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Rebound pain after peripheral nerve blocks reduces the benefits of regional anesthesia and increases opioid consumption. This rebound pain most likely results from suboptimal pain management, as patients receiving a peripheral nerve block are typically not given scheduled opioid doses. Oral Patient Controlled Analgesia (PCA) consists of an oral morphine prescription that allows patients to self-administer doses based on their pain score.
This study will compare patients undergoing elective orthopaedic surgery under general anaesthesia or sedation with a peripheral nerve block, receiving oral morphine PCA either with or without additional scheduled oral morphine doses.
This study contains two parts, one for the upper limb and one for the lower limb. Each part will be published independently.
This registration concerns the lower limb cohort.
Patients from each cohort (upper limb and lower limb) will be randomized into two groups of 25 patients each, for a total enrollment plan of 50 patients per cohort. After written informed consent, patients will be allocated to one of the two groups according to a computer-generated randomization list.
In the control group, morphine will be administered exclusively on demand via oral PCA,based on pain intensity assessed using a numeric rating scale (VAS > 4). For oral PCA, one10 mg morphine tablet is placed on the patient's bedside table by the nursing staff. When the patients experience pain, they may take the tablet autonomously and subsequently inform the nurse, who then prepares and places a new tablet at bedside for the next potential pain episode. No scheduled or prophylactic opioid administration will be provided in this group. The maximal allowed dose through oral PCA will be 6 tablets (10mg each) per 24-hour period.
In the intervention group, morphine will be administered at predefined regular intervals, starting immediately in the postoperative period in addition to the availability of oral PCA morphine as mentioned above. Scheduled doses of 20mg slow-release oral morphine will be given at fixed 12 hour intervals. Patients will therefore receive regular morphine to ensure continuous baseline analgesia while still having access to an additional tablet via oral PCA in case of breakthrough pain, following the same nursing procedure as in the control group.
In both groups, standardized multimodal analgesia will be provided
The primary objective of this study is to assess and compare the highest pain score within the first 24 postoperative hours between the two groups using the Visual Analog Scale (VAS). The secondary objective is to assess the effect of the intervention on postoperative pain and analgesic outcomes, including morphine consumption, pain scores, need for additional nerve blocks, incidence of chronic pain, duration of analgesia, postoperative side effects, complications, and hospital length of stay.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Scheduled group | Experimental | Oral morphine administered at predefined regular intervals starting immediately after surgery, with additional access to oral PCA. |
|
| On-demand group | Active Comparator | Oral morphine administered on demand via PCA. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Morphine provided via oral PCA | Drug | Morphine will be administered according to a scheduled regimen (20mg slow release oral morphine at fixed 12-hour intervals), with additional oral PCA on demand for breakthrough pain (VAS > 4), following the same bedside tablet procedure as in the control group. The maximum allowed dose through oral PCA will be 6 tablets (10mg each) per 24-hour period. |
| Measure | Description | Time Frame |
|---|---|---|
| Worst pain score during the first 24 hours after surgery | Highest postoperative pain score during the first 24 hours after surgery, measured using a 0-10 Visual Analog Scale (VAS), where 0 indicates no pain and 10 indicates the worst pain imaginable | 24 hours postoperatively |
| Measure | Description | Time Frame |
|---|---|---|
| Minimal pain score during the first 12 hours after surgery | Lowest postoperative pain score during the first 12 hours after surgery, measured using a 0-10 Visual Analog Scale (VAS), where 0 indicates no pain and 10 indicates the worst pain imaginable | 12 hours postoperatively |
| Rebound pain score measured using the Visual Analog Scale (VAS) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Eric Albrecht, Prof. | Contact | +41 79 556 63 41 | eric.albrecht@chuv.ch | |
| Iliana Mrazek | Contact | +41 79 556 85 06 | iliana.mrazek@chuv.ch |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHUV, Centre Hospitalier Vaudois | Lausanne | Canton of Vaud | 1000 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25822923 | Background | Abdallah FW, Halpern SH, Aoyama K, Brull R. Will the Real Benefits of Single-Shot Interscalene Block Please Stand Up? A Systematic Review and Meta-Analysis. Anesth Analg. 2015 May;120(5):1114-1129. doi: 10.1213/ANE.0000000000000688. | |
| 40987657 | Background | Wu CL, Badani S, Tedore TR. Peripheral nerve blocks for perioperative analgesia: das Kind mit dem Bade ausschutten...throwing the baby out with the bathwater? Br J Anaesth. 2025 Nov;135(5):1147-1150. doi: 10.1016/j.bja.2025.08.017. Epub 2025 Sep 22. |
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This is a single-center, prospective, superiority, randomized, double-blind, parallel-group study
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|
| Morphine provided via oral PCA + morphine administered at a scheduled regimen | Drug | morphine will be administered according to a scheduled regimen (20mg slow-release oral morphine at fixed 12-hour intervals), with additional oral PCA on demand for breakthrough pain (VAS > 4), following the same bedside tablet procedure as in the control group. The maximum allowed dose through oral PCA will be 6 tablets (10mg each) per 24-hour period. |
|
Rebound pain score calculated as the difference between the highest postoperative pain score within the first 24 hours after surgery and the lowest postoperative pain score within the first 12 hours after surgery. Pain intensity is assessed using a Visual Analog Scale (VAS) ranging from 0 to 10, where 0 indicates no pain and 10 indicates the worst pain imaginable. Higher rebound pain scores indicate greater pain rebound |
| From surgery until 24 hours postoperatively |
| Rest and dynamic pain scores | Rest and dynamic pain scores, measured using a 0-10 Visual Analogue Score (VAS), where 0 indicates no pain and 10 indicates the worst pain imaginable | At 2, 12, 24, 36, 48, 60, and 72 hours after surgery |
| Incidence of severe pain | Pain evaluated at >7/10, measured using a 0-10 Visual Analog Scale (VAS), where 0 indicates no pain and 10 indicates the worst pain imaginable | From surgery through 3 months after surgery |
| Persistence of pain | Incidence of persistent pain at 4 weeks and chronic pain at 3 months | During the follow-up period from discharge till 4 weeks and 3 months |
| Morphine consumption in the recovery room | consumption in mg | from admission until discharge from the recovery room, up to 2 hours |
| PCA administered morphine consumption at day 1, 2 and 3 | Consumption in mg administered by PCA | Day 1, 2 and 3 postoperatively |
| Total administered morphine consumption at day 1, 2, and 3 | Total consumption in mg | Day 1, 2 and 3 postoperatively |
| Incidence of postoperative nausea and vomiting | Presence of nausea or vomiting in the postoperative period | At 2 hours, day 1, day 2 and day 3 postoperatively |
| Incidence of pruritus | Presence of pruritus in the postoperative period | At 2 hours, day 1, day 2 and day 3 postoperatively |
| Incidence of urinary retention requiring bladder catheterisation | Urinary retention requiring catheterisation | At 2 hours, day 1, day 2 and day 3 postoperatively |
| Hospital length of stay | Duration of hospitalization, measured as the number of days from surgery (baseline) to hospital discharge. Higher values indicate longer hospital stays. | At hospital discharge (typically within 5 days, according to our hospital's standard practice) |
| Requirement for a new peripheral nerve block | Requirement for a new peripheral nerve block | On postoperative day 1, 2 and 3 |
| Duration of analgesia | Time between block performance and the first dose of morphine | From the time the block is performed up to 36 hours after surgery |
| 26869374 | Background | Galos DK, Taormina DP, Crespo A, Ding DY, Sapienza A, Jain S, Tejwani NC. Does Brachial Plexus Blockade Result in Improved Pain Scores After Distal Radius Fracture Fixation? A Randomized Trial. Clin Orthop Relat Res. 2016 May;474(5):1247-54. doi: 10.1007/s11999-016-4735-1. Epub 2016 Feb 11. |
| 39929722 | Background | Makkar JK, Singh NP, Khurana BJK, Chawla JK, Singh PM. Efficacy of different routes of dexamethasone administration for preventing rebound pain following peripheral nerve blocks in adult surgical patients: a systematic review and network meta-analysis. Anaesthesia. 2025 Jun;80(6):704-712. doi: 10.1111/anae.16566. Epub 2025 Feb 10. |
| 33551124 | Background | Hamilton DL. Rebound pain: distinct pain phenomenon or nonentity? Br J Anaesth. 2021 Apr;126(4):761-763. doi: 10.1016/j.bja.2020.12.034. Epub 2021 Feb 5. No abstract available. |
| 30124544 | Background | Lavand'homme P. Rebound pain after regional anesthesia in the ambulatory patient. Curr Opin Anaesthesiol. 2018 Dec;31(6):679-684. doi: 10.1097/ACO.0000000000000651. |
| 37642227 | Background | Schubert AK, Wiesmann T, Volberg C, Riecke J, Schneider A, Wulf H, Dinges HC. Rebound pain and postoperative pain profile following brachial plexus block compared to general anaesthesia-An observational study. Acta Anaesthesiol Scand. 2023 Nov;67(10):1414-1422. doi: 10.1111/aas.14318. Epub 2023 Aug 29. |
| 29052225 | Background | Henningsen MJ, Sort R, Moller AM, Herling SF. Peripheral nerve block in ankle fracture surgery: a qualitative study of patients' experiences. Anaesthesia. 2018 Jan;73(1):49-58. doi: 10.1111/anae.14088. Epub 2017 Oct 19. |
| 40032279 | Background | Singla P, Ye Y, Elkassabany NM, Mariano ER. 'Pain as regional anaesthesia wears off' or 'rebound pain': what's in a name? Anaesthesia. 2025 Jun;80(6):607-611. doi: 10.1111/anae.16583. Epub 2025 Mar 3. No abstract available. |
| 33390261 | Background | Barry GS, Bailey JG, Sardinha J, Brousseau P, Uppal V. Factors associated with rebound pain after peripheral nerve block for ambulatory surgery. Br J Anaesth. 2021 Apr;126(4):862-871. doi: 10.1016/j.bja.2020.10.035. Epub 2020 Dec 31. |
| 40701886 | Background | Touil N, Pavlopoulou A, Barbier O, Libouton X, Gruson D, Gala JL, Lavand'homme P. Factors associated with a reduction in the preventive effect of intravenous dexamethasone on rebound pain after axillary brachial plexus block. Br J Anaesth. 2025 Oct;135(4):1059-1066. doi: 10.1016/j.bja.2025.05.055. Epub 2025 Jul 22. |
| 32773724 | Background | Munoz-Leyva F, Cubillos J, Chin KJ. Managing rebound pain after regional anesthesia. Korean J Anesthesiol. 2020 Oct;73(5):372-383. doi: 10.4097/kja.20436. Epub 2020 Aug 10. |
| 40610285 | Background | Chung AR, Mather RV, Gutierrez R, Liu R, Leung CFA, Zhang M, Santa Cruz Mercado LA, Houle TT, Bittner EA, Purdon PL. Association of peripheral nerve blocks with increased postoperative pain and opioid use in orthopaedic surgery: a single-centre retrospective cohort study. Br J Anaesth. 2025 Nov;135(5):1286-1296. doi: 10.1016/j.bja.2025.05.030. Epub 2025 Jul 3. |
| 32472958 | Background | Holmberg A, Hassellund SS, Draegni T, Nordby A, Ottesen FS, Gulestol A, Raeder J. Analgesic effect of intravenous dexamethasone after volar plate surgery for distal radius fracture with brachial plexus block anaesthesia: a prospective, double-blind randomised clinical trial. Anaesthesia. 2020 Nov;75(11):1448-1460. doi: 10.1111/anae.15111. Epub 2020 May 30. |
| 39454286 | Background | Yang ZS, Lai HC, Jhou HJ, Chan WH, Chen PH. Rebound pain prevention after peripheral nerve block: A network meta-analysis comparing intravenous, perineural dexamethasone, and control. J Clin Anesth. 2024 Dec;99:111657. doi: 10.1016/j.jclinane.2024.111657. Epub 2024 Oct 24. |
| 26650425 | Background | Sunderland S, Yarnold CH, Head SJ, Osborn JA, Purssell A, Peel JK, Schwarz SK. Regional Versus General Anesthesia and the Incidence of Unplanned Health Care Resource Utilization for Postoperative Pain After Wrist Fracture Surgery: Results From a Retrospective Quality Improvement Project. Reg Anesth Pain Med. 2016 Jan-Feb;41(1):22-7. doi: 10.1097/AAP.0000000000000325. |
| ID | Term |
|---|---|
| D010149 | Pain, Postoperative |
| D000377 | Agnosia |
| ID | Term |
|---|---|
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D010468 | Perceptual Disorders |
| D019954 | Neurobehavioral Manifestations |
| D009422 | Nervous System Diseases |
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