Impact of Nociception Level (NOL)-Guided Remifentanil Infusion on Intraoperative Arterial Pressure and Vasopressor Necessity

Maxillofacial Surgery Clinical Trial

Official title:

Impact of Nociception Level (NOL)-Guided Remifentanil Infusion and Entropy-guided Propofol Infusion on Intraoperative Arterial Pressure and Vasopressor Necessity A Prospective, Randomized, Controlled Trial.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04963036
• Other study ID #: B0762021210506
• Status: Recruiting
• Phase: N/A
• Start date: July 28, 2021
• Est. completion date: June 2022

Study information

• Verified date: July 2021
• Source: Centre Hospitalier Universitaire Saint Pierre
• Contact: Panayota Kapessidou, MD,PhD
• Phone: +32.2.535
• Email: pkapessi[@]ulb.ac.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to determine if Nociception Level (NOL)-guided Remifentanil analgesia, combined with Entropy-guided Propofol anesthesia, has a significant beneficial effect on the incidence of intraoperative hypotension episodes and/or on vasopressor requirements, during long-lasting major surgeries for high risk patients. The investigator will also investigate the effects of guided anesthesia on postoperative Myocardial Injury in Non-cardiac Surgery (MINS) and Postoperative cognitive dysfunction (POCD), amongst other frequent postoperative complications, in this population.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: June 2022
• Est. primary completion date: June 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age =18

• Elective high-risk head and neck or maxillo-facial surgery

Exclusion Criteria:

• Patient refusal

• Reduced ejection fraction below 40% and heart failure

• History of atrial Fibrillation, pulmonary embolism, recent cardioversion, recent cardiac ischemic episode, chronic hypotension, chronic kidney insufficiency (serum creatinine > 1.5)

• Septic state

• Baseline heart-rate < 50 or > 90 bpm

• History of psychiatric disease or medication

Related Conditions & MeSH terms

• Maxillofacial Surgery

Intervention

Other:
• Entropy and NOL-Guided Goal Directed Anesthesia
Entropy-guided Anesthesia (Propofol infusion in order to maintain Entropy between 45 and 55) and NOL-guided Analgesia (Remifentanil infusion in order to maintain NOL-Index between 10 and 25).
• Standard of Care Group (Entropy and blinded NOL)
Entropy-guided Anesthesia (Propofol infusion in order to obtain Entropy between 45 and 55) and Remifentanil infusion at the discretion of the anesthetist in charge, based on current practice: patient vitals (Heart Rate, Blood Pressure, Respiratory Rate…), movements, spontaneous breathing, experience.... In this group, nociception monitor screen will be concealed and the NOL index will not be available for guidance of remifentanil dosing).

Locations

Country	Name	City	State
Belgium	CHU Saint-Pierre	Bruxelles

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire Saint Pierre

Country where clinical trial is conducted

Belgium, 

References & Publications (19)

Belrose JC, Noppens RR. Anesthesiology and cognitive impairment: a narrative review of current clinical literature. BMC Anesthesiol. 2019 Dec 27;19(1):241. doi: 10.1186/s12871-019-0903-7. Review. — View Citation

Danielson M, Wiklund A, Granath F, Blennow K, Mkrtchian S, Nellgård B, Oras J, Jonsson Fagerlund M, Granström A, Schening A, Rasmussen LS, Erlandsson Harris H, Zetterberg H, Ricksten SE, Eriksson LI. Neuroinflammatory markers associate with cognitive decline after major surgery: Findings of an explorative study. Ann Neurol. 2020 Mar;87(3):370-382. doi: 10.1002/ana.25678. Epub 2020 Jan 25. — View Citation

De Jonckheere J, Bonhomme V, Jeanne M, Boselli E, Gruenewald M, Logier R, Richebé P. Physiological Signal Processing for Individualized Anti-nociception Management During General Anesthesia: a Review. Yearb Med Inform. 2015 Aug 13;10(1):95-101. doi: 10.15265/IY-2015-004. Review. — View Citation

Evered LA, Silbert BS. Postoperative Cognitive Dysfunction and Noncardiac Surgery. Anesth Analg. 2018 Aug;127(2):496-505. doi: 10.1213/ANE.0000000000003514. Review. — View Citation

Feng X, Hu J, Hua F, Zhang J, Zhang L, Xu G. The correlation of intraoperative hypotension and postoperative cognitive impairment: a meta-analysis of randomized controlled trials. BMC Anesthesiol. 2020 Aug 5;20(1):193. doi: 10.1186/s12871-020-01097-5. — View Citation

Futier E, Lefrant JY, Guinot PG, Godet T, Lorne E, Cuvillon P, Bertran S, Leone M, Pastene B, Piriou V, Molliex S, Albanese J, Julia JM, Tavernier B, Imhoff E, Bazin JE, Constantin JM, Pereira B, Jaber S; INPRESS Study Group. Effect of Individualized vs Standard Blood Pressure Management Strategies on Postoperative Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery: A Randomized Clinical Trial. JAMA. 2017 Oct 10;318(14):1346-1357. doi: 10.1001/jama.2017.14172. — View Citation

Greaves D, Psaltis PJ, Davis DHJ, Ross TJ, Ghezzi ES, Lampit A, Smith AE, Keage HAD. Risk Factors for Delirium and Cognitive Decline Following Coronary Artery Bypass Grafting Surgery: A Systematic Review and Meta-Analysis. J Am Heart Assoc. 2020 Nov 17;9(22):e017275. doi: 10.1161/JAHA.120.017275. Epub 2020 Nov 7. — View Citation

Krzych LJ, Pluta MP, Putowski Z, Czok M. Investigating Association between Intraoperative Hypotension and Postoperative Neurocognitive Disorders in Non-Cardiac Surgery: A Comprehensive Review. J Clin Med. 2020 Sep 30;9(10). pii: E3183. doi: 10.3390/jcm9103183. Review. — View Citation

Ledowski T. Monitoring nociception-getting 'there yet' might be easier with a road map. Br J Anaesth. 2017 Oct 1;119(4):716-717. doi: 10.1093/bja/aex277. — View Citation

Ledowski T. Objective monitoring of nociception: a review of current commercial solutions. Br J Anaesth. 2019 Aug;123(2):e312-e321. doi: 10.1016/j.bja.2019.03.024. Epub 2019 Apr 30. Review. — View Citation

Martini CH, Boon M, Broens SJ, Hekkelman EF, Oudhoff LA, Buddeke AW, Dahan A. Ability of the nociception level, a multiparameter composite of autonomic signals, to detect noxious stimuli during propofol-remifentanil anesthesia. Anesthesiology. 2015 Sep;123(3):524-34. doi: 10.1097/ALN.0000000000000757. — View Citation

Meijer F, Honing M, Roor T, Toet S, Calis P, Olofsen E, Martini C, van Velzen M, Aarts L, Niesters M, Boon M, Dahan A. Reduced postoperative pain using Nociception Level-guided fentanyl dosing during sevoflurane anaesthesia: a randomised controlled trial. Br J Anaesth. 2020 Dec;125(6):1070-1078. doi: 10.1016/j.bja.2020.07.057. Epub 2020 Sep 17. — View Citation

Meijer FS, Martini CH, Broens S, Boon M, Niesters M, Aarts L, Olofsen E, van Velzen M, Dahan A. Nociception-guided versus Standard Care during Remifentanil-Propofol Anesthesia: A Randomized Controlled Trial. Anesthesiology. 2019 May;130(5):745-755. doi: 10.1097/ALN.0000000000002634. — View Citation

Ruetzler K, Khanna AK, Sessler DI. Myocardial Injury After Noncardiac Surgery: Preoperative, Intraoperative, and Postoperative Aspects, Implications, and Directions. Anesth Analg. 2020 Jul;131(1):173-186. doi: 10.1213/ANE.0000000000004567. Review. — View Citation

Salmasi V, Maheshwari K, Yang D, Mascha EJ, Singh A, Sessler DI, Kurz A. Relationship between Intraoperative Hypotension, Defined by Either Reduction from Baseline or Absolute Thresholds, and Acute Kidney and Myocardial Injury after Noncardiac Surgery: A Retrospective Cohort Analysis. Anesthesiology. 2017 Jan;126(1):47-65. — View Citation

Saugel B, Sessler DI. Perioperative Blood Pressure Management. Anesthesiology. 2021 Feb 1;134(2):250-261. doi: 10.1097/ALN.0000000000003610. Review. — View Citation

Sessler DI, Bloomstone JA, Aronson S, Berry C, Gan TJ, Kellum JA, Plumb J, Mythen MG, Grocott MPW, Edwards MR, Miller TE; Perioperative Quality Initiative-3 workgroup; POQI chairs, Miller TE, Mythen MG, Grocott MP, Edwards MR; Physiology group; Preoperative blood pressure group; Intraoperative blood pressure group; Postoperative blood pressure group. Perioperative Quality Initiative consensus statement on intraoperative blood pressure, risk and outcomes for elective surgery. Br J Anaesth. 2019 May;122(5):563-574. doi: 10.1016/j.bja.2019.01.013. Epub 2019 Feb 27. — View Citation

Sessler DI, Khanna AK. Perioperative myocardial injury and the contribution of hypotension. Intensive Care Med. 2018 Jun;44(6):811-822. doi: 10.1007/s00134-018-5224-7. Epub 2018 Jun 4. Review. — View Citation

Walsh M, Devereaux PJ, Garg AX, Kurz A, Turan A, Rodseth RN, Cywinski J, Thabane L, Sessler DI. Relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery: toward an empirical definition of hypotension. Anesthesiology. 2013 Sep;119(3):507-15. doi: 10.1097/ALN.0b013e3182a10e26. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of intraoperative hypotension	Occurrence of intraoperative hypotension is defined by at least 1 minute under the hypotension thresholds.; Moderate and Severe Hypotension are respectively defined as a Mean Blood Pressure <65 mmHg or <55 mmHg and <75 or <65 mmHg for patient with history of chronic hypertension	during surgery
Primary	Total Vasopressor Dose	Total Vasopressor Dose used throughout the intervention to maintain Arterial Pressure within a pre-defined individualized ranges (= 65 mmHg or =75 mmHg for patient with history of chronic hypertension, and = 100 mmHg)	during surgery
Primary	Number of interventions to cure intraoperative hypotension	Number of vasopressor boli or vasopressor infusion dose adjustments	during surgery
Primary	Total Time under hypotension thresholds	Hypotension Thresholds ( <65 mmHg or < 75mmHg for patient with history of chronic hypertension)	during surgery
Secondary	Myocardial Injury in Non-Cardiac Surgery (MINS) marker (Troponin T)	Troponin T level measured before surgery, at end of surgery, 4 hours, 8 hours, 24 hours, 36 hours and 48 hours after surgery. The threshold is a postoperative concentration = 20 ng/L with an increase from baseline of at least 5 ng/L, or a postoperative concentration = 65 ng/L.	up to 48 hours after surgery
Secondary	Postoperative Acute Kidney Injury (AKI) marker (creatinin/Glomerular Filtration Rate)	Creatinin level measured before surgery, at end of surgery, 24 hours and 48 hours after surgery. The thresholds are defined by the Kidney Disease: Improving Global Outcomes (KDIGO) classification without the oliguria criteria.	up to 48 hours after surgery
Secondary	Postoperative Cognitive Decline (POCD)	POCD will be evaluated by cognitive dysfunction battery tests (written Montreal Cognitive Assessment (MOCA) Test) at days 5,10, 15, hospital discharge, 3 and 6 postoperative months	up to 6 months after surgery
Secondary	PostOperative Delirium (PO Delirium)	PO Delirium will be evaluated by the Confusion Assessment Method (CAM) at days 5, 10, 15, hospital discharge, 3 and 6 postoperative months	up to 6 months after surgery
Secondary	Dosage of Stress Hormones	Adrenocorticotropic Hormone (ACTH) and Cortisol will be measured in blood samples at the end of surgery, at the arrival in the ICU and at 4 hours after surgery.	up to 4 hours after surgery
Secondary	Dosage of Neuro-Inflammatory Markers	Interleukine-6 and Interleukine-8 will be measured in blood and saliva samples before surgery and during the postoperative period (4 hours, 24 hours and 48 hours after surgery).	up to 48 hours after surgery
Secondary	Olfactory Function assessment as an indicator of Neuro-Inflammation	A rapid quantitative olfactory function test, the University of Pennsylvania Smell Identification -Test (UPSIT-Test) will be performed before surgery and during the postoperative period (4 hours, 24 hours and 48 hours after surgery).	up to 48 hours after surgery
Secondary	Length of Intensive Unit Care (IUC) stay		up to 10 Days after surgery
Secondary	Length of hospital stay		up to 15 Days after surgery
Secondary	Adverse Event (blood loss, infection)		up to 15 Days after surgery