nasal CPAP
• babies who are oxygen dependant, usually by nasal prongs

The most common clinical scenario is the 23 - 26 week gestation baby who, over a period of 4 - 10 weeks, progresses from MV, NCPAP through to requiring supplementary oxygen. These babies are usually transferred to a level 2 Special Care Nursery (SCN) for ongoing care. Although some of these babies spend many weeks on NCPAP it is common to see rapid improvement in their respiratory stability once weaned from NCPAP. Respiratory stability off NCPAP is the single most important criterion that determines suitability for transfer to a SCN. It is important to understand the tertiary unit's experience with babies at these gestations as it has a significant impact on decision making with respect to transfer to level 2 SCNs. Issues include

• all tertiary units experience late deaths of extremely premature babies due to chronic lung disease
  
  
• when prolonged MVis needed there are often many weeks before one can reassure the family with confidence that the baby is likely to survive. Once a baby is showing consistent growth associated with an oxygen requirement less than 40% the recovery process is likely to be successful
  
  
• some babies cope for many months on NCPAP in high (more than 40%) oxygen concentrations before dying. Fortunately this group is rare

These factors make the care of babies with BPD extremely demanding for babies and their families, as well as for nursing, medical and ancillary staff.

Management of BPD in Level 3 Units

Respiratory support

• endotracheal ventilation is increasingly being replaced by NCPAP, for even the tiniest babies many are being managed with NCPAP from birth. Results from a recent randomised controlled trial have shown that 50% of babies 25-28 weeks gestation are able to manage without ever requiring intubation and ventilation, and that infants of this age who commence NCPAP from birth have no increased risk of death or BPD, and in fact are less likely to be in oxygen at 28 days of age.

• for those who do require intubation and ventilation there is an intense focus on minimizing ventilator associated lung injury from the moment a baby is placed on a ventilator. Synchronised modes of MV with close monitoring of tidal volumes are key features of current practice. In addition there is a more liberal approach to carbon dioxide control, allowing CO₂ to rise into the 50's and 60's providing the pH remains better than 7.25
  
  
• oxygen damages delicate lung tissue as well as the immature retina. Pulse oximetry targets are typically set between 85 to 94% in the first weeks after birth
  
  
• ongoing randomised trials (BOOST2 trial in Australia) are attempting to determine whether we should be aiming for the bottom or top end of this target range. Babies in this trial may be transferred to level 2 nurseries with their trial saturation monitors in place as we continue to try to answer this question. 
  
• babies who require endotracheal ventilation are aggressively weaned and extubated to NCPAP often within 1-2 days of birth

Drug Therapy for established/evolving BPD

• Corticosteroids
  • dexamethasone is effective in achieving short-term improvement in the status of ventilator dependant babies as well as longer term reductions in BPD, however, there is now level evidence showing that dexamethasone in the first week of life is associated with an increased risk of cerebral palsy in survivors
  • safety of corticosteroids used later in the course of evolving BPD between 14 - 28 days is unresolved and the Cochrane review of current evidence suggests reserving the use of late corticosteroids to infants who cannot be weaned from mechanical ventilation, and minimising the dose and duration of treatment.
  • in light of this evidence frequency of the use of steroids for BPD in NICUs has dramatically declined in the past 5 years  and a "low" dose regimen (eg 0.15 - 0.25mg/kg/day) weaned and ceased over a 7 - 10 day period is recommended
  • typical clinical scenarios where steroids would be considered are a baby > 2 weeks of age who is unable to be weaned from endotracheal MV
  • there is no place for the use of steroids in the treatment of BPD outside a tertiary neonatal unit
  • early use of inhaled steroids is ineffective in preventing BPD, although there is some evidence they can be used to assist extubation in ventilator dependant infants. More work is needed in this area before this approach is taken.
• Diuretics
  • insufficient studies of suitable size reporting on important outcomes exist to strongly support the use of diuretics for the treatment of BPD
  • diuretics are an effective short term therapy for ventilated babies
  • There is no evidence for efficacy in non ventilated babies therefore diuretic therapy should be weaned and ceased once babies are stable off mechanical ventilation
  • typical combinations include hydrochlorothiazide and spironolactone
  • NaCl and KCl supplementation are commonly required
  • chronic frusemide administration is generally avoided, as it has been associated with the development of nephrocalcinosis and hyperchloremic metabolic alkalosis
  • there is no place for long term therapy with diuretics in level 2 SCN's

Nutrition

• provision of adequate calories in a nutritionally appropriate form is  critical, infants with BPD utilise 20-40% more kcal than infants without BPD
• caloric requirements of babies with moderate to severe lung disease can be as high as 130 - 150 calories/kg/day
• babies with BPD tolerate fluid overload poorly and are modestly fluid restricted (150 - 160mL/kg/day) and fed fortified breast milk or low birthweight formula
• growth is closely monitored and caloric intake titrated against growth
• Vitamin A supplementation reduces death and oxygen requirements at 36 weeks corrected gestational age. Vitamiin A is currently given as Pentavite to all infants from day 5 until discharge.
• babies sufficiently stable to transfer to a level 2 unit should not require a caloric density of > 24 cal/30mls

Oxygen Therapy

• oxygen is the one constant in the treatment of BPD but it has been poorly studied
• once weaned from NCPAP, oxygen is delivered by nasal prongs using low flow (<0.5L/min)
• there is no consensus on how to wean oxygen in babies with BPD
• weaning is dictated to some extent by the equipment available. Some tertiary centres have only recently moved from having flow meters with a lower limit of 0.25L/min/O2. Other units use flow meters that allow weaning down to as low as 0.005mL/min/O2. Most believe that weaning should be slow, but what this means varies from institution to institution
• babies with BPD have a degree of pulmonary hypertension, and are therefore likely to benefit from a more generous oxygen administration regimen rather than from a restrictive policy, however the corrected gestational age and the state of vascularistion of the retina needs to be taken into consideration before saturation targets are liberalised . Whilst there is some logic to this approach, there is indirect evidence from randomized controlled trials conducted for other reasons suggesting that a more liberal oxygen policy in these babies can actually increase the pulmonary morbidity. RCT's are in progress to address this question

Respiratory Criteria for Transfer to a Level 2 Hospital

• absolute minimum of 7 days off respiratory support including NCPAP or "high flow"(1-2L/min) subnasal oxygen
• maximum of 1 apnoea/bradycardias that require no or minimal stimulation for recovery
• consistent, stable oxygen saturation on ‹ 0.5L/min subnasal oxygen, or 35% headbox oxygen
• not receiving corticosteroids for BPD
• preferably the baby should not be diuretic dependant for respiratory stability
• consistent growth on 2-3 hourly bolus feeds with a caloric density no more than 24 cals/30mls
• there is a small number of babies with severe but nonNCPAP dependant BPD who are transferred to level 2 units. These are a specific group of babies where the decision to transfer and the principles of ongoing medical management require an individualised management plan worked out between referring and receiving Consultant Medical staff, preferably in collaboration with a Paediatric Thoracic Consultant. The principles of care of such babies is beyond the scope of this chapter

Management in the Level 2 SCN

The transition from a tertiary hospital nursery to a level 2 SCN is a difficult time for parents as they adjust to different staff and practices. Both tertiary and level 2 staff should be proactive in anticipating and addressing these issues. If the referring Neonatologist believes a particular approach should be considered for a particular baby, this should be discussed with the receiving Paediatrician directly so that a consistent message goes to the parents.

It is common in Victoria for level 2 SCN's to have oxygen flow meters that do not permit accurate delivery of subnasal oxygen below 0.25L/min. Parents must be educated about this in advance so they do not see the increased FiO2 dose as "wrong" or "bad" therapy or as an indication their baby has deteriorated. Clearly Victoria needs to work towards a consistent approach to equipment such as oxygen flow meters as the current system is illogical and confusing.

It is strongly recommended that these babies to be nursed in the SCN rather than the Paediatric ward even if post term corrected age. This should reduce the risk of developing nosocomial infection particularly respiratory viral infections.

Nutrition

• Aim to achieve an intake of 120cal/kg/day
• Breast milk fortifier or a low birthweight formula can be continued until at least term without adverse effects if caloric supplementation is required, and is recommended until at least 3kg
• For babies on tube feeds oral feeds should be cautiously introduced eg. initially one oral feed/day then 2 etc as the baby copes with the previous increment

Oxygen

General considerations

• Aim to move to intermittent oximetry rather than continuous once it is clear the baby is not having apnoea or bradycardia
• Saturation goals to be used lack consensus between the tertiary perinatal hospitals. At RWH the desired saturation range is 88-92% until post term and retina fully vascularised. At the Mercy Hospital the desired saturation range is 85-95%. At Monash Medical Centre fro infants <36 weeks the desired range is 88-92% and greater than 95% after 36 weeks
• Brief periods where the saturation drops to the low 90's are not of concern
• During feeding and certain parts of sleep are the times where a baby's oxygen demand is higher. Therefore if one is looking to see if a baby will manage in less oxygen saturations should be monitored over several feed periods or for several hours during sleep
• For babies in headbox/tent oxygen do not wean oxygen by more than 1% in a 24 hour period even if the saturations are 100%
• For babies on low flow subnasal oxygen do not wean by more than 10mls/24 hours
• If the lowest accurate flow deliverable is 0.25L/min then the only option is to periodically (eg twice/week) turn off the oxygen and carefully monitor the saturations
• Blood gas monitoring is not required in stable babies
• The indications for blood transfusion in a growing stable baby with a mild oxygen requirement have been the subject of a recent trail. The authors demonstrate that there is no benefit in maintaining higher haemoglobin levels. For babies receiving supplemental oxygen the authors showed no benefit to transfusion if the Hb was above 85g/L on a capillary sample (or 77g/L on venous sampling).   This conservative approach would be especially supported if there is a good reticulocyte count
  

Ceasing oxygen

• A prolonged period (8-12 hours) of saturation monitoring should be undertaken that captures extended periods of sleep and several feeds
• Babies with BPD should not be discharged until at least 72 hours after ceasing oxygen

Home oxygen

This will be the subject of a separate chapter, however some general points can be made.

Criteria for Home Oxygen - General

• Appropriate social/home environment including reasonable accessibility to medical care
• Baby is on 4 hourly or demand oral feeding regimen
• Baby is normothermic in an open cot
• Satisfactory growth
• All babies discharged from tertiary units on home oxygen have specific Paediatric Thoracic specialist follow up. It is strongly recommended that Paediatricians manage babies on home oxygen in collaboration with a Paediatric Thoracic physician

Criteria for Home Oxygen - Respiratory

• Baby must pass an "air test". The oxygen is turned off, the nasal prongs removed and the baby monitored over 30 minutes
• If saturations are maintained >86% for 30 minutes the test should be repeated in 48 hours. If a second test is satisfactory the baby is eligible for discharge on home oxygen on respiratory grounds. In other words the baby has demonstrated a reasonable level of respiratory reserve

Follow up

• These babies require term follow up throughout childhood
• There is an increased pulmonary morbidity in the first 2 years of life. Parents should be counselled about this morbidity and ways to minimise it.
• Influenza vaccine is recommended for infants with ongoing cardiac, respiratory or neurological illnesses at 6 months of age. Recommendations are 2 doses, 4 weeks apart
• Influenza vaccine is not officially recommended for these babies
• RSV prophylaxis is not routinely recommended, the American Academy of Pediatrics recommends use of RSV prophlaxis for infants <2yrs, with BPD requiring treatment within the last 6 months, who are discharged home prior to the RSV season. The Department of Health in the UK recommends its use in children <2yrs with BPD on home oxygen or who have had prolonged use of oxygen 

References

Jobe A, Bancalari E. Bronchopulmonary Dysplasia, NICHD/NHLBI/ORD Workshop Summary. Am J Respir Crit Care Med. 163 1723-1729, 2001

Barrington KJ and Finer NN. Treatment of Bronchopulmonary Dysplasia - A Review. Clinics in Perinatology 25 1 March 1998 177-202

Brion L et al. Diuretics acting on the distal renal tubule for preterm infants with (or developing) chronic lung disease. Cochrane Neonatal group, Cochrane database of systematic reviews, Issue 3, 2001.

Shah V, Ohlsson A, Hallidah HL, Dunn MS. Early administration of inhaled corticosteroids for prevention of chronic lung disease in ventilated VLBW preterm neonates. Cochrane Neonatal group, Cochrane database of systematic reviews, Issue 3, 2001.

Halliday HL and Ehrenkranz RA. Early postnatal corticosteroids for the prevention of chronic lung disease in preterm babies. Cochrane Neonatal group, Cochrane database of systematic reviews, Issue 3, 2001.

Chronic Lung Disease. Department of Neonatal Medicine Protocol Book, Royal Prince Alfred Hospital, Sydney, NSW. www.cs.nsw.gov.au/rpa/neonatal

Oxygen Therapy. Department of Neonatal Medicine Protocol Book, Royal Prince Alfred Hospital, Sydney, NSW. www.cs.nsw.gov.au/rpa/neonatal

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. N Engl J Med. 2008 Feb 14;358(7):700-8. Erratum in: N Engl J Med. 2008 Apr 3;358(14):1529.

Darlow BA, Graham PJ. Vitamin A supplementation to prevent mortality and short and long-term morbidity in very low birthweight infants. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD000501. Review.

Kirpalani H, Whyte RK, Andersen C, et al The Premature Infants in Need of Transfusion (PINT) study: a randomized, controlled trial of a restrictive (low) versus liberal (high) transfusion threshold for extremely low birth weight infants. J Pediatr. 2006 Sep;149(3):301-307

The Australian Immunisation Handbook, 9th Edition 2008, Australian Government;Department of Health and Ageing;National Health and Medical Research Council

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