Surgical Repair of Transposition of the Great Arteries in Neonates With Persistent Pulmonary Hypertension

Surgical Repair of Transposition of the Great Arteries in Neonates With Persistent Pulmonary Hypertension Giovanni Battista Luciani, MD, Anthony C. Chang, MD, and Vaughn A. Starnes, MD Divisions of Cardiothoracic Surgery and Cardiology, Childrens Hospital Los Angeles, and Departments of Surgery and Pediatrics, University of Southern California School of Medicine, Los Angeles, California Background. Pulmonary hypertension due to persistent fetal circulation is rarely associated with transposition of the great arteries and intact ventricular septum. Previous attempts at management of affected neonates using prostaglandin E1 and balloon atrial septotomy followed by surgical repair have been largely unsuccessful. Methods. Between September 1992 and April 1995, 45 neonates underwent repair of transposition of the great arteries with the arterial switch operation. Two patients (4%) with transposition of the great arteries and intact ventricular septum presented with profound reversed differential desaturation and right-to-left shunting at the level of the ductus arteriosus after balloon atrial septotomy. A diagnosis of persistent pulmonary hypertension was established and both neonates entered an experimental management protocol using inhaled nitric oxide and rapid arterial switch operation. Results. Preoperative hemodynamic stabilization was achieved in 1 patient using 40 parts per million of inhaled nitric oxide, whereas the other required in addition extracorporeal membrane oxygenation for severe biventricular dysfunction. Both underwent successful surgical repair 4 to 5 after admission, but received postoperatively 1 week of inhaled nitric oxide therapy for persistent pulmonary hypertension. Follow-up echocardiography at 3 months showed good biventricular function and normal geometry of the ventricular septum, suggesting low pulmonary artery pressure, in both. Conclusions. A management protocol using inhaled nitric oxide and extracorporeal membrane oxygenation followed by the arterial switch operation was successfully used in neonates with transposition of the great arteries, intact ventricular septum, and persistent pulmonary hypertension. Wider use of preoperative and postoperative inhaled nitric oxide may improve the surgical outcome of this difficult subset of patients. (Ann Thorac Surg 1996;61:800-5) he results of the surgical repair of transposition of the T great arteries (TGA) with intact ventricular septum (WS) using the arterial switch operation (ASO) are well documented, with a perioperative mortality of 2% to 5% and a neglegible late mortality [1]. Aside from anatomic variables, there exist physiologic variables that represent incremental risk factors for early mortality [1, 2]. Among these is the presence of pulmonary hypertension (PHT) due to persistent fetal circulation, which is associated with about 1% to 2% of all cases of TGA/IVS [2-5]. Management of these patients using balloon atrial septotomy (BAS) and prostaglandin E 1 (PGE1) infusion alone has yielded uniformly poor results [3-5]. Recent attempts at hemodynamic stabilization by decreasing the pulmonary vascular resistance with alkalinization and early surgical correction with the ASO have been more encouraging [5, 6]. We report our preliminary clinical experience with 2 neonates presenting with TGA/IVS and PHT who did not respond to previously proposed medical treatment. The use of inhaled nitric oxide (NO) and Accepted for publication Oct 11, 1995~ Address reprint requests to Dr Luciani, Division of Cardiovascular Surgery, University of Verona, OCM Piazzale Stefani 1, Verona, 37126, Italy. extracorporeal membrane oxygenation (ECMO) allowed for adequate preoperative and postoperative support and successful surgical repair with the ASO. Patients and Methods Between September 1992 and April 1995, 45 neonates with TGA underwent surgical repair with the ASO. Twenty-six patients presented with TGA/IVS, whereas 19 had TGA and ventricular septal defect. All patients with TGA/IVS (26) and 10 with TGA/ventricular septal defect underwent BAS at birth to establish adequate atrial level mixing. During this study period, 2 neonates (4%) who presented with profound cyanosis and were diagnosed with TGA/1VS at birth remained profoundly cyanotic after BAS (arterial oxygen saturation [SaO2] = 40% to 50% on an inspired oxygen fraction of 1.0). Given the echocardiographic evidence of unidirectional right-to-left shunting at the ductal level in both, the diagnosis of TGA/IVS/PHT was reached. Nitric Oxide Investigative Protocol Evidence of unidirectional right-to-left shunting at the ductal level and profound desaturation on mechanical 1996 by The Society of Thoracic Surgeons 0003-4975/96/$15.00 Published by Elsevier Science Inc SSDI 0003-4975(95)01089-0

Ann Thorac Surg LUCIANI ET AL 801 1996;61:800-5 PULMONARY HYPERTENSION IN TRANSPOSITION ventilation with an inspired oxygen fraction of 1.0, PGE 1 infusion, narcotic anesthesia, and neuromuscular blockade was used as indication for a trial of NO therapy. Measurements of hemodynamic profile (heart rate, mean arterial blood pressure, central venous pressure, and mean pulmonary arterial pressure) as well as arterial and mixed venous blood gases were made at baseline and during the induction phase of the NO inhalation therapy. The protocol for induction consisted of progressive increments of the NO dose (5, 20, 40, and 80 ppm) every 15 minutes for the first hour. After induction, weaning back to the maintenance dose was rapidly done. The maintenance dose was identified as the dose at which an appreciable (->20% change from baseline) hemodynamic benefit (increase in SaO 2 or increase in mean systemic pressure or decrease in mean pulmonary artery pressure or decrease in metabolic acidosis) could be derived. During this study period, no ventilator changes were made and no drug infusions were altered. An attempt to wean the NO to the lowest effective dose was routinely made every 24 hours if hemodynamic stability and arterial oxygenation were maintained. Monitoring of toxicity was done by surveillance of the methemoglobin level and the percentage of inhaled nitrogen dioxide. Methemoglobin levels, expressed as percent of total hemoglobin, were measured every 3 hours during the therapy with a cooximeter (AV Laboratories, Graz, Austria). The chemiluminescence analyzer (Thermoenvironmental Instruments, Franklin, MA) used to continuously monitor inhaled NO was also used to assess levels of nitrogen dioxide. The protocol dictated suspension of inhaled NO therapy if the methemoglobin level was 5% or greater, or if the nitrogen dioxide level was 5 ppm or greater. Methods of Operation All ASOs were performed using previously published techniques [1], under deep hypothermic (20 C core temperature) low-flow perfusion (50 ml.kg 1. rain-l). Cold (4 C) sanguineous cardioplegia (12 to 15 ml/kg) and continuous cold (4 C) saline pericardial irrigation were used for myocardial protection. Infusion of cold cardioplegia in the neo-aortic root was routinely repeated only once, upon completion of the coronary translocation and anastomosis of the ascending aorta to the pulmonary root. Separation from cardiopulmonary bypass was aided by the use of inotropic agents (dopamine, 5 /~g kg 1. min -1, and dobutamine, 5/~g kg -1 rain-l). Intraoperative transesophageal echocardiography (TEE) was routinely performed before and after the ASO to assess the adequacy of the repair. Methods of Extracorporeal Membrane Oxygenation Venoarterial perfusion with gravity drainage was used in all neonates with TGA who required preoperative or postoperative ECMO support. Standard cannulation involved surgical dissection of the internal jugular vein and carotid artery, with direct-vision catheterization of both vessels. Transesophageal echocardiography was used to evaluate the recovery of ventricular function upon weaning from ECMO support. Results There was only one operative death in the entire series, giving an early (<30 ) mortality of 2%. The patient was a neonate with TGA/VSD and parachute mitral valve who was judged to have postoperative severe left ventricular dysfunction. There was one late death (2%), occurring 4 months after successful ASO, in 1 of the 2 reported patients who presented with TGA/IVS/PHT. The overall 1-month, 12-month, and 24-month survival was 97%, 95%, and 95%, with a total follow-up of 610 patient-months and mean of 13.8 -- 9.7 months (range, 1 to 31 months). Clinical Course of Patients With Transposition of the Great Arteries, Intact Ventricular Septum, and Pulmonary Hypertension PATIENT 1. Patient 1 was a 4-day-old boy with TGA/IVS who presented with reversed differential cyanosis and systemic hypotension, which persisted after two BAS procedures on PGE 1 infusion (Fig 1). Emergency transfer to our institution for NO therapy and possible surgical treatment was prompted. On arrival, the patient required resuscitation with atropine and epinephrine boluses and a short period of closed chest compression for profound hypotension (40/20 mm Hg) and bradycardia (40 beats/ rain). Admission ph was 6.69, with an arterial oxygen tension of 21 mm Hg, arterial carbon dioxide tension of 68 mm Hg, and base excess of -28 on full mechanical ventilatory support. Right-to-left ductal and atrial level shunting with profound biventricular dysfunction were evident at echocardiography. While the ECMO circuit was being assembled, the first trial of inhaled NO therapy was begun. At 40 ppm of NO, neutralization of the ph and improvement in SaO 2 were achieved (ph, 7.46; arterial carbon dioxide tension, 21 mm Hg; arterial oxygen tension, 31 mm Hg; base excess, -7.0; SaO2, 59%). Because the infant remained anuric and vasoconstricted, a repeat echocardiogram on 40 ppm of inhaled NO and maximal ventilatory support was done, showing now bidirectional shunting at the ductal level but persistent biventricular dysfunction. Total cardiopulmonary bypass (100 to 120 ml. kg 1. rain-l) was thus established using ECMO to completely unload the left ventricle from the increased pulmonary vascular resistance and allow for recovery of right and left ventricular function. Bypass was continued until appropriate recovery of biventricular function and bidirectional ductal shunting were observed at TEE on gradual weaning of the ECMO support. After 5, the patient was transferred to the operating room and underwent ASO repair of TGA/IVS while on ECMO. Intraoperative TEE demonstrated satisfactory biventricular function on high inotropic support (dopamine, 10 /~g kg i. rain 1; dobutamine, 10 /~g kg -1 rain-l; and epinephrine, 0.05/~g. kg l. rain 1) and PGE 1 infusion (0.05 ~g kg -I rain 1). Cardiopulmonary by-

802 LUCIANI ET AL Ann Thorac Surg PULMONARY HYPERTENSION IN TRANSPOSITION 1996;61:800-5 120! 09 40 20 4o ECMO ASOI ECMO ECMOotI NO 4o~pm ECMO off/ NO t0ppm NOoff o i I l l l l h h l l l l l l ~ o I I I I ~ 1 I I ±_ i I ~ _.1 ~ I J k i I e~ubatlon 1-7 - Fig 1. Preoperative and postoperative clinical course of patient 1 and the response to nitric oxide (NO) and extracorporeal membrane oxygenation (ECMO). (ASO = arterial switch operation; BE = base excess; PAP = pulmonary arterial pressure; SaO 2 = arterial oxygen saturation; SAP = systemic arterial pressure.) pass could therefore be discontinued; the sternotomy wound was left open to allow for cardiocirculatory stabilization. Postoperatively, anuria, systemic hypotension (52/38 mm Hg), pulmonary hypertension (38/22 mm Hg), systemic venous hypertension (central venous pressure, 20 to 22 mm Hg), and mixed venous desaturation (myocardial oxygen consumption, 50% to 52%) persisted. In an attempt to control the right ventricular failure due to increased pulmonary vascular resistance, inhaled NO was restarted (second trial). Using 40 ppm of inhaled NO, the hemodynamics temporarily stabilized (systemic pressure, 63/42 mm Hg; pulmonary pressure, 28[14 mm Hg; central venous pressure, 18 mm Hg; and myocardial oxygen consumption, 61%), but metabolic acidosis and oliguria persisted. Given the evidence of left ventricular dysfunction at TEE, despite maximal inotropic support, ECMO support was restarted 6 hours after surgical repair. On this occasion, it was felt that both pulmonary hypertension and left ventricular "deconditioning,'" due to preoperative total cardiopulmonary bypass, were responsible for the hemodynamic deterioration. Discontinuation of ECMO was achieved after 6 of support, using high-dose inotropic support (dopamine, 8 /zg kg -1 rain-l; dobutamine, 10 p,g. kg 1. min 1; and epinephrine, 0.05 /zg kg 1 min 1) and inhaled NO (third trial). Indications for NO therapy were persistence of mild pulmonary hypertension (32/16 mm Hg) and, more importantly, profound arterial desaturation (SaO 2, 65%), thought to be due to pulmonary microatelectasis and edema resulting in ventilation/perfusion mismatch. Improvement in SaO 2 (86% to 89%) and decrease in pulmonary arterial pressure (24/15 mm Hg) were observed using 10 ppm of inhaled NO. Delayed sternal closure was possible 3 after restarting the NO therapy and 8 after the ASO. Support with NO at 10 ppm was prolonged for 10, until clinical (arterial oxygen tension from 34 to 94 mm Hg) and radiologic improvement of the adult respiratory distress syndrome was obtained. After weaning from the NO therapy, the patient's recovery progressed slowly but steadily; extubation was possible on postoperative day 41 and transfer from the intensive care unit 2 later. The infant was discharged on postoperative day 51 in good clinical condition on oral digitalis and furosemide therapy. A follow-up echocardiogram 4 months after discharge showed good biventricular function and normal geometry of the ventricular septum, suggesting less than half systemic pulmonary artery pressure. PATIENT 2. The patient was a full-term female infant, cyanotic at birth, diagnosed with TGA/IVS, who, after a first unsuccessful BAS, was transferred to our hospital for further medical and surgical management (Fig 2). Shortly after admission, she underwent a second BAS, which resulted in creation of a large interatrial communication. The patient remained profoundly cyanotic (upper limb pulse oxymeter SaO 2, 35% to 50%; lower limb, 55% to 65%) despite full mechanical ventilatory support under neuromuscular blockade with narcotic (fentanyl, 5 /zg kg 1.min 1) andpge linfusion(0.5/~g.kg 1.min 1). Systemic hypotension (55/30 mm Hg), peripheral vasoconstriction, and metabolic acidosis (base excess, -8), were also present. A repeat echocardiogram showed an adequate-sized atrial septal defect but unidirectional shunt at the atrial and ductal level. A presumptive diagnosis of TGAIIVS/PHT was established and inhaled NO therapy at 40 ppm was begun (first trial). Rapid improvement of the SaO 2 reaching the 75% to 80% range, stabilization of the systemic blood pressure, and improved peripheral perfusion were observed. Four after admission, the neonate underwent an uncomplicated ASO. The sternotomy wound was left open to allow for cardiocirculatory stabilization. Discontinuation of cardiopulmonary bypass was attempted using dopamine, 5 /zg kg i min 1, and dobutamine, 5 /~g kg -1 min l. However, the intraoperative pulmonary artery pressures reached systemic

Ann Thorac Surg LUCIANI ET AL 803 1996;61:800-5 PULMONARY HYPERTENSION IN TRANSPOSITION NO40 ppm ASOI NO 10 ppro NOoff extubation NOoIf '2L............... 8 I ~60 20 o i i ] l l l l l l l l l [ l l " I 10 ~o~, I i l r l l l L I I I I I _ ~ I I I I I d I I ~ 1 I o I I I i 1 I I Fig 2. Preoperative and postoperative clinical course of patient 2 and the response to nitric oxide (NO). (ASO = arterial switch operation; BE - base excess; PAP = pulmonary arterial pressure; SaO 2 arterial oxygen saturation; SAP = systemic arterial pressure.) values (54/38 mm Hg versus 55/20 mm Hg, systemic versus pulmonary) and TEE showed flattening of the interventricular septum with biventricular dysfunction. Because PGE1 infusion did not prove beneficial, inhaled NO therapy (second trial) at 10 ppm was restarted in the operating room. Again, gradual reduction of the pulmonary pressure and an increase in the systemic pressure and SaO2 were witnessed. Treatment with NO was continued until stabilization of the systemic (mean, 48 to 53 mm Hg) and pulmonary artery (mean, 14 to 20 mm Hg) pressures was achieved. The sternotomy wound was closed 4 after the ASO. Weaning from NO was possible on postoperative day 5, and extubation was done on postoperative day 7. Recovery of the patient was slowed by repeated episodes of aspiration of gastric contents, due to gastroesophageal reflux, and respiratory failure, due to coexistent bronchopulmonary dysplasia, resulting in intermittent need for ventilatory support. Transthoracic echocardiog- raphy I month after the ASO showed brisk biventricular function with no flattening of the ventricular septum, suggesting normal pulmonary artery pressure. The further clinical course of the patient was complicated by multiple episodes of sepsis, the last of which resulted in irreversible hepatic and renal failure, ultimately leading to death of the infant 4 months after the successful ASO. Comment The analysis of a decade of surgical experience with the ASO for transposition of the great arteries has shown very low (2% to 5%) early mortality and negligible late mortality [1, 2]. Our early results with 45 neonates undergoing this operative procedure continue to support this treatment modality. The wider application of the BAS and the earlier timing of anatomic repair, as well as the evolution of preoperative and postoperative intensive care and surgical techniques, have been responsible for the improved survival and quality of life after the ASO. However, there remain anatomic, a few physiologic, and procedural variables that have been identified as incremental risk factors for perioperative morbidity and mortality [1, 2]. Among such factors, the rare association of TGA with persistent fetal circulation, responsible for neonatal pulmonary hypertension, has been shown to be extremely unfavorable [3-5]. The exact prevalence of TGA/IVS/PHT is not well established. Review of the scattered reports of affected patients suggests that 1% to 3% of all neonates with TGA/IVS will present with persistent fetal circulation [1, 3, 4]. The pathologic substrate of TGA/IVS/PHT has been shown to be the increased thickness of the wall of the pulmonary arterioles (<150/~m diameter), due to extension of smooth muscle to the peripheral vessels [3, 5]. Based on experimental evidence, intrauterine hypoxia has been proposed as one mechanism accounting for the increase in distal muscularity [3I. The pathophysiology of TGA/IVS/PHT is rather complicated. Although infusion of PGE 1 (initially) and creation of a large interatrial communication by means of a BAS (subsequently) seem rational in a neonate presenting with TGA/IVS and profound cyanosis, inability of the patient to improve after these maneuvers is to be expected in the presence of PHT [4, 5]. Due to the increased atrial and ductal anatomic right-to-left shunting promoted by BAS and PGE 1 infusion, the amount of blood bypassing the pulmonary circulation increases, making the systemic oxygen desaturation more profound [5]. Analysis of the overall experience with the management of TGA/IVS/PHT underlines the uniformly poor response to PGE 1 infusion and BAS alone, with half of the reported patients requiring multiple septotomies or surgical septectomy (Table 1). In addition, hemodynamic instability persisted in the majority of patients, leading to death before surgical repair or to the need for emergent physiologic repair using the ASO (see Table 1). Although application of the atrial switch procedure to neonates with TGA/WS/PHT has proved unsuccessful [3-5], more recent attempts at preoperative stabilization of these

804 LUCIANI ET AL Ann Thorac 8urg PULMONARY HYPERTENSION IN TRANSPOSITION 1996;61:800-5 Table 1. Mangement of Neonates With Transposition of the Great Arteries~Intact Ventricular Septum and Pulmonary Hypertension First No. of PGE 1 BAS/BH NO ECMO Repair Surgical Author Year Patients (patients) (patients) (patients) (patients) (patients) Outcome Follow-up Hawker 1974 4 None 4/1 None None 2 atrial/2 none 3 dead/1 alive a Lost to follow-up Dick 1981 2 1 2b[1 None None 1 atrial/1 none 2 dead... Chang 1991 2 2 2/none None None 2 ASO 2 alive 2 alive (2 too) Kumar 1993 3 3 3b[2 None None 2 atrial/1 ASO 3 dead... Luciani 1996 2 2 2b/none 2 ~ 2 c 2 ASO 2 alive 1 alive (4 too)/1 dead (4 too) a Patient who underwent only a Blalock-Hanlon atrial septectomy, b Multiple atrial septotomies, c Preoperative and postoperative support. ASO - arterial switch procedure; atrial = atrial switch procedure; BAS balloon atrial septotomy; BH - Blalock-Hanlon atrial septectomy; ECMO = extracorporeal membrane oxygenation; NO = nitric oxide; PGE 1 -- prostaglandin Ev critically ill infants and early anatomic repair with the ASO have yielded encouraging results (5) (see Table 1). In an analysis of 2 such cases, Chang and associates [6] recommended use of BAS to increase 02 delivery and narcotic anesthesia with neuromuscular blockade to reduce 0 2 consumption as first-line measures to improve the hernodynamics. Control of the pulmonary vascular resistance by alkalinization (hyperventilation, sodium bicarbonate infusion) or by infusion of vasodilators (PGE 1) was also advised to further ameliorate the circulatory instability. Despite these maneuvers, however, the 2 neonates reported continued to show intermittent crises of profound desaturation and systemic hypotension until the time of the ASO [6]. Our experience with TGAI1VSIPHT confirms the limitations of the previously proposed treatment modalities. The two neonates described in the present study underwent multiple BAS procedures. In spite of the infusion of PGE 1 and the satisfactory anatomic result of BAS, both patients continued to deteriorate. Only using inhaled NO therapy [7], associated with ECMO support in 1 patient with biventricular dysfunction, could the cardiocirculatory conditions be effectively stabilized. Decrease in the pulmonary vascular resistance, indirectly assessed by the appearance of bidirectional ductal level shunting at echocardiography, occurred 3 to 5 after the initiation of supportive therapy and was used as a criterion to time the ASO. The complete resolution of PHT, however, did not prove to be rapid, as both neonates showed systemic pulmonary artery pressures after the ASO and required a second trial of NO therapy. Although ECMO may prove life-saving when ventricular failure combines with PHT, the need for stabilization of the pulmonary circulation must be carefully weighed against the risk of left ventricular deconditioning, as it appeared in 1 of the 2 patients who required a second period of complete life support after the ASO. Based on experimental evidence [8], one could speculate that the duration of ECMO support before the ASO should not exceed 3. Inhalation therapy with NO proved effective and safe in both cases, as the methernoglobin and nitrogen dioxide levels never rose to more than 3% and 1 ppm, respectively. Even though the ultimate outcome of 1 infant was compromised by the presence of associated lesions [2], the present experience validates the use of inhaled NO and ECMO to achieve preoperative and postoperative control of PHT. With the above treatment modality, both neonates underwent a successful repair with the ASO and showed echocardiographic evidence of normal pulmonary pressure 2 to 3 weeks after operation. In conclusion, PHT due to persistent fetal circulation should be suspected whenever profound cyanosis persists despite PGE 1 infusion and successful BAS in neonates with TGA/IVS. We recommend preoperative and postoperative stabilization with inhaled NO combined with early anatomic surgical repair by means of the ASO. Extracorporeal membrane oxygenation support may be needed when PHT is associated with severe ventricular dysfunction. References 1. Wernovsky G, Mayer JE, Jonas RA, et al. Factors influencing early and late outcome of arterial switch operation for transposition of the great arteries. J Thorac Cardiovasc Surg 1995;109:289-302. 2. Kirklin JW, Blackstone EH, Tchervenkov CI, Castafieda AR, Congenital Heart Surgeon Society. Clinical outcomes after the arterial switch operation for transposition. Patient, support, procedural, and institutional risk factors. Circulation 1992;86:1501-15. 3. Dick M, Heidelberger K, Crowley D. Quantitative morphometric analysis of the pulmonary arteries in two patients with D-transposition of the great arteries and persistent fetal circulation. Pediatr Res 1981;15:1397-401. 4. Hawker RE, Freedom RM, Rowe RD. Persistence of fetal pattern of circulation in transposition of the great arteries. Hopkins Med 1974;134:107-17. 5. Kumar A, Taylor GP, Sandor GG, Patterson MW. Pulmonary vascular disease in neonates with transposition of the great arteries and intact ventricular septum. Br Heart J 1993;69: 442-5. 6. Chang AC, Wernovsky G, Kulik TJ, Jonas RA, Wessel DL. Management of the neonate with transposition of the great arteries and persistent pulmonary hypertension. Am J Cardiol 1991;68:1253-5. 7. Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med 1993;2002-12. 8. Di Donato RM, Fujii AM, Jonas RA, Castafieda AR. Agedependent ventricular response to pressure overload. Considerations for the arterial switch operation. J Thorac Cardiovasc Surg 1992;104:713-22.

Ann Thorac Surg LUCIANI ET AL 805 1996;61:800-5 PULMONARY HYPERTENSION IN TRANSPOSITION INVITED COMMENTARY Luciani and colleagues herein describe the course of two neonates with the rare combination of transposition of the great arteries/intact ventricular septum and severe, reactive pulmonary hypertension. This anatomic and physiologic combination is uniformly fatal without prompt recognition of the abnormal physiology and institution of intensive support geared at minimizing pulmonary vascular resistance and increasing intercirculatory mixing. The last decade has seen the introduction of pulmonary-specific vasodilation (nitric oxide) and "portable" cardiopulmonary support (extracorporeal membrane oxygenation); both of these modalities were used in this small series. As Luciani and colleagues clearly state, the diagnosis of persistent pulmonary hypertension must be suspected in any neonate with transposition who remains profoundly cyanotic after adequate balloon atrial septostomy and maintenance of ductal patency with prostaglandin E 1. After establishment of anatomic sites for intercirculatory mixing, the single best predictor of arterial oxygen saturation is the magnitude of pulmonary blood flow. In transposition of the great arteries, the aortic-to-pulmonary artery shunt at the ductal level must be balanced by a left atrial-to-right atrial shunt to maintain equal volumes in the two parallel circulations. Reduction of total pulmonary blood flow due to pulmonary arteriolar vasoconstriction results in decreased left atrial return of oxygenated blood. This results in a dramatic decrease in both effective pulmonary and systemic flow. The ascending aorta is desaturated to a greater extent than the descending aorta, further decreasing myocardial oxygen delivery through the coronary arteries and frequently resulting in ventricular dysfunction. This complex "'spiral" needs to be addressed promptly or will result in death. It is important to initially manage these patients by decreasing total body oxygen demand (sedation, paralysis), increasing oxygen delivery (myocardial support, treatment of anemia), and instituting pharmacologic management of pulmonary hypertension. The use of inhaled nitric oxide has been shown to be beneficial in many forms of pulmonary hypertension and was documented to have similar beneficial effects in both patients presented in this report. The use of extracorporeal membrane oxygenation, while stabilizing the circulation before surgical intervention, does significantly reduce preload of the myocardium and may result in "deconditioning" as was described. With this experience in mind, one should advocate a gradual wean of extracorporeal membrane oxygenation to allow gradual "reconditioning" of the ventricular myocardium for a few before surgical intervention. Gil Wernovsky, MD Cardiac Intensive Care Unit Children's Hospital of Philadelphia 34th St and Civic Center Blvd Philadelphia, PA 19104