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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]