Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT01546857 |
| Other study ID # |
2011001012 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
March 2012 |
| Est. completion date |
December 2016 |
Study information
| Verified date |
January 2021 |
| Source |
Rutgers, The State University of New Jersey |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This study is being done to determine if a drug called gabapentin helps in the postoperative
management of patients undergoing hip and knee operations. The investigators wish to
determine the effect of gabapentin on pain and sleep following surgery. If we can lessen a
patient's pain and improve sleep, the patient will be better able to participate in their
physical therapy. Gabapentin has already been shown to lessen postoperative pain when given
before surgery. In healthy patients, it has also been shown to improve certain aspects of
sleep. We hope to identify the effect of the drug, when given after surgery, on patients'
pain and sleep.
Description:
Recent studies have also supported the use of gabapentin as an adjuvant medication in
postoperative pain management. Gabapentin decreased the pain associated with movement in
post-mastectomy patients. Gilron et al showed a combination of gabapentin and rofecoxib
superior to either medication alone in relieving pain after hysterectomy. Later, Gilron et al
showed that adding meloxicam to gabapentin in patients undergoing outpatient laparoscopic
surgery provided little additional benefit. Clarke et al demonstrated the decrease in the use
of opioids in patients who received preoperative and postoperative gabapentin after total
knee arthroplasty. They also noted that optimum timing and dosage of the gabapentin needed to
be further elucidated. However, in the same year, Clarke et al also reported that gabapentin
provided no benefit after total hip arthroplasty when a robust multimodal analgesic regimen
was combined with spinal anesthesia. The side effects of gabapentin include sleepiness, which
may be of benefit in the postoperative period. In a meta-analysis, Peng showed a 35 %
decrease in total opioid consumption in the first 24 hours postoperatively. However, they did
note an increase in sleepiness and dizziness. While a recent investigation did not find a
connection between sleep disturbances and postoperative pain, a questionnaire study found
that the most common reason for nighttime awakenings was pain, and that analgesia was the
most helpful intervention. Gabapentin, a structural analogue to y-aminobutyric acid, has been
shown in healthy subjects to increase SWS; maintain a stable REM; and reduce arousals,
awakenings, and stage shifts-all of which are features of sleep fragmentation. Gabapentin is
currently used to treat epilepsy, diabetic neuropathy, postherpetic neuralgia, as well as
restless legs syndrome, and its effect on sleep patterns may attribute to its therapeutic
success with these disorders Sleep deviates from the normal sleeping pattern in the
postoperative patient. Total sleep time, proportion of REM sleep, and proportion of slow wave
sleep (SWS) are all reduced. Sleep postoperatively tends to be highly fragmented with
multiple spontaneous awakenings and movement arousals. Most of these changes occur during
postoperative days 1 and 2; however, patients also incur a REM sleep rebound in days 3 and 4
that can extend up to a week. Studies have demonstrated that these postoperative sleep
disturbances, notably the prolonged REM sleep rebound, may contribute to the development of
altered mental function, postoperative episodic hypoxemia, and hemodynamic instability. A
recent study even found that postoperative sleep disruptions independently predicted
functional limitations three months following surgery in patients who underwent total knee
replacement. The pathogenesis of these sleep changes appears to be strongly correlated to the
magnitude of the surgery as opposed to the type of anesthesia used. Many specific mediators
of surgical stress response have been indicated, including catecholamines, cortisol, and
IL-1; however, as REM sleep is controlled by many regions of the brain, disturbances may be
due to a global excitatory CNS effect.
Our study will recruit 90 patients between the ages of 18 and 70 who are undergoing total hip
arthroplasty, hip fracture repair, or total knee arthroplasty and have been assigned an ASA
rating of I-III, who are not pregnant. After Institutional Review Board approval, a written
informed consent will be obtained from the patient. The study protocol, use of the Patient
Controlled Analgesia (PCA) pump, sleep scale, sedation scale, and visual analogue scale for
pain will all be explained. Demographic information will be obtained including age, gender,
past medical history, past surgical history, hospitalizations, current medications,
allergies, and history of drug and alcohol abuse. In addition, a preoperative sleep history
will be obtained using the Pittsburgh Sleep Quality Index (PSQI) [14, 15]. The 50 patients
will be randomized into two groups: (1) placebo, (2) gabapentin. An Excel generated
randomization schedule will be employed. The dosage of gabapentin administered will be 400mg.
Prior to surgery, all patients will be administered midazolam 1-3mg IV to achieve anxiolysis.
They will also receive a lumbar plexus block or a femoral nerve block, depending on the
surgery to be done, as this has become the standard of care for orthopedic patients at
University Hospital. All patients will receive celecoxib 200 mg po bid for three
postoperative days. In the operating room, standard general anesthesia technique will be
utilized. Upon extubation, the patient will be transferred to the postanesthesia care unit
(PACU), where baseline pain and sedation scores will be obtained using the Visual Acuity
Scale (VAS), the Richmond Agitation Sedation Scale (RASS), and Ramsay Sedation Scale (RSS),
respectively. All pain scores will be assessed with subjects in the resting position. A
continuous infusion of bupivacaine 0.125mg/L will be started at a rate of 10mL/hr and
continued to postoperative day 2. An I.V. PCA hydromorphone pump will be initiated and set to
deliver a 0.2mg bolus per demand with a 5 minute lockout and no background infusion. All
patients will be instructed to maintain their VAS pain score at less than 4 out of 10. If the
VAS pain score is 5 or greater at rest on two consecutive pain assessments, the dose of
intravenous PCA hydromorphone will be increased to deliver a 0.3mg bolus per demand.
At approximately 9pm on the day of the procedure the first dose of placebo/gabapentin will be
given. The gabapentin or placebo treatment will be given once more at 9 pm on postoperative
day 1. The surgical team will be asked not to order any additional medication for sleep. The
following mornings, on POD1 and POD2, a questionnaire addressing the quality of sleep, hours
of sleep, number of awakenings throughout the night, and contributing reasons for these
awakenings (pain, noise, urination, temperature discomfort, positional discomfort, for
nursing care, or other reasons) will be given. Patients will also be assessed for pain,
sedation, as well as the incidence of any side effects, including nausea, vomiting,
dizziness, and pruritus. In addition, all patients will begin an as-tolerated weight-bearing
rehabilitation program for range of motion, strengthening, balance and ambulation beginning
the first day after surgery. Success in completion of the physical therapy goals of being out
of bed in a chair by postop day 1 and ambulating by postop day 2 will be determined for each
group.
The purpose of this study is to determine if a single dose of gabapentin decrease patients'
postoperative pain. The primary endpoint will be opioid consumption; additional assessments
will include: subjective sleep scales, pain scores, and patient's ability to reach
postoperative rehabilitation goals
