Clinical trial NCT04713358: Effect of Nalmefene on the Quality of Resuscitation in Patients Under General Anesthesia
Official title: Effect of Nalmefene on the Quality of Resuscitation in Patients Under General Anesthesia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Resuscitation
Keywords: nalmefene
quality of resuscitation
general anesthesia
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
Collaborators: name: Shanghai Tong Ren Hospital
name: First Affiliated Hospital of Guangxi Medical University
name: The First Affiliated Hospital of Zhengzhou University
First posted: 2021-01-19
Enrollment: 520
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Time stay in PACU
timeFrame: From the end of the operation to the time that patient leave to inpatient ward up to 2hours
Secondary outcomes:
measure: Extube time
timeFrame: From the end of the operation to the time that patient leave to inpatient ward up to 2hours
measure: Sedation - agitation score
timeFrame: From the end of the operation to the time that patient leave to inpatient ward up to 2hours
measure: the directional force The time at which the Montreal score was ≥5
timeFrame: From the end of the operation to the time that patient leave to inpatient ward up to 2hours
measure: Whether to use remedial analgesic drug (sufentanil) in PACU and the dosage
timeFrame: From the end of the operation to the time that patient leave to inpatient ward up to 2hours
measure: VAS pain score (assessment time Aldrete score ≥9 points, 1h after surgery, 24h after surgery)
timeFrame: 1h after surgery, and 24h after surgery
measure: The incidence of nausea and vomiting in PACU
timeFrame: From the end of the operation to the time that patient leave to inpatient ward up to 2hours
measure: Incidence of itch in PACU
timeFrame: From the end of the operation to the time that patient leave to inpatient ward up to 2hours
measure: Incidence of nausea and vomiting 0-24h after surgery
timeFrame: From the end of operation up to 24h after surgery
measure: Incidence of pruritus 0-24h after surgery
timeFrame: From the end of operation up to 24h after surgery
Other outcomes:
Locations:
city: Guangxi
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Shanghai
country: China
facility: Shanghai Tong Ren Hospital
state: Shanghai
city: Shanghai
country: China
facility: Renji Hospital
state: Shanghai
city: Henan
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Zhengzhou
Study officials:
affiliation: Department of Anesthesiology, Renji Hospital, School of Medicine, SJTU
name: Weifeng Yu
role: STUDY_CHAIR
References: