Title: Effect of Pre-Emptive Gabapentin for Post-Operative Analgesia in Vaginal Hysterectomy under Spinal Anaesthesia
Authors: Pradipta Kumar Patel, Sumati Kandi, Aparna Sahu, Sapan Kumar Jena, Siddhanta Choudhury, Saurabh Agrawal
DOI: https://dx.doi.org/10.18535/jmscr/v7i1.161
Abstract
Background and Aims: Various drugs and methods have been tried to alleviate postoperative pain, perioperative anxiety, and apprehension. Opioids, Non-steroidal anti-inflammatory drugs, Cyclooxygenase inhibitors, and many local anesthetic techniques have been used, but every approach has their own side effects and limitations. Recent works have shown that gabapentin may have an opioid-sparing effect and anxiolytic property, without any respiratory depression, gastrointestinal, hematological, renal and hepatic adverse effects.
We conducted this study to assess the efficacy of a single dose oral gabapentin as pre-emptive analgesia in comparison to placebo for postoperative pain control in adult subjects undergoing vaginal hysterectomy under spinal anesthesia.
Material & Methods: This randomised double-blind study was conducted in 100 ASA grade I and II patients of age 40-60 years posted for abdominal hysterectomy. Patients were divided into two groups of 50 each. Group G received 600mg oral gabapentin 1 hour before vaginal hysterectomy and Group C received placebo. Total abdominal hysterectomy was carried out under spinal anesthesia. Pulse rate, SBP, DBP, and SpO2 over a 24-hour period, Total tramadol consumption, sedation scores, incidence of nausea and vomiting and other adverse effects were noted. Data was analysed with SPSS version 23 using appropriate statistical tests.
Results: There were significantly lower pain scores and reduced analgesic requirements in gabapentin group over a 24-hour period. There was better hemodynamic stability in the gabapentin group. Incidence of nausea, vomiting, and adverse events was higher in patients of gabapentin group, although not significant statistically.
Conclusion: Gabapentin used a pre-emptive analgesic, reduces post-operative analgesic requirements.
Keywords: Gabapentin, Post-operative analgesia, Pre-emptive analgesia, Abdominal Hysterectomy.
References
- Brown JG. Systemic opioid analgesia for postoperative pain management. Anesthesiology Clinics of North America. 1989 Mar 1;7(1):51-62.
- Reuben SS, Vieira P, Faruqi S, Verghis A, Kilaru PA, Maciolek H. Local Administration of Morphine for Analgesia after Iliac Bone Graft Harvest: Retracted. Anesthesiology: The Journal of the American Society of Anesthesiologists. 2001 Aug 1;95(2):390-4.
- Opioid Analgesics and Antagonists: Essentials of Medical Pharmacology, 4th edition update reprint: K.D. Tripathi; Jaypee Brothers Medical Publishers (P) Ltd. 2001: 432-49.
- Barber A, Bartoszyk GD, Greiner HE, Mauler F, Murray RD, Seyfried CA, Simon M, Gottschlich R, Harting J, Lues I. Central and peripheral actions of the novel κ‐opioid receptor agonist, EMD 60400. British journal of pharmacology. 1994 Mar 1;111(3):843-51.
- Hiller A, Silvanto M, Savolainen S, Tarkkila P. Propacetamol and diclofenac alone and in combination for analgesia after elective tonsillectomy. Acta anaesthesiologica scandinavica. 2004 Oct;48(9):1185-9.
- Yee J, Brown C, Allison C, Wildman K. Analgesia from intramuscular ketorolac tromethamine compared to morphine (ms) in severe pain following major surgery. inclinical pharmacology & therapeutics 1985 Jan 1 (Vol. 37, No. 2, pp. 239-239).
- Nonopioid analgesic and Nonsteroidal Antiinflammatory drugs: Essentials of Medical Pharmacology, 4th edition updated reprint: K.D.Tripathi; Jaypee Brothers Medical Publishers(P) Ltd.2001:450-67.
- Burkle H, Gogarten W, Van Aken H. Intravenous non-opioid analgesics in anaesthesia-the role of paracetamol, metamizol, tenoxicam and parecoxib in the perioperative treatment of acute pain. Anasthesiologie & Intensivmedizin. 2003 Apr 1;44(4):311-20.
- Barden J, Edwards JE, McQuay HJ, Moore RA. Oral valdecoxib and injected parecoxib for acute postoperative pain: a quantitative systematic review. BMC anesthesiology. 2003 Dec;3(1):1.
- Groudine SB, Fisher HA, Kaufman RP, Patel MK, Wilkins LJ, Mehta SA, Lumb PD. Intravenous lidocaine speeds the return of bowel function, decreases postoperative pain, and shortens hospital stay in patients undergoing radical retropubic prostatectomy. Anesthesia & Analgesia. 1998 Feb 1;86(2):235-9.
- Carli F, Trudel JL, Belliveau P. The effect of intraoperative thoracic epidural anesthesia and postoperative analgesia on bowel function after colorectal surgery. Diseases of the colon & rectum. 2001 Aug 1;44(8):1083-9
- Hamunen K. Ventilatory effects of morphine, pethidine and methadone in children. BJA: British Journal of Anaesthesia. 1993 Apr 1;70(4):414-8.
- Szczeklik A, Stevenson DD. Aspirin-induced asthma: advances in pathogenesis, diagnosis, and management. Journal of Allergy and Clinical Immunology. 2003 May 1;111(5):913-21.
- Strom BL, Berlin JA, Kinman JL, Spitz PW, Hennessy S, Feldman H, Kimmel S, Carson JL. Parenteral ketorolac and risk of gastrointestinal and operative site bleeding: a postmarketing surveillance study. Jama. 1996 Feb 7;275(5):376-82.
- Cheng HF, Harris RC. Cyclooxygenases, the kidney, and hypertension. Hypertension. 2004 Mar 1;43(3):525-30.
- Clark DW, Layton D, Shakir SA. Do some inhibitors of COX-2 increase the risk of thromboembolic events?. Drug Safety. 2004 Jun 1;27(7):427-56.
- Giebler RM, Scherer RU, Peters J. Incidence of neurologic complications related to thoracic epidural catheterization. Anesthesiology: The Journal of the American Society of Anesthesiologists. 1997 Jan 1;86(1):55-63.
- Vandermeulen EP, Van Aken H, Vermylen J. Anticoagulants and spinal-epidural anesthesia. Anesthesia & Analgesia. 1994 Dec 1;79(6):1165-77.
- Bach S, Noreng MF, Tjéllden NU. Phantom limb pain in amputees during the first 12 months following limb amputation, after preoperative lumbar epidural blockade. Pain. 1988 Jun 1;33(3):297-301.
- Jahangiri M, Jayatunga AP, Bradley JW, Dark CH. Prevention of phantom pain after major lower limb amputation by epidural infusion of diamorphine, clonidine and bupivacaine. Annals of the Royal College of Surgeons of England. 1994 Sep;76(5):324.
- Schug SA, Burrell R, Payne J, Tester P. Pre-emptive epidural analgesia may prevent phantom limb pain. Regional anesthesia. 1995;20(3):256.
- Katz J, Jackson M, Kavanagh BP, Sandler AN. Acute pain after thoracic surgery predicts long-term post-thoracotomy pain. The Clinical journal of pain. 1996 Mar 1;12(1):50-5.
- Perkins FM, Kehlet H. Chronic pain as an outcome of surgeryA review of predictive factors. Anesthesiology: The Journal of the American Society of Anesthesiologists. 2000 Oct 1;93(4):1123-33.
- Poobalan AS, Bruce J, Smith WC, King PM, Krukowski ZH, Chambers WA. A review of chronic pain after inguinal herniorrhaphy. The Clinical Journal of Pain. 2003 Jan 1;19(1):48-54.
- Backonja M, Beydoun A, Edwards KR. Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: a randomized controlled trial. JAMA (1998); 280:1831–6.
- Donovan-Rodriguez T, Dickenson AH, Urch CE. Gabapentin normalizes spinal neuronal responses that correlate with behavior in a rat model of cancer-induced bone pain. Anesthesiology (2005); 102:132–40.
- Gottrup H, Juhl G, Kristensen AD, et al. Chronic oral gabapentin reduces elements of central sensitization in human experimental hyperalgaesia. Anesthesi-ology (2004) ;101:1400–8.
- Hahn K, Arendt G, Braun JS, et al. A placebo-controlled trial of gabapentin for painful HIV-associated sensory neuropathies. J Neurol (2004) 251:1260–6.
- Mellick LB, Mellick GA. Successful treatment of reflex sympathetic dystrophy with gabapentin. Am J Emerg Med (1995); 13:96.
- Nicholson B. Gabapentin use in neuropathic pain syndromes. Acta Neurol Scand (2000) ;101:359–71.
- Rosenberg JM, Harrell C, Ristic H, Werner RA, de Rosayro AM. The effect of gabapentin on neuropathic pain. Clin J Pain (1997); 13:251–5.
- 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.
- Dirks J, Fredensborg BB, Christensen D, et al. A randomized study of the effects of single dose gabapentin versus placebo on postoperative pain and morphine consumption after mastectomy. Anesthesiology 2002; 97: 560–4.
- Jun JH, Yaksh TL: The effect of intrathecal gabapentin and 3-isobutyl gamma-aminobutyric acid on the hyperalgesia observed after thermal injury in the rat. Anesth Analg 1998; 86: 348-54.
- Chapman V, Suzuki R, Chamarette HL, Rygh IJ, Dickenson AH: Effects of systemic carbamazepine and gabapentin on spinal neuronal responses in spinal nerve ligated rats. Pain 1998; 75: 261-72.
- Field MJ, Holloman EF, McCleary S, Singh L: Evaluation of gabapentin and S-(+)-3-isobutylgaba in a rat model of postoperative pain. J. Pharmacol Exp Ther 1997; 282: 1242-6.
- Patel S, Naeem S, Kesingland A, Capogna M, Urban L, Fox A : The effects of GABA b agonists and gabapentin on mechanical hyperalgesia in models of neuropathic and inflammatory pain in the rat. Pain 2001; 90: 217-26.
- Gilron I, Orr E, Tu D, O’Neill JP, Zamora JE, Bell AC. A placebo-controlled randomized clinical trial of perioperative administration of gabapentin, rofecoxib and their combination for spontaneous and movement-evoked pain after abdominal hysterectomy. Pain (2005); 113:191–200.
- Rorarius MGF, Mennander S, Suominen P, et al. Gabapentin for the prevention of postoperative pain after vaginal hysterectomy. Pain (2004) 110:175–81.
- Fassoulaki A, Patris K, Sarantopoulos C, Hogan Q. The analgesic effect of gabapentin and mexiletine after breast surgery for cancer. Anesth Analg (2002); 95:985–91.
- Pandey CK, Priye S, Singh S, Singh U, Singh RB, Singh PK. Preemptive use of gabapentin significantly decreases postoperative pain and rescue analgesic requirement in laparoscopic cholecystec-tomy. Can J Anaesth (2004); 51:358–63.
- Turan A, Karamanlolu B, Memi D, Usar P, Pamukçu Z, Türe M. The analgesic effects of gabapentin after total abdominal hysterectomy. Anesth Analg (2004); 98:1370–3.
- Pandey CK, Sahay S, Gupta D, et al. Preemptive gabapentin decreases postoperative pain after lumbar discoidectomy. Can J Anesth (2004) ;51:986-9.
- Radhakrishnan M, Bithal PK, Chaturvedi A. Effect of preemptive gabapentin on postoperative pain relief and morphine consumption following lumbar laminectomy and discectomy. J Neurosurg Anesthesiol (2005); 17:125–8.
- Bonhaus DW, Loo C, Secchi R, et al. Effects of the GABAB receptor antagonist CGP 55845 on the anticonvulsant and anxiolytic actions of gabapentin (XIVth World Congress of Pharmacology, San Francisco: ASPET). Pharmacologist (2002) ;44:A100.
- Bertrand S, Ng GY, Purisai MG. The anticonvulsant, antihyperalgesic agent gabapentin is an agonist at brain gamma-aminobutyric acid type B receptors negatively coupled to voltage-dependant calcium channels. J Pharmacol Exp Ther (2001) ;298:15–24.
- Ng GY, Bertrand S, Sullivan R, et al. gamma-aminobutyric acid type B receptors with specific heterodimer composition and postsynaptic actions in hippocampal neurons are targets of anticonvulsant gabapentin action. Mol Pharmacol (2001);59:144–52.
- Gu Y, Huang LY. Gabapentin potentiates N-methyl-D-aspartate receptor mediated currents in rat GABAergic dorsal horn neurons. Neurosci Lett (2002); 324:177–80.
- Chizh BA, Scheede M, Schlutz H. Antinociception and (R,S)-alpha-amino-3-hydoxy-5-methyl-4-isoxazole propionic acid antagonism by gabapentin in the rat spinal cord in vivo. Naunyn Schmiedebergs Arch Pharmacol (2000) ; 362:197–200.
- Shimoyama M, Shimoyama N, Hori Y. Gabapentin affects glutamatergic excitatory neurotransmission in the rat dorsal horn. Pain (2000); 85:405–14.
- Gidal BE, Radulovic LL, Kruger S, Rutecki P, Pitterle M, Bockbrader HN. Inter- and intra-subject variability in gabapentin absorption and absolute bioavailability. Epilepsy Res (2000); 40:123–7.
- Su TZ, Lunney E, Campbell G. Transport of gabapentin, a -amino acid drug, by system 1 alpha-amino acid transporters: a comparative study in astrocytes, synaptosomes, and CHO cells. J Neurochem (1995) ;64:2125–31.
- Freiman TM, Kukolja J, Heinemeyer J, et al. Modulation of K+-evoked [3H]-noradrenaline release from rat and human brain slices by gabapentin: involvement of KATP channels. Naunyn Schmiedebergs Arch Pharmacol (2001); 363:537–42.
- Mixcoatl-Zecuatl T, Medina-Santillán R, Reyes-Garcia G, Vidal-Cantú GC, Granados-Soto V. Effect of K+ channel modulators on the antiallodynic effect of gabapentin. Eur J Pharmacol (2004); 484:201–8.
- Surges R, Freiman TM, Feuerstein TJ. Gabapentin increases the hyperpolarization-activated cation current Ih in rat CA1 pyramidal cells. Epilepsia (2003) ;44:150–6.
- Surges R, Freiman TM, Feuerstein TJ. Input resistance is voltage dependent due to activation of Ih channels in rat CA1 pyramidal cells. J Neurosci Res (2004); 76:475–80.
- Fink K, Dooley DJ, Meder WP, et al. Inhibition of neuronal Ca2+ influx by gabapentin and pregabalin in the human neocortex. Neuropharmacology (2002); 42:229–36.
- Gee NS, Brown JP, Dissanayake VU, Offord J, Thurlow R, Woodruff GN. The novel anticonvulsant drug, gabapentin (Neurontin), binds to the alpha2delta subunit of a calcium channel. J Biol Chem (1996); 271:5768–76.
- Stefani A, Spadoni F, Bernardi G. Gabapentin inhibits calcium currents in isolated rat brain neurons. Neuropharma-cology (1998) ;37:83–91.
- Coderre TJ, Kumar N, Lefebvre CD, Yu JSC. Evidence that gabapentin reduces neuropathic pain by inhibiting the spinal release of glutamate. J Neurochem (2005); 94:1131–9.
- Feng Y, Cui M, Willis WD. Gabapentin markedly reduces acetic acid-induced visceral nociception. Anesthesiology (2003); 98:729–33.
- Fehrenbacher JC, Taylor CP, Vasko MR. Pregabalin and gabapentin reduce release of substance P and CGRP from rat spinal tissues only after inflammation or activation of protein kinase C. Pain (2003) ;105:133–41.
- Suzuki R, Rahman W, Rygh LJ, Webber M, Hunt SP, Dickenson AH. Spinal-supraspinal serotonergic circuits regulating neuropathic pain and its treatment with gabapentin. Pain (2005) ;117:292–303.
- Tanabe M, Takasu K, Kasuya N, Shimizu S, Honda M, Ono H. Role of descending noradrenergic system and spinal alpha2-adrenergic receptors in the effects of gabapentin on thermal and mechanical nociception after partial nerve injury in the mouse. Br J Pharmacol (2005); 144:703–14.
- 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.
- Gregg AK, Francis S, Sharpe P, Rowbotham DJ. Analgesic effect of gabapentin premedication in laparoscopic cholecystectomy: a randomized double-blind placebo controlled trial. Br. J. Anesth 2001; 87:174P(abstract).
- Dirks J, Fredensborg BB, Christensen D, Fomsgaard JS, Flyger H, Dahl JB. A randomized study of the effects of single-dose gabapentin versus placebo on postoperative pain and morphine consumption after mastectomy. Anesthesiology (2002) ;97:560–4.
- Fassoulaki A, Patris K, Sarantopoulos C, Hogan Q. The analgesic effect of gabapentin and mexiletine after breast surgery for cancer. Anesth Analg (2002); 95:985–91.
- Dierking G, Duedahl TH, Rasmussen ML, et al. Effects of gabapentin on postoperative morphine consumption and pain after abdominal hysterectomy: a randomized, double-blind trial. Acta Anaesthesiol Scand (2004) ;48:322–7.
- Pandey CK, Priye S, Singh S, Singh U, Singh RB, Singh PK. Preemptive use of gabapentin significantly decreases postoperative pain and rescue analgesic requirement in laparoscopic cholecyst-ectomy. Can J Anaesth (2004); 51:358–63.
- Pandey CK, Sahay S, Gupta D, et al. Preemptive gabapentin decreases postoperative pain after lumbar discoid-ectomy. Can J Anesth (2004) ;51:986-9.
- Turan A, Karamanlioglu B, Memis D, et al. Analgesic effects of gabapentin after spinal surgery. Anesthesiology (2004) 100:935–8.
- Rorarius MGF, Mennander S, Suominen P, et al. Gabapentin for the prevention of postoperative pain after vaginal hysterectomy. Pain (2004) 110:175–81.
- Pandey CK, Navkar DV, Giri PJ, et al. Evaluation of the optimal preemptive dose of gabapentin for postoperative pain relief after lumbar diskectomy. J Neurosurg Anesthesiol (2005); 17:65–8.
- Turan A, Kaya G, Karamanlioglu B, Pamukçu Z, Apfel CC. Effect of oral gabapentin on postoperative epidural analgesia. Br J Anaesth (2006) ;96:242–6.
- Al-Mujadi H, A-Refai AR, Katzarov MG, Dehrab NA, Batra YK, Al-Qattan AR. Preemptive gabapentin reduces postoperative pain and opioid demand following thyroid surgery. Can J Anesth (2006) ;53:268–73
- Ménigaux C, Adam F, Guignard B, Sessler DI, Chauvin M. Preoperative gabapentin decreases anxiety and improves early functional recovery from knee surgery. Anesthesia and analgesia. 2005 May;100(5):1394.
- Chouinard G, Beauclair L, Belanger MC. Gabapentin: long-term antianxiety and hypnotic effects in psychiatric patients with comorbid anxiety-related disorders. Can J Psychiatry. 1998;43:305.
- Pollack MH, Matthews J, Scott EL. Gabapentin as a potential treatment for anxiety disorders. Am J Psychiatry. 1998;155:992–3. [PubMed]
- Pande AC, Pollack MH, Crockatt J, et al. Placebo-controlled study of gabapentin treatment of panic disorder. J Clin Psychopharmacol. 2000;20:467–71.
- de-Paris F, Sant'Anna MK, Vianna MR, et al. Effects of gabapentin on anxiety induced by simulated public speaking. J Psychopharmacol. 2003;17:184–8
- de-Paris F, Busnello JV, Vianna MR, et al. The anticonvulsant compound gabapentin possesses anxiolytic but not amnesic effects in rats. Behav Pharmacol. 2000;11:169–73.
- Lynch EP, Lazor MA, Gellis JE, et al. Patient experience of pain after elective noncardiac surgery. Anesth Analg. 1997;85:117–23.
- Kalkman CJ, Visser K, Moen J, et al. Preoperative prediction of severe postoperative pain. Pain. 2003;105:415–23.
- Rose MS, Kam PC. Gabapentin: pharmacology and its use in pain management. Anaesthesia. 2002;57:451–62.
