Single-dose preemptive pregabalin is used as an adjuvant to control acute and chronic postoperative pain but its effect is unclear. Pregabalin is a structural γ-aminobutyric acid analogue. Its mechanism of action is not fully understood. Recent studies have shown that pregabalin might have a role in postoperative pain management.1 Each year, approximately 20 000 000 inguinal hernia repairs are performed worldwide. Meshes, which are used in hernia repair, may lead to both acute and chronic pain development by increasing the inflammatory response.2 The aim of this study was to investigate the effects of a single-dose preemptive pregabalin on the duration of postoperative analgesia, opioid consumption and chronic pain in patients who had undergone inguinal hernia repair with mesh under spinal anaesthesia.
After obtaining approval of the ethics committee (ethical approval provided by the Ethical Committee of Ataturk University Hospitals, Erzurum, Turkey, on 24 April 2014), 60 patients, aged between 18 and 65 years, scheduled to undergo inguinal hernia repair with mesh under spinal anaesthesia and American Society of Anesthesiologists (ASA) physical status I to II, were included in the study. This study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN): (ACTRN1265000435583). The study was planned to be randomised and double blind. Written informed consent was obtained from all patients.
Exclusion criteria were as follows: ASA III and over; allergy to pregabalin; use of antiepileptic drugs; severe hepatic or renal failure; history of long-term usage of nonsteroidal anti-inflammatory and opioid analgesics; diabetes mellitus and other neuropathic disorders; and contraindications to spinal anaesthesia.
Patients were randomly divided into two groups by using randomisation software. In the pregabalin group (group pregabalin, n = 30), 150 mg pregabalin (Alyse, Abdi Ibrahim, Turkey) was administered orally, 1 h before the operation; in the other group (group placebo, n = 30), the placebo capsule, prepared by emptying the contents of the same pharmaceutical, was given.
In the sitting position, through the L3-L4 or L4-L5 space, by using a 25-gauge pencil point spinal needle (Egemen, Izmir, Turkey), heavy bupivacaine (Marcaine Spinal Heavy, Astra Zeneca, Istanbul, Turkey) 3 ml/15 mg was injected into the subarachnoidal space over 30 s. After 5 min, the patients were placed in the supine position. All operations were performed by the same surgeon and the same technique, using Ethicon polypropylene knitted non-absorbable mesh. Two ml/50 mg dexketoprofen trometamol (Arveles ampule, I.E. Ulagay, Istanbul, Turkey) was administered intravenously, 30 min before the end of the operation and at postoperative 12th hour again in all patients. A Patient Controlled Analgesia device, prepared with fentanyl, was started in the postoperative recovery room and it was programmed as 10 μg concentration, 10 min lockout interval, 25 μg bolus dose and without baseline infusion; it was continued for 24 h.
Postoperative analgesia was assessed by using visual analogue scale (VAS) during resting and active movement (VAS 0 = no pain, VAS 10 = the most severe pain that can be imagined). Active movement was defined as moving from a lying to a sitting position. In patients with VAS scores 4 and over, rescue analgesia was given using 50 mcg fentanyl. Sedation, confusion, dizziness, headache, dry mouth, nausea, vomiting, pruritis, peripheral oedema and diplopia were recorded.
Postoperative chronic pain was assessed by telephone calls to the patients made by an anaesthesiologist at postoperative first, third and sixth months and by using numerical rating scale (NRS) (NRS 0 = no pain, NRS 10 = worst possible pain). Patients with NRS above 3 were considered to have chronic pain.
The primary outcome of the study was the total dose of fentanyl consumption in the 24-h postoperative period. In our preliminary study, we found that the SD was 201.71 in group pregabalin and 289.59 in group placebo. We aimed to detect a difference between the two groups was at least 200 μg fentanyl consumption in the 24-h postoperative period. Accordingly, we determined that the number of patients required in every group was 30, based on power of 86%, the α error of 0.05 by using Russ Lenth's Piface Java module (Piface by Russell V. Lenth Version 1.76).
IBM SPSS 20.0 (SPSS Inc., Chicago, Illinois, USA) software program was used to perform the statistical analysis. The distribution of the variables was evaluated for normality using the Kolmogorov–Smirnov test. Descriptive statistics were expressed as mean ± SD. Categorical variables were analysed using the χ2 test. The normally distributed data comprising continuous variables were analysed using Student's t test. Otherwise, the Mann–Whitney U test was used. A value of P less than 0.05 was considered statistically significant.
When compared with the placebo group, VAS values with active and passive movement were statistically significantly lower at 4, 8, 12 and 24 h in the pregabalin group (P < 0.05) (Fig. 1). The 24-h opioid consumption was statistically significantly higher in the placebo group when compared with the pregabalin group (481.33 ± 276.03 and 295.00 ± 213.79 μg, P = 0.005, respectively). Duration of postoperative analgesia was 354.00 ± 150.59 min in the pregabalin group and 243.00 ± 113.71 min in the placebo group (P = 0.02). There were no differences between groups in terms of side-effects. When groups were compared in terms of chronic pain, there were no statistically significant differences at one, three and six months.
There are various reports showing pregabalin efficacy in the prevention of postoperative pain in various doses and surgeries.1,3 Our study has shown that pregabalin administered prior to spinal anaesthesia increased the duration of post-spinal analgesia. This result supports the publications that have reported extended durations of post-spinal analgesia.4
The role of pregabalin in the prevention of chronic postoperative pain is controversial. Although some authors5,6 have reported that pregabalin had no role in prevention of chronic pain, other authors have claimed that preemptive pregabalin prevented the development of chronic pain.7 We found no significant difference between the two groups in terms of the development of chronic pain in our study.
In conclusion, administration of preemptive pregabalin with a single dose of 150 mg prior to spinal anaesthesia in patients undergoing inguinal hernia repair with mesh reduced their opioid consumption by 38% in the first postoperative 24 h. It also prolonged the post-spinal analgesia period. However, it was found to have no effect on preventing the development of chronic pain following surgery for inguinal hernia.
Acknowledgements relating to this article
Assistance with the study: none.
Financial support and sponsorship: none.
Conflicts of interest: none.
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