HFOV fits within the spectrum of the other high-frequency ventilation modes whose common underlying concept is the delivery of breaths at high frequencies and low tidal volumes (V_t), which are often below the anatomic dead space. The high-frequency modes are generally divided into those in which the expiratory phase is passive and those in which expiration is active. High-frequency jet ventilation and high-frequency positive pressure ventilation are examples of devices employing passive expiration.

High-frequency positive pressure ventilation was first developed in the 1960s and typically uses a flow generator that is time cycled and achieves flow rates of 175–250 l/min. The respiratory rate is usually 60–100 breaths/min and achieves V_t values of 3–4 ml/kg. Although theoretically attractive, this mode seems to offer little advantage over conventional ventilation in patients with lung injury and, as such, application is limited. In high-frequency jet ventilation, gas is delivered through a small cannula under high pressures (70–350 kPa) and, combined with entrainment of humidified gas by the Venturi effect, adequate tidal volumes are achieved. Although high-frequency jet ventilation is sometimes used in patients with bronchopleural fistulae, most centers limit their use to rescue situations. For more detailed reviews of these modes of ventilation, the reader is referred to a few of the many reviews on these topics [2,3].

This damage has been termed ventilator-induced lung injury, and can mimic the histological, radiographic, and clinical changes that occur in patients with ARDS [5]. The damage is thought to result from excess airway pressures (barotrauma), from high lung volumes (volutrauma), or from the repetitive opening and closing of collapsed lung units with successive tidal breaths (atelectrauma) [6]. Evidence for this comes from numerous studies in animals, which have shown that the ventilator can induce pathologic changes in normal lungs and have shown that strategies minimizing these effects are beneficial [6-9]. In addition, we now know that lung injury itself (ventilator induced or otherwise) can propagate the proinflammatory cytokine cascade (biotrauma) and can contribute to the development of multisystem organ failure in humans with ARDS [10,11]. It is important to note that multisystem organ failure is often the cause of death in those patients that die from ARDS [12-14].

Previous ventilator strategies have focused on normalization of arterial blood gases [15]. The tidal volumes and subsequent airway pressures needed to achieve these goals are typically safe in normal lungs; however, it is currently felt that these levels are probably injurious in patients with lung injury, where the same volumes are delivered to a much smaller lung volume, resulting in overdistension [16]. Two large randomized, controlled trials in humans with ARDS have shown that ventilatory strategies limiting overdistension using low tidal volumes can have a mortality benefit [17,18]. One of these studies also included efforts to recruit collapsed lung units and to keep these units open [18]. The benefit of 'opening' the lung either with recruitment maneuvers, with application of higher levels of positive end-expiratory pressure (PEEP), or with high P_aw, such as that achieved with HFOV, is more controversial because recruitment with any of these strategies can result in overdistension of more 'normal' lung regions. Overall, the use of these techniques is supported by a large body of animal literature for the use of PEEP [19-22] and, to a lesser degree, by clinical trials [18,23,24]. There is also some suggestion that the benefit of recruitment maneuvers themselves depends on several patient-specific factors [25].

These ventilators operate on the following principle (Fig. ​(Fig.1).1). A bias flow of fresh, heated, humidified gas is provided across the proximal endotracheal tube. The bias flow is typically set at 20–40 l/m in, and the P_aw at the proximal endotracheal tube is set at a relatively high level (25–35 cmH₂O). An oscillating piston pump akin to the woofer of a loudspeaker vibrates this pressurized, flowing gas at a frequency that is generally set between 3 and 10 Hz. A portion of this flow is thereby pumped into and out of the patient by the oscillating piston. The P_aw achieved is sensitive to the rate of bias flow but can be adjusted by varying the back pressure on the mushroom valve through which the bias flow vents into the room. The P_aw can thus be modified by either adjusting the bias flow rate or the back pressure.

The set power on the ventilator controls the distance that the piston pump moves and, hence, controls the tidal volume. The result is a visible wiggle of the patient's body, which is typically titrated to achieve acceptable CO₂ elimination. The oscillatory pressure amplitude (ΔP) is measured in the ventilator circuit and is therefore only a surrogate of the actual pressure oscillations in the airways. These pressures are generally greatly attenuated through the endotracheal tube and larger airways so the press ure swings in the alveoli are much less. The P_aw, on the other hand, is believed to be similar in the ventilator circuit and the alveoli.

The operator uses the parameters of power (which results in ΔP) and frequency (reductions in which improve CO₂ clearance) to manipulate the V_t. It seems counterintuitive that reductions in frequency would improve alveolar ventilation; however, HFOV differs from conventional ventilation in that the lung never achieves an equilibrium volume during inspiration and expiration. Lowering the frequency therefore allows more time for a larger V_t to occur. With HFOV, CO₂ elimination is proportional to the V_t and the frequency, but increases in the V_t achieved by lowering the frequency are thought to more than compensate for the reduction in frequency. It is also important to note that the actual V_t received by the patient depends on a number of factors, including the size of the endotracheal tube, the airway resistance, and the compliance of the total respiratory system. Unfortunately, there are no predictable relationships between power and ΔP with the V_t received by the patient. In addition, the V_t can change on a breath-to-breath basis, and therefore ventilator settings are used with clinical factors such as the amount of wiggle in monitoring the patient.

As with conventional ventilation, oxygenation is primarily determined by the P_aw, by the lung volume, and by the fractional inspired concentration of oxygen (FiO₂). The initial settings are typically chosen to achieve a P_aw value roughly 5 cmH₂O greater than that achieved with conventional ventilation. Failure to adequately oxygenate the patient is frequently remedied by increasing the P_aw or the FiO₂. There is no evidence guiding exactly how ventilator adjustments should be made in the hypoxemic patient on HFOV. Generally, when FiO₂ > 0.6, our approach has been to increase the P_aw. These increases are made slowly to give time for alveolar recruitment and to assess for cardiovascular impairment. In addition, these increases are frequently made in conjunction with a recruitment maneuver. P_aw values as high as 35–45 cmH₂O have been used and tolerated [30,31]. In our experience, a higher P_aw may result in hemodynamic impairment, especially if the intravascular volume is inadequate. Should significant derecruitment from oscillator disconnects or circuit changes occur, our experience suggests that recruitment maneuvers are also helpful in this situation. Many pediatric and adult trials using HFOV (discussed later), however, have not utilized such an approach. Once the patient improves and the FiO₂ can be decreased to below 0.6–0.4, the P_aw is generally weaned slowly, decreasing P_aw by 1–2 cmH₂O and assessing response.

HFOV has until recently mostly been investigated as a rescue therapy for patients with ARDS who are failing conventional mechanical ventilation, because of difficulty in achieving either adequate ventilation or oxygenation within safe ventilator parameters. Two case series with a total of 41 ARDS patients provided encouraging results suggesting that HFOV may be beneficial in these patients [30,31]. Mehta and colleagues studied 24 patients with severe ARDS (lung injury score = 3.4 ± 0.6 [41], pressure of arterial oxygen [PaO₂]/FiO₂ ratio = 98.8 ± 39.0) failing conventional ventilation (determined by ongoing hypoxemia or high plateau pressures), and showed that HFOV could achieve an improvement in the PaO₂/FiO₂ ratio within 8 hours [31]. Fort and colleagues studied 17 patients also with severe ARDS (lung injury score = 3.81 ± 0.23, PaO₂/FiO₂ ratio = 68.6 ± 21.6) deemed to be failing conventional ventilation, and found similar improvements in oxygenation [30]. Both studies suggested that mortality was improved in patients who had fewer pre-oscillator ventilator days. Although refractory hypoxemia can be problematic in managing patients with ARDS, multiple organ failure (possibly exacerbated by biotrauma) is often the cause of the patient's death [12-14]. It is therefore reasonable to assume that any ventilation strategy, if it is to be effective at achieving a mortality benefit, must be applied early in the course of illness and/or before biotrauma begins.

A prospective, multicenter, randomized study has recently been published. The Multicenter Oscillatory Ventilation for Acute Respiratory Distress Syndrome Trial investigators randomized 150 patients with ARDS to HFOV (starting frequency = 5 Hz, P_aw = 5 cmH₂O greater than that on conventional ventilation) or to conventional ventilation using pressure control, with aims of achieving a tidal volume of 6–10 cm³/kg actual body weight [42]. The patients in this study were ventilated conventionally for an average of 2–4 days prior to randomization. The primary outcome measure was survival without need for mechanical ventilation at 30 days. There was no significant difference between groups in the primary outcome measure. However, there was a nonsignificant trend towards a lower mortality at 30 days with HFOV versus conventional ventilation (37% versus 52%, P = 0.102). This trial was only powered to detect equivalency, and therefore interpreting trends in the data should be done with caution. In addition, there was a significant improv ement in the PaO₂/FiO₂ ratio (P = 0.008) with HFOV for the first 24 hours, but this effect did not persist. Similar to the previous uncontrolled studies, the use of HFOV appeared to be safe, with no increased rates of barotrauma or hemodynamic instability. It should be noted that the control arm of this study may not be considered the gold standard of ventilation in ARDS today, and volume recruitment maneuvers, which may be important [43], were not incorporated into either arm of this study or any of the previous pilot studies of HFOV in adults [30,31]. Despite this, the results are very encouraging and point to the need for further investigation.