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Introduction Paradoxical agitation following benzodiazepine administration is an uncommon but clinically significant complication of procedural sedation. It is characterized by behavioral disinhibition, agitation, and aggression rather than the expected sedative effect. Although reported in approximately 1-2% of patients, it is likely underrecognized, particularly in procedural settings where agitation may be attributed to anxiety, pain, or delirium. In the event of diagnostic cerebral angiography, other differentials such as contrast induced encephalopathy are considered. Early identification is critical, as additional benzodiazepine administration may exacerbate symptoms and lead to severe behavioral dyscontrol requiring escalation of care.Case Presentation We report a case of an 18-year-old male with a history of hyperlipidemia, migraines, and attention deficit disorder who underwent diagnostic cerebral angiography for evaluation of a suspected 3-mm anterior communicating artery aneurysm identified on computed tomography angiography. Following the procedure, he experienced anxiety and nausea, hence IV Midazolam and antiemetics were administered with subsequent increased anxiety and new agitation. The patient then complained of a headache and palpitations, for which a migraine cocktail was administered. Due to escalating agitation, the patient received an additional dose of IV Midazolam. Marked worsening of agitation was noted, requiring restraints. His heart rate and SBP also increased. An additional dose of IV Midazolam was administered with profound agitation and physical aggression requiring six security personnel to restrain him. Escalation of care and transfer to the emergency department was needed. Administration of IV Haldol temporarily improved agitation, however, the patient continued to be disoriented and displayed further aggression. Subsequently, IV Ketamine was administered which resulted in restoration of behavioral control and orientation. After a few hours, the patient returned to baseline and could not recall any events after being positioned on the angiography table prior to the start of the procedure. At outpatient follow-up a month later, the patient was back at school with baseline performance.Discussion This case illustrates a severe paradoxical reaction to midazolam with escalating agitation following repeat benzodiazepine administration. The diagnosis is clinical and should be suspected when agitation develops shortly after benzodiazepine administration, particularly when symptoms worsen with additional dosing. Proposed mechanisms include cortical disinhibition, altered serotonergic signaling, and genetic variability in GABA-A receptor function. Risk factors include younger age, psychiatric or neurodevelopmental conditions, and stimulant use. Importantly, the differential diagnosis for acute agitation in the procedural setting is broad and includes hypoxia, hypercapnia, pain, delirium, substance-related causes, post-contrast encephalopathy, and neurologic complications including seizure or ischemia, all of which must be carefully considered. Recognition of paradoxical benzodiazepine reactions is essential, as management differs from typical sedation-related agitation. Further benzodiazepine administration should be avoided, and treatment should instead focus on patient safety and the use of alternative agents such as antipsychotics and, in severe cases, ketamine. Flumazenil may be considered in select patients but requires caution due to the risk of precipitating seizures. Once this reaction is identified and managed adequately, the symptoms are reversible with full expected recovery. It is essential for staff working in interventional neuroradiology to be familiar with this entity.Disclosures J. Thomas: None. D. Qaryouti: None.