Clinical trial NCT05066035: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Neuromuscular Blockade
Sugammadex
Neostigmine
Complication of Anesthesia
Postoperative Residual Curarization
Rocuronium
Keywords: Residual Curarization
Postoperative
Complication
Neuromuscular blockade
Neostigmine
Sugammadex
Rocuronium
Lead sponsor: Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital
Sponsor class: OTHER_GOV
First posted: 2021-10-04
Enrollment: 113
Sex: ALL
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized prospective clinical trial
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence of postoperative residual neuromuscular blockade (rNMB)
timeFrame: After operation within 24 hours
measure: Recovery time-1
timeFrame: After operation within 120 minutes
measure: Recovery time-2
timeFrame: After operation within 120 minutes
measure: Recovery time-3
timeFrame: After operation within 24 hours
measure: Muscle strength after extubation
timeFrame: After operation within 24 hours
Secondary outcomes:
measure: Adverse events-1
timeFrame: After operation within 24 hours
measure: Adverse events-2
timeFrame: After operation within 24 hours
measure: Rescue medication neostigmine
timeFrame: After operation within 120 minutes
measure: Rescue medication sugammadex
timeFrame: After operation within 120 minutes
measure: Time frame-1
timeFrame: After operation within 30 minutes
measure: Time frame-2
timeFrame: After operation within 30 minutes
measure: Time frame-3
timeFrame: After operation within 60 minutes
measure: Time frame-4
timeFrame: After operation within 120 minutes
measure: Aldrete Score greater than nine in the recovery room
timeFrame: After operation within 120 minutes
Other outcomes:
measure: Noninvasive mean arterial pressure
timeFrame: During operation every 5 minutes and after operation in the recovery room every five minutes until discharge.
measure: Heart rate
timeFrame: During operation every 5 minutes and after operation in the recovery room every five minutes until discharge.
measure: Peripheral oxygen saturation
timeFrame: During operation every minute and after operation in the recovery room every minute until discharge.
Locations:
Study officials:
affiliation: Kartal Kosuyolu High Speciality Training and Research Hospital
name: Ayşe Baysal
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.