Cerebral oximetry – The holy grail of non-invasive cerebral perfusion monitoring in cardiac arrest or just a false dawn?

Abstract

Although one of the major goals of resuscitation is maintaining end organ perfusion, to date there have been no standard real-time clinical methods available to determine effective brain perfusion. While the electroencephalogram (EEG) has been used to assess cerebral ischaemia, it does not provide a real-time measure of oxygen delivery to the brain and cannot be used reliably in clinical practice. Recently, a small portable EEG device using bispectral technology (BIS Monitoring – Aspect Medical Systems, Norwood, MA, USA) has been studied in cardiac arrest; however, it was found to be susceptible to movement artifact and is therefore unreliable.1Fatovich D. Jacobs I. Celenza A. Paech M. An observational study of bispectral index monitoring for out of hospital cardiac arrest.Resuscitation. 2006; 69: 207-212Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar Another non-invasive technology that has emerged, which is not susceptible to motion artifact, is cerebral oximetry using near infrared spectroscopy (NIRS). This is an optical monitoring technique that is based on the Beer Lambert's law and assesses regional cerebral oxygen saturation (rSO2) and provides a real-time indicator of the balance between oxygen supply and demand.2Pollard V. Prough D.S. Cerebral oxygenation: near-infrared spectroscopy in principles and practice of intensive care monitoring. McGraw Hill, 1997Google Scholar In biological tissue, the use of NIRS is made possible because while the tissues themselves are relatively transparent to near infrared light in the 400–1000 nm range, specific chromophores present in tissues absorb wavelengths of light in this spectrum.2Pollard V. Prough D.S. Cerebral oxygenation: near-infrared spectroscopy in principles and practice of intensive care monitoring. McGraw Hill, 1997Google Scholar Furthermore, water and melanin both express low optical absorption, thus enabling near infrared light to pass through several centimetres of tissue, including skin, subcutaneous tissue, and bone without being significantly absorbed.2Pollard V. Prough D.S. Cerebral oxygenation: near-infrared spectroscopy in principles and practice of intensive care monitoring. McGraw Hill, 1997Google Scholar Near infrared spectroscopy measures the reduction in optical intensity, expressed as the change in optical density per centimeter of tissue.3Tamura T. Hazeki O. Takada M. Tamura M. Absorbance profile of red blood cell suspension in vitro and in situ.Adv Exp Med Biol. 1985; 191: 211-217Crossref PubMed Scopus (1) Google Scholar, 4Pollard V. Prough D.S. DeMelo A.E. et al.Validation in volunteers of a near-infrared spectroscope for monitoring brain oxygenation in vivo.Anesth Analg. 1996; 82: 269-277PubMed Google Scholar Since 70% of blood in the measured areas of brain tissue is venous, this data mainly represents cerebral venous saturation and thus generally acceptable normal values for rSO2 are in the range of 60–80%.5McCormick P.W. Stewart M. Ray P. et al.Measurement of regional cerebrovascular hemoglobin oxygen saturation in cats using optical spectroscopy.Neurol Res. 1991; 13: 65-70PubMed Google ScholarEven though this technology has been validated and used as a tool for cerebral perfusion monitoring in many diverse clinical settings,6Kurth C.D. Steven J.L. Montenegro L.M. et al.Cerebral oxygen saturation before congenital heart surgery.Ann Thorac Surg. 2001; 72: 187-192Abstract Full Text Full Text PDF PubMed Scopus (144) Google Scholar, 7Taillefer M.C. Denault A.Y. Cerebral near-infrared spectroscopy in adult heart surgery: systematic review of its clinical efficacy.Can J Anaesth. 2005; 52: 79-87Crossref PubMed Scopus (123) Google Scholar, 8Shojima M. Watanabe E. Mayanagi Y. Cerebral blood oxygenation after cerebrospinal fluid removal in hydrocephalus measured by near-infrared spectroscopy.Surg Neurol. 2004; 62: 312-318Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar it has been used only to a limited extent during cardiac arrest and these studies have indicated a potential role in predicting survival and neurological outcome.9Newman D.H. Callaway C.W. Greenwald I.B. Freed J. Cerebral oximetry in out-of-hospital cardiac arrest: standard CPR rarely provides detectable hemoglobin-oxygen saturation to the frontal cortex.Resuscitation. 2004; 63: 189-194Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar, 10Müllner M. Sterz F. Binder M. Hirschl M.M. Janata K. Laggner A.N. Near infrared spectroscopy during and after cardiac arrest—preliminary results.Clin Intensive Care. 1995; 6: 107-111PubMed Google Scholar, 11Nemoto E.M. Yonas H. Kassam A. Clinical experience with cerebral oximetry in stroke and cardiac arrest.Crit Care Med. 2000; 28: 1052-1054Crossref PubMed Scopus (76) Google Scholar In one of the earliest small studies evaluating its role in prognosis, it was demonstrated that a mean rSO2 of 17% or less achieved during out-of-hospital cardiac arrest predicted non-survival.9Newman D.H. Callaway C.W. Greenwald I.B. Freed J. Cerebral oximetry in out-of-hospital cardiac arrest: standard CPR rarely provides detectable hemoglobin-oxygen saturation to the frontal cortex.Resuscitation. 2004; 63: 189-194Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar This finding complimented the results of another earlier small out-of-hospital study which demonstrated that all patients surviving for one week (n = 9) achieved a significantly higher median rSO2 during cardiac arrest than non-survivors (63% versus 46%, p = 0.003).10Müllner M. Sterz F. Binder M. Hirschl M.M. Janata K. Laggner A.N. Near infrared spectroscopy during and after cardiac arrest—preliminary results.Clin Intensive Care. 1995; 6: 107-111PubMed Google Scholar In a more recent larger study of 132 out-of-hospital cardiac arrests, among 33 patients with an rSO2 of ≤15% on arrival at the emergency room, none survived.12Ito N. Nanto S. Nagao K. Hatanaka T. Kai T. Regional cerebral oxygen saturation predicts poor neurological outcome in patients with out-of-hospital cardiac arrest.Resuscitation. 2010; 81: 1736-1737Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar Although none of these early studies had focused on neurological outcomes, in this issue, Ito and coworkers have followed up their earlier study by reporting that among patients with out-of-hospital cardiac arrest admitted to the emergency room, of 22 with a rSO2 > 40% 11 (50%) had a good neurological outcome, whereas those with rSO2 < 25% all had a poor neurological outcome.13Ito N. Nanto S. Nagoa K. Regional cerebral oxygen saturation on hospital arrival is a potential novel predictor of neurological outcomes at hospital discharge in patients with out-of-hospital cardiac arrest.Resuscitation. 2011; 82PubMed Google Scholar Even though these limited studies suggest that a low rSO2 may predict poor outcome, in our experience care should be exercised in interpreting these data. Cerebral oxygen saturation as measured by NIRS is a dynamic, not a static measure, and therefore a low rSO2 may suggest a poor outcome where either an intervention aimed at improving cerebral perfusion has not been made, or attempted interventions have been ineffective. By analogy, in the same way that most would interpret a profoundly low oxygen saturation of hemoglobin measured by pulse oximetry as an indicator for a timely intervention such as mechanical ventilation, a low rSO2 in the context of cardiac arrest would be better interpreted as signifying the need for appropriate interventions aimed at improving cerebral perfusion through quality resuscitation. If despite all interventions rSO2 remains critically low then a poor outcome may be inevitable. The potential to improve rSO2 has been illustrated in several case reports. In one case of prolonged cardiac arrest in an 87-year-old having aortic valve surgery, rSO2 dropped rapidly from around 70% to approximately 30% after cardiac arrest, but effective cardiopulmonary resuscitation led to an increase to approximately 50% and the initiation of cardiopulmonary bypass elevated rSO2 to pre cardiac arrest levels.14Paarmann H. Heringlake M. Sier H. Schön J. The association of non-invasive cerebral and mixed venous oxygen saturation during cardiopulmonary resuscitation.Interact Cardiovasc Thorac Surg. 2010; 11: 371-373Crossref PubMed Scopus (21) Google Scholar Interestingly, Kämäräinen and colleagues who studied rSO2 in nine in-hospital cardiac arrests, and whose data is published in this issue, observed that improving CPR quality did not significantly increase rSO2.15Kämäräinen A. Quality controlled manual chest compressions and cerebral oxygenation during in-hospital cardiac arrest.Resuscitation. 2011; 82PubMed Google Scholar However, a closer look at their data indicates that this observation may simply reflect the fact that resuscitation had only been carried out for a relatively short period of time. Among their nine patients, CPR was attempted for only 4–7 min, which may be too short a time for the positive impact of quality CPR on cerebral perfusion, and hence rSO2, to manifest itself, as illustrated by some of the published case reports.14Paarmann H. Heringlake M. Sier H. Schön J. The association of non-invasive cerebral and mixed venous oxygen saturation during cardiopulmonary resuscitation.Interact Cardiovasc Thorac Surg. 2010; 11: 371-373Crossref PubMed Scopus (21) Google Scholar, 16Howells M. Green D.W. Cerebral oximetry monitoring during unexpected cardiopulmonary arrest and tension pneumothorax.Eur J Anaesthesiol. 2006; 23: 266-268Crossref PubMed Scopus (8) Google Scholar Interestingly, in their study Kämäräinen and colleagues further concluded that rSO2 was higher (reaching approximately 30%) in patients with return of spontaneous circulation (ROSC) and that after a further 8 min rSO2 had reached approximately 60%, thus indicating both the dynamic nature of this measurement, and its ability to change with resuscitation. When examined together, these studies suggest that a longer period of time using quality CPR may be needed to improve organ perfusion and ultimately achieve ROSC. This matches our own experience, where although most patients have a very low rSO2 (15–20%) at the onset of witnessed cardiac arrest, the incorporation of quality resuscitation leads to a gradual increase in rSO2 and ultimately ROSC sometimes over tens of minutes. Although the role of cerebral oximetry in the post resuscitation period has not yet been studied in detail, the observation by Putzer and associates, published in this issue, demonstrating the effect of hypothermia in improving rSO2,17Putzer G. iefenthaler W. Mair P. Near-infrared spectroscopy during cardiopulmonary resuscitation of a hypothermic polytraumatized cardiac arrest patient.Resuscitation. 2011; 82Google Scholar together with a case report by Mayr and coauthors,18Mayr P.N. Martin K. Hausleiter J. Tassani P. Measuring cerebral oxygenation helps optimizing post – resuscitation therapy.Resuscitation. 2011; 82: 1110-1111Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar in which cerebral oximetry was used during the post resuscitation period, raises the tantalizing possibility that cerebral oximetry may also have a role in predicting neurological outcomes and optimisation of cerebral perfusion during post resuscitation and hypothermia. While further data and research is clearly needed, these early studies suggest that by providing a real-time non-invasive marker of cerebral perfusion, cerebral oximetry may have a role in optimising cerebral perfusion in cardiac arrest and improving survival, neurological and functional outcomes.Conflict of interest statementNo conflict of interest to declare. Although one of the major goals of resuscitation is maintaining end organ perfusion, to date there have been no standard real-time clinical methods available to determine effective brain perfusion. While the electroencephalogram (EEG) has been used to assess cerebral ischaemia, it does not provide a real-time measure of oxygen delivery to the brain and cannot be used reliably in clinical practice. Recently, a small portable EEG device using bispectral technology (BIS Monitoring – Aspect Medical Systems, Norwood, MA, USA) has been studied in cardiac arrest; however, it was found to be susceptible to movement artifact and is therefore unreliable.1Fatovich D. Jacobs I. Celenza A. Paech M. An observational study of bispectral index monitoring for out of hospital cardiac arrest.Resuscitation. 2006; 69: 207-212Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar Another non-invasive technology that has emerged, which is not susceptible to motion artifact, is cerebral oximetry using near infrared spectroscopy (NIRS). This is an optical monitoring technique that is based on the Beer Lambert's law and assesses regional cerebral oxygen saturation (rSO2) and provides a real-time indicator of the balance between oxygen supply and demand.2Pollard V. Prough D.S. Cerebral oxygenation: near-infrared spectroscopy in principles and practice of intensive care monitoring. McGraw Hill, 1997Google Scholar In biological tissue, the use of NIRS is made possible because while the tissues themselves are relatively transparent to near infrared light in the 400–1000 nm range, specific chromophores present in tissues absorb wavelengths of light in this spectrum.2Pollard V. Prough D.S. Cerebral oxygenation: near-infrared spectroscopy in principles and practice of intensive care monitoring. McGraw Hill, 1997Google Scholar Furthermore, water and melanin both express low optical absorption, thus enabling near infrared light to pass through several centimetres of tissue, including skin, subcutaneous tissue, and bone without being significantly absorbed.2Pollard V. Prough D.S. Cerebral oxygenation: near-infrared spectroscopy in principles and practice of intensive care monitoring. McGraw Hill, 1997Google Scholar Near infrared spectroscopy measures the reduction in optical intensity, expressed as the change in optical density per centimeter of tissue.3Tamura T. Hazeki O. Takada M. Tamura M. Absorbance profile of red blood cell suspension in vitro and in situ.Adv Exp Med Biol. 1985; 191: 211-217Crossref PubMed Scopus (1) Google Scholar, 4Pollard V. Prough D.S. DeMelo A.E. et al.Validation in volunteers of a near-infrared spectroscope for monitoring brain oxygenation in vivo.Anesth Analg. 1996; 82: 269-277PubMed Google Scholar Since 70% of blood in the measured areas of brain tissue is venous, this data mainly represents cerebral venous saturation and thus generally acceptable normal values for rSO2 are in the range of 60–80%.5McCormick P.W. Stewart M. Ray P. et al.Measurement of regional cerebrovascular hemoglobin oxygen saturation in cats using optical spectroscopy.Neurol Res. 1991; 13: 65-70PubMed Google Scholar Even though this technology has been validated and used as a tool for cerebral perfusion monitoring in many diverse clinical settings,6Kurth C.D. Steven J.L. Montenegro L.M. et al.Cerebral oxygen saturation before congenital heart surgery.Ann Thorac Surg. 2001; 72: 187-192Abstract Full Text Full Text PDF PubMed Scopus (144) Google Scholar, 7Taillefer M.C. Denault A.Y. Cerebral near-infrared spectroscopy in adult heart surgery: systematic review of its clinical efficacy.Can J Anaesth. 2005; 52: 79-87Crossref PubMed Scopus (123) Google Scholar, 8Shojima M. Watanabe E. Mayanagi Y. Cerebral blood oxygenation after cerebrospinal fluid removal in hydrocephalus measured by near-infrared spectroscopy.Surg Neurol. 2004; 62: 312-318Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar it has been used only to a limited extent during cardiac arrest and these studies have indicated a potential role in predicting survival and neurological outcome.9Newman D.H. Callaway C.W. Greenwald I.B. Freed J. Cerebral oximetry in out-of-hospital cardiac arrest: standard CPR rarely provides detectable hemoglobin-oxygen saturation to the frontal cortex.Resuscitation. 2004; 63: 189-194Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar, 10Müllner M. Sterz F. Binder M. Hirschl M.M. Janata K. Laggner A.N. Near infrared spectroscopy during and after cardiac arrest—preliminary results.Clin Intensive Care. 1995; 6: 107-111PubMed Google Scholar, 11Nemoto E.M. Yonas H. Kassam A. Clinical experience with cerebral oximetry in stroke and cardiac arrest.Crit Care Med. 2000; 28: 1052-1054Crossref PubMed Scopus (76) Google Scholar In one of the earliest small studies evaluating its role in prognosis, it was demonstrated that a mean rSO2 of 17% or less achieved during out-of-hospital cardiac arrest predicted non-survival.9Newman D.H. Callaway C.W. Greenwald I.B. Freed J. Cerebral oximetry in out-of-hospital cardiac arrest: standard CPR rarely provides detectable hemoglobin-oxygen saturation to the frontal cortex.Resuscitation. 2004; 63: 189-194Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar This finding complimented the results of another earlier small out-of-hospital study which demonstrated that all patients surviving for one week (n = 9) achieved a significantly higher median rSO2 during cardiac arrest than non-survivors (63% versus 46%, p = 0.003).10Müllner M. Sterz F. Binder M. Hirschl M.M. Janata K. Laggner A.N. Near infrared spectroscopy during and after cardiac arrest—preliminary results.Clin Intensive Care. 1995; 6: 107-111PubMed Google Scholar In a more recent larger study of 132 out-of-hospital cardiac arrests, among 33 patients with an rSO2 of ≤15% on arrival at the emergency room, none survived.12Ito N. Nanto S. Nagao K. Hatanaka T. Kai T. Regional cerebral oxygen saturation predicts poor neurological outcome in patients with out-of-hospital cardiac arrest.Resuscitation. 2010; 81: 1736-1737Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar Although none of these early studies had focused on neurological outcomes, in this issue, Ito and coworkers have followed up their earlier study by reporting that among patients with out-of-hospital cardiac arrest admitted to the emergency room, of 22 with a rSO2 > 40% 11 (50%) had a good neurological outcome, whereas those with rSO2 < 25% all had a poor neurological outcome.13Ito N. Nanto S. Nagoa K. Regional cerebral oxygen saturation on hospital arrival is a potential novel predictor of neurological outcomes at hospital discharge in patients with out-of-hospital cardiac arrest.Resuscitation. 2011; 82PubMed Google Scholar Even though these limited studies suggest that a low rSO2 may predict poor outcome, in our experience care should be exercised in interpreting these data. Cerebral oxygen saturation as measured by NIRS is a dynamic, not a static measure, and therefore a low rSO2 may suggest a poor outcome where either an intervention aimed at improving cerebral perfusion has not been made, or attempted interventions have been ineffective. By analogy, in the same way that most would interpret a profoundly low oxygen saturation of hemoglobin measured by pulse oximetry as an indicator for a timely intervention such as mechanical ventilation, a low rSO2 in the context of cardiac arrest would be better interpreted as signifying the need for appropriate interventions aimed at improving cerebral perfusion through quality resuscitation. If despite all interventions rSO2 remains critically low then a poor outcome may be inevitable. The potential to improve rSO2 has been illustrated in several case reports. In one case of prolonged cardiac arrest in an 87-year-old having aortic valve surgery, rSO2 dropped rapidly from around 70% to approximately 30% after cardiac arrest, but effective cardiopulmonary resuscitation led to an increase to approximately 50% and the initiation of cardiopulmonary bypass elevated rSO2 to pre cardiac arrest levels.14Paarmann H. Heringlake M. Sier H. Schön J. The association of non-invasive cerebral and mixed venous oxygen saturation during cardiopulmonary resuscitation.Interact Cardiovasc Thorac Surg. 2010; 11: 371-373Crossref PubMed Scopus (21) Google Scholar Interestingly, Kämäräinen and colleagues who studied rSO2 in nine in-hospital cardiac arrests, and whose data is published in this issue, observed that improving CPR quality did not significantly increase rSO2.15Kämäräinen A. Quality controlled manual chest compressions and cerebral oxygenation during in-hospital cardiac arrest.Resuscitation. 2011; 82PubMed Google Scholar However, a closer look at their data indicates that this observation may simply reflect the fact that resuscitation had only been carried out for a relatively short period of time. Among their nine patients, CPR was attempted for only 4–7 min, which may be too short a time for the positive impact of quality CPR on cerebral perfusion, and hence rSO2, to manifest itself, as illustrated by some of the published case reports.14Paarmann H. Heringlake M. Sier H. Schön J. The association of non-invasive cerebral and mixed venous oxygen saturation during cardiopulmonary resuscitation.Interact Cardiovasc Thorac Surg. 2010; 11: 371-373Crossref PubMed Scopus (21) Google Scholar, 16Howells M. Green D.W. Cerebral oximetry monitoring during unexpected cardiopulmonary arrest and tension pneumothorax.Eur J Anaesthesiol. 2006; 23: 266-268Crossref PubMed Scopus (8) Google Scholar Interestingly, in their study Kämäräinen and colleagues further concluded that rSO2 was higher (reaching approximately 30%) in patients with return of spontaneous circulation (ROSC) and that after a further 8 min rSO2 had reached approximately 60%, thus indicating both the dynamic nature of this measurement, and its ability to change with resuscitation. When examined together, these studies suggest that a longer period of time using quality CPR may be needed to improve organ perfusion and ultimately achieve ROSC. This matches our own experience, where although most patients have a very low rSO2 (15–20%) at the onset of witnessed cardiac arrest, the incorporation of quality resuscitation leads to a gradual increase in rSO2 and ultimately ROSC sometimes over tens of minutes. Although the role of cerebral oximetry in the post resuscitation period has not yet been studied in detail, the observation by Putzer and associates, published in this issue, demonstrating the effect of hypothermia in improving rSO2,17Putzer G. iefenthaler W. Mair P. Near-infrared spectroscopy during cardiopulmonary resuscitation of a hypothermic polytraumatized cardiac arrest patient.Resuscitation. 2011; 82Google Scholar together with a case report by Mayr and coauthors,18Mayr P.N. Martin K. Hausleiter J. Tassani P. Measuring cerebral oxygenation helps optimizing post – resuscitation therapy.Resuscitation. 2011; 82: 1110-1111Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar in which cerebral oximetry was used during the post resuscitation period, raises the tantalizing possibility that cerebral oximetry may also have a role in predicting neurological outcomes and optimisation of cerebral perfusion during post resuscitation and hypothermia. While further data and research is clearly needed, these early studies suggest that by providing a real-time non-invasive marker of cerebral perfusion, cerebral oximetry may have a role in optimising cerebral perfusion in cardiac arrest and improving survival, neurological and functional outcomes. Conflict of interest statementNo conflict of interest to declare. No conflict of interest to declare.