Sensitivity of the Baroreceptors and the State of the Autonomic Nervous System in Patients with Chronic Impairment of Consciousness Due to Severe Brain Damage

Purpose of the study: to examine sensibility of baroreceptors and the autonomic nervous in the passive orthostatic test in patients with chronic impairment of consciousness due to severe brain damage and determine their role in the rehabilitation process.
Materials and methods. The study included 30 patients with long-term impairment of consciousness due to severe brain damage (group 1), 10 of them being in the vegetative state (VS) and 20 being in the minimally conscious state (MCS). Craniocerebral trauma was the main cause of severe damage in that group (53% of patients). The comparison group included 24 patients with focal neurological symptoms caused predominantly — 79.2% of cases — by cerebrovascular disorders (group 2). The control group (group 3) consisted of 22 healthy volunteers of a comparable age. All measurements were done with the help of a Task Force Monitor 1030i (CNSystem, Austria) in the course of passive orthostatic test at 0°–30°–60°–0°. Changes in the power of low-frequency (LFS) and highfrequency spectrum (HFS) of heart rate variability and baroreceptors sensibility (BRS) were analyzed. Statistical analysis was carried out using Statistica-10 software. Significance of inter-group differences on unrelated samples was determined by the Mann–Whitney U-test. Differences between groups were considered significant at P 0.05.
Results. Maximal background values of BRS were found in the control group. In group 1 and 2 patients, considerable decrease of that index was noted, which was proportional to the brain damage severity. Similar dynamics was observed for the indices of autonomic nervous system sensibility (LFS and HFS). The main trend of orthostatic changes of BRS, LFS, and HFS was characterized by progressive decrease of the indices with increase of the patients’ angle of tilting and their return to the baseline level after the patients were put back into the horizontal position. 4 patients of group 1 (14%) displayed signs of orthostatic disorders upon tilting to 30°: in 3 cases, orthostatic hypotension was observed, and in one case the postural orthostatic tachycardia syndrome (POTS) was diagnosed. Those patients differed by lower BRS and higher sympathetic system activity (LFS) vs. the same indices of other patients in that group.
Conclusion. Patients with chronic impairment of consciousness during the post-comatose period after a severe brain damage display a significant decrease of baroreceptors sensibility and autonomic nervous system disorders manifesting in significantly lower activity of the sympathetic and parasympathetic systems. The prominence of such disorders is associated with brain damage severity. Their risk of developing orthostatic hypotension during tilting towards a vertical position is higher in patients who have lower baroreceptors sensibility, and this should be taken into account beginning the process of their verticalization.

1. Nepomnyashchij V.P., Lihterman L.B., Yarcev V.V., Akshulakov S.K. Epidemiology of traumatic brain injury and its consequences. In the book: Konovalov A.N., Likhterman L.B., Potapov A.A. (Ed.). Clinical Guide to Traumatic Brain Injury. М., Antodor, 1998; (1): 131–136 [In Russ.].

2. Stahovskaya L.V., Klochikhina O.A., Bogatyreva M.D., Kovalenko V.V. Epidemiology of stroke in Russia according to the results of the territorial-population register. (2009–2010) Zhurnal nevrologii i psikhiatrii. 2013; 5: 4–10 [In Russ.].

3. Piradov M.A., Gulevskaya T.S., Gnedovskaya E.V., Lebedeva E.V., Ryabinkina YU.V., Morgunov V.A., Chajkovskaya R.P., Rebrova O.Yu. Syndrome of multiple organ failure in severe stroke (clinical and morphological study). Nevrologicheskij zhurnal. 2006; 11 (5): 9–13 [In Russ.].

4. Serebryakova E.N., Volosnikov D.K., Glazyrina G.A. Multiple organ failure syndrome: current state of the problem. Vest. Anestesiol. Reanimatol. 2013; 10 (5): 60–66 [In Russ.].

5. Nemchenko N.S., Denisov A.V., Zhirnova N.A. Features of the syndrome of multiple organ failure in severe trauma: diagnosis of the risk of development. Mediko-biologicheskie i socialno-psihologicheskie problemy bezopasnosti v chrezvychajnyh situaciyah.2012; 3: 18–23 [In Russ.].

6. Dewar D, Moore F.A., Moore E.E., Balogh Z. Postinjury multiple organ failure. Injury, Int. J. Care Injured. 2009; 40: 912–918. PMID: 19541301, DOI: 10.1016/j.injury.2009.05.024

7. Lausevic Z, Lausevic M, Trbojevic-Stankovic J, Krstic S, Stojimirovic B. Predicting multiple organ failure in patients with severe trauma. Can J Surg. 2008; 51 (2): 97–102. PMID: 18377749, PMCID: PMC2386337

8. Belkin A.A., Alasheev A.M., Davydova N.S., Levit A.L., Khalin A.V. The rationale for resuscitation rehabilitation in the prevention and treatment of the syndrome after intensive care (ICU syndrome). Vestnik vosstanovitelnoj mediciny.2014; 1: 37–43 [In Russ.].

9. Suvorov A.Yu., Ivanova G.E., Belkin A.A., Stakhovskaya L.V. Verticalization of patients with the risk of ICU syndrome. Vestnik vosstanovitelnoj mediciny.2015; 4: 37–43 [In Russ.].

10. Kong K.H., Chuo A.M. Incidence and outcome of orthostatic hypotension in stroke patients undergoing rehabilitation. Arch. Phys. Med. Rehabil. 2003; 84 (4): 559–562. DOI: 10.1053/apmr.2003.50040. PMID: 12690595.

11. Luther M.S., Krewer C., Müller F., Koenig E. Comparison of orthostatic reactions of patients still unconscious within the first three months of brain injury on a tilt table with and without integrated stepping. A prospective, randomized crossover pilot trial. Clin. Rehabil. 2008; 22 (12): 1034–1041. DOI: 10.1177/0269215508092821. PMID: 19052242.

12. O’Leary D.D., Kimmerly D.S., Cechetto A.D., Shoemaker J.K. Differential effect of head-up tilt on cardiovagal and sympathetic baroreflex sensitivity in humans. Exp Physiol. 2003; 88 (6): 769–774. PMID: 14603376

13. Hainsworth R. Cardiovascular control from cardiac and pulmonary vascular receptors. Exp Physiol 2014, 99, (2): 312–319. PMID: 24058186, DOI: 10.1113/expphysiol.2013.072637

14. Stauss H.M. Baroreceptor reflex function. Am J Physiol Regul Integr Comp Physiol. 2002; 283 (2): 284–286. DOI: 10.1152/ajpregu.00219.2002

15. Kamiya A., KawadaT., Shimizu S., Iwase S., Sugimachi M., Tadaaki Mano T. Slow head-up tilt causes lower activation of muscle sympathetic nerve activity: loading speed-dependence of orthostatic sympathetic activation in humans. Am.J.Physiol.HeartCirc.Physiol. 2009; 297: 53–58. PMID: 25071601, PMCID: PMC4086024, DOI: 10.3389/fphys.2014.00256

16. Lavi S., Nevo O., Thaler I., Rosenfeld R., Dayan L., Hirshoren N., Gepstein L., Jacob G. Effect of aging on the cardiovascular regulatory systems in healthy women. Am J Physiol Regul. Integr. Comp. Physiol. 2007; 292 (2): 788–793. PMID: 16946083, DOI: 10.1152/ajpregu.00352.2006

17. Thrasher T.N., Chen H.G., and Keil L.C. Arterial baroreceptors control plasma vasopressin responses to graded hypotension in conscious dogs. Am. J. Physiol. Regulatory Integrative Comp Physiol. 2000; 278, 469–475. PMID: 10666149, DOI: 10.1152/ajpregu.2000.278.2.R469

18. Winchell R.J., Hoyt D.B. Analysis of heart-rate variability: a noninvasive predictor of death and poor outcome in patients with severe head injury. J. Trauma. 1997; 43: 927–933. PMID: 9420107, DOI: 10.1097/00005373-199712000-00010

19. Kahraman S., Dutton R.P., Hu P., Stansbury L., Xiao Y., Stein D.M., Scalea T.M. Heart rate and pulse pressure variability are associated with intractable intracranial hypertension after severe traumatic brain injury. J. Neurosurg. Anesthesiol. 2010; 22: 296–302. PMID: 20622688, DOI: 10.1097/ANA.0b013e3181e25fc3

20. Marthol H., Intravooth T., Bardutzky J., De Fina P., Schwab S., Hilz M.J. Sympathetic cardiovascular hyperactivity precedes brain death. Clin Auton Res. 2010; 20: 363–369. PMID: 20461435, DOI: 10.1007/s10286-010-0072-8

21. Baillard C., Vivien B., Mansier P., Mangin L., Jasson S., Riou B., Swynghedauw B.. Brain death assessment using instant spectral analysis of heart rate variability. Crit Care Med. 2002; (30): 306–310. PMID: 11889299, DOI: 10.1097/00003246-200202000-00007

22. Kiryachkov Y.Y., Grechko A.V., Kolesov D.L., Loginov A.A., Petrova M.V., Pryanikov I.V., Shchelkunova I.G., Pradkhan P. Functional Activity of the Autonomous Nervous System at Different Levels of Consciousness in Patients with a Brain Damage. Obschaya Reanimatologiya=General Reanimatology. 2018; 14 (2): 4–12. [In Russ.] DOI: 10.15360/1813-9779-2018-2-4-12

23. Papaioannou V., Giannakou M., Maglaveras N., Sofianos E., Giala M. Investigation of heart rate and blood pressure variability, baroreflex sensitivity, and approximate entropy in acute brain injury patients. J. Crit. Care. 2008; 23 (3): 380–386. DOI: 10.1016/j.jcrc.2007.04.006. Epub 2007 Dec 11.

24. McMahon C.G., Kenny R., Bennett K., Little R., Kirkman E. Effect of acute traumatic brain injury on baroreflex function. Shock. 2011; 35 (1): 53–58. DOI: 10.1097/SHK.0b013e3181e687c6. PMID: 20458265.

25. Dorogovtsev V.N., Skvortsov A.E., Yudina E.A. Changes in Systemic Hemodynamics in Orthostasis in Patients With Long-Term Impairment of Consciousness. Obschaya Reanimatologiya=General Reanimatology. 2018; 14 (6): 12–22. [In Russ.]. DOI: 10.15360/1813-9779-2018-6-12-22

26. Parati G., Omboni S., Frattola A., Di Rienzo M., Zanchetti A., Mancia G. Dynamic evaluation of the baroreflex in ambulant subject. In: Blood pressure and heart rate variability, edited by di Rienzo. IOS Press, 1992; 123–137.

27. La Rovere M.T., Pinna G.D., Raczak G. Baroreflex sensitivity: measurement and clinical implications. Ann Noninvasive Electrocardiol. 2008; 13: 191–207. DOI: 10.1111/j.1542-474X.2008. 00219.x

28. Schlogl A., Flotzinger D., Pfurtscheller G. Adaptive autoregressive modeling used for single-trial EEG classification. Biomed. Tech (Berl), 1997; 42 (6): 162–167. PMID: 9246870

29. Camm J., Malik M. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Eur. Heart J. 1996; 17: 354–381. PMID: 8737210

30. Mosqueda-Garcia R., Furlan R., Fernandes-Violante R. Sympathetic and baroreceptor reflex function in neurally mediated syncope evoked by tilt. J. Clin. Invest. 1997; 99 (11): 2736–2744.

31. Haji-Michael P.G., Vincent J.L., Degaute J.P., van de Borne P. Power spectral analysis of cardiovascular variability in critically ill neurosurgical patients. Crit. Care. Med. 2000; 28 (7): 2578–2583.

32. Yiallourou S.R., Sands S.A., Walker A.M., Horne R.S. Postnatal development of baroreflex sensitivity in infancy. J. Physiol. 2010; 588 (Pt 12): 2193–2203. DOI: 10.1113/jphysiol.2010.187070. Epub 2010 Apr 26.

33. Anderson I.D., Little R.A., Irving M.H. An effect of trauma on human cardiovascular control: baroreflex suppression. J. Trauma. 1990; 30 (8): 974–981.

34. Conci F., Di Rienzo M., Castiglioni P. Blood pressure and heart rate variability and baroreflex sensitivity before and after brain death. J. Neurol. Neurosurg. Psychiatry. 2001; 71 (5): 621–631.

35. Baillard C., Vivien B., Mansier P., Mangin L., Jasson S., Riou B., Swynghedauw B. Brain death assessment using instant spectral analysis of heart rate variability. Crit. Care Med. 2002; 30: 306–310. PMID: 11889299, DOI: 10.1097/00003246-200202000-00007

36. Marthol H., Intravooth T., Bardutzky J., De Fina P., Schwab S., Hilz M.J. Sympathetic cardiovascular hyperactivity precedes brain death. Clin. Auton. Res. 2010; 20: 363–369. PMID: 20461435, DOI: 10.1007/s10286-010-0072-8

37. Zhang J., Mifflin S.W. Subthreshold aortic nerve inputs to neurons in nucleus of the solitary tract. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2000; 278 (6): 595–604. PMID: 10848529

38. Stauss H.M. Baroreceptor reflex function. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2002; 283 (2): R284–6.

39. Kamiya A, Kawada T, Sugimachi M. Systems physiology of the baroreflex during orthostatic stress: from animals to humans. Front Physiol. 2014 8; 5: 256. PMID: 25071601, PMCID: PMC4086024, DOI: 10.3389/fphys.2014.00256