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Tumor-specific electroporation (TSE) is a technique involving the application of high voltage pulsed electric impulses to the tumor lesions. We performed TSE in four patients with different indications and airway scenarios. We kept all four patients under conscious sedation using trans-nasal humidified rapid-insufflation ventilatory exchange (THRIVE) and dexmedetomidine infusion. This case series reflects those various untoward effects of general anesthesia that can be avoided by oxygenating the patient with THRIVE and dexmedetomidine infusion, which provide analgesia, sedation, and amnesia.