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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Adolescent Idiopathic Scoliosis (AIS)
• Intervention / Treatment: Combination product: Ketamine-Morphine PCA; Drug: Morphine (Intravenous patient-controlled analgesia)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 114
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: MUHAMMAD FAEEZ BIN MOHD YUSOH, MBBS; Phone Number: +6013-5233915; Email: faeez@ummc.edu.my

Study Locations

• Malaysia
  • Kuala Lumpur
    • Kuala Lumpur, Kuala Lumpur, Malaysia, 59100
      • University Malaya Medical Centre
      • Contact: NIK SHERINA HAIDI BINTI HANAFI, MBBS; Phone Number: +6079492802; Email: niksherina@um.edu.my

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

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

Exclusion criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine-Morphine PCA (1:1 ratio); This group receives a ketamine-morphine PCA solution (1 mg mL-¹ + 1 mg mL-¹). This device deliver a 1 mL bolus, enforce a five-minute lock-out and cap delivery at 20 mL per four hours, with no background infusion. The patient will use PCA for at least 48 hours duration.	Combination product: 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.; Other Names: K-M
Active Comparator: Morphine only PCA; This group receives morphine alone PCA (1 mg mL-¹). This device deliver a 1 mL bolus, enforce a five-minute lock-out and cap delivery at 20 mL per four hours, with no background infusion. The patient will use PCA for at least 48 hours duration.	Drug: Morphine (Intravenous patient-controlled analgesia); This patient will receive PCA Morphine only (1mg/mL).; Other Names: M

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Morphine Consumption	Total amount of intravenous morphine (in milligrams) administered via the Patient-Controlled Analgesia (PCA) device. This includes both the demand doses and any clinician-administered boluses.	From end of surgery (Hour 0) to 48 hours post-operation (Day 2).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-operative Pain Intensity	Patient-reported pain intensity measured using a Visual Analogue Scale (VAS). The scale ranges from 0 (no pain) to 10 (worst imaginable pain). Higher scores indicate greater pain intensity.	At 6, 12, 18, 24, 30, 36, 42, and 48 hours post-operatively.
Incidence of Opioid-Related Adverse Events (ORAEs)	The number of participants experiencing one or more of the following opioid-related adverse events: nausea, vomiting, pruritus (itching), excessive sedation (defined by a Richmond Agitation-Sedation Scale (RASS) score of -1 and below), or respiratory depression (respiratory rate < 8 breaths per minute).	From the end of surgery through 48 hours post-operatively.
Duration of Hospital Stay	The total number of days from the date of surgery (Day 0) to the date of hospital discharge.	From date of surgery until hospital discharge (approximately 3-7 days).
Time to First Post-operative Flatus	The time interval (in hours) from the end of surgery until the patient first reports the passage of gas (flatus). This serves as a proxy for the resolution of post-operative ileus.	Up to 48 hours post-operatively.
Time to First Ambulation	The time interval (in hours) from the end of surgery until the patient first takes steps outside of their bed with or without assistance.	Up to 48 hours post-operatively.
Patient Satisfaction With Pain Management	Patient-reported satisfaction with their pain management experience using a 5-point Likert scale. The scale consists of: = Very Dissatisfied; = Dissatisfied; = Neutral; = Satisfied; = Very Satisfied Total scores range from 1 to 5, where higher scores indicate greater satisfaction with the pain management protocol.	At the time of hospital discharge (approximately Day 3 to Day 7 post-operatively).

Collaborators and Investigators

• Sponsor: University of Malaya
• Investigators: Principal Investigator: SITI NADZRAH BINTI YUNUS, MBBS, University of Malaya

Publications and helpful links

General Publications

• Zin CS, Nazar NI, Rahman NSA, et al. Patterns of initial opioid prescription and its association with short-term and long-term use among opioid-naïve patients in Malaysia: a retrospective cohort study. BMJ Open. 2019;9:e027203. doi:10.1136/bmjopen-2018-027203
• Sveticic G, Gentilini A, Eichenberger U, Luginbühl M, Curatolo M. Combinations of morphine with ketamine for patient-controlled analgesia: a randomized, double-blind, cross-over study. Anesthesiology. 2003;98(5):1195-1205. doi:10.1097/00000542-200305000-00014
• Sveticic G, Farid R, Lauretti GR, et al. A safety audit of patient-controlled analgesia with ketamine and morphine after major surgery. Acta Anaesthesiol Scand. 2005;49(6):870-875. doi:10.1111/j.1399-6576.2005.00736.x
• 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, Møller AM. Adding ketamine to morphine for intravenous patient-controlled analgesia for acute postoperative pain: a qualitative review of randomised trials. Br J Anaesth. 2010;104:401-6.
• 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.
• Tornøe 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;67(10):1306-21. doi:10.1111/aas.14307
• Pendi A, Field R, Farhan SD, Eichler M, Bederman SS. Perioperative ketamine for analgesia in spine surgery: a meta-analysis of randomized controlled trials. Spine. 2018;43(5):E299-E307.
• Schmid RL, Sandler AN, Katz J. Use and efficacy of low-dose ketamine in the management of acute postoperative pain: a review. Pain. 1999;82:111-25.
• Hasan MS, Abdul Razak N, Yip HW, Lee ZY, Chan CYW, Kwan MK, et al. Association between intraoperative remifentanil use and postoperative hyperalgesia in adolescent idiopathic scoliosis surgery: a retrospective study. BMC Anesthesiol. 2023;23:177. doi:10.1186/s12871-023-02127-8
• Flood P, Rathmell JP, Shafer SL. Stoelting's Pharmacology and Physiology in Anesthetic Practice. 5th ed. New York: Wolters Kluwer; 2015.
• Himmelseher S, Duriex ME. Ketamine for perioperative pain management. Anesthesiology. 2005;102:211-20.
• Hasan MS, Selvanathan P, Lee ZY, Chiu CK, Chan CYW, Kwan MK, Yunus SN. Perioperative intravenous lidocaine as an analgesic adjunct in adolescent idiopathic scoliosis surgery. Spine (Phila Pa 1976). 2020;45(20):E1261-E1269. doi:10.1097/BRS.0000000000003611
• Fletcher D, Stamer UM, Pogatzki-Zahn E, et al. Pain management after surgery: a consensus statement from the ESA. Eur J Anaesthesiol. 2015;32:88-98.
• Kaye AD, Urman RD, Rappaport Y, et al. Multimodal analgesia as an essential part of enhanced recovery protocols in the ambulatory settings. J Anaesthesiol Clin Pharmacol. 2019;35(Suppl 1):S40-5.
• Kwan MK, Chiu CK, Chan TS, Chong KI, Mohamad SM, Hasan MS, Chan CYW. Trajectory of postoperative wound pain within the first 2 weeks following posterior spinal fusion surgery in adolescent idiopathic scoliosis patients. Spine (Phila Pa 1976). 2019;44(18):E1075-E1082.
• Chiu CK, Chong KI, Chan TS, et al. The anatomical locations of postoperative pain and their recovery trajectories following posterior spinal fusion surgery in adolescent idiopathic scoliosis patients. Med J Malaysia. 2020;75(1):12-7.
• Yrjälä T, Helenius I, Rissanen T, Ahonen M, Taittonen M, Helenius L. The extension of surgery predicts acute postoperative pain, while persistent postoperative pain is related to the spinal pathology in adolescents undergoing posterior spinal fusion. Children. 2022;9(11):1729. https://doi.org/10.3390/children9111729
• Seki H, Ideno S, Ishihara T, et al. Postoperative pain management in patients undergoing posterior spinal fusion for adolescent idiopathic scoliosis: a narrative review. Scoliosis. 2018;13:17.
• Deepak AS, Ong JY, Choon D, Lee K, Chiu CK, Chan C, Kwan K. The clinical effectiveness of a school screening programme for idiopathic scoliosis in Malaysia. Malays Orthop J. 2017;11(3):41-6. https://doi.org/10.5704/MOJ.1703.018
• Lee JY, Moon SH, Kim HJ, Park M, Suh BK, Nam J, Jung J, Lee HM. The prevalence of idiopathic scoliosis in eleven-year-old Korean adolescents: A 3-year epidemiological study. Yonsei Med J. 2014;55(3):773-8. https://doi.org/10.3349/ymj.2014.55.3.773
• Lee WS, Tay CG, Lum SH. Textbook of Paediatrics and Child Health. Kuala Lumpur: Universiti Malaya Press; 2020. p. 547-8.

Study record dates

Study Major Dates

• Study Start (Estimated): February 2, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): January 30, 2028

Study Registration Dates

• First Submitted: February 16, 2026
• First Submitted That Met QC Criteria: March 1, 2026
• First Posted (Actual): March 5, 2026

Study Record Updates

• Last Update Posted (Actual): March 5, 2026
• Last Update Submitted That Met QC Criteria: March 1, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Adolescent; Analgesia; Ketamine; Pain management; Morphine; Spinal fusion; Pain-controlled
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neurobehavioral Manifestations; Perceptual Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Agnosia; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Anesthesia and Analgesia; Heterocyclic Compounds, 4 or More Rings; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Morphine Derivatives; Analgesia; Morphine; Analgesia, Patient-Controlled
• Other Study ID Numbers: 2025817-15467

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared due to ethical and confidentiality considerations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No