1. Con Position: APRV should be used in ARDS
Timothy Scialla, MD
Assistant Professor
Division of Pulmonary and Critical Care
Duke University
09/07/2017

2. COI disclosure slide
I am a co-investigator for on-site clinical research trials sponsored by:
GSK
AstraZeneca
Sanofi
Genentech
NHLBI

3. ARDS epidemiology 190,000 cases / year in the USA Mortality 40%
50% Moderate (PaO2/FiO )
25% Severe (PaO2/FiO2 < 100)
Mortality 40%
Early (underlying cause)
Late (sepsis / nosocomial pneumonia /MODS)
Ventilatory failure (ie. Hypoxemia) uncommon
High Morbidity (cognitive, psychological, physical)

4. The ARDS Industrial Complex
Nearly 2 decades of well-funded research
Multiple large randomized trials
Pharmacotherapy
Ventilator strategies
Hemodynamic monitoring/management
Lessons learned
Heterogeneous disease process
Different ARDS phenotypes
Few successes
Extensive Animal Studies

5. Studies with mortality benefit
ARMA trial
Neuromuscular blockade in ARDS
Prone positioning in ARDS
All three:
Avoid ventilator-induced lung injury

6. The ventilator is an agent of harm
Risk of overdistension injury 12 12
Lung volume 6 6 6 6
Risk of atelectasis injury
Time

7. Lung Protective Strategies
“Low VT” strategy
Minimize stress and strain
Limit VT and plateau pressure (<30cm H20)
“Open Lung” strategy:
recruiting nonaerated lung regions
Keep open with adequate levels of PEEP.
Minimize hyperinflation and atelectrauma with alveolar recruitment.

8. ARDS Network Low vs. Traditional VT
P=0.007
6 ml/kg
12 ml/kg
Absolute risk reduction = 9% (31% vs 40% mort)
Relative risk reduction = 22%
Lower oxygenation
Worse ventilation
ARDS Network NEJM 2000

9. Lung Protective Ventilation and Knowledge Translation Needham et al
Lung Protective Ventilation and Knowledge Translation Needham et al. BMJ. 2012
180/485 patients (37%) never had LPV
417/485 (86%) adherent 50% or less
Prospective cohort of patients with ALI
13 ICUs at 4 hospitals in Baltimore
485 patients
Primary outcome was 2 year survival
64% of patients died at 2 years. 30 day mortality was 44%. 90 day mortality was 52%. 1 year was 62%.
100% adherence to LPV associated with 8% absolute risk reduction. 50% adherence with 4%

10. NMB in early ARDS. Papazian et. al. NEJM. 2010
340 patients randomized
Sedative: Ramsey Level = 6 (very very sedated)
Cisatracurium group:
15mg bolus followed by continuous infusion for 48hrs
Open label 20mg IV bolus of cisatracurium allowed in either group if Pplat>32.
Adjusted Cox regression model: HR 0.68 (95% CI, 0.48 to 0.98; p=.04)
Adjustments made for PaO2/FiO2; Pplat, SAPS II

11. Open Lung Strategy: Metaanalysis: High vs Low PEEP.
Higher PEEP (n=1136) Low PEEP (n=1163)
Higher PEEP: better PaO2 transiently (same at day 7)
Higher PEEP:  Pplat; PEEP
Briel et al. JAMA

12. Why these results? Responders Nonresponders
Applied lower (12hours) and higher PEEP (12hours) strategy from ALVEOLI trial to 19 patients
Found nine recruiters Alveolar recruitment, decreased lung elastance, better oxygenation
Nonrecruiters: worse lung elastance.
Grasso et al. High vs Low PEEP. AJRCCM

13. HFO: The perfect scenario
Risk of overdistension injury
Lung volume
Rapid oscillations of a diaphragm
Results in active insp and expiration
Little pressure to distal airways (Vt)
Decouple oxygenation & ventilation
O2 depends on mPaw
CO2 depends on Hz and P
Mechanism of Gas transport
Bulk flow
Cardiac oscillation
Molecular diffusion
Risk of atelectasis injury
Time 13

14. Risk of overdistension injury Risk of atelectasis injury
Avoid this
Risk of overdistension injury
Lung volume
Risk of atelectasis injury
Time 14

15. HFOV: Our curiosity with this mode has come to an end
OSCILLATE trial
548 patients
HFO group
Increased sedation/paralytics
More pressors/high mean airway pressures
Less refractory hypoxemia
Increased mortality?
N=146
P=.08
Ferguson et al. NEJM. 2013

16. Prone Positioning in ARDS: Mount Everest in Kansas
Recruited more severely hypoxemic patients
Prone group with higher PaO2:FiO2 ratio at days 3 and 5
Prone group had lower Pplatrs lower at days 3 and 5
NNT to prevent one death was 6
466 patients
16 vs 32% 28-day mortality. HR 0.39
12-24 hours stabilization period before final inclusion
Stop proning if after 4hrs in supine position ratio> 150 with PEEP 10 and FiO2 60%
28 days of proning possible
Guerin et al. NEJM. 2013

17. Pleural pressure in dependent and non-dependent regions
More homogenous ventilation. Less collapse in dependent zones.
Fessler and Talmor. Respiratory Care. 2010

18. APRV: Evidence & Limitations
Limited, small, mostly trauma patients
One RCT: APRV vs LOVT
Intubated trauma patients at risk for ARDS
LOVT = SIMV (VT = 6ml/kg PS=10 cm H20)
Limitations
At Phigh: spont breaths can add to strech
Plow to Phigh: shearing/atelectrauma
N=31
N=32
LOVT= low tidal volume ventilation
Maxwell et al. J Trauma. 2010

19. ↑ Mean Airway Pressure ≠ ↑ PaO2/FiO2

20. Conclusions 2 decades of extensive prospective studies
APRV = 1 very small RCT (negative study)
Longer time on ventilator
No improvements in oxygenation
Trend towards more sedation!
Low tidal volume ventilation is GOLD STANDARD
Severe cases
Neuromuscular blockage
Prone ventilation
Neither requires tertiary care center/ high technology

21. Sage Advice from the master