Non-Invasive Regional Cerebral Oxygen Saturation (rSO₂) and Postoperative Neurological Dysfunction

Introduction

Regional Cerebral oxygen saturation (rSO₂) is the one non-invasive monitoring technique for bedside cerebral oxygen saturation, which has the advantages of real-time, sensitivity, rapidity, and persistence. It is the most widely used method for monitoring cerebral oxygen saturation at present. The application of near-infrared spectroscopy to the monitoring of rSO₂ was reported for the first time in 1977 by Jobsis [1]. In recent years, there has been a significant increase in the use of rSO₂ during perioperative period, especially in cardiac [2], aortic [3], carotid surgery [4-5], thoracic [6-8], resuscitation [9- 10], neonatal [11], and geriatric surgery [12]. In recent years, with the increasing use of rSO₂ in clinical practice, a large number of literatures show that maintain a certain range of rSO₂ can shorten the length of tracheal extubation, stay in intensive care unit and in hospital [2,14-15]. Finally, it can improve the prognosis of patients, reduce the occurrence of postoperative neurological dysfunction reduce the mortality of patients [16-18].

The Principle and Detection Method of rSO₂

Continuous noninvasive monitoring of regional cerebral oxygen saturation (rSO₂) was carried out by Near-Infrared Spectroscope (NIRS) technique. The principle of NIRS monitoring system is that near infrared light (wavelength range 700-950 nm) that transmitted and absorbed through tissues [19]. Near infrared light can penetrate the scalp, skull and brain tissue to detect brain rSO₂. Based on Lambert Beer Law and light scattering theory, chromophore biomolecules have different optical densities in near infrared spectra, and their concentration can be determined in the range of relative absorption wavelength [20-22]. By measure the difference of optical absorption coefficient between reduced hemoglobin and oxygenated hemoglobin that is the most commonly used chromophore [23]. Then calculating the absorption spectrum ratio, the concentration of local two kinds of hemoglobin can be obtained. In the brain, the arterial blood volume is about 20%, capillary blood volume is about 5%, and the remaining 75% is venous blood volume, so in fact, rSO₂ is similar to cerebral venous oxygen saturation [24]. Finally, the weighted average value of blood oxygen saturation of the three blood vessels was used to reflect the changes of oxygen supply and consumption balance in the brain [24]. Near-infrared light cannot pass through the entire head, both near-infrared light sources and detection devices are located on the same side of the brain, a few centimeters apart, so that rSO₂ actually detects the cortex of the brain.

Threshold and Availability of rSO₂

The normal range of rSO₂ in healthy adult volunteers was (71.2±3.9) % under the normal air condition [25]. Most studies suggest that the normal range of average rSO₂ value is 55%~75%, but there is a large variation among individuals [11]. Hirofumi believe that rSO₂ decrease to 55% means there is a risk of neurological complications after surgery and clinicians need to intervene accordingly [26]. Shmigeskii also found that if the rSO₂ value is less than 55%, the probability of cerebral ischemia and hypoxia is high, which suggests that anesthsiologts should make appropriate treatment and rescue measures as soon as possible [27]. The current research tends to use relative values to represent the range of rSO₂. Samra continuously monitored rSO₂ in CEA patients and found that rSO₂ was 20% lower than the baseline value and could predict postoperative neurological dysfunction. The sensitivity and specificity were 80% and 82% respectively [28]. A study of 70 patients with cardiac operation under cardiopulmonary bypass found that rSO₂ decreased by 10% (6% to 15%), suggesting insufficient cerebral perfusion and requiring intervention [29]. A recent study of 50 beach chair patients undergoing shoulder surgery showed an 18% decrease in cerebral oxygen saturation during the perioperative period. The maximum decrease of rSO₂ from the baseline was 32%, and the average duration was more than 3 min will lead to the bad outcome in the patients. Kobayashi and Colak suggested that the decrease of rSO₂ from the initial value of 20% to 30% or as low as 40% to 50% absolute value was abnormal and was related to the lack of oxygen supplyment in the brain [30-31]. In one 594 patients study with carotid stenosis of more than 70% were assigned to shunt based on changes in rSO₂ levels, the relative decrease of rSO₂ was more reliable than the absolute decline to detect brain low oxygen supply [32]. During CEA surgery under general anesthesia, the monitoring of rSO₂ the reliability was 95.38%, the sensitivity was 100%, and the specificity was 95.36%. A brief relative decline in rSO₂ to 20% baseline is allowed for 2 min to automatic adjustment of fluctuations. Another algorithms for rSO₂, the duration of rSO₂ AUC score 50% area [50%-(rSO₂- 50%)]* duration time is used as the index [33]. Although rSO₂-directed ischemic thresholds have not been verified, clinical research and management processes often use absolute rSO₂ values of less than 50% or a 20% decline from baseline as the trigger point for initiating improvements in cerebral oxygenation [34]. Slater et al came to a similar conclusion that patients with rSO₂ reduction score 13000s during CABG were more likely to have cognitive impairment after CABG, and the risk of prolonged hospitalization increased nearly threefold [33]. Although rSO₂-directed thresholds for ischemia have not been verified, clinical research and management processes often use absolute rSO₂ values of less than 50% or a 20% decline from baseline as the trigger point for initiating elevate cerebral oxygenation.

Advantages and Influencing Factors of rSO₂

Unlike noninvasive arterial blood pressure monitoring, rSO₂ which represents regional oxygen supply and oxygen consumption balance does not rely on the measurement of blood flow pulsation [35- 37]. Therefore, even in the special cases of hypotension, weak pulse and circulatory arrest, continuous monitoring of cerebral oxygen metabolism and oxygen consumption can be carried out to evaluate the oxygenation status of brain tissue. The signal of monitoring cerebral oxygen saturation mainly comes from venous blood, so rSO₂ is not affected by hypothermic arterial vasoconstriction. Furthermore, unlike Electroencephalogram (EEG) and autologous evoked potentials (SEPs), rSO₂ did not change because of any sedation and analgesic medicine intervention [38-39]. All in all, a series of studies have shown that continuous monitoring of rSO₂ during operation to predict cerebral ischemia is reliable and sensitive and can enable clinicians to timely detect the occurrence of intraoperative cerebral ischemia and hypoxia and make timely intervention. Although rSO₂ is widely used in clinic, it is also affected by some physiological variables, including blood pH, arterial oxygen saturation (PaO2), arterial CO2 partial pressure (PaCO2), hemoglobine concentration, cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen metabolism rate (COMR) [40, 37-38]. The skull thickness, skin pigments and the position of the probe also have a weak effect for rSO₂ [39]. There was a negative correlation between rSO₂ and age, and a positive correlation between rSO₂ and hemoglobine concentration. One of the major challenges of rSO₂ accuracy is acute brain injury from intracranial hematoma, cerebral edema or subarachnoid hemorrhage, which may invalidate based on rSO₂ related algorithms.

rSO₂ and Post-Operative Cognitive Dysfunction (POCD)

Post-Operative Cognitive Dysfunction (POCD) is a common complication after anesthesia and operation. The clinical manifestations are memory deficit, cognitive dysfunction, changes in personality and social integration ability, etc. In severe cases these patients may evolved to Alzheimer’s disease. The incidence of POCD after cardiac surgery in elderly patients can be as high as 19% within 24 hours post-operation, especially in abdominal surgery may increase to 40%. The incidence of POCD can be as high as 50%~70% one week and 30% ~50% after 2 months, seriously decrease the quality of life and long-term survival of patients [40]. At present, the pathogenesis of POCD is still unclear, which may involve many factors, including embolism, hypoperfusion, hypoxia, inflammatory reaction, advanced age, cerebrovascular disease and so on [41-42]. However, these factors are ultimately related to cerebral ischemia and imbalance of oxygen supply and consumption in the whole or the part of the brain. The patients underwent cardiac surgery and CPB were monitored by rSO₂. The value of rSO₂ was maintained above 80% of the baseline or 55% of the obsolute value of the rSO₂ by interventions during the operation. Cognitive function was assessed by a series of scales such as trailing test (TMT) before and 5 days after operation. The results showed that the incidence of POCD was 43%, which was not significantly different from the incidence of POCD in previous observational studies, and the analysis of the operating characteristic curve AUC of subjects showed that the rSO₂ value <65% showed a sensitivity of 86.7% and a specificity of 65% in predicting POCD occurrence, respectively [43]. According to Monk studies, the incidence of postoperative cognitive impairment in elderly patients is closely related to the frequent occurrence of low rSO₂ during operation, and these patients stay in hospital for a relatively long time. Compared with the patients without ASEM and MMSE, the patients with damaged ASEM and MMSE had a greater decrease in rSO₂ value during operation. Multivariate regression analysis showed that 40% decrease of rSO₂ was an independent risk factor for ASEM and MMSE damage [44]. Another multivariate regression analysis showed that rSO₂ AUC >3000% significantly increased the risk of POCD in the early postoperative period and increased the risk of prolonged hospitalization nearly threefold. A randomized trial was carried out on the elderly patients undergoing major abdominal surgery. The intervention group received continuous monitoring of rSO₂ during the operation, make the rSO₂ >75% of the baseline, interventions were taken by raising Fi02, EtC02 and blood pressure. The results showed that there was a significant difference between the intervention group and the control group in the average value of rSO₂. Slater get the coincidence result under CABG patients [45]. Casati found every four patients undergoing abdominal surgery in a healthy elderly population experienced intraoperative low rSO₂, which is associated with a decline in early cognitive levels [46- 47]. The MMSE score of the control group was significantly lower than that of the intervention group on the 7^th day after operation, and the resuscitation time and hospitalization time in the postanesthesia monitoring room were significantly longer than those in the intervention group. In de Tournay Jette study, the patients with rSO₂ <50%, were 7.69 times more likely to develop POCD a week after surgery than those without rSO₂ <50% [48].

rSO₂ and Delirium and Stroke

A large number of literatures have shown that rSO₂ monitoring can reduce the incidence of delirium after cardiac surgery and shorten the length of stay in hospital [49]. A recent systematic review has concluded that only low-level evidence suggests that intraoperative decreased cerebral oxygenation is associated with postoperative stroke [39]. rSO₂ monitoring can reduce the incidence of stroke after CEA surgery [50]. Reducing the risk of cerebral ischemia and anoxia patients undergoing beach chair surgery have a higher risk of hypotension related cerebral ischemia after anesthesia, so it is important to monitor cerebral oxygen saturation during perioperative period in this kind of operation. Morimoto found the delirium rate positive correlated with age and basic of rSO₂ [51]. Continuous monitoring of rSO₂ during operation can effectively prevent perioperative death and stroke associated with carotid endarterectomy CEA. The current research found, in terms of perfusion parameters, postoperative rSO₂ was lower in the delirium than the non-delirium group (65±10% vs. 74±5%), but the delta-rSO₂ (the difference between means post-operative and intra-operative) was associated with post-operative delirium. Treatment with Oxygen concentration, liquid resucetation based on the SO2 will reduce the delirium [52]. Some study indicated that cerebral aortic blood flow changes significantly correlated with rSO₂ and reduced its value 13% as the beginning of cerebral infarction [53].

Conclusion

The rSO₂ a continuous, noninvasive, sensitive and specific method for detect cerebral oxygen saturation guide the prevention and reduction of cerebral ischemia and hypoxia injury in real time and play a guiding role in anesthetic management during operation. It is one of the core tasks of perioperative anesthesia management to maintain the balance of cerebral oxygen supply and demand to ensure the metabolism of brain tissue. Monitoring regional cerebral oxygen saturation using near infrared spectroscopy can detect the balance between cerebral oxygen supply and demand, cerebral perfusion and cerebral blood flow as early as possible, and judge the degree of cerebral ischemia and hypoxia, the change of cerebral function. rSO₂ is helpful timely adjustment of anesthesia plan, finally reduce the occurrence of postoperative neurological dysfunction, shorten the period of hospitalization, and improve the quality of life of patients.

References

1. Jobsis FF. Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters. Science. 1977; 198: 1264- 1267.
2. Murkin JM, Adams SJ, Novick RJ, Monitoring brain oxygen saturation during coronary bypass surgery: a randomized, prospective study. Anesth Analg. 2007; 104: 51-58.
3. Harrer M, Waldenberger FR, Weiss G. Aortic arch surgery using bilateral antegrade selective cerebral perfusion in combination with near-infrared spectroscopy. Eur J Cardiothorac Surg. 2010; 38: 561-567.
4. Faulkner JT, Hartley M, Tang A. Using cerebral oximetry to prevent adverse outcomes during cardiac surgery. Perfusion. 2011; 26: 79-81.
5. Vemick WJ, Oware A. Early diagnosis of superior vena cava obstruction facilitated by the use of cerebral oximetry. J Cardiothorae Vasc Anesth. 2011; 25: 1101-1103.
6. Wang MH, Xie H, Wang C. Effects of sevoflurane and propofol on cerebral oxygen saturation during the period of single lung ventilation in elderly patients. Journal of Soochow University: Medical Edition. 2012; 32: 410-419.
7. Hemmefling TIM, Bluteau MC, Kazan R. Significant decrease of cerebral oxygen saturation during single lung ventilation measured using absolute oximetry. Br J Anaesth. 2008; 101: 870-875.
8. Yamada N, Nagata H, Sato Y. Effects of propefol or sevoflurane on cerebral regional oxygen saturation (rS0₂) during one-lung ventilation. Masui. 2008; 57: 1388-1397.
9. Sanfulippo F, Serena G, Corredor C. Cerebral oximetry and return of spontaneous circulation after cardiac arrest: A systematic review and meta analysis. Resuscitation. 2015; 94: 67-72.
10. Ito N, Nanto S, Nagao K. Regional cerebral oxygen saturation predicts poor neurological ourcome in patients without of hospital cardiac arrest. Resuscitaion. 2018; 81: 1736-1737.
11. Dix LM, Van Bel F, Lemmers PM. Monitoring cerebral oxygenation in neonates: An update. Front Pediatr. 2017; 5: 46.
12. Ahn A, Nasir A, Malik H. A pilot study examining the role of regional cerebral oxygen saturation monitoring as a marker of return of spontaneous circulation in shakable (VF/VT) and nonshockable (PEA/Asystole) causes of cardiac arrest. Resuscitation. 2013; 84: 1713-1716.
13. Palmbergen WA, Van Sonderen A, KeyhanFalsafi AM. Improved perioperative neurological monitoring of coronary artery bypasee graft patients reduces the incidence of postoperative delirium: The Hafa Brain Care Strategy. Interact Cardiovasc Thorac Surg. 2012; 5: 671-677.
14. Palmbergen WA, Van Sonderen A, KeyhanFalsafi AM. Improved perioperative neurological monitoring of coronary artery bypasee graft patients reduces the incidence of postoperative delirium: The Hafa Brain Care Strategy. Interact Cardiovasc Thorac Surg. 2012; 5: 671-677.
15. Kotekar N, Kuruvil la CS, Murthy V. Post operative cognitive dysfunction in the elderly: A prospective clinical study. Indian J Anaesth. 2014; 58: 263-268.
16. Aktuerk D, Mishra PK, Luckraz H. Cerebral oxygnenation monitoring in patients with bilateral carotid stenosis undergoing urgent cardiacsurgery: Observational case series. Ann Card Anaesth. 2016; 19: 59-62.
17. Ghos A, El well C, Smith M. Review article: Cerebral near infrared spectroscopy in adults: Aworking progress. Anesth Analg. 2012; 115: 1373- 1383.
18. Vohra HA, Modi A, Ohri SK. Does use of intra-operative cerebral reginal oxygen saturation monitoring during cardiac surgery lead ro improved clinical outcomes? Interact Cardiovas Thorac Surg. 2009; 9: 318-322.
19. Beena G, Sood, Kathleen Mclaughl, Josef Cortez. Near-infraraed spectroscopy: Applications in neonates. Seminars in Fetal& Neonatal Medicine. 2015; 20: 164.
20. Scheeren TW, Schober P, Schwarte LA. Monitoring tissue oxygenation by Near Infrared Spectroscopy (NIRS) background and current applications. J Clin Monit Comput. 2012; 26: 279-287.
21. Brawanski A, Fahermeier R, Rothoerl RD. Comparison of near-infrared spectroscopy and tissue P(0₂)time series in patients after severe head injury andaneurysmalsubaraehnoid hemorrhage. J Cereb Blood Flow Metal. 2002; 22: 605-611.
22. Pellieer A, Bravo Mdel C. Near infrared spectroscopy a methodology focused review. Semin Fetal Neonatal Med. 201 1; 16: 42-49.
23. Murkin JM, Arango M. Near-infrared spectroscopy a8 an index of brain and tissue oxygenation. Br J Anaesth. 2009; 103: 13-113.
24. Plachky J, Hofer S, Volkman NM. Reginal cerebral oxygen saturation iaasensitive marker of cerebral hypoperfusion during orthotopic liver transplantation. Anesth Analg. 2004; 99: 344-349.
25. Ehara N, Hirose T, Shiozaki T. The relationship between cerebral regional oxygen saturation during extracorporeal cardiopulmonary resuscitation and the neurological outcome in a retrospective analysis of 16 cases. J Intensive Care. 2017; 5: 20.
26. Hirofumi O, Otone E, Hiroshi. The effectiveness of regional cerebral oxygen saturation monitoring using near infrared spectroscopy in carotid endarterectomy.J Clin Neurosci. 2003; 10: 79-83.
27. Shmigelskii AV, Lubnin A, Sazonova OB. Cerebral oximetry in neurosurgical patients with cerebrovascular diseases.Analysis of causes of intraoperative changes in rSO₂ values and its prognostic significance. Anesthesiol Reanimato. 2000; 11-19.
28. Samra SK, Or EA, Welch K. Evaluation of a cerebral oximetera monitor of cerebral ischemia during carotid endarterectomy. Anesthesiology. 2000; 93: 964-970.
29. Fearn SJ, Pole R, Wesnes K. Cerebral injury during cardiopulmonary bypass: Embol impair memory. J Thorac Cardiovasc Surg. 2001; 121: 1150-1160.
30. Kobayashi K, Kitamura T, Kohira S. Factors associated with alow initial cerebral oxygen saturation value in patients undergoing cardiac surgery. J Artif Organs. 2017; 20: 110-116.
31. Colak Z, Borojevic M, Bogovic A. Influence of intraoperative cerebral oximetry monitoring on neuro cognitive function after coronary artery bypass surgery: A randomized prospective study. Eur J Cardiothorac Surg. 2015; 47: 447- 454.
32. Mille T, Tachimiri ME, Klersy C. Near infrared spectroscopymonitoring during carotid endartereetomy which threshold alue is critical? Eur J Vasc Endovasc Surg. 2004; 27: 646-650.
33. Slater JP, Guarino T, Stack J. Cerebral oxygen desaturation predicts cognitive decline and longer hospital stay after cardiac surgery. Ann Thorac Surg. 2009; 87: 36-45.
34. Fudickar A, Peters S, Stapelfeldt C. Postoperative cognitive deficit after cardiopulmonary bypass with preserved cerebral oxygenation: a prospective observational pilot study. BMC Anesthesiol. 2011; 11: 7.
35. Murkin JM, Arango M, Near-infrared spectroscopy a8 an index of brain and tissue oxygenation. Br J Anaesth. 2009; 103: 13-113.
36. Madsen PL, Seeher NH. Near-infrared oximetry of the brain.Pmg Neurobiol. 1999; 58: 541-560.
37. Kishi K, Kawaguchi M, Yoshitani K. Influence of patient variables and sensor location on regional cerebral oxygen saturation measured by INVOS 4100 near infrared spectrophotometers. J Neumsurg Aneathesiol. 2003; 15: 302- 306.
38. Kim MB, Ward DS, Cartwright CR. Estimation of jugular venous S0₂ saturation from cerebral oximetry or arterial 0₂ saturation during isocapnic hypoxia. J ClinMonitComput. 2000; 16: 191-199.
39. Goldman S, Sutter F, Ferdinand F. Optimizing intraoperative cerebral oxygen delivery using noninvasive cerebral oximetry decreases the incidence of stroke for cardiac surgical patients. Heart Surg Forum. 2004; 7: 376-381.
40. Slater JP, Guarino T, Stack J. Cerebral oxygen desaturation predicts cognitive decline and longer hospital stay after cardiac surgery. Ann Thorac Surg. 2009; 87: 36-45.
41. Bruggemans EF. Cognitive dysfunction after cardiac surgery: Pathophysiological mechanisms and preventive strategies. Neth Heart J. 2013; 21: 70 - 73.
42. Zanatta P, Messerotti BS, Valfre C. The role of asymmetry and the nature of microembolization in cognitive decline after heart valve surgery: a pilot study. Perfusion. 2012; 27: 199-206.
43. FudickarA, PetersS, StapelfeldtC. Postoperative cognitive deficit after cardiopulmonary bypass with preserved cerebral oxygenation: a prospective observational pilot study. BMC Anesthesiol. 2011; 11: 7.
44. Reents W, Muellges W, Franke D. Cerebral oxygen saturation assessed by near-infrared spectroscopy during coronary artery bypass grafting and early postoperative cognitive function. Ann Thorac Surg. 2002; 74: 109-114.
45. deTournay-Jetté E, Dupuis G, Bherer L. The relationship between cerebral oxygen saturation changes and postoperative cognitive dysfunction in elderly patients after coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth. 2011; 25: 95-104.
46. Casati A, Fanelli G, Pietrupaoli P. Continuous monitoring of cerebral oxygen saturation in elderly patients undergoing major abdomianal surgery minizes brain exposure to potential hypoxia. Anesth Analg. 2005; 101: 740-747.
47. Casati A, Fanelli G, Pietropaoli P. Monitoring cerebral oxygen saturation in elderly patients undergoing general abdominal surgery a prospective cohort study. Eur J Anaesthesiol. 2007; 24: 59-65.
48. Hong SW, Shim JK, Choi YS. Prediction of cognitive dysfunction and patients’ outcome following valvular heart surgery and the role of cerebral oximetry. Eur J Cardiothorac Surg. 2008; 33: 560-565.
49. Zheng F, Sheinberg R, Yee MS. Cerebral near-infrared spectroscopy monitoring and neurelogic outcomes in adult cardiac surgery patients a systematic review. Anesth Analg. 2013; 116: 663-676.
50. Kamii H, Sato K, Matsumoto Y. Periprocedural monitoring with regional cerebral oxygen saturation in carotid artery stenting. Interv Neumradiol. 2007; 13: 53-57.
51. Morimoto Y, Yoshimura M, Utada K. Prediction of postoperative delirium after abdominal surgery in the elderly. J Anesth. 2009; 23: 51-56.
52. Bjorkelund KB, Hommel A, Thomgren KG. Reducing delirium in elderly patients with hip fracture a multi-factorial intervention study. Acta Anaesthesiot Scand. 2010; 54: 678-688.
53. Gottesman RF, Sherman PM, Grega MA. Watershed stroke after cardiac surgery diagnosis etiology and outcome. Stroke. 2006; 37: 2306-2311.