Critical Care, Airway, Research

Critical Care Alert: Comparing Early APRV and LTV in ARDS Patients in ICU

ARTICLE
Zhou Y, Jin X, Lv Y, et al. Early application of airway pressure release ventilation may reduce the duration of mechanical ventilation in acute respiratory distress syndrome. Intensive Care Med. 2017;43(11):1648-1659.

OBJECTIVE
To evaluate whether early use of airway pressure release ventilation (APRV) would improve oxygenation, improve lung compliance and shorten the time of mechanical ventilation compared to low volume tidal ventilation (LTV).

BACKGROUND
Mechanical ventilation during ARDS can lead to pulmonary injury caused by regional alveolar stretch along with repetitive alveolar collapse which causes atelectrauma. Balancing recruitment and over-distention for each individual patient remains a concern as ARDS mortality is high even with LTV.

APRV ventilation delivers a continuous positive airway pressure with a brief pause. It allows for spontaneous ventilation throughout the high level and only release of partial lung volume during the ventilatory pause. Recent experiments and theoretical physiological models suggesting that APRV may have benefit compared to LTV in ARDS. However, until this time there has been no RCT to show any benefit.

DESIGN
Study Design: Randomized, non-blinded, single center study
• Sites: West China Hospital of Sichuan University MICU
• Time: May 2015-October 2016

Sponsor: None

Intervention: APRV versus LTV
APRV initial settings: high airway pressure (Phigh) set at last plateau airway pressure (Pplat), not to exceed 30cm H20, low airway pressure (Plow) set at 5cm H2O; the release phase (Tlow) setting adjusted to terminate the peak expiratory flow rate to to ≥ 50%; release frequency of 10-14 cycles/min.

LTV settings: target tidal volume 6ml/kg of predicted body weight; Pplat not exceeding 30cm H2O; PEEP guided by the PEEP-FIO2 table from the ARDSnet protocol.

Randomization: Patients were assigned by using a computer-generated random block design which were then placed in opaque sealed envelopes. These envelopes were randomly selected for each patient.

Inclusion Criteria:
- Fulfilled the Berlin definition of ARDS
- Had a Pa02:FI02 ≤250 during invasive mechanical ventilation
- Received endotracheal intubation and ventilation for <48h

Exclusion Criteria:
- Pregnancy
- Anticipated course of <48h of mechanical ventilation
- Intracranial hypertension (suspected of confirmed)
- Neuromuscular disorders known to prolong intubation
- Severe COPD
- Preexisting conditions with an expected 6 months mortality exceeding 50%
- Presence of documented barotrauma
- On ECMO at enrollment
- Refractory shock
- Lack of commitment to life support
- <18 years or >85 years of age

Primary Outcome: Number of ventilator-free days at day 28

Secondary Outcome:
- Oxygenation and respiratory mechanics such as plateau pressure, mean airway pressure, and respiratory system oxygenation at baseline and on days 1,2,3, and 7.
- Length of stay in the ICU and in the hospital
- ICU and hospital mortality
- Occurrence of adverse events

KEY RESULTS
Primary Outcome: The APRV group was associated with an increase in ventilator-free days at 28 days compared to the LTV group. The APRV group had a median of 19 ventilator-free days compared to a median of 2 for the LTV group.

Secondary Outcomes:
1. The APRV group had a lower median amount of days ventilated compared to the LTV group at 8 days versus 15 days.
2. Patients spent fewer days in the ICU.
3. There were fewer tracheostomies in the APRV group compared to the LTV group.
4. The ICU and hospital mortality, along with the length of stay in the hospital and incidence of pneumothorax, were similar between the two groups.
5. More patients in the LTV group received neuromuscular blockers, recruitment maneuvers, and prone ventilation than in the APRV group.
6. On days 1,2,3, and 7 the APRV group had a higher mean airway pressure with respiratory system compliance and Pa02:FI02 significantly improved compared to the LTV group.
7. The APRV group required less sedation and pain control than the LTV group.
8. There was a higher rate of successful extubations in the APRV group than the LTV group at 66.2% vs 38.8%.

Strengths
- Largest RCT of APRV to date
- Randomized controlled trial
- Study included follow-up for up to 28 days

Limitations
- Single center study
- Small sample size
- Higher comorbidities in the LTV group
- Open Label (which is unavoidable given the obvious differences in ventilation to providers)
- There are many ways to perform APRV. The optimal settings for APRV have not been conclusively proven yet.

CONCLUSIONS
This is the largest RCT to be performed on evaluation of APRV utilization for ARDS. Early application APRV cohort was associated with better oxygenation, less sedation, fewer days on mechanical ventilation, and shorter ICU stays. It opens up the possibility of APRV being a front-line ventilator modality for ARDS. However, we still need a robust, reproducible, multi-center RCTs to further confirm this conclusion.

ED Take-Away
APRV might be another ventilator strategy option for ARDS patients, and possibly a superior strategy compared to the LTV. However, at this time it is probably not ready for prime time in the ED.