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This study is a multicenter, randomized, controlled, double-blinded, and parallel design study. A total of 96 patients were decided to be recruited considering a 10% dropout rate. Patients are randomized to receive a deep block or a moderate block. The randomization numbers are generated using a computer-generated randomization code (1) and are sealed in the opaque envelope until they are handed over to the anesthesiologist in charge of anesthesia management after the induction of anesthesia. Patients, surgeons reporting the scale of surgical status, and another researcher analysing the cytokines levels are blinded to the patient group. Patients aged 18-65 yr, ASA 1 or 2, and are scheduled for elective laparoscopic gastrectomy are included. Patients with severe respiratory or cardiac disease, hepatic or renal function impairment, on medications affecting neuromuscular function, and with known allergy to the drugs to be used are excluded.
Induction and maintenance of anesthesia
Premedication is done with midazolam 0.03 mg/kg IV at reception area. Anesthesia is induced and maintained with intravenous propofol, remifentanil, and rocuronium. The dose of propofol is adjusted to maintain BIS value to 40-60, remifentanil to maintain blood pressure within 20% of preoperative value, and rocuronium to maintain PTC 1-2 (deep block) or TOF1-2 (moderate block). The monitoring consists of ECG, NIBP, pulse oximetry, temperature, ETCO2, BIS, and neuromuscular monitoring with acceleromyography (TOF-Watch SXTM, Organon Ltd., Dublin, Ireland).
Management and monitoring of neuromuscular block
After induction of anesthesia, continuous neuromuscular monitoring is started after calibration and stabilization of the signal as recommended by good clinical research practice; 50 Hz tetanic stimulation for 5 s, calibration, stabilization for at least 2 min 2. After stabilization, rocuronium 0.6 mg/kg is administered IV within 5 s for tracheal intubation. Maintenance dose of 0.1-0.2 mg/kg rocuronium is administered as needed for the maintenance of PTC1-2 (deep block) or TOF1-2 (moderate block). At the end of surgery, sugammadex 4 mg/kg for deep block group or neostigmine 50 ㎍/kg with glycopyrrolate 10 ㎍/kg for moderate block group are administered IV for reversal of neuromuscular block.
Evaluation of surgical conditions
A 5-point surgical rating scale (1 = excellent, 2 = good, 3 = acceptable, 4 = poor, 5 = extremely poor) is rated by the surgeon who is in charge of the patient's operation and is blind to the patient's group assignment. Intraoperative patient movement reported by surgeon, checked by restoration of spontaneous respiration or sudden increase in PIP, and any other movement are also recorded.
Measurement of cytokines and acute phase reactants
Blood samples are collected from the antecubital vein of the arm not used for IV infusion preoperatively, at the end of peritoneal closure, and 1, 2, & 48 hr after the end of operation for analysis of TNF-α, IL-1β, 6, 8 and CRP. The blood samples are collected at test tubes and sent to the laboratory on ice. Cytokines are analyzed with enzyme-linked immunosorbent assay and CRP is determined by an institutional chemistry analyzer.
Postoperative pain measurement
Postoperative pain is evaluated by verbal numerical rating scale (VNRS, 0 = no pain, 10 = the severest pain imaginable) at postoperative 1, 2, 6, 24, and 48 hr. Postoperative pain is controlled by IV patient controlled analgesia using fentanyl. If patient complain of severe pain (VNRS score of 7 or more), additional analgesics can be used according to the attending physician. The amount of fentanyl used and additional analgesic drugs used are reported.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| deep block | Experimental | After induction of anesthesia, continuous neuromuscular monitoring is started after calibration and stabilization of the signal as recommended by good clinical research practice; 50 Hz tetanic stimulation for 5 s, calibration, stabilization for at least 2 min 2. After stabilization, rocuronium 0.6 mg/kg is administered IV within 5 s for tracheal intubation. Maintenance dose of 0.1-0.2 mg/kg rocuronium is administered as needed for the maintenance of post tetanic count 1-2 (deep block). At the end of surgery, sugammadex 4 mg/kg are administered IV for reversal of neuromuscular block. |
|
| moderate block | No Intervention | After induction of anesthesia, continuous neuromuscular monitoring is started after calibration and stabilization of the signal as recommended by good clinical research practice; 50 Hz tetanic stimulation for 5 s, calibration, stabilization for at least 2 min 2. After stabilization, rocuronium 0.6 mg/kg is administered IV within 5 s for tracheal intubation. Maintenance dose of 0.1-0.2 mg/kg rocuronium is administered as needed for the maintenance of train of four count 1-2 (moderate block). At the end of surgery neostigmine 50 ㎍/kg with glycopyrrolate 10 ㎍/kg are administered IV for reversal of neuromuscular block. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| deep block | Drug | sugammadex 4 mg/kg are administered IV for reversal of neuromuscular block |
|
| Measure | Description | Time Frame |
|---|---|---|
| IL-6 | Blood samples are collected from the antecubital vein of the arm not used for IV infusion 1 hr after the end of operation for analysis of IL- 6. | 1 hr after the end of operation |
| Measure | Description | Time Frame |
|---|---|---|
| TNF-α | Blood samples are collected from the antecubital vein of the arm not used for IV infusion at the end of peritoneal closure for analysis of TNF-α. | 30min before end of operation |
| IL-1β | Blood samples are collected from the antecubital vein of the arm not used for IV infusion at the end of peritoneal closure for analysis of IL-1β. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ah-Young Oh, MD.,Ph.D. | Seoul national univ. BUNDANG hospital | Study Chair |
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| ID | Title | Description |
|---|---|---|
| FG000 | Deep Block | Maintenance dose of 0.1-0.2 mg/kg rocuronium is administered as needed for the maintenance of post tetanic count 1-2 (deep block). At the end of surgery, sugammadex 4 mg/kg are administered IV for reversal of neuromuscular block. |
| FG001 | Moderate Block | Maintenance dose of 0.1-0.2 mg/kg rocuronium is administered as needed for the maintenance of train of four count 1-2 (moderate block). At the end of surgery neostigmine 50 ㎍/kg with glycopyrrolate 10 ㎍/kg are administered IV for reversal of neuromuscular block. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Deep Block | After induction of anesthesia, continuous neuromuscular monitoring is started after calibration and stabilization of the signal as recommended by good clinical research practice; 50 Hz tetanic stimulation for 5 s, calibration, stabilization for at least 2 min 2. After stabilization, rocuronium 0.6 mg/kg is administered IV within 5 s for tracheal intubation. Maintenance dose of 0.1-0.2 mg/kg rocuronium is administered as needed for the maintenance of post tetanic count 1-2 (deep block). At the end of surgery, sugammadex 4 mg/kg are administered IV for reversal of neuromuscular block. deep block: sugammadex 4 mg/kg are administered IV for reversal of neuromuscular block |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | IL-6 | Blood samples are collected from the antecubital vein of the arm not used for IV infusion 1 hr after the end of operation for analysis of IL- 6. | Posted | Mean | Standard Deviation | pg / ml | 1 hr after the end of operation |
|
adverse event data were not collected
All-Cause Mortality, Serious, and Other (Not Including Serious) Adverse Events were not monitored/assessed.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Deep Block | After induction of anesthesia, continuous neuromuscular monitoring is started after calibration and stabilization of the signal as recommended by good clinical research practice; 50 Hz tetanic stimulation for 5 s, calibration, stabilization for at least 2 min 2. After stabilization, rocuronium 0.6 mg/kg is administered IV within 5 s for tracheal intubation. Maintenance dose of 0.1-0.2 mg/kg rocuronium is administered as needed for the maintenance of post tetanic count 1-2 (deep block). At the end of surgery, sugammadex 4 mg/kg are administered IV for reversal of neuromuscular block. deep block: sugammadex 4 mg/kg are administered IV for reversal of neuromuscular block |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Bon-wook Koo | SNUBH | +82-10-7227-1379 | tendong2@gmail.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 13, 2018 | Mar 15, 2018 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000077122 | Sugammadex |
| ID | Term |
|---|---|
| D047408 | gamma-Cyclodextrins |
| D003505 | Cyclodextrins |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
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| 30min before end of operation |
| IL-8 | Blood samples are collected from the antecubital vein of the arm not used for IV infusion 1 hr after the end of operation for analysis of IL- 8. | 1 hr after end of operation |
| CRP | Blood samples are collected from the antecubital vein of the arm not used for IV infusion 48 hr after the end of operation for analysis of CRP. | 48 hr after end of operation |
| BG001 | Moderate Block | After induction of anesthesia, continuous neuromuscular monitoring is started after calibration and stabilization of the signal as recommended by good clinical research practice; 50 Hz tetanic stimulation for 5 s, calibration, stabilization for at least 2 min 2. After stabilization, rocuronium 0.6 mg/kg is administered IV within 5 s for tracheal intubation. Maintenance dose of 0.1-0.2 mg/kg rocuronium is administered as needed for the maintenance of train of four count 1-2 (moderate block). At the end of surgery neostigmine 50 ㎍/kg with glycopyrrolate 10 ㎍/kg are administered IV for reversal of neuromuscular block. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| stress response | Stress response were analyzed Cytokines(TNF-α, IL-1β, IL-6, IL-8, and C-reactive protein) Blood samples were collected from the antecubital vein of the arm not used for IV infusion at preoperatively, at the end of peritoneal closure, and at 2 and 48hrs after the end of operation for analysis of TNF-α, IL-1β, IL-6, IL-8, and C-reactive protein (CRP). Cytokines were analysed with enzyme-linked immunosorbent assay kit(R&D Systems, Minneapolis, Minnesota, USA) and CRP was determined by an institutional chemistry analyser(Beckman Coulter, Brea, Califonia, USA). | Count of Participants | Participants |
|
| OG001 | Moderate Block | After induction of anesthesia, continuous neuromuscular monitoring is started after calibration and stabilization of the signal as recommended by good clinical research practice; 50 Hz tetanic stimulation for 5 s, calibration, stabilization for at least 2 min 2. After stabilization, rocuronium 0.6 mg/kg is administered IV within 5 s for tracheal intubation. Maintenance dose of 0.1-0.2 mg/kg rocuronium is administered as needed for the maintenance of train of four count 1-2 (moderate block). At the end of surgery neostigmine 50 ㎍/kg with glycopyrrolate 10 ㎍/kg are administered IV for reversal of neuromuscular block. |
|
|
| Secondary | TNF-α | Blood samples are collected from the antecubital vein of the arm not used for IV infusion at the end of peritoneal closure for analysis of TNF-α. | Posted | Mean | Standard Deviation | pg / ml | 30min before end of operation |
|
|
|
| Secondary | IL-1β | Blood samples are collected from the antecubital vein of the arm not used for IV infusion at the end of peritoneal closure for analysis of IL-1β. | Posted | Mean | Standard Deviation | pg / ml | 30min before end of operation |
|
|
|
| Secondary | IL-8 | Blood samples are collected from the antecubital vein of the arm not used for IV infusion 1 hr after the end of operation for analysis of IL- 8. | Posted | Mean | Standard Deviation | pg / ml | 1 hr after end of operation |
|
|
|
| Secondary | CRP | Blood samples are collected from the antecubital vein of the arm not used for IV infusion 48 hr after the end of operation for analysis of CRP. | Posted | Mean | Standard Deviation | pg / ml | 48 hr after end of operation |
|
|
|
| 0 |
| 44 |
| 0 |
| 44 |
| 0 |
| 44 |
| EG001 | Moderate Block | After induction of anesthesia, continuous neuromuscular monitoring is started after calibration and stabilization of the signal as recommended by good clinical research practice; 50 Hz tetanic stimulation for 5 s, calibration, stabilization for at least 2 min 2. After stabilization, rocuronium 0.6 mg/kg is administered IV within 5 s for tracheal intubation. Maintenance dose of 0.1-0.2 mg/kg rocuronium is administered as needed for the maintenance of train of four count 1-2 (moderate block). At the end of surgery neostigmine 50 ㎍/kg with glycopyrrolate 10 ㎍/kg are administered IV for reversal of neuromuscular block. | 0 | 44 | 0 | 44 | 0 | 44 |
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| D003912 |
| Dextrins |
| D013213 | Starch |
| D005936 | Glucans |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |