Muscle Relaxation
Conditions
Keywords
Rocuronium, Sugammadex, Succinylcholine, Cisatracurium, Neostigmine, acceleromyography (TOF-Watch®)
Brief summary
This study is comparing of rocuronium-sugammadex and succinylcholine during LMS surgery that is characterized by short operation time, required intense paralysis and ambulatory setting, has not been investigated.
Detailed description
Laser microlaryngeal surgery (LMS) requires brief and intense paralysis in the short operation time and the ambulatory setting. The ideal muscle relaxant with rapid onset time, short duration of action and minimal side effects is not yet available. Succinylcholine (SCC) is commonly used muscle relaxant for LMS because of its rapid onset time and short duration of action. The use of SCC for tracheal intubation is usually followed by repeated small boluses or drip of SCC or small boluses of nondepolarizing muscle relaxants with intermediate duration. As an alternative to SCC, the non-depolarizing neuromuscular blocking agent rocuronium can be used for LMS. The onset of rocuronium 1mg/kg is around 60s that is similar to SCC. However higher doses of rocuronium have a long duration of action; this is inappropriate in ambulatory surgery that requires rapid recovery of neuromuscular function and rapid turnover. Sugammadex has recently been introduced as a selective relaxant-binding agent that allows for rapid reversal of rocuronium-induced neuromuscular blockade. Even profound neuromuscular block with rocuronium can be quickly antagonized with sugammadex. After obtaining Institutional Review Board approval and written informed consent, 80 patients is enrolling in this study. Patients is divided by two groups randomly as the Rocuronium-Sugammadex group(R-S group) and the Succinylcholine - Cisatracurium- Neostigmine group(S-C-N group) . Anesthesia was induced with intravenous propofol 1.5-2.5 mg/kg, together with fentanyl1.5 mcg/kg After induction of anesthesia, neuromuscular monitoring is performed continuously at the adductor pollicis muscle with acceleromyography (TOF-Watch®). Subsequently, in the R-S group, patients receive rocuronium 1mg/kg and in the S-C-N group, patients receive SCC 1mg/kg. After T1 assessed as being zero by neuromuscular monitoring, endotracheal intubation is performed. After endotracheal intubation, in the S-C-N group, cisatracurium 0.08mg/kg is injected and in the R-S group, the same volume of normal saline is injected. Anesthesia is maintained with desflurane with air during the surgery. Additive dose of rocuronium 0.15mg/kg or SCC 10mg is given as necessary to ensure that neuromuscular blockade remains below T2 during surgery. After the surgical procedure ends, patients receive sugammadex 2mg/kg in the R-S group, and pyridostigmine 0.2 mg/kg with atropine 10mcg/kg in the S-C-N group at the appearance of second TOF twitch (T2). Patient will be assessed for the time to recovery of the TOF ratio to 0.9, surgical rating scale (1- extremely poor conditions, 2- poor conditions, 3- acceptable conditions, 4- good conditions, 5- optimal conditions), and anesthesia time.
Interventions
DRUGSugammadex
Sugammadex 2mg/kg was injected to patients to R-S group, as reversal of neuromuscular blockade.
DRUGNeostigmine
Neostigmine (pyridostigmine) 0.2 mg/kg mg was injected to patients to S-C-N group, as reversal of neuromuscular blockade.
Sponsors
Korea University Anam Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* American Society of Anesthesiologist\[ASA\] class 1-3 * scheduled Laser microlaryngeal surgery under general anesthesia * written informed consent
Exclusion criteria
* suspected difficult tracheal intubation * disorder affecting neuromuscular blockade * known or suspected significant renal dysfunction * known or suspected severe hepatic dysfunction * history of malignant hyperthermia * allergy of opioids, neuromuscular blocking drugs or other medications used during general anesthesia * contraindication to pyridostigmine and/or atropine * pregnancy * breast feeding * body mass index \> 27kg/m2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Addition of Neuromuscular Blocking Agents | during surgery | Repeated small boluses or drip of Succinylcholine, or small boluses of nondepolarizing muscle relaxants with intermediate duration are usually followed. In this protocol, cisatracurium was injected after intubation to maintain neuromuscular blockade during surgery. We measure the requirement of additive dose of neuromuscular blocker to ensure that neuromuscular blockade remains below T2 during surgery |
| Recovery of T1 to 90% | from the end of surgery(when the surgeon removes the suspension laryngoscope ) to time when the TOF ratio is 0.9, up to 30 minutes | we measure the time from the end of surgery to recovery of the TOF 0.9. The end of surgery is defined as the time when the direct laryngoscope, aided by an operation microscope, is removed. |
| Surgical Rating Score | during surgery | describe by surgeon under his subjective opinion. 1 - extremely poor conditions 2- poor conditions 3- acceptable conditions 4- good conditions 5- optimal conditions |
| Recovery of T1 to 10% | from the end of surgery to time when the TOF ratio is 0.1, up to 30 minutes | we measure the time from the end of surgery to recovery of the TOF 0.1. The end of surgery is defined as the time when the direct laryngoscope, aided by an operation microscope, is removed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Eye Opening | from end of surgery to opening of the eyes to verbal commands | We expected the emergence time is shorter in R-S group than S-C-N group. So we measure the time from the end of surgery to opening of the eyes to verbal commands. |
| Time to Extubation | from the end of surgery to extubate a tracheal tube | We expected the emergence time is shorter in R-S group than S-C-N group. So we measure the time from the end of surgery to recovery of the TOF 0.9, and the time from the end of surgery to extubation |
| Time to First Spontaneous Breath | from end of surgery to first spontaneous breaths | time from end of surgery to first spontaneous breaths |
Other
| Measure | Time frame | Description |
|---|---|---|
| Length of Stay in te Operating Room | time from in to out of the operating room | LMS surgery has short operation time and ambulatory setting. So the length of stay in the operating room will have significant. We expected the lengh of stay in the operating room is more shorter in R-S group than S-C-N group. |
| Anesthesia Time | from the anesthesia start to end | time from propofol injection to extubation |
Participant flow
Recruitment details
Recruitment period : 2015.2.10 - 2015.6.30 Location : Korea University Medical Center Anam Hospital
Participants by arm
| Arm | Count |
|---|---|
| R-S Group Rocuronium-Sugammadex group
1. Induction agent :
* IV Propofol 1.5-2.5 mg/Kg and fentanyl 1.5mcg/kg
2. During induction of anesthesia, as muscle relaxant agent
* Rocuronium 1mg/kg
3. After endotracheal intubation
* normal saline(0.025 ml/kg)
4. Additive dose, for ensuring that neuromuscular blockade remains below T2 during surgery
* Rocuronium 0.15mg/kg
5. Relaxant agent reversal. at the the end of surgery.
* sugammadex 2mg/kg | 40 |
| S-C-N Group Succinylcholine-Cisatracurium-Neostigmine group
1. Induction agent :
* IV Propofol 1.5-2.5 mg/Kg and fentanyl 1.5mcg/kg
2. During induction of anesthesia, as muscle relaxant agent
* Succinylcholine 1mg/kg
3. After endotracheal intubation,
* Cisatracurium 0.08mg/kg
4. Additive dose, for ensuring that neuromuscular blockade remains below T2 during surgery
* Succinylcholine 10mg
5. Relaxant agent reversal. at the appearance of second TOF twitch (T2).
* Neostigmine 0.2 mg/kg with atropine 10μg/kg (for preventing side effects of neostigmine) | 40 |
| Total | 80 |
Baseline characteristics
| Characteristic | R-S Group | S-C-N Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 8 Participants | 11 Participants |
| Age, Categorical Between 18 and 65 years | 37 Participants | 32 Participants | 69 Participants |
| Age, Continuous | 48 years STANDARD_DEVIATION 12 | 52 years STANDARD_DEVIATION 15 | 50 years STANDARD_DEVIATION 13 |
| Sex: Female, Male Female | 18 Participants | 16 Participants | 34 Participants |
| Sex: Female, Male Male | 22 Participants | 24 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 40 | 0 / 40 |
| serious Total, serious adverse events | 0 / 40 | 0 / 40 |
Outcome results
Primary
Addition of Neuromuscular Blocking Agents
Repeated small boluses or drip of Succinylcholine, or small boluses of nondepolarizing muscle relaxants with intermediate duration are usually followed. In this protocol, cisatracurium was injected after intubation to maintain neuromuscular blockade during surgery. We measure the requirement of additive dose of neuromuscular blocker to ensure that neuromuscular blockade remains below T2 during surgery
Time frame: during surgery
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| R-S Group | Addition of Neuromuscular Blocking Agents | 0 participants |
| S-C-N Group | Addition of Neuromuscular Blocking Agents | 20 participants |
Primary
Recovery of T1 to 10%
we measure the time from the end of surgery to recovery of the TOF 0.1. The end of surgery is defined as the time when the direct laryngoscope, aided by an operation microscope, is removed.
Time frame: from the end of surgery to time when the TOF ratio is 0.1, up to 30 minutes
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| R-S Group | Recovery of T1 to 10% | 271 seconds |
| S-C-N Group | Recovery of T1 to 10% | 190 seconds |
Primary
Recovery of T1 to 90%
we measure the time from the end of surgery to recovery of the TOF 0.9. The end of surgery is defined as the time when the direct laryngoscope, aided by an operation microscope, is removed.
Time frame: from the end of surgery(when the surgeon removes the suspension laryngoscope ) to time when the TOF ratio is 0.9, up to 30 minutes
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| R-S Group | Recovery of T1 to 90% | 377 seconds |
| S-C-N Group | Recovery of T1 to 90% | 240 seconds |
Primary
Surgical Rating Score
describe by surgeon under his subjective opinion. 1 - extremely poor conditions 2- poor conditions 3- acceptable conditions 4- good conditions 5- optimal conditions
Time frame: during surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| R-S Group | Surgical Rating Score | 5.0 score |
| S-C-N Group | Surgical Rating Score | 5.0 score |
Secondary
Time to Extubation
We expected the emergence time is shorter in R-S group than S-C-N group. So we measure the time from the end of surgery to recovery of the TOF 0.9, and the time from the end of surgery to extubation
Time frame: from the end of surgery to extubate a tracheal tube
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| R-S Group | Time to Extubation | 430 seconds |
| S-C-N Group | Time to Extubation | 380 seconds |
Secondary
Time to Eye Opening
We expected the emergence time is shorter in R-S group than S-C-N group. So we measure the time from the end of surgery to opening of the eyes to verbal commands.
Time frame: from end of surgery to opening of the eyes to verbal commands
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| R-S Group | Time to Eye Opening | 340 seconds |
| S-C-N Group | Time to Eye Opening | 300 seconds |
Secondary
Time to First Spontaneous Breath
time from end of surgery to first spontaneous breaths
Time frame: from end of surgery to first spontaneous breaths
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| R-S Group | Time to First Spontaneous Breath | 263 seconds |
| S-C-N Group | Time to First Spontaneous Breath | 240 seconds |
Other Pre-specified
Anesthesia Time
time from propofol injection to extubation
Time frame: from the anesthesia start to end
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| R-S Group | Anesthesia Time | 28.4 minutes | Standard Deviation 7.5 |
| S-C-N Group | Anesthesia Time | 35.2 minutes | Standard Deviation 7 |
Other Pre-specified
Length of Stay in te Operating Room
LMS surgery has short operation time and ambulatory setting. So the length of stay in the operating room will have significant. We expected the lengh of stay in the operating room is more shorter in R-S group than S-C-N group.
Time frame: time from in to out of the operating room
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| R-S Group | Length of Stay in te Operating Room | 31.0 minutes | Standard Deviation 7.7 |
| S-C-N Group | Length of Stay in te Operating Room | 38.6 minutes | Standard Deviation 7.5 |