spa meeting reviews

AAP Ask the Experts Panels

By Valerie E. Armstead, MD, FAAP
Children’s Regional Hospital at Cooper
Camden, NJ

This AAP Ask the Experts Panel was moderated by Courtney A. Hardy MD (Lurie Children’s Hospital, Chicago).  The topics were:

  • Neurodevelopmental Outcomes After Cardiac Surgery presented by Dean B. Andropoulos, MD, MHCM, (Texas Children’s Hospital, Houston)

  • High Risk Cardiac Lesions for Non-cardiac Surgery - Williams Syndrome, Pulmonary  Hypertension, Sinusoids-Oh My! presented by Annette Y. Schure, MD, DEAA, FAAP, (Boston Children’s Hospital, Boston)

After a number of disclosures including being on the scientific advisory board for Smart Tots, extramural funding sources, Hospira providing dexmedetomidine (Dex) at no cost for one of his studies and that use of Dex in his lecture is off-label,  Dr. Andropoulos introduced the three major learning objectives of his presentation.

  • Describe some of the major risk factors for neurodevelopmental outcome problems in patients with congenital heart disease (CHD).

  • Discuss the role of anesthetic drugs and doses in neurodevelopmental outcomes

  • Know research approaches that can be explored representing alternative anesthetic management strategies that could affect neurodevelopmental outcomes in congenital heart surgery.

Dr. Andropoulos began with background data that CHD affects 8 per 1000 infants in the U.S.  CHD is the most common birth defect requiring treatment. Approximately 40,000 infants born with CHD, or 25% will require surgery or invasive cardiac interventional treatment in the first year of life (Mozaffarian D, et al. Circulation 2015;131:e29-e322).  Dr. Andropoulos reminded us the 2010-2013 data presented at the 2015 CCAS annual meeting by David Vener, M.D., CCAS Database Chair, that single ventricle CHD makes up 11.3 % of all patients and that overall surgical mortality is now less than 5%.

Throughout the presentation, Dr. Andropoulos noted he and others found that a percentage of infants with CHD may have abnormal brain MRIs prior to interventional or surgical procedures.  Moreover, 10-20% of CHD patients have accompanying chromosomal abnormalities or extra cardiac anomalies that may adversely affect neurodevelopment.  Partial deletion 22q11.2 is the most common chromosomal anomaly in CHD.

Neurodevelopmental outcomes after cardiac surgery in infancy studies have shown that 30-50% of neonates undergoing cardiac surgery have neurodevelopmental problems in later infancy and preschool years.  These problems are similar to those experienced by ex-premature infants such as deficits in cognitive, memory, language, fine motor, behavior, attention, and executive functioning.

At age 16, 65% of patients with D-TGA who had the arterial switch operation as neonates utilized special education services.  Academic achievement, memory, executive functions, visual-spatial skills, attention, and social cognition were all below population norms (Snookes J. Pediatrics 2010; 125:e818; Bellinger D. Circulation 2011; 124:1361).
Dr. Andropoulos shared additional valuable information on risk factors that were noted as a result of a study by the International Cardiac Collaborative on Neurodevelopment (ICCON) Investigators (Gaynor J, et al. Pediatrics 2015) in a article that will appear in the 2015, May 1st volume of Pediatrics entitled Neurodevelopmental Outcomes After Cardiac Surgery in Infancy.  In this collaborative work,  1770 patients from 22 institutions were assessed at 14.5 ± 3.7 months with the Bayley Scales of Infant Development-II after cardiac surgery at age< 9 months from1996-2009.  The primary outcome was the Psychomotor Development Index (PDI).  A secondary outcome was the Mental Development Index (MDI).  Established population norms for these indices are 100 ± 15 (± 1 SD).  The mean values of these indices after cardiac surgery were PDI 77.6 ± 18.8 and MDI 88.2 ± 16.7 both of these values were quite significantly below the norm of 100 with p values < 0.001.  Identified risk factors for lower PDI were lower birth weight, white race or genetic/extracardiac anomaly.  Lower MDI indices were more significant also included lower birth weight, and genetic/extracardiac anomaly as well as male gender and less maternal education as risk factors.  Although these results & risk factors are concerning, Dr. Andropoulos added a positive note that after adjustment for major risk factors, scores improve about 0.4 points per year.

To address the second objective, Dr. Andropoulos presented data from a paper published in 2014 (Andropoulos, DB, et al, Pediatric Anesthesia, 24, 266-274, 2014) that demonstrated an association between volatile anesthetic exposure, postoperative brain MRI abnormality and negative neurodevelopmental outcomes in a relatively small (59) number of infants.

Dr. Andropoulos covered the third objective as he presented data from human clinical studies that demonstrated ways in which anesthetic & surgical approaches could prevent negative neurologic outcomes after congenital heart surgery in infancy.  These strategies included retrograde cerebral perfusion during deep hypothermic circulatory arrest (DHCA), limiting periods of DHCA, monitoring (cerebral oxygenation saturation and limiting the exposure to volatile anesthetic agents.

Toward the end of his presentation, Dr. Andropoulos spoke of the potential, off-label use of Dexmedetomidine (Dex) in surgery or intervention for CHD.  Dex has been shown in humans to minimize respiratory depression and reduce doses of volatile anesthetic agents (VAA), opioids, benzodiazepines.  Animal studies have shown that Dex does not cause neuroapoptosis in the developing brain and blocks neuroapoptosis by anesthetic agents.  It is also neuroprotective in hypoxia-ischemia in animals.  Dr. Andropoulos included, as a reference, information on the noble gas, Xenon as an alternative or supplement to volatile anesthetics, but did not have time to discuss its potential use.

Dr. Andropoulos presented details of an ongoing NIH-funded Phase I Study of Dexmedetomidine Bolus and Infusion in Corrective Infant Cardiac Surgery: Safety and Pharmacokinetics (Phase I trials usually are conducted for safety & pharmacokinetic data)at Texas Childrens.  Dr. Andropoulos shared plans for a multicenter randomized controlled trial of anesthetic technique and neurodevelopmental outcomes in CHD.

Dr. Andropoulos, in closing provided the following summary:

  • Up to 50% of neonates having congenital heart surgery have neurodevelopmental problems in later infancy and childhood

  • Single ventricle cardiac lesions and chromosome abnormalities are associated with neurodevelopmental problems

  • NIRS monitoring with goal directed therapy may improve neurodevelopmental outcomes in surgery for CHD.

  • Bypass techniques avoiding or minimizing DHCA can lead to improved neurodevelopmental outcomes in infants with CHD.

  • Larger doses of volatile anesthetic agents are associated with lower neurodevelopmental scores at 12 months in infants undergoing CHD repair.

Selected references used by Dr. Andropoulos in order of presentation:

  1. Mozaffarian D, et al. Circulation 2015;131:e29-e322.
  3. Data courtesy David Vener, M.D., CCAS Database Chair
  4. Snookes J. Pediatrics 2010;125:e818; Bellinger D. Circulation 2011;124:1361
  5. Marino et al. Circulation 2012;126:1143
    (The author of this SPA session review highly recommends this AHA Scientific Statement article endorsed by all major pediatric care organizations including the AAP.  A free PDF is available at
  6. J Thorac Cardiovasc Surg. 2013 Nov;146(5):1153-64. doi: 10.1016/j.jtcvs.2012.12.060. Epub 2013 Jan 12.
  7. Andropoulos, DB, et al, Pediatric Anesthesia, 24, 266-274, 2014
  8. Anesth Analg 2010;110:1383
  9. Anesthesiology 2009; 110:1077
  10. Acta Anaesthesiol Scand 2010;54:710
  11. Neurosci Lett 2006;409:128

Dr. Schure offered three case presentations for examples of high risk CHD patients scheduled for non-cardiac procedures.

  1. Nine year old girl with Williams Syndrome for bilateral strabismus surgery
  2. 12 year old with pulmonary hypertension for Broviac insertion
  3. One month old infant with pulmonary atresia and intact ventricular septum (PA/IVS) s/p repair for lap G-tube

The Objectives in presenting these three cases were:

  • Describe the pathophysiology and anesthetic concerns for patients with Williams syndrome.
  • Discuss the preoperative evaluation and anesthetic management of patients with pulmonary HTN.
  • Understand the treatment strategies for patients with Sinusoids and the anesthetic implications for non-cardiac surgery.

Williams (Williams-Beuren) Syndrome pathophysiology and anesthetic concerns:
Williams-Beuren Syndrome (WS) first described in 1961 has a prevalence of 1:10 000 or less.  Genetically it is a spontaneous microdeletion syndrome of 26-28 genes missing in a specific segment on chromosome 7.  This results in abnormalities of the elastin gene (ELN).

Dr. Schure provided a list of the potential organ system features of WS:

  • Auditory - ear, nose throat hyperacusis, recurrent otitis media, hearing loss later in life
  • Cardiovascular - Elastin arteriopathy, vascular stenosis: supravalvar aortic stenosis (SVAS), pulmonary stenosis,
  • Coronary artery disease (CAD), hypertension (HTN), stroke
  • Development/Cognition - Global impairment, characteristic pattern: strong language skills, poor visuospatial skill
  • Dental - Small or unusual shaped teeth, malocclusion
  • Endocrine - Hypercalcemia, glucose intolerance, early onset of puberty, osteopenia, hypothyroidism
  • GI - Feeding intolerance, poor weight gain, GERD-, constipation, diverticulitis
  • GU - Renal anomalies, bladder diverticula, nephrocalcinosis, delayed toilet training, UTIs
  • Musculoskeletal - Short statue, scoliosis, joint contractures or laxity
  • Neurologic - Hypotonia, hyperreflexia, poor balance and coordination, Type I Chiari malformation
  • Ophthalmologic - Strabismus, poor vision, narrow lacrimal duct
  • Personality - Friendly, “cocktail party”, ADHD, anxiety and phobias
  • Skin and integument - Soft skin, premature aging, premature graying of hair

Dr. Schure stressed the anesthesia concerns in WS.  Generalized elastin arteriopathy results in reduced amount of elastin in media of great vessels.  Hypertrophy of smooth muscle cells and collagen causes stiff arteries resulting in loss of the windkessel effect (To view normal windkessel effect visit  There is a wide pulse pressure and hypertension.   Patients have impaired coronary perfusion as a result of ostial occlusions from membranes or coronary artery stenosis.  70% of WS patients have SVAS at the sinotubular junction, which has a characteristic hourglass on imaging.  There may be peripheral or main pulmonary stenosis.  WS arteriopathy may involve the aortic arch, descending aorta, renal and mesenteric arteries.  Bilateral cardiac outflow obstruction can cause biventricular hypertrophy, CAD, and HTN.  As a result of all these cardiac problems, there have been a string of cardiac deaths due to mismanagement of WS patients.  Oftentimes the patient are dehydrated and have cardiac arrest unresponsive to resuscitative efforts during the early part of anesthetic care.  “Preparedness for the worst case scenario is the best way to care for WS” was the take away message.

Dr. Schure then turned attention to discuss the preoperative evaluation and anesthetic management of patients with pulmonary HTN.  Dr. Schure noted the incidence of anesthesia related death is 0.98 per 10, 000 anesthetics and pulmonary hypertension is involved in 50% (5 out of 10 deaths).  Panama Classification of Pediatric PHVD breaks down 10 different categories of PH. Dr. Schure presented a new definition of the “Panama” Criteria.  If the circulation is Biventricular: mPAP > 25mmHg + PVR > 3 Wood units/m sq. is considered pulmonary HTN.  For single ventricular Circulation: (s/p cavopulmonary anastomosis) PVR > 3 Wood Units/m sq or TPG > 6mmHg is considered pulmonary HTN, even if mPAP < 25mmHg.

Children with pulmonary HTN are at major anesthetic risk even for minor procedures. This is also a perioperative risk.  All anesthetic techniques have been used successfully.  Goals are to maintain optimal pulmonary vascular resistance (PVR) and avoid triggers of increased PVR.  Severe cyanosis can occur if “pop off” connections are present.  This can also cause paradoxical emboli.  The decision to use spontaneous vs controlled ventilation is determined by the effect on PVR & the right ventricle (RV).  Positive pressure ventilation or hypoventilation with hypoxia and hypercarbia can increase afterload for the RV. Never switch off Nitric oxide (NO) or prostacyclin infusions as this can cause rebound pulmonary HTN.  Anesthesia plans should include thorough preoperative risk/benefit discussion with family and care team; careful sedation if indicated and necessary.   A proper ventilation strategy with high inspired oxygen concentration, avoidance of hypercarbia, mild hyperventilation without excessive peak airway pressures, sufficient tidal volumes to avoid atelectasis, long expiratory phase, no or minimal PEEP as well as ample depth of anesthesia for periods of intense stimulation should assure success in preventing pulmonary hypertensive crises.  Maintenance of normal preload for a hypertrophied RV and early use of inotropic support for the RV, maintenance of adequate coronary perfusion pressure with nitric oxide at the ready can also stave off disaster. Appropriate postoperative monitoring and pain control is also important to keep the patient with pulmonary HTN from taking a wrong turn after sailing through surgery or an interventional procedure.

The third scenario presented by Dr. Schure was intended to help comprehend the treatment strategies for patients with sinusoids and the anesthetic implications for non-cardiac surgery in patients with Pulmonary Atresia and Intact Ventricular Septum (PA/IVS) with sinusoids.  PA/IVS accounts for nearly 3% of CHD or 4-8 / 100,000 live births. Symptoms develop later than pulmonary artery atresia with a VSD.  The pulmonary arteries may be normal size with the intact ventricular septum.  There is heterogeneous morphology with a spectrum of lesions.  Dr. Schure advised heightened awareness of the lesions involving sinusoids & RV dependent coronary circulation.  Blood in a hypoplastic RV with PA/IVS is under high pressure.  If there is no outflow, sinusoids persist in developing fetal myocardium which results in extensive ventricular-coronary communications.  Turbulent flow and endothelial injury result in coronary stenosis and can lead to a dire coronary steal phenomenon when the RV is decompressed. Dr. Schure also discussed ventricular interdependence.

Dr. Schure concluded the session by emphasizing the need to do the following with all of the CHD lesions she presented: Have an earnest risk/benefit discussion with all parties.  Perform a thorough preoperative evaluation, review the most recent cardiology note and imaging studies & contact the cardiologist.  Choose an appropriate venue, procedure time and staff.  There should be a detailed anesthesia plan and sufficient monitoring with 5 lead ECG, emergency drugs, defibrillator pads, extended PACU stay/ICU admission planning ahead of time.

Dr. Schure left a comprehensive list of references which are listed below.

References for Williams Syndrome

  1. Pober BR. Williams-Beuren syndrome. The New England journal of medicine. 2010 Jan 21;362(3):239-52. PubMed PMID: 20089974.
  2. Burch TM, McGowan FX, Jr., Kussman BD, Powell AJ, DiNardo JA. Congenital supravalvular aortic stenosis and sudden death associated with anesthesia: what's the mystery? Anesthesia & Analgesia. 2008 Dec;107(6):1848-54. PubMed PMID: 19020129.
  3. Collins RT, 2nd.Cardiovascular Disease in Williams Syndrome. Circulation. 2013 May; 127: 2125-2134. PubMed PMID: 2371681
  4. Gupta P, Tobias JD, Goyal S, Miller MD, Melendez E, Noviski N, et al. Sudden cardiac death under anesthesia in pediatric patient with Williams syndrome: a case report and review of literature. Annals of Cardiac Anaesthesia. 2010 JanApr;13(1):44-8. PubMed PMID: 20075535.
  5. Olsen M, Fahy CJ, Costi DA, Kelly AJ, Burgoyne LL. Anaesthesia-related haemodynamic complications in Williams syndrome patients: a review of one institution's experience. Anaesthesia and intensive care. 2014 Sep;42(5):619-24. PubMed PMID: 25233176.
  6. Collins RT, 2nd, Aziz PF, Gleason MM, Kaplan PB, Shah MJ. Abnormalities of cardiac repolarization in Williams syndrome. The American Journal of Cardiology. 2010 Oct 1;106(7):1029-33. PubMed PMID: 20854969.
  7. Collins RT, 2nd, Aziz PF, Swearingen CJ, Kaplan PB. Relation of ventricular ectopic complexes to QTc interval on ambulatory electrocardiograms in Williams syndrome. The American Journal of Cardiology. 2012 Jun 1;109(11):1671-6. PubMed PMID: 22459308.

References for Pulmonary Hypertension

  1. Van der Griend BF, Lister NA, McKenzie IM, Martin N, Ragg PG, Sheppard SJ, et al. Postoperative mortality in children after 101,885 anesthetics at a tertiary pediatric hospital. Anesthesia & Analgesia. 2011 Jun;112(6):1440-7. PubMed PMID: 21543787.
  2. Fraisse A, Jais X, Schleich JM, di Filippo S, Maragnes P, Beghetti M, et al. Characteristics and prospective 2-year follow-up of children with pulmonary arterial hypertension in France. Archives of Cardiovascular Diseases. 2010 Feb;103(2):66-74. PubMed PMID: 20226425.
  3. Barst RJ, McGoon MD, Elliott CG, Foreman AJ, Miller DP, Ivy DD. Survival in childhood pulmonary arterial hypertension: insights from the registry to evaluate early and long-term pulmonary arterial hypertension disease management. Circulation. 2012 Jan 3;125(1):113-22. PubMed PMID: 22086881.
  4. McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association. Circulation. 2009 Apr 28;119(16):2250-94. PubMed PMID: 19332472.
  5. Del Cerro MJ, Abman S, Diaz G, Freudenthal AH, Freudenthal F, Harikrishnan S, Haworth SG, Ivy D, Lopes AA, Raj JU, Sandoval J, Stenmark K, Adatia I. A consensus approach to the classification of pediatric pulmonary hypertensive vascular disease: Report from the PVRI Pediatric Taskforce, Panama 2011. Pulm Circ 2011;1:286-98.
  6. Mullen MP. Diagnostic strategies for acute presentation of pulmonary hypertension in children: particular focus on use of echocardiography, cardiac catheterization, magnetic resonance imaging, chest computed tomography, and lung biopsy. Pediatric critical care medicine: a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2010 Mar;11(2 Suppl):S23-6. PubMed PMID: 20216157.
  7. Farber HW , Loscalzo J. Pulmonary arterial hypertension. The New England Journal of Medicine. 2004 Oct 14;351(16):1655-65. PubMed PMID: 15483284.
  8. Bronicki RA, Baden HP. Pathophysiology of right ventricular failure in pulmonary hypertension. Pediatric critical care medicine: a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2010 Mar;11(2 Suppl):S15-22. PubMed PMID: 20216156.
  9. Shukla AC, Almodovar MC. Anesthesia considerations for children with pulmonary hypertension. Pediatric critical care medicine: a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2010 Mar;11(2 Suppl):S70-3. PubMed PMID: 20216167.

References for Sinusoids

  1. Ahmed AA, Snodgrass BT, Kaine S. Pulmonary atresia with intact ventricular septum and right ventricular dependent coronary circulation through the "vessels of Wearn". Cardiovascular Pathology: The official journal of the Society for Cardiovascular Pathology. 2013 Jul-Aug;22(4):298-302. PubMed PMID: 23332812.
  2. Guleserian KJ, Armsby LB, Thiagarajan RR, del Nido PJ, Mayer JE, Jr. Natural history of pulmonary atresia with intact ventricular septum and right-ventricle-dependent coronary circulation managed by the single-ventricle approach. The Annals of Thoracic Surgery. 2006 Jun;81(6):2250-7; discussion 8. PubMed PMID: 16731162.
  3. Cheung EW, Richmond ME, Turner ME, Bacha EA, Torres AJ. Pulmonary atresia/intact ventricular septum: influence of coronary anatomy on single-ventricle outcome. The Annals of Thoracic Surgery. 2014 Oct;98(4):1371-7. PubMed PMID: 25152382.
  4. Sadler TW. Chapter 12: Cardiovascular System. In “Langman’s Medical Embryology” 11th ed, 2010 Lippincott Williams & Wilkins
  5. Svrivastava D, Baldwin S. Molecular Determinants of Cardiac Development. In Moss and Adams’ “Heart Disease in Infants, Children and Adolescents” Vol 1. 6th ed. 2001 Lippincott Williams & Wilkins

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