Dosage of Epidural Morphine in Elderly Patients

Epidural Morphine for Geriatrics Undergoing Lower Abdominal Cancer Surgery: a Dose Response Study

This a clinical trial that evaluates the efficacy and safety of three different doses of morphine, namely 1.5 mg, 3 mg and 4.5 mg, via the epidural route regarding reducing pain in elderly patients after a cancer surgery in the lower abdomen

Study Overview

• Status: Completed
• Conditions: Abdominal Cancer; Age Problem
• Intervention / Treatment: Drug: Normal saline; Drug: 1.5 mg of Morphine Sulfate; Drug: 3 mg of Morphine Sulfate; Drug: 4.5 mg of Morphine Sulfate

Detailed Description

Acute postoperative pain is a common complaint for several days after surgery. However, acute postoperative pain remains even more under controlled in elderly patients, especially those with cognitive impairment and malignancy. Geriatric population is reported to be at higher risk for unwanted side effects from analgesic treatments compared to younger patients due to different major risk factors such as: decline in organ function, polypharmacy, pharmacokinetics, drug sensitivity, and frailty. Despite of the higher risk of opioids, especially morphine, causing toxicity and adverse effect; they are still the cornerstone treatment of severe acute postoperative pain. Morphine in those patients is very likely to cause toxicity because of accumulation of its active metabolites compared to other opioids with fewer or no active metabolites. Epidural morphine is an effective route for an effective drug. Furthermore, unwanted side effects with neuraxial opioids are minor and managed easily. Regarding clinical outcomes, clinical studies showed a lot of improvements associated with postoperative opioid analgesia. Now, there is a clinical necessity to achieve the best management of acute postoperative pain in elderly patients with the least possibility of adverse side effects. We aim in this randomized, assessor blinded, clinical trial at Assuit University to determine the optimum dose of epidural morphine for the highest control of acute postoperative pain in geriatrics who are planned to have lower abdominal cancer surgery.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Assuit, Egypt, 71515
    • Assuit university

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Men and women aged ≥ 60 years, who are planned to undergo lower abdominal cancer surgery.

2- ASA I and II classifications. 2. Surgeries via infra-umbilical abdominal incision is considered eligible.

Exclusion Criteria:

1. Patient refusal.
2. Patients who are morbidly obese (body mass index ≥ 40 kg/m2).
3. Those with contraindications to neuraxial analgesia. 4- psychiatric illness that would interfere with the perception and the assessment of pain.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Group D; A total volume of 10 mL injection 5 mL of bupivacaine hydrochloride 0.125% diluted in 5 mL preservative-free normal saline by the hospital pharmacist.	Drug: Normal saline; Normal saline will be given epidurally.; Other Names: D
Active Comparator: Group A; A total volume of 10 mL injection: 5 mL of bupivacaine hydrochloride 0.125% with 1.5 mg of preservative-free morphine diluted in 5 mL preservative-free normal saline by the hospital pharmacist.	Drug: 1.5 mg of Morphine Sulfate; 1.5 mg of Morphine Sulphate will be given epidurally.; Other Names: A
Active Comparator: Group B; A total volume of 10 mL injection: 5 mL of bupivacaine hydrochloride 0.125% with 3 mg of preservative-free morphine diluted in 5 mL preservative-free normal saline by the hospital pharmacist.	Drug: 3 mg of Morphine Sulfate; 3 mg of Morphine Sulphate will be given epidurally.; Other Names: B
Active Comparator: Group C; A total volume of 10 mL injection: 5 mL of bupivacaine hydrochloride 0.125% with 4 mg of preservative-free morphine diluted in 5 mL preservative-free normal saline by the hospital pharmacist.	Drug: 4.5 mg of Morphine Sulfate; 4.5 mg of Morphine Sulphate will be given epidurally.; Other Names: C

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Patient-controlled Analgesia (PCA) Morphine Sulphate (MS) Consumption.	The mean total PCA morphine consumption (mg) in the first 72 hr. postoperatively	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Analog Scale	Visual Analog Scale is a visual chart scored from 0 (no pain) to 10 ( the worst pain ever) used by the patient to report the severity of their pain to assess the pain intensity, and all patients were instructed how to evaluate their pain and how to use the patient-controlled analgesia.	72 hours
Modified Ramsay Sedation Scale	It is an six-point scale informed by degree of responsiveness to verbal and tactile stimulus where awake levels were as follows: I = anxious, agitated, or restless; II = cooperative, oriented, and tranquil; III = response to command, and asleep levels were dependent on the patient's response to a light glabellar tap or loud auditory stimulus; IV = brisk response; V = a sluggish response; and VI = no response	Modified Ramsay Sedation Scale at 2 hours postoperative
Nausea Score	It is a subjective scale to assess the nauseating side effects of morphine at eight time points (0, 2, 8, 16, 24, 36, 48 and 72 h). The 72-hour score for this side effect was the sum of these eight scores. Nausea scores were recorded on a scale with a minimum of 0 to a maximum of 2; where: 0 was recorded if the side effect was absent; if the side effect was minimal and did not require treatment;; if the side effect was moderate or severe and required treatment.	72 hours
Vomiting Score	It is a subjective scale to assess the vomiting as a side effect of epidural morphine at eight time points (0, 2, 8, 16, 24, 36, 48 and 72 h). The 72-hour score for this side effect was the sum of these eight scores. Vomiting scores were recorded on a scale with a minimum of 0 to a maximum of 2; where: 0 was recorded if the side effect was absent; if the side effect was minimal and did not require treatment;; if the side effect was moderate or severe and required treatment.	72 hours
Pruritus Score	It is a subjective scale to assess the pruritus as a side effect of morphine at eight time points (0, 2, 8, 16, 24, 36, 48 and 72 h). The 72-hour score for this side effect was the sum of these eight scores. Pruritus scores were recorded on a scale with a minimum of 0 to a maximum of 2; where: 0 was recorded if the side effect was absent; if the side effect was minimal and did not require treatment;; if the side effect was moderate or severe and required treatment.	72 hours

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Study Director: Diab Hetta, MD, Assiut University

Publications and helpful links

General Publications

• McKeown JL. Pain Management Issues for the Geriatric Surgical Patient. Anesthesiol Clin. 2015 Sep;33(3):563-76. doi: 10.1016/j.anclin.2015.05.010. Epub 2015 Jul 3.
• Palmer CM, Nogami WM, Van Maren G, Alves DM. Postcesarean epidural morphine: a dose-response study. Anesth Analg. 2000 Apr;90(4):887-91. doi: 10.1097/00000539-200004000-00021.

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2020
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: March 19, 2020
• First Submitted That Met QC Criteria: March 19, 2020
• First Posted (Actual): March 20, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 27, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Injections, Epidural; Morphine Sulfate
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Abdominal Neoplasms; Physiological Effects of Drugs; Peripheral Nervous System Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics; Analgesics, Opioid; Narcotics; Morphine
• Other Study ID Numbers: EPMDose

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The datasets generated during and/or analyzed during the current study will be available from the corresponding author on reasonable request. The data will not be publicly available due to containing information that could compromise research participant privacy/consent.
• IPD Sharing Time Frame: The data will not be publicly available due to containing information that could compromise research participant privacy/consent.
• IPD Sharing Access Criteria: The data will not be publicly available due to containing information that could compromise research participant privacy/consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No