2009;122(21):2672-2674

Case 1
A 2.8-kg male neonate was born via cesarean delivery with an Apgar score of 10 after an uneventful 40-week gestational period. He was admitted to neonatal intensive care unit (NICU) on day 2 after birth because of cyanosis and tachypnea. On physical examination, he was significant for a SpO₂ of 65% and a grade of II/6 systolic heart murmur. Echocardiogram demonstrated D-TGA with atrial septal defect (ASD) and patent ductus arteriosus (PDA). He had bilateral subependymal hemorrhage (grade I) preoperatively identified by cranial ultrasound. He was then put on prostaglandin E₁ infusion to keep the ductus open and his SpO₂ rose to 85%.

He underwent arterial switch operation and repair of ASD and PDA under cardiopulmonary bypass (CPB) on day 7 of life. He was found to have a coronary artery type of AB-I⁵ and the surgical procedure was unremarkable. He failed to be weaned from CPB because of a low blood pressure of 39/30 mmHg, a highly elevated left atrial pressure (LAP) of more than 20 mmHg even with the use of high doses of inotropes (epinephrine 0.3 μg∙kg^-1∙min^-1, milrinone 0.56 μg∙kg^-1∙min^-1, dopamime 10 μg∙kg^-1∙min^-1 and dobutamine 10 μg∙kg^-1∙min^-1). Electrocardiogram showed sinus tachycardia. Echocardiogram showed the left ventricle ejection fraction (LVEF) of 22%. He was diagnosed with severe left ventricular failure and in a life-threatening situation. An urgent veno-arterial ECMO was set up and connected directly to the patient in the operating room. A standardized ECMO circuit including a servo-regulated flow system driven by a roller pump (COBE International, Arvade, CO, USA) with a membrane oxygenator (Medtronic, Minneapolis, MN, USA) was used. He remained cannulated through the right atrium and the aorta in situ. Skin was directly closed, with cannulas exiting through the upper and lower poles of the wound. Heparin was provided through the ECMO circuit to achieve activated clotting times (ACT) of 180–200 seconds. Patient was then sent to ICU on ECMO. The doses of inotropic drugs were reduced accordingly to maintain a mean blood pressure greater than 45 mmHg. Mechanical ventilation parameters were set down to minimize pulmonary barotrauma and provide lowest cardiac filling pressures as well.

He received a desired flow rate of 150–200 ml∙kg^-1∙min^-1 for the first 44 hours. On arriving ICU, he had volume overload manifested by a high LAP of 25 mmHg. The LAP decreased to 12 mmHg after removing 85 ml water by ultrafiltration by ECMO. During the first 4 hours after surgery, he had major bleeding and deteriorated with low blood pressure and concomitantly increased LAP. He was suspicious of having tamponade. An urgent mediastinal re-exploration was performed to evacuate clot and control bleeding. Major bleeding was resolved by reducing heparin and component blood transfusion. His blood pressure fluctuated with a narrow pulse pressure on postoperative day 1. He was getting more hemodynamically stable the next day. Meanwhile serum lactate level decreased gradually from 11.2 mmol/L to 2.4 mmol/L. LVEF on days 1, 2, and 3 following ECMO was 20%, 34% and 43% respectively. Thereafter pump flow rate was set down to train the left ventricle with the prerequisite of stable hemodynamics and good tissue perfusion, and this process lasted for 39 hours. He was successfully weaned from ECMO on postoperative day 4. The duration of ECMO was totally 87 hours. On day 3 after initiation of ECMO, he developed mild jaundice and resolved with phototherapy. There was no obvious new change of the bilateral subependymal hemorrhage during and after ECMO compared with that of preoperation. He had delayed sternal closure on postoperative day 8.

He was not extubated successfully until postoperative day 26. He was identified to suffer from ventilator-associated pneumonia with multiple pathogens cultured from the lower respiratory tract. The pathogens included Enterobacter cloacae, Pseudomonas aeruginosa, Klebsiella pneumoniae, Stenotrophomonas maltophilia, Acinetobacter baumanni on postoperative days 14, 20, 33, 36 and 39 respectively. He was re-intubated on postoperative day 37 because his pneumonia aggravated. He was then extubated on postoperative day 41, nasal continuous positive airway pressure (CPAP) machine was instantly used and lasted for 2 days. From then on, he has been stable and was weaned from all the inotropes and antibiotics on postoperative days 50 and 54 respectively. On postoperative day 58 he was discharged home and had no symptom of the neurological disorders.

Case 2
A 4.0-kg male full-term infant was admitted on day 27 after birth because of cyanosis and heart murmur. On physical examination, he had a SpO₂ of 76% and a grade of III/6 systolic heart murmur. Echocardiogram demonstrated D-TGA with ASD and three muscular ventricular septal defects (VSD). Preoperative cranial ultrasound showed no significant findings.

He underwent arterial switch operation and repair of ASD and VSD on day 4 after admission. The coronary artery type and surgical procedure were unremarkable. He failed to be weaned from CPB because of a severe hypotension (blood pressure 40/30 mmHg), a highly elevated LAP (>30 mmHg) even with the use of high doses of inotropes (epinephrine 0.4 μg∙kg^-1∙min^-1, milrinone 0.4 μg∙kg^-1∙min^-1, dopamime 8 μg∙kg^-1∙min^-1 and dobutamine 8 μg∙kg^-1∙min^-1). Electrocardiogram showed sinus tachycardia. Echocardiogram showed LVEF of 37.5% and a small residual muscular VSD with a diameter of 0.3 cm. He was considered in a life-threatening heart failure status and an urgent veno-arterial ECMO was set up and put on him to provide a short-term circulatory support to enable myocardial recovery. He followed the same ECMO protocol as case 1. He received a desired flow rate of 100–150 ml∙kg^-1∙min^-1 for the first 13 hours. The pump flow rate was set down to 25–45 ml∙kg^-1∙min^-1 in the next 9 hours. Echocardiogram showed LVEF improved to 54.3%. He was successfully weaned from ECMO on postoperative day 1. The duration of ECMO was totally 22 hours. He had delayed sternal closure on postoperative day 4. He was hemodynamically stable and was successfully weaned from mechanical ventilator on postoperative day 5. Acinetobacter baumannii was identified from the lower respiratory tract. He was discharged home on postoperative day 19. He showed no intracranial hemorrhage in cranial ultrasound and no symptom of the neurological disorders.

On follow-ups, these 2 patients showed no sign and symptom of cognitive and neuromotor abnomalities.

The first successful use of ECMO was reported by Dr. Bartlett and his colleagues in 1976.⁶ In China, there have not been many hospitals so far utilizing ECMO because of the limitations of resources. However, with the development of both the economy and health care in China, there has been increasing complicated surgical procedures in neonates and infants with complex congenital heart disease, which have led to increased ECMO application in cardiac failure. During the recent five years, there were some experiences of ECMO in China, most of the successful patients were adults, adolescents and young children.^7-9 Our experiences on these first two successfully neonatal ECMO in China are as follows.

Fail to wean from CPB has been the indication for ECMO in these 2 patients. The identification of patients with reversible ventricular function is of great importance to achieve a good outcome with ECMO treatment. These two cases were placed on ECMO support because of severe heart failure due to unprepared left ventricle and insufficient function despite the establishment of an adequate coronary circulation after arterial switch operation for D-TGA. Myocardial inflammation, ischemia and reperfusion injury related to open-heart surgery is likely to improve within 48 to 72 hours of ECMO support.¹⁰ In these two patients, ECMO support had perfused the vital organs, restored oxygen delivery and rested the myocardium whilst recovery occurred. The ventricular function improved soon with increased LVEF and was able to maintain a workload. Significant residual cardiovascular lesions should be aggressively sought, since these lesions would place a strain on an already compromised ventricle and are associated with worse outcomes. Irreversible myocardial damage due to extensive infarction is associated with poor chances of recovery too.

The daily management of the patients on ECMO requires a meticulous assessment of cardiorespiratory function, end-organ perfusion and injury, evolving complications such as bleeding or sepsis, and the mechanics of the ECMO circuit. Organ failure is the major reason for death during ECMO.¹¹ Severe or irreversible organ dysfunction, in particular brain injury, would therefore be a contra-indication for ECMO support. Adequate vital organ perfusion including kidney and satisfied hemostasis were achieved successfully in these two cases, which contributed to the good outcomes. One of the patients developed serious bleeding and tamponade, prompt control of bleeding had a direct influence on his subsequent outcome.

Hemorrhagic and thrombotic events are often cited as the most frequent cause of neurological complications of ECMO. But the neurodevelopmental abnormalities might be attributable to cyanosis, congenital heart disease, CPB or ECMO when all are frequently combined in this population. Hamrick et al¹² studied 53 infants supported with ECMO after cardiac surgery. The in-hospital survival was 32%. On long-term neurodevelopmental follow-ups of the survivors, 29% of them had abnormal cognitive outcome and 21% had abnormal neuromotor outcome. Currently, there has been increased attention worldwide paid to the neuroprotection in patients on ECMO. The two patients in our study showed no abnormalities in development testing, and no sign and symptom of neuromotor abnormalities on follow-ups, such as clumsiness, tremor, cerebral palsy, diplegias and hemiplegias etc.

A professional and effective ECMO team must be established to ensure the success of ECMO procedures. It is essential to provide a good teamwork by specialists including an ECMO nurse or therapist, intensivists, perfusionists and cardiac surgeons, because the care of these children is a multidisciplinary effort.¹³ Social factors deserve attention, including the economic situation of the family, and an assessment of the potential emotional impact on the family of a sudden, unexpected intraoperative death, versus a prolonged ICU death etc.

In conclusion, ECMO has been successfully used as an effective rescue therapy for neonates with life-threatening heart failure following open-heart surgery in the mainland of China.

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