Interaction Between Magnesium and Neostigmine or Sugammadex for the Reversal of a Rocuronium-induced Neuromuscular Block

NCT03497923 | Completed Phase 4

• 1 other identifier: CCER 2016-00018
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief Summary

Magnesium sulphate is regularly used in perioperative medicine. During and after general anesthesia, it enhances the effect of muscle relaxants because it reduces the liberation of acetylcholine at the neuromuscular junction. When administered immediately after spontaneous recovery of a neuromuscular block (NMB), magnesium may cause a recurrence of NMB and compromise patient safety. Rocuronium is a neuromuscular blocking agent which is frequently used to facilitate intubating and surgical conditions. At the end of the procedure, there are two ways to accelerate the reversal of a neuromuscular block induced by rocuronium: 1. Administration of neostigmine, an anticholinesterase agent and competitive antagonist; 2. Administration of sugammadex, a γ-cyclodextrin compound and specific encapsulator of rocuronium. The study is done in patients receiving rocuronium and either neostigmine or sugammadex for reversal of NMB. It is hypothesized that when sugammadex is used as an antagonist of a rocuronium-induced NMB, it prevents the reappearance of NMB when magnesium is injected, because sugammadex should inactivate all remaining rocuronium molecules and restore neuromuscular reserve of the neuromuscular junctions. Further more it is hypothesized that reversal with neostigmine will not prevent a magnesium-induced recurrence of NMB to the same extent. The primary objective of the study is to show that after reversal with sugammadex there is no or only very little re-occurrence of neuromuscular block after a magnesium perfusion. Furthermore we want to show that after reversal with neostigmine there is a re-occurrence of neuromuscular block.

Conditions

Neuromuscular Blockade

Keywords

rocuronium, magnesium sulphate, neostigmine, sugammadex

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with a decrease in TOF ratio after magnesium administration

  Two consecutive measures with a value inferior to TOF 0.9

  Patients will be followed over 24 hours

Secondary Outcomes (2)

• Lowest TOF ratio measured after starting the magnesium perfusion

  120 minutes

• Time required for the TOF ratio to reach a TOF 0.9

  120 minutes

Study Arms (2)

Neostigmine

ACTIVE COMPARATOR

Patients are anesthesized with Propofol and receive 0.6mg-1 of rocuronium for tracheal intubation. Neuromuscular monitoring will be done on the ulnar nerve by train-of-four (TOF) using a TOF-Watch-SX® acceleromyograph (Organon \[Ireland\] Ltd). After spontaneous recovery of 2 twitches at the train-of-four monitor (TOF), patients receive neostigmine 50 μg kg-1.

Drug: Magnesium Sulfate

Sugammadex

EXPERIMENTAL

Patients are anesthesized with Propofol and receive 0.6mg-1 of rocuronium for tracheal intubation. Neuromuscular monitoring will be done on the ulnar nerve by train-of-four (TOF) using a TOF-Watch-SX® acceleromyograph (Organon \[Ireland\] Ltd). After spontaneous recovery of 2 twitches at the train-of-four monitor (TOF), patients receive sugammadex (Bridion®) 2 mg kg-1.

Drug: Magnesium Sulfate

Interventions

Magnesium Sulfate DRUG

After reversal the obention of a TOF ratio of 0.9 is avaited. 10 minutes later patients will receive a perfusion of magnesium 60 mg kg-1 over 5 minutes.

Neostigmine; Sugammadex

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients, age ≥18 to and ≤ 65 years
• American Society of Anesthesiology \[ASA\] status I or II
• Patient is able to read and understand the information sheet and to sign and date the consent form
• Patient scheduled of elective surgery lasting ≥100 minutes
• For women of childbearing age: negative pregnancy test (urinary or blood test)
• For women of childbearing age: women on the pill should be advised to follow the missed dose advice in the product information; women using non-oral hormonal contraceptives, such as depot formulation, should be advised to use additional contraception for the next seven days

You may not qualify if:

• A history of allergy or hypersensitivity to rocuronium, glycopyrronium bromide, neostigmine methylsulfate, sugammadex, or magnesium sulphate
• Neuromuscular disease receiving medications known to influence neuromuscular function (for instance, aminoglycosides or phenytoine)
• Preoperative medications known to influence neuromuscular function (for instance aminoglycosides, phenytoin, lidocaine)
• Patients under toremifene, flucloxacillin and fusidic acid treatment (interaction with sugammadex cannot not be excluded)
• Documented electrolyte abnormalities (for instance, hypermagnesemia)
• Documented atrioventricular heart block
• Patients with a body mass index \<19 or \>30 kg/m2
• Patient having participated in any clinical trial within 30 days, inclusive, of signing the informed consent form of the current trial.
• Patients undergoing interventions that need a continuous deep NMB (for surgical reasons).
• Pregnant or breast feeding women

Sponsors & Collaborators

• Christoph Czarnetzki: lead
• Hôpital du Valais: collaborator

Study Sites (2)

University Hospital of Geneva, Anesthesia Department

Geneva, Canton of Geneva, 1211, Switzerland

Location

Hôpital du Valais

Sion, 1951, Switzerland

Location

MeSH Terms

Interventions

Magnesium Sulfate

Intervention Hierarchy (Ancestors)

Magnesium Compounds; Inorganic Chemicals; Sulfates; Sulfuric Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Christoph Czarnetzki, MD, MBA

  University Hospital Geneve

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: quadruple
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Doctor, MBA

Model Details: 2 arms, randomized, double blind trial

Study Record Dates

• First Submitted: December 26, 2017
• First Posted: April 13, 2018
• Study Start: February 11, 2019
• Primary Completion: April 12, 2023
• Study Completion: April 13, 2023
• Last Updated: April 18, 2023

Record last verified: 2023-04

Locations

CH (2)