Did APRV kill the OSCILLATErStar?

John Davies MA RRT FAARC FCCPDuke Health System

Durham, North Carolina, USA

john.davies@duke.edu

HFOV – Theoretical advantages

Atelectrauma Volutrauma

HFOV

HFOV – Oscar Trial

• Young, et al. NEJM 2013;368:806.

• 398 patients in 29 centers in Great Britain

• HFOV vs. local physician practice

• No difference in mortality

• 3 centers had experience with HFOV, 6 centers “limited” experience and 20 centers no previous experience with HFOV

HFOV – Oscillate Trial

Ferguson, et al. NEJM 2013

• 548 pts, 39 centers, 5 countries

• HFOV vs. Low Vt, high PEEP strategy in ARDS

• In hospital mortality in the HFOV group was 47% vs. 35% in the control group

• Concerns:

• Used higher mean airway pressures

• 2/3 pts were on pressors

• Many centers had little or no experience with the oscillator

• 75 pts were not enrolled because investigators felt HFOV would be of benefit

HFOV – Meta analysis

Meade, et al. AJRCCM 2017;196:727.

• Meta-analysis of 4 large studies

• Looked at the different subgroups of ARDS

• Concluded that:

• “HFOV increases mortality for most patients with ARDS but may improve survival among patients with severe hypoxemia on conventional mechanical ventilation”

APRV

Airway pressure release ventilation (APRV) was first described and introduced to clinical practice over 20 years ago. It became commercially available in the mid-1990s

• It is a mode of mechanical ventilation that is based on the open lung concept

• Inverse ratio ventilation

• Phigh, Plow, Thigh, Tlow

APRV

• Long periods of inspiratory stretch (CPAP)

• More time for recruitment

• Oxygenation

• Release periods (exhalation)

• CO2 elimination

• Use autoPEEP to maintain recruitment

Long inspiratory stretch period

Rapid flow reversals

Added end -inspiratory volume

APRV – Theoretical advantages

• Most of the evidence comes from animal studies

• Cannot necessarily extrapolate these results to humans

• Kacmarek, et al. AJRCCM 2006; 173:882

APRV – Theoretical advantages

• Improved oxygenation

• Long I times

• Lung protective

• Improved comfort

• Spontaneous breathing encouraged• Fewer releases than conventional ventilation

• Outcomes

• Is it effective as a rescue therapy?

APRV – Improved oxygenation

• The main causes of hypoxemia in ARDS are shunting due to alveolar collapse and reduction in functional residual capacity

• A prolonged inspiratory time is presumed to increase alveolar recruitment because it allows time for slow lung units a non-homogenous lung fields to inflate

APRV

APRV – Cautions

• Tidal overinflation

• Driving pressure

• Using oxygenation as a surrogate endpoint

• Potential for unsafe Vt’s

• Increased comfort???

• Potential for unsafe transpulmonarypressure

• Meaningful outcomes?

APRV – Tidal overinflation

• AutoPEEP is established

mainly in lung units with long

expiratory time constants

• Ranieri, et al. JAMA 1999;

282:54

• Long expiratory time constants

result from:

– Increased compliance

– Increased airway resistance

• In ARDS the lung units in

which peep is needed are the

ones with the shortest exp time

constants

APRV – Driving pressure

Amato MB et al. N Engl J Med 2015;372:747-755.

APRV – Oxygenation as a surrogate endpoint

• Many will cite an improvement in oxygenation as a positive outcome

• However, consider the ARDSnet 6 vs 12 ml/kg IBW

NEJM 2000;342:1301

APRV – Potential for unsafe Vt’s

• Hirshberg, et al. CCM 2018;46:1946

• Randomized Feasibility Trial - 52 pts, 4 centers:

• Low Vt - APRV Protocol

• Traditional APRV

• Volume Control Ventilation Protocols

• The study was stopped early because of low enrollment and inability to consistently achieve Vt’s < 6.5 mL/kg in the low Vt – APRV arm

APRV –Potential for unsafe Vt’s

• Conclusion:

• APRV resulted in release volumes often exceeding 12 mL/kg despite a protocol designed to target low tidal volume ventilation

• Current airway pressure release ventilation protocols are unable to achieve consistent and reproducible delivery of low tidal volume ventilation goals

APRV – Increased comfort?

• Maxwell, et al. J Trauma 2010;69:501

• 163 pts APRV vs LOVT (6 ml/kg PBW)

• APRV resulted in:

• Increased sedation use

APRV – Potential for unsafe transpulmonarypressure

Transpul Press35

high 25

Spont effort:- -10

APRV – Outcomes

• Maxwell, et al. J Trauma 2010;69:501

• 63 pts APRV vs LOVT ( SIMV, 6 ml/kg PBW)

• APRV resulted in:

• Increase in vent days, ICU LOS and VAP

APRV – Outcomes

• Zhou, et al. Intensive Care Med 2017; 43:1648

• 138 pts APRV vs LTV

• APRV group had more ventilator-free days

• “In the APRV group, respiratory therapists would titrate APRV settings and dosages of analgesics and sedatives to achieve the target level of spontaneous breathing level”

APRV - Summary

Oxygenation

• Long I times may help with recruitment

• Potential for large Vts and high driving pressures

• Not an endpoint

Comfort

• Spontaneous breathing may have some benefits hemodynamically but may produce harmful increases in transpulmonary pressure

• Conflicting evidence

Outcomes

• None demonstrated as better to date

APRV – Survey

• Miller, et al. Respir Care 2017;62:1264

• Survey of the use of APRV

• 60 centers responded

• Take away message from this survey is that there is limited consensus on how to use APRV

• Some of the responses also indicated that practitioners may not appreciate the potential for VILI with APRV

APRV

• Considering the fact that APRV has been around since 1986 and the fact that there are NO meaningful outcome studies that show a benefit it would seem that there are no advantages to using this mode

Prone Ventilation - Proseva Study

• Guerin, et alI. NEJM 2013;368:2159

• Multicenter, prospective, randomized, controlled trial, 466 patients with severe ARDS:

• Prone-positioning of 16 hours vs

• Supine position

• 28 day mortality:

• Prone – 16%

• Supine – 33%

ECMO – CESAR Trial

• Peek, et al. Lancet 2009;374:1351

• UK-based multicenter trial 180 adults:

• Conventional management

• Referral to consideration for treatment by ECMO

• In the ECMO group only 68/90 (75%) pts actually required ECMO

ECMO group - 63% six month survivalConventional - 47% six month survival (p = 0.03)

ECMO - Growth

Conclusion

• APRV did not kill the OSCILLATE Star

• It was more the technological advances of ECMO, ECMO availability and the positive mortality benefit of prone ventilation

• OSCILLATE trial did teach us that, in many cases, we were using HFOV on the wrong patients