Monitoring of the Effectiveness of Intensive Care and Rehabilitation by Evaluating the Functional Activity of the Autonomic Nervous System in Patients with Brain Damage

Purpose: evaluation of the clinical significance of parametric monitoring of the effectiveness of intensive care and rehabilitation based on the analysis of the functional state of the autonomous nervous system in patients with brain damage of different genesis.

Materials and methods. The study included 66 patients on day 20—50 after the traumatic brain injury; anoxic damage; and stroke consequences. The isolation of clinical groups and subsequent analysis of clinical status is based on the analysis of the functional state of the autonomic nervous system based on the dynamics of the heart rate variability (HRV) parameters. Findings obtained in studies of 500 patients in the postoperative period with a 5-minute HRV were tested as normal and abnormal ANS parameters [1]. Parasympathetic hyperactivity was measured within the limits for SDNN (standard deviation of all normal-to-normal R-R intervals) > 41.5 ms; for rMSSD (root-meansquare of the successive normal sinus R-R interval difference) > 42.4 ms; for pNN50% (the percentage of interval differences in successive NN intervals greater than 50 ms (NN50) / total number of NN intervals) > 8.1%; for SI (Baevsky stress index, in normalized units) < 80 n. u.; for TP (total power of variance of all NN intervals) > 2000 ms2. Sympathetic hyperactivity was determined within the limits for following parameters: SDNN, < 4.54 ms; rMSSD, < 2.25 ms; pNN50%, < 0.109%; SI, > 900 n. u.; TP < 200 ms2. Normal HRV parameters were selected within the limits of the values for: SDNN [13.31-41.4ms]; rMSSD [5.78—42.3 ms]; pNN50% [0.110—8.1%]; SI [80—900 nu]; for TP [200—2000 ms2]. To verify the parasympathetic or sympathetic hyperactivity within these limits, 3 of 5 parameters were chosen [1].

Results. Based on the dynamics of the HRV parameters before the intensive care and on days 30—60 of the intensive therapy and rehabilitation of patients with traumatic and non-traumatic brain injuries, 5 main clinical groups of patients were identified. Group 1 (n=27) consisted of patients with normal parameters of the ANS functional activity (both at the time of admission to the hospital and on the 30—60th day of the intensive therapy and rehabilitation). Group 2 (n=9) included patients with the baseline sympathetic hyperactivity of the ANS at admission to the intensive care unit and normal functional activity of the ANS on the 30—60th day of the intensive care and rehabilitation. Group 3 (n=8) included patients with baseline normal functional state of the ANS and the signs of sympathetic hyperactivity of the ANS on the 30—60th day of the intensive care and rehabilitation. Group 4 (n=15) consisted of patients with signs of sympathetic hyperactivity of the ANS both initially and on the 30—60th day of the intensive care and rehabilitation. Group 5 (n=7) included patients with signs of parasympathetic hyperactivity of the ANS (according to the parameters of HRV) both at baseline, at admission to the intensive care unit, and on the 30—60th day of the intensive care and rehabilitation.

Conclusion: The normalization of HRV parameters is accompanied by patients’ recovery from the vegetative state and coma to minimal consciousness or normal consciousness; the index of disability rate decreases, the social reintegration grows, according to the DRS scale (M. Rappaport, 1982); dependence on mechanical ventilation reduces, and the muscle tone normalizes.

1. Kiryachkov Yu.Yu., Saltanov A.I., Khmelevsky Ya.M. Computed analysis of heart rate variability. New opportunities for an anesthesiologist and doctors of other specialties. Vestnik Intensivnoi Terapii. 2002; 1: 3-8. [In Russ.]

2. Malik M., Huikuri H., Lombardi F., Schmidt G.; e-Health/Digital Rhythm Study Group of the European Heart Rhythm Association. The purpose of heart rate variability measurements. Clin. Auton. Res. 2017; 27 (3): 139140. DOI: 10.1007/s10286-017-0416-8. PMID: 28349277

3. Sadaka F., Pate D., Lakshmanan R. The FOUR score predicts outcome in patients after traumatic brain injury. Neurocrit. Care. 2012; 16 (1): 95101. DOI: 10.1007/s12028-011-9617-5. PMID: 21845490

4. Jalali R., Rezaei M. A comparison of the Glasgow coma scale score with full outline of unresponsiveness scale to predict patients’ traumatic brain injury outcomes in intensive care units. Crit. Care Res. Pract. 2014; 2014: 289803. DOI: 10.1155/2014/289803. PMID: 25013727

5. Teasdale G.M., Pettigrew L.E., Wilson J.T., Murray G., Jennett B. Analyzing outcome of treatment of severe head injury: a review and update on advancing the use of the Glasgow outcome scale. J. Neurotrauma. 1998; 15 (8): 587-597. DOI: 10.1089/neu.1998.15.587. PMID: 9726258

6. Edlow B.L., Chatelle C., Spencer C.A., Chu C.J., Bodien Y.G., O’Connor K.L., Hirschberg R.E., Hochberg L.R., Giacino J.T., Rosenthal E.S., Wu O. Early detection of consciousness in patients with acute severe traumatic brain injury. Brain. 2017; 140 (9): 2399-2414. DOI: 10.1093/brain/awx176. PMID: 29050383

7. Giacino J.T., Ashwal S., Childs N., Cranford R., Jennett B., Katz D.I., Kelly J.P., Rosenberg J.H., Whyte J., Zafonte R.D., Zasler N.D. The minimally conscious state: definition and diagnostic criteria. Neurology. 2002; 58 (3): 349-353. DOI: 10.1212/WNL.58.3.349. PMID: 11839831

8. Kupas D.F., Melnychuk E.M., Young A.J. Glasgow coma scale motor component («Patient Does Not Follow Commands») performs similarly to total Glasgow coma scale in predicting severe injury in trauma patients. Ann. Emerg. Med. 2016; 68 (6): 744.e3-750.e3. DOI: 10.1016/j.annemergmed.2016.06.017. PMID: 27436703

9. Bohannon R.W., Smith M.B. Assessment of strength deficits in eight paretic upper extremity muscle groups of stroke patients with hemiplegia. Phys. Ther. 1987; 67 (4): 522-525. DOI: 10.1093/ptj/67.4.522. PMID: 3562543

10. Rappaport M., Hall K.M., Hopkins K., Belleza T., Cope D.N. Disability rating scale for severe head trauma: coma to community. Arch. Phys. Med. Rehabil. 1982; 63 (3): 118-123. PMID: 7073452

11. Meseguer-Henarejos A.B., Sánchez-Meca J., López-Pina J.A., CarlesHernández R. Interand intra-rater reliability of the Modified Ashworth Scale: a systematic review and meta-analysis. Eur. J. Phys. Rehabil. Med. 2018; 54 (4): 576-590. DOI: 10.23736/S1973-9087.17.04796-7. PMID:

12. 28901119 Ciliberti M.P., Santoro F., Di Martino L.M., Rinaldi A.C., Salvemini G., Cipriani F., Triggiani A.I., Moscatelli F., Valenzano A., Di Biase M., Brunetti N.D., Cibelli G. Predictive value of very low frequency at spectral analysis among patients with unexplained syncope assessed by head-up tilt testing. Arch. Cardiovasc. Dis. 2018; 111 (2): 95-100. DOI: 10.1016/j.acvd.2017.04.006. PMID: 28958870

13. Brisinda D., La Brocca L., Sorbo A.R., Lombardi G., Fioravanti F., Fenici R. Psychophysiological evaluation of patients with transient loss of consciousness of uncertain origin. Kardiol. Pol. 2018; 76 (3): 566-573. DOI: 10.5603/KP.a2017.0254. PMID: 29297196

14. Wang F.F., Xu L., Chen B.X, Cui M., Zhang Y. Anorexia with sinus bradycardia: a case report. Beijing Da Xue Xue Bao Yi Xue Ban. 2016; 48 (1): 180-182. PMID: 26885932

15. Emren V., Kocabasø U. Is heart rate recovery index a predictive factor for cardioinhibitory syncope. Kardiol. Pol. 2018; 76 (2): 347-352. DOI: 10.5603/KP.a2017.0228. PMID: 29192954

16. Chanavirut R., Tong-Un T., Jirakulsomchok D., Wyss J.M., Roysommuti S. Abnormal autonomic nervous system function in rural Thai men: a potential contributor to their high risk of sudden unexplained nocturnal death syndrome. Int. J. Cardiol. 2017; 226: 87-92. DOI: 10.1016/j.ijcard.2016.10.001. PMID: 27792993

17. Kim M.H., Choi E.J., Jang B.H., Kim K.S., Ko S.G., Choi I. Autonomic function in adults with allergic rhinitis and its association with disease severity and duration. Ann. Allergy Asthma Immunol. 2017; 118 (2): 174-178. DOI: 10.1016/j.anai.2016.11.012. PMID: 28041676

18. Liccardi G., Salzillo A., Calzetta L., Cazzola M., Matera M.G., Rogliani P. Can bronchial asthma with an highly prevalent airway (and systemic) vagal tone be considered an independent asthma phenotype? Possible role of anticholinergics. Respir. Med. 2016; 117: 150-153. DOI: 10.1016/j.rmed.2016.05.026. PMID: 27492525

19. Kalla M., Herring N., Paterson D.J. Cardiac sympatho-vagal balance and ventricular arrhythmia. Auton. Neurosci. 2016; 199: 29-37. DOI: 10.1016/j.autneu.2016.08.016. PMID: 27590099

20. Kabbach E.Z., Mazzuco A., Borghi-Silva A., CabidduR., Agnoleto A.G., Barbosa J.F., de Carvalho Junior L.C.S., Mendes R.G. Increased parasympathetic cardiac modulation in patients with acute exacerbation of COPD: how should we interpret it? Int. J. Chron. Obstruct. Pulmon. Dis. 2017; 12: 2221-2230. DOI: 10.2147/COPD.S134498. PMID: 28814850

21. Gallo C., Bocchino P.P., Magnano M., Gaido L., Zema D., Battaglia A., Anselmino M., Gaita F. Autonomic tone activity before the onset of atrial fibrillation. J. Cardiovasc. Electrophysiol. 2017; 28 (3): 304-314. DOI: 10.1111/jce.13150. PMID: 27966276

22. Esterov D., Greenwald B.D. Autonomic dysfunction after mild traumatic brain injury. Brain Sci. 2017; 7(8): pii: E100. DOI: 10.3390/brainsci 7080100. PMID: 28800081

23. Majdan M., Brazinova A., Rusnak M., Leitgeb J. Outcome prediction after traumatic brain injury: comparison of the performance of routinely used severity scores and multivariable prognostic models. J. Neurosci. Rural. Pract. 2017; 8 (1): 20-29. DOI: 10.4103/0976-3147.193543. PMID: 28149077

24. Hilz M.J., Aurnhammer F., Flanagan S.R., Intravooth T., Wang R., Hösl K.M., Pauli E., Koehn J. Eyeball pressure stimulation unveils subtle autonomic cardiovascular dysfunction in persons with a history of mild traumatic brain injury. J. Neurotrauma. 2015; 32 (22): 1796-1804. DOI: 10.1089/neu.2014.3842. PMID: 26192266

25. Hilz M.J., Wang R., Markus J., Ammon F., Hösl K.M., Flanagan S.R., Winder K., Koehn J. Severity of traumatic brain injury correlates with long-term cardiovascular autonomic dysfunction. J. Neurol. 2017; 264 (9): 19561967. DOI: 10.1007/s00415-017-8581-1. PMID: 28770375

26. Rogobete A.F., Sandesc D., Papurica M., Stoicescu E.R., Popovici S.E., Bratu L.M., Vernic C., Sas A.M., Stan A.T., Bedreag O.H. The influence of metabolic imbalances and oxidative stress on the outcome of critically ill polytrauma patients: a review. Burns Trauma. 2017; 5: 8. DOI: 10.1186/s41038-017-0073-0. PMID: 28286784

27. Zafar S.F., Postma E.N., Biswal S., Fleuren L., Boyle E.J., Bechek S., O’Connor K., Shenoy A., Jonnalagadda D., Kim J., Shafi M.S., Patel A.B., Rosenthal E.S., Westover M.B. Electronic health data predict outcomes after aneurysmal subarachnoid hemorrhage. Neurocrit. Care. 2018; 28 (2): 184193. DOI: 10.1007/s12028-017-0466-8. PMID: 28983801

28. Abou El Fadl M.H., O’Phelan K.H. Management of traumatic brain injury: an update. Neurol. Clin. 2017; 35 (4): 641-653. DOI: 10.1016/j.ncl.2017.06.003. PMID: 28962805

29. Bartolo M., Bargellesi S., Castioni C.A., Intiso D., Fontana A., Copetti M., Scarponi F., Bonaiuti D.; Intensive Care and Neurorehabilitation Italian Study Group. Mobilization in early rehabilitation in intensive care unit patients with severe acquired cerebral injury: an observational study. J. Rehabil. Med. 2017; 49 (9): 715-722. DOI: 10.2340/16501977-2269. PMID: 28980699

30. Martinell L., Nielsen N., Herlitz J., Karlsson T., Horn J., Wise M.P., Undén J., Rylander C. Early predictors of poor outcome after out-of-hospital cardiac arrest. Crit. Care. 2017; 21 (1): 96. DOI: 10.1186/s13054-017-1677-2. PMID: 28410590

31. Osteraas N.D., Lee V.H. Neurocardiology. Handb. Clin. Neurol. 2017; 140: 49-65. DOI: 10.1016/B978-0-444-63600-3.00004-0. PMID: 28187814

32. Riganello F., Cortese M.D., Arcuri F., Dolce G., Lucca L., Sannita W.G. Autonomic nervous system and outcome after neuro-rehabilitation in disorders of consciousness. J. Neurotrauma. 2016; 33 (4): 423-424. DOI: 10.1089/neu.2015.3906. PMID: 26203818

33. Allanson F., Pestell C., Gignac G.E., Yeo Y.X., Weinborn M. Neuropsychological predictors of outcome following traumatic brain injury in adults: a meta-analysis. Neuropsychol. Rev. 2017; 27 (3): 187-201. DOI: 10.1007/s11065-017-9353-5. PMID: 28681109

34. Hung C.Y., Tseng S.H., Chen S.C., Chiu H.C., Lai C.H., Kang J.H. Cardiac autonomic status is associated with spasticity in post-stroke patients. NeuroRehabilitation. 2014; 34 (2): 227-233. DOI: 10.3233/NRE-131027. PMID: 24401824

35. Hoarau X., Richer E., Dehail P., Cuny E. Comparison of long-term outcomes of patients with severe traumatic or hypoxic brain injuries treated with intrathecal baclofen therapy for dysautonomia. Brain Inj. 2012; 26 (12): 1451-1463. DOI: 10.3109/02699052.2012.694564. PMID: 22725634

36. Lee H.S., Oh H.S., Shin J.H. Paroxysmal autonomic instability with dystonia managed using chemodenervation including alcohol neurolysis and botulinum toxin type a injection: a case report. Ann. Rehabil. Med. 2015; 39 (2): 308-312. DOI: 10.5535/arm.2015.39.2.308. PMID: 25932429

37. Popovic-Maneski L., Aleksic A., Metani A., Bergeron V., Cobeljic R., Popovic D.B. Assessment of spasticity by a pendulum test in SCI patients who exercise FES cycling or receive only conventional therapy. IEEE Trans. Neural. Syst. Rehabil. Eng. 2018; 26 (1): 181-187. DOI: 10.1109/TNSRE.2017.2771466. PMID: 29324409

38. Rossetto O. The binding of botulinum neurotoxins to different peripheral neurons. Toxicon. 2018; 147: 27-31. DOI: 10.1016/j.toxicon.2017.10.010. PMID: 29042309

39. Garrison M.K., Schmit B.D. Flexor reflex decreases during sympathetic stimulation in chronic human spinal cord injury. Exp. Neurol. 2009; 219 (2): 507-515. DOI: 10.1016/j.expneurol.2009.07.004. PMID: 19615998

40. Eldahan K.C., Rabchevsky A.G. Autonomic dysreflexia after spinal cord injury: systemic pathophysiology and methods of management. Auton. Neurosci. 2018; 209: 59-70. DOI: 10.1016/j.autneu.2017.05.002. PMID: 28506502

41. Manogue M., Hirsh D.S., Lloyd M. Cardiac electrophysiology of patients with spinal cord injury. Heart Rhythm. 2017; 14 (6): 920-927. DOI: 10.1016/j.hrthm.2017.02.015. PMID: 28215570