Secondary Logo

Journal Logo


Flow-controlled ventilation with the Evone ventilator and Tritube versus volume-controlled ventilation

A clinical cross-over pilot study describing oxygenation, ventilation and haemodynamic variables

Sebrechts, Tom; Morrison, Stuart G.; Schepens, Tom; Saldien, Vera

Author Information
European Journal of Anaesthesiology: February 2021 - Volume 38 - Issue 2 - p 209-211
doi: 10.1097/EJA.0000000000001326


The Evone ventilator (Ventinova, Eindhoven, The Netherlands) produces pulmonary ventilation at a constant flow during inspiration and expiration, between preset end-expiratory and peak airway pressures.1 Tidal volumes depend on respiratory system compliance, but unlike volume-controlled ventilation (VCV), expiration is active, due to an internal Bernoulli Effect, producing a linear decrease in pulmonary airway pressure. Until recently, this so-called flow-controlled ventilation (FCV) has only been possible through narrow-bore tubes, for example Tritube (OD 4.4 mm, Ventinova).2 Preliminary animal studies suggested that systemic arterial oxygenation is improved by flow-controlled ventilation when compared with VCV.3,4 We therefore conducted a clinical pilot study, with the aim of collecting data to aid statistical planning and design for further research. Arterial blood gas values, respiratory variables and haemodynamic data were examined.

Following approval by the Ethics Committee of Antwerp University Hospital (EC 18/45/512, 10 December 2018, chairman Patrick Cras), the study was registered at (NCT03873233). All patients provided written informed consent. Eight adults undergoing nonvascular intracranial surgery in the supine position, were enrolled between 15 March and 6 August 2019. Exclusion criteria were BMI ≥ 30 kg m−2, respiratory disease, severe cardiovascular disease (NHYA class ≥3), nonsinus rhythm, poorly controlled hypertension, allergy for the anaesthetic agents used, pregnancy and emergency procedures. A randomised cross-over design was used with all patients receiving both ventilatory modes for 15 min before surgery. A computer-generated list was used for randomisation (R, v 3.4.4, R Foundation, Vienna, Austria) – VCV-FCV or FCV-VCV.

Intravenous anaesthesia was provided with propofol and remifentanil infusions, following placement of standard monitors and pre-oxygenation. Rocuronium was administered to maintain a train of four count = 0, and noradrenaline was infused to maintain haemodynamic stability. Following tracheal intubation with a cuffed tracheal tube (ID 8.0), baseline VCV was established: FIO2 0.3, I:E ratio 1 : 1, zero inspiratory pause, end-expiratory pressure +5 cm H2O, tidal volume 6 to 7 ml kg-1 ideal body weight and respiratory frequency adjusted for a PETCO2 of 38 to 42 mmHg (Aisys Carestation; GE Healthcare, Chicago, Illinois, USA). The long inspiratory time was chosen to mimic Evone ventilation. A radial arterial catheter was inter-faced via a FloTrac sensor to the EV1000 monitor (Edwards Lifesciences, Irvine, California, USA) for continuous haemodynamic monitoring.

Pre-oxygenation with 100% O2 for 3 min, during baseline VCV, was followed by lung recruitment (see Table, Supplemental Digital Content 1,, which provides details). Disconnecting the breathing system for 1 min then allowed passage of a small-bore Tritube through the tracheal tube for flow-controlled ventilation: FIO2 0.3, I:E ratio 1 : 1, end-expiratory pressure +5 cmH2O, peak inspiratory pressure adjusted for a tidal volume of 6 to 7 ml kg-1 ideal body weight and flow adjusted, aiming for a PETCO2 of 38 to 42 mmHg. When the study sequence was VCV-FCV, ventilation continued with baseline settings, after a sham disconnection. Following data collection, ventilation modes were switched (Fig. 1). As the recruitment manoeuvre was only possible with the Aisys Carestation ventilator, this occurred before disconnection (VCV-FCV) or after reconnection (FCV-VCV).

Fig. 1:
Summary of the study protocol for the two ventilatory modes. FCV, flow-controlled ventilation (Evone ventilator); RM, recruitment manoeuvre (Aisys Carestation); VCV, volume-controlled ventilation (Aisys Carestation).

Results are expressed as median [range] and statistical comparisons made using the Wilcoxon signed rank test (R v 3.4.4).

The mean ± SD age and BMI of the patients (two men, six women) was 52 ± 10 years and 24.5 ± 3.1 kg m−2, respectively. Individual patient characteristics are summarised in the table (Supplemental Digital Content 2, Anaesthetic, respiratory and haemodynamic data are summarised in Table 1.

Table 1 - Anaesthetic, respiratory and haemodynamic variables
TCI propofol [μg ml−1] 3.5 [3.2 to 3.8] 3.5 [3.3 to 3.8] 1.00
Remifentanil [μg kg−1 min−1] 0.11 [0.10 to 0.15] 0.11 [0.10 to 0.15] 1.00
Noradrenaline [μg kg−1 min−1] 0.03 [0.02 to 0.04] 0.03 [0.02 to 0.04] 1.00
Respiratory frequency [min−1] 11 [9 to 16] 13 [9 to 19] 0.033
Tidal volume per IBW [ml kg−1] 6.5 [5.9 to 7.6] 6.1 [4.4 to 7.3] 0.036
Minute volume [l min−1] 5.1 [3.9 to 7.1] 5.3 [4.0 to 7.1] 0.078
PETCO2 [mmHg] 40 [36 to 41] 39 [35 to 42] 0.67
pH 7.40 [7.36 to 7.43] 7.45 [7.37 to 7.47] 0.014
PaCO2 [mmHg] 43 [38 to 47] 38 [32 to 41] 0.014
PaO2 [mmHg] 129 [101 to 144] 142 [82 to 152] 0.64
Heart rate [min−1] 62 [53 to 72] 63 [51 to 82] 0.18
Mean arterial pressure [mmHg] 81 [60 to 103] 93 [59 to 101] 0.042
Cardiac index [l min−1 m−2] 2.5 [1.7 to 4.0] 2.5 [1.9 to 4.1] 0.93
Data are median [range]. Wilcoxon signed rank test (n = 8).IBW, ideal body weight; PETCO2, end-tidal CO2 partial pressure; TCI, target-controlled infusion.

Our results indicate no difference in PaO2 (VCV: 129 [101 to 144] mmHg versus FCV: 142 [82 to 152] mmHg, P = 0.64). This may reflect the small sample size, as the number of patients included is insufficient to allow sound statistical comparison between VCV and flow-controlled ventilation. Although differences in the techniques need to be judged on the basis of clinical relevance, the results can be used to calculate sample size for future studies. On the basis of the variability and correlation between measurements in the same individual, 21 patients per group would be required to show a 15% difference in PaO2, with 80% power at a significance level of 0.05. Assuming a drop-out/missing data rate of 10%, 46 patients in total would be necessary for a parallel group design.

Lung recruitment would have influenced lung aeration during the short study time and may have masked any intrinsic difference between the ventilatory modes. Another limitation is the timing of the recruitment and disconnection manoeuvres. In all patients, recruitment was followed by disconnection before flow-controlled ventilation, whereas 50% of patients in the VCV group were recruited after reconnection. Therefore, disconnection-related atelectasis may have reduced oxygenation to a greater extent in the flow-controlled ventilation group. Furthermore, unlike previous studies, we tried to replicate inspiratory flow-controlled ventilation conditions during VCV by choosing an I:E ratio of 1 : 1 with no inspiratory pause. Even if expiratory flow returned to zero with each breath, we cannot rule out the possibility of auto-PEEP in the VCV group. A recent clinical study demonstrated improved oxygenation with flow-controlled ventilation after short-term ventilation, but this was in comparison with standard VCV using an I:E ratio of 1 : 2 and no recruitment.5 The authors attributed their results to higher mean intratracheal pressures and reduced lung atelectasis with flow-controlled ventilation.

During VCV, increased respiratory frequency limits alveolar ventilation if expiratory time becomes too short. Our ventilation end-point (PETCO2), as measured by the respective ventilators, was similar in both groups, although these technical differences may invalidate direct comparison. However, the lower PaCO2 values and similar minute volumes during flow-controlled ventilation suggests that this technique removes CO2 more efficiently [VCV: 43 [38 to 47] mmHg versus FCV: 38 [32 to 41], P = 0.014]. Lower flow rates during flow-controlled ventilation may have resulted in similar PaCO2 values, associated with lower minute volumes and respiratory frequencies. This would correspond with the findings of Weber et al.5

Dosing of anaesthetic agents, as well as noradrenaline, was similar in both groups. As haemodynamic variables were also comparable between the groups, clinically relevant differences in cardiovascular function between flow-controlled ventilation and VCV seem unlikely. However, further studies comparing flow-controlled ventilation and VCV over longer periods are warranted and our results can facilitate their design.

Acknowledgements relating to this article

Assistance with the study: We would like to thank Dr. Kristien Wouters for her statistical assistance with this study.

Financial support and sponsorship: This work was supported by the Department of Anaesthesiology, Antwerp University Hospital.

Conflicts of interest: None.


1. Schmidt J, Günther F, Weber J, et al. Flow-controlled ventilation during ear, nose and throat surgery: a prospective observational study. Eur J Anaesthesiol 2019; 36:327–334.
2. Kristensen MS, de Wolf MWP, Rasmussen LS. Ventilation via the 2.4 mm internal diameter Tritube( with cuff - new possibilities in airway management. Acta Anaesthesiol Scand 2017; 61:580–589.
3. Schmidt J, Wenzel C, Mahn M, et al. Improved lung recruitment and oxygenation during mandatory ventilation with a new expiratory ventilation assistance device: a controlled interventional trial in healthy pigs. Eur J Anaesthesiol 2018; 35:736–744.
4. Schmidt J, Wenzel C, Spassov S, et al. Flow-controlled ventilation attenuates lung injury in a porcine model of acute respiratory distress syndrome: a preclinical randomized controlled study. Crit Care Med 2019; 48:e241–e248.
5. Weber J, Schmidt J, Straka L, et al. Flow-controlled ventilation improves gas exchange in lung-healthy patients: a randomized interventional cross-over study. Acta Anaesthesiol Scand 2020; 64:481–488.

Both Tom Sebrechts and Stuart G. Morrison participated equally in the study.

Supplemental Digital Content

Copyright © 2020 European Society of Anaesthesiology. All rights reserved.