Session Information Session Title : NRP: Climbing the Olympic Hill to Better Evidence, Implementation, and Outcomes T

1. Session Information Session Title: NRP: Climbing the Olympic Hill to Better Evidence, Implementation, and Outcomes TEN KEY PAPERS Session Number: C6000 Faculty Name: Steven Ringer, MD, PhD Jay Goldsmith MD George Little MD Faculty Institutions: Harvard Medical School, Tulane University, Dartmouth Hitchcock Medical Center

2. Faculty Disclosure Information In the past 12 months, we have had no financial relationships with the manufacturer(s) of any commercial product(s) and/or provider(s) of commercial service(s) discussed in this CME activity: we do not intend to discuss an unapproved/investigative use of a commercial product/device in my presentation.

3. Key papers on newborn resuscitation, spanning 50 years Primary studies on physiology of transition and effect of depression Investigations on best approaches Evolution of educational modalities Potential future changes Expansion to all newborns Ten Key Papers

4. Problem or intervention is defined A hypothesis is stated Evidence is sought using numerous search engines i.e. Pubmed, Embase, ECC library etc Evidence includes both human and animal data (distinguishes this process from Cochrane) 8 levels of evidence Evidence is evaluated for quality and then placed in grids either supporting or opposing the question The data are summarized and a scientific statement with a class of recommendation is made Evidenced Based Process

5. Review and Debate of Literature Step 1: Define existing and proposed guidelines Step 2A: Gather the Evidence

6. Review and Debate of Literature Step 2b: Classify the Level of Evidence Level 1: Randomized controlled trial with large effect Level 2: Randomized controlled trial with small effect Level 3: Prospective controlled non-randomized study Level 4: Historic, non-randomized cohort study Level 5: Non-controlled case series Level 6 Animal or mechanical model study Level 7: Extrapolation or theoretical analysis Level 8: Rational conjecture (common practice)

7. Review and Debate of Literature Step 2b: Classify the Level of Evidence

8. Review and Debate of Literature Step 2b: Classify the Level of Evidence

9. Review and Debate of Literature Step 2c: Evaluate the Quality of Evidence

10. Neutral evidence table denotes key article(s)

11. Opposing evidence table denotes key article(s)

12. Present a key summary graph or table Citation #1 Key studies

13. Summary Outcomes (example) Copy and Paste Summary Table from Worksheet

14. Insert Summary statement(s) from worksheet(eg. Evidence from 3 observational studies and 7 animal studies confirm consistent benefits for Parachutes over Handkerchiefs when assessing the following outcome variables: . . .) Some harm was noticed when parachutes failed to open (NNH= 1) Consensus on Science statements

15. Insert Treatment Recommendations from worksheet e.g.. Parachutes should be used in all planned and unplanned jumps from altitude. Handkerchiefs should not be used in jumps from altitude Draft Treatment Recommendations

16. Other specific worksheets that would be helpful Relationship with training to ETT success Specific research required Adult ETT vs. BVM Knowledge Gaps (e.g.. ETT vs. BVM)

17. Class 1: Always acceptable, proven safe, definitely useful Class IIa: Acceptable, safe, useful (standard of care intervention of choice) Class IIb: Acceptable, safe, useful (within the standard of care or an optional or alternative intervention) Class Indeterminate: Preliminary research stage with promising results but insufficient available evidence to support a final class decision Class III: Unacceptable, no documented benefit, may be harmful Clinical Interpretationof Classes of Recommendation Newer system is more direct and clear than the previously used classes of recommendation:

18. Review a central group of papers that impact how we care for newborns now (How and why we do) Consider recent results that may guide practice in the future (What will we be doing) Examine the papers advocating a change in education and training for resuscitation (How we teach) Session Goals

19. Adamsons K Jr, Behrman R, Dawes GS, Dawkins MJ, James LS, Ross BB. The Treatment of acidosis with alkali and glucose during asphyxia in foetal rhesus monkeys. J Physiol. 1963 Dec;169:679-89 A review of the early work by Dawes, Adamsons and others examining the effects of experimental acute asphyxia on newborn Rhesus monkeys. Central paper demonstrating physiologic response, primary and secondary apnea, effectiveness of resuscitation Level of Evidence (LOE) 6 1. Physiologic effect of asphyxia

20. Rhesus monkeys delivered at term by cesarean section Controlled Asphyxiation by slipping saline filled rubber bag over head, tying umbilical cord, for 10-15 minutes Placed on table at 30 degrees C. Umbilical artery catheterized, infant monitored Resuscitation with PPV, Oxygen, Cardiac massage as needed Physiologic responseto asphyxia

21. Identified pattern of initial gasping, primary apnea, gasping followed by “last gasp” and secondary apnea Demonstrated the development of bradycardia and hypotension over course of experiment, recovery with resuscitation Defined the relationship between length of asphyxia and time for recovery Physiologic responseto asphyxia

22. Asphyxia and Cardiac Function Adamsons, et al

23. Recovery from asphyxia Time for recovery depends on length of asphyxia Adamsons, et al

24. These and related papers defined the response of the newborn to acute asphyxia, and set the stage for techniques of resuscitation in humans Demonstrated the resuscitation before the “last gasp” (~8.4 minutes) resulted in absent or trivial cerebral damage Resuscitation after 12.5 minutes accompanied by widespread and severe damage Asphyxia does not end with ventilation, continued support and ongoing evaluation needed Physiologic responseto asphyxia

25. Wiswell TE, Gannon CM, Jacob J, Goldsmith L, Szyld E, Weiss K, Schutzman D, Cleary GM, Filipov P, Kurlat I, Caballero CL, Abassi S, Sprague D, Oltorf C,Padula M. Delivery room management of the apparently vigorous meconium-stained neonate: results of the multicenter, international collaborative trial. Pediatrics. 2000;105:1-7 The management of the baby with MSF has evolved dramatically over past 30 years. Most babies not depressed Randomized MCT of > 2000 babies compared intubation vs. expectant care Demonstrated lack of utility of intubation and suctioning in vigorous infants with MSF LOE 1 2. Management of MeconiumStained Fluid (MSF)

26. Vain NE, Szyld EG, Prudent LM, Wiswell TE, Aguilar AM, Vivas NI. Oropharyngeal and nasopharyngeal suctioning of meconium-stained neonates before delivery of their shoulders: multicentre, randomised controlled trial. Lancet. 2004;364(9434):597-602. Naso or oropharyngeal suctioning of MSF before delivery of shoulders compared with no suctioning, randomized trial, >2500 infants. No differences in Meconium Aspiration syndrome, need for ventilation, mortality or length of care Routine suctioning not recommended LOE 1 3. Management of MeconiumStained Fluid (MSF)

27. Saugstad OD, Rootwelt T, Aalen O. Resuscitation of asphyxiated newborn infants with room air or oxygen: an international controlled trial: the Resair 2 study. Pediatrics. 1998;102(1):e1. ResAir 2 was the second of two large trials, with >600 babies enrolled, randomized to 100% Oxygen or air Study demonstrates efficacy of room air resuscitation in a full term cohort, with equal or better safety LOE 2 4. Room Air or 100% Oxygen

28. No difference in mortality 12.1% RA vs. 15% oxygen Death within 7 days or moderate/severe hypoxic ischemic encephalopathy: 21.2% RA vs. 23.1% oxygen (NS) No difference in growth or neurologic disability at 18-24 mo. (only 70% of population) Cochrane Review concludes there is insufficient evidence to recommend one or the other (Lancet meta-analysis with different conclusion) Room Air or100% Oxygen?

29. Key Human Studies:Term and Premature Infants

30. Time Needed for Onset of Sustained Respirations Vento et al., Biol Neonate, 2001

31. Vento, 2003

32. Meta-analysis of 5 human studies (2004) Relative risk of death favored RA group OR 0.71; 95% CI 0.54-0.94 Only 1302 infants included in analysis No infants <1000 grams; few prematures ? Truly asphyxiated (entry criteria questioned) Randomization not optimal Only 2 studies were blinded 168 of 635 infants in RA group received cross-over oxygen 100% Oxygen vsAir: Human Studies

33. Meta-analysis of 5 human studies (2004) 174 of 177 deaths in developing countries No details of causes of death No plausible mechanism for deaths in oxygen group proposed Entry criteria may not have selected babies who were truly asphyxiated 100% Oxygen vs. Air: Human Studies

34. Tan A, Schulze A, O’Donnell CPF, Davis PG: Cochrane Library, Issue 3, 2004 “There is insufficient evidence at present on which to recommend a policy of using room air over 100% oxygen, or vice versa, …” “We note the use of back-up 100% oxygen in more that a quarter of infants randomised to room air.” Davis PG, Tan A, O’Donnell CPF, Schulze A: Lancet 364:2004 “The pooled analysis showed a significant mortality benefit for infants resuscitated with air (RR 0.71 [95% CI 0.54-0.94]; RD – 0.05).” Causes of death were not given. Most babies in all 5 studies were recruited from developing countries. “For term and near term infants, air should be used initially, with oxygen as back-up if initial resuscitation fails” Meta-Analyses ofKey Human Studies

35. Risk of oxygen toxicity increased in premature infants, prompting RA or low O2 resuscitation Randomized trial of infants ≤ 28 weeks- starting with low (30%) or high (90%) O2 Weaned up for bradycardia, down for high saturations Both groups ended up in 45% oxygen, no short term differences 5. Room Air or Oxygen in Prematures? Escrig R, Arruza L, Izquierdo I, et al. Achievement of Targeted Saturation Values in Extremely Low Gestational Age Neonates Resuscitated With Low or High Oxygen Concentrations: A Prospective, Randomized Trial. Pediatrics 2008; 121: 875-80.

36. Proportion of infants ventilated with room air in first 20 minutes Escrig, 2008

37. SpO2 Values infirst 20 minutes Escrig, 2008

38. Wang CL, Anderson C, Leone TA, Rich W, Govindaswami B, Finer NN. Resuscitation of preterm neonates by using room air or 100% oxygen. Pediatrics 2008;121(6):1257. Small trial (41 infants) of RA vs. 100% oxygen as initial gas for infants 23-32 weeks Weaned up for low saturation, and to 100% for low HR or chest compressions, down for high saturation All RA patients required rescue, failed to meet target saturations without O2, so RA not recommended LOE 2 5. Room Air or Oxygen in Prematures?

39. Mean SpO2 ateach minute of life Wang et al, 2008

40. Morley CJ, Davis PG, Doyle LW, Brion LP, Hascoet JM, Carlin JB. Nasal CPAP or Intubation at Birth for Very Preterm Infants. N Engl J Med 2008; 358:700. Randomized 610 infants 25-28.6 weeks gestation to CPAP+8 or intubation @ 5 min, multicenter Babies deemed to need immediate intubation were excluded Infants given mask ventilation at birth if needed, assessed at 5 minutes for need for ongoing support CPAP by nasal prongs at 8 cm H20 CPAP infants intubated for: Unresponsive apnea, respiratory acidosis or unresponsive metabolic acidosis, need for >60% oxygen 6. CPAP for Resuscitation

41. 46% of CPAP group were intubated , median time 6.6 hours 33.7% of CPAP group had BPD or died, vs.38.9% of intubated group, not significant Lower risk of oxygen need or death @ 28 d, no difference in mortality, fewer vent. days 9% pneumothorax in CPAP group, vs. 3 % in other CPAP for resuscitation

42. CPAP did not reduce death or BPD in 25-28 week gestation infants Did result in less oxygen use at 28 days, but more pneumothoraces, no difference in associated morbidities Results suggest that starting with CPAP is appropriate, and that not all small babies need surfactant CPAP used at 8 cm H2O, not started until 5 minutes, so less easy to generalize LOE 1-2 6. CPAP for Resuscitation

43. Tyson JE, Parikh NA, Langer J, Green C, Higgins RD. Intensive Care for Extreme Prematurity- Moving beyond Gestational Age. NEJM 2008; 358:1672 Outcome evaluated in over 4100 ELBW infants Death or degree of impairment evaluated Not only Gestational age, but sex, exposure to antenatal steroids, singleton or multiple, birthweight have impact LOE 1 7. Moving beyond Gestational age for prognosis

44. Ohlinger J, Kantak A, Lavin JP Jr, Fofah O, Hagen E, Suresh G, Halamek LP,Schriefer JA.Evaluation and development of potentially better practices for perinatal and neonatal communication and collaboration. Pediatrics. 2006;118 Suppl 2:S147-52. Halamek LP. The simulated delivery-room environment as the future modality for acquiring and maintaining skills in fetal and neonatal resuscitation. Semin Fetal Neonatal Med. 2008; (Jun)2. Simulation training has increased in sophistication over the past several years Effective simulation does not require high technology, but a commitment to “suspend disbelief” and work as a team The use of simulation in team teaching and training is becoming the standard, is the future for NRP 8.Simulation training/Debriefing

45. Delivery of optimum care requires more than just assimilation of content knowledge and proficiency in technical skills Skills needed include: Cognitive, or content knowledge “think” Technical, or manual skills “do” Behavioral “think and do, as part of a team” 8.Simulation training/Debriefing

46. 1. Know your environment. 2. Anticipate and plan. 3. Assume the leadership role. 4. Communicate effectively. 5. Delegate workload optimally. 6. Allocate attention wisely. 7. Use all available information. 8. Use all available resources. 9. Call for help when needed. 10. Maintain professional behavior. Behavioral skills

47. • Classroom environment • Characterized primarily by passive, not active, learning opportunities • May be primarily focused on teaching rather than learning • Lacks realistic cues, distracters and pressures • Unable to adequately prepare for practice in the real environment • Clinical environment • Places patients at some degree of risk • Learning opportunities (cases) present randomly • Learning limited by fast pace, production pressure, inherent high cost and other competing priorities Traditional learning environments not ideal

48. Highly realistic scenarios and environment Allow learners to work through clinical challenges as best they can, then “debrief” Learners must “suspend disbelief ” Self reflection is key component Simulation basedtraining

49. • Creates no risk to human patients • Provides structured learning opportunities with defined learning objectives • Allows practice without interruption/interference • Can be scheduled at times convenient to trainees and instructors • Easily tailored to the needs of individual trainees Can be scaled in intensity to meet the needs of learners at all levels of experience • Allows practice of routine and rare situations • Fosters integration of cognitive, technical and behavioral skills • Facilitates multidisciplinary team training Simulation-Advantages

50. Is becoming the standard for teaching/learning It isn't the sophistication of the equipment, but how it is used As behavior is better understood, techniques and value of simulation will increase Simulation and NRP