Combined Use of Low-dose Sugammadex Plus Neostigmine Administered for Reversal of Rocuronium

NCT ID: NCT03328312

Last Updated: 2017-11-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-01
• Study Completion Date: 2018-06-01

Brief Summary

Reversal of rocuronium-induced neuromuscular block by the combination of low-doses of neostigmine plus sugammadex decreases the cost of anesthetic medications, while maintaining efficacy of reversal in obese patients.

Detailed Description

Background Neuromuscular paralysis is a frequent requirement to facilitate airway management and surgery. Patients receiving neuromuscular blocking agents (NMBAs) are at risk of residual neuromuscular blockade (RNMB) that can lead to postoperative cardio-pulmonary complications, and may increase postoperative morbidity and mortality.1-2 NMBAs can be antagonized with the cholinesterase inhibitor neostigmine; however, this agent has several undesirable side effects because of its parasympathetic stimulation.3 Thus, muscarinic receptor antagonists, such as atropine, are used along with cholinesterase inhibitors; however, these drugs also have their own set of adverse effects. Despite its relatively slow onset of action and inability to antagonize profound blockade, neostigmine is still used frequently for reversal of rocuronium-induced neuromuscular blockade because of its low cost. Sugammadex is a selective relaxant biding agent, developed to encapsulate the steroidal NMBAs, and proved to be extremely effective for the reversal of either shallow (dose of 2 mg/kg), deep (dose of 4 mg/kg), or even profound (dose of 16 mg/kg) neuromuscular blockade. However, routine use of sugammadex is limited by its relatively high cost compared with neostigmine.

The purpose of the study is to investigate drug costs and adverse effects of low-dose neostigmine (0.025 mg/kg) plus low-dose sugammadex (1 mg/kg) for reversal of rocuronium-induced neuromuscular block, and compare efficacy of antagonism and costs of this combination therapy with the current standard therapies: full-dose sugammadex (2 mg/kg) and full-dose neostigmine (0.05 mg/kg) plus atropine.

Randomization and blinding On randomization, each patient will be allocated by a unique identifying number into study groups "A", "B", or "C". The allocation of a patient to the specific group will be only known by the research assistant. The participating anaesthetists as well as the research staff who collect patient data will remain blinded until after the completion of the study.

For reversal of rocuronium neuromuscular- block we used:

• Group A - Sugammadex (Bridion®) 2 mg/kg,
• Group B - Neostigmine (Miostin®; Stigmosan®) 0.05 mg/kg and atropine 1 mg/ dose.
• Group C - Neostigmine (Miostin®; Stigmosan®) 0.025 mg/kg and atropine 0.5 mg/dose followed within 3 min by Sugammadex 1 mg/kg.

Monitoring the neuromuscular blockade After induction of anesthesia and before administration of rocuronium, monitoring of neuromuscular blockade at the adductor pollicis muscle is initiated using acceleromyography (TOF-Watch SX, Organon, Dublin, Ireland). After degreasing the skin, two surface electrodes are placed above the ulnar nerve near the wrist. After induction of general anesthesia, 50-Hz tetanic stimulation is applied for 5 sec and followed after 1 min by train-of-four (TOF) stimulation every 15 sec. If the response to TOF is stable, calibration and supramaximal stimulation are ensured by built-in calibration function (CAL2). After at least 2 min of a stable baseline documentation of the response to TOF, rocuronium is administered.

At the end of surgery, inhalational agent (sevoflurane) will be discontinued. Once the end-tidal concentration of sevoflurane reaches 0.4-0.6%, the previously randomized reversal study drug will be administrated at shallow neuromuscular block (TOF count of 2). The primary efficacy variable is the incidence of residual neuromuscular block (defined as TOFR <0.90) measured at least 15 min. after the administration of the reversal agent. In case of residual block, a rescue dose of 2 mg/kg sugammadex will be administrated before tracheal extubation. Extubation is performed once patient is deemed fully recovered (TOFR = 1.0)

Conditions

Incidence of Postoperative Residual Curarization

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Sugammadex

For reversal of rocuronium neuromuscular- block we will use Sugammadex

Group Type: ACTIVE_COMPARATOR

Sugammadex

Intervention Type: DRUG

Time period from administration of the reversal agent to recovery of TOFR \>0.9

neostigmine+atropine

For reversal of rocuronium neuromuscular- block we will use Neostigmine (Miostin®; Stigmosan®) 0.05 mg/kg and atropine 1 mg/ dose.

Group Type: PLACEBO_COMPARATOR

neostigmine+atropine

Intervention Type: DRUG

Number and time of bradycardic episodes (HR\<60 bpm) as well as that of tachycardic episodes (HR\>100 bpm) before tracheal extubation

neostigmine+atropine+sugammadex

For reversal of rocuronium neuromuscular- block we will use Neostigmine (Miostin®; Stigmosan®) 0.025 mg/kg and atropine 0.5 mg/dose followed within 3 min by Sugammadex 1 mg/kg.

Group Type: EXPERIMENTAL

neostigmine+atropine+sugammadex

Intervention Type: DRUG

4\. Time of extubation

Interventions

Sugammadex

Time period from administration of the reversal agent to recovery of TOFR \>0.9

Intervention Type: DRUG

neostigmine+atropine

Number and time of bradycardic episodes (HR\<60 bpm) as well as that of tachycardic episodes (HR\>100 bpm) before tracheal extubation

Intervention Type: DRUG

neostigmine+atropine+sugammadex

4\. Time of extubation

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients scheduled for elective abdominal surgery
• 16-65 years of age
• BMI 30-39.9 ( obese class I-II)
• American Society of Anesthesiologists (ASA) physical status II.
• Surgery scheduled for general anesthesia and tracheal intubation and planned extubation at the end of surgery
• Surgical procedures with an anticipated length of at least 60 min.

Exclusion Criteria

• Emergency surgery

• Patients unable to consent to study participation
• Patients expected to be maintained on mechanical ventilation postoperatively
• Contraindication to any of the study drugs
• Patients with existing neuromuscular disease
• Acute or chronic renal failure (GFR-EPI <30 mL/min/1.73 m2)
• Acute/chronic liver disease (Child-Pugh Score >1)
• Hyperkalemia (> 5.3 mmol/l)
• Pregnancy
• History of stroke or ongoing paresis
• Glaucoma
• Breast feeding
• Sepsis

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Iuliu Hatieganu University of Medicine and Pharmacy

OTHER

Sponsor Role: lead

Responsible Party

Breazu Caius Mihai

Assistant professor MD,PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Caius Breazu, Md,PhD

Role: PRINCIPAL_INVESTIGATOR

Iuliu Hatieganu University of medicine and pharmacy cluj-Napoca

Central Contacts

Calin I Mitre, MD,PhD

Role: CONTACT

Phone: 004074157497

Email: cmitre2001@gmail.com

Caius M Breazu, MD,PhD

Role: CONTACT

Phone: 0040743010012

Email: csbreazu@yahoo.com

Other Identifiers

36325348/2017

Identifier Type: -

Identifier Source: org_study_id