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

Neuromuscular Blockade Clinical Trial

Official title:

The Reversal of Residual Neuromuscular Blockade After Neostigmine and Half-dose Sugammadex: A Comparison With Standard Reversal of Full-dose Neostigmine

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05066035
• Other study ID #: 2013.3/12
• Status: Completed
• Phase: Phase 4
• Start date: May 1, 2013
• Est. completion date: December 30, 2016

Study information

• Verified date: September 2021
• Source: Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 113
• Est. completion date: December 30, 2016
• Est. primary completion date: October 1, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Complication of Anesthesia
• Delayed Emergence from Anesthesia
• Neostigmine
• Neuromuscular Blockade
• Postoperative Residual Curarization
• Rocuronium
• Sugammadex

Intervention

Drug:
• Neostigmine
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.
• Sugammadex
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital

References & Publications (5)

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 — View 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 — View 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. — View Citation

Pühringer 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 — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Noninvasive mean arterial pressure	Mean arterial blood pressure measurements during operation and after operation	During operation every 5 minutes and after operation in the recovery room every five minutes until discharge.
Other	Heart rate	Heart rate measurements during operation and after operation	During operation every 5 minutes and after operation in the recovery room every five minutes until discharge.
Other	Peripheral oxygen saturation	Peripheral oxygen saturation during operation and after operation	During operation every minute and after operation in the recovery room every minute until discharge.
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Adverse events-1	Adverse events related to administration of reversal medications	After operation within 24 hours
Secondary	Adverse events-2	Adverse events related to residual paralysis	After operation within 24 hours
Secondary	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.	After operation within 120 minutes
Secondary	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	After operation within 120 minutes
Secondary	Time frame-1	The time period between the last dose of intravenous rocuronium and administering a reversal agent	After operation within 30 minutes
Secondary	Time frame-2	The time period between administering a reversal agent to extubation	After operation within 30 minutes
Secondary	Time frame-3	The time period between administering a reversal agent to operating room discharge	After operation within 60 minutes
Secondary	Time frame-4	The time period between discharge from the operating room amd discharge from recovery room	After operation within 120 minutes
Secondary	Aldrete Score greater than nine in the recovery room	The criteria for patient discharge from the recovery room	After operation within 120 minutes