Anesthesia, Neuromuscular Blockade
Conditions
Keywords
Sugammadex, Neostigmine, Reversal of neuromuscular block
Brief summary
The aim of this study is to evaluate whether the use of Sugammadex for reversing the neuromuscular blocking effects of rocuronium during neurointerventional procedures can speed recovery of neuromuscular function. Half of participates will receive Neostigmine with glycopyrrolate, while the other half will receive Sugammadex.
Detailed description
Incomplete recovery from neuromuscular blocking agents (NMBAs) residual block after anesthesia and surgery continues to be a common problem in the postanesthesia care (PACU). Neostigmine remains the most common acetylcholinesterase inhibitor in the United States. However, administration of the drug significantly impairs genioglossus muscle activity when administered after full recovery from neuromuscular block. Moreover, doses of neostigmine exceeding 0.06 mg/kg increase the risk of respiratory complications independent of NMBAs effects. Sugammadex is a modified γ-cyclodextrin that rapidly reverses that effect of the steroidal nondepolarizing NMBAs rocuronium and vecuronium. Sugammadex forms a stable, inactive 1:1 complex with rocuronium or vecuronium, reducing the amount of free NMBA available to bind to nicotinic acetylcholine receptors at the neuromuscular junction. Unlike neostigmine, sugammadex completely reverses even dense neuromuscular blocks. Patients having catheter-based neurointerventional procedures are kept deeply anesthetized. It is common to find patients nearly completely paralyzed at the end of neurointerventional procedures and have a markedly delayed emergence while waiting for muscle function to recover sufficiently to safely antagonize with neostigmine.
Interventions
DRUGNeostigmine
Neostigmine injection
DRUGGlycopyrrolate
Glycopyrrolate injection
DRUGSugammadex
Sugammadex injection
Sponsors
The Cleveland Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years; * American Society of Anesthesiologists (ASA) physical status 1-3; * Scheduled for catheter-based neurointerventional procedures including coiling and stent insertion; * General anesthesia.
Exclusion criteria
* Suspected difficult intubation; * Neuromuscular disorder; * Renal impairment creatinine ≥ 2 mg /dl; * Hepatic dysfunction; * History of malignant hyperthermia; * Allergy to neuromuscular blocking drugs, Sugammadex, neostigmine or glycopyrrolate; * Perioperative respiratory infections and/or pneumonia; * Intubated or unresponsive; * Pregnancy or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time in Minutes to Reach Train of Four (TOF) Ratio ≥ 0.9 After the Administration of Reversal Agent | within 90 minutes after endotracheal extubation | The primary outcome was a time-to-TOF ratio ≥ 0.9 after the administration of the reversal agent. The TOF ratio was measured in a continuous manner every 12 seconds from the administration of the reversal drug until TOF ratio ≥ 0.9 or until 90 minutes after administration of the reversal agent. |
| TOF Ratio at 90 Min | at 90 minutes after the administration of the reversal agent | TOF (train of four), also known as a peripheral nerve stimulator, is used to assess nerve function in patients receiving neuromuscular blocking agents (paralytic medications). Before giving the medications, the baseline must be measured because this tells how much electrical stimulation the patient needs for nerve stimulation without any paralytic on board. Our primary outcome TOF ratio between TOF at 90 minutes after the administration of the reversal agent versus the TOF at baseline tells us how well the treatment is working to reverse the rocuronium Neuromuscular. This is a sensitivity analysis of primary analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Time for Extubation After Administration of Reversal Agents | Up to 4 hours after administration of reversal agents | Time from administration of reversal agent to tracheal extubation |
| Change of Diaphragmatic Contractility Speed- Sniff (Breathing From the Nose), cm/s | from baseline to 90 minutes after the administration of the reversal agent | The change of diaphragmatic contractility speed was defined as baseline minus postoperative diaphragmatic contraction. |
| Change of Diaphragmatic Contractility Speed, Deep Breathing From Mouth, cm/s | from baseline to 90 minutes after the administration of reversal agent | The change of diaphragmatic contractility speed was defined as baseline minus postoperative diaphragmatic contraction. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Neostigmine With Glycopyrrolate Neostigmine 0. 07 mg/kg with glycopyrrolate 0.01 mg/kg with ceiling dose of 5 mg neostigmine with 1 mg of glycopyrrolate at the end surgery
Neostigmine: Neostigmine injection
Glycopyrrolate: Glycopyrrolate injection | 33 |
| Sugammadex Sugammadex 4 mg/kg at the end surgery
Sugammadex: Sugammadex injection | 35 |
| Total | 68 |
Baseline characteristics
| Characteristic | Total | Sugammadex | Neostigmine With Glycopyrrolate |
|---|---|---|---|
| Age, Continuous | 56 years STANDARD_DEVIATION 14 | 54 years STANDARD_DEVIATION 15 | 59 years STANDARD_DEVIATION 12 |
| Alcohol abuse | 1 Participants | 1 Participants | 0 Participants |
| Arterial hypertension | 43 Participants | 23 Participants | 20 Participants |
| ASA II | 6 Participants | 3 Participants | 3 Participants |
| ASA III | 64 Participants | 32 Participants | 32 Participants |
| Asthma | 6 Participants | 3 Participants | 3 Participants |
| Cancer | 2 Participants | 2 Participants | 0 Participants |
| Chronic pain requiring opioids | 1 Participants | 1 Participants | 0 Participants |
| Chronic pulmonary disease | 8 Participants | 3 Participants | 5 Participants |
| Current recreational drug user | 0 Participants | 0 Participants | 0 Participants |
| Current smoker | 13 Participants | 8 Participants | 5 Participants |
| Diabetes mellitus | 10 Participants | 6 Participants | 4 Participants |
| Intraoperative Ephedrine | 16 Participants | 9 Participants | 7 Participants |
| Intraoperative fentanyl | 68 Participants | 35 Participants | 33 Participants |
| Intraoperative fentanyl, mg | 0.10 mg | 0.10 mg | 0.10 mg |
| Intraoperative midazolam, mg | 0 mg | 0 mg | 0 mg |
| Intraoperative Norepinephrine | 0 Participants | 0 Participants | 0 Participants |
| Intraoperative Phenylephrine | 50 Participants | 25 Participants | 25 Participants |
| Intraoperative propofol, mg | 200 mg | 200 mg | 200 mg |
| Intraoperative remifentanil | 22 Participants | 8 Participants | 14 Participants |
| Intraoperative remifentanil, μg | 0 μg | 0 μg | 0 μg |
| Ischemic heart disease | 2 Participants | 2 Participants | 0 Participants |
| Myocardial infarction | 2 Participants | 1 Participants | 1 Participants |
| Neurologic diseases | 16 Participants | 7 Participants | 9 Participants |
| No medical history | 6 Participants | 3 Participants | 3 Participants |
| Obstructive sleep apnea | 10 Participants | 4 Participants | 6 Participants |
| Race/Ethnicity, Customized Race Afirican American | 6 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Caucasian | 61 Participants | 32 Participants | 29 Participants |
| Sex: Female, Male Female | 46 Participants | 27 Participants | 19 Participants |
| Sex: Female, Male Male | 22 Participants | 8 Participants | 14 Participants |
| Time-weighted average minimum alveolar concentration | 0.78 percent at 1 atmosphere | 0.78 percent at 1 atmosphere | 0.79 percent at 1 atmosphere |
| Weight | 91 kg STANDARD_DEVIATION 35 | 92 kg STANDARD_DEVIATION 38 | 90 kg STANDARD_DEVIATION 32 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 35 |
| other Total, other adverse events | 0 / 33 | 0 / 35 |
| serious Total, serious adverse events | 0 / 33 | 0 / 35 |
Outcome results
Primary
Time in Minutes to Reach Train of Four (TOF) Ratio ≥ 0.9 After the Administration of Reversal Agent
The primary outcome was a time-to-TOF ratio ≥ 0.9 after the administration of the reversal agent. The TOF ratio was measured in a continuous manner every 12 seconds from the administration of the reversal drug until TOF ratio ≥ 0.9 or until 90 minutes after administration of the reversal agent.
Time frame: within 90 minutes after endotracheal extubation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Neostigmine With Glycopyrrolate | Time in Minutes to Reach Train of Four (TOF) Ratio ≥ 0.9 After the Administration of Reversal Agent | 8 minutes |
| Sugammadex | Time in Minutes to Reach Train of Four (TOF) Ratio ≥ 0.9 After the Administration of Reversal Agent | 3 minutes |
p-value: <0.00195% CI: [2.2, 6.5]Cox proportional hazard model
Primary
TOF Ratio at 90 Min
TOF (train of four), also known as a peripheral nerve stimulator, is used to assess nerve function in patients receiving neuromuscular blocking agents (paralytic medications). Before giving the medications, the baseline must be measured because this tells how much electrical stimulation the patient needs for nerve stimulation without any paralytic on board. Our primary outcome TOF ratio between TOF at 90 minutes after the administration of the reversal agent versus the TOF at baseline tells us how well the treatment is working to reverse the rocuronium Neuromuscular. This is a sensitivity analysis of primary analysis.
Time frame: at 90 minutes after the administration of the reversal agent
Population: Eight patients were removed due to missing TOF at 90 min or TOF count not larger than 4.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Neostigmine With Glycopyrrolate | TOF Ratio at 90 Min | 1.07 ratio |
| Sugammadex | TOF Ratio at 90 Min | 1.16 ratio |
p-value: 0.1395% CI: [-2, 14]Wilcoxon (Mann-Whitney)
Secondary
Change of Diaphragmatic Contractility Speed, Deep Breathing From Mouth, cm/s
The change of diaphragmatic contractility speed was defined as baseline minus postoperative diaphragmatic contraction.
Time frame: from baseline to 90 minutes after the administration of reversal agent
Population: There were 6 (17%) missing in sugammadex group and 5 (15%) missing in neostigmine group on diaphragmatic function outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Neostigmine With Glycopyrrolate | Change of Diaphragmatic Contractility Speed, Deep Breathing From Mouth, cm/s | -0.02 cm/s | Standard Deviation 1.43 |
| Sugammadex | Change of Diaphragmatic Contractility Speed, Deep Breathing From Mouth, cm/s | 0.80 cm/s | Standard Deviation 1.51 |
p-value: 0.0495% CI: [-0.18, 1.81]t-test, 2 sided
Secondary
Change of Diaphragmatic Contractility Speed- Sniff (Breathing From the Nose), cm/s
The change of diaphragmatic contractility speed was defined as baseline minus postoperative diaphragmatic contraction.
Time frame: from baseline to 90 minutes after the administration of the reversal agent
Population: There were 6 (17%) missing in sugammadex group and 5 (15%) missing in neostigmine group on diaphragmatic function outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Neostigmine With Glycopyrrolate | Change of Diaphragmatic Contractility Speed- Sniff (Breathing From the Nose), cm/s | -0.04 cm/s | Standard Deviation 0.85 |
| Sugammadex | Change of Diaphragmatic Contractility Speed- Sniff (Breathing From the Nose), cm/s | 0.29 cm/s | Standard Deviation 1.13 |
p-value: 0.2195% CI: [-0.35, 1]t-test, 2 sided
Secondary
The Time for Extubation After Administration of Reversal Agents
Time from administration of reversal agent to tracheal extubation
Time frame: Up to 4 hours after administration of reversal agents
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Neostigmine With Glycopyrrolate | The Time for Extubation After Administration of Reversal Agents | 8 minutes |
| Sugammadex | The Time for Extubation After Administration of Reversal Agents | 8 minutes |
p-value: 0.395% CI: [0.43, 1.34]Cox proportional hazard model