1. Respiratory support and respiratory outcome in preterm infants PD Dr. med. Ulrich Thome Division of Neonatolgy and Pediatric Critical Care University Children’s Hospital Ulm, Germany

2. Topics Sequelae of lung injury Conventional ventilation strategies Synchronized ventilation Volume-controlled ventilation High frequency ventilation Permissive hypercapnia Non-invasive ventilation

3. Sequelae of lung injury –Acute lung injury (air leaks) –Bronchopulmonary dysplasia (BPD) Conventional ventilation strategies Synchronized ventilation Volume-controlled ventilation High frequency ventilation Permissive hypercapnia Non-invasive ventilation Topics

4. Bronchopulmonary dysplasia (Northway 1967) –Epithelial metaplasia –Fibrosis –Smooth muscle hypertrophy –Heterogenous inflation “New BPD“ (Jobe 1999) –Extremely immature preterm infants, surfactant-treated –Arrested lung development Reduced alveolar formation Reduced gas exchange area Reduced microvascular development Definition: Oxygen or ventilator support needed at 36 weeks PMA BPD

5. Sequelae of lung injury Conventional ventilation strategies –Avoiding volutrauma –Avoiding atelectotrauma Synchronised ventilation Volume controlled ventilation High frequency ventilation Permissive hypercapnia Non-invasive ventilation Topics

6. ventilator-induced lung injury Volutrauma rather than barotrauma ( Dreyfuss D et al. AJRCCM 1998) Multicenter trial in adults: Lower VT reduced mortality, lung injury and multi- organ failure (N Engl J Med 2000; 342:1301-8) =>↓ Tidal volume: Decreases lung injury May result in “permissive hypercapnia” Operator Mechanical ventilation is harmful!

7. B Normal V T, high PEEP AHigh V T low PEEP DOptimal A B Time → Volutrauma Zone C atelectasis overdistention D CNormal V T low PEEP W. A. Carlo Which volumes cause lung injury?

8. Effect of 6 inadequately large breaths

9. MV = V T * f Reduced tidal volume can be compensated by increase of rate Respiratory minute ventilation

10. NNT Pneu:11NNT PIE:5 Trend towards reduced mortality However: no reduction in BPD

11. B Normal V T, high PEEP AHigh V T low PEEP DOptimal A B Time → Volutrauma Zone C atelectasis overdistention D CNormal V T low PEEP W. A. Carlo Which volumes cause lung injury?

12. Animal studies indicate increased lung injury at too low or too high PEEP levels Multicenter trial of two PEEP levels in adults with ARDS: no difference (N Engl J Med 2004; 351:327-336) No randomized studies on preterm infants available Optimal PEEP level

13. Sequelae of lung injury Conventional ventilation strategies Synchronised ventilation Volume controlled ventilation High frequency ventilation Permissive hypercapnia Non-invasive ventilation Topics

14. Possible advantages: higher patient comfort more stable gas exchange because of the patients’ own regulatory mechanisms Possible disadvantage: increased volutrauma Flow sensors used for triggering: – 1 ml of dead space = 33% of V T in 500g infant More frequent occurrence of Head’s reflex Pediatr Pulmonol. 1997, 24:195-203 Why synchronize?

15. BPD at 28 days postnatal age BPD at 36 weeks postmenstrual age Synchronized Ventilation

16. Air leaks Death

17. Sequelae of lung injury Conventional ventilation strategies Synchronized ventilation Volume controlled ventilation High frequency ventilation Permissive hypercapnia Non-invasive ventilation Topics

18. Two forms –Volume controlled –Volume guarantee Automatically adjusts peak pressure to ensure correct tidal volume –Immediately responds to inadvertent changes in lung mechanics Requires a flow sensor –Increased deadspace may lead to increased volutrauma in extremely small infants (< 1000g) Volume controlled ventilation

20. Sequelae of lung injury Conventional ventilation strategies Synchronized ventilation Volume controlled ventilation High frequency ventilation Permissive hypercapnia Non-invasive ventilation Topics

21. High frequency (300-1200/min = 5-20 Hz) Very small tidal volumes Incomplete inspiration and expiration Dampening of oscillations in the airways => Very small intra-alveolar pressure amplitude Features of HFV

22. Thome U et al.: ADC F&N ed., in press

24. Sequelae of lung injury Conventional ventilation strategies Synchronised ventilation Volume controlled ventilation High frequency ventilation Permissive hypercapnia Non-invasive ventilation Topics

25. Less than normal PaCO 2 requires higher work of breathing. Higher than normal PaCO 2 impairs oxygenation Mechanical ventilation - normal PaCO 2 not needed: Impaired oxygenation can be easily compensated by ↑FiO 2 Increased PACO 2 improves CO 2 removal Higher PaCO 2 goal provides a greater margin of safety against hypocapnia Why maintain a PaCO2 of 40 mmHg?

26. Randomised trials

27. Sequelae of lung injury Conventional ventilation strategies Synchronised ventilation Volume controlled ventilation High frequency ventilation Permissive hypercapnia Non-invasive ventilation –Nasal CPAP –Nasal IMV Topics

28. NNT Failure: 4.0; NNT Mortality: 4.5; NNH Pneumotx. : 8 CDP n=71, standard care n=74 nCPAP or CNP for RDS

29. NNT Failure:6 nCPAP n=239, headbox n=240 nCPAP after Extubation

30. nIPPV vs nCPAP after Extubation

31. High rate (60/min) low tidal volume ventilation: –better short-term results than low rate ventilation Synchronized and volume controlled ventilation: –not shown to improve long-term outcome –need dead space increasing flow sensors –may be associated with increased V T High frequency ventilation: –no better outcome than high rate low tidal volume ventilation Permissive hypercapnia: –not shown to improve long-term outcome –moderately high PaCO 2 goals safe Non-invasive ventilation: –reduces the need for intubation and invasive ventilation –increases success rate after extubation: nIMV > nCPAP –increased incidence of air leaks compared to no ventilation Summary

32. Use only when absolutely necessary Machine: any Rate: high (>60/min) PEEP: sufficient (3-6 mbar) Tidal volume: as small as possible (don’t measure) Synchronization, volume-controlled, volume- guarantee: use under special circumstances, flow sensor contraindicated <1000g HFOV: not necessary for usual infants Permissive hypercapnia: moderately high PaCO 2 g Non-invasive ventilation: use instead of invasive vent. whenever possible, don’t use in too healthy pts Recommendation for ventilation