|Year : 2014 | Volume
| Issue : 1 | Page : 18-21
The effect of pregabalin for relief of postoperative pain after abdominal hysterectomy
Tashi Chotton, Nongthombam Ratan Singh, Langpolakpam Chaoba Singh, Pradipkumar Singh Laithangbam, Haorongbam Shanti Singh
Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal, Manipur, India
|Date of Web Publication||24-Jun-2014|
Dr. Pradipkumar Singh Laithangbam
Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal, Manipur
Source of Support: None, Conflict of Interest: None
Background: Failure to provide postoperative pain relief is morally and ethically unacceptable. Combination of nonopioid analgesics is being increasingly used to reduce opioid-related side effects. Pregabalin, having an inhibitory modulation of neuronal excitability, is being evaluated in this randomized controlled trial. Materials and Methods: Following institutional ethical clearance, 90 adult females (aged 18-60 years, ASA I and II) undergoing elective abdominal hysterectomy were randomized into two groups (n = 45). Group A patients received pregabalin 150 mg and Group B patients received placebo (vitamin C), 1 h prior to induction of anesthesia. Intraoperative analgesia was provided with paracetamol infusion 1,000 mg over 15 min. Postoperative pain (visual analog scale/VAS), postoperative nausea and vomiting ( four point ordinal scale ) and sedation scale ( Ramsay ) were monitored at 0, 0-4, 4-12, and 12-24 h time intervals. Results: Both static (at rest) and dynamic (during coughing) pain score (VAS) and the consumption of rescue analgesia (ketorolac) were significantly (<0.001) less in the pregabalin group. There were no significant differences in the postoperative nausea and vomiting, and Ramsay sedation scale. Conclusion: Preoperative pregabalin had significant effect in relieving postoperative pain when given as an adjuvant.
Keywords: Abdominal hysterectomy, Postoperative pain, Pregabalin, Placebo
|How to cite this article:|
Chotton T, Singh NR, Singh LC, Laithangbam PS, Singh HS. The effect of pregabalin for relief of postoperative pain after abdominal hysterectomy. J Med Soc 2014;28:18-21
|How to cite this URL:|
Chotton T, Singh NR, Singh LC, Laithangbam PS, Singh HS. The effect of pregabalin for relief of postoperative pain after abdominal hysterectomy. J Med Soc [serial online] 2014 [cited 2020 Oct 20];28:18-21. Available from: https://www.jmedsoc.org/text.asp?2014/28/1/18/135219
| Introduction|| |
Pain is a consistent and predominant complaint of most individuals following surgical interventions. Failure to relieve pain is morally and ethically unacceptable. Adequate pain relief could be considered a basic human right. A visit to most postoperative wards will show the time honored ritual of inadequate postoperative pain management. Patients expect effective postoperative pain relief, and their carers ensure that they are not disappointed.  Effective control of postoperative pain is still a major challenge. It is thought to be inadequately treated in one half of all the surgical procedures. , Proper pain relief is a major concern and area of focus in the medical science. Although opioids continue to play an important role in postoperative pain management, they have their own limitations. Although pain is a predictable part of the postoperative experience, inadequate management of pain is common and can have profound implications. It may result in clinical and psychological changes that increase morbidity and mortality as well as costs and that decrease quality of life. Early postoperative pain is the most common complaint and is one of the primary reasons for prolonged convalescence after surgery.
Consequently, optimal treatment with minimal side effects is essential to allow early mobility, optimal functional recovery, and to reduce postoperative morbidity and mortality. ,
Pregabalin (S-[+]-3 isobutylgaba) was designed as a lipophilic GABA (γ-aminobutyric acid) analog substituted at the '3' position to facilitate diffusion across the blood-brain barrier. It has been shown to be effective in several models of neuropathic pain, incisional injury, inflammatory injury, and formalin induced injury. Though the precise mode of action of pregabalin has not been fully elucidated, it does interact with the same binding site, and has a similar pharmacologic profile but a superior pharmacokinetic profile as gabapentin. Its main site of action appears to be on the (α2 - δ) subunit, and potency, is six times more than that of gabapentin. Pregabalin appears to produce an inhibitory modulation of neuronal excitability, particularly in areas such as the neocortex, amygdala, and hippocampus. It has a role in treating neuropathic pain. 
This study is therefore designed to evaluate the role of single oral dose of pregabalin for attenuating postoperative pain and analgesic consumption in patient undergoing abdominal hysterectomy.
| Materials and Methods|| |
After approval from the Institutional Ethical Committee, 90 patients with ASA physical status I and II, age (18-60 years), normotensive, undergoing abdominal hysterectomy under general anesthesia were enrolled in this randomized clinical trial, single-blinded study.
Patients with impaired kidney or liver functions, history of chronic pain or daily intake of analgesics, uncontrolled medical diseases (diabetes mellitus and hypertension), history of intake of non steroidal anti-inflammatory drugs within 24 h before surgery were excluded from the study. Patients were randomized into two groups of 45 each using lottery method - Group A received pregabalin (150 mg) and Group B received a matching placebo (vitamin C) orally 1 h prior to the induction of anesthesia. Simultaneously, the patients were also premedicated with injection ranitidine 50 mg i.v and inj. Ondansetron 4 mg i.v in the preoperative room.
Patients were induced with propofol 2 mg/kg; orotracheal intubation was facilitated by succinylcholine 1.5 mg/kg, Inj. paracetamol 1,000 mg was infused over 15 min prior to incision for intraoperative pain. Anesthesia was maintained with 66% nitrous oxide in oxygen and traces of isoflurane. At the end of the surgery, residual neuromuscular paralysis was antagonized with neostigmine 0.05 mg/kg and glycopyrrolate 0.005 mg/kg.
Primary outcomes were severity of postoperative pain and postoperative analgesic requirement. Secondary outcomes were incidence and severity of side effects such as postoperative nausea and vomiting (PONV), sedation.
Assessment of pain at rest (static) and during coughing (dynamic) was done by a 100 mm visual analogue scale (VAS); 0, no pain; 100; worst imaginable pain. Assessment of pain was done on the arrival of the patient to the post anesthesia care unit (PACU) (0) and till the end of the study, that is, 24 h after operation. The maximum pain scores at different time intervals[0, 0-4, 4-12, and 12-24 h] for each patient was considered for statistical analysis.
The severity of postoperative nausea and vomiting (PONV)  was graded on four point ordinal scale[0, no nausea or vomiting; 1, mild nausea; 2, moderate nausea; and 3 severe nausea and vomiting].
The rescue anti emetic[ondansetron] and analgesia[ketorolac] were given to patients with PONV of grade >2 and VAS > 40 and the times were noted.
The Ramsay sedation scale  [Awake levels: 1, anxious, agitated, or restless; 2, co-operative, oriented, and tranquil; 3, responds to command; Asleep levels: Dependent on patient's response to a light glabellar tap or loud auditory stimulus; 4 brisk response, 5 a sluggish response; and 6 no response] were used to assess the sedation.
Patient characteristic data were analyzed with t-test for continuous variables and χ2 test for categorical variables. Postoperative analgesic and antiemetic consumption, the VAS pain scores and the incidences of side-effects were analyzed with χ2 test. The package SPSS 16.0 (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. P < 0.05 was considered significant.
| Results|| |
A total of 90 patients enrolled completed the study and there were no substantial differences among the groups with regard to age, weight, sex, duration of anesthesia, duration of surgery (P > 0.05)[Table 1].
Postoperative pain (static and dynamic) and postoperative analgesic consumption were reduced in the pregabalin group when compared with placebo (P < 0.05)[ [Figure 1], [Figure 2] and [Table 2].
|Figure 1: Showing VAS static. Postoperative pain (static) is expressed as median VAS scores. (P value: 0-4 h < 0.001, 4-12 h < 0.001, 12-24 h = 0.013|
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|Figure 2: Showing VAS dynamic. Postoperative pain (dynamic) is expressed as median VAS scores. (P value: 0-4 h < 0.001, 4-12 h < 0.001, 12-24 h = 0.009)|
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There were no significant between two groups (P > 0.05) in the incidence and severity of sedation as shown in [Table 3].
Incidence and severity of PONV, number of patients requiring antiemetics, were similar among the groups (P > 0.05)[Table 4] with no significant difference between the two groups.
| Discussion|| |
We observed that preoperative single-dose pregabalin (150 mg) was effective in reducing both the static and the dynamic components of postoperative pain along with postoperative rescue analgesic consumption 23.33 ± 12.61 (pregabalin group), 90 ± 1 (placebo group) in subjects undergoing abdominal hysterectomy. No significant differences in PONV and Ramsay sedation scale and rescue antiemetic requirement was observed in both the groups. Pregabalin (150 mg) was administered 1 h before the surgery as a protective premedication - by reducing the degree of central sensitization - as the plasma concentration of the drug peaks within 1 h after oral administration. , It also provided analgesic coverage immediately after surgery, where it would be difficult to administer orally during the initial postoperative period.
Pain scores were reduced with a single preoperative dose of pregabalin in our study which is consistent with previous studies. ,,
The incidence of sedation, nausea, and vomiting (P < 0.05, and P = 0.315) showed no significant difference between the groups. The most common side effects of pregabalin are somnolence and dizziness, which occur more frequently at higher doses. ,,, A recent study conducted by White et al.  demonstrated that preoperative pregabalin administration (75-300 mg orally) increased perioperative sedation and dizziness in a dose-related fashion. In this study, the incidence of sedation and dizziness was not significant statistically and it did not hinder pain assessment. This may be because only 150 mg was used, where as studies found more sedation in doses higher than 150 mg. 
It is possible that a larger dose of pregabalin could have more analgesic potency but also more side effects. The most common of these side effects were dizziness, somnolence, and vomiting. In another study, in which a 150 mg dose of pregabalin was compared in combination with celecoxib with both of the analgesics alone after spinal fusion surgery, the incidence of side effects after the combination of pregabalin 150 mg and celecoxib 400 mg was lower than after placebo.  Judging from the results of all these pregabalin trials, it is possible that the concomitant administration of NSAIDs and pregabalin is beneficial as regards the side effect profile of pregabalin. In fact, this finding is in accordance with the original idea of a multimodal analgesic approach.  We administered paracetamol 1,000 mg intraoperatively for both the groups to maintain uniformity and also for intraoperative pain, because the placebo group was devoid of such an analgesic. It may be because of additive paracetamol  that the pregabalin group had better analgesia with minimum sedation and dizziness.
As for postoperative nausea and vomiting, there was no significant difference among the groups (P = 0.315). Dauri et al. worked on gabapentin and pregabalin for postoperative pain management and it was observed that gabapentin and pregabalin reduce pain and opioid consumption after surgery in comparison with placebo but it does not seem to have any influence on the prevention of PONV. The reasons could be that they did not premedicate with antiemetic where as we premedicated the patients with antiemetic 1 h before surgery. We did not use any opioid for rescue analgesia.
Chang et al.  studied on evaluation of perioperative pregabalin for prevention and attenuation of postoperative shoulder pain after laparoscopic cholecystectomy and concluded that the perioperative administration of two doses of pregabalin 300 mg, 12 h apart did not reduce the frequency or severity of post laparoscopic shoulder pain as well as the severity of surgical pain after laparoscopic cholecystectomy rather, it was associated with an increased incidence of undesirable sedation in the early postoperative period. This may be due to the difference in the nature of surgery and another reason could be that central sensitization, a process shown to be reduced by pregabalin, may not be a major mechanism in the development of PLSP.
Paech et al.  studied on a randomized, double blind, parallel group, placebo controlled trial in 90 women having minor gynecological surgery involving the uterus. Patients received either oral pregabalin 100 mg (Group PG) or placebo (Group C) approximately 1 h before surgery and concluded that a single preoperative dose of 100 mg pregabalin does not reduce acute pain or improve recovery after minor surgery involving only the uterus. The difference in the results from our study could possibly be because of the fact that Paech and colleagues administered a smaller dose (100 mg), that is, subtherapeutic dose, against the recommended starting dose of 150 mg. 
| Conclusion|| |
The dose response or the effect of continuation of therapy was not evaluated in the present study. So, conclusion about the optimal dose and duration of treatment could not be made. We therefore, suggest that oral pregabalin 150 mg administered before operation is effective in reducing postoperative pain and requirement of rescue analgesia in patients undergoing abdominal hysterectomy.
| References|| |
|1.||James D, Justins D. Acute post-operative pain. In: Healy TE, Knight PR, editors. Wylie and Churchill Davidson's. A practice of Anaesthesia. 7 th ed. London: Arnold Publishers;2003. p. 1213-34. |
|2.||Agarwal A, Gautam S, Gupta D, Agarwal S, Singh PK, Singh U. Evaluation of single pre-operative dose of pregabalin for attenuation of postoperative pain after laparoscopic cholecystectomy. Br J Anaesth 2008;101:700-4. |
|3.||Gottschalk A, Smith DS. New concepts in acute pain therapy: Preemptive analgesia. Am Fam Physician 2001;63:1979-84. |
|4.||Mathiesen O, Jacobsen LS, Houn 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. |
|5.||Fischer HB, Simansk CJ. A procedure-specific systematic review and consensus recommendations for analgesia after total hip replacement. Anaesthesia 2005;60:1189-202. |
|6.||Gajraj NM. Pregabalin: Its pharmacology and use in pain management. Anaesth Analg 2007;105:1805-15. |
|7.||Kim SY, Jeong JJ, Chung WY, Jookim H, Nan KH, Shim YH. Peri-operative administration of pregabalin for pain after robotic assisted endoscopic thyroidectomy: A randomized clinical trial. Surg Endosc 2010;24:2776-81. |
|8.||Jokela R, Ahonen J, Tallgren M, Haanpaa N, Kortilla K. Premedication with pregabalin 75 or 150mg with ibuprofen to control pain after day-case gynaecological laparoscopic surgery. Br J Anaesth 2008;100:834-40. |
|9.||Baidya DK, Agarwal A, Khanna P, Kumar M. Pregabalin in acute and chronic pain. J Anaesthesiol Clin Pharmacol 2011;27:307-14. |
|10.||Bansal A, Tewari A, Garg S, Gupta A. Pregabalin: Pharmacology and use in pain management. J Anaesth Clin Pharmacol 2009;25:321-6. |
|11.||Ben-Menachem E. Pregabalin pharmacology and its relevance to clinical practice. Epilepsia 2004;45:13-8. |
|12.||White PF, Tutanoqullari B, Taylor J, Klein K. The effect of pregabalin on preoperative anxiety and sedation levels: A dose ranging study. Anaesth Analg 2009;108:1140-5. |
|13.||Reuben SS,Buvanendran A, Kroin JS, Raghunathan K. The analgesic efficacy of celecoxib, pregabalin, and their combination for spinal fusion surgery. Anaesth Analg 2006;103:1271-7. |
|14.||Kehlet H, Dahl JB. The value of "multimodal" or "balanced analgesia" in postoperative pain treatment. Anesth Analg 1993;77:1048-56. |
|15.||Remy C, Marret E, Bonnet F. Effects of acetaminophen on morphine side-effects and consumption after major surgery: Meta-analysis of randomized controlled trials. Br J Anaesth 2004;94:505-13. |
|16.||Dauri M, Faria S, Gatti A, Celidoni L, Carpenido R, Sabato AF. Gabapentin and pregabalin for acute post-operative pain management. A systemic-narrative review of the recent clinical evidences. Curr Drug Targets 2009;10:716-33. |
|17.||Chang SH, Lee HW, Kim HK, Kim SH, Kim DK. An evaluation of perioperative pregabalin for prevention and attenuation of postoperative shoulder pain after laparoscopic cholecystectomy. Anaesth Analg 2009;109:1284-6. |
|18.||Paech MJ, Goy R, Chua S, Scott K, Christmas T, Doherty DA. A randomized placebo- controlled trial of preoperative oral pregabalin for post-operative pain relief after minor gynaecological surgery. Anaesth Analg 2007;105:1449-53. |
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]
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