Orthostatic Hemodynamic Changes in Brain Damage

Aim: to study orthostatic hemodynamic changes in patients with chronic disorders of consciousness after critical brain damage. patients) and cerebrovascular accidents (CVA) (23.3%). The rest of the patients had posthypoxic encephalopa-thy or were after brain tumor removal surgery. Passive orthostatic test (POT) 0° to 60° to 0° was performed using an electrically driven tilt table (Vario Line). Hemodynamic monitoring during the verticalization was done using a non-invasive oscillometric recording of blood pressure on the brachial artery, stroke volume (SV) and cardiac minute output (CMO) were measured by impedance cardiography with the multifunctional «Task Force Monitor 3010i» (CNSystem, Aus-tria). Data were statistically analyzed using the Statistica 10 software package. Results. Orthostatic hemodynamic stability was found in 26 out of 30 patients with chronic disorders of consciousness after critical brain damage. It was manifested by stable systolic blood pressure (SBP) in tilted orthostatic and horizontal position (120.7±2.2 and 121.1±3.6 mmHg, respectively, P >0.05). Orthostatic hypotension was observed in 3 patients and postural tachycardia syndrome (PTS) in one patient. We compared orthostatic hemodynamic changes in the studied cohort versus published data on orthostatic hemodynamic changes uncluding POT revealed in patients with severe brain damage examined before and after brain death. Conclusion. Orthostatic stability of blood circulation can be maintained for a short period of time in patients surviving after critical diﬀuse brain damage associated with chronic disorders of consciousness. Critical brain damage resulting in brain death associates with a signiﬁcant reduction of all hemodynamic parameters and severe orthostatic hypotension with restoration of initial blood pressure values when the patient is returned to the horizontal position.

Passive orthostatic test (POT) 0° to 60° to 0° was performed using an electrically driven tilt table (Vario Line). Hemodynamic monitoring during the verticalization was done using a non-invasive oscillometric recording of blood pressure on the brachial artery, stroke volume (SV) and cardiac minute output (CMO) were measured by impedance cardiography with the multifunctional «Task Force Monitor 3010i» (CNSystem, Austria). Data were statistically analyzed using the Statistica 10 software package.
Results. Orthostatic hemodynamic stability was found in 26 out of 30 patients with chronic disorders of consciousness after critical brain damage. It was manifested by stable systolic blood pressure (SBP) in tilted orthostatic and horizontal position (120.7±2.2 and 121.1±3.6 mmHg, respectively, P>0.05). Orthostatic hypotension was observed in 3 patients and postural tachycardia syndrome (PTS) in one patient. We compared orthostatic hemodynamic changes in the studied cohort versus published data on orthostatic hemodynamic changes uncluding POT revealed in patients with severe brain damage examined before and after brain death.
Conclusion. Orthostatic stability of blood circulation can be maintained for a short period of time in patients surviving after critical diffuse brain damage associated with chronic disorders of consciousness. Critical brain damage resulting in brain death associates with a significant reduction of all hemodynamic parameters and severe orthostatic hypotension with restoration of initial blood pressure values when the patient is returned to the horizontal position.
The aim of our study was to investigate the orthostatic hemodynamic changes in patients with chronic disorders of consciousness after critical brain damage.

Materials and Methods
We examined 30 patients (10 women and 20 men) with chronic consciousness disorders after severe brain damage at the age of 45±7 years. 53.3% of patients were after severe traumatic brain injury, 23.3% after cerebrovascular accident, 10% after global cerebral ischemia and the rest (13.4%) were after neurosurgical interventions to remove large brain tumors. At the time of the study, there were 10 patients in the vegetative state, and the remaining 20 patients had minimal consciousness state. The average time from the disease onset to the beginning of the study was 124 days.
Complex analysis of systemic hemodynamic parameters in all participants was performed using the multifunctional Task Force Monitor with registration of the following parameters: brachial systolic and diastolic blood pressure (SBP, DBP) by oscillometric method, heart rate (HP) determined by ECG with permanent R-R interval measurement, stroke volume (SV) measured by impedance cardiography method using software based on Kubichek formula [11], cardiac minute output (CMO) and total peripheral resistance (TPR). The patient was placed on a tilt table and connected to a multifunctional monitor. The study protocol included recording the above-mentioned hemodynamic values for 10 minutes in each of the successive positions of the tilt table: the initial horizontal position, an inclined position with the head end raised at 60°, the final horizontal position. The calculations were based on hemodynamic averages in each position for the last 5 of 10 minutes.
During the passive orthostatic test (POT), 4 patients out of 30 developed orthostatic disorders that required the study to be stopped. The most dangerous of them was orthostatic hypotension manifested by a decrease of SBP by 20 mm Hg and/or DBP by 10 mm Hg or more during orthostatic tilt compared to the horizontal position [12]. This disorder was found in 3 patients. In one patient postural tachycardia syndrome was observed, characterized by the increase in HR by 30 or more beats per minute on orthostatic tilt compared to this parameter in the horizontal position [13]. The disorders required immediate cessation of patients' verticalization, so these data were not included in the statistical analysis of the results.

Results and Discussion
Orthostatic hemodynamic stability was revealed in 26 out of 30 patients with chronic disorders of consciousness after critical brain damage.
The main systemic hemodynamic parameters of patients are presented in the table. In all the patients the conversion of the tilt table from the inclined to the horizontal position resulted in the return of hemodynamic parameters to the baseline seen in horizontal position, so these data were presented in the table only once.
The most important indicators for the diagnosis of orthostatic hemodynamic disorders are SBP, DBP and HR. In our study, orthostatic changes of SBP and DBP in the tilt position compared to horizontal were statistically insignificant (for both parameters P>0.05). The orthostatic increase in the HR and CMO was significant (P<0.01).
Further development of the disease in patients with chronic disorders of consciousness in the post-comatose period of critical brain damage may follow different scenarios. Most favorable is regaining consciousness and transfer of the patient to rehabilitation treatment. Another scenario, death, is usually due to multi-organ pathology. A high level of intensive care may postpone lethal outcome, but in such cases brain death may occur.
With advances made recently in transplantology, the brain death issue appears to be relevant from legal, scientific and medical points of view. In our studies, we have examined orthostatic hemodynamic changes and the mechanisms of sympathetic baroreflex, which plays a key role in adaptation processes, and revealed significant disorders associated with diffuse severe brain damage. Even under these conditions, the human body is able to provide short-term orthostatic stability of blood circulation. Hence, the question is: what happens to these systems after the brain death and can orthostatic regulation exist under spinal regulation, functioning nerve ganglia and cardiovascular system automation?
Brain death associates with cerebral blood flow interruption in the internal carotid and vertebral artery regions, global brain necrosis with the demarcation line at the level of upper cervical segments [17,18]. Under such conditions vital functions can be maintained from several minutes to several days due to artificial ventilation of lungs, hemodynamic support by vasopressors and corticosteroids, fluid-electrolyte balance correction, etc. Thus, a pathophysiological clinical model for the study of blood circulation with only the spinal level of regulation preserved appears. The information presented in the literature concerns issues of brain death diagnosis, main body systems condition be-
We have found only one study of orthostatic changes in blood circulation before and after brain death development, which we did 30 years ago at the Research Institute of Neurology of the USSR Academy of Medical Sciences [19]. At that time, we observed 2 patients in acute period of severe ischemic stroke before and after brain death who were investigated similarly to the patients involved in this study with hemodynamic monitoring using a similar protocol. A minor difference between the protocols was that the angle of tilt in patients with brain death was 50°, while in the present study it was 60°. Before brain death, hemodynamic parameters of both patients were similar to the ones of patients included in this study, except for moderate hypertension in one of them. The hemodynamic response to orthostatic tilt was also similar and did not indicate any orthostatic disorders. The upward tilt was characterized by relative stability of SBP and DBP and typical orthostatic hemodynamic changes similar to the data presented in Table 1, indicating satisfactory orthostatic hemodynamic stability during an acute phase of a massive ischemic stroke. After the brain death development in the initial (horizontal) position we observed a significant decrease in all systemic hemodynamic parameters: SBP was 70 mm Hg, DBP was 40 mm Hg, HR reached 69 bpm, CMO was 2.4 l/min, and TPR was 1665 din•sec•cm -5 . The orthostatic test with a slope of 50° caused an even greater reduction in all hemodynamic parameters: SBP dropped by 28.6%, DBP -by 50%, SV -by 9%, CMO -by 17%, HRby 4.3%, TPR -by 28.6% vs baseline, which indicated severe orthostatic hypotension. After returning to the horizontal position, within 15 minutes, all hemodynamic parameters returned to values close to baseline. Similar systemic hemodynamic changes were observed in the second patient.
The transition to the brain death was characterized by a significant decrease in BP and other systemic hemodynamic parameters, which suggested absence of a sympathetic baroreflex and the switching on of adaptive neurohumoral systems that provide stability of blood flow in the organs in changes of body position [20]. This is confirmed by the literature data showing that in patients with severe brain damage the sensitivity of sympathetic baroreflex decreases to 11.2±8.5 msec/mmHg, and after the brain death it decreases to 0. At the same time, there was a significant decrease in sympathetic system parameters [21,22]. The literature data suggested that the physiological mechanisms of sympathetic baroreflex were «switched off» and the whole system of central regulation of blood circulation providing orthostatic hemodynamic stability was destroyed. These data explain the critical orthostatic disorders of the systemic circulation in brain death. сохранного только спинального уровня регуляции. Информация, представленная в литературе, касается вопросов диагностики СМ, состояния основных систем организма до и после развития СМ, поддержания жизненных процессов в этом состоянии.

Conclusion
Orthostatic stability of blood circulation can be maintained for a short time in patients with chronic disorders of consciousness who have survived critical diffuse brain damage. Critical brain damage leading to brain death associates with a significant reduction of all hemodynamic parameters and severe orthostatic hypotension with restoration of initial blood pressure values when the patient is returned to the horizontal position.