Continuous cerebral perfusion - A strategy to limit the duration of deep hypthermic circulatory arrest

James Tweddell, MD, pediatric cardiothoracic surgeon and medical director, Cardiothoracic Surgery, Children's Hospital of Wisconsin; associate professor, Cardiothoracic Surgery, Medical College of Wisconsin.

The initial pioneering efforts at complete repair of congenital heart disease in newborns and small infants in the 1970s and 1980s were complicated by the cardiopulmonary bypass (CPB) support systems available at that time. Compared to the CPB systems available today, these early systems resulted in far greater whole body inflammatory response and capillary leak syndrome. Furthermore other components of the bypass system, such as cannulas, had not yet been refined for small infant surgery. As a result, the strategy of deep hypothermic circulatory arrest (DHCA) was developed and used extensively in congenital heart surgery for intracardiac and aortic arch repairs.

A heat exchanger combined with the cardiopulmonary bypass circuit cools the blood perfusing the patient. Circulation is halted at a temperature of less than 18-20ºC (64-68º F). Hypothermia protects the brain by limiting metabolic activity. The use of DHCA minimized duration of CPB, provided excellent exposure and a quiet bloodless field for the surgeon. Indeed the movement toward neonatal and early infant repairs of complex congenital heart disease was only possible using this technique. With the early CPB systems DHCA resulted in less inflammatory response and capillary leak syndrome than techniques of continuous perfusion. DHCA was the first perfusion strategy that could be applied to reconstruction of the aortic arch, the origin of the blood vessels to the brain.

Although the safe duration of circulatory arrest has not been determined, up to 45 minutes generally is regarded as safe with the risk of neurologic injury increasing with longer duration of arrest thereafter.

Over the last two decades CPB systems have improved and small volume oxygenators and small, delicate cannulas specifically designed for infants have become available. The availability of these new CPB systems that result in less inflammatory response and capillary leak syndrome allowed for more complex and longer procedures to be performed without the use of DHCA. The Circulatory Arrest Trial at the Boston Children's Hospital raised concerns about DHCA. In this study, newborns and infants undergoing the arterial switch procedure were randomized to either continuous CPB or DHCA. Neurodevelopmental outcomes at 1 year of age were significantly worse in the DHCA group. Given the concerns raised by the Boston Circulatory Arrest Trial and the evolution of neonatal CPB systems, many congenital heart surgeons abandoned routine use of DHCA except for cases involving arch reconstruction for which DHCA was still considered essential in order to provide neuroprotection and exposure.

Beginning in the late 90s, groups in Japan and the U.S. began to use perfusion techniques that allowed for continuous perfusion of the brain, most commonly via the innominate artery. We have adopted this technique for the Norwood procedure and other arch reconstruction procedures. Arterial cannulation is achieved through a Gore-Tex graft anastomosed to the innominate artery and destined to become the systemic to pulmonary artery (Blalock-Taussig) shunt (See figure).

After cooling to less than 20ºC, the origin of the innominate artery is occluded with a snare and perfusion is maintained only to the innominate artery at reduced flow rates. Arch reconstruction is then carried out during this period of continuous cerebral perfusion. Initial efforts at continuous cerebral perfusion were complicated by identification of safe flow rates. High flow rates could result in cerebrovascular hypertension with intracranial hemorrhage or cerebral edema. Cerebral flow rates are modified based on arterial pressure (measured from the bypass circuit or right radial arterial line), venous saturation and near infrared spectroscopy (NIRS). NIRS allows for qualitative estimation of brain tissue oxygen content (See July 2001 issue of HeartMatters).

In our experience and those of other groups, flow rates of 30ml/kg/min have resulted in maintenance of brain tissue oxygen as determined by NIRS, adequate oxygen delivery as assessed by venous oxygen content and have not resulted in arterial hypertension as measured from the right radial artery. We continue to use phenoxybenzamine and an alpha stat pH management strategy to achieve maximal vasodilation during the period of continuous cerebral perfusion. Maximal vasodilation prevents cerebral vascular hypertension and may augment flow beyond the cerebral circulation. We have used this perfusion strategy on over 20 neonates undergoing the Norwood procedure with uniform early and late survival. We have identified no cases of intracranial hemorrhage among patients managed with continuous cerebral perfusion. In addition to a significant improvement in early survival, initial evaluation suggests that patients who were managed with continuous cerebral perfusion have shorter hospital stay and improved oral intake. Ability to feed orally, although influenced by many factors, is a mark of neurologic outcome for neonates undergoing complex cardiac surgery. Although additional assessment of neurodevelopmental outcome is pending, early results suggest improved outcome for patients managed with continuous cerebral perfusion.

Home surveillance program prevents interstage mortality following Norwood procedure

Nancy Ghanayem, MD, pediatric critical care specialist, Children's Hospital of Wisconsin; assistant professor, Critical Care, Medical College of Wisconsin.

Data presented at American Association of Thoracic Surgery, Washington, DC, May 2002 and is work in progress by members of the Department of Pediatrics, Divisions of Cardiology and Critical Care, Department of Anesthesia and Department of Surgery, Division of Cardiothoracic Surgery, National Outcomes Center, Inc., Children's Hospital of Wisconsin and Medical College of Wisconsin, Milwaukee.

Despite improved early outcomes following stage 1 palliation (S1P) - the Norwood procedure for hypoplastic left heart syndrome (HLHS) - there continues to be a 10-15 percent incidence of late death prior to stage 2 palliation (S2P) - the bidirectional cavopulmonary connection. Significant interim mortality continues to be associated with anatomic lesions leading to progressive hypoxemia and impaired myocardial performance. Hypovolemia and worsening hypoxemia secondary to common childhood illnesses also are associated with interval mortality in infants following S1P. To determine whether early identification of physiologic variances secondary to either anatomic or medical disease would reduce interstage mortality, we developed a home surveillance program for this at-risk population by enlisting parents to monitor daily arterial oxygen saturation (SpO2) and weights at home between S1P and S2P.

Cohorts were created from patients who underwent S1P at Children's Hospital of Wisconsin from July 1996 to November 2001. Patients discharged prior to initiation of home surveillance (Group A, n=63) were compared to patients discharged with an infant scale and pulse oximeter (Group B, n=24). Interstage weights and SpO2 were obtained at periodic clinic visits for Group A patients and compared to prospectively collected data on patients discharged with home monitoring equipment. Anatomic and perioperative variables at S1P were compared, as were outpatient oxygen saturation detected by pulse oximeter (SpO2) and weights. Interstage mortality and age at S2P also were compared.

Follow-up data was available for 100 percent of the patients. Early survival following S1P was 90.4 percent (57/63) for Group A and 100 percent (24/24) for Group B. Interstage mortality among hospital survivors prior to S2P was 15.8 percent (9/57) in Group A and 0 percent (0/24) in Group B (p = 0.039). Actuarial survival from birth through S2P was 74.6 percent (48/63) in Group A and 100 percent (24/24) in Group B (p=0.009). In the home surveillance group (Group B), the age of S2P was younger at 4.3±1.6 months compared to 5.6 ± 2.1 months in Group A (p=0.016). Home detected desaturation was the primary reason parents sought early medical attention in 12/24 Group B patients; 4/12 also reported concomitant decreased feeding and slower weight gain. Three patients were evaluated for poor feeding and poor weight gain without a notable change in SaO2. As a result of physiologic data initially ascertained through home monitoring, 13/24 (54 percent) patients in Group B had timing of S2P at a mean age of 3.7 ± 1.1 months. This was significantly younger than the mean age of S2P (5.2 ± 2.0 months, p=0.028) for the other 11 home monitored patients. There was one hospital death among patients undergoing a S2P in Group A; there were no hospital deaths in Group B.

Ten (17.5 percent) patients in Group A were discharged to home on supplemental oxygen as were 4 (16.7 percent) patients in Group B. Mean SpO2 upon discharge was 81.1 ± 4.2 percent in Group A and 82.4 ± 2.8 percent in Group B. At the time of S2P, SpO2 in Group A was 74.2 ± 6 percent and 72.5 ± 5.4 percent in Group B. Within Group B, patients who underwent an intervention as a result of increased cyanosis detected at home were more hypoxemic at S2P than those patients who did not have increased cyanosis detected at home.

Weights at hospital discharge following S1P were not different between groups: 3.35 ± 0.63 kg in Group A and 3.21 ± 0.40 kg in Group B. Similarly, despite younger age of S2P for Group B, weights between groups were not different at the time of S2P (5.70 ± 1.35 kg in Group A and 5.34 ± 0.80 kg in Group B). A growth curve (not shown here) was developed for all of the survivors to S2P that includes 1,400 data points. Unlike the growth curve of a normal infant who usually doubles the birth weight by 5 months of age, the patient with HLHS who has undergone S1P appears to have limited growth potential with a plateau phase of weight gain after 120 days.

The effectiveness of staged single ventricle palliation of HLHS has been limited by high mortality. Improved postoperative management that focuses on control of the pulmonary to systemic flow ratio combined with early identification of inadequate perfusion has resulted in improved S1P survival. Mortality prior to S2P remains high, and it is unclear whether improvements in S1P management have had an impact on this interstage period of risk. Even the optimal S1P patient remains with at risk physiology, specifically, parallel circulation, volume overload and cyanosis, following hospital discharge. The introduction of the S2P as an intermediate step in single ventricle palliation was a milestone that resulted in improved survival and allowed the practical application of the Fontan pathway to patients with HLHS. The benefits of the S2P include relief of excess volume load and improvement in arterial saturation. Following S2P, patients are at substantially decreased risk of death, show improved growth, better tolerance of intercurrent illness, and are low risk candidates for completion Fontan.

The primary goal of the home monitoring program was to develop a simple, reliable strategy to identify worsening systemic oxygenation and acute dehydration. Patients were discharged with infant scales to identify dehydration as acute weight loss, as well as failure to gain weight and pulse oximeters to identify worsening desaturation. These were devices with which the parents already were familiar and which were straightforward to use. Improvements in S1P survival were, in our experience, the result of objective assessment of the circulatory status of the patients through improved physiologic monitoring. Improved interstage survival has been the result of continued collection of patient data through home monitoring in order to identify the patient at risk for interstage mortality. This type of frequent sampling may identify trends in SpO2 or weight gain, which may indicate that treatment for intercurrent illness is necessary or further investigation to look for recurrent or residual lesions is indicated. In this small series we found that early identification of illness or residual/recurrent lesions led to altered treatment, early S2P, and overall improved survival.

Adult with congenital heart disease

Alexis Sullivan, RN, pediatric nurse, Pediatric Intensive Care Unit, Children's Hospital of Wisconsin

Earlier this year, Robert Jaquiss, MD, pediatric cardiothoracic surgeon at Children's Hospital of Wisconsin and assistant professor of Cardiothoracic Surgery at the Medical College of Wisconsin, presented "Adults with congential heart disease" (CHD) to Children's Hospital staff. This growing patient population accounts for about 10,000 to 15,000 admissions per year in the U.K. and encompasses about 100,000 to 500,000 patients in the U.S. We are unsure how many U.S. admissions occur annually as hospital coding is not uniform for this patient population.

There essentially are three kinds of adults with congenital heart disease (ACH):

1. Minor lesions, such as an unoperated ASD, small VSD, mild PS (pulmonary stenosis) and mild AS (aortic stenosis). These patients have few problems initially and may or may not receive SBE prophylaxis. This population raises the question, "Should these patients even go to the operating room?" if their shunt gradient is <1.5:1.
2. Significant unoperated lesions, such as a large ASD, VSD or PDA and those with a univentricular heart (UVH). These lesions can lead to pulmonary hypertension and Eisenmenger syndrome. Some varients of tetrology of Fallot may have their first operation in adulthood and may have significant physiological derangements.
3. Significant lesions that have been operated on and have either residual lesions, require homograft changes, have recurrent coarctations, patch leaks, or develop branch PS.

Jaquiss discussed major differences between adults with CHD and pediatric patients with CHD.

• ACH patients self-consent for procedures and should be very involved and informed in their plan of care as opposed to the young pediatric patient.
• ACH patients are sick longer due to:
  1. Long-term damage to their myocardium due to stenosis, which leads to pressure loading, which causes dilatation and/or stretching and neither of these may be reversible.
  2. Long-term damage to the pulmonary vascular bed causing irreversible pulmonary hypertension - in its most severe form this can lead to Eisenmenger syndrome. Moderate pulmonary hypertension also can cause problems as it places a huge load on the right ventricle.
• Female ACH patients need to have pregnancy tests done before procedures and, if pregnant, they may need their medication doses changed to avoid teratogenesis.
• ACH patients also may have acquired diseases of aging, such as:
  1. Obesity due to sedentary lifestyle.
  2. Hypertension.
  3. Diabetes.
  4. Renal failure (caused by decreased cardiac output and/or medications.
  5. Stroke/cerebrovascular disease as a sequelae of prior surgery, disease or right to left shunt.
  6. COPD (chronic obstructive pulmonary disease).
  7. Venous thromboembolism.
• ACH medications are not dosed on a per kg basis. For example, digoxin, lidocaine and captopril.
• Psychosocially, ACH patients often face a dependency on their parents or spouses.

Specific medical issues facing ACH patients
Arrhythmias -
Atrial - Afib/flutter is the most common ACH arrhythmia and causes low cardiac output, which is critical in abnormal circulation. There may be a 30 percent loss in cardiac output with TGA patients and increased risk of systemic thromboembolism. Treatment includes rate control with digoxin, diltiazem, beta blocker, AV node ablation or flutter pathway ablation. Other treatment involves cardioversion, either electric or pharmacologic with amiodarone or procainamide, or the maze procedure.

Ventricular - V-tach can occur due to surgical scar, ischemic scar, or chronic pressure loading such as with aortic stenosis causing fibrosis. V-tach is inherently dangerous, but may be tolerated. If slow, it may be self-limited or degenerate into V-fib. Treatment with medications may be worse as some drugs are proarrhythmic. Treatment with automatic internal cardiac device (AICD) implantation may be necessary. Occasionally, as with tetrology of Fallot, an area of arrythmic scar can be identified and ablated.

Bradyarrhythmias - Includes heart block or sick sinus syndrome (SSS). Heart block may be caused by surgical trauma (VSD, conal septectomy) or may be part of the lesion as with L-TGA. SSS may be inherent in the disease process or due to surgical trauma.

Anticoagulation -
There are long-term risks with coumadin in ACH patients. There is a .5 percent annual risk of bleeding or thrombosis with a mechanical valve. Coumadin also is a teratogenic and is difficult to manage.

Cardiac rehabilitation -
ACH patients are or will be deconditioned. Supervised rehab with graded exercise is crucial to optimizing outcomes. Initially, rehab is inpatient, but primarily it is an outpatient effort. Patients also may need psychiatric rehab due to depression and body image issues.

Psychosocial -
There is a dependancy on parents or spouse.

• Many ACH patients can't get insurance.
• Illness can be a major marital stressor.
• Parenthood and competing needs self vs. child.
• Fear of losing job related to illness.
• Uncertainty as there is no data on long-term prognosis.

Finally, these patients are somewhat displaced in settings currently available - as adults in pediatric hospitals or as patients with congenital heart disease in adult hospitals. Possibilities of an ACH unit would need to include pediatric cardiologists, adult cardiologists, obstetricians, internists, social workers, cardiothoracic surgeons and specialized nurses. This leaves us with the unanswered question, "Where should they currently be seen/hospitalized until this type of ACH unit is widely available?"

Heart Center research update

Kathy Mussatto, RN, cardiothoracic research coordinator, Children's Hospital of Wisconsin.

Through research, Children's Hospital of Wisconsin has been able to dramatically improve care provided to children and families. Heart Center staff have taken a lead role in making the care of congenital heart disease safer for even the smallest, most vulnerable patients. New devices and medications can help children avoid a surgical procedure, while others help children heal faster with fewer complications.

Heart Center staff have been involved in numerous clinical trials and are active in laboratory, pharmaceutical and quality-of-life research. Research protocols are in constant development by our investigators involving the expertise and efforts of the whole multidisciplinary patient care team. These studies further the search for the newest techniques and procedures to increase success rates and improve the lives of patients and their families.

If you have questions about any of the research listed below, please contact Kathy Curro, RN, at (414) 266-2384, or me at (414) 266-2073.

Ongoing research endeavor
The Wisconsin Pediatric Cardiac Registry (WPCR) is an official record of infants born in Wisconsin with congenital heart defects. Every child born since Jan. 1, 2000 in Wisconsin with a congenital heart defect is eligible for entry into the registry.

For more information, visit our Web site at www.chw.org, heart center, for professionals, HeartMatters volume 3 issue 4 (October 2000), or call Andrew Pelech, MD, at (414) 266-2380.

Clinical and laboratory research

• Identification of Earliest, Non-Invasive, Echocardiographic Marker of Atrioventricular Nodal Dysfunction and/or Myocardial Injury in Fetuses at Risk for Congenital Heart Block. Investigators: Michele Frommelt, Thomas Wigton and Randall Kuhlman.
• A Pilot Study to Evaluate Neurodevelopmental Outcome, Quality of Life and Impact on the Family in Survivors of Complex Congenital Heart Disease. Investigators: Kathy Mussatto, Cheryl Brosig, Jim Tweddell, S. Bert Litwin, Andrew Pelech and Ramesh Sachdeva.
• Use of Parenteral Phenoxybenzamine in Infants and Children During Surgery for Congenital Heart Disease. Investigators: S. Bert Litwin, Jim Tweddell, George Hoffman.
• Identification of Factors Influencing the Longevity of Homograft Valved Conduits. Investigators: Andrew Pelech, Stuart Berger, Kathy Mussatto, Ramesh Sachdeva, Jim Tweddell and S. Bert Litwin.
• Bioelectrical Impedence Analysis of Intracellular and Extracellular Fluid Volume in Children Undergoing Open Heart Surgery. Investigators: Robert Jaquiss, Nancy Ghanayem, Peter Frommelt, Kathy Mussatto, S. Bert Litwin and Jim Tweddell.
• Doppler Tissue Imaging Echocardiographic Study of Right Ventricular Function in Patients with Cystic Fibrosis. Investigators: Stuart Berger, Julie Biller and Peter Frommelt.
• Growth Velocity in Infants with Hypoplastic Left Heart Syndrome. Investigators: Nancy Rudd, Kathy Mussatto, Stephanie Frisbee, Nancy Ghanayem, Peter Frommelt.
• Evaluation of a Home Surveillance Program to Reduce Interstage Mortality Following the Norwood Procedure. Investigators: Nancy Ghanayem, George Hoffman, Kathy Mussatto, Nancy Rudd, Michelle Steltzer, Sara Bevandic, Robert Jaquiss, Jim Tweddell and S. Bert Litwin.
• Comparison of Hospital Charges, Survival and Reported Quality of Life Between Children with Hypoplastic Left Heart Syndrome and Children with Congenital Diaphragmatic Hernia. Investigators: Ray Fedderly, Steve Leuthner, Ramesh Sachdeva and Kathy Mussatto.
• Radio Frequency Perforation to Permit Transcatheter Balloon Valvuloplasty of Pulmonary Atresia/Pulmonary Valve Stenosis with the BMC Radio Frequency Perforation System. Investigators: Andrew Pelech, Stuart Berger and Ray Fedderly.
• Evaluation of the Reliability of Echocardiogram in Identifying Coronary Artery Anatomy in Children and Adolescents. Investigators: Peter Frommelt and Michele Frommelt.
• Evaluation of Normal Indexed Ventricular Area Dimensions in Infants and Children by Echocardiographic Review. Investigators: Peter Frommelt and Michele Frommelt.
• The Impact of Prenatal versus Postnatal Diagnosis on Coping in Parents of Children with Severe Congenital Heart Disease. Investigators: Michele Frommelt, Beth Whitstone, Steve Leuthner and Cheryl Brosig.
• Medical Strategies to Address Persistent Chest Tube Drainage after the Fontan Procedure. Investigators: Joe Cava and Ray Fedderly.
• Impact of Biocompatible Cardiopulmonary Bypass Coatings on Outcomes Following Open Heart Surgery. Investigators: Robert Jaquiss, Christopher Brabant, Patrick Vanderwal, Kathy Mussatto, S. Bert Litwin and Jim Tweddell.
• Chronic Hypoxia and Resistance to Myocardial Ischemia/Role of Reactive Oxygen Species in Flow-Mediated Vasodilation. Investigators: John Baker, David Gutterman, Jim Tweddell and S. Bert Litwin.
• Health-Related Quality of Life and Functionality in Subjects with Complex Congenital Heart Disease. Investigators: Kathy Mussatto, Stephanie Frisbee, Robert Jaquiss, Jim Tweddell, S. Bert Litwin and Ramesh Sachdeva.

Drug and Device Trials

• Use of CardioSEAL Septal Occluder for Patent Foramen Ovale with Recurrent Stroke or Transient Ischemic Attack. Investigators: Andrew Pelech, Stuart Berger, Ray Fedderly, Mike Cinquegrani and D. Marks.
• Use of CardioSEAL Septal Occluder for Fenestration Closure After the Fontan Procedure. Investigators: Stuart Berger, Andrew Pelech and Ray Fedderly.
• Randomized, Double-Blind, Placebo-Controlled Trial of Daily Oral Dexamethasone in Autoimmune-Associated Congenital Heart Block Diagnosed in Utero. Investigators: Michele Frommelt, Thomas Wigton and Randall Kuhlman.
• A Multicenter, Placebo-Controlled, 8-month Study of the Effect of Twice Daily Carvedilol in Children with Congestive Heart Failure Due to Systemic Ventricular Systolic Dysfunction. Investigators: Stuart Berger and Joe Cava.
• A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Parallel-Group Study to Determine the Antihypertensive Dose Range, Efficacy, Safety, Tolerability and Pharmacokinetics of Metoprolol Succinate in Hypertensive Pediatric Patients. Investigators: Stuart Berger.
• A Multicenter, Open-Label Study to Determine the Antihypertensive Safety and Tolerability of Metoprolol Succinate in Hypertensive Pediatric Subjects. Investigators: Stuart Berger.
• A Multicenter Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Brevibloc (Esmolol Hydrochloride) for the Treatment of Hypertension in Infants and Children after Surgical Repair of Coarctation of the Aorta. Investigators: Jim Tweddell, Andrew Pelech and Eckehard Stuth.