Preoperative Oral Gabapentin Provides No Difference in Pain Scores Post Operatively

Objective: The objective of this pain study is to assess the efficacy and safety of one time dose of preoperative gabapentin on the postoperative outcomes after total knee replacement.

Research Design/ Methods: A randomized, placebo-controlled, double-blind study evaluated efficacy of 1200mg gabapentin administered 1 hour before knee surgery. The surgical procedure was performed by the same surgeon and all patients post-operatively received opioid by patient-controlled analgesia. Patients reported pain intensities were recorded every shift by numeric (0-10) pain scores. Distance ambulated with physical therapy, joint flexion, and opioid related side effects were recorded.

Results: Opioid consumption at 18 hours and 36 hours was trending toward less in the gabapentin group, but did not reach a clinically significant difference (p > 0.05). Ambulation distance, pain scores, and knee flexion were no different in either study group. There were no differences between groups in adverse effects.

Conclusion: Preoperative oral gabapentin indicated a trend toward opioid sparing effects without an impact on postoperative ambulation.

This randomized, controlled trial examined the effects of preoperative oral gabapentin 1200 mg on postoperative pain and opioid consumption. This small study indicates a trend that preoperative oral gabapentin is opioid sparing in the immediate hours after total knee replacement surgery.

Hutchison Jr RW (2014) Preoperative Oral Gabapentin Provides No Difference in Pain Scores Post Operatively J Clin Pharm 1(1): 1002.

During the immediate 48-72 hours after surgery, postoperative pain may be severe and adequate pain management requires multi-modal therapy [1,2]. In recent meta-analysis, 11% of post operative patients experience severe pain [1]. Opioid sparing effects, that is, reducing the amount of opioid needed by using an additional mechanisms of action to treat pain, may reduce complication rates the recovery period; and currently. Opioids are number three in the top ten medications involved in fatal overdoses [3]. Reducing the amount of opioid needed in high risk patient groups such as obstructive sleep apnea may help reduce complications during the hospital stay [4]. Because of themultiplicity of mechanisms involved in postoperative pain, a multimodal analgesia regimen, with a combination of opioid andnon-opioid analgesic drugs is often used to enhance analgesic efficacy and reduce opioid requirements and side effects. With recent adverse event reports among the nonsteroidal antiinflammatory agents (NSAIDs), the use of this class of analgesics is less preferred and studies evaluating the efficacy of other nonopioid analgesic modalities are needed [5,6].

Gabapentin, a structural analog of γ-aminobutyric acid, is used as an anticonvulsant drug. In addition, it has been effective in neuropathic pain, diabetic neuropathy, postherpetic neuralgia, and reflex sympathetic dystrophy [7-9]. Pretreatment with gabapentin can block the development of hyperalgesia [10]. Studies have demonstrated that mechanical hyperalgesia surrounding the wound in postoperative patients and experimentally, heat-induced, secondary hyperalgesia share a common mechanism and that central neuronal sensitization contributes to postoperative pain [8].Gabapentin has a selective effect on the nociceptive process involving central sensitization [11].

Gabapentin and morphine have synergistic analgesic effects in animals and in humans [12]. In a recent meta-analysis, a single dose of oral gabapentin reduced postoperative morphine consumption and movement-related pain after radical mastectomy [13].

The aim of the present study was to determine the effect of gabapentin on postoperative pain and on PCA tramadol consumptionin patients after abdominal hysterectomy.

After obtaining the approval of the Institutional Review Board and written informed consentfrom the patients, 24 patients, ASA physical status I–II, undergoing elective total knee replacement were studied. Patients were eligible for participation if theywere at least 18 yr old, reported no allergy to gabapentin, not pregnant or breast feeding, and not using sustained release opioid for a chronic pain condition other than for knee pain.

In this double blinded study, twenty four patients were randomized into a control group or gabapentin group resulting in 12 patients in each group. The control group received a placebo which appeared identical to the 1200mg gabapentin dosage form. Patients received the placebo or gabapentin 1 hour prior to surgery.

Anesthesia was induced by the same anesthesiologist in each patient with propofol and maintained with desflurane, propofol and fentanyl. Local anesthetic in all cases consisted of local femoral nerve block with 1.5% mepivacaine 20ml & 0.5% ropivacaine 20ml. The total knee replacement procedure was preformed by the same surgeon in all patients.

Post-operatively the patients received opioid by patient controlled analgesia. The amount of opioid, acetaminophen, and NSAIDs were recorded in each patient. Patients reported pain intensities were recorded every shift by numeric (0-10) pain scores. The scores were assessed while at rest and at 8 hour intervals. Distance ambulated with physical therapy, joint flexion, and opioid related side effects were also recorded. The occurrence of any side effects, such as nausea and vomiting, constipation, respiratory depression, dizziness, somnolence, peripheral edema,diarrhea, headache, and pruritus was recorded.

Table 1: Patient Characteristics and Demographics (No clinical significant differences).

* The percentage of patients in each study group receiving this analgesic.

Table 2: Average Numeric Pain Scores 0 – 10.

Twenty four consecutive patients who fulfilled the inclusion criterion were included in the study. All the patients allocated were able to complete the study. The groups were comparable with respect to gender distribution, body mass index, age time in recovery room, and the use of other non-opioid analgesics (Table 1). The numeric scores (0 being no pain and 10 extremely severe pain) were slightly less in gabapentin group on the day of surgery and on post operative day 1; however, with the small number of patients this did not equate to a clinical significant difference. (Table 2). Sedation scores were similar at allthe measured times in the gabapentin and placebo groups.

1. Macintyre PE, Huxtable CA, Flint SL, Dobbin MD. Costs and consequences: a review of discharge opioid prescribing for ongoing management of acute pain. Anaesth Intensive Care. 2014; 42: 558- 574.

2. Argoff CE. Recent management advances in acute postoperative pain. Pain Pract. 2014; 14: 477-487.

3. Mowry JB, Spyker DA. US National Poison Data System data: 2012- 2013. Clin Toxicol. 52.

4. Chung F, Liao P, Elsaid H, Shapiro CM, Kang W. Factors associated with postoperative exacerbation of sleep-disordered breathing. Anesthesiology. 2014; 120: 299-311.

5. Singh G, Wu O, Langhorne P, Madhok R. Risk of acute myocardial infarction with nonselective non-steroidal anti-inflammatory drugs: a meta-analysis. Arthritis Res Ther. 2006; 8: R153.

6. McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA. 2006; 296: 1633-1644.

7. Wong K, Phelan R, Kalso E, Galvin I, Goldstein D, Raja S, et al. Antidepressant drugs for prevention of acute and chronic postsurgical pain: early evidence and recommended future directions. Anesthesiology. 2014; 121: 591-608.

8. Moore A, Wiffen P, Kalso E. Antiepileptic drugs for neuropathic pain and fibromyalgia. JAMA. 2014; 312: 182-183.

9. Rowbotham M, Harden N, Stacey B, Bernstein P, Magnus-Miller L. Gabapentin for the treatment of postherpetic neuralgia: a randomized controlled trial. JAMA. 1998; 280: 1837-1842.

10. Mao J, Chen LL. Gabapentin in pain management. Anesth Analg. 2000; 91: 680-687.

11. Dirks J, Møiniche S, Hilsted KL, Dahl JB. Mechanisms of postoperative pain: clinical indications for a contribution of central neuronal sensitization. Anesthesiology. 2002; 97: 1591-1596.

12. Bao YH, Zhou QH, Chen R, Xu H, Zeng LL, Zhang X, et al. Gabapentin enhances the morphine anti-nociceptive effect in neuropathic pain via the interleukin-10-heme oxygenase-1 signalling pathway in rats. J Mol Neurosci. 2014; 54: 137-146.

13. Alayed N, Alghanaim N, Tan X, Tulandi T. Preemptive use of gabapentin in abdominal hysterectomy: a systematic review and meta-analysis. Obstet Gynecol. 2014; 123: 1221-1229.