|Year : 2014 | Volume
| Issue : 2 | Page : 99-104
Pre-emptive use of Gabapentin for post-operative pain relief in upper abdominal surgeries
Chetna A. Jadeja, Rashida Jadaliwala, Manoj Kathiria
Department of Anaesthesiology, Pandit Deendayal Upadhyay Medical College Medical College, Rajkot, Gujarat, India
|Date of Web Publication||20-May-2014|
Chetna A. Jadeja
31, University Karmachari Society, Behind FSL, University Road, Rajkot - 360 005, Gujarat
Source of Support: None, Conflict of Interest: None
Background: Pain of upper abdominal surgeries not only distresses the patient but also results in inadequate respiratory efforts and cough reflex. So pain relief in these surgeries bears more significance than mere patient comfort. Gabapentine has been found effective for post-operative pain relief in many surgeries including spine surgeries, radical mastectomies etc. We carried out this study to find out the effectiveness of gabapentine for post-operative pain relief in upper abdominal surgeries. Materials and Methods: The present study was randomized, double-blind and prospective, designed to evaluate synergistic effect of gabapentine and total requirement of tramadol in various upper abdominal surgeries. The study was carried out in 50 patients of American Society of Anesthesiologists (ASA) grade I and II of either sex, aged between 20 to 60 years, divided into two groups of 25 patients each. Group P (placebo group) received oral placebo capsule (3 placebo capsule) and Group G (study group) received oral gabapentine capsule (1200 mg) (3 capsules of 400 mg each) pre-operatively 2 hrs before surgery. Patients were observed 24 hrs postoperatively for pain via visual analog scale (VAS), tramadol requirement (consumption) and side effects. Results: It was observed that patients in gabapentine group had statistically significant lower pain score at all time interval in comparison to placebo group. It was demonstrated that pre-emptive oral gabapentine significantly reduced tramadol consumption until 24 hrs post-operatively. Mild sedation was observed in gabapentine group but was comparable with Group P. Conclusion: Gabapentine significantly reduces post-operative pain and post-operative tramadol consumption in upper abdominal surgeries. Mild sedation was observed with gabapentine group but was comparable with placebo.
Keywords: Gabapentine, post-operative pain, pre-emptive analgesia, upper abdominal surgeries
|How to cite this article:|
Jadeja CA, Jadaliwala R, Kathiria M. Pre-emptive use of Gabapentin for post-operative pain relief in upper abdominal surgeries. Indian J Pain 2014;28:99-104
|How to cite this URL:|
Jadeja CA, Jadaliwala R, Kathiria M. Pre-emptive use of Gabapentin for post-operative pain relief in upper abdominal surgeries. Indian J Pain [serial online] 2014 [cited 2019 Nov 19];28:99-104. Available from: http://www.indianjpain.org/text.asp?2014/28/2/99/132848
| Introduction|| |
The upper abdominal incisions caused substantial respiratory disturbance including hypoxia, hyper-ventilation and pulmonary shut down due to pain. So adequate analgesia in upper abdominal surgeries carries more significance than mere patient comfort.  The concept of pre-emptive analgesia was introduced to protect the central nervous system from deleterious effect of noxious stimuli and patient from resulting allodynia and increased pain. 
Gabapentine, was introduced in 1994 as an anti-epileptic drug, particularly for partial seizure.  It alleviates pain and/or prevent acute nociceptive and inflammatory pain both in animals and volunteers especially when given before trauma. , Studies have shown synergistic effect of gabapentine with regard to analgesic action of morphine in animal experiment and in humans.  We have conducted this study with primary aim of comparing effect of gabapentine on post-operative analgesia with placebo. Our secondary aim was to observe total post-operative tramadol consumption and side effects of gabapentine.
| Materials and Methods|| |
This randomized, double-blind, prospective study was conducted after institutional ethical committee approval and informed written consent from all patients. Fifty ASA physical status I-II patients between 20 to 60 years of age, scheduled for elective upper abdominal surgery under general anesthesia were taken for study. We included upper abdominal surgeries like open cholecyctectomy, nephrolithotomy, pyelolithotomy, liver hydatid cyst excision, pseudopancreatic cyst excision, choledochoduodenostomy, nephrectomy and upper ureterolithotomy for our study.
Patients with known allergy to gabapentine, history of drug or alcohol abuse, chronic pain or daily intake of analgesic or corticosteroids, diabetes or impaired kidney function and pregnant women were excluded from study. In all patients, hospital stay was minimum of 24 hrs. All the patients were made familiar with a standard 10 cm visual analog scale (VAS) on pre-operative visit to assess their post-operative pain severity. The study drugs were prepared by pharmacy into identical capsules. They were packed in sequentially numbered packages, which were given to recruited patient in random order by a trained nurse, who was not involved in any other part of study. Group P (placebo group) received oral placebo capsule (3 placebo capsule) and Group G (study group) received oral gabapentine capsule (1200 mg) (3 capsules of 400 mg each) pre-operatively 2 hrs before surgery. All the patients were pre-medicated with injection (inj.) diclofenac sodium 75 mg (I. V.), injection glycopyrrolate 0.2 mg (I. V.), injection ranitidine 50 mg (I. V.) and injection ondansatron 4 mg (I. V.) 10 minutes before induction. Patients were monitored with non-invasive blood pressure (NIBP), electrocardiograph (ECG) and pulse oximetry. Pre-oxygenation was done with 100% oxygen (O 2 ) for 3 minutes. Induction was done with injection thiopentone sodium 5-7 mg/kg till loss of eyelash reflex. Endotracheal intubation was facilitated with injection succinylcholine 1.5 mg/kg (I. V.). Appropriate size cuffed endotracheal tube was inserted and anesthesia was maintained with sevoflurane, 50% N 2 O and 50% O 2 . Neuromuscular blockade was maintained with vecuronium bromide. Concentration of sevoflurone was adjusted to maintain adequate depth of anesthesia. At the end of surgery (closure), incisional infiltration with 0.25% bupivacaine 10 ml-15 ml was done in each patient. At the end of surgery, residual neuromuscular block was reversed with injection glycopyrrolate 0.08 mg/kg and neostigmine 0.05 mg/kg I. V. After tracheal extubation, patients were transferred to post-anesthesia care unit. Assessment of VAS pain score were made at 1, 2, 4, 6, 12, 18 and 24 hrs in post-operative periods. Inj. tramadol 50 mg intravenous bolus dose was given if VAS was 3 or more. Repeat inj. tramadol 25 mg I. V. bolus given if no pain relief after 10 minutes. Total tramadol dose used was recorded and total requirement (24 hrs.) was calculated. Injection diclofenac sodium was given intravenous 8 hourly, during first post-operative day. Postoperatively, for 24 hrs patients were observed for sedation, nausea, vomiting, diarrhea, constipation and urinary retention. Assessment of sedation score was made as per Ramsay sedation scale: 1. Anxious, restless or both, 2. Cooperative, oriented and tranquill, 3. Responding to commands, 4. Brisk response to stimulus, 5. Sluggish response to stimulus, 6. No response to stimulus. Injection ondansatron 4 mg intravenous was given if patient had complaints of vomiting.
All data were collected and analyzed with Statistical Package for the Social Sciences software (SPSS version 14.0). All quantitative data were expressed as mean ± SD. Power of study was 80% and P value of less than 0.05 was considered significant.
| Observations and Results|| |
A total of 50 patients were recruited and studied. Demographic data regarding age and sex were comparable in both the groups [Table 1].
Post-operative pain scores were significantly lower in gabapentine group at all time intervals [Table 2]. It was highly significant (P < 0.0001) till 24 hrs postoperatively.
Post-operative tramadol consumption was also significantly less with gabapentine group (P < 0.0001) as compared with placebo [Figure 1]. None of the patients required tramadol after 8 hrs postoperatively.
Out of 25 patients, 8 patient in gabapentine group and 3 out of 25 patients in placebo group had mild sedation (ramsay sedation scale 2 or 3) postoperatively (P < 0.08). Post-operative vomiting was observed in 3 out of 25 patients in gabapentine group and 5 out of 25 patients in placebo group [Table 3]. However, it was relieved with inj. ondansatron 4 mg I. V.
| Discussion|| |
Post-operative pain is an important factor that affects recovery from anesthesia and surgery. Given that multiplicity of mechanisms involved in postoperative pain, a multimodal analgesia regimen using a combination of opioid and non-opioid analgesics has become the treatment of choice for facilitating the recovery process. Peri-operative analgesia has been traditionally provided by opioid analgesics. However, extensive use of opioids has been associated with well- known side effects like respiratory depression, vomiting, pruritis, urinary retention, etc. 
There are different methods used for post-operative pain relief. Combination of opioid and non-opioid analgesics drugs may improve quality of post-operative analgesia as well as reduce opioid requirement and their associated side effects.  Main aim in combining different analgesic drugs is to obtain synergistic or additive analgesia, allowing a smaller dose of each drug with improved safety profiles. This can be achieved by combining analgesic drugs acting at different location, for example, centrally acting and peripherally acting analgesics.  Patients' self-report is the best assessment for the severity of pain, which may be aided by VAS . As described by the World Health Organization (WHO), step-wise escalation of analgesic therapy should usually follow the pain ladder. 
The present study demonstrated significant analgesic effects of the pre-emptive use of 1200 mg oral gabapentin after upper abdominal surgery. A significant decrease in total postoperative tramadol consumption along with a significant decrease in VAS was found in gabapentine group in comparison to patients who received placebo [Table 2]. This suggests that the pre-operative administration of gabapentine has the synergistic effect with opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) and thereby prolonging its analgesic action.
Why Upper Abdominal Surgery Selected
Minica Zelico and Pagorelic Zenon et al.,  observed that all lower abdominal incision were found to entail significantly less respiratory disturbances, lower post-operative pain and lower tramadol consumption when compared to upper abdominal incisions. So, adequate analgesia in upper abdominal surgeries carries more significance than mere patient comfort. Hence, we selected upper abdominal surgeries for study.
Chandrakant Pandey et al.,  studied that pre-operative use of gabapentine significantly decreases post-operative pain and lowers pain score at all time interval and reduces postoperative analgesic requirement in laproscopic cholecystecomy. D. J. Rowbotham et al.,  studied that there was significant reduction in post-operative analgesic requirement 24 hrs after surgery, when gabapentine was given pre-operatively. In our study of post-operative analgesia in upper abdominal surgery there was significant decrease in VAS score for 24 hrs postoperatively as compared with placebo group.
Opioid Sparing Effect
Alparsion Turon et al.,  showed that gabapentine given preoperatively in total abdominal hysterectomy enhanced analgesic effect of tramadol and also decreasing tramadol consumption in post-operative period. Rachael K. Seib, Ma et al.,  concluded that gabapentine given pre-operatively decreases pain score and lowers opioid consumption in first 24 hrs period after surgery. Dirks J, Fredensorg BB et al.,  showed that a single dose of 1200 mg oral gabapentine resulted in substantial reduction in post-operative morphine consumption and movement related pain after radical mastectomy without significant side effects. Gabapentine enhanced analgesic effect of tramadol in healthy volunteers and combination produced better and prolonged analgesia. Another study of 22 human volunteers, who received 1200 mg of gabapentine or placebo in double-blind, randomized cross-over fashion or two separate study days, demonstrated reduced primary mechanical allodynia in acute inflammation following a first degree thermal injury, suggesting that gabapentine had clinical potential in treatment of post-operative pain.  In our study, we found reduction in pain score throughout 24-hr period as compared with placebo group. Tramadol consumption was significantly reduced in first 24 hrs as shown in [Figure 1].
Dose of Gabapentine
Hoky, Gants et al.,  studied sixteen valid randomized controlled trials, where they gave single pre-operative dose of gabapentine 1200 mg. When gabapentine was administered at doses less than 1200 mg pain intensity was lower at 6 hrs and 24 hrs with comparable side effect profile. Cumulative opioid consumption at 24 hours was significantly decreased with gabapentine. Pandey CK, Singh U et al.,  studied that gabapentin 600 mg was optimal dose for post-operative pain relief following lumbar discectomy. Dirks J, Fredensborg BB et al.,  used single dose of gabapentine (1200 mg) for mastectomy. It resulted in substantial reduction in morphine consumption. Navkan DV, Giri PJ et al.,  divided patients in 4 groups to receive gabapentine 300, 600, 900, 1200 mg 2 hrs before surgery. Patients who received 600, 900, and 1200 mg had lower VAS score at all time points than patients who received gabapentine 300 mg. Increasing dose of gabapentine from 600 mg to 1200 mg did not decrease VAS score nor did decrease opioid consumption. Greegg AK, Franciss et al.,  observed that in day-care laproscopic procedures, gabapentine 300 mg had no significant effect on post-operative pain. They studied that smaller doses are ineffective. Rachael K. Seib, MA et al.,  studied that with dose of 1200 mg being more effective in reducing analgesic consumption than dose of 300 or 400 mg, they showed dosing may play role in reducing analgesic consumption. In our study, 25 patients were given single oral dose of 1200 mg, which was proved to be significant enough to reduce opioid requirement and decreased the VAS score. We choose higher dose of gabapentin as upper abdominal surgery is comparatively a more painful procedure and is situated higher on WHO pain ladder.
Goa KL, Sorkin EM et al.,  demonstrated that after single oral dose of 300 mg gabapentine, mean maximum plasma concentration was attained in 2 to 3 hrs. Absorption kinetics of gabapentine is dose-dependent, possibly due to saturable transport system. Eckhardt K, Amman S, et al.,  studied that pre-emptive administration of gabapentine approximately 2 hrs before surgery appears rational in order to attain maximal plasma concentration at the time of surgical stimuli. Alparsion Turon et al;  gave 1200 mg gabapentine 1 hr before spinal surgery in randomized fashion and found reduction in morphine consumption. Vinay Singhal et al.,  studied that there was no difference in terms of VAS score, rescue analgesic requirement and side effects, whether gabapentine is administered 2 hrs before, or immediately after, surgical incision in case of open donor nephrectomy. This difference may be because they used fentanyl for induction, which prevented central neuronal sensitization. In our study, we had given 1200 mg oral gabapentin 2 hrs before upper abdominal surgery. Synergistic effects with NSAIDs are the commonly used analgesics for minor surgery and are useful adjunctive analgesics in patients undergoing major surgery, decreasing pain and opioid requirement. They are well established, effective and inexpensive.
NSAID should be given shortly before or at induction of anesthesia or during surgery.  Picazo A et al.,  studied that low dose diclofenac gabapentine combination can interact synergistically at peripheral level; and therefore, may represent a therapeutic advantage for clinical treatment of inflammatory pain. Nikkelsons S et al.,  found that combination of rafecoxib and gabapentine could improve pain relief and reduce opioid requirement, compared with rafecoxib alone, during first 5 days after tonsillectomy. Durmus M et al.,  studied that single dose of gabapentine as well as combination of gabapentine and paracetamol decreased opioid requirement in patients undergoing abdominal hysterectomy. In our study, we have used Inj. diclofenac 75 mg i. v. intraoperatively in both groups showing decreased opioid requirement for its synergistic effect with gabapentine.
Local anesthetic instillation: Local anesthetics prevent transmission of nerve signals from the trauma site to spinal cord and reduce neurogenic local inflammation at trauma site. Argyro Fasoulaki et al.,  studied gabapentine 1600 mg/day and local anesthesia to surgical area in form of solution and cream proved as effective as previous analgesic regimens to prevent acute post-operative pain but superior in preventing chronic pain after breast surgery for cancer. A. Fassosoulaki, A Meleni et al.,  studied that gabapentine and continuous wound infusion with bupivacaine 0.75% decreased the analgesia needs and late pain in patients undergoing abdominal hysterectomy. In our study, we installed local anesthetic bupivacaine (0.25%) at incisional site and found decreased analgesic needs. Side effects Alparson Turon et al.,  did not observe any significant side effect associated with single dose of gabapentine in abdominal hysterectomy. Rachael K Seib MA et al.,  observed despite reducing opioid consumption, gabapentine did not reduce incidence of opioid related side effects. Studies on safety issue have demonstrated following adverse effects: Dizziness, sommnolence, confusion, headache, nausea, ataxia and weight gain. , In our study, the most commonly observed side effect was sedation. The sedation was not to the point of respiratory depression or desaturation as seen on SpO 2 monitor. So, no patient required supplementary oxygen inhalation in post-operative period. We have used anti-emetic (ondancetron) for vomiting, which was comparable in both groups.
| Conclusion|| |
In our study, it was observed that patients in gabapentin group had significantly lower pain score at all time interval in comparison to placebo group.
Our clinical study demonstrated that pre-emptive oral gabapentin significantly reduced postoperative pain and tramadol consumption up to 24 hours of postoperation. Anti-hyperalgesic drug such as gabapentin may have role in post-operative pain and in combination with other anti-nociceptive drug produce synergistic analgesic effects. Sedation and dizziness were common in gabapentin group in comparison with placebo group.
| References|| |
|1.||Mimica Z, Pogoreliæ Z, Perko Z, Srsen D, Stipiæ R, Dujmoviæ D. Effect of surgical incision on pain and respiratory function after abdominal surgery: A randomized clinical trial. Hepatogastroenterology 2007;54:2216-20. |
|2.||Woolf CJ, Chong MS. Preemptive analgesia-treating postoperative pain by preventing the establishment of central sensitization. Anaesth Analg 1993;77:362-79. |
|3.||Rosher H, Rubin L, Kesterbaun A. Gabapentin adjunctive therapy in neuropathic pain state. Clin J Pain 1996;12:56-8. |
|4.||Mellick GA, Mellick LB. Reflex sympathetic dystrophy treated with gabapentin. Arch Phys Med Rehabil 1997;78:98-105. |
|5.||Werner MU, Perkins FM, Holte K, Pedersen JL, Kehlet H. Effect of gabapentin in acute inflammatory pain humans. Reg Anesth Pain Med 2001;26:322-8. |
|6.||Shimoyama M, Shimoyama N, Inturrisi CE, Elliott KJ. Gabapentin enhance the antinociceptive effect of spinal morphine in rat tail-flick test. Pain 1997;72:375-82. |
|7.||Husain F, Gurha P, Tiwari S. Premedication with a combination of gabapentin and etoricox versus pethidine and promethazine-effects on post operative pain scores and oploid consumption after major orthopaedic surgeries. J Anaesth Clin Pharmacol 2009;25:477-82. |
|8.||Turon A, Karamonloglu B, Memis D, Hamamcioglu MK, Tükenmez B, Pamukçu Z, et al. Analgesic effect of gabapentine after spinal surgery. Anesthesiology 2004;100:935-8. |
|9.||Sihoe AD, Lee TW, Wan IY, Thung KH, Yim AP. The use of gabapentin for post-operative and post-traumatic pain in thoracic surgery patients. Eur J Cardiothorac Surg 2006;29:795-9. |
|10.||Jost LM, ESMO Guideline Task Force. ESMO minimum clinical recommendation for the management of cancer pain. Ann Oncol 2005;16:i83-5. |
|11.||Pandey CK, Priye S, Singh S, Singh U, Singh RB, Singh PK. Preemptive use of gabapentin significantly decreases postoperative pain and reduce analgesic requirement in laparoscopic cholecystectomy. Can J Anaesth 2004;51:358-63. |
|12.||Rowbotham M, Harden N, Stacey B, Bernstein P, Magnus-Miller L. Gabapentine for treatment of postherpatic neuralgia: A randomized controlled trial. JAMA 1998:280:1837-42. |
|13.||Turan A, Karamanlioðlu B, Memiþ D, Usar P, Pamukçu Z, Türe M. The analgesic effect of gabapentin after total abdominal hysterectomy. Anesth Analog 2004;98:1370-3. |
|14.||Seib RK, Paul JE. Preoperative gabapentine for postoperative analgesia: A meta-analysis. Can J Anaesth 2006;53:461-9. |
|15.||Dirk J, Fredensorg BB, Christenson D, Fomsgaard JS, Flyger H, Dahl JB. A randomized study of the effect of single-dose gabapentin versus placebo on postoperative pain and morphine consumption after mastectomy. Anesthesiology 2002;97:560-4. |
|16.||Ho KY, Gan TJ, Habib AS. Gabapentin and postoperative pain-a systemic review of randomized controlled trials. Pain 2006;126:91-101. |
|17.||Pandey CK, Navkar DV, Giri PJ, Raza M, Behari S, Singh RB, et al. Evaluation of optimal preemptive dose of gabapentin for postoperative pain relief after lumber diskectomy: A randomized, double-blind, placebo-controlled study. J Neurosurg Anesthesiol 2005;17:65-8. |
|18.||Greegg AK, Franciss SP. Analgesic effect of gabapentin premedication in laprascopic cholecystectomy: A randomized double-blind placebo-controlled trial. Br J Anaesth 2001; 87:174. |
|19.||Goa KL, Sorkin EM. Gabapentin. A review of its pharmacological properties and clinical potential in epilepsy. Drug 1993:46:409-27. |
|20.||Eckhardt K, Ammar S, Hofmann U, Riebe A, Gugeler N, Mikus G. Gabapantin enhance the analgesic effect of morphin in healthy volunteers. Anesth Analg 2000;91:185-91. |
|21.||Pandey CK, Singhal V, Kumar M, Lakra A, Ranjan R, Pal R, et al. Gabapentine provide effective postoperative analgesia whether administered pre-emptively or post-incision. Can J Anaesth 2005;52:827-31. |
|22.||Picazo A, Castañeda-Hernández G, Ortiz MI. Examination of interacting between peripheral diclofenac and gabapentin on the 5% formalin test in rats. Life Sci 2006;79:2283-7. |
|23.||Mikkelsons S, Hilsted KL, Andersen PJ, Hjortsø NC, Enggaard TP, Jørgensen DG, et al. The effect of gabapentin on post-operative pain following tonsillectomy in adults. Acta Anaesthesiol Scand 2006;50:809-15. |
|24.||Durmus M, Kadir But A, Saricicek V, Ilksen Toprak H, Ozcan Ersoy M. The postoperative analgesic effect of a combination of gabapentin and paracetamol in patients undergoing abdominal hysterectomy: A randomized clinical trial. Acta Anaesthesiol Scand 2007;51:200-304. |
|25.||Fassoulaki A, Triga A, Melemeni A, Sarantopoulos C. Multimodal analgesia with gabapentin and local anesthetics prevents acute and chronic pain after breast surgery for cancer. Anesth Analg 2005;101:1427-32. |
|26.||Mao J, Chen LL. Gabapentine in pain management. Anesth Analg 2000;91:680-7. |
|27.||McLean MJ, Morrel MJ, Willmore LJ, Privitera MD, Faught RE, Holmes GL, et al. Safety and tolerability of gabapentin as adjunctive therapy in large, multicenter study. Epilepsia 1999;40:965-72. |
[Table 1], [Table 2], [Table 3]
|This article has been cited by|
||Gabapentin for post-operative pain management - a systematic review with meta-analyses and trial sequential analyses
| ||M. L. Fabritius,A. Geisler,P. L. Petersen,L. Nikolajsen,M. S. Hansen,V. Kontinen,K. Hamunen,J. B. Dahl,J. Wetterslev,O. Mathiesen |
| ||Acta Anaesthesiologica Scandinavica. 2016; |
|[Pubmed] | [DOI]|
||A systematic review and meta-regression analysis of prophylactic gabapentin for postoperative pain
| ||B. Doleman,T. P. Heinink,D. J. Read,R. J. Faleiro,J. N. Lund,J. P. Williams |
| ||Anaesthesia. 2015; 70(10): 1186 |
|[Pubmed] | [DOI]|