Effectiveness of Sugammadex in LMS Surgery

• ClinicalTrials.gov Identifier: NCT02329964
• Recruitment Status: Unknown
• First Posted: January 1, 2015
• Results First Posted: September 28, 2015
• Last Update Posted: September 28, 2015
• Sponsor: Korea University Anam Hospital
• Information provided by (Responsible Party): Seol Ju, Park, Korea University Anam Hospital

Study Description

Brief Summary:

This study is comparing of rocuronium-sugammadex and succinylcholine during LMS surgery that is characterized by short operation time, required intense paralysis and ambulatory setting, has not been investigated.

Condition or disease	Intervention/treatment	Phase
Muscle Relaxation	Drug: Sugammadex; Drug: Neostigmine	Phase 4

Detailed Description:

Laser microlaryngeal surgery (LMS) requires brief and intense paralysis in the short operation time and the ambulatory setting.

The ideal muscle relaxant with rapid onset time, short duration of action and minimal side effects is not yet available.

Succinylcholine (SCC) is commonly used muscle relaxant for LMS because of its rapid onset time and short duration of action.

The use of SCC for tracheal intubation is usually followed by repeated small boluses or drip of SCC or small boluses of nondepolarizing muscle relaxants with intermediate duration.

As an alternative to SCC, the non-depolarizing neuromuscular blocking agent rocuronium can be used for LMS. The onset of rocuronium 1mg/kg is around 60s that is similar to SCC. However higher doses of rocuronium have a long duration of action; this is inappropriate in ambulatory surgery that requires rapid recovery of neuromuscular function and rapid turnover.

Sugammadex has recently been introduced as a selective relaxant-binding agent that allows for rapid reversal of rocuronium-induced neuromuscular blockade. Even profound neuromuscular block with rocuronium can be quickly antagonized with sugammadex.

After obtaining Institutional Review Board approval and written informed consent, 80 patients is enrolling in this study.

Patients is divided by two groups randomly as the Rocuronium-Sugammadex group(R-S group) and the Succinylcholine - Cisatracurium- Neostigmine group(S-C-N group) .

Anesthesia was induced with intravenous propofol 1.5-2.5 mg/kg, together with fentanyl1.5 mcg/kg After induction of anesthesia, neuromuscular monitoring is performed continuously at the adductor pollicis muscle with acceleromyography (TOF-Watch®).

Subsequently, in the R-S group, patients receive rocuronium 1mg/kg and in the S-C-N group, patients receive SCC 1mg/kg.

After T1 assessed as being zero by neuromuscular monitoring, endotracheal intubation is performed.

After endotracheal intubation, in the S-C-N group, cisatracurium 0.08mg/kg is injected and in the R-S group, the same volume of normal saline is injected.

Anesthesia is maintained with desflurane with air during the surgery. Additive dose of rocuronium 0.15mg/kg or SCC 10mg is given as necessary to ensure that neuromuscular blockade remains below T2 during surgery.

After the surgical procedure ends, patients receive sugammadex 2mg/kg in the R-S group, and pyridostigmine 0.2 mg/kg with atropine 10mcg/kg in the S-C-N group at the appearance of second TOF twitch (T2).

Patient will be assessed for the time to recovery of the TOF ratio to 0.9, surgical rating scale (1- extremely poor conditions, 2- poor conditions, 3- acceptable conditions, 4- good conditions, 5- optimal conditions), and anesthesia time.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Supportive Care
• Official Title: Comparison of the Effectiveness of Rocuronium - Sugammadex With Succinylcholine-Cisatracurium-Neostigmine in Patients Undergoing Laser Microlaryngeal Surgery
• Study Start Date: February 2015
• Actual Primary Completion Date: August 2015
• Estimated Study Completion Date: September 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: R-S group; Rocuronium-Sugammadex group; Induction of anesthesia : 1% propofol 1.5-2.5 mg/kg with fentanyl 1.5 mcg/kg; Muscle relaxant agent : Rocuronium 1mg/kg; After endotracheal intubation : normal saline(0.025 ml/kg); Additive dose, for ensuring that neuromuscular blockade remains below T2 during surgery : Rocuronium 0.15mg/kg; Relaxant agent reversal. at the the end of surgery : sugammadex 2mg/kg	Drug: Sugammadex; Sugammadex 2mg/kg was injected to patients to R-S group, as reversal of neuromuscular blockade.; Other Name: Bridion
Active Comparator: S-C-N group; Succinylcholine-Cisatracurium-Neostigmine group; Induction of anesthesia :1% propofol 1.5-2.5 mg/kg with fentanyl 1.5 mcg/kg; Muscle relaxant agent :Succinylcholine 1mg/kg; After endotracheal intubation : Cisatracurium 0.08mg/kg; Additive dose, for ensuring that neuromuscular blockade remains below T2 during surgery : Succinylcholine 10mg; Relaxant agent reversal at the appearance of second TOF twitch (T2) : Neostigmine 0.2mg/kg with atropine 10 mcg/kg (for preventing side effects of neostigmine)	Drug: Neostigmine; Neostigmine (pyridostigmine) 0.2 mg/kg mg was injected to patients to S-C-N group, as reversal of neuromuscular blockade.; Other Name: Pyridostigmine(Pyrinol)

Outcome Measures

Primary Outcome Measures :

1. Recovery of T1 to 90% [ Time Frame: from the end of surgery(when the surgeon removes the suspension laryngoscope ) to time when the TOF ratio is 0.9, up to 30 minutes ]
   we measure the time from the end of surgery to recovery of the TOF 0.9. The end of surgery is defined as the time when the direct laryngoscope, aided by an operation microscope, is removed.
2. Surgical Rating Score [ Time Frame: during surgery ]

   describe by surgeon under his subjective opinion.

   1 - extremely poor conditions 2- poor conditions 3- acceptable conditions 4- good conditions 5- optimal conditions

3. Addition of Neuromuscular Blocking Agents [ Time Frame: during surgery ]

   Repeated small boluses or drip of Succinylcholine, or small boluses of nondepolarizing muscle relaxants with intermediate duration are usually followed.

   In this protocol, cisatracurium was injected after intubation to maintain neuromuscular blockade during surgery.

   We measure the requirement of additive dose of neuromuscular blocker to ensure that neuromuscular blockade remains below T2 during surgery

4. Recovery of T1 to 10% [ Time Frame: from the end of surgery to time when the TOF ratio is 0.1, up to 30 minutes ]
   we measure the time from the end of surgery to recovery of the TOF 0.1. The end of surgery is defined as the time when the direct laryngoscope, aided by an operation microscope, is removed.

Secondary Outcome Measures :

1. Time to Extubation [ Time Frame: from the end of surgery to extubate a tracheal tube ]
   We expected the emergence time is shorter in R-S group than S-C-N group. So we measure the time from the end of surgery to recovery of the TOF 0.9, and the time from the end of surgery to extubation
2. Time to First Spontaneous Breath [ Time Frame: from end of surgery to first spontaneous breaths ]
   time from end of surgery to first spontaneous breaths
3. Time to Eye Opening [ Time Frame: from end of surgery to opening of the eyes to verbal commands ]
   We expected the emergence time is shorter in R-S group than S-C-N group. So we measure the time from the end of surgery to opening of the eyes to verbal commands.

Other Outcome Measures:

1. Length of Stay in te Operating Room [ Time Frame: time from in to out of the operating room ]
   LMS surgery has short operation time and ambulatory setting. So the length of stay in the operating room will have significant. We expected the lengh of stay in the operating room is more shorter in R-S group than S-C-N group.
2. Anesthesia Time [ Time Frame: from the anesthesia start to end ]
   time from propofol injection to extubation

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• American Society of Anesthesiologist[ASA] class 1-3
• scheduled Laser microlaryngeal surgery under general anesthesia
• written informed consent

Exclusion Criteria:

• suspected difficult tracheal intubation
• disorder affecting neuromuscular blockade
• known or suspected significant renal dysfunction
• known or suspected severe hepatic dysfunction
• history of malignant hyperthermia
• allergy of opioids, neuromuscular blocking drugs or other medications used during general anesthesia
• contraindication to pyridostigmine and/or atropine
• pregnancy
• breast feeding
• body mass index > 27kg/m2

Contacts and Locations

Sponsors and Collaborators

Korea University Anam Hospital

Investigators

• Principal Investigator: Jangeun Cho, M.D.,Ph.D.; Anesthesia and pain medicine department, Korea University Anam Hospital

More Information

Publications of Results:

Lee C, Jahr JS, Candiotti KA, Warriner B, Zornow MH, Naguib M. Reversal of profound neuromuscular block by sugammadex administered three minutes after rocuronium: a comparison with spontaneous recovery from succinylcholine. Anesthesiology. 2009 May;110(5):1020-5. doi: 10.1097/ALN.0b013e31819dabb0.

• Responsible Party: Seol Ju, Park, Resident, Korea University Anam Hospital
• ClinicalTrials.gov Identifier: NCT02329964
• Other Study ID Numbers: LMS-sugammadex study KoreaUH
• First Posted: January 1, 2015
• Results First Posted: September 28, 2015
• Last Update Posted: September 28, 2015
• Last Verified: August 2015

Keywords provided by Seol Ju, Park, Korea University Anam Hospital:

Rocuronium; Sugammadex; Succinylcholine; Cisatracurium; Neostigmine; acceleromyography (TOF-Watch®)

Additional relevant MeSH terms:

Neostigmine; Pyridostigmine Bromide; Cholinesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Parasympathomimetics; Autonomic Agents; Peripheral Nervous System Agents