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CLINICAL INVESTIGATION
Year : 2008  |  Volume : 52  |  Issue : 4  |  Page : 428 Table of Contents     

To Evaluate the Role of Gabapentin as Preemptive Analgesic in Patients Undergoing Total Abdominal Hysterectomy in Epidural Anaesthesia


1 Lecturer, Dept of Obst & Gynae, R.I.M.S,Etawah,U.P, India
2 Senior Resident, Dept of Obst & Gynae, V.M.M.C & Safdarjung Hospital ,New Delhi, India
3 Professor& Head, Department of Anaesthesiology & Critical Care, G. S. V. M. Medical College, Kanpur, U.P., India
4 P.G.Student, Department of Anaesthesiology & Critical Care, G. S. V. M. Medical College, Kanpur, U.P, India

Date of Acceptance03-Jun-2008
Date of Web Publication19-Mar-2010

Correspondence Address:
Anil Verma
Department of Anaesthesiology & Critical Care, G. S. V. M. Medical College, Kanpur, U.P
India
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Source of Support: None, Conflict of Interest: None


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Gabapentin, a structural analogue of gamma-amino butyric acid, has been used as an anticonvulsant and antinociceptive drug but its mode of action is not well understood. Gabapentin has been demonstrated in various clinical studies to be of value as preemptive analgesic, and has shown to reduce the postoperative requirement of opioids. This study was conducted to evaluate the role of gabapentin as preemptive analgesic in patients undergoing total abdominal hysterectomy. Fifty patients with ASA grade I and II were assigned to receive 300mg gabapentin or placebo 2hr before surgery. Surgeries were conducted under combined spinal epidural anaesthesia. Post operatively, pain was assessed by visual analogue score (VAS) at 2, 4,8,12 and 24hrs. Patients were given epidural boluses of bupivacaine (0.125%) on demand. Total numbers of epidural boluses during first 24 hrs postoperatively were noted. Patients in gabapentin group have significantly lower VAS score 2, 4,8,12 and 24hrs postoperatively as compared to the placebo (1.3 ± 1.3, 2.3±1.4, 3.2 ± 2.1, 1.8 ± 1.7, 1.2 ± 1.3 vs. 2.1 ± 1.7, 3.2±1.6, 4.4 ± 1.2, 3.3 ± 1.1, 2.1 ± 1.2 respectively; P <0.05). Total numbers of epidural boluses were significantly less in gabapentin group (3.4±1.6 vs. 5.6±2.1, P<0.05). We conclude that preemptive use of gabapentin 300mg orally significantly reduces the number of postoperative epidural bolus requirement and postoperative pain in patients undergoing total abdominal hysterectomy under combined spinal epidural anaesthesia.

Keywords: Gabapentin, Total abdominal hysterectomy, Preemptive analgesia.


How to cite this article:
Verma A, Arya S, Sahu S, Lata I, Pandey H D, Singh H. To Evaluate the Role of Gabapentin as Preemptive Analgesic in Patients Undergoing Total Abdominal Hysterectomy in Epidural Anaesthesia. Indian J Anaesth 2008;52:428

How to cite this URL:
Verma A, Arya S, Sahu S, Lata I, Pandey H D, Singh H. To Evaluate the Role of Gabapentin as Preemptive Analgesic in Patients Undergoing Total Abdominal Hysterectomy in Epidural Anaesthesia. Indian J Anaesth [serial online] 2008 [cited 2019 Sep 21];52:428. Available from: http://www.ijaweb.org/text.asp?2008/52/4/428/60657


   Introduction Top


Gabapentin [1-(aminomethyl)cyclohexane acetic acid]is a structural analog of gamma aminobutyric acid (GABA), which was initially introduced in 1994 as an antiepileptic drug, particularly for partial seizures. It was soon found to be promising in treating neuropathic pain associated with postherpetic neuralgia (PHN) [1],[2] , post poliomyelitis neuropathy [3] , and reflex sympathetic dystrophy [4] . Placebo-controlled clinical trials also have indicated a role of gabapentin in treating pain related to diabetic neuropathy (DNP) [5] and PHN [6] . The concept of preemptive analgesia to reduce postoperative pain was founded on a series of successful animal experi­mental studies that demonstrated central nervous sys­tem plasticity and sensitization after nociception [7] . Pre­emptive analgesia is defined as an antinociceptive treat­ment that prevents the establishment of altered central processing of afferent input, which amplifies postop­erative pain [8] . By decreasing the altered central sen­sory processing, preemptive analgesia is thought to consequently decrease the incidence of hyperalgesia and allodynia after surgery [9] . Gabapentin has demon­strated analgesic effects in clinical trials as a pre-emptive analgesic and in acute postoperative pain management; however, experience with gabapentin is limited [10],[11],[12] .There has not been a separate study about the pre­-emptive use of gabapentin in cases conducted under regional anaesthesia and its effects on requirement on postoperative epidural requirement of local anaesthetics. We therefore designed the present study to investigate whether pre-emptive use of gabapentin 300 mg orally could reduce postopera tive pain and number of epi­dural boluses in the initial 24 hours in patients undergo­ing total abdominal hysterectomy.


   Methods Top


After getting approval from institutional ethical committee. Written and informed consent was taken from each of the patients. Fifty patients of ASA status I an II undergoing total abdominal hysterectomy between age group 20 -60yrs of age were selected for the study. Patients with allergy to gabapentin, suffering from epi­lepsy, liver disease, renal disease, suffering from any chronic pain syndrome, having psychiatric illness or patients who have taken NSAID in last 48 hrs were excluded from the study.

Assuming that following therapy VAS would re­duce by 50%, one would need to enroll 23 patients in each group for the results to be statistically significant at a power of 80% with a level of confidence of 5%. In considering any dropouts, we included 25 patients in each group. The patients were randomly divided into 2 groups with 30 patients in each.

The study design was randomized and double­blind. Patients were randomly allocated into 2 equal groups of 25 each with the help of a computer-gener­ated table of random numbers. All study medications were given orally with sips of water 2 hour preopera­tively by a staff nurse who was not involved in the study. Patients in study Group-G (gabapentin) received tab gabapentin 300mg; whereas in study Group-P (pla­cebo) patients received matching placebo. All patients were premedicated with ranitidine and metoclopramide I.V. 1hr before surgery. Routine monitoring with pulse oximetry, NIBP, ECG, temperature and urine output with an indwelling catheter was initiated in the opera­tion theatre.

All patients were preloaded with 10ml.kg -1 of lac­tated Ringers' solution and combined spinal epidural were performed at interspace L2-L3 or L3-L4 in sitting posi­tion. 4ml of hyperbaric solution of 0.5% bupivaciane was given in the subarachnoid space. After confirmation of the successful blockade and proper height of anaesthesia all patients were sedated with infusion of propofol at rate of 25-50µg.kg -1 .min -1 . propofol infusion was stopped at the beginning of the skin sutures. After surgery patients were shifted to recovery room. Patients were given 12 ml of epidural bupivaciane 0.125% boluses for pain relief on demand. VAS scores were assessed by an independent physician (AV) who was not aware of the group alloca­tion on a scale of 0-10cm (0 mean no pain, 10 equals to worst imaginable pain) after 2, 4, 8, 12 and 24hrs after the surgery at the same time patients were asked for any com­plication suffered by them. Total numbers of epidural bo­luses received by each patient were noted. The data were entered into the statistical software package SPSS 9. The mean ± SD from maximum pain scores for all patients in both groups at time intervals of 0-2, 2-4, 4-8, 8-12 and 12-24 hr were calculated. Similarly, epidural bupivaciane 0.125% consumption in each group was calculated. A value of P < 0.05 was considered significant. VAS scores were analyzed with two-factor ANOVA for repeated measures. The total epidural bupivaciane 0.125% con­sumed in each group (mean ± SD) in 24 hr was com­pared using an unpaired t test.


   Results Top


There was no difference in age, sex, body weight, and duration of anesthesia between the two groups [Table 1].

Patients in the Group-G (gabapentin) had signifi­cantly lower VAS scores at all times 2, 4, 8, 12 and 24hrs than those in the Group-P (placebo) [Table 2], [Figure 1]. The total number epidural boluses demanded after surgery in the first 24 hr in the Group-G (gabapentin) (3.4±1.6 , mean ± SD) was significantly less than in the Group-P (placebo) ( 5.6±2.1, P<0.05, [Figure 2])

The incidence of adverse effects (nausea 5 vs 4, vomiting 3 vs 4, fatigue 1 vs 0, light headedness 1 vs 0 and dizziness 1 vs 0) was similar in the Group-G (gabapentin) and Group-P (placebo).


   Discussion Top


In present study we have demonstrated that 300mg of gabapentin taken 2hrs before surgery results in substantial reduction in pain and requirement of the epidural boluses in patients undergoing total abdominal hysterectomy and that gabapentin was not associated with more side effects when compared with placebo.

After a single oral dose of 300 mg, mean maxi­mum plasma concentrations are attained in 2-3 hours. The pre-emptive administration of gabapentin approxi­mately two hours before surgery appears optimal in order to attain maximal plasma concentrations at the time of surgical stimuli. In animal models of nociception, gabapentin reduces hypersensitivity associated with nerve injury, inflammation, and pain after surgery[13],[14],[15] . Mechanical hyperalgesia surrounding the wound in post­-operative patients, and experimental, heat-induced sec­ondary hyperalgesia share a common mechanism- central neuronal sensitization-that may contribute to some aspects of postoperative pain. Antihyperalgesic drugs such as gabapentin may have a role in postop­erative pain.[16] It has also been demonstrated that a 600 mg single dose of gabapentin enhanced the effect of morphine, but side effects appeared in approximately 40% of volunteers when these drugs were used con­comitantly. [17] Another study of 22 human volunteers who received 1,200 mg of gabapentin or placebo in a double-blind, randomized cross-over fashion on two separate study days, demonstrated reduced primary mechanical alloying in acute inflammation following a first degree thermal injury, suggesting that gabapentin had clinical potential in the treatment of postoperative pain. [18] In another study, gabapentin was shown to re­duce the requirement of fentanyl for postoperative pain relief in patients undergoing lumbar discoidectomy [19] . Gabapentin is well tolerated. It has few side effects and minor interactions with other drugs when used for the treatment of chronic pain [20] . We did not observe any significant side effects associated with a single oral dose of gabapentin.

In conclusion, single oral dose of gabapentin given 2hrs before surgery provides better pain control as compared to the placebo and also reduces the require­ment of epidural boluses in patients undergoing total abdominal hysterectomy with out increase in frequency of side effects.

 
   References Top

1.Segal AZ, Rordorf G. Gabapentin as a novel treatment for postherpetic neuralgia. Neurology 1996; 46: 1175-6.  Back to cited text no. 1  [PUBMED]    
2.Rosner H, Rubin L, Kestenbaum A. Gabapentin adjunc­tive therapy in neuropathic pain states. Clin J Pain 1996; 12: 56-8.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]  
3.Zapp JJ. Postpoliomyelitis pain treated with gabapentin [letter]. Am Fam Physician 1996; 53: 2442.  Back to cited text no. 3  [PUBMED]    
4.Mellick GA, Mellick LB. Reflex sympathetic dystrophy treated with gabapentin. Arch Phys Med Rehabil 1997; 78: 98-105.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]  
5.Backonja M, Beydoun A, Edwards KR, et al. Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: a randomized controlled trial. JAMA 1998; 280: 1831-6.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]  
6.Rowbotham M, Harden N, Stacey B, et al. Gabapentin for the treatment of postherpetic neuralgia: a random­ized controlled trial. JAMA 1998; 280: 1837-42.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]  
7.Woolf CJ, Wall PD. Morphine-sensitive and morphine insensitive actions of C-fiber input on the rat spinal cord.Neurosci Lett 1986; 64:221-5.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]  
8.Kissin I. Preemptive analgesia. Anesthesiology 2000;93: 1138-43.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]  
9.Wilder-Smith OH. Pre-emptive analgesia and surgical pain. Prog Brain Res 2000; 129:505-24.  Back to cited text no. 9  [PUBMED]    
10.Chiaretti A, Viola L, Pietrini D, et al. Preemptive analge­sia with tramadol and fentanyl in pediatric neurosur­gery. Childs Nerv Syst 2000; 16:93-9.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]  
11.Naguib M, Seraj M, Attia M, et al. Perioperative antinociceptive effects of tramadol. A prospective, ran­domized, double-blind comparison with morphine. Can J Anaesth 1998; 45:1168-75.  Back to cited text no. 11  [PUBMED]    
12.Fassoulaki A, Patris K, Sarantopoulos C, Hogan Q. The analgesic effect of gabapentin and mexilentine after breast surgery for cancer. Anesth Analg 2002; 95:985­91.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]  
13.Cheong JK, Pan HL, Eisenach JC. Antiallodynic effect of intrathecal gabapentin and its interaction with clonidine in a rat model of postoperative pain. Anesthe­siology 2000; 92:1126-31.  Back to cited text no. 13      
14.Field MJ, Holloman EF, McCleary S, et al. Evaluation of gabapentin and S-(_)-3-isobutylgaba in a rat model of postoperative pain. J Pharmacol Exp Ther 1997; 282:1242-6.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]  
15.Dirks J, Petersen KL, Rowbotham MC, Dahl JB. Gabapentin suppresses cutaneous hyperalgesia follow­ing heat/capsaicin sensitization. Anesthesiology 2002; 97:102-6.  Back to cited text no. 15  [PUBMED]  [FULLTEXT]  
16.Dirks J, Moiniche S, Hilsted KL, Dahl JB. Mechanisms of postoperative pain: clinical indications for a contri­bution of central neuronal sensitization. Anesthesiol­ogy 2002; 97:1591-6.  Back to cited text no. 16      
17.Eckhardt K, Ammon S, Hofmann U, et al. Gabapentin enhances the analgesic effect of morphine in healthy volunteers. Anesth Analg 2000; 91:185-91.  Back to cited text no. 17  [PUBMED]  [FULLTEXT]  
18.Werner MU, Perkins FM, Holte K, Pedersen JL, Kehlet H. Effects of gabapentin in acute inflammatory pain in humans. Reg Anesth Pain Med 2001; 26:322-8.  Back to cited text no. 18  [PUBMED]  [FULLTEXT]  
19.Pandey CK, Sahay S, Gupta D, Ambesh SP, Singh RB, Raza M, Singh U, Singh PK.Preemptive gabapentin de­creases postoperative pain after lumbar discoidectomy.Can J Anaesth 2004; 51:986-9.  Back to cited text no. 19  [PUBMED]    
20.McLean MJ, Morrell MJ, Willmore LJ, et al. Safety and tolerability of gabapentin as adjunctive therapy in a large, multicenter study. Epilepsia 1999; 40:965-72.  Back to cited text no. 20  [PUBMED]    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2]



 

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