Clinical trial NCT04569864: Mild vs Moderate Hypothermic Circulatory Arrest With Unilateral Anterograde Cerebral Perfusion in Hemiarch Replacement
Official title: Comparing Mild Versus Moderate Hypothermic Circulatory Arrest With Unilateral Anterograde Cerebral Perfusion in Hemiarch Replacement
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Aortic Aneurysm
Lead sponsor: Tomsk National Research Medical Center of the Russian Academy of Sciences
Sponsor class: OTHER
First posted: 2020-09-30
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The total patient population will be randomized into 2 groups. The first group of the patients during aortic hemiarch replacement, mild hypothermia (30-32°C) will be used during circulatory arrest. (main group). The second group of the patients during aortic hemiarch replacement, moderate hypothermia (26-28°C) will be used during circulatory arrest. (control group).
Primary purpose: TREATMENT

Brief summary: The aim of our study is to analyze the immediate and long-term results between patients undergoing hemiarch replacement with ACP under mild hypothermic (30-32 °C) circulatory arrest versus moderate hypothermic (26-28 °C) circulatory arrest. It is hypothesized that circulatory arrest using mild hypothermia (30-32°C) and uSACP will result in complications reduction, during aortic hemiarch replacement, when compared to moderate hypothermia (26-28°C) and uSACP. For this purpose all of the patient population will be randomized into 2 groups. The first group of the patients during aortic hemiarch replacement, mild hypothermia (30-32°C) will be used during circulatory arrest. The second group of the patients during aortic hemiarch replacement, moderate hypothermia (26-28°C) will be used during circulatory arrest.

Detailed description: Mild versus moderate hypothermic circulatory arrest during aortic hemiarch replacement Hypothermic circulatory arrest with unilateral selective anterograde cerebral perfusion (SACP) is an important surgical technique, allowing complex aortic surgeries to be performed safely. One of the main positive aspects of the strategy for changing the hypothermia temperature is to reduce the systemic inflammatory response, minimize visceral organ dysfunction, and reduce the risk of postoperative bleeding - the adverse effects of hypothermia Patients will be operated for ascending aortic aneurysm in a hypothermic circulatory arrest with unilateral SACP. The main difference is during aortic hemiarch replacement, moderate hypothermia (26-28°C) and mild hypothermia (30-32°C) will be used during circulatory arrest. All data will be prospectively collected and recorded. All surgeries will be perform concurrently in the same time period. Experienced in aortic pathology surgeons will perform these operations.

Description of the procedures:

All surgical procedures will be performed via median sternotomy. During the aortic arch anastomosis, continuous, unilateral SACP using innominate artery will be employed. Unilateral SACP may be converted to bilateral ACP at the surgeon's discretion if adequate cerebral flows are not achieved or if there are concerns with cerebral oximetry measurements.

Once on CPB, the patient will be cooled to a nasopharyngeal (NP) temperature of either 30-32 °C or 26-28 °C, depending on to which treatment arm the patient has been randomized. Rectal temperature with be monitored as an additional temperature sites. Unilateral SACP will only be initiated once the target temperature has been reached. SACP via the innominate artery will be commenced with target flows of 8-10 ml/kg/min and perfusion pressure of 60-80 mmHg. Perfusion adequacy will be evaluated using measurement of blood pressure in both radial arteries and cerebral oximetry using near-infrared spectroscopy (NIRS).

After completion of the aortic hemiarch replacement, CPB will be resumed and the patient re-warmed to 36 °C prior to coming off CPB, with a = 1 °C temperature difference between temperature monitoring sites (NP and rectal).

Intraoperative information will be collected from the anesthetic record, surgical notes and perfusion records. Intraoperative data collection will include total operative time, CPB time, cross-clamp time, hypothermic cardiac arrest time, uSACP time, lowest nasopharyngeal and rectal temperature, arterial pressure in both radial arteries, perfusion rate and perfusion pressure during both of CPB and unilateral SACP, lowest hemoglobin concentration (g/L) and hematocrit (%), acid-base indices, intraoperative red blood cell transfusion (units), highest dose/agent used for intraoperative inotrope or vasopressor support. Also during the surgery will be performed NIRS and BIS-monitoring.

Postoperative data will include valuation of following indicators: mortality (hospital mortality and death from any cause); neurological injury (TIA, stroke, delirium), MRI and CT-scan only in event of postoperative stroke; acute kidney injury (creatinine level prior and 1, 2, 4 postoperative day (POD), urine output-up to 24-48 h, renal replacement therapy (dialysis); time of mechanical ventilation; re-exploration for bleeding, tamponade or other reasons; postoperative transfusion (packed red blood cells, platelets, fresh frozen platelets, cryoprecipitate); postoperative myocardial infarction (electrocardiogram and troponins); inotropic support during 24-48 h (agent and dose (VIS)); length of stay (intensive care unit and total hospital days).

Before surgery and on 12-16 POD, patients will undergo neurocognitive screening by trained personnel. Neurocognitive tests will include: MOCA examinations, Schulte Table and The Bourdon Test.

In addition, indicators of specific markers of brain damage will be evaluated. Indicators such as neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF) will be evaluated before surgery and on first POD. Also will be evaluated indicators of the hemostatic system: thrombin-antithrombin (TAT) complexes, prothrombin fragments 1+2, glu-plasminogen, tissue plasminogen activator (t-PA), endothelin 1-21 and thromboelastography (TEG) in following points - before surgery, lowest temperature during arrest time, after inactivation of heparin and 4 h after surgery.

Follow-up information will be collected using direct or phone contact with patients, relatives, or physicians.

Eligibility criteria: Inclusion Criteria:

* Patients with ascending aortic aneurysm
* Elective aortic hemiarch replacement
* Able to provide written informed consent

Exclusion Criteria:

* Surgery for acute aortic dissection or emergent operations
* Patients with known/documented coagulopathy
* Oncological disease (high degrees)
* Severe chronic heart failure
* Refusal of surgical treatment
* Patients in renal failure or currently being treated with renal replacement therapy (RRT) or estimated glomerular filtration rate (eGFR) \< 30 ml/min/1.73m2
* Severe carotid disease, defined as: any patient with previously documented carotid stenosis of \> 70%, without neurological deficits; or carotid stenosis \> 50% with neurological deficits; or previous carotid endarterectomy or stenting
* Pre-existing severe neurological impairment or inability to accurately assess neurocognitive function as determined by the operating surgeon

Primary outcomes:
measure: Operative mortality
timeFrame: During the first 30 days after the procedure
measure: Composite of neurologic injury
timeFrame: During the first 30 days after the procedure
measure: Incidence of Acute Kidney Injury (AKI)
timeFrame: During the first 30 days after the procedure
Secondary outcomes:
measure: Respiratory failure
timeFrame: During the first 30 days after the procedure
measure: Perioperative Myocardial Infarction
timeFrame: During the first 30 days after the procedure (assessed by daily serum assay and ECG in the ICU and every 5 days after discharge from ICU. )
measure: Rates of re-exploration for bleeding
timeFrame: During the first 3 days after the procedure
measure: Volume of perioperative blood transfusion
timeFrame: During the first 3 days after the procedure
measure: The duration of a patient's stay in the intensive care unit and on the hospital ward
timeFrame: Up to 90 days after surgery
measure: Duration of cardiopulmonary bypass
timeFrame: During the index procedure
Other outcomes:
Locations:
city: Tomsk
country: Russian Federation
facility: Tomsk NRMC
Study officials:
affiliation: Tomsk National Research Medical Center of the Russian Academy of Sciences
name: Dmitry S Panfilov, PhD
role: PRINCIPAL_INVESTIGATOR
References: