Ethics, consent and permission
The study was approved by the Ethics Committee of the University Medical Centre of
Freiburg (Engelbergstr. 21, 79106 Freiburg, Germany, Ethical Committee N° 179/18)
on 29th March 2018 (Chairperson Prof. Dr. R. Korinthenberg) and registered at the German
Register for Clinical Trials (DRKS00014925). Please note that this study adheres to
Study design and patient population
In order to cope with potential interindividual variability, the study was designed
as a randomized controlled interventional cross-over trial. After obtaining written
informed consent, we studied twenty-three obese patients with body mass index (BMI)
≥ 30 kg∙m-2. Patients eligible for enrolment were patients with physical status ASA ≤ III, undergoing
elective bariatric surgery. Exclusion criteria were ASA physical status >III, age
< 18 years, pregnancy, emergency procedure, cardiac pacemaker and other active implants,
chronic obstructive pulmonary disease classified as GOLD stage > II and refusal of
participation. The trial was conducted at the University Medical Center Freiburg,
Germany. Participants were enrolled and assigned by a study related anesthesiologist.
Data were collected at the University Medical Center of Freiburg, Germany.
After obtaining written informed consent, 23 patients were included in the study.
After primary recruitment and preoperative evaluation, the patients received routine
monitoring (electrocardiography, SpO2, noninvasive blood pressure measurement; Infinity Delta XL, Dräger Medical, Lübeck,
Germany) and a 18-20-G intravenous catheter was established. After preoxygenation
to an fraction of expired oxygen of 0.8, the anesthesia was induced with 0.3-0.5 µg∙kg-1 predicted body weight  (PBW) iv sufentanil (Janssen-Cilag, Neuss, Germany) and
2-3 mg∙kg-1 iv propofol 1% actual body weight (ABW) (Fresenius Kabi, Bad Homburg vor der Höhe, Germany). Tracheal
intubation was facilitated with 0.6 mg∙kg-1 PBW iv rocuronium (Fresenius Kabi). If the patient required a rapid sequence induction,
neuromuscular blockage was performed by the administration of 1.0 mg∙kg-1 PBW iv rocuronium. Neuromuscular blockage was monitored with a mechanomyograph (TOFscan;
Dräger Medical). For tracheal intubation, we used tracheal tubes (TT) with low pressure
cuffs (internal diameter of 7.0-7.5 mm for women and 8.0 mm for men; Mallinckrodt
Hallo-Contour; Covidien, Neustadt an der Donau, Germany). After adequate placement
of the TT, propofol was administered continuously (between 110 and 150 µg∙kg-1∙min-1).Potential hypotension (defined as mean arterial pressure < 65 mmHg) was treated with
a continuous infusion of iv noradrenaline (0.03-0.2 µg∙kg-1∙min-1). Perioperative volume requirements were addressed with a crystalloid solution (8
ml∙kg-1∙h-1, Jonosteril; Fresenius Kabi). According to our local standard, mechanical ventilation
was started as volume-controlled baseline (BL) ventilation (Fabius Tiro, Dräger Medical)
with a tidal volume (VT) of 7 ml∙kg-1 PBW, inspiration-to-expiration (I:E) ratio of 1:2, a positive end-expiratory-pressure
(PEEP) of 9 cmH2O and ventilation frequency (VF) set to maintain an end-tidal carbon dioxide partial
pressure between 4.7 and 5.1 kPa. After 7 min of BL ventilation, all patients were
randomly allocated to one of two cross-over groups to receive ventilation sequences
either VCV-FCV or FCV-VCV for 7 min per ventilation mode. For adequate allocation,
a computer generated randomisation in blocks was used. Disclosure of the randomisation was requested right after induction of anesthesia.
A study related anesthesiologist conducted the randomisation in blocks, enrolled participants
and assigned participants to the interventions. During the study protocol, ventilation variables were kept constant as set during
the BL ventilation. To prevent from the risks of extubation and reintubation, FCV
was performed by introducing the narrow-bore tracheal tube (Tribute, Ventinova Medical
B.V.) into the standard TT. Blocking the cuff of the Tritube in the lumen of the TT
tube provided a sufficient seal. By controlling both tube’s markings, placement of
the Tritube’s tip exceeding that of the standard TT by 2-5 mm was ensured, and the
potential risk of bronchial intubation was avoided. Respiratory data were collected
from both ventilators via the respective serial communication interface and analysed
offline. Electrical impedance tomography (EIT) was performed with PulmoVista 500 (Dräger
Medical) in all patients to measure regional ventilation, changes in relative thoracic
electrical impedance during the different ventilation phases, relative end-expiratory
lung volume (ΔEELV) and to compare the expiratory decrease in intrapulmonary air [9–11].
Tritube and FCV
To perform FCV, all patient were ventilated by introducing the Tritube (Ventinova
Medical B.V.) into the standard tracheal tube (Mallinckrodt Hallo-Contour; Covidien).
The Tritube has a total of three lumens: One for ventilation, one for tracheal pressure
measurement and one for inflating/deflating the cuff. The Tritube has a length of
40 cm and an outer diameter of 4.4 mm. The ventilation lumen has a cross sectional
area of nearly 2.4 mm . To ventilate patients with FCV via this tracheal tube,
a specific ventilator is needed (Evone, Ventinova Medical B.V.). The Evone ventilator
is currently the only ventilator to enable FCV. During FCV, patients are ventilated
with a constant positive flow during inspiration and a constant negative flow during
expiration. To avoid intrinsic PEEP, the intratracheal pressure is monitored continously
via a dedicated pressure measurement lumen of the Tritube.
During FCV, the operator is able to adjust the inspiratory flow rate, I:E ratio, peak
inspiratory pressure, end-expiratory pressure and the inspiratory concentration of
oxygen. In this special ventilation mode, there is no direct way to control minute
volume via tidal volumes and/or respiratory rate. However, the respiratory rate depends
on the peak inspiratory pressure, the set (positive) end-expiratory pressure, the
set inspiratory flow rate, the I:E ratio and the patient’s lung compliance .
End points and data collection
ΔEELV was the primary endpoint of this study. We derived ΔEELV from adjusting end-expiratory impedance changes by VT and tidal impedance changes as described before [6, 9]. Secondary endpoints were
the respiratory system variables: plateau pressure (PPlat), mean tracheal pressure (Pmean), respiratory system compliance (CRS). Non-invasively collected hemodynamic variables included mean systolic blood pressure
(RRsys), mean diastolic blood pressure (RRdias), mean arterial pressure (MAP) and heart rate. To compare relative intrapulmonary
air distribution, baseline tidal impedance curves for ventral and dorsal lung areas
were determined and compared as described before [6, 10]. The differences in mean
lung volume (ΔMLV) between BL ventilation and VCV and FCV were calculated, respectively.
Further, the decrease in global thoracic electrical impedance during each ventilation
mode was separated into four equal sections (ΔEI25, ΔEI50, ΔEI75 and ΔEI100), then matched with the correlating decrease in VT and compared successively.
Pressure data from the Evone are based on direct tracheal pressure measurement via
a dedicated lumen of the Tritube. To allow for comparability of pressure data from
both ventilators, airway pressure data from the Dräger Fabius Tiro were generally
converted into tracheal pressure data by calculating the flow dependent pressure drop
across the respective TT and pointwise subtracting this value from airway pressure
. Thus all pressure data in the following refer to the respective tracheal pressure.
The datasets used and alanysed during the current study are available from the corresponding
author on request. Please note that EIT data files require large memory. A separate
data transfer service will be used to transfer EIT data files.
Sample size calculation and statistical analysis
In regard to the cross-over design (paired test conditions) and an assumed standardized
effect size of the primary endpoint of 0.7, 19 patients were required to reach a test
power of 0.8 with a desired level of significance of 0.05. To compensate for potential
incomplete data sets, 23 patients were included in the study. Lilliefors tests were
used to confirm that the assumed normal distribution cannot be rejected.
Values are presented as mean (standard deviation), unless indicated otherwise. Statistical
analysis was done using Matlab (R2014, The MathWorks Inc., Natick, MA, USA). Linear
mixed effects model analyses were performed to check for differences between the ventilation
phases using R based software (jamovi project (2018), jamovi (Version 0.9.2.3), retrieved
from https://www.jamovi.org). P < 0.05 was considered statistically significant.