SpR Training Day, 5/10/06 Dr Russell Peek Chronic Lung Disease SpR Training Day, 5/10/06 Dr Russell Peek

Objectives By the end of this session, you will: have evaluated the use of systemic corticosteroids in the ventilated preterm infant; be able to discuss the role of other treatments in prevention and management of chronic lung disease; appreciate important issues in discharge planning for the infant with chronic lung disease; understand long term outcomes for infants with chronic lung disease.

Systemic Corticosteroids Chronic lung disease is an inflammatory process Corticosteroids are potent anti-inflammatory agents Why not try corticosteroids to prevent or treat chronic lung disease?

Scenario Peter, born after spontaneous preterm labour at 26 weeks, is now 15 days old. He has been ventilated since birth. A patent arterial duct was successfully treated with a single course of ibuprofen. SIMV 28/6 FiO2 0.45. Not tolerant of weaning. Chest xray: evolving CLD. Should he receive steroids?

Task In 3 groups discuss the Cochrane reviews of early, moderately early and late use of corticosteroids.

Task Prepare a brief presentation to give to the rest of the group considering the following issues: effectiveness in preventing chronic lung disease short term side effects long term outcomes clinical ‘bottom line’

Cochrane Conclusions Methodological quality of long term studies limited Assessment before school age in most Insufficient power to detect adverse long term outcomes. Benefits may not outweigh potential adverse effects Use as rescue therapy Minimise dose and duration.

Recent evidence: The DART study Low dose dexamethasone facilitates extubation, (OR 11.2) shortens duration of intubation, (14 vs. 21 days) reduces oxygen requirements no significant effect on blood glucose or BP mortality or oxygen requirement at 36 weeks Low-dose dexamethasone facilitates extubation among chronically ventilator dependent infants: a multicenter, international, randomised controlled trial. Doyle et al. Pediatrics (2006): 117; 75-83

Kaplan-Meier Plot

Counselling parents Having discussed the Cochrane reviews and the DART study, how would you counsel parents if you were considering corticosteroids for their child?

Other Treatment Strategies Other prophylaxis or treatment strategies: anti-inflammatory bronchodilation specific nutritients antibiotic etc

Inhaled Corticosteroids No difference in effectiveness or side-effect profiles for inhaled versus systemic steroids No long term outcome data Not recommended based on current evidence

Sodium Cromoglycate A mast cell stabiliser that inhibits neutrophil activation and neutrophil chemotaxis. No evidence from RCTs of a role in prevention of CLD.

Inhaled Bronchodilators Insufficient data to reliably assess use of salbutamol for prevention of CLD. Further clinical trials are necessary to assess bronchodilators for prophylaxis or treatment.

Vitamin A Vitamin A is necessary for normal lung growth and integrity of respiratory tract epithelial cells Studies involved repeat im. doses Modest reduction in death or oxygen dependence at 1 month (RR 0.93, NNT 20) Modest reduction in oxygen dependence at 36 weeks postnatal age (RR 0.87, NNT 14)

Vitamin E An antioxidant Deficiency worsens oxygen toxicity No evidence that routine supplementation prevents CLD

Inositol component of phospholipids critical role in surfactant synthesis supplementation reduced risk of CLD or death in 1 small study further evidence required

Selenium a part of glutathione peroxidase acts synergistically with vitamin E supplementation produced no reduction in CLD or days of oxygen therapy

Glutamine essential for rapidly dividing cells not present in routine TPN supplementation produced no reduction in BPD in one study

Superoxide Dismutase Free oxygen radicals implicated in the pathogenesis of chronic lung disease in preterm infants Currently insufficient evidence about efficacy in preventing chronic lung disease

Diuretics - systemic Lung disease in preterm infants is often complicated with lung oedema Administration of diuretics improves pulmonary mechanics in CLD Little evidence to support any benefit on need for ventilatory support, length of hospital stay or long-term outcome In preterm infants > 3 weeks of age with CLD

Diuretics - inhaled A single dose of aerosolized furosemide improves pulmonary mechanics Lack of data concerning effects on important clinical outcomes Not currently recommended

Antibiotics Ureaplasma urealyticum postulated as a cause of CLD (not proven) Erythromycin has been investigated in 2 small studies No statistically significant effect on CLD, death or combined outcome of CLD or death

Alpha 1 Proteinase inhibitor Aim to counteract enzymatic damage to lung tissues with prophylactic proteinase inhibitor No reduction in risk of CLD at 36 weeks No reduction in adverse neuro-developmental outcomes No significant difference in other respiratory parameters.

Nutrition Babies with CLD feed less well than other preterm infants have lower fluid intakes have increased energy expenditure often have abnormal growth patterns are at risk of ongoing faltering growth

The Energy Balance Equation

Nutrition No evidence base for nutrition in CLD ideal energy intake optimum mix of protein/CHO/fat rates of growth In general, supplemented feeds are used

Nutrition Monitor weight, height and OFC Height ‘catch up’ can continue to age 10 Weight gain is often more problematic

Discharge Planning Peter is now 1 week past term and has stable saturations in 50cc low flow oxygen. He is fully bottle fed. What issues should be considered before discharge and at the discharge planning meeting?

Discharge Planning Home oxygen therapy Resuscitation training oximeter? apnoea alarm? Resuscitation training Vaccination Risks of smoking and infection Nutrition and growth Medication Follow up

Oxygen therapy In adults, pulmonary hypertension occurs <90% saturation Normal babies have saturations >95% Growth is poorer with saturations <92% Aim for >94% at home; minimise time <90%

O2 Saturation Study

Long term outlook Pulmonary function Improvement occurs to age 8 Reduced lung volumes (VC, FEV1) Decreased lung compliance Decreased airway conductance Improvement occurs to age 8 Generally fail to achieve normal values

Long term outlook Functional outcome - illness More respiratory morbidity in early life Cough and wheeze with respiratory viruses Functional outcome - exercise Similar endurance in mid childhood Similar maximal oxygen consumption More desaturation Faster, shallower breathing

Objectives By the end of this session, you will: have evaluated the use of systemic corticosteroids in the ventilated preterm infant; be able to discuss the role of other treatments in prevention and management of chronic lung disease; appreciate important issues in discharge planning for the infant with chronic lung disease; understand long term outcomes for infants with chronic lung disease.

Any Questions?

Summary Chronic lung disease is associated with morbidity into childhood and adolescence Few pharmacological approaches to treatment or prevention have proven useful Attention should be given to optimising oxygen saturations and nutrition Discharge planning is essential