Impact of cerebral oximetry on cardiac surgery

Technologic advances in cardiac surgery have resulted in an impressively low mortality rate. Unfortunately, vital organ morbidity remains a cause for concern. Brain and kidney seem to bear the brunt of this injury because of their inordinately high blood flow and oxygen requirements. The landmark multi-center study of Roach et al.1 established a 6% incidence of major neurologic injury associated with coronary artery bypass graft (CABG) surgery. The incidence of more subtle cognitive deficits appears to exceed 40%.2 Numerous studies have demonstrated associations between neurocognitive deficit and both longer hospital stays and cost of care.3 A startlingly high 30% injury rate also occurs in the kidney following adult cardiac surgery.4

Causes of Injury

The cause of injury in both organs is widely viewed as multi-factorial: emboli, hypoxia, ischemia, suboptimal cooling and hyperthermia.5 At the cellular level, the factor common to all these insults is an imbalance between local tissue demand for oxygen and its supply. Recognition of this principle formed the rationale underpinning for the development of cerebral oximetry, which was designed to detect local oxygen imbalance and guide its correction.

The brain has by far the highest oxygen demand of any vital organ. The adult brain represents only 4% of body mass, but requires 20% of the entire arterial blood flow. Two fundamental concepts derive from this physiologic fact. First, clinically important oxygen imbalance in a single brain region may be invisible to whole-body or even whole-head measures of oxygenation. This explains the oft-reported finding that neither blood pressure nor arterial oxygen saturation is predictive of post-surgical neurocognitive outcome.6 Second, correction of brain regional imbalance should also benefit other vital organs, because of their lower oxygen requirements.

Cerebral Oximetry Technology

Cerebral tissue oximetry is based on the long-established technology of near-infrared spectroscopy utilized in pulse (i.e., whole-body arterial), mixed venous (i.e., whole-body) and jugular bulb (i.e., whole-head venous) oximetry. Each device uses multiple wavelengths of light to measure oxygen saturation (i.e., the percentage of hemoglobin present in its fully oxygenated state). Monitoring arterial oxygen saturation is analogous to examining bank account deposits. Both measure input, not account balance. Consequently, “silent” life- or brain-threatening decline in brain oxygen balance may go undetected by arterial oxygen saturation.7 In contrast, tissue and venous oxygen saturation resemble ending account balance by providing a more complete picture of the functional state.

During tissue infrared transillumination, the volume of hemoglobin in blood vessels larger than 1 mm is sufficient to absorb all in-coming photons, so that surface recordings measure only light transmitted through or reflected from the smallest blood vessels.8 Because this microcirculation is the region of respiratory gas exchange, saturation measurement at this site provides the best available estimate of oxygen within a thimble-sized volume of tissue. Measurement of photon pulsations (i.e., pulse oximetry) gives an exclusively arterial estimate of saturation, whereas the non-pulsatile component is predominantly venous.

Non-invasive transcranial measurement of brain oxygen saturation is possible, in part, because skin and bone are translucent to infra-red light (Figure 1). Most photons are scattered by cerebrospinal fluid or absorbed by hemoglobin, but a small fraction are reflected to the skin surface. Measurement is achieved with forehead-mounted self-adhesive sensor patches containing an infrared light source and multiple photon detectors (Figure 1). The process of spatial resolution (Figure 1) removes surface reflections so that at least 85% of the resultant signal is derived from brain tissue.8

Figure 1 (left panel) illustrates photon migration through the adult human skull. The -middle panel shows typical sensor placement on the forehead and the brain regions measured. The right panel depicts the path of photons reflected from surface structures (i.e., scalp/skull) and deeper brain tissue.

As with pulse, mixed venous, and jugular bulb oximetry, normative cerebral oximetry values have now been established for adults. Our pre-operative measurement of regional brain tissue oxygen saturation (rSO2) in one thousand CABG patients defined the normal range (65±9%) and a threshold of 50% for abnormality.9 A wide variety of clinical and experimental studies also established a 25% saturation decrease from baseline as an alternative alarm threshold.10 Many studies have now reported associations between these two thresholds and both clinical11 and economic12 indices of adverse outcome. In contrast to mean arterial pressure and arterial oxygen saturation, prolonged low rSO2 has recently been shown to be a highly significant predictor of brain injury after CABG surgery.13

Cerebral Oximetry Monitoring Approach

Cerebral oximetry should aid in the management of any surgical or critical care patient with an increased risk of brain injury.12 However, to date, most clinical investigations have focused on cardiac surgery because of the high incidence of potentially preventable vital organ insult. The following perspective derives from my 16-year oximetry research experience and neuromonitoring in over 6,500 cardiac surgeries.

We try to monitor all elective and emergent cardiac surgeries, since major neurologic injury most frequently occurs in low-to-medium risk patients.14 Our goal is to detect early signs of developing brain oxygen imbalance, determine the most appropriate treatment and assess immediate patient response to therapeutic intervention. This process involves all members of the cardiac surgery team. Each should have familiarity with cerebral oximetry technology and the rationale for its use during cardiac surgery. Fortunately, detailed descriptions of the monitoring technique are now widely available in respected peer-reviewed medical journals9 and text books.15-17

Low oxygen delivery

The relationship between blood oxygen partial pressure and saturation is non-linear (Figure 2, right panel). With typical high oxygen partial pressure in arterial blood, substantial declines in the nearly horizontal portion of the curve may result in only small decreases in % saturation. In contrast, small oxygen partial pressure declines in the nearly vertical venous portion of the curve produce larger decreases in % saturation. Consequently, impaired oxygen delivery will be manifested first and most clearly by local declines in brain venous oxygen saturation. The dramatic changes accompanying an inability to ventilate a patient with a difficult airway are depicted in Figure 2 (left panel). Regional cerebral tissue oximetry immediately identified an interruption of oxygen delivery to the brain, guided the decision for an emergent tracheostomy and documented its success. In addition to the immediate clinical benefit in such crisis situations, retrospective review of cerebral oximetry trends has proven invaluable to hospital risk managers in clarifying the actual magnitude and time course of a presumed brain insult.

The oxygen dissocation curve is shown in the right panel of Figure 2. It displays the non-linear relationship between the partial pressure of oxygen in blood (horizontal axis) and the percentage of blood hemoglobin that is fully saturated with oxygen (vertical axis). Observe that arterial saturation (SaO2) resides on the horizontal portion of the curve, while regional tissue (rSO2) and systemic venous (SvO2) oxygen saturation are located on the vertical portion. The left panel characterizes the time course (horizontal axis) of the profound decrease in regional brain oxygen saturation (rSO2, vertical axis) associated with a failed attempt to insert an endotracheal tube in an anesthetized, chemically immobilized patient. Note the immediate recovery in brain oxygen balance with the successful tracheostomy.

Dysautoregulation

Of all vital organs, the brain is unique in its ability to maintain, during cardiopulmonary bypass, precise regulation of blood flow to match local metabolic demand. This cerebral autoregulation assures adequate blood flow despite moderate declines in blood pressure. Unfortunately, autoregulation is diminished or absent in a minority of patients due to pre-existing disease or the effects of anesthesia and/or extracorporeal circulation. In these patients, relatively small decreases in blood pressure may cause marked reduction of cerebral blood flow. This potentially injurious dysautoregulation can be detected and corrected through the continuous monitoring of brain blood flow or oxygenation. Figure 3 illustrates the value of cerebral oximetry in managing blood pressure in such a patient.

Figure 3 is an example of dysautoregulation – a cerebral oxygen imbalance caused by the development of moderate hypotension. Correction of low blood pressure restored oxygen balance to baseline level. The localized imbalance was not manifested by a decline in arterial oxygen saturation.

Cerebral Inflow Obstruction

During cardiopulmonary bypass, oxygenated blood from the heart-lung machine is usually delivered to the patient via a large cannula placed in the ascending aorta. A malpositioned cannula can direct the high velocity jet flow away from the arteries carrying blood to the brain. This localized but catastrophic event may be invisible to systemic measures of blood pressure and arterial or venous oxygenation. Fortunately, it is readily detected by cerebral oximetry, as shown in Figure 4.

Figure 4 illustrates the effect of aortic perfusion cannula malposition on cerebral oxygen balance. Cannula repositioning promptly restored balance. The malposition had no effect on arterial or mixed venous oxygen saturation or blood pressure.

Cerebral Outflow Obstruction

Brain blood flow also can be compromised by obstructing its outflow. As with inflow obstruction, this hazardous situation may be unrecognized by traditional systemic hemodynamic and oxygenation monitors. Figure 5 depicts a profound oxygen imbalance in the right cerebral hemisphere accompanying the insertion of a large coronary sinus catheter into the right jugular vein. Cerebral oximetry led to catheter removal and alteration of the surgical approach from minimally invasive to one using a standard sternotomy.

Obstruction of blood outflow from the brain may also result in local oxygen imbalance, as shown in Figure 5. Insertion of a coronary sinus catheter in the right jugular vein obstructed outflow from the right cerebral hemisphere. Head rotation to the neutral position only slightly improved balance. Baseline brain oxygen saturation was promptly restored with catheter removal. As a result, the surgical plan for mitral valve replacement was changed from minimally invasive to the standard approach via a median sternotomy. Both blood pressure and arterial oxygen saturation remained within normal limits during the right hemisphere imbalance.

Suboptimal Brain Cooling

Currently, deep cooling is the most efficacious technique available to protect the brain when surgical repair requires blood flow to be temporarily reduced or stopped.18 Maximal protection requires the creation of a uniformly hyperoxic state throughout the entire brain.19 Production of this ideal environment depends on optimal management of extracorporeal circulation. Figure 6 compares typical changes in brain oxygen balance observed with optimal and suboptimal cooling techniques. Cerebral oximeter-guided cooling shown in the lower panel achieved the optimal results, while disregarding oximeter information (upper panel) resulted in ineffective brain cooling.

In the upper panel, despite rapid cooling of the patient to a nasopharyngeal temperature of 15° C, brain oxygen balance was not improved because of suboptimal perfusion technique. As a consequence, marked imbalance in brain oxygenation occurred during the following 22 minutes of circulatory arrest. Note the rSO2 values below the dotted line alarm threshold. In contrast, the lower panel depicts the benefit of oximeter-optimized cooling. Cooling to 17° C created a hyperoxic state that helped to maintain brain oxygen balance above the alarm threshold during 30 minutes of circulatory arrest.

Current Status of Cerebral Oximetry

Sackett et al.20 popularized the current notion that randomized clinical trials are the only acceptable approach to establish diagnostic or therapeutic efficacy. Indeed, such trials are necessary to completely avoid unintentional experimental bias and scientifically prove cause and effect. However, the standardized protocols and patient selection process inherent in randomized trials are often unrepresentative of actual clinical practice. Therefore, it is now recognized that non-randomized or case control retrospective analyses are also essential to measure clinical effectiveness – apparent benefit in real-world settings.21

To date, eight effectiveness studies involving more than seven thousand patients have found that cerebral oximetry use during CABG surgery is associated with reductions in neurocognitive decline and/or hospital cost.22-29 No retrospective study of cerebral oximetry during cardiac surgery that used a standardized intervention protocol has failed to find effectiveness.

Recently, the evidence-based medicine criterion has also been achieved. Murkin et al.30 used a prospective randomized design in 200 CABG patients with standardized intervention. The group benefiting from cerebral oximetric monitoring had reductions in hospital and ICU lengths of stay, duration of post-operative ventilator support, stroke incidence and major organ morbidity (P<.05). I determined that these clinical benefits were also associated with apparent in-hospital net savings of $1,843/patient, based on current direct costs for oximeter sensors, amortized monitoring hardware, stroke ($16,000)3, post-operative ventilator support ($1/min)31, ICU care without ventilator ($913/day)31, and hospital stay ($539/day)32.

Because of the published evidence of clinical efficacy and effectiveness, as well as the apparent cost benefit, cerebral oximetry utilization for cardiac surgery has experienced explosive growth world-wide. Until very recently, the only FDA-cleared cerebral oximeter has been the Somanetics Corp. INVOS® System. The U.S.-installed base currently exceeds 600 hospitals utilizing INVOS in approximately 150,000 procedures annually. In addition, the device is available throughout the rest of North America, Europe, South Africa, Asia and Australia. As yet, there are no utilization data available for the recently released FDA-cleared Fore-Sight® cerebral oximeter, manufactured by Cas Medical.

Summary

The technology underlying cerebral oximetry is sound and well-established. Normative values, alarm thresholds and monitoring technique for adult cardiac surgery patients have been published in popular peer-reviewed medical journals and text books. The clinical effectiveness has been repeatedly demonstrated and efficacy established in a recent randomized clinical trial. Cost-benefit estimates based on this trial are compelling. This overwhelming evidence makes it difficult to justify avoidance of this brain- and life-saving technology.

References

1. Roach GW et al. 1996. New Engl J Med 335:1857.
2. Ahlgren E et al. 2003. Eur J Cardiothorac Surg 23:334.
3. Puskas JD et al. 2000. Ann Thorac Surg 69:1053.
4. Stafford-Smith M et al. 2006. Heart Surg Forum Rev 4:22.
5. Selim M 2007. New Engl J Med 258:708.
   
6. Moller JT et al. 1998. Lancet 351:857.
7. Hoffman GM 2006. Ann Thorac Surg 81:S2373.
8. Ferari M et al. 2004. Can J Appl Physiol 29:463.
9. Edmonds HL Jr. et al. 2004. Sem Cardiothorac Vasc Anesth 8:147.
10. Singer I et al. 1998. J Inteven Cardiol 11:205.
11. Yao F-S et al. 2004. J Cardiothorac Vasc Anesth 18:552.
12. Casati A et al. 2005. Anesth Analg 101 :740.
13. Slater JP et al. 2007. Proc Soc Thorac Surg 104.
14. Likosky DS et al. 2003. Ann Thorac Surg 76:428.
15. Edmonds HL Jr. et al. 2004a. Intraoperative cerebral monitoring. In Yang S & Cameron D (Eds.) Current Trends in Thoracic and Cardiovascular Surgery. Philadelphia, Harcourt, p. 591.
16. Edmonds HL Jr. 2006. Central nervous system monitoring. In Kaplan J (Ed.) Cardiac Anesthesia 5th Edition, Philadelphia, Elsevier, p. 529.
17. Lake CL et al. 2005. Monitoring the pediatric cardiac patient. In Lake CL & Booker CT (Eds.) Pediatric Cardiac Anesthesia 4th Edition, Philadelphia, Lippincott Williams & Wilkins, p. 190.
18. Thong WY et al. 2002. Anesth Analg 95:1489
19. Pearl JM et al. 20009. Ann Thorac Surg 70:751.
20. Sackett DL et al. 1995. J Royal Soc Med 88:620.
21. Orkin FK 1999. Application of outcomes research to clinical decision-making in cardiovascular medicine. In Tuman K (Ed.) Outcome Measurements in Cardiovascular Medicine. Philadelphia, Lippincott Williams & Wilkins, p. 39.
22. Edmonds HL Jr et al. 1997. Anesthesiol 87:A426.
23. Edmonds HL Jr et al. 1999. Anesth Analg 88:SCA26.
24. Schmahl TM 2000. Anesthesiol 94:A399
25. Yao F-S et al. 2001. Anesth Analg 92:SCA86.
26. Yao F-S et al. 2001. Anesthesiol 95:A152.
27. Alexander JC et al. 2002. Ann Thorac Surg 373-C
28. Goldman S et al. 2004. Heart Surg Forum 7:E376.
29. Olsson CJ et al. 2006. J Thorac Cardiovasc Surg 131:371.
    
30. Murkin JM et al. 2007. Anesth Analg 104:51.
31. Dasta JF et al. 2005. Crit Care Med 33:1266.
32. American Hospital Association 2005. Hospital Statistics.

For 28 years, Prof. Edmonds served as Research Professor and Director of Research for the Department of Anesthesiology, University of Louisville. In addition to conducting his own research in neuroprotection, he developed and directed an intraoperative neuromonitoring program encompassing many Louisville hospitals. Since his retirement from the University in 2005 and clinical practice in early 2007, he continues his research and training missions through his consulting practice.