|Year : 2018 | Volume
| Issue : 4 | Page : 257-260
Effect of preemptive pregabalin for postoperative pain relief in myringoplasty
Ashish Dhakal, Bikash Lal Shrestha, Monika Pokharel, Pradeep Rajbhandari, Sameer Karmacharya
Department of ENT-HNS, Dhulikhel Hospital, Kathmandu University Hospital, Kavre, Nepal
|Date of Web Publication||15-Mar-2019|
Dr. Ashish Dhakal
Department of ENT-HNS, Dhulikhel Hospital, Kathmandu University Hospital, Dhulikhel, Kavre
Source of Support: None, Conflict of Interest: None
Context: Myringoplasty is a common surgical procedure done by ENT surgeons. Postoperative period requires use of analgesics which are being given on a regular basis. Aims: The aim of this study was to investigate the effect of preemptive pregabalin on postoperative pain reduction after endoscopic myringoplasty. Settings and Design: This was a prospective, experimental study conducted in the department of ENT and Head and Neck surgery in Dhulikhel Hospital, Kathmandu University Hospital, Kavre from September 2015 to December 2017. Subjects and Methods: Patient were randomly assigned to one of the two groups with 30 participants each by lottery method. Pregabalin group received capsule pregabalin 150 mg and placebo group were given Vitamin B capsule 1 h before surgery. Statistical Analysis Used: Normally distributed variables were analyzed with the Student's t-test and nonnormally distributed variables with the Mann–Whitney test. SPSS v. 21.0 for Windows (SPSS Inc., Chicago, USA) was used for the statistical data analysis. Results: Pain scores were significantly lower in pregabalin group as compared to placebo group at 6 h (U = 123, P < 0.01), 12 h (U = 107.5, P < 0.01), 24 h (U = 160.5, P < 0.01), and 48 h (U = 121.5, P < 0.01). Number of patients who required rescue analgesics and dosage was lower in pregabalin group than placebo group (P < 0.01). Conclusions: The preemptive administration of single dose of pregabalin 150 mg is an effective way to reduce postoperative pain and analgesic consumption in patients undergoing endoscopic myringoplasty.
Keywords: Endoscopic ear surgery, myringoplasty, postoperative analgesia, preemptive analgesia, pregabalin
|How to cite this article:|
Dhakal A, Shrestha BL, Pokharel M, Rajbhandari P, Karmacharya S. Effect of preemptive pregabalin for postoperative pain relief in myringoplasty. Indian J Otol 2018;24:257-60
|How to cite this URL:|
Dhakal A, Shrestha BL, Pokharel M, Rajbhandari P, Karmacharya S. Effect of preemptive pregabalin for postoperative pain relief in myringoplasty. Indian J Otol [serial online] 2018 [cited 2019 Aug 22];24:257-60. Available from: http://www.indianjotol.org/text.asp?2018/24/4/257/254238
| Introduction|| |
Preemptive analgesia can reduce pain in immediate postoperative period and prevent the development of chronic pain by decreasing the altered central sensory processing. Premedication with gabapentinoid drugs (gabapentin and pregabalin) has been found to decrease postoperative pain and reduce opioid consumption in patients undergoing major surgeries.,,,,,,,,
Pregabalin is a structural analog of gamma-aminobutyric acid, which shows analgesic, anticonvulsant, and anxiolytic effects. Its role in the control of neuropathic pain is by presynaptic binding to the alpha2-delta subunit of voltage-dependent calcium channels that are widely distributed in the spinal cord and brain. It is rapidly absorbed with peak blood concentration reaching in 1 h. It does not undergo hepatic metabolism, and 98% of the absorbed drug is excreted unchanged in urine.,,
Myringoplasty is a common surgical procedure done by ENT surgeons. Postoperative period requires use of analgesics which are being given on a regular basis.
The aim of this study is to assess the efficacy of single dose of preemptive pregabalin in reducing postoperative pain in patients following myringoplasty. This type of study has not been done for endoscopic myringoplasty; so, it would be a new knowledge to share.
| Subjects and Methods|| |
This was a prospective, experimental study conducted in the Department of Otorhinolaryngology and Head and Neck surgery from September 2015 to December 2017. Approval from Institutional Review Committee of Kathmandu University School of Medical Sciences, Dhulikhel Hospital was taken, and informed consent was obtained from the patient.
Patients were randomly assigned to one of the two groups with 30 participants each by lottery method. Pregabalin group received capsule pregabalin 150 mg and placebo group were given Vitamin B capsule 1 h before surgery.
Clinical examinations (general ENT examination, microscopic examination of ear, tuning fork tests) were done and hearing assessment was performed with pure tone audiometry. All the patients were made familiar with a standard 10 cm visual analog scale (VAS) on preoperative visit, in which 0 represents no pain at all and 10 represents the worst pain imaginable.
Inclusion criteria – cases of chronic otitis media mucosal inactive planned for endoscopic myringoplasty under local anesthesia and age ≥18 years of either sex.
Exclusion criteria – revision cases, pregnancy or breastfeeding, known or suspected sensitivity or contraindication to pregabalin, patient using medication for chronic pain, history of seizure disorder, and mental retardation.
All patients underwent endoscopic myringoplasty with tragal cartilage and perichondrium graft. Surgical procedure was done under local anesthesia. 5 ml of 2% xylocaine with 1:200,000 adrenalin was infiltrated in the four quadrants of external ear canal and on tragus. Around 2 cm incision was given on canal surface of tragus and around 1.5 cm × 1.5 cm cartilage-perichondrium graft was obtained. The skin was closed with 4/0 prolene interrupted suture. Using rigid Hopkins II 0-degree endoscope (Karl Storz) with 4-millimeter diameter and 18-centimeter length, margin of perforation was refreshed. Gelatin sponge was kept in the middle ear and cartilage perichondrium graft was placed. The canal was then packed with gelatin soaked in ciprofloxacin ear drops followed by ribbon pack medicated with soframycin. Small dressing was applied over it.
Postoperative pain severity was assessed with VAS scale at 6, 12, 24, and 48 h. Rescue analgesia is given with injection ketorolac (30 mg IV) or tablet flexon (ibuprofen 400 mg + paracetamol 500 mg) whenever the patient required. Side effects (nausea, vomiting, headache, and dizziness), if present, were noted.
The Shapiro–Wilk test was used to check the normality of the quantitative data distribution. Normally distributed variables were analyzed with the Student's t-test and nonnormally distributed variables with the Mann–Whitney test. SPSS v. 21.0 for Windows (SPSS Inc., Chicago, USA) was used for the statistical data analysis.
| Results|| |
A total of 60 patients were enrolled in the study with 30 each in pregabalin and placebo group with age ranging from 18 to 57 years (mean age of 28.52 ± 9.9 years). There were total 29 males (48.3%) and 31 females (51.7%) in the study. In placebo group, there were 16 males and 14 females, and in pregabalin group, there were 13 males and 17 females [Table 1].
Pain score was recorded with VAS at 6, 12, 24, and 48 h postoperatively. At 6 h postoperatively, the mean VAS was 2.33 ± 1.32 in pregabalin group and 4.53 ± 1.432 in placebo group (U = 123, P < 0.01). At 12-h postoperative, the score was 1.93 ± 1.41 in pregabalin group and 4.03 ± 1.06 in placebo group (U = 107.5, P < 0.01). At 24-h postoperative, scores were 1.77 ± 1.27 in pregabalin group and 3.33 ± 1.06 in placebo group (U = 160.5, P < 0.01). Similarly, at 48-h postoperative, scores were 1.4 ± 1.16 in pregabalin group and 2.8 ± 0.84 in placebo group (U = 121.5, P < 0.01) [Figure 1].
|Figure 1: Distribution of postoperative pain score in pregabalin and placebo group|
Click here to view
The number of rescue analgesics used during hospitalization was lower in the pregabalin group than placebo group (P < 0.01). About 86.7% of placebo group required flexon and 10% required both flexon and ketorolac whereas 53.3% of pregabalin group did not require any postoperative analgesia, 43.3% required flexon, and 3.3% required both [Figure 2].
|Figure 2: Requirement of rescue analgesic is low in pregabalin group than placebo group|
Click here to view
The incidence of mild postoperative nausea was present in 6 cases belonging to the pregabalin group.
| Discussion|| |
Management of pain in the postoperative period is important for decreasing patient morbidity and pain-related clinical complications. Opioid and nonopioid analgesics are widely used to treat postoperative pain but the use of opioids is associated with significant side effects such as nausea, vomiting, sedation, and respiratory depression.
Tissue damage leads to sensitization of peripheral and central pain pathways due to transmission of pain signals. After activation of these pathways, a barrage of pain signals from the nociceptors leads to prolonged alterations in pain and touch sensation. Pain signals are amplified (hyperalgesia), and pressure signals are interpreted not as touch, but as pain (allodynia). Preemptive analgesia is the treatment which is initiated before a surgical procedure that reduces this sensitization thus decreasing pain severity and duration. Woolf, in 1983, was the first one to introduce preemptive analgesia.
Although both gabapentin and pregabalin were first identified as treatments for neuropathic pain, pregabalin has been reported to be as effective for acute postoperative pain control as gabapentin.,,,,,,
Recently, an increasing number of studies are focusing on the preemptive analgesic use of gabapentin or pregabalin for postoperative pain relief in varied surgical methods.,,,,,,
In these mechanisms, Dahl et al. suggest that a transient or reversible type of neuropathic pain plays a significant role in postoperative pain. This may explain why gabapentin and pregabalin, commonly used to treat chronic neuropathic pain, are effective for controlling postoperative pain.
In this study, we administered pregabalin 150 mg orally at 1 h before surgery. Postoperative pain was assessed with the help of VAS at 6, 12, 24, and 48 h postoperatively.
A meta-analysis done by Lam et al. showed 6 studies in ENT with a total of 265 patients taking pregabalin and 266 patients on the control treatment in this group. Pregabalin reduced the pain score at rest 2 h postoperatively (P < 0.0001) and pain score at rest at 24 h postoperatively. No statistically significant reduction in morphine-equivalent consumption was seen (P = 0.568).
Jadeja et al. in their case–control study of elective middle ear surgery with single dose of preemptive pregabalin found improved analgesia in the early postoperative period.
Demirhan et al., Kim et al., and Sagit et al. in their surgeries of the nose (septoplasty and rhinoplasty) found similar reductions of pain scores postoperatively with different preemptive doses of pregabalin.,,,
Mathiesen et al. suggested pregabalin and pregabalin + dexamethasone reduced postoperative pain scores and consumption of ketobemidone following tonsillectomy.
In our study, rescue analgesia was given for postoperative pain with injection ketorolac (30 mg IV) or table flexon (ibuprofen 400 mg + paracetamol 500 mg) whenever the patient required. The postoperative analgesic consumption was significantly reduced. Fifty-three percent of patients did not require additional analgesics in the postoperative period.
Similarly, in our study, the only side effect present in pregabalin group was postoperative nausea which was present in 6 cases (20%) but was of mild grade not requiring medications.
Jadeja et al. in their study of middle ear surgeries found statistically significant sedation in early postoperative period in the pregabalin group.
| Conclusions|| |
Our study demonstrated that premedication with single dose of oral pregabalin (150 mg) was effective in reducing postoperative pain and analgesic requirement in the patient undergoing myringoplasty, with tolerable side effects.
We would like to thank Dr. Pratiksha Pathak for help in statistical analysis.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Woolf CJ, Chong MS. Preemptive analgesia – Treating postoperative pain by preventing the establishment of central sensitization. Anesth Analg 1993;77:362-79.
Agarwal A, Gautam S, Gupta D, Agarwal S, Singh PK, Singh U, et al.
Evaluation of a single preoperative dose of pregabalin for attenuation of postoperative pain after laparoscopic cholecystectomy. Br J Anaesth 2008;101:700-4.
Jokela R, Ahonen J, Tallgren M, Haanpää M, Korttila K. A randomized controlled trial of perioperative administration of pregabalin for pain after laparoscopic hysterectomy. Pain 2008;134:106-12.
Jokela R, Ahonen J, Tallgren M, Haanpää M, Korttila K. Premedication with pregabalin 75 or 150 mg with ibuprofen to control pain after day-case gynaecological laparoscopic surgery. Br J Anaesth 2008;100:834-40.
Kim SY, Jeong JJ, Chung WY, Kim HJ, Nam KH, Shim YH, et al.
Perioperative administration of pregabalin for pain after robot-assisted endoscopic thyroidectomy: A randomized clinical trial. Surg Endosc 2010;24:2776-81.
Kim SY, Song JW, Park B, Park S, An YJ, Shim YH, et al.
Pregabalin reduces post-operative pain after mastectomy: A double-blind, randomized, placebo-controlled study. Acta Anaesthesiol Scand 2011;55:290-6.
Mathiesen O, Jacobsen LS, Holm HE, Randall S, Adamiec-Malmstroem L, Graungaard BK, et al.
Pregabalin and dexamethasone for postoperative pain control: A randomized controlled study in hip arthroplasty. Br J Anaesth 2008;101:535-41.
Pandey CK, Priye S, Singh S, Singh U, Singh RB, Singh PK, et al.
Preemptive use of gabapentin significantly decreases postoperative pain and rescue analgesic requirements in laparoscopic cholecystectomy. Can J Anaesth 2004;51:358-63.
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.
Durmus M, Kadir But A, Saricicek V, Ilksen Toprak H, Ozcan Ersoy M. The post-operative analgesic effects of a combination of gabapentin and paracetamol in patients undergoing abdominal hysterectomy: A randomized clinical trial. Acta Anaesthesiol Scand 2007;51:299-304.
Field MJ, Cox PJ, Stott E, Melrose H, Offord J, Su TZ, et al.
Identification of the alpha2-delta-1 subunit of voltage-dependent calcium channels as a molecular target for pain mediating the analgesic actions of pregabalin. Proc Natl Acad Sci U S A 2006;103:17537-42.
Dirks J, Møiniche S, Hilsted KL, Dahl JB. Mechanisms of postoperative pain: Clinical indications for a contribution of central neuronal sensitization. Anesthesiology 2002;97:1591-6.
Dworkin RH, Backonja M, Rowbotham MC, Allen RR, Argoff CR, Bennett GJ, et al.
Advances in neuropathic pain: Diagnosis, mechanisms, and treatment recommendations. Arch Neurol 2003;60:1524-34.
Woolf CJ. Evidence for a central component of post-injury pain hypersensitivity. Nature 1983;306:686-8.
Dahl JB, Mathiesen O, Møiniche S. 'Protective premedication': An option with gabapentin and related drugs? A review of gabapentin and pregabalin in in the treatment of post-operative pain. Acta Anaesthesiol Scand 2004;48:1130-6.
Reuben SS, Buvanendran A, Kroin JS, Raghunathan K. The analgesic efficacy of celecoxib, pregabalin, and their combination for spinal fusion surgery. Anesth Analg 2006;103:1271-7.
Freedman BM, O'Hara E. Pregabalin has opioid-sparing effects following augmentation mammaplasty. Aesthet Surg J 2008;28:421-4.
Mathiesen O, Rasmussen ML, Dierking G, Lech K, Hilsted KL, Fomsgaard JS, et al.
Pregabalin and dexamethasone in combination with paracetamol for postoperative pain control after abdominal hysterectomy. A randomized clinical trial. Acta Anaesthesiol Scand 2009;53:227-35.
Mathiesen O, Møiniche S, Dahl JB. Gabapentin and postoperative pain: A qualitative and quantitative systematic review, with focus on procedure. BMC Anesthesiol 2007;7:6.
Tiippana EM, Hamunen K, Kontinen VK, Kalso E. Do surgical patients benefit from perioperative gabapentin/pregabalin? A systematic review of efficacy and safety. Anesth Analg 2007;104:1545-56.
Turan A, Memiş D, Karamanlioǧlu B, Yaǧiz R, Pamukçu Z, Yavuz E, et al.
The analgesic effects of gabapentin in monitored anesthesia care for ear-nose-throat surgery. Anesth Analg 2004;99:375-8.
Lam DM, Choi SW, Wong SS, Irwin MG, Cheung CW. Efficacy of pregabalin in acute postoperative pain under different surgical categories: A Meta-analysis. Medicine (Baltimore) 2015;94:e1944.
Jadeja CA, Khatri H, Oza V, Parmar V. Comparative study of single dose pre-emptive pregabalin vs. Placebo for post-operative pain relief in middle ear surgery. Int J Biomed Adv Res. 2014;5:170-3.
Sagit M, Yalcin S, Polat H, Korkmaz F, Cetinkaya S, Somdas MA, et al.
Efficacy of a single preoperative dose of pregabalin for postoperative pain after septoplasty. J Craniofac Surg 2013;24:373-5.
Kim JH, Seo MY, Hong SD, Lee J, Chung SK, Kim HY, et al.
The efficacy of preemptive analgesia with pregabalin in septoplasty. Clin Exp Otorhinolaryngol 2014;7:102-5.
Demirhan A, Tekelioglu UY, Akkaya A, Bilgi M, Apuhan T, Karabekmez FE, et al.
Effect of pregabalin and dexamethasone addition to multimodal analgesia on postoperative analgesia following rhinoplasty surgery. Aesthetic Plast Surg 2013;37:1100-6.
Demirhan A, Akkaya A, Tekelioglu UY, Apuhan T, Bilgi M, Yurttas V, et al.
Effect of pregabalin and dexamethasone on postoperative analgesia after septoplasty. Pain Res Treat 2014;2014:850794.
Mathiesen O, Jørgensen DG, Hilsted KL, Trolle W, Stjernholm P, Christiansen H, et al.
Pregabalin and dexamethasone improves post-operative pain treatment after tonsillectomy. Acta Anaesthesiol Scand 2011;55:297-305.
[Figure 1], [Figure 2]