Sedline

We will monitor the depth of anesthesia using Sedline^® (Masimo Corporation, Irvine, CA, USA) and titrate sevoflurane concentration to maintain the patient state index range of 25–50 during the surgery. Regional cerebral oximetry from the left and right forehead will be monitored using O3 sensors (Masimo Corporation, Irvine, CA, USA) and recorded throughout anesthesia. Blood pressure and heart rate will be maintained at ±20% of the preoperatively measured values at the ward. Transfusion of red blood cells, fresh frozen plasma, and platelets will be performed according to our institutional protocol. Packed red blood cells will be transfused when hemoglobin levels are < 8 g/dL in non-cyanotic infants and < 10 g/dL in cyanotic infants. Fresh frozen plasma or platelet concentrates will be administered on the basis of rotational thromboelastometry (ROTEM, TEM International GmbH, Munich, Germany), and a fibrinogen test (FIBTEM) and external test (EXTEM) will be used to obtain data after administration of protamine.

Cerebral activity during general anaesthesia was monitored using a Masimo™ SedLine® device with a four-frontal electrode EEG montage (Fp1, Fp2, F7, and F8, referenced on Cz), sampled at 63 Hz by default. EEG sub-hairline electrodes were placed a few minutes before general anaesthesia induction and removed shortly after recovery of consciousness. Intraoperative EEG data were then extracted from the device, anonymised, cleaned from burst suppression and artifacts, and stored on a file server in enhanced disk format (EDF). In other words, EEG segments containing burst suppression were never used for model construction. We retrieved patient characteristics (age, gender, weight, height, and BMI) and clinical information (type of anaesthetic drug and ASA score) from the anaesthetic assessment consultation.

Patients who underwent noncardiac surgery under general anesthesia at our institution from September 2020 to March 2023 were retrospectively studied. Patients aged ≥ 20 years who underwent invasive arterial pressure measurements and in whom only remimazolam or sevoflurane was used for anesthetic maintenance were included. Patients who discontinued surgery, had a < 10-min observation period for arterial pressure measurement, or had incomplete data were excluded. The patients were divided into two groups according to the drug used for anesthetic maintenance: the sevoflurane group (Group S) and remimazolam group (Group R). The choice of anesthetic drug, intraoperative anesthetic depth, and hemodynamic control were at the discretion of the anesthesiologist in charge of the patient. Electroencephalography monitoring was used for patients with SedLine® (Masimo Corporation, Irvine, CA, USA) or Bispectral Index™ monitors (Medtronic Inc., Minneapolis, MN, USA) as needed.

EEG from the PATHFINDER control cohort (n = 2) and MMGA cohort (n = 18) was recorded intraoperatively and analyzed postoperatively for retrospective analysis. EEG data were recorded with a pre-amplifier bandwidth of 0.5 to 92 Hz, sampling rate of 178Hz, with 16-bit, 29 nV resolution. The standard Sedline (Masimo Corporation, Irvine, CA, United States) electrode array records from electrodes located approximately at positions Fp1, Fp2, F7, and F8, with ground electrode at Fpz, and reference electrode approximately 1 cm above Fpz. Electrode impedance was less than 5 kΩ in each channel. The EEG was analyzed using the multi-taper spectrogram intraoperatively to manage unconscious and nociceptive state, and postoperatively to retrospectively observe unconsciousness (see Figure 3). EEG was also analyzed for suppression events, which are common during coma-like deep states of unconsciousness. Suppression identification was achieved using a recursive variance tracking algorithm (27 (link)) with an adaptive threshold that was determined by a second estimate of the variance evolving on a slower timescale. Suppressions are thus characterized as segments of EEG where the local variance is small relative to the long-term baseline variance. All data analyses were performed using the scientific Python stack (28 (link)).

When the patient arrived in the operating room, the following monitoring devices were mounted on the patient: noninvasive blood pressure, electrocardiography, oxygen saturation, peripheral nerve stimulator, and patient state index using a SedLine^® electroencephalograph sensor (Masimo Corp., Irvine, CA, USA). Then, 0.1 mg of glycopyrrolate was administered intravenously (IV) as a premedication; thereafter, anesthesia was induced with propofol 1–2 mg/kg and remifentanil 0.05–0.1 µg/kg. Tracheal intubation was facilitated with rocuronium 0.6 mg/kg after loss of consciousness. Mechanical ventilation was started with an inspiratory–expiratory ratio of 1:2, positive end-expiratory pressure of 5 cm H2O, and target tidal volume of 8 mL/kg ideal body weight. The respiratory rate was adjusted to maintain the end-expiratory carbon dioxide between 35–42 mmHg. Anesthesia was maintained with remifentanil 0.03–0.1 µg/kg/min and sevoflurane (0.6–1.0 age-adjusted minimum alveolar concentration). Postoperative neuromuscular blockade was evaluated using a nerve stimulator and antagonized with IV sugammadex (Bridion^®, MSD, Seoul, Korea).

Propofol at 2 mg/kg, rocuronium at 1 mg/kg, and remifentanil at 0.5–1 µg/kg were used to induce anesthesia. A radial artery catheter and peripheral venous line were inserted following intubation. Sevoflurane (0.8–1 × the age-adjusted minimal alveolar concentration in 50% O₂/air) and remifentanil (0.05–0.15 µg/kg/min) were used to maintain anesthesia. A SedLine^® electroencephalograph sensor (Masimo Corp., Irvine, CA, USA) was used to monitor the Patient State Index. Pulse oximetry, ECG, invasive arterial blood pressure, oropharyngeal temperature, end-tidal carbon dioxide (EtCO₂) concentration, and end-tidal sevoflurane concentration (EtSevo) were monitored. RALP was performed in the 30° Trendelenburg position with CO₂ pneumoperitoneum (intra-abdominal pressure, 12 mmHg).