Background. At the same time, the main effect of the use of this drug is the elimination of the autonomic nervous system dysfunction and sympatholysis. It seems important to search for a method of indications and selection of a dose of dexmedetomidine in intensive care. Aims - to improve the clinical effectiveness of the electrophysiological navigation of the prolonged use of dexmedetomidine in patients with brain pathology of various origins. Methods. The study included 83 patients 20-50 days after the traumatic brain injury, anoxic damage; consequences of acute disorders of cerebral. 37 patients comprised the 1st intervention group with a clinical course of dexmedetomidine (male - 28; female - 9; average age 49.6 ± 2.3 years) and 46 patients comprised the 2nd control group without pharmacological correction with dexmedetomidine (male - 23; female - 23, average age 51 ± 2.5 years). Criteria for the inclusion of prolonged infusion of the drug dexmedetomidine (Orion Pharma, Finland) are based on heart rate variability (HRV) indicators characteristic of sympathetic hyperactivity, the target task of titration of doses of dexmedetomidine served as the parameters for achieving normal HRV indicators, the appearance of parasympathetic hyperactivity served as the basis for reducing the dosage of the drug or stopping it of application. HRV parameters were recorded before dexmetomedine infusion-initially, on 1-3; 4-5; 9-10; 15-20 days of drug administration. Results. The starting dose of dexmedetomidine with sympathetic hyperactivity in patients was 0.12 to 0.24 μg.kg-1.hr-1 (average dose 0.16 ± 0.01; total 200 mg/day). According to digital data from HRV, the effective dose of dexmedetomidine ED50 was 0.26 ± 0.03 μg.kg-1.hr-1 (total daily 353.8 ± 35.1 μg) and was achieved on day 9-10 using dexmedetomidine. Conclusions. The protective role of dexmedetomidine with correction of sympathetic hyperactivity based on electrophysiological navigation according to the HRV is reliable in the following indicators: The improvement of consciousness; a significant decrease in the incidence of distress lung syndrome; septic shock; mortality. © 2020 Izdatel'stvo Meditsina. All rights reserved.