Postoperative Sugammadex After COVID-19

A Double-blind, Randomized, Parallel Design Study to Compare Postoperative Recovery Between the Sugammadex Group and the Neostigmine Group in Patients After COVID-19.

Researcher want to compare and evaluate the effect of sugammadex on postoperative recovery, with a focus on the occurrence of postoperative urinary dysfunction, in patients who have undergone regular abdominal surgery within a year of being infected with and treated for COVID-19.

Post COVID-19 condition is a new and poorly understood clinical syndrome with potentially significant and life-altering consequences. Recent studies suggest that patients who have recovered from COVID-19 may experience autonomic dysfunction and be at risk for autonomic dysregulation/syndrome. In most patients undergoing general anesthesia, neuromuscular blockers are used, and their residual effects delay the recovery of autonomic function after surgery, leading to problems such as worsening bladder and bowel function. Therefore, reversal agents are used to aid in postoperative muscle recovery, with sugammadex and neostigmine being commonly used in clinical practice. While sugammadex is generally expected to result in faster postoperative recovery, limited reports exist on its effectiveness in patients who have recovered from COVID-19. This study aims to verify whether sugammadex is more effective than neostigmine in aiding the recovery of bowel and pulmonary function after surgery in patients who have recovered from COVID-19.

Study Overview

• Status: Not yet recruiting
• Conditions: COVID-19; General Anesthesia
• Intervention / Treatment: Drug: Sugammadex Sodium; Drug: neostigmine 50µg/kg + glycopyrollate 0.01mg/kg

Detailed Description

The COVID-19 has had a huge impact on the world, infected tens of millions and killed hundreds of thousands, and has become a threat to humanity's medical defense system. COVID-19 was understood as an acute infection among infections, and it was expected that there would be little or no other risk if the acute symptoms were treated. Contrary to our expectations, however, patients with a history of infection with the coronavirus have reported patients with sequelae lasting for more than several months. The symptoms shown by these patients were not limited to some tissues and organs, but were distributed in various ways throughout our body. These symptoms were defined as 'long COVID'. In particular, among the symptoms of long COVID patients, there were patients who were diagnosed with orthostatic hypotension, vasovagal syncope, and orthostatic tachycardia syndrome from symptoms such as palpitations, shortness of breath, and chest pain. What these diseases have in common is that they are autonomic nervous system diseases. Therefore, it can be assumed that long COVID patients have damage to the function of the autonomic nervous system due to past infections, and many studies have been conducted on this.

The main components of general anesthesia are known to be unconsciousness, muscle relaxation, analgesia, and reflex suppression. Among these, the reasons why muscle relaxation is necessary in general anesthesia include ease of intubation and suppression of unnecessary patient movements during surgery to create a suitable environment for surgery. For muscle relaxation, anesthesiologists administer neuromuscular relaxants, mainly non-depolarizing muscle relaxants. Neuromuscular relaxants have the role of inhibiting neurotransmission by acting on the motor nerve endings of skeletal muscles, because they act on nicotinic cholinergic receptors in motor nerve endings. However, neuromuscular relaxants also act on muscarinic cholinergic receptors to inhibit neurotransmission. Since these muscarinic cholinergic receptors are distributed in the parasympathetic nerves of the autonomic nervous system, neuromuscular relaxants also inhibit the autonomic nerve system controlled by the parasympathetic nerves.

Since neuromuscular relaxants are eliminated from the body by pharmacokinetics, the function of the autonomic nervous system, which has been suppressed by using neuromuscular relaxants, gradually recovers over time. However, if the action of a neuromuscular relaxant remains after surgery, the patient will experience autonomic dysfunction even after surgery, which causes considerable discomfort to the patient. Among them, the symptoms of autonomic dysfunction related to the parasympathetic nerve that patients mainly feel are related to the bladder and bowel. Therefore, after the surgery, the anesthesiologist performs the process of reversing the action of the neuromuscular relaxant when ending general anesthesia, which makes it possible to expect the recovery of the patient's autonomic nervous system function.

There are two main mechanisms of the drugs used for reversal of nondepolarizing neuromuscular relaxants. First, there is a drug that inhibits the action of the neuromuscular relaxant by directly attaching to the neuromuscular relaxant, and second, there is a drug that competitively inhibits the neuromuscular relaxant by increasing the amount of ach in the neuromuscular junction. In the meantime, many studies have shown that a drug with the former mechanism (sugammadex) is superior to the latter drug (typically neostigmine) in the recovery of patients after surgery. However, there is a lack of research on whether the same research results will be shown in long COVID patients who have caused damage to the autonomic nervous system.

Therefore, in this study, sugammadex and neostigmine as described above are divided and administered to approximately 300 long COVID patients in a double-blind manner, and the degree of urinary retention is compared to prove that sugammadex is superior to neostigmine in postoperative recovery even for long COVID patients.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Too Jae Min, M.D., Ph.D.; Phone Number: 82-10-7296-0353; Email: minware2@nate.com
• Study Contact Backup: Name: Sang Min Yoon, M.D.; Phone Number: 82-10-8805-8619; Email: ekha00041@naver.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ages between 19 and 70 Male and Female All ethnicity Patients who are scheduled to take non-emergency abdominal surgery under general anesthesia.

Patients who had the diagnosis of covid-19 by PCR, hospitalized, and applied O2 supplement therapy.

ASA classification ≤ 3 Patients who had Covid-19 PCR positive within 1 year Patients who had hospitalized by Covid-19, followed by O2 therapy (nasal prong, continuous positive airway pressure (CPAP), ventilator etc.) Patients who hospitalized more than 48 hours after surgery. Patients who had a surgery for more than 1 hour.

Exclusion Criteria:

• Not meeting inclusion criteria Declined to participate Active Covid-19 patients with PCR positive. Patients are under 19 or over 70 years old

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sugammadex; sugammadex 2mg/kg	Drug: Sugammadex Sodium; Sugammadex Sodium 2mg/kg when TOF >= 2, postoperative period; Other Names: Bridion
Active Comparator: Neostigmine; neostigmine 50µg/kg + glycopyrollate 0.01mg/kg	Drug: neostigmine 50µg/kg + glycopyrollate 0.01mg/kg; neostigmine 50µg/kg + glycopyrollate 0.01mg/kg when TOF >= 2, postoperative period; Other Names: neostigmine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
urinary retention incidence	urinary retention incidence	postoperative 1 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
surgery time and anesthesia time	surgery time and anesthesia time	perioperative period
recovery time after anesthesia	recovery time after anesthesia	postoperative period, within 1 hour
intraoperative blood loss	estimated blood loss	perioperative period
perioperative vital signs	serial follow up during surgery and postoperative recovery room	perioperative period
additional sugammadex administration	incidence and dosage	postoperative period, within 1 hour
bladder volume evaluated	Sono-calculated (summation of self-voiding volume during self-voiding)	postoperative 1 hour
recovery score	postoperative recovery score at PACU	postoperative 1 hour
pain score	NRS	postoperative 1 hour
urinary retention	presence of complication	postoperative 24 and 48 hour
acute lesion on chest X-ray	presence of complication	2 days after surgery
actual dosage of drugs for pain and nausea control	pain (ketorolac, fentanyl, tramadol, acetaminophen, nalbuphine, pethidcine, ketoprofen, propacetamol) nausea(ramosetron, metoclopramide, palonosetron)	postoperative period, within 1 hour
other intraoperative events (awakening (eye opening), involuntary movement, occurrence of adverse events and unexpected side effects, etc.)	presence of complication	perioperative period

Collaborators and Investigators

• Sponsor: Korea University Ansan Hospital
• Investigators: Study Chair: Too Jae Min, M.D., Ph.D., Korea University Ansan Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): April 20, 2023
• Primary Completion (Anticipated): December 25, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: April 11, 2023
• First Submitted That Met QC Criteria: April 16, 2023
• First Posted (Actual): April 18, 2023

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 16, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: COVID-19; Postoperative Complications
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Enzyme Inhibitors; Cholinesterase Inhibitors; Parasympathomimetics; Neostigmine
• Other Study ID Numbers: 2023AS0079

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share IPD

Drug and device information, study documents

• 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