Anesthesia, Neuromuscular Blockade
Conditions
Brief summary
The Bispectral Index (BIS) monitor is used in many operating rooms to provide information to the anesthesiologist about a patient's level of consciousness. The Composite Variability Index (CVI) is a new index that may provide the anesthesiologist with more information about the condition of the patient. The CVI is a measure of the combined variability in BIS (bispectral index) and frontal electromyography (EMG) activity that may be useful in assessing the nociception/anti-nociception balance for patients under general anesthesia.The purpose of this study is to determine if a commonly used anesthetic drug (rocuronium) affects the CVI measurement differently with different doses. Rocuronium is a neuromuscular blocking agent (NMBA) routinely used during surgery. It is expected that the group given the highest dose of rocuronium will have diminished CVI values. This study will randomize patients to one of four doses of rocuronium: no rocuronium, 0.2, 0.4, and 0.6 milligrams per kilo of body weight; the last dose is the standard amount for adults. It is expected that the group given the highest dose of rocuronium will have diminished CVI values. By including intermediate doses, information about the function of CVI in states of less than full muscle relaxation, or paralysis, will be obtained. This information is critically important for the development of the composite variability index, because during general anesthesia patients are usually maintained in a state of less than full paralysis. If the CVI response to stimulation in the intermediate groups is similar to the group receiving no rocuronium, the monitor may find wide clinical applicability. If the response is similar to the maximal rocuronium group, the index may only be reliable in states with no muscle relaxant, which will greatly limit clinical utility.
Detailed description
Consented subjects randomized to one of four doses of rocuronium will be transported to the operating room and be connected to routine monitors that included a BIS (Covidien), M-Entropy sensor (GE Healthcare) and TOF (train of four) monitor. Following preoxygenation, general anesthesia will be induced with propofol and remifentanil using traditional syringe pumps. The induction doses given and subsequent infusion rates will be determined by utilizing pharmacokinetic (Pk) models (Marsh model for propofol, Minto model for remifentanil). Unconsciousness will be confirmed by performing the usual clinical assessments and by obtaining a BIS value between 40 and 50. Once the subject is unconsciousness, they will be given the assigned dose of rocuronium, after which the study anesthesiologist will perform a laryngoscopy. The anesthesiologist performing the laryngoscopy will not know what dose of rocuronium the subject received. Neuromuscular blockade (NMB) will be monitored by a train-of-four twitch monitor (TOF Watch-SX) at the adductor pollicis muscle (2 HZ, 50mAmp) every 15 seconds. At three minutes after the rocuronium administration, a standardized 20-second laryngoscopy will be applied. The CVI, entropy, and hemodynamic responses (heart rate, blood pressure measurement each minute) and train-of-four measurements will be monitored for three minutes before and after the laryngoscopy.
Interventions
DRUGSaline 0.06 ml/kg
IV Infusion x1 prior to laryngoscopy
DRUGRocuronium 0.2 mg/kg
IV Infusion x1 prior to laryngoscopy
DRUGRocuronium 0.4 mg/kg
IV Infusion x1 prior to laryngoscopy
IV Infusion x1 prior to laryngoscopy
Sponsors
Medtronic - MITG
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* American Society of Anesthesia (ASA) physical status class I or II. * Body mass index between 18 and 35 kg m-2. * No use of psychotropic or neuropsychiatric medications. * A airway assessment with no indication of a difficult intubation including a class I or II Mallampati airway and a mandible-to-hyoid distance of greater than three fingerbreadths. * Age between 18-75 years.
Exclusion criteria
* Does not meet inclusion criteria.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Mean Difference in CVI Between Pre-laryngoscopy and Post-laryngoscopy for Each of the Four Rocuronium Groups | Six minutes after the dose of rocuronium with laryngoscopy at 3 minutes after the study intervention | The difference between the mean CVI in three minutes prior to laryngoscopy and three minutes following laryngoscopy reported as the mean change in CVI and the +/- 95% confidence interval for each group. The Composite Variability Index (CVI) scale is a logistic regression of three measures of processed electroencephalography (EEG) signals. These signals are Bispectral Index (BIS), the variability of electromyelogram (sEMG), and the variability of BIS (sBIS). The scale ranges from 0 to 100 where a lower CVI value represents a lower likelihood of intraoperative somatic responses, and a higher CVI value represents a higher likelihood of intraoperative somatic responses. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Average CVI During the Maintenance Phase of Anesthesia for the Two Remifentanil Groups | Maintenance Anesthesia | Mean CVI from incision to propofol off reported as the mean CVI +/- 95% confidence interval for the two groups |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 Rocuronium dose 0 mg/kg prior to laryngoscopy | 19 |
| Group 2 Rocuronium dose 0.2 mg/kg prior to laryngoscopy | 19 |
| Group 3 Rocuronium dose 0.4 mg/kg prior to laryngoscopy | 20 |
| Group 4 Rocuronium dose 0.6 mg/kg prior to laryngoscopy | 17 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Physician Decision | 1 | 1 | 0 | 3 |
Baseline characteristics
| Characteristic | Total | Group 1 | Group 2 | Group 3 | Group 4 |
|---|---|---|---|---|---|
| Age, Continuous | 37.9 years STANDARD_DEVIATION 11.34 | 35.9 years STANDARD_DEVIATION 12.3 | 38.6 years STANDARD_DEVIATION 14.6 | 39.4 years STANDARD_DEVIATION 12.7 | 32.9 years STANDARD_DEVIATION 6.4 |
| Sex: Female, Male Female | 34 Participants | 9 Participants | 8 Participants | 8 Participants | 9 Participants |
| Sex: Female, Male Male | 41 Participants | 10 Participants | 11 Participants | 12 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 19 | 0 / 19 | 0 / 20 | 0 / 17 |
| serious Total, serious adverse events | 0 / 19 | 0 / 19 | 0 / 20 | 0 / 17 |
Outcome results
Primary
The Mean Difference in CVI Between Pre-laryngoscopy and Post-laryngoscopy for Each of the Four Rocuronium Groups
The difference between the mean CVI in three minutes prior to laryngoscopy and three minutes following laryngoscopy reported as the mean change in CVI and the +/- 95% confidence interval for each group. The Composite Variability Index (CVI) scale is a logistic regression of three measures of processed electroencephalography (EEG) signals. These signals are Bispectral Index (BIS), the variability of electromyelogram (sEMG), and the variability of BIS (sBIS). The scale ranges from 0 to 100 where a lower CVI value represents a lower likelihood of intraoperative somatic responses, and a higher CVI value represents a higher likelihood of intraoperative somatic responses.
Time frame: Six minutes after the dose of rocuronium with laryngoscopy at 3 minutes after the study intervention
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Group 1 | The Mean Difference in CVI Between Pre-laryngoscopy and Post-laryngoscopy for Each of the Four Rocuronium Groups | 2.40 units on a scale |
| Group 2 | The Mean Difference in CVI Between Pre-laryngoscopy and Post-laryngoscopy for Each of the Four Rocuronium Groups | 1.39 units on a scale |
| Group 3 | The Mean Difference in CVI Between Pre-laryngoscopy and Post-laryngoscopy for Each of the Four Rocuronium Groups | 0.48 units on a scale |
| Group 4 | The Mean Difference in CVI Between Pre-laryngoscopy and Post-laryngoscopy for Each of the Four Rocuronium Groups | 0.17 units on a scale |
Comparison: Null hypothesis that neuromuscular blocking drugs have no effect on CVI with 95% confidence.p-value: <0.05ANOVA
Secondary
The Average CVI During the Maintenance Phase of Anesthesia for the Two Remifentanil Groups
Mean CVI from incision to propofol off reported as the mean CVI +/- 95% confidence interval for the two groups
Time frame: Maintenance Anesthesia
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Group 1 | The Average CVI During the Maintenance Phase of Anesthesia for the Two Remifentanil Groups | 1.73 units on a scale |
| Group 2 | The Average CVI During the Maintenance Phase of Anesthesia for the Two Remifentanil Groups | 1.38 units on a scale |