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

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

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.

Study Overview

• Status: Completed
• Conditions: Hypotension
• Intervention / Treatment: Device: EEG-guided general anesthesia

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Hamburg, Germany, 20251
    • University Medical Center Hamburg-Eppendorf

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EEG-guided general anesthesia; 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; 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.
No Intervention: Routine care; 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?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative AKI	Postoperative AKI defined as an increase in serum creatinine concentration of ≥0.3 mg/dL within any 48 h period within 7 postoperative days or of ≥50% from baseline within the first 7 postoperative days (based on: Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Acute Kidney Injury. The preoperative baseline serum creatinine concentration will be defined as the most recent recorded measurement within 30 days before the surgery. We will consider AKI as a binary outcome (no AKI vs. AKI of any stage). We will consider serum creatinine values when measured per routine care.	30 days before the surgery until the first 7 postoperative days

Collaborators and Investigators

• Sponsor: Universitätsklinikum Hamburg-Eppendorf

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2022
• Primary Completion (Actual): March 2, 2023
• Study Completion (Actual): August 16, 2023

Study Registration Dates

• First Submitted: March 3, 2022
• First Submitted That Met QC Criteria: March 23, 2022
• First Posted (Actual): March 24, 2022

Study Record Updates

• Last Update Posted (Estimated): November 20, 2023
• Last Update Submitted That Met QC Criteria: November 17, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypotension; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics
• Other Study ID Numbers: 2020-10155-BO-ff

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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