Influence of Inspiratory Pause on Ventilatory Efficiency in Robotic Surgery. A Prospective Paired Study.

April 2, 2024 updated by: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

Influence of Inspiratory Pause on Ventilatory Efficiency and Tidal Volume Distribution in Patients Undergoing Robotic Prostate Surgery and Ventilated With an Individualized Open Lung Approach. A Prospective Paired Study.

The investigators aim to determine if the modification of the end inspiratory pause (EIP) during mechanical ventilation adds benefit when applied to patients undergoing robotic surgery and who are ventilated under an individualized open lung approach (iOLA) strategy. The EIP is an adjustable parameter of volume controlled ventilation modes usually set as a percentage of the total inspiratory time. It represents the phase comprised between the moment in which the volume programmed in the ventilator has already been administered (which marks the end of the inspiratory flow), and the opening of the expiratory valve (which marks the beginning of expiration).

The investigators will study whether modifications of the EIP produce variations in the "quantity" of the lung that participates in gas exchange (respiratory volume). To do so, the investigators will sequentially apply different EIP to participants (paired study). The investigators´ hypothesis is that increasing the EIP up to a level, may diminish the lung volume that does not participate in breathing (the physiological dead space- VDphys), thereby increasing the respiratory volume. To note: the VDphys includes the "conduction" volume, that represented by trachea, bronchi, et cetera, which is in charge of driving the "air" towards the respiratory zones, and the alveolar dead space (those zones of the respiratory volume that due to different reasons do not directly participate in gas exchange: alveoli ventilated but not perfused, areas of overdistension, etc. The investigators will measure dead volumes by mean of specific non-invasive monitoring (volumetric capnography) coupled to the anesthesia workstation, and the mechanics of lung and the distribution of the gas within it by means of electric impedance tomography, a non-invasive technique showing continuous images of patient's lung. The estimation of the respiratory volume will help the investigators to more precisely adjust the amount of oxygen and anesthetic gases that must be administered in function of patients´ gases consumption, a calculated parameter that is function of the respiratory volume and that will also be tested during the study. The investigators will also accurately measure patient oxygenation by means of arterial blood samples extracted from a radial artery catheter. Apart from sequential modifications in the EIP, the ventilation strategy applied to patients will be that used in the investigators´ usual practice (described below).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Introduction

Mechanical ventilation (MV) during general anesthesia entails some adverse effects that cannot be completely avoided. In recent years, pulmonary protective ventilation (PPV) strategies, based on the use of a low tidal volume (TV) with the intention of reducing the biological trauma associated to MV, are gaining prominence in surgical and intensive care patients. A tailored open-lung approach (tOLA) has recently emerged as one of these PPV strategies. It combines the use of alveolar recruitment manoeuvers (ARM), aiming to "open" collapsed areas of the lung, with the application of individualised positive end expiratory pressure (PEEP) with the objective of avoiding the re-collapse of those areas during expiration. The rationale supporting OLA strategies assumes that achieving more homogeneous alveolar ventilation by preventing atelectasis, while avoiding alveolar overdistension, leads to a more efficient gas distribution and exchange. This allows less traumatic ventilation and reduces the inflammatory response. The use of a tOLA has shown promising results in terms of improving oxygenation and reducing the risk of severe postoperative pulmonary complications.

Along with the above, prolonging the end inspiratory pause (EIP), while maintaining an adequate expiratory time, has shown benefits in terms of improving effective alveolar ventilation and enhancing gas exchange. The investigators recently demonstrated the effects of increasing the EIP when ventilating patients with a tOLA strategy. In that work, the investigators examined the effects of two EIP (10 and 30% of the inspiratory time) on the respiratory mechanics of patients undergoing major surgery. The investigators studied the effect of EIP on driving pressure (Pdriv), plateau pressure (Pplat), compliance of the respiratory system (Crs) and PEEP. The investigators also evaluated the dynamic distribution of TV during the ventilatory cycle using electrical impedance tomography (EIT) and studied the effect of EIP on gas exchange by means of arterial gasometry. In that study, the benefits of a longer EIP were seen with both standard PPV (TV of 7 mL of predicted body weight (PBW) and a PEEP of 5 cmH2O), and with a tOLA. The tOLA strategy was associated with a significant increase in PEEP, Pplat, arterial pressure of oxygen (PaO2), and Crs, with a significant decrease in Pdriv and arterial pressure of carbon dioxide (PaCO2), and with a more homogeneous gas distribution compared to standard PPV. On the other hand, the use of a longer EIP showed a significantly lower PEEP, Pdriv and mean airway pressure (Pmean) together with a higher Crs among patients ventilated under a tOLA strategy. However, it was not an objective of the addressed work to study the effects of the EIP modification on ventilatory efficiency, measured as the relation between VDphys and TV (VDphys/TV), something that the investigators will address in this work.

The investigators hypothesize that increasing the EIP in the context of a tOLA may improve alveolar ventilation by reducing the VDphys/TV ratio; in other words, by reducing the dead volume. To test this hypothesis, the investigators will study patients submitted to abdominal robotic surgery. The investigators´ intention is to verify if the potential benefits associated with the combined use of a tOLA and a longer EIP are observed in this type of surgery, where the gas insufflated into the abdomen together with the surgical position (forced trendelenburg) are known to jeopardize ventilation conditions.

Methods

Prospective, paired study with consecutive recruitment of participants to be carried out in a tertiary care teaching hospital (Hospital Universitario Virgen del Rocío). Approval for this study will be sought from the local ethics committee. The recruitment will be made on investigators availability.

Study protocol. Following standard monitoring on arrival to the operating room, participants will be slightly sedated with intravenous midazolam 1-2 mg and remifentanil infusion 0.03-0.05 µg/kg/min The left radial artery will be catheterized under local anesthesia. For EIT monitoring, the PulmoVista 500 system (Dräger, Lübeck, Germany) will be used. Four regions of interest (ROI) will be defined as quadrants one through four, corresponding to top left and right (one, two) and bottom left and right (three, four). Global and regional impedance waveforms will be displayed continuously. The distribution of ventilation by ROI will be expressed as the regional proportion of gas distribution relative to total lung ventilation. Baseline data will be recorded during full consciousness with 0.21 fraction of inspired oxygen (FiO2). The investigators will then pre-oxygenate the participants through a face mask for 5 min in spontaneous ventilation with FIO2 of 0.8 and a fresh gas flow of 6 L/min. Anesthesia induction will performed with propofol (1-1.5 mg/kg PBW) and rocuronium 0.8 mg/kg PBW, proceeding with tracheal intubation. Patients will be ventilated through a Primus anesthesia workstation (Drager, Telford, PA, USA) using a TV of 7 mL/kg PBW. The ventilation mode used will be volume control, which will include an inspiration: expiration ratio of 1:2 and a respiratory rate of 12-15 breaths/min to maintain CO2 at the end of expiration between 35 and 40 mmHg and an initial PEEP of 5 cmH2O. A 10% EIP will be scheduled for all participants. A fresh gas flow of 0.5 to 1 L/min with an FIO2 of 0.5 will be used throughout the procedure. Anesthesia will be maintained with remifentanil 0.03 to 0.05 µg/kg/min and sevoflurane, with a minimum alveolar concentration of 0.6 to 0.8, which will be adjusted to the patient's age to ensure a Bispectral Index (BIS Quatro; Covidien Ilc , Mansfield, MA, USA) between 40-60. Rocuronium will be administered to ensure deep neuromuscular blockade during the study, which will be monitored by train of four neuromuscular relaxation (TOF-watch®, Organon Ltd., Swords, Co. Dublin, Ireland). All ventilation parameters will remain stable throughout the study except PEEP, which will be titrated according to the principles of tOLA, and EIP, which will be modified according to the study protocol (see Arms and Interventions section). Airway pressure (Paw), esophageal pressure (Pes) and gas flow will be measured with a Fluxmed® monitor (MBMED, Buenos Aires, Argentina). The data will be downloaded to a laptop after proper calibration of the flow and pressure sensors. The computer, through the FluxView software (MBMED, Buenos Aires, Argentina), will automatically calculate the following parameters:alveolar, airway and physiological dead volumes (VDalv, VDaw and VDphys, respectively) and its values related to the TV. Airway resistance (Raw = Ppeak-Pplat/inspiratory flow) will also be recorded, where Ppeak is peak pressure. A Pes measurement catheter (MBMED, Buenos Aires, Argentina) will be placed in the mid-esophageal position. Its position will be checked using the occlusion method described for patients with mechanical ventilation35. An acceptable catheter position will be found when the ΔPes/ΔPaw ratio is close to 1. Transpulmonary pressure (PTP) will be calculated as the difference between Paw and Pes. Transpulmonary driving pressure (PTPdriv) will be calculated as end-inspiratory transpulmonary pressure (PTPei) minus end-expiratory transpulmonary pressure (PTPee). Lung stress will be defined as PTPei. The elastance of the respiratory system (Ers= Pplat-PEEP/ TV) will be divided into its lung (El = Plei- Plee / TV) and chest wall (Ecw = Pesei- Pesee/TV) components. The anesthesia workstation will be used for continuous monitoring of Ppeak, Pplat, PEEP, Crs, FiO2 and CO2 at the end of expiration. An ABL90 FLEX PLUS device (Radiometer Medical, Copenhagen, Denmark) will be used for gas analysis.

Study sequence (detailed in the Arms and Interventions section):

Phase 1) The investigators will evaluate the impact of modifying the EIP (10 to 40%) in patients ventilated under an tOLA strategy before the instauration of surgical pneumoperitoneum.

Phase 2) The investigators will evaluate the impact of robotic conditions (pneumoperitoneum + forced trendelenburg) while applying different EIPs (10 to 40%).

Statistical analysis will be performed by the principal investigator. For data analysis, the statistical software IBM SPSS Statistics for Windows, version 24 (IBM Corp., Armonk, NY, USA) will be used. The investigators will perform an exploratory analysis of the data, using the mean ± standard deviation or the median with interquartile range for quantitative variables, and using percentages for the analysis of qualitative variables. The normality of data distribution will be checked with the Kolmogorov-Smirnov test or with the Shapiro-Wilk test for variables with less than 50 records. The Student's t test for paired samples will be used to study the behavior of the quantitative variables at different times (intragroup comparisons).

Calculation of the sample size was carried out by the main investigator, using version 4.2 of the EPIDAT statistical program (General Directorate of Innovation and Public Health Management of the Health Council of the Galician Government). The sample size was calculated based on the data from the previous work of the researchers, in which the investigators studied the influence of EIP on respiratory mechanics and the distribution of TV in surgical patients ventilated under an tOLA strategy (REF). The sample size was estimated assuming the differences in Crs when going from an EIP of 10% to 30% (paired sample). The investigators determined an average difference of 17 mL/cm H2O between both interventions. The sample size was calculated to obtain a power of 80% to detect differences in the contrast of the null hypothesis h₀: μ₁ = μ₂ using a two-sided Student's t-test for two related samples, considering a significance level of 5% and assuming the respective standard deviation in each group. Taking into account an expected percentage of dropouts of 20%, the sample size has been estimated at 17 pairs of experimental units under study (17 participants with paired treatment in the sample).

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Spain
      • Seville, Spain, 41013
        • Hospital Universitario Virgen del Rocio

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 97 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adult subjects (≥ 18 years) scheduled for robotic prostatic surgery at the investigators´ institution
  • Written informed consent

Exclusion Criteria:

  • Participation in another interventional study
  • Participants unable to understand the information contained in the informed consent
  • American Society of Anesthesiologists (ASA) classification grade = IV
  • Patient in dialysis
  • Chronic obstructive pulmonary disease (COPD) grade Global Initiative for Chronic Obstructive Lung Disease(GOLD) > 2
  • Functional vital capacity < 60% or > 120% of the predicted
  • Body mass index (BMI) > 35 kg/m2
  • Relation PaO2/FiO2 <200 mmHg in the baseline sample
  • Presence of mechanical ventilation in the 72 hours prior to enrollment
  • New York Heart Association (NYHA) functional class ≥ 3
  • Clinically suspected heart failure
  • Diagnosis or suspicion of intracranial hypertension
  • Presence of pneumothorax or giant bullae on preoperative imaging tests
  • Use of Continuous Positive Airway Pressure (CPAP).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: End inspiratory pause under tOLA

Application of four different end inspiratory pauses (EIP) corresponding to 10, 20, 30 and 40% of inspiratory time.

Phase 1) before the application of pneumoperitoneum and forced trendelenburg. Phase 2) during the application of pneumoperitoneum and forced trendelenburg. During both phases, all patients will be ventilated under a tOLA strategy (see Study Description section).
Procedure: Modifying EIP under a tOLA before pneumoperitoneum

Phase 1:

Moment (M) 1) Standard PPV and an initial EIP of 10%

M 2) ARM with titration of optimal PEEP (PEEPop) on a decremental PEEP trial, followed by a new ARM and setting a tailored open-lung PEEP (tOL-PEEP), that 2 cm H2O higher than PEEPop

M 3) Incremental modification of the EIP in steps of 10% (from 10 to 40%)

Procedure: Modifying EIP under a tOLA with pneumoperitoneum

Phase 2:

M 4) The investigators will apply the EIP that guarantees the lowest Pdriv

M 5) After applying pneumoperitoneum and trendelenburg

M 6) Atelectasis test (see below)

M 7) M 7a) In case of atelectasis test = negative: the investigators will modify the EIP in incremental or decremental steps of 10% M 7b) In case of atelectasis test=positive: ARM

M 8) In those cases recruited (M 7b), modify the EIP (as in M 7a)

Once the EIP that guarantees the best ventilation conditions has been stablished based on the lowest Pdriv (and higher Crs), the investigators will maintain these conditions until the end of surgery, with periodic evaluation of the pulmonary collapse by means of the atelectasis test (see below) performed every 40 minutes or regardless of time if an oxygen saturation by pulse oximetry (SpO2) < 97% is detected.

Procedure: Atelectasis test
It is performed during mechanical ventilation, due to suspicion of alveolar collapse. Alveolar collapse will be suspected on observation of a reduction in Crs > 10% over post-recruitment values. In these cases the atelectasis test will be performed, consisting of a reduction in FiO2 to 0.21, maintaining this FiO2 for 5 minutes. If lung collapse is >10%, a fall in SpO2 below 97% will be expected (positive atelectasis test), in which case, an ARM and a PEEPop titration test will be performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in physiological dead space volume (VDphys)
Time Frame: Through the study completion: assessed in moments 1, 2, 3, 5, 7a and 8
VDphys is that percentage of the tidal volume not participating of gas exchange
Through the study completion: assessed in moments 1, 2, 3, 5, 7a and 8

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in intra-tidal gas distribution
Time Frame: Through the study completion: assessed in moments 1, 2, 3, 5, 7a and 8
The distribution of the tidal gas within the lung during mechanical ventilation will be evaluated by means of EIT. It will be expressed as percentage of tidal gas distribution per region of interest (ROI).
Through the study completion: assessed in moments 1, 2, 3, 5, 7a and 8
Changes in arterial partial pressure of oxygen
Time Frame: Through the study completion: assessed in moments 1, 3, 7b and 8
The investigators will measure patient oxygenation by means of arterial blood samples extracted from a radial artery catheter.
Through the study completion: assessed in moments 1, 3, 7b and 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

Investigators

  • Principal Investigator: Manuel de la Matta, MD, Hospitales Universitarios Virgen del Rocío

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2023

Primary Completion (Actual)

May 30, 2023

Study Completion (Actual)

November 30, 2023

Study Registration Dates

First Submitted

August 18, 2022

First Submitted That Met QC Criteria

August 22, 2022

First Posted (Actual)

August 24, 2022

Study Record Updates

Last Update Posted (Actual)

April 3, 2024

Last Update Submitted That Met QC Criteria

April 2, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EIP2022.FISEVI

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All the IPD collected, suitably anonymized, will be available to other researchers upon request by email.

IPD Sharing Time Frame

After finishing data analysis

IPD Sharing Access Criteria

Upon other researchers request, through mail contact with the principal researcher

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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