Effect of EEG-guided General Anesthesia on Cumulative Dose of Norepinephrine

Study Overview
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Brief Summary
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Intraoperative hypotension is common in patients having non-cardiac surgery under general anesthesia and is associated with major postoperative complications including myocardial injury, AKI, and death. Intraoperative hypotension is also common in patients having vascular surgery. To treat intraoperative hypotension, vasopressors - such as norepinephrine - and fluids are used. However, high-dose vasopressor and excessive fluid therapy are also associated with postoperative complications. The depth of general anesthesia may be a modifiable cause of intraoperative hypotension. Deep levels of general anesthesia may cause cardiovascular depression with intraoperative hypotension and higher vasopressor requirements. Optimal depth of general anesthesia is defined as a state in which the patient is at low risk of recall of intraoperative events while maintaining blood pressure stability with minimal intervention. Depth of anesthesia can be confirmed using clinical signs, the concentration of inhaled or intravenous anesthetics, or neuromonitoring such as processed electroencephalography (pEEG). pEEG presents an opportunity to monitor changes in human brain electrical activity and to help estimating the patients' level of (un)consciousness and the optimal depth of anesthesia. EEG-guided general anesthesia may thus decrease norepinephrine doses needed to treat intraoperative hypotension in patients having surgery.

Official Title
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EEG-guided General Anesthesia vs. Routine Care and Cumulative Dose of Norepinephrine in Patients Having Vascular Surgery: a Pilot Randomized Trial

Conditions
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Hypotension

Intervention / Treatment
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* Device: EEG-guided general anesthesia


Participation Criteria
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Eligibility Criteria
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We will include consenting patients ≥45 years scheduled for elective vascular surgery under general anesthesia if: surgery is expected to last at least 60 min AND the estimated blood loss during surgery is less than 1000 mL AND intraarterial blood pressure monitoring (arterial catheter) is planned during surgery We will not include patients with previous transplantation of kidney, liver, heart, or lung and those who are septic (according to current Sepsis-3 definition). And we will not include patients with American Society of Anesthesiologists' physical status V and VI, or pregnancy. We will exclude patients after randomization if they were treated with vasopressors others than norepinephrine during surgery. Written informed consent will be obtained from all patients prior to study inclusion.

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EEG-guided general anesthesia<br>EEG-guided general anesthesia group (i.e., intervention group): For pEEG monitoring we will use the SEDLine monitor (Masimo, Irvine, CA) which provides the patient state index (PSi; a processed EEG parameter with values from 1 to 100), density spectral array (DSA; a display that represents the frequencies and amplitudes of brain waves through time), spectral edge frequency (SEF), and the raw EEG signal. | Device: EEG-guided general anesthesia<br>* pEEG monitoring will start with the beginning of induction of general anesthesia and will end with the end of surgery (surgical suture). In the EEG-guided group, depth of anesthesia will be adjusted to target PSI values between 25 and 50 and spectral edge frequency between 10 and 15. In case of contradictory values, the raw EEG waveforms, ARTF, EMG, as well as the overall clinical situation will be evaluated for decision making.<br>|
| No Intervention: Routine care<br>Routine care group (i.e., control group): Adjustment of depth of general anesthesia will be at the discretion of the treating anesthesiologist. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative norepinephrine dose | Time-weighted cumulative norepinephrine dose normalized to the patient's actual body weight: cumulative norepinephrine dose [µg] / body weight [kg] / length of surgery [min]; unit: µg/kg/min | Outcome meassure will be assessed at the end of surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of intraoperative hypotension | Cumulative minutes below MAP of 65 mmHg | Outcome meassure will be assessed at the end of surgery | 
| Incidence and severity of intraoperative hypotension | Area under a mean arterial pressure of 65 mmHg | Outcome meassure will be assessed at the end of surgery | 
| Incidence and severity of intraoperative hypotension | Time-weighted average MAP under 65 mmHg | Outcome meassure will be assessed at the end of surgery | 
| Hospital length of stay | Hospital length of stay | Through study completion, an average of 1 year | 
| ICU length of stay | ICU length of stay | Through study completion, an average of 1 year | 
| Hospital mortality | Hospital mortality | Through study completion, an average of 1 year |