- Open Access
Effect of high-frequency oscillatory ventilation on esophageal and transpulmonary pressures in moderate-to-severe acute respiratory distress syndrome
© The Author(s) 2016
Received: 4 May 2016
Accepted: 10 August 2016
Published: 30 August 2016
High-frequency oscillatory ventilation (HFOV) has not been shown to be beneficial in the management of moderate-to-severe acute respiratory distress syndrome (ARDS). There is uncertainty about the actual pressure applied into the lung during HFOV. We therefore performed a study to compare the transpulmonary pressure (P L) during conventional mechanical ventilation (CMV) and different levels of mean airway pressure (mPaw) during HFOV.
This is a prospective randomized crossover study in a university teaching hospital. An esophageal balloon catheter was used to measure esophageal pressures (Pes) at end inspiration and end expiration and to calculate P L. Measurements were taken during ventilation with CMV (CMVpre) after which patients were switched to HFOV with three 1-h different levels of mPaw set at +5, +10 and +15 cm H2O above the mean airway pressure measured during CMV. Patients were thereafter switched back to CMV (CMVpost).
Ten patients with moderate-to-severe ARDS were included. We demonstrated a linear increase in Pes and P L with the increase in mPaw during HFOV. Contrary to CMV, P L was always positive during HFOV whatever the level of mPaw applied but not associated with improvement in oxygenation. We found significant correlations between mPaw and Pes.
HFOV with high level of mPaw increases transpulmonary pressures without improvement in oxygenation.
Moderate or severe acute respiratory distress syndrome (ARDS)  is associated with substantial mortality. Use of a lung-protective strategy with low tidal volume (V t) of 6 ml/kg of predicted body weight has been associated with improved outcomes . High-frequency oscillatory ventilation (HFOV) is a non-conventional mode which has been proposed to achieve the targets of protective ventilation with very low V t  and a greater alveolar stability due to relatively constant mean airway pressure (mPaw) . However, two large recently published randomized clinical trials, OSCAR  and OSCILLATE , failed to prove any clinical benefit when HFOV was applied in adults with moderate-to-severe ARDS as compared with a strategy with low tidal volume, high positive expiratory pressure (PEEP) and limited plateau pressure (Pplat). In the latter study, side effects of HFOV were observed with more requirements for vasopressors, likely due to right ventricular failure secondary to high mPaw used [7, 8].
Another possible explanation of the lack of clinical benefit with HFOV in adults with ARDS may be due to the occurrence of pulmonary overdistension in non-dependant areas of the lung . Because mPaw during HFOV does not reflect of the real pressure applied to the alveoli , with non-predictable attenuation all along the trachea–bronchial tree, it is not possible to know the true pulmonary distending pressure. Esophageal pressure (Pes) is an approximation of the pleural pressure, and its use has shown a possible clinical benefit when PEEP was set according to the value of Pes in moderate-to-severe ARDS . Esophageal pressure measurement allows the calculation of the maximal and minimal transpulmonary pressures (P L) applied during mechanical ventilation. Data reporting P L during HFOV are scarce  and only describe the feasibility of the technique but not the comparison of range of P L occurring during the switch from CMV to an HFOV trial. Therefore, we performed a prospective study of P L determination in moderate-to-severe ARDS during and after an HFOV trial.
This is an ancillary study of a previously published study .
The study was approved by the ethics committee of the Marseille University Hospital (Comité de Protection des Personnes Sud Méditerranée, ID RCB:2008-A00077-48). Written informed consent was obtained from each patient’s next of kin. Patients admitted in the intensive care unit of a university teaching hospital during a 10-month period were screened if they met inclusion criteria: moderate-to-severe ARDS with a PaO2/FiO2 ratio ≤150 mmHg at a PEEP ≥8 cm H2O. Exclusion criteria were age <18 years, moribund status, risks associated with HFOV (head injury, pneumothorax or a chest tube in place with persistent air leak) and contraindications to the placement of a nasogastric probe. All patients were sedated and continuously paralyzed . The severity of illness was determined according to the Simplified Acute Physiologic II Score, the Sepsis-related Organ Failure Assessment Score and the Lung Injury Score [14, 15].
Tested ventilatory strategies
Esophageal and transpulmonary pressure measurements
Data are presented as mean ± SD or median (interquartile range) as required. Normality of variables was tested according the Kolmogorov–Smirnov test. Repeated-measures analysis of variance or Friedman’s test was used to evaluate the effect of time and mPaw level. The Tukey test or the Wilcoxon test was used for intergroup comparisons. Bivariate correlations with Spearman’s test for each period of ventilation were performed. All statistics and figures were performed with the SPSS 20.0 package (SPSS, Chicago, IL, USA).
Among the 16 patients included in the princeps study , ten patients were monitored by the esophageal catheter and were used in this study.
Patient characteristics and respiratory data at inclusion
63 ± 15
Gender (male), n (%)
Body mass index (kg/m2)
29 ± 8
SAPS II at the admission
49 ± 23
SOFA at the admission
11 ± 3
ICU mortality, n (%)
Direct lung injury, n (%)
CT scan or X-ray presentation (lobar/diffuse), n
PaO2/FiO2 ratio (mmHg)
131 ± 51
0.74 ± 0.17
46 ± 7
PEEP (cm H2O)
13 ± 3
V t (mL)/(mL/kg/IPBW)
382 ± 41/6.6 ± 0.7
Respiratory rate (cycle/min)
26 ± 4
Plateau airway pressure (cm H2O)
24 ± 4
Driving pressure (cm H2O)
12 ± 3
mPaw (cm H2O)
18 ± 3
17 ± 9
Lung Injury Score at the inclusion
3.0 ± 0.5
Time from ARDS to inclusion (d)
0 ± 0.5
Gas exchanges and respiratory mechanics
HFO + 5
HFO + 10
HFO + 15
p value time
mPaw (cm of H2O)
18 ± 4a,b,c
23 ± 4b,c,d,e
28 ± 4a,c,d,e
33 ± 4a,b,d,e
17 ± 4a,b,c
PaO2/inspired O2 fraction (mmHg)
131 ± 51
132 ± 56
125 ± 23
138 ± 49
139 ± 34
Inspired O2 fraction
74 ± 17
71 ± 16
72 ± 16
77 ± 18
67 ± 10d
7.29 ± 0.04
7.31 ± 0.09
7.31 ± 0.01
7.29 ± 0.1
7.32 ± 0.06
46 ± 7
47 ± 12
46 ± 14
46 ± 9
42 ± 7
PEEP (cm of H2O)
13 ± 3
12 ± 3
V t (ml/kg)
6.6 ± 0.7
6.7 ± 0.8
Plateau airway pressure (cm of H2O)
24.5 ± 4
23.5 ± 4
Driving pressure (cm of H2O)
11.8 ± 3.4
11.5 ± 3.3
Power of oscillations, %
73 ± 23
79 ± 29
81 ± 24
Respiratory rate (cycle/min)
26 ± 4
25 ± 6
Oscillatory frequency (Hz)
4.8 ± 1
4.7 ± 0.7
4.6 ± 1
Inspiratory esophageal pressure
15 [11.5; 21.2]
14 [10.2; 17.2]
Expiratory esophageal pressure
12.5 [5.1; 13.5]
9.1 [5.4; 13.5]
Mean esophageal pressure (cm of H2O)
12.4 [10.6; 16.7]b,c
16.7 [12.5; 18.7]a,c
19.1 [16.7; 23.3]a,b
Inspiratory P L (cm of H2O)
8.1 [5.7; 12.8]
11.8 [5; 12.1]
Expiratory P L (cm of H2O)
−1 [−3; + 0.7)
+3.5 [−3; + 6]
Mean P L (cm of H2O)
10.5 [7.3; 13.8]c
13.1 [9.2; 14.7]
14 [11.5; 16.3]a
Respiratory system elastance (cm of H2O/L)
31.2 ± 9.7
29.9 ± 8
Chest wall elastance (cm of H2O/L)
15.7 ± 6
11.1 ± 4.5
Pulmonary elastance (cm of H2O/L)
15.9. ± 11
18.9 ± 6
During HFO, mPaw was correlated with Pesmean at HFO + 5 and HFO +15 periods (respectively, ρ = 0.71, p = 0.02 and ρ = 0.84, p = 0.02) but at no time with P Lmean.
The present study assessing the use of esophageal pressure measurements in patient with moderate-to-severe ARDS on whom a trial of HFOV is performed demonstrates (1) a linear increase in transpulmonary pressures with the increase in mPaw during HFOV, (2) a minimal transpulmonary pressure which was always >0 during HFOV and (3) a correlation between mean esophageal pressure and mPaw.
For decades, HFOV has been used for respiratory failure in both adults and children who were inadequately responsive to conventional mechanical ventilation. However, recently the results of the OSCAR  and OSCILLATE  studies performed on adults have not shown benefit to HFOV over conventional ventilation. A recent study in the pediatric population has also shown equivocal results with HFOV . Indeed, positive studies on HFOV are limited [16, 19] and predate the era of low tidal volume conventional mechanical ventilation. During HFOV, there is uncertainty about the real pressure that is applied to the alveoli and therefore the distending pressure applied into the lung. Henderson et al.  have previously described the use of esophageal manometry to measure P L during HFOV. With a mean airway pressure of 27 ± 5 cm H2O during HFOV, they measured a mean esophageal pressure of 14 ± 4 cm H2O and computed a mean P L of 18 ± 4 cm H2O. These data are consistent with the present results, namely a mPaw of 28 ± 4 cm H2O, results in a median of 16.7 IQR [12.5; 18.7] cm H2O range of Pes and a median of 13.1 IQR [9.2; 14.7] cm H2O range of P L. The safe range of P L during HFO is not known. However, during conventional mechanical ventilation for ARDS, a P L > 27 cm H2O is associated with an unacceptably high level of strain . The P L value recorded during HFO remains below this threshold whatever the level of mPaw.
One interesting result is the correlation between mPaw and esophageal pressure that we obtained; the more mPaw is set, the more Pes is measured. In clinical practice, levels of mPaw in the OSCAR and OSCILLATE trials [5, 6] were not exactly the same. During the first 2 days of the studies, mPaw was set at 5 cm H2O higher in the Canadian trial than in the UK trial. These differences could have led to more pulmonary overdistension and side effects that could explain the deleterious outcomes observed with HFOV in the OSCILLATE trial.
An ongoing study, the EPOCH study , which aim is to compare a strategy of preventing atelectrauma with a P L of 0 cm H2O at end expiration to a strategy of lung recruitment to target P L of 15 cm H2O at end-inspiratory volume in a crossover design either with CMV and either with HFOV will clarify the protective or deleterious roles of HFOV as compared to CMV.
First, as measurements of esophageal pressure could not be taken in static conditions during HFO periods, we cannot rule out a possible bias of measurements due to cardiac artifacts. However, the use of mean esophageal pressure reduces this bias. Second, during HFOV, due to the lack of V t monitoring, we use the calculation of P L derived from Pes measurements  and not the elastance-derived measurements of P L  which could lead to different results . Indeed, experimental data have shown that although recorded value of Pes is a quite accurate approximation of measured pleural pressure in the middle part of the lungs, Pes can overestimate or underestimate the value of pleural pressure whether in the non-dependant part and whether in the dependant part of the lungs . The more convincing results are that the variations of Peso reflect those in pleural pressure whatever the parts of the lung . There is still a matter of controversy on the use of the former or the latter method. A prospective ongoing study could bring a response to the clinical utility of the method used . Third, because we have not performed the registration of airway pressure during HFO, we cannot exclude negative P L during the active expiratory phase, and further studies are needed to conclude. And fourth, from a technical point of view, we also cannot exclude that larger inflation volume as demonstrated by Mojoli et al.  could have led to different results. However, our study precedes the one from Mojoli, and we used the volume and the proceeding recommended by the manufacturer.
We cannot speculate whether lower mPaw during HFOV, the same range as recorded in CMV, could lead to lower esophageal and transpulmonary pressures recorded. A level of <+10 cm H2O of mPaw during HFO does not increase significantly Peso and P L. Only a level of ≥+15 cm H2O of mPaw increases significantly both Peso and P L.
The use of high mean airway pressures during HFOV leads to increase in transpulmonary pressures. Contrary to CMV, during HFOV, transpulmonary pressure remains always positive.
CG, JMF and LP designed the study. CG and JMF coordinated the study. CG, JMF, SH, AR and LP were responsible for patient enrolment and measurements of esophageal pressures. CG and JMF performed statistical analysis. CG, JMF, DT and LP analysed the data and wrote the manuscript. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
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