Prehospital Management

Infants with cyanosis and/or respiratory distress, including those with tetralogy of Fallot (TOF), require oxygen. Blow-by O2 (BBO2) is the least objectionable. Use the open-end of a cannula or tube. Permit the baby to remain with the mother or father. Do not provoke the infant by attempting to start an intravenous (IV) line, especially if one is not skilled in pediatric IV placement. However, an intraosseous (IO) insertion could be an immediate life-saving tool in emergent situations.

Emergency Department Management

The emergency physician should be able to recognize and treat a hypercyanotic episode (tet spell) as one of the very few pediatric cardiology emergencies that may present to the emergency department (ED). Hypercyanotic episodes are characterized by paroxysms of hyperpnea, prolonged crying, intense cyanosis, and decreased intensity of the murmur of pulmonic stenosis. The mechanism is secondary to infundibular spasm and/or decreased systemic vascular resistance (SVR) with increased right-to-left shunting at the ventricular septal defect (VSD), resulting in diminished pulmonary blood flow. If left untreated, it may result in syncope, seizure, stroke, or death.

Treatment for the acute setting of hypercyanosis

Place the baby on the mother's shoulder with the infant's knees tucked up underneath. This provides a calming effect, reduces systemic venous return, and increases SVR. Oxygen is of limited value, as the primary abnormality is reduced pulmonary blood flow. Morphine sulfate, 0.1-0.2 mg/kg intramuscularly (IM) or subcutaneously (SC), may reduce the ventilatory drive and decrease systemic venous return. Phenylephrine, 0.02 mg/kg IV, is used to increase SVR. Case reports in the literature describe using a dexmedetomidine infusion to ameliorate symptoms in hypercyanotic neonates.[3] Caution is warranted and the drug must be carefully titrated by initiating at a very low dose of 0.1-0.125 mcg/kg/hour (without a bolus).[15] A case report of a 3-year old child with history of tetralogy of Fallot repair at age 9 months describes atrial standstill following mitral valve replacement.[16] Treating acidosis with sodium bicarbonate may reduce the respiratory center stimulating effect of acidosis.

As a last resort, use general anesthesia.

Medical Treatment
Asymptomatic infants need no special medical treatment. Surgery is the definitive treatment for the cyanotic patient with tetralogy of Fallot (TOF). The primary role of medical therapy is in preparation for surgery. Most infants have adequate saturations and usually undergo elective repair. In infants with acute cyanotic episodes, placing them in a knee-chest position may prove helpful in addition to administering oxygen and intravenous (IV) morphine. In severe episodes, IV propranolol (Inderal) may be administered, which relaxes the infundibular muscle spasm causing right ventricular (RV) outflow tract obstruction (RVOTO). Progressive hypoxemia and the occurrence of cyanotic spells are indications for early surgery. Consult a pediatric cardiologist and pediatric surgeon.

Surgical Considerations
Because tetralogy of Fallot (TOF) is a progressive disorder, most infants require some type of surgical procedure. The timing of complete surgical repair is dependent on numerous variables, including symptoms and any associated lesions (eg, multiple ventricular septal defect [VSD], pulmonary atresia). Currently, the trend is to perform a complete surgical procedure (often electively) before the age of 1 year and preferably by the age of 2 years. Studies have shown, however, that surgery is preferably done at or about 12 months of age. The majority of patients born with tetralogy of Fallot now thrive well into their adult years.[17] Most surgeons today recommend the primary corrective procedure, and current results are excellent. Infants with cyanosis are stabilized by administering prostaglandins (to maintain the ductus in an open state). The use of prostaglandins has significantly decreased the need to perform urgent surgery. Instead of performing systemic-topulmonary artery shunts on critically ill cyanotic-hypoxic infants, surgeons now have the luxury of having extra time to assess the patient's anatomy and to perform the primary procedure on an elective basis. Primary repair avoids prolonged right ventricular (RV) outflow obstruction and the subsequent right ventricular hypertrophy (RVH), prolonged cyanosis, and postnatal angiogenesis.

Factors that increase risk for early repair of tetralogy of Fallot (TOF) include the following[18] :

Low birth weight Pulmonary artery atresia Major associated anomalies Multiple previous surgeries Absent pulmonary valve syndrome Young or old age Severe annular hypoplasia Small pulmonary arteries High peak RVtoleft ventricular pressure ratio Multiple VSDs Coexisting cardiac anomalies

Contraindications
Contraindications to primary repair in tetralogy of Fallot include the following:

The presence of an anomalous coronary artery Very low birth weight Small pulmonary arteries Multiple VSDs Multiple coexisting intracardiac malformations

Palliative Procedures
The goals of palliation for tetralogy of Fallot (TOF) are to increase pulmonary blood flow independent of ductal patency and to allow pulmonary artery growth and even total correction. Occasionally, an infant with pulmonary atresia or an anomalous left anterior descending (LAD) coronary artery that crosses the right ventricular (RV) outflow tract (RVOT) may not be a surgical candidate for establishing transannular RVtopulmonary artery continuity and may require placement of a conduit. Although artificial conduits can be used, infants with extremely small pulmonary arteries may not tolerate total correction in infancy. These infants may require palliation instead of corrective surgery. Various types of palliative procedures have been developed, but the current procedure of choice is the Blalock-Taussig shunt. The Potts shunt has been abandoned because of a tendency toward increased pulmonary blood flow and increasing difficulty with takedown at the time of corrective surgery. The Waterston shunt is sometimes used, but it also increases pulmonary artery blood flow. This shunt is more related to pulmonary artery stenosis, which generally requires reconstruction. The Glenn shunt is no longer used because of difficulty in performing a subsequent definitive repair.

Blalock-Taussig shunt
Given the problems associated with the aforementioned shunts, placement of the modified Blalock-Taussig shunt (using a Gore-Tex graft between the subclavian artery and pulmonary artery) is the procedure of choice (see the following images). Advantages of the modified Blalock-Taussig shunt include: (1) preservation of the subclavian artery, (2) suitability for use on either side, (3) good relief of cyanosis, (4) easier control and closure at time of primary repair, (5) excellent patency rate, and (6) decreased incidence of iatrogenic pulmonary/systemic artery trauma.

This image shows completed blocking with a Taussig shunt

This image shows a closed ventricular septal defect and

closure of right ventriculotomy with Gore-Tex. is used for complete closure of right ventriculotomy.

Gore-Tex

The mortality rate is reportedly less than 1% when placing this shunt. However, the Blalock-Taussig shunt elicits a few complications, including hypoplasia of the arm, digital gangrene, phrenic nerve injury, and pulmonary artery stenosis. The longevity of palliation after shunt placement varies according to the patient's age at the time of surgery and the type of shunt.

Other palliation procedures

Other forms of palliation that are rarely used today include patching of the RVTO without cardiopulmonary bypass (CPB). This procedure can cause destruction of the pulmonary valve and significant intrapericardial adhesions, and the increased pulmonary artery blood flow can result in congestive heart failure (CHF); therefore, its role is limited to treatment of infants with tetralogy of Fallot complicated by pulmonary atresia and/or hypoplasia of the pulmonary artery. In very ill neonates with multiple medical problems, balloon pulmonary valvulotomy has been shown to increase oxygen saturation, thus obviating the need for emergency palliative surgery. However, perforation of the pulmonary artery is a risk with this procedure in neonates. A study by Park et al indicated that shunting or primary repair of neonates with symptomatic tetralogy of Fallot produced similar mortality and results.[19] A study by Robinson et al found that intraoperative balloon valvuloplasty is associated with significant longitudinal annular growth, with normalization of annular size over time. This technique may be most useful in patients with moderate pulmonary stenosis and moderate pulmonary valve dysplasia.[20]

Corrective Surgery
Primary correction is the ideal operation for treatment of tetralogy of Fallot (TOF) and is usually performed under cardiopulmonary bypass (CPB). The aims of the surgery are to close the ventricular septal defect (VSD), resect the area of infundibular stenosis, and relieve the right ventricular (RV) outflow tract obstruction (RVOTO). Before cardiopulmonary bypass is initiated, previously placed systemic-to-pulmonary artery shunts are isolated and taken down. Patients then undergo cardiopulmonary bypass. Associated anomalies, such as atrial septal defect (ASD) or patent foramen ovale, are closed.

Postoperative Monitoring and Results

All infants undergoing open-heart procedures are sent to the pediatric intensive care unit (PICU). Hemodynamic parameters must be followed postoperatively. One study of children who underwent complex open heart surgery procedures found short-term outcome may be predicted by the amount of inotropic and pressor support received in the ICU. The greater the support, the worse the outcome.[21] All infants initially remain intubated on a ventilator until cardiac and respiratory statuses stabilize. To maintain systemic peripheral perfusion, adequate cardiac output and atrial pacing may be required. Patients should be weighed daily to follow volume status. Patients with heart block should have temporary atrioventricular (AV) pacing. If intrinsic conduction has not returned in 5-6 days, the patient probably needs a permanent pacemaker.

Results
The outcome of surgical repair is excellent with minimal morbidity and mortality. To date, no difference in operative mortality rates has been noted between transventricular and transatrial approaches.[22] The occasional patient may have an elevated right ventricle (RV)toleft ventricle (LV) pressure ratio. This may be due to a number of causes including a residual ventricular septal defect (VSD), pulmonary artery stenosis, and pulmonary artery and valve atresia. These patients tend to do poorly, and echocardiography is warranted to find the cause. Surgical revision may be required to correct the etiology of the high RV pressures. As in previous studies, it is now apparent that preservation of pulmonary annulus can decrease the rate of reoperation. With improved techniques, excellent results with early 1-stage repair in infants have been reported. Overall, the mortality rate in most series is 1-5% when the repair is performed primarily or after a systemic-to-pulmonary artery shunt. Similarly, the mortality rate of infants undergoing palliative shunt placement is low (0.5-3%). The survival rate at 20 years is approximately 90-95%. Improved techniques of myocardial protection with hypothermia, cardioplegia, and even total circulatory arrest are providing excellent results by enabling more precise anatomic repairs in younger infants. Nevertheless, infants receiving complete correction before age 1 year have an increased risk compared with patients older than 1 year.

Revision/reoperation
The literature suggests that approximately 5% of individuals will need a revision/reoperation at some point. Indications for early reoperation include a residual VSD or a residual RV outflow tract obstruction (RVOTO). Residual VSDs are poorly tolerated in patients with tetralogy of Fallot (TOF), because these individuals cannot tolerate an acutely imposed volume overload. Small, residual VSDs are common after surgical repair and are usually clinically insignificant. A residual VSD with a 2:1 shunt or an RVOTO of greater than 60 mm Hg is an urgent indication for reoperation. Surgery can be performed with low risk and can result in dramatic improvements. Occasionally, pulmonary valve insufficiency may increase and may be associated with RV failure. Once tetralogy of Fallot has been repaired in infancy or childhood, about 5% of individuals require repair or replacement of the pulmonary valve. Because of better results from surgery in the present era, long-term survivors are increasingly reported. In most of these individuals, pulmonary regurgitation is the clinical presentation and can be treated with a prosthetic tissue valve.[23]

This problem is generally treated with a pulmonary valve replacement. Porcine valves are preferred over mechanical valves, because they have lesser tendency to thrombose.

Surgical Complications
Early postoperative complications following repair of tetralogy of Fallot (TOF) include the creation of heart block and residual ventricular septal defects (VSDs). Ventricular arrhythmias are more common and are reportedly the most frequent cause of late postoperative death. Sudden death from ventricular arrhythmias has been reported in 0.5% of individuals within 10 years of repair. The arrhythmias are thought to occur in fewer than 1% of patients having an early operation. As with most heart surgery, the risk of endocarditis is lifelong, but the risk is much less than in a patient with an uncorrected tetralogy of Fallot.

Future
In the present day, some patients with tetralogy of Fallot have survived for longer than 15-20 years after their first operation. The major problem encountered by these individuals is the development of pulmonary valvular regurgitation. It appears that a number of these individuals require pulmonary valve replacement.[24] Most individuals receive a pericardial homograft, and only time will tell how long these valves will last. However, the last decade has seen great advances in percutaneous technology and tissue engineering, and perhaps the role of surgery may decline.[25]

Medication Summary
The goals of tetralogy of Fallot (TOF) therapy are to reduce the ventilatory drive, increasing systemic venous return, and to increase peripheral vascular resistance.

Analgesics
Class Summary
Analgesic agents reduce ventilatory drive. In addition, pain control ensures patient comfort and promotes pulmonary toilet. Most analgesic agents have sedating properties, which are beneficial for patients who are having hypercyanotic episodes. View full drug information

Morphine sulfate (Duramorph, Astramorph, MS Contin)

Morphine is the drug of choice (DOC) for narcotic analgesia because of its reliable and predictable effects, safety profile, and ease of reversibility with naloxone. This agent is administered intravenously (IV), may be dosed in number of ways, and is commonly titrated until the desired effect is obtained.

Alpha-adrenergic Agonists
Class Summary
Alpha-adrenergic agents improve hemodynamic status by improving myocardial contractility and increasing heart rate, resulting in increased cardiac output. Peripheral resistance is increased by vasoconstriction, increased cardiac output, and elevated blood pressure. View full drug information

Phenylephrine

Phenylephrine is a strong postsynaptic alpha-receptor stimulant with little beta-adrenergic activity. This drug produces vasoconstriction of arterioles, thereby increasing peripheral venous return.