A History of CPAP for Infants
Alan H. Jobe, MD, PhD
Cincinnati 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
VIENNA-09
Editorial in NEJM – December, 1970, Claude Lenfant
8 Patients with “Severe Acute Respiratory Failure” Ventilated using
a PEEP of 13 cmH2O
Kunar, et al., NEJM, 1970
VIENNA-09
Responses of Switching 8 Patients
from PEEP=13 cmH2O to No PEEP
Kunar, et al., NEJM, 1970
VIENNA-09
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)
VIENNA-09
Pediatr, 1968
VIENNA-09
5 Infants tested for change in Oxygenation
with Intubation - on 90-95% Oxygen
PaO2 Values
Before Intubated
91 ± 91
Intubated
61 ± 58*
Extubated
93 ± 92
*1.8±0.4 kg; Pco2=51±7
p<0.001
Harrison, et al., Pediatr, 1968
Nasal Piece and Fleish Tube used for PFT Measurements
Fig. 1. Fleisch 00 Pnumotachograph, T-junction, and nasal piece.
Harrison, et al., Pediatr, 1968
Abstract for SPR/APS Meeting 1970
VIENNA-09
VIENNA-09
20 Infants Treated with CPAP over 16 Months
51 Infants with IRDS
UA lines, O2 for Pao2 of 50-70 mmHg
25 - Increased O2 Only
All
Survived
20 - Required 100%
or had Apnea
5 - Apnic at
Birth
1 - Ventilated
from Birth
Bag & Mask
Ventilation
Ventilated
1 Survived
CPAP
All Died
16
Survived
VIENNA-09
Data from Gregory NEJM, 1971
CPAP Device for use with Endotracheal Tube
Gregory, et al., NEJM, 1971
VIENNA-09
CPAP Device for use with Endotracheal Tube
Gregory, et al., NEJM, 1971
VIENNA-09
Head Box for CPAP without Endotracheal Tube
VIENNA-09
Gregory, et al., NEJM, 1971
Provided by G. Gregory
Results:
Provided by A. Wilkinson
•
CPAP
0
(mmHg)
6
FRC
(ml)
Provided by A. Wilkinson
CPAP (mmHg)
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
A Bag and Y-Connector for CPAP
VIENNA-09
Barrie, The Lancet, 1973
Caliumi-Pellegrini, et al., Arch Dis Child, 1974
VIENNA-09
Schematic representation of the system used for applying continuous
positive airway pressure (adapted from Gregory, et al.)
VIENNA-09
Cumarasamy, et al., Pediatrics, 1973
Artificial Ventilation in HMD: the use of
PEEP and CPAP
Treatment Outcomes with PEEP + CPAP by Year
Years
Number of Patients
% Ventilated
% Survival
Overall
Ventilated
1969
1970
1971
36
36%
38
58%
46
78%
53%
44%
74%
23%
23%
70%
Cumarasamy, Nussli, Vischer, Dangel & Duc, Pediatrics, 1973
VIENNA-09
Effect of CPAP (PEEP) on Intubated and
Ventilated Infants with RDS
VIENNA-09
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
CPAP
Number
11
8
Birth Weight (kg)
1.6±0.2 2.2±0.2
Gestational Age (weeks)
31.7±0.6 34.1±1.1
Duration of Supplemental O2 > 60% (hr) 38±10
11±3
Duration of IPPV (hr)
56±10
Duration of CPAP (hr)
48±9
Stocks and Godfrey, Pediatrics, 1976
Airway Conductance Measured at Term and at 411 Months Post-Delivery
CPAP
Stocks & Godfrey, Pediatrics, 1976
Meta-Analysis of CPAP vs. No CPAP for
Infants with RDS
Outcome
Require Mech Vent
Air Leaks
BPD
Death
NNRisk
Studies Patients Ratio
4
145
0.66
4
165
2.62
2
100
0.87
4
165
0.66
95% CI
0.50-0.86
1.28-5.36
0.33-2.31
0.45-0.97
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
Effect of a change in delivery room
management for infants <1000g - allowing
spontaneous breathing with FRC recruitment
and CPAP
(N)
Intubation & Vent in DR
Never intubated
Pco2 on NICU admit
BPD
IVH G III & IV
Death
1994
(56)
84%
7%
3811 mmHg
32%
24%
27%
1996
(67)
40%*
25%*
5415 mmHg*
12%*
12%
22%
Lindner et al., Pediatr. 103:961, 1999
IMHR PI
CPAP-VENT
The Danish Approach to the Initiation
of Ventilation and Surfactant
Description of Population of Infants <30
Weeks GA
Number
GA
BW
Antenatal Steroids
Initially given CPAP
No or Mild RDS
Given Surfactant
Ventilated by 7d
Ve rd e r, et al
Nu tr i
CPAP-VENT
397
27.2±1.6
1033±274
80%
94%
54%
30%
42%
. , P e d i a tr . 103: e 24 , 1999
The Coin Trial
Ventilation
CPAP P
N
303
307
BW
952
964
% Intubated by 5d
100%
46%
*
% Surfactant by 5d
77%
38%
*
Morley, et al., NEJM, 2008
Ventilation CPAP
Pneumothorax
Median Vent days
Death
BPD - 28d
BPD - 36wk
O2 Concentration at
36wk >30%
P
3%
4
5.9%
63%
31%
9%
3
6.5%
51%
29%
<0.01
<0.01
NS
0.01
NS
8.8%
9.4%
NS
Morley, et al., NEJM, 2008
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
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