A History of CPAP for Infants

Alan H. Jobe, MD, PhDCincinnati Children’s Hospital

University of Cincinnati

Cincinnati, Ohio

Neonatal Bioethics: The Moral Challenges of medical Intervention

• The era of innovation and individualism 1965-1982– Mechanical Ventilation– CPAP– Total Parental Nutrition– Regionalization

• Era of exposed ignorance – 1982-1992

• The End of Medical Progress – after 1992

Lantos and Meadow, Neonatal Bioethics, 2006

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

VIENNA-09

VIENNA-09

8 Patients with “Severe Acute Respiratory Failure” Ventilated using a PEEP of 13 cmH2O

Kunar, et al., NEJM, 1970

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Responses of Switching 8 Patients from PEEP=13 cmH2O to No PEEP

Kunar, et al., NEJM, 1970

Status of Hyaline Membrane Disease – Late 1960’s

• HMD was leading cause of death for preterms (27%-43% survival with assisted ventilation worldwide) 1968-1971

• 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

VIENNA-09

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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Pediatr, 1968

5 Infants tested for change in Oxygenation with Intubation - on 90-95% Oxygen

PaO2 Values

Before Intubated Intubated Extubated91 ± 91 61 ± 58* 93 ± 92

*1.8±0.4 kg; Pco2=51±7 p<0.001

Harrison, et al., Pediatr, 1968

Fig. 1. Fleisch 00 Pnumotachograph, T-junction, and nasal piece.

Nasal Piece and Fleish Tube used for PFT Measurements

Harrison, et al., Pediatr, 1968

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Abstract for SPR/APS Meeting 1970

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25 - Increased O2 Only

51 Infants with IRDS

All Survived

20 - Required 100% or had Apnea

Bag & Mask Ventilation

CPAP

16 Survived

5 - Apnic at Birth

Ventilated

1 - Ventilated from Birth

1 Survived

All Died

20 Infants Treated with CPAP over 16 Months

UA lines, O2 for Pao2 of 50-70 mmHg

Data from Gregory NEJM, 1971

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CPAP Device for use with Endotracheal Tube

Gregory, et al., NEJM, 1971

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CPAP Device for use with Endotracheal Tube

Gregory, et al., NEJM, 1971

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Head Box for CPAP without Endotracheal Tube

Gregory, et al., NEJM, 1971

Provided by G. Gregory

Results:

Provided by A. Wilkinson

CPAP (mmHg)

0 6

CPAP (mmHg)

FRC (ml)

Provided by A. Wilkinson

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 01448 from National

Auxiliary Publications Service – (the physiologic data has been lost)

VIENNA-09

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)VIENNA-09

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A Bag and Y-Connector for CPAP

Barrie, The Lancet, 1973

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Caliumi-Pellegrini, et al., Arch Dis Child, 1974

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Schematic representation of the system used for applying continuous positive airway pressure (adapted from Gregory, et al.)

Cumarasamy, et al., Pediatrics, 1973

Artificial Ventilation in HMD: the use of PEEP and CPAP

Treatment Outcomes with PEEP + CPAP by Year

Years 1969 1970 1971Number of Patients% Ventilated% Survival Overall

3636%

53%

3858%

44%

4678%

74%

Ventilated 23% 23% 70%

Cumarasamy, Nussli, Vischer, Dangel & Duc, Pediatrics, 1973

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VIENNA-09

Effect of CPAP (PEEP) on Intubated and Ventilated Infants with RDS

deLemos, McLaughlin, Robison, Schulz, Kirby, Anesthesia & Analgesia, 1973

Nasal Prongs for CPAP

Kattwinkel, Fleming, Cha, and Fanaroff, Pediatrics, 1973

Nasal CPAP (2-5 cmH2O) for Infants with Apnea. BW average = 1kg, age of study – 14 days

Kattwinkel, et al., J. Pediatr, 1975

Follow-up Measurements to Evaluate Mechanical Ventilation, Oxygen, and CPAP for

Lung Damage

Ventilated CPAPNumberBirth Weight (kg)Gestational Age (weeks)Duration of Supplemental O2 > 60% (hr)Duration of IPPV (hr)Duration of CPAP (hr)

111.6±0.2

31.7±0.638±1056±10

-

82.2±0.2

34.1±1.111±3

-48±9

Stocks and Godfrey, Pediatrics, 1976

CPAP

Airway Conductance Measured at Term and at 4-11 Months Post-Delivery

Stocks & Godfrey, Pediatrics, 1976

Meta-Analysis of CPAP vs. No CPAP for Infants with RDS

Outcome N-Studies

N-Patients

Risk Ratio

95% CI

Require Mech VentAir LeaksBPDDeath

4424

145165100165

0.662.620.870.66

0.50-0.861.28-5.360.33-2.310.45-0.97

Bancalari & Sinclair, in Effective Care of the Newborn Infant: Sinclair and Bracken, 1992

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

CPAP was used frequently for -

• Apnea of prematurity

• Post extubation after mechanical ventilation

• RDS in some locations (Columbia, Univ. Scandinavia)

CPAP-VENT

CPAP-VENT

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

1994 1996(N)Intubation & Vent in DRNever intubatedPco2 on NICU admitBPDIVH G III & IVDeath

(56)84%7%

3811 mmHg32%24%27%

(67)40%*25%*

5415 mmHg*12%*12%22%

Lindner et al., Pediatr. 103:961, 1999

IMHRPI

CPAP-VENT

The Danish Approach to the Initiation of Ventilation and Surfactant

Description of Population of Infants <30Weeks GA

NumberGABWAntenatal SteroidsInitially given CPAPNo or Mild RDSGiven SurfactantVentilated by 7d

39727.2±1.61033±274

80%94%54%30%42%

Verder, et al., Pediatr. 103:e24, 1999

Nutri

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

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

<0.01

NS

0.01

NS

NS

Morley, et al., NEJM, 2008

• The era of innovation and individualism 1965-1982– Mechanical Ventilation– CPAP– Total Parental Nutrition– Regionalization

• Era of exposed ignorance – 1982-1992

• The End of Medical Progress

Neonatal Bioethics: The Moral Challenges of medical Intervention

Lantos and Meadow, Neonatal Bioethics, 2006

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

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