A prospective randomized trial on the role of perioperative celecoxib administration for total knee arthroplasty: improving clinical outcomes.

BACKGROUND: Total knee arthroplasty (TKA) is associated with considerable postoperative pain, which, if unrelieved, may result in prolonged hospital stay, inability to participate in rehabilitation programs, poor outcomes, and greater use of healthcare resources. The hypothesis of this study is that perioperative administration of celecoxib will improve analgesic efficacy, with a resultant improvement in short- and long-term clinical outcomes after TKA. METHODS: We studied 200 patients undergoing elective TKA in a prospective, randomized, double-blind, placebo-controlled fashion. All patients underwent a similar perioperative anesthetic/analgesic procedure. After completion of surgery, patients were started on an epidural infusion with patient-controlled epidural analgesia. Patients were instructed to keep their numerical rating score pain < or = 3. Patients were randomly assigned to one of two groups: celecoxib or placebo. The celecoxib group received celecoxib 100 mg orally twice a day 7 days before surgery. On the day of surgery, celecoxib 400 mg was administered 1-2 h before surgery and then 200 mg every 12 h for 10 postoperative days. The control group received matching placebo capsules at the same times. The primary objective of this study was to determine whether the perioperative use of celecoxib reduces the amount of postoperative opioid consumption. Secondary objectives were to determine whether celecoxib is associated with improved clinical outcomes and a reduction in opioid-related adverse effects. RESULTS: The celecoxib group required less patient-controlled epidural analgesia over the 40-h postoperative period: placebo 232.8 +/- 2.0 mL, celecoxib 209.1 +/- 1.8 mL (P < 0.001). At home over days 4-10 after surgery, the celecoxib group had reduced pain intensity with movement (F = 109.7, P < 0.001) at all time points. The celecoxib group also consumed less oxycodone at home than placebo group (F = 417.8, P < 0.001). With active movement, range of motion (ROM) differed between the two groups over postoperative days 1-3 (F = 50.7, P < 0.001), with the celecoxib group having greater ROM at all time points. There was earlier achievement of 90 degrees knee flexion with celecoxib compared with placebo (P < 0.001). Celecoxib patients had a better overall Knee Society Score (93.3 +/- 0.6) than placebo patients (86.4 +/- 0.9) at 12-mo follow-up (P < 0.001). The incidence of side effects (nausea, vomiting, and pruritus) in the immediate postoperative period was less in the celecoxib group. CONCLUSIONS: Perioperative use of celecoxib reduces postoperative pain, opioid consumption, opioid-related adverse effects, and is associated with long-term benefits including improved knee function and less time to achieve effective knee ROM after TKA.

Update on the role of nonsteroidal anti-inflammatory drugs and coxibs in the management of acute pain.

PURPOSE OF REVIEW: Although NSAIDs have been shown to reduce postoperative analgesics, their ability to reduce opioid-related adverse effects and improve functional outcomes is questioned. Further, perioperative NSAID use may contribute to cardiovascular toxicity and impaired bone healing. This review highlights recent advances in our understanding of the role perioperative NSAIDs have on modulating nociception, their benefits when utilized as components of a multimodal analgesic regimen, and potential deleterious cardiovascular and osteogenic effects. RECENT FINDINGS: Recent research indicates that, in addition to peripheral blockade of prostaglandin synthesis, central inhibition of cyclooxygenase-2 may play an important role in modulating nociception. Although nonspecific NSAIDs provide analgesic efficacy similar to coxibs, their use has been limited in the perioperative setting because of platelet dysfunction and gastrointestinal toxicity. Coxibs may be a safer alternative in that setting. Both coxibs and traditional NSAIDs may contribute to a dose-dependent increase in cardiovascular toxicity and impaired osteogenesis. When used short term at the lowest effective dose, however, NSAIDs may provide for analgesic benefit without significant toxicity. SUMMARY: When utilized as a component of a multimodal analgesic regimen for acute pain, short-term NSAID administration reduces opioid-related side effects and may contribute to improved functional outcomes without significant adverse effects.

Preventing the development of chronic pain after orthopaedic surgery with preventive multimodal analgesic techniques.

The prevalences of complex regional pain syndrome, phantom limb pain, chronic donor-site pain, and persistent pain following total joint arthroplasty are alarmingly high. Central nervous system plasticity that occurs in response to tissue injury may contribute to the development of persistent postoperative pain. Many researchers have focused on methods to prevent central neuroplastic changes from occurring through the utilization of preemptive or preventive multimodal analgesic techniques. Multimodal analgesia allows a reduction in the doses of individual drugs for postoperative pain and thus a lower prevalence of opioid-related adverse events. The rationale for this strategy is the achievement of sufficient analgesia due to the additive effects of, or the synergistic effects between, different analgesics. Effective multimodal analgesic techniques include the use of nonsteroidal anti-inflammatory drugs, local anesthetics, alpha-2 agonists, ketamine, alpha(2)-delta ligands, and opioids.

Evaluating the analgesic efficacy of administering celecoxib as a component of multimodal analgesia for outpatient anterior cruciate ligament reconstruction surgery.

BACKGROUND: Cyclooxygenase-2 inhibitors may play an important role in multimodal management of pain after orthopedic surgery. We examined the analgesic efficacy of administering celecoxib as a component of a multimodal analgesic regimen for outpatient anterior cruciate ligament (ACL) surgery. METHODS: Two-hundred consecutive patients were randomized to receive acetaminophen 1000 mg and either celecoxib 400 mg or placebo 1-2 h before ACL surgery. All patients received intraarticular analgesics (bupivacaine, clonidine, and morphine) and had an external cooling system applied to the operative knee. After discharge, patients were instructed to take acetaminophen 1000 mg every 6 h and either celecoxib 200 mg every 12 h or matching placebo for the first 14 days postoperatively. Oxycodone 5-10 mg was available for rescue analgesia. RESULTS: Patients in the celecoxib group were more likely to experience less pain in the recovery room (P < 0.01) and require less opioids (P < 0.001) for postoperative analgesia. These patients reported a lower incidence of postoperative nausea and vomiting (P < 0.05) and were discharged home earlier (P < 0.05). While at home, patients in the celecoxib group reported lower pain scores both at rest (P < 0.05) and with movement (P < 0.01), and used less oxycodone at all postoperative time intervals. CONCLUSIONS: The perioperative administration of celecoxib decreases postoperative pain, opioid use, postoperative nausea and vomiting, and recovery room length of stay. These results support the use of celecoxib as a component of a preventive multimodal analgesic technique for ACL surgery.

The effect of initiating a preventive multimodal analgesic regimen on long-term patient outcomes for outpatient anterior cruciate ligament reconstruction surgery.

BACKGROUND: Unrelieved postoperative pain may impair rehabilitation, delay recovery, and result in poor outcomes. Preventive multimodal analgesic techniques may improve long-term outcome after surgery. METHODS: We randomized 200 consecutive patients to receive acetaminophen 1000 mg and either celecoxib 400 mg or placebo 1-2 h before anterior cruciate ligament surgery. All patients received intraarticular analgesics and had an external cooling system applied to the operative knee. After discharge patients were instructed to take acetaminophen 1000 mg every 6 h and either celecoxib 200 mg every 12 h or matching placebo for the first 14 days postoperatively. All patients were enrolled in an accelerated rehabilitation program. Six months postoperatively, the level of activity was assessed, as was the presence of patellofemoral complications including: anterior knee pain, flexion contracture, quadriceps weakness, and complex regional pain syndrome. RESULTS: More patients in the control group developed patellofemoral complications compared to the celecoxib group (P = 0.001) including anterior knee pain (14/96; 15%) vs (4/95; 1%), complex regional pain syndrome (7/96; 7%) vs (1/95; 1%), flexion contractures (9/96; 9%) vs (2/95; 2%), and scar tissue requiring re-arthroscopy (8/96; 8%) vs (2/95; 2%) respectively. More patients in the celecoxib group returned to a higher activity level (84% vs 65%) (P < 0.01), were able to participate at a more intense level (P < 0.02), and return to full sports activity (P < 0.05). CONCLUSIONS: The administration of celecoxib as a component of a preventive multimodal analgesic technique for anterior cruciate ligament reconstruction reduces long-term patellofemoral complications and increases the likelihood of returning to a preinjury level of activity.

The efficacy of postoperative perineural infusion of bupivacaine and clonidine after lower extremity amputation in preventing phantom limb and stump pain.

We report the efficacy of perioperative infusion of clonidine and bupivacaine for above-knee amputation in a patient with a history of phantom limb pain in the same extremity after a previous below-knee amputation. The patient underwent general anesthesia. Before transection, the sciatic nerve was infiltrated with 0.25% bupivacaine 5 mL and clonidine 50 microg. After the nerve was severed, a 20-gauge epidural catheter was inserted into the nerve sheath and externalized laterally through a separate skin incision. Before closure, 0.25% bupivacaine 10 mL and clonidine 50 microg was injected, and 0.1% bupivacaine and clonidine two microg/mL was infused at 10 mL/h for the first 96 hours postoperatively. There were no incidents of hypotension, bradycardia, or sedation during the infusion period. The mean postoperative pain score (from 0 to 10) for 96 hours was 1.2 +/- 0.7. The patient required a total of 10 mg of oxycodone postoperatively. The patient did not report either stump or phantom pain for 12 months after surgery.

Chronic pain after surgery: what can we do to prevent it.

The development of chronic pain after surgery is not an uncommon event. Despite increased attention devoted to this topic in the recent medical literature, little is known about the underlying mechanisms, natural history, and response to therapy of each syndrome. Central nervous system plasticity that occurs in response to tissue injury may contribute to the development of persistent postsurgical pain. As evidence continues to accumulate concerning the role of central sensitization in the prolongation of postoperative pain, many researchers have focused on methods to prevent central neuroplastic changes from occurring through the use of preemptive or preventative analgesic techniques. Effective preventative analgesic techniques may be useful in reducing not only acute pain but also chronic postsurgical pain and disability. This review examines the efficacy of using a variety of analgesic techniques aimed at preventing or reducing chronic pain after surgery. Specific chronic postsurgical pain syndromes evaluated include complex regional pain syndrome, phantom limb pain, chronic donor site pain, post-thoracotomy pain syndrome, and postmastectomy pain syndrome.

The analgesic efficacy of celecoxib, pregabalin, and their combination for spinal fusion surgery.

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.

Acute post-surgical pain management: a critical appraisal of current practice, December 2-4, 2005.

The Acute Pain Summit 2005 was convened to critically examine the perceptions of physicians about current methods used to control postoperative pain and to compare those perceptions with the available scientific evidence. Clinicians with expertise in treatment of postsurgical pain were asked to evaluate 10 practice-based statements. The statements were written to reflect areas within the field of acute-pain management, where significant questions remain regarding everyday practice. Each statement made a specific claim about the usefulness of a specific therapy (eg, PCA or epidural analgesia) or the use of pain-control modalities in specific patient populations (eg, epidural analgesia after colon resection). Members of the American Society of Regional Anesthesia and Pain Medicine (ASRA) were asked, via a Web-based survey, to rate their degree of agreement with each of the 10 statements; 22.8% (n = 632) of members responded. In preparation for the pain summit, a panel member independently conducted a literature search and summarized the available evidence relevant to each statement. Summit participants convened in December 2005. The assigned panel member presented the available evidence, and workshop participants then assigned a category for the level of evidence and recommendation for each statement. All participants then voted about each statement by use of the same accept/reject scale used earlier by ASRA members. This manuscript details those opinions and presents a critical analysis of the existing evidence supporting new and emerging techniques used to control postsurgical pain.

Postoperative modulation of central nervous system prostaglandin E2 by cyclooxygenase inhibitors after vascular surgery.

BACKGROUND: The clinical availability of injectable cyclooxygenase inhibitors allows examination of the importance of cyclooxygenase 1 and 2 after surgery. The authors hypothesize that spinal prostaglandin E2 increases with lower extremity vascular surgery and that spinal prostaglandin E2 decreases with intravenous postsurgical administration of either a mixed cyclooxygenase 1/2 inhibitor (ketorolac) or a cyclooxygenase 2 selective inhibitor (parecoxib). METHODS: Thirty patients undergoing elective lower extremity revascularization under continuous spinal anesthesia had cerebrospinal fluid obtained at baseline and then up to 6 h after the start of surgery. Four hours after surgical incision, patients were randomized to receive intravenous parecoxib 40 mg, ketorolac 30 mg, or preservative-free normal saline. Patients were administered intravenous fentanyl in the postanesthesia care unit and acetaminophen/oxycodone on the surgical ward to control pain. RESULTS: Cerebrospinal fluid prostaglandin E2 concentrations were increased during and after surgery. After surgery, intravenous parecoxib 40 mg rapidly decreased cerebrospinal fluid prostaglandin E2, and intravenous ketorolac 30 mg also reduced cerebrospinal fluid prostaglandin E2 compared with placebo, but not as much as parecoxib. Postanesthesia care unit pain scores were reduced in the two drug groups compared with placebo, and surgical ward pain scores were also decreased for both drug groups, especially with parecoxib. No patient receiving parecoxib required postoperative intravenous fentanyl. Acetaminophen/oxycodone consumption was reduced in both drug groups compared with placebo, more so with parecoxib. CONCLUSIONS: Cerebrospinal fluid prostaglandin E2 is elevated in patients after lower extremity vascular surgery. Postsurgical intravenous administration of the cyclooxygenase 1/2 inhibitor ketorolac, and especially the cyclooxygenase 2 inhibitor parecoxib, reduces cerebrospinal fluid prostaglandin E2 concentration and postoperative pain.

The effect of cyclooxygenase-2 inhibition on acute and chronic donor-site pain after spinal-fusion surgery.

BACKGROUND AND OBJECTIVES: The development of chronic pain after spinal-fusion surgery represents a significant source of morbidity. One of the predictive factors for the development of chronic postsurgical pain is inadequate acute postoperative pain management. Further, the up-regulation of cyclooxygenase-2 (COX-2) after surgery may result in neuro-plastic changes that may contribute to a progression from acute to chronic pain. The goal of this prospective, randomized, double-blind study was to examine the effect of perioperative COX-2 inhibition on acute and chronic donor-site pain in patients undergoing spinal-fusion surgery. METHODS: Eighty patients scheduled to undergo instrumented posterior spinal fusion were randomized to either receive celecoxib 400 mg 1 hour before surgery, and then 200 mg every 12 hours after surgery for the first 5 days or receive matching placebo at similar time intervals. Patients were administered morphine via patient-controlled analgesia pump for the first 24 hours, and then acetaminophen and oxycodone tablets. Patients were asked to quantify their average pain on postoperative days 1 to 5. At 1 year after surgery, patients were questioned about the presence and subjective characteristics of any residual donor-site pain. RESULTS: Patients administered celecoxib reported lower pain scores and less opioid use during the first 5 postoperative days. Chronic donor-site pain was significantly higher (P<.01) in the placebo group (12 of 40, or 30%) compared with the celecoxib group (4 of 40, or 10%) at 1 year after surgery. CONCLUSIONS: The administration of celecoxib for the first 5 days after spinal-fusion surgery resulted in improved analgesia and a reduction in chronic donor-site pain at 1 year after surgery.

The incidence of complex regional pain syndrome after fasciectomy for Dupuytren's contracture: a prospective observational study of four anesthetic techniques.

The development of complex regional pain syndrome (CRPS) is not an uncommon complication after Dupuytren's surgery. Despite increasing research interest, little is known regarding which patients are at increased risk for developing CRPS and what is the optimal perioperative treatment strategy for preventing the occurrence of this disease after surgery. We prospectively evaluated the use of four anesthetic techniques (general anesthesia, axillary block, and IV regional anesthesia [IVRA] with lidocaine with or without clonidine) for patients undergoing fasciectomy for Dupuytren's contracture. All patients were followed in the Pain Management Center at 1, 3, and 12 mo postoperatively by a blinded physician to evaluate the presence of CRPS. Significantly (P < 0.01) more patients developed postoperative CRPS in the general anesthesia group (n = 25; 24%) and the IVRA lidocaine group (n = 12; 25%) compared with either the axillary block group (n = 5; 5%) or the IVRA lidocaine and clonidine group (n = 3; 6%). We conclude that axillary block or IVRA with clonidine offers a significant advantage for decreasing the incidence of CRPS compared with either IVRA with lidocaine alone or general anesthesia for patients undergoing Dupuytren's surgery.

High dose nonsteroidal anti-inflammatory drugs compromise spinal fusion.

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 (< or = 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 (< or = 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.

The effect of cyclooxygenase-2 inhibition on analgesia and spinal fusion.

BACKGROUND: Cyclooxygenase (COX)-2-specific inhibitors demonstrate analgesic efficacy comparable with that of conventional nonsteroidal anti-inflammatory drugs but are associated with reduced gastrointestinal side effects and an absence of antiplatelet activity. Thus, they can be administered to patients undergoing spinal fusion surgery without an added risk of bleeding. However, concerns regarding a possible deleterious effect on bone-healing have limited their routine use. Celecoxib, a COX-2 inhibitor, recently was approved for the treatment of acute pain. The goals of the present study were to examine the analgesic efficacy of celecoxib and to determine the incidence of nonunion at one year following spinal fusion surgery. METHODS: Eighty patients who were scheduled to undergo spinal fusion received either celecoxib or placebo one hour before the induction of anesthesia and every twelve hours after surgery for the first five postoperative days. Pain scores and morphine use were recorded one hour after arrival in the post-anesthesia care unit and at four, eight, twelve, sixteen, twenty, and twenty-four hours later. Intraoperative blood loss was recorded. The status of the fusion was determined radiographically at the time of the one-year follow-up. RESULTS: There were no differences in demographic data or blood loss between the two groups. Pain scores were lower in the celecoxib group at one, four, eight, sixteen, and twenty hours postoperatively. There were no differences between the two groups with regard to the pain scores at twelve and twenty-four hours postoperatively. Morphine use was lower in the celecoxib group at all postoperative time-intervals. There was no difference between the celecoxib group and the placebo group with regard to the incidence of nonunion at the time of the one-year follow-up (7.5% [three of forty] compared with 10% [four of forty]). CONCLUSIONS: The perioperative administration of celecoxib resulted in a significant reduction in postoperative pain and opioid use following spinal fusion surgery. In addition, the short-term administration of this COX-2-specific non-steroidal anti-inflammatory drug had no apparent effect on the rate of nonunion at the time of the one-year follow-up.

Surgery on the affected upper extremity of patients with a history of complex regional pain syndrome: the use of intravenous regional anesthesia with clonidine.

STUDY OBJECTIVES: To evaluate the efficacy of intravenous regional anesthesia (IVRA) with clonidine in patients with a previous history of complex regional pain syndrome (CRPS) who are undergoing upper extremity hand surgery. DESIGN: Prospective, randomized, double-blind study. SETTING: Operating suites and Pain Management Center of a large university-affiliated medical center. PATIENTS: 84 patients with a previous history of upper extremity CRPS undergoing surgery on the affected extremity. All signs and symptoms of CRPS had resolved prior to the time of surgery. INTERVENTIONS: Patients were randomized to receive IVRA with 0.5 % lidocaine with either 1 mL normal saline (n=42) or clonidine 1 microg/kg (n=42) added to the lidocaine solution. MEASUREMENTS: Recurrence of CRPS symptoms at 1 year following surgery were recorded. MAIN RESULTS: The recurrence rate of CRPS was significantly lower (p <0.001) in those patients receiving IVRA with lidocaine and clonidine (10%, n=4) compared with those patients receiving IVRA lidocaine only (74%, n=31). CONCLUSIONS: Intraoperative IVRA with lidocaine and clonidine on patients with a history of CRPS can significantly reduce the recurrence rate of this disease process.

Analgesic effect of clonidine added to bupivacaine 0.125% in paediatric caudal blockade.

BACKGROUND: Caudals are a common method of providing pain relief in children undergoing surgery. Clonidine, an alpha(2) agonist, exhibits significant analgesic properties. The current investigation sought to determine whether caudal clonidine added to caudal bupivacaine would decrease pain in paediatric patients undergoing surgery. METHODS: Thirty-six children undergoing elective surgery were studied. Following anaesthetic induction, a caudal was placed (1 mg.kg(-1) bupivacaine 0.125%) with an equal volume of either clonidine (2 microg.kg(-1)) or saline. Perioperative analgesic requirements in the postanaesthesia care unit (PACU) and at home following hospital discharge, and parental pain scores were evaluated. RESULTS: There were no significant demographic, haemodynamic, or pain score differences between the groups. There was no difference in analgesic duration between groups. There were significantly more children who vomited during the first 24 postoperative hours in the clonidine group than in the saline group (eight in clonidine, two in saline; P < 0.05). CONCLUSION: We do not recommend adding clonidine (2 microg.kg(-1)) to a bupivacaine (0.125%) caudal block in children undergoing surgery.