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Stephan Schug,1,2 Esther Pogatzki-Zahn,3 Lawrence D Phillips,4 Margaret Noyes Essex,5 Feng Xia,5 Alison J Reader,6 Robert Pawinski6 1Discipline of Anaesthesiology and Pain Medicine, Medical School, University of Western Australia, Perth, WA, Australia; 2Department of Anaesthesia and Pain Medicine, Royal Perth Hospital, Perth, WA, Australia; 3Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital of Muenster, Muenster, Germany; 4Department of Management, London School of Economics and Political Science, London, UK; 5Pfizer Inc, New York, NY, USA; 6Pfizer Ltd, Walton Oaks, Tadworth, UKCorrespondence: Margaret Noyes Essex Tel +1 212 733 8018Fax +1 646 441 5967Email margaret.essex@pfizer.comBackground: Identifying the optimal treatment in an acute postoperative setting remains a challenge. Multiple analgesic options are available, but comparing outcomes is limited by a lack of head-to-head trials. In addition, decisions based on efficacy only do not take drug safety into account. In such cases, multi-criteria decision analysis (MCDA) can be utilized to quantify and compare the efficacy and safety data of various drugs.Methodology: The efficacy-safety profiles of eight parenteral, postoperative analgesics (acetaminophen, diclofenac, ketorolac, metamizole, morphine, nefopam, parecoxib, tramadol) widely used in Europe were evaluated using an MCDA model that included 17 criteria: three for efficacy and 14 for safety. Each drug was scored on each criterion on a scale from 0 (worst) to 100 (best), according to published data and the judgment of an expert panel. A weighting process was then applied to standardize the impact of each criterion and adjust drugs’ preference scores accordingly, normalizing them on the 0– 100 scale. Sensitivity analyses were also performed, including a model in which analgesic profiles were compared when opioid sparing effect was set at a zero value for all drugs.Results: In the primary model, efficacy and safety had relative weightings of 64% and 36%, respectively. Efficacy and safety criteria with the highest values were pain relief (relative weight, 29%) and gastrointestinal effects (12%). Parecoxib received the highest overall score (93), followed by diclofenac (80), and ketorolac (75). Morphine scored the lowest (57), due to the lack of an opioid sparing effect. When opioid sparing was given a zero rating, parecoxib remained the highest scoring analgesic (93), followed by diclofenac (80), metamizole (76), and morphine (76). Parecoxib remained the most preferred analgesic in several other sensitivity analyses.Conclusion: This MCDA-based assessment suggests that parecoxib has the most favorable efficacy-safety profile among the assessed postoperative analgesics.Keywords: multi-criteria decision analysis, parenteral analgesics, postoperative pain

Bruce Parsons,1 Rainer Freynhagen,2,3 Stephan Schug,4,5 Ed Whalen,1 Marie Ortiz,1 Pritha Bhadra Brown,1 Lloyd Knapp61Pfizer Inc, New York, NY, USA; 2Department of Anesthesiology, Critical Care Medicine, Pain Therapy & Palliative Care, Pain Center Lake Starnberg, Benedictus Hospital, Tutzing, Germany; 3Department of Anesthesiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; 4Discipline of Anaesthesiology and Pain Medicine, Medical School, University of Western Australia, Perth, WA, Australia; 5Department of Anaesthesia and Pain Medicine, Royal Perth Hospital, Perth, WA, Australia; 6Pfizer Inc, Groton, CT, USACorrespondence: Bruce ParsonsPfizer Inc, 235 East 42nd Street, New York, NY, USATel +1 212 573 1649Email bruce.parsons@pfizer.comBackground: Euphoria is a complex, multifactorial problem that is reported as an adverse event in clinical trials of analgesics including pregabalin. The relationship between the reporting of euphoria events and pregabalin early treatment responses was examined in this exploratory post-hoc analysis.Methods: Data were from patients with neuropathic or non-neuropathic chronic pain enrolled in 40 randomized clinical trials, who received pregabalin (75–600 mg/day) or placebo. Reports of treatment-emergent euphoria events were based on the Medical Dictionary of Regulatory Activities preferred term “euphoric mood”. Prevalence rates of euphoria events overall and by indication were assessed. Post-treatment endpoints included ≥30% improvements in pain and sleep scores up to 3 weeks as well as a ≥1-point improvement in daily pain score up to 11 days after treatment.Results: 13,252 patients were analyzed; 8,501 (64.1%) and 4,751 (35.9%) received pregabalin and placebo, respectively. Overall, 1.7% (n=222) of patients reported euphoria events. Among pregabalin-treated patients, a larger proportion who reported euphoria events achieved an early pain response compared with those who did not report euphoria (30% pain responders in week 1 with euphoria events [43.0%], without euphoria events [24.2%]). Results were similar for weeks 2 and 3. For Days 2–11, a larger proportion of pregabalin-treated patients with (relative to without) euphoria events were 1-point pain responders. Findings were similar in pregabalin-treated patients for sleep endpoints (30% sleep responders in week 1 with euphoria events [50.7%], without euphoria events [36.1%]). Similar results were found for weeks 2 and 3. Patients who received placebo showed similar patterns, although the overall number of them who reported euphoria events was small (n=13).Conclusion: In patients who received pregabalin for neuropathic or non-neuropathic chronic pain, those who experienced euphoria events may have better early treatment responses than those who did not report euphoria events.Keywords: euphoria, pain, pregabalin, sleep

Sonya Ting,1 Stephan Schug2,3 1Department of Anaesthesia, Sir Charles Gairdner Hospital, Perth, WA, Australia; 2Anaesthesiology Unit, School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia; 3Department of Anaesthesia and Pain Medicine, Royal Perth Hospital, University of Western Australia Anaesthesiology Unit, Royal Perth Hospital, Perth, WA, Australia Abstract: Pain is a common symptom that can be complex to treat. Analgesic medications are the mainstay treatment, but there is wide interindividual variability in analgesic response and adverse effects. Pharmacogenomics is the study of inherited genetic traits that result in these individual responses to drugs. This narrative review will attempt to cover the current understanding of the pharmacogenomics of pain, examining common genes affecting metabolism of analgesic medications, their distribution throughout the body, and end organ effects. Keywords: cytochrome P450, COMT, pharmacokinetics, pharmacodynamics, inherited traits

Summary: Video‐assisted thoracoscopic surgery has become increasingly popular due to faster recovery times and reduced postoperative pain compared with thoracotomy. However, analgesic regimens for video‐assisted thoracoscopic surgery vary significantly. The goal of this systematic review was to evaluate the available literature and develop recommendations for optimal pain management after video‐assisted thoracoscopic surgery. A systematic review was undertaken using procedure‐specific postoperative pain management (PROSPECT) methodology. Randomised controlled trials published in the English language, between January 2010 and January 2021 assessing the effect of analgesic, anaesthetic or surgical interventions were identified. We retrieved 1070 studies of which 69 randomised controlled trials and two reviews met inclusion criteria. We recommend the administration of basic analgesia including paracetamol and non‐steroidal anti‐inflammatory drugs or cyclo‐oxygenase‐2‐specific inhibitors pre‐operatively or intra‐operatively and continued postoperatively. Intra‐operative intravenous dexmedetomidine infusion may be used, specifically when basic analgesia and regional analgesic techniques could not be given. In addition, a paravertebral block or erector spinae plane block is recommended as a first‐choice option. A serratus anterior plane block could also be administered as a second‐choice option. Opioids should be reserved as rescue analgesics in the postoperative period. [ABSTRACT FROM AUTHOR]

Summary: Chronic postoperative pain is common after breast cancer surgery. Peri‐operative lidocaine infusion may prevent the development of chronic postoperative pain, but a large‐scale trial is required to test this hypothesis. It is unclear whether a pragmatic, multicentre trial design that is consistent with expert guidance, addresses the limitations of previous studies, and overcomes existing translational barriers is safe, effective and feasible. We conducted a double‐blind, randomised controlled pilot study in 150 patients undergoing breast cancer surgery across three hospitals in Western Australia. Patients received lidocaine, or equivalent volumes of saline, as an intravenous bolus (1.5 mg.kg‐1) and infusion (2 mg.kg‐1.h‐1) intra‐operatively, and a subcutaneous infusion (1.33 mg.kg‐1.h‐1) postoperatively for up to 12 h on a standard surgical ward, with novel safety monitoring tools in place. The co‐primary outcomes were: in‐hospital safety events; serum levels of lidocaine during intravenous and subcutaneous infusion; and annualised enrolment rates per site with long‐term data capture. In‐hospital safety events were rare, and similar in the placebo and lidocaine arms (3% vs. 1%). Median (IQR [range]) serum lidocaine levels during intravenous (2.16 (1.74–2.83 [1.12–6.06]) µg.ml‐1, n = 41) and subcutaneous (1.52 (1.28–1.83 [0.64–2.85]) µg.ml‐1, n = 48) infusion were comparable with previous trials reporting improved pain outcomes. Annualised enrolment approximated 50 patients per site per year, with high levels of protocol adherence and ≥ 99% capture of outcomes at 3 and 6 months. The adjusted odds ratio (95%CI) for postoperative pain at 6 months in the lidocaine arm was 0.790 (0.370–1.684). We conclude that this trial, as designed, is safe, effective and feasible in patients undergoing breast cancer surgery, and a larger‐scale trial is planned. [ABSTRACT FROM AUTHOR]

Summary: Tonsillectomy is one of the most frequently performed surgical procedures; however, pain management remains challenging. Procedure‐specific efficacy as well as specific risks of treatment options should guide selection of pain management protocols based on evidence and should optimise analgesia without harm. The aims of this systematic review were to evaluate the available literature and develop recommendations for optimal pain management after tonsillectomy. A systematic review utilising preferred reporting items for systematic reviews and meta‐analysis guidelines with procedure‐specific postoperative pain management (PROSPECT) methodology was undertaken. Randomised controlled trials published in the English language up to November 2019 assessing postoperative pain using analgesic, anaesthetic or surgical interventions were identified. Out of the 719 potentially eligible studies identified, 226 randomised controlled trials met the inclusion criteria, excluding the studies examining surgical techniques. Pre‐operative and intra‐operative interventions that improved postoperative pain were paracetamol; non‐steroidal anti‐inflammatory drugs; intravenous dexamethasone; ketamine (only assessed in children); gabapentinoids; dexmedetomidine; honey; and acupuncture. Inconsistent evidence was found for local anaesthetic infiltration; antibiotics; and magnesium sulphate. Limited evidence was found for clonidine. The analgesic regimen for tonsillectomy should include paracetamol; non‐steroidal anti‐inflammatory drugs; and intravenous dexamethasone, with opioids as rescue analgesics. Analgesic adjuncts such as intra‐operative and postoperative acupuncture as well as postoperative honey are also recommended. Ketamine (only for children); dexmedetomidine; or gabapentinoids may be considered when some of the first‐line analgesics are contra‐indicated. Further randomised controlled trials are required to define risk and combination of drugs most effective for postoperative pain relief after tonsillectomy. [ABSTRACT FROM AUTHOR]

Summary: Caesarean section is associated with moderate‐to‐severe postoperative pain, which can influence postoperative recovery and patient satisfaction as well as breastfeeding success and mother‐child bonding. The aim of this systematic review was to update the available literature and develop recommendations for optimal pain management after elective caesarean section under neuraxial anaesthesia. A systematic review utilising procedure‐specific postoperative pain management (PROSPECT) methodology was undertaken. Randomised controlled trials published in the English language between 1 May 2014 and 22 October 2020 evaluating the effects of analgesic, anaesthetic and surgical interventions were retrieved from MEDLINE, Embase and Cochrane databases. Studies evaluating pain management for emergency or unplanned operative deliveries or caesarean section performed under general anaesthesia were excluded. A total of 145 studies met the inclusion criteria. For patients undergoing elective caesarean section performed under neuraxial anaesthesia, recommendations include intrathecal morphine 50–100 µg or diamorphine 300 µg administered pre‐operatively; paracetamol; non‐steroidal anti‐inflammatory drugs; and intravenous dexamethasone administered after delivery. If intrathecal opioid was not administered, single‐injection local anaesthetic wound infiltration; continuous wound local anaesthetic infusion; and/or fascial plane blocks such as transversus abdominis plane or quadratus lumborum blocks are recommended. The postoperative regimen should include regular paracetamol and non‐steroidal anti‐inflammatory drugs with opioids used for rescue. The surgical technique should include a Joel‐Cohen incision; non‐closure of the peritoneum; and abdominal binders. Transcutaneous electrical nerve stimulation could be used as analgesic adjunct. Some of the interventions, although effective, carry risks, and consequentially were omitted from the recommendations. Some interventions were not recommended due to insufficient, inconsistent or lack of evidence. Of note, these recommendations may not be applicable to unplanned deliveries or caesarean section performed under general anaesthesia. [ABSTRACT FROM AUTHOR]

Rotator cuff repair can be associated with significant and difficult to treat postoperative pain. We aimed to evaluate the available literature and develop recommendations for optimal pain management after rotator cuff repair. A systematic review using procedure-specific postoperative pain management (PROSPECT) methodology was undertaken. Randomised controlled trials published in English from 1 January 2006 to 15 April 2019 assessing postoperative pain after rotator cuff repair using analgesic, anaesthetic or surgical interventions were identified from MEDLINE, Embase and Cochrane Databases. Out of 322 eligible studies identified, 59 randomised controlled trials and one systematic review met the inclusion criteria. Pre-operative and intra-operative interventions that improved postoperative pain were paracetamol, cyclo-oxygenase-2 inhibitors, intravenous dexamethasone, regional analgesia techniques including interscalene block or suprascapular nerve block (with or without axillary nerve block) and arthroscopic surgical technique. Limited evidence was found for pre-operative gabapentin, perineural adjuncts (opioids, glucocorticoids, or α-2-adrenoceptor agonists added to the local anaesthetic solution) or postoperative transcutaneous electrical nerve stimulation. Inconsistent evidence was found for subacromial/intra-articular injection, and for surgical technique-linked interventions, such as platelet-rich plasma. No evidence was found for stellate ganglion block, cervical epidural block, specific postoperative rehabilitation protocols or postoperative compressive cryotherapy. The analgesic regimen for rotator cuff repair should include an arthroscopic approach, paracetamol, non-steroidal anti-inflammatory drugs, dexamethasone and a regional analgesic technique (either interscalene block or suprascapular nerve block with or without axillary nerve block), with opioids as rescue analgesics. Further randomised controlled trials are required to confirm the influence of the recommended analgesic regimen on postoperative pain relief. [ABSTRACT FROM AUTHOR]

Effective peri-operative pain management is a prerequisite for optimal recovery after surgery. Despite published evidence-based guidelines from several professional groups, postoperative pain management remains inadequate. The procedure-specific pain management (PROSPECT) collaboration consists of anaesthetists and surgeons with broad international representation that provide healthcare professionals with practical and evidence-based recommendations formulated in a way that facilitates clinical decision-making across all stages of the peri-operative period on a procedure-specific basis. The aim of this manuscript is to provide a detailed description of the current PROSPECT methodology with the intention of providing the rigour and transparency in which procedure-specific pain management recommendations are developed. The high methodological standards of the recommendations should improve the quality of clinical practice. [ABSTRACT FROM AUTHOR]

Background: Whiplash-associated disorders (WAD) are an enormous and costly burden to Australian society. Up to 50% of people who experience a whiplash injury will never fully recover. Whiplash is resistant to treatment and no early management approach has yet been shown to prevent chronic pain. The early presence of central sensitization is associated with poor recovery. Pregabalin's effects on central sensitization indicate the potential to prevent or modulate these processes after whiplash injury and to improve health outcomes, but this has not been investigated. This paper describes the protocol for a feasibility study for a randomised controlled trial of pregabalin plus evidence-based advice compared to placebo plus evidence-based advice for individuals with acute whiplash injury who are at risk of poor recovery.Methods: This double blind, placebo-controlled randomised feasibility study will examine the feasibility and potential effectiveness of pregabalin and evidence-based advice (intervention) compared to placebo and evidence-based advice (control) for individuals with acute whiplash injury at risk of poor recovery. Thirty participants (15 per group) aged 18-65 years with Grade II WAD, within 48 hours of injury and currently experiencing at least moderate pain (NRS: ≥ 5/10) will be recruited from Emergency Departments of public hospitals in Queensland, Australia. Pregabalin will be commenced at 75 mg bd and titrated up to 300 mg bd as tolerated for 4 weeks followed by 1 week of weaning.Results: The feasibility of trial procedures will be tested, as well as the potential effect of the intervention on the outcomes. The primary outcome of neck pain intensity at 3 months from randomisation will be compared between the treatment groups using standard analysis of variance techniques.Discussion: Feasibility and potential effectiveness data will inform an appropriately powered full trial, which if successful, will provide an effective and cost-effective intervention for a costly and treatment resistant condition. It will also have implications for the early management of other traumatic conditions beyond whiplash.Trial Registration: Clinical Trials Primary Registry: Australian and New Zealand Clinical Trials Registry.Clinical Trial Registration Number: ACTRN12617000059369 . Date of Registration: 11/01/2017. Primary Trial Sponsor: The University of Queensland, Brisbane QLD 4072 Australia. [ABSTRACT FROM AUTHOR]

The quality and accessibility of anaesthesia-related information available to patients on the Internet is a growing concern for the specialty. We sought to evaluate the quality of anaesthesia-related websites using a simple scoring system. The scoring system comprised quality and technical scores individually, and these were also combined into a total score. Test-retest reliability was assessed by calculating intraclass correlation coefficients. We employed the four most popular search engines and one meta-search engine, using the search term "general anaesthesia". Only the first 10 sites retrieved were scored. The intraclass correlation coefficients for all terms demonstrated at least moderate agreement and the total scores demonstrated high consistency r = 0.852, 0.774 (P < 0.001, and P < 0.003 respectively). There were 18 duplicate websites and 32 were scored. There was no difference between search engines for any of the three scores awarded. The majority of websites were rated as either 'poor' or fair' across all scores. Our study indicates that quality anaesthesia-related information is unlikely to be retrieved by patients using the Internet. [ABSTRACT FROM AUTHOR]

The author discusses the International Association for the Study of Pain (IASP) which has promoted 2017 as the Global Year Against Pain After Surgery. He said that the campaign focuses on the treatment of acute postsurgical pain and relief from suffering. He also said that anaesthetists are finding ways to improve and speed up postoperative recovery, enable active postoperative rehabilitation and to reduce postoperative morbidity or mortality.

The National Prescribing Service (NPS) in collaboration with State DUE Groups is undertaking a quality improvement initiative aimed at improving Acute Post Operative Pain management (the APOP project) in 63 Australian hospitals. Following discussions between NPS and ANZCA, it was decided to undertake a national survey of key acute pain service (APS) contacts to aid development of educational messages for the APOP project. The ANZCA Trials Group research co-ordinator and NPS supported survey development and processing. Purpose of the study: To gain an understanding of what expert acute pain service clinicians see as common prescribing errors and poor pain management practice in the postoperative patient, and to investigate the degree of consensus which exists for specific aspects of basic analgesic prescribing, monitoring and documentation. Methods: A postal questionnaire consisting of an open question regarding prescribing errors and 27 opinion statements was sent to 144 key APS contacts across Australia. This group included medical and nursing co-ordinators and a small group of clinical pharmacists with expertise in acute pain management. Opinion statements covered a range of topics including prescribing of opioids, tramadol, NSAIDs, and paracetamol, patient monitoring, and discharge medications. Results: A response rate of 74% was achieved, with extensive use of the open question and comments space. Common areas of concern included both under- and overdosing of opioids, use of multiple opioids via multiple routes, inappropriate dose intervals and under-use of paracetamol. There were high levels of agreement regarding several opinion statements, particularly the inappropriate use of pethidine, but divergent views on others, such as the maximum daily dose of tramadol. Conclusions: The survey provided information to the APOP project by identifying areas of educational need, highlighting specific analgesic prescribing practices judged to be correct by most experts as well as highlighting those where there is a lack of consensus. [ABSTRACT FROM AUTHOR]