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The management of the pain therapy (ischemic pain, neoplastic pain) in hemodialysis patients has become a frequent challenge in the last years. These patients often require the prescription of major analgesic drugs such as Opioids like Fentanyl, in order to control the pain. It is necessary to pay attention to the correct dosage and to the half life of these drugs, that results prolonged in the chronic renal insufficiency. The main side effect of opioids is respiratory depression which is well known, however, up to date, there is a lack of reports about other less frequent side effects, such as epilepsy or status epilepticus, in the literature. We report two cases of chronic hemodialysed patients who developed a generalized nonconvulsive status epilepticus secondary to Fentanyl intoxication administered for the pain therapy. These cases required a synergic team management with involvement of the nephrologist, the neurologist and the intensivist. The generalized non convulsive status epilepticus could be an important and serious side effect of Fentanyl in hemodialysis patients and it is therefore necessary a close monitoring of the pain therapy in these subjects.