Single Dose Preoperative Gabapentin Use in Minimally Invasive Hysterectomy for Acute Pain Management

Study Overview
=================
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.

Official Title
-----------------
Single Dose Preoperative Gabapentin Use in Minimally Invasive Hysterectomy for Acute Pain Management

Conditions
-----------------
Pain, Postoperative

Intervention / Treatment
-----------------
* Drug: Gabapentin
* Drug: Acetaminophen
* Drug: Celecoxib


Participation Criteria
=================
Eligibility Criteria
-----------------
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.)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Gabapentin<br>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 | Drug: Gabapentin<br> <br> Drug: Acetaminophen<br> <br> Drug: Celecoxib<br> <br> |
| Placebo Comparator: Control<br>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 | Drug: Acetaminophen<br> <br> Drug: Celecoxib<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 24 hours | 
| 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. | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 24 hours | 
| 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 | 2 weeks | 
| 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 | 2 weeks | 
| 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 | 2 weeks |