Transcript Neonatal Non-Invasive Respiratory Support: Overview and

CPAP: The New (old) Gold Standard
for Respiratory Management
Morgan Stanley Children’s Hospital
Columbia University
Richard A. Polin M.D.
Disclosures
• I am a consultant for
Fisher & Paykel and Ikaria
Outline
• Rationale for use of CPAP as an initial
mode of respiratory support in neonates
with respiratory distress
• Differences in CPAP delivery systems
• Conclusions and Recommendations
Case
A 0.75 kg infant is born following a 27 week gestation. The infant
exhibits immediate signs of respiratory distress and is administered
30% O2 in the delivery room. He is given ampicillin and gentamicin
and transported to the NICU. A chest x-ray demonstrates a ground
glass appearance with air bronchograms. What should be done
now?
A. Intubate and administer surfactant; wean ventilation as tolerated
B. Intubate, administer surfactant and rapidly extubate to NPCPAP
(INSURE).
C. Withhold surfactant. Place the infant IMV-NPCPAP.
D. Withhold surfactant. Place on the infant on NPCPAP and
observe.
Immature Lung
•
Nitric oxide
•
Diuretics
• Superoxide
Dismutase
•
Gentle
Resuscitation
•
Antenatal
steroids
•
Surfactant
•
Permissive
Hypercapnia
• Permissive
hypoxemia
Modified from Thomas W & Speer CP Neonatology 2011
Genetic Predisposition
• Caffeine
• Postnatal
steroids
• Vitamin A
• CPAP
Lung Injury in the Neonate:
Fundamental Concept
• If you don’t ventilate an infant,
it’s hard to cause BPD!
CPAP is Controversial
Respiratory Support Strategies
U.K.
IPPV
HFO
IMV
A/C
SIMV
VG
CPAP
Acute RDS
73%
2%
N/A
4%
13%
5%
2%
Sharma A & Greenough. Acta Paediatrica 96: 1115-1117, 2007
Weaning
N/A
N/A
13%
15%
73%
6%
N/A
Pulmonary Morbidity According to
Gestational Age for VLBW Infants
Characteristic
22 wk
23 wk
24 wk
25 wk
26 wk
27 wk
28 wk
Total
Severe BPD
56%
39%
37%
26%
17%
13%
8%
18%
Surfactant
97%
97%
95%
90%
86%
78%
65%
82%
Ventilation
96%
94%
89%
76%
61%
49%
40%
62%
0%
3%
8%
18%
30%
36%
38%
26%
CPAP
N = 8575 VLBW infants (2003-2007)
Stoll B et al Pediatrics 126: 443, 2010
Surfactant: Systematic ReviewsMortality
RR
95%CI
NNT
95% CI
Natural surfactant
0.86
0.76-0.98
50
20-1000
Multiple doses
0.63
0.39-1.02
14
7-1000
Prophylaxis
0.61
0.48-0.77
20
14-50
Early
0.87
0.77-0.99
33
17-1000
HL Halliday Journal of Perinatology 28: s47, 2008
Critique of the Surfactant Trials
• Low rates of exposure to antenatal
steroids
• Infants randomized to control arms of
these trials were routinely ventilated
(without surfactant) rather than receiving
CPAP
“Simplicity is the
Ultimate sophistication”
KISS: Keep it simple stupid!
CPAP is an evidence-based
treatment for preterm
infants with RDS
Summary of CPAP Trials
Gestational age
N
Death or BPD
Air-leaks
CPAP/control
CPAP/control
Support
240/7-276/7
1316
47.8%/51.1%
6.8%/7.4%
COIN
250/7-286/7
610
33.9%/38.9%
9.1%/3.0%
VON
266/7-296/7
648
29.6%/36.5%
4.8%/5.4%
Neocosur
800-1500g
256
13.7%/19.2%
3.1%/5.6%
CURPAP
250/7-286/
208
21.0%/21.9%
4.9%/9.5%
3038
29.2%/33.52%
5.7%/6.18%
Total
Why is CPAP Only Marginally Better
than Intubation/Surfactant?
• Inexperience with CPAP in the centers
participating in RCTs
• Greater skill with other forms of
respiratory support.
• Limited duration of ventilation in the RCTs
• Some CPAP delivery systems, may be
more effective than others
% intubated**
nCPAP/control
% Surfactant
nCPAP/control
Duration ventilation
nCPAP/control
87.0%100%
67.1%/98.9%
10 days / 13 days@
COIN
58%%/100%
38%/77%
3 days / 4 days
VON
45%/98.6%
45%/98.2%
9.2 days / 12.5 days
Support
% ventilated
Neocosur
26%/39%
12%/100%**
3.3 days / 4.3 days
CURPAP
33%/31.4%
48.5%/100%
5.5 days / 5.4 days@
* CPAP vs. INSURE
** DR or NICU
@
median values
There’s a Learning Curve to
Success with CPAP
A comparison of 3 periods before and after the routine
application of nCPAP in ELBW infants with respiratory distress.
Pre-CPAP
Tercile 1
Tercile 2
Tercile 3
ENCPAP application
11.1%
17.6%
61.8%
66.7%
CPAP failure*
18.2%
29.4%
11.8%
9.1%
Surfactant
51.5%
48.0%
13.3%
33.3%
BPD
33.3%
46.2%
25.9%
11.1%
* First week of life
Aly et al. Pediatrics 114: 697, 2004
Columbia Experience
• 4 year retrospective analysis
(2008-11)
• 297 consecutive inborn infants
BW ≤ 1000 gm
Respiratory Outcomes with CPAP
2008-2011
CPAP success@
(n = 151)
Weeks
Weight (g)
26.9 ± 1.8*
CPAP failure
(n = 84)
25.6 ± 1.3*
792.7 ± 136.1 723.1 ± 152.
Ventilated Started
(n =62)
24.8 ± 1.5*
658.6 ± 141.2
*P < .001 CPAP success vs. CPAP failure & ventilated vs. CPAP failure
@ CPAP success rate 64%
Respiratory Outcomes with CPAP
2008-2011
CPAP success
CPAP failure
Ventilated Started
(n = 151)
(n = 84)
31.8%
73.8%
72.9%
3.6%
15.4%
13.5%
23.9%
50.7%
54.0%
Pneumothorax
3.2%
13.4%
8.1%
Mortality
8.6%
22.6%
40.3%
Death or O2 (36 wks)
11.9%
34.5%
Oxygen at 28 days
Oxygen at 36 weeks
Severe BPD (NICHD)
(n =62)
48.4%
Time course of CPAP failure in
first 72 hr life
Surfactant pools were lower in lambs
that failed BCPAP
A
7.5
Total Lung Sat PC
60
(µmol/kg)
(µmol/kg)
80
40
20
BALF Sat PC
D
Large Aggregate
5.0
2.5
0.0
0
10
B
C
75
% Secreted
8
%
50
6
%
4
25
2
0
0
Success
Fail
Mulrooney et al. Am. J Respir. Crit. Care Med. 171: 488, 2005
Success
Fail
Prophylactic Surfactant vs. Selective Treatment
of RDS Neonatal Mortality
Study or
Subgroup
Prophylactic
Events Total
Selective
Events Total Weight
1.6.1 Studies without routine application of CDP
Bevilacqua 1996
28
136
46
132
Bevilacqua 1997
9
49
9
44
Dunn 1991
9
62
8
60
Egberts 1993
8
75
14
72
Kattwinkel 1993
3
627
11
621
Kendig 1991
23
235
40
244
Merritt 1991
27
76
21
72
Walti 1995
15
134
23
122
Subtotal (95% Cl)
1394
1367
Total events
122
124
Total (95% Cl)
Total events
0.59 [0.39, 0.89]
0.90 [0.39, 2.06]
1.09 [0.45, 2.63]
0.55 [0.24, 1.23]
0.27 [0.08, 0.96]
0.60 [0.37, 0.97]
1.22 [0.76, 1.95]
0.59 [0.33, 1.08]
0.69 [0.56, 0.85]
33.8%
2.8%
36.7%
1.23 [0.96, 1.58]
1.32 [0.53, 3.28]
1.24 [0.97, 1.58]
100.0%
0.89 [0.76, 1.04]
102
2256
246
16.9%
3.4%
3.0%
5.2%
4.0%
14.2%
7.8%
8.7%
63.3%
Risk Ratio
M-H, Fixed,95% Cl
172
1.1.2 Studies with routine application of CDP
Support 2010
114
653
94
663
Von 2010
10
209
8
221
Subtotal (95% Cl)
862
884
Total events
Risk Ratio
M-H, Fixed,95% Cl
2251
274
.2
.5
1
Favors prophylactic
Rojas & Soll 2010 unpublished
2
5
Favors selective
Prophylactic surfactant vs. treatment of established
respiratory distress in preterm infants,
Chronic lung disease or death
Risk Ratio
Prophylactic Selective M-H, Fixed,
n/N
Study or subgroup
n/N
95% Cl
Prophylactic
Weight
Risk Ratio
M-H, Fixed,
95% Cl
12/60
3.1%
1.29 [0.67, 2.49]
60
3.1%
1.29 [0.67, 2.49]
67/220
323/663
16.4%
80.6%
1.29 [0.92, 1.57]
1.11 [1.00, 1.23]
Subtotal (95% Cl)
861
Total events 429 (Prophylactic), 390 (Selective)
883
96.9%
1.12 [1.02, 1.24]
Total (95% Cl
923
Total events 445 (Prophylactic), 402 (Selective)
943
100.0%
1.13 [1.02, 1.25]
1. Studies without routine application
of CPAP
Dunn 1991
16/62
Subtotal (95% Cl)
62
Total events 16 (Prophylactic), 12 (Selective)
2. Studies with routine application of CPAP
Dunn 2011
76/208
Support 2010
353/653
0.5 0.7
Favors
experiments
1
1.5 2
Favors
control
INSURE
Intubation >> Surfactant >> Extubation
VON Delivery Room Management
(DRM) Groups
• Intubation, prophylactic surfactant administration
with subsequent stabilization on ventilator
support (PS Group)
• Intubation, prophylactic surfactant administration
and rapid extubation to NCPAP (ISX Group)
• Early stabilization on NCPAP and selective
intubation and surfactant administration for
clinical indications (NCPAP Group)
Gestational age 26+0 to 29+6 weeks
Study assignment was made prior to delivery
Von Delivery Room Management
Trial
Death or CLD At 36 Weeks Post Menstrual Age
% Cases
50
40
30
20
36.5%
RR 0.78
(95% CI 0.59, 1.03)
28.5%
36.5%
28.5%
RR 0.83
(95% CI 0.64, 1.09)
30.5%
30.5%
10
0
Death or CLD
PS
Rojas and Soll 2010 unpublished
ISX
NCPAP
VON-DRM
• In the nasal CPAP group 48% were
managed without intubation and 54%
without surfactant.
The Stable Microbubble Test for
Determining CPAP Success
• Stable microbubbles were counted in gastric
aspirates taken at 1 hour of age in 68 infants
(mean GA 28 weeks) who received CPAP from
birth.
• Infants who failed had a lower GA and higher
FiO2 on admission to the NICU
• 8 microbubbles/mm3 had a sensitivity of 53%, a
specificity of 100% a positive predictive value of
of 100% and a negative predictive value of 60%
for predicting CPAP success.
Bhatia et al Neonatology 2013
Risk Factors: CPAP success vs. Failure
Mother Hispanic
Hypertension
Maternal diabetes
Antenatal steroids
Magnesium
GBS pos
Multiple birth
Vaginal delivery
SGA <10th %tile
1st ABG (min)
BWT<750 g
pH
Male
pCO2
Apgar <5 (1min)
pO2
BE
Apgar <5 (5min)
Intrapartum Antibiotics
Fetal distress
BWT (g)
Initial fiO2 (%)
GBS unknown
PPROM>18 hrs
Clinical
chorioamnionitis
Maternal fever
GA (wks)
Severe RDS (CXR)
AaDO2
PaO2/fiO2
Performance of Composite
Variables
Sensitivity
Specificity
PPV
NPV
27.4
98.7
92
29
10
99.2
88.9
37.1
Severe RDS + (AaDO2>180)
11.2
63.4
81.8
36.6
Severe RDS+ (paO2/fiO2≤100)
19.3
68.2
84.2
31.8
Severe RDS + (GA≤26 wk)
Severe RDS + (pH≤7.27)
Summary
• Based on the data from our NICU from the past
4 years (2008-11), if we have a baby with
• Severe RDS by CXR
– The probability of CPAP failure is 82%.
With
• Severe RDS and (GA≤ 26 wks)
– The probability of CPAP failure is 92%
• These criteria will identify ¼-⅓ of the babies
who actually fail.
Is Bubble CAP Equivalent to or Superior
to Other Methods of Delivering CPAP
• Tagare et al 2013. (n = 145, mean GA 32 weeks) Bubble (B)
CPAP vs. Ventilator (V) CPAP. 82.5% of infants in the BCPAP
group vs. 63.2% in the VCPAP met success criteria.
• Mohammad-Bagher et al 2012. (n =161 mean GA ~ 30 weeks)
BCPAP vs. Medinjet system (variable flow CPAP system)
No significant differences in the duration of CPAP use.
• Yadav et al 2011 (n = 32, mean GA ~ 28 weeks) BCPAP vs.
VCPAP. No significant difference in the rate of extubation
failure.
Yadav, Indian Journal of Pediatrics 2012
Tagare Journal Tropical of Pediatrics 2013
Mohammad-Bagher Turkish Journal of Pediatrics 2012
Is Bubble CAP Equivalent to or Superior
to Other Methods of Delivering CPAP
• Courtney et al 2011 (n = 18, mean GA ~ 28 weeks) BCPAP vs. V-CPAP crossover trial. Transcutaneous O2
was higher in the B-CPAP group, but work of breathing
was identical*.
• Lipsten et al 2011 (n = 18, < 1500 grams) Both B-CPAP
and IFD increased inspiratory work of breathing.
Resistive work of breathing was greater with B-CPAP
vs. IFD**.
*Courtney et al J Perinatology 2011
**Lipsten et al J Perinatology 2005
Randomized controlled Trial of Postextubation Bubble CPAP vs. Infant Flow
Driver in Preterm Infants with RDS
Gupta et al 2009 (n=140, mean GA ~ 27 weeks) BCPAP vs.
Infant Flow Driver IFD). No significant differences in the
rate of post extubation failure; however, in infants
intubated < 14 days, infants on BCPAP had a significantly
lower extubation failure rate.
Randomized controlled Trial of Postextubation Bubble CPAP vs. Infant Flow
Driver in Preterm Infants with RDS
Cum Survival
1.0
80
IFD CPAP
Bubble CPAP
0.8
70
p=0.046
60
0.6
50
%*
0.4
30
0.2
28.6%
40
14.1%
20
10
0.0
0
0
10
20
30
40
50
Days CPAP Use
60
Bubble
CPAP
Ventilated for ≤14 days
*% CPAP failure
Gupta S et al J Pediatr. 154: 645, 2009
IFD
CPAP
Bubble CPAP enhances lung volume
and gas exchange in preterm lambs
Preterm lambs (133 days gestation) were
intubated and randomized to bubble CPAP
(8 or 12 liters/min) or constant pressure
CPAP (ventilator).
Pillow J, Hillman N, Moss TJM, Polglase, Bold G, Beaumont, C Ikegami M & AH Jobe AJRCCM 2008
Bubble CPAP enhanced ventilation
7.5
Bubble CPAP
Constant Pressure CPAP
**
*
7.3
pH
7.2
*
PaCO2 (mmHg)
7.4
100
60
40
20
7.0
0
30
60
90
Time (min)
120
150
**
80
7.1
0
*
*
0
30
60
90
120
Time (min)
Pillow J, Hillman N, Moss TJM, Polglase, Bold G, Beaumont, C Ikegami M & AH Jobe AJRCCM 2008
150
Bubble CPAP improved
oxygenation
*
PaO2 (mmHg)
400
300
200
Bubble CPAP
Constant Pressure CPAP
100
0
0
30
60
90
120
150
Time (min)
Pillow J, Hillman N, Moss TJM, Polglase, Bold G, Beaumont, C Ikegami M & AH Jobe AJRCCM 2008
Bubble CPAP enhanced O2
extraction
A
p=0.041
10
% O2 extraction
p=0.045
8
6
4
2
0
Constant Bubble
Pressure 8 L/min
Bubble
12 L/min
Pillow J, Hillman N, Moss TJM, Polglase, Bold G, Beaumont, C Ikegami M & AH Jobe AJRCCM 2008
Physiological Explanation of the
Advantages of Bubble CPAP
• The more efficient utilization of inspired O2
in the bubble CPAP groups are suggestive
of increased airway patency.
Concerns about Bubble CPAP
• BCPAP may be most effective when lung compliance is
low (early in RDS)
• The amount of positive airway pressure constantly
fluctuates around a mean (immersing the expiratory limb
to a depth of 5 cm will deliver pressures ranging from
3-7).
• In a test lung system, condensate forming in the
expiratory limb, dramatically increased the amplitude of
the pressure oscillations (when the pressure was set at 8
cm H2O, the *Younquist
oscillations
as high
as 13 cm H2O).*
et al were
Respiratory
case 2013
CPAP: Conclusions
• Early use of CPAP with subsequent selective
surfactant administration in extremely preterm
infants results in lower rates of BPD/death when
compared to treatment with prophylactic or early
surfactant therapy (LOE 1).
• If it is likely that respiratory support with a
ventilator will be needed, early administration of
surfactant followed by rapid extubation, is
preferable to prolonged ventilation (LOE 1).
Recommendation for Preterm
Infants with RDS
• Preterm infants with RDS weighing < 1500 gms.
should be allowed time to demonstrate if they
can achieve acceptable ventilation and
oxygenation on CPAP. During that time period,
these infants must be monitored closely. If
ventilation is not improving or oxygenation is
worsening, or inadequate with an FiO2 of 60%,
these infants should be intubated.
• Should infants < 26 weeks gestation receive
prophylactic surfactant?