Anesthetic Guidance of Depth of Anesthesia and Indirect Cardiac Output Monitoring in Thoracic Surgery

Study Overview
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Brief Summary
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Patients undergoing thoracotomy in thoracic surgery are prone to have complications of delayed recovery from general anesthesia and perioperative instable hemodynamics due to the relatively invasive procedures and patient's underlying morbidity. Therefore, intraoperative monitoring and corresponding management are of great importance to prevent relevant complications in thoracic surgery. This study aims to investigate the clinical benefits of two intraoperative monitoring techniques in patients undergoing thoracotomy surgery, including depth of anesthesia and minimally invasive cardiac output monitoring. First, M-Entropy system will be used to measure the depth of anesthesia and be evaluated regarding the effect of spectral entropy guidance on postoperative recovery. Second, we will apply ProAQT device in guiding goal-directed hemodynamic therapy and assess its impact on occurrence of postoperative pulmonary complications and recovery. In this study, we will conduct a factorial parallel randomized controlled trial and use the method of stratified randomization to evaluate both two monitoring technologies in the same patient group. The results of this study will provide important evidence and clinical implication for precision anesthesia and enhanced recovery after surgery (ERAS) protocol in thoracic surgery.

Official Title
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An Investigation of the Impact of Anesthetic Guidance of Depth of Anesthesia and Indirect Cardiac Output Monitoring on the Clinical Outcomes of Patients Undergoing Thoracic Surgery: A Factorial Parallel Randomized Controlled Trial

Conditions
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Anesthesia, Hemodynamic Instability, Postoperative Respiratory Complication

Intervention / Treatment
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* Device: M-Entropy guidance of anesthesia depth
* Device: ProAQT in guiding goal-directed hemodynamic therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing video-assisted thoracotomy for lung resection at Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan. Exclusion Criteria: Age < 20 years Pregnancy End-stage renal disease Emergency surgery Presence of circulatory shock needing vasoactive drugs before surgery Any diagnosis of aortic diseases Cerebral vascular diseases or trauma High-degree cardiac arrythmia (e.g. atrial fibrillation) Uses of cardiac pacemaker or automated implantable cardioverter defibrillator New York Heart Association functional classification 4 Long-term use of psychiatric medications Intraoperative blood loss > 1 L Intraoperative blood transfusion Planned or unanticipated transferal to ICU for postoperative mechanical ventilation Patient refusal to participate

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: M-Entropy guidance of anesthesia depth<br>In the M-Entropy group, dosage of volatile anesthetics will be adjusted to achieve the response and state entropy values between 40 and 60 from the start of anesthesia to the end of surgery. In the control group, dosage of volatile anesthetics will be titrated according to clinical judgment. | Device: M-Entropy guidance of anesthesia depth<br>* In the M-Entropy group, dosage of volatile anesthetics will be adjusted to achieve the response and state entropy values between 40 and 60 from the start of anesthesia to the end of surgery. In the control group, dosage of volatile anesthetics will be titrated according to clinical judgment.<br>|
| Active Comparator: ProAQT in guiding goal-directed hemodynamic therapy<br>Subjects randomized to the GDT group will be managed according to the ERAS algorithm utilizing ProAQT variables (mean arterial pressure, stroke volume variation and cardiac index) If stroke volume variation is ≥ 10%, a bolus of 150 ml of crystalloid fluid will be given until the stroke volume variation is < 10%. If mean arterial pressure is < 70 mmHg and/or cardiac index < 2.5 l·min-1·m-2 despite the stroke volume variation of < 10% following fluid challenge, single or consecutive boluses of ephedrine 4 mg and/or continuous intravenous infusion of norepinephrine 2-10 μg·min-1 will be administered. | Device: ProAQT in guiding goal-directed hemodynamic therapy<br>* If stroke volume variation is ≥ 10%, a bolus of 150 ml of crystalloid fluid will be given until the stroke volume variation is < 10%. If mean arterial pressure is < 70 mmHg and/or cardiac index < 2.5 l·min-1·m-2 despite the stroke volume variation of < 10% following fluid challenge, single or consecutive boluses of ephedrine 4 mg and/or continuous intravenous infusion of norepinephrine 2-10 μg·min-1 will be administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to spontaneous eye opening | The interval from the cessation of anesthetics to spontaneous eye opening | At the end of surgery | 
| Rate of in-hospital postoperative pulmonary complications | This includes atelectasis, pleural effusion, pneumonia, empyema, pulmonary embolism, re-operation, and respiratory failure. The diagnosis of atelectasis and pleural effusion will be made based on routinely performed chest radiographs on postoperative days 1 and 3. Pneumonia will be diagnosed if a patient presents with fever, leukocytosis and new infiltrates on chest radiography. Pleural empyema and pulmonary embolism will be confirmed by spiral computed tomography scan. Respiratory failure is defined as described in the protocol. | Within 30 days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to tracheal extubation | The interval from the cessation of anesthetics to tracheal extubation | At the end of surgery | 
| Time to orientation in time and place | The interval from the cessation of anesthetics to orientation in time and place | At the end of surgery | 
| Time to leave operating room | The interval from the cessation of anesthetics to leave operating room | At the end of surgery | 
| Rate of emergence agitation | Richmond Agitation-Sedation Scale will be used to evaluate the level of agitation and sedation promptly after extubation. This is defined as +4 combative, +3 very agitated, +2 agitated, +1 restless, 0 alert and calm, -1 drowsy, -2 light sedation, -3 moderate sedation, -4 deep sedation, and -5 unarousable. | During the recovery from anesthesia | 
| Rate of postoperative delirium | Events of delirium will be evaluated using the Confusion Assessment Method at the postanesthetic care unit. | 30 minutes after tracheal extubation | 
| Rate of intraoperative recall or awareness | As titled | One day after surgery | 
| Arterial partial pressure of oxygen (PaO2) / fraction of inspired oxygen (FiO2) | The relative change of PaO2/FiO2 values after induction of anesthesia and at the end of surgery | After induction of anesthesia and at the end of surgery | 
| Rate of cardiac complications | Myocardial infarction diagnosed by electrocardiogram and troponin T serum concentration; newly developed atrial fibrillation. | Within 30 days after surgery | 
| Rate of hypotensive episodes | This is defined as a decrease in mean arterial pressure > 20% for more than 15 min requiring vasopressors. | Within 30 days after surgery | 
| Rate of newly developed stroke | This will be based on the finding of imaging tests. | Within 30 days after surgery | 
| Length of hospital stay | As titled | Within 30 days after surgery |