The optimization of intraoperative ventilation is important in patients under general
anesthesia, when physiologic breathing is replaced by non- physiologic artificial
ventilation. Especially in patients undergoing robot- assisted laparoscopic surgery,
intraoperative ventilation can be challenging, because of changes in compliance of the
respiratory system and associated problems in gas exchange, due to the pneumoperitoneum
and often extreme body positioning. Intraoperative lung-protection strategies have
steadily improved in recent years to reduce complications from mechanical ventilation,
but postoperative pulmonary complications remain a risk factor for increased morbidity
and mortality. This pilot trial will be conducted to evaluate the safety and feasibility
of intraoperative FCV during robot-assisted laparoscopic abdominal, urologic, or
gynecologic surgery, and will inform the design of a future trial that will test the
efficacy of intraoperative FCV compared to PCV in these patients. In an international
multicenter randomized clinical pilot trial, intraoperative flow-controlled ventilation
(FCV) will be compared with pressure-controlled ventilation (PCV) in patients scheduled
for robot-assisted laparoscopic abdominal, urologic, or gynecologic surgery. This pilot
trial is designed to test the safety and feasibility of FCV, and to inform the design of
a future trial testing the efficacy of FCV with regard to postoperative outcomes,
including postoperative pulmonary complications. The ventilation modes are conducted with
CE-marked medical devices (anesthesia ventilators or medical ventilators), however these
medical devices themselves are not under investigation. All CE-marked standard medical
devices from varied manufacturers in use at the participating study centers will be used
in full accordance with the instructions for use.
Given that ventilation strategies inherently carry certain risks, yet remain essential in
the context of general anesthesia and surgery, it is ethically justified to first conduct
a pilot trial. The potential benefits of FCV are significant and warrant investigation.
Therefore, the investigators find it appropriate to compare FCV with existing strategies
such as PCV, as the investigators anticipate meaningful improvements in patient outcomes
with minimal additional risk.
The investigators hypothesize, that FCV is a safe and feasible ventilation strategy in
patients undergoing robot-assisted laparoscopic surgery.
The primary objective of this study is to evaluate the safety of intraoperative FCV in
patients undergoing robot-assisted laparoscopic surgery, with a focus on: gas exchange,
including both oxygenation and decarboxylation; minute ventilation, during all phases of
intraoperative ventilation; key ventilator settings and ventilation parameters;
respiratory complications, including pneumothorax and hemodynamic complications,
including hypotension and arrhythmias.
The secondary objectives are to assess the feasibility of intraoperative FCV and the
study protocol in patients undergoing robot-assisted laparoscopic surgery, including an
evaluation of the use of FCV. The need for rescue ventilation strategies, i.e., whether
FCV (as well as PCV) can be used during all phases of intraoperative ventilation; and
compliance with the study protocol, omissions in the eCRF, and the feasibility of
follow-up, i.e., how well each PPC can be captured.
The explorative secondary objective concerns the primary endpoint of a future randomized
clinical trial testing the efficacy of FCV, i.e., its effects on postoperative pulmonary
complications. Herein the investigators will determine the exact incidence, and define
the effect size of the intervention.
The primary endpoint of this pilot trial is a set of safety parameters for FCV,
including: gas exchange: (hourly) PaO2, PaCO2, SpO2 and end-tidal CO2; minute
ventilation: (hourly) total minute volume; ventilator settings and ventilation
parameters: (hourly) tidal volume, respiratory rate, PEEP and PIP, FiO2, driving pressure
and mechanical power of ventilation, and respiratory system compliance and elastance;
intraoperative respiratory complications: (any time point) pneumothorax. intraoperative
hemodynamic complications: (any time point) occurrence of hypotension, defined as a mean
arterial pressure (MAP) below 65 mm Hg, lasting longer than 1 minute (not related to the
surgical course or anesthetic interventions, according to the attending
anesthesiologist); and (hourly) vasopressor support and dose; and (any time point)
occurrence of arrhythmias, and intervention for arrhythmias.
Secondary endpoints focus on evaluating the feasibility of intraoperative FCV and the
study protocol, including: ventilation protocol adherence; and study protocol adherence;
and completeness of the eCRF and follow-up of PPCs.
The explorative secondary endpoint will compare FCV with PCV ventilation with respect to
predefined and previously used postoperative (pulmonary) complications in the first seven
postoperative days, including: mild respiratory failure, defined as the occurrence of one
or multiple of the following conditions after more than two days postoperatively: the
occurrence of oxygen saturation (SpO2) < 90% or partial pressure of oxygen in the
arterial blood (PaO2) < 7.9 kPa (or < 50 mm Hg) on room air, but responding to
supplemental oxygen; or a sudden increase in supplemental oxygen requirement to maintain
adequate saturation (SpO2 > 90%) in patients receiving routine postoperative oxygen
therapy; or any level of supplemental oxygen; severe respiratory failure, defined as need
for noninvasive or invasive mechanical ventilation, or a PaO2 < 60 mm Hg (or < 7.9 kPa)
or SpO2 <90% despite supplemental oxygen in spontaneously breathing patients; dyspnea,
defined as the patient's perception of an uncomfortable abnormal awareness of breathing
or respiratory limitation (shortness of breath, inability to take a deep breath, or chest
tightness); productive cough, defined as cough that produces sputum or mucus;
bronchospasm, defined as newly detected expiratory wheezing treated with bronchodilators;
suspected pulmonary infection, defined as receiving antibiotics and meeting at least one
of the following criteria: new or changed sputum, new or changed lung opacities on chest
radiograph when clinically indicated, tympanic temperature > 38.3°C, white blood cell
count > 12,000/μL; pulmonary infiltrate, defined as any unilateral or bilateral
infiltrates on chest radiography; aspiration pneumonitis, defined as respiratory failure
after the inhalation of regurgitated gastric contents; atelectasis, defined as lung
opacification with shift of the mediastinum, hilum, or hemidiaphragm towards the affected
area, and compensatory overinflation in the adjacent non-atelectatic lung on chest
radiography; ARDS (according to the new global definition of ARDS); pleural effusion,
defined as blunting of the costophrenic angle, loss of the sharp silhouette of the
ipsilateral hemidiaphragm in upright position, evidence of displacement of adjacent
anatomical structures or (in supine position) a hazy opacity in one hemithorax with
preserved vascular shadows on chest radiography; pneumothorax, defined as air in the
pleural space with no vascular bed surrounding the visceral pleura on chest radiography;
cardiopulmonary edema, defined as clinical signs of congestion, including dyspnea, edema,
rales and jugular venous distention, with the chest radiograph demonstrating increase in
vascular markings and diffuse alveolar interstitial infiltrates; and death in hospital
(defined as death from any cause during hospitalization)
The patient population will be selected by the following criteria:
Inclusion criteria: aged ≥ 18 years; and scheduled for elective robot-assisted
laparoscopic abdominal, urologic or gynecologic surgery in supine or Trendelenburg
position; AND with an increased risk of PPC, according to the ARISCAT risk score (≥ 26
points); OR the combination of age > 40 years, scheduled surgery lasting > 2 hours and
planned to receive an intra-arterial catheter for blood pressure monitoring during the
surgery; and able to give written informed consent.
Exclusion criteria: body weight < 40 kg; ASA Physical Status Classification System score
IV - VI; previous enrolment in the current study; being the study investigator of this
study, his/her family members, employees and other dependent persons; known pregnancy or
a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or
lactating; or no written informed consent.
The sample size calculation is based on the following assumption:
To estimate the appropriate sample size for this pilot trial, the investigators
considered both safety and feasibility across multiple centers. Assuming a target of 10
to 15 participants per randomization group in each of the four centers, the total sample
size would range from 80 to 120 participants (4 centers × 10-15 participants × 2
randomization groups). For practical purposes and to ensure a robust assessment of the
trial's objectives, the investigators have selected a total sample size of 100
participants. This number balances logistical feasibility with the need for adequate data
to assess safety outcomes.
The statistical analysis will be performed accordingly. Balance between study groups will
be ensured by randomization and an appropriate sample size. Baseline characteristics will
be assessed by appropriate tests to demonstrate balance between groups. The investigators
will primarily perform an intention to treat analysis, and will add a per protocol
analysis as sensitivity analysis. Tests for normal distribution of the data will include
QQ-plot assessments. Potential differences between the two groups in the distribution of
dichotomous data are analyzed by chi-square statistics.
Continuous data are analyzed by parametric (t-test, ANOVA) or non-parametric
(Mann-Whitney U) test for unpaired comparison as appropriate. A sub-analysis related to
sex, age, type of surgery will be performed for all study endpoints.
Datasets to be analyzed, analysis populations All participants will be analyzed in terms
of the respective endpoint parameters. The data of patients who leave the study
prematurely are analyzed independently of the completion of the study (intention to
treat). A subgroup analysis with respect to sex, age, type of surgery will be performed
for all study endpoints.