Effect of Nalmefene on the Quality of Resuscitation in Patients Under General Anesthesia

NCT ID: NCT04713358

Last Updated: 2022-10-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 520 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-24
• Study Completion Date: 2023-12-31

Brief Summary

Postoperative recovery is an important part of the patient's experience. A good recovery period is an important guarantee for the recovery of postoperative organs and functions after surgery. However, the delay in awakening after general anesthesia remains one of the biggest challenges facing anesthesiologists. The time of resuscitation depends on patient factors, effects of anesthetic factors, duration of surgery, and painful stimulation.

The delay of recovery after anesthesia was mainly caused by the use of anesthetic drugs during the perioperative period. The drugs commonly used during the perioperative period are opioid analgesics, sedatives and muscle relaxants. Studies have shown that intravenous opioids are more difficult to control than neuromuscular relaxants. Opioids can extend the recovery time after anesthesia by direct sedation of opioid receptors. It also reduces the sensitivity of brainstem chemoreceptors to carbon dioxide, leading to dose-dependent respiratory depression and hypercapnia, which affects the removal of volatile substances and carbon dioxide, and ultimately leads to coma. In addition, the active metabolites of some opioids can prolong the duration of action, especially in the case of impaired renal function, which can lead to delayed awakening.

As an opioid antagonist, nalmefene can inhibit or reverse the respiratory inhibition, sedation and hypotension effects of opioid drugs. Moreover, it has no opioid excitatory activity, does not produce respiratory inhibition, hallucinogenic effect or pupil dilation. In terms of inducing wakefulness during anesthesia, nalmefene can effectively reverse the sedative effect caused by opioids. There have been reports at home and abroad that nalmefene can be used to improve the effect of post-anesthesia resuscitation and reduce agitation during the waking period, but there is still a lack of large sample and well-designed randomized controlled studies to provide important data on how to improve the quality of anesthetized resuscitation. This study will conduct a rigorous randomized controlled studies,with large sample, and the research indicators for patients from the PACU roll-out to ordinary ward, using Aldrete score , in order to obtain a series of data of nalmefene used for anesthesia recovery , and to set the foundation of related research of nalmefene and similar drugs in clinical application in the future.

Detailed Description

Postoperative recovery is an important part of the patient's experience, regardless of the type of surgery. The recovery and prognosis of postoperative anesthesia have gradually become important indicators for judging the efficacy and quality of anesthesia. The recovery period of general anesthesia is an important transition period from anesthesia to wakefulness, and a good recovery period is an important guarantee for the recovery of postoperative organs and functions after surgery. However, the delay in awakening after general anesthesia remains one of the biggest challenges facing anesthesiologists. Postoperative resuscitation is the result of the removal of anesthetics from the brain. The time of resuscitation depends on patient factors, effects of anesthetic factors, duration of surgery, and painful stimulation.

The delay of recovery after anesthesia was mainly caused by the use of anesthetic drugs during the perioperative period. The drugs commonly used during the perioperative period are opioid analgesics, sedatives and muscle relaxants. Studies have shown that intravenous opioids are more difficult to control than neuromuscular relaxants. Opioids can extend the recovery time after anesthesia by direct sedation of opioid receptors. It also reduces the sensitivity of brainstem chemoreceptors to carbon dioxide, leading to dose-dependent respiratory depression and hypercapnia, which affects the removal of volatile substances and carbon dioxide, and ultimately leads to coma. In addition, the active metabolites of some opioids can prolong the duration of action, especially in the case of impaired renal function, which can lead to delayed awakening.

As an opioid antagonist, nalmefene can inhibit or reverse the respiratory inhibition, sedation and hypotension effects of opioid drugs. Moreover, it has no opioid excitatory activity, does not produce respiratory inhibition, hallucinogenic effect or pupil dilation. No pharmacological effects were observed without the administration of opioid agonists. In terms of inducing wakefulness during anesthesia, nalmefene can effectively reverse the sedative effect caused by opioids. There have been reports at home and abroad that nalmefene can be used to improve the effect of post-anesthesia resuscitation and reduce agitation during the waking period, but there is still a lack of large sample and well-designed randomized controlled studies to provide important data on how to improve the quality of anesthetized resuscitation. In order to speed up the awakening after anesthesia, promote the patients' consciousness and respiratory recovery, and improve the quality of awakening patients after anesthesia, the patients should control postoperative pain immediatly, improve the comfort of patients in the PACU, reduce the residence time of patients, speed up the circulation of operated patients, reduce the costs of PACU, and reduce the staff workload in the PACU. This study will conduct a rigorous randomized controlled studies, large sample, and the research indicators for patients from the PACU roll-out to ordinary ward, using Aldrete score , in order to obtain a series of data of nalmefene used for anesthesia recovery , and to lay the foundation of related research of nalmefene and similar drugs in clinical application in the future.

Conditions

Resuscitation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Nalmefene group

for the nalmefene group, immediately Intravenous injection of Nalmefene (0.25 g/kg, plus normal saline to 1ml) after surgery

Group Type: EXPERIMENTAL

Nalmefene

Intervention Type: DRUG

Immediately Intravenous injection of Nalmefene (0.25 g/kg, plus normal saline to 1ml) after surgery

Control group

Intravenous injection of normal saline 1ml immediately after surgery

Group Type: PLACEBO_COMPARATOR

normal Saline

Intervention Type: DRUG

Immediately Intravenous injection of normal saline 1ml after surgery

Interventions

Nalmefene

Immediately Intravenous injection of Nalmefene (0.25 g/kg, plus normal saline to 1ml) after surgery

Intervention Type: DRUG

normal Saline

Immediately Intravenous injection of normal saline 1ml after surgery

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age is greater than or equal to 18 years old and less than 65 years old

2. Patients who need tracheal intubation under general anesthesia at the right time for orthopedics, urology, and thoracic elective surgery

3. Patients with American Society of Anesthesia physical status I or II

4. BMI≥18kg/m2, and ≤30kg/m2

5. The estimated anesthesia time is 1-4 hours.

6. The intraoperative narcotic analgesics (Sufentanil and Remifentanil)

7. The patient uses electronic intravenous analgesia pump after surgery

8. The patient has informed consent

Exclusion Criteria

1. patients who refused to participate in the study

2. pantients who refuse intravenous analgesia

3. medical history or family history of cognitive disorders,delirium, epilepsy, abalienation, anxiety or depression;

4. recent use of anticholinergic drugs, antidepressants, antianxietics or anticonvulsants

5. medical history of organic brain diseases or cranial vascular diseases

6. patients with a history of allergy to any drug used in the study

7. History of drug addiction and alcoholic intemperance or drug abuse

8. The patient is diagnosed with severe heart and lung disease, or active heart disease, or severe hepatic dysfunction (ChildePugh class C), or severe renal dysfunction (undergoing dialysis before surgery) ,critical illness (preoperative ASA physical status classification > =3)

9. Participate in other clinical trials within 4 weeks

10. Patients who, during surgery, presented complications （cerebrovascular accidents、heart failure、pneumothorax）or transfer to the intensive care unit during hospitalization, and patients who chose to abandon.

11. Inability to communicate in the preoperative period because of coma, profound dementia, language barrier, or incapacity from severe disease

12. Anesthesia time is <1 hour or >4 hours

13. Patients had chronic pain (unsatisfied pain control for at least 1 month).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Tong Ren Hospital

OTHER

Sponsor Role: collaborator

First Affiliated Hospital of Guangxi Medical University

OTHER

Sponsor Role: collaborator

The First Affiliated Hospital of Zhengzhou University

OTHER

Sponsor Role: collaborator

RenJi Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Weifeng Yu

Role: STUDY_CHAIR

Department of Anesthesiology, Renji Hospital, School of Medicine, SJTU

Locations

The First Affiliated Hospital of Guangxi Medical University

Guangxi, Guangxi, China

Site Status: NOT_YET_RECRUITING

Shanghai Tong Ren Hospital

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Renji Hospital

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

The First Affiliated Hospital of Zhengzhou University

Henan, Zhengzhou, China

Site Status: RECRUITING

Countries

China

Central Contacts

Diansan Su, MD,PHD

Role: CONTACT

diansansu@yahoo.com

+86 18616514088

Facility Contacts

Li Li, MD,PHD

Role: primary

3196274@qq.com

13878185242

Guangming Zhang, MD,PHD

Role: primary

18121226630

Jueying Liu

Role: primary

fuliuzh@aliyun.com

Jianjun Yang, MD,PHD

Role: primary

jianjunyang1971@163.com

13783537619

References

Ma X, Liu J, Tang Y, Lian Q, Huai X, Liu W, Su D. The efficacy of nalmefene on anesthetic recovery of patients: a study protocol for a multicenter randomized controlled trial. Trials. 2023 Mar 1;24(1):156. doi: 10.1186/s13063-023-07169-4.

Reference Type: DERIVED

PMID: 36859316 (View on PubMed)

Other Identifiers

2020-sx004

Identifier Type: -

Identifier Source: org_study_id