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Canadian Journal of Anesthesia 54:342-348 (2007)
© Canadian Anesthesiologists' Society, 2007
Reports of Original Investigations

Effect of short-term postoperative celecoxib administration on patient outcome after outpatient laparoscopic surgery

[Effet de l’administration postopératoire à court terme de célécoxib sur l’évolution des patients après une chirurgie par laparoscopie sans hospitalisation]

Paul F. White, PhD MD FANZCA, Ozlem Sacan, MD, Burcu Tufanogullari, MD, Matthew Eng, Nina Nuangchamnong and Babatunde Ogunnaike, MD

From the Department of Anesthesiology & Pain Management, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA.

Address correspondence to: Dr. Paul F. White, Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390-9068, USA. Phone: 214-648-6424; Fax: 214-648-2229; E-mail: paul.white{at}utsouthwestern.edu


   Abstract
TOP
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Purpose: Non-opioid analgesics are increasingly used as part of a multimodal regimen for pain management. This prospective, randomized, double-blinded, placebo-controlled study was designed to evaluate the effect of short-term postoperative administration of celecoxib on pain management and recovery outcomes following laparoscopic surgery.

Methods: Eighty consenting ASA I–III outpatients undergoing laparoscopic surgery were randomly assigned to one of two treatment groups: Control (placebo) or Celecoxib (celecoxib, 400 mg·day–1). The initial dose (celecoxib 400 mg or placebo po) was administered in the recovery room, and celecoxib 200 mg (or a placebo) po bid was continued for three additional days after surgery. Postoperative pain scores and the need for opioid- containing analgesics were recorded at specific intervals in the recovery room. Follow-up evaluations were performed at 24 hr, 48 hr, 72 hr and seven days and one month after surgery to assess post-discharge pain, analgesic requirements, complications, quality of recovery, and resumption of normal activities, as well as patient satisfaction with their pain management.

Results: Celecoxib reduced mean pain scores and the need for analgesics at 24 hr and 48 hr postoperatively. Patient satisfaction with their postoperative pain management was also higher in the Celecoxib group (94 ± 8 vs 80 ± 25, P < 0.05). Quality of recovery scores were significantly higher in the Celecoxib group on the first and second postoperative days (17 ± 1 vs 15 ± 2, and 18 ± 1 vs 16 ± 2, respectively). Finally, bowel function recovered an average of one day earlier and patients resumed activities of daily living two days earlier in the Celecoxib group (P < 0.05).

Conclusion: Short-term administration of celecoxib, 400 mg·day–1 po, decreased postoperative pain and the need for opioid-containing analgesic medication, leading to an improved quality of recovery after outpatient laparoscopic surgery.


   Introduction
TOP
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
NONSTEROIDAL anti-inflammatory drugs (NSAIDs) are widely used as part of a multimodal analgesic regimen for preventing pain after ambulatory surgery. 1 Ketorolac has been found to reduce postoperative pain and the need for opioid analgesics after laparoscopic surgery,2 and facilitate an earlier discharge after anorectal surgery.3 Nevertheless, concerns persist regarding the use of non-selective NSAIDs like ketorolac during the perioperative period because of the risk of operative site and gastrointestinal mucosal bleeding due to blockade of prostaglandin synthesis at the cyclooxygenase-1 (COX-1) receptor.4,5

Studies involving COX-2 selective inhibitors have demonstrated that they can improve pain control after a wide variety of ambulatory surgery procedures.6–14 Nevertheless, questions remained regarding the efficacy of perioperative administration of COX-2 inhibitors in improving the later recovery processes (e.g., recovery of bowel function, resumption of normal activities of daily living). For example, perioperative administration of rofecoxib improved the quality of recovery in the early postoperative period after outpatient hernia surgery, but failed to facilitate resumption of normal activities of daily living.12 Similarly, it was shown that perioperative celecoxib reduced postoperative pain and opioid-related side effects (e.g., constipation) after ambulatory arthroscopic knee surgery without improving late recovery events.14 Preoperative parecoxib followed by short-term postoperative valdecoxib improved recovery after laparoscopic cholecystectomy procedures.13 However, studies involving perioperative administration of these two COX-2 inhibitors in patients undergoing cardiac surgery found an increased incidence of postoperative wound infections15 and cardiovascular complications.16

Since both valdecoxib and rofecoxib have been withdrawn from the market because of patient safety concerns, we designed this randomized, double-blinded, placebo-controlled study to test the hypothesis that postoperative administration of oral celecoxib (400 mg·day–1 for four days) would lead to an improved quality of recovery and earlier resumption of normal activities of daily living after laparoscopic surgery.


   Methods
TOP
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
After obtaining Institutional Review Board approval at the University of Texas Southwestern Medical Center at Dallas and written informed consent, 80 American Society of Anesthesiologists (ASA) physical status I–III outpatients undergoing laparoscopic surgery (e.g., tubal ligation, cholecystectomy, diagnostic) at Parkland Memorial Hospital were enrolled in this randomized, double-blinded, placebo-controlled clinical study. Patients were excluded if they had difficulty understanding English, had an allergy or contraindication to taking NSAIDs, chronically used NSAIDs, had received an opioid analgesic medication within a 12-hr period prior to the operation, were pregnant or breast-feeding, had a history of alcohol or drug abuse, had a bleeding disorder, or had clinically-significant neurologic, cardiovascular, renal, hepatic or gastrointestinal diseases. Patients meeting the inclusion criteria were assigned to one of two treatment groups, Control (placebo) or Celecoxib 400 mg·day–1, based on a computer-generated randomization table.

In the preoperative holding area, patients were asked to complete baseline verbal rating scales (VRS) for pain and nausea using an 11-point VRS, with 0 = none to 10 = maximum. Immediately prior to leaving the preoperative holding area, patients were premedicated with midazolam, 20 µg·kg–1 iv. Upon arrival in the operating room, standard monitoring devices were applied and non-invasive arterial blood pressure, heart rate, hemoglobin oxygen saturation, and end-tidal concentrations of carbon dioxide and desflurane were monitored throughout the operation.

Anesthesia was induced with propofol 2 mg·kg–1 iv, and fentanyl 1 µg·kg–1 iv, and tracheal intubation was facilitated with rocuronium 0.6 mg·kg–1 iv. Anesthesia was maintained with desflurane 4–6% in combination with air (1 L·min–1) and oxygen (1 L·min–1). A combination of droperidol, 0.625 mg iv, and dexamethasone, 4 mg iv, was administered after induction of anesthesia for antiemetic prophylaxis. Bupivacaine 0.25% was locally infiltrated at the incision sites prior to wound closure. At the end of the surgical procedure, residual neuromuscular block was reversed with neostigmine, 2–5 mg iv, and glycopyrrolate, 0.3–1 mg iv, the desflurane was discontinued, and the inspired oxygen flow was increased to 5 L·min–1. Upon awakening from anesthesia, patients were extubated and transferred directly to the postanesthesia care unit (PACU).

The study medication (i.e., placebo or Celecoxib 200 mg) was prepared in identical-appearing capsules by the manufacturer of celecoxib (Pfizer, Inc., New York, NY, USA). The initial dose of study medication was administered by mouth 10–20 min after patients arrived in the PACU (i.e., either two celecoxib 200 mg or two placebo capsules). The patients were given a numbered envelope containing six additional capsules, and they were instructed to take one capsule twice a day for the subsequent three postoperative days (PODs). The patients, observers, and anesthesiologists directly involved in the patients’ care were all "blinded" as to the content of the study medication.

Patients were asked to evaluate their pain and nausea on the 11-point VRS at 30, 60, 120 and 240 min intervals after surgery, as well as immediately prior to receiving any "rescue" analgesic medication. Patients complaining of moderate-to-severe pain (VRS > 3) were treated with fentanyl, 25 µg iv boluses. In accordance with the standard hospital PACU nursing practice, the nurses were not required to titrate fentanyl to achieve a specific VRS pain score. Patients requesting analgesic medication with pain scores of 2–3 received a combination of oral hydrocodone (5 mg) and acetaminophen (500 mg). If the patient complained of nausea or experienced repeated episodes of retching or vomiting in the PACU, they were treated with promethazine, 6.25 mg iv boluses, administered to a maximum (total) dose of 25 mg. "Home readiness" was determined using standardized postanesthetic discharge criteria.17

A "blinded" interviewer contacted each patient by telephone at 24 hr, 48 hr and 72 hr after discharge to inquire about their maximum VRS pain score, use of oral opioid-containing analgesic medication (i.e., number of pills), occurrence of any emetic symptoms, and use of rescue antiemetic therapy. The patient quality of recovery scores were also assessed using a standardized nine-item questionnaire.18 Patient satisfaction with postoperative pain management (using a 100-point scale from 1 = highly dissatisfied to 100 = highly satisfied), the times (i.e., number of days after surgery) to tolerate normal fluids and solid food, have a bowel movement, and to resume their normal activities of daily living after surgery were recorded at the 72 hr and/or seven-day follow-up evaluation. The presence of wound (e.g., hematomas, infections) and cardiovascular complications were assessed at the time of the initial postsurgical clinic visit and at the one month follow-up telephone interview, respectively.

Statistical analysis
The group sizes (n = 40) were calculated to detect a one-day reduction in the times to resume normal dietary, bowel and physical activities after surgery in the Celecoxib (vs Control) group, with a power of 80% and a significance level of 0.05. The statistical analysis was performed using SPSS Software (Chicago, IL, USA). For continuous variables, the Student’s t test was used to analyze the parametric data, and discrete (categorical) variables were analyzed using the {chi}2 test. A repeated measures of analysis of variance was performed to examine differences in the VRS pain and quality of recovery scores over time, with a Bonferroni correction applied for multiple comparisons. Data are expressed as mean ± standard deviation, medians (interquartile ranges), percentages (%), and numbers (n), and a P-value < 0.05 was considered statistically significant.


   Results
TOP
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Of 133 patients who were initially screened, 39 were excluded due to difficulty understanding English, and 14 refused to sign the consent form. Eighty patients met the inclusion criteria, and were subsequently enrolled and randomized to receive the initial dose of the study medication or placebo. Follow-up evaluations were incomplete in three patients (two in group Control, and one in group Celecoxib); none of the data from these patients was included in the final statistical evaluation. The groups were similar with respect to age, weight, height, gender, ASA physical status, and durations of surgery and anesthesia (Table IGo). The mean amount of propofol, end-tidal desflurane, and fentanyl administered during the operative period did not differ between the two treatment groups.


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  		TABLE I Patient demographic characteristics, durations of surgery and anesthesia, and anesthetic drug dosages in the two study groups{dagger}
 
Even though the percentage of the patients requiring rescue analgesics in the PACU was similar in the two treatment groups, the amount of fentanyl administered was less in the Celecoxib group compared to the Control group (84 ± 45 µg vs 127 ± 58 µg iv, respectively, P < 0.05). There were no between-group differences in the mean pain scores at PACU discharge; however, the average pain scores on the first, second and third PODs were significantly lower in the Celecoxib group (Table IIGo). Furthermore, the percentages of patients who required "rescue" analgesic medication at 24 hr, 48 hr, and 72 hr after discharge was significantly reduced in the Celecoxib (vs Control) group (54 vs 90%, 39 vs 88%, 31 vs 84%, respectively, all P < 0.05).


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  		TABLE II Pain scores, need for rescue analgesic medication in the PACU, as well as on postoperative day one (< 24 hr), day two (< 48 hr), and day three (< 72 hr), and patient satisfaction with their pain management in the two study groups{dagger}
 
Patient satisfaction with their pain management and the quality of recovery scores on the first, second, and third PODs were significantly higher in the Celecoxib group (Table IIIGo). Recovery of the bowel function occurred earlier (2 ± 1 vs 3 ± 2 days, P < 0.05), and more importantly, the time to resumption of normal daily living activities after surgery was shorter in the Celecoxib (vs Control) group (4 ± 2 vs 6 ± 3, respectively, P < 0.05) (Table IIIGo).


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  		TABLE III Quality of recovery scores, postoperative nausea and vomiting, and primary outcome variables in the two study groups{dagger}
 
Postoperative emetic symptoms did not differ significantly between the two treatment groups (Table IIIGo). No patient in either group experienced either wound or cardiovascular complications at the seventh day and one-month follow-up periods after discharge from the hospital.


   Discussion
TOP
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
Effective pain management has been reported to facilitate the recovery process and enhance patient satisfaction after outpatient surgery.1 In the current study involving an adult ambulatory surgery population undergoing laparoscopic surgery, the postoperative administration of oral celecoxib (400 mg·day–1) for four days immediately after surgery was found to be effective in reducing pain, improving patient satisfaction with their pain management and facilitating the recovery of activities of daily living. This study confirms the previously published study by Gan et al.13 where a combination of parecoxib and valdecoxib was administered for five days in patients undergoing laparoscopic cholecystectomy procedures. Our findings are also of clinical importance because it has been recently suggested that inadequately treated acute postoperative pain may lead to chronic pain, even in outpatients undergoing minor surgical procedures.19

The use of COX-2 selective inhibitors has become increasingly controversial following the withdrawal of rofecoxib and valdecoxib from the market due to concerns regarding the occurrence of cardiovascular complications even after relatively short-term (10–14 days) administration to patients undergoing cardiac surgery.15,16 In the study by Nussmeier et al.,16 the perioperative use of the COX-2 inhibitors parecoxib and valdecoxib was associated with an increased incidence of cardiovascular events within the 30-day follow-up period after cardiac surgery. Despite this observation, many non-cardiac surgery studies6–14 have confirmed that administration of COX-2 inhibitors before and/or after surgery has beneficial effects with respect to improving postoperative pain management without causing serious complications.20

In contrast to their short-term use (< one week) in the perioperative period, long-term use (> 12 months) of celecoxib21 and rofecoxib22 for chronic pain conditions has been reported to increase the incidence of cardiovascular adverse events. In a recent metaanalysis, Zhang et al.23 reported that rofecoxib was associated with an increased risk of renal and cardiac complications, but a COX-2 inhibitor "class" effect was not demonstrated because celecoxib (and other investigational COX-2 inhibitors) did not appear to be associated with an increased risk of cardiovascular complications. Despite extensive world-wide use of COX-2 inhibitors in the perioperative period, there have been no reports of serious cardiovascular complications associated with short-term use of COX-2 inhibitors in non-cardiac surgery patients.24

The concerns about the potential for COX-2 inhibitors to increase prothrombotic complications have lead to the search for "alternative" non-opioid analgesics.25 The gabapentinoid compounds, gabapentin26,27 and pregabalin28 are an interesting class of non-opioid analgesics which appear to possess similar benefits to the COX-2 inhibitors in improving patient satisfaction and facilitating the recovery process after surgery. Other non-opioid compounds (e.g., iv acetaminophen, longer-acting local anesthetics) are also being evaluated as alternatives to the COX-2 inhibitors for minimizing the opioid analgesic requirement and improving patient outcomes after surgery.29 The current study can be criticized because we failed to include an "active" comparator drug (e.g., ibuprofen). Future studies should compare celecoxib to the less costly non-selective NSAIDs like ibuprofen when administered alone and in combination with acetaminophen immediately after surgery.

In contrast to the study by Buvanendran et al.30 in patients undergoing knee replacement surgery, the patients in our current study only received the COX-2 inhibitor after their operation. The benefits of short-term postoperative administration of celecoxib in this laparoscopic surgery population were similar to those reported after knee replacement surgery with respect to improved pain management and outcome measures. Our rationale for administering celecoxib only in the postoperative period was because we have found no advantage with peri- vs postoperative celecoxib administration with respect to reducing pain or improving patient outcomes after major plastic surgery procedures.31 Although Reuben et al.8 reported that administration of a COX-2 inhibition before surgery provides a longer duration of analgesia, less than 24 hr opioid use and lower pain scores compared to administration of the same dose of the drug after surgery, a qualitative and quantitative systematic review of the peer-reviewed literature, questioned the importance of the timing of analgesia.32

Despite the opioid-sparing effect of the COX-2 inhibitor in this outpatient surgery population, the overall incidence of postoperative nausea and vomiting was not significantly reduced in this study. The routine administration of droperidol and dexamethasone for antiemetic prophylaxis and the avoidance of nitrous oxide during the maintenance anesthetic period clearly contributed to the low incidence of postoperative emetic symptoms in both treatment groups. Additionally, the study was insufficiently powered to find a difference between the groups with respect to this secondary outcome variable. The failure to find a significant difference between the two study groups in the mean pain scores on POD three was probably related to the fact that the celecoxib-treated patients were more active at 48–72 hr after surgery. Finally, pharmacoeconomic studies are clearly needed to compare the analgesic efficacy and safety of oral COX-2 inhibitors with other less costly non-opioid analgesics (e.g., ibuprofen, acetaminophen) after surgery.33,34

In conclusion, administration of celecoxib (400 mg·day–1 po) for four days after laparoscopic surgery decreased postoperative pain and the need for analgesic rescue medication, contributing to improved patient satisfaction and their quality of recovery. These data suggest that celecoxib appears to be an acceptable alternative to the parecoxib-valdecoxib combination13 in this surgical population. The short-term use of the COX-2 inhibitor did not result in any postoperative wound (e.g., hematoma formation, infections) or cardiovascular complications. Therefore, celecoxib (400 mg·day–1 po) facilitated the resumption of normal activities of daily living after discharge in patients undergoing laparoscopic surgery without any serious complications.


Figure 1
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  		Twillingate - Newfoundland

 

   Acknowledgments
 
The authors sincerely thank Isabel Hernandez for her valuable assistance in the preparation of this manuscript.


   Footnotes
 
Financial support: This investigator–initiated, FDA–approved study was supported in part by an unrestricted educational grant from Pfizer, Inc. (New York, NY), endowment funds from the Margaret Milam McDermott Distinguished Chair in Anesthesiology, and the White Mountain Institute, a non-profit private foundation (Paul F. White, President).

Accepted for publication January 12, 2007. Revision accepted.


   References
TOP
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
1 White PF. The role of non-opioid analgesic techniques in the management of pain after ambulatory surgery. Anesth Analg 2002; 94: 577–85.[Free Full Text]

2 Liu J, Ding Y, White PF, Feinstein R, Shear JM. Effects of ketorolac on postoperative analgesia and ventilatory function after laparoscopic cholecystectomy. Anesth Analg 1993; 76: 1061–6.[Abstract/Free Full Text]

3 Coloma M, White PF, Huber PJ Jr, Tongier WK, Dullye KK, Duffy LL. The effect of ketorolac on recovery after anorectal surgery: intravenous versus local administration. Anesth Analg 2000; 90: 1107–10.[Free Full Text]

4 Rusy LM, Houck CS, Sullivan LJ, et al. A double-blind evaluation of ketorolac tromethamine versus acetaminophen in pediatric tonsillectomy: analgesia and bleeding. Anesth Analg 1995; 80: 226–9.[Abstract]

5 Souter AJ, Fredman B, White PF. Controversies in the perioperative use of nonsteroidal anti-inflammatory drugs. Anesth Analg 1994; 79: 1178–90.[Free Full Text]

6 Reuben SS, Fingeroth R, Krushell R, Maciolek H. Evaluation of the safety and efficacy of the perioperative administration of rofecoxib for total knee arthroplasty. J Arthroplasty 2002; 17: 26–31.[Medline]

7 Issioui T, Klein KW, White PF, et al. The efficacy of premedication with celecoxib and acetaminophen in preventing pain after otolaryngologic surgery. Anesth Analg 2002; 94: 1188–93.[Abstract/Free Full Text]

8 Reuben SS, Bhopatkar S, Maciolek H, Joshi W, Sklar J. The preemptive analgesic effect of rofecoxib after ambulatory arthroscopic knee surgery. Anesth Analg 2002; 94: 55–9.[Abstract/Free Full Text]

9 Issioui T, Klein KW, White PF, et al. Cost-efficacy of rofecoxib versus acetaminophen for preventing pain after ambulatory surgery. Anesthesiology 2002; 97: 931–7.[Medline]

10 Watcha MF, Issioui T, Klein KW, White PF. Costs and effectiveness of rofecoxib, celecoxib, and acetaminophen for preventing pain after ambulatory otolaryngologic surgery. Anesth Analg 2003; 96: 987–94.[Abstract/Free Full Text]

11 Recart A, Issioui T, White PF, et al. The efficacy of celecoxib premedication on postoperative pain and recovery times after ambulatory surgery: a dose-ranging study. Anesth Analg 2003; 96: 1631–5.[Abstract/Free Full Text]

12 Ma H, Tang J, White PF, et al. Perioperative rofecoxib improves early recovery after outpatient herniorrhaphy. Anesth Analg 2004; 98: 970–5.[Abstract/Free Full Text]

13 Gan TJ, Joshi GP, Viscusi E, et al. Preoperative parenteral parecoxib and follow-up oral valdecoxib reduce length of stay and improve quality of patient recovery after laparoscopic cholecystectomy surgery. Anesth Analg 2004; 98: 1665–73.[Abstract/Free Full Text]

14 Ekman EF, Wahba M, Ancona F. Analgesic efficacy of perioperative celecoxib in ambulatory arthroscopic knee surgery: a double-blind, placebo-controlled study. Arthroscopy 2006; 22: 635–42.[Medline]

15 Ott E, Nussmeier NA, Duke PC, et al.; Multicenter Study of Perioperative Ischemia (McSPI) Research Group; Ischemia Research and Education Foundation (IREF) Investigators. Efficacy and safety of the cylcooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery. J Thorac Cardiovasc Surg 2003; 125: 1481–92.[Abstract/Free Full Text]

16 Nussmeier NA, Whelton AA, Brown MT, et al. Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. N Engl J Med 2005; 352: 1081–91.[Abstract/Free Full Text]

17 Aldrete JA. The post-anesthesia recovery score revisited. J Clin Anesth 1995; 7: 89–91.[Medline]

18 Myles PS, Hunt JO, Nightingale CE, et al. Development and psychometric testing of a quality of recovery score after general anesthesia and surgery in adults. Anesth Analg 1999; 88: 83–90.[Abstract/Free Full Text]

19 Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet 2006; 367: 1618–25.[Medline]

20 Nussmeier NA, Whelton AA, Brown MT, et al. Safety and efficacy of the cyclooxygenase-2 inhibitors parecoxib and valdecoxib after noncardiac surgery. Anesthesiology 2006; 104: 518–26.[Medline]

21 Solomon SD, Pfeffer MA, McMurray JJ, et al.; APC and PreSAP Trial Investigators. Effect of celecoxib on cardiovascular events and blood pressure in two trials for the prevention of colorectal adenomas. Circulation 2006; 114: 1028–35.[Abstract/Free Full Text]

22 Bresalier RS, Sandler RS, Quan H, et al.; Adenomatous Polyp Prevention on Vioxx (APPROVe) Trial Investigators. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 2005; 352: 1092–102.[Abstract/Free Full Text]

23 Zhang J, Ding EL, Song Y. Adverse effects of cyclooxygenase 2 inhibitors on renal and arrhythmia events: meta-analysis of randomized trials. JAMA 2006; 296: 1619–32.[Medline]

24 Naesh O. Back to the future: postoperative pain management beyond COX-2 inhibitors. N Z Med J 2006; 119: U2170.[Medline]

25 White PF. Changing role of COX-2 inhibitors in the perioperative period: is parecoxib really the answer? Anesth Analg 2005; 100: 1306–8.[Free Full Text]

26 Gilron I, Orr E, Tu D, O’Neill JP, Zamora JE, Bell AC. A placebo-controlled randomized clinical trial of perioperative administration of gabapentin, rofecoxib and their combination for spontaneous and movementevoked pain after abdominal hysterectomy. Pain 2005; 113: 191–200.[Medline]

27 Turan A, White PF, Karamanlioglu B, et al. Gabapentin: an alternative to the cyclooxygenase-2 inhibitors for perioperative pain management. Anesth Analg 2006; 102: 175–81.[Abstract/Free Full Text]

28 Reuben SS, Buvanendran A, Kroin JS, Raghunathan K. The analgesic efficacy of celecoxib, pregabalin, and their combination for spinal fusion surgery. Anesth Analg 2006; 103: 1271–7.[Abstract/Free Full Text]

29 White PF. The changing role of non-opioid analgesic techniques in the management of postoperative pain. Anesth Analg 2005; 101(5 Suppl): S5–22.[Abstract/Free Full Text]

30 Buvanendran A, Kroin JS, Tuman KJ, et al. Effects of perioperative administration of a selective cyclooxygenase 2 inhibitor of pain management and recovery of function after knee replacement: a randomized controlled trial. JAMA 2003; 290: 2411–8.[Abstract/Free Full Text]

31 Sacan O, Romero G, Coleman JE, White PF. Effect of peri- vs postoperative celecoxib administration on recovery after major plastic surgery procedures. Anesthesiology 2005; 103: A977 (abstract).

32 Moiniche S, Kehlet H, Dahl JB. A qualitative and quantitative systematic review of preemptive analgesia for postoperative pain relief: the role of timing of analgesia. Anesthesiology 2002; 96: 725–41[Medline]

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34 Gajraj NM. Cyclooxygenase-2 inhibitors. Anesth Analg 2003; 96: 1720–38.[Free Full Text]




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