Clinical trial NCT06872944: Effect of Melatonin on Postoperative Pain After Simple Nephrectomy
Official title: Effect of Melatonin on Postoperative Pain After Simple Nephrectomy: A Randomized Double-Blinded Controlled Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Pain Score (VAS) at 24 h Postoperatively
Lead sponsor: Cairo University
Sponsor class: OTHER
First posted: 2025-03-12
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The aim of the study is to evaluate the role of melatonin in the management of postoperative pain in patients undergoing simple nephrectomy regarding:

* Pain score (VAS).
* Total Morphine consumption is 1st 24 hr.
* Time to the 1st rescue analgesia.
* Intra-operative and post-operative hemodynamics.
* Anxiety.
* Patient satisfaction.
* Adverse events.

Detailed description: This study will be conducted in Cairo University Hospitals at Uorolgy OR. This study will include 40 patients divided into two groups, aged 18 to 65 years, both sexes, belonging to the American Society of Anesthesiologists (ASA) physical status I, II undergoing simple nephrectomy.

1. Inclusion criteria

   * Age from 18 to 65 years.
   * Both sexes.
   * (ASA) physical status I, II.
   * Patients undergoing simple nephrectomy.
2. Exclusion criteria

   * Patient refusal.
   * Patients with a history of allergic reactions to melatonin.
   * Patients receiving drugs with known analgesic and sedative properties.
   * Body Mass Index (BMI) over 30 kg/m2.
   * Drug or alcohol abuse.
   * History of cardiovascular disease.
   * Renal Failure.
   * Mental impairment.
   * Renal impairment.

Medical and surgical history of the patients will be taken, clinical examination of the patients will be performed and routine laboratory investigations as CBC, coagulation studies, renal function and liver function will be done.

Preoperative visit will be conducted the day before surgery. All patients will be evaluated by the same anesthesia resident, who provided information on the preoperative course and instructed them on the procedure.

Each patient will be instructed about postoperative pain assessment with the visual analog scale (VAS) which \[0 represents "no pain" while 10 represents "the worst pain imaginable"\] and level of anxiety.

Intraoperative management All patients will be connected to standard monitoring which include electrocardiography (ECG), non-invasive arterial blood pressure (NIBP), pulse oximetry, temperature probe, and capnography (will be connected after induction of general anesthesia).

Induction of general anesthesia will be done after inserting 20G venous cannula by IV propofol 2-2.5 mg / kg and IV fentanyl 2ug / kg. After IV Atracurium 0.5mg / kg, endotracheal intubation will be done.

Maintenance of anesthesia will be isoflurane (1-1.5%) with 50-100% oxygen. Incremental doses of IV Atracurium 0.1mg/Kg will be given every 20 min. Patients will be mechanically ventilated and end-tidal CO2 will be maintained between 35-45 mmHg.

Additional fentanyl bolus dosages of 1 µg/kg IV will be administered if heart rate or mean arterial blood pressure elevated more than 20% of the baseline (after exclusion of other causes than pain).

At the end of the surgery, inhalational anesthetics will be stopped waiting for motor power and conscious level to be regained. Then the reversal will be given IV Neostigmine 0.03-0.07 mg/kg + Atropine 0.02 mg/kg.

A standardized analgesic regimen will be prescribed in the post-operative period. All patients will receive paracetamol 1 gm every 6 h as routine analgesia.

Rescue analgesia of morphine will be given as 3 mg bolus if the VAS \> 3 to be repeated after 30 min if pain persists until the VAS \< 4. VAS will be assessed at 0, 2, 4, 6, 8, 12, 18, and 24 h postoperatively. The adverse effects will be assessed: hypotension (decrease in basal mean arterial blood pressure by 20%) will be treated with I.V. fluid, bradycardia (defined by decrease in basal heart rate by 20%) will be treated by I.V. atropine 0.02 mg/kg, respiratory depression (the SpO2 \< 95% and need O2 supplementation), and 4 mg of ondansetron every 6 hours will be administered for postoperative nausea/vomiting (PONV) as required.

Eligibility criteria: Inclusion Criteria:

* Age from 18 to 65 years.
* Both sexes.
* (ASA) physical status I, II.
* Patients undergoing simple nephrectomy.

Exclusion Criteria:

* Patient refusal.

  * Patients with a history of allergic reactions to melatonin.
  * Patients receiving drugs with known analgesic and sedative properties.
  * Body Mass Index (BMI) over 30 kg/m2.
  * Drug or alcohol abuse.
  * History of cardiovascular disease.
  * Renal Failure.
  * Mental impairment.
  * Renal impairment.

Primary outcomes:
measure: Pain score (VAS) at 24 h postoperatively
timeFrame: 24 hours postoperative
Secondary outcomes:
measure: Time to the 1st rescue analgesia
timeFrame: (time from end of surgery to first dose of morphine administrated 24 hours postoperative.
measure: Total Morphine consumption is 1st 24 hr (mg).
timeFrame: 24 hours postoperative
measure: Degree of patient satisfaction
timeFrame: 24 hours postoperative
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Faculty of Medicine-Cairo Univeristy
city: Cairo
country: Egypt
facility: Faculty of Medicine- Cairo University
Study officials:
References:
citation: Bonmati-Carrion MA, Rol MA. Melatonin as a Mediator of the Gut Microbiota-Host Interaction: Implications for Health and Disease. Antioxidants (Basel). 2023 Dec 23;13(1):34. doi: 10.3390/antiox13010034.
citation: Kiabi FH, Emadi SA, Jamkhaneh AE, Aezzi G, Ahmadi NS. Effects of preoperative melatonin on postoperative pain following cesarean section: A randomized clinical trial. Ann Med Surg (Lond). 2021 May 12;66:102345. doi: 10.1016/j.amsu.2021.102345. eCollection 2021 Jun.
citation: Andersen LP. The analgesic effects of exogenous melatonin in humans. Dan Med J. 2016 Oct;63(10):B5289.
citation: Delgado DA, Lambert BS, Boutris N, McCulloch PC, Robbins AB, Moreno MR, Harris JD. Validation of Digital Visual Analog Scale Pain Scoring With a Traditional Paper-based Visual Analog Scale in Adults. J Am Acad Orthop Surg Glob Res Rev. 2018 Mar 23;2(3):e088. doi: 10.5435/JAAOSGlobal-D-17-00088. eCollection 2018 Mar.
citation: Chen Q, Beal EW, Okunrintemi V, Cerier E, Paredes A, Sun S, Olsen G, Pawlik TM. The Association Between Patient Satisfaction and Patient-Reported Health Outcomes. J Patient Exp. 2019 Sep;6(3):201-209. doi: 10.1177/2374373518795414. Epub 2018 Aug 27.