D-transposition of the great arteries (D-TGA) is a congenital heart defect in which normal atrioventricular connections coexist with discordance of ventriculoarterial connections. Parallel circulations result with the left heart recirculating oxygenated blood to the lungs, while the right heart recirculates deoxygenated blood to the brain and body. TGA accounts for 5% to 7% of congenital heart defects.1
Infants with D-TGA rely on the presence of communication(s) between the left (pulmonary) and right-sided (systemic) circulations to allow oxygenated blood to mix into the systemic output. In most children with D-TGA, communications are in the form(s) of a patent foramen ovale (PFO), atrial septal defect, ventricular septal defect, patent ductus arteriosus, or bronchopulmonary collaterals. Rarely, infants with D-TGA do not have mixing between right and left circulations, and death occurs quickly after separation from the placenta.2–4
We report a case of a full-term infant boy with D-TGA, intact atrial and ventricular septa, and flow-restricted ductus arteriosus in whom veno-venous (VV) extracorporeal membrane oxygenation (ECMO) and open atrial septectomy immediately followed scheduled cesarean delivery. This manuscript was reviewed by the IRB who approved submission without parental consent.
Our perinatal physicians diagnosed D-TGA without ventricular septal defect in a fetus after their evaluation of a 35-year-old G4P3 mother. Fetal echocardiogram demonstrated D-TGA with a small PFO, intact ventricular septum, and flow-restricted ductus arteriosus. Serial echocardiograms documented closure of the PFO by 29.5 weeks. Left atrial enlargement, bowing of the atrial septum, and dilated pulmonary veins suggested left atrial and pulmonary venous hypertension. The mother declined transfer to a center where an ex-utero intrapartum therapy procedure could be used to facilitate initiation of ECMO. The parents requested alternative options for delivery. A multidisciplinary team met to discuss the infant’s perinatal management. Cardiologists emphasized the flow restriction present between right and left circulations, confirmed that the parents understood the significance of the lesion, and informed the group that based on literature review the infant might suffer hypoxemic cardiac arrest within 1 minute of birth.2–4 Options for management included combinations of (a) immediate initiation of ECMO (VV or veno-arterial [VA]), (b) balloon atrial septostomy, and (c) an open atrial septectomy.
Our cardiologists were not confident they could accomplish an effective balloon atrial septostomy within the brief resuscitation window, and further felt that effectiveness of atrial mixing would be limited by the thickened septum. Cardiovascular surgeons did not believe they could establish transthoracic cardiopulmonary bypass (CPB) as rapidly as ECMO could be initiated via neck vessels and noted that chest compressions would have to be interrupted during transthoracic cannulation. Our cardiologists emphasized that the final selected plan needed to relieve left heart distention, pulmonary venous hypertension, and establish definitive intercirculation mixing.
We selected perinatal institution of VV ECMO via the right internal jugular vein, with conversion to VA ECMO (right carotid artery) in the event of circulatory failure. Open atrial septectomy on CPB would immediately follow ECMO initiation as the most definitive procedure to meet the physiologic objectives. It was anticipated that the patient would likely require postoperative VV ECMO until lung compliance improved, circulatory mixing was adequate, and pulmonary vascular reactivity was minimal.
The plan specified scheduled cesarean delivery at 37 weeks to be performed in an operating suite in the children’s hospital to ensure the presence of all principal participants. The infant would be moved to the adjacent pediatric cardiothoracic surgery suite for the initiation of VV ECMO and atrial septectomy. Four rehearsals were performed to refine the sequence of clinical interventions, location of equipment and specialty teams, and methods to minimize nonessential communication (Fig. 1). Alternate contingencies were prepared for potential failure at each step in the resuscitation sequence. Experienced nursing staff was selected to allow them to support multiple medical specialties.
Standard equipment for pediatric cardiovascular surgery was prepared. In addition, prostaglandin E1 infusion, ECMO circuit primed with type O negative red blood cells (hematocrit 40%), single dual-lumen VV ECMO cannula, and separate single-lumen VA ECMO cannulae were available. A syringe containing ketamine and atropine was provided for IM injection before umbilical cord ligation. Inhaled nitric oxide (iNO) was added to the inspiratory limb of the anesthetic circuit (20 ppm), and personnel were designated to perform chest compressions.
An infant boy (3.2 kg) was born by cesarean delivery under spinal anesthesia at 37 weeks gestation at 07:47 AM. While attached to the placenta, atropine sulfate (0.04 mg/kg) and ketamine (5 mg/kg) were injected into the infant’s quadriceps by the obstetrician to minimize hypoxia-mediated bradycardia, and allow for absorption of sympathomimetic parenteral anesthesia while spontaneous circulation was present. We chose immediate IM administration because (a) IV access might be difficult, (b) inhaled volatile anesthetic might not be able to be delivered to the segregated systemic circulation, and (c) volatile anesthesia might not be tolerated in this hemodynamically unstable infant.
The pharynx was suctioned, the umbilical cord was cut, and the infant was moved to the adjoining operating room. He was dried, and chest compressions were initiated as monitors were applied. The first anesthesiologist ventilated the lungs with 100% oxygen and iNO by mask. His initial heart rate was 79 bpm, and the oxyhemoglobin saturation (SpO2) was 50% by pulse-oximetry on the right hand. Differential cyanosis was not observed. IM succinylcholine (4 mg/kg) and rocuronium (2 mg/kg) were administered as monitors were placed. Other routes for medication administration were contemplated in the event of difficult IV access (intraosseous, endotracheal tube, umbilical vein), but the second anesthesiologist inserted a saphenous vein catheter before monitors were applied (by 07:48 AM), and administered IV epinephrine (5 mcg/kg) along with IV doses of rocuronium (1 mg/kg) and atropine (0.1 mg).
Chest compressions were stopped within 45 seconds when by 07:49 AM oxyhemoglobin saturations had increased to 57% to 65% and heart rate to 125 to 135 bpm. The infant’s trachea was intubated with a 3.0 cuffed endotracheal tube. Placement was confirmed by bronchoscopy due to the anticipated presence of minimal end-tidal carbon dioxide. By 07:51 AM, the neonatology team had inserted an umbilical venous catheter while the surgical team prepared the infant’s neck. IV heparin (50 units/kg), pancuronium (0.1 mg/kg), fentanyl (5 mcg/kg), and methylprednisolone (10 mg/kg) were administered via an umbilical venous catheter. Umbilical artery catheterization was abandoned when surgeons indicated they were ready to place their sterile drapes. Neck skin incision occurred at 07:52 AM, and his systolic blood pressure (SBP) remained 50 to 60 mm·Hg by noninvasive cuff.
The internal jugular vein was cannulated with a dual-lumen cannula. VV ECMO was begun at 08:01 AM. Oxyhemoglobin saturation increased from 50% to 60% to 87% to 89%, and heart rate increased from 120 to 160 bpm as ECMO flow was increased to 100 mL/kg/min. A right radial arterial catheter was inserted, and arterial blood gas analysis at 08:15 AM revealed pH 7.24, PaCO2 47 mm·Hg, PaO2 60 mm·Hg, and base deficit −7 meq/L. His lactic acid was 2.8 mmol/L. His SBP increased to 60 to 70 mm·Hg, fentanyl infusion was commenced (6 mcg/kg/h), and vancomycin (15 mg/kg), gentamycin (2.5 mg/kg), and sodium bicarbonate (2 meq/kg) were administered. Increased peak inspiratory pressure and small tidal volumes suggested diminished lung compliance. Activated clotting time was 180 to 200 seconds.
At 09:01 AM, median sternotomy for atrial septectomy commenced. At 09:34 AM, ECMO was discontinued, additional heparin was administered, and CPB was begun (activated clotting time >400 seconds). Isoflurane was administered via CPB oxygenator. At 09:45 AM, the aorta was cross-clamped, cardioplegia was administered, and atrial septectomy was performed. At 09:59 AM, the cross-clamp was removed, milrinone bolus (50 mcg/kg), milrinone (0.5 mcg/kg/min) and dopamine (5 mcg/kg/min) infusions were administered to maintain SBP >60 mm·Hg. Sevoflurane was added to the inhaled gas (0.1%–0.2%), fentanyl infusion continued (6 mcg/kg/h), prostaglandin E1 was discontinued, and VV ECMO was resumed. Opioid and volatile anesthetic were titrated while maintaining SBP 58 to 65 mm Hg.
Cardiopulmonary function improved as evidenced by improved oxyhemoglobin saturation, lung compliance, and radiographic appearance of the lungs. Brain ultrasonography did not reveal intraventricular hemorrhage. ECMO was discontinued on the third postoperative day.
Echocardiograms during the first week of life demonstrated normal biventricular function, adequate left to right atrial mixing, and increasing pressure gradient across, and blood flow through, the ductus arteriosus and nitric oxide and inotrophic support were gradually withdrawn. At 2 weeks of age, the patient underwent an arterial switch procedure. The patient’s postoperative course was uneventful. He is now 3 years old and has normal neurologic development and cardiovascular function. A ventriculoperitoneal shunt was required due to the development of hydrocephalus.
It is rare for newborn infants with D-TGA to lack communication between pulmonary and systemic circulations. Review of a multi-institutional prospective database, retrospective review of data at The Hospital for Sick Children (Toronto) and autopsy series suggest that 4% of infants with D-TGA die before repair.5,6 During a 10-year period at 1 medical center, 2 cases of infants with D-TGA, intact atrial and ventricular septum, and restricted ductus arteriosus were detected on autopsy.3 Surgical mortality for infants with D-TGA and adequate mixing between circulations is low in experienced centers. Therefore, detection and planning for delivery of infants with this lethal constellation is essential.7
The normal fetus receives oxygenated blood from the placenta via the umbilical vein and ductus venosus.8 Oxygenated ductus venosus flow is shunted through the foramen ovale to the left heart for delivery to the systemic circulation.8 Infants with D-TGA demonstrate the same preferential streaming patterns at the atrial level, resulting in delivery of oxygenated blood to the pulmonary arteries instead. Increased pulmonary artery oxygen tension results in decreased pulmonary vascular resistance, increased pulmonary blood flow, increased return to the left atrium, closure of the foramen ovale, diminished ductal shunting, and decreased diameter of the ductus arteriosus.8–12 The sum of these many factors determines net pulmonary circulation in the fetus. It is not understood that factors result in the development of this lethal circulation.
Antenatal restriction of the foramen ovale and constriction of the ductus arteriosus are associated with mortality after birth in infants with D-TGA.3,13,14 Ultrasound studies of humans and animals with D-TGA suggest that maladaptive changes occur in the last trimester of pregnancy.3,8,10,11 These findings, along with uniformly fatal outcomes of infants born with this circulation, underscore the importance of echocardiographic surveillance during the third trimester.
We used iNO during resuscitation recognizing that downstream obstruction of the left heart might be exacerbated by iNO but judged that potential benefits of transient improvement in oxygenation outweighed risk of exacerbation of pulmonary vascular congestion. We did not observe any benefit from iNO. In retrospect, it might have been withheld until after the atrial septectomy was performed.
Donofrio2 reported the management and outcome of a similar infant delivered emergently at 34 weeks gestation. The baby was born by cesarean delivery, underwent median sternotomy for placement of VA ECMO cannulae, and survived the immediate perinatal period. Unfortunately, the infant suffered intracranial hemorrhage and died after withdrawal of support.2 To our knowledge, planned VV ECMO after elective cesarean delivery, followed by open atrial septectomy in infants with TGA and flow-restricted circulation, has not been reported. Although ECMO has been used for many pre- and postoperative indications in infants with D-TGA,15–19 we could not identify a case in the literature describing successful, elective use of VV ECMO in the delivery room for this indication. The ELSO Registry does not contain information required to identify such cases (personal communication, Peter Rycus, ELSO).
We have reported the successful outcome of resuscitation of an infant born with D-TGA and inadequate systemic pulmonary mixing. VV ECMO and open atrial septectomy were used to resuscitate the infant. Prenatal definition of cardiac anatomy and flow patterns allowed the team to predict and prepare for physiologic consequences after birth. Multidisciplinary planning and practice contributed to minimal interference between clinical services and an optimal clinical outcome.
1. . Report of the New England Regional Infant Cardiac Program. Pediatrics. 1980;65(Suppl):375–461
2. Donofrio MT. Images in cardiovascular medicine. Premature closure of the foramen ovale and ductus arteriosus in a fetus with transposition of the great arteries. Circulation. 2002;105:e65–6
3. Maeno YV, Kamenir SA, Sinclair B, van der Velde ME, Smallhorn JF, Hornberger LK. Prenatal features of ductus arteriosus constriction and restrictive foramen ovale in d-transposition of the great arteries. Circulation. 1999;99:1209–14
4. Chiou HL, Moon-Grady A, Rodriguez R, Konia T, Parrish M, Milstein J. A rare lethal combination of premature closure of the foramen ovale and d-transposition of the great arteries with intact ventricular septum. Int J Cardiol. 2008;130:e57–9
5. Kirklin JW, Blackstone EH, Tchervenkov CI, Castaneda AR. Clinical outcomes after the arterial switch operation for transposition. Patient, support, procedural, and institutional risk factors. Congenital Heart Surgeons Society. Circulation. 1992;86:1501–15
6. Soongswang J, Adatia I, Newman C, Smallhorn JF, Williams WG, Freedom RM. Mortality in potential arterial switch candidates with transposition of the great arteries. J Am Coll Cardiol. 1998;32:753–7
7. Wernovsky G, Mayer JE Jr, Jonas RA, Hanley FL, Blackstone EH, Kirklin JW, Castaneda AR. Factors influencing early and late outcome of the arterial switch operation for transposition of the great arteries. J Thorac Cardiovasc Surg. 1995;109:289–301; discussion 301–2
8. Rudolph AM. Aortopulmonary transposition in the fetus: speculation on pathophysiology and therapy. Pediatr Res. 2007;61:375–80
9. Cohn HE, Sacks EJ, Heymann MA, Rudolph AM. Cardiovascular responses to hypoxemia and acidemia in fetal lambs. Am J Obstet Gynecol. 1974;120:817–24
10. Lewis AB, Heymann MA, Rudolph AM. Gestational changes in pulmonary vascular responses in fetal lambs in utero. Circ Res. 1976;39:536–41
11. Rasanen J, Wood DC, Debbs RH, Cohen J, Weiner S, Huhta JC. Reactivity of the human fetal pulmonary circulation to maternal hyperoxygenation increases during the second half of pregnancy: a randomized study. Circulation. 1998;97:257–62
12. Cassin S, Dawes GS, Mott JC, Ross BB, Strang LB. The vascular resistance of the foetal and newly ventilated lung of the lamb. J Physiol. 1964;171:61–79
13. Jouannic JM, Gavard L, Fermont L, Le Bidois J, Parat S, Vouhé PR, Dumez Y, Sidi D, Bonnet D. Sensitivity and specificity of prenatal features of physiological shunts to predict neonatal clinical status in transposition of the great arteries. Circulation. 2004;110:1743–6
14. Berry LM, Padbury J, Novoa-Takara L, Emmanouilides GC. Premature “closing” of the foramen ovale in transposition of the great arteries with intact ventricular septum: rare cause of sudden neonatal death. Pediatr Cardiol. 1998;19:246–8
15. Rogers AJ, Trento A, Siewers RD, Griffith BP, Hardesty RL, Pahl E, Beerman LB, Fricker FJ, Fischer DR. Extracorporeal membrane oxygenation for postcardiotomy cardiogenic shock in children. Ann Thorac Surg. 1989;47:903–6
16. Alexi-Meskishvili V, Nürnberg JH, Werner H, Lange PE, Hetzer R. Long-term extracorporeal membrane oxygenation in a newborn child after arterial switch operation. Cardiovasc Surg. 1996;4:258–60
17. Bisoi AK, Sharma P, Chauhan S, Reddy SM, Das S, Saxena A, Kothari SS. Primary arterial switch operation in children presenting late with d-transposition of great arteries and intact ventricular septum. When is it too late for a primary arterial switch operation? Eur J Cardiothorac Surg. 2010;38:707–13
18. Chauhan S, Malik M, Malik V, Chauhan Y, Kiran U, Bisoi AK. Extra corporeal membrane oxygenation after pediatric cardiac surgery: a 10 year experience. Ann Card Anaesth. 2011;14:19–24
19. Luciani GB, Chang AC, Starnes VA. Surgical repair of transposition of the great arteries in neonates with persistent pulmonary hypertension. Ann Thorac Surg. 1996;61:800–5