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Background and Aims This case report details the complex perioperative management of a 57-year-old ASA-4 female with significant comorbidities undergoing surgical repair of a left humeral non-union fracture. The patient‘s extensive medical history (25 medical conditions) including morbid obesity, antiphospholipid syndrome,recurrent venous thromboembolism, cardiac disease, and neurological impairments, presented unique challenges for anaesthesia and surgical planning, particularly in the context of effective pain management while minimising systemic opioid exposure. The primary aim is to highlight the utility of a novel regional anaesthesia technique in optimising outcomes in such high-risk surgical patients.Methods The patient, with a BMI of 52.3 and a non-union of the proximal one-third left humerus had pain score 7–9/10 and functional impairment. Proposed surgery involved a Long Philos plate and nail with bone graft. Perioperative planning necessitated careful consideration of her anticoagulation regimen, severe obstructive sleep apnea, aspiration risk due to multiple sclerosis-related dysphagia, GLP-1 agonists and history of sepsis. To provide optimal pain relief and minimise respiratory depression risks, a novel regional anesthesia technique, specifically a low-volume superior trunk block with percutaneous neuromodulation (STB-PTNS) with catheter and infraclavicular brachial plexus block was chosen as a cornerstone of anaesthetic plan.Results With meticulous preoperative management, the application of the STB-PTNS with a catheter along with infraclavicular block facilitated excellent intraoperative and postoperative analgesia, completely abolished the need for systemic opioids. Anaesthesia management was tailored to mitigate risks with the regional block playing a crucial role in maintaining respiratory drive. Postoperative care focused on Intensive care monitoring for complications. She had an uneventful recovery without needing any opioids and was discharged home after 24 hours. The analgesia of the block continued for 4 days without any need for opioids.Abstract P260 Figure 1Fracture siteAbstract P260 Figure 2Nail in situ with incision extending from shoulder to elbowConclusions A comprehensive, multidisciplinary approach, integrating advanced regional anesthesia techniques, is crucial for ensuring patient safety and improving outcomes in such challenging scenarios.