What Now for Prone

Positioning?

Luciano Gattinoni, MD, FRCP

Università di Milano

Fondazione IRCCS Ca’ Granda

Ospedale Maggiore Policlinico

Milan, Italy

2013, Toronto

1976

1977

… nothing happened

5 cm H2O

PaO2: 97 mm Hg

d. 59%

d. 56%

PaO2: 103 mm Hg

10 cm H2O

d. 53%

PaO2: 104 mm Hg

15 cm H2O

No response to PEEP

1986

Gattinoni L et al. Intensive Care Med. 1986;12(3):137-42.

d. 70%

PaO2 : 34 mm Hg

5 cm H2O

d. 52%

PaO2 : 49 mm Hg

10 cm H2O

d. 32%

PaO2 : 121 mm Hg

15 cm H2O

Great response to PEEP!

1986

Gattinoni L et al. Intensive Care Med. 1986;12(3):137-42.

First hypothesis

PaO2 PaO2

High perfusion High perfusion

1988

End Expiration Supine

Prone

Supine

Supine

100%

U

L

0%

50%

50%

U

L

50%

Prone

100%

U

L

0%

50%

75%

U

L

25%

Gattinoni L et al. Intensive Care Med. 2013 Nov;39(11):1909-15.

Gattinoni L et al. Anesthesiology 74: 15-23, 1991

1991

Without

gravity

Interstitial edema

and increased mass

The Sponge Model

g/t - 0.6

g/t - 0.6

g/t - 0.6

With

gravity

Superimposed

Pressure

Interstitial edema, increased mass

and collapse

g/t - 0.2

g/t - 1.0

g/t - 0.5

Shifting from

oxygenation to lung

protection:

Lung homogeneity

Altezza (mm)

0

10

20

30

40

50

N° immagine

80 0 20 40 60

2005

Valenza F et al, Crit Care Med. 2005 Feb;33(2):361-7

SUPINE vs PRONE

lung regions

1 2 3 4

mean

HU

-600

-500

-400

-300

prone

supine

Valenza F et al, Crit Care Med. 2005 Feb;33(2):361-7

2005

Shape matching Shape matching

and gravity Isolated lung

Absence of gravity Gravity S

upin

e P

ron

e

A B C

D E F

Gattinoni L et al. Am J Respir Crit Care Med. 2013 Oct 17. [Epub ahead of print]

Prone position attenuates VILI

Broccard CCM 2000

Dog, normal P vs. S Histology, W/D

Du Acta An Scand 1997

Dog, oleic acid P vs. LD Histology, PaO2

Nishimura ICM 2000

Rabbit, normal P vs. S Histology, CT scan, time

SUPINE PRONE

Vt (mL/Kg)

RR (bpm)

Pawm (cmH2O)

W/D

Ers%

31 ± 2.94

24 ± 11

6.61 ± 0.11

6.54 ± 0.46

158 ± 5

30 ± 3.76

24 ± 11

6.56 ± 0.15

6.57 ± 0.79

155 ± 5

p = 0.80

p = 0.79

p = 0.29

p = 0.91

p = 0.14

min

0 20 40 60 80 100 120 140 160

Time

Equal VILI

p = 0.01

Valenza F et al, Crit Care Med. 2005 Feb;33(2):361-7

2008

2000

Ventilation with Low

Tidal Volume

Atelectrauma

and PEEP 2004

Neuromuscolar

Blockade 2010

STUDY CHARACTERISTICS

Patients (n)

Study period

(years)

Enrolment rate

(pts/month/unit)

Trial ended early

Gattinoni

et al.

304

1996-1999

0.28

Yes (slow

enrolment)

Guérin

et al.

802

1998-2002

0.24

No

Mancebo

et al.

142

1998-2002

0.24

Yes (slow

enrolment)

Taccone

et al.

344

2004-2008

0.26

No

2001 2004 2006 2009

ENROLLMENT

Enrollment

criteria

Average PaO2/FiO2

at enrollment

Average PEEP at

Enrollment (cmH2O)

Average enrollment

SAPS II

Gattinoni

et al.

ALI/ARDS with

PEEP≥5 cmH2O

127

10

40

Guérin

et al.

Hypoxemic acute

respiratory failure

(413 ALI/ARDS

pts)

152

8

46

Mancebo

et al.

ARDS with

four-quadrant

infiltrates on

CXR

105

7

41

Taccone

et al.

ARDS with

PEEP≥5

cmH2O

113

10

41

Time after meeting

enrollment criteria

Not

pre-specified >12-24 h <48 h <72 h

2001 2004 2006 2009

ENROLLMENT

Planned duration

of prone posit. (avg)

Actual duration

of prone posit. (avg)

Protective mechanical

ventilation

Crossover (supine to

Prone group)

Gattinoni

et al.

6h/day for

10 days

7 h for

5 days

No

12/152

(7.9%)

Guérin

et al.

≥8h/day until

weaning criteria

9 h for

4 days

No

81/378

(21.4%)

Mancebo

et al.

20h/day until

weaning criteria

17 h for

10 days

Yes

(VT≤10 ml/kg

of PBW or ABW)

5/60

(8.3%)

Taccone

et al.

20h/day until

weaning criteria

18 h for

8 days

Yes

(VT≤8 ml/kg

of PBW )

20/174

(11.5%)

2001 2004 2006 2009

OUTCOME

Last follow-up

Mortality (prone vs

supine)

P value

Gattinoni

et al.

6 months

62.2%

vs

58.3%

0.50

Guérin

et al.

90 days

43.3%

vs

42.2%

0.74

Mancebo

et al.

Hospital

discharge

50.0%

vs

60.0%

0.22

Taccone

et al.

6 months

47.6%

vs

52.9%

0.33

2001 2004 2006 2009

Abroug F. et al. Intensive Care Med. 2008 Jun;34(6):1002-11

Effect of ventilation in prone position on mortality.

Conclusions:

Prone position is not associated with a significant reduction in mortality from ALI/ARDS

despite a significant increase in PaO2/FiO2, is safe, and tends to decrease VAP. Published

studies exhibit substantial clinical heterogeneity, suggesting that an adequately sized study

optimising the duration of proning and ventilation strategy is warranted to enable definitive

conclusions to be drawn.

Effect of prone ventilation on mortality (at hospital discharge or longest duration of follow-up)

Sud et al. Intensive Care Med. 2010 Apr;36(4):585-99.

Kaplan-Meier survival curves at 6 months

of the EUPAPS population

Minerva Anestesiol. 2010 Jun;76(6):448-54

Kaplan-Meier survival curves at 6 months

of the EUPAPS population

Minerva Anestesiol. 2010 Jun;76(6):448-54

Gattinoni L. et al. Minerva

Anestesiol. 2010 Jun;76(6):448-54

Guerin C. et al. N Engl J Med.

2013 Jun 6;368(23):2159-68

Mild Moderate Severe

300 200 100

ALTERNATIVE

TREATMENTS

ECMO

ECCO2-R

Neuromusc.

Blockade

Prone Position

Paw plat/PL plat ≤ 30 cmH2O/≤ 20 cmH2O

Tidal Volume/strain 6 ml/kg IBW/≤ 1.5-2

PEEP ≈ 10 cmH2O > 15 cmH2O

ARDS