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Residual Paralysis and Reversal With Routine Neostigmine Versus Half-dose Sugammadex and Routine Neostigmine

Primary Purpose

Neuromuscular Blockade, Sugammadex, Neostigmine

Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Neostigmine
Sugammadex
Sponsored by
Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuromuscular Blockade focused on measuring Residual Curarization, Postoperative, Complication, Neuromuscular blockade, Neostigmine, Sugammadex, Rocuronium

Eligibility Criteria

40 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Inclusion criteria:
  • 40 and 65 years of age,
  • American Society of Anesthesiologists Physical Status (ASA-PS) of 3 and 4,
  • Elective lower gastrointestinal tumor resection surgeries,
  • Supine positioning,
  • Surgery requiring use of general anesthesia and muscle relaxation,
  • Use of inhalational agent of sevoflurane anesthesia,
  • Surgical duration of about three to six hours.

Exclusion Criteria:

  • History of known or suspected neuromuscular disease,
  • History of renal or hepatic dysfunction,
  • Hyperkalemia,
  • Patients receiving antibiotics, anticonvulsants, or magnesium,
  • History of stroke,
  • History of glaucoma,
  • History of pregnancy or breastfeeding,
  • Suspicion of abdominal infection or sepsis,
  • Suspected history of malignant hyperthermia,
  • An allergy to medications used during general anesthesia

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Active Comparator

    Arm Label

    Neostigmine

    Neostigmine and Sugammadex

    Arm Description

    The Group N (Neostigmine) (n=48), patients received standard intravenous neostigmine 0.05 mg/kg and atropine 0.02 mg/kg doses before extubation. A train-of-four (TOF) count of 2 in TOF Watch monitoring provides information of a shallow neuromuscular block. If at least two twitches are on the TOF watch monitor, the study investigators administer reversal medication for neuromuscular blockade in both groups. At this point, depending on randomization, a reversal agent is administered for each randomized group by an anesthesia resident or nurse who is blinded to the study protocol. The study investigators record the recovery periods between the start of administering the reversal agent to the recovery of TOF ratio < 0.9 to 0.7 and TOF ratio ≥ 0.9 if it occurs. These time periods are in minutes.

    In Group N+S (Neostigmine+Sugammadex) (n=50), patients received standard intravenous neostigmine 0.05 mg/kg and atropine 0.02 mg/kg doses before extubation. After a three-minute waiting period, the study investigators administered an intravenous bolus half-dose of 1 mg/kg of sugammadex after the standard reversal dose. A train-of-four (TOF) count of 2 in TOF Watch monitoring provides information of a shallow neuromuscular block. If at least two twitches are on the TOF watch monitor, the study investigators administer reversal medication for neuromuscular blockade in both groups. At this point, depending on randomization, a reversal agent is administered for each randomized group by an anesthesia resident or nurse who is blinded to the study protocol. The study investigators record the recovery periods between the start of administering the reversal agent to the recovery of TOF ratio < 0.9 to 0.7 and TOF ratio ≥ 0.9 if it occurs. These time periods are in minutes.

    Outcomes

    Primary Outcome Measures

    Incidence of postoperative residual neuromuscular blockade (rNMB)
    Incidence of postoperative residual neuromuscular blockade (rNMB) (defined as a train-of-four ratio, TOFR <0.9) measured 15 min after administration of the reversal agent.
    Recovery time-1
    The comparison of the recovery periods between groups when the start of administering reversal agent to the recovery of TOF ratio < 0.9 to 0.7
    Recovery time-2
    The comparison of the recovery periods between groups when the start of administering reversal agent to the recovery of TOF ratio < 0.7
    Recovery time-3
    The comparison of the recovery periods between groups when the start of administering reversal agent to the recovery of TOF ratio≥ 0.9
    Muscle strength after extubation
    The clinical assessment of muscle strength in the operating room are as follows; awake status, The investigated parameters were; arousable with minimal stimulation, cooperativeness, responsive only to tactile stimulation, cooperativeness, and able to perform five-second head lift.

    Secondary Outcome Measures

    Adverse events-1
    Adverse events related to administration of reversal medications
    Adverse events-2
    Adverse events related to residual paralysis
    Rescue medication neostigmine
    A rescue dose of intravenous neostigmine at a dose of 0.03 mg/kg in the operating room after 15 minutes before discharge to recovery room.
    Rescue medication sugammadex
    A rescue dose of intravenous sugammadex at a dose of 1 mg/kg in the recovery room after 15 minutes before discharge to the ward from recovery room
    Time frame-1
    The time period between the last dose of intravenous rocuronium and administering a reversal agent
    Time frame-2
    The time period between administering a reversal agent to extubation
    Time frame-3
    The time period between administering a reversal agent to operating room discharge
    Time frame-4
    The time period between discharge from the operating room amd discharge from recovery room
    Aldrete Score greater than nine in the recovery room
    The criteria for patient discharge from the recovery room

    Full Information

    First Posted
    September 9, 2021
    Last Updated
    September 23, 2021
    Sponsor
    Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05066035
    Brief Title
    Residual Paralysis and Reversal With Routine Neostigmine Versus Half-dose Sugammadex and Routine Neostigmine
    Official Title
    The Reversal of Residual Neuromuscular Blockade After Neostigmine and Half-dose Sugammadex: A Comparison With Standard Reversal of Full-dose Neostigmine
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2021
    Overall Recruitment Status
    Completed
    Study Start Date
    May 1, 2013 (Actual)
    Primary Completion Date
    October 1, 2016 (Actual)
    Study Completion Date
    December 30, 2016 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    Sugammadex may prevent residual neuromuscular blockade by providing rapid reversal at the end of the operation. Our goal is to compare the half-dose use of sugammadex for reversing residual blockade after administration of neostigmine and atropine to the routine use of reversal medication.
    Detailed Description
    Background: Postoperative residual neuromuscular block (PONB) may be observed in patients in the recovery room after surgery, and this event causes significant adverse events such as respiratory muscle weakness, decreased tidal volumes causing hypoxemia, reintubation, prolonged mechanical ventilation, and possible risk for a cardiopulmonary arrest. Goal: The study investigators hypothesized to investigate the effects of the half-dose use of sugammadex for reversing residual blockade after administration of neostigmine and atropine and compare these results to the routine full-dose use neostigmine and atropine. The Study Design: The study investigators planned to perform a prospective, single-blinded, randomized trial. The study Protocol: The investigators enrolled patients undergoing lower abdominal tumor resection surgery under general anesthesia who fulfill our inclusion criteria. The study is single-blinded because the anesthesia resident, anesthesia technician, and anesthesia personnel, including the data collector, were blinded to the randomization. The supervising anesthesiologist was also a data collector, and she was not blinded to the study protocol. The randomization into two groups required the use of a computer system. The study investigators performed a random allocation sequence by the use of randomized block design codes that are generated from a computer. Afterward, the study investigators opened an opaque and sealed envelope that contained the generated codes and randomly divided patients into two groups. During this process, they made sure that all study personnel was blinded to the randomization. The study investigators divide patients into two groups after the randomization process, and the groups are as follows: The first group of 48 patients is called Group N. In this group of patients, and we administer intravenous neostigmine 0.05 mg/kg and atropine 0.02 mg/kg in a single syringe before extubation. The second group of 50 patients is called Group N+S. In Group N+S, the study investigators administered the standard reversal medications of intravenous neostigmine 0.05 mg/kg and atropine 0.02 mg/kg. Three minutes later, the study 'investigators administered an intravenous bolus dose of 1 mg/kg sugammadex in a different syringe prepared earlier as a reversal agent. The Study Measurement of Parameters. The patients require general anesthesia induction with an intermediate-acting neuromuscular blocking age, rocuronium, at a dose of 0.06 mg/kg intravenously. After induction of anesthesia and before administration of rocuronium, the investigators monitored train-of-four (TOF) counts using a monitoring device of neuromuscular blockade at the patient's ulnar nerve. For this purpose, they placed two surface electrodes above the ulnar nerve near the wrist. To monitor the nerve stimuli at the adductor pollicis muscle using acceleromyography (TOF Watch SX, Schering-Plough Ireland, Dublin, Ireland). After induction of general anesthesia, the TOF Watch device provided 50-Hz tetanic stimulation for 5 seconds, and one minute after this tetanic stimulation, it offered a train-of-four (TOF) stimulation. Depending on the TOF-watch-related parameters, they decided to administer rocuronium, the neuromuscular agent, or not. At the end of the surgery, all anesthetics needed to be discontinued, including inhalational agents who were sevoflurane and nitrous oxide. Once the end-tidal concentration of sevoflurane reached a 0.4-0.6% level, the investigators administered the previously randomized reversal study drug. For the administration of the reversal agents, there was a need for a TOF count of 2 observed in the TOF Watch device. A TOF count of 2 in TOF Watch monitoring provided information of a shallow neuromuscular block. The Collected Parameters. They observed the clinical signs of recovery using several parameters. These parameters are level of consciousness, head-lift test, ability to sustain head lift, general muscle weakness, laryngospasm, and desaturation. The study investigators collected the periods between the last dose of intravenous rocuronium and administering a reversal agent, administering a reversal agent to extubation, and administering a reversal agent to operating room discharge. These periods were in minutes. They also collected the recovery periods between the start of helping reversal agent to the recovery of TOF ratio < 0.9 to 0.7 and TOF ratio ≥ 0.9, which were in minutes. They collected hemodynamical data, including; noninvasive mean arterial pressure, heart rate measurements, and peripheral oxygen saturation values before and subsequently at 2, 5, 10, and 30 minutes after administering the reversal drugs and in the recovery room. The primary outcome was the incidence of a train-of-four (TOF) ratio less than 0.9 at tracheal extubation. The secondary outcomes were periods between the start of administering reversal agents and extubation or operating room discharge in minutes to achieve recovery of TOF ratio < 0.9 to 0.7 and TOF ratio ≥ 0.9.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Neuromuscular Blockade, Sugammadex, Neostigmine, Complication of Anesthesia, Postoperative Residual Curarization, Rocuronium
    Keywords
    Residual Curarization, Postoperative, Complication, Neuromuscular blockade, Neostigmine, Sugammadex, Rocuronium

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Model Description
    Randomized prospective clinical trial
    Masking
    ParticipantCare ProviderOutcomes Assessor
    Masking Description
    The study protocol was masked to an outcomes assessor and the persons for this duty include an observer, a resident, or an anesthesia nurse during the anesthesia process but not to the care provider or the supervising physician.
    Allocation
    Randomized
    Enrollment
    113 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Neostigmine
    Arm Type
    Active Comparator
    Arm Description
    The Group N (Neostigmine) (n=48), patients received standard intravenous neostigmine 0.05 mg/kg and atropine 0.02 mg/kg doses before extubation. A train-of-four (TOF) count of 2 in TOF Watch monitoring provides information of a shallow neuromuscular block. If at least two twitches are on the TOF watch monitor, the study investigators administer reversal medication for neuromuscular blockade in both groups. At this point, depending on randomization, a reversal agent is administered for each randomized group by an anesthesia resident or nurse who is blinded to the study protocol. The study investigators record the recovery periods between the start of administering the reversal agent to the recovery of TOF ratio < 0.9 to 0.7 and TOF ratio ≥ 0.9 if it occurs. These time periods are in minutes.
    Arm Title
    Neostigmine and Sugammadex
    Arm Type
    Active Comparator
    Arm Description
    In Group N+S (Neostigmine+Sugammadex) (n=50), patients received standard intravenous neostigmine 0.05 mg/kg and atropine 0.02 mg/kg doses before extubation. After a three-minute waiting period, the study investigators administered an intravenous bolus half-dose of 1 mg/kg of sugammadex after the standard reversal dose. A train-of-four (TOF) count of 2 in TOF Watch monitoring provides information of a shallow neuromuscular block. If at least two twitches are on the TOF watch monitor, the study investigators administer reversal medication for neuromuscular blockade in both groups. At this point, depending on randomization, a reversal agent is administered for each randomized group by an anesthesia resident or nurse who is blinded to the study protocol. The study investigators record the recovery periods between the start of administering the reversal agent to the recovery of TOF ratio < 0.9 to 0.7 and TOF ratio ≥ 0.9 if it occurs. These time periods are in minutes.
    Intervention Type
    Drug
    Intervention Name(s)
    Neostigmine
    Other Intervention Name(s)
    Routine full-dose reversal medication
    Intervention Description
    The study investigators administer neostigmine at the end of operation to reverse neuromuscular blockade, and the routine dose of the intravenous neostigmine is 0.05 mg/kg and atropine 0.02 mg/kg. The dose is given in a single syringe, and later they administer this reversal medication before extubation. In the case of a residual block, the neostigmine group of patients receives a rescue dose of neostigmine at a dose of 0.03 mg/kg in the operating room fifteen minutes before discharge.
    Intervention Type
    Drug
    Intervention Name(s)
    Sugammadex
    Other Intervention Name(s)
    Routine full-dose reversal medication and half-dose sugammadex
    Intervention Description
    The study investigators administer the routine full-dose neostigmine reversal medication and three minutes later, they administer an intravenous bolus dose of 1 mg/kg sugammadex in a different syringe prepared earlier as a reversal agent. The anesthesia team considers using an intravenous rescue dose of 1 mg/kg sugammadex for this group of patients in the recovery room if patients do not show a complete recovery of TOF ratio equal to >0.9 in the recovery room before discharge to the ward.
    Primary Outcome Measure Information:
    Title
    Incidence of postoperative residual neuromuscular blockade (rNMB)
    Description
    Incidence of postoperative residual neuromuscular blockade (rNMB) (defined as a train-of-four ratio, TOFR <0.9) measured 15 min after administration of the reversal agent.
    Time Frame
    After operation within 24 hours
    Title
    Recovery time-1
    Description
    The comparison of the recovery periods between groups when the start of administering reversal agent to the recovery of TOF ratio < 0.9 to 0.7
    Time Frame
    After operation within 120 minutes
    Title
    Recovery time-2
    Description
    The comparison of the recovery periods between groups when the start of administering reversal agent to the recovery of TOF ratio < 0.7
    Time Frame
    After operation within 120 minutes
    Title
    Recovery time-3
    Description
    The comparison of the recovery periods between groups when the start of administering reversal agent to the recovery of TOF ratio≥ 0.9
    Time Frame
    After operation within 24 hours
    Title
    Muscle strength after extubation
    Description
    The clinical assessment of muscle strength in the operating room are as follows; awake status, The investigated parameters were; arousable with minimal stimulation, cooperativeness, responsive only to tactile stimulation, cooperativeness, and able to perform five-second head lift.
    Time Frame
    After operation within 24 hours
    Secondary Outcome Measure Information:
    Title
    Adverse events-1
    Description
    Adverse events related to administration of reversal medications
    Time Frame
    After operation within 24 hours
    Title
    Adverse events-2
    Description
    Adverse events related to residual paralysis
    Time Frame
    After operation within 24 hours
    Title
    Rescue medication neostigmine
    Description
    A rescue dose of intravenous neostigmine at a dose of 0.03 mg/kg in the operating room after 15 minutes before discharge to recovery room.
    Time Frame
    After operation within 120 minutes
    Title
    Rescue medication sugammadex
    Description
    A rescue dose of intravenous sugammadex at a dose of 1 mg/kg in the recovery room after 15 minutes before discharge to the ward from recovery room
    Time Frame
    After operation within 120 minutes
    Title
    Time frame-1
    Description
    The time period between the last dose of intravenous rocuronium and administering a reversal agent
    Time Frame
    After operation within 30 minutes
    Title
    Time frame-2
    Description
    The time period between administering a reversal agent to extubation
    Time Frame
    After operation within 30 minutes
    Title
    Time frame-3
    Description
    The time period between administering a reversal agent to operating room discharge
    Time Frame
    After operation within 60 minutes
    Title
    Time frame-4
    Description
    The time period between discharge from the operating room amd discharge from recovery room
    Time Frame
    After operation within 120 minutes
    Title
    Aldrete Score greater than nine in the recovery room
    Description
    The criteria for patient discharge from the recovery room
    Time Frame
    After operation within 120 minutes
    Other Pre-specified Outcome Measures:
    Title
    Noninvasive mean arterial pressure
    Description
    Mean arterial blood pressure measurements during operation and after operation
    Time Frame
    During operation every 5 minutes and after operation in the recovery room every five minutes until discharge.
    Title
    Heart rate
    Description
    Heart rate measurements during operation and after operation
    Time Frame
    During operation every 5 minutes and after operation in the recovery room every five minutes until discharge.
    Title
    Peripheral oxygen saturation
    Description
    Peripheral oxygen saturation during operation and after operation
    Time Frame
    During operation every minute and after operation in the recovery room every minute until discharge.

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    40 Years
    Maximum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Inclusion criteria: 40 and 65 years of age, American Society of Anesthesiologists Physical Status (ASA-PS) of 3 and 4, Elective lower gastrointestinal tumor resection surgeries, Supine positioning, Surgery requiring use of general anesthesia and muscle relaxation, Use of inhalational agent of sevoflurane anesthesia, Surgical duration of about three to six hours. Exclusion Criteria: History of known or suspected neuromuscular disease, History of renal or hepatic dysfunction, Hyperkalemia, Patients receiving antibiotics, anticonvulsants, or magnesium, History of stroke, History of glaucoma, History of pregnancy or breastfeeding, Suspicion of abdominal infection or sepsis, Suspected history of malignant hyperthermia, An allergy to medications used during general anesthesia
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Ayşe Baysal
    Organizational Affiliation
    Kartal Kosuyolu High Speciality Training and Research Hospital
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    We plan to share our data with individuals or organizations who reach us via phone, e-mail, or address.
    IPD Sharing Time Frame
    In a month after the release of the registration at https://register.clinicaltrials.gov.
    IPD Sharing Access Criteria
    The study is under peer review at a journal, and after its publication, we are planning to share our data individually by responding to each request.
    Citations:
    PubMed Identifier
    19933538
    Citation
    Duvaldestin P, Kuizenga K, Saldien V, Claudius C, Servin F, Klein J, Debaene B, Heeringa M. A randomized, dose-response study of sugammadex given for the reversal of deep rocuronium- or vecuronium-induced neuromuscular blockade under sevoflurane anesthesia. Anesth Analg. 2010 Jan 1;110(1):74-82. doi: 10.1213/ANE.0b013e3181c3be3c. Epub 2009 Nov 21.
    Results Reference
    background
    PubMed Identifier
    20876699
    Citation
    Puhringer FK, Gordon M, Demeyer I, Sparr HJ, Ingimarsson J, Klarin B, van Duijnhoven W, Heeringa M. Sugammadex rapidly reverses moderate rocuronium- or vecuronium-induced neuromuscular block during sevoflurane anaesthesia: a dose-response relationship. Br J Anaesth. 2010 Nov;105(5):610-9. doi: 10.1093/bja/aeq226. Epub 2010 Sep 28.
    Results Reference
    result
    PubMed Identifier
    28399799
    Citation
    Aouad MT, Alfahel WS, Kaddoum RN, Siddik-Sayyid SM. Half dose sugammadex combined with neostigmine is non-inferior to full dose sugammadex for reversal of rocuronium-induced deep neuromuscular blockade: a cost-saving strategy. BMC Anesthesiol. 2017 Apr 11;17(1):57. doi: 10.1186/s12871-017-0348-9.
    Results Reference
    result
    PubMed Identifier
    20885293
    Citation
    Schaller SJ, Fink H, Ulm K, Blobner M. Sugammadex and neostigmine dose-finding study for reversal of shallow residual neuromuscular block. Anesthesiology. 2010 Nov;113(5):1054-60. doi: 10.1097/ALN.0b013e3181f4182a.
    Results Reference
    result
    PubMed Identifier
    26634077
    Citation
    Cheong SH, Ki S, Lee J, Lee JH, Kim MH, Hur D, Cho K, Lim SH, Lee KM, Kim YJ, Lee W. The combination of sugammadex and neostigmine can reduce the dosage of sugammadex during recovery from the moderate neuromuscular blockade. Korean J Anesthesiol. 2015 Dec;68(6):547-55. doi: 10.4097/kjae.2015.68.6.547. Epub 2015 Nov 25.
    Results Reference
    result

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    Residual Paralysis and Reversal With Routine Neostigmine Versus Half-dose Sugammadex and Routine Neostigmine

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