Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

High dose nonsteroidal anti-inflammatory drugs compromise spinal fusion

De fortes doses d’anti-inflammatoires non stéroïdiens compromettent l’arthrodèse vertébrale

  • 988 Accesses

  • 84 Citations

Abstract

Purpose

Although nonsteroidal anti-inflammatory drugs (NSAIDs) provide benefit to patients following spinal fusion surgery, their routine administration has remained controversial due to concerns about possible deleterious effects on bone healing. The goal of this retrospective study was to assess the incidence of non-union following the perioperative administration of ketorolac, celecoxib, or rofecoxib.

Methods

We retrospectively analyzed the data of 434 patients receiving perioperative ketorolac (20–240 mg·day-1), celecoxib (200–600 mg·day-1), rofecoxib (50 mg·day-1), or no NSAIDs in the five days following spinal fusion surgery.

Results

There were no significant differences in the incidence of non-union among the groups that received no NSAIDs (11/130; 8.5%), celecoxib 5/60; 8.3%), or rofecoxib (9/124; 7.3%). In contrast, 23/120 of patients (19.2%) that received ketorolac had a higher incidence (P < 0.001) of non-union compared to non-NSAID users. However, only 3/50 patients (6%) receiving low-dose ketorolac (≤110 mg·day-1) resulted in non-union which was not significantly different from non-NSAID users. Patients administered higher doses of ketorolac (120–240 mg·day-1) resulted in a higher incidence (P < 0.0001) of non-union (20/70; 29%) compared to non-NSAID users. For those patients developing non-union, there was a higher incidence comparing smokers vs non-smokers (P < 0.0001) and one level fusion vs two level fusions (P < 0.001).

Conclusions

This study revealed that the short-term perioperative administration of celecoxib, rofecoxib, or low-dose ketorolac (≤ 110 mg·day-1) had no significant deleterious effect on non-union. In contrast, higher doses of ketorolac (120–240 mg·day-1), history of smoking, and two level vertebral fusions resulted in a significant increase in the incidence of non-union following spinal fusion surgery.

Résumé

Objectif

Les anti-inflammatoires non stéroïdiens (AINS) sont bénéfiques après une arthrodèse vertébrale, mais leur administration régulière demeure controversée à cause des effets nuisibles possibles sur la cicatrisation de l’os. Notre étude rétrospective voulait évaluer l’incidence d’absence de fusion à la suite de l’administration périopératoire de kétorolac, célécoxib ou rofécoxib.

Méthode

Nous avons procédé à l’analyse rétrospective de données sur 434 patients qui ont reçu du kétorolac (20–240 mg·jour-1), du célécoxib (200–600 mg·jour-1), du rofécoxib (50 mg·jour-1) ou aucun AINS dans les cinq jours suivant une arthrodèse vertébrale.

Résultats

L’incidence d’absence de fusion osseuse n’était pas significativement différente entre les patients sans AINS (11/130 ; 8,5 %) et ceux qui ont eu du célécoxib 5/60 ; 8,3 %) ou du rofécoxib (9/124 ; 7,3 %). Par ailleurs, 23/120 des patients (19,2 %) qui ont reçu le kétorolac ont présenté une incidence plus élevée (P < 0,001) d’absence de fusion en comparaison de ceux qui ont pris des AINS. Seulement 3/50 patients (6 %) recevant de faibles doses de kétorolac (≤ 110 mg·jour-1) ont présenté une absence de fusion, ce qui n’est pas significativement différent des non-utilisateurs d’AINS. Des doses plus élevées de kétorolac (120–240 mg·jour-1), comparées aux non-AINS, ont provoqué une plus haute incidence (P < 0,0001) d’absence de fusion (20/70 ; 29 %). L’incidence d’absence de fusion était plus élevée si on compare les fumeurs vs les non-fumeurs (P < 0,0001) et la fusion à un niveau vs à deux niveaux (P < 0,001).

Conclusion

L’étude a révélé que l’administration périopératoire à court terme de célécoxib, de rofécoxib ou de faibles doses de kétorolac (≤ 110 mg·jour-1) n’a pas d’effet nuisible significatif sur l’absence de fusion. Par contre, des doses plus élevées de kétorolac (120–240 mg·jour-1), le tabagisme et des fusions vertébrales à deux niveaux augmentent significativement l’incidence d’absence de fusion à la suite d’une arthrodèse vertébrale.

References

  1. 1

    McCormack K. Non-steroidal anti-inflammatory drugs and spinal nociceptive processing. Pain 1994; 59:9–43.

  2. 2

    Souter AJ, Fredman B, White PF. Controversies in the perioperative use of nonsteroidal antiinflammatory drugs. Anesth Analg 1994; 79:1178–90.

  3. 3

    Dahl JB, Kehlet H. Non-steroidal anti-inflammatory drugs: rationale for use in severe postoperative pain. Br J Anaesth 1991; 66:703–12.

  4. 4

    U.S. Department of Health and Human Services. Acute Pain Management Guideline Panel. Acute pain management: operative or medical procedures and trauma. Clinical practice guideline. AHCPR Pub. No. 92-0032. Rockville, MD: Agency for Health Care Policy and Research, Public Health Service, 1992; Feb: 15–26.

  5. 5

    Ashburn MA, Caplan RA, Carr DB, et al. Practice guidelines for acute pain management in the perioperative setting. An updated report by the American Society of Anesthesiologists Task Force on acute pain management. Anesthesiology 2004; 100:1573–81.

  6. 6

    Kehlet H, Dahl JB. The value of “multimodal” or “balanced Analgesia” in postoperative pain treatment. Anesth Analg 1993; 77:1048–6.

  7. 7

    Kehlet H, Wilmore DW. Multimodal strategies to improve surgical outcome. Am J Surg 2002; 183:630–41.

  8. 8

    Kinsella J, Moffat AC, Patrick JA, Prentice JW, McArdle CS, Kenny GN. Ketorolac trometamol for postoperative analgesia after orthopaedic surgery. Br J Anaesth 1992; 69:19–22.

  9. 9

    Reuben SS, Connelly NR, Steinberg R. Ketorolac as an adjunct to patient-controlled morphine in postoperative spine surgery patients. Reg Anesth 1997; 22:343–6.

  10. 10

    Reuben SS, Connelly NR, Lurie S, Klatt M, Gibson CS. Dose-response of ketorolac as an adjunct to patientcontrolled analgesia morphine in patients after spinal fusion surgery. Anesth Analg 1998; 87:98–102.

  11. 11

    Reuben SS, Connelly NR. Postoperative analgesic effects of celecoxib or rofecoxib after spinal fusion surgery. Anesth Analg 2000; 91:1221–5.

  12. 12

    Reuben S, Ekman EF. The effect of cycolo-oxygenase-2 inhibition on analgesia and spinal fusion. J Bone Joint Surg Am 2005; 87:536–42.

  13. 13

    Turner DM, Warson JS, Wirt TC, Scalley RD, Cochran RS, Miller KJ. The use of ketorolac in lumbar spine surgery: a cost-benefit analysis. J Spinal Disord 1995; 8:206–12.

  14. 14

    Cousins MJ, Power I, Smith G. 1996 Labat lecture: pain-a persistent problem. Reg Anesth Pain Med 2000; 25:6–21.

  15. 15

    Perkins FM, Kehlet H. Chronic pain as an outcome of surgery. A review of predictive factors. Anesthesiology 2000; 93:1123–33.

  16. 16

    Samad TA, Sapirstein A, Woolf CJ. Prostanoids and pain: unraveling mechanisms and revealing therapeutic targets. Trends Mol Med 2002; 8:390–6.

  17. 17

    Gajraj NM. The effect of cyclooxygenase-2 inhibitors on bone healing. Reg Anesth Pain Med 2003; 28:456–65.

  18. 18

    Dumont AS, Verma S, Dumont RJ, Hurlbert J. Nonsteroidal anti-inflammatory drugs and bone metabolism in spinal fusion surgery: a pharmacological quandary. J Pharmacol Toxicol Methods 2000; 43:31–9.

  19. 19

    Maxy RJ, Glassman SD. The effect of nonsteroidal anti-inflammatory drugs on osteogenesis and spinal fusion. Reg Anesth Pain Med 2001; 26:156–8.

  20. 20

    Wedel DJ, Berry D. “He said, she said, NSAIDs”. Reg Anesth Pain Med 2003; 28:372–5.

  21. 21

    Deguchi M, Rapoff AJ, Zdeblick TA. Posterolateral fusion for isthmic spondylolisthesis in adults: analysis of fusion rate and clinical results. J Spinal Disord 1998; 11:459–64.

  22. 22

    Steinmann JC, Herkowitz HN. Pseudarthrosis of the spine. Clin Orthop 1992; 284:80–90.

  23. 23

    Lee C, Dorcil J, Radomisli TE. Nonunion of the spine: a review. Clin Orthop 2004; 419:71–5.

  24. 24

    Toradol IV/IM (package insert). Nutley, NJ: Roche Laboratories; 1994.

  25. 25

    Choo V, Lewis S. Ketorolac doses reduced. Lancet 1993; 342:109.

  26. 26

    Sevarino FB, Sinatra RS, Paige D, Ning T, Brull SJ, Silverman DG. The efficacy of intramuscular ketorolac in combination with intravenous PCA morphine for postoperative pain relief. J Clin Anesth 1992; 4:285–8.

  27. 27

    Glassman SD, Rose SM, Dimar JR, Puno RM, Campbell MJ, Johnson JR. The effect of postoperative nonsteroidal anti-inflammatory drug administration on spinal fusion. Spine 1998; 23:834–8.

  28. 28

    O’Hara D, Fragen R, Kinzer M, Pemberton D. Ketorolac tromethamine as compared with morphine sulfate for treatment of postoperative pain. Clin Pharmacol Ther 1987; 41:556–61.

  29. 29

    Yee JP, Koshiver JE, Allbon C, Brown CR. Comparison of intramuscular ketorolac tromethamine and morphine sulfate for analgesia of pain after major surgery. Pharmacotherapy 1986; 6:253–61.

  30. 30

    Folsland B, Skulberg A, Halvorsen P, Helgesen KG. Placebo-controlled comparison of single intramuscular doses of ketorolac tromethamine and pethidine for post-operative analgesia. J Int Med Res 1990; 18:305–14.

  31. 31

    Strom BL, Berlin JA, Kinman JL, et al. Parenteral ketorolac and risk of gastrointestinal and operative site bleeding. A postmarketing surveillance study. JAMA 1996; 275:376–82.

  32. 32

    Ho ML, Chang JK, Wang GJ. Antiinflammatory drug effects on bone repair and remodeling in rabbits. Clin Orthop 1995; 313:270–8.

  33. 33

    Schafer AI. Effects of nonsteroidal anti-inflammatory therapy on platelets. Am J Med 1999; 106:25S-35S.

  34. 34

    Gilron I, Milne B, Hong M. Cyclooxygenase-2 inhibitors in postoperative pain management: current evidence and future directions. Anesthesiology 2003; 99:1198–208.

  35. 35

    Sinatra R. Role of COX-2 inhibitors in the evolution of acute pain management. J Pain Symptom Manage 2002; 24 (1 Suppl.):S18–27.

  36. 36

    Long J, Lewis S, Kuklo T, Zhu Y, Riew KD. The effect of cyclooxygenase-2 inhibitors on spinal fusion. J Bone Joint Surg Am 2002; 84:1763–8.

  37. 37

    Simon AM, Manigrasso MB, O’Connor JP. Cyclo-oxygenase 2 function is essential for bone fracture healing. J Bone Miner Res 2002; 17:963–76.

  38. 38

    Gerstenfeld LC, Thiede M, Seibert K, et al. Differential inhibition of fracture healing by non-selective and cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs. J Orthop Res 2003; 21:670–5.

  39. 39

    Gerstenfeld LC, Einhorn TA. COX inhibitors and their effects on bone healing. Expert Opin Drug Saf 2004; 3:131–6.

  40. 40

    Lagerkranser M. Better to stigmatize smoking and not NSAID in connection with bone surgery! (Swedish). Lakartidningen 2002; 99:3338–9.

Download references

Author information

Correspondence to Scott S. Reuben or David Ablett or Rachel Kaye.

Additional information

Support was provided solely from institutional and/or departmental source.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Reuben, S.S., Ablett, D. & Kaye, R. High dose nonsteroidal anti-inflammatory drugs compromise spinal fusion. Can J Anesth 52, 506–512 (2005). https://doi.org/10.1007/BF03016531

Download citation

Keywords

  • Celecoxib
  • Rofecoxib
  • Ketorolac
  • Spinal Fusion
  • Level Fusion