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SPINE Volume 33, Number 19, pp 2079 –20822008, Lippincott Williams & Wilkins Ketorolac and Spinal Fusion
Does the Perioperative Use of Ketorolac Really Inhibit
Spinal Fusion?
Ben B. Pradhan, MD, MSE,* Robert L. Tatsumi, MD,† Jason Gallina, MD,‡Craig A. Kuhns, MD,§ Jeffrey C. Wang, MD,¶ and Edgar G. Dawson, MD࿣ benefits of NSAIDs include reduced pain, improved post- Study Design. Retrospective review.
operative ambulation, shorter hospitalization and de- Objective. To evaluate the effect of postoperative use
creased nausea, emesis and sedation.2–4 NSAIDs have of ketorolac (Toradol) on spinal fusion in humans.
documented efficacy when administered as the sole anal- Summary of Background Data. The value of parenteral
ketorolac in postoperative analgesia has been well docu- gesic after minor surgical procedures and adjuvants to mented across surgical specialties. However, some stud- other analgesics after major surgery.5,6 Ketorolac (Tor- ies have shown that ketorolac may adversely affect osteo- adol, Roche Laboratories, Nutley, NJ), approved by the genic activity and fracture healing.
Food and Drug Administration in November 1989 for Methods. A total of 405 consecutive patients who un-
the control of postoperative pain, enhances the effect of derwent primary lumbar posterolateral intertransverseprocess fusion with pedicle screw instrumentation were narcotics, and decreases narcotic requirement.2,4,7–15 included in this retrospective study. A subtotal of 228 Empirically the authors have observed a more comfort- patients received Toradol after surgery for adjunctive an- able postoperative hospital course in spinal fusion pa- algesia. Each patient received a mandatory dose of 30 mg tients who received parenteral Ketorolac at our institu- intravenously every 6 hours for 48 hours. The same sur- tion without any attendant increase in complications.
geon performed the fusion procedure on all of these pa-tients. Historical controls included 177 patients who did NSAIDs, however, have a myriad of undesirable side not receive Toradol after surgery. The minimum fol- effects especially in the perioperative period and includes low-up period was 24 months. Nonunions were diag- gastrointestinal bleeding or ulcers, wound healing prob- nosed by analyzing sequential radiographs, flexion-ex- lems or bleeding, and renal failure.7,16–25 NSAIDs may tension radiographs, and computed tomography with also adversely affect osteogenic activity and fracture multiplanar reconstructions. The gold standard of surgi-cal exploration was performed in symptomatic patients healing.26 –29 Regarding spinal surgery, a number of with diagnostic ambiguity or nonunions diagnosed by studies have shown adverse effects on fusion rates in an- imals.30–33 This may occur through any one or all of Results. There were no smokers in the study popula-
several mechanisms.28,31,34 Glassman et al35 examined tion. Pseudarthrosis was identified in 12 of 228 patients the influence of ketorolac on spinal fusion in humans and (5.3%) who received Toradol after surgery, and in 11 of177 patients (6.2%) who did not. There was no significant concluded that this drug significantly inhibited fusion at difference detected in the nonunion rates between the doses typically used for postoperative pain control and two groups (P Ͼ 0.05, ␹2 method).
that NSAIDs should be avoided in the early postopera- Conclusion. Use of ketorolac after spinal fusion sur-
gery in humans, limited to 48 hours after surgery for The goal of this retrospective study was to determine adjunctive analgesia, has no significant effect on ultimatefusion rates.
the nonunion rate at 34 months after spine surgery in Key words: spinal fusion, pseudoarthrosis, ketorolac,
patients who were given a short-term amount of ketoro- nonsteroidal analgesics. Spine 2008;33:2079 –2082
Materials and Methods
Nonsteroidal anti-inflammatory drugs (NSAIDs) are Nonsmoking patients who underwent 1, 2, or 3 level lumbar commonly used for pain control and are the most often posterolateral intertransverse process fusion with pedicle prescribed class of medication around the world.1 The screw instrumentation and decompression by a single sur-geon (EGD) were given ketorolac intravenously as a manda-tory drug, and not as a prn (as needed) drug. Every patient From the *Risser Orthopaedic Group, Pasadena, CA; the †Pacific received the same dose and duration of the drug–30 mg Spine Specialists, Tualatin, OR; ‡New York, NY; the §University ofMissouri School of Medicine, Columbia, MO; ¶UCLA School of Med- intravenously every 6 hours for a total of 48 hours (total 240 icine, Los Angeles, CA. ࿣Edgar G. Dawson, MD, is deceased.
mg). No loading dose was given. Patient’s were contraindi- Acknowledgment date: November 25, 2007. Acceptance date: Febru- cated to have ketorolac if they had a documented allergy to NSAIDs, history of peptic ulcer disease, congestive heart The device(s)/drug(s) is/are FDA-approved or approved by correspond-ing national agency for this indication.
failure, liver disease, bleeding disorder, serum creatinine No funds were received in support of this work. No benefits in any form have been or will be received from a commercial party related Patient’s who underwent the same procedure by the senior directly or indirectly to the subject of this manuscript.
author (EGD) before November 1989 (before the introduction Address correspondence and reprint requests to Ben B. Pradhan, MD, of ketorolac) and by another surgeon (JCW) were not given MSE, Risser Orthopaedic Group, 2627 East Washington Boulevard, Pas-adena, CA 91107; E-mail: [email protected] Ketorolac after surgery. All patients were given patient con- 2080 Spine • Volume 33 • Number 19 • 2008
Table 1. Patient Demographics
Table 2. Nonunion Results
Discussion
trolled analgesia transitioned to prn acetaminophen and opioid The use of posterolateral fusion in the treatment of de- tablets. No oral NSAIDs were given after surgery.
generative, traumatic, and other unstable spinal disor- The status of the fusion was determined based on antero- ders has been one of the most popular methods in spine posterior and flexion-extension radiographs or computerizedtomography at the time of 1-year follow-up. Pseudarthrosis surgery.36 –38 Pseudarthrosis rates for posterolateral (nonunion) was defined as the absence of bridging bone for- lumbar spine fusions has been quoted to be anywhere mation without trabeculation, Ͼ2° of motion on flexion- from 3% to 35% in the literature.39–42 The addition of extension radiographs, and/or radiolucency around the instrumentation has not eliminated this problem.43–45 Various factors may contribute to pseudarthrosis which Demographic data (age, sex, height, weight), the level of may include smoking and long-term NSAID usage.
fusions, and the use of iliac crest bone graft (ICBG) were ana- Smoking has been shown to increase pseudarthrosis rates lyzed with analysis of variance (Table 1). The incidence of 2- to 5-fold.39,41,46,47 Long-term, high dose, NSAID use pseudarthrosis was evaluated by a ␹2 analysis.
after fusion surgery has been shown to adversely affectfusion rates in animals.30–33,48,49 NSAIDs are commonly used for pain control and are the Four hundred five patients underwent primary lumbar most often prescribed class of medications around the posterolateral intertransverse process fusion with pedicle world.1 Ketorolac has been used in the perioperative period screw instrumentation and decompression. Two hun- frequently and safely in many surgical procedures.12,50–55 dred twenty-eight patients received ketorolac and 177 A number of studies have specifically examined the use of patient’s did not receive this drug and these patients were ketorolac after orthopaedic and spine surgery, finding no split approximately equally between 2 surgeons, (EGD) increase in complications.2,4,8,11–14,56,57 Aubrun et al13 de- tected no difference in perioperative complications with in- There was no significant difference between the 2 travenous ketoprofen use after adult spinal fusion surgery.
groups for age, gender, height, weight, or number of Munro et al15 and Vitale et al58 found no increase in com- levels fused. There was also no significant difference de- plication rates after pediatric scoliosis fusion surgery. Le tected between the 2 groups for pseudarthrosis or any Roux and Samudrala14 arrived at similar findings after differences between the 2 surgeons. Nonunion was diag- lumbar disc surgery. Gora-Harper et al59 noted less mor- nosed in 12 of 228 (5.3%) patients who received Tor- bidity and lower cost after joint and spine procedures adol, and in 11 of 177 (6.2%) of patients who did not receive ketorolac (Table 2). When comparing the pa- The adverse effects of NSAIDs on spinal fusion seen in tients the senior surgeon (EGD) operated on, there was animal studies are likely dose and duration-depen- a higher nonunion rate when he did not use ketorolac; dent.30,60,61 The dose of ketorolac for humans in this study however, this difference was not significant under sta- was approximately 1.5 mg/kg/d for the first 48 hours only.
tistical analysis. There was a trend toward higher non- Studies involving spinal fusions in animals have dosed union rates with 3 level fusions as opposed to 1–2 NSAIDs anywhere from 3 mg/kg/d to 10 mg/kg/d for du- levels, however, there was limited data to find statisti- rations from 7 days to 12 weeks.30–33,60,62 Ho et al60 dis- covered that while 4 mg/kg/d of ketorolac given for 6 weeks A large proportion of patients in this study did not delayed endochondral ossification in rabbit ulnar fractures, receive autogenous ICBG to augment fusion. The per- a dosing schedule of 2 mg/kg/d for 6 weeks seemed to have centage of patients receiving ICBG was significantly little or no effect. The latter in fact is one of the lowest lower in the Toradol treated group than in the non- dosing schedules in the literature. Table 3 lists the break- Toradol treated group (54.8% vs. 86.4%, P Ͻ 0.05).
down of the cumulative doses of NSAIDs administered in Ketorolac and Spinal Fusion • Pradhan et al 2081
Table 3. Cumulative Doses of NSAIDs on
Bone Formation
● Ketorolac is a good adjuvant with other analge- sics after major surgical procedures.
● The use of ketorolac after primary lumbar spinalfusion surgery in humans did not affect fusion rates when compared with surgical patients who did not References
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