Clinical and Physiological Assessment of a Nearly Ultra-protective Lung Ventilation Strategy: A Quasi-experimental Preliminary Study in ARDS Patients
Phase: NA
Conditions: ARDS, Volumetric Capnography
Sponsor: Clinica las Condes, Chile

Documents: Study protocol and statical analysis plan
Document date: September 17, 2018
Official title:
Effect of Mechanical
power on
dead
space assessed with volumetric
capnography:
Preliminary studies and pilot testing in ARDS patients.
Objectives
1- The objective of this study will be to evaluate the behavior of the dead space monitored by
volumetric capnography after using mechanical ventilation strategies aimed at reducing
mechanical power, maintaining constant positive end-expiratory pressure (PEEP) levels in
ARDS patients.
2- Describe each ventilatory strategy used and evaluate their association with dead space and
alveolar ventilation monitored by volumetric capnography.
Materials and methods:
Design: An observational, prospective, and single-center study. Preliminary studies and pilot
testing in ARDS patients.
Sample size: 10 participants.
Place of study: Clínica las Condes, Santiago, Chile.
Variable records in the study: Variables will be measured and recorded at baseline, and
every time the mechanical ventilator setting is modified. Each phase will last 30 minutes. The
estimated time of recording will be 150 min.
Inclusive Criteria
- Patients with pulmonary and extra-pulmonary ARDS.
- The partial pressure of arterial oxygen over fraction of inspired oxygen (PaO2/FiO2) under
200 mmHg.
Exclusion criteria
- Pregnancy.
- Under 18 years old.
- Heart failure stage IV.
- COPD with home oxygen.
- Bronchopulmonary fistula.
- Hypovolemic Shock with active hemorrhage.
- Gastrointestinal bleeding.
- Oesophageal Varices.
- Nasopharynx surgery, recent oesophageal or gastric surgery
- Massive Pulmonary Thromboembolism.
- Patients with catastrophic respiratory failure that require urgent extracorporeal life support.
- Respiratory acidosis. Basal pH less than 7.20 and basal PaCO2 greater than 60 mmHg.
Study time: 12 months.
Study protocol
Tests and sequential proceedings during the study: After 30 minutes of monitoring in each
phase, ventilatory mechanics, VD/Vt Bohr fraction, and arterial gasometry will be performed.

Baseline: Variables in basal conditions will be registered to allow comparison among the
several phases of the study.
The tidal volume (VT) at baseline will be set at 7 ml/kg/Predicted body weight (PBW) with
PEEP set at the value that allows a transpulmonary pressure at end-expiratory equal to 0 - +5
cmH20 and a respiratory rate between 22 and 30 per minute. Patients whose baseline arterial
pH is less than or equal to 7.20 and or PaCO2 greater than or equal to 60 mmHg will be
excluded from the study.
In each phase will be documented: peak pressure (Ppeak), end inspiring plateau pressure
(Pplateau), mean airway pressure, PEEP, respiratory rate (RR), flow, Raw, End-inspiratory
pause prolongation, inspiratory-expiratory relation (I:E), driving pressure of respiratory system,
Compliance (Csr), Elastance (Esr), end-inspiratory transpulmonary pressure (PL at the
end-inspiratory),
end-expiratory
trans-pulmonary
pressure
(PL
at
end-expiratory),
and
transpulmonary driving pressure (PL driving pressure) PL driving pressure. Will be used to
measure oesophageal pressure, a FluxMed GrT– FluxView MBMed device.
Mechanical Power: Mechanical power will be calculated with the following equation:
PowerRS = 0,0098 . RR . { Vt2 . [ 1/2 . EL rs + RR . (1+ I:E)/ (60. I:E) . Raw] + Vt . PEEP }
Power: Mechanical power, 0,098: constant, RR: respiratory rate, V: Tidal volume, ELrs:
Respiratory System Elastance, I:E: inspiratory time relation with expiratory time, Raw: airway
resistance, PEEP: positive end-expiratory pressure.
This equation is included in an Excel calculating sheet with data of each variable, and the
mechanical power value will be registered automatically in Joules/min.
Volumetric capnography: Volumetric capnography will be recorded with a carbon dioxide
(CO2) analyzer (mainstream) connected to between the orotracheal tube and the proximal
flow sensor. The signals will be analyzed by the FluxMed monitor and the FluxView software.
The device has software programmed in MatLab ® (Mathworks, Natick, MA, USA) that allows
analyzing
respiration
to
volumetric
capnograms,
using
a
mathematical
algorithm
(Levenberg-Marquardt) that allows adjusting the volume to the expired CO2. In this way, it will
be possible to obtain all the variables under study that allow obtaining the results of dead
space and alveolar ventilation.
Protocol design The protocol will start recording the data during baseline protective ventilation.
After 30 minutes of data recording, we studied four levels of setting in mechanical ventilation.
Each level will last 30 minutes.
Variables that will be obtained from the Volumetric capnography monitoring: Bohr's dead
space to tidal volume ratio (VDBohr/VT), Enghoff's index of gas exchange (VDEnhoff/VT),
physiological dead space (VDphys), airway dead space (VDaw), alveolar dead space (VDalv),
VTalv alveolar expiratory tidal volume, VDaw/VTe airway dead space to tidal volume ratio,
alveolar dead space to expiratory tidal volume ratio (VDalv/VT), alveolar dead space to
alveolar tidal volume ratio (VDalv/VTalv), tidal elimination of carbon dioxide VTCO2br,
normalized slope of phase III (SnIII), end-tidal CO2 (ETCO2), mean alveolar partial pressure
of CO2 (PACO2), and mixed-expired partial pressure of CO2 (PECO2)
We will analyze the last 20 breaths of each step of the protocol and calculate the average
value to obtain the result of dead space and all its variables by volumetric capnography.
Respiratory, hemodynamic, and arterial blood gas analysis will also be recorded.
Cardiac output: Continuous measurement of cardiac output and the cardiac index will be
conducted using Volume View or Flow Track Vigileo devices. These are minimally invasive
devices that are connected to an arterial line.
Esophageal
Temperature:
Continuous
measurement
of
central
Temperature
will
be
registered in all patients. It must be constant with a variability of +/- 0,3°C to avoid generating
variations in the volumetric capnography results.
Phase 1: Reduction of tidal volume
The tidal volume will be decreased from baseline Vt of 7 ml/kg/PBW to 6 ml/kg/PBW.

Phase 2: Reduction of tidal volume:
The tidal volume will be decreased from baseline Vt of 6 ml/kg/PBW to 5 ml/kg/PBW.
Phase 3: End-inspiratory pause prolongation
The end-inspiratory pause will be increased until it results in an I: E ratio equal to 1.
Phase 4: Respiratory rate reduction.
Reduce respiratory rate to 20% of the baseline condition. The study will be suspended in
patients who at the beginning of phase 3 present Ph less than 7.20 or PaCO2 more significant
than 60.
Study suspension
The recording of physiological variables will be suspended in the following clinical situations,
which are conditioned by the severity of each patient:
- Vasopressor refractory hypotension.
- Ventricular arrhythmias,
- Symptomatic bradycardia,
- Cardiopulmonary arrest.
- Catastrophic respiratory failure.
Sampling size
Due to the specific characteristics of the study subjects and the lack of scientific evidence
available, this project intends to study 10 patients.
Statistical analysis plan
We will perform the Shapiro Wilks’s statistic test to confirm normal distribution. Data will be
expressed as mean ± standard deviation, median, and interquartile range (IQR), as
appropriate. Within each ventilatory strategy, a paired t-test or Wilcoxon signed-rank test
(WST) will be used as appropriate. Continuous variables among ventilatory strategies will be
compared using repeated measure ANOVA with Bonferroni post hoc analysis or Friedman test
and Kruskal Wallis test for multiple comparisons. Pearson or Spearman correlation test will be
used to compare data and correlations between phases and variables. Percentages will be
analyzed using two- proportion z-test. Categorical variables will be compared with the X2 test.
The SPSS software (version 22.0, IBM SPSS Inc., Chicago, IL, USA) A probability value
(p-value) of less than 0.05 will be considered statistically significant.
Ethical principles
Document date: January 9, 2019
The present research project has been revised and approved by the ethics and research
committee of Clínica Las Condes. It will carry out the process of execution authorization of the
study. The internal number of the project is S022018.