DiGeorge syndrome, 22q11 deletion, truncus arteriosus with interrupted aortic arch: Making sense of it all

L. Eliot May, PA-C, Herma Heart Center, Children's Hospital of Wisconsin.

We have heard the term "DiGeorge syndrome," we have seen patients with truncus arteriosus – some with associated interrupted aortic arch – and we have heard of "22q11 deletion syndrome." How does it all fit together?

DiGeorge syndrome is characterized by abnormal facies, congenital heart disease, hypocalcemia and increased susceptibility to infections. Most patients with DiGeorge syndrome have deletion of a part of the 22nd chromosome.

Syndromes associated with 22q11 deletion have many overlapping characteristics and have names like Velocardiofacial syndrome, Shprintzen syndrome, Conotruncal Anomaly Face syndrome and Catch-22 syndrome. Diagnosis is made by clinical identification of patients with characteristic findings and FISH testing (fluorescence in situ hybridization). Prevalence ranges from approximately one in 4,000 to one in 6,000 live births.

The syndrome involving 22q11 deletion results in numerous morphologic manifestations; congenital heart disease (74 percent), mostly comprised of conotruncal malformations like tetralogy of Fallot, interrupted aortic arch, ventricular septal defect and truncus arteriosus. In addition, palate abnormalities (69 percent), characteristic facial features and learning difficulties (70-90 percent), immune deficiency due to thymic hypoplasia (77 percent), hypocalcemia due to parathyroid hypoplasia (50 percent), feeding problems (30 percent), renal abnormalities (37 percent), hearing loss, laryngotracheoesophageal anomalies, growth hormone deficiencies and skeletal abnormalities are commonly associated findings.
Management of these patients involves careful treatment of the metabolic derangements, repair of congenital heart defects, avoidance of infection (due to their compromised immune system) and treatment of other systemic manifestations as needed.

Truncus arteriosus is a congenital cardiac anomaly characterized by failure of conotruncal development, and is manifested by ventricular septal defect and a single "truncus" arising from the heart. The truncus has characteristics of an aorta and a pulmonary artery combined, and supplies both systemic and pulmonary blood flow. The truncal valve has variable leaflet morphology, often having more than three leaflets. The pulmonary artery branches arise from the back, side or sides of this truncal root. Interruption of the aortic arch occurs relatively frequently (10-20 percent). A right aortic arch often is present (25-33 percent). The interruption of the aorta can occur at varying positions along the aortic arch.

Clinically, the patient with truncus arteriosus will show signs of large left-to-right shunt. As with other left-to-right lesions such as aorticopulmonary window, ventricular septal defect and patent ductus arteriosus (PDA), pulmonary overcirculation occurs. This happens because pulmonary artery resistance falls after birth, while systemic vascular resistance remains high. Blood will tend to go where the resistance is lowest (the lungs). Congestive heart failure ensues, resulting in typical clinical manifestations such as poor weight gain, tachypnea, prominent cardiac impulse and excessive sweating (especially with feeds). Early efforts are aimed at treating the congestive heart failure and attempting to even the balance of pulmonary to systemic blood flow, but surgical intervention usually is necessary very early in life.

When interrupted aortic arch is present, ductal patency is maintained with an infusion of prosta-glandin E1 to prevent ductal closure since blood flow to the lower body is dependent upon ductal patency. 

Surgical repair of truncus arteriosus requires cardiopulmonary bypass and aortic cross-clamping. A special cardiopulmonary bypass circuit is utilized when interrupted aortic arch is present, providing an arterial branch to the ductus arteriosus and descending aorta. The repair involves closure of the ventricular septal defect so that all of the left ventricular blood flow is directed to the truncal root. The pulmonary artery branches are next separated from the aortic truncus and connected to the right ventricle with a valved pulmonary or aortic homograft. Any truncal valve abnormalities are addressed at this time. In patients with associated interrupted aortic arch, the PDA is resected and the transverse aortic arch is connected to the aorta beyond the interruption.

While surgical repair of these anomalies is a major undertaking, full attention must be given to the multisystem manifestations of patients with DiGeorge syndrome and 22q11 deletion. Particular attention must be paid to calcium management, infection prophylaxis and use of irradiated blood products only since DiGeorge patients are susceptible to graft-versus-host disease when transfused with non-irradiated blood products. Excellent results can be obtained, but overall morbidity and mortality remains relatively high when compared to other neonatal cardiac anomalies.

New ECMO coagulation management

Jeanne Braby, RN, MSN, CCRN, ECMO clinician, Pediatric Intensive Care Unit,
Children's Hospital of Wisconsin.

Because most of our extracorporeal membrane oxygenation (ECMO) patients now are cardiac patients who may have received Aprotinin in the operating room, we have begun using the Hemochron Signature Plus with the ACT+ cuvette on all ECMO patients.

Activated clotting times (ACT) ranges differ based on the instrument and the cuvette that is being used (see information below). The ACT+ cuvette has a lower normal and therapeutic range than the ACT-LR cuvette which was previously used on ECMO patients. The default therapeutic range for the ACT+ cuvette is 180-200 on non-bleeding ECMO patients and 160-180 on bleeding ECMO patients.  The Hepcon instrument (which is used in the operating room) can be used to obtain heparin levels at the bedside on patients with questionable ACT results.

ECMO order sets include orders for routine ACT testing; however, if an ACT is needed on a non-ECMO post-op cardiac patient, an ACT Point of Care-physician order is entered. An ECMO-trained nurse then runs the test at the bedside on the Hemochron Signature Plus instrument using the ACT+ cuvette. If a heparin level is needed on an ECMO patient, a perfusionist should be notified and a Heparin Concentration-Point of Care should be entered. The perfusionist will obtain the Hepcon instrument from the operating room and will run the test at the bedside. 

There also are guidelines available with recommendations for ECMO coagulation management based on the patient's bleeding risk: average risk, increased risk and active bleeding. Basically, the guidelines suggest raising the platelet count and lowering the ACT range as the patient's risk for bleeding increases or if the patient is actively bleeding. In general, any coagulopathy should be corrected immediately after ECMO is initiated, or as soon as it is detected with component replacement (platelets, FFP, cryoprecipitate, antithrombin III). In addition, if the ECMO disposable circuit is felt to be a major contributor to an ongoing consumptive coagulopathy, it may need to be replaced.

History of ECMO ACT management

1986 Hemochron 401/801 Celite glass tube technology

• 0.4 cc sample size.
• Normal (non-heparinized) range 110-182.
• Therapeutic range on ECMO originally 240-270 for non-bleeding patients and 210-240 for bleeding patients (range was lowered throughout the years to 180-220).
• ACT falsely elevated with Aprotinin.

2003 Hemochron Signature Plus-cuvette technology-LR cuvette (low-range cuvette) recommended for low-range heparin (0-2.5 units/ml)

• 0.1 cc sample size.
• Normal (non-heparinized) range 124-196.
• Therapeutic range on ECMO 220-250.
• 0.1 cc sample size.
• Normal (non-heparinized) range 99-150. 
• Used in catheterization lab at Children's Hospital of Wisconsin with therapeutic range 2 to 2 1/2 times baseline ACT.
• Therapeutic range for ECMO patients 180-200 if non-bleeding and 160-180 if bleeding.
• Not affected by Aprotinin.
• Correlates well
• Used in dialysis.
• ACT LR falsely elevated with Aprotinin.

2003 Hemochron Signature Plus-cuvette technology-ACT+ cuvette (moderate-high range heparin (1-6 units/ml)

• with Hepcon ACT. 

Changes to resuscitation guidelines

Karen Bauer, life support program coordinator, Children's Hospital of Wisconsin.

Nov. 28, 2005, the American Heart Association (AHA) released the 2005 Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Similar to other areas of health care, research studies and new information guide ongoing improvements to practice. Although these changes have been released, they will not take effect until the materials and full guidelines have been rolled out to AHA instructors and training organization.

The main emphasis of the new guidelines is that high-quality chest compressions are key to successful cardiac resuscitations. The more effective the compressions the more they will create increased blood flow through the heart to the rest of the body. This body flow must remain adequate until an automated external defibrillator (AED) can arrive. The emphasis on rescuers minimizing the interruption of chest compressions during CPR will be encouraged during instruction. 

The change of compression-to-ventilation ratio is the most significant change to CPR in the 2005 guidelines. The new single rescuer ratio will be 30:2 for all adults, children and infants. Newborns will not be included in this change.  This 30:2 ratio was the result of studies showing the blood flow increase with compressions and needs to be built up after chest compression interruptions. As a second healthcare provider rescuer responds, the ratio becomes 15:2 for infants and children. Adult ratios remain at the 30:2 compression-to-ventilation rates.

AED availability and use also are emphasized in the 2005 guideline changes. There will be a continued push to have AEDs implemented in public locations. The guidelines will continue to encourage proper training and implementation practices. AED use, in conjunction with proper CPR guidelines, also has changed. The new guidelines recommend that the rescuer should re-analyze the heart rhythm after about two minutes of CPR. Many studies showed AED will stop an abnormal cardiac arrest rhythm after the first shock and continued CPR. To make CPR even more effective, health care providers should insert airway devices and administer resuscitation drugs without delaying CPR.

As a reminder, the AHA recommends that children older than 1 year of age receive external defibrillation. The use of an upgraded AED with pediatric pads is recommended, but if only an AED with adult pads is available, it should be used.
EMS and early response times also are highlighted in the 2005 guidelines. The recommendation is that EMS dispatchers more effectively are trained to guide 911 callers to recognize signs and symptoms of cardiac arrest and stroke as well as walk callers through steps of CPR. This should assist with increasing the response time. 
These guidelines are based on evidence evaluation by the International Liaison Committee on Resuscitation (ILCOR), an international group of representatives from many world resuscitation councils. ILCOR established six task forces to research scientific studies from 380 international rescusitation experts for all aspects of resuscitation treatment including basic life support, advanced life support, acute coronary syndromes, pediatric life support and neonatal life support. In addition, it established a task force to address overlapping topics such as education. The AHA also developed two additional task forces to study stroke and first aid. Once the task forces evaluated the studies, they weighed the evidence and recommend changes to practice. The AHA and Emergency Cardiovascular Care Committee (ECC) then constructed the new guidelines. 

The 2000 guidelines still should be used until the full 2005 guidelines rollout has been completed. The 2000 guidelines are not wrong, but the 2005 guidelines will be more effective.  

Additional information on the 2005 Guidelines can be found on the American Heart Association Web site at www.americanheart.org/eccguidelines.

Cardiologist joins Herma Heart Center

David Friedberg, MD, is a pediatric cardiologist in the Herma Heart Center at Children's Hospital of Wisconsin and a clinical professor of Pediatrics (Cardiology) at the Medical College of Wisconsin. He moved his practice to within the Herma Heart Center in December 2005 and has an interest in congenital heart disease, non-invasive procedures and follow-up care of adolescents and young adults with congenital heart disease.

A graduate of Harvard Medical School, Boston, he completed residencies in Pediatrics at Strong Memorial Hospital, Rochester, N.Y., and Internal Medicine and Pediatric Cardiology at Boston Children's Hospital. He is board certified in Pediatrics and Pediatric Cardiology.