|Year : 2017 | Volume
| Issue : 2 | Page : 133-137
Role of oral gabapentin as preemptive adjuvant with spinal anesthesia for postoperative pain in patients undergoing surgeries under spinal anesthesia
Roshan Lal Gogna1, Deepak Dwivedi2, Urvashi Tandon2, Kunal Sarin2, Vidhu Bhatnagar2
1 Department of Anaesthesia and Critical Care, Mahatma Gandhi Mission Institute of Health Sciences, Mumbai, Maharashtra, India
2 Department of Anaesthesia and Critical Care, Institute of Naval Medicine, INHS Asvini, Maharashtra, India
|Date of Web Publication||6-Sep-2017|
Department of Anaesthesia and Critical Care, Institute of Naval Medicine, INHS Asvini, Colaba, Mumbai - 400 005, Maharashtra
Source of Support: None, Conflict of Interest: None
Background and Aims: The study was undertaken to evaluate postoperative benefit in patients administered tablet gabapentin as premedication with the primary outcome determining the effect on duration of analgesia with total analgesic requirement and measurement of postoperative sedation scores as our secondary outcomes. Methods: The study was a prospective randomized observational study in sixty patients undergoing surgeries in spinal anesthesia (SA). Patients were randomly assigned into two groups. Group A (n = 30) patients received tablet gabapentin (600 mg) while Group B (n = 30) received a placebo (Vitamin B complex) orally 2 h before surgery. Postoperative pain was managed with intravenous tramadol 2 mg/kg. Postoperative monitoring and assessment included pain assessment every 2 h with Numeric Rating Scale (0–10) for 12 h and then at 24 h. Results: On comparison of intergroup data, the duration of analgesia was prolonged in Group A (288.79 ± 38.81 min) as compared to Group B (218.67 ± 37.62 min) with P (0.0001). Total opioid requirement was higher in placebo group as compared to the Group A (P = 0.025). Statistical difference in mean (standard deviation) pain score at 24 h was statistically significant (P = 0.0002). Sedation scores were significantly higher in Group A at 2 and 4 h post-SA. Conclusion: Single dose of gabapentin administered 2 h before surgery provides better pain control as compared to placebo. It prolongs the duration of analgesia, reduces the total analgesic requirement during the postoperative period.
Keywords: Analgesia, anesthesia, gabapentin, pain measurement, spinal
|How to cite this article:|
Gogna RL, Dwivedi D, Tandon U, Sarin K, Bhatnagar V. Role of oral gabapentin as preemptive adjuvant with spinal anesthesia for postoperative pain in patients undergoing surgeries under spinal anesthesia. Indian J Pain 2017;31:133-7
|How to cite this URL:|
Gogna RL, Dwivedi D, Tandon U, Sarin K, Bhatnagar V. Role of oral gabapentin as preemptive adjuvant with spinal anesthesia for postoperative pain in patients undergoing surgeries under spinal anesthesia. Indian J Pain [serial online] 2017 [cited 2020 May 28];31:133-7. Available from: http://www.indianjpain.org/text.asp?2017/31/2/133/214121
| Introduction|| |
Pain as a sensation has strong psychological and emotional components. The International Association for the study of pain has defined pain as an “unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.”, The main objective of the anesthesiologist in the management of perioperative pain is to minimize pain, improve function, and enhance the patient's overall sense of wellbeing. Uncontrolled postoperative pain evokes a neuroendocrine response to pain and can lead to increased incidence of deep vein thrombosis, vascular graft failure, and myocardial ischemia. In addition, the wound healing is delayed causing depression of immune system and other systemic effects. Various techniques are employed to treat acute postoperative pain. These include the use of systemic opioid, nonsteroidal anti-inflammatory drugs, regional analgesia, and other techniques. However, maximum benefit is derived from a multi-modal management of pain.
Surgical incision leads to sensitization, both central and peripheral, resulting in hyperalgesia and allodynia seen as movement-evoked pain in the postoperative patient. Anticonvulsants have shown promising results while treating chronic neuropathic pain. Several reviews have shown the utility of anticonvulsants as adjuvant drugs as a result of their opioid-sparing effects.,
Gabapentin, a drug used for neuropathic pain acts on peripheral sodium channels, voltage dependent calcium channels, and decreases glutaminergic transmission in the spinal cord. It inhibits central neuronal sensitization and hyperalgesia by acting on calcium channels located at postsynaptic and presynaptic junctions resulting in the inhibition of the calcium influx thereby decreasing excitatory amino acid neurotransmission.
By decreasing the central sensory input processing, gabapentin is considered to provide preemptive analgesia hence, decreasing the incidence of hyperalgesia and allodynia after surgery.
The present study was undertaken to evaluate the efficacy of a single preemptive dose of gabapentin (600 mg) on the duration of postoperative analgesia in patients undergoing surgeries in spinal anesthesia (SA), which was considered as a primary outcome. Total opioid consumption (mean ± standard deviation [SD]) in the first 24 h and postoperative sedation scores due to the somnolence effect of gabapentin were measured in both groups as secondary outcomes.
| Methods|| |
A prospective randomized observational study was planned in sixty patients undergoing surgeries in SA, for example, laminectomies, hernia repairs, total abdominal hysterectomies, and total knee replacement. Approval from the institutional ethics committee obtained. The sample size was calculated keeping the mean (SD) duration of analgesia as a primary outcome. The sample size was calculated based on the study done by Bafna et al. with an alpha error of 5% and keeping the power of study at 80%. Minimum sample size calculated was 29 in each group; however, we took thirty subjects for each group.
The patients aged between 18 and 60 years in the American Society of Anesthesiologists (ASA) physical I or II were included in the study. The exclusion criteria included (a) patients who were unwilling to participate, (b) patients who had a history of known hypersensitivity to any drugs which were being used in study, (c) patients with spinal deformities and chronic back ache, (d) patients who were receiving any analgesics 24 h before the surgery, (e) patients undergoing lower segment cesarean section, and (f) patients suffering from epilepsy, liver disease, renal disease, suffering from any chronic pain syndrome, or having any psychiatric illness.
Preanesthetic check-up was performed. The patients were explained the Numeric Rating Scale (NRS) of pain, which is a 10 cm horizontal line with the extreme right end marked as “10” denoting the worst imaginable pain and the extreme left end marked as “0” as no pain. Patients were asked to rate their pain on the scale of ten.
Each patient was randomly allocated using sealed envelope in either of two groups – Group A (gabapentin) and Group B (placebo) using random number tables. Thirty patients of Group A received 600 mg gabapentin orally 2 h before surgery while the thirty patients of Group B received a placebo 2 h before surgery. In the operation theater, all patients were preloaded with the 15 ml/kg of intravenous (IV) balanced salt solution. SA was given with 3 ml of 0.5% hyperbaric bupivacaine at L2–L3/L3–L4 space. Standard monitoring included heart rate, noninvasive blood pressure, electrocardiography, and oxygen saturation. Significant hypotension (defined as >20% fall in mean arterial blood pressure) was treated with injection ephedrine and IV crystalloids.
Postoperative monitoring and assessment of pain were done by an independent observer who was blinded to the group allocation. Postoperative pain was managed with injection tramadol 2 mg/kg IV slow infusion. The pain was assessed postoperatively using NRS score at 2, 4, 8, 12, and 24 h. The rescue analgesia was administered when the NRS of pain was above three and the total duration of analgesia was noted in both groups. Total dose (mean ± SD) of rescue analgesia consumed was calculated for the 24 h. Sedation scale was assessed using the Ramsay Sedation Scale at 2, 4, 8, and 24 h. Any side effects such as nausea, vomiting, and urinary retention was noted.
Continuous variables such as age and weight, duration of anesthesia, and the duration of analgesia were analyzed with unpaired t-test. Sex and ASA grading were represented in percentages. Postoperative NRS scores and sedation scores were analyzed using nonparametric analysis (Mann–Whitney U-test). Statistical Package for Social Sciences (Version 15.0 Inc., Chicago IL, USA) software was utilized for analysis. The difference was considered statistically significant when P < 0.05.
| Results|| |
The study enrolled sixty ASA physical status Class I and II patients of either sex, between 18 and 60 years, scheduled for elective surgeries under SA and allocated randomly into two groups, Group A (n = 30) and Group B (n = 30) [Figure 1]. Demographic variables such as age weight, sex, duration of surgery, and type of surgery were comparable in both groups [Table 1] and [Figure 2].
When the total duration of analgesia (mean ± SD) in minutes was compared, Group A patients required first rescue analgesia at (288.79 ± 38.81) min whereas, in Group B patient's (mean ± SD) duration of analgesia lasted till (218.67 ± 37.62) min with P = 0.0001 which is significant. [Table 2].
Sedation scores were significantly higher in Group A at 2 h and 4 h post-SA. Overall mean (SD) sedation scores of Group A when compared with Group B at 24 h were significant (P = 0.0001) [Table 2] and [Figure 3]. Intergroup mean (SD) pain scores when compared at 2, 4, 8, 12, 24 h were lower in Group A [Figure 4]. Cumulative (mean ± SD) pain scores when added after 24 h in Group A (7.57 ± 2.31) were lower and significant in comparison to Group B (10.09 ± 2.61) with P = 0.0002 [Table 2]. Total opioid consumption in milligrams postoperatively at 24 h was significantly lower in the Group A, (123.33 ± 34.07) when compared with Group B (140 ± 20.34) with P = 0.025. Postoperatively, six patients (two from Group A and four from Group B) had one episode of vomiting. All were treated with injection ondansetron 4 mg IV stat after which there were no further episodes. Urinary retention requiring one-time catheter evacuation of bladder was done in two patients each in both groups. No other significant side effects were recorded.
| Discussion|| |
Postoperative pain is heralded by the adverse outcomes such as prolonged hospital stay, impaired wound healing, and infections. Expansion of the knowledge of pain pathways leads to the inclusion of multimodal analgesia model as the recommended model combating postoperative pain with multiple drugs targeting not only the nociceptive inputs but also the inputs from viscera, inflammation, and neurogenic components.
This study demonstrates the analgesic efficacy of 600 mg of gabapentin in subjects undergoing surgeries under SA which appears to reduce abnormal hypersensitivity induced by inflammatory responses or nerve injury. In our study, we selected the dose of 600 mg gabapentin administered 2 h before surgery keeping in mind the bioavailability of the drug which is described as disproportional. Studies have shown that increasing the dose beyond 600 mg the absorption is nonlinear and the bioavailability decreases., However, Elazzazi H et al., in their quest to find optimum dose of gabapentin concluded that 1500 mg oral dose given preoperatively reduced pain severity up to 24 h. Schmidt et al., from their review concluded that higher preoperative dose of gabapentin (1200 mg) is more effective than lower doses and further added that continuing gabapentin postoperatively is more effective as compared to the single dose. The preemptive administration of gabapentin approximately 2 h before surgery appears optimal to attain maximal plasma concentrations at the time of surgical stimuli.
Various studies have shown the efficacy of gabapentin in reducing the pain scores and increasing the mean duration of the analgesia when used for varied surgeries performed under SA such as total abdominal hysterectomy, orthopedic surgeries, and surgeries on spine.,,,,
The subjects who received gabapentin preoperatively, 2 h before incision in our study had significantly lower pain scores at all point of time compared to placebo [Figure 4]. The mean duration of analgesia was prolonged in Group A in contrast to placebo group with P = 0.0001 [Table 2]. Preincision analgesia has proved to be more effective in control of postoperative pain by modulating the central nervous system conditioning from deleterious effects of noxious stimuli. Anil Verma et al., also demonstrated that 300 mg of gabapentin taken 2 h before surgery resulted in substantial reduction in pain and requirement of the epidural boluses in patients undergoing total abdominal hysterectomy.
Opioid sparing effect was observed in our study. The mean (SD) total dose of opioid (tramadol) consumed was significantly lower in Group A in comparison to placebo group with P = 0.025 [Table 2]. Similar studies have proved that gabapentin enhanced the analgesic effect of morphine  and Eckhardt et al., demonstrated that a 600 mg single dose of gabapentin also increases the adverse effects when these drugs were used concomitantly. Pandey et al. showed that gabapentin reduced the requirement of fentanyl for postoperative pain relief in patients undergoing lumbar discoidectomy. Gabapentin, therefore, has a definite role in alleviating acute nociceptive and inflammatory pain and improved pain scores both at rest and with movement when administered as a preemptive analgesia thereby modulating the central neuronal mechanism., The contrary results have been reported by the systematic review and meta-analysis done by Fabritius et al., where there were inconsistency and lack of solid evidence regarding the role of gabapentin in reducing the 24 h opioid consumption with increased incidence of adverse effects when combined with multimodal analgesia.
Few studies have also confirmed the prolongation of both the sensory and motor recovery post-SA after the consumption of gabapentinoids.,
Chang et al., review showed that gabapentin is well tolerated. Adverse effects, however, most commonly reported are dizziness, sedation or drowsiness, nausea, vomiting, and shivering. Sedation scores were significantly higher in Group A (P = 0.0001), and the difference was significant at 2 and 4 h [Figure 3]. Studies have shown increased incidence of drowsiness varying from 33% to 42%., Sedation occurs primarily due to the inhibitory effect and modulation of the release of the excitatory neurotransmitter (glutamate, substance P, etc.) centrally. Meta-analysis by Peng et al., confirmed the increased incidence of the sedation and dizziness with gabapentin. Decreased incidence of vomiting was noted in our study in gabapentin group (6.6%) with contrast to placebo group (13.3%). A study by Vasigh et al., showed 10.3% patients had vomiting in gabapentin group as compared to placebo group with 39.5%. The theory behind its antiemetic effect is supposed to be due inhibition of neurotransmitter tachykinin.
Limitations of the study were due to the inclusion of heterogeneous group of surgeries which were not matched in both groups. Therefore, the extent of tissue handling and incision could have been a confounding factor in assessing the pain scores. Although an attempt was made to limit the variation between both groups, still some unforeseen bias might have been introduced.
| Conclusion|| |
The study has shown that single dose of gabapentin (600 mg) given orally 2 h before surgery provides better pain control as compared to placebo. It reduces the total analgesic requirement during the postoperative period and delays the onset of pain after the surgery. Gabapentin is an effective tool in the armamentarium of anesthesiologist in the treatment of perioperative pain which can be used as a part of multimodal therapy.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Anand KJ, Craig KD. New perspectives on the definition of pain. Pain 1996;67:3-6.
Kelly DJ, Ahmad M, Brull SJ. Preemptive analgesia I: Physiological pathways and pharmacological modalities. Can J Anaesth 2001;48:1000-10.
Mao J, Chen LL. Gabapentin in pain management. Anesth Analg 2000;91:680-7.
Gilron I. Review article: The role of anticonvulsant drugs in postoperative pain management: A bench-to-bedside perspective. Can J Anaesth 2006;53:562-71.
Hurley RW, Cohen SP, Williams KA, Rowlingson AJ, Wu CL. The analgesic effects of perioperative Gabapentin on postoperative pain: A meta-analysis. Reg Anesth Pain Med 2006;31:237-47.
Bafna U, Rajarajeshwaran K, Khandelwal M, Verma AP. A comparison of effect of preemptive use of oral Gabapentin and pregabalin for acute post-operative pain after surgery under spinal anesthesia. J Anaesthesiol Clin Pharmacol 2014;30:373-7.
] [Full text]
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.
Modak SD, Magar J, Kakad V. Pre-emptive Gabapentin for postoperative pain relief in abdominal hysterectomy. Int J Res Med Sci 2016;4:3755-9.
Pandey CK, Navkar DV, Giri PJ, Raza M, Behari S, Singh RB, et al.
Evaluation of the optimal preemptive dose of Gabapentin for postoperative pain relief after lumbar diskectomy: A randomized, double-blind, placebo-controlled study. J Neurosurg Anesthesiol 2005;17:65-8.
Elazzai H, Atalla R. Evaluation of the optimum preemptive dose of Gabapentin and its postoperative morphine – Sparing effect after debridement of burned patient. Ain Shams J Anesthesiol 2014;7:138-42.
Schmidt PC, Ruchelli G, Mackey SC, Carroll IR. Perioperative gabapentinoids: Choice of agent, dose, timing, and effects on chronic postsurgical pain. Anesthesiology 2013;119:1215-21.
Parikh HG, Dash SK, Upasani CB. Study of the effect of oral Gabapentin used as preemptive analgesia to attenuate post-operative pain in patients undergoing abdominal surgery under general anesthesia. Saudi J Anaesth 2010;4:137-41.
] [Full text]
Khetarpal R, Kataria AP, Bajaj S, Kaur H, Singh S. Gabapentin vs. pregabalin as a premedication in lower limb orthopaedics surgery under combined spinal epidural technique. Anesth Essays Res 2016;10:262-7.
] [Full text]
Vasigh A, Najafi F, Khajavikhan J, Jaafarpour M, Khani A. Comparing Gabapentin and celecoxib in pain management and complications after laminectomy: A randomized double-blind clinical trial. Iran Red Crescent Med J 2016;18:e34559.
Verma A, Arya S, Sahu S, Lata I, Pandey HD, Singh H. To evaluate the role of Gabapentin as preemptive analgesic in patients undergoing total abdominal hysterectomy in epidural anaesthesia. Indian J Anaesth 2008;52:428-31. [Full text]
Turan A, Karamanlioglu B, Memis D, Usar P, Pamukçu Z, Türe M. The analgesic effects of Gabapentin after total abdominal hysterectomy. Anesth Analg 2004;98:1370-3.
Eckhardt K, Ammon S, Hofmann U, Gugeler N, Mikus G. Gabapentin enhances the analgesic effect of morphine in healthy volunteers. Anesth Analg 2000;91:185-9.
Pandey CK, Sahay S, Gupta D, Ambesh SP, Singh RB, Raza M, et al.
Preemptive Gabapentin decreases postoperative pain after lumbar discoidectomy. Can J Anaesth 2004;51:986-9.
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.
Dirks J, Petersen KL, Rowbotham MC, Dahl JB. Gabapentin suppresses cutaneous hyperalgesia following heat-capsaicin sensitization. Anesthesiology 2002;97:102-7.
Fabritius ML, Geisler A, Petersen PL, Nikolajsen L, Hansen MS, Kontinen V, et al.
Gabapentin for post-operative pain management - A systematic review with meta-analyses and trial sequential analyses. Acta Anaesthesiol Scand 2016;60:1188-208.
Lakshmana Rajan KM, Sudhakar DS, Thirunavukarasu T. Efficacy of Gabapentin on combined spinal epidural anesthesia for lower limb orthopedic surgeries. Int Arch Integr Med 2016;8:170-8.
Park M, Jeon Y. Preoperative pregabalin prolongs duration of spinal anesthesia and reduces early postoperative pain: A double-blind, randomized clinical CONSORT study. Medicine (Baltimore) 2016;95:e4828.
Chang CY, Challa CK, Shah J, Eloy JD. Gabapentin in acute postoperative pain management. Biomed Res Int 2014;2014:631756.
Peng PW, Wijeysundera DN, Li CC. Use of Gabapentin for perioperative pain control - A meta-analysis. Pain Res Manag 2007;12:85-92.
Pandey CK, Priye S, Ambesh SP, Singh S, Singh U, Singh PK. Prophylactic Gabapentin for prevention of postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy: A randomized, double-blind, placebo-controlled study. J Postgrad Med 2006;52:97-100.
] [Full text]
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]