Cardiac arrest after induction of anesthesia in a 2-month-old infant with undiagnosed Williams syndrome.

A 2-month-old male infant presented for elective repair of inguinal hernias. His preoperative medical history and physical examination were unremarkable. During induction of anesthesia, the infant sustained an adverse cardiac event. The event was characterized by tachycardia, hypotension, and massive ST-segment elevation. Despite vigorous resuscitation, spontaneous hemodynamic stability could not be achieved and extracorporeal membrane oxygenation was required. A transthoracic echocardiogram revealed severe hypoplasia of the ascending aorta. As effective cardiac function did not recover and there was evidence of diffuse ischemic brain injury, life support was withdrawn. Genetic testing performed postoperatively was definitive for Williams syndrome.

Introduction

Williams syndrome is a multisystem genetic disorder caused by a hemizygous deletion in the long arm of chromosome 7 in the region 7q11.23. Loss of one of the ELN genes from this chromosome band results in a deficiency of elastin.[12] Congenital cardiac defects are common in children with Williams syndrome. These defects include supravalvular aortic stenosis (SVAS), pulmonary artery stenosis, and coronary arterial ostial stenosis.[34] Fusion of the aortic valve leaflets to the aortic wall can produce functional coronary artery stenosis and reduce cardiac blood flow. Stenoses of the abdominal aorta, renal arteries, and intracranial arteries can also occur. Reduced elastin in the large arteries causes increased arterial stiffness that promotes early-onset hypertension.[5] Arterial elasticity is important to cardiac mechanics as energy is stored in the arterial wall during systole and released during diastole. This effect promotes cardiac efficiency, improves peripheral blood flow, reduces left ventricular afterload, and increases coronary blood flow.[67] Elastin deficiency in the myocardium may directly reduce cardiac performance.[89]

Noncardiovascular features of Williams syndrome include elfin facies, growth retardation, endocrine dysfunction, and pulmonary emphysema.[10] The risk of sudden death from cardiomyopathy is 25–100 times greater than the normal population.[11]

The risk of an adverse cardiac event during anesthesia may be as high as 11%.[12] Focused specialty care may significantly reduce that risk if the diagnosis of Williams syndrome is known before anesthesia.[13] We report a case of cardiac arrest in a 2-month-old infant with undiagnosed Williams syndrome.

Written permission from the patient's mother and approval from the Indiana University Institutional Review Board for the publication of case report were obtained.

Case Report

The patient was a term, 2-month-old male weighing 4.8 kgs, who presented for the elective repair of inguinal hernia. The medical history was unremarkable, and no cardiac murmurs were detected during routine pediatric examinations. Preoperative vital signs were: temperature 36.6°C, heart rate 154/min, blood pressure 107/59, respiratory rate 44/min, and arterial oxygen saturation 100% (room air). No cardiac murmurs were heard.

Anesthesia was induced with sevoflurane in oxygen to a maximum sevoflurane concentration of 8%, and an intravenous catheter was inserted. Propofol (2 mg/kg intravenous) was administered, and the trachea was intubated with a 3.0 mm internal diameter cuffed tracheal tube. The inspired concentration of sevoflurane was reduced to 3% immediately after intubation. Heart rate at that time was 146 bpm and systolic blood pressure was between 70 and 80 mmHg. Five minutes after intubation, there was a significant change in the electrocardiogram that appeared to be a wide QRS complex tachycardia. As the systolic blood pressure decreased to 58/26, resuscitation was initiated with chest compressions, and repeated doses of epinephrine and sodium bicarbonate. Although epinephrine boluses transiently increased systolic blood pressure but subsequently, it became very low (30-40 mmHg to immeasurable. Over 20 min, nine doses of epinephrine (2–10 μg/kg), four doses of sodium bicarbonate (2–5 mEq/kg), one dose of calcium gluconate (5 mg/kg), one dose of magnesium sulfate (30 mg/kg), and one electrical countershock were administered, and an epinephrine infusion at 50 μg/kg/min was initiated. It became evident that the change in the QRS pattern was actually secondary to massive elevation of the ST segment. Despite aggressive resuscitation efforts, spontaneous circulation could not be restored. Extracorporeal membrane oxygenation (ECMO) was established within 1 h of the arrest, and the patient was transferred to the Intensive Care Unit (ICU). A transthoracic echocardiogram showed moderate-to-severe decreased left ventricular function and a diffusely hypoplastic (4.5 mm, normal 7.5–9 mm[14]) and thickened ascending aorta. The aortic valve was tri-leaflet and normal. Over the next 48 h in the ICU, while on ECMO, the infant suffered a series of seizures. Serial echocardiograms showed no improvement in cardiac function, and cranial computed tomography demonstrated diffuse hypoxic-ischemic injury. Life support was withdrawn. Cytogenetic analysis with fluorescence in situ hybridization was positive for deletion in the Williams syndrome critical region. One chromosome showed signals for ELN, LIMK1, and D7S613. These signals were absent in the other chromosome 7.

Discussion

The increased risk of anesthesia for patients with Williams syndrome has been reported by several sources.[15161718192021] Patients at highest risk are those with SVAS when a decrease in diastolic blood pressure reduces coronary blood flow, leading to myocardial ischemia. Recommendations for anesthesia are similar to those for adults with ischemic heart disease.[222324] These recommendations include maintenance of cardiac preload, myocardial contractility, and systemic vascular resistance (SVR) directed at optimization of coronary blood flow. Although the recommendations for administering an anesthetic that minimizes a reduction of diastolic blood pressure and maintains coronary blood flow are logical, the situation in patients with Williams syndrome may be more complex than that of adult patients with coronary artery disease. Reduced compliance of the aorta due to elastin deficiency in Williams patients can cause marginal blood flow to the subendocardium under normal physiologic conditions. Endocardial perfusion could be further compromised by the effects of anesthetics that are usually well tolerated by normal infants. This may explain the rapidity with which severe hypotension occurs during anesthesia and the poor response to resuscitation in Williams patients. There may be electrophysiologic mechanisms for cardiac arrest such as ventricular dysrhythmia secondary to prolongation of the Q-T interval.[25] Prolongation of the Q-T interval in patients with Williams syndrome resembles the increase in Q-T interval of patients with ischemic heart disease.

The diagnosis of Williams syndrome in an infant can be difficult as many of the signs of the disease are not present at an early age. Williams patients with SVAS and a cardiac murmur are typically diagnosed at 1–1.5 years of age. Detection, however, may be delayed until 4–5 years of age if SVAS is not present.[26] The cardiovascular pathology of our patient was atypical and different from other reported cases. Most patients with Williams syndrome have SVAS with or without coronary artery anomalies. Our patient had a severely hypoplastic aorta without detectable coronary stenosis and no cardiac murmur. The only preoperative clue may have been the elevated systolic blood pressure of 107 mmHg. Accurate measurement of blood pressure in a young infant, however, is influenced by many variables, and systolic blood pressure of 107 mmHg does not generally cause concern.[27]

We can only speculate as to the mechanism of the cardiac arrest in our patient. Sevoflurane and propofol both decrease (SVR) and sevoflurane is known to increase the Q-T interval.[28293031] Although the infant tolerated the induction with sevoflurane, a further decrease in SVR caused by propofol could have reduced myocardial blood flow. This is the youngest reported patient with undiagnosed Williams syndrome who suffered a cardiac arrest during anesthesia and underscores the increased risk of anesthesia for these patients.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient's mother has given his consent for his images and other clinical information to be reported in the journal. The patient's mother understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.