NRP 2006: The Canadian Context Therapeutic Use of Oxygen (In Newborn Resuscitation)

1. NRP 2006: The Canadian ContextTherapeutic Use of Oxygen(In Newborn Resuscitation) D.D. McMillan,MD November 17, 2006

2. Half of what we know today will be shown not to be true within 10 years

3. But which half!

4. “New” Equipment- NRP 2006 • Blended oxygen • Pulse oximeter • Ventilation with PEEP • Laryngeal mask airway • CO2 detector • Servocontrol probe • Plastic baggies

5. Methods for Blended Oxygen • Blender • Air and O2 flowmeters Air (L/Min) O2(L/Min) O2 Concentration(%) 5 0 21 4 1 37 3 2 53 2 3 68 1 4 84 0 5 100

6. Body Utilization of Oxygen • Cytochrome oxidase producing energy (>90%) • Oxidoreductases (eg. Xanthine oxidase) • Incorporation into substrate (eg.Oxygenases) • Non enzymatic (<1%)

7. Frank, 1980

8. Organ Site Of Free Oxygen Radical Damage • Lungs • Eyes • Brain • Gastrointestinal Tract • Kidneys • Other

9. Lambs Breathing 100% O2Bressack 1979

10. Lambs Breathing 100% O2Bressack 1979

11. AAP NRP Guidelines 2006Babies Born At Term • Use 100% oxygen when a baby is cyanotic or when positive-pressure ventilation is required • Research suggests that resuscitation with less than 100% may be just as successful. • If resuscitation is started with less than 100% oxygen, administer supplemental oxygen up to 100% if there is no improvement within 90 seconds following birth. • If supplemental oxygen is unavailable, use room air for positive-pressure ventilation.

12. AAP NRP Guidelines 2006Preterm Babies (<32 Weeks Gestation) • Use an oxygen blender and pulse oximeter during resuscitation. • Begin PPV with oxygen concentration between room air and 100% oxygen. No studies justify starting at any particular concentration. • Adjust oxygen concentration to achieve an oxyhemoglobin saturation that gradually increases toward 90%. Decrease the oxygen concentration as saturations rise over 90%. • If heart rate does not respond to >100 bpm, correct ventilation problems & use 100% oxygen.

13. What is the Evidence to Support Room Air over 100% Oxygen for Newborn Resuscitation?

14. Treatment Allocation & Follow Up Ramji, 1993

15. Neonates With Abnormal Neurologic Examination During The First Week Ramji, 1993

16. Saugstad, 1998

17. Kaplan-Meier plot showing the proportion that had not taken the first breath in room air- and oxygen-resuscitated newborn infants. Time to first breath was significantly longer in the oxygen-resuscitated group compared with the room air-resuscitated group. In the oxygen group, 60/313 (19.2%) required >3 minutes to take the first breath compared with 28/284 (9.9%) in the room air group (OR = 0.47; 95% CI = 0.29-0.76). Saugstad, 1998

18. Mortality with Oxygen or Air for Resuscitation- Saugstad, 2005

19. Mortality with Oxygen or Air for Resuscitation- Saugstad 2005

20. Room Air Versus 100% OxygenDeath At Latest Follow Up Tan, 2006

21. Room Air Versus 100% OxygenH.I.E. Grade 2 or 3 Tan, 2006

22. Tan 2006- Room Air Versus 100% OxygenFirst Arterial Blood Gas Within 2hours After Birth

23. Tan 2006Room Air Versus 100% OxygenFirst Arterial Blood Gas Within 2hours After Birth

24. Problems with studies • Limited number of studies/babies • Majority in developing countries • High mortality rates • Variable/imprecise criteria for resuscitation • Failure to blind • Design to show equivalence

25. Possible Mechanisms of Effects • Oxygen free radical damage • Upregulation of NO in PMNS (peroxynitrites) • Activation of inflammatory mediators • Oxidation of DNA & phenylalanine • Decreased cerebral blood flow • Increased oxygen consumption • Increase in intracellular calcium • Upregulation of pro-aptoptotic pathways • Increased apoptosis & neural stem cells

26. Brain Injury and Oxygen Exposure First 8 Days After Birth Collins Ped Res, 2001

27. Is there Opposing Evidence? • No human studies • Newborn piglets resuscitated with air (Solas) - Increased CNS amino acids (eg.glutamate) - Increased oxygen delivery to brain (No change in glutamate) - Lower mean BP & CNS microcirculation (No change in CNS amino acids) • Others show no difference in animal studies

28. Rabi, 2006

29. Rabi, 2006

30. Oxygen Saturation After Birth

31. Does it have to be “all or none”? Can we titrate oxygen to meet the “needs” of the newborn baby?

32. Smoothed Frequency Distribution of Actual Oxygen-Saturation Values on Pulse Oximetry During Oxygen Therapy After Randomization Askie, 2003

34. Canadian Recommendations For Oxygen During Resuscitation • Positive-pressure ventilation should be initiated with air (21% oxygen). • Supplemental oxygen should be used if the baby remains cyanotic or heart rate is less than 100 bpm at 90 seconds. • Blended gases should be available in the delivery room and during transport to the NICU. • To avoid hyperoxemia, pulse oximetry should be available in rooms for delivery of babies <33 weeks gestation. Even without clear definition of hyperoxia for preterm infants, avoid saturations above 95% when supplemental oxygen is used.

35. Where are we Now?Survey of U.S. Deliveries (Leone 2006) • 52% Pulse oximeters • 42% Blenders -77% Oxygen to start -68% Use pulse oximeters to adjust • 76% PEEP for preterms (58% flow-inf, 19% self-inf, 16% T-piece)

36. Thankyou