Scott S. Reuben

Postoperative analgesic effects of celecoxib or rofecoxib after spinal fusion surgery

UNLABELLED Nonsteroidal antiinflammatory drugs are recommended for the multimodal management of postoperative pain and may have a significant opioid-sparing effect after major surgery. The analgesic efficacy of the cyclooxygenase-2 nonsteroidal antiinflammatory drugs, celecoxib and rofecoxib, have not been evaluated after major orthopedic surgery. This study was designed to determine whether the administration of a preoperative dose of celecoxib or rofecoxib to patients who have undergone spinal stabilization would decrease patient-controlled analgesia (PCA) morphine use and/or enhance analgesia. We evaluated 60 inpatients undergoing spine stabilization by one surgeon. All patients received PCA morphine. The patients were divided into three groups. Preoperatively, they were given oral celecoxib 200 mg, rofecoxib 50 mg, or placebo. The outcome measures included pain scores and 24-h morphine use at six times during the first 24 postoperative h. The total dose of morphine and the cumulative doses for each of the six time periods were significantly more in the placebo group than in the other two groups. The morphine dose was significantly less in five of the six time intervals in the rofecoxib group compared with the celecoxib group. The pain scores were significantly less in the rofecoxib group than in the other two groups at two of the six intervals, and less than the placebo group in an additional interval. Although both rofecoxib and celecoxib produce similar analgesic effects in the first 4 h after surgery, rofecoxib demonstrated an extended analgesic effect that lasted throughout the 24-h study. We thus recommend that rofecoxib be used as a preoperative component of pain management that includes PCA morphine in patients undergoing spine stabilization surgery. IMPLICATIONS The cyclooxygenase-2-specific nonsteroidal antiinflammatory drugs, celecoxib and rofecoxib, both demonstrate an opioid-sparing effect after spinal fusion surgery. Celecoxib resulted in decreased morphine use for the first 8 h after surgery, whereas rofecoxib demonstrated less morphine use throughout the 24-h study period.

Acute Post-Surgical Pain Management: A Critical Appraisal of Current Practice

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 analgesia for outpatient arthroscopic knee surgery with intraarticular clonidine and/or morphine.

Both clonidine, an &agr;2 agonist, and morphine, an opioid agonist, provide enhanced patient analgesia after arthroscopic knee surgery when administered via the intraarticular (IA) route. Clonidine potentiates morphine analgesia in the animal model. We designed this study to determine whether clonidine or morphine results in better analgesia and whether their combination would provide superior analgesia to either drug alone. We evaluated 60 patients undergoing arthroscopic knee meniscus repair under local anesthesia with sedation. After surgery, patients were randomized into four IA groups: Group B received 30 mL 0.25% bupivacaine; Group BC received 30 mL 0.25% bupivacaine and clonidine 1 &mgr;g/kg; Group BM received 30 mL 0.25% bupivacaine and morphine 3 mg; and Group BCM received 30 mL 0.25% bupivacaine, clonidine 1 &mgr;g/kg, and morphine 3 mg. This study revealed a significant benefit from the individual IA administration of both clonidine and morphine. The combination of these drugs resulted in decreased postoperative pain and analgesic use, as well as an increased analgesic duration compared with either drug alone. We conclude that IA clonidine and morphine improved comfort compared with either drug alone in patients undergoing knee arthroscopy. Implications The intraarticular administration of both clonidine and morphine along with bupivacaine improves postoperative analgesia compared with either drug alone. There was an increased time to first analgesic request, decreased need for postoperative analgesics, and lower pain scores after arthroscopic knee surgery.

Postoperative Analgesia for Outpatient Arthroscopic Knee Surgery with Intraarticular Bupivacaine and Ketorolac

Intraarticular (IA) local anesthetics are often used for the management and prevention of pain after arthroscopic knee surgery.Systemic ketorolac is also useful in the management of these patients. Ketorolac, a nonsteroidal antiinflammatory drug (NSAID), alters the sensitivity of peripheral nociceptors by reducing the local concentration of allogenic chemicals which are activated by peripheral tissue injury. It is interesting to speculate that placing a NSAID at the site of injury might result in more profound pain relief. However, IA ketorolac has not been evaluated in arthroscopic patients. This study thus was designed to determine which regimen would result in the most effective analgesic benefit. The four groups evaluated received ketorolac (either via the parenteral or IA route) or saline placebo with or without IA bupivacaine, as follows: Group 1 received IA bupivacaine; Group 2, intravenous ketorolac and IA bupivacaine; Group 3, IA bupivacaine with ketorolac; and Group 4, IA ketorolac. The results of this study revealed a significant difference in analgesia from the IA administration of ketorolac. The group who received a combination of IA bupivacaine and IA ketorolac had decreased postoperative pain, a decreased need for postoperative analgesics, and an increased analgesic duration. We conclude that the use of IA ketorolac improved comfort in patients undergoing knee arthroscopy. (Anesth Analg 1995;80:1154-7)

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.

Postoperative analgesia with controlled-release oxycodone for outpatient anterior cruciate ligament surgery.

UNLABELLED Reconstruction of the anterior cruciate ligament (ACL) of the knee is associated with a considerable degree of postoperative pain. Although immediate-release oral opioids are usually effective in relieving moderate to severe pain, they must be given every 4-6 h. A controlled-release (CR) formulation of oxycodone maintains therapeutic opioid concentrations for a more prolonged period, thus providing sustained pain relief. We designed this study to determine whether CR oxycodone is more effective and clinically acceptable than immediate-release oxycodone for managing pain after ambulatory ACL repair surgery. All patients received a standard general anesthetic and postoperative analgesic regimen with one of three oxycodone dosing regimens: oxycodone 10 mg every 4 h as needed, oxycodone 10 mg every 4 h, and CR oxycodone 20 mg every 12 h. Rescue analgesic consisted of oxycodone 5 mg every 6 h as needed. At 24, 36, 48, 60, and 72 h, there was a difference in pain scores among the groups (P < 0.0001); there was less pain in the CR oxycodone group. At most times, the fixed-dose group had lower pain scores than the as-needed group. The sedation scores were significantly different at 12 h (P < 0.02) and at 24, 36, 48, 60, and 72 h (P < 0.0001); the patients were more alert in the CR oxycodone group. The 72-h consumption of oxycodone was less in the CR oxycodone group (P < 0.0001). The patients had less sleep disturbance (P < 0.0001), were more satisfied (P < 0.0001), and experienced less vomiting (P < 0.02) in the CR oxycodone group compared with the other two groups. In conclusion, using CR oxycodone in the immediate 72 h after ambulatory ACL surgery provides more effective analgesia with less sedation, sleep disturbance, and postoperative vomiting compared with oxycodone prescribed on either a fixed dose or as-needed schedule. IMPLICATIONS A controlled-release formulation of oxycodone in patients undergoing anterior cruciate ligament repair on an ambulatory basis provides significant analgesic benefit and a lowering of side effects compared with either fixed-dose or as-needed oxycodone regimens.

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.

Intravenous Regional Anesthesia Using Lidocaine and Ketorolac

Nonsteroidal antiinflammatory drugs (NSAIDs) interfere with the synthesis of inflammatory mediators and can supplement postoperative pain relief.We postulated that using the parenterally available NSAID ketorolac (K) as a component of intravenous regional anesthesia (IVRA) would suppress intraoperative tourniquet pain and enhance postoperative analgesia. Sixty patients were assigned randomly and blindly to receive either intravenous (IV) saline and IVRA with 0.5% lidocaine, IV K and IVRA 0.5% lidocaine, or IV saline and IVRA 0.5% lidocaine with K. The patients who received IVRA K reported significantly less intraoperative tourniquet pain, with lower verbal analog pain scores at 15 and 30 min after tourniquet inflation. Similarly, IVRA-K patients experienced less postoperative pain with lower visual analog scale (VAS) pain scores at 30 and 60 min, and required no fentanyl for control of early postoperative pain in the postanesthesia care unit (PACU). They also required fewer analgesic tablets in the first 24 h (1.9 +/- 1.4 Tylenol No. 3 Registered Trademark tablets compared to the other two groups, 4.6 +/- 1.3 and 3.0 +/- 1.1; P < 0.05). We conclude that K improves IVRA with 0.5% lidocaine both in terms of controlling intraoperative tourniquet pain and by diminishing postoperative pain. (Anesth Analg 1995;81:110-3)

Preventing the development of complex regional pain syndrome after surgery

COMPLEX regional pain syndrome (CRPS), previously known as reflex sympathetic dystrophy (RSD), is used to describe a syndrome of pain and sudomotor or vasomotor instability. This pain syndrome usually has an initiating noxious event in the periphery, is not limited to the distribution of a single nerve, and is disproportionate to the inciting event. The Consensus Conference of the International Association for the Study of Pain has subclassified CRPS into two forms: CRPS I (formerly RSD) and CRPS II (formerly causalgia). According to the International Association for the Study of Pain, the diagnosis of CRPS I requires (1) continuing pain, allodynia, or hyperalgesia disproportionate to the injury; (2) evidence at some time of edema, changes in skin blood flow, or abnormal sudomotor activity in the region of pain; and (3) no other conditions that would otherwise account for the degree of pain and dysfunction. Motor disturbances and trophic changes, such as altered nail and hair growth, may be observed in some cases. CRPS II is a pain syndrome that starts after a nerve injury and is not necessarily limited to the distribution of the injured nerve. The diagnostic criteria are the same as those of CRPS I. Patients with CRPS I or CRPS II can have sympathetically maintained pain or sympathetically independent pain. Sympathetically maintained pain, a term introduced in 1986 by Roberts, is pathologic pain that is supported by sympathetic efferent activity, circulating catecholamines, and/or increased sensitivity of -adrenergic receptors. Sympathetically maintained pain is identified by the ability to lessen the pain by sympatholytic blocks or interventions. Sympathetically independent pain has components of pain from sources other than sympathetic innervation and is believed to be most commonly observed in advanced cases of CRPS that do not respond to sympathetic blocks. Patients with CRPS may present with components of only sympathetically maintained pain or sympathetically independent pain or, more commonly, a combination of pain from each. Despite increasing research interest, little is known regarding which patients are at increased risk for development of postoperative CRPS and what the optimal perioperative treatment strategy is for those patients undergoing surgery who have a previous history of CRPS. This review outlines the surgical procedures that are believed to increase risk for development of CRPS and describes pharmacologic and regional analgesic techniques that may be of benefit for preventing the development of CRPS after surgery.

Dose-response of ketorolac as an adjunct to patient-controlled analgesia morphine in patients after spinal fusion surgery.

This randomized, blind study was designed to determine the appropriate dose of ketorolac (a drug used as a supplement to opioids) to administer to patients who have undergone spinal stabilization surgery.The ketorolac was administered every 6 h, in addition to patient-controlled analgesia (PCA) with morphine, to 70 inpatients undergoing spine stabilization by one surgeon. The study was performed to determine the analgesic efficacy and incidence of side effects with different doses of ketorolac. The patients were divided into seven groups. They were given either IV saline (control group) or IV ketorolac (5, 7.5, 10, 12.5, 15, or 30 mg) every 6 h. The outcomes measured included pain scores, 24-h morphine usage, level of sedation, and side effect profile six times during the first 24 h postoperatively. The total dose of morphine was significantly larger in the control and 5 mg ketorolac groups than in the other five groups. Morphine consumption was similar in all groups receiving >or=to7.5 mg of ketorolac. The pain scores were significantly higher in the control group than in some of the larger dose groups at three of the study intervals. The 5 mg group had higher pain scores than the other groups at most of the time intervals studied. There were no significant differences in pain scores among the other five groups. Sedation scores were higher (i.e., patients were more sedated) in the control group than in the other six groups at three of the time periods. We conclude that the administration of ketorolac 7.5 mg every 6 h has a morphine-sparing effect equivalent to that of larger doses in patients undergoing spine stabilization surgery. Using larger doses of ketorolac did not result in less somnolence, lower morphine use, or less pain. We recommend that ketorolac 7.5 mg be given every 6 h to patients undergoing spinal fusion surgery in addition to PCA morphine. Implications: Using smaller doses of ketorolac (e.g., 7.5 mg every 6 h) as a supplement to morphine patient-controlled analgesia is as effective as larger doses in patients who have undergone spine stabilization surgery. (Anesth Analg 1998;87:98-102)