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Transpulmonary Pressure Patient Engagement, Systems Science, and the Elimination of Preventable Harm Daniel Talmor, MD, MPH
Transpulmonary Pressure
Patient Engagement, Systems Science, and the Elimination of Preventable Harm
Daniel Talmor, MD, MPH
Disclosures
• Research funding
– NHLBI
– CMS
– Gordon and Betty Moore Foundation
• Advisor
– Intensix
– Medial
• In debt
– To many people, but in particular to Dr. Steve Loring
ARDS Patient
• Post traumatic ARDS
• 46 y/o male s/p MVC, fractured pelvis
• Compromise of circulation to the legs
• Anasarca and a tense abdominal wall
• Initial ventilator settings– CMV
– TV= 535 cc
– Fi02= 1
– PEEP= 13
ARDS Mortality: What More Can We Do?
0.5
0.6
0.7
0.8
0.9
1
0 7 14 21 28
Proportion Surviving
Days after study entry
Vt = 12
Vt = 6
Slide courtesy BT Thompson
Animal Experiments Show That Adequate PEEPCan Reduce VILI
• Faridy et al. – Large volume mechanical ventilation increased surface tension
– At a given VT, effect attenuated by higher PEEP
• Wyszogrodski et al. – High volume ventilation inactivated surfactant in cats
– At a given VT, effect less with higher PEEP
• Webb and Tierney – High volume ventilation caused hemorrhagic edema and hyaline membranes in rats
– At constant peak pressure, effect less with higher PEEP
• Muscedere et al. – Even low volume ventilation in lavaged rat lungs caused histological damage.
– Effects were reduced or eliminated with higher PEEP.
• Chiumello et al. – Ventilation of injured rat lungs released inflammatory cytokines.
– At a given VT, effects were less with higher PEEP.
Clinical Trials of Higher PEEP
• Amato demonstrated a benefit to a low tidal volume
strategy combined with PEEP set by LIP of the PV
curve.
• ARIES trial seemed to confirm this
• ALVEOLI trial stopped early for futility
• LOVS trial showed no benefit.
• The EXPRESS trial which set PEEP based on the
airway plateau pressure showed mixed results
“The LOV study and the Express study not only should conclude the era of comparing PEEP levels in unselected populations with
ALI and ARDS, but also underscore the need for a new definition of ARDS aimed at
identifying patients with greater lung edema and larger recruitability …”
Gattinoni L, Caironi P; JAMA. 2008 Feb 13;299(6):691-3.
Briel M, JAMA, 2010; 303: 865
Optimal Risk/Benefit of PEEP May Depend on Recruitability
0
10
20
30
P=0.566 ml/kg
6 ml/kg
Pplat
Driving Pressure
PEEP(cm H20)
6 ml/kgNon-
recruitable 6 ml/kgRecruitable
Injury >Benefit
Benefit>Injury
Lower PEEP
Higher PEEP
Vent
PL = Pao - PPlPao
PPl
Lung
Chest Wall
PL is the pressure actually distending the lung.
This may be very different from the pressure measured at the airway.
PL May be more important then Pao
Vent
PL = Pao - PPlPao
PPl
Lung
Chest Wall
Titrating ventilation based on ventilator pressures does not allow us to take this variability into account
PL May be Very Different then Pao
Esophageal Pressure to Estimate Pleural Pressure
Mechanical ventilation: Passive
Pes
Volume
Volume
0 25
P-V curveof passiveChest Wall
Pes (cmH2O)
Pressure transducing wafers implanted in dog lungs revealed differences in pleural pressure due to the gravitational effect of the dependant vs. non-dependant regions of the lung.
Pes Values Reflect High Pleural Pressures
-7
+4
Pes 0
Non-Dependant
Mid-Lung
Dependant
Pelosi Am J Respir Crit Care Med 2001; 164:122-130
Relationship Between Transpulmonary and
Airway Pressure
Talmor et al. CCM 2006
Sample Data From Anesthetized Obese
Subject
Paw
Pes
Vol.
Flow
Threshold Paw
Expanded Time Scale
Paw
Pes
Vol.
Flow
6 sec.
In Humans
Gattinoni. Am J Respir Crit Care Med Vol 164. pp 1701–1711, 2001
PT 1 Initial Ventilator settings on PCV
Paw
-10
50
0
Pes
PL
50
040
Paw = 13 to 40
Pes = 20 to 33
Ptp = -8 to 6
Ventilator pressures:
PEEP 13 26
which raised
Pplateau 40 46
Pt 1 Strategy: Change ventilator pressures to optimize PL
Pt 1 After Ventilator Changes to Optimize PL
Paw
-10
50
0
Pes
PL
50
040
Paw = 26 to 46
Pes = 22 to 33
Ptp = 4 to 12
Talmor D, N Eng J Med, 2008; 359:2095
N Eng J Med, 2008; 359:2095
6- Month Survival
N001 Baseline
17 cmH2O
Pao
Flow
Pes
Ptp
28 cmH2O
-11 cmH2O
N001 Day 1
33 cmH2O
Pao
Flow
Pes
Ptp
34 cmH2O
-0.8 cmH2O
Echocardiography
Hemodynamics
Sarge et al. ATS 2012
Mechanical ventilation: Passive
Pes
Volume
Volume
0 25
P-V curveof passiveChest Wall
Pes (cmH2O)
Elastance Derived Measurement of Transpulmonary Pressure
ECW = ΔPES/ VT
ERS = ΔPAO / VT
ΔPAO
PL= PAO * EL/ERS
ECW – based Method
Assumption: Measured slope
of chest wall P-V curve is
accurate, but
Ppl = 0 when Pao = 0
Pressure (cmH2O)V
olu
me
rela
tive
to
Ve
eo
(mL)
PL,eeo = Pao,eeo – Pes,eeo
PL,eio = Pao,eio – Pes,eio
Pressure (cmH2O)
Vo
lum
e re
lati
ve t
o V
eeo
(mL)
Pes – based Method
Assumption: Measured Pes is
approximately equal to Ppl
P-V CurvesRespiratory systemChest wall (Pes – based)Chest wall (ECW – based)
Maintain slope but shift chest wall P-V curve to pass through origin
PL,eio = Pao,eio – (Pao,eio ×
ECW/ERS)
Pressure (cmH2O)
Vo
lum
e re
lati
ve t
o V
eeo
(mL)
PL,eeo = Pao,eeo –(Pao,eeo × ECW/ERS)
Clinical Use of Elastance-Derived PL
Grasso S, Ranieri VM, Intensive Care Med, 2012
RCTs of Higher PEEP
Amato Villar
P=0.56
Vt
6Vt
12
PPlat
Driving
Pressure
PEEP
(cm H20)
Vt
7
ALVEOLI Express LOVS
Vt
10 Vt
6
Vt
6
Vt
6
Vt
6 Vt
6
Vt
6
Beneficial Non-Beneficial
EPVent
Vt
7
Vt
7
?
+RM +RM
Slide courtesy BT Thompson
EPVent II- Overall Concept
• A phase II prospective randomized controlled trial of ventilation directed by esophageal
pressure measurements.
• Enroll 200 patients with moderate to severe ARDS by the Berlin conference definition in 10
academic medical centers in North America.
• Randomized to EPVent group or empiric high-PEEP control group.
EPVent2 05-2015
Transpulmonary Pressure
Patient Engagement, Systems Science, and the Elimination of Preventable Harm
Daniel Talmor, MD, MPH
