Vascular Injury in Mechanical Ventilation: a Proof-of-Concept Study

Investigation of the effect of mechanical ventilation on biomarkers of microvascular damage

Study Overview

• Status: Completed
• Conditions: Endothelial Dysfunction; Mechanical Ventilation Complication; Vascular Injury
• Intervention / Treatment: Procedure: Mechanical Ventilation

Detailed Description

The objective of this study is to determine the effect of mechanical ventilation (MV) on endothelial biomarkers associated with ventilator-induced vascular injury (VIVI), and determine the correlation of these biomarkers with non-invasive microvascular perfusion monitoring data and semaphorin 3E levels.

Blood samples will be collected immediately pre-operatively and post-operatively.

Biomarkers will be expressed as an absolute value and as a relative percentage change from baseline to account for inter-individual variability. Hemodynamic and surgical variables will be extracted from the OR data: blood pressure, oxygen saturation, blood loss, fluid administration, length of surgery, and MV parameters such as tidal volume, inspired oxygen, respiratory rate, and positive end-expiratory pressure.

During surgery, patients will be monitored using a non-invasive near-infrared spectroscopy technique to quantify skeletal muscle microvascular perfusion. These devices will be applied immediately prior to induction of anesthetic and data collected until immediately prior to transfer to the post-anesthesia care unit.

• Study Type: Observational
• Enrollment (Actual): 19

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Adult patients undergoing elective orthopedic, endourologic, or plastic surgery procedure amenable to both general anesthetic or regional/neuraxial anesthesia.

Description

Inclusion Criteria:

• Age 18 years or greater
• Patients undergoing elective orthopedic, endourologic, or plastic surgery procedure which is amenable to both general anesthetic or regional/neuraxial anesthesia

Exclusion Criteria:

• Emergency surgery
• Polytrauma
• Tourniquet use
• Controlled hypotension
• Mechanical ventilation less than 60 minutes in duration
• American Society of Anesthesiologists class 4 or greater
• Status postpneumonectomy
• Pulmonary hypertension
• Oxygen therapy during last month
• Severe obesity (body mass index ≥40 kg/m2)
• Immunosuppression within 3 months
• Diagnosed infection
• Shock

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Mechanical Ventilation; Cohort will undergo standard of care treatment utilizing a general anesthetic with mechanical ventilation for a surgical procedure.	Procedure: Mechanical Ventilation; Positive pressure mechanical ventilation
Control; Cohort will undergo standard of care treatment utilizing a regional or neuraxial anesthetic without mechanical ventilation for a surgical procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative change of postoperative Granulocyte-macrophage colony-stimulating factor (GM-CSF) plasma concentration relative to preoperative plasma concentration	Percentage change in concentration from immediately prior to surgical procedure to immediately after surgical procedure	Immediately prior to surgical procedure to immediately after surgical procedure
Relative change of postoperative Interferon gamma (IFNγ) plasma concentration relative to preoperative plasma concentration	Percentage change in concentration from immediately prior to surgical procedure to immediately after surgical procedure	Immediately prior to surgical procedure to immediately after surgical procedure
Relative change of postoperative Interleukin-1β plasma concentration relative to preoperative plasma concentration	Percentage change in concentration from immediately prior to surgical procedure to immediately after surgical procedure	Immediately prior to surgical procedure to immediately after surgical procedure
Relative change of postoperative Interleukin-1RA plasma concentration relative to preoperative plasma concentration	Percentage change in concentration from immediately prior to surgical procedure to immediately after surgical procedure	Immediately prior to surgical procedure to immediately after surgical procedure
Relative change of postoperative Interleukin-2 plasma concentration relative to preoperative plasma concentration	Percentage change in concentration from immediately prior to surgical procedure to immediately after surgical procedure	Immediately prior to surgical procedure to immediately after surgical procedure
Relative change of postoperative Interleukin-4 plasma concentration relative to preoperative plasma concentration	Percentage change in concentration from immediately prior to surgical procedure to immediately after surgical procedure	Immediately prior to surgical procedure to immediately after surgical procedure
Relative change of postoperative Interleukin-5 plasma concentration relative to preoperative plasma concentration	Percentage change in concentration from immediately prior to surgical procedure to immediately after surgical procedure	Immediately prior to surgical procedure to immediately after surgical procedure
Relative change of postoperative Interleukin-6 plasma concentration relative to preoperative plasma concentration	Percentage change in concentration from immediately prior to surgical procedure to immediately after surgical procedure	Immediately prior to surgical procedure to immediately after surgical procedure
Relative change of postoperative Interleukin-8 plasma concentration relative to preoperative plasma concentration	Percentage change in concentration from immediately prior to surgical procedure to immediately after surgical procedure	Immediately prior to surgical procedure to immediately after surgical procedure
Relative change of postoperative Interleukin-10 plasma concentration relative to preoperative plasma concentration	Percentage change in concentration from immediately prior to surgical procedure to immediately after surgical procedure	Immediately prior to surgical procedure to immediately after surgical procedure
Relative change of postoperative Interleukin-12(p40) plasma concentration relative to preoperative plasma concentration	Percentage change in concentration from immediately prior to surgical procedure to immediately after surgical procedure	Immediately prior to surgical procedure to immediately after surgical procedure
Relative change of postoperative Interleukin-12(p70) plasma concentration relative to preoperative plasma concentration	Percentage change in concentration from immediately prior to surgical procedure to immediately after surgical procedure	Immediately prior to surgical procedure to immediately after surgical procedure
Relative change of postoperative Interleukin-13 plasma concentration relative to preoperative plasma concentration	Percentage change in concentration from immediately prior to surgical procedure to immediately after surgical procedure	Immediately prior to surgical procedure to immediately after surgical procedure
Relative change of postoperative Monocyte Chemoattractant Protein-1 (MCP-1) plasma concentration relative to preoperative plasma concentration	Percentage change in concentration from immediately prior to surgical procedure to immediately after surgical procedure	Immediately prior to surgical procedure to immediately after surgical procedure
Relative change of postoperative Tumor Necrosis Factor Alpha (TNFα) plasma concentration relative to preoperative plasma concentration	Percentage change in concentration from immediately prior to surgical procedure to immediately after surgical procedure	Immediately prior to surgical procedure to immediately after surgical procedure
Relative change of postoperative Soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1) plasma concentration relative to preoperative plasma concentration	Percentage change in concentration from immediately prior to surgical procedure to immediately after surgical procedure	Immediately prior to surgical procedure to immediately after surgical procedure
Relative change of postoperative Vascular Cell Adhesion Molecule 1 (VCAM-1) plasma concentration relative to preoperative plasma concentration	Percentage change in concentration from immediately prior to surgical procedure to immediately after surgical procedure	Immediately prior to surgical procedure to immediately after surgical procedure
Relative change of postoperative Vascular Endothelial Growth Factor (VEGF) plasma concentration relative to preoperative plasma concentration	Percentage change in concentration from immediately prior to surgical procedure to immediately after surgical procedure	Immediately prior to surgical procedure to immediately after surgical procedure
Relative change of postoperative Angiopoietin 2 (Ang-2) plasma concentration relative to preoperative plasma concentration	Percentage change in concentration from immediately prior to surgical procedure to immediately after surgical procedure	Immediately prior to surgical procedure to immediately after surgical procedure
Relative change of postoperative Tyrosine-protein kinase receptor Tie-2 (sTIE-2) plasma concentration relative to preoperative plasma concentration	Percentage change in concentration from immediately prior to surgical procedure to immediately after surgical procedure	Immediately prior to surgical procedure to immediately after surgical procedure
Relative change of postoperative Soluble platelet selectin (sP-selectin) plasma concentration relative to preoperative plasma concentration	Percentage change in concentration from immediately prior to surgical procedure to immediately after surgical procedure	Immediately prior to surgical procedure to immediately after surgical procedure
Relative change of postoperative Soluble endothelial selectin (sE-selectin) plasma concentration relative to preoperative plasma concentration	Percentage change in concentration from immediately prior to surgical procedure to immediately after surgical procedure	Immediately prior to surgical procedure to immediately after surgical procedure
Relative change of postoperative Soluble intercellular adhesion molecule-1 (sICAM-1) plasma concentration relative to preoperative plasma concentration	Percentage change in concentration from immediately prior to surgical procedure to immediately after surgical procedure	Immediately prior to surgical procedure to immediately after surgical procedure
Relative change of postoperative thrombomodulin plasma concentration relative to preoperative plasma concentration	Percentage change in concentration from immediately prior to surgical procedure to immediately after surgical procedure	Immediately prior to surgical procedure to immediately after surgical procedure
Relative change of postoperative von Willebrand factor (vWF) plasma concentration relative to preoperative plasma concentration	Percentage change in concentration from immediately prior to surgical procedure to immediately after surgical procedure	Immediately prior to surgical procedure to immediately after surgical procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative change of postoperative Semaphorin 3E (sema3E) plasma concentration relative to preoperative plasma concentration	Percentage change in concentration from immediately prior to surgical procedure to immediately after surgical procedure	Immediately prior to surgical procedure to immediately after surgical procedure

Collaborators and Investigators

• Sponsor: University of Manitoba
• Investigators: Principal Investigator: Asher Mendelson, Ph.D., University of Manitoba

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2022
• Primary Completion (Actual): May 19, 2023
• Study Completion (Actual): May 19, 2023

Study Registration Dates

• First Submitted: September 11, 2022
• First Submitted That Met QC Criteria: September 11, 2022
• First Posted (Actual): September 14, 2022

Study Record Updates

• Last Update Posted (Actual): August 24, 2025
• Last Update Submitted That Met QC Criteria: August 19, 2025
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Wounds and Injuries; Vascular System Injuries
• Other Study ID Numbers: HS25427

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No