Inhaled Anesthetics and Myocardial Strain

Effect of Inhalational Anesthetics on Myocardial Deformation Indices - A Dose-Response Cross-over Study

Speckle tracking imaging measuring software will be used for offline analysis of transesophageal echocardiogram (TEE) -acquired images of the left ventricle(LV) in four chambers(4C), two chambers (2C) and long axis (LAX) views to calculate global longitudinal strain (GLS) of LV for comparisons between sevoflurane and isoflurane at the same minimum alveolar concentration ( MAC) levels.

Study Overview

• Status: Completed
• Conditions: Heart Diseases
• Intervention / Treatment: Drug: Sevoflurane; Drug: Isoflurane

Detailed Description

The primary research activity will be: baseline transthoracic echocardiogram (TTE) views taken upon the patient entering the operating room by one of the cardiothoracic anesthesiology fellows or attendings, TEE views taken by the echocardiography fellow or attending in the mid-esophageal 4C, 2C and LAX views once the patient has reached sevoflurane end-tidal minimum alveolar concentration (MAC) of 0.5, 1.0, and 1.5. Following this, sevoflurane will be changed to isoflurane and wait till complete washout of sevoflurane (i.e. end-tidal sevoflurane concentration reaches zero). Isoflurane concentration will be adjusted according to bispectral index and hemodynamics to maintain anesthesia during this period. Once complete sevoflurane wash-out has been achieved, isoflurane concentration will be adjusted and repeat images taken at the 0.5, 1.0, and 1.5 MAC values.

Investigators will establish stability at each MAC level (0.5, 1.0 and 1.5) for 5 minutes before obtaining TEE images. The whole study is done during pre- cardiopulmonary bypass(CPB) period while surgeon spending time dissecting internal mammary artery or other parts of surgical dissection before heparinization. The entire study duration will be a maximum of 35-40 minutes and this will not prolong the operating time. The adjustment of the anesthetic will be performed by the cardiac anesthesiology fellow or senior resident involved in this research along with the faculty officially performing the case. All images will be acquired prior to the initiation of cardiopulmonary bypass by the echocardiography rotating resident or research resident, cardiac anesthesiology fellow or cardiac anesthesiology attending anesthesiologist (all received extensive training in TEE to obtain those required images). Following the completion of the case and the uploading of images to a central echocardiography server, one of the study personnel will perform analysis of the images in the anesthesiology offices on a computer with post-processing software to determine strain.

MAC up to 1.5 is very well tolerated in cardiac surgical patients and is routinely used to achieve hemodynamic conditions during surgery. Use of vasopressor and inotrope to allow maintain depth of anesthesia with inhalation anesthesia agents is also routine in cardiac surgical patients and not in any way different from routine clinical care.

Hemodynamic information (heart rate, blood pressure, central venous pressure, cardiac index or pulmonary artery pressure) will be obtained after stabilization with each MAC and will be recorded immediately or extracted from the electronic medical records.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ezeldeen Abuelkasem, MD, MSc; Phone Number: 4122099819; Email: abuelkaseme@upmc.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Presbyterian Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Adult Patients (> 18 years of age) undergoing cardiovascular surgery at University of Pittsburgh Medical Center (UPMC) Presbyterian hospital.

Exclusion Criteria:

Inability to comprehend and understand the study, Pregnancy Malignant hyperthermia Acute cardiogenic shock and ongoing chest pain Permanent pacemaker with pacemaker dependency Abnormal cardiac rhythms ( e.g. atrial fibrillation) Contraindications to TEE examination such as recent esophageal surgery, esophageal cancer/stricture The use of anesthesia maintenance with intravenous anesthesia drugs such as propofol infusions

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sevoflurane then isoflurane	Drug: Sevoflurane; The patient will receive Sevoflurane in incremental doses titrated to obtain end-tidal minimum alveolar concentration (MAC) of 0.5, 1.0, and 1.5.; Drug: Isoflurane; The patient will receive isoflurane in incremental doses titrated to obtain end-tidal minimum alveolar concentration (MAC) of 0.5, 1.0, and 1.5.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global longitudinal strain of myocardium, unitless (Comparison between two inhalational anesthetics, isoflurane and sevoflurane)	Global longitudinal Strain measures changes in longitudinal length of myocardium and is a unitless measure. TEE images will be taken during surgery, stored on central echocardiography server, then analyzed offline using a special software to calculate global longitudinal strain (GLS). GLS of LV will then be compared between isoflurane and sevoflurane at the same MAC concentrations.	Intraoperative period during cardiac surgery before initiation of cardiopulmonary bypass

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global longitudinal strain of myocardium, unitless (Dose dependent effect of sevoflurane)	Global longitudinal Strain measures changes in longitudinal length of myocardium and is a unitless measure. TEE images will be taken during surgery, stored on central echocardiography server, then analyzed offline using a special software to calculate global longitudinal strain (GLS). GLS of LV will then be compared at increasing MAC of sevoflurane.	Intraoperative period during cardiac surgery before initiation of cardiopulmonary bypass
Global longitudinal strain of myocardium, unitless (Dose dependent effect of isoflurane)	Global longitudinal Strain measures changes in longitudinal length of myocardium and is a unitless measure. TEE images will be taken during surgery, stored on central echocardiography server, then analyzed offline using a special software to calculate global longitudinal strain (GLS). GLS of LV will then be compared at increasing MAC of isoflurane.	Intraoperative period during cardiac surgery before initiation of cardiopulmonary bypass

Collaborators and Investigators

• Sponsor: Kathirvel Subramaniam
• Investigators: Principal Investigator: Kathirvel Subramaniam, MD, MSc, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2018
• Primary Completion (Actual): December 6, 2018
• Study Completion (Actual): May 4, 2023

Study Registration Dates

• First Submitted: June 1, 2018
• First Submitted That Met QC Criteria: June 13, 2018
• First Posted (Actual): June 26, 2018

Study Record Updates

• Last Update Posted (Actual): October 5, 2023
• Last Update Submitted That Met QC Criteria: October 3, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, General; Anesthetics; Platelet Aggregation Inhibitors; Anesthetics, Inhalation; Sevoflurane; Isoflurane
• Other Study ID Numbers: PRO17080624

Drug and device information, study documents

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