Volume-Targeted Ventilation in

Newborn Respiratory Support

Martin Keszler, MD
Professor of Pediatrics
Brown University
Women and Infants Hospital
Providence, RI
Ventilatory Support in Neonatology:
State-of-the-Art 2011
PSV
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Outline of Lecture:
Basic Concepts of Mechanical
Ventilation and Lung Injury

Pros-cons of Volume vs. Pressure

Volume -Targeted vs. Volume-
Controlled Ventilation

Evidence base for VG

Practical aspects of VG ventilation


Unique Challenges in NB Ventilation
Children 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
Location of flow sensor
Need for a specialty Neonatal Ventilator
Volume or Pressure Ventilation?
Bourns LS104
BP 200
Volume vs. Pressure Ventilation
Volume Ventilation
- Controls the set flow rate
- Cycles when set volume is
delivered
- Pressure rises passively
Pressure Ventilation
- Controls the set pressure
- Cycles when set time or flow is
reached
- Volume depends on compliance
Volume vs. Pressure Ventilation
Volume Ventilation
- Controls the set flow rate
- Cycles when set volume is
delivered
- Pressure rises passively
Pressure Ventilation
- Controls the set pressure
- Cycles when set time or flow is
reached
- Volume depends on compliance
Pressure-limited IMV
Patient
Patient
Spont.
breath
Continuous flow Continuous flow
Pressure
limit
Expiration Inspiration
Leak
PEEP
valve
Limitations of Volume - Controlled
Ventilation in Newborns
Tubing System and Humidifier
Respiratory
System
V
TLung
= V
T set C
T
C
RS
1
1 +
*
Actual tidal volume is influenced by:
1) Ratio of circuit compliance to
respiratory system compliance
Flow
Sensor
C T
V
.
Vent


V
.
C
RS
Humid
C RS
2) compressible volume of the circuit, including humidifier
Leak
Why Volume-Targeted
Ventilation?
Volutrauma not Barotrauma

Inadvertent hyperventilation is common (Luyt
2001)

Hypocarbia is bad for the brain and the lungs

Adult-type volume controlled ventilation
doesnt work well 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
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 H
2
O),
high volume
- Low (negative)
pressure, high
volume
- High pressure
(45 cm H
2
O), low
volume (strapped
chest & abdomen) *P<0.01.
*
PIP is Excessive Relative to Compliance!
!
P
V
T

FRC
E
I
!!
Hypocarbia in First 3 Days of Life
Proportion of infants with PaCO2 < 25 mm Hg
0%
5%
10%
15%
20%
25%
30%
35%
Day 1 Day 2 Day 3
IMV
PTV
Luyt, et al 2001
Both High and Low PCO
2
Increase Risk of IVH
Fabres, et al, Pediatrics 2007
Modalities of Volume -Targeted Ventilation
Controls Adjusts Based on
Servo (PRVC) V
T
to circuit PIP
Inspiratory V
T
of last breath

VIP Bird (VAPS)
Minimum V
T
to patient
Inspiratory
time ( )
Inspiratory V
T

Bear Cub 750
(Volume Limit)
Max. V
T
to
patient
Inspiratory
time ( )
Inspiratory V
T

Avea (VAPS
+ VL)
Min/Max V
T
to circuit/pt
Inspiratory
time ( )
Inspiratory V
T

P. Bennett 840
(Volume Vent +)
V
T
to circuit
Inspiratory
time / flow
Inspiratory V
T

Babylog 8000+
& VN 500 (VG)
V
T
to
patient
PIP
Exhaled V
T
of
last breath
Comparison between ventilator and Bicore CP-100
Tidal Volume Measurement
Chow, et al, Pediatr Pulmonol 2002
PRVC/VG Control Algorithm
Volume Limit
PRESSURE
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 limit
Working
Pressure
V
T
= V
T
set by user
The PIP (working
pressure) is servo-
regulated within preset
limits (pressure limit)
to achieve V
T
that is
set by the user.
Regulation of PIP is in
response to exhaled V
T

to minimize artifact
due to ETT leak.
Breath terminates if
130% of TV
T
reached.
Separate algorithm for
spontaneous and
machine breaths.
Working
Pressure
VOLUME
Target tidal volume
Pressure Limit
PRESSURE
Benefits of VG
Maintenance of (relatively) constant tidal
volumes / avoidance of hypocapnia
Prevention of overdistention and volutrauma
due to
Surfactant administration
Lung volume recruitment
Clearance of lung fluid
Automatic lowering of pressure support
level during weaning weans in real-time
Compensation for variable respiratory drive
stabilization of tidal volume and minute
ventilation due to changes of respiratory
drive (periodic breathing)
The benefits of VTV can not be
realized without ensuring that the
tidal volume is evenly distributed
throughout an open lung!!!
Expiration
Inspiration
Ventilated
Stable
Ventilated
Unstable
Unventilated
Atelectotrauma
Non-Homogenous Aeration in RDS
Recruitment/ de-
recruitment injury
Shear
forces
Adequate PIP, Adequate PEEP
COP
CCP
FRC
P
V
V
T
P
Good oxygenation, low FiO2, minimal lung injury
CCP = critical closing pressure; COP = critical opening pressure
OLC Prevents Lung Injury
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
Spontaneous Hyperventilation and VG
0
2
4
6
8
10
12
14
16
18
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
0
2
4
6
8
10
12
14
16
18
PIP
PIP limit
PEEP
VT
Set VT
Breath #
PIP (cm H2O) V
T
(ml)
Note the large V
T
, generated by the infant, while the PIP
drops near the PEEP level as the ventilator in VG mode
responds appropriately to the large V
T
by reducing PIP.
VG Combined with A/C v. SIMV
0
2
4
6
8
10
12
VT variance SpO2 variance
A/C + VG
SIMV + VG
* P < 0.001
*
*
Variance of VT and SpO2
Abubakar, et al, J Perinatol 2005
VG Combined with A/C v. SIMV
Ventilator Variables Mechanical Breaths
0
2
4
6
8
10
12
14
16
18
PIP MAP VT MV (L/min x
10)
A/C + VG
SIMV + VG
# P < 0.005
#
#
Abubakar, et al, J Perinatol 2005
Lung Volume
Patients
Pleural
Pressure
Machine
Generated
Pressure
Lung Volume
SIMV vs. A/Cor PSV:
Work of Breathing and VT
CPAP/SIMV
(unsupported)
A/C or PSV
Machine
Generated
Pressure
Patients
Pleural
Pressure
Lung Volume
SIMV
(supported)
Patients
Pleural
Pressure
Machine
Generated
Pressure
0
1
2
3
4
5
6
7
m
l
/
k
g
SIMV SIMV+PS3 SIMV SIMV+PS6
VT SIMV VT spont
SIMV: Uneven V
T

(Osorio, et al. J Perinat Apr 05)
VG Combined with A/C v. SIMV
Cardio-Respiratory Variables
0
20
40
60
80
100
120
140
160
180
HR RR SpO2
A/C + VG
SIMV + VG
*
*
*
* P < 0.001
Abubakar,et al, J Perinatol 2005
VG vs NAVA or PAV

Extreme Periodic Breathing
Owen, et al, ADC 2010

Cochrane Review: Duration of MV
Wheeler, et al 2010
Cochrane Review: Death or BPD @ 36 wk
Wheeler, et al 2010
Cochrane Review: Pneumothorax
Wheeler, et al 2010
Effect of VG on Markers of Lung Inflammation
Lista, 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 H
2
O)

Summary of VG Studies
When compared to PLV, VG results in:
Same or lower PIP
1,2,3
More stable VT
1,3

Less hypocapnia
3
Faster recovery from forced exhalation episodes
3
Works better with A/C than SIMV
4
Faster recovery from suctioning
4

Pro-inflammatory cytokines decreased @ 5 ml/kg
5
Faster weaning from mechanical ventilation
5

Higher VT needed in RLBW* infants
6

Higher VT needed with advancing post-natal age
3

1 Herrera et al, 2 Cheema, et al, 3 Keszler, et al, 4 Abubakar, et al, 5 Lista, et al
6 Montazami, et al * RLBW = Ridiculously low birth weight infant (<600g)

VG-Clinical Guidelines
Initiation
VG should be implemented immediately upon
initiation of mechanical ventilation.
The usual starting target V
T
is 4 - 5 mL/kg during
the acute phase of the illness.
Use corrected V
T
if ETT leak (VN 500)
Larger V
T
is needed with SIMV, in ELBW infants,
those with MAS and older infants with BPD!
PIP limit should be set 20% above the PIP currently
needed to deliver the target V
T
in order to give the
device adequate room to adjust PIP.
Record both the PIP limit and the working pressure.

VT in infants with MAS
Sharma, et al ESPR 2011
Relationship of Birthweight and V
T

Montazami,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)
V
T

(
m
l
/
k
g
)
R= -0.563 p<0.001
ELBW RLBW *
*RLBW = Ridiculously LBW
Conventional Physiology
Anatomical 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
Time to Eliminate CO
2
from Test Lung
2.5 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 -1.5
Tidal Volume (ml)
Seconds
Keszler, et al. ADC FN in print (Published Online 18 November 2011)
Fresh gas inflow spikes through DS gas
Mixing when flow abruptly stops
Exhaled gas spikes through mixed DS gas
Gas Flow Through Narrow ETT
Hendersons Experiment 1915
Relationship of Post-Natal
Age and V
T
(mL/Kg)
Keszler,et al, Arch Dis Child 09
Day 1-2
n = 251
Day 5-7
n = 185
Day 14-17
n = 216
Day 18-21
n = 176
VT (mL/kg) 5.15 + 0.6 5.24 + 0.7 5.63 + 1.0 6.07 + 1.4
PCO
2
(torr) 44.0 + 5.4 46.3 + 5.2 53.9 + 7.3 53.9 + 6.2
MV and Anatomical Dead Space
in ELBW Infants
As gas is delivered under pressure
to the newborn lung, the airway
expands in proportion to its
compliance.
1

Over time, elasticity is lost and
airway becomes larger than
normal
.

Preterm infants who are mechanically
ventilated have larger tracheal widths
than nonventilated neonates (Figure)
2
1. Greenspan JS, et al. Neonatal Netw. 2006;25:159-166.
2. Bhutani VK, et al. Am J Dis Child. 1986;140:449-452.
750 1,000 1,250 1,500
Study Weight, g
T
r
a
c
h
e
a
l
W
i
d
t
h
,

m
m

0
1.0
2.0
3.0
4.0
5.0
Ventilated
Non-ventilated
VG Clinical Guidelines:
Subsequent Adjustments
Adjustment to target V
T
may be made, based on
PaCO
2.
Usual increment is 0.5 mL/kg.
PIP limit needs to be adjusted from time to time to
keep the PIP limit close to the actual PIP.
PIP will default to the limit if sensor is out or when
giving a manual breath!
Consider light sedation if infant is agitated despite
good support
Pay attention to alarms, graphics (beware of leaks)!
If the low V
T
alarm sounds repeatedly, increase the
pressure limit AND INVESTIGATE THE CAUSE
VG Clinical Guidelines: Weaning
If target V
T
is set at low normal (usually ~4 mL/kg in first
few days, higher later on) and PaCO
2
is allowed to rise
to the mid - high 40s (pH <7.35), weaning occurs
automatically (self-weaning). Avoid VT <4 mL/kg.
If V
T
is set too high and/or the pH

is too high, the baby
will not have a respiratory drive and will not self-wean.
Avoid sedation during the weaning phase!
If significant oxygen requirement persists, PEEP may
need to be increased to maintain mean airway pressure
as PIP is automatically lowered.
Most infants can be extubated when they consistently
maintain V
T
at or above the target value with working
PIP < 10-12 cm H
2
O (< 12-15 cm H
2
O in infants > 1 kg)
with FiO
2
< 0.35 and good sustained respiratory effort.

Work of Breathing @ Different VT target
Patel, et al Pediatrics 2009
VG-SIMV: Minute Ventilation
Herrera, et al, Pediatr 2002
0
50
100
150
200
250
SIMV SIMV+VG4.5 SIMV+VG3
Total
Mech
Spont
ml/kg/min
Troubleshooting
There will be more alarms (interactive mode,
gives useful information, pay attention to it)
Avoid excessive alarms (they get ignored!
Common causes:
- Limits are too tight (most often pressure limit)
- Excessive ETT leak (change ETT if leak > 40%
(Much less of a problem with the VN 500)
- Forced exhalation episodes
- Agitation
Excessive noise
handling
lack of boundaries
mkeszler@WIHRI.org
Thank You