High-Frequency Ventilation

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52 High-Frequency Ventilation

Mah Chou Liang, Niall D. Ferguson, Thomas E. Stewart, Sangeeta Mehta

High-frequency ventilation is a collection of ventilator modes in which small tidal volumes are delivered at supra-physiologic frequencies. Various types of high-frequency ventilation have been developed over the last 3 decades, including high-frequency positive-pressure ventilation, high-frequency percussive ventilation, high-frequency jet ventilation, and the most commonly employed mode, high-frequency oscillatory ventilation. Initially, high-frequency ventilation was used mainly in neonates with respiratory distress syndrome (RDS); however, there has been increased interest in its use in adults with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), given its potential for lung protection.

Over the last 30 years, our understanding of the potential harm of mechanical ventilation has evolved, and it has been clearly demonstrated that lung injury may occur through injurious mechanical forces generated during mechanical ventilation. Potential causes of lung injury include gross air leaks (barotrauma), diffuse alveolar injury due to overdistension (volutrauma), injury due to repeated cycles of recruitment and derecruitment (atelectrauma), and injury due to the release of mediators from the lung (biotrauma).^1,² Importantly, volutrauma and atelectrauma lead to biotrauma, which affects not only the lung but may also contribute to multiple organ dysfunction, the major cause of death in patients with ARDS. Lung-protective mechanical ventilation strategies aim to reduce these injurious forces and subsequent lung damage while providing adequate ventilation and oxygenation. The mechanics of high-frequency ventilation, particularly high-frequency oscillatory ventilation (HFOV), make it particularly well suited to protect the lung, and there is growing clinical experience with the use of high-frequency ventilation as an alternative to conventional mechanical ventilation or as salvage therapy in patients failing conventional ventilation strategies.

Description and Classification

High-Frequency Positive-Pressure Ventilation

High-frequency positive-pressure ventilation (HFPPV) delivers small volumes (approximately 3-4 mL/kg) of conditioned gas at high frequencies (60-100 breaths/minute) using a conventional mechanical ventilator. Valves in the inspiratory and expiratory limbs of the ventilator circuit allow control of the generally high inspiratory flow rate and positive end-expiratory pressure (PEEP), respectively. Expiration is passive and relies on the elastic recoil of the patient’s respiratory system. The clinician controls the respiratory rate, inspiratory flow rate, driving pressure, and PEEP. Because high respiratory rates leave little time for passive expiration, there is a risk of gas trapping, with hyperinflation and resultant overdistention injury.

HFPPV was first described in 1969 as an experimental technique ³ and has subsequently found only limited clinical use in specialized upper-airway surgical procedures and bronchoscopy.⁴ Published clinical experience with HFPPV is largely limited to neonatal populations. One meta-analysis in newborn infants found that synchronized mechanical ventilation delivered as HFPPV was associated with reduced barotrauma and shorter hospital stay compared with conventional mechanical ventilation (CMV),⁵ but the effect on mortality and chronic oxygen dependency was unclear. In adult patients, HFPPV has been used only in specialized applications in the field of anaesthesia.⁶^–⁸

High-Frequency Percussive Ventilation

High-frequency percussive ventilation (HFPV) is a hybrid mode that combines the principles of high frequency and CMV using a proprietary mechanical ventilator.⁹ A conventional ventilation circuit is fitted with a gas-driven piston at the end of the endotracheal tube. The reciprocating piston generates pressure oscillations at 3 to 15 Hz, with short expiratory times that are superimposed on the conventional inspiratory-expiratory pressure waves. The high-frequency beats are delivered in bursts to generate auto-PEEP through breath stacking, and then are interrupted to allow alveolar pressure to return to baseline. It has been hypothesized that the auto-PEEP generated improves alveolar recruitment without exposing the alveoli to the high peak airway pressures that would be generated with comparable CMV. Although the high-frequency pressure oscillations are driven actively in both directions, the bulk of exhalation is passive, from the underlying CMV breaths. The high-frequency percussion also provides some internal mucokinesis, potentially improving pulmonary toilet and reducing endotracheal suctioning requirements.¹⁰ Indeed, it may be because of this property that HFPV has been most commonly used in adult patients with inhalational injury, burns, and trauma.

High-Frequency Jet Ventilation

High-frequency jet ventilation (HFJV) employs a small-aperture nozzle inserted into the endotracheal tube in order to direct a high-pressure stream of gas into the lung (Figure 52-1). During inspiration, a high-pressure jet streams into the proximal airways, entraining air from the circuit, and tidal volume is therefore largely dependent on the Venturi and Coanda effects. The parameters controlled by the clinician are frequency, inspiratory time, jet drive pressure, and PEEP applied through the ventilator circuit. Tidal volumes are determined by the jet driving pressure and inspiratory time (i.e., larger tidal volumes can be delivered by increasing jet drive pressure and inspiratory time). Tidal volumes will also be augmented by using a larger jet catheter and a larger endotracheal tube, which increase the amount of jet flow and gas entrainment, respectively. Because expiration is passive, gas trapping may occur at higher frequencies with progressively shorter expiratory times.

Figure 52-1 Theoretic comparison of the alveolar pressure swings seen with high-frequency ventilation versus conventional mechanical ventilation.

A complication specific to HFJV is traumatic upper airway injury. The high-velocity inspiratory jet may cause direct trauma to the proximal airways, and necrotizing tracheobronchitis is a recognized complication of HFJV in both infants and adults.^11,¹² Gas conditioning during HFJV, particularly humidification and warming, is also problematic. Although the gas entrained from the proximal circuit is warmed and humidified, the gas injected from the jet nozzle expands and cools, compromising the overall conditioning of the inspired gas. It has also been hypothesized that high gas flow rates and rapid increases in lung volume could cause lung injury through the generation of shear forces at the interface of adjacent compliant and atelectatic lung units.¹³

The clinical utility of HFJV is specific to certain clinical settings such as pulmonary air leak syndromes, when the ability to achieve adequate gas exchange with lower peak airway pressures may be advantageous.¹⁴ In addition, the decreased reliance on bulk flow with HFJV may improve gas distribution and gas exchange in the presence of large air leaks, although this theoretical advantage has not been borne out in clinical studies.¹⁵

The published clinical experience with HFJV in acute respiratory failure remains small, and to date, the greatest clinical experience is in the neonatal and pediatric populations and in anesthesia for airway stability during respiratory tract surgery. There is limited research in its utility in adult respiratory failure, although many intensive care units (ICUs) have sizable anecdotal experience. Comparative clinical trials have shown that high-frequency jet ventilation is safe and offers improved oxygenation and ventilation compared with CMV, while improving respiratory parameters and decreasing required peak pressures.¹⁶^–¹⁸ None of these trials, however, demonstrated a significant survival advantage.

High-Frequency Oscillatory Ventilation

During HFOV, a piston pump oscillates a diaphragm at frequencies between 3 and 15 Hz (180-900 breaths/min) to create pressure waves in the ventilator circuit (see Figure 52-1). Because the diaphragm is actively driven in both directions, the ventilator creates both inspiratory and expiratory pressure waves, meaning that expiration is also active. The use of active expiration distinguishes HFOV from other forms of high-frequency ventilation, in which expiration is passive and dependent on the elastic recoil of the respiratory system. Active expiration may be advantageous in controlling CO₂ and preventing hyperinflation. Indeed, HFOV has been shown to be associated with less gas trapping than other forms of high-frequency ventilation.¹⁹ The mean airway pressure is maintained by a resistance valve in the circuit, together with the inspiratory bias flow. Changes in alveolar pressure are kept low by small excursions of the piston. Humidification is achieved by passing the bias flow of gas through a humidifier.²⁰

It is this ability to deliver very small tidal volumes at a relatively constant mean airway pressure that makes HFOV theoretically ideal for minimizing ventilator-induced lung injury (VILI) in addition to being an effective mode for oxygenation in severe ARDS. In view of these unique features of HFOV, recent research has focused on this particular mode of high-frequency ventilation in the management of adult patients with ARDS.

Mechanisms of Gas Transport with High-Frequency Oscillatory Ventilation

During CMV, gas exchange is largely related to bulk flow of gas to the alveoli. However, since the tidal volumes generated during HFOV may be smaller than the anatomic dead space, ventilation relies on alternative gas exchange mechanisms related largely to enhanced gas mixing within the lung. These gas exchange mechanisms are summarized in Table 52-1 ²¹ and Figure 52-2. Experimental models suggest that in contrast to CMV, CO₂ elimination is a product of the frequency and the square of the tidal volume (VCO₂ α = f × VT²)²² such that adequate CO₂ elimination may become problematic as tidal volumes decrease, unless accompanied by proportionately larger increases in frequency. Regardless, clinical experience has demonstrated that adequate gas exchange can be achieved in adults with HFOV using frequencies in the 8- to 10-Hz range, delivering tidal volumes that are less than anatomic dead space.²³

TABLE 52-1 Mechanisms of Gas Exchange During High-Frequency Oscillatory Ventilation

Site	Proposed Mechanism
Proximal airway	Bulk flow—remains an important mechanism of gas transport in proximal airways
Mid-airway	Pendelluft—phenomenon of regional gas movement that occurs as a result of heterogeneity in alveolar filling and emptying rates. Adjacent lung units with different time constants may fill at different rates during inspiration. Following inspiration, there is redistribution of inspired gas from full, fast-filling units to slower-filling units, augmenting gas exchange.⁹ Taylor dispersion—enhanced diffusion augmented by radial transport mechanisms Asymmetrical velocity profiles—results in a net convective transport of material, especially at airway bifurcations. Fresh gas streams toward alveoli along inner airway walls, while “alveolar” gas streams cranially along outer airway wall.
Distal airway	Cardiogenic mixing—rhythmic contraction of heart promotes peripheral gas mixing by generating flow within neighboring parenchymal regions Collateral ventilation—gas exchange between noncommunicating neighboring alveoli via collateral channels

From Chang HK. Mechanisms of gas transport during ventilation by high-frequency oscillation. J Appl Physiol. 1984;56(3):553-563.

Figure 52-2 Mechanism of gas exchange during high-frequency oscillatory ventilation (HFOV).

(From Slutsky AS, Drazen JM. Ventilation with small tidal volumes. N Engl J Med. 2002;347:630-631.)

Rationale for High-Frequency Oscillatory Ventilation

In the last few decades, there has been an enormous increase in understanding of the effects of mechanical ventilation on the lung and elucidation of VILI and its pathophysiology, namely volutrauma, atelectrauma, and biotrauma. Furthermore, the clinical relevance of VILI was solidified by a landmark study published by the ARDS Network in 2000 that demonstrated a 9% absolute mortality reduction in patients with ARDS ventilated with tidal volumes of 6 mL/kg ideal body weight compared with 12 mL/kg.²⁴

HFOV would appear to be the ideal lung-protective ventilation strategy in patients with ALI/ARDS because of two principal properties: (1) prevention of VILI by delivery of small tidal volumes with limitation of alveolar overdistention and (2) promotion of alveolar recruitment through application of a higher mean airway pressure than can be safely applied with CMV, promoting more alveolar recruitment and avoiding cyclic opening and closing of alveolar units throughout the respiratory cycle. Indeed, there is a wealth of preclinical animal data demonstrating that compared with both injurious and lung-protective conventional ventilation, HFOV is advantageous in terms of gas exchange, markers of inflammation, and lung pathology scores.²⁵

Does High-Frequency Oscillatory Ventilation Truly Deliver Small Tidal Volumes?

Although tidal volumes are not measured directly on the oscillator that is commercially available in the United States, several investigators have measured delivered tidal volumes. In a sheep saline-lavage model of ALI, Sedeek et al. measured delivered tidal volumes with a pneumotachograph ²⁶ and found that HFOV applied with a frequency of 4 Hz and pressure amplitude of 60 cm H₂O resulted in tidal volumes of 4 mL/kg—not large, but not as small as had been anticipated. More recently, however, Hager and colleagues measured tidal volumes in adults with ARDS receiving HFO using a hot-wire anemometer, which may provide more accurate measurements. These investigators found that usual tidal volumes delivered during adult HFOV were indeed small, in the 1 to 2 mL/kg range, and that frequency²⁷ rather than pressure amplitude was the dominant determinant of tidal volume in adults with ARDS. These authors emphasized that while low tidal volumes can be delivered during HFO, at low frequencies, tidal volumes may be larger than anticipated. This suggests that a strategy that achieves acceptable CO₂ clearance while employing the highest tolerated frequency is likely to be most lung protective. To practically achieve these goals, we generally use a relatively high power set to achieve a pressure amplitude (delta P [ΔP]) of 90 cm H₂O, and then adjust frequency as high as tolerated to achieve an adequate pH (>7.25), at times using a partial leak around the endotracheal tube cuff to facilitate CO₂ clearance and higher frequency tolerance.

Does High-Frequency Oscillatory Ventilation Promote Alveolar Recruitment?

Alveolar recruitment refers to the dynamic process of reopening unstable collapsed alveoli. Easley et al. performed a study in healthy dogs, using computer tomographic imaging to look at the distribution of lung volume.²⁸ They matched the mean airway pressure with conventional CPAP and noted small decreases in total and regional lung volume with HFOV, especially at lower mean airway pressure and accompanying lower frequency. These authors concluded that there was low risk of occult regional overdistention during HFOV in healthy lungs despite the very high respiratory rates.

In a way, HFOV is like any other mode of mechanical ventilation: success relies not only on selecting the mode that makes a difference but on how that mode is employed. A key factor in the use of HFOV that has emerged from both animal and neonatal literature is the need for HFOV to be used as part of a lung recruitment strategy. To achieve this goal, clinicians generally either (1) select a starting mean airway pressure (mPaw) approximately 5 cm H₂O above that used on conventional ventilation and titrate mPaw up to achieve adequate oxygenation; or (2) in an approach we favor, begin oscillation with 1 or more sustained inflation recruitment maneuvers followed by downward titration of mPaw from a relatively high mPaw (30-35 cm H₂O), using oxygenation as a surrogate for lung recruitment.²⁹

Does High-Frequency Oscillatory Ventilation Improve Outcome in Adult Patients with acute respiratory distress syndrome?

HFOV in principle fulfils the criteria for lung-protective ventilation and can achieve effective ventilation despite very small tidal volumes. However, it is not yet clear whether this ventilatory mode impacts the outcome of adult patients with ARDS. The clinical trials and systematic reviews evaluating HFOV in adults are summarized in Tables 52-2 and 52-3, respectively. Based on the current evidence presented in these two tables, we can conclude the following regarding the use of HFOV in adults with ARDS:

1 Most studies utilized HFOV as rescue therapy in patients with severe ARDS.

2 The use of HFOV was associated with improvements in oxygenation.

3 The use of HFOV was well tolerated and not associated with harm.

4 All of the previous randomized controlled trials have been underpowered to detect a mortality benefit with HFOV; however, a recent meta-analysis did show significant reduction in mortality (risk ratio [RR] 0.77 with 95% confidence interval [CI] of 0.46-0.99), but this conclusion is still based on a relatively small number of patients.

5 Many of the studies on HFOV are confounded by a comparison with CMV that would not be considered optimally lung protective with current practice guidelines.

TABLE 52-2 Clinical Trials Evaluating High-Frequency Oscillatory Ventilation in Adults

TABLE 52-3 Systematic Reviews Evaluating High-Frequency Oscillatory Ventilation in Adults with Acute Respiratory Distress Syndrome

Publication	Number of Studies/Patients	Study Summary/Major Findings
Bollen et al., 2005⁵⁷ Systematic review	ARDS 2 RCT 7 Observational studies	Systematic review of determinants of mortality in HFOV in ARDS Prolonged CMV prior to HFOV did not relate to mortality OI associated with mortality independently of other disease markers and could be important for selecting ARDS pt that could benefit from HFOV
Wunsch et al., 2004⁵⁸ Cochrane Systematic Review [Abstract]	ARDS 2 RCTs Children, N=58 Adult, N=148	Systematic review comparing HFOV and CMV Inadequate evidence to conclude whether HFOV reduces morbidity or mortality in pts with ALI or ARDS
Sud et al., 2010⁴⁴ Systematic review and meta-analysis	ARDS 8 RCTs N=419	HFOV may improve survival; unlikely to cause harm Reduced mortality (RR 0.77, 95% CI 0.61-0.98) and treatment failure (refractory hypoxemia, hypercapnia, hypotension, barotrauma, RR 0.67, 95% CI 0.46-0.99)

ARDS, Acute respiratory distress syndrome; CI, confidence interval; CMV, conventional mechanical ventilation; HFOV, high-frequency oscillatory ventilation; OI, oxygenation index; Pt(s), patient(s); RCT, randomized controlled trial; RR, risk ratio.

Thus, despite the increasing number of studies on HFOV, no large prospective randomized controlled trials have yet been completed to evaluate the efficacy of HFOV against the best conventional lung protective ventilation, and the question about any survival benefit due to the use of HFOV remains unanswered.

Current High-Frequency Oscillatory Ventilation Practices in Patients with Acute Respiratory Distress Syndrome

High-frequency ventilation has been in use for at least 3 decades, and the clinical application has evolved over the years. For a detailed discussion of specific recommendations regarding HFOV settings and monitoring, readers are referred to a recent roundtable report on HFOV use.³⁰

Frequency

In adults, HFOV frequency is most commonly 5 to 7 Hz, while higher frequencies are used in neonates (8-15 Hz).³¹ If there is a need for greater CO₂ clearance, the most common approach is to decrease the frequency to less than 5 Hz after ΔP has been optimized. This approach, however, results in delivery of larger tidal volumes and may not optimize the potential of HFOV to deliver small tidal volumes. A recent study in adults²³ demonstrated that frequencies greater than 6 Hz (with 1 patient reaching 15 Hz) can maintain adequate gas exchange. In that study, an endotracheal cuff leak was applied in 30% of patients to aid CO₂ clearance. The rationale for exploring higher frequencies during HFOV is the ability to achieve smaller tidal volumes and attenuate potential overdistention injury.

Timing of High-Frequency Oscillatory Ventilation

In early studies, HFOV was initiated approximately 5 days following the start of CMV.³² However, several observational studies have suggested better outcomes if HFOV is initiated earlier.^32,³³ David et al.³⁴ observed that mortality was reduced when HFOV was initiated within 3 days following the start of CMV, compared to after 3 days (20% versus 64%, respectively). Thus in recent years, investigators have initiated HFOV earlier: 1.9 days in the trial by Derdak et al.³⁵ and 1.8 days in the trial by Bollen et al.³⁶ Nonetheless, a meta-analysis evaluating determinants of mortality with HFOV in adults with ARDS did not find a relationship between late initiation of HFOV and higher mortality.³⁶

Recruitment Maneuvers

The use of recruitment maneuvers has gathered intense interest in the management of adults with ARDS and has been incorporated by some intensivists with the use of high-frequency ventilation. A pilot study by Ferguson et al. found that the combination of recruitment maneuvers and HFOV can be safely applied and results in rapid and sustained improvement in oxygenation.²⁹

Complications of High-Frequency Oscillatory Ventilation

HFOV has generally been shown to be safe if applied appropriately. However, as with all modes of mechanical ventilation, there are potential complications.

Barotrauma

Given the higher mean airway pressures applied during HFOV, there is a concern regarding the risk of barotrauma. The incidence of pneumothorax with the use of HFOV in observational studies varies from 2.4%³⁴ to 21.8%³⁷; however, HFOV was generally applied as rescue therapy in patients with severe ARDS, who are likely to already be at greater baseline risk of developing barotrauma. In two published randomized controlled trials^35,³⁶ comparing HFOV with CMV, there was no difference in the incidence of pneumothorax between CMV and HFOV groups.

Hemodynamic Instability

Another potential effect of a high mean airway pressure, regardless of mode of ventilation, is a reduction in venous return secondary to increased intrathoracic pressure. Thus it is important to consider the patient’s volume status prior to and during the transition from CV to HFOV, and consider judicious volume administration to ensure adequate intravascular volume.^20,³⁸

Inadequate Humidification

Inadequate humidification of inspired gas may lead to desiccation of secretions, potentially mucous inspissation and obstruction of the endotracheal tube. This is uncommon during HFOV,^32,³³ as adequate humidification can usually be achieved by passing the bias flow of gas through a humidifier.³⁹ However, problems with endotracheal tube obstruction may occasionally arise and can be indicated by a sudden rise in generated pressure amplitude for a given power setting.

Sedation and Paralysis

Unlike neonates, the majority of adults require suppression of their respiratory efforts during HFOV so their inspiratory flow rate does not outstrip the provided bias flow. Heavy sedation and occasionally paralysis are required in the majority of patients ³⁷; patient selection is therefore important to ensure that the severity of illness is sufficiently high to justify the use of sedation and paralysis, given the adverse effects of these agents.^40,⁴¹ In contrast to previous literature associating neuromuscular blockade with the development of critical illness polyneuropathy,⁴² the early short-term use of paralytic agents has recently been reported to improve survival in patients with ARDS.⁴³

The Future of High-Frequency Oscillatory Ventilation

After several decades of research regarding the physiologic principles and clinical application of HFOV (and high-frequency ventilation in general), many questions have been addressed, but other important issues remain unresolved, particularly regarding the utility of HFOV as a primary mode for reducing mortality in adults with ARDS. The optimal settings to maximize lung protection, lung recruitment, and gas exchange are unclear for many modes of high-frequency ventilation. Nonetheless, advances have been made with the use of HFOV, with evidence demonstrating that targeting lung recruitment and delivering low tidal volumes may be the optimal strategy to reduce the risk of overdistention injury and cyclic alveolar collapse, utilizing alternative gas transport mechanisms.

One of the most important questions regarding HFOV is whether it truly improves mortality when compared to lung-protective conventional ventilation. To date, several small studies ^35,³⁶ and a meta-analysis⁴⁴ suggest that HFOV may be beneficial, but there are issues with many of these studies which used antiquated strategies for both CMV and HFOV. For the definitive answer to this question, we will need to await the results of two large phase 3 studies comparing HFOV with best current conventional ventilation.^45,⁴⁶