1. A History of CPAP for Infants
Alan H. Jobe, MD, PhD Cincinnati Children’s Hospital
University of Cincinnati
Cincinnati, Ohio

2. Neonatal Bioethics: The Moral Challenges of medical Intervention
The era of innovation and individualism
Mechanical Ventilation
CPAP
Total Parental Nutrition
Regionalization
Era of exposed ignorance –
The End of Medical Progress – after 1992
Lantos and Meadow, Neonatal Bioethics, 2006

3. First Reference to CPAP in Pub Med: Revival of an Old Battle: Intermittent vs. Continuous Positive-Pressure Breathing
Continuous Pressure Breathing – effective in WWII for high altitude pilots, but increases work of breathing and decreases cardiac output.
Advantages of CPB over IPB
Improved oxygenation at lower FiO2
Disadvantages of CPP over IPB
Need to measure CO
“Indicated only in cases where alveolar pressure is not transmitted to the intra plural spaces”
Alveolar rupture and Pneumothorax
Editorial in NEJM – December, 1970, Claude Lenfant
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4. VIENNA-09
8 Patients with “Severe Acute Respiratory Failure” Ventilated using a PEEP of 13 cmH2O
Kunar, et al., NEJM, 1970

5. Responses of Switching 8 Patients from PEEP=13 cmH2O to No PEEP
Kunar, et al., NEJM, 1970
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6. Status of Hyaline Membrane Disease – Late 1960’s
HMD was leading cause of death for preterms (27%-43% survival with assisted ventilation worldwide)
Ventilation resulted in Bronchopulmonary Dysplasia (oxygen toxicity) – Northway (1967)
* No antenatal testing for lung maturation – (Gluck, 1971)
* No antenatal corticosteroids (Liggins – 1972)
* No surfactant treatments (Fujuwara – 1980)
* No effective therapy other than supplemental oxygen
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7. Information about HMD in Late 1960’s
Atelectasis in HMD interfered with oxygenation
Normal lungs contained surfactant (Clements – 1957)
HMD lungs were surfactant deficient (Avery and Mead – 1959)
Intubation of HMD infants abolished grunting and decreased oxygenation (Harrison, et al., 1968)
Ventilation with a long Ti increased oxygenation (Smith, et al., 1969)
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8. Pediatr, 1968
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9. 5 Infants tested for change in Oxygenation with Intubation - on 90-95% Oxygen
PaO2 Values
Before Intubated
Intubated
Extubated
91 ± 91
61 ± 58*
93 ± 92
*1.8±0.4 kg; Pco2=51±7
p<0.001
Harrison, et al., Pediatr, 1968

10. Nasal Piece and Fleish Tube used for PFT Measurements
Fig. 1. Fleisch 00 Pnumotachograph, T-junction, and nasal piece.
Harrison, et al., Pediatr, 1968

11. Abstract for SPR/APS Meeting 1970
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12. VIENNA-09

13. 20 - Required 100% or had Apnea 1 - Ventilated from Birth
20 Infants Treated with CPAP over 16 Months
51 Infants with IRDS
UA lines, O2 for Pao2 of mmHg
20 - Required 100% or had Apnea
5 - Apnic at Birth
1 - Ventilated from Birth
25 - Increased O2 Only
All Survived
Bag & Mask Ventilation
Ventilated
1 Survived
CPAP
All Died
16 Survived
Data from Gregory NEJM, 1971
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14. CPAP Device for use with Endotracheal Tube
Gregory, et al., NEJM, 1971
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15. CPAP Device for use with Endotracheal Tube
Gregory, et al., NEJM, 1971
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16. Head Box for CPAP without Endotracheal Tube
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Gregory, et al., NEJM, 1971

17. CPAP Provided by G. Gregory
This is a trash bag with gas inflow. It was closed loosely about the neck and pressure could be maintained easily and constantly. This was about the 5th or 6th patient we treated.
Provided by G. Gregory

18. • 20 infants, BW 930 to 3,830g • Severe HMD (PaO2 <50 mmHg in % O2 or apneic) • Range of highest CPAP: 6-12 mmHg • PES by only 20% of applied CPAP • Duration of CPAP: 2-29 d • 16 of 20 survived • No CLD (chronic lung disease)
Results:
Provided by A. Wilkinson

19. Effects of CPAP on Lung Volume
CPAP (mmHg)
CPAP (mmHg)
FRC
(ml)
Provided by A. Wilkinson

20. From Gregory, et al., NEJM - 1971
“We did not consider an elevation in Paco2 to be an indicator for mechanical ventilation as long as pH was greater than 7.20.”
Footnote for physiologic data –
Order NAPS document from National Auxiliary Publications Service – (the physiologic data has been lost)
.20
VIENNA-09

21. CPAP Worked – and Rapid Innovation Occurred
Continuous negative Pressure (Chernick and Vidyasargar – 1972)
Fanaroff, et al. (1973)
Pressurized bag over head (Barrie, 1973)
Mask that covers the mouth and nose (Harris, 1972)
Nasal CPAP (Kattwinkel, et al., 1973)
Ventilation + CPAP = PEEP (Cumarassamy, et al., 1973)
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22. A Bag and Y-Connector for CPAP
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Barrie, The Lancet, 1973

23. Caliumi-Pellegrini, et al., Arch Dis Child, 1974
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24. Schematic representation of the system used for applying continuous positive airway pressure (adapted from Gregory, et al.)
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Cumarasamy, et al., Pediatrics, 1973

25. Artificial Ventilation in HMD: the use of PEEP and CPAP
Treatment Outcomes with PEEP + CPAP by Year
Years
1969
1970
1971
Number of Patients
% Ventilated
% Survival
Overall 36
36%
53% 38
58%
44% 46
78%
74%
Ventilated
23%
70%
Cumarasamy, Nussli, Vischer, Dangel & Duc, Pediatrics, 1973
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26. Effect of CPAP (PEEP) on Intubated and Ventilated Infants with RDS
deLemos, McLaughlin, Robison, Schulz, Kirby, Anesthesia & Analgesia, 1973
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27. Nasal Prongs for CPAP
Kattwinkel, Fleming, Cha, and Fanaroff, Pediatrics, 1973

28. Nasal CPAP (2-5 cmH2O) for Infants with Apnea.
BW average = 1kg, age of study – 14 days
Kattwinkel, et al., J. Pediatr, 1975

29. Follow-up Measurements to Evaluate Mechanical Ventilation, Oxygen, and CPAP for Lung Damage
Ventilated
CPAP
Number
Birth Weight (kg)
Gestational Age (weeks)
Duration of Supplemental O2 > 60% (hr)
Duration of IPPV (hr)
Duration of CPAP (hr) 11
1.6±0.2
31.7±0.6
38±10
56±10 - 8
2.2±0.2
34.1±1.1
11±3
48±9
Stocks and Godfrey, Pediatrics, 1976

30. Airway Conductance Measured at Term and at 4-11 Months Post-Delivery
CPAP
Stocks & Godfrey, Pediatrics, 1976

31. Meta-Analysis of CPAP vs. No CPAP for Infants with RDS
Outcome N-
Studies
N-Patients
Risk Ratio
95% CI
Require Mech Vent
Air Leaks
BPD
Death 4 2
145
165
100
0.66
2.62
0.87
Bancalari & Sinclair, in Effective Care of the Newborn Infant: Sinclair and Bracken, 1992

32. 1980’s through early 2000
Ventilation replaced CPAP as primary therapy for RDS
Antenatal steroids and surfactant decreased severity of RDS
BPD was frequent in VLBW infants

33. CPAP was used frequently for -
Apnea of prematurity
Post extubation after mechanical ventilation
RDS in some locations (Columbia, Univ. Scandinavia)

34. CPAP-VENT

35. Effect of a change in delivery room management for infants <1000g - allowing spontaneous breathing with FRC recruitment and CPAP
CPAP-VENT

36. The Danish Approach to the Initiation of Ventilation and Surfactant
CPAP-VENT

37. The Coin Trial Ventilation CPAP P N BW % Intubated by 5d
% Surfactant by 5d
303
952
100%
77%
307
964
46%
38% *
Morley, et al., NEJM, 2008

38. The Coin Trial - 36 Week Outcome
Ventilation
CPAP P
Pneumothorax
Median Vent days
Death
BPD - 28d
BPD - 36wk
O2 Concentration at
36wk >30% 3% 4
5.9%
63%
31%
8.8% 9% 3
6.5%
51%
29%
9.4%
<0.01 NS
0.01
Morley, et al., NEJM, 2008

39. Neonatal Bioethics: The Moral Challenges of medical Intervention
The era of innovation and individualism
Mechanical Ventilation
CPAP
Total Parental Nutrition
Regionalization
Era of exposed ignorance –
The End of Medical Progress
Lantos and Meadow, Neonatal Bioethics, 2006

40. CPAP in 2009 – A New Enthusiasm
Again frequently used as an initial therapy for RDS ± surfactant
Early (delivery room) use popular and under study
New types of CPAP
Nasal CPAP + Ventilatory assist (synchronized, NAVA)
Multiple CPAP devices (NeopuF)
High flow nasal cannula
Variable pressure CPAP

41. My thanks to George Gregory for his help with this brief history of CPAP