Advances in the Management of Acute Postsurgical Pain: A Review.

Despite the millions of surgeries performed every year around the world, postoperative pain remains prevalent and is often addressed with inadequate or suboptimal treatments. Chronic postsurgical pain is surprisingly prevalent, and its rate varies with the type of surgery, as well as with certain patient characteristics. Thus, better clinical training is needed as well as patient education. As pain can be caused by more than one mechanism, multimodal or balanced postsurgical analgesia is appropriate. Pharmacological agents such as opioid and nonopioid pain relievers, as well as adjuvants and nonpharmacologic approaches, can be combined to provide better and opioid-sparing pain relief. Many specialty societies have guidelines for postoperative pain management that emphasize multimodal postoperative analgesia. These guidelines are particularly helpful when dealing with special populations such as pregnant patients or infants and children. Pediatric pain control, in particular, can be challenging as patients may be unable to communicate their pain levels. A variety of validated assessment tools are available for diagnosis. Related to therapy, most guidelines agree on the fact that codeine should be used with extreme caution in pediatric patients as some may be "rapid metabolizers" and its use may be life-threatening. Prehabilitation is a preoperative approach that prepares patients in advance of elective surgery with conditioning exercises and other interventions to optimize their health. Prehabilitation may have aerobic, strength-training, nutritional, and counseling components. Logistical considerations and degree of patient adherence represent barriers to effective prehabilitation programs. Notwithstanding all this, acute postoperative pain represents a clinical challenge that has not yet been well addressed.

Intrathecal opioids for the management of post-operative pain.

Intrathecal opioids are highly effective in the management of post-operative pain. The technique is simple with a very low risk of technical failure or complications, and it does not require additional training or expensive equipment such as ultrasound machines and, therefore, is widely practised around the world. The high-quality pain relief is not associated with sensory, motor or autonomic deficits. This study focuses on intrathecal morphine (ITM) which is the only US Food and Drug Administration-approved opioid for intrathecal administration and remains the most commonly used as well as extensively studied. The use of ITM is associated with prolonged analgesia lasting 20-48 h after a variety of surgical procedures. ITM has a well-established role in thoracic, abdominal, spinal, urological and orthopaedic surgeries. It is considered the 'gold standard' analgesia technique for caesarean delivery which is generally performed under spinal anaesthesia. As the role of epidural technique in post-operative pain management continues to decrease, ITM has emerged as the neuraxial technique of choice for pain management after a major surgery as a component of multimodal analgesia in Enhanced Recovery After Surgery (ERAS) protocols. ITM is recommended by many scientific groups and societies such as ERAS, PROSPECT, the National Institute for Health and Care Excellence and the Society of Obstetric Anesthesiology and Perinatology. The doses of ITM have decreased successively; today they are a fraction of those used in the early 1980s. With these dose reductions, the risks have decreased; current evidence shows that the risk of the much-feared respiratory depression with low-dose ITM (up to 150 mcg) is no greater than that with systemic opioids used in routine clinical practice. Patients receiving low-dose ITM can be nursed in regular surgical wards. The monitoring recommendations from societies such as the European Society of Regional Anaesthesia and Pain Therapy (ESRA), the American Society of Regional Anesthesia and Pain Medicine and the American Society of Anesthesiologists need to be updated so that the requirements for extended or continuous monitoring at postoperative care units (PACUs), step-down units, high-dependency units, and intensive care units can be eliminated, thereby reducing additional costs and inconvenience and making this simple, versatile and highly effective analgesia technique available to a wider patient population in resource-limited settings.

Current status of the combined spinal-epidural technique in obstetrics and surgery.

Epidural and spinal blocks are well-accepted neuraxial techniques but both have several disadvantages. Combined spinal-epidural (CSE) can combine the best features of both techniques and reduce or eliminate these disadvantages. It provides the rapidity, density, and reliability of subarachnoid block with the flexibility of catheter epidural technique to extend the duration of anesthesia/analgesia (and to improve spinal block). It is an excellent technique for determining minimum intrathecal drug doses. Although most commonly employed in obstetric practice, CSE is also used in a wide variety of non-obstetric surgical procedures including orthopedic, vascular, gynecological, urological, and general surgical procedures. The needle-through-needle technique remains the most commonly used method to perform CSE. Several technical variations including Sequential CSE and Epidural Volume Extention (EVE) are commonly used particularly in obstetric and high-risk patients such as those with cardiac disease where a slower onset of sympathetic block is desirable. The risks of complications such as epidural catheter migration through the dural hole, neurological complications, and subarachnoid spread of epidurally administered drugs are possible but have not been a clinically relevant problem in the 40+ years of their existence. In obstetrics, CSE is used for labor pain because it produces rapid-onset analgesia with reduced local anesthetic consumption and less motor block. The epidural catheter placed as part of a CSE is more reliable than a catheter placed as part of a conventional epidural. Less breakthrough pain throughout labor is noted and fewer catheters require replacing. Side effects of CSE include greater potential for hypotension and more fetal heart rate abnormalities. CSE is also used for cesarean delivery. The main purpose is to decrease the spinal dose so that spinal-induced hypotension can be reduced. However, reducing the spinal dose requires an epidural catheter to avoid intra-operative pain when surgery is prolonged.

Pain management after total knee arthroplasty: PROcedure SPEcific Postoperative Pain ManagemenT recommendations.

BACKGROUND: The PROSPECT (PROcedure SPEcific Postoperative Pain ManagemenT) Working Group is a global collaboration of surgeons and anaesthesiologists formulating procedure-specific recommendations for pain management after common operations. Total knee arthroplasty (TKA) is associated with significant postoperative pain that is difficult to treat. Nevertheless, pain control is essential for rehabilitation and to enhance recovery. OBJECTIVE: To evaluate the available literature and develop recommendations for optimal pain management after unilateral primary TKA. DESIGN: A narrative review based on published systematic reviews, using modified PROSPECT methodology. DATA SOURCES: A literature search was performed in EMBASE, MEDLINE, PubMed and Cochrane Databases, between January 2014 and December 2020, for systematic reviews and meta-analyses evaluating analgesic interventions for pain management in patients undergoing TKA. ELIGIBILITY CRITERIA: Each randomised controlled trial (RCT) included in the selected systematic reviews was critically evaluated and included only if met the PROSPECT requirements. Included studies were evaluated for clinically relevant differences in pain scores, use of nonopioid analgesics, such as paracetamol and nonsteroidal anti-inflammatory drugs and current clinical relevance. RESULTS: A total of 151 systematic reviews were analysed, 106 RCTs met PROSPECT criteria. Paracetamol and nonsteroidal anti-inflammatory or cyclo-oxygenase-2-specific inhibitors are recommended. This should be combined with a single shot adductor canal block and peri-articular local infiltration analgesia together with a single intra-operative dose of intravenous dexamethasone. Intrathecal morphine (100 µg) may be considered in hospitalised patients only in rare situations when both adductor canal block and local infiltration analgesia are not possible. Opioids should be reserved as rescue analgesics in the postoperative period. Analgesic interventions that could not be recommended were also identified. CONCLUSION: The present review identified an optimal analgesic regimen for unilateral primary TKA. Future studies to evaluate enhanced recovery programs and specific challenging patient groups are needed.

Epidural analgesia for postoperative pain: Improving outcomes or adding risks?

Current evidence shows that the benefits of epidural analgesia (EA) are not as impressive as believed in the past, while the risks of adverse effects and serious complications are greater than previously estimated. There are many reasons for the decreasing role of epidural technique in clinical practice (table). Indeed, EA can cause harm and hinder early mobilization in enhanced recovery after surgery (ERAS) programmes. Some ERAS interventions are complex, confusing, sometimes contradictory and apparently unimplementable. In spite of much hype and after almost 25 years, the originator of the concept has described the current status of ERAS as 'far from good'. Outpatient surgery setup has been a remarkable success for many major surgical procedures, and it predates ERAS and appears to be a simpler and better model for reducing postoperative morbidity and hospitalization times. Systematic reviews of comparative studies have shown that less invasive and safer but equally effective alternatives to EA are available for almost all major surgical procedures. These include: paravertebral block, peripheral nerve blocks, catheter wound infusion, periarticular local infiltration analgesia, preperitoneal catheters and transversus abdominis plane block. Increasingly, these non-EA methods are being used as surgeon-delivered regional analgesia (RA) techniques. This encouraging trend of active surgeon participation, with anaesthesiologist collaboration, will undoubtedly improve the decades-old twin problems of underused RA techniques and undertreated postoperative pain. The continued use of EA at any institution can only be justified by results from its own audits; however, regrettably only very few institutions perform such regular audits.

PROSPECT guideline for hallux valgus repair surgery: a systematic review and procedure-specific postoperative pain management recommendations.

Hallux valgus repair is associated with moderate-to-severe postoperative pain. The aim of this systematic review was to assess the available literature and develop recommendations for optimal pain management after hallux valgus repair. A systematic review using PROcedure SPECific Postoperative Pain ManagemenT (PROSPECT) methodology was undertaken. Randomized controlled trials (RCTs) published in the English language from inception of database to December 2019 assessing postoperative pain using analgesic, anesthetic, and surgical interventions were identified from MEDLINE, EMBASE, and Cochrane Database, among others. Of the 836 RCTs identified, 55 RCTs and 1 systematic review met our inclusion criteria. Interventions that improved postoperative pain relief included paracetamol and non-steroidal anti-inflammatory drugs or cyclo-oxygenase-2 selective inhibitors, systemic steroids, ankle block, and local anesthetic wound infiltration. Insufficient evidence was found for the use of gabapentinoids or wound infiltration with extended release bupivacaine or dexamethasone. Conflicting evidence was found for percutaneous chevron osteotomy. No evidence was found for homeopathic preparation, continuous local anesthetic wound infusion, clonidine and fentanyl as sciatic perineural adjuncts, bioabsorbable magnesium screws, and plaster slippers. No studies of sciatic nerve block met the inclusion criteria for PROSPECT methodology due to a wider scope of included surgical procedures or the lack of a control (no block) group. The analgesic regimen for hallux valgus repair should include, in the absence of contraindication, paracetamol and a non-steroidal anti-inflammatory drug or cyclo-oxygenase-2 selective inhibitor administered preoperatively or intraoperatively and continued postoperatively, along with systemic steroids, and postoperative opioids for rescue analgesia.

Thirty-five Years of Acute Pain Services: Where Do We Go From Here?

Acute pain services (APS) have developed over the past 35 years. Originally implemented solely to care for patients with regional catheters or patient-controlled analgesia after surgery, APS have become providers of care throughout the perioperative period, with some institutions even taking the additional step toward providing outpatient services for patients with acute pain. Models vary considerably in terms of tasks and responsibilities, staffing, education, protocols, quality, and financing. Many challenges face today's APS, including the increasing number of patients with preexisting chronic pain, intake of analgesics and opioids before surgery, substance-dependent patients needing special care, shorter hospital stays, early discharge of patients in need of further analgesic treatment, prevention and treatment of chronic postsurgical pain, minimization of adverse events, and side effects of treatment. However, many APS lack a clear-cut definition of their structures, tasks, and quality. Development of APS in the future will require us to face urgent questions, such as, "What are meaningful outcome variables?" and, "How do we define high quality?" It is obvious that focusing exclusively on pain scores does not reflect the complexity of pain and recovery. A broader approach is needed-a common concept of surgical and anesthesiological services within a hospital (eg, procedure-specific patient pathways as indicated by the programs "enhanced recovery after surgery" or the "perioperative surgical home"), with patient-reported outcome measures as one central quality criterion. Pain-related functional impairment, treatment-induced side effects, speed of mobilization, as well as return to normal function and everyday activities are key.

Anesthesia and Analgesia Practice Pathway Options for Total Knee Arthroplasty: An Evidence-Based Review by the American and European Societies of Regional Anesthesia and Pain Medicine.

In 2014, the American Society of Regional Anesthesia and Pain Medicine in collaboration with the European Society of Regional Anaesthesia and Pain Therapy convened a group of experts to compare pathways for anesthetic and analgesic management for patients undergoing total knee arthroplasty in North America and Europe and to develop a practice pathway. This review is intended to be an analysis of the current literature to assist individuals and institutions in designing a pathway for total knee arthroplasty that is based on existing evidence and expert recommendation and may be customized according to individual settings.

Open versus Laparoscopic Surgery: Does the Surgical Technique Influence Pain Outcome? Results from an International Registry.

Postoperative pain management relevant for specific surgical procedures is debated. The importance of evaluating pain with consideration given to type of surgery and the patient's perspective has been emphasized. In this prospective cohort study, we analysed outcome data from 607 patients in the international PAIN OUT registry for assessment and comparison of postoperative pain outcome within the 24 first hours after laparoscopic and open colonic surgery. Patients from the laparoscopic group scored minimum pain at a higher level than the open group (P = 0.012). Apart from minimum pain, no other significant differences in patient reported outcomes were observed. Maximum pain scores >3 were reported from 77% (laparoscopic) and 68% (open) patients (mean ≥ 5 in both groups). Pain interference with mobilization was reported by 87-93% of patients. Both groups scored high levels of patient satisfaction. In the open group, a higher frequency of patients received a combination of general and regional anaesthesia, which had an impact of the minimum pain score. Our results from registry data indicate that surgical technique does not influence the quality of postoperative pain management during the first postoperative day if adequate analgesia is given.

Current issues in postoperative pain management.

Postoperative pain has been poorly managed for decades. Recent surveys from USA and Europe do not show any major improvement. Persistent postoperative pain is common after most surgical procedures, and after thoracotomy and mastectomy, about 50% of patients may experience it. Opioids remain the mainstay of postoperative pain treatment in spite of strong evidence of their drawbacks. Multimodal analgesic techniques are widely used but new evidence is disappointing. Regional anaesthetic techniques are the most effective methods to treat postoperative pain. Current evidence suggests that epidural analgesia can no longer be considered the 'gold standard'. Perineural techniques are good alternatives for major orthopaedic surgery but remain underused. Infiltrative techniques with or without catheters are useful for almost all types of surgery. Simple surgeon-delivered local anaesthetic techniques such as wound infiltration, preperitoneal/intraperitoneal administration, transversus abdominis plane block and local infiltration analgesia can play a significant role in improvement of postoperative care, and the last of these has changed orthopaedic practice in many institutions. Current postoperative pain management guidelines are generally 'one size fits all'. It is well known that pain characteristics such as type, location, intensity and duration vary considerably after different surgical procedures. Procedure-specific postoperative pain management recommendations are evidence based, and also take into consideration the role of anaesthetic and surgical techniques, clinical routines and risk-benefit aspects. The role of acute pain services to improve pain management and outcome is well accepted but implementation seems challenging. The need for upgrading the role of surgical ward nurses and collaboration with surgeons to implement enhanced recovery after surgery protocols with regular audits to improve postoperative outcome cannot be overstated.

Routines for reducing the occurrence of emergence agitation during awakening in children, a national survey.

Emergence agitation following anesthesia in children is not uncommon. It is, although generally self-limiting, associated with both patient and parents distress. We conducted a national survey around the management of behavioral and neurocognitive disturbances after surgery/anesthesia including a case scenario about a child at risk for emergence reaction. Premedication with clonidine or midazolam would have been used 58 and 37% of responders respectively. A propofol based anesthesia was the most common anesthetic technique, however sevoflurane or desflurane was an option for 45 and 8% of responders. Before awakening 65% would have administered an opioid, 48% a low-dose of propofol and 25% clonidine. Sign or symptoms of behavioral disturbance was not assessed by standardize assessment tools. A majority of Swedish anesthesia personnel would undertake some preventive action when handling a child at risk for an emergence reaction, the preventive measure differed and it seems as there is an obvious room for further improvements.

PAIN OUT: an international acute pain registry supporting clinicians in decision making and in quality improvement activities.

RATIONALE, AIMS AND OBJECTIVES: Management of post-operative pain is unsatisfactory worldwide. An estimated 240 million patients undergo surgery each year. Forty to 60% of these patients report clinically significant pain. Discrepancy exists between availability of evidence-based medicine (EBM)-derived knowledge about management of perioperative pain and increased implementation of related practices versus lack of improvement in patient-reported outcomes (PROs). We aimed to assist health care providers to optimize perioperative pain management by developing and validating a medical registry that measures variability in care, identifies best pain management practices and assists clinicians in decision making. METHODS: PAIN OUT was established from 2009 to 2012 with funding from the European Commission. It now continues as a self-sustaining, not-for-profit project, targeting health care professionals caring for patients undergoing surgery. RESULTS: The growing registry includes data from 40 898 patients, 60 hospitals and 17 countries. Collaborators upload data (demographics, clinical, PROs) from patients undergoing surgery in their hospital/ward into an Internet-based portal. Two modules make use of the data: (1) online, immediate feedback and benchmarking compares PROs across sites while offline analysis permits in-depth analysis; and (2) the case-based clinical decision support system offers practice-based treatment recommendations for individual patients; it is available now as a prototype. The Electronic Knowledge Library provides succinct summaries on perioperative pain management, supporting knowledge transfer and application of EBM. CONCLUSION: PAIN OUT, a large, growing international registry, allows use of 'real-life' data related to management of perioperative pain. Ultimately, comparative analysis through audit, feedback and benchmarking will improve quality of care.

AAI-guided anaesthesia is associated with lower incidence of 24-h MMSE < 25 and may impact the IL-6 response.

INTRODUCTION: Trauma stress and neuro-inflammation caused by surgery/anaesthesia releases cytokines. This study analysed impact of Auditory Evoked Potential Index (AAI) depth-of-anaesthesia titration on the early plasma IL-6 release after eye surgery under general anaesthesia. METHOD: This is a subgroup analysis of a prospective randomized study on the effect of auditory evoked potential guided anaesthesia for eye surgery. Plasma IL-6 levels taken before, 5 and 24 h after end of surgery from 450 patients undergoing elective ophthalmic surgery under desflurane anaesthesia were analysed. Minimal mental state examination (MMSE) was also tested at 24-h. RESULTS: IL- 6 increased significantly at both 5 and further at 24 h after surgery (3.2, 4.5 and 5.1 base-line, 5 and 24-h respectively), the IL-6 increase showed different patterns between the 2 groups; IL-6 was significantly increased in the control group of patients between preoperative baseline and 24 h after surgery (p = 0.008) also between 5 h and 24 h, (p = 0.006) after surgery while the AAI-group had only minor non-significant changes. The 18 patients that showed a 24-h MMSE score less than 25 had a significant higher 24-h IL-6 compared to the 390 patients with a MMSE score > 24 (p = 0.002). CONCLUSION: The IL-6 increase after surgery was less pronounced in patients where anaesthesia was titrated by AAI compared to anaesthesia adjusted on clinical signs only. IL-6 were also found to be higher in patients with a MMSE < 25 at 24-h. Further studies are warranted evaluating the role of depth of anaesthesia monitoring on the risk for early cognitive impairment and neuro-inflammation. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NA/study were conducted between January 2005-April 2008.

Perioperative management in order to minimise postoperative delirium and postoperative cognitive dysfunction: Results from a Swedish web-based survey.

UNLABELLED: Cognitive side-effects such as emergence agitation (EA), postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are not infrequently complicating the postoperative care especially in elderly and fragile patients. The aim of the present survey was to gain insight regarding concern and interest in prevention and treatment strategies for postoperative delirium and dysfunction, and the use of EEG-based depth-of-anaesthesia monitoring possibly reducing the risk for cognitive side effects among anaesthesia personnel. METHODS: A web-based validated questionnaire was sent to all Swedish anaesthesiologists and nurse anaesthetists during summer 2013. The questionnaire consisted of 3 sections, subjective preferences, routines and practices related to the perioperative handling of EA, POD, POCD. RESULTS: The response rate was 52%. Cardiovascular/pulmonary risks where assessed as importance by 98, 97% of responders while 69% considered the risk of neurocognitive side-effects important. When asked explicitly around cognitive side-effects 89%, 37% and 44% assessed awareness, POC and POD respectively of importance. EEG-based depth-of-anaesthesia monitors were used in 50% of hospitals. The responders were not convinced about the benefits of such monitors even in at-risk patients. Structured protocols for the management of postoperative cognitive side-effects were available only in few hospitals. CONCLUSION: Swedish anaesthesia personnel are concerned about the risk of postoperative cognitive side-effects but are more concerned about cardiovascular/pulmonary risks, pain, PONV and the rare event of awareness. Most respondents were not convinced about the use of depth-of-anaesthesia monitors. There is a need to improve knowledge around risk factors, prevention and management of postoperative cognitive side effects.

Evaluation of etoricoxib in patients undergoing total knee replacement surgery in a double-blind, randomized controlled trial.

BACKGROUND: Optimal postoperative pain management is important to ensure patient comfort and early mobilization. METHODS: In this double-blind, placebo- and active-controlled, randomized clinical trial, we evaluated postoperative pain following knee replacement in patients receiving placebo, etoricoxib (90 or 120 mg), or ibuprofen 1800 mg daily for 7 days. Patients ≥18 years of age who had pain at rest ≥5 (0-10 Numerical Rating Scale [NRS]) after unilateral total knee replacement were randomly assigned to placebo (N = 98), etoricoxib 90 mg (N = 224), etoricoxib 120 mg (N = 230), or ibuprofen 1800 mg (N = 224) postoperatively. Co-primary endpoints included Average Pain Intensity Difference at Rest over Days 1-3 (0- to 10-point NRS) and Average Total Daily Dose of Morphine over Days 1-3. Pain upon movement was evaluated using Average Pain Intensity Difference upon Knee Flexion (0- to 10-point NRS). The primary objective was to demonstrate analgesic superiority for the etoricoxib doses vs. placebo; the secondary objective was to demonstrate that the analgesic effect of the etoricoxib doses was non-inferior to ibuprofen. Adverse experiences (AEs) including opioid-related AEs were evaluated. RESULTS: The least squares (LS) mean (95% CI) differences from placebo for Pain Intensity Difference at Rest over Days 1-3 were -0.54 (-0.95, -0.14); -0.49 (-0.89, -0.08); and -0.45 (-0.85, -0.04) for etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively (p < 0.05 for etoricoxib vs. placebo). Differences in LS Geometric Mean Ratio morphine use over Days 1-3 from placebo were 0.66 (0.54, 0.82); 0.69 (0.56, 0.85); and 0.66 (0.53, 0.81) for etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively (p < 0.001 for etoricoxib vs. placebo). Differences in LS Mean Pain Intensity upon Knee Flexion were -0.37 (-0.85, 0.11); -0.46 (-0.94, 0.01); and -0.42 (-0.90, 0.06) for etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively. Opioid-related AEs occurred in 41.8%, 34.7%, 36.5%, and 36.3% of patients on placebo, etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively. CONCLUSIONS: Postoperative use of etoricoxib 90 and 120 mg in patients undergoing total knee replacement is both superior to placebo and non-inferior to ibuprofen in reducing pain at rest and also reduces opioid (morphine) consumption. CLINICAL TRIAL REGISTRATION: NCT00820027.

Patients' perception of postoperative pain management: validation of the International Pain Outcomes (IPO) questionnaire.

UNLABELLED: PAIN OUT is a European Commission-funded project aiming at improving postoperative pain management. It combines a registry that can be useful for quality improvement and research using treatment and patient-reported outcome measures. The core of the project is a patient questionnaire-the International Pain Outcomes questionnaire-that comprises key patient-level outcomes of postoperative pain management, including pain intensity, physical and emotional functional interference, side effects, and perceptions of care. Its psychometric quality after translation and adaptation to European patients is the subject of this validation study. The questionnaire was administered to 9,727 patients in 10 languages in 8 European countries and Israel. Construct validity was assessed using factor analysis. Discriminant validity assessment used Mann-Whitney U tests to detect mean group differences between 2 surgical disciplines. Internal consistency reliability was calculated as Cronbach's alpha. Factor analysis resulted in a 3-factor structure explaining 53.6% of variance. Cronbach's alpha at overall scale level was high (.86), and for the 3 subscales was low, moderate, or high (range, .53-.89). Significant mean group differences between general and orthopedic surgery patients confirmed discriminant validity. The psychometric quality of the International Pain Outcomes questionnaire can be regarded as satisfactory. PERSPECTIVE: The International Pain Outcomes questionnaire provides an instrument for postoperative pain assessment and improvement of quality of care, which demonstrated good psychometric quality when translated into a variety of languages in a large European and Israeli patient population. This measure provides the basis for the first comprehensive postoperative pain registry in Europe and other countries.

Perioperative use of etoricoxib reduces pain and opioid side-effects after total abdominal hysterectomy: a double-blind, randomized, placebo-controlled phase III study.

OBJECTIVE: To evaluate the effects of two different doses of etoricoxib delivered perioperatively compared with placebo and standard pain management on pain at rest, pain with mobilization, and use of additional morphine/opioids postoperatively. RESEARCH DESIGN AND METHODS: In this double-blind, placebo-controlled, randomized clinical trial, we evaluated postoperative pain following total abdominal hysterectomy over 5 days in patients receiving placebo or etoricoxib administered 90 min prior to surgery and continuing postoperatively. Patients were randomly assigned to receive either placebo (n = 144), etoricoxib 90 mg/day (n = 142), or etoricoxib 120 mg/day (n = 144). Average Pain Intensity at Rest over days 1-3 (0- to 10-point numerical rating scale [NRS]) was the primary efficacy endpoint. Secondary endpoints included Average Pain Intensity upon Sitting, Standing, and Walking over days 1-3 (0- to 10-point NRS) as well as Average Total Daily Dose of Morphine over days 1-3. CLINICAL TRIAL REGISTRATION: This trial is registered on www.clinicaltrials.gov (NCT00788710). RESULTS: The least squares (LS) means (95% CI) for the primary endpoint were 3.26 (2.96, 3.55); 2.46 (2.16, 2.76); and 2.40 (2.11, 2.69) for placebo, etoricoxib 90 mg, and etoricoxib 120 mg, respectively, significantly different for both etoricoxib doses versus placebo (p < 0.001). Patients on etoricoxib 90 mg and 120 mg required ~30% less morphine per day than those on placebo (p < 0.001), which led to more rapid bowel recovery in the active treatment groups by ~10 hours vs. placebo. A greater proportion of patients on etoricoxib (10-30% greater than placebo) achieved mild levels of pain with movement, defined as pain ≤3/10. LIMITATIONS: A key limitation for this study was that movement-evoked pain measurements were not designated as primary endpoints. CONCLUSION: In patients undergoing total abdominal hysterectomy, etoricoxib 90 mg and 120 mg dosed preoperatively and then continued postoperatively significantly reduces both resting and movement-related pain, as well as reduced opioid (morphine) consumption that led to more rapid bowel recovery.