Effect of Oral Melatonin Versus Intraoperative Lidocaine Infusion on Incidence of Postoperative Delirium in Elderly Patients Undergoing Total Hip Arthroplasty

Effect of Oral Melatonin Versus Intraoperative Lidocaine Infusion on Incidence of Postoperative Delirium in Elderly Patients Undergoing Total Hip Arthroplasty: Prospective Randomized Controlled Blinded Study

The aim of this study is to assess the effect of oral melatonin versus intraoperative lidocaine infusion on incidence of postoperative delirium in elderly patients undergoing total hip arthroplasty under spinal anesthesia.

Study Overview

• Status: Recruiting
• Conditions: Postoperative Delirium; Elderly Patients; Total Hip Arthroplasty; Lidocaine Infusion; Oral Melatonin
• Intervention / Treatment: Drug: Melatonin; Drug: Lidocaine; Drug: Placebo

Detailed Description

Delirium is defined according to The American Psychiatric Association's fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), as disturbance in attention and awareness developed over a short period of time , its severity tends to fluctuate during the course of a day, these disturbances cannot be better explained by other pre-existing neurocognitive disorders and do not occur in severely reduced arousal level such as coma. Delirium can be further classified into hyperactive, hypoactive and mixed.Postoperative delirium (POD) usually occurs in the recovery room and appears up to 5 days after surgery.

The prevalence of POD in elderly patients undergoing surgery varies from 20% to 45%. Patients undergoing hip fracture surgery are at higher risk of POD than patients undergoing other types of surgery. This may be related to their older age, higher incidence of comorbidities, and greater physical weakness.

Melatonin (N-acetyl-5-methoxytryptamine) is a neurohormone that is discharged by the pineal gland produced from the amino acid tryptophan. Synthetic melatonin has been effectively utilized in the treatment of sleep disorders. It was likewise utilized as a premedication and it provided excellent anxiolysis, sedation, and sympatholytic impacts with the merit of not influencing the patients' cognition in addition to its analgesic effect.

Lidocaine, an amide local anesthetic and class-1 antiarrhythmic with sedative and anti-inflammatory properties, is increasingly used as a part of a multimodal intraoperative anesthetic adjunct in a variety of surgical procedures.

• Study Type: Interventional
• Enrollment (Estimated): 135
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alshaimaa S Alasrag, Master; Phone Number: 00201018940354; Email: alshaimaa.alasrag@med.tanta.edu.eg

Study Locations

• Egypt
  • El-Gharbia
    • Tanta, El-Gharbia, Egypt, 31527
      • Recruiting
      • Tanta university
      • Sub-Investigator: Shaimaa E Shaban, MD
      • Sub-Investigator: Hoda A Ezz, MD
      • Contact: Alshaimaa S Alasrag, Master; Phone Number: 00201018940354; Email: alshaimaa.alasrag@med.tanta.edu.eg
      • Sub-Investigator: Kamal E Heikal, MD
      • Sub-Investigator: Naglaa K Khalil, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Elderly patients aged >65 years old undergoing unilateral total hip arthroplasty.
• Patients with body mass index (BMI) (18-30) kg/m2.
• American Society of Anesthesiologists (ASA) physical status I-III, scheduled to undergo unilateral total hip arthroplasty.

Exclusion Criteria:

• History of mental illness or scoring less than 8 using abbreviated mental test (AMT) before operation.
• Obvious sinus bradycardia (heart rate of <50 beats per minute) or other serious cardiovascular diseases.
• Symptomatic cerebrovascular disease (such as previous stroke).
• History of liver and kidney dysfunction.
• Allergy to lidocaine or melatonin.
• Metabolic disorders and fluid, electrolytes disturbances.
• Alcohol dependence or drug abuse.
• Redo surgery or infectious complications.
• CNS medications (antipsychotics, anticonvulsants, antiparkinsonian, antidepressants).
• History of deep vein thrombosis.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Melatonin group; Patients will receive one capsule of melatonin (5mg) orally the night before surgery at 9 pm, the night of the operation, and two nights after the surgical operation at 9 pm, also the patients will receive 10 ml bolus of saline intravenous (IV) over 10 min before induction of anesthesia, then continuous infusion of saline (20 ml/hr) until the end of surgery.	Drug: Melatonin; Patients will receive one capsule of melatonin (5mg) orally the night before surgery at 9 pm, the night of the operation, and two nights after the surgical operation at 9 pm, also the patients will receive 10 ml bolus of saline intravenous (IV) over 10 min before induction of anesthesia, then continuous infusion of saline (20 ml/hr) until the end of surgery.
Experimental: Lidocaine group; Patients will receive a bolus (10 ml) of intravenous lidocaine (1mg/kg) diluted with saline over 10 min before induction of anesthesia. Continuous infusion of 1.5 mg/kg/hr of intravenous lidocaine diluted with saline (20 ml/hr) will be administered until the end of the surgery, also will receive placebo capsule the night before surgery at 9 pm, the night of operation and two nights after the surgical operation at 9 pm.	Drug: Lidocaine; Patients will receive a bolus (10 ml) of intravenous lidocaine (1mg/kg) diluted with saline over 10 min before induction of anesthesia. Continuous infusion of 1.5 mg/kg/hr of intravenous lidocaine diluted with saline (20 ml/hr) will be administered until the end of the surgery, also will receive placebo capsule the night before surgery at 9 pm, the night of operation and two nights after the surgical operation at 9 pm.
Placebo Comparator: Control group; Patients will receive a bolus (10 ml) of saline over 10 min before induction of anesthesia, then continuous infusion of saline (20 ml/hr) and placebo capsule the night before surgery at 9 pm, the night of the operation and two nights after the surgical operation at 9 pm.	Drug: Placebo; Patients will receive a bolus (10 ml) of saline over 10 min before induction of anesthesia, then continuous infusion of saline (20 ml/hr) and placebo capsule the night before surgery at 9 pm, the night of the operation and two nights after the surgical operation at 9 pm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of postoperative delirium (POD)	Incidence of postoperative delirium in elderly patients undergoing total hip arthroplasty will be recorded	1st five days postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of delirium	Severity of delirium will be assessed using (CAM-S) score. The sum of the CAM-S scores ranges from 0 to 7 (7 = most severe).	1st five days postoperatively
Onset of delirium	The onset of delirium will be recorded.	1st five days postoperatively
Duration of delirium	The duration of delirium will be recorded.	1st five days postoperatively
Degree of pain	Postoperative pain will be assessed using the visual analogue scale (VAS) score (0 point indicates no pain and 10 indicate maximum pain). Patients will receive epidural analgesia if VAS score is ≥4.	24 hours postoperatively
Length of hospital stay	Length of hospital stay will be recorded from the admission till the discharge from the hospital.	Till the discharge from the hospital (up to 2 weeks).
Adverse effects	Any undesirable side effects that may occur intraoperatively or postoperatively will be recorded and treated (e.g., nausea, vomiting, bradycardia, hypotension, respiratory depression and local anesthetic toxicity).	24 hours Postoperatively

Collaborators and Investigators

• Sponsor: Tanta University

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: January 6, 2025
• First Submitted That Met QC Criteria: January 6, 2025
• First Posted (Actual): January 10, 2025

Study Record Updates

• Last Update Posted (Actual): April 15, 2025
• Last Update Submitted That Met QC Criteria: April 12, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Postoperative Complications; Pathologic Processes; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Emergence Delirium; Delirium; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Anti-Arrhythmia Agents; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Antioxidants; Protective Agents; Lidocaine; Melatonin
• Other Study ID Numbers: 36265MD277/9/24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data will be available upon a reasonable request from the corresponding author after the end of study for one year.
• IPD Sharing Time Frame: After the end of study for one year.
• IPD Sharing Access Criteria: The data will be available upon a reasonable request from the corresponding author
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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