Korean J Pain.  2011 Mar;24(1):22-30. 10.3344/kjp.2011.24.1.22.

A Randomised, Placebo-controlled Trial of the Effects of Preoperative Pregabalin on Pain Intensity and Opioid Consumption following Lumbar Discectomy

• Hegarty DA
• Shorten GD

• KMID: 2278093
• DOI: http://doi.org/10.3344/kjp.2011.24.1.22

Abstract

BACKGROUND
Pregabalin has been shown to have analgesic effect in acute pain models. The primary objective was to examine the efficacy a single dose of pregabalin, would have on morphine consumption following lumbar discectomy.
METHODS
With ethical approval a randomized, placebo-controlled prospective trial was undertaken in 32 patients (ASA I-II, 18-65 years) with radicular low back pain for > 3 months undergoing elective lumbar discectomy. Patients received either oral pregabalin 300 mg (PG Group) or placebo (C Group) one hour before surgery. Pain intensity, the accumulative morphine consumption and adverse effects were recorded for 24 hours following surgery. Functional, psychological and quantitative sensory testing were also assessed.
RESULTS
Fourteen patients out of the 32 recruited were randomized to receive pregabalin. Morphine consumption was reduced (absolute difference of 42.3%) between groups with medium effect size. (Mann-Whitney; U = 52.5, z-score= 2.84, P = 0.004, r = 0.14). This was not associated with a significant difference in the incidence of adverse effects between the two groups. The median pain intensity (VAS) on movement was not significantly different between groups.
CONCLUSIONS
A single pre-operative dose of pregabalin (300 mg) did not result in a reduction in pain intensity compared to placebo in this patient cohort but the significant reduction in morphine consumption suggests that a fixed peri-operative dosing regime warrants investigation.

Keyword

morphine consumption; post-operative pain; pregabalin

MeSH Terms

Acute Pain
Cohort Studies
Diskectomy
gamma-Aminobutyric Acid
Humans
Incidence
Low Back Pain
Morphine
Prospective Studies
Pregabalin
Morphine
gamma-Aminobutyric Acid

Figure

• 

  Fig. 1 Flow diagram of patient distribution.

• 

  Fig. 2 This figure represents accumulative 24 hour morphine consumption (mg) in the 24 hours following lumbar discectomy. C group: the placebo, PG group: pregabalin group. Boxes show interquartile ranges and the bars are the 10th and 90th percentiles. Mann-Whitney analysis shows a significant difference in median morphine consumption between the C group and the PG group with medium effect size (r) (U = 52.5, z-score = 2.84, P = 0.004, r = 0.14).

• 

  Fig. 3 Peri-operative pain intensity score (VAS) on movement are showing. Boxes show interquartile ranges and the bars are the 10th and 90th percentiles. Krushall-Wallis testing showed a significant reduction in pain scores within both the PGB group (H(4) = 35.8, P = 0.001) and the placebo group (H(4) = 52.9, P < 0.001). Post hoc Mann-Whitney analysis showed no significant difference between tow groups.

Reference

1. Apfelbaum JL, Chen C, Mehta SS, Gan TJ. Postoperative pain experience: results from a national survey suggest postoperative pain continues to be undermanaged. Anesth Analg. 2003; 97:534–540. PMID: 12873949.

2. Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006; 367:1618–1625. PMID: 16698416.

3. Buvanendran A, Kroin JS, Kari M, Tuman KJ. Can a single dose of 300 mg of pregabalin reach acute antihyperalgesic levels in the central nervous system? Reg Anesth Pain Med. 2010; 35:535–538. PMID: 20975469.

4. Kehlet H, Wilmore DW. Multimodal strategies to improve surgical outcome. Am J Surg. 2002; 183:630–641. PMID: 12095591.

5. Hill CM, Balkenohl M, Thomas DW, Walker R, Mathé H, Murray G. Pregabalin in patients with postoperative dental pain. Eur J Pain. 2001; 5:119–124. PMID: 11465977.

6. Paech MJ, Goy R, Chua S, Scott K, Christmas T, Doherty DA. A randomized, placebo-controlled trial of preoperative oral pregabalin for postoperative pain relief after minor gynecological surgery. Anesth Analg. 2007; 105:1449–1453. PMID: 17959981.

7. Némethy M, Paroli L, Williams-Russo PG, Blanck TJ. Assessing sedation with regional anesthesia: inter-rater agreement on a modified Wilson sedation scale. Anesth Analg. 2002; 94:723–728. PMID: 11867405.

8. Melzack R. The McGill pain questionnaire: from description to measurement. Anesthesiology. 2005; 103:199–202. PMID: 15983473.

9. Ostelo RW, de Vet HC, Knol DL, van den Brandt PA. 24-item Roland-Morris disability questionnaire was preferred out of six functional status questionnaires for post-lumbar disc surgery. J Clin Epidemiol. 2004; 57:268–276. PMID: 15066687.

10. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983; 67:361–370. PMID: 6880820.

11. Bjelland I, Dahl AA, Haug TT, Neckelmann D. The validity of the hospital anxiety and depression scale. An updated literature review. J Psychosom Res. 2002; 52:69–77. PMID: 11832252.

12. Sullivan MJ, Lynch ME, Clark AJ. Dimensions of catastrophic thinking associated with pain experience and disability in patients with neuropathic pain conditions. Pain. 2005; 113:310–315. PMID: 15661438.

13. Agarwal A, Gautam S, Gupta D, Agarwal S, Singh PK, Singh U. Evaluation of a single preoperative dose of pregabalin for attenuation of postoperative pain after laparoscopic cholecystectomy. Br J Anaesth. 2008; 101:700–704. PMID: 18716003.

14. Taylor CP. Mechanisms of analgesia by gabapentin and pregabalin--calcium channel alpha2-delta [Cavalpha2-delta] ligands. Pain. 2009; 142:13–16. PMID: 19128880.

15. Tuchman M, Barrett JA, Donevan S, Hedberg TG, Taylor CP. Central sensitization and Ca(V)α₂ δ ligands in chronic pain syndromes: pathologic processes and pharmacologic effect. J Pain. 2010; 11:1241–1249. PMID: 20472509.

16. 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; 134:106–112. PMID: 17507163.

17. 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; 101:535–541. PMID: 18653493.

18. Buvanendran A, Kroin JS, Della Valle CJ, Kari M, Moric M, Tuman KJ. Perioperative oral pregabalin reduces chronic pain after total knee arthroplasty: a prospective, randomized, controlled trial. Anesth Analg. 2010; 110:199–207. PMID: 19910619.

19. Straube S, Derry S, McQuay HJ, Moore RA. Enriched enrollment: definition and effects of enrichment and dose in trials of pregabalin and gabapentin in neuropathic pain. A systematic review. Br J Clin Pharmacol. 2008; 66:266–275. PMID: 18489611.