| Abstract|| |
Noonan syndrome (NS) is one of the most common non chromosomal syndrome presenting to the cardiac anesthesiologist for the management of various cardiac lesions, predominantly pulmonary stenosis (PS) (80%) and hypertrophic obstructive cardiomyopathy (HOCM) (30%). The presence of HOCM in NS makes these children susceptible to acute congestive heart failure due to hemodynamic fluctuations, thus necessitating optimization of drug and fluid therapy, careful conduct of anesthesia and providing adequate analgesia in the perioperative period. We describe a case of four year old boy with NS who presented to us for the management of PS and HOCM. In our case, transesophageal echocardiography (TEE) played a major role in confirmation of the preoperative findings, detection of any new anomalies missed during the preoperative evaluation, intraoperative monitoring and assessment of the adequacy of repair in the immediate postoperative period. TEE provided invaluable help in taking critical surgical decisions, resulting in a favorable outcome.
Keywords: Hypertrophic obstructive cardiomyopathy, Noonan syndrome, pulmonary stenosis, transesophageal echocardiography
|How to cite this article:|
Aggarwal V, Malik V, Malhotra Kapoor P, Kiran U. Noonan syndrome: An anesthesiologist's perspective. Ann Card Anaesth 2011;14:214-7
|How to cite this URL:|
Aggarwal V, Malik V, Malhotra Kapoor P, Kiran U. Noonan syndrome: An anesthesiologist's perspective. Ann Card Anaesth [serial online] 2011 [cited 2020 Jun 1];14:214-7. Available from: http://www.annals.in/text.asp?2011/14/3/214/84024
| Introduction|| |
Noonan syndrome (NS) with its worldwide occurrence  has fascinated pediatricians, cardiologists and physicians alike. It was first reported by Kobylinski  in 1883, followed by a vivid description of nine cases by J A Noonan in 1963.  It is a non-chromosomal syndrome with autosomal dominant inheritance as well as sporadic occurrence. ,
The affected children have a characteristic facies, short stature, chest deformity and possible cryptorchidism along with a structural cardiac abnormality. Pulmonary stenosis (PS) and hypertrophic obstructive cardiomyopathy (HOCM) are the most common cardiac anomalies found in combination with other lesions like atrial septal defect (ASD), ventricular septal defect, tetralogy of Fallot, aortic stenosis, coarctation of aorta, Ebstein's malformation, total anomalous pulmonary venous return, ostium primum ASD and patent ductus arteriosus. 
The presence of HOCM predisposes the NS children to a risk for acute congestive heart failure in the perioperative period.  We describe the anesthetic implications in a child with NS who presented to us for the correction of HOCM and PS. Transesophageal echocardiography (TEE) provided immense help not only as an interrogative and monitoring tool but also in taking critical surgical decisions in our case.
| Case Report|| |
A four-year-old boy [height 80 cm, weight 15 kg, body surface area (BSA) 0.54 m 2 ] with clinical diagnosis of NS presented to us with complaints of tachypnea, dyspnea on exertion and easy fatigability. There was no history of cyanosis or spells. No other family member was afflicted with similar disease. The child was on tab. Propanolol 10 mg thrice a day . He had short stature, sloping and broad forehead, hypertelorism, ptosis, antimongoloid palpebral fissure, low-set ears, short webbed neck, broad chest with widely spaced nipples and undescended testis on the left side.
Electrocardiogram (ECG) showed left axis deviation with dominant S waves in leads V1 TO V6. Chest X-ray showed increased cardiac silhouette. Transthoracic echocardiography revealed thickening of all the four valves. There was HOCM with systolic anterior motion (SAM) of the anterior leaflet of the mitral valve (MV). The dysplastic MV, along with SAM resulted in moderate mitral regurgitation (MR). The right ventricular outflow tract (RVOT) showed a gradient of 50 mm Hg due to the dysplastic pulmonary valve and an obstruction at the infundibular level whereas the left ventricular outflow tract (LVOT) had a gradient of 100 mm Hg due to HOCM and a possible supravalvular aortic stenosis (AS). An ostium secundum ASD was also present. On cardiac catheterization pressures in the right ventricle (RV), left ventricle (LV) and aorta were 120/13, 180/15 and 120/86 mmHg respectively with severe biventricular hypertrophy and subpulmonary stenosis. Subaortic obstruction due to HOCM was noted to be the main reason for the gradient between the LVOT and the aorta. However, the cardiologists were not sure of the supravalvular AS.
After parental consent, the child was scheduled for cardiac surgery for the relief of HOCM and PS. Repair of supravalvular AS if needed, was to be done based on intraoperative TEE findings. In the operating room, ECG, pulse oximetry and noninvasive blood pressure monitoring was instituted. Intravenous (IV) access was obtained and a bolus of 150 ml of crystalloid was administered over 15 min to replace the likely fasting deficit. The cardiopulmonary bypass (CPB) pump was assembled and the perfusionist was kept on standby for any emergency.
Anesthesia induction was performed with IV etomidate (total 0.3 mg/kg) and fentanyl (total 5 μg/kg), given in titrable doses. Rocuronium (1 mg/kg) was administered for endotracheal intubation. Hemodynamic parameters were maintained at baseline values with judicious use of IV fluids and ionotropic agents. Maintenance of anesthesia and adequate analgesia was provided with a combination of oxygen, air, sevoflurane, midazolam, fentanyl and vecuronium. The cannulation of the right femoral artery, for invasive arterial pressure and right internal jugular vein for central venous pressure monitoring was obtained with difficulty as the skin was lax with abundant subcutaneous tissue.
A pediatric TEE probe (S7-3t/ Pediatric) compatible with iE33 echocardiography machine (Phillips Ultrasound, Bothell, WA) was inserted. TEE revealed hypertrophy of the interventricular septum (IVS) [Video 1]. In the transgastric short axis view, concentric hypertrophy of the LV could be appreciated, with anterior wall and IVS thickness of 1.2 and 1.4 cm respectively [Video 2], [Figure 1]. The Z- score for IVS thickness was 5.03 [thickness range of 0.33-0.68 cm in normal children corresponding to patient's BSA (Detroit data)].  The maximal hypertrophy of the IVS was observed 1.6 cm below the aortic annulus. Hypertrophy resulted in diastolic dysfunction with impaired relaxation of the left ventricle resulting in E/A ratio of <1 [Figure 2]. The SAM (dynamic obstruction of the LVOT due to HOCM) and the dysplasia of the MV, resulted in mild to moderate MR [Video 3].
|Figure 1: Transesophageal echocardiography. Transgastric mid-short axis view (SAX), showing concentric hypertrophy of the left ventricle. Anterior Wall (AW) thickness measured is 1.24 cm|
Click here to view
|Figure 2: Transesophageal echocardiography. Mid-esophageal four-chamber view. Probe rotated to left Pulsed Wave Doppler at the level of mitral valve tips. Delayed relaxation of left ventricle (E|
Click here to view
The aortic valve (AV) was dysplastic. The tip of the non-coronary cusp was tethered to the wall of the ascending aorta [Video 3]. We found mild to moderate stenotic gradient (mean pressure gradient = 15 mm Hg, peak pressure gradient = 42 mm Hg) across the LVOTO [Figure 3], due to a combination of HOCM and supra-aortic valvular stenosis. An ostium secundum ASD, along with infundibular thickening and dysplastic pulmonary valve was also seen [Video 4]. The gradient across the RVOT was estimated to be 42 mm Hg suggesting moderate pulmonary stenosis. TEE was also used as a guide to estimate the left ventricular volume, for supplementation of intravascular fluids.
|Figure 3: Transesophageal echocardiography. Transgastric long axis view. Continuous wave Doppler put across left ventricular outflow tract (LVOT). Measurements showing obstruction across LVOT (mean gradient 15 mmHg, peak gradient 42 mmHg)|
Click here to view
Patient was adequately heparinized, aorto-bicaval cannulation was performed and CPB was instituted. Cold blood cardioplegia was administered and the patient was cooled to 32°C. Based on TEE findings of supravalvular AS, aortotomy was performed. The tip of non-coronary cusp was tethered to the aortic wall. A supra-aortic membrane was also seen. Appropriate resection with Doty's repair was performed. Doty's repair is augmentation of the ascending aorta with pulmonary homograft. Interventricular septectomy was performed 1.5 to 2.5 cm below the aortic annulus, at a point beyond the anterior mitral leaflet-IVS junction. Pulmonary valvotomy, infundibular resection and autologous pericardial patch augmentation for RVOT obstruction was performed and ASD closed. However, in view of the anticipated low cardiac output state in the immediate postoperative period, the patent foramen ovale was left open.
TEE performed after termination of CPB showed that the repair was good. The infusions of nitroglycerine (NTG) and dobutamine were started. The child was put on fentanyl infusion to provide optimal postoperative analgesia. The postoperative course of the patient was normal and the inotrope and vascodilatory medications were stopped and subsequently, the child was extubated on postoperative Day one and shifted to the ward on postoperative Day three.
| Discussion|| |
Noonan syndrome is commonly associated with PS in more than 80% and with HOCM in 20-30% of the cases respectively. , HOCM presents a restrictive diastolic dysfunction with a possibility of acute congestive heart failure,  in the presence of hemodynamic fluctuations. The goals for anesthesia management in HOCM are maintenance of increased preload and afterload along with decreased heart rate and contractility. These factors tend to increase the ventricular end-diastolic volume and delay the closure of LVOT, thus reducing the dynamic obstruction.  The anesthesia management starts during the pre-anesthesia checkup. The parental anxiety is allayed and the child advised adequate sedative to have a calm, event-free, parental separation. Beta-blockers being administered for negative ionotropic and chronotropic action should be continued.
The IV site should be adequately anesthetized and the patient should be adequately hydrated to prevent any intravascular hypovolemia and any unwanted hypotension during anesthesia induction.  Intravenous induction of anesthesia may be helpful as any hypotension resulting from administration of general anesthetic drugs may be countered by administration of alpha-agonist (e.g. phenylephrine) and IV fluids. Ketamine though traditionally used, can cause unwarranted tachycardia. Etomidate with its cardio-stable properties is better suited in HOCM. In the absence of IV access, sevoflurane is commonly used but with an inherent risk of hypotension. Bispectral index monitoring can be applied for appropriate anesthesia induction and maintenance. All anesthetics should be slowly administered in titrable doses. Appropriate analgesia with adequate supplementation at anticipated times of surgical stress, should be administered in the perioperative period. In the postoperative period, due to some amount of residual hypertrophy, the same anesthetic goals should be followed and if needed, ionotropic support may be started.
TEE as a diagnostic tool has immense value in NS due to the complex cardiac anatomy. In our case, too it was instrumental in the diagnosis of supravalvular AS for appropriate surgical intervention. Erin et al.,  used TEE as a guide, to evaluate the extent of muscle resection in HOCM and to decide whether or not go for concomitant MV surgery for MR, which was followed in our case also.
| Conclusion|| |
The presence of HOCM in NS requires an anesthesiologist to be vigilant in regard to fluid management and the administration of anesthetic drugs to maintain stable hemodynamics in the perioperative period. TEE plays a vital role in the diagnosis, monitoring and surgical decision-making in this subset of patients. 
| References|| |
|1.||Noonan J, O'Connor' W. Noonan syndrome: A clinical description emphasizing the cardiac findings. Acta Paediatr Jpn 1996;38:76-83. |
|2.||Kobylinski 0. Ueber Eine Flughoutahnbiche Ausbreitung. Am Halse Arch Anthropol 1883;14:342-8. |
|3.||Noonan JA, Ehmke DA. Associated noncardiac malformation in children with congenital heart disease. J Pediatr 1963;63:468-9. |
|4.||Noonan JA. Noonan syndrome and related disorders. Prog Pediatr Cardiol 2005;20:177-185. |
|5.||Mckenzie IM, Weintraub RG. Cardiomyopathies. In: Lake CL, Booker PD editors. Pediatric Cardiac Anaesthesia. 4 th Ed. Philadelphia: Lipincott Williams and Williams; 2005;Pg 530-6. |
|6.||Pettersen MD, Du W, Skeens ME, Humes RA. Regression equations for calculation of z scores of cardiac structures in a large cohort of healthy infants, children, and adolescents: An echocardiographic study. J Am Soc Echocardiogr 2008;21:922-34. |
|7.||Yu EH, Omran AS, Wigle ED, Williams WG, Siu SC, Rakowski H. Mitral Regurgitation in Hypertrophic Obstructive Cardiomyopathy: Relationship to obstruction and Relief with Myectomy. J Am Coll Cardiol 2000;36:2219-25. |
|8.||Goens MB, Campbell D, Wiggins JW. Spontaneous chylothorax in Noonan syndrome. Treatment with prednisone. Am J Dis Child 1992;146:1453-6. |
Poonam Malhotra Kapoor
Department of Cardiac Anesthesia, C.N. Centre, A.I.I.M.S., New Delhi - 110 029
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3]