MODERATE RECOMMENDATION The Pregabalin recommendation has been downgraded one level because of inconsistent evidence.
Single Dose:
Lee (TKA & THA) 43 min, Omara (femur fracture with intramedullary nail) 140 min, Sebastian (“lower limb orthopedic surgeries”) 70 min, Ahn (arthroscopic shoulder surgery) decreased incidence at 24 hr (40% vs. 13%) and 48 hr (40% vs. 10%) of rescue IV ketorolac in control vs. pregabalin group respectively. Line 2000 – Lee, Omara, Sebastian – same study population as above for line 1997. Lee regression of sensory & motor block was 15 min and 11 min longer for pregabalin, respectively; Omara regression of sensory & motor block was 14 min and 15 min longer for pregabalin, respectively; Sebastian regression of sensory block was 20 min longer for pregabalin. For Rahat the population was “orthopedic surgeries for tibial fractures” and the “duration for analgesia” was 148 min longer for the pregabalin group.
Three high quality (Lee, 2018; Omara, 2019; Sebastian, 2016) studies and one moderate quality (Rahat, 2018) study found an increased duration of spinal anesthetic. Omara and Lee also found an increased duration of motor block.
Lee, Ahn, Omara population groups (orthopaedic surgeries) are all the same as previously listed. The only new study is Akhavanakbari with a study population only detailed as “lower limb orthopedic surgery.
Three high quality studies (Lee, 2018; Ahn, 2016; Akhavanakbari, 2013) found improved pain scores on VAS or NRS.
Omara (2019) found sleep quality was improved in the first 24 hours as a secondary outcome.
Significant side effects included dizziness (Rahat, 2018, Akhavanakbari, 2013; Sebastian, 2016), sedation (Sebastian, 2016; Lee, 2018), hypotension (Sebastian, 2016), and blurred vision (Lee, 2018).
Multi-dose:
Two high quality studies (Clarke, 2015; Cho, 2019) and one moderate quality study (Eskander, 2013) of multi-dose pregabalin found that pain was lower on post-op day 7 by numerical rating scale, 14 days by visual analogue scale (VAS), and through 8 hours by VAS in TKA, ACL, and shoulder arthroscopy cohorts respectively. However, pain in the Clarke study in a TKA population was a secondary outcome measure.
One high quality study (Buvanendran, 2015) suggests improvement in neuropathic pain at 3 and 6 months (primary measure) and sleep quality in the first 24 hours (secondary measure) with multi-dose pregabalin in a TKA population.
Two high quality studies (Buvanendran, 2015; Singla, 2015) suggest multidose pregabalin may increase ROM in the first 30 and 3 days respectively (secondary measures) in a TKA population.
Two high quality (Clarke, 2015; Singla, 2015) studies in TKA populations and one moderate quality (Eskandar 2013) study in shoulder arthroplasty found a decrease in opioid consumption within the first week in pregabalin groups on secondary measures.
One high quality study (Yik, 2019) found no difference in any primary (morphine equivalents) or secondary (VAS, ROM, KSS, WOMAC, SF-36) measures in a TKA population.
Feasibility
Pregabalin is NOT FDA approved for perioperative use.
Future Research
The literature would benefit from high level studies addressing outcomes on function, standardization of dosing (timing, strength and duration), as well has having non-industry backed studies as 3 studies (Bhuvanendran, 2010; Clarke, 2015; Signla, 2015) with supportive findings disclosed industry support. Many of the statistically significant findings in support of pregabalin were in secondary measures. These findings need to be replicated in studies powered with these outcomes as primary measures.
- Ahn, S., Byun, S. H., Park, K., Ha, J. L., Kwon, B., Kim, J. C. Analgesic efficacy of preemptive pregabalin administration in arthroscopic shoulder surgery: a randomized controlled trial. Can J Anaesth 2016; 3: 283-9
- Akhavanakbari, G., Entezariasl, M., Isazadehfar, K., Mirzarahimi, T. The effects of oral pregabalin on post-operative pain of lower limb orthopedic surgery: A double-blind, placebo-controlled trial. Perspect Clin Res 2013; 3: 165-8
- Buvanendran, A., Kroin, J. S., Della Valle, C. J., Kari, M., Moric, M., Tuman, K. J. Perioperative oral pregabalin reduces chronic pain after total knee arthroplasty: a prospective, randomized, controlled trial. Anesth Analg 2010; 1: 199-207
- Cho, E. A., Kim, N., Lee, B., Song, J., Choi, Y. S. The Effect of Perioperative Pregabalin on Pain after Arthroscopic Anterior Cruciate Ligament Reconstruction: A Randomized Controlled Trial. J Clin Med 2019; 9:
- Clarke, H., Page, G. M., McCartney, C. J., Huang, A., Stratford, P., Andrion, J., Kennedy, D., Awad, I. T., Gollish, J., Kay, J., Katz, J. Pregabalin reduces postoperative opioid consumption and pain for 1 week after hospital discharge, but does not affect function at 6 weeks or 3 months after total hip arthroplasty. Br J Anaesth 2015; 6: 903-11
- Eskandar, A. M., Ebeid, A. M. Effect of pregabalin on postoperative pain after shoulder arthroscopy. Egyptian Journal of Anaesthesia 2013; 4: 363-367
- Lee, C., Lee, J., Lee, G., Lee, H., Koh, E., Hwang, J. Pregabalin and Dexmedetomidine Combined for Pain After Total Knee Arthroplasty or Total Hip Arthroplasty Performed Under Spinal Anesthesia. Orthopedics 2018; 6: 365-370
- Omara, A. F., Ahmed, S. A., Abusabaa, M. M. The Effect Of The Use Of Pre-Emptive Oral Pregabalin On The Postoperative Spinal Analgesia In Patients Presented For Orthopedic Surgeries: Randomized Controlled Trial. J Pain Res 2019; 0: 2807-2814
- Rahat Dahmardeh, A., Moosavi, A., Nasir-Al-Din Tabatabaei, S. M., Ordoni Avval, J., Sistanizad, M. The Effect of a Single Dose Oral Pregabalin on Hemodynamic Changes and Duration of Analgesia after Spinal Anesthesia in Orthopedic Surgeries of Tibial Fractures. Iran J Pharm Res 2018; 0: 2-7
- Sebastian, B., Talikoti, A. T., Nelamangala, K., Krishnamurthy, D. Effect of Oral Pregabalin as Preemptive Analgesic in Patients Undergoing Lower Limb Orthopedic Surgeries under Spinal Anaesthesia. J Clin Diagn Res 2016; 7: Uc01-4
- Singla, N. K., Chelly, J. E., Lionberger, D. R., Gimbel, J., Sanin, L., Sporn, J., Yang, R., Cheung, R., Knapp, L., Parsons, B. Pregabalin for the treatment of postoperative pain: results from three controlled trials using different surgical models. J Pain Res 2015; 0: 9-20
- Yik, J. H., Tham, W. Y. W., Tay, K. H., Shen, L., Krishna, L. Perioperative pregabalin does not reduce opioid requirements in total knee arthroplasty. Knee Surg Sports Traumatol Arthrosc 2019; 7: 2104-2110