8 th Pulmonary Medicine Update February 6, 2008 Physiology of PEEP in ARDS Richard K. Albert, M.D. Chief of Medicine Denver Health Professor of Medicine University of Colorado Adjunct Professor of Engineering and Computer Science University of Denver Denver Health

Objectives PEEP  Effect on lung PV curve  Pleural pressure gradient  VILI  Does the lung recruit?  Physiologic complications Denver Health

Physiology of Ventilating Patients with ARDS -10 -20 -30 2 4 6 Ptp (cm H 2 O) V L (L)  V  P Governing variables  V T  EELV (PEEP) Implications  V modes  P modes  “ Fancy” modes offer nothing (Assuming  V T and EELV)  Mean Paw is meaningless Denver Health

How Did it Get So Complicated? Webb and Tierney, ARRD 1974 Denver Health

ARDS Net Low-Stretch Ventilation Study ARDS Net Low-Stretch Ventilation Study  Test of low-vs. “standard”-stretch  -  6 vs 12 mL/kg (IBW)  -  Mean PEEP ~ 8-9 cm H 2 O - 861 patients   mortality - 40% to 31% (23%  )  VILI contributes to mortality in ARDS VILI may cause biotrauma Denver Health

Ventilator-Induced Lung Injury Overdistension  Endothelial/epithelial stretch  Capillary stress failure   by PEEP Cyclical opening and closing (?)  Shear stress - At interface of open and closed regions  PEEP -  if derecruitment prevented -  if  recruitment-derecruitment Denver Health

The Culprit Denver Health

Pleural Pressure Gradient 0 3 -3 Ppl (cm H 2 O) Control 0.53 ± 0.1 Mutoh, JAP 1992 Injured 0.71 ± 0.1 26 cm chest = Normal: 13 cmH 2 O Ppl  ARDS: 18 cmH 2 O Ppl  Denver Health D ND ND D

PV Relationships (ARDS, Supine) 5 10 15 20 25 V L (% TLC) Ptp (cm H 2 O) 0 -5 -10 -15 -20 30 FRC TLC               Denver Health Ventral Alveoli        Dorsal Alveoli      

Effect of PEEP on Regional Air Density Control 32 24 16 8 0 Dependent Non-Dependent 32 24 16 8 0 Denver Health

Prone Position  Overinflation and Regional V L Heterogeneity Injured 0 5 10 15 Dependent Non-Dependent 0 5 10 15 20 Denver Health

Ppl Gradient Implications  Range of opening pressures  Range of closing pressures  Any given PEEP produces a range - Ptps - EELVs  Range  -  V-D dimension (to 75 cmH 2 0 in obese patients) - Lung injury  Lung PV curve cannot describe regional mechanics Denver Health

Opening and Closing Pressures in ARDS Crotti, AJRCCM 2001 Opening Pressures Closing Pressures Denver Health

Problem for All PEEP Titration and Recrutment Strategies Airspace (inside) pressure is uniform Ppl (outside) pressure is heterogeneous  Heterogeneous Ptp  Heterogenous lung expansion  Recruiting dependent regions will overdistend non-dependent regions Denver Health

Effect of Prone Position on Response to Recruitment Maneuver % Total Volume Right Left 100 75 50 25 0 Galiatsou, AJRCCM 2006 Over-Inflated Partially Aerated Well-Aerated Non-Aerated 40/20 x 30 sec, then  PEEP to  CL Denver Health

Overinflation During Tidal Breathing V T = 6 ml/kg PEEP = 10 Pplat = 27 Terragni, AJRCCM 2007 Denver Health

Martynowicz, Hubmyar et al AJRCCM 1999 Oleic acid-induced ALI Measured regional lung volume  Parenchymal markers - 1 mm metal beads - Transthoracic insertion into caudal lobe - Biplane fluoro -  20 beads (79 tetrahedra)/animal  Measures actual tissue dimensions Denver Health

No Loss of Lung Volume After Oleic Acid After injury:  EELV   Cyclical V L changes  Martynowicz, AJRCCM 1999 Denver Health Pre-Injury Post-Injury Tetrahedral Volume (Vol/TLC)

No Effect of Injury on Regional Lung Volume Tetrahedral Volume (/TCL) Vertical Centroid Location (cm) Martynowicz, AJRCCM 1999 Denver Health

PEEP  Cyclical Changes in V L and  EELV Above Resting V L Martynowicz, AJRCCM 1999 Denver Health

Martynowicz, Hubmyar et al Summary Lung volume preserved post-injury  No atelectasis  “ Recruitment” ? - Airway fluid pushing into, and overdistending alveoli No cyclical airspace opening/closing  Mechanisms of PEEP protection not clear Denver Health

Collaborators Johns Hopkins  Brett Simon. M.D., Ph.D.  Blaine Easley, M.D., University of Iowa  Eric Hoffman, Ph.D .,  Joe Reinhart, Ph.D.,  Ken Beck, Ph.D. Denver Health

Assessment of Lung Volume Non-Dependent Dependent Denver Health

Volume:Density Relationship (Injured, Apex, Supine) Volume (/Vol @ PEEP 32, Control) Density (HU) 0 32 0 32 Dependent lung:  volume with no  density (i.e., distal fluid displacement) Mid lung: no  volume to PEEP 24 but big  density (air replacing fluid) Volume at PEEP 0 is 40-50% of volume at PEEP 32 (control) Non-Dependent to Dependent 0 32 0 32 Denver Health

PEEP Titration Endpoints:  Best PaO 2  Lowest shunt  Best O 2 delivery  Best Q t  Highest C L  Lowest V D /V T  Pplat < 30 cm H 2 O  Best CT aeration  Until P/V curve becomes concave Denver Health

Problem for All PEEP Titration and Recrutment Strategies Airspace (inside) pressure is uniform Ppl (outside) pressure is heterogeneous  Heterogeneous Ptp  Heterogenous lung expansion  Recruiting dependent regions will overdistend non-dependent regions Denver Health

Why Use Higher Levels of PEEP? Open Lung (?)  Plusses -  Better gas exchange -  Lower F I O 2 -  Less cyclic airspace opening/closing  Minuses - Over-inflation - Limits V T (PaCO 2 , sedation, paralysis) - Complications Denver Health

PEEP Comparison ARDS Network RCT 549 pts V T = 6 ml/kg PEEP: 8 vs 13 cm H 2 O NEJM 2004 Denver Health

Complications of PEEP Adverse effects of PEEP   Cardiac output  Volutrauma   Lung water   High V A /Q   Dead space   Endothelial permeability   Epithelial permeability   Bronchial blood flow Denver Health

Effect of PEEP on the Heart  Juxtacardiac pressure  RA:  venous return - Venous return = (MSVP-Pra)/Rveins (Guyton) - Can overcome with volume - PEEP  MSVP and Rveins Denver Health

Effect of PEEP on Mean Systemic Venous Pressure Fessler, ARRD 1993 MSVP Pra Denver Health

Effect of PEEP on Venous Return Fessler, ARRD 1993 Denver Health

Effect of PEEP on Venous Return Fessler, ARRD 1993 Denver Health

Effect of PEEP on the Heart  Juxtacardiac pressure  RA:  venous return - Venous return = (MSVP-Pra)/Rveins (Guyton) - Can overcome with volume - PEEP  MSVP and Rveins  LV:  afterload (~ 10%) PEEP  Pjc  Depends on - Heart volume - Lung volume - Lung compliance  May be regional effects Denver Health

Effect of PEEP on Lung Perfusion Permutt, JAP 1961 P A Pvas constant relative to Ppl Denver Health

P A

Pvas constant

relative to Ppl

Effect of PEEP on Lung Perfusion (Normal Lungs) 2.0 1.0 0.5 1.5 0.0 Relative Q 0.0 0.2 0.4 0.6 0.8 1.0 V L /TLC  • • • • • Ppa-P A = 25 • • • • Ppa-P A = 17 • • • • • Ppa-P A = 11 Ppa-P A = 5.6 • • Beck, JAP 1985 P A Pvas constant relative to P A Denver Health

P A

Pvas constant

relative to P A

PEEP  Lung Water Demling & Staub, JAP 1975 PEEP = 0 PEEP = 10 Denver Health

PEEP  Lung Water Albert, JAP 1980 Denver Health

PEEP  Dead Space and High V A /Q Ralph, ARRD 1985 Denver Health

PEEP (Lung Stretch)  Endothelial Permeability Parker, 1984 Denver Health

PEEP  Alveolar Epithelial Permeabaility Kim, JAP 1982 15 min Denver Health

PEEP  Bronchial Blood Flow Baile, 1984 Denver Health

Ventilating Patients with ARDS Summary  What variable defines “best” PEEP?  Can’t be a single PEEP that is “best” for both dependent and non-dependent lung  PV curve measured at the airway cannot reflect regional PV differences  High PEEP has several bad physiological effects  May have to rethink “recruitment” and “ cyclic airspace opening/closing” Denver Health

Setting PEEP with Low V T in ALI What do I do?  Low V T ventilation (with considerations)  - Consider the “chest wall” re: Pplat  - Concerned about oversedation to blunt drives  Assess PaO 2 response to PEEP - Very rarely > 20 cm H 2 O - Rarely > 15 cm H 2 O - Watch Pplat (< 30 unless  C CW ) - Early use of prone rather than  PEEP  No routine use of recruiting maneuver Denver Health