Pain, Postoperative
Conditions
Brief summary
The purpose of the investigators' study is to assess the efficacy of a single dose of preoperative gabapentin within an enhanced recovery after surgery protocol in acute postoperative pain reduction for women undergoing a minimally invasive hysterectomy. Participants who consent to participate will be randomized to either a control group without gabapentin or to a study arm and receive gabapentin 600 mg prior to their planned surgery. The investigators will collect data on postoperative narcotic use, subjective pain as rated by a numeric pain scale, in addition to any adverse effects of single dose gabapentin use.
Detailed description
Multimodal postoperative analgesia after a hysterectomy has been mainly based on a combination of nonsteroidal anti-inflammatory drugs and opioids. However, adverse effects including nausea, vomiting, sedation, and pruritus may limit use of opioids. As the side effects are dose related, minimizing opioid exposure may significantly reduce these risks. Thus, there has been an interest in evaluating preemptive as well as post-operative administration of non-opioids. Additional regimens have been suggested to minimize opioid use and its associated adverse effects including injection of local anesthetics, epidural analgesia, and anticonvulsants, such as gabapentin or pregabalin. Gabapentin, a widely used anticonvulsant used for treatment of neuropathic pain, has recently been suggested to improve postoperative analgesia and reduce opioid requirements. Gabapentin is thought to modulate calcium channels on the presynaptic nociceptive neurons, which in turn modulate or inhibit the release of excitatory neurotransmitters from activated nociceptors. In addition to inhibiting pain transmission, gabapentin may exert an analgesic effect by activating descending inhibitory noradrenergic pathways. Many studies have demonstrated the safety and efficacy of gabapentin for perioperative use in a variety of procedures across disciplines including thoracotomy, laparoscopic cholecystectomy, tonsillectomy, major orthopedic surgery, cesarean sections, and abdominal hysterectomy. Several randomized trials have evaluated the effects of gabapentin administered preoperatively only as well as given pre- and postoperatively for hysterectomy. In a systematic review of 14 studies conducted between 2004 and 2013, with samples ranging from 40 to 200, investigators identified 8 trials in which gabapentin was administered only preoperatively to reduce pain associated with abdominal hysterectomy surgery. Analysis of those data clearly demonstrates that preemptive gabapentin reduced the postoperative visual analog scale (VAS) pain score by approximately 50% and postoperative use of morphine by approximately 37%. The incidence of pruritus and dry mouth in those receiving preemptive gabapentin appeared similar to those receiving placebo, however there was a higher rate of reported dizziness (not statistically significant) associated with gabapentin. In contrast, multiple postoperative doses of gabapentin in addition to the preoperative dose was found to have no significant effect on VAS scores at 24 hours, thus favoring a single preoperative dose. Although initial results have been encouraging, uptake of gabapentin in routine clinical use remains limited due to mixed results and variability between gabapentin protocols, including dosing and duration. Christiana Care Health System (CCHS) plans to implement the Enhanced Recovery After Surgery (ERAS) protocol which administers preoperative medications to reduce postoperative pain, including acetaminophen, celecoxib, dexamethasone, and gabapentin. Therefore the aim of this study is to assess the efficacy of a single dose of preoperative gabapentin protocol to reduce acute postoperative pain in women undergoing a minimally invasive hysterectomy.
Interventions
DRUGGabapentin
DRUGAcetaminophen
DRUGCelecoxib
Sponsors
Christiana Care Health Services
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* undergoing a minimally invasive hysterectomy with surgeons operating within the Christiana Care Health System at the Newark location only. * at least 18 years of age * able to swallow tablets or capsules
Exclusion criteria
* liver failure * renal failure * prior gastric bypass * gastroparesis * recent or current regular gabapentin use * hypersensitivity to gabapentin, acetominophen, or celecoxib * procedure is converted to laparotomy for any indication. (Mini-laparotomy for specimen removal alone will not be excluded.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Narcotic Use at 24 Hours Postop | 24 hours | Assessment of the amount of narcotic use postoperatively at 24 hours. will use opioid equivalence table to convert all narcotic use to oxycodone equivalents |
| Subjective Pain at 24 Hours Postoperative | 24 hours | Pain score assesses patient subjective pain via patient reported numeric analogue scale, range 0-10 with 0 being no pain and 10 being severe pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patient With Gabapentin Adverse Effects at 24 Hours Postoperatively | 24 hours | Will assess for known symptoms of gabapentin postoperatively at 24 hours. We will survey subjects regarding their experience of the following symptoms: dizziness/drowsiness, fatigue, loss of balance, blurry vision, tremulousness, swelling, nausea, vomiting, diarrhea, and allergic reaction |
| Number of Patient With Gabapentin Adverse Effects at 2 Weeks Postoperatively | 2 weeks | Will assess for known symptoms of gabapentin postoperatively at 2 weeks. We will survey subjects regarding their experience of the following symptoms: dizziness/drowsiness, fatigue, loss of balance, blurry vision, tremulousness, swelling, nausea, vomiting, diarrhea, and allergic reaction |
| Narcotic Use at 2 Weeks Postop | 2 weeks | Assessment of the amount of narcotic use postoperatively at 2 weeks. will use opioid equivalence table to convert all narcotic use to oxycodone equivalents |
| Subjective Pain at 2 Weeks Postop | 2 weeks | Assessment of the subject pain score postoperatively at 2 weeks. will use a numeric analog scale from 0-10. The pain scale ranging from 0-10 with 0 representing No Pain and 10 representing the Worst Pain Possible |
Countries
United States
Participant flow
Recruitment details
Patient were recruited from June 2016 to July 2017 via phone or in the office setting. Potential subjects were informed of the study by investigators and if they desired to participate, they either signed consents forms in the office or on the day of surgery.
Pre-assignment details
There were no events prior to assignment in study arm after participant enrollment.
Participants by arm
| Arm | Count |
|---|---|
| Gabapentin As per the enhanced recovery after surgery protocol at our health institution, subject will receive oral medications prior to surgery including acetaminophen, celecoxib, and gabapentin x 1 dose given preoperatively. The number of tablets and capsules will remain identical in both study arms. Medications given include:
Gabapentin 600 mg (two capsules of gabapetin 300 mg); Acetaminophen 975 mg (three tablets of acetaminophen 325 mg); Celecoxib 400 mg (two capsules of celecoxib 200 mg) = Total 3 tablets, 4 capsules
Gabapentin
Acetaminophen
Celecoxib | 68 |
| Control As per the enhanced recovery after surgery protocol at our health institution, subject will receive oral medications prior to surgery including acetaminophen and celecoxib x 1 dose given preoperatively. The number of tablets and capsules will remain identical in both study arms. Medications given include:
Acetaminophen 975 mg (three tablets of acetaminophen 325 mg); Celecoxib 400 mg (four capsules of celecoxib 100 mg) = Total total 3 tablets, 4 capsules
Acetaminophen
Celecoxib | 61 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 24 Hours Postoperative Assessment | excluded from analysis per protocol | 1 | 2 |
| 24 Hours Postoperative Assessment | Lost to Follow-up | 1 | 4 |
| 2 Weeks Postoperative Assessment | Lost to Follow-up | 10 | 10 |
Baseline characteristics
| Characteristic | Gabapentin | Control | Total |
|---|---|---|---|
| Age, Continuous | 49.7 years STANDARD_DEVIATION 12.56 | 52.3 years STANDARD_DEVIATION 11.6 | 51.2 years STANDARD_DEVIATION 12.17 |
| BMI < 30 kg/m^2 | 36 Participants | 28 Participants | 64 Participants |
| BMI >/= 30 kg/m^2 | 32 Participants | 33 Participants | 65 Participants |
| Estimated blood loss | 118.6 mL STANDARD_DEVIATION 106.6 | 155.9 mL STANDARD_DEVIATION 271.2 | 137.3 mL STANDARD_DEVIATION 206.9 |
| History chronic pain | 26 Participants | 24 Participants | 50 Participants |
| Hysterectomy Surgical Approach Laparoscopic | 26 Participants | 21 Participants | 47 Participants |
| Hysterectomy Surgical Approach Robotic | 25 Participants | 24 Participants | 49 Participants |
| Hysterectomy Surgical Approach Vaginal | 17 Participants | 16 Participants | 33 Participants |
| Method of specimen removal colpotomy | 56 Participants | 56 Participants | 112 Participants |
| Method of specimen removal Minilaparotomy | 10 Participants | 5 Participants | 15 Participants |
| Method of specimen removal Power morcellation | 2 Participants | 0 Participants | 2 Participants |
| Narcotic Use within week prior to surgery | 11 Participants | 18 Participants | 29 Participants |
| OR time | 186.3 minutes STANDARD_DEVIATION 84.3 | 178.9 minutes STANDARD_DEVIATION 74.6 | 183.8 minutes STANDARD_DEVIATION 80.4 |
| Preoperative pain score, in prep and hold | 1.0 units on a scale STANDARD_DEVIATION 2 | 0.6 units on a scale STANDARD_DEVIATION 1.4 | 0.7 units on a scale STANDARD_DEVIATION 1.7 |
| Preoperative pain score, within past 24 hours | 1.2 units on a scale STANDARD_DEVIATION 2.5 | 1.1 units on a scale STANDARD_DEVIATION 2.5 | 1.1 units on a scale STANDARD_DEVIATION 2.5 |
| Preoperative pain score, within past week | 1.7 units on a scale STANDARD_DEVIATION 2.9 | 2.0 units on a scale STANDARD_DEVIATION 3.2 | 1.7 units on a scale STANDARD_DEVIATION 3 |
| Prior abdominal surgery | 43 Participants | 44 Participants | 87 Participants |
| Procedure other than Hysterectomy Anterior/posterior repair | 9 Participants | 12 Participants | 21 Participants |
| Procedure other than Hysterectomy Cystoscopy | 48 Participants | 49 Participants | 97 Participants |
| Procedure other than Hysterectomy Lysis of Adhesions | 9 Participants | 5 Participants | 14 Participants |
| Procedure other than Hysterectomy Oophorectomy | 14 Participants | 21 Participants | 35 Participants |
| Procedure other than Hysterectomy Paravaginal repair | 2 Participants | 3 Participants | 5 Participants |
| Procedure other than Hysterectomy Sacral colpopexy | 7 Participants | 6 Participants | 13 Participants |
| Procedure other than Hysterectomy Sacropinous ligament fixation | 2 Participants | 0 Participants | 2 Participants |
| Procedure other than Hysterectomy Salpingectomy | 61 Participants | 56 Participants | 117 Participants |
| Procedure other than Hysterectomy Sling | 9 Participants | 14 Participants | 23 Participants |
| Procedure other than Hysterectomy Use of mesh | 11 Participants | 15 Participants | 26 Participants |
| Procedure other than Hysterectomy Uterosacral ligament fixation | 9 Participants | 13 Participants | 22 Participants |
| Race/Ethnicity, Customized African American/African | 25 Participants | 15 Participants | 40 Participants |
| Race/Ethnicity, Customized Caucasian | 43 Participants | 46 Participants | 89 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 4 Participants | 5 Participants |
| Region of Enrollment United States | 68 participants | 61 participants | 129 participants |
| Sex: Female, Male Female | 68 Participants | 61 Participants | 129 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Surgery Indication Abnormal uterine bleeding | 31 Participants | 21 Participants | 52 Participants |
| Surgery Indication Adenomyosis | 1 Participants | 2 Participants | 3 Participants |
| Surgery Indication Endometriosis | 2 Participants | 3 Participants | 5 Participants |
| Surgery Indication Hyperplasia | 0 Participants | 2 Participants | 2 Participants |
| Surgery Indication Leiomyomas | 28 Participants | 18 Participants | 46 Participants |
| Surgery Indication Pelvic pain | 15 Participants | 18 Participants | 33 Participants |
| Surgery Indication Prolapse/Incontinence | 21 Participants | 25 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 70 | 0 / 67 |
| other Total, other adverse events | 0 / 70 | 0 / 67 |
| serious Total, serious adverse events | 0 / 70 | 0 / 67 |
Outcome results
Primary
Narcotic Use at 24 Hours Postop
Assessment of the amount of narcotic use postoperatively at 24 hours. will use opioid equivalence table to convert all narcotic use to oxycodone equivalents
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gabapentin | Narcotic Use at 24 Hours Postop | 158.8 morphine milligram equivalents | Standard Deviation 109.6 |
| Control | Narcotic Use at 24 Hours Postop | 175.0 morphine milligram equivalents | Standard Deviation 162.5 |
Primary
Subjective Pain at 24 Hours Postoperative
Pain score assesses patient subjective pain via patient reported numeric analogue scale, range 0-10 with 0 being no pain and 10 being severe pain.
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gabapentin | Subjective Pain at 24 Hours Postoperative | 3.4 score on a scale | Standard Deviation 2.5 |
| Control | Subjective Pain at 24 Hours Postoperative | 3.4 score on a scale | Standard Deviation 2.5 |
Secondary
Narcotic Use at 2 Weeks Postop
Assessment of the amount of narcotic use postoperatively at 2 weeks. will use opioid equivalence table to convert all narcotic use to oxycodone equivalents
Time frame: 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gabapentin | Narcotic Use at 2 Weeks Postop | 167.2 morphine milligram equivalents | Standard Deviation 79.3 |
| Control | Narcotic Use at 2 Weeks Postop | 187.3 morphine milligram equivalents | Standard Deviation 185.5 |
Secondary
Number of Patient With Gabapentin Adverse Effects at 24 Hours Postoperatively
Will assess for known symptoms of gabapentin postoperatively at 24 hours. We will survey subjects regarding their experience of the following symptoms: dizziness/drowsiness, fatigue, loss of balance, blurry vision, tremulousness, swelling, nausea, vomiting, diarrhea, and allergic reaction
Time frame: 24 hours
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Gabapentin | Number of Patient With Gabapentin Adverse Effects at 24 Hours Postoperatively | Somnolence | 20 Participants |
| Gabapentin | Number of Patient With Gabapentin Adverse Effects at 24 Hours Postoperatively | Tremulousness | 11 Participants |
| Gabapentin | Number of Patient With Gabapentin Adverse Effects at 24 Hours Postoperatively | Blurred Vision | 7 Participants |
| Gabapentin | Number of Patient With Gabapentin Adverse Effects at 24 Hours Postoperatively | Nausea | 24 Participants |
| Gabapentin | Number of Patient With Gabapentin Adverse Effects at 24 Hours Postoperatively | Difficulty walking | 13 Participants |
| Gabapentin | Number of Patient With Gabapentin Adverse Effects at 24 Hours Postoperatively | Vomiting | 9 Participants |
| Gabapentin | Number of Patient With Gabapentin Adverse Effects at 24 Hours Postoperatively | Dizziness | 17 Participants |
| Control | Number of Patient With Gabapentin Adverse Effects at 24 Hours Postoperatively | Vomiting | 15 Participants |
| Control | Number of Patient With Gabapentin Adverse Effects at 24 Hours Postoperatively | Dizziness | 8 Participants |
| Control | Number of Patient With Gabapentin Adverse Effects at 24 Hours Postoperatively | Blurred Vision | 4 Participants |
| Control | Number of Patient With Gabapentin Adverse Effects at 24 Hours Postoperatively | Somnolence | 23 Participants |
| Control | Number of Patient With Gabapentin Adverse Effects at 24 Hours Postoperatively | Difficulty walking | 11 Participants |
| Control | Number of Patient With Gabapentin Adverse Effects at 24 Hours Postoperatively | Tremulousness | 6 Participants |
| Control | Number of Patient With Gabapentin Adverse Effects at 24 Hours Postoperatively | Nausea | 25 Participants |
Secondary
Number of Patient With Gabapentin Adverse Effects at 2 Weeks Postoperatively
Will assess for known symptoms of gabapentin postoperatively at 2 weeks. We will survey subjects regarding their experience of the following symptoms: dizziness/drowsiness, fatigue, loss of balance, blurry vision, tremulousness, swelling, nausea, vomiting, diarrhea, and allergic reaction
Time frame: 2 weeks
Population: participants included in analysis differs from participant flow due to subjects loss to follow up at the 2 weeks time frame. study powered to primary outcome at 24 hours postoperative. 10 subjects were lost to follow up at 2 weeks postoperative in both the gabapentin and control arm.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Gabapentin | Number of Patient With Gabapentin Adverse Effects at 2 Weeks Postoperatively | Somnolence | 18 Participants |
| Gabapentin | Number of Patient With Gabapentin Adverse Effects at 2 Weeks Postoperatively | Tremulousness | 4 Participants |
| Gabapentin | Number of Patient With Gabapentin Adverse Effects at 2 Weeks Postoperatively | Blurred vision | 4 Participants |
| Gabapentin | Number of Patient With Gabapentin Adverse Effects at 2 Weeks Postoperatively | Nausea | 12 Participants |
| Gabapentin | Number of Patient With Gabapentin Adverse Effects at 2 Weeks Postoperatively | Difficulty walking | 5 Participants |
| Gabapentin | Number of Patient With Gabapentin Adverse Effects at 2 Weeks Postoperatively | Vomiting | 0 Participants |
| Gabapentin | Number of Patient With Gabapentin Adverse Effects at 2 Weeks Postoperatively | Dizziness | 12 Participants |
| Control | Number of Patient With Gabapentin Adverse Effects at 2 Weeks Postoperatively | Vomiting | 1 Participants |
| Control | Number of Patient With Gabapentin Adverse Effects at 2 Weeks Postoperatively | Dizziness | 8 Participants |
| Control | Number of Patient With Gabapentin Adverse Effects at 2 Weeks Postoperatively | Blurred vision | 3 Participants |
| Control | Number of Patient With Gabapentin Adverse Effects at 2 Weeks Postoperatively | Somnolence | 21 Participants |
| Control | Number of Patient With Gabapentin Adverse Effects at 2 Weeks Postoperatively | Difficulty walking | 5 Participants |
| Control | Number of Patient With Gabapentin Adverse Effects at 2 Weeks Postoperatively | Tremulousness | 2 Participants |
| Control | Number of Patient With Gabapentin Adverse Effects at 2 Weeks Postoperatively | Nausea | 7 Participants |
Secondary
Subjective Pain at 2 Weeks Postop
Assessment of the subject pain score postoperatively at 2 weeks. will use a numeric analog scale from 0-10. The pain scale ranging from 0-10 with 0 representing No Pain and 10 representing the Worst Pain Possible
Time frame: 2 weeks
Population: participants included in analysis differs from participant flow due to subjects loss to follow up at the 2 weeks time frame. study powered to primary outcome at 24 hours postoperative. 10 subjects were lost to follow up at 2 weeks postoperative in both the gabapentin and control arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gabapentin | Subjective Pain at 2 Weeks Postop | 1.3 score on a scale | Standard Deviation 2 |
| Control | Subjective Pain at 2 Weeks Postop | 1.4 score on a scale | Standard Deviation 1.8 |