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

NCT05066035 | Completed Phase 4 DMC

• 1 other identifier: 2013.3/12
• Study Type: interventional
• Target: 113
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Neuromuscular Blockade; Sugammadex; Neostigmine; Complication of Anesthesia; Postoperative Residual Curarization; Rocuronium

Keywords

Residual Curarization; Postoperative; Complication; Neuromuscular blockade; Neostigmine; Sugammadex; Rocuronium

Outcome Measures

Primary Outcomes (5)

• 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.

  After operation within 24 hours

• 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

  After operation within 120 minutes

• 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

  After operation within 120 minutes

• 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

  After operation within 24 hours

• 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.

  After operation within 24 hours

Secondary Outcomes (9)

• Adverse events-1

  After operation within 24 hours

• Adverse events-2

  After operation within 24 hours

• Rescue medication neostigmine

  After operation within 120 minutes

• Rescue medication sugammadex

  After operation within 120 minutes

• Time frame-1

  After operation within 30 minutes

Other Outcomes (3)

• Noninvasive mean arterial pressure

  During operation every 5 minutes and after operation in the recovery room every five minutes until discharge.

• Heart rate

  During operation every 5 minutes and after operation in the recovery room every five minutes until discharge.

• Peripheral oxygen saturation

  During operation every minute and after operation in the recovery room every minute until discharge.

Study Arms (2)

Neostigmine

ACTIVE COMPARATOR

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.

Drug: Neostigmine

Neostigmine and Sugammadex

ACTIVE COMPARATOR

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.

Drug: Sugammadex

Interventions

Neostigmine DRUG

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.

Also known as: Routine full-dose reversal medication

Neostigmine

Sugammadex DRUG

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.

Also known as: Routine full-dose reversal medication and half-dose sugammadex

Neostigmine and Sugammadex

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital: lead

Related Publications (5)

• 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.

  PMID: 19933538 BACKGROUND

• 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.

  PMID: 20876699 RESULT

• 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.

  PMID: 28399799 RESULT

• 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.

  PMID: 20885293 RESULT

• 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.

  PMID: 26634077 RESULT

MeSH Terms

Conditions

Delayed Emergence from Anesthesia

Interventions

Neostigmine; Sugammadex

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenylammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; gamma-Cyclodextrins; Cyclodextrins; Macrocyclic Compounds; Polycyclic Compounds; Dextrins; Starch; Glucans; Polysaccharides; Carbohydrates

Study Officials

• Ayşe Baysal

  Kartal Kosuyolu High Speciality Training and Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Anesthesiology and Reanimation

Model Details: Randomized prospective clinical trial

Study Record Dates

• First Submitted: September 9, 2021
• First Posted: October 4, 2021
• Study Start: May 1, 2013
• Primary Completion: October 1, 2016
• Study Completion: December 30, 2016
• Last Updated: October 4, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: In a month after the release of the registration at https://register.clinicaltrials.gov.
• 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.