Effect of MGRNOX-Guided General Anesthesia on Opioid Consumption in Patients

Official title

Effect of MGRNOX-Guided General Anesthesia on Opioid Consumption in Patients:A Randomized Controlled Trial

Overview

1. Pain management is a crucial part of general anesthesia surgery. Nociception monitoring can help anesthesiologists better titrate the use of intraoperative analgesic drugs, especially the opioid. 2. Although a variety of nociception monitoring devices have been developed to date, there is not a specific monitoring indicator that serves as the "gold standard" to objectively guide analgesic management in general anesthesia. 3. The MGRNOX index, which is derived from electroencephalogram (EEG), is used to reflect the correlation between noxious stimuli and opioid analgesics in a state of general anesthesia by converting and quantifying the EEG signals collected by the instrument. However, no studies have so far verified the effect of the MGRNOX index-guided analgesic management of general anesthesia on the consumption of opioids in patients. 4. This study aims to explore the effect of MGRNOX index-guided general anesthesia on opioid consumption in patients undergoing laparoscopic cholecystectomy and the primary hypothesis of our study is that using the MGRNOX index to guide intraoperative pain management during general anesthesia can significantly reduce the consumption of remifentanil during the surgery.

Detailed description

Pain management is a critical component of perioperative anesthesia. Traditionally, anesthesiologists adjust analgesic dosages based on intraoperative heart rate or blood pressure, relying heavily on personal clinical experience. This approach often leads to over- or under-administration of analgesics. Currently, opioids remain the primary analgesics used in general anesthesia. Excessive opioid doses can result in postoperative hyperalgesia, delayed recovery, respiratory and circulatory depression, and increased hepatic/renal burden. Conversely, insufficient opioid doses may lead to inadequate analgesia, intraoperative hemodynamic instability, postoperative pain, and agitation.

In recent years, various nociception monitoring devices (e.g., SPI, ANI, qNOX) have been developed to quantify intraoperative nociception, assisting anesthesiologists in optimizing analgesic administration to achieve precision and balanced anesthesia. Studies suggest that nociception-guided analgesia during general anesthesia surgery reduces opioid consumption, alleviates postoperative pain, and improves hemodynamic stability compared to traditional standardized management. However, due to the limitations of existing indices, no specific parameter has yet been established as a gold standard for objectively reflecting intraoperative nociception levels.

The MGRNOX index, a China-developed metric based on central nervous system monitoring, derives from processed and quantified electroencephalographic (EEG) signals under general anesthesia to reflect a patient's analgesic state. As clinical evidence for MGRNOX remains limited and its impact on intraoperative opioid usage remains unvalidated, the investigators designed this randomized controlled trial to investigate whether MGRNOX-guided general anesthesia reduces opioid consumption during laparoscopic cholecystectomies. Our primary hypothesis is that intraoperative MGRNOX-guided analgesia will significantly decrease remifentanil requirements.

Interventions

• Device MGRNOX index-guided analgesia
  After anesthesia induction, the remifentanil plasma target concentration was adjusted intraoperatively to maintain the MGRNOX index between 30 and 50,but MAP and HR also were considered .In case the MGRNOX index was below 30 for more than 1 minute, remifentanil target-controlled infusion levels were lowered in steps of 0.5 ng/ml , whereas in case of a value greater than 50 for more than 1 minute, remifentanil target-controlled infusion levels were increased in steps of 0.5 ng/ml.
• Device Standard Clinical Care
  After anesthesia induction, if hypertension (MAP \> 100 mmHg) or tachycardia (heart rate \> 90 bpm) persists for more than 2 minutes, remifentanil target-controlled infusion levels were increased in steps of 0.5 ng/ml.If there is no response to remifentanil or the MAP and HR exceed a certain threshold, then urapidil or esmolol will be administered.For hypotension (50 mmHg \< MAP ≤ 60 mmHg) persisting for more than 2 minutes, remifentanil target-controlled infusion levels were lowered in steps of

Primary outcome measures

• opioids [Time frame: From the beginning of anesthesia induction until surgical procedure end（time of final wound closure）,assessed during surgery.]

Secondary outcome measures (5)

• pain score [Time frame: One hour after extubation]
• Incidence of unexpected events [Time frame: From the beginning of anesthesia induction until surgical procedure end（time of final wound closure）,assessed during surgery.]
• incidence of complications [Time frame: during PACU（at least 1 hour)]
• the consumption of sedative drug [Time frame: From the beginning of anesthesia induction until 5 minutes before the end of the surgery.]
• the consumption of vasoactive drug [Time frame: From the beginning of anesthesia induction until surgical procedure end（time of final wound closure）,assessed during surgery.]

Eligibility criteria

Inclusion criteria

• Age ≥18 years old and < 65 years old；
• American Society of Anesthesiologists (ASA) class I-II；
• Scheduled to undergo elective laparoscopic cholecystectomy undergeneral anesthesia （without epidural anesthesia, local blocks, or infiltration）

Exclusion criteria

• Pregnancy or lactation period；
• BMI ≥35 kg/m² or <18.5 kg/m²；
• Anticipated difficult airway；
• Previous diagnosis of hypertension；
• History of drug or alcohol abuse within the past 6 months；
• Preoperative acute or chronic pain history (routine preoperative use of opioid or non-opioid analgesics), peripheral or central nervous system-related disorders；
• Definitively diagnosed psychiatric disorders or other neuropsychiatric conditions severely affecting cognitive judgment, history of psychotropic medication use；
• Allergy or intolerance to anesthetic agents；
• Baseline mean arterial pressure (MAP) <60 mmHg or >120 mmHg; baseline heart rate (HR) <45 bpm or >90 bpm (Baseline values defined as first measurement taken in the ward after admission)；
• History of severe underlying diseases (untreated or ongoing peripheral/central cardiovascular diseases, severe hepatic disorders with elevated bilirubin/INR or hypoalbuminemia, severe renal diseases with elevated creatinine, severe pulmonary diseases potentially causing acute respiratory failure or persistent dyspnea)；
• Implanted pacemaker, chronic arrhythmia, preoperative use of prescribed anticholinergics, α2-adrenergic agonists, beta-1 adrenergic antagonists, or antiarrhythmic medications.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Peking University Shenzhen Hospital — Shenzhen

Publications

• Desborough JP. The stress response to trauma and surgery. Br J Anaesth. 2000 Jul;85(1):109-17. doi: 10.1093/bja/85.1.109. No abstract available. PMID 10927999
• Egan TD. Are opioids indispensable for general anaesthesia? Br J Anaesth. 2019 Jun;122(6):e127-e135. doi: 10.1016/j.bja.2019.02.018. Epub 2019 Mar 28. PMID 31104756
• Fletcher D, Martinez V. Opioid-induced hyperalgesia in patients after surgery: a systematic review and a meta-analysis. Br J Anaesth. 2014 Jun;112(6):991-1004. doi: 10.1093/bja/aeu137. PMID 24829420
• Gruenewald M, Ilies C. Monitoring the nociception-anti-nociception balance. Best Pract Res Clin Anaesthesiol. 2013 Jun;27(2):235-47. doi: 10.1016/j.bpa.2013.06.007. PMID 24012235
• Kutlu Yalcin E, Araujo-Duran J, Turan A. Emerging drugs for the treatment of postsurgical pain. Expert Opin Emerg Drugs. 2021 Dec;26(4):371-384. doi: 10.1080/14728214.2021.2009799. Epub 2021 Nov 28. PMID 34842026
• Bergmann I, Gohner A, Crozier TA, Hesjedal B, Wiese CH, Popov AF, Bauer M, Hinz JM. Surgical pleth index-guided remifentanil administration reduces remifentanil and propofol consumption and shortens recovery times in outpatient anaesthesia. Br J Anaesth. 2013 Apr;110(4):622-8. doi: 10.1093/bja/aes426. Epub 2012 Dec 5. PMID 23220856
• Upton HD, Ludbrook GL, Wing A, Sleigh JW. Intraoperative "Analgesia Nociception Index"-Guided Fentanyl Administration During Sevoflurane Anesthesia in Lumbar Discectomy and Laminectomy: A Randomized Clinical Trial. Anesth Analg. 2017 Jul;125(1):81-90. doi: 10.1213/ANE.0000000000001984. PMID 28598927
• Jiang Y, Ding JM, Hao XX, Fang PP, Liu XS. EEG-derived pain threshold index-guided versus standard care during propofol-remifentanil anesthesia: A randomized controlled trial. Heliyon. 2023 Aug 1;9(8):e18604. doi: 10.1016/j.heliyon.2023.e18604. eCollection 2023 Aug. PMID 37593599

Identifiers

NCT: NCT07004686 · 2025-024

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗