Small Study Comparing Two Pain Medicines in Teenagers for Pain Control After Scoliosis Corrective Surgery.

Официальное название

Patient-Controlled Analgesia (PCA) With Ketamine-Morphine (PCA KetaMorph) vs PCA Morphine for Postoperative Analgesia in Idiopathic Scoliosis Surgery - A Randomized Controlled Trial

Обзор

The goal of this clinical trial is to evaluate whether adding low-dose ketamine to PCA morphine reduces opioid requirements after posterior spinal fusion surgery in adolescent idiopathic scoliosis patients. Selected patients aged 10-18 years undergoing elective AIS surgery at University Malaya Medical Centre will be randomised to ketamine-morphine or morphine-only PCA. The primary outcome is cumulative morphine consumption at 48 hours, with secondary outcomes including pain scores, opioid-related adverse effects, time to ambulation, and patient satisfaction. This study aligns with national priorities for safe opioid stewardship and enhanced peri-operative care in Malaysia.

Подробное описание

Posterior spinal fusion (PSF) is the definitive surgical treatment for patients with scoliosis. However, the procedure involves extensive tissue dissection, resulting in significant postoperative pain. Although patient-controlled analgesia (PCA) with intravenous morphine remains the current standard, the large doses required are frequently associated with side effects such as nausea, vomiting, pruritus, and sedation \[4-6\]. These complications delay mobilisation, prolong hospital stay, increase healthcare costs, and may contribute to opioid tolerance, undermining effective pain control.

Enhanced Recovery After Surgery (ERAS) protocols strongly promote multimodal analgesia, which combines opioid and non-opioid agents to achieve synergistic pain relief while minimising opioid exposure. This strategy has been shown to reduce side effects, improve recovery, shorten hospital stay, and lower the risk of opioid-related tolerance, hyperalgesia, and potential long-term dependence. Despite these advantages, evidence for the use of ketamine-morphine PCA in scoliosis surgery remains limited, and subanaesthetic ketamine-though effective intraoperatively as an opioid-sparing agent-remains underutilised in postoperative PCA regimens. Our previous study demonstrated that co-administration of subanaesthetic ketamine (0.5 mg/kg) at induction reduced postoperative pain sensitivity and hyperalgesia typically associated with high-dose remifentanil infusion, a strong opioid analgesic \[13\]. This finding underscores the potential role of ketamine as an opioid-sparing adjunct.

Building on this, we propose a single-centre, double-blind, randomised controlled trial in 114 idiopathic scoliosis patients undergoing elective PSF at University Malaya Medical Centre. Participants will be randomised to receive PCA containing ketamine-morphine (1 mg/mL + 1 mg/mL) or morphine (1 mg/mL) alone, with identical syringes to ensure allocation concealment. The primary endpoint is cumulative morphine consumption at 48 hours, while secondary outcomes include pain scores, opioid-related side effects, time to ambulation, and patient satisfaction.

This study aims to provide the first Malaysian evidence on an opioid-sparing PCA regimen, addressing national ERAS priorities and contributing to global opioid stewardship.

Вмешательства

• Комбинированный продукт Ketamine-Morphine PCA
  The patient in this group will receive PCA Morphine (1mg/mL) with addition of Ketamine (1mg/mL) in comparison with the other group.
• Препарат Morphine (Intravenous patient-controlled analgesia)
  This patient will receive PCA Morphine only (1mg/mL).

Первичные конечные точки

• Cumulative Morphine Consumption [Срок оценки: From end of surgery (Hour 0) to 48 hours post-operation (Day 2).]

Вторичные конечные точки (6)

• Post-operative Pain Intensity [Срок оценки: At 6, 12, 18, 24, 30, 36, 42, and 48 hours post-operatively.]
• Incidence of Opioid-Related Adverse Events (ORAEs) [Срок оценки: From the end of surgery through 48 hours post-operatively.]
• Duration of Hospital Stay [Срок оценки: From date of surgery until hospital discharge (approximately 3-7 days).]
• Time to First Post-operative Flatus [Срок оценки: Up to 48 hours post-operatively.]
• Time to First Ambulation [Срок оценки: Up to 48 hours post-operatively.]
• Patient Satisfaction With Pain Management [Срок оценки: At the time of hospital discharge (approximately Day 3 to Day 7 post-operatively).]

Критерии участия

Критерии включения

• Aged > 10 years old
• Idiopathic scoliosis scheduled for single-stage posterior spinal fusion (PSF).
• American Society of Anaesthesiologists (ASA) physical status I-II.

Критерии исключения

• Known hypersensitivity to morphine, ketamine or formulation excipients.
• Hepatic dysfunction (ALT or AST > 2 × upper limit of normal).
• Renal impairment (eGFR ≤ 60 mL min-¹ 1·73 m-²).
• Uncontrolled asthma or severe restrictive lung disease.
• Cardiac disease or clinically significant arrhythmia.
• Epilepsy.
• Intellectual disability precluding PCA use.
• Chronic opioid therapy or pre-operative pain > 3 months.
• Concomitant monoamine-oxidase inhibitor or tricyclic antidepressant therapy.
• History of severe postoperative delirium.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Малайзия · 1 центр

• University Malaya Medical Centre — Kuala Lumpur

Публикации

• Zin CS, Nazar NI, Rahman NSA, Ahmad WR, Rani NS, Ng KS. Patterns of initial opioid prescription and its association with short-term and long-term use among opioid-naive patients in Malaysia: a retrospective cohort study. BMJ Open. 2019 Jul 2;9(7):e027203. doi: 10.1136/bmjopen-2018-027203. PMID 31270113
• Sveticic G, Gentilini A, Eichenberger U, Luginbuhl M, Curatolo M. Combinations of morphine with ketamine for patient-controlled analgesia: a new optimization method. Anesthesiology. 2003 May;98(5):1195-205. doi: 10.1097/00000542-200305000-00023. PMID 12717142
• Sveticic G, Eichenberger U, Curatolo M. Safety of mixture of morphine with ketamine for postoperative patient-controlled analgesia: an audit with 1026 patients. Acta Anaesthesiol Scand. 2005 Jul;49(6):870-5. doi: 10.1111/j.1399-6576.2005.00740.x. PMID 15954974
• Hodgman-Korth E, Kenyon NJ. Stability of morphine-ketamine admixtures for patient-controlled analgesia. J Pain Palliat Care Pharmacother. 2009;23:272-6.
• Roy JJ, Fortier C, Drolet P, et al. Physical compatibility of ketamine and morphine mixtures in PCA reservoirs. Can J Hosp Pharm. 2000;53:16-21.
• Carstensen M, Moller AM. Adding ketamine to morphine for intravenous patient-controlled analgesia for acute postoperative pain: a qualitative review of randomized trials. Br J Anaesth. 2010 Apr;104(4):401-6. doi: 10.1093/bja/aeq041. Epub 2010 Mar 5. PMID 20207747
• Minoshima T, Fukushima S, Yokoyama H, et al. Intra-operative ketamine infusion reduces morphine requirement after adolescent spinal fusion: a randomised trial. Paediatr Anaesth. 2017;27:1064-71.
• Tornoe AS, Pind AH, Laursen CCW, Andersen C, Maagaard M, Mathiesen O. Ketamine for postoperative pain treatment in spinal surgery: Systematic review with meta-analysis and trial sequential analysis. Acta Anaesthesiol Scand. 2023 Nov;67(10):1306-1321. doi: 10.1111/aas.14307. Epub 2023 Jul 19. PMID 37468443

Идентификаторы

NCT: NCT07452705 · 2025817-15467

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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