Diaphragmatic Dysfunction, Muscle Fatigue, Muscle Weakness
Conditions
Brief summary
The effect of neuromuscular blocking agents (NMBA, e.g. rocuronium) on respiratory muscle activity is well known. However, since the availability of sugammadex, to our knowledge, no study has been conducted to evaluate the effect of this novel product on these muscles. Our hypothesis is that by applying a different strategy in the use of neuromuscular blocking agents and their reversal agents we might see a different activity of the respiratory muscles.
Interventions
DRUGsugammadex 2mg/kg
DRUGneostigmine
DRUGsugammadex 4mg/kg
DRUGplacebo
DRUGSingle rocuronium dose
DRUGRepeated rocuronium dose
DRUGContinuous rocuronium infusion
Sponsors
University Hospital, Antwerp
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Each participant must have the mental capacity to decide whether he/she takes part in the trial or not. Each participant must voluntarily give his/her written informed consent. In case a participant is physically unable to give a written informed consent, a legal representative is to perform this. * Each participant must be at least eighteen years of age. Participants can be of either sex and of any ethnical background. * Each participant must meet the American Society of Anesthesiologists class II, II or III criteria. * Each participant must be scheduled for intracranial surgery. During general anesthesia rocuronium must be used as a neuromuscular blocking agent. * Each participant must be a suitable candidate for the rapid reversal of the neuromuscular blockade. * Each female participant of sexually active age and of childbearing potential must agree to the use of a medically accepted method of contraception through seven days after the day of surgery. Postmenopausal (defined as at least twelve consecutive months without spontaneous menstrual period) women are not obliged to use contraceptives.
Exclusion criteria
* The participant is known or suspected to have a neuromuscular disorder. * The participant is known or suspected to have an allergic reaction to sugammadex, rocuronium, anesthetic or narcotic medications, or any drugs used during general anesthesia. * The participant is known or suspected to have an anatomical malformation impeding a proper intubation. * The participant is known or suspected to have a history of malignant hyperthermia. * The participant is pregnant (or intends to become pregnant within the presurgical period) or lactating. * The participant is known to have a renal insufficiency (defined as a serum creatinine concentration of two times the upper limit, or a glomerular filtration rate of less than 60 ml/min). * The participant is known or suspected to have a chronic obstructive pulmonary disease GOLD classification 2 or higher or has any respiratory disease that impairs his respiratory function to a NYHA III level or worse. * The participant is known to have an infection of the upper or lower airways, as diagnosed by clinical or laboratory findings. * The participant is known or suspected to have congestive heart failure. * The participant is obese, as defined by a body mass index of 30 kg/m2 or more. * The participant is known or suspected to have a major hepatic dysfunction. * The participant has received or is scheduled to receive toremifene and/or an intravenous administration of fusidic acid within a time span of twenty-four hours before and twenty-four hours after the surgery. * The participant is known or suspected to have any condition contraindicating the administration of sugammadex, neostigmine, glycopyrrolate or placebo. * The participant is known or suspected to be directly involved in this study and/or is employed by or is a family member of any person employed by the investigator, at the investigational site, or by the sponsor.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Electric Activity of the Diaphragm (Microvolts) | From the start of spontaneous breathing till extubation, limited to maximum ten minutes after the onset of spontaneous breathing |
Secondary
| Measure | Time frame |
|---|---|
| Electric Activity of the Intercostal Muscles | From the start of spontaneous breathing till extubation, limited to maximum ten minutes after the onset of spontaneous breathing |
Other
| Measure | Time frame |
|---|---|
| Centroid Frequency of the EMG, as Trend Variability (Change in %) From First to Last Recording | From the start of spontaneous breathing till extubation, limited to maximum one hour after the onset of spontaneous breathing |
Countries
Belgium
Participant flow
Recruitment details
Patients were screened for inclusion and approached the night prior to their elective surgery
Participants by arm
| Arm | Count |
|---|---|
| Single Rocuronium Dose - Placebo The patients will receive a single rocuronium dose, and no reversal agent.
placebo
Single rocuronium dose | 12 |
| Single Rocuronium Dose - Sugammadex The patients will receive a single rocuronium dose and sugammadex 2mg/kg as a reversal agent
sugammadex 2mg/kg
Single rocuronium dose | 11 |
| Repeated Rocuronium Dose - Neostigmine The patients will receive multiple rocuronium doses and neostigmine 50 mcg/kg as a reversal agent
neostigmine
Repeated rocuronium dose | 10 |
| Repeated Rocuronium Dose - Sugammadex The patients will receive multiple rocuronium doses and neostigmine 2mg/kg as a reversal agent
sugammadex 2mg/kg
Repeated rocuronium dose | 13 |
| Continuous Rocuronium Dose The participants will receive a continuous rocuronium infusion and sugammadex 4 mg/kg as a reversal agent
sugammadex 4mg/kg
Continuous rocuronium infusion | 9 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Data quality insufficient | 2 | 0 | 3 | 1 | 4 |
| Overall Study | Incorrect data recorded | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Insufficient data | 0 | 2 | 1 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 1 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Single Rocuronium Dose - Placebo | Single Rocuronium Dose - Sugammadex | Repeated Rocuronium Dose - Neostigmine | Repeated Rocuronium Dose - Sugammadex | Continuous Rocuronium Dose | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 54 years | 51 years | 56 years | 54 years | 55 years | 55 years |
| Body Mass Index | 26 kg/m2 | 27 kg/m2 | 25 kg/m2 | 26 kg/m2 | 24 kg/m2 | 26 kg/m2 |
| Sex: Female, Male Female | 6 Participants | 8 Participants | 6 Participants | 7 Participants | 6 Participants | 33 Participants |
| Sex: Female, Male Male | 6 Participants | 3 Participants | 4 Participants | 6 Participants | 3 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 |
Outcome results
Primary
Electric Activity of the Diaphragm (Microvolts)
Time frame: From the start of spontaneous breathing till extubation, limited to maximum ten minutes after the onset of spontaneous breathing
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Single Rocuronium Dose - Placebo | Electric Activity of the Diaphragm (Microvolts) | 3.7 microvolt |
| Single Rocuronium Dose - Sugammadex | Electric Activity of the Diaphragm (Microvolts) | 4.5 microvolt |
| Repeated Rocuronium Dose - Neostigmine | Electric Activity of the Diaphragm (Microvolts) | 3.2 microvolt |
| Repeated Rocuronium Dose - Sugammadex | Electric Activity of the Diaphragm (Microvolts) | 2.9 microvolt |
| Continuous Rocuronium Dose | Electric Activity of the Diaphragm (Microvolts) | 4.4 microvolt |
Secondary
Electric Activity of the Intercostal Muscles
Time frame: From the start of spontaneous breathing till extubation, limited to maximum ten minutes after the onset of spontaneous breathing
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Single Rocuronium Dose - Placebo | Electric Activity of the Intercostal Muscles | 2.4 microvolt |
| Single Rocuronium Dose - Sugammadex | Electric Activity of the Intercostal Muscles | 2.2 microvolt |
| Repeated Rocuronium Dose - Neostigmine | Electric Activity of the Intercostal Muscles | 1.5 microvolt |
| Repeated Rocuronium Dose - Sugammadex | Electric Activity of the Intercostal Muscles | 2.2 microvolt |
| Continuous Rocuronium Dose | Electric Activity of the Intercostal Muscles | 1.8 microvolt |
Other Pre-specified
Centroid Frequency of the EMG, as Trend Variability (Change in %) From First to Last Recording
Time frame: From the start of spontaneous breathing till extubation, limited to maximum one hour after the onset of spontaneous breathing