Page 1

Introduction •

Mechanical ventilation can perpetuate lung injury

Repetitive overstretching or collapse of lung units can generate local and systemic inflammation, multiorgan failure and death

Clinical trials support the use: - Smaller tidal volumes (6 ml/kg) - Higher levels of PEEP

High-frequency oscillatory ventilation (HFOV) - Deliver small tidal volumes (1 to 2 ml/kg) - High rates (3 to 15 breaths/sec) Randomized trials suggest that HFOV improve oxygenation and survival •

These trials were limited by small sample sizes and outdated ventilation strategies for the control group •

They compared HFOV with a conventional ventilation in patients with new-onset, moderate-to-severe ARDS

Methods •

Multicenter randomized trial

We enrolled patients at the 27 centers in Canada, United States, Saudi Arabia, Chile, and India from July 2009 through August 2012

The trial protocol was approved by the research ethics board at each participating site

For HFOV, we used the Sensor Medics 3100B HighFrequency Oscillatory Ventilator

Patients Patients were eligible for inclusion: If they had onset of pulmonary symptoms within the previous 2 weeks •

Tracheal intubation

Hypoxemia (Pao2/Fio2 ≤200, Fio2 ≥0.5)

Bilateral air-space opacities on chest radiography

Patients excluded •

Hypoxemia related to left atrial hypertension

Expected 6-month mortality exceeding 50%

Suspected vasculitic pulmonary hemorrhage

Risk for intracranial hypertension

Neuromuscular disorders

< 16 years or > 85 years

Severe chronic respiratory disease

Weight was less than 35 kg

After enrollment, standardized ventilator settings was: Pressure control mode:

- Vt 6 ml/kg - Fio2: 0.60 with PEEP 10 cm H2O or higher

After 30 minutes If the Pao2/Fio2 remained at 200 or lower, patients underwent randomization

Eligible patients were randomly assigned in a 1:1 ratio to the HFOV group or to the conventional-ventilation group

HFOV Protocol

Control Ventilation Protocol •

Vt: 6 ml/kg, plateau Paw: 35 cm H2O or less, and high levels of PEEP

After an initial recruitment maneuver (same for the HFOV group)

Used pressure-control mode with PEEP: 20 cm H2O

For patients receiving pressure support with PEEP: 10 cm H2O or less and an Fio2 of 0.4 or less, there were no limits on Vt or Paw

Procedures in Both Groups â&#x20AC;˘

Patients with hypoxemia (Fio2 of 0.9 or greater), clinicians could institute prone positioning or NO

Statistical Analysis •

We summarized data using means with standard deviations, medians, interquartile ranges, proportions

Normally distributed data were compared with the use of Student’s t-test

Non normally distributed data with the use of Wilcoxon rank-sum test

Proportions with the use of Mantel–Haenszel chi-square test

Statistical Analysis â&#x20AC;˘

Primary outcome was in-hospital mortality


We used logistic regression to adjust the treatment effect for baseline variables: - Age - APACHE II - Presence or absence of sepsis - Duration of hospitalization before randomization

Results Early Termination of the Trial After the 500-patient analysis, the steering committee terminated the trial â&#x20AC;˘

At the time of termination 548 patients had undergone randomization: â&#x20AC;˘

- 275 to the HFOV group - 273 to the control-ventilation group

Cardiorespiratory Results •

On day 1, mPaw in HFOV group: 31±2.6 cm H2O, Frequency: 5.5±1.0 Hz Control group underwent ventilation with: Vt: 6.1±1.3 ml/kg, PEEP: 18±3.2, Pplt: 32±5.7 cm H20

The mean Fio2 in the control group was similar to HFOV group

Fluid balance was higher in the HFOV group

Discussion â&#x20AC;˘

Early application of HFOV in patients with moderate to severe ARDS was associated with higher mortality than CV


HFOV was associated with higher mPaw, greater use of sedatives, neuromuscular blockers, and vasoactive drugs

Reasons to end study

Increased mortality with HFOV in three consecutive analyses

Increased need for vasoactive drugs in the HFOV group suggested a mechanism of harm

Put patients at risk with little likelihood of benefit

Plausible mechanisms that may contribute to increased mortality with HFOV •

Higher mPaw may result in hemodynamic compromise

Decreasing venous return or directly affecting right ventricular function

Increased use of vasodilating sedative agents

Possibility of increased barotrauma

It is possible that an HFOV protocol that uses lower mean airway pressures, a different ratio of inspiratory-toexpiratory time, or a lower oscillatory frequency might have led to different results


In adults with moderate-to-severe ARDS, early application of HFOV, as compared with a ventilation strategy of low tidal volume and high positive endexpiratory pressure, does not reduce, and may increase, in-hospital mortality


High-Frequency Oscillation in Early ARDS  

Previous trials suggesting that high-frequency oscillatory ventilation (HFOV) reduced mortality among adults with the acute respiratory dist...

Read more
Read more
Similar to
Popular now
Just for you