Bispectral index (BIS) measures the degree of consciousness analyzing the electroencephalogram (EEG) and provides an objective value of anesthetic depth in the patients undergoing general anesthesia in real- time method. Using BIS, clinicians can optimize the anesthetic depth and prevent hemodynamic side effects (e.g., hypotension, etc.) due to excessive use of anesthetics or arousal due to insufficient dose of anesthetics. BIS can be useful in general anesthesia using inhaled anesthetics such as sevoflurane, as well as intravenous anesthesia. 
Patients undergoing general anesthesia requires muscle relaxation for endotracheal intubation and surgical approach. Muscle relaxation is reversed at the end of the surgery using a reversal agent. Rocuronium is a steroid-based muscle relaxant that effectively relaxes skeletal muscle within 1-2 minutes when used 0.6-0.8 mg per body weight. Sugammadex is an ultra-rapid reversal agent for a steroidal neuromuscular blocking agent such as rocuronium with an onset time of 1.5-3 minutes. It is useful to completely reverse the muscle relaxation to secure the airway at the end of surgery especially which needs deep neuromuscular blockade. 
However, when the sugammadex is injected at the end of a surgery, a patient could show unwanted awakening signs which can be accompanied by an elevation in BIS value even if the concentration of anesthetic gas is maintained. The elevation of BIS value and undesirable wakefulness during neuromuscular blockade reversal is known to be caused by an afferent signal of neurons in skeletal muscle.(1) This undesirable wakefulness can cause irritation of an endotracheal tube which leads to sore throat and laryngospasm. There need to be an effort to predict and reduce this undesirable wakening. 
Guen et al. reported alertness signs with elevation in BIS were often observed with rapid reversal of deep neuromuscular blockade using sugammadex.(2) In contrast, in case of moderate neuromuscular blockade, Ilman et al. reported conflicting results.(3) As the previous studies reported, according to the level of the blockade, clinical signs of awakening after the injection of the reversal agent of neuromuscular blockade seems to appear differently. Therefore, we aimed to compare the clinical sign of awakening and alteration in BIS value depending on the degree of neuromuscular blockade when sugammadex is administrated, deep and moderate blockade, respectively.


(1) Lanier WL, Iaizzo PA, Milde JH, Sharbrough FW. The cerebral and systemic effects of movement in response to a noxious stimulus in lightly anesthetized dogs. Possible modulation of cerebral function by muscle afferents. Anesthesiology 1994; 80(2): 392-401

(2)  Le Guen, M., et al. "Reversal of neuromuscular blockade with sugammadex during continuous administration of anaesthetic agents: a double‐blind randomised crossover study using the bispectral index." Anaesthesia 75.5 (2020): 583-590.

(3)  Illman, Hanna, Heikki Antila, and Klaus T. Olkkola. "Reversal of neuromuscular blockade by sugammadex does not affect EEG derived indices of depth of anesthesia." Journal of clinical monitoring and computing 24.5 (2010): 371-376.

Others

(Comparison of awakening signs after administration of sugammadex according to the degree of neuromuscular blockade (deep vs moderate blockade))

Both group will undergo sevoflurane anesthesia for the scheduled operation and muscle relaxation will be maintained by continuous infusion of rocuronium (0.01-0.012 mg/kg/min). When the post tetanic count (PTC) and Train of four (TOF) count rise above the target range, additional 0.2mg/kg of rocuronium will be injected. When skin sutures are begun, 0.5mcg/kg of fentanyl will be injected to control pain, and the sevoflurane concentration (ETsevo 1.4- 2.6%) will be maintained to keep the bispectral index between 40-50. After maintaining a steady state for 5 minutes, sugammadex will be administrated as follows and clinical signs of awakening and alteration of the bispectral index (BIS) will be recoreded for 10 minites.

1. Deep neuromuscular blockade group
    During the surgery : maintain the post tetanic count (PTC) between 1 to 2 
    At the end of the surgery : IV sugammadex 4mg/kg will be administrated.

2. Intermediate neuromuscular blockade group
    During the surgery : maintain the Train of four (TOF) count between 1 to 2 
    At the end of the surgery : IV sugammadex 2mg/kg will be administrated.

Arm Label

Target Number of Participant

Arm Type

Arm Description

The patiens will undergo sevoflurane anesthesia for the scheduled operation and muscle relaxation will be maintained by continuous infusion of rocuronium (0.01-0.012 mg/kg/min) to maintain the post tetanic count (PTC) between 1 to 2.  When the PTC rises above the target range, additional 0.2mg/kg of rocuronium will be injected. When skin sutures are begun, 0.5mcg/kg of fentanyl will be injected to control pain, and the sevoflurane concentration (ETsevo 1.4- 2.6%) will be maintained to keep the bispectral index between 40-50. After maintaining a steady state for 5 minutes, 4mg/kg of sugammadex will be administrated and clinical signs of awakening and alteration of the bispectral index (BIS) will be recoreded for 10 minites.

Arm Label

Target Number of Participant

Arm Type

Arm Description

The patiens will undergo sevoflurane anesthesia for the scheduled operation and muscle relaxation will be maintained by continuous infusion of rocuronium (0.01-0.012 mg/kg/min) to maintain the train of four (TOF) count between 1 to 2.  When the TOF rises above the target range, additional 0.2mg/kg of rocuronium will be injected. When skin sutures are begun, 0.5mcg/kg of fentanyl will be injected to control pain, and the sevoflurane concentration (ETsevo 1.4- 2.6%) will be maintained to keep the bispectral index between 40-50. After maintaining a steady state for 5 minutes, 2mg/kg of sugammadex will be administrated and clinical signs of awakening and alteration of the bispectral index (BIS) will be recoreded for 10 minites.

Gender

Age

Description

1) Patents who have American society of anesthesiologist physical status either class I or II 
2) Patients who are sheduled to elective orthopedic surgery under sevoflurane anesthesia which will take one hour or more.

1) Pediatric patient under age 19. 
2) Body Mass Index > 30 kg / m 2 or <18.5 kg / m 2 
3) Severe liver disease 
4) chronic renal disease with glomerular filtration rate under 30 mLmin-1 1.73 m-2  or on hemodialysis 
5) Neuromuscular disease or mental illness 
6) Those diagnosed with metabolic diseases 
7) Drug addiction or alcohol addiction 
8) Emergency surgery 
9) Pregnant women or nursing women 
10) People who have contraindications to muscle relaxants (rocuronium) and sugammadex 
- Patients who have allergies to drugs or have a history of hypersensitivity reactions, respiratory disease patients, arrhythmia patients
11)  A person who is in the taboo of using sevoflurane 
- Patients with a history of allergy or hypersensitivity reactions, and malignant hyperthermia.

To compare clinical signs of awakening (ex : eye opening, cough, spontaneous movement, complete recovery, response to simple commands) depending on the degree of neuromuscular blockade (Deep NMB vs intermediate NMB)

for 10 minutes after administration of the sugammadex

change in bispectral index (BIS)

before and 10 minutes after the sugammadex injection

change in BIS Electromyography (EMG) signal

before and 10 minutes after the sugammadex injection

change in observer's assessment of the alertness/ sedation scale

before and 10 minutes after the sugammadex injection

time to reach 90% of TOF ratio

after the sugammadex injeciton, upto the 90% of TOF ratio

duration from the administration of sugammadex to extubation

when the patient extubated after the injection of sugammadex

the incidence of using rescue sugammadex

10 minutes after the first sugammadex injection

satisfaction of the patients

when the patient leaves the post-anesthetic care unit (PACU) after the surgery