High-Frequency Oscillation in Early ARDS

Introduction •

Mechanical ventilation can perpetuate lung injury

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

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These trials were limited by small sample sizes and outdated ventilation strategies for the control group •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

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

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

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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

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Hypoxemia (Pao2/Fio2 ≤200, Fio2 ≥0.5)

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Bilateral air-space opacities on chest radiography

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Patients excluded •

Hypoxemia related to left atrial hypertension

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Expected 6-month mortality exceeding 50%

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Suspected vasculitic pulmonary hemorrhage

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Risk for intracranial hypertension

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Neuromuscular disorders

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< 16 years or > 85 years

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Severe chronic respiratory disease

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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

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

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Used pressure-control mode with PEEP: 20 cm H2O

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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

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

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

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

Statistical Analysis â&#x20AC;˘

Primary outcome was in-hospital mortality

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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 •

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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

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

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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

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

Reasons to end study

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Increased mortality with HFOV in three consecutive analyses

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

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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

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Decreasing venous return or directly affecting right ventricular function

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Increased use of vasodilating sedative agents

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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

Conclusions

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

Thanks