Anesthesiology

Ross procedure

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What the Anesthesiologist Should Know before the Operative Procedure

The Ross procedure was first described in 1967 for the surgical treatment of aortic stenosis. The procedure consists of replacement of the diseased aortic valve with patient's own pulmonary valve (pulmonary valve autograft) and use of cryopreserved homograft to replace the harvested pulmonary valve (pulmonary allograft). The coronary arteries are then reimplanted in the autograft.

In the past 10 years, the Ross procedure has become the operation of choice at many centers in selected patients who need aortic valve replacement. The Ross operation is an excellent option for aortic valve replacement in physically active young children and young women of childbearing age. It is considered the most versatile operation because it can be performed in infants and adults less than 50 years of age.

This type of surgery has several advantages including: 1) growth potential in children; 2) no need for anticoagulation; 3) low incidence of thromboembolism; 4) low incidence of endocarditis; and 5) excellent hemodynamics.

Disadvantages include: 1) the procedure is more complex than standard aortic valve replacement because two cardiac valves are involved; 2) the operation is technically more demanding. Consequently it requires a longer cardiopulmonary bypass time; 3) the mortality rate is higher when performed in neonates and infants compared to older children; and 4) hospital stay is longer.

The replaced aortic valve can last indefinitely, however, there is a small risk of early failure, usually due to progressive aortic annular dilatation. There is also the possible need for pulmonary valve replacement due to pulmonary homograft calcification/failure after 10-20 years.

There are some caveats to be considered when contemplating the Ross procedure. These include: the operation should not be considered in patients with aortic root dilatation due to the risk of developing aortic insufficiency in the translocated valve; the procedure is contra-indicated in patients with Marfan syndrome, a connective tissue disorder associate with aneurysmal dilation and progressive aortic dissection. In many centers it is considered as a last-ditch option in the very young infant with aortic stenosis that is refractory to first tier therapies including balloon valvuloplasty or open valvotomy/commissurotomy.

1. What is the urgency of the surgery?

What is the risk of delay in order to obtain additional preoperative information?

The Ross procedure is usually an elective procedure. While aortic valve stenosis can present at any age from birth through adulthood, neonates with critical aortic stenosis comprise a unique population. They often rely on persistent patency of the ductus arteriosus to provide for systemic blood flow. When the ductus arteriosus closes (typically several days after delivery), neonates with previously undiagnosed critical aortic stenosis often present in profound cardiogenic shock. Medical therapy with a continuous infusion of prostaglandin E1 (Alprostadil) is necessary to re-open the ductus arteriosus and provide for systemic blood flow. Once this is accomplished, a decision regarding balloon valvuloplasty or surgical treatment is made. Rarely in this patient population a Ross procedure is indicated.

For patients with aortic insufficiency, an elective Ross procedure should be accomplished before left ventricular dilatation occurs.

Cardiac catheterization with coronary angiography should be performed prior to elective Ross procedure to delineate the origin of the coronaries arteries if they have not been adequately identified by noninvasive techniques.

  1. Emergent- Percutaneous balloon valvuloplasty is the first option for congenital aortic stenosis. If this procedure is not successful or if there is a procedural complication such as avulsion of the aortic valve leaflets these patients can emergently present to the operating room with severe aortic regurgitation. Rarely the Ross procedure is performed in an emergency setting.

  2. Urgent- If severe aortic insufficiency occurs after attempted balloon valvuloplasty an urgent Ross procedure may be contemplated.

  3. Elective- This is the most common scenario. Children with symptomatic aortic stenosis present for elective Ross procedure. Symptoms of aortic stenosis include chest pain and syncope. Most patients are asymptomatic with mild to moderate aortic stenosis. Patients with aortic regurgitation are similarly asymptomatic if they have mild-moderate disease. Individuals with severe aortic regurgitation usually presents with florid congestive heart failure.

2. Preoperative evaluation

Approach the patients according to age and type of aortic lesion (aortic stenosis, aortic insufficiency, or mixed lesion). Neonates with aortic stenosis have severe congestive heart failure and often are on inotropes, diuretics, and mechanical ventilator support. Symptoms of congestive heart failure in neonates and infants include difficulty feeding, diaphoresis and irritability. Older children and adolescents with aortic stenosis have typically been followed by cardiologists for several years prior to intervention and are generally better compensated than neonates and infants. Valve gradients of 25 mmHg or less are considered trivial, those between 50 and 75 mmHg are deemed moderate, while gradients above 75 are severe.

Older children with aortic stenosis are often asymptomatic. The preoperative evaluation should be attempt to elicit symptoms of CHF in this population. These symptoms include easy fatigability, dyspnea on exertion, chest pain and syncope. The latter two are ominous and should trigger prompt referral and intervention.

Aortic regurgitation in children is often an acquired lesion. It could occur following an intervention for aortic stenosis such as balloon valvuloplasty or surgical commisurotomy. Echocardiogram evaluates the degree of regurgitation and assesses ventricular function. Increasing left ventricular dilation and worsening left ventricular systolic function prompt surgical referral.

Infants can have associated congenital heart abnormalities such as sub-aortic left ventricular outflow tract obstruction (LVOTO). These patients may require a modified operation such as Ross- Konno procedure. In this operation the ventricular septum is incised and muscle is resected in order to enlarge the LVOT to accommodate the pulmonary autograft. Preoperative echocardiographic evaluation is mandatory when contemplating the Ross procedure. It is vital that the pulmonary valve be absolutely normal prior to translocation to the aortic position.

  1. Medically unstable conditions warranting further evaluation include: Infants with critical aortic stenosis frequently present in cardiogenic shock, on inotropic support. Severe left ventricular failure often leads to pulmonary venous hypertension and resultant pulmonary edema with congestive heart failure. These patients often come to the operating room on mechanical assisted ventilation.

  2. Delaying surgery may be indicated if: The patient is in severe cardiogenic shock requiring extracorporeal membrane oxygenation (ECMO) as bridge to definitive therapy.

3. What are the implications of co-existing disease on perioperative care?

  1. Perioperative evaluation- Valvar aortic stenosis is often an isolated defect. Occasionally, however, valvar aortic stenosis occur in conjunction with either subvalvar or supravalvar obstruction. Supravalvar aortic stenosis is seen in up to 50% of patients with Williams syndrome. Williams syndrome is an inherited disorder characterized by developmental delay, elfin facies and a "cocktail party" personality. Patients with Williams syndrome can have anatomic abnormalities of the upper airway that can make for difficult visualization of laryngeal structures during laryngoscopy. Subvalvar aortic stenosis is the second most common cause of aortic stenosis. Subvalvar aortic stenosis is often caused by either a thin discrete membrane, a thicker ridge of tissue like a diaphragm, or a more diffuse longer segment of narrowing of the left ventricular outflow tract (LVOT). Left ventricular hypertrophy is the final common pathophysiologic manifestation of left ventricular outflow obstruction (LVOTO). The preoperative evaluation of patients with LVOTO includes echocardiogram evaluation to ascertain the severity of the outflow tract obstruction and degree of left ventricular hypertrophy. Right and left heart catheterization are also recommended because of the high occurrence of associated cardiac defects.

  2. Perioperative risk reduction strategies- Some patients with subvalvar aortic stenosis are on beta blocker therapy. This may be continued in the peri-operative period.

  3. In neonates with aortic stenosis, four factors appear predictive of a higher mortality risk. These factors are: 1) echocardiogram finding of an LV long axis to heart long axis ratio of < 0.8; 2) an aortic root diameter of < 0.8; 3) mitral valve area of < 4.75 cm/m2; 4) left ventricular mass of < 36 gm/m2. Congenital valvar aortic stenosis that presents after neonatal period has a better prognosis than neonatal aortic stenosis.

b. Cardiovascular system

  1. Acute/unstable conditions: Critical valvar aortic stenosis in the neonate is often accompanied by cardiogenic shock and acidosis if antegrade flow through the stenotic valve is sufficiently limited. Systemic perfusion is often dependent on patency of the ductus arteriosus. Thus is accomplished with the continuous infusion of prostaglandin E1. These patients are frequently intubated and mechanically ventilated due to severe congestive heart failure. They typically receive continuous infusion of inotropic agents such as epinephrine.

  2. Baseline coronary artery disease or cardiac dysfunction - Goals of management: The Ross procedure involves coronary reimplantation in the autograft. Preoperative evaluation of the origin and course of the coronary arteries is imperative. This is usually accomplished by an echocardiogram or cardiac catheterization with coronary angiography.

c. Pulmonary

Reactive airway disease (Asthma): Older patients with valvar aortic stenosis/ regurgitation are often asymptomatic. Easy fatigability is the most common symptom in this population. These patients usually self-limit their activity. Older patients with more advanced aortic stenosis who manifest chest pain and/or syncope will have activities such as sports restricted due to the risk of sudden cardiac death. Otherwise, the incidence of other pulmonary diseases such as asthma is no different than that of the general population.

d. Renal-GI:

e. Neurologic:

Neonates with left sided obstructive lesions in the valvar aortic stenosis spectrum often have co-existing structural central nervous system abnormalities demonstrated on brain magnetic resonance imaging. There is a possibility of neurodevelopmental delay due to prior cardiac surgeries.

f. Endocrine:

Neonatal and infants can have adrenal insufficiency in which steroids supplementation may be needed. We typically administer hydrocortisone 50 mg/M2/day in three divided doses. Also in this population thyroid function needs to be assessed and supplementation with thyroid hormone may be necessary.

g. Additional systems/conditions which may be of concern in a patient undergoing this procedure and are relevant for the anesthetic plan (eg. musculoskeletal in orthopedic procedures, hematologic in a cancer patient)

4. What are the patient's medications and how should they be managed in the perioperative period?

Neonates with critical aortic stenosis are on prostaglandins infusion. Side effects include: tissue edema, vasodilatation, apnea, and hypotension. Typically these infusions are turned off when the patient arrives in the operating room as their biological half life is longer than their pharmacologic half life.

To attenuate the inflammatory resonse to cardiopulmonary bypass in infants, methylprednisone 10 mg/kg IV is administered twice: six hours before incision and, again on call to the operating room.

Low cardiac output is supported with an epinephrine infusion (0.02 - 0.05 mcg/kg/min).

Patients with aortic insufficiency and CHF may be administered digoxin, diuretics, and after load reduction drugs such as ACE inhibitors, angiotensin receptor blockers. These medications usually are held on the day of surgery to avoid hypotension during anesthesia induction. Readers are advised to be aware of the possible interaction between digoxin and dexmedetomidine resulting in severe bradycardia.

Patients on beta blockers: usually recommended to be taken on the day of surgery.

If patients are taking nutriceuticals or herbals supplements (common herbals products are Echinacea, Feverfew, Garlic, Ginger, Ginkgo Biloba, Ginseng, Hoodia, Kava, St John's Wort, and Valerian) it is necessary to discontinue them 2 weeks before surgery. The most concerning side effects of these agents are risk of bleeding, changes in blood pressure, and potentiation of the sedative effects of anesthetics.

h. Are there medications commonly seen in patients undergoing this procedure and for which should there be greater concern?

i. What should be recommended with regard to continuation of medications taken chronically?

Psychiatric

All chronic medications may be continued in the peri-operative period but some medications need to be held on the day of surgery due to risk of anesthetics drugs interaction (see above).

Older children may be taking medications for attention deficit hyperactivity disorder (ADHD) or behavioral problems. Some of these drugs if acutely discontinued can lead to an abstinence syndrome. If patients are taking non stimulants drugs such as guanfacine (IntunivR) for ADHD be aware of the potential risk of hypotension and arrhythmia.

j. How To modify care for patients with known allergies -

k. Latex allergy- If the patient has a sensitivity to latex (eg. rash from gloves, underwear, etc.) versus anaphylactic reaction, prepare the operating room with latex-free products.

Standard latex free operating rooms are strongly recommended. If not, latex precautions protocol should be implemented.

l. Does the patient have any antibiotic allergies- - Common antibiotic allergies and alternative antibiotics]

For beta-lactams allergy:

Vancomycin 10 -15 mg/kg or adult dose (1 gm) over 60 minutes. Should be given within 120 minutes before incision.

The NSIPP (National Surgical Infection Prevention Project) recommends either vancomycin or clindamycin (10-20 mg/kg).

m. Does the patient have a history of allergy to anesthesia?

  1. Malignant hyperthermia:

    1. Documented- avoid all trigger agents such as succinylcholine and inhalational agents:

      1. Proposed general anesthetic plan: Utilize a non-triggering anesthetic.

      2. Insure MH cart available: [- MH protocol]

    2. Family history or risk factors for MH: Generally neonates are not deemed to be at risk for Malignant hyperthermia. However, if there is a positive family history of malignant hyperthermia (first degree relatives) the patient should be presumed at risk and a non-triggering anesthetic should be administered.

  2. Local anesthetics/ muscle relaxants:

5. What laboratory tests should be obtained and has everything been reviewed?

Routine laboratory tests include complete blood count and differential (CBC), electrolytes, coagulation panel, and type and screen.

Routine neonate screen should evaluate thyroid function. Neonates with suspected adrenocortical insufficiency will have had ACTH stimulation test and serum cortisol level to detect patients at risk of adrenal insufficiency.

Chest x ray films re usually normal in children with aortic diseases, but occasionally these patients could have aortic dilatation. Cardiomegaly can be present if the patient is in CHF or has severe aortic regurgitation.

Neonates with critical aortic stenosis and CHF can have ground glass lung fields associated with pulmonary edema.

EKG is usually normal or demonstrates LVH with or without strain.

Intraoperative Management: What are the options for anesthetic management and how to determine the best technique?

Young children may need heavy premedication and inhalational induction with nitrous oxide/sevoflurane before IV insertion.

If oral premedication is necessary we recommend midazolam 0.5 mg/kg PO. If history of allergy or paradoxal reaction to benzodiazepines, alternative options include ketamine PO (3 - 5 mg/kg), clonidine PO (2 mcg/kg), dexmedetomidine nasal (1 - 2 mcg/kg). The alpha 2 agonists have longer latency time (30 - 45 minutes) compared to midazolam (latency time of 15 minutes).

If an IV is already in place: young children will benefit from iv sedation with a benzodiazepine such as midazolam (0.05 mg/kg).

Following premedication the child is brought to the operating room where monitors are applied. The monitors include ECG, NIBP, SpO2, and near infrared reflectance spectroscopy (NIRS rSO2), nasopharygeal and rectal temperature. If an intravenous line is in place Induction is accomplished with the above-listed agents. If there is no intravenous access, an inhalational induction is performed with Sevoflurane/O2/N20. It is preferable to have two large bore peripheral intravenous access. Once intravenous access is secured, laryngoscopy is facilitated with the appropriate neuromuscular blocking drug. The patient's trachea is intubated via either the nasal or oral route. A percutaneous arterial line is started and a central venous catheter is placed (typically in the right internal jugular vein). The urethra is catheterized.

Maintenance of anesthesia is with an opioid-benzodiazepine combination listed below supplemented with low dose inhalational anesthetic.

a. Regional anesthesia

Regional anesthesia is not indicated in the authors' opinion due to the risk of epidural hematoma due to systemic anticoagulation for cardiopulmonary bypass. The risk of the procedure exceeds the perceived benefits.

b. General Anesthesia

Anesthetic considerations for aortic stenosis include maintenance of a normal heart rate (avoidance of tachy- or bradycardia), maintenance of systemic vascular resistance and cardiac output. Patients with aortic stenosis have a "fixed" cardiac output. Cardiac output is the product of heart rate and stroke volume. Any agents that decrease either heart rate and stroke volume will further impair cardiac output. The determinance of stroke volume are preload, afterload and contractility.

Intravenous induction with a narcotic such as fentanyl supplemented by either a benzodiazepine (midazolam) or low dose of sedative-hypnotic such as propofol is suggested. The choice of neuromuscular blocker depends on the aortic lesion. Some patients with aortic stenosis could benefit from a vagolytic drug such as pancuronium which counterbalances the negative chronotropic effects of the potent synthetic opioid fentanyl. However may practitioners prefer a neuromuscular blocking drug that has no effect on heart rate such as vecuronium. The goal is to maintain a heart rate as close to normal as possible and avoid tachycardia.

Anesthetic management will depend on the patient's hemodynamic profile. Although some patients could present with aortic regurgitation, most patients will have aortic stenosis. This is true, even in so-called mixed lesions. Anesthetic management will focus on the predominant lesion. Aortic stenosis leads to left ventricular hypertrophy and decrease in compliance. Hence there is pre-load dependency and it is difficult to adequately fill the cardiac chamber. If there is aortic stenosis with left ventricular hypertrophy: 1) avoid tachycardia (HR< 80 bpm); 2) maintain pre-load (need high filling pressure); 3) avoid vasodilation (aortic stenosis has "fixed" cardiac output. Anesthetics can lead to decrease in systemic vascular resistance, consequently decrease in cardiac output); 4) maintain sinus rhythm (left ventricular filling depends on atrial contraction, so loss of atrial "kick" will decrease stroke volume by 15 - 20%.

Induction is typically with fentanyl, a benzodiazepine (midazolam), propofol (avoid high doses), and vecuronium to keep low HR and avoid decrease in SVR. Maintenance is with opioids and inhalational anesthetic such as sevoflurane or isoflurane. The aim is to maintain pre-load, keep the SVT high to normal, avoid hypotension to keep the coronary arteries adequately perfused. Phenylephrine is often used to maintain mean aortic pressure and perfuse the coronary arteries. In addition, in patients with an intact baro-receptor reflex phenylephrine administration can result in reflex slowing of the heart rate which is desirable.

Patients with aortic insufficiency (AI) have chronic changes which manifest as adaptation to ventricular volume overload. However, if there is acute AI and surgery is emergent, there will be left ventricular failure with pulmonary edema. If the predominant pathophysiology is that of aortic insufficiency: 1) avoid bradycardia (HR > 90 bpm). Higher heart rates will decrease diastolic regurgitation and improve cardiac output, and promote forward flow; 2) vasodilatation is advised as decreases in afterload will improve stroke volume. In summary, for AI, higher heart rate, decrease in afterload, maintain pre-load, and avoid myocardial depression.

For patients with aortic insufficiency decreases in heart rate can exacerbate the regurgitant flow. Pancuronium or rocuronium are excellent choices. Both agents increase heart rate.

It is desirable to decrease systemic vascular resistance in patients with aortic regurgitation. Decreases in systemic vascular resistance promote forward flow in this patient population.

For maintenence of general anesthesia, we utilize moderate doses of a potent synthetic opioid (either fentanyl or sufentanyl). Sufentanyl is 5 -7 times more potent than fentanyl. Inhalational anesthetics are often used to supplement the balanced technique at doses of 0.5 MAC.

Typical doses of fentanyl are 15-20 mcg/kg. However, in some cases doses up to 50-75 mcg/kg are administered. Equianalgesic doses of sufentanyl are 3 - 5 mcg/kg (some cases up to 10 mcg/kg). Extubation is usually accomplished post operatively in the intensive care unit.

c. Monitored Anesthesia Care

6. What is the author's preferred method of anesthesia technique and why?

  1. What prophylactic antibiotics should be administered? Based on guidelines the authors routinely use a second generation cephalosporin such as cefuroxime 50 mg/kg. For children weighing more than 30 kg we administer the standard adult dose of 1.5 gm. The first dose should be given within 1 hour of incision and the second dose after separation from cardiopulmonary bypass and conclusion of modified ultrafiltration. Guidelines for antimicrobial prophylaxis for cardiac surgery state: 1) antimicrobial prophylaxis should be given to all patients undergoing cardiac surgery; 2) First or second-generation cephalosporins (cefazolin or cefuroxime) are the antibiotics of choice. The American Heart Association guidelines state that cefuroxime is superior in efficacy to other cephalosporins; 3) duration of antimicrobial prophylaxis use should not be longer than 48 hours; 4) the timing of the first dose should be given within 60 minutes prior to the skin incision.

  2. What can I do intraoperatively to assist the surgeon and optimize patient care? When the diseased aortic valve is replaced by the patient's own pulmonary valve and a pulmonary allograft is used to replace the pulmonary valve, the anesthesiologist can assist the surgeon in several ways. First, transesophageal echocardiography is used to measure the aortic annulus and evaluate the pulmonary valve apparatus. The size discrepancy between the pulmonary autograft and the aortic annulus should not exceed 2 mm. The goal is to prevent incompetence of the newly transplanted autograft. TEE is also used to assure the normal origin and course of the coronary arteries. The coronary arteries are excised and re-implanted onto the newly transposed pulmonary autograft. A continuous infusion of nitroglycerine (1-2 mcg/kg/min) is used to prevent coronary spasm. Secondly, a critical portion of the Ross operation is separation of the pulmonary trunk from the right ventricular outflow tract. During surgical dissection, injury to the first septal branch of the left anterior descending coronary artery is possible. Assiduous attention must be paid to the electrocardiogram for the occurrence of ST segment changes indicative of myocardial ischemia. In addition, a cell saver is used to decrease blood transfusion. Antifibrinolytics are often used to minimize the risk of bleeding. We use aminocaproic acid (AmicarR) 150 mg/kg bolus over 30 minutes, then an infusion of 33 mg/kg/hour). Some institutions use different doses (100 mg/kg bolus after induction, 100 mg/kg on pump, and 100 mg/kg after coming off CPB). Still other centers utilize tranexamic acid (loading dose of 30 mg/kg, then 2mg/kg on pump and infusion at 10 mg/kg/ hour). Goals after CPB include tight control of arterial blood pressure to both 1) prevent bleeding from the arterial anastomoses (use nitroprusside or nicardipine infusion) and 2) to provide for sufficient blood pressure to maintain coronary perfusion. TEE is used to check for regional wall motion abnormalities and intracavitary air. There is a risk of life threatening arrhythmias due to air embolism. Very small amounts of air can be dislodged into the reimplanted coronaries leading to ventricular fibrillation during chest closure or when moving the patient from the operating room table to the ICU bed. It is advisable to have an external pacemaker/defibrillator pad on the patient and cardioverter/defibrillator on continuously on stand-by including during transport to ICU. TEE can also demonstrate coronary abnormalities that may prompt surgical revision. It is advisable to avoid left ventricular over distension (avoid volume overload) as this may place stress on the newly re-implanted coronary arteries.

  3. What are the most common intraoperative complications and how can they be avoided/treated? If the patient is undergoing redo sternotomy there is an increased risk of bleeding. This may necessitate rapidly going on CPB using femoral cannulation. It is advisable to have blood immediately available for rapid transfusion. These patients are at increased risk of myocardial ischemia. If aortic regurgitation is predominant, myocardial protection strategies include the use of retrograde cardioplegia through the coronary sinus. Air embolism is a particular concern. Meticulous attention is paid to clearing before separation from CPB. There is a risk of arrhythmias due to air in coronaries. For this reason, a cardioverter/defibrillator is immediately available at all times. Bleeding after heparin reversal with protamine is an ever-present concern, particularly after a long CPB time and extensive suture lines under high pressure. The most common cause of bleeding after CPB in these cases is platelet dysfunction. Factor deficiency is also common particularly in neonates. For this reason, component therapy with cryoprecipitate and fresh frozen plasma is common. A coagulation panel and/or thromboelastogram (TEG) can be useful to guide therapy for restoration of hemostasis. Low cardiac output due to decrease in myocardial function is treated with continuous infusions of intropic agents- typically epinephrine and milrinone. Heart block can be seen particularly with the Ross-Konno procedure. Temporary epicardial pacing wires are left in place for this reason.

  1. Cardiac complications- see above

  2. Pulmonary- Lung injury after CPB can be due to the deleterious pulmonary effects of bypass itself (surfactant depletion) or due to transfusion of multiple units of banked blood and blood-products (transfusion acquired lung injury or TRALI).

  3. Neurologic: There is a small but present risk of stroke or CNS injury due to CPB. Seizures after by bypass can occur in up to 20% of neonates.

a. Neurologic

b. If the patient is intubated, are there any special criteria for extubation?

Patients undergoing the Ross procedure are typically extubated in the intensive care unit after surgery. In addition to the usual clinical criteria of normothermia and adequate muscle strength, the patient should demonstrate stable hemodynamics and the absence of bleeding from chest tubes and mediastinal drains.

c. Postoperative management

  1. What analgesic modalities can I implement? We utilize multimodal analgesia which includes intravenous acetaminophen, opioids, and alpha 2 adrenergic agonists such as dexmedetomidine. We avoid NSAIDS such as ketorolac because of their adverse effects on platelet function and the potential for exacerbating renal injury due to cardiopulmonary bypass. Older children (above 5 years of age) typically use a patient controlled analgesia device once tracheal extubation occurs.

What's the Evidence?

Ross, DN. "Replacement of aortic and mitral valves with a pulmonary autograft". Lancet. vol. 2. Nov 4 1967. pp. 956-958.

Schoof, PH, Cromme-Dijkhuis, AH, Bogers, JJ. "Aortic root replacement with pulmonary autograft in children". J Thorac Cardiovasc Surg. vol. 107. Feb 1994. pp. 367-373.

Dacey, LJ. "Pulmonary homografts: current status". Curr Opin Cardiol. vol. 15. Mar 2000. pp. 86-90.

Chauhan, S, Gharde, P, Bisoi, A, Kale, S, Kiran, U. "A comparison of aminocaproic acid and tranexamic acid in adult cardiac surgery". Ann Card Anaesth. vol. 7. Jan 2004. pp. 40-43.

Watabe, A, Saito, H, Harasawa, K, Moriomoto, Y. "Anesthetic management of severe aortic regurgitation in an infant repaired by Ross procedure". J Anesth. vol. 23. 2009. pp. 270-274.

Bonow, RO, Carabello, BA, Chatterjee, K. "2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of patients with valvular heart disease):endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons". Circulation. vol. 118. Oct 7 2008. pp. e523-661.

Kadner, A, Raisky, O, Degandt, A. "The Ross procedure in infants and young children". Ann Thorac Surg. vol. 85. Mar 2008. pp. 803-808.

Sievers, HH, Stierle, U, Charitos, EI. "Major adverse cardiac and cerebrovascular events after the Ross procedure: a report from the German-Dutch Ross Registry". Circulation. vol. 122. Sep 14 2010. pp. S216-223.

Stulak, JM, Burkhart, HM, Sundt, TM. "Spectrum and outcome of reoperation after the Ross procedure". Circulation. vol. 122. Sep 21 2010. pp. 1153-1158.

Martin, K, Gertler, R, Liermann, H. "Switch from aprotinin to {varespsilon}-aminocaproic acid: impact on blood loss, transfusion, and clinical outcome in neonates undergoing cardiac surgery". Br J Anaesth. Aug 19 2011.

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