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Background and Aims The purpose of this study is to describe a patient with knee osteoarthritis (KOA), where both pharmacological and non-pharmacological regiments proved inadequate and could not undergo surgery for total joint replacement (TJR). At this dead-end, intra-articular (IA) combination of various agents was applied aiming for a multifactorial approach. Currently there is no literature regarding similar treatment.

Methods A 81 years old female with KOA was treated gradually with paracetamol, diclofenac and later with tramadol/dexketoprofane but reported minimal improvement of her condition after two months. After IA injections of hyaluronic acid initially and platelet-rich plasma later seemed to offer no results, an IA combination of fentanyl 50mcg, dexamethasone 8mg, clonidine 150mcg, ropivacaine 7.5% 5ml dextrose 30% 5ml and natural saline 0.9% 5ml was applied after the patient’s informed consent.

Results The treatment led to pain absence that lasted for about two years.

Conclusions As the patient was not eligible for IA Stem Cells or TJR and was non responsive to both pharmacological and invasive treatments, the resulting dead- end urged for improvisation. The multifactorial approach seems to offer satisfactory and encouraging results as the quality of life improvement helped the patient not only physically but also psychologically. The authors now plan to perform a randomized control trial using the aforementioned agents in order to assess the results in a larger scale.