Martin Keszler, MD, FAAPProfessor of Pediatrics
Brown UniversityWomen and Infants Hospital
Providence, RI
Lung Protective Ventilation Strategies
Alphabet Soup of Respiratory Support: State-of-the-Art 2014
PSV
?
??
???
BiPAP
Unique Challenges in NB VentilationChildren ≠ Small Adults!
Newborns ≠ Small Children!� Transitional circulation� Compliant chest wall, stiff lungs
� Unfavorable chest wall mechanics� Limited muscle strength and endurance� Immature respiratory control
� Rapid RR, short time constants� Small trachea, high ETT resistance� Uncuffed ETT
� Tidal volume measurement� Awake, breathing patient
Need to understand the pathophysiology
Matthay MA and Zimmerman GA. 2005 Am J Respir Cell Mol Biol 33:319–327
Fetal LungDevelopment
Postnatal Lung Growth and Development
Antenatal
Steroids
Postnatal
Steroids
Chorioamnionitis
Preterm Labor
Initiation
of air-
breathing
Mechanical
Ventilation Oxygen Infection
Cannalicular Stage
Saccular StageAlveolar Stage
The Pathogenesis of BPD
PDA
Pulmonary
outcome
Preterm
Delivery
Nutrition, antioxidants,
?iNO, ???
Fluid
intake
!!!
Compliant chest wall
Fluid filled lungs
Limited muscle strength
Respiratory depression
Limited ability to establish FRC
C-section/ absence of labor
Effect of PEEP on
Rabbit Lung Aeration:
Phase contrast radiographs after
20 breaths.Siew, et al, JAP
2009
SI in preterm rabbitste-Pas, et al, Pediatr Res 2009
RCT of SI + PEEP vs PEEPte Pas, et al, Pediatrics 2007
SI + PEEP n=104
PEEP n=103
p value
Intubated in DR 17% 36% 0.002
Length of RS (d) 2.7 [0.5-10] 4.3 [0.5-20] 0.01
>1 dose of Surf 10% 21% 0.02
Survival 98% 96% 0.4
BPD 22% 34% 0.05
IVH 3-4/PVL 9% 8% 0.4
Sustained Lung Inflation in DR: 25 cm H2O for 15 s Lista, et al, Neonatology 2010
Volume or Pressure Ventilation?
Bourns LS 104 -150 BP 200
Why Volume-Targeted Ventilation?
� Volutrauma not Barotrauma
� Inadvertent hyperventilation is common
� Hypocarbia is bad for the brain and the lungs
� Adult-type volume controlled ventilation poses challenges in NB
Effect of Pressure v. Volume on Lung Injury Hernandez, et al, J Appl Physiol 1989
Capillary filtration coefficient: measure of acute lung injury
PIP is Excessive Relative to Compliance!
!P
VT
FRC
E
I
!!
Dreyfuss D et al. Am Rev Respir Dis. 1988;137:1159-1164.
10
8
6
4
2
0
Qwl/BW(mL/kg)
DLW/BW(g/kg)
Albumin space(%)
* *1.2
0.9
0.6
0.3
0
100
0
80
60
40
20
Ventilator-Induced Lung Injury:Volutrauma, not Barotrauma
Rodents ventilated with 3 modes:
- High pressure (45 cm H2O), high volume
- Low (negative) pressure, high volume
- High pressure (45 cm H2O), low volume (strapped chest & abdomen) *P<0.01.
*
Limitations of Volume - Controlled Ventilation in Newborns
Tubing System and Humidifier
Respiratory System
VTLung = VT set CT
CRS
1
1 + *
Actual tidal volume is influenced by:1) Ratio of circuit compliance to respiratory system compliance
Flow Sensor
C TV.
VentV.
CRS
Humid
C RS
2) compressible volume of the circuit, including humidifier
Leak
Both High and Low PCO2 Increase Risk of IVHFabres, et al, Pediatrics 2007
Modalities of Volume -Targeted Ventilation
Controls Adjusts Based on
Servo (PRVC) VT to circuit PIPInspiratory VT
of last breath
VIP Bird (VAPS)Minimum VT
to patientInspiratory time ( ) Inspiratory VT
Bear Cub 750 (Volume Limit)
Max. VT to patient
Inspiratory time ( ) Inspiratory VT
Avea (VAPS + VL)
Min/Max VT
to circuit/ptInspiratory time ( ) Inspiratory VT
P. Bennett 840 (Volume Vent +) VT to circuit Inspiratory
time / flow Inspiratory VT
Babylog, Evita (VG, Neoflow) VT to patient PIP Exhaled VT of
last breath
VTV Control Algorithm
Volume LimitPRESSURE
FLOW
VOLUME
Volume Limit
Pressure limited breaths
Volume limited breath
Decreased
compliance
or decreased
patient effort
Increased compliance or increased patient effort
Volume Limit
Volume “Guarantee”Principles of operation
Pressure limitWorking Pressure
VT = VT set by user
The PIP (“working pressure”) is servo-regulated within preset limits (“pressure limit”) to achieve VT that is set by the user. Regulation of PIP is in response to exhaled VT
to minimize artifact due to ETT leak. Breath terminates if 130% of TVT reached. Separate algorithm for spontaneous and machine breaths.
Working Pressure
VOLUME
Target tidal volume
Pressure Limit
PRESSURE
Extreme Periodic Breathing Owen, et al, ADC 2010
VG vs. NAVA / Proportional Assist
(or PAV)
Benefits of VG� Maintenance of (relatively) constant tidal
volumes � Prevention of overdistention and volutrauma
due to• Surfactant administration• Lung volume recruitment• Clearance of lung fluid
� Automatic lowering of pressure support level during weaning
� Compensation for variable respiratory drive• stabilization of tidal volume and minute ventilation due to changes of respiratory drive (periodic breathing)
PLV vs. VTV MAA: Mortality Peng, et al, ADC-FNN 2014
PLV vs. VTV MAA: BPD Peng, et al, ADC-FNN 2014
Outcome No. of Studies
No. of Subjects
RR (95% CI) or Mean diff (95%CI)
Any IVH 11 759 0.65 (0.42-0.99)
Grade 3-4 IVH 11 707 0.55 (0.39-0.79)
Cystic PVL 7 531 0.33 (0.15-0.72)
Pneumothorax 8 595 0.46 (0.25-0.86)
Any hypocapnia 2 58 0.56 (0.33-0.96)
Failure of assigned mode 4 405 0.64 (0.43-0.94)
Duration of suppl. O2 (d) 2 133 -1.68 (-2.5to-0.88)
PLV vs. VTV MAA: Other outcomes Peng, et al, ADC-FNN 2014
Barriers to acceptance
� Inertia / fear of the unknown� Rationalization: need more evidence� Lack of understanding of
- Rationale
- Functionality
- Appropriate settings
- Limitations
The benefits of VTV can not berealized without ensuring that thetidal volume is evenly distributedthroughout an “open lung”!!!
Expiration
InspirationVentilatedStable
VentilatedUnstable
Unventilated
“Atelectotrauma”
Non-Homogenous aeration in RDSRecruitment/ de-recruitment injury
Shear forces
Adequate PIP, Adequate PEEP
COPCCP
FRC
P
V
VT
P
Good oxygenation, low FiO2, minimal lung injury
CCP = critical closing pressure; COP = critical opening pressure
Alveolar Recruitment maneuvre
Lung volume recruitment
Ventilation on the expiratory limb of the P-V loop, once recruitment occurs.
Berger, et al Neonatology 2013
Oxygenation guided lung recruitmentDe Jaegere, et al AJRCCM 2006
Alveolar instability in an injured lung
OLC Prevents Lung InjuryvanKaam, et al Pediatr Res 2003
VG reduces markers of lung inflammationLista, et al 2005 & 2006
� Two prospective randomized trials
� A/C vs. A/C + VG
� BAL on days 1,3,5
� VG @ 5 mL/kg reduced pro-inflammatory cytokine levels and decreased duration of ventilation
� VG @ 3 mL/kg increased pro-inflammatory cytokine levels
� Low PEEP (3-4 cm H2O)
0%
10%
20%
30%
40%
50%
60%
VT>6/kg PaCO2<35
A/C
A/C+VG
**
Proportion of values outside the target range
Keszler, et al. Ped Pulmonol ‘04* p < 0.001
VG-Clinical Caveats• VG should be implemented immediately upon
initiation of mechanical ventilation.
• The usual starting target VT is 4 - 5 mL/kg during the acute phase of the illness.
• Larger VT is needed in ELBW infants, those with MAS and older infants with chronic lung disease!
• PIP limit should be set 25% above the PIP currently needed to deliver the target VT and adjusted as needed.
• PIP will default to the limit if sensor is out or when giving a manual breath!
• If the low VT alarm sounds repeatedly, increase the pressure limit AND INVESTIGATE THE CAUSE
VT in infants with MASSharma, et al in press
Relationship of Birthweight and VTMontazami,et al, Ped Pulmonol 2009
3
3.5
4
4.5
5
5.5
6
6.5
0.3 0.4 0.5 0.6 0.7 0.8 0.9
Weight (kg)
VT
(m
l/kg
)
R= -0.563 p<0.001
ELBWRLBW *
*RLBW = Ridiculously LBW
Conventional PhysiologyAnatomical dead-space = 2mL/kg. Instrumental dead-space is fixed.
Anatomical + Instrumental dead-space = 3mL in a typical 1 kg infant
Anatomical + Instrumental dead-space = 2.5mL in a typical 0.5 kg infant
Alveolar ventilation = tidal volume – dead-space volume) x RR
VT = 5mL , DS=3mL VT = 4mL , DS=3mL VT = 3mL , DS=3mL
Alveolar ventilation = X Alveolar ventilation = 0.5 X
Alveolar ventilation = 0
Fresh gas inflow spikes through DS gas
Mixing when flow abruptly stops
Exhaled gas spikes through mixed DS gas
Gas Flow Through Narrow ETT
Time to Eliminate CO2 from Test Lung2.5 mm ETT, DS = 3.5 ml
0
50
100
150
200
250
300
350
400
450
500
DS + 2 DS+ 1 DS DS -0.5 DS - 1 DS -1.5Tidal Volume (ml)
Seconds
Keszler, et al. ADC FN in print
Relationship of Post-Natal Age and VT (mL/Kg)
Keszler et al, Arch Dis Child ‘09
Day 1-2n = 251
Day 5-7n = 185
Day 14-17n = 216
Day 18-21n = 176
VT(mL/kg)
5.15 + 0.6 5.24 + 0.7 5.63 + 1.0 6.07 + 1.4
PCO2 (torr)
44.0 + 5.4 46.3 + 5.2 53.9 + 7.3 53.9 + 6.2
Corrected VT
Herber-Jonat, Ped Crit Care Med 2008
Lung Injury: Strategies for Prevention
� Optimal DR stabilization (?SI)
� Avoidance of mechanical ventilation
� Avoid excessive VT
� Optimize lung volume / avoid atelectasis
� Surfactant replacement PRN
� Volume-targeted ventilation
� High-frequency ventilation
� Permissive hypercapnia/lower SPO2 (?)
Thank You
VG Clinical Caveats: Weaning• If target VT is set at low normal (usually 4 mL/kg in
first few days, higher later on) and PaCO2 is allowed to rise to the mid - high 40s (pH <7.35), weaning occurs automatically (“self-weaning”).
• If VT is set too high and/or the pH is too high, the baby will not have a respiratory drive and will not “self-wean”.
• If the VT is set too low, there will be excessive WOB !
• Most infants can be extubated when they consistently maintain VT at or above the target value with working PIP < 10-12 cm H2O (< 12-15 cm H2O in infants > 1 kg) with FiO2 < 0.35 and good sustained respiratory effort.
Work of Breathing @ Different VT targetPatel, et al Pediatrics 2009