Optimal Ventilator Strategies in Acute Respiratory Distress Syndrome

Michael C. Sklar, MD; Bhakti K. Patel, MD; Jeremy R. Beitler, MD, MPH; Thomas Piraino, RRT; Ewan C. Goligher, MD, PhD


Semin Respir Crit Care Med. 2019;40(1):81-93. 

In This Article

High Frequency Oscillatory Ventilation

HFOV is a unique mode of mechanical ventilation that utilizes nonconventional gas exchange mechanisms to deliver ventilation at very low tidal volumes and high frequencies. The rationale and clinical evidence are briefly reviewed here; interested readers are guided to a recently published comprehensive review of this topic.[115]

Rationale for use in ARDS

As described earlier, VILI is thought to result from excess tidal volume and pressure applied to the lung and the recurrent recruitment and collapse of lung units (atelectrauma).[116] HFOV is theoretically ideal for avoiding VILI because it delivers small (sub-dead space) VT while preventing atelectasis with a consistently elevated mean airway pressure (mPaw).[117]

Working Principles and Physiology

The oscillator circuit is relatively simple, with heated and humidified bias flow gas traversing a rapidly oscillating membrane. The set oscillatory frequency typically ranges from 3 to 15 Hz. This rapid oscillatory motion generates VT lower than anatomic dead space, generally in the range of 1 to 3 mL/kg PBW. During HFOV, oxygenation and ventilation are independently controlled, with the former determined by the fraction of inspired oxygen and mPaw, while the latter is influenced by the frequency, amplitude of oscillations, and inspiratory time.[118]

During HFOV, ventilation (CO2 clearance) is achieved despite the delivery of VT below physiological dead space through several theorized mechanisms.[119–124] Convective bulk flow is a major mechanism of gas exchange. Typically, bulk flow is most pronounced in the proximal gas exchange units.[121] Here, convection is possible due to the asymmetric velocity profiles of inspired and expired gasses creating opposing convection currents—a phenomenon where gas exchange is even more pronounced at airway bifurcations.[125] Other mechanisms of gas exchange during HFOV include pendelluft[126] and cardiac oscillations.[127] The movement of gas between lung units with differing time constants for inflation and deflation (pendelluft) promotes gas exchange[128] and cardiac contractions cause a percussive movement of gas molecules allowing gas exchange to occur.[129]

Current Evidence Base

Several RCTs have compared HFOV to CMV.[74,113,114,130–132] Early trials in ARDS patients were underpowered to detect clinically relevant differences in mortality and demonstrated nonsignificant effects in opposing directions.[74,130,131] When employed intermittently as a strategy to mimic a recruitment maneuver, HFOV was associated with significant improvements in oxygenation, lung compliance, and mortality (risk ratio [RR]: 0.59; 95% confidence interval [CI]: 0.41–0.85).[132]

Meta-analysis of these early trials found that the risks of complications such as barotrauma and hemodynamic instability were not different between HFOV and CMV, and suggested that mortality was significantly lower with HFOV.[133] One must cautiously interpret these findings given that many of these trials were published before the wide adoption of plateau pressure and tidal-volume-limited CMV.

The large multicenter RCTs OSCAR[114] and OSCILLATE[113] were designed to definitively elucidate the role of HFOV in early ARDS. In the OSCILLATE trial, HFOV was applied using recruitment maneuvers and relatively high mPaw and titrated according to the severity of hypoxemia. The CMV arm employed a low VT and a high PEEP strategy.[67] OSCILLATE was stopped early after enrolling just under half of a planned 1,200 patients because mortality was significantly higher in the HFOV group compared with CMV (47 vs. 35%; RR: 1.33; 95% CI: 1.09–1.64). Vasopressor use and net fluid balance were higher in the HFOV arm, suggesting that HFOV may have significantly impaired hemodynamics, possibly contributing to the worsened outcome.

The OSCAR trial included almost 800 patients with moderate–severe ARDS, with HFOV titrated similarly to OSCILLATE. In contrast, however, mP aw was generally lower in OSCAR and employed a lower PEEP strategy in the CMV arm. Mortality was no different between the trial arms (41.7% in HFOV vs. 41.1% in CMV; RR: 1.02; 95% CI: 0.86–1.20) and no significant difference in vasopressor requirements. A detailed comparison of these two trials is depicted in Table 2.

An individual patient meta-analysis was then performed on 1,552 patients across four trials of HFOV versus CMV,[134] demonstrating that HFOV was associated with worse outcomes in less severe ARDS, while possibly exerting a mortality benefit in very severe hypoxemia (P/F ratio ≤ 65 mm Hg). These findings suggest HFOV could have a limited role in very severe ARDS, reserved as a rescue strategy as reflected in current guidelines for ARDS management.[135]

Risks of HFOV

Despite low VT as delivered with HFOV, experimental studies suggest that high respiratory rates can cause cellular injury by influencing the elastic and frictional properties of pulmonary epithelium, leading to increased local stress, edema formation, and fracture of liquid bridges in airspaces.[136–138] The use of high mPaw (and therefore high PEEP) during HFOV is thought to prevent atelectasis; however, it is possible that such elevated pressures may necessarily result in volutrauma.[139] Finally, there is emerging evidence that HFOV can place the lung above its natural resonance frequency where ventilation heterogeneity can significantly increase, potentially worsening ventilation–perfusion mismatch, exacerbating hypoxemia[140] and amplifying (to injurious levels) delivered VT.[141]

HFOV must be carefully applied to avoid hemodynamic impairment. Through elevated mPaw, HFOV can have a profound impact on the right ventricle (RV) by increasing afterload and reducing preload.[142,143] Direct measurement of intracardiac pressures in animal studies[144] and echocardiography studies in humans (demonstrating progressive RV dysfunction with increasing mPaw) corroborate these findings.[143] RV dysfunction, suggested by the significant increase in vasopressor use and fluid balance with HFOV in the OSCILLATE trial, may explain the increased mortality rate with HFOV observed in that study.[113]

Despite consistently improving oxygenation, HFOV is associated with worse outcomes in unselected ARDS patients and currently recommended as rescue therapy only. Cardiopulmonary effects likely limit the effectiveness of this technique.