title: High-dose ketorolac affects adult spinal fusion: a meta-analysis of the effect of perioperative nonsteroidal anti-inflammatory drugs on spinal fusion.
abstract: METHODS
  Meta-analysis of literature.
  
  
  OBJECTIVE
  To evaluate the effect of perioperative nonsteroidal anti-inflammatory drugs (NSAIDs) on the success rate of adult spinal fusion.
  
  
  BACKGROUND
  NSAIDs are commonly used to treat postsurgical orthopedic pain. Studies on animal models have shown a significant inhibiting effect of NSAIDs on osteogenesis process, on which spinal fusion also depends. Recently, great interest has been shown in the effect of NSAIDs on the success rate of adult spinal fusion. Clinical trials have tested the effect of perioperative NSAIDs in spinal fusion procedures. A cumulative result of these studies would give more credit to the final conclusions.
  
  
  METHODS
  A systematic search of electronic databases and references from eligible articles was conducted. Comparative studies reporting on the results of primary spinal fusion including treatment group of NSAIDs perioperatively were regarded eligible. A pooled estimate of effect size was produced using both random and fixed effect model.
  
  
  RESULTS
  Five retrospective comparative studies (n = 1403 participants) were included in the present study. The mean age of these patients was more than 40 years and none of them had NSAIDs for longer than 14 days following spinal fusion surgery. High-dose ketorolac showed a statistically significant adverse effect on spinal fusion (P = 0.001, RR = 2.87, 95% CI = 1.53 = - 5.38) with no statistical heterogeneity (I = 3%, P = 0.38), whereas normal-dose NSAIDs (ketorolac, diclofenac sodium, celecoxib, or rofecoxib) did not appear to produce inferior results than the no-NSAIDs group (P = 0.30, RR = 1.39, 95% CI = 0.74 - 2.61) with no statistical heterogeneity (I² = 0%, P = 0.50).
  
  
  CONCLUSIONS
  Although randomized controlled trials would be optimal for meta-analyses, the data of this review revealed that short-time (<14 days) exposure to normal-dose NSAIDs (ketorolac, diclofenac sodium, celecoxib, or rofecoxib) were safe after spinal fusion, whereas short-time (<14 days) exposure to high-dose ketorolac increased the risk of nonunion, which meant that the effect of perioperative NSAIDs on spinal fusion might be dose-dependent. Further studies would be needed to find out whether long-time exposure to normal-dose NSAIDs could also increase the risk of nonunion and which type of NSAIDs would like to have a worse effect on spinal fusion.
authors.affiliation: Department of Orthopedics, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Li
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Zhang
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Cai
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D020910:Ketorolac / Q000008:administration & dosage* / Q000009:adverse effects; D010149:Postoperative Pain / Q000209:etiology / Q000517:prevention & control*; D019990:Perioperative Care / Q000379:methods; D011183:Postoperative Complications / Q000139:chemically induced; D012189:Retrospective Studies; D013123:Spinal Fusion / Q000009:adverse effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D020910:Ketorolac