Reversal of Neuromuscular Blockade
Conditions
Keywords
neuromuscular blockade, Sugammadex, Neostigmine, Myasthenia gravis, Postoperative Residual Curarization
Brief summary
The purpose of this study was to demonstrate in patients with myasthenia gravis (MG) undergoing thoracoscopic thymectomy faster recovery from a moderate neuromuscular block induced by rocuronium after reversal at reappearance of T2 by 2.0 mg/kg sugammadex compared to 50 ug/kg neostigmine. Methods: A total of 64 patients with MG undergoing thoracoscopic thymectomy will be randomly divided into two groups: Sugammadex group (S group) and Neostigmine group (N group). The same anesthesia methods will be applied in both groups. Patients of S group will receive a dose of 2.0 mg/kg sugammadex after the last dose of rocuronium, at reappearance of T2. Patients of N group will receive a dose of 50 ug/kg neostigmine after the last dose of rocuronium, at reappearance of T2. The primary endpoint is time from start of administration of sugammadex or neostigmine to recovery of train-of-four stimulation ratio (TOFr) to 0.9. Secondary end points include time from start of administration of sugammadex or neostigmine to recovery of TOFr to 0.8 and 0.7, time to extubation, clinical signs of neuromuscular recovery, hemodynamic changes after muscle relaxation antagonism, adverse effects, time to operating room (OR) discharge, time to post-anesthesia care unit (PACU) discharge, and pulmonary complications within 7 days after the operation.
Detailed description
Due to neuromuscular transmission and functioning deficits, patients with myasthenia gravis (MG) are at increased risk of postoperative residual curarization (PORC), and may even develop into postoperative myasthenia crisis (PMC), which is a serious complication after thymectomy and increases the risk of death, with an incidence of up to 18.2%. Effective reversal of neuromuscular blockade is crucial to ensure patient safety, reduce the incidence of PORC or PMC and prompt postoperative recovery. Traditionally, neostigmine, an acetylcholinesterase inhibitor, can be employed for neuromuscular blocking agent (NMBA) reversal. However, neostigmine is associated with potential drawbacks, such as delayed recovery and adverse muscarinic side effects. Sugammadex, a selective relaxant binding agent, represents a relatively new alternative for NMBA reversal, specifically designed to encapsulate and inactivate aminosteroid NMBAs. The clinical benefits of sugammadex have been documented in several studies, demonstrating faster reversal of neuromuscular blockade and more predictable recovery profiles compared to neostigmine. However, the use of sugammadex in patients with MG remains an area of limited evidence. To date, to the best of our knowledge, there is a lack of prospective research to elucidate the application value of sugammadex in thymectomy in patients with MG. This study is a prospective randomized controlled trial aimed at exploring the efficacy and safety of sugammadex compared to neostigmine for the reversal of neuromuscular blockade in patients with myasthenia gravis after thoracoscopic thymectomy.
Interventions
DRUGSugammadex
After the last dose of rocuronium, at reappearance of T2, a dose of 2.0 mg/kg sugammadex was administered. Dose will be according to participant actual body weight.
DRUGNeostigmine
After the last dose of rocuronium, at reappearance of T2, a dose of 50 ug/kg neostigmine (up to 5 mg maximum dose) plus atropine 0.02 mg/kg (up to 2 mg maximum dose) was administered. Dose will be according to participant actual body weight.
Sponsors
The First Affiliated Hospital with Nanjing Medical University
Beijing Tongren Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
The doctors making the follow-up assessment were unaware of the treatment received, and none of the doctors who administered the injections carried out the follow- up evaluations. Thus, both the patients and the assessing doctors were remained unaware of the treatment received throughout the trial
Intervention model description
Randomized parallel controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* • Patients with MG scheduled for elective thoracoscopic thymectomy * Aged 18 to 65 years * American society of Anesthesiologists (ASA) physical status classification system: I - III
Exclusion criteria
* Inability to obtain written informed consent * With severe renal or hepatic dysfunction * A plan to return to ICU with intubation postoperation * A family history of malignant hyperthermia * Suspected difficult airway * Allergy to medications involved in the study * A contraindication for neostigmine or sugammadex administration * The patient's arm is not available for neuromuscular monitoring * Patients receiving medication known to interfere with NMBAs (e.g., anticonvulsants, antibiotics, magnesium salts) * Pregnant or lactating patients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recovery time | After operation within 24 hours | The comparison of the recovery periods between groups when the start of administering reversal agent to the recovery of TOF ratio≥ 0.9 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time from start of administration of sugammadex or neostigmine to the train-of-four stimulation ratio (TOFr) 0.7. | After operation within 120 minutes | Muscle relaxation monitoring was performed with an accelero-myography (AMG) neuromuscular monitor by assessment of the TOF responses of adductor pollicis muscle to ulnar nerve stimulation every 15 seconds. T1 and T4 refer to the amplitudes of the first and fourth twitches, respectively, after TOF nerve stimulation. The TOFr, that is T4/T1 Ratio (expressed as a decimal of up to 1.0) represents the extent of recovery from neuromuscular blockade (NMB). A faster time to TOFr 0.7 indicates a faster recovery from NMB. |
| Extubation time | After operation within 60 minutes | The time period between administering a reversal agent to extubation |
| Time to discharge from the operating room | After operation within 60 minutes | The time period between administering a reversal agent to operating room discharge |
| Time to discharge from recovery room | After operation within 120 minutes | The time period between entering the recovery room amd discharge from recovery room |
| Incidence of postoperative residual neuromuscular blockade (rNMB) | After operation within 24 hours | Incidence of postoperative residual neuromuscular blockade (rNMB) (defined as a train-of-four ratio, TOFR \<0.9) measured 30 min after administration of the reversal agent. |
| The incidence of adverse effects | Within 48 hours after operation | Unit: %; This value is a percentage. Any adverse effects in the operating room or in PACU include procedural pain, nausea, vomiting, dizziness, pruritus, reintubation, incision site complication, postprocedural nausea, vomiting, flatulence, procedural complication, insomnia, muscular weakness, headache, pharyngolaryngeal pain. |
| Time from start of administration of sugammadex or neostigmine to the train-of-four stimulation ratio (TOFr) 0.8 | After operation within 120 minutes | Muscle relaxation monitoring was performed with an accelero-myography (AMG) neuromuscular monitor by assessment of the TOF responses of adductor pollicis muscle to ulnar nerve stimulation every 15 seconds. T1 and T4 refer to the amplitudes of the first and fourth twitches, respectively, after TOF nerve stimulation. The TOFr, that is T4/T1 Ratio (expressed as a decimal of up to 1.0) represents the extent of recovery from neuromuscular blockade (NMB). A faster time to TOFr 0.8 indicates a faster recovery from NMB. |
| The incidence of mean arterial blood pressure fluctuations ≥20% | After operation within 24 hours | The proportion of patients in this group who experience mean arterial blood pressure fluctuation ≥ 20% within 30 minutes after administration of antagonists compared with before administration of antagonists |
| The incidence of heart rate fluctuations ≥20% | After operation within 24 hours | The proportion of patients in this group who experience heart rate fluctuation ≥ 20% within 30 minutes after administration of antagonists compared with before administration of antagonists |
| The incidence of postoperative pulmonary complications | Within the first 7 days after surgery | Unit: %; This value is a percentage. Postoperative pulmonary complications include pneumonia; aspiration pneumonitis; atelectasis; respiratory failure; bronchospasm; pulmonary congestion; pleural effusion; pneumothorax. |
| Unplanned ICU hospitalization rate | 1 months after operation | Unit: %; This value is a percentage. |
| Hypoxemic events | participants will be followed for the duration of the PACU stay, an expected average of 2 hours, up to 7 days | Blood oxygenation values will be measured using pulse oximetry from the time of PACU admission until discharge from the PACU |
| Number of patients who need rescue medication | After operation within 24 hours | After extubation to prior to discharge from the recovery room, record the number of patients who need rescue medication because of clinical signs of residual paralysis (i.e. if a patient complain about muscle weakness, difficulty breathing, or oxygen desaturation ≤ 95%) |
Countries
China
Outcome results
None listed