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8 th  Pulmonary Medicine Update February 7, 2008 Prone Ventilation for ARDS:  Does it Do More Than Improve Oxygenation? Richard K. Albert, M.D. Chief of Medicine Denver Health Medical Center Professor of Medicine University of Colorado Adjunct Professor of Engineering and Computer Science University of Denver Denver Health
Colorado Skiing Denver Health
Objectives To describe:    Hx of prone ventilation    Effects on:  -  O 2 -  Regional lung volume and perfusion -  Response to recruitment maneuvers -  VILI  Clinical studies  Unpublished data Denver Health
History of Prone Ventilation Douglas et al, ARRD 1977    Six pts, individual PaO 2 ’s, supine and prone, early and later in course  Piehl and Brown, CCM 1976    Five case reports, mean ABG data Bryan, ARRD 1974  First suggested based on studies of sedation and paralysis on diaphragm Denver Health
Collaborators U. Washington U. Colorado   Lisa Embree   Wayne Lamm   Josh Saliman Mike Graham   David Leasa   Sun Jong Kim Bob Guest   Takashi Mutoh   Ivor Douglas Robb Glenny   Tom Robertson     Jae Hwa Cho Jack Hildebrandt  Mary Sanderson  Seok Chan Kim Mike Hlastala     Charlie Wiener  Wayne Kirk  Mayo Clinic   Rolf Hubmayr   U. Barcelona   Johns Hopkins   U. Iowa   Jordi Mancebo     Blaine Easley   Ken Beck Brett Simon Eric Hoffman Denver Health
Effect of Prone Positioning on PaO 2 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],100 200 300 400 500 PaO 2  (mm Hg) N = 20 F I O 2  = 0.9 ± 0.1 PEEP = 10 ± 1.5                Supine Prone                   67 ± 5 169 ± 35*    Denver Health
Prone Position Improves V A /Q Lamm, ARRD 1994 Relative V A /Q Voxels (N) Denver Health
Mechanisms for    Shunt Hypothesis: Dependent Lung: -  More edema -  More Q Prone positioning redistributes Q to  ventral lung Shunt (Q without V) Redistribute Q to areas of V Redistribute V to areas of Q Denver Health
Effect of Prone Position on Regional Lung Injury Supine 10 7.5 5.0 2.5 BF Wet/Dry Dorsal Ventral Wiener, JAP 1990 D Mid ND D Mid ND Prone Dorsal Ventral Denver Health
Effect of Prone Position on Regional Perfusion Percent Flow 25 50 0 Supine Dorsal Ventral Wiener, JAP 1990 Mid D ND Prone Ventral Dorsal D Mid ND Denver Health
Zonal Theory of Pulmonary Blood Flow Distribution Flow Vertical Height Ppa > Ppv > P A   Zone III Ppa > Ppv > P A   Zone IV P A  > Ppa > Ppv Zone I Ppa > P A  > Ppv Zone II Denver Health
Theoretical Effect of Position on Perfusion Distribution Glenny, JAP 1991 Denver Health
Measured Effect of Position on Perfusion Distribution Glenny, JAP 1991 Denver Health
Zonal Theory of Pulmonary Blood Flow Distribution Flow Vertical Height Zone II Zone III Zone IV Top Bottom Denver Health
Effect of Position on Perfusion Distribution Glenny, JAP 1991 Denver Health
Effect of Prone Position on Gravitational Q Gradient in  Humans Methods  SPECT  CT angiograms  PET Methodological issues  Assessing Q relative to what? -  Gram of lung tissue ? -  Alveolar volume ?  Normal vs injured lung  Effect of PEEP  Area of interest Denver Health
Treatment of Hypoxemia Shunt (Q without V) Redistribute Q to areas of V Redistribute V to areas of Q Denver Health
Ventilation Distribution Milic-Emili, 1960s    Gravitational distribution of Ppl -  More negative in nondependent region    Upright, supine, decubitus positions Denver Health
Effect of Prone Position on Ppl Gradient 0 3 -3 Ppl (cm H 2 O) Supine Prone Control Mutoh, JAP 1992 0.53 ± 0.1 D 0.17 ± 0.1 D ND ND Denver Health
Effect of PEEP on Regional Air Density Control Supine Prone Dep Non-Dep Dep Non-Dep 32 24 16 8 0 32 24 16 8 0 Denver Health
Prone Position Improves Dorsal Lung V/Q Lamm, ARRD 1994 Control Denver Health
Dual  Effect of Prone Position on Ppl Gradient in ALI 0 3 -3 Ppl (cm H 2 O) Supine Supine Prone Prone Control Edema Mutoh, JAP 1992 0.53 ± 0.1 D 0.17 ± 0.1 D 0.71 ± 0.1 D 0.27 ± 0.1 D ND ND ND ND Denver Health
Prone Position    Overinflation and Regional V L  Heterogeneity Supine Prone Injured Dep Non-Dep Dep Non-Dep 0 0 5 5 10 10 15 15 20 20 Denver Health
Prone Position Improves Dorsal Lung Ventilation Lamm, ARRD 1994 Oleic Acid Denver Health
Effect of Body Position on Ppl Gradient How lungs fit into the thorax   Lung distensibility     Thorax distensibility -   Lung volume -   Chest wall mass -   Air- or liquid-filled -   Chest wall compliance -   Abdominal mass -   Abdominal compliance -   Heart mass -   Mediastinal mass -   Diaphragm curvature Denver Health
Weight of the Lung Denver Health
Triangular Shaped Lung Denver Health
Weight of the Lung Denver Health
Weight of the Lung Denver Health
Effect of Heart Weight (Supine) Albert, AJRCCM 2000 41% of left lung under the heart Malbouisson, ’00 -  64% of LLL -  ARDS patients -     heart size Denver Health
Effect of Heart Weight (Prone) Albert, AJRCCM 2000 Denver Health
Prone Position    Lung Compression by Abdominal Contents Supine Prone 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) -  PEEP and FIO 2  controlled by protocol  -  Mean PEEP  ~  8-9 cm H 2 O - 861 patients    mortality    40% to 31%  9% absolute, 23% relative VILI/Biotrauma contributes to mortality NEJM 2000 Denver Health
Most ARDS Develops During  Hospitalization Hudson et al, AJRCCM 1995 Denver Health
VILI/Biotrauma Pathophysiology Overdistension  Endothelial/epithelial stretch  Capillary stress failure    Surfactant alteration Cyclical airspace opening and closing    Shear stress    Surfactant alteration       by PEEP Something else Denver Health
Effect of Prone Position on Response to Recruitment Maneuver Pelosi, AJRCCM 2002 N = 10 ARDS 3 x 45 cmH 2 0/min EELV measured with helium Denver Health
Effect of Prone Position on Response to Recruitment Maneuver % Total Volume Right Lung Left Lung 100 75 50 25 0 Supine Supine Prone Prone OI PA WA NA Galiatsou, AJRCCM 2006 N = 21 Lobar ALI 40/20 x 30 sec PEEP    to    C L No ventral derecruitment Denver Health
Cyclical Airspace Opening and Closing End-Exhalation Mid-Inhalation End-Inhalation Lavage-Induced ALI, PEEP 10 cm H 2 O Denver Health
Italian Prone Ventilation Trial (Gattinoni et al, NEJM 2001) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Denver Health
Italian Prone Ventilation Trial (Gattinoni et al, NEJM 2001) Problems:  Proning protocol - Application: 7 hrs/day (   17 hrs/day supine) - Institution: late (decubiti) - Duration: 10 day maximum  Protocol breaks: 134 in 53 pts  Underpowered  (N = 308) - Trend toward    mortality (25% vs 21.1%, 16%   ) - Stopped because of investigator bias  No ventilation protocol    No weaning protocol Denver Health
French Prone Ventilation Trial (Guerin et al, JAMA 2004) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Denver Health
French Prone Ventilation Trial (Guerin et al, JAMA 2004) Problems:  Only 413 with ARDS or ALI (51%) -  No condition-specific data  Underpowered    81 (21%) crossovers (supine to prone)     Proning protocol: - Application: 8 hrs/day (16 hrs/day supine) >   25% < 8 hrs/day  - Duration: 4 days    No ventilation protocol  Denver Health
Spanish Prone Ventilation Trial (Mancebo et al, AJRCCM 2006) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Denver Health
Spanish Prone Ventilation Trial (Mancebo et al, AJRCCM 2006) Mortality (%) 20 40 60 80 Hospital 37/58 64% 39/75 52% ICU 34/58 59% 33/75 44% 25%   P < 0.12 P < 0.02  (adjusted by SAPS) 19%   P < 0.20 Denver Health Prone Supine
Prone Ventilation in ARDS Summary     PaO 2  in 66-75% of patients -     F I O 2  (   O 2  toxicity),    PEEP (   overdistension)   No substantive side-effects  More homogeneous EELV -     Overinflation -     Airspace opening and closing -     Recruitment     Ventilator-induced lung injury (?)     Biotrauma (?)       Mortality (?) Denver Health
Some New Stuff  Pre-B Cell Colony Enhancing Factor-1  First found in endometrial tissue  Lung endothelium/epithelium     in PMNs of septic pts     IL-6 and IL-8  Induced by - Mechanical stress - LPS, IL-1  , TNF  , IL-6 - VILI Denver Health
Prone Position    High V T -Induced Regional PBEF-1 Expression 40 80 60 20 Relative PBEF-1 Expression (/  -Actin) Control Low V T  (Spine) High V T  (Supine) High V T  (Prone) Cephalad Caudal Cephalad Caudal Non-Dependent Dependent Denver Health
PBEF Expression (IHC) Endothelial and Epithelial Expression Denver Health 20x
Objectives Summarize:    Hx of prone ventilation    Effects on:  -  O 2 -  Regional lung volume and perfusion -  Response to recruitment maneuvers -  VILI  Clinical studies  Unpublished data Denver Health
Prone Ventilation in ARDS Conclusion: Don’t do anything on your back –  You might get ARDS Denver Health

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Prone Ventilation In ARDS

  • 1. 8 th Pulmonary Medicine Update February 7, 2008 Prone Ventilation for ARDS: Does it Do More Than Improve Oxygenation? Richard K. Albert, M.D. Chief of Medicine Denver Health Medical Center Professor of Medicine University of Colorado Adjunct Professor of Engineering and Computer Science University of Denver Denver Health
  • 3. Objectives To describe:  Hx of prone ventilation  Effects on: - O 2 - Regional lung volume and perfusion - Response to recruitment maneuvers - VILI  Clinical studies  Unpublished data Denver Health
  • 4. History of Prone Ventilation Douglas et al, ARRD 1977  Six pts, individual PaO 2 ’s, supine and prone, early and later in course Piehl and Brown, CCM 1976  Five case reports, mean ABG data Bryan, ARRD 1974  First suggested based on studies of sedation and paralysis on diaphragm Denver Health
  • 5. Collaborators U. Washington U. Colorado Lisa Embree Wayne Lamm Josh Saliman Mike Graham David Leasa Sun Jong Kim Bob Guest Takashi Mutoh Ivor Douglas Robb Glenny Tom Robertson Jae Hwa Cho Jack Hildebrandt Mary Sanderson Seok Chan Kim Mike Hlastala Charlie Wiener Wayne Kirk Mayo Clinic Rolf Hubmayr U. Barcelona Johns Hopkins U. Iowa Jordi Mancebo Blaine Easley Ken Beck Brett Simon Eric Hoffman Denver Health
  • 6.
  • 7. Prone Position Improves V A /Q Lamm, ARRD 1994 Relative V A /Q Voxels (N) Denver Health
  • 8. Mechanisms for  Shunt Hypothesis: Dependent Lung: - More edema - More Q Prone positioning redistributes Q to ventral lung Shunt (Q without V) Redistribute Q to areas of V Redistribute V to areas of Q Denver Health
  • 9. Effect of Prone Position on Regional Lung Injury Supine 10 7.5 5.0 2.5 BF Wet/Dry Dorsal Ventral Wiener, JAP 1990 D Mid ND D Mid ND Prone Dorsal Ventral Denver Health
  • 10. Effect of Prone Position on Regional Perfusion Percent Flow 25 50 0 Supine Dorsal Ventral Wiener, JAP 1990 Mid D ND Prone Ventral Dorsal D Mid ND Denver Health
  • 11. Zonal Theory of Pulmonary Blood Flow Distribution Flow Vertical Height Ppa > Ppv > P A Zone III Ppa > Ppv > P A Zone IV P A > Ppa > Ppv Zone I Ppa > P A > Ppv Zone II Denver Health
  • 12. Theoretical Effect of Position on Perfusion Distribution Glenny, JAP 1991 Denver Health
  • 13. Measured Effect of Position on Perfusion Distribution Glenny, JAP 1991 Denver Health
  • 14. Zonal Theory of Pulmonary Blood Flow Distribution Flow Vertical Height Zone II Zone III Zone IV Top Bottom Denver Health
  • 15. Effect of Position on Perfusion Distribution Glenny, JAP 1991 Denver Health
  • 16. Effect of Prone Position on Gravitational Q Gradient in Humans Methods  SPECT  CT angiograms  PET Methodological issues  Assessing Q relative to what? - Gram of lung tissue ? - Alveolar volume ?  Normal vs injured lung  Effect of PEEP  Area of interest Denver Health
  • 17. Treatment of Hypoxemia Shunt (Q without V) Redistribute Q to areas of V Redistribute V to areas of Q Denver Health
  • 18. Ventilation Distribution Milic-Emili, 1960s  Gravitational distribution of Ppl - More negative in nondependent region  Upright, supine, decubitus positions Denver Health
  • 19. Effect of Prone Position on Ppl Gradient 0 3 -3 Ppl (cm H 2 O) Supine Prone Control Mutoh, JAP 1992 0.53 ± 0.1 D 0.17 ± 0.1 D ND ND Denver Health
  • 20. Effect of PEEP on Regional Air Density Control Supine Prone Dep Non-Dep Dep Non-Dep 32 24 16 8 0 32 24 16 8 0 Denver Health
  • 21. Prone Position Improves Dorsal Lung V/Q Lamm, ARRD 1994 Control Denver Health
  • 22. Dual Effect of Prone Position on Ppl Gradient in ALI 0 3 -3 Ppl (cm H 2 O) Supine Supine Prone Prone Control Edema Mutoh, JAP 1992 0.53 ± 0.1 D 0.17 ± 0.1 D 0.71 ± 0.1 D 0.27 ± 0.1 D ND ND ND ND Denver Health
  • 23. Prone Position  Overinflation and Regional V L Heterogeneity Supine Prone Injured Dep Non-Dep Dep Non-Dep 0 0 5 5 10 10 15 15 20 20 Denver Health
  • 24. Prone Position Improves Dorsal Lung Ventilation Lamm, ARRD 1994 Oleic Acid Denver Health
  • 25. Effect of Body Position on Ppl Gradient How lungs fit into the thorax   Lung distensibility   Thorax distensibility - Lung volume - Chest wall mass - Air- or liquid-filled - Chest wall compliance - Abdominal mass - Abdominal compliance - Heart mass - Mediastinal mass - Diaphragm curvature Denver Health
  • 26. Weight of the Lung Denver Health
  • 27. Triangular Shaped Lung Denver Health
  • 28. Weight of the Lung Denver Health
  • 29. Weight of the Lung Denver Health
  • 30. Effect of Heart Weight (Supine) Albert, AJRCCM 2000 41% of left lung under the heart Malbouisson, ’00 - 64% of LLL - ARDS patients -  heart size Denver Health
  • 31. Effect of Heart Weight (Prone) Albert, AJRCCM 2000 Denver Health
  • 32. Prone Position  Lung Compression by Abdominal Contents Supine Prone Denver Health
  • 33. ARDS Net Low-Stretch Ventilation Study ARDS Net Low-Stretch Ventilation Study  Test of low-vs. “standard”-stretch  -  6 vs 12 mL/kg (IBW) -  PEEP and FIO 2 controlled by protocol  -  Mean PEEP ~ 8-9 cm H 2 O - 861 patients  mortality  40% to 31%  9% absolute, 23% relative VILI/Biotrauma contributes to mortality NEJM 2000 Denver Health
  • 34. Most ARDS Develops During Hospitalization Hudson et al, AJRCCM 1995 Denver Health
  • 35. VILI/Biotrauma Pathophysiology Overdistension  Endothelial/epithelial stretch  Capillary stress failure  Surfactant alteration Cyclical airspace opening and closing  Shear stress  Surfactant alteration   by PEEP Something else Denver Health
  • 36. Effect of Prone Position on Response to Recruitment Maneuver Pelosi, AJRCCM 2002 N = 10 ARDS 3 x 45 cmH 2 0/min EELV measured with helium Denver Health
  • 37. Effect of Prone Position on Response to Recruitment Maneuver % Total Volume Right Lung Left Lung 100 75 50 25 0 Supine Supine Prone Prone OI PA WA NA Galiatsou, AJRCCM 2006 N = 21 Lobar ALI 40/20 x 30 sec PEEP  to  C L No ventral derecruitment Denver Health
  • 38. Cyclical Airspace Opening and Closing End-Exhalation Mid-Inhalation End-Inhalation Lavage-Induced ALI, PEEP 10 cm H 2 O Denver Health
  • 39.
  • 40. Italian Prone Ventilation Trial (Gattinoni et al, NEJM 2001) Problems:  Proning protocol - Application: 7 hrs/day (  17 hrs/day supine) - Institution: late (decubiti) - Duration: 10 day maximum  Protocol breaks: 134 in 53 pts  Underpowered (N = 308) - Trend toward  mortality (25% vs 21.1%, 16%  ) - Stopped because of investigator bias  No ventilation protocol  No weaning protocol Denver Health
  • 41.
  • 42. French Prone Ventilation Trial (Guerin et al, JAMA 2004) Problems:  Only 413 with ARDS or ALI (51%) - No condition-specific data  Underpowered  81 (21%) crossovers (supine to prone)  Proning protocol: - Application: 8 hrs/day (16 hrs/day supine) > 25% < 8 hrs/day - Duration: 4 days  No ventilation protocol Denver Health
  • 43.
  • 44. Spanish Prone Ventilation Trial (Mancebo et al, AJRCCM 2006) Mortality (%) 20 40 60 80 Hospital 37/58 64% 39/75 52% ICU 34/58 59% 33/75 44% 25%  P < 0.12 P < 0.02 (adjusted by SAPS) 19%  P < 0.20 Denver Health Prone Supine
  • 45. Prone Ventilation in ARDS Summary   PaO 2 in 66-75% of patients -  F I O 2 (  O 2 toxicity),  PEEP (  overdistension)  No substantive side-effects  More homogeneous EELV -  Overinflation -  Airspace opening and closing -  Recruitment   Ventilator-induced lung injury (?)   Biotrauma (?)   Mortality (?) Denver Health
  • 46. Some New Stuff Pre-B Cell Colony Enhancing Factor-1  First found in endometrial tissue  Lung endothelium/epithelium   in PMNs of septic pts   IL-6 and IL-8  Induced by - Mechanical stress - LPS, IL-1  , TNF  , IL-6 - VILI Denver Health
  • 47. Prone Position  High V T -Induced Regional PBEF-1 Expression 40 80 60 20 Relative PBEF-1 Expression (/  -Actin) Control Low V T (Spine) High V T (Supine) High V T (Prone) Cephalad Caudal Cephalad Caudal Non-Dependent Dependent Denver Health
  • 48. PBEF Expression (IHC) Endothelial and Epithelial Expression Denver Health 20x
  • 49. Objectives Summarize:  Hx of prone ventilation  Effects on: - O 2 - Regional lung volume and perfusion - Response to recruitment maneuvers - VILI  Clinical studies  Unpublished data Denver Health
  • 50. Prone Ventilation in ARDS Conclusion: Don’t do anything on your back – You might get ARDS Denver Health