An interventional study of Volume Control Ventilation and Pressure Control Ventilation in Mechanical Ventilation and Critical Illness, sponsored by Evangelismos Hospital. Not yet recruiting at 1 site in Greece. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-07-24.
Sponsored by Evangelismos Hospital · Not applicable, Interventional, and Other
The goal of this clinical trial is to explore whether different modes of mechanical ventilation affect pupillary constriction velocities in critically ill patients without brain injury. The study aims to determine whether the type of mechanical ventilation (volume control, pressure control, or pressure-regulated volume control) influences the maximum and mean constriction velocity measured by automated pupillometry. The trial also investigates whether changes in pupil dynamics reflect subtle alterations in brainstem-autonomic interaction induced by ventilation mode.
The comparison involves volume control, pressure control, and pressure-regulated volume control in a randomized crossover design to assess whether ventilation mode has a measurable effect on pupil response.
Eligible participants will be intubated ICU patients receiving assist control ventilation who are not yet ready for spontaneous breathing trials. Serial pupillometry measurements will be conducted while participants are ventilated with each mode for at least 15 minutes. Sedation and lighting conditions will remain consistent throughout the protocol. Participants with acute or chronic neurologic conditions or ventilator dyssynchrony will be excluded.
This is a prospective, randomized, crossover study designed to evaluate the effect of different modes of mechanical ventilation on pupillary constriction velocity in critically ill patients. Recent data suggest that even in the absence of direct pulmonary or neurologic injury, mechanical ventilation with positive pressure may impact brain function, possibly through vagal-brainstem-autonomic pathways. These effects may be subtle and difficult to detect with standard neurological examination but may be reflected in changes in the dynamic pupillary light reflex.
The pupillary light reflex (PLR), measured using automated infrared pupillometry, provides a quantitative, non-invasive assessment of brainstem and autonomic nervous system function. IThe investigators aim to determine whether the PLR, specifically, the mean and maximum constriction velocity, differs across three commonly used ventilation modes: Volume Control (VC), Pressure Control (PC), and Pressure-Regulated Volume Control (PRVC).
All included participants will be mechanically ventilated, sedated, and not yet candidates for spontaneous breathing trials. Exclusion criteria include any acute or chronic neurologic disorder or signs of ventilator dyssynchrony. Sedation regimens (e.g., propofol, remifentanil, dexmedetomidine) will be kept constant during the study, and ambient light will remain unchanged.
Each participant will undergo the three ventilation modes in a randomized order, with each mode applied for a minimum of 15 minutes to ensure washout before pupillometry measurements are performed. Physiological parameters such as respiratory rate, minute ventilation, FiO₂, heart rate, and mean arterial pressure will be recorded in parallel with pupil measurements. Blood gas analysis and full pupillometry data, including pupil size, constriction and dilation velocities, latency, and the Neurological Pupil Index (NPi), will also be collected.
The primary outcome is the difference in maximum pupillary constriction velocity between ventilation modes. Secondary outcomes include mean constriction velocity, NPi, and other pupillary metrics. Based on pilot data, a total of 36 participants are required to detect a significant difference in the primary outcome. Statistical analysis will include repeated measures ANOVA or the Friedman test, with post hoc Wilcoxon Signed-Rank testing as appropriate.
The findings of this study may provide support for the use of pupillometry as a tool to assess subtle CNS effects of mechanical ventilation and could support the theory of ventilation-brainstem interactions during mechanical ventilation.
1,780 studies on the registry are indexed under Critical Illness; 442 are open to participants now.
This study's planned enrollment of 36 is below the median of 90 across 926 interventional studies indexed under Critical Illness.
Browse Critical Illness studies →Evangelismos Hospital is the lead sponsor of 29 studies on the registry; 6 are open to participants now.
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Inclusion Criteria
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants receive mechanical ventilation in the following sequence: Volume Control (VC), followed by Pressure Control (PC), then Pressure-Regulated Volume Control (PRVC). Pupillometry is performed after each mode following a 15-minute stabilization period.
Other: Volume Control Ventilation · Other: Pressure Control Ventilation · Other: Pressure-Regulated Volume Control (PRVC)
Participants receive mechanical ventilation in the following sequence: Volume Control (VC), followed by Pressure-Regulated Volume Control (PRVC), then Pressure Control (PC). Pupillometry is performed after each mode following a 15-minute stabilization period.
Other: Volume Control Ventilation · Other: Pressure Control Ventilation · Other: Pressure-Regulated Volume Control (PRVC)
Participants receive mechanical ventilation in the following sequence: Pressure Control (PC), followed by Volume Control (VC), then Pressure-Regulated Volume Control (PRVC). Pupillometry is performed after each mode following a 15-minute stabilization period.
Other: Volume Control Ventilation · Other: Pressure Control Ventilation · Other: Pressure-Regulated Volume Control (PRVC)
Participants receive mechanical ventilation in the following sequence: Pressure Control (PC), followed by Pressure-Regulated Volume Control (PRVC), then Volume Control (VC). Pupillometry is performed after each mode following a 15-minute stabilization period.
Other: Volume Control Ventilation · Other: Pressure Control Ventilation · Other: Pressure-Regulated Volume Control (PRVC)
Participants receive mechanical ventilation in the following sequence: Pressure-Regulated Volume Control (PRVC), followed by Volume Control (VC), then Pressure Control (PC). Pupillometry is performed after each mode following a 15-minute stabilization period.
Other: Volume Control Ventilation · Other: Pressure Control Ventilation · Other: Pressure-Regulated Volume Control (PRVC)
Participants receive mechanical ventilation in the following sequence: Pressure-Regulated Volume Control (PRVC), followed by Pressure Control (PC), then Volume Control (VC). Pupillometry is performed after each mode following a 15-minute stabilization period.
Other: Volume Control Ventilation · Other: Pressure Control Ventilation · Other: Pressure-Regulated Volume Control (PRVC)
Standard mode of mechanical ventilation delivering a preset tidal volume. Commonly used in ICU patients requiring controlled ventilation.
Pressure-targeted ventilation mode that delivers breaths at a fixed pressure. Commonly used in critically ill patients.
Hybrid ventilation mode that automatically adjusts inspiratory pressure to achieve a preset tidal volume.
Maximum Pupillary Constriction Velocity
Change in maximum pupillary constriction velocity (mm/s) in response to standardized light stimulus, as measured by the NPi-200 pupillometer, under three modes of mechanical ventilation: Volume Control (VC), Pressure Control (PC), and Pressure-Regulated Volume Control (PRVC).
Time frame: At 30 minutes after each ventilation mode initiation (VC, PC, PRVC).
Neurological Pupil Index (NPi)
Change in NPi value recorded under each ventilation mode, reflecting pupillary reactivity and brainstem function.
Time frame: At 30 minutes after each ventilation mode initiation (VC, PC, PRVC).
Constriction Latency
Change in latency to onset of pupil constriction (seconds), measured using the NPi-200.
Time frame: At 30 minutes after each ventilation mode initiation (VC, PC, PRVC).
Dilation Velocity
Change in maximum dilation velocity (mm/s) following light stimulus, measured with the NPi-200.
Time frame: At 30 minutes after each ventilation mode initiation (VC, PC, PRVC).
Maximum Pupil Diameter
Change in maximum pupil diameter (mm) measured before light stimulation under each ventilation mode.
Time frame: At 30 minutes after each ventilation mode initiation (VC, PC, PRVC).
Minimum Pupil Diameter
Change in minimum pupil diameter (mm) recorded after light stimulation.
Time frame: At 30 minutes after each ventilation mode initiation (VC, PC, PRVC).
Percent Constriction
Percent change in pupil diameter from baseline in response to light stimulus.
Time frame: At 30 minutes after each ventilation mode initiation (VC, PC, PRVC).
Exploratory Outcome Measure - Heart Rate Variability (HRV)
HRV derived from ECG to explore autonomic nervous system modulation across ventilation modes (optional, if data acquisition becomes feasible).
Time frame: Time interval between 15-30 minutes after the initiation of each ventilation mode (VC, PC, PRVC)
Systolic Blood Pressure (mmHg)
Systolic blood pressure will be recorded during each ventilation mode to assess cardiovascular stability.
Time frame: At 30 minutes after each ventilation mode initiation (VC, PC, PRVC).
Diastolic Blood Pressure (mmHg)
Diastolic blood pressure will be recorded during each ventilation mode to assess cardiovascular stability.
Time frame: At 30 minutes after each ventilation mode initiation (VC, PC, PRVC).
Mean Arterial Pressure (mmHg)
Mean arterial pressure (MAP) will be recorded to evaluate overall hemodynamic stability.
Time frame: At 30 minutes after each ventilation mode initiation (VC, PC, PRVC).
Heart Rate (beats per minute)
Heart rate will be recorded to evaluate cardiovascular stability.
Time frame: At 30 minutes after each ventilation mode initiation (VC, PC, PRVC).
Arterial Partial Pressure of Oxygen, PaO₂ (mmHg)
PaO₂ will be measured via arterial blood gas to assess oxygenation.
Time frame: At 30 minutes after each ventilation mode initiation (VC, PC, PRVC).
Arterial Partial Pressure of Carbon Dioxide, PaCO₂ (mmHg)
PaCO₂ will be measured via arterial blood gas to assess ventilation efficiency.
Time frame: At 30 minutes after each ventilation mode initiation (VC, PC, PRVC).
Tidal Volume (mL)
Tidal volume will be recorded to ensure ventilator setting consistency.
Time frame: At 30 minutes after each ventilation mode initiation (VC, PC, PRVC).
Respiratory Rate (breaths per minute)
Respiratory rate will be recorded to monitor respiratory drive and ventilation stability.
Time frame: At 30 minutes after each ventilation mode initiation (VC, PC, PRVC).
Minute ventilation (L/min)
Minute ventilation will be recorded to assess ventilatory effectiveness and ensure consistency across modes.
Time frame: At 30 minutes after each ventilation mode initiation (VC, PC, PRVC).
Ambient Illumination (lux)
Ambient light intensity will be recorded to confirm consistent lighting conditions for pupillometry.
Time frame: At 30 minutes after each ventilation mode initiation (VC, PC, PRVC).
Plan to share: Yes — De-identified individual participant data (IPD) related to primary and secondary outcome measures will be made available to other researchers upon reasonable request, after publication of the main study results.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
Time frame: Beginning 6 months after publication of the primary manuscript and continuing for 3 years.
Access criteria: Access will be granted to qualified researchers for scientifically sound proposals. Requesters will need to submit a brief proposal outlining the purpose and methods of the secondary analysis.
Data sharing details ↗ · www.evaggelismos-hosp.gr
This study is not yet recruiting, as verified in Jul 2025. You cannot join it, but the record below documents what was studied.
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