Comparison Between Opioid-sparing Anesthesia Guided by the CARDEAN® Index and Opioid-free Anesthesia During Total Hip Arthroplasty

Official title

Comparaison Entre anesthésie Avec épargne Morphinique guidée Par l'Index CARDEAN® et anesthésie Sans Morphinique au Cours Des Arthroplasties Totales de Hanche : étude randomisée

Overview

The proposed study compares two anesthesia techniques; the hypothesis being tested is that titrating sufentanil based on the CARDEAN® index (titrated OSA) does not increase post-operative morphine consumption compared to opioid-free anesthesia (OFA). This CARDEAN®-guided titrated anesthesia approach could potentially allow for hospital discharge as early as 24 hours post-operatively and is compatible with ERAS protocols. The primary objective is to demonstrate that sufentanil administration guided by the CARDEAN® index (titrated OSA) does not increase postoperative morphine consumption compared to opioid-free anesthesia (OFA). This is a prospective, single-center, randomized, single-blind, non-inferiority study. Two groups of 70 patients each (140 patients in total) are compared based on the type of intraoperative analgesia: titrated OSA (Arm 1) versus OFA (Arm 2). Randomization will be performed at a 1:1 ratio and stratified by surgical approach (anterior or lateral approach).

Interventions

• Procedure Titrated Opioid Sparing Anesthesia
  Opioid-sparing anesthesia using the CARDEAN® index, which enables specific monitoring of nociception during general anesthesia. By adjusting sufentanil administration in real time based on variations in surgical painful stimuli, the CARDEAN® index enables titrated opioid-sparing anesthesia (titrated OSA).
• Procedure opioid free anesthesia
  anesthesia performed without opioid administration

Primary outcome measures

• Total dose of morphine required to maintain a pain score ≤ 3 on a numerical scale of 1 to 10 during the first 24 hours (dose expressed as oral morphine equivalent, OME) [Time frame: During the first 24 hours after the start of anesthesia]

Secondary outcome measures (12)

• Stability of heart rate (HR) and mean arterial pressure (MAP) [Time frame: During intervention]
• Speed of emergence from anesthesia in the post-anesthesia care unit (PACU) [Time frame: Time interval between the end of the procedure and extubation]
• Postoperative pain control [Time frame: During awakening, at day 1 and day 2 after surgery]
• Adverse effects of postoperative opioids [Time frame: During the awakening]
• Discharge from the hospital is possible as early as 24 hours post-procedure for patients deemed eligible for early discharge (determined by the surgeon prior to the intervention). [Time frame: Until 24 hours after surgery]
• Patient satisfaction: satisfaction questionnaire (completed on the day of discharge) regarding the management of any pain. [Time frame: At discharge (between 24 and 48 hours after surgery)]
• Maximum pain score on a 0-10 numerical rating scale (NRS max) at rest and during movement [Time frame: On postoperative days 1 and 2]
• IV morphine dose received in the PACU, expressed in MME [Time frame: during the awakening]
• Morphine dose received in the surgical ward, expressed in MME, at 6, 12, 18, 24, 36, and 48 hours post-surgery (H0 = start of surgery) [Time frame: Every 6 hours until 48 hours after surgery]
• Number of patients not receiving morphine in the PACU [Time frame: during the awakening, 24 hours after surgery, 48 hours after surgery]
• Presence of postoperative nausea and/or vomiting (PONV) [Time frame: Until up to 48 hours after surgery]
• Acute urinary retention (defined by the presence of a bladder volume > 600 ml requiring urinary catheterization) [Time frame: Until up to 48 hours after surgery]

Eligibility criteria

Inclusion criteria

• Men and women
• Patient aged at least 18 years
• Signed informed consent
• American Society of Anesthesiologists (ASA) Class 1 to 3
• Scheduled total hip arthroplasty under general anesthesia (anterior or lateral approach) with local analgesic infiltration performed by the surgeon at the end of the procedure
• Affiliated with or a beneficiary of a social security scheme.

Exclusion criteria

• ASA Class 4 or 5
• Emergency hip surgery
• Indication for an anesthesia technique other than general anesthesia (patient preference, benefit-risk ratio, etc.)
• Permanent cardiac arrhythmia or permanent cardiac pacing (invalid CARDEAN® index)
• Resting bradycardia < 50 bpm
• Second- or third-degree atrioventricular block
• Chronic opioid user
• Refusal of consent
• Patient unable to read, write, or understand French
• Vulnerable patient as defined by Article L1121-6 of the Public Health Code (CSP)
• Adult patient under guardianship, curatorship, or judicial protection
• Patient unable to personally provide consent as defined by Article L.1121-8 of the CSP, or an adult under legal protection
• Pregnant or breastfeeding woman as defined by Article L1121-5 of the CSP

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

Single blind

Primary purpose

Treatment

Study locations

France · 1 center

• Pole Sante Oreliance, Polyclinique des Longues Allees — Saran

Publications

• Pedersen C, Vilhelmsen FJ, Laigaard J, Mathiesen O, Karlsen APH. Opioid consumption and non-opioid multimodal analgesic treatment in pain management trials after hip and knee arthroplasties: A meta-epidemiological study. Acta Anaesthesiol Scand. 2023 May;67(5):613-620. doi: 10.1111/aas.14213. Epub 2023 Feb 21. PMID 36759566
• Laigaard J, Pedersen C, Ronsbo TN, Mathiesen O, Karlsen APH. Minimal clinically important differences in randomised clinical trials on pain management after total hip and knee arthroplasty: a systematic review. Br J Anaesth. 2021 May;126(5):1029-1037. doi: 10.1016/j.bja.2021.01.021. Epub 2021 Mar 5. PMID 33678402
• Wey PF, Loheas D, Lamblin A, Riche B, Rabilloud M, Escarment J, Puidupin M, Quintin L, Martinez JY, Cividjian A. A beat-by-beat cardiovascular index, CARDEAN, to titrate opioid administration in the setting of orthopaedic surgery: a prospective randomized trial. J Clin Monit Comput. 2021 Dec;35(6):1311-1324. doi: 10.1007/s10877-020-00597-6. Epub 2020 Oct 6. PMID 33025323
• Papaioannou V, Chouvarda I, Gaertner E, Benyamina M, Ferry A, Maurel V, Soussi S, Blet A, Chaouat M, Plaud B, Mebazaa A, Legrand M; PRONOBURN Group. Heart rate variability and cardiac baroreflex inhibition-derived index predicts pain perception in burn patients. Burns. 2016 Nov;42(7):1445-1454. doi: 10.1016/j.burns.2016.04.017. Epub 2016 May 8. PMID 27170468
• Rossi M, Cividjian A, Fevre MC, Oddoux ME, Carcey J, Halle C, Frost M, Gardellin M, Payen JF, Quintin L. A beat-by-beat, on-line, cardiovascular index, CARDEAN, to assess circulatory responses to surgery: a randomized clinical trial during spine surgery. J Clin Monit Comput. 2012 Dec;26(6):441-9. doi: 10.1007/s10877-012-9372-y. Epub 2012 Jun 10. PMID 22684738
• Martinez JY, Wey PF, Lions C, Cividjian A, Rabilloud M, Bissery A, Bourdon L, Puidupin M, Escarment J, Quintin L. A beat-by-beat cardiovascular index, CARDEAN: a prospective randomized assessment of its utility for the reduction of movement during colonoscopy. Anesth Analg. 2010 Mar 1;110(3):765-72. doi: 10.1213/ANE.0b013e3181cc9ebe. PMID 20185655
• Cividjian A, Martinez JY, Combourieu E, Precloux P, Beraud AM, Rochette Y, Cler M, Bourdon L, Escarment J, Quintin L. Beat-by-beat cardiovascular index to predict unexpected intraoperative movement in anesthetized unparalyzed patients: a retrospective analysis. J Clin Monit Comput. 2007 Apr;21(2):91-101. doi: 10.1007/s10877-006-9061-9. Epub 2006 Dec 22. PMID 17186401
• Ao Y, Ma J, Zheng X, Zeng J, Wei K. Opioid-Sparing Anesthesia Versus Opioid-Free Anesthesia for the Prevention of Postoperative Nausea and Vomiting after Laparoscopic Bariatric Surgery: A Systematic Review and Network Meta-Analysis. Anesth Analg. 2025 Feb 1;140(2):385-396. doi: 10.1213/ANE.0000000000006942. Epub 2024 Apr 5. PMID 38578868

Identifiers

NCT: NCT07747142 · ID-RCB-2026-A00810-51

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗