High Frequency Oscillator Ventilation (HFOV) a new strategy in the treatment

of patients with the Acute Respiratory Distress Syndrome and low lung

compliance pathologies


Amanda Alves*

Interna Internato Complementar Medicina Interna

S. Medicina, Hospital Garcia de Orta

Almada, Portugal



Several lung protective ventilator strategies for treating patients with ARDS have been investigated. These strategies aim to reverse atelectasis by increasing alveolar recruitment, without overdistension of the existing healthy alveolar units. Both derecruitment and overdistension appear to play an active role in ongoing acute lung injury (ALI). Such ventilator strategies, using conventional modes of ventilation, have been limited by the risk of barotrauma, haemodynamic compromise and severe carbon dioxide (CO2) retention.

HFOV is a ventilatory mode in which high frequency, low amplitude, pressure oscillations of gas at 5-15 Hz (up to 900 breaths/min), are generated in the airways, resulting in high mean airway pressures and low tidal volumes (Vt) of 1-2ml/Kg. Both the inspiratory and expiratory phases of ventilation are active. A high bias flow of fresh gas is applied (20-60L/min).Gas exchange is achieved utilising sub-deadspace tidal volumes, and as such may provide a less traumatic way of recruiting and stabilising lung volumes. Five mechanisms of gas transport are thought to be important when using HFOV. These are bulk axial flow, interregional gas mixing, axial and radial augmented dispersion (Taylor dispersion), convective dispersion and molecular diffusion. Efficient gas transport seems to involve all five mechanisms and the overall coefficient of gas transport during HFOV is a combined function of  Vt2 and frequency. HFOV is coupled to a lung volume optimisation protocol, which initially uses high mean airway pressures (AW), to achieve optimal lung volumes via active alveolar recruitment. Optimising lung volume, improves gas exchange and reduces shear stress forces between expanded and collapsed lung units.

HFOV was originally used as a rescue technique in neonates with ARDS when conventional ventilation failed. A number of studies indicate that early application of this ventilatory mode may significantly improve the outcome of this serious lung condition and reduce the development of chronic complications in ARDS survivors.


Key words: High Frequency Oscillator Ventilator, Acute Respiratory Distress Syndrome

High Frequency Oscillator Ventilation (HFOV)




Patients suffering from the Acute Respiratory Distress Syndrome (ARDS) pose a challenge to all intensivists. The multifactorial origins which lead to the development of the “Leaky Lung” syndrome, together with the associated high mortality of this condition, has motivated critical care doctors to develop a number of lung protective ventilator strategies. The objectives of such measures are to reverse atelectasis by increasing alveolar recruitment, without overdistension of the existing healthy lung units. Examples of such strategies are “optimal” positive end expiratory pressure (PEEP), inverse ratio pressure-controlled ventilation, low tidal volumes (Vt) < 6ml/kg, patient positional changes and permissive hypercapneia. These measures are limited by the risk of barotrauma, haemodynamic compromise and severe carbon dioxide (CO2) retention.

HFOV is a ventilatory mode in which high frequency, low amplitude, pressure oscillations of gas, at 5-15 Hz (up to 900 breaths/min), are generated in the airways, together with high mean airway pressures (AW) and low tidal volumes (1-2ml/Kg). Both the inspiratory and expiratory phases of ventilation are active. CO2 elimination is separated from oxygen (O2) delivery. CO2 removal is effected by using a continuous high bias flow of fresh gas (20-60L/min). This ventilatory mode, together with a lung volume optimisation protocol to expand atelectatic lung regions, is a new strategy for the treatment of ARDS and low lung compliance pathologies.

Gas Transport

Classical respiratory physiology considers gas transport to occur via the concept of bulk axial flow. Two lung compartments are considered:

1.      The lung compartment in which homogeneous  alveolar gas is exchanged with   

      the blood by molecular diffusion

2.      The dead space (VD )where no gas exchange occurs


Using this model, under stable conditions, gas exchange is proportional to alveolar ventilation (VA) and when VT£ VD  no gas exchange occurs:

VA = VT -  VD

( VT = Tidal volume and  VD = Dead space)

Alternative theories for gas exchange have been proposed, during recent years, in an attempt to understand how patients ventilate adequately, using HFOV ventilation. Five different mechanisms have been proposed [1]:

1.      Transit Time Profile

2.      Interregional Gas Mixing

3.      Augmented Dispersion (Taylor Dispersion)

4.      Asymmetric Velocity Profiles

5.      Molecular Diffusion


Transit Time Profile

Using the classic gas transport model, it is assumed that all gas moves along the airways at an equal velocity, forming a uniform front across which no gas exchange occurs. The lung compartment is not a uniform structure and transit times to alveolar units will vary in proportion to the length of the bronchial airways.  Proximal alveolar units with short transit times will therefore ventilate before distal units and adequate gas exchange may occur in proximal units, by direct bulk convection, when tidal volumes are low.


Interregional Gas Mixing

The time that alveolar units take to  fill during ventilation depends on their compliance (C) and resistance (R) to airflow:

T = R x C

(T = Time constant of a given lung unit, R = Resistance to airflow, C = Compliance of alveolar unit)

Consequently, units with short time constants (low compliance, low resistance) fill and empty more rapidly. The concept of inhomogeneity of lung regional time constants was first introduced by Otis et al. [2] He proposed that asynchronous filling and emptying of alveolar units occurs and that at the end of expiration, units with short time constants (fast units) are empty and ready to fill, whereas units with long time constants (slow units) are still emptying. Consequently, gas moves from slow units to fast units. During inspiration the opposite occurs and gas moves from fast to slow units. This movement has been named Pendelluft movement.

During normal physiological conditions, the time of inspiration is always greater than the transit time of the slow units. However in pathological conditions where the respiratory cycle length is decreased especially where ventilatory strategies such as inverse ratio ventilation or HFOV are used, interregional to-and-fro mixing (Pendelluft) may positively influence gas transport. In these circumstances, the sum of the individual regional expansions is much greater than the VT delivered, indicating that parenchymal VT changes are enhanced by re-circulating gases.


Augmented Dispersion (Taylor Dispersion)

The concept of gas dispersion was first described by Taylor in 1953 [3,4]:


Gas dispersion results from the interaction between the axial velocity profile and radial diffusion of gases in motion.


In the lungs, the branching network of the airways together with Pendelluft movement, leads to gas turbulence and mixing between the core and the periphery of the gas column and radial dispersion is eliminated. This results in greater gas mixing with lower tidal volumes.


Asymmetric Velocity Profiles

Axial gas velocity profiles in branching systems, such as that encountered in the tracheobronchial tree have been studied. Under such conditions, the inspiratory profile is more skewed than the expiratory profile. Turbulence, accentuated velocities, eddies and swirls of gas all occur at the bifurcations in the airways which results in greater gas dispersion. At higher frequencies, inertial effects become more marked and the velocity profiles are more exaggerated. The net effect is, that even though bulk axial flow is low with ventilatory modes such as HFOV, the altered velocity profiles and interactions which occur in a branching system, result in greater gas dispersion.


Molecular Diffusion

Molecular diffusion results from the random motion of gas molecules. Gas transport across the alveolar membrane occurs via this mechanism. The diffusion gradient generated in the alveolus leads to transport of oxygen (O2) from the alveolus (high O2) to the pulmonary circulation (low O2)and removal of CO2 by a diffusion gradient in the opposite direction. When O2 passes from the alveolus into the pulmonary circulation, the drop in alveolar O2 provokes a similar diffusion gradient between the mouth and the alveolus. Diffusion is a slow process and while HFOV may enhance molecular diffusion, this theory of gas exchange has not been shown to be more important during HFOV than it is during conventional ventilatory modes.


In Summary


Overall, effective ventilation using HFOV involves all of the five gas transport mechanisms described. The different mechanisms may have greater bearing at different levels of the tracheobronchial tree (Fig 1). The overall coefficient of gas transport during HFOV has been shown to be a function of the product of VT2 and frequency (f). [5,6]





Figure 1: Different mechanisms of gas transport.1= convection; 2= Taylor dispersion; 3= Velocity profiles; 4= Interregional and 5 = Molecular diffusion. (Taken from Wetzel RC, Gioia FR. High frequency Ventilation. Pediatr Clin North America 1987 Feb;34(1):15-38.)



Mechanisms of Acute Lung Injury (ALI)


The ongoing pathological process which occurs in ARDS patients has been extensively studied. Ventilator patterns have been shown to influence the extent of acute lung injury [7].The stress invoked by the shear forces exerted on healthy overdistended alveolar units, during the cyclic alveolar/airway expansion and collapse which occurs during conventional ventilatory modes (CMV), is thought to be one of the most important factors in the development of hyaline membrane disease. The presence of polymorphonuclear neutrophils (PMNs) in ARDS is a well documented phenomenon. [8] PMNs appear to have a role in this process, particularly when activated. Masatoshi and co-workers studied neutrophil influx and activation in surfactant-depleted rabbit lungs (i.e atelectasis-prone), while applying different ventilator patterns [8]. They showed that when CMV’s were used an influx of PMNs occurred which became functionally activated and developed chemotactic properties. The lungs in these animals went on to develop the characteristic reduced gas exchange and marked pressure-volume (P-V) curve abnormalities seen in ARDS. In comparison, the animals ventilated using HFOV had a similar influx of PMNs but functional activation was not present and progressive deterioration in gas exchange and V-P curves did not occur. The study showed that prevention of the cyclic alveolar/airway expansion and collapse in surfactant-deficient lungs minimised activation of PMNs and subsequent development of ALI.


The low tidal volumes applied during HFOV prevent overdistension of the few healthy alveolar units. This results in a lower level of shear forces developing in the healthy units and consequently a lower associated immunological cascade. The study by Masatoshi et al further suggests that application of such a ventilatory mode earlier, rather than later (as a rescue technique), would lead to less pulmonary damage in ARDS patients.


HFOV was first used in neonates suffering from ARDS. High AW are initially applied together with HFOV, as a lung volume optimisation manoeuvre, in order to actively recruit and maintain open, alveoli, in atelectatic lung regions. Possible haemodynamic compromise, as a result of such high AW, was investigated by Gutierrez and co-workers [9]. They studied the haemodynamic profile via pulmonary artery catheters, in neonates suffering from ARDS, ventilated with HFOV. They found that although the initial AW was higher than that applied when using CMV, no adverse haemodynamic effects occurred. Pressure transmission in non-compliant lungs, where high resistance exists, appears to behave differently to pressure transmission in normal lungs. [10] Less pressure is transmitted to intrathoracic, extrapulmonary structures and haemodynamic compromise has not been a problem. [9, 11]

Use of this technique in the paediatric area indicated that, early application significantly improved outcome and reduced the number of chronic complications in ARDS survivors.[12,13] Development of more powerful HFO ventilators  with the capacity to ventilate adults, lead to a study by Fort et al in 1997 in which HFOV, together with a lung volume optimisation protocol, was used in adults suffering from ARDS. [11] The investigators applied a lung volume recruitment strategy which involved incremental increases in AW to achieve a PaO2 of ³ 60 torr, with an FiO2 of £ 0.6. The study showed that gas exchange improved significantly in the majority of patients as well as the Pao2/FiO2 ratio (p < 0.02). No significant compromise in cardiac output or oxygen delivery (DO2) was observed despite significant increases in AW (31.2 ± 10.3 to 34.0 ± 6.7 cm H2O. p < 0.05).


The accompanying editorial [14] of this article describes the advances in the development of this ventilatory mode  since the original concept of High Velocity Jet Ventilation was first introduced sixteen years prior to HFOV. The negative effect of CMV, which have resulted in repeated overdistension of healthy lung regions and ongoing atelectasis leading to worsening of the underlying pathophysiological process, is clearly stated. The  need to apply practically, what is now known experimentally, namely the application of an as even as possible expansion pattern in the atelectasis-prone lung, could improve outcome in this serious condition. HFOV together with high AW, offers a means of keeping below the upper inflection point of the P-V curve (where alveolar overdistension occurs), without haemodynamic compromise. The separation of O2 delivery from CO2 elimination removes the associated problem of hypercarbia.




Figure 2: HFOV ventilator



Figure 3: Patient with ARDS ventilated using HFOV




In conclusion, HFOV is still a new technique at present. It was originally studied using surfactant depleted rabbit models and then applied in paediatric neonatal patients with ARDS. It is currently being used in adults. A number of studies are underway which should clarify its role, as one of the treatment options available, for patients with ARDS and low lung compliance pathologies.



I would like to thank the staff, in particular my tutor Dr. Angela McLuckie, of the Guys and St. Thomas’s Hospital Trust Intensive Care Unit, for the theoretical and practical guidance offered to me concerning HFOV during a three-month ICU placement .




2.      Wetzel RC, Gioia FR. High frequency Ventilation. Pediatr Clin North America 1987 Feb;34(1):15-38.


3.      Arthur B. Otis et al.  Mechanical Factors in Distribution of Pulmonary Ventilation. J.Appl Physiol 8:427-433,1956.


4.      Taylor G I. Dispersion of soluble matter  in solvent flowing slowly through a tube. Proc R Soc London 219: 186-203, 1953.


5.      Taylor  G I. The dispersion of matter in turbulent flow through a pipe. Proc R Soc London 223:446-468,1954.


6.      Carlon GC, Ray C Miodownik S et al. Physiologic implications of high- frequency jet ventilation techniques. Crit Care Med 11:508-514,1983.


7.      Chang H K: Mechanisms of gas transport during ventilation by high-frequency oscillation. J.Appl Physiol 556:553-563,1984.


8.      Pamela R. McCulloch, P. Gek Forkert and Alison B.Froese. Lung Volume Maintenance prevents Lung Injury during High-frequency oscillatory ventilation in Surfactant-deficient Rabbits. Am Ver Resp Dis 1988; 137:1185- 1192.


9.      Masatoshi Sugiura et al. Ventilator pattern influences neutrophil influx and activation in atelectasis-prone rabbit lung. The American Physiological Society 1994 1355-1365.


10. J A Gutierrez, D L Levin and L O Toro-Figuerosa. Hemodynamic effects of high-frequency oscillatory ventilation in severe pediatric respiratory failure. Intensive Care Med (1995) 21:505-510.


11. Dale R. Gerstmann, Janie M. Fouke, Dean C. Winter et al. Proximal,   Tracheal and Alveolar pressures during High-frequency oscillatory  

ventilation in a Normal Rabbit model. Paediatric Research 1990 Vol. 28 Nº 4: 367-373.


12. Peter Fort MD et al. High-frequency oscillatory ventilation for adult  

respiratory distress syndrome-a pilot study. Crit Care Med 1997 Vol.25,  



13. John H. Arnold,MD; James H. Hanson,MD; Luis O. Toro-Figueiro et al.

Prospective, randomized comparison of high-frequency oscillatory 

ventilation and conventional mechanical ventilation in pediatric respiratory failure. Crit. Care Med 1994 Vol. 22, Nº 10: 1530-1539.


14. Reese H. Clarke,MD; Dale R. Gerstmann,MD; Donald M. Null,MD et al. Pulmonary Interstistitial emphysema treated by High-frequency oscillatory ventilation. Crit. Care Med. 1986 Vol.14: 926-939.



15. Alison B.Froese,MD,FRCP.High-frequency oscillatory ventilation for adult respiratory distress syndrome : Let´s get it right this time! Crit. Care Med 1997 Vol. 25, Nº 6: 907-908.