Cerebral Oximetry - A New Way to Help Protect the Brain

Robert Jaquiss, MD, pediatric cardiothoracic surgeon, Children's Hospital of Wisconsin; assistant professor, Surgery, Medical College of Wisconsin.

As the field of pediatric cardiac surgery has evolved, and operative mortality rates have correspondingly plummeted, the focus of concern has changed to the early and late neurologic consequences for children undergoing surgical repair of congenital heart defects.

As more and more survivors of even the most complex reconstructive operations grow up, there is growing recognition that a number of these patients sustained neuropsychiatric injury during their cardiac surgical procedure. The incidence and severity of such injury varies widely, depending on both the intensity of the diagnostic measures used to find it as well as the type of cardiac lesion and surgical strategy used.

Based on the descriptive literature to date, the only generally accepted conclusion is that the use of deep hypothermic circulatory arrest (DHCA) should be minimized or avoided altogether if possible. In addition to the use of DHCA, a variety of other clinical variables relating to cardiopulmonary bypass (CPB) have been proposed as potentially important targets for improved neurologic outcomes.

Variables such as cooling strategy on CPB (alpha-stat vs. pH stat), target hematocrit on CPB (low 20 percent vs. high 30 percent), use of vasodilators (e.g. phenoxybenzamine), and potential "brain protecting" medications (barbiturates and others) all have been evaluated in laboratory animals. However, evaluations of potential brain protection techniques in humans have been hampered by the need to wait until after the operation to assess the brain, using imaging modalities such as MRI scanning, functional assessment (such as EEG), or measurement of blood levels of markers of brain injury (such as S-100 protein).

It would be highly desirable to have a clinical test that would allow detection of potential brain injury before it occurs or as it is occurring, when we could intervene and reverse or prevent the brain injury.

A new technology, cerebral near-infrared spectroscopy (NIRS), now is being evaluated at Children's Hospital of Wisconsin. It has the potential for immediate real-time assessment of the adequacy of brain perfusion, allowing for immediate intervention to protect the brain.

NIRS represents an elegant application of a familiar technology, hemoglobin oximetry, to assess brain perfusion. So-called "pulse oximetry," which measures the level of oxygen-saturated hemoglobin in peripheral blood, now is a standard monitoring modality for virtually all children hospitalized with cardio-respiratory disorders. The underlying physical principle for all types of oximetry is that oxygenated hemoglobin (saturated) transmits light of certain wavelengths (infrared region) much more efficiently than deoxygenated hemoglobin. Thus, a light-emitting/detecting system that is "tuned" to the appropriate light frequency can be used to assess the relative amount of oxygen saturated hemoglobin in the tissue being sampled. The system employed in pulse oximetry involves the transmission of light through a relatively thin amount of tissue, such as a finger or toe, and includes a microprocessor, which analyzes the detected signal to allow precise determination of the degree of oxygen saturation of the blood on a beat-to-beat basis.

Another relatively familiar example of oximetry applied to physiologic monitoring is the use of an indwelling vascular catheter to measure the oxygen saturation of venous blood. Such catheters may be placed in the pulmonary artery in children with biventricular hearts and no septal defects, or in the superior vena cava in children with univentricular hearts. The underlying light absorption/transmission principle is the same as pulse oximetry. What is different is the light-emission/detection system. With intravascular oximetry, the light is emitted and detected through a fiberoptic cable, which is placed in one lumen of a double lumen catheter.

The application of oximetry to brain perfusion involves overcoming two basic engineering challenges. Unlike finger or toe oximetry, the tissue of interest is not thin so transmission oximetry isn't possible. And, unlike intravascular oximetry, the tissue is not homogeneous like blood, so focusing of the sampling area is required. (We don't really care about the saturation of the scalp or the skull). The inability to transmit light is overcome by sampling the reflected or scattered light, i.e. the light which "bounces back." The focusing of the sampling area is accomplished by taking advantage of the fact that "shallow" tissue (scalp and skull) bounce light back closer to the original source than deep tissue (see diagram). The microprocessor in the NIRS system in effect subtracts or filters the signal received from the shallow tissues and reports on the saturation of the deep, i.e. cerebral tissue. This parameter is referred to as rSO2, referring to the fact that this data indicates regional oxygen saturation. The majority of the blood in any sampled region of the brain will be venous blood. So, as with mixed venous saturation data, lower saturations indicate lower flow. The light-emission detection apparatus is a small (~2 by 1 cm.) adhesive patch which is applied transversely across the forehead.

To date NIRS has been evaluated almost exclusively in adults undergoing cardiac, carotid and neurologic surgery. In one study of adults undergoing cardiac surgery, the importance of the NIRS data was validated by the demonstration of a very high correlation between low cerebral oxygenation and poor neurologic outcome. A more exciting study in adults has demonstrated that intra-operative manipulations such as pharmacological increase in blood pressure or increasing CPB flow resulted in normalization of rSO2. So far there is very little published on the use of NIRS in children. In one small study from the Children's Hospital of Pittsburgh, Dr. Frank Pigula and his colleagues were able to demonstrate that children whose cardiac operations were performed with DHCA had significantly lower rSO2 than children undergoing the same operations without DHCA. In a study of 250 patients from Kosair Children's Hospital in Louisville, Dr. Erle Austin and his colleagues were able to detect significant decreases in rSO2 in more than 70 percent of their patients undergoing cardiac surgical procedures. In approximately 75 percent of these cases, intra-operative interventions were successful in improving or restoring the rSO2.

As part of the institutional commitment at Children's Hospital to improving short- and long-term outcomes for children with heart disease, a thorough evaluation of NIRS will be undertaken. It is anticipated that the majority of data will be obtained in the operating room during the period of anesthesia. For children whose recovery includes a significant period of post-operative mechanical ventilation and sedation, it is likely that the use of NIRS in the Pediatric Intensive Care Unit may provide additional useful clinical information.

Other clinical areas in which NIRS may be evaluated include patients on ECMO, patients undergoing cardiac catheterization, trauma patients with head injury, neurosurgical patients, and patients in the Neonatal Intensive Care Unit.

Click here for updated information on Project ADAM.

Project ADAM Goes National

Karen Bauer, Educational Services, Children's Hospital of Wisconsin;
Stuart Berger, MD, medical director, The Heart Center, Children's Hospital of Wisconsin; associate professor, Pediatrics, Medical College of Wisconsin.

U.S. Senator Russ Feingold announced new legislation to bring Project ADAM (Automatic Defibrillators in Adam's Memory) to the national level June 4 at Children's Hospital of Wisconsin.

Called the Adam Act, the bill would follow up on Project ADAM's successes by establishing a national Project ADAM resource center for schools that wish to implement a public access to defibrillation program.

Project ADAM arose from a series of sudden deaths among high school athletes in southeastern Wisconsin. Many of these deaths appear due to ventricular fibrillation. Project ADAM helps schools implement public access defibrillation (PAD) programs, from conceptualization and planning through training individuals to perform CPR and use AEDs.

The project began through the joint efforts of David Ellis and Children's Hospital. David was a friend of Adam Lemel, a 17-year-old Whitefish Bay High School student who collapsed and died during a basketball game. David's original goal was to raise money to buy an AED for his own school, Homestead High. With the help of Children's Hospital, that goal expanded to include teaching CPR to all high school students and placing defibrillators in all high schools in the state of Wisconsin.

The proposed national resource center Feingold is championing would provide support to school-based CPR/AED training programs, foster new community partnerships among public and private organizations and create a way to track and conduct research in the area of cardiac arrest among children. The legislation, now in the hands of the United States Senate, specifically mentions the success of Children's Hospital of Wisconsin and uses Project ADAM as a model.

A budget will be attached to this program and will be available by a competitive granting application process administered through the Department of Health and Human Services. Though this grant will not provide funds for AEDs and training, there is evidence to suggest that other federal funds may be available to provide the equipment for high schools throughout the U.S.

The emphasis to place AEDs in high schools and provide CPR training to staff began in January 1999. Since then, there have been 12 cases of children and adolescents who have experienced sudden cardiac death in southeastern Wisconsin. Of these, four survived. In each case, their survival was dependent on immediate CPR and rapid use of a defibrillator. These are part of the critical chain of survival, which also includes early access to 911 responders and early advanced medical care. Each of the survivors was cared for at Children's Hospital of Wisconsin.

Project ADAM was developed to help schools start and maintain a public access defibrillation program. Children's Hospital has supported schools by being a central resource for schools. This includes providing:

• Written materials and answers to questions about training, policies and medical direction.
• Answers to questions related to liability and other issues.
• Individual consultation for schools.

We recently completed a study that suggests a public access defibrillator program aimed at children and adolescents, such as Project ADAM, can be cost effective. We presented our findings at the World Congress of Pediatric Cardiology and Cardiac Surgery meeting in Toronto.

Cooperating Project ADAM agencies include; American Heart Association of Wisconsin, American Red Cross - Greater Milwaukee Chapter, EMP-America, Medical College of Wisconsin, National Safety Council, the Paramedic Training Center of Milwaukee County, and Children's Health Education Center and Maxishare, both part of the Children's Hospital family.

3rd World Congress of Pediatric Cardiology and Cardiac Surgery

Kathleen Mussatto, RN, BSN, cardiothoracic surgery outcomes research coordinator, Children's Hospital of Wisconsin;
Beth Newbury Whitstone, RN, MA, cardiology research coordinator, Children's Hospital of Wisconsin.

Held in May in Toronto, this international meeting gathered pediatric cardiologists, cardiovascular surgeons, nurses and other staff involved in caring for patients with congenital heart disease. It is held every four years providing a forum for presenting the latest research and techniques in the management of congenital heart disease.

More than 2,500 people representing 75 countries from around the world attended this year. The conference information was organized into more than 300 faculty presentations and 1,800 research posters. An impressive 22 poster presentations came from the Heart Center at Children's Hospital of Wisconsin. Six of these were presented by slides in moderated sessions, and 16 were general posters. James Tweddell, MD, director of Cardiothoracic Surgery, and Kathy Mussatto, RN, BSN, also represented the Heart Center as invited moderators for sessions during the congress. The research posters will be on display in the Pediatric ICU and on the research bulletin board in the MACC Fund building. They also will be added to The Heart Center Web site under the "For Professionals" link. For further information, please contact the lead author on any of the posters.

Tweddell was invited to speak as guest faculty on the techniques utilized at Children's Hospital of Wisconsin for management of the patient undergoing Stage I Palliation of Hypoplastic Left Heart Syndrome. In one session he presented a video highlighting surgical technique in a Stage I Norwood with a coarctectomy and patch arch reconstruction and management of the small ascending aorta.

In a symposium titled, "Strategic Management of the Patient after Surgery," Tweddell reviewed the physiology of parallel circulation in the single ventricle population and the importance of controlling systemic and pulmonary vascular resistance to optimize cardiac output.

Stuart Berger, MD, medical director of the Heart Center, presented a moderated session titled "ECMO and Transcatheter Left Heart Decompression in an Infant with Acute, Severe Left Heart Failure," in which he described the treatment and subsequent recovery of a 14-month old baby who presented with acute heart failure secondary to myocarditis. Co-authors included Joseph Cava, MD, PhD; Andrew Pelech, MD; Peter Frommelt, MD; George Hoffman, MD; Robert Jaquiss, MD; and Tweddell.

In a second moderated session, Berger presented, "A Cost-Effectiveness Analysis of Project ADAM" (see accompanying story). Co-authors included: Beth Newbury Whitstone, RN, MA; Stephanie Frisbee, MSc; Karen Bauer, RT; Anwer Dhala, MD; David Ellis; Ronald Pirrallo, MD; Lauryl Pukansky; Becki Jo Wolkenheim, RN, MS; and Ramesh Sachdeva, MD, PhD, MBA.

Project ADAM is an initiative to place public access defibrillators in area high schools. It is believed that placement of defibrillators, combined with educating students and faculty in CPR and in the use of the defibrillators, will help increase survival rates in sudden cardiac death among young athletes. Working with Sachdeva and Frisbee of the Outcomes Research Center, Berger developed a cost-effectiveness analysis that demonstrated that Project ADAM would be cost-effective if it saves five to seven lives over a 5-year period - not an unrealistic goal.

George Hoffman, MD, pediatric anesthesiologist, presented two moderated posters, "Relationship Between Venous Saturation and Anaerobic Metabolism in Neonates Following One or Two Ventricle Procedures" and "Differences in Anaerobic Threshold Predict Mid-term Survival after the Norwood Operation for Hypoplastic Left Heart Syndrome." He also presented a general poster, "Phenoxybenzamine Prevents Hemodynamic Deterioration at High Arterial Saturation in Neonates after the Norwood Procedure for Hypoplastic Left Heart Syndrome." Co-authors included Nancy Ghanayem, MD; Mussatto; Berger; Raymond Fedderly, MD; Ekehard Stuth, MD and Tweddell.

This research was generated from a prospective database containing 48 hours of hemodynamic data on neonates undergoing major open heart procedures. Hoffman's analysis of these data has identified physiologic risk factors and patterns of response to surgery in this complex population.

At another moderated session, Peter Frommelt, MD, presented "Doubly Committed VSD with Absent Subarterial Conus - the 'Non-spelling' Form of Tetralogy of Fallot" (co-author: Michele Frommelt, MD). This paper was based on research that reviewed information on all patients diagnosed at Children's Hospital with Tetralogy of Fallot. The presentation described nine patients with a unique form of this abnormality.

Nursing presentations
Cardiac nursing also was represented in a moderated session at the congress, as Newbury Whitstone presented findings of a long-term study she conducted with M. Frommelt and Steven Leuthner, clinical psychologist Cheryl Brosig and biostatistician Stephanie Frisbee. "The Impact of Prenatal vs. Postnatal Diagnosis on Psychological Distress in Parents of Children with Severe Congenital Heart Disease" involved serial, semi-structured interviews with parents and attempted to evaluate the psychological effects of a diagnosis of congenital heart disease.

Poster sessions
The Heart Center also was well represented by a number of general session posters. These included:

"Anomalous Left Coronary Artery from the Pulmonary Artery - Variable Presentation with Excellent Surgical Outcome" (M. Frommelt; P. Frommelt; Tweddell; Jaquiss; S. Bert Litwin, MD, director emeritus, Cardiothoracic Surgery) which reviewed 16 patients with ALCAPA and found no mortality in the surgically repaired group although residual mitral valve dysfunction that necessitates long-term follow-up was identified in several subjects.

"Aortic Valve Stenosis - a Thirty Year Experience" (Pelech; Curtis Strong; Marc Dao; Berger; Fedderly; David Friedberg, MD; John Thomas, MD; Tweddell; Litwin). Pelech led a review of 238 aortic valve procedures in 173 patients at Children's Hospital. Both surgical and balloon valvuloplasty were found to be equally effective in the infant with critical aortic stenosis however in the older "non-critical" form of AS, open commissurotomy provided a more effective and longer lasting result.

"Chronic and Continuous Measurement of Mixed Venous Oxygen Saturation and Pulmonary Artery Pressure in Patients with Pulmonary Hypertension: Effects of Exercise" (Berger; Hoffman; Pelech; P. Frommelt; Fedderly) reported results on the use of a 4Fr oximetric catheter in two non-surgical patients for continuous hemodynamic data measurements during exercise.

"Community Acquired Endocarditis in a Pediatric Population in the 1990's" (P. Frommelt and Robert Kilpatrick) - 18 episodes of community acquired endocarditis (CAE) were identified in the Children's Hospital database during the 1990s. CAE is associated with significant morbidity in the CHD population with 59 percent of patients requiring urgent surgery and 50 percent experiencing significant complications.

"The Experience with Primary Pulmonary Hypertension at Children's Hospital of Wisconsin: Can We Predict Who Will Respond to Vasodilator Therapy?" (Berger; Newbury Whitstone; Hoffman; Pelech; Jaquiss; Tom Rice, MD; Jane Zlotocha, RN; Sarah Bevandic, RN; Mary Hintermeyer, RN, MSN; Tweddell) explored the use of vasodilator therapy in the PPH population. Berger identified that vasodilator therapy improves symptoms and survival in children with PPH; that younger age is associated with better response to drugs - however some patients do not respond acutely; and that atrial septum dilation and lung transplantation remain important therapeutic options.

"Growth Velocity of Infants with HLHS: A Comparison of Enteral Feeding Strategies" (Nancy Rudd, RN, MSN, CPNP; Zlotocha; Mussatto; Frisbee; Pelech; P. Frommelt) addressed an important concern in infants with HLHS - failure to thrive and feeding difficulties. Infants that were able to achieve full oral feeding were found to demonstrate the greatest growth velocity from birth to stage II palliation when compared to those requiring partial or full tube feedings.

"Human and Rabbit Hearts Adapt to Chronic Hypoxia by Activation of Protein Kinase Signal Transduction Pathways" (P. Rafiee; Y. Shi; KA Pritchard; Tweddell; Litwin; Mussatto; John Baker, PhD). Baker's group has demonstrated cardioprotective effects of chronic hypoxia in a rabbit model. In this research, similar results have been shown in tissue obtained from human hearts with cyanotic vs. acyanotic CHD. Manipulation of these protein kinase signaling pathways could provide cardioprotection to humans undergoing heart repairs.

"Internet Based Environmental and Genetic Research: The Wisconsin Pediatric Cardiac Registry (WPCR)" (Pelech; Peter Tonellato, PhD; Kathleen Hanson-Morris, RN) reviews the development of the WPCR and its unique on-line data acquisition program. The registry has the capability to provide an Internet-based questionnaire that provides confidentiality, security and a very cost-effective, user-friendly method of data collection.

"Mitral Valve Disease Associated with Shone's-like Complex: Anatomic Predictors of Severe Stenosis" (P. Frommelt and M. Frommelt) - 24 subjects presenting with Shone's complex as neonates were reviewed. The presence of a supramitral ring, aortic-mitral discontinuity and tunnel subaortic stenosis were found to be predictors of severe stenosis.

"Reducing Early Mortality after the Norwood Procedure: Integrating Research into Nursing Practice"(Mussatto; Maryanne Kessel, RN; Deb Soetenga, RN, MSN; Martha Fillinger, RN; Jaquiss; Ghanayem; Hoffman; Tweddell) summarized changes in the management of the Norwood patient since 1996 and their impact on patient survival. Ongoing research, intensive monitoring, and education of caregivers on the unique Norwood physiology has resulted in 100 percent early survival (to POD 10) in these high risk neonates.

"Safety of Aprotinin Use and Re-Use in Pediatric Cardiothoracic Surgery" (Jaquiss; Tweddell; Ghanayem; Mussatto; MC Zacharisen, Litwin). The incidence and impact of reactions to aprotinin, a bovine protein, were explored in 645 subjects treated during cardiac surgery. Although reactions were more likely to occur with re-exposure, the rate of reaction remains very low (less than 4 percent) even in patients with multiple re-exposures.

"Selection of Occlusion Devices for PDA: Gianturco Coil and/or Amplatzer Duct Occluder?" (Fedderly; Pelech; Tony Cousineau, MD; Berger). Fedderly compared the efficacy of two different PDA occlusion devices and presented a decision making strategy for device selection. Use of the Amplatzer device in PDAs >2.0mm and a coil in PDAs <2.0mm has been effective at Children's Hospital.

"Stroke in a Young Man with Cystic Fibrosis after Lung Transplantation" (Berger; Julie Biller, MD; Pelech; Cava; Michael Recto, MD; Tony Lamorgese, RN; David Daniels, MD; Jaquiss; George Haasler, MD). The presence of a PFO with a right to left shunt and its subsequent transcatheter closure with a CardioSeal device are described. It is suggested that contrast ECHO may be useful in hypoxemic CF patients to identify PFOs and allow closure at the time of lung transplantation.

"Surgical Management of Simple and Complex Aortopulmonary Window" (Jaquiss; Tweddell; Kristopher Kallin, MD; Mussatto; Litwin). Fifteen patients with this rare defect were reviewed. There was no early surgical mortality in the group. In eight subjects other complex CHD lesions were associated with the AP window. This increased hospital length of stay but did not affect operative risk.