Review ArticleReviews

Reflections on Pediatric High-Frequency Oscillatory Ventilation From a Physiologic Perspective

Martin CJ Kneyber, Marc van Heerde and Dick G Markhorst
Respiratory Care September 2012, 57 (9) 1496-1504; DOI: https://doi.org/10.4187/respcare.01571

Abstract

Mechanical ventilation using low tidal volumes has become universally accepted to prevent ventilator-induced lung injury. High-frequency oscillatory ventilation (HFOV) allows pulmonary gas exchange using very small tidal volume (1–2 mL/kg) with concomitant decreased risk of atelectrauma. However, its use in pediatric critical care varies between only 3% and 30% of all ventilated children. This might be explained by the fact that the beneficial effect of HFOV on patient outcome has not been ascertained. Alternatively, in contrast with present recommendations, one can ask if HFOV has been employed in its most optimal fashion related especially to the indications for and timing of HFOV, as well as to using the best oscillator settings. The first was addressed in one small randomized study showing that early use of HFOV, instead of rescue use, was associated with improved survival. From a physiologic perspective, the oscillator settings could be refined. Lung volume is the main determinant of oxygenation in diffuse alveolar disease, suggesting using an open-lung strategy by recruitment maneuvers, although this is in practice not custom. Using such an approach, the patient can be oscillated on the deflation limb of the pressure-volume (P-V) curve, allowing less pressure required to maintain a certain amount of lung volume. Gas exchange is determined by the frequency and the oscillatory power setting, controlling the magnitude of the membrane displacement. Experimental work as well as preliminary human data have shown that it is possible to achieve the smallest tidal volume with concomitant adequate gas exchange when oscillating at high frequency and high fixed power setting. Future studies are needed to validate these novel approaches and to evaluate their effect on patient outcome.

Introduction

Mechanical ventilation (MV) is intimately linked with the daily care of critically ill children admitted to the pediatric ICU. Indications for MV include diffuse alveolar disease (DAD) including acute lung injury, or ARDS. Although life-saving, MV is also linked with ventilator-induced lung injury (VILI) and the development of multiple system organ failure.1 This has led to the concept of lung-protective ventilation, which has become standard of care nowadays.2 High-frequency oscillatory ventilation (HFOV) is, at least theoretically, an ideal tool for lung-protective ventilation, as it allows pulmonary gas exchange using very small tidal volume (VT) and decreases the risk of atelectrauma.3–15 Animal studies have pointed out that HFOV might be preferable over conventional MV, given its more beneficial effects on oxygenation, lung compliance, attenuation of the pulmonary inflammation and histologic injury, and better alveolar stability.16,17 HFOV allows the decoupling of oxygenation and ventilation. Simplified, oxygenation is dependent on lung volume, which is controlled by the continuous distending pressure (CDP). The CDP is depicted by the oscillator as mean airway pressure. CO2 clearance (V̇CO2) is relatively independent of lung volume, but influenced by oscillatory frequency (f) and the square of VT (V̇CO2 = F × VT2).18–22

The 3100 A/B HFO ventilator (SensorMedics, Yorba Linda, California) is the most commonly used HFOV device in pediatrics. With this system, pressure oscillations with a frequency of 3–15 Hz are superimposed upon a CDP in a square-wave manner. The CDP is generated by a fixed fresh gas flow/bias flow leaving the ventilator circuit by an expiratory balloon valve. A membrane superimposes high-frequency pressure oscillations around the CDP. The oscillatory pressure amplitude is highly attenuated over the ETT and the airways, and results in the delivery of a very small VT, usually lower than anatomical dead space.23 Because of this small VT, there is a decreased risk of entering the so-called non-safe zones within the pressure-volume loop of the diseased lung.22

The use of HFOV in pediatric critical care varies between 3% and 30% of all ventilated children.23–27 This relatively low use may be explained by several factors. First, lack of equipment or disbelief of the attending physician because of the absence of sound evidence of effect. Second, and perhaps even more importantly, many aspects of pediatric HFOV remain to be explored, including among others the identification of patients who are most likely to benefit from HFOV, timing of HFOV (early vs rescue), optimal oscillator settings, and monitoring during HFOV.

The purpose of this paper is to review published clinical experiences with HFOV and to reflect on how its use might be improved in light of the physiological properties of specific lung diseases and data from animal as well as bench studies.

Clinical Experiences

The effect of HFOV on mortality was compared with conventional MV in 2 randomized controlled trials (RCTs) (Table).28–42 The largest of the 2 was performed 15 years ago, in 5 centers, during a 3.5 year period.28 In this cross-over study, 58 patients with acute respiratory failure or pulmonary barotrauma, and an oxygenation index (OI) > 13, demonstrated by 2 consecutive measurements over a 6 hour period, were randomized to either HFOV (n = 29) using a strategy of aggressive increase in CDP targeted at SpO2 ≥ 90% with FIO2 ≤ 0.6, or conventional mechanical ventilation (n = 29), using a strategy utilizing PEEP and limited inspiratory pressures. Patients with obstructive airway disease (OAD), intractable septic or cardiogenic shock, or non-pulmonary terminal diagnosis were excluded. Targeted blood gas values were equal for each group. The main finding was that HFOV did not improve survival (HFOV 66% vs 59%) or total ventilator days (HFOV 20 ± 27 vs 22 ± 17), compared with conventional mechanical ventilation, when the data were analyzed by initial assignment. However, the percentage of survivors requiring supplemental oxygen at 30 days was significantly lower in the HFOV group (21% vs 59%, P = .039). Furthermore, mortality was only 6% (n = 1/17) in patients who were exclusively managed on HFOV, whereas it was 42% (n = 8/19) for patients who failed conventional mechanical ventilation and were transitioned to HFOV. Yet, mortality in patients who were exclusively managed with conventional mechanical ventilation was 40% (n = 4/10). Samransamruajkit et al reported the results of a small single-center study comparing HFOV (n = 7 patients) with conventional mechanical ventilation (n = 9 patients) with ARDS in a 2-year study period.29 Survival was higher with HFOV (71%), compared with conventional mechanical ventilation (44%), and predicted by plasma levels of soluble intercellular adhesion molecule 1.

View this table:
Table.

Summary of Clinical Experiences With High-Frequency Oscillatory Ventilation in Critically Ill Children

Both RCTs have not been repeated so far, but various institutions have described their (limited) experiences with HFOV (see the Table).30–43 Overall survival varied between 40% and 90%. The largest cohort study came from a collaborative of 10 pediatric centers reporting 232 patients.35 Duration of conventional mechanical ventilation prior to HFOV was between 2.2 ± 4.2 to 4.5 ± 3.1 days, whereas patients with preexisting lung injury were managed for up to 11.4 ± 45.5 days before transfer to HFOV. Thirty-day mortality ranged from 30% for patients with respiratory syncytial virus lower respiratory tract disease, to 59% for patients with congenital heart disease. Mortality was independently predicted by the OI 24 hours after start of HFOV and the presence of immunocompromise. The applicability of the OI as a predictor for patient outcome during HFOV has been confirmed by others.31,41 Some have linked failure of the OI to improve by at least 20% 6 hours after transition to HFOV with adverse outcome.33,40

The use of HFOV in pulmonary conditions with increased airway resistance and prolonged time constants, such as virus-induced OAD, remains a subject of debate because of the assumed risk of dynamic air-trapping resulting from inadequate egress of air during expiration, as seen in high-frequency jet ventilation. However, the SensorMedics 3100 A/B oscillator has an active expiratory phase. Nevertheless, several institutions have reported safe and beneficial use of HFOV in this patient population.30,34,35,37,39,44

It can thus be concluded that at present a beneficial effect of HFOV on mortality has not been established. This may be explained by various factors. First, the knowledge on lung-protective ventilation has significantly increased over the past years. It is now universally accepted that a low VT should be applied. However, the study by Arnold and colleagues28 was conducted in the era prior to the ARDS Network trial. In their study, the authors did not specify the VT used on conventional mechanical ventilation. Similar criticisms can be made toward the study by Samransamruajkit et al,29 so that it is not unthinkable that patients on conventional mechanical ventilation were subjected to high VT. Second, both RCTs were not powered to detect statistically significant differences in mortality.

Critical Appraisal of the HFOV Strategy Employed

Alternatively, the question could also be raised whether HFOV was applied in its most optimal fashion. These issues (among others) include identification of the patient who will benefit the most from HFOV, the timing of cross-over from conventional mechanical ventilation to HFOV, as well as determining the best oscillator settings.

Indications for and Timing of HFOV

The indications for HFOV are ill-defined and usually depend upon the personal preference of the attending physician. In general, HFOV is considered only as a rescue approach when conventional mechanical ventilation fails. One group of investigators have evaluated the early use of HFOV instead of using it as rescue therapy.42 In their small observational study of 26 patients, it was found that the group of patients who was transitioned to HFOV within 24 hours of conventional mechanical ventilation had a significantly higher 30-day survival rate (58.8 vs 12.5%). We suggest that HFOV should be considered if oxygenation remains severely impaired (in our institution defined by SpO2 < 88% and/or PaO2 < 50 mm Hg with FIO2 > 0.6) despite the application of maximal lung-protective conventional mechanical ventilation (ie, limiting peak inspiratory pressures to 30–35 cm H2O and sufficient level of PEEP) in children with acute lung injury/ARDS. Alternatively, the OI can be used, although a specific threshold needs to determined. For patients with OAD no guideline is available for when to consider HFOV. Based upon our own experiences we consider HFOV when refractory respiratory acidosis persists despite maximum conservative measures such as nebulization or intravenous administration of bronchodilators, use of heliox, or use of external PEEP to stent occluded airways.

In our opinion there are no known contraindications for HFOV, although its safety has been questioned in patients with severe traumatic brain injury, based upon the assumption that the high intrathoracic pressures are propagated toward the brain and impede the cerebral circulation. However, this has been refuted by both animal and clinical data.45,46

Best HFOV Approach and Oscillator Settings for Oxygenation

Lung volume is the main determinant of oxygenation in DAD during HFOV. Simplified, the PaO2 increases linearly with lung volume up to a certain point when alveoli become overdistended.47 This suggests that an open-lung strategy (ie, opening up the lung and keeping it open) in DAD by (repeated) recruitment maneuvers (RM) should be considered when switching to HFOV. Furthermore, pressure oscillations are less dampened in lungs with ongoing atelectasis, thus exposing the conducting airways to higher injurious pressure swings.48 Animal work has indeed shown improved lung compliance and less hyaline membrane formation when such strategies were applied.15,49,50 However, in both pediatric RCTs, as well as in nearly half of all observational cohort studies, there is no mention of RMs being performed.28,29,31–33,36,40,41 Also, there is much ongoing scientific debate related to use and efficacy of RMs. Not all lung diseases are recruitable, and in general the potential for lung recruitability is highly variable.51 Furthermore, there are so far no clinical studies establishing the beneficial effects of RMs during HFOV, let alone determining the best RM.

The latter has been addressed in one study in which 4 different RM approaches were compared: a step-wise pressure increase over 6 min; a 20 s sustained dynamic inflation (either one or repeated 6 times); and a standard approach (setting mean airway pressure direct at start).52 This study showed that a step-wise pressure increase produced the greatest increase in lung volume and resolution of atelectasis. Thus, this study suggests that the stepwise increase pressure approach might be considered for optimizing lung volume during HFOV, as it incorporates not only pressure but also adequate duration of the RM. The clinical benefits of RMs during HFOV have been addressed in a recently completed phase II trial in critically ill adults comparing HFOV with and without RMs (www.clinicaltrials.gov NCT00399581). Unfortunately, a pediatric counterpart is lacking, but the adult results are eagerly awaited.

Another, at least theoretical, benefit of RMs is that it allows oscillating the patient on the deflation limb of the P-V curve, thereby (partially) avoiding injurious hyperinflation and atelectasis.22,53–59 By doing so, less CDP is needed to maintain a certain lung volume on the inflation limb, because of the hysteresis of the respiratory system. In our view and practice, this can be achieved in clinical practice in patients with DAD by initially setting the CDP 3–5 cm H2O above the mean airway pressure on conventional mechanical ventilation, as the distal CDP is lower than the set proximal CDP.60,61 Then the CDP should be increased stepwise over a certain period of time until the point where oxygenation (either the SpO2 or the PaO2) does not improve at a fixed FIO2 (suggestive of approximating total lung capacity). Also, with increasing compliance the ΔP depicted by the oscillator may decrease; hence, it may be indicative for approximating total lung capacity when ΔP increases again.62 The next step would be to reduce the CDP to the point where oxygenation starts to decrease after initial improvement (suggestive of derecruitment). The ΔP depicted by the oscillator may initially decrease, but may increase again when derecruitment on the deflation limb occurs. Ultimately, the CDP will finally set 2–4 cm H2O above this point. We have adopted such an approach in our clinical practice. A positive effect of sustained inflations prior to the stepwise increase in CDP has not been demonstrated.52,63

HFOV may also be considered in patients with refractory OAD. However, in these patients the purpose of the stepwise increase in CDP is to splint open and stent the airways to a certain point when the PaCO2 starts to drop, in order to prevent relatively healthy alveoli being exposed to high pressures once the airways are open.64 Importantly, the novel approach toward optimizing oxygenation as discussed needs to be studied for safety and effectiveness.

Best HFOV Approach and Oscillator Settings for Ventilation

The V̇CO2 is determined by patient-related characteristics and oscillator settings. The first include compliance and resistance of the respiratory system.62,65 With reduced compliance in unresolved atelectasis there is a marked increase in transmission of the peak-to-trough ΔP to the alveoli and bronchi. Increased resistance decreases the transmission of the peak-to-trough ΔP over the airways to the alveoli.62 Oscillator settings include oscillatory power setting (magnitude of membrane displacement), frequency (f), in Hertz (Hz), inspiratory to expiratory ratio, position of the membrane, endotracheal tube (ETT) length and diameter, and the presence of ETT leakage.20,66,67

The ETT constitutes the major work load to the oscillator and is an important determinant of VT.68,69 VT is proportional to the ETT inner cross-sectional area, because the impedance of the ETT exceeds the impedance of the lung.70,71 Increasing diameter (inner diameter 2.5–4.0 mm) of the ETT increases pressure transmission.62

The manufacturer's manual recommends setting f and power according to the patient's age, ventilator settings, and observation of chest wiggle. This recommendation has been adopted into clinical practice, using the f and power in a weight and age-dependent manner in both RCTs, as well as in the observational cohort studies.28–30,33–39,41,42

We propose that these recommendations may be refined. From a physiological perspective it seems more appropriate to use the highest possible f in DAD. First, f determines the rate of oscillations and directly influences the VT. Hence, the higher the f, the smaller the VT, because changes in f are inversely proportional to the distal oscillatory pressure amplitude. Consequently, it becomes easier to stay within the limits of the safe zone (ie, the zone with the smallest risk of injurious hyperinflation or atelectasis) of the P-V loop. Second, collapsed lung regions are more easily opened at higher f.72 Third, the delivered VT is more equally distributed, as it becomes less dependent on regional compliance at higher f.73 Lastly, the square block waveform is better preserved, allowing a more constant VT.74,75 Needless to say, it is necessary to maintain an appropriate CDP when setting the f.

The next question, then, is what could be considered as optimal f. Venegas and Fredberg have proposed that how f needs to be set depends upon the so-called corner frequency (Fc) of the lung, Fc = 1/(2πRC), where R is resistance and C compliance.59 Fc defines the optimal frequency at which there is adequate gas transport during HFOV in combination with the least injurious pressures, and is influenced by the underlying disease (Figure). It is increased in lung diseases characterized by short time constants and low compliance, such as in DAD. This implies that at higher f, alveoli are ventilated at a lower pressure cost of ventilation, as opposed to lung diseases characterized by prolonged time constants (for example OAD).

Figure.
Figure.

Corner frequency (Fc) of the lung in patients with decreased compliance, such as acute lung injury/ARDS and increased resistance, such as obstructive airway disease. Fc (graphically depicted by the dot) defines the optimal frequency at which there is adequate gas transport during HFOV in combination with the least injurious pressures. It is defined by 1/2πRC, where R is resistance and C compliance. (From Reference 59, with permission.)

Importantly, f is intimately linked with ΔP. Basically, the higher the ΔP, the larger the VT. Yet, we (unpublished data) and others have observed in bench test studies that VT was smaller when combining high f (15 Hz) and high power (set to achieve a ΔP of 90), compared with low f (5 Hz) and low power settings, as the distal pressure amplitude was much lower but still associated with a sufficient V̇CO2.76 These findings were in agreement with the work from Hager and co-workers. They have measured VT in adult patients with ARDS managed on HFOV and found smaller VT with the combination high f and high power setting.69 The use of these higher f did not impair gas exchange.77

Importantly, how are these theoretical benefits translated into clinical practice? At present it is impossible to detect the Fc and thus impossible to identify the optimal f. Furthermore, what ΔP should be targeted? Based upon our own experiences, we propose using the highest f in combination with a fixed power setting that is associated with acceptable CO2 elimination (in our view pH > 7.25) in patients with DAD. For patients with OAD the initial f should theoretically be between 5 and 7 Hz. The ΔP should not exceed 70–90, because higher pressures may theoretically expose the proximal airways to injurious pressures. Again, this novel approach toward optimizing ventilation during HFOV requires further evaluation for its safety and efficacy. For instance, it has been suggested that the use of high amplitudes might lead to gas trapping due to the development of so-called choke points causing expiratory flow limitation, especially at low CDP.78 However, the occurrence of choke points has never been demonstrated.

Monitoring During HFOV

At present, physicians have the SpO2, blood gas analysis, ΔP, and chest radiography at their disposal for evaluating the response of a patient to HFOV. It is often advised to obtain chest radiographs to evaluate the optimal lung inflation. However, such an approach has never been validated, and we therefore do not routinely obtain chest radiographs. Repeated daily blood gas analyses may be informative to assess if targets of ventilation (ie, permissive hypercapnia [pH > 7.15–7.25]) are being met. Transcutaneous CO2 (Ptco2) monitoring may be used as a noninvasive alternative.79 Developments are being made with respect to electrical impedance tomography and respiratory inductance plethysmography incorporated in the Bicore II as tools for the determination of the optimal CDP.80,81

We have recently begun to explore the use of respiratory inductance plethysmography in guiding the stepwise increase in CDP. Alternatively, the optimal CDP may be recognized when both lung compliance and OI (calculated by CDP × FIO2 × 100/PaO2) are optimal.82 The benefit of the OI over the PaO2/FIO2 ratio is that it takes the degree of ventilator settings (as summarized by the mean airway pressure) into account. Van Genderingen and co-workers found that the lowest OI during the RM indicated at which CDP the oxygenation was considered to be optimal; this also indicated the point on the deflation limb of the P-V curve where physiologic shunt fraction was the lowest.83

The oscillatory pressure ratio (OPR) may also aid in the identification.65 OPR is defined as the ratio of the distal and proximal ETT pressure swings. To calculate the OPR it is necessary to measure the tracheal pressure. In a 3.0 mm ETT neonatal respiratory distress syndrome simulated model, OPR decreased when the CDP was increased (suggestive of lung recruitment) but increased when the CDP was increased further. This suggested hyperinflation. The OPR was the lowest at maximum compliance. The OPR was also affected by frequency, ΔP, and ETT inner diameter. The OPR was further evaluated in an animal model of acute lung injury.84 One of the main findings of this study was that, after lung recruitment, similar oxygenation with smaller pressure swings could be achieved with a lower CDP set by the deflation limb of the P-V curve rather than the inflation limb. The clinical use of these potential aids, however, needs to be established.

Spontaneous Breathing During HFOV

Maintaining spontaneous breathing during HFOV improves oxygenation and regional ventilation.85,86 Spontaneous breathing during HFOV is feasible for small children but becomes more difficult when the patient demands high inspiratory flows. The maximal possible bias flow delivered by the oscillator may be well below the needs of the patient. This will lead to increased work of imposed breathing, as shown by our group in a bench test model.87 Because of this, many older children on the oscillator are likely to need sedatives and neuromuscular blockade during their illness, prohibiting spontaneous breathing.

Conclusions

The beneficial effect of HFOV on outcome in critically ill children remains unclear. However, based upon the physiologic properties of the oscillator, one can ask if HFOV has been employed in its most optimal fashion. We suggest that in patients with diffuse alveolar disease, convert to HFOV early in the disease course; employ an open-lung strategy using (repeated) RMs; and use the highest frequency and high fixed power setting, providing that adequate gas exchange is maintained. For patients with OAD, HFOV may be considered to open up and stent the airways. Importantly, future studies are needed to validate these novel approaches and to evaluate their effect on patient outcome.

Footnotes

  • Correspondence: Martin CJ Kneyber MD PhD, Department of Pediatrics, Division of Pediatric Intensive Care, Beatrix Children's Hospital, University Medical Center Groningen, Internal Postal Code CA80, PO Box 30.001, 9700 RB Groningen, The Netherlands. E-mail: m.c.j.kneyber{at}umcg.nl.

  • The authors have disclosed no conflicts of interest.

References

  1. 1.↵
    1. Tremblay LN,
    2. Slutsky AS
    . Ventilator-induced lung injury: from the bench to the bedside. Intensive Care Med 2006;32(1):24–33.
    OpenUrlCrossRefPubMed
  2. 2.↵
    1. Esan A,
    2. Hess DR,
    3. Raoof S,
    4. George L,
    5. Sessler CN
    . Severe hypoxemic respiratory failure: part 1: ventilatory strategies. Chest 2010;137(5):1203–1216.
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Imai Y,
    2. Slutsky AS
    . High-frequency oscillatory ventilation and ventilator-induced lung injury. Crit Care Med 2005;33(Suppl 3):S129–S134.
    OpenUrlCrossRefPubMed
  4. 4.
    1. Slutsky AS,
    2. Drazen FM,
    3. Ingram RH Jr.,
    4. Kamm RD,
    5. Shapiro AH,
    6. Fredberg JJ,
    7. et al
    . Effective pulmonary ventilation with small-volume oscillations at high frequency. Science 1980;209(4456):609–671.
    OpenUrlAbstract/FREE Full Text
  5. 5.
    1. Bohn DJ,
    2. Miyasaka K,
    3. Marchak BE,
    4. Thompson WK,
    5. Froese AB,
    6. Bryan AC
    . Ventilation by high-frequency oscillation. J Appl Physiol 1980;48(4):710–716.
    OpenUrlAbstract/FREE Full Text
  6. 6.
    1. Aspros AJ,
    2. Coto CG,
    3. Lewis JF,
    4. Veldhuizen RA
    . High-frequency oscillation and surfactant treatment in an acid aspiration model. Can J Physiol Pharmacol 2010;88(1):14–20.
    OpenUrlPubMed
  7. 7.
    1. Shimaoka M,
    2. Fujino Y,
    3. Taenaka N,
    4. Hiroi T,
    5. Kiyono H,
    6. Yoshiya I I.
    . High frequency oscillatory ventilation attenuates the activation of alveolar macrophages and neutrophils in lung injury. Crit Care 1998;2(1):35–39.
    OpenUrlCrossRefPubMed
  8. 8.
    1. Muellenbach RM,
    2. Kredel M,
    3. Said HM,
    4. Klosterhalfen B,
    5. Zollhoefer B,
    6. Wunder C,
    7. et al
    . High-frequency oscillatory ventilation reduces lung inflammation: a large-animal 24-h model of respiratory distress. Intensive Care Med 2007;33(8):1423–1433.
    OpenUrlCrossRefPubMed
  9. 9.
    1. Nakagawa R,
    2. Koizumi T,
    3. Ono K,
    4. Yoshikawa S,
    5. Tsushima K,
    6. Otagiri T
    . Effects of high-frequency oscillatory ventilation on oleic acid-induced lung injury in sheep. Lung 2008;186(4):225–232.
    OpenUrlPubMed
  10. 10.
    1. Sugiura M,
    2. McCulloch PR,
    3. Wren S,
    4. Dawson RH,
    5. Froese AB
    . Ventilator pattern influences neutrophil influx and activation in atelectasis-prone rabbit lung. J Appl Physiol 1994;77(3):1355–1365.
    OpenUrlAbstract/FREE Full Text
  11. 11.
    1. Jian MY,
    2. Koizumi T,
    3. Yokoyama T,
    4. Tsushima K,
    5. Kubo K
    . Comparison of acid-induced inflammatory responses in the rat lung during high frequency oscillatory and conventional mechanical ventilation. Inflamm Res 201;59(11):931–937.
  12. 12.
    1. Takata M,
    2. Abe J,
    3. Tanaka H,
    4. Kitano Y,
    5. Doi S,
    6. Kohsaka T,
    7. et al
    . Intraalveolar expression of tumor necrosis factor-alpha gene during conventional and high-frequency ventilation. Am J Respir Crit Care Med 1997;156(1):272–279.
    OpenUrlPubMed
  13. 13.
    1. der Hardt K,
    2. Kandler MA,
    3. Fink L,
    4. Schoof E,
    5. Dotsch J,
    6. Brandenstein O,
    7. et al
    . High frequency oscillatory ventilation suppresses inflammatory response in lung tissue and microdissected alveolar macrophages in surfactant depleted piglets. Pediatr Res 2004;55(2):339–346.
    OpenUrlCrossRefPubMed
  14. 14.
    1. Rotta AT,
    2. Gunnarsson B,
    3. Fuhrman BP,
    4. Hernan LJ,
    5. Steinhorn DM
    . Comparison of lung protective ventilation strategies in a rabbit model of acute lung injury. Crit Care Med 2001;29(11):2176–2184.
    OpenUrlCrossRefPubMed
  15. 15.↵
    1. McCulloch PR,
    2. Forkert PG,
    3. Froese AB
    . Lung volume maintenance prevents lung injury during high frequency oscillatory ventilation in surfactant-deficient rabbits. Am Rev Respir Dis 1988;137(5):1185–1192.
    OpenUrlPubMed
  16. 16.↵
    1. Imai Y,
    2. Nakagawa S,
    3. Ito Y,
    4. Kawano T,
    5. Slutsky AS,
    6. Miyasaka K
    . Comparison of lung protection strategies using conventional and high-frequency oscillatory ventilation. J Appl Physiol 2001;91(4):1836–1844.
    OpenUrlAbstract/FREE Full Text
  17. 17.↵
    1. Carney D,
    2. DiRocco J,
    3. Nieman G
    . Dynamic alveolar mechanics and ventilator-induced lung injury. Crit Care Med 2005;33(Suppl 3):S122–S128.
    OpenUrlCrossRefPubMed
  18. 18.↵
    1. Schindler M,
    2. Seear M
    . The effect of lung mechanics on gas transport during high-frequency oscillation. Pediatr Pulmonol 1991;11(4):335–339.
    OpenUrlPubMed
  19. 19.
    1. Boynton BR,
    2. Hammond MD,
    3. Fredberg JJ,
    4. Buckley BG,
    5. Villanueva D,
    6. Frantz ID III.
    . Gas exchange in healthy rabbits during high-frequency oscillatory ventilation. J Appl Physiol 1989;66(3):1343–1351.
    OpenUrlAbstract/FREE Full Text
  20. 20.↵
    1. Slutsky AS,
    2. Kamm RD,
    3. Rossing TH,
    4. Loring SH,
    5. Lehr J,
    6. Shapiro AH,
    7. et al
    . Effects of frequency, tidal volume, and lung volume on CO2 elimination in dogs by high frequency (2-30 Hz), low tidal volume ventilation. J Clin Invest 1981;68(6):1475–1484.
    OpenUrlPubMed
  21. 21.
    1. Kamitsuka MD,
    2. Boynton BR,
    3. Villanueva D,
    4. Vreeland PN,
    5. Frantz ID III.
    . Frequency, tidal volume, and mean airway pressure combinations that provide adequate gas exchange and low alveolar pressure during high frequency oscillatory ventilation in rabbits. Pediatr Res 1990;27(1):64–69.
    OpenUrlPubMed
  22. 22.↵
    1. Froese AB
    . High-frequency oscillatory ventilation for adult respiratory distress syndrome: let's get it right this time! Crit Care Med 1997;25(6):906–908.
    OpenUrlCrossRefPubMed
  23. 23.↵
    1. Santschi M,
    2. Jouvet P,
    3. Leclerc F,
    4. Gauvin F,
    5. Newth CJ,
    6. Carroll CL,
    7. et al
    ; PALIVE Investigators; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network; European Society of Pediatric and Neonatal Intensive Care (ESPNIC). Acute lung injury in children: therapeutic practice and feasibility of international clinical trials. Pediatr Crit Care Med 2010;11(6):681–689.
    OpenUrlPubMed
  24. 24.
    1. Erickson S,
    2. Schibler A,
    3. Numa A,
    4. Nuthall G,
    5. Yung M,
    6. Pascoe E,
    7. et al
    . Acute lung injury in pediatric intensive care in Australia and New Zealand: a prospective, multicenter, observational study. Pediatr Crit Care Med 2007;8(4):317–323.
    OpenUrlCrossRefPubMed
  25. 25.
    1. Flori HR,
    2. Glidden DV,
    3. Rutherford GW,
    4. Matthay MA
    . Pediatric acute lung injury: prospective evaluation of risk factors associated with mortality. Am J Respir Crit Care Med 2005;171(9):995–1001.
    OpenUrlCrossRefPubMed
  26. 26.
    1. Randolph AG,
    2. Meert KL,
    3. O'Neil ME,
    4. Hanson JH,
    5. Luckett PM,
    6. Arnold JH,
    7. et al
    . The feasibility of conducting clinical trials in infants and children with acute respiratory failure. Am J Respir Crit Care Med 2003;167(10):1334–1340.
    OpenUrlCrossRefPubMed
  27. 27.↵
    1. Zimmerman JJ,
    2. Akhtar SR,
    3. Caldwell E,
    4. Rubenfeld GD
    . Incidence and outcomes of pediatric acute lung injury. Pediatrics 2009;124(1):87–95.
    OpenUrlAbstract/FREE Full Text
  28. 28.↵
    1. Arnold JH,
    2. Hanson JH,
    3. Toro-Figuero LO,
    4. Gutierrez J,
    5. Berens RJ,
    6. Anglin DL
    . Prospective, randomized comparison of high-frequency oscillatory ventilation and conventional mechanical ventilation in pediatric respiratory failure. Crit Care Med 1994;22(10):1530–1539.
    OpenUrlPubMed
  29. 29.↵
    1. Samransamruajkit R,
    2. Prapphal N,
    3. Deelodegenavong J,
    4. Poovorawan Y
    . Plasma soluble intercellular adhesion molecule-1 (sICAM-1) in pediatric ARDS during high frequency oscillatory ventilation: a predictor of mortality. Asian Pac J Allergy Immunol 2005;23(4):181–188.
    OpenUrlPubMed
  30. 30.↵
    1. Slee-Wijffels FY,
    2. van der Vaart KR,
    3. Twisk JW,
    4. Markhorst DG,
    5. Plotz FB
    . High-frequency oscillatory ventilation in children: a single-center experience of 53 cases. Crit Care 2005;9(3):R274–R279.
    OpenUrlPubMed
  31. 31.↵
    1. Lochindarat S,
    2. Srisan P,
    3. Jatanachai P
    . Factors effecting the outcome of acute respiratory distress syndrome in pediatric patients treated with high frequency oscillatory ventilation. J Med Assoc Thai 2003;86(Suppl 3):S618–S627.
    OpenUrlPubMed
  32. 32.
    1. Watkins SJ,
    2. Peters MJ,
    3. Tasker RC
    . One hundred courses of high frequency oscillatory ventilation: what have we learned? Eur J Pediatr 2000;159(1-2):134.
    OpenUrlPubMed
  33. 33.↵
    1. Sarnaik AP,
    2. Meert KL,
    3. Pappas MD,
    4. Simpson PM,
    5. Lieh-Lai MW,
    6. Heidemann SM
    . Predicting outcome in children with severe acute respiratory failure treated with high-frequency ventilation. Crit Care Med 1996;24(8):1396–1402.
    OpenUrlCrossRefPubMed
  34. 34.↵
    1. Berner ME,
    2. Hanquinet S,
    3. Rimensberger PC
    . High frequency oscillatory ventilation for respiratory failure due to RSV bronchiolitis. Intensive Care Med 2008;34(9):1698–1702.
    OpenUrlCrossRefPubMed
  35. 35.↵
    1. Arnold JH,
    2. Anas NG,
    3. Luckett P,
    4. Cheifetz IM,
    5. Reyes G,
    6. Newth CJ,
    7. et al
    . High-frequency oscillatory ventilation in pediatric respiratory failure: a multicenter experience. Crit Care Med 2000;28(12):3913–3919.
    OpenUrlCrossRefPubMed
  36. 36.↵
    1. Brogan TV,
    2. Bratton SL,
    3. Meyer RJ,
    4. O'Rourke PP,
    5. Jardine DS
    . Nonpulmonary organ failure and outcome in children treated with high-frequency oscillatory ventilation. J Crit Care 2000;15(1):5–11.
    OpenUrlCrossRefPubMed
  37. 37.↵
    1. Martinon Torres F,
    2. Rodriguez Nuñez A,
    3. Jaimovich DG,
    4. Martinon Sanchez JM
    . [High-frequency oscillatory ventilation in pediatric patients. protocol and preliminary results]. An Esp Pediatr 2000;53(4):305–313. Article in Spanish.
    OpenUrlPubMed
  38. 38.
    1. Ben Jaballah N,
    2. Khaldi A,
    3. Mnif K,
    4. Bouziri A,
    5. Belhadj S,
    6. Hamdi A,
    7. et al
    . High-frequency oscillatory ventilation in pediatric patients with acute respiratory failure. Pediatr Crit Care Med 2006;7(4):362–367.
    OpenUrlCrossRefPubMed
  39. 39.↵
    1. Duval EL,
    2. Markhorst DG,
    3. Gemke RJ,
    4. van Vught AJ
    . High-frequency oscillatory ventilation in pediatric patients. Neth J Med 2000;56(5):177–185.
    OpenUrlCrossRefPubMed
  40. 40.↵
    1. Anton N,
    2. Joffe KM,
    3. Joffe AR
    . Inability to predict outcome of acute respiratory distress syndrome in children when using high frequency oscillation. Intensive Care Med 2003;29(10):1763–1769.
    OpenUrlPubMed
  41. 41.↵
    1. Rosenberg RB,
    2. Broner CW,
    3. Peters KJ,
    4. Anglin DL
    . High-frequency ventilation for acute pediatric respiratory failure. Chest 1993;104(4):1216–1221.
    OpenUrlPubMed
  42. 42.↵
    1. Fedora M,
    2. Klimovic M,
    3. Seda M,
    4. Dominik P,
    5. Nekvasil R
    . Effect of early intervention of high-frequency oscillatory ventilation on the outcome in pediatric acute respiratory distress syndrome. Bratisl Lek Listy 2000;101(1):8–13.
    OpenUrlPubMed
  43. 43.↵
    1. Dobyns EL,
    2. Anas NG,
    3. Fortenberry JD,
    4. Deshpande J,
    5. Cornfield DN,
    6. Tasker RC,
    7. et al
    . Interactive effects of high-frequency oscillatory ventilation and inhaled nitric oxide in acute hypoxemic respiratory failure in pediatrics. Crit Care Med 2002;30(11):2425–2429.
    OpenUrlCrossRefPubMed
  44. 44.↵
    1. Leipala JA,
    2. Sharma A,
    3. Lee S,
    4. Milner AD,
    5. Greenough A
    . An in vitro assessment of gas trapping during high frequency oscillation. Physiol Meas 2005;26(3):329–336.
    OpenUrlPubMed
  45. 45.↵
    1. David M,
    2. Markstaller K,
    3. Depta AL,
    4. Karmrodt J,
    5. Herweling A,
    6. Kempski O,
    7. et al
    . Initiation of high-frequency oscillatory ventilation and its effects upon cerebral circulation in pigs: an experimental study. Br J Anaesth 2006;97(4):525–532.
    OpenUrlAbstract/FREE Full Text
  46. 46.↵
    1. O'Rourke J,
    2. Sheeran P,
    3. Heaney M,
    4. Talbot R,
    5. Geraghty M,
    6. Costello J,
    7. et al
    . Effects of sequential changes from conventional ventilation to high-frequency oscillatory ventilation at increasing mean airway pressures in an ovine model of combined lung and head injury. Eur J Anaesthesiol 2007;24(5):454–463.
    OpenUrlPubMed
  47. 47.↵
    1. Suzuki H,
    2. Papazoglou K,
    3. Bryan AC
    . Relationship between PaO2 and lung volume during high frequency oscillatory ventilation. Acta Paediatr Jpn 1992;34(5):494–500.
    OpenUrlPubMed
  48. 48.↵
    1. Sakai T,
    2. Kakizawa H,
    3. Aiba S,
    4. Takahashi R,
    5. Yoshioka T,
    6. Iinuma K
    . Effects of mean and swing pressures on piston-type high-frequency oscillatory ventilation in rabbits with and without acute lung injury. Pediatr Pulmonol 1999;27(5):328–335.
    OpenUrlPubMed
  49. 49.↵
    1. Bond DM,
    2. McAloon J,
    3. Froese AB
    . Sustained inflations improve respiratory compliance during high-frequency oscillatory ventilation but not during large tidal volume positive-pressure ventilation in rabbits. Crit Care Med 1994;22(8):1269–1277.
    OpenUrlPubMed
  50. 50.↵
    1. Bond DM,
    2. Froese AB
    . Volume recruitment maneuvers are less deleterious than persistent low lung volumes in the atelectasis-prone rabbit lung during high-frequency oscillation. Crit Care Med 1993;21(3):402–412.
    OpenUrlCrossRefPubMed
  51. 51.↵
    1. Gattinoni L,
    2. Caironi P,
    3. Cressoni M,
    4. Chiumello D,
    5. Ranieri VM,
    6. Quintel M,
    7. et al
    . Lung recruitment in patients with the acute respiratory distress syndrome. N Engl J Med 2006;354(17):1775–1786.
    OpenUrlCrossRefPubMed
  52. 52.↵
    1. Pellicano A,
    2. Tingay DG,
    3. Mills JF,
    4. Fasulakis S,
    5. Morley CJ,
    6. Dargaville PA
    . Comparison of four methods of lung volume recruitment during high frequency oscillatory ventilation. Intensive Care Med 2009;35(11):1990–1908.
    OpenUrlPubMed
  53. 53.↵
    1. Boynton BR,
    2. Villanueva D,
    3. Hammond MD,
    4. Vreeland PN,
    5. Buckley B,
    6. Frantz ID III.
    . Effect of mean airway pressure on gas exchange during high-frequency oscillatory ventilation. J Appl Physiol 1991;70(2):701–707.
    OpenUrlAbstract/FREE Full Text
  54. 54.
    1. Goddon S,
    2. Fujino Y,
    3. Hromi JM,
    4. Kacmarek RM
    . Optimal mean airway pressure during high-frequency oscillation: predicted by the pressure-volume curve. Anesthesiology 2001;94(5):862–869.
    OpenUrlPubMed
  55. 55.
    1. Luecke T,
    2. Meinhardt JP,
    3. Herrmann P,
    4. Weisser G,
    5. Pelosi P,
    6. Quintel M
    . Setting mean airway pressure during high-frequency oscillatory ventilation according to the static pressure: volume curve in surfactant-deficient lung injury: a computed tomography study. Anesthesiology 2003;99(6):1313–1322.
    OpenUrlCrossRefPubMed
  56. 56.
    1. Kacmarek RM,
    2. Malhotra A
    . High-frequency oscillatory ventilation: what large-animal studies have taught us! Crit Care Med 2005;33(Suppl 3):S148–S154.
    OpenUrlCrossRefPubMed
  57. 57.
    1. Markhorst DG,
    2. van Genderingen HR,
    3. van Vught AJ
    . Static pressure-volume curve characteristics are moderate estimators of optimal airway pressures in a mathematical model of (primary/pulmonary) acute respiratory distress syndrome. Intensive Care Med 2004;30(11):2086–2093.
    OpenUrlCrossRefPubMed
  58. 58.
    1. Tingay DG,
    2. Mills JF,
    3. Morley CJ,
    4. Pellicano A,
    5. Dargaville PA
    . The deflation limb of the pressure-volume relationship in infants during high-frequency ventilation. Am J Respir Crit Care Med 2006;173(4):414–420.
    OpenUrlCrossRefPubMed
  59. 59.↵
    1. Venegas JG,
    2. Fredberg JJ
    . Understanding the pressure cost of ventilation: why does high-frequency ventilation work? Crit Care Med 1994;22(Suppl 9):S49–S57.
    OpenUrlPubMed
  60. 60.↵
    1. Chan V,
    2. Greenough A,
    3. Giffin F
    . Disease severity and optimum mean airway pressure level on transfer to high frequency oscillation. Pediatr Pulmonol 1994;17(3):178–182.
    OpenUrlPubMed
  61. 61.↵
    1. Pillow JJ,
    2. Neil H,
    3. Wilkinson MH,
    4. Ramsden CA
    . Effect of I/E ratio on mean alveolar pressure during high-frequency oscillatory ventilation. J Appl Physiol 1999;87(1):407–414.
    OpenUrlAbstract/FREE Full Text
  62. 62.↵
    1. Pillow JJ,
    2. Sly PD,
    3. Hantos Z,
    4. Bates JH
    . Dependence of intrapulmonary pressure amplitudes on respiratory mechanics during high-frequency oscillatory ventilation in preterm lambs. Pediatr Res 2002;52(4):538–544.
    OpenUrlCrossRefPubMed
  63. 63.↵
    1. Muellenbach RM,
    2. Kredel M,
    3. Zollhoefer B,
    4. Wunder C,
    5. Roewer N,
    6. Brederlau J
    . Sustained inflation and incremental mean airway pressure trial during conventional and high-frequency oscillatory ventilation in a large porcine model of acute respiratory distress syndrome. BMC Anesthesiol 2006;6:8.
    OpenUrlCrossRefPubMed
  64. 64.↵
    1. Kneyber MC,
    2. Plotz FB,
    3. Sibarani-Ponsen RD,
    4. Markhorst DG
    . High-frequency oscillatory ventilation (HFOV) facilitates CO2 elimination in small airway disease: the open airway concept. Respir Med 2005;99(11):1459–1461.
    OpenUrlPubMed
  65. 65.↵
    1. van Genderingen HR,
    2. Versprille A,
    3. Leenhoven T,
    4. Markhorst DG,
    5. van Vught AJ,
    6. Heethaar RM
    . Reduction of oscillatory pressure along the endotracheal tube is indicative for maximal respiratory compliance during high-frequency oscillatory ventilation: a mathematical model study. Pediatr Pulmonol 2001;31(6):458–463.
    OpenUrlCrossRefPubMed
  66. 66.↵
    1. Scalfaro P,
    2. Pillow JJ,
    3. Sly PD,
    4. Cotting J
    . Reliable tidal volume estimates at the airway opening with an infant monitor during high-frequency oscillatory ventilation. Crit Care Med 2001;29(10):1925–1930.
    OpenUrlCrossRefPubMed
  67. 67.↵
    1. Hamel DS,
    2. Katz AL,
    3. Craig DM,
    4. Davies JD,
    5. Cheifetz IM
    . Carbon dioxide elimination and gas displacement vary with piston position during high-frequency oscillatory ventilation. Respir Care 2005;50(3):361–366.
    OpenUrlAbstract/FREE Full Text
  68. 68.↵
    1. Gavriely N,
    2. Solway J,
    3. Loring SH,
    4. Butler JP,
    5. Slutsky AS,
    6. Drazen JM
    . Pressure-flow relationships of endotracheal tubes during high-frequency ventilation. J Appl Physiol 1985;59(1):3–11.
    OpenUrlAbstract/FREE Full Text
  69. 69.↵
    1. Hager DN,
    2. Fessler HE,
    3. Kaczka DW,
    4. Shanholtz CB,
    5. Fuld MK,
    6. Simon BA,
    7. et al
    . Tidal volume delivery during high-frequency oscillatory ventilation in adults with acute respiratory distress syndrome. Crit Care Med 2007;35(6):1522–1529.
    OpenUrlCrossRefPubMed
  70. 70.↵
    1. Niederer PF,
    2. Leuthold R,
    3. Bush EH,
    4. Spahn DR,
    5. Schmid ER
    . High-frequency ventilation: oscillatory dynamics. Crit Care Med 1994;22(Suppl 9):S58–S65.
    OpenUrlPubMed
  71. 71.↵
    1. Hirao O,
    2. Iguchi N,
    3. Uchiyama A,
    4. Mashimo T,
    5. Nishimura M,
    6. Fujino Y
    . Influence of endotracheal tube bore on tidal volume during high frequency oscillatory ventilation: a model lung study. Med Sci Monit 2009;15(1):MT1–MT4.
    OpenUrlPubMed
  72. 72.↵
    1. Bauer K,
    2. Brucker C
    . The role of ventilation frequency in airway reopening. J Biomech 2009;29;42(8):1108–1113.
    OpenUrl
  73. 73.↵
    1. Tsuzaki K,
    2. Hales CA,
    3. Strieder DJ,
    4. Venegas JG
    . Regional lung mechanics and gas transport in lungs with inhomogeneous compliance. J Appl Physiol 1993;75(1):206–216.
    OpenUrlAbstract/FREE Full Text
  74. 74.↵
    1. Custer JW,
    2. Ahmed A,
    3. Kaczka DW,
    4. Mulraeany DG,
    5. Simon BA,
    6. Easley RB
    . In vitro performance comparison of the Sensormedics 3100A and B high-frequency oscillatory ventilators. Pediatr Crit Care Med 2010;12(4):e176–e180.
    OpenUrl
  75. 75.↵
    1. Meyer J,
    2. Cox PN,
    3. McKerlie C,
    4. Bienzle D
    . Protective strategies of high-frequency oscillatory ventilation in a rabbit model. Pediatr Res 2006;60(4):401–406.
    OpenUrlCrossRefPubMed
  76. 76.↵
    1. Van de Kieft M,
    2. Dorsey D,
    3. Morison D,
    4. Bravo L,
    5. Venticinque S,
    6. Derdak S
    . High-frequency oscillatory ventilation: lessons learned from mechanical test lung models. Crit Care Med 2005;33(Suppl 3):S142–S147.
    OpenUrlPubMed
  77. 77.↵
    1. Fessler HE,
    2. Hager DN,
    3. Brower RG
    . Feasibility of very high-frequency ventilation in adults with acute respiratory distress syndrome. Crit Care Med 2008;36(4):1043–1048.
    OpenUrlCrossRefPubMed
  78. 78.↵
    1. Bryan AC,
    2. Slutsky AS
    . Long volume during high frequency oscillation. Am Rev Respir Dis 1986;133(5):928–930.
    OpenUrlPubMed
  79. 79.↵
    1. Tobias JD
    . Transcutaneous carbon dioxide monitoring in infants and children. Paediatr Anaesth 2009;19(5):434–444.
    OpenUrlCrossRefPubMed
  80. 80.↵
    1. van Genderingen HR,
    2. van Vught AJ,
    3. Jansen JR
    . Regional lung volume during high-frequency oscillatory ventilation by electrical impedance tomography. Crit Care Med 2004;32(3):787–794.
    OpenUrlPubMed
  81. 81.↵
    1. Habib RH,
    2. Pyon KH,
    3. Courtney SE
    . Optimal high-frequency oscillatory ventilation settings by nonlinear lung mechanics analysis. Am J Respir Crit Care Med 2002;166(7):950–953.
    OpenUrlCrossRefPubMed
  82. 82.↵
    1. Markhorst DG,
    2. Jansen JR,
    3. van Vught AJ,
    4. van Genderingen HR
    . Breath-to-breath analysis of abdominal and rib cage motion in surfactant-depleted piglets during high-frequency oscillatory ventilation. Intensive Care Med 2005;31(3):424–430.
    OpenUrlPubMed
  83. 83.↵
    1. van Genderingen HR,
    2. van Vught JA,
    3. Jansen JR,
    4. Duval EL,
    5. Markhorst DG,
    6. Versprille A
    . Oxygenation index, an indicator of optimal distending pressure during high-frequency oscillatory ventilation? Intensive Care Med 2002;28(8):1151–1156.
    OpenUrlCrossRefPubMed
  84. 84.↵
    1. van Genderingen HR,
    2. van Vught AJ,
    3. Duval EL,
    4. Markhorst DG,
    5. Jansen JR
    . Attenuation of pressure swings along the endotracheal tube is indicative of optimal distending pressure during high-frequency oscillatory ventilation in a model of acute lung injury. Pediatr Pulmonol 2002;33(6):429–436.
    OpenUrlCrossRefPubMed
  85. 85.↵
    1. van HM,
    2. Roubik K,
    3. Kopelent V,
    4. Plotz FB,
    5. Markhorst DG
    . Demand flow facilitates spontaneous breathing during high-frequency oscillatory ventilation in a pig model. Crit Care Med 2009;37(3):1068–1073.
    OpenUrlPubMed
  86. 86.↵
    1. van HM,
    2. Roubik K,
    3. Kopelent V,
    4. Kneyber MC,
    5. Markhorst DG
    . Spontaneous breathing during high-frequency oscillatory ventilation improves regional lung characteristics in experimental lung injury. Acta Anaesthesiol Scand 2010;54(10):1248–1256.
    OpenUrlCrossRefPubMed
  87. 87.↵
    1. van Heerde M,
    2. van Genderingen HR,
    3. Leenhoven T,
    4. Roubik K,
    5. Plotz FB,
    6. Markhorst DG
    . Imposed work of breathing during high-frequency oscillatory ventilation: a bench study. Crit Care 2006;10(1):R23.
    OpenUrlCrossRefPubMed
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