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ANALGESIA

The Analgesic Efficacy of Celecoxib, Pregabalin, and Their Combination for Spinal Fusion Surgery

Scott S. Reuben, MD^*, Asokumar Buvanendran, MD, Jeffrey S. Kroin, PhD, and Karthik Raghunathan, MD^*

From the *Department of Anesthesiology, Baystate Medical Center, Springfield, Massachusetts; and Department of Anesthesiology, Rush Medical College, Chicago, Illinois.

Address correspondence and reprint requests to Dr. Reuben, Department of Anesthesiology, Baystate Medical Center, 759 Chestnut St., Springfield, MA 01199. Address e-mail to scott.reuben{at}bhs.org.

Abstract

BACKGROUND: As optimal pain relief after surgery is difficult to achieve with the use of just one drug, many pain experts advocate the use of two or more classes of medications so as to reduce the side effects from any one drug. In this trial, we assessed the analgesic efficacy of administering perioperative celecoxib, pregabalin, or both after spinal fusion surgery.

METHODS: Eighty patients scheduled to undergo elective decompressive lumbar laminectomy with posterior spinal fusion were randomized to receive oral medications: placebo 1 h before and 12 h after surgery, celecoxib 400 mg 1 h before and celecoxib 200 mg 12 h after surgery, pregabalin 150 mg 1 h before and 12 h after surgery, or a pregabalin/celecoxib combination of 400 mg/150 mg 1 h before and 200 mg/150 mg 12 h after surgery.

RESULTS: The pregabalin/celecoxib group consumed the least patient-controlled morphine. Celecoxib alone or pregabalin alone also reduced opioid use compared with placebo, but not as much as when combined. The pregabalin/celecoxib combination was the most effective treatment for reducing pain both at rest and with movement over the 24-h postoperative time period. Hemodynamics and respiratory rate did not differ among the four treatment groups. Fewer patients experienced nausea in the pregabalin/celecoxib group compared with that in the placebo group.

CONCLUSION: The perioperative administration of the combination of celecoxib and pregabalin improved analgesia and caused fewer side effects, than either analgesic drug alone after spinal fusion surgery.

Despite major improvements in our understanding of acute pain physiology over the past decade, approximately 80% of patients undergoing surgical procedures experience postoperative pain (1). Acute postoperative pain is a predictor of chronic pain syndromes as a result of surgery (2). Although opioids are an important component of postoperative pain management, they are associated with side effects (3), and so, the multimodal analgesic approach has been recommended for the management of acute postoperative pain (4,5).

Cyclooxygenase (COX)-2 specific nonsteroidal antiinflammatory drugs (NSAIDs) and ₂- subunit calcium channel ligands (gabapentin and pregabalin) are two mechanistically different types of analgesics that have demonstrated efficacy after a variety of surgical procedures (6,7). Gabapentin can enhance the analgesic effect of morphine in both animal models (8) and volunteers (9). Both ₂- ligands and NSAIDs can interact synergistically or additively to reverse hyperalgesia associated with peripheral inflammation (10). The combination of gabapentin and rofecoxib, a COX-2 selective NSAID, was shown to be superior to either single drug alone for postoperative pain management (7). Recently, both celecoxib (11,12) and gabapentin (13) have been demonstrated to have analgesic efficacy after spinal fusion surgery.

Although structurally similar to gabapentin, pregabalin has greater analgesic efficacy in rodent models of neuropathic pain (14,15), and exhibits linear pharmacokinetics across its therapeutic dose range with low intersubject variability (14,15). No study has evaluated the efficacy of administering pregabalin with or without a NSAID for postsurgical analgesia.

The hypothesis of this prospective, double-blind, randomized, placebo-controlled trial is that after spinal fusion surgery, a combination of celecoxib and pregabalin will demonstrate superior analgesic efficacy than either drug alone and cause fewer side effects.

METHODS

Patients
After IRB approval, written informed consent was obtained between July 2004 and October 2005 from patients scheduled to undergo elective decompressive lumbar laminectomy with instrumented posterior spinal fusion. Patients were eligible for participation if they were at least 18 years old, weighed more than 40 kg, and could operate a patient-controlled analgesia (PCA) device after presurgery instructions. Exclusion criteria included known allergy, sensitivity, or contraindications to sulfa, morphine, or any NSAID; renal insufficiency; a history of peptic ulcer; a history of alcohol or substance abuse; ongoing therapy with sustained-release opioids; seizure disorder; and pregnancy.

Study Design
Study medications were celecoxib 200 mg capsules, pregabalin 150 mg capsules, and placebo capsules that matched the celecoxib or pregabalin capsules in color and size. Patients were assigned to one of four treatment groups in a parallel double-blind randomized manner:

1. The placebo group received placebo capsules (2) 1 h before the anesthetic induction and 12 h after surgery (identically matched to study drugs).
   
2. The celecoxib group received celecoxib 400 mg and a placebo capsule 1 h before the anesthetic induction and celecoxib 200 mg and placebo capsules, 12 h after surgery.
   
3. The pregabalin group received pregabalin 150 mg and placebo capsules 1 h before the anesthetic induction and pregabalin 150 mg and placebo capsules, 12 h after surgery.
   
4. The pregabalin/celecoxib group received celecoxib 400 mg and pregabalin 150 mg 1 h before the anesthetic induction and celecoxib 200 mg and pregabalin 150 mg 12 h after surgery.
   

Before the start of the study, a medical center pharmacist prepared an allocation protocol which randomized these four drug treatments among 100 patients. Each new patient was assigned a consecutive study number. The study medications were administered at the medical center on the day of surgery by a nurse. The celecoxib dose of 400 mg 1 h before anesthetic induction and 200 mg 12 h after surgery was based on a previous study in which these doses and daily timing were administered after spinal fusion surgery (11). The pregabalin dose of 150 mg 1 h before anesthetic induction and 150 g 12 h after surgery was based on the product information sheet that recommends a maximum dose of 300 mg/day for pain syndromes (14,15).

Spinal fusion was performed at either one or two levels from L4 to S1 using similar carbon fiber cages with pedicle screw and plate instrumentation. All procedures were performed by use of a partial-thickness, posterior iliac-crest bone graft harvested through a lateral oblique incision just cephalad to the crest. Before surgery, both the laminectomy and iliac-crest harvest incision sites were infiltrated with 10 mL bupivacaine 0.25%.

Anesthesia was induced with propofol (2 mg/kg), morphine 0.3 mg/kg, and maintained with isoflurane 70% N₂O in O₂. Patients were connected to a PCA pump (Abbott PCA Plus, Abbott Park, Chicago, IL) on arrival in the postanesthesia care unit. Initial settings were as follows: incremental dose, 2 mg; lockout interval, 8 min; and 4-h limit, 40 mg. The incremental dose was increased to 2.5 mg, and the 4-h limit was increased to 50 mg if analgesia was inadequate after 1 h. If analgesia remained inadequate after an additional hour, the incremental dose was further increased to 3.0 mg, and the 4-h limit was increased to 60 mg.

No other analgesic supplement was given. However, any patient with severe pain that was not adequately controlled by PCA morphine could, by agreement with the principal investigator, be withdrawn from the study so that alternative analgesic dosing could be offered. Any patient in this category would not be replaced with a newly enrolled patient.

Outcomes
Outcome measures for the study were assessed by a research or acute pain service nurse who was blinded to patients' group assignments. Patients were asked to quantify their pain on a verbal rating scale between 0 and 10, with 0 representing no pain and 10 the worst imaginable pain. Pain assessments were made both at rest and with movement. Pain with movement was recorded after the patient completed a 90° logroll while in bed.

Intraoperative blood loss was determined by combining the blood collected in the suction canister as well as by estimating the blood present in the surgical sponges.

Sedation scores were measured on a numerical score of 1–5 (1, completely awake; 2, awake but drowsy; 3, asleep but responsive to verbal commands; 4, asleep but responsive to tactile stimulus; 5, asleep and not responsive to any stimulus).

Pain scores, sedation scores, heart rate, oxygen saturation (SpO₂), mean arterial blood pressure, respiratory rate, and morphine use were recorded by a study nurse 1 h after arrival in the postanesthesia care unit and subsequently at 4, 8, 12, 16, 20, and 24 h. Bed rest was enforced for the first 24 h postoperatively. The incidences of respiratory depression (respiratory rate < 8 breaths/min or SpO₂ < 90% without oxygen supplementation) and hypotension (mean arterial blood pressure < 80% of baseline) were recorded. Other symptoms were assessed, including nausea, vomiting, constipation, difficulty passing urine, difficulty concentrating, drowsiness or difficulty staying awake, feeling light-headed or dizzy, feeling confused, feelings of general fatigue or weakness, itchiness, dry mouth, and headache.

Statistical Analysis
Sample size was estimated by analyzing previous data from studies comparing verbal rating-scale pain scores between patients receiving a COX-2 selective inhibitor and those receiving placebo after spinal fusion surgery (11,12). With 90% power, a mean difference of 2.9, a standard deviation of 1.0, and = 0.05, a power analysis of ANOVA testing on four independent means would require 16 patients per group. To be conservative, we planned to initially enroll 20 patients per group. At the end of the study, if there was a drop-out in any group due to a protocol violation, new patients would be enrolled and randomly assigned to treatment groups to increase the total to 20 per group. Morphine consumption, pain at rest, pain with movement, heart rate, mean arterial blood pressure, and respiratory rate were compared among the four groups over the postoperative time points, with repeated measures linear fixed model. If group differences were significant (P < 0.05), then treatment groups were compared at each time point with Tukey-Kramer post hoc testing. Sedation scores were compared among the four groups by repeated measures analysis of variance for assessment of time and treatment effects. If differences were found, a Bonferroni post hoc test was performed. Total PCA morphine use, duration of surgery, and intraoperative blood loss were compared among the four groups with ANOVA, and Tukey-B post hoc testing. Demographic data were analyzed using ANOVA or ² test, as appropriate. The incidence of each side effect was compared with an omnibus ² test, and if significant (P < 0.05), pairwise post hoc comparisons of each of the three drug groups to the placebo group were made with Fisher's exact test (P < 0.0167 for significance).

RESULTS

Patients
The clinical trial was conducted between July 2004 and October 2005. Seven patients were withdrawn from the study due to protocol violation: two patients had more than two levels of fusion, two patients used cadaver rather than autogenous iliac crest graft, and three patients were not administered their study drugs according to protocol. These subjects were replaced by new study patients to make the number of patients in each group = 20. No patient was withdrawn from the study because of severe pain requiring additional analgesic beyond the PCA protocol. Table 1 lists the characteristics of the 80 patients completing the clinical trial. There were no differences in demographic characteristics, surgical duration, or number of spinal levels fused.

Morphine Consumption
Figure 1 shows the average PCA-administered drug consumption at each of the postoperative time intervals up to 24 h. Repeated measure analysis demonstrated a difference among the four treatment groups (F = 283.3, P < 0.001), and also a group by time interaction (F = 17.83, P < 0.001). Post hoc analysis showed that the pregabalin/celecoxib group required the least amount of opioid. Celecoxib alone or pregabalin alone also reduced morphine consumption compared with placebo, but not as much as when combined. Total 24-h cumulative morphine consumption was different among the four treatment groups (F = 269.1, P < 0.001), with each group statistically different from each other: placebo 134.0 ± 3.3 mg, celecoxib 88.0 ± 2.4 mg, pregabalin 77.4 ± 1.7 mg, pregabalin/celecoxib 43.0 ± 1.3 mg (mean ± sem).

View larger version (20K): [in this window] [in a new window]   Figure 1. Morphine delivered by patient-controlled analgesia (PCA) after arrival in the postanesthesia care unit (PACU). The group receiving perioperative pregabalin/celecoxib consumed the least amount of morphine over this 24-h postoperative period. Data are shown as mean ± sem; *different from placebo (P < 0.01); different from celecoxib (P < 0.01); different from pregabalin (P < 0.01); different from pregabalin/celecoxib combination (P < 0.01).

Pain Scores
Figures 2 and 3 display postoperative pain scores over time both at rest and with movement. At rest, pain scores differed among the four groups (F = 28.9, P < 0.001), and also group by time (F = 5.64, P < 0.001). Post hoc testing showed that the pregabalin/celecoxib treatment group consistently reduced pain intensity at rest throughout the postoperative period. With movement, pain scores differed by group (F = 69.6, P < 0.001), and group by time (F = 2.25, P = 0.003). Post hoc testing demonstrated that the pregabalin/celecoxib combination was the most effective treatment for reducing pain with movement.

View larger version (19K): [in this window] [in a new window]   Figure 2. Verbal rating scale (VRS) pain at rest over the 24-h postoperative period after arrival at the postanesthesia care unit (PACU). The group receiving perioperative pregabalin/celecoxib experienced the least amount of pain. Data are shown as mean ± sem; *different from placebo (P < 0.05); different from celecoxib (P < 0.05); different from pregabalin/celecoxib combination (P < 0.05).

View larger version (20K): [in this window] [in a new window]   Figure 3. Verbal rating scale (VRS) pain with movement over the 24-h postoperative period after arrival at the postanesthesia care unit (PACU). The group receiving perioperative pregabalin/celecoxib experienced the least amount of pain. Data are shown as mean ± sem; *different from placebo (P < 0.05); different from celecoxib (P < 0.05); different from pregabalin (P < 0.05); different from pregabalin/celecoxib combination (P < 0.05).

DISCUSSION

This study revealed that the perioperative administration of the combination of celecoxib and pregabalin resulted in improved analgesia compared with either analgesic drug alone after spinal fusion surgery. This combination produced a significant reduction in pain scores and in morphine use during the first 24 postoperative hours. The pregabalin/celecoxib combination was the only treatment that significantly reduced the incidence of nausea and excess sedation.

Pregabalin has demonstrated analgesic efficacy for neuropathic pain (14,15), fibromyalgia syndrome (16), and in a postdental pain model (17). Biochemical studies have identified the ₂- (Type 1) receptor as the primary binding site for both gabapentin and pregabalin (18,19). Binding of pregabalin to the ₂- subunit of voltage-gated calcium channels alters the kinetics and voltage dependence of calcium currents (20). By reducing calcium influx at nerve terminals, pregabalin reduces the release of several neurotransmitters, including glutamate, noradrenaline, calcitonin gene-related peptide, and substance P (21–23). This reduction in neurotransmitter release is presumed to account for pregabalin's analgesic actions. As demonstrated in the present study, pregabalin had no effect on arterial blood pressure or heart rate, which is consistent with animal experiments showing that intrathecal administration of the related compound gabapentin does not alter resting or acutely evoked autonomic outflow (24).

Although parenteral opioids are still considered the foundation for the treatment of moderate to severe pain (25), sufficient analgesia cannot be achieved without the risk of significant adverse events (26). The opioid doses necessary for complete relief of spontaneous pain at rest (tonic pain) have no effect on movement-associated (phasic) pain (27,28). Both COX-2 NSAIDs (29) and ₂- ligands (6) have been demonstrated to have analgesic efficacy during pain at rest and with movement. Although both analgesics alone are capable of reducing postoperative opioid use by 20–50%, it remains to be determined whether this can result in a significant reduction in opioid-related adverse events, thereby accelerating the rehabilitation process and reducing postoperative morbidity (30). Only one clinical study evaluating the perioperative analgesic effect of gabapentin (13) demonstrated a reduction in opioid-related side effects (vomiting and urinary retention). Meta-analysis studies of NSAIDs and COX-2 inhibitors highlight the importance of using more than one nonopioid analgesic in the multimodal management of acute pain (31,32).

Without a full dose-response study and associated ED50s, it is not possible to infer that the combination of celecoxib and pregabalin has more than just an additive effect. Another study with rofecoxib and gabapentin perioperative administration for abdominal hysterectomy did not support synergy between a COX-2 inhibitor and a ₂- ligand (7). Another limitation of our study is that preoperative narcotic usage was not used as a covariant in analyzing postoperative opioid requirements.

In summary, the present study demonstrates that the perioperative administration of the pregabalin/celecoxib combination reduces both postoperative pain and opioid-related side effects more effectively than either drug alone. These results from spinal fusion surgery support the wider clinical use of this specific drug combination in the postsurgical setting.

Footnotes

Accepted for publication June 20, 2006.

Presented in part at the International Anesthesia Research Society 80th Clinical and Scientific Congress, March 20, 2006, San Francisco, CA.

REFERENCES

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; 97:534–40.[Abstract/Free Full Text]
2. Perkins FM, Kehlet H. Chronic pain as an outcome from surgery. A review of predictive factors. Anesthesiology 2000;93:1123–33.[Web of Science][Medline]
3. Kehlet H, Wilmore DW. Multimodal strategies to improve surgical outcome. Am J Surg 2002;183:630–41.[Web of Science][Medline]
4. Kehlet H, Dahl JB. The value of "multimodal" or "balanced analgesia" in postoperative pain treatment. Anesth Analg 1993;77:1048–56.[Free Full Text]
5. Acute Pain Management Guideline Panel. Acute pain management: operative or medical procedures and trauma-clinical practice guideline. Rockville, MD: US Department of Health and Human Services, Agency for Health Care Policy and Research, Public Health Service; February 15–26, 1992. AHCPR Pub. No. 92-0032.
6. Dahl JB, Mathiesen O, Moniche S. "Protective premedication": an option with gabapentin and related drugs? A review of gabapentin and pregabalin in the treatment of post-operative pain. Acta Anaesthesiol Scand 2004;48:1130–6.[Web of Science][Medline]
7. Gilron I, Orr E, Tu D, et al. A placebo-controlled randomized clinical trial of perioperative administration of gabapentin, rofecoxib and their combination for spontaneous and movement-evoked pain after abdominal hysterectomy. Pain 2005;113:191–200.[Web of Science][Medline]
8. Shimoyama M, Shimoyama N, Inturrisi CE, Elliot KJ. Gabapentin enhances the antinociceptive effects of spinal morphine in the rat tail-flick test. Pain 1997;72:375–82.[Web of Science][Medline]
9. Eckhardt K, Ammon S, Hofman U, et al. Gabapentin enhances the analgesic effect of morphine in healthy volunteers. Anesth Analg 2000;91:185–91.[Abstract/Free Full Text]
10. Hurley RW, Chatterjea D, Rose Feng M, et al. Gabapentin and pregabalin can interact synergistically with naproxen to produce antihyperalgesia. Anesthesiology 2002;97:1263–73.[Web of Science][Medline]
11. Reuben SS, Ekman E. The effect of cyclooxygenase-2 inhibition on analgesia and spinal fusion. J Bone Joint Surg Am 2005; 87:536–42.[Abstract/Free Full Text]
12. Reuben SS, Ekman EF, Raghunathan K, et al. The effect of cyclooxygenase-2 inhibition on acute and chronic pain after spinal-fusion surgery. Reg Anesth Pain Med 2006;31:6–13.[Web of Science][Medline]
13. Turan A, Karamanlioglu B, Memis D, et al. Analgesic effects of gabapentin after spinal surgery. Anesthesiology 2004;100:935–8.[Web of Science][Medline]
14. Frampton JE, Scott LJ. Pregabalin in the treatment of painful diabetic peripheral neuropathy. Drugs 2004;64:2813–20.[Web of Science][Medline]
15. Frampton JE, Foster RH. Pregabalin in the treatment of postherpetic neuralgia. Drugs 2005;65:111–8.[Web of Science][Medline]
16. Crofford LJ, Rowbotham MC, Mease PJ, et al.; Pregabalin 1008-105 Study Group. Pregabalin for the treatment of fibromyalagia syndrome: results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2005;52:1264–73.[Web of Science][Medline]
17. Hill CM, Balkenohl M, Thomas DW, et al. Pregabalin in patients with postoperative dental pain. Eur J Pain 2001;5: 119–24.[Web of Science][Medline]
18. Gee NS, Brown JP, Dissanayake VU, et al. The novel anticonvulsant drug, gabapentin (Neurontin), binds to the ₂- subunit of a calcium channel. J Biol Chem 1996;271:5768–76.[Abstract/Free Full Text]
19. Qin N, Yagel S, Momplaisir ML, et al. Molecular cloning and characterization of the human voltage-gated calcium channel ₂-4 subunit. Mol Pharmacol 2002;62:485–96.[Abstract/Free Full Text]
20. Arikkath J, Campbell KP. Auxiliary subunits: essential components of the voltage-gated calcium channel complex. Curr Opin Neurobiol 2003;13:298–307.[Web of Science][Medline]
21. Dooley DJ, Donovan CM, Pugsley TA. Stimulus-dependent modulation of [³H]norepinephrine release from rat neocortical slices by gabapentin and pregabalin. J Pharmacol Exp Ther 2000;295:1086–93.[Abstract/Free Full Text]
22. Dooley DJ, Mieske CA, Borosky SA. Inhibition of K⁺-evoked glutamate release from rat neocortical and hippocampal slices by gabapentin. Neurosci Lett 2000;280:107–110.[Web of Science][Medline]
23. Fehrenbacher JC, Taylor CP, Vasko MR. Pregabalin and gabapentin reduce release of substance P and CGRP from rat spinal tissues only after inflammation or activation of protein kinase C. Pain 2003;105:133–41.[Web of Science][Medline]
24. Yoon MH, Yaksh TL. The effect of intrathecal gabapentin on pain behavior and hemodynamics on the formalin test in the rat. Anesth Analg 1999;89:434–9.[Abstract/Free Full Text]
25. Walder B, Schafer M, Henzi I, Tramer MR. Efficacy and safety of patient-controlled opioid analgesia for acute postoperative pain. A quantitative systematic review. Acta Anaesthesiol Scand 2001;45:795–804.[Web of Science][Medline]
26. Wheeler M, Oderda GM, Ashburn MA, Lipman AG. Adverse events associated with postoperative opioid analgesia: a systematic review. Clin J Pain 2002;3:159–80.
27. Tverskoy M, Oren M, Dahkovsky I, Kissin I. Alfentanil dose-response relationships for relief of postoperative pain. Anesth Analg 1996;83:387–93.[Abstract]
28. Ryan SM, Watkins LR, Mayer DJ, Maier SF. Spinal pain suppression mechanisms may differ for phasic and tonic pain. Brain Res 1985;334:172–5.[Web of Science][Medline]
29. Gilron I, Milne B, Hong M. Cyclooxygenase-2 inhibitors in postoperative pain management. Current evidence and future directions. Anesthesiology 2003;99:1198–208.[Web of Science][Medline]
30. Kehlet H. Postoperative opioid sparing to hasten recovery: what are the issues? Anesthesiology 2005;102:1083–5.[Web of Science][Medline]
31. Marret E, Kurdi O, Zufferey P, Bonnet F. Effect of nonsteroidal anti-inflammatory drugs on patient-controlled analgesia morphine side effects. Anesthesiology 2005;102:1249–60.[Web of Science][Medline]
32. Elia N, Lysakowski C, Tramer MR. Does multimodal analgesia with acetaminophen, nonsteroidal anti-inflammatory drugs, or selective cyclooxygenase-2 inhibitors and patient-controlled analgesia morphine offer advantages over morphine alone? Anesthesiology 2005;103:1296–13.[Web of Science][Medline]

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (16) Citing Articles via Google Scholar Google Scholar Articles by Reuben, S. S. Articles by Raghunathan, K. Search for Related Content PubMed PubMed Citation Articles by Reuben, S. S. Articles by Raghunathan, K. Related Collections Pain Pharmacology