Abdominal Cancer, Age Problem
Conditions
Keywords
Injections, Epidural, Morphine Sulfate
Brief summary
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
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.
Interventions
DRUG1.5 mg of Morphine Sulfate
1.5 mg of Morphine Sulphate will be given epidurally.
DRUGNormal saline
Normal saline will be given epidurally.
DRUG3 mg of Morphine Sulfate
3 mg of Morphine Sulphate will be given epidurally.
DRUG4.5 mg of Morphine Sulfate
4.5 mg of Morphine Sulphate will be given epidurally.
Sponsors
Assiut University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
SINGLE (Outcomes Assessor)
Intervention model description
This randomized, double blinded, clinical trial was approved by the local ethics committee of faculty of medicine, Assuit University, Assuit, Egypt. The maximum total PCA morphine consumption was 12 ± 16 mg while in healthy controls was 70± 35 mg. We aim to enroll at least 60-80 participants considering the following assumptions: * Main statistical test is ANOVA\\t-test to detect the difference of the difference of PCA morphine consumption between the four groups. * Main outcome variable is total PCA morphine consumption after lower abdominal cancer surgery in elderly patients receiving three different doses of epidural morphine in comparison with its consumption in healthy controls not receiving epidural morphine. * Effect size = 0.75, Alpha = 0.05, Power = 0.80 * Allocation ratio N4/N3/N2/N1 = 1/1/1/1. * 22 patients should be enrolled in each group to account for dropouts.
Eligibility
Sex/Gender
ALL
Age
60 Years to 100 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Patient-controlled Analgesia (PCA) Morphine Sulphate (MS) Consumption. | 72 hours | The mean total PCA morphine consumption (mg) in the first 72 hr. postoperatively |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Visual Analog Scale | 72 hours | 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. |
| Modified Ramsay Sedation Scale | Modified Ramsay Sedation Scale at 2 hours postoperative | 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 |
| Nausea Score | 72 hours | 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; 1. if the side effect was minimal and did not require treatment; 2. if the side effect was moderate or severe and required treatment. |
| Vomiting Score | 72 hours | 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; 1. if the side effect was minimal and did not require treatment; 2. if the side effect was moderate or severe and required treatment. |
| Pruritus Score | 72 hours | 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; 1. if the side effect was minimal and did not require treatment; 2. if the side effect was moderate or severe and required treatment. |
Countries
Egypt
Participant flow
Recruitment details
The study was conducted at South Egypt Cancer institute and Assiut university hospitals according to Consolidated Standards of Reporting Trials (CONSORT) statement. Patients were recruited from the departments of surgical oncology between March 2020 and June 2021.
Pre-assignment details
A total of 102 patients were assessed for eligibility. Three of them refused to participate in the study, and three did not meet the inclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Group A Participants allocated to receive 1.5 mg epidural morphine. | 22 |
| Group B Participants allocated to receive 3 mg epidural morphine. | 22 |
| Group C Participants allocated to receive 4.5 mg epidural morphine. | 22 |
| Group D Participants allocated to receive 0 mg epidural morphine. | 22 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Protocol Violation | 2 | 2 | 2 | 2 |
Baseline characteristics
| Characteristic | Group A | Group B | Group C | Group D | Total |
|---|---|---|---|---|---|
| Age, Continuous | 66.82 Years STANDARD_DEVIATION 7.5 | 65.32 Years STANDARD_DEVIATION 5.498 | 65.27 Years STANDARD_DEVIATION 5.373 | 64.32 Years STANDARD_DEVIATION 4.145 | 65.43 Years STANDARD_DEVIATION 5.629 |
| Body Mass Index | 25 kg/m^2 STANDARD_DEVIATION 3.423 | 26.18 kg/m^2 STANDARD_DEVIATION 3.202 | 24.59 kg/m^2 STANDARD_DEVIATION 4.148 | 26.18 kg/m^2 STANDARD_DEVIATION 3.711 | 25.49 kg/m^2 STANDARD_DEVIATION 3.621 |
| Race/Ethnicity, Customized Egyptian Population | 22 Participants | 22 Participants | 22 Participants | 22 Participants | 88 Participants |
| Region of Enrollment Egypt | 22 participants | 22 participants | 22 participants | 22 participants | 88 participants |
| Sex: Female, Male Female | 14 Participants | 16 Participants | 12 Participants | 15 Participants | 57 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 10 Participants | 7 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 22 | 0 / 22 | 1 / 22 | 0 / 22 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Total Patient-controlled Analgesia (PCA) Morphine Sulphate (MS) Consumption.
The mean total PCA morphine consumption (mg) in the first 72 hr. postoperatively
Time frame: 72 hours
Population: Main statistical test is ANOVA\\t-test to detect the difference of PCA morphine consumption between the four groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A | Total Patient-controlled Analgesia (PCA) Morphine Sulphate (MS) Consumption. | 27.182 mg | Standard Deviation 5.6115 |
| Group B | Total Patient-controlled Analgesia (PCA) Morphine Sulphate (MS) Consumption. | 9.182 mg | Standard Deviation 3.5273 |
| Group C | Total Patient-controlled Analgesia (PCA) Morphine Sulphate (MS) Consumption. | 6.273 mg | Standard Deviation 3.4307 |
| Group D | Total Patient-controlled Analgesia (PCA) Morphine Sulphate (MS) Consumption. | 38.136 mg | Standard Deviation 4.8037 |
Secondary
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
Time frame: Modified Ramsay Sedation Scale at 2 hours postoperative
Population: Main statistical test is ANOVA\\t-test to detect the difference between the four groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A | Modified Ramsay Sedation Scale | 1.95 score on a scale | Standard Deviation 0.375 |
| Group B | Modified Ramsay Sedation Scale | 2.18 score on a scale | Standard Deviation 0.395 |
| Group C | Modified Ramsay Sedation Scale | 3.05 score on a scale | Standard Deviation 0.375 |
| Group D | Modified Ramsay Sedation Scale | 1.86 score on a scale | Standard Deviation 0.468 |
Secondary
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; 1. if the side effect was minimal and did not require treatment; 2. if the side effect was moderate or severe and required treatment.
Time frame: 72 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A | Nausea Score | 4.41 scores on a scale | Standard Deviation 0.796 |
| Group B | Nausea Score | 4.45 scores on a scale | Standard Deviation 0.739 |
| Group C | Nausea Score | 4.59 scores on a scale | Standard Deviation 0.734 |
| Group D | Nausea Score | 4.82 scores on a scale | Standard Deviation 0.733 |
Secondary
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; 1. if the side effect was minimal and did not require treatment; 2. if the side effect was moderate or severe and required treatment.
Time frame: 72 hours
Population: Main statistical test is ANOVA\\t-test to detect the difference of between the four groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A | Pruritus Score | 3.36 score on a scale | Standard Deviation 0.953 |
| Group B | Pruritus Score | 3.68 score on a scale | Standard Deviation 1.086 |
| Group C | Pruritus Score | 3.23 score on a scale | Standard Deviation 0.752 |
| Group D | Pruritus Score | 1.91 score on a scale | Standard Deviation 1.377 |
Secondary
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.
Time frame: 72 hours
Population: Main statistical test is ANOVA\\t-test to detect the difference of between the four groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A | Visual Analog Scale | 3.95 units on a scale | Standard Deviation 1.09 |
| Group B | Visual Analog Scale | 2.00 units on a scale | Standard Deviation 0.756 |
| Group C | Visual Analog Scale | 1.68 units on a scale | Standard Deviation 1.041 |
| Group D | Visual Analog Scale | 4.32 units on a scale | Standard Deviation 1.129 |
Secondary
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; 1. if the side effect was minimal and did not require treatment; 2. if the side effect was moderate or severe and required treatment.
Time frame: 72 hours
Population: Main statistical test is ANOVA\\t-test to detect the difference of between the four groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A | Vomiting Score | 3.18 score on a scale | Standard Deviation 0.958 |
| Group B | Vomiting Score | 3.00 score on a scale | Standard Deviation 1.902 |
| Group C | Vomiting Score | 3.86 score on a scale | Standard Deviation 2.122 |
| Group D | Vomiting Score | 1.45 score on a scale | Standard Deviation 1.224 |