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 (?)

mkeszler@WIHRI.org

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