Post Operative Pain
Conditions
Keywords
pregabalin, postoperative pain, abdominal hysterectomy
Brief summary
This study aims to compare the effect of pre-operative oral pregabalin on post operative morphine consumption after abdominal hysterectomy with/without salpingo-oophorectomy.
Detailed description
The participants are randomized into two groups by computer randomization. The patient undergo spinal anesthesia with 0.5% Heavy bupivacaine with morphine 0.2 mg. IV PCA morphine is initiate in the post-anesthetic care unit. We compare post operative morphine consumption in the first 24 hours, time to first analgesia, adverse event, and patient satisfaction.
Interventions
DRUGplacebo
Placebo in capsule is prescribed to the patient 60 min prior to the surgery. Ringer Lactate Solution preload 15 mL/kg prior to surgery. Spinal anesthesia is done with 0.5% Heavy bupivacaine + morphine 0.2 mg total volume 3.0 - 3.6 mL. IV PCA Morphine is applied at PACU (bolus dose only 1 mg, lockout interval 5 min, 4 hr limit 35 mg). As soon as the patient is allowed to sip, paracetamol (500 mg) 1 tab PO every 6 hours is prescribed.
DRUGPregabalin
Pregabalin (150 mg) one capsule is prescribed to the patient 60 min prior to the surgery. Ringer Lactate Solution preload 15 mL/kg prior to surgery. Spinal anesthesia is done with 0.5% Heavy bupivacaine + morphine 0.2 mg total volume 3.0 - 3.6 mL. IV PCA Morphine is applied at PACU (bolus dose only 1 mg, lockout interval 5 min, 4 hr limit 35 mg). As soon as the patient is allowed to sip, paracetamol (500 mg) 1 tab PO every 6 hours is prescribed.
Sponsors
Mahidol University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. ASA classification 1-2 undergoing abdominal hysterectomy with/without salpingo-oophorectomy under spinal anesthesia with intrathecal morphine 2. Patient can use patient-controlled analgesia (IV PCA)
Exclusion criteria
1. History of drug allergy to gabapentinoid and related drug 2. History of regular analgesic drug use, psychiatric drug usage, drug abuse, alcohol addiction or chronic pain patient 3. Renal disease (Creatinine Clearance \< 60), Liver disease, Seizure disorder and Psychiatric disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Post Operative Morphine Consumption | 6, 12, and 24 hours after operation | Cumulative morphine consumption in the first 24 hours is recorded from IV PCA |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Analgesia | 24 hours | Time to first analgesia is recorded from IV PCA. |
| Pain Scores on the Visual Analog Scale | 24 hours | Pain score is evaluated by nurses using Numerical Rating Scale (NRS) Minimum score 0 (no pain), Maximum score 10 (worst imaginable pain), lower scores mean a better outcome |
| Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | 24 hours | Measure sedation score by evaluate and observe; measure pruritus, PONV, dizziness, visual disturbance using questionnaire |
| Number of Patients Evaluating Their Satisfaction | 24 hours | Using four-point scale to evaluate patient satisfaction. Patients indicated if their satisfaction was Unsatisfied, Less Satisfied, Moderately Satisfied, or Good Satisfied. |
Countries
Thailand
Participant flow
Recruitment details
142 patients on gynecology unit during December 2014 - January 2016 were assessed for eligibility, 17 patient were not randomized due to didn't meet inclusion criteria (n=6), met exclusion criteria (n=4), declined to participate (n=7).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo in capsule is prescribed to the patient 60 min prior to the surgery.
placebo: Placebo in capsule is prescribed to the patient 60 min prior to the surgery.
Ringer Lactate Solution preload 15 mL/kg prior to surgery. Spinal anesthesia is done with 0.5% Heavy bupivacaine + morphine 0.2 mg total volume 3.0 - 3.6 mL. IV PCA Morphine is applied at PACU (bolus dose only 1 mg, lockout interval 5 min, 4 hr limit 35 mg). As soon as the patient is allowed to sip, paracetamol (500 mg) 1 tab PO every 6 hours is prescribed. | 58 |
| Pregabalin Pregabalin (150 mg) one capsule is prescribed to the patient 60 min prior to the surgery.
Pregabalin: Pregabalin (150 mg) one capsule is prescribed to the patient 60 min prior to the surgery.
Ringer Lactate Solution preload 15 mL/kg prior to surgery. Spinal anesthesia is done with 0.5% Heavy bupivacaine + morphine 0.2 mg total volume 3.0 - 3.6 mL. IV PCA Morphine is applied at PACU (bolus dose only 1 mg, lockout interval 5 min, 4 hr limit 35 mg). As soon as the patient is allowed to sip, paracetamol (500 mg) 1 tab PO every 6 hours is prescribed. | 61 |
| Total | 119 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | not abdominal hysterectomy | 2 | 0 |
| Overall Study | Not spinal anesthesia | 3 | 1 |
Baseline characteristics
| Characteristic | Pregabalin | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 45.9 years STANDARD_DEVIATION 5.3 | 46.2 years STANDARD_DEVIATION 5.7 | 46.4 years STANDARD_DEVIATION 6.1 |
| ASA physical status I | 27 Participants | 62 Participants | 35 Participants |
| ASA physical status II | 34 Participants | 57 Participants | 23 Participants |
| Sex: Female, Male Female | 61 Participants | 119 Participants | 58 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 63 | 0 / 62 |
| other Total, other adverse events | 0 / 63 | 0 / 62 |
| serious Total, serious adverse events | 0 / 63 | 0 / 62 |
Outcome results
Primary
Post Operative Morphine Consumption
Cumulative morphine consumption in the first 24 hours is recorded from IV PCA
Time frame: 6, 12, and 24 hours after operation
Population: Only 47 and 53 participants from placebo and pregabalin group, respectively, received IV-PCA morphine in the 1st 24 hours. The rest didn't require morphine consumption.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Post Operative Morphine Consumption | Morphine consumption 6 hr | 1 mg |
| Placebo | Post Operative Morphine Consumption | Morphine consumption 12 hr | 1 mg |
| Placebo | Post Operative Morphine Consumption | Morphine consumption 24 hr | 4 mg |
| Pregabalin | Post Operative Morphine Consumption | Morphine consumption 24 hr | 5 mg |
| Pregabalin | Post Operative Morphine Consumption | Morphine consumption 6 hr | 0 mg |
| Pregabalin | Post Operative Morphine Consumption | Morphine consumption 12 hr | 1 mg |
p-value: 0.6Wilcoxon (Mann-Whitney)
Secondary
Number of Patients Evaluating Their Satisfaction
Using four-point scale to evaluate patient satisfaction. Patients indicated if their satisfaction was Unsatisfied, Less Satisfied, Moderately Satisfied, or Good Satisfied.
Time frame: 24 hours
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Patients Evaluating Their Satisfaction | Unsatisfied | 0 Participants |
| Placebo | Number of Patients Evaluating Their Satisfaction | Less satisfied | 1 Participants |
| Placebo | Number of Patients Evaluating Their Satisfaction | Moderate satisfied | 19 Participants |
| Placebo | Number of Patients Evaluating Their Satisfaction | Good satisfied | 38 Participants |
| Pregabalin | Number of Patients Evaluating Their Satisfaction | Good satisfied | 31 Participants |
| Pregabalin | Number of Patients Evaluating Their Satisfaction | Unsatisfied | 0 Participants |
| Pregabalin | Number of Patients Evaluating Their Satisfaction | Moderate satisfied | 25 Participants |
| Pregabalin | Number of Patients Evaluating Their Satisfaction | Less satisfied | 5 Participants |
p-value: 0.05Chi-squared
Secondary
Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability
Measure sedation score by evaluate and observe; measure pruritus, PONV, dizziness, visual disturbance using questionnaire
Time frame: 24 hours
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Placebo | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Pruritus | No | 7 Participants |
| Placebo | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Pruritus | Mild | 35 Participants |
| Placebo | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Pruritus | Moderate | 15 Participants |
| Placebo | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Pruritus | Severe | 1 Participants |
| Placebo | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Nausea | No | 18 Participants |
| Placebo | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Nausea | Mild | 24 Participants |
| Placebo | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Nausea | Moderate | 16 Participants |
| Placebo | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Nausea | Severe | 0 Participants |
| Placebo | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Vomiting | No | 31 Participants |
| Placebo | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Vomiting | Mild | 10 Participants |
| Placebo | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Vomiting | Moderate | 12 Participants |
| Placebo | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Vomiting | Severe | 5 Participants |
| Placebo | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Dizziness | No | 18 Participants |
| Placebo | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Dizziness | Mild | 31 Participants |
| Placebo | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Dizziness | Moderate | 9 Participants |
| Placebo | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Dizziness | Severe | 0 Participants |
| Placebo | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Visual disturbance | No | 51 Participants |
| Placebo | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Visual disturbance | Mild | 7 Participants |
| Placebo | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Visual disturbance | Moderate | 0 Participants |
| Placebo | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Visual disturbance | Severe | 0 Participants |
| Pregabalin | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Visual disturbance | Mild | 16 Participants |
| Pregabalin | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Pruritus | No | 17 Participants |
| Pregabalin | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Vomiting | Moderate | 8 Participants |
| Pregabalin | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Pruritus | Mild | 31 Participants |
| Pregabalin | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Dizziness | Severe | 1 Participants |
| Pregabalin | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Pruritus | Moderate | 10 Participants |
| Pregabalin | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Vomiting | Severe | 6 Participants |
| Pregabalin | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Pruritus | Severe | 3 Participants |
| Pregabalin | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Visual disturbance | Severe | 0 Participants |
| Pregabalin | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Nausea | No | 23 Participants |
| Pregabalin | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Dizziness | No | 14 Participants |
| Pregabalin | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Nausea | Mild | 21 Participants |
| Pregabalin | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Visual disturbance | No | 45 Participants |
| Pregabalin | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Nausea | Moderate | 17 Participants |
| Pregabalin | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Dizziness | Mild | 39 Participants |
| Pregabalin | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Nausea | Severe | 0 Participants |
| Pregabalin | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Visual disturbance | Moderate | 0 Participants |
| Pregabalin | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Vomiting | No | 38 Participants |
| Pregabalin | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Dizziness | Moderate | 7 Participants |
| Pregabalin | Numbers of Participants With Adverse Events as a Measure of Safety and Tolerability | Vomiting | Mild | 9 Participants |
Comparison: For pruritusp-value: 0.16Chi-squared
Comparison: For Nauseap-value: 0.66Chi-squared
Comparison: For Vomitingp-value: 0.46Chi-squared
Comparison: For Dizzinessp-value: 0.54Chi-squared
Comparison: For visual disturbancep-value: 0.05Chi-squared
Secondary
Pain Scores on the Visual Analog Scale
Pain score is evaluated by nurses using Numerical Rating Scale (NRS) Minimum score 0 (no pain), Maximum score 10 (worst imaginable pain), lower scores mean a better outcome
Time frame: 24 hours
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Pain Scores on the Visual Analog Scale | At rest | 2 score on a scale |
| Placebo | Pain Scores on the Visual Analog Scale | At movement | 4 score on a scale |
| Pregabalin | Pain Scores on the Visual Analog Scale | At rest | 2 score on a scale |
| Pregabalin | Pain Scores on the Visual Analog Scale | At movement | 4 score on a scale |
Comparison: for NRS at restp-value: 0.33Wilcoxon (Mann-Whitney)
Comparison: for NRS at movementp-value: 0.75Wilcoxon (Mann-Whitney)
Secondary
Time to First Analgesia
Time to first analgesia is recorded from IV PCA.
Time frame: 24 hours
Population: Only 47 and 53 participants from placebo and pregabalin group, respectively, received IV-PCA morphine in the 1st 24 hours. The rest didn't require morphine consumption.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to First Analgesia | 4.6 hour |
| Pregabalin | Time to First Analgesia | 7.7 hour |
p-value: 0.1Wilcoxon (Mann-Whitney)