Effect of Ventilation Mode in the Pupillary Light Reflex: A Crossover Study

NCT ID: NCT07082569

Last Updated: 2025-07-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-07-15

Study Completion Date

2026-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Mechanical Ventilation Critical Illness

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Each participant will receive three different modes of mechanical ventilation (Volume Control, Pressure Control, Pressure-Regulated Volume Control) in a randomized order. Pupillometry measurements will be taken after each mode, with a 15-minute washout period between modes.
Primary Study Purpose

OTHER

Blinding Strategy

SINGLE

Outcome Assessors
The outcome assessor will be masked to the ventilation mode sequence applied during each pupillometry measurement. Pupillometry data will be anonymized and coded prior to statistical analysis to prevent bias in outcome evaluation.

Study Groups

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Sequence A: VC → PC → PRVC

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.

Group Type EXPERIMENTAL

Volume Control Ventilation

Intervention Type OTHER

Standard mode of mechanical ventilation delivering a preset tidal volume. Commonly used in ICU patients requiring controlled ventilation.

Pressure Control Ventilation

Intervention Type OTHER

Pressure-targeted ventilation mode that delivers breaths at a fixed pressure. Commonly used in critically ill patients.

Pressure-Regulated Volume Control (PRVC)

Intervention Type OTHER

Hybrid ventilation mode that automatically adjusts inspiratory pressure to achieve a preset tidal volume.

Sequence B: VC → PRVC → PC

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.

Group Type OTHER

Volume Control Ventilation

Intervention Type OTHER

Standard mode of mechanical ventilation delivering a preset tidal volume. Commonly used in ICU patients requiring controlled ventilation.

Pressure Control Ventilation

Intervention Type OTHER

Pressure-targeted ventilation mode that delivers breaths at a fixed pressure. Commonly used in critically ill patients.

Pressure-Regulated Volume Control (PRVC)

Intervention Type OTHER

Hybrid ventilation mode that automatically adjusts inspiratory pressure to achieve a preset tidal volume.

Sequence C: PC → VC → 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.

Group Type OTHER

Volume Control Ventilation

Intervention Type OTHER

Standard mode of mechanical ventilation delivering a preset tidal volume. Commonly used in ICU patients requiring controlled ventilation.

Pressure Control Ventilation

Intervention Type OTHER

Pressure-targeted ventilation mode that delivers breaths at a fixed pressure. Commonly used in critically ill patients.

Pressure-Regulated Volume Control (PRVC)

Intervention Type OTHER

Hybrid ventilation mode that automatically adjusts inspiratory pressure to achieve a preset tidal volume.

Sequence D: PC → PRVC → VC

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.

Group Type OTHER

Volume Control Ventilation

Intervention Type OTHER

Standard mode of mechanical ventilation delivering a preset tidal volume. Commonly used in ICU patients requiring controlled ventilation.

Pressure Control Ventilation

Intervention Type OTHER

Pressure-targeted ventilation mode that delivers breaths at a fixed pressure. Commonly used in critically ill patients.

Pressure-Regulated Volume Control (PRVC)

Intervention Type OTHER

Hybrid ventilation mode that automatically adjusts inspiratory pressure to achieve a preset tidal volume.

Sequence E: PRVC → VC → PC

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.

Group Type OTHER

Volume Control Ventilation

Intervention Type OTHER

Standard mode of mechanical ventilation delivering a preset tidal volume. Commonly used in ICU patients requiring controlled ventilation.

Pressure Control Ventilation

Intervention Type OTHER

Pressure-targeted ventilation mode that delivers breaths at a fixed pressure. Commonly used in critically ill patients.

Pressure-Regulated Volume Control (PRVC)

Intervention Type OTHER

Hybrid ventilation mode that automatically adjusts inspiratory pressure to achieve a preset tidal volume.

Sequence F: PRVC → PC → VC

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.

Group Type OTHER

Volume Control Ventilation

Intervention Type OTHER

Standard mode of mechanical ventilation delivering a preset tidal volume. Commonly used in ICU patients requiring controlled ventilation.

Pressure Control Ventilation

Intervention Type OTHER

Pressure-targeted ventilation mode that delivers breaths at a fixed pressure. Commonly used in critically ill patients.

Pressure-Regulated Volume Control (PRVC)

Intervention Type OTHER

Hybrid ventilation mode that automatically adjusts inspiratory pressure to achieve a preset tidal volume.

Interventions

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Volume Control Ventilation

Standard mode of mechanical ventilation delivering a preset tidal volume. Commonly used in ICU patients requiring controlled ventilation.

Intervention Type OTHER

Pressure Control Ventilation

Pressure-targeted ventilation mode that delivers breaths at a fixed pressure. Commonly used in critically ill patients.

Intervention Type OTHER

Pressure-Regulated Volume Control (PRVC)

Hybrid ventilation mode that automatically adjusts inspiratory pressure to achieve a preset tidal volume.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Adult patients (≥18 years old)
* Receiving positive-pressure mechanical ventilation
* Under light or no sedation (e.g., RASS score between -2 and 0)
* Clinically assessed by the treating physician as not yet ready for weaning from mechanical ventilation
* Hemodynamically stable at the time of measurement
* Presence of an arterial catheter in place for blood gas analysis

Exclusion Criteria

* Acute or chronic neurological disease affecting brainstem function or pupillary responses
* Dyssynchrony with the ventilator or need for high ventilatory support adjustments
* Facial injuries, edema, or conditions precluding accurate pupillometry
* Use of neuromuscular blocking agents within the prior 6 hours
* Severe metabolic or acid-base imbalances that may influence autonomic regulation
* Concurrent participation in another interventional study that could affect neurological or autonomic outcomes
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Evangelismos Hospital

OTHER

Sponsor Role lead

Responsible Party

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Charikleia Vrettou

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Charikleia S Vrettou, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

!st ICU dpt., Evangelismos General Hospital

Locations

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!st ICU dpt., Evangelismos Hospital

Athens, , Greece

Site Status

Countries

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Greece

Central Contacts

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Charikleia S. Vrettou, MD, PhD

Role: CONTACT

+302132105621 ext. 5621

References

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Sibbald B, Roberts C. Understanding controlled trials. Crossover trials. BMJ. 1998 Jun 6;316(7146):1719. doi: 10.1136/bmj.316.7146.1719. No abstract available.

Reference Type BACKGROUND
PMID: 9614025 (View on PubMed)

World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013 Nov 27;310(20):2191-4. doi: 10.1001/jama.2013.281053. No abstract available.

Reference Type BACKGROUND
PMID: 24141714 (View on PubMed)

Muppidi S, Adams-Huet B, Tajzoy E, Scribner M, Blazek P, Spaeth EB, Frohman E, Davis S, Vernino S. Dynamic pupillometry as an autonomic testing tool. Clin Auton Res. 2013 Dec;23(6):297-303. doi: 10.1007/s10286-013-0209-7. Epub 2013 Jul 24.

Reference Type BACKGROUND
PMID: 23880969 (View on PubMed)

Bassi TG, Rohrs EC, Fernandez KC, Ornowska M, Nicholas M, Gani M, Evans D, Reynolds SC. Transvenous Diaphragm Neurostimulation Mitigates Ventilation-associated Brain Injury. Am J Respir Crit Care Med. 2021 Dec 15;204(12):1391-1402. doi: 10.1164/rccm.202101-0076OC.

Reference Type BACKGROUND
PMID: 34491883 (View on PubMed)

Cinnella G, Conti G, Lofaso F, Lorino H, Harf A, Lemaire F, Brochard L. Effects of assisted ventilation on the work of breathing: volume-controlled versus pressure-controlled ventilation. Am J Respir Crit Care Med. 1996 Mar;153(3):1025-33. doi: 10.1164/ajrccm.153.3.8630541.

Reference Type BACKGROUND
PMID: 8630541 (View on PubMed)

Walter K. Mechanical Ventilation. JAMA. 2021 Oct 12;326(14):1452. doi: 10.1001/jama.2021.13084. No abstract available.

Reference Type BACKGROUND
PMID: 34636861 (View on PubMed)

Other Identifiers

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PSVCPC

Identifier Type: -

Identifier Source: org_study_id

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