Assessment of the Cerebral Perfusion During the Period of Deep Hypothermia at 18°C in Patient Undergoing Pulmonary Endarterectomy Surgery. (HYPO-TEP)

Cardiopulmonary bypass (CPB) surgery present risk of acute postoperative neurological complications. These complications are most often postoperative cognitive dysfunction (confusion, cognitive disorders, executive disorders) with a prevalence of up to 40% at 5 years, and ischemic (stroke) with an incidence of between 0.4 and 14%. The causes are usually multifactorial, but altered cerebral perfusion during CPB surgery is an important prognostic factor. Data regarding the effect of deep hypothermia on cerebral perfusion during CPB in adult are scarce. Currently, aortic arch replacement following aortic dissection or aneurysm, and pulmonary artery endarterectomy (PAE) in the treatment of pulmonary hypertension of post embolic origin are performed under deep hypothermia.

In this latter indication, the need to obtain a completely bloodless operating field necessitates complete circulatory arrest during short period of time to enable the surgeon to optimally remove the clot materials located into the pulmonary arteries.

To protect the brain and avoid irreversible brain injury during circulatory arrest(s), body temperature is lowered at 18-20°C. Deep hypothermia can lead to significant arterial vasoconstriction, which can reduce the blood supply to the brai. It also increases the solubility of CO2 in the blood, leading to respiratory alkalosis, which can also lead to vasoconstriction of cerebral vessels, increasing the risk of ischemic lesions.

In adult there is no consistent data on the cerebral perfusion during PAE surgery under deep hypothermia at 18-20°C. Animal studies showed that cerebral regulation seems to be preserved under these conditions. A better understanding of the effect of deep hypothermia on cerebral perfusion during PAE surgery is essential to adapt our management to limit the occurrence of postoperative neurological complications.

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Hypertension; Hypothermia; Cerebral Perfusion; Transcranial Doppler Ultrasound
• Intervention / Treatment: Procedure: Bilateral trans-cranial Doppler ultrasound

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Florence LECERF; Phone Number: +33140942517; Email: f.lecerf@ghpsj.fr
• Study Contact Backup: Name: Sylvain DIOP, Dr; Phone Number: +33140948637; Email: sdiop@ghpsj.fr

Study Locations

• France
  • Le Plessis-Robinson, France, 92350
    • Recruiting
    • Hopital Marie Lannelongue
    • Contact: Helene BEAUSSIER, Dr; Email: hbeaussier@ghpsj.fr
    • Principal Investigator: Sylvain DIOP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Scheduled for pulmonary artery thromboendarterectomy surgery.
• Patient with free, written and informed consent.
• Patient affiliated to a social security scheme (beneficiary or beneficiary's beneficiary).
• French-speaking patient.

Exclusion Criteria:

• Patient refusing to participate in the study.
• Patient under guardianship.
• Patient deprived of liberty.
• Pregnant or breast-feeding women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• 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: Patients with thromboendarterectomy surgery; Anesthesia was induced with sufentanil 0.3 g/kg, etomidate 0.3-0.4 mg/kg, rocuronium 0.4 mg/kg and maintained with continuous infusion Propofol and sufentanil. A pulmonary arterial catheter was inserted in all patients. Patients were cooled by means of the oxygenator heat exchanger at a rate of one degree Celsius every three minutes. Rewarming was achieved at a rate of one degree Celsius every five to ten minutes. The following measures were performed: Measure 1: In normo-thermia after induction of general anesthesia Measure 2: On CPB, before circulatory arrest and in hypothermia at 18-20°C Measure 3: On bypass, after circulatory arrest and in hypothermia at 18-20°C Measure 4: At the end of the procedure, after weaning from the bypass and in normothermia. For each measure mean arterial pressure, cardiac output, PaCO2, pH, bilateral NIRS value were also recorded.

Procedure: Bilateral trans-cranial Doppler ultrasound; Velocity measurements in the middle cerebral artery are made using an ultrasound probe applied to the patient's temple during surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of cerebral blood perfusion during deep hypothermia	Cerebral blood perfusion during deep hypothermia (18-20°C) will be assessed by measuring mean blood flow velocities in the middle cerebral arteries (MCAs) using trans-cranial Doppler ultrasound (DTC) at different time of the surgery (Four measures in total). All measure are performed during the time of the surgery. The first measure (M1) is baseline to which the other measure will be compared to.	M1: Baseline-normothermia after induction of general anesthesia (H0) M2: During CPB-at 18°C-before cardiac arrest (H2) M3: After cardiac arrest-at 18°C before (H4) M4: End of surgery-normothermia (H6)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between NIRS and middle cerebral arteries velocity values for each measure.	For each measure of middle cerebral arteries blood flow velocity performed during the surgery, the value of the near infrared spectroscopy (NIRS) is recorded. A total of four measures is performed during the time of the surgery.	M1: Baseline-normothermia after induction of general anesthesia (H0) M2: During CPB-at 18°C-before cardiac arrest (H2) M3: After cardiac arrest-at 18°C before (H4) M4: End of surgery-normothermia (H6)
Seek for post-circulatory arrest hyperemia	Comparison of the middle cerebral arteries blood flow velocities during the period of hypothermia, before and after cardiac arrest.	M2: During CPB after cooling at 18°C before cardiac arrest (H2). M3: After cardiac arrest at 18°C before rewarming period (H4).

Collaborators and Investigators

• Sponsor: Fondation Hôpital Saint-Joseph

Publications and helpful links

General Publications

• Brown CH 4th, Neufeld KJ, Tian J, Probert J, LaFlam A, Max L, Hori D, Nomura Y, Mandal K, Brady K, Hogue CW; Cerebral Autoregulation Study Group; Shah A, Zehr K, Cameron D, Conte J, Bienvenu OJ, Gottesman R, Yamaguchi A, Kraut M. Effect of Targeting Mean Arterial Pressure During Cardiopulmonary Bypass by Monitoring Cerebral Autoregulation on Postsurgical Delirium Among Older Patients: A Nested Randomized Clinical Trial. JAMA Surg. 2019 Sep 1;154(9):819-826. doi: 10.1001/jamasurg.2019.1163.
• Liu Y, Chen K, Mei W. Neurological complications after cardiac surgery: anesthetic considerations based on outcome evidence. Curr Opin Anaesthesiol. 2019 Oct;32(5):563-567. doi: 10.1097/ACO.0000000000000755.

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2023
• Primary Completion (Estimated): February 24, 2025
• Study Completion (Estimated): May 24, 2025

Study Registration Dates

• First Submitted: January 12, 2024
• First Submitted That Met QC Criteria: January 31, 2024
• First Posted (Actual): February 9, 2024

Study Record Updates

• Last Update Posted (Actual): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 22, 2024
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Hypothermia; Cardiopulmonary bypass; cerebral perfusion; Pulmonary endarterectomy; Transcranial doppler ultrasound
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Body Temperature Changes; Hypertension; Hypertension, Pulmonary; Hypothermia
• Other Study ID Numbers: 2023-A00270-45

Drug and device information, study documents

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