Pediatric cardiac surgical ECMO: Multivariate analysis of risk factors for hospital death

Pediatric Cardiac Surgical ECMO: Multivariate Analysis of Risk Factors for Hospital Death Henry L. Walters III, MD, Mehdi Hakimi, MD, Michael D. Rice, BS, Juanita M. Lyons, MS, Grant C. Whittlesey, CCP, and Michael D. Klein, MD Departments of Cardiovascular Surgery and Pediatric General Surgery, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, Michigan

Background. Extracorporeal membrane oxygenation (ECMO) has emerged as an effective technique for the mechanical support of many pediatric postcardiotomy patients with medically refractory cardiac failure. Methods. We retrospectively reviewed the records of 73 pediatric patients with congenital heart disease who were placed on ECMO support between August 1984 and February 1994. The patients were divided into groups defined by the timing of ECMO cannulation relative to the time of operation. Group I patients (n = 7, 9.6%) were placed on ECMO preoperatively. Group 2 patients (n = 66, 90.4%) were a heterogeneous population placed on ECMO at any interval after cardiac repair. Subgroup 2A consisted of patients (n = 17, 25.8f4) w h o could not be weaned from cardiopulmonary bypass and were converted directly to ECMO support immediately after repair. Subgroup 2B patients (n = 49, 74.2%) were cannulated postoperatively after an initial period of clinical stability.

Results. Hospital survival for all study patients (42/73) and for group 2 patients (38/66) was 58%. Only 4 group 2A patients (23.5%) survived their hospitalization compared with 34 group 2B patients (69.4%) (p = 0.001). Multivariate analysis identified elevated right atrial pressure after ECMO decannulation (p = 0.049) and, possibly, membership in group 2A (p = 0.061) as independent risk factors for hospital death. Conclusions. Extracorporeal membrane oxygenation is most effective in salvaging pediatric cardiac surgical patients w h o demonstrate medically refractory hemodynamic deterioration at s o m e interval after being successfully weaned from cardiopulmonary bypass. The right atrial pressure after extracorporeal membrane oxygenation decannulation is an independent predictor of hospital death.

xtracorporeal m e m b r a n e oxygenation (ECMO) provides prolonged mechanical c a r d i o p u l m o n a r y support by combining venoarterial bypass with m e m b r a n e oxygenation. Its use in patients with congenital heart disease dates back to 1970 when Baffes and colleagues [11 reported using ECMO to s u p p o r t infants with congenital heart defects and in unstable condition who were undergoing palliative cardiac surgical procedures. Seven years later, Bartlett and associates [2] reported promising results in 28 adult and pediatric patients treated with ECMO for various forms of c a r d i o p u l m o n a r y disease and predicted a future e x p a n d e d role for this technique in the treatment of pediatric patients with refractory cardiac failure. Since that time, a n u m b e r of pediatric postcardiotomy ECMO series [3-121 with varying rates of hospital survival have been published. Despite the availability of intraaortic balloon counterpulsation for children [13-16], ECMO has e m e r g e d as an effective technique for the mechanical support of m a n y pediatric postcardiotomy patients with medically refrac-

tory cardiac failure. Pediatric applications of intraaortic balloon counterpulsation have been h a m p e r e d by difficulties in balloon placement, constraints on balloon size i m p o s e d by the smaller pediatric vessel caliber, difficulties in synchronization of the balloon cycle to the faster pediatric heart rates, and the r e d u c e d diastolic a u g m e n tation achieved with the intraaortic balloon p u m p because of the very elastic pediatric aorta. Further, intraaortic balloon counterpulsation primarily supports the left ventricle and does little to treat the right heart failure that frequently accompanies pediatric low cardiac output (LCO) after cardiotomy. ] h e p u r p o s e of this retrospective review of our past 9Ve years' experience with pediatric ECMO in cardiac surgical patients was to analyze our results and to identify i n d e p e n d e n t risk factors for hospital death.

E

Presented at the l'hirty-lirst Annual Meeting of lhe Society of lhorack Surgeons, Palm Springs, CA, Jan 30-Fvb I, lt)~B. Address reprint requests to Dr Waltt'rs. Department of Cardiovascular Surgery, Children's tlo~pita] of Michigan, 3901 Beaubien Bird, Detroit, MI 48201. © 1995 by l h e Societx of Fhoracic Surgeons

(Ann Thorac Surg 1995;60:329-37)

M a t e r i a l and M e t h o d s

Total Patient Population and Definition of Groups The medical records of 73 pediatric patients with congenital heart disease who were placed on ECMO at Child r e n ' s Hospital of Michigan between August 1984 and F e b r u a r y 1994 w e r e r e t r o s p e c t i v e l y r e v i e w e d . This ECMO population represented 1.6% of the 4,595 total pediatric patients u n d e r g o i n g a cardiac operation and 0003-4975/95/$9.50 0003-4975(95)00410-M

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Table 1. Demographics" Variable

Group 1 (n 7)

Group 2 (n 66)

Subgroup 2A (n 17)

Subgroup 2B (n 49)

Total (n - 73)

Sex b Male Female Median age at operation (too)< Median weight at operation (kg)
5 (71.4) 2 (28.6) 0.1 3.9

39 (59.1) 27 (40.9) 7.9 6.2

13 (76.5) 4 (23.5) 7.1 5.3

26 (53.1) 23 (46.9) 9.0 6.3

44 (60.3) 29 (39.7) 7.2 5.6

•' Numbers in parentheses are percentages, i, Significance (male to female ratio): p 0.696(Fisher's exact test) between groups 1 and 2 and p - 0.091 0(2 test) between subgroups 2A and 2B. Significance: p 0.002between groups 1 and 2 and p 0.291 between subgroups 2A and 2B (Mann-Whitney U test), d Significance: p 0.010between groups 1 and 2 and p 0.215between subgroups 2A and 2B (Mann-Whitney U test).

3.0% of t h e 2,452 p a t i e n t s h a v i n g o p e n c a r d i o t o m y d u r i n g t h a t s a m e i n t e r v a l . A p p r o x i m a t e l y 189 v a r i a b l e s w e r e c o l l e c t e d for e a c h p a t i e n t . T h e s e v a r i a b l e s w e r e a r b i trarily g r o u p e d into p r e - E C M O , o n - E C M O , a n d p o s t ECMO categories. T h e s e 73 p e d i a t r i c c a r d i a c s u r g i c a l E C M O p a t i e n t s w e r e d i v i d e d i n t o g r o u p s d e f i n e d b y t h e t i m i n g of E C M O c a n n u l a t i o n r e l a t i v e to t h e t i m e of e a c h p a t i e n t ' s c a r d i a c o p e r a t i o n . G r o u p 1 p a t i e n t s (n 7, 10%) w e r e p l a c e d o n E C M O p r e o p e r a t i v e l y . G r o u p 2 p a t i e n t s (n - 66, 90%) w e r e a h e t e r o g e n e o u s p o p u l a t i o n p l a c e d o n E C M O at any interval after cardiac repair. Group 2 patients were a r b i t r a r i l y d i v i d e d i n t o two s u b g r o u p s . S u b g r o u p 2A c o n s i s t e d of p a t i e n t s (n 17, 26°,,i.) w h o c o u l d n o t b e w e a n e d f r o m c a r d i o p u l m o n a r y b y p a s s (CPB) a n d w e r e c o n v e r t e d d i r e c t l y to E C M O s u p p o r t w h i l e still in t h e o p e r a t i n g r o o m . S u b g r o u p 2B p a t i e n t s (n = 49, 7 4 % ) w e r e s u c c e s s f u l l y w e a n e d f r o m CPB a f t e r t h e s u r g i c a l r e p a i r a n d w e r e t r a n s f e r r e d to t h e p e d i a t r i c i n t e n s i v e care unit. M e d i c a l l y r e f r a c t o r y c a r d i a c or p u l m o n a D' failure or b o t h d e v e l o p e d a f t e r 32.8 + 4.2 h o u r s ( m e a n + s t a n d a r d e r r o r of t h e m e a n ) of initial clinical stability, a n d t h e p a t i e n t s were then placed on ECMO support.

m o r i b u n d at p r e s e n t a t i o n b e c a u s e of s e v e r e p u l m o n a r y v e n o u s o b s t r u c t i o n r e l a t e d to total a n o m a l o u s p u l m o n a r y v e n o u s c o n n e c t i o n (n = 3) a n d cor t r i a t r i a t u m (n = 1). T h e fifth p a t i e n t w a s s e e n w i t h p r o f o u n d h y p o x i a r e s u l t i n g f r o m t r a n s p o s i t i o n of t h e g r e a t a r t e r i e s w i t h i n t a c t i n t e r v e n t r i c u l a r s e p t u m . D e s p i t e t h e p r e s e n c e of a p a t u lous, n o n r e s t r i c t i v e i n t e r a t r i a l c o m m u n i c a t i o n a f t e r b a l l o o n atrial s e p t o s t o m y a n d a l a r g e p a t e n t d u c t u s a r t e r i o s u s o n p r o s t a g l a n d i n E3 i n f u s i o n , p r o f o u n d h y p o x i a w i t h acidosis persisted. These 5 patients were placed on E C M O to s t a b i l i z e t h e i r clinical c o n d i t i o n p r i o r to d e f i n itive c a r d i a c r e p a i r . T w o g r o u p 1 p a t i e n t s (28.6%) w e r e p l a c e d o n E C M O w i t h a p r e s u m e d d i a g n o s i s of p e r s i s t e n t p u l m o n a r y h y p e r t e n s i o n of t h e n e w b o r n a f t e r t h e i r t r u e c o n g e n i t a l cardiac diagnosis was not detected on the routine echoc a r d i o g r a m m a d e p r i o r to E C M O . T h e c o r r e c t c a r d i a c diagnoses were later established by echocardiography ( t r a n s p o s i t i o n of t h e g r e a t a r t e r i e s w i t h i n t a c t i n t e r v e n t r i c u l a r s e p t u m ) or c a r d i a c c a t h e t e r i z a t i o n (total a n o m a lous p u l m o n a r y v e n o u s c o n n e c t i o n ) . All 7 g r o u p 1 p a t i e n t s u n d e r w e n t n e c k c a n n u l a t i o n at t h e t i m e E C M O was instituted.

Group 1 (Placed on ECMO Preoperatively)

Demographics for Total Population and Group 2

G r o u p I h a d 5 b o y s (71.4%) a n d 2 girls (28.6%). T h e i r m e d i a n age a n d w e i g h t w e r e s i g n i f i c a n t l y less t h a n t h o s e of t h e g r o u p 2 p a t i e n t s (0.1 m o n t h v e r s u s 7.9 m o n t h s [p = 0.002] a n d 3.9 kg v e r s u s 6.2 kg [p - 0.01]) ( T a b l e 1). Five g r o u p 1 p a t i e n t s (71.4%) w e r e s e e n w i t h p r o f o u n d LCO, h y p o x i a , or b o t h ( T a b l e 2). F o u r of t h e s e 5 p a t i e n t s w e r e

T h e d e m o g r a p h i c d a t a for all s t u d y g r o u p s a r e s u m m a r i z e d in T a b l e 1. T h e total E C M O p o p u l a t i o n c o n s i s t e d of 44 b o y s (60.3%) a n d 29 girls (39.7%) w i t h a m e d i a n a g e at o p e r a t i o n of 7.2 m o n t h s a n d a m e d i a n w e i g h t of 5.6 kg. G r o u p 2 ( c a n n u l a t e d at a n y i n t e r v a l a f t e r r e p a i r ) c o m p r i s e d 39 b o y s (59.1%) a n d 27 girls (40.9%) w i t h a m e d i a n

Table 2. Indications fi~r Extracorporeal Membrane Oxygenation'";' Indication

Group 1 (n 7)

Group 2 (n : 66)

Subgroup 2A (n 17)

Subgroup 2B (n - 49)

Total (n - 73)

Cardiac arrhythmia Cardiac arrest Hypoxia Low cardiac output Mistaken diagnosis No spontaneous electric activitv Pulmonary. artery, hypertension

0 1 (]4.3) 5 (71.4) 3 (42.9) 2 (28.6) 0 0

] (].5j 4 (6.1) 0 61 (92,4) 0 1 (1.5) 14 (21.2)

0 0 0 16 (94.1) 0 1 (5.9) 2 (11.8)

1 (2.0) 4 (8.2) 0 45 (91.8) 0 0 12 (24.5)

I (1.4) 5 (6.8) 5 (6.8) 64 (87.7) 2 (2.7) 1 (1.4) 14 (19.2)

"~Numbers in parentheses are percentages. ~"Eighteen (24.7"<,)ot total patients, 4 (57.3%) of group 1 patients, 14 (21.2%) of group 2 patients, 2 (11.8)of group 2B patients were seen with multiple indications.

A n n Thorac S u r g 1995;60:329-37

age of 7.9 m o n t h s and a m e d i a n weight of 6.2 kg. There were no significant differences in d e m o g r a p h i c variables b e t w e e n subgroup 2A and s u b g r o u p 2B (see Table 1).

Cardiac Diagnoses for Group 2 Of the 20 congenital cardiac diagnoses r e p r e s e n t e d in the study population, complete atrioventricular canal defect (n = 13, 19.7%), single ventricle (n - 11, 16.7%), tetralogy of Fallot (n ; 9, 13.6%), total a n o m a l o u s p u l m o n a r y venous connection (n = 5, 7.6%), and double-outlet right ventricle (n - 5, 7.6%) were the most c o m m o n in group 2. All of the patients with complete atrioventricular canal defect were in group 2, and all h a d associated trisomy 21.

Indications for ECMO in Total Population and Group 2 The indications for ECMO included the following medically refractory clinical conditions: (1) LCO, (2) p u l m o nary artery hypertensive crisis (PAHCs), (3) profound hypoxia, (4) cardiac arrest, (5) cardiac arrhythmia, and (6) lack of resumption of s p o n t a n e o u s electric activity after surgical repair (see Table 2). O u r patients were placed on ECMO only after all reasonable alternative therapies had b e e n exhausted, a n d it was thought that the patient's death was inevitable within the next 12 to 24 hours without mechanical support. Absolute contraindications to ECMO included the presence of multiple-organ failure, severe neurologic dysfunction, and uncontrollable hemorrhage. A relative contraindication was the presence of a s y s t e m i c - t o - p u l m o n a r y artery shunt a n d docum e n t e d untreated sepsis. The a d e q u a c y of the cardiac repair was confirmed in all patients by two-dimensional echocardiography, cardiac catheterization with angiography, or both. Eighteen patients (24.7%) in the total study population were seen with more than one indication for ECMO. The most c o m m o n indications for ECMO in the total group were LCO (n = 64, 87.7%) and PAHC (n = 14, 19.2%). Low cardiac output (n = 61, 92.4%) and PAHC (n = 14, 21.2%) were also the most c o m m o n indications for institution of ECMO s u p p o r t in the patients who were cannulated at any interval after cardiac repair (group 2) (see Table 2).

ECMO Protocol CANNULATION. Neck cannulation, if not anatomically contraindicated, was generally preferred to reduce the probability of mediastinal sepsis. However, as might be expected, a higher proportion of s u b g r o u p 2A patients were c a n n u l a t e d in the chest than in s u b g r o u p 2B (58.8% versus 16.3%; p = 0.001) because the cannulas were a l r e a d y in place, and the institution of ECMO involved only switching the cannula connections to the ECMO circuit. In s u b g r o u p 2B, chest cannulation was reserved for patients whose a n a t o m y p r e c l u d e d the p l a c e m e n t of neck cannulas or for patients in w h o m it was thought that a d e q u a t e cardiac decompression was not achieved by neck cannulation. Hence, 83.7°4. of s u b g r o u p 2B patients were cannulated in the neck rather than the chest. Cannulation was p e r f o r m e d by placing the tip of the venous cannula in the right atrium through the right

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331

internal jugular vein (ECMO cannula; Bio-Medicus, Inc, Eden Prairie, MN) or by placing it directly t h r o u g h the open s t e r n u m (Pacifico venous cannula; DLP, Inc, G r a n d Rapids, MI). W h e n chest cannulation was employed, a left atrial cannula was placed, if necessary, to separately d e c o m p r e s s the left side of the heart. The arterial cannula was placed in the aortic arch through the right c o m m o n carotid artery (Bio-Medicus ECMO cannula) or into the ascending aorta (Argyle angled aortic perfusion cannula; S h e r w o o d Medical, St. Louis, MO) directly through the open sternum. ECMO CIRCUIT. Blood d r a i n e d by gravity through the venous cannula into a servoregulating venous return monitor (Seabrook Medical Systems, Inc, Cincinnati, OH) to a roller p u m p (Cobe Laboratories, Inc, Lakewood, CO). The venous blood was then p u m p e d t h r o u g h an a p p r o p r i a t e l y sized m e m b r a n e oxygenator and heat exchanger (Avecor Cardiovascular, Inc, Plymouth, MN) to be r e t u r n e d to the patient through the arterial cannula. T e m p e r a t u r e (Seabrook, Medical Systems, Inc), pressure (Escort patient monitor; Medical Data Electronics, Inc, Arleta, CA), and oxygen saturation (7820 oxygen monitor; Puritan-Bennett, Inc, Carlsbad, CA) monitors as well as an air detector (Minnilert RS-3275; Minnitech Corporation, Inc, Minneapolis, MN) are s t a n d a r d c o m p o n e n t s of our circuit. A gas b l e n d e r with two flowmeters (for oxygen a n d carbon dioxide) to the m e m b r a n e oxygenator facilitate control of the arterial oxygen tension a n d arterial carbon dioxide tension without changing the p u m p t'Iox4z.

ANTICOAGULATION. Anticoagulation was achieved b y a constant heparin sodium infusion maintaining an activated clotting time of 180 to 220 seconds. Platelet transfusions were given to maintain a platelet count of greater than 100,000[p,L [17]. The p r o t h r o m b i n time was kept as near normal as possible with the infusion of 10 mL/kg of fresh frozen p l a s m a every 6 hours and with vitamin K administration. The h e m o g l o b i n was m a i n t a i n e d greater than 10 mg/dL with transfusions of p a c k e d r e d blood cells as indicated. In patients with an open fontanel, daily cranial ultrasound studies were obtained to detect intracranial hemorrhage. FLOWS. W h e r e a s the p u m p flows are adjusted to maintain satisfactory oxygenation in a neonate with persistent p u l m o n a r y hypertension, the p r i m a r y goal of postcardiotomy ECMO therapy usually is to restore a n d maintain optimal tissue perfusion while cardiac recovery takes place. The partial or nearly total bypass p r o d u c e d b y ECMO in these patients d e c o m p r e s s e s the heart and reduces the work it must perform, thereby decreasing its energy requirements. The i m p r o v e m e n t in arterial oxygen saturations p r o d u c e d by the m e m b r a n e oxygenator also lowers p u l m o n a r y vascular resistance. This theoretically maximizes the potential for myocardial recovery, resolution of the PAHC, or both. P u m p flows (100 to 150 m L . k g 1 . m i n i) were targeted to maintain a urine

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output of greater than I m L . kg ~. h ~, toe temperatures greater than 30°C, and a brisk capillary refill and to reduce left and right atrial pressures maximally. Immediately after the institution of ECMO, all inotropic medications, except renal dose d o p a m i n e hydrochloride, were discontinued. A peripheral vasodilator, such as sodium nitroprusside, was frequently used to treat systemic arterial hypertension I181 a n d to improve peripheral perfusion. VENTILATOR. Shortly after the institution of ECMO, the ventilator inspired oxygen fraction was typically reduced to 0.25 if the patient was totally bypassed without any major cardiac contribution to the total systemic flow. The positive end-expiratory pressure was set at 6 to 10 cm H 2 0 , and the respiratory rate was reduced to 15 to 25 breaths/rain. During periods of partial bypass, w h e n the patient's own ejection contributed to the total systemic flow, the inspired oxygen fraction was elevated to at least 0.40 to ensure adequate arterial oxygen saturations at the level of the coronary ostia. At all times during the ECMO run, the arterial oxygen saturations were maintained at 98% to 100%, and the acid-base status was adjusted to within the normal range. The patient's temperature was m a i n t a i n e d as close to n o r m o t h e r m i a as possible. FLUID MANAGEMENT.Prior to the institution of ECMO, the intravascular volume was invariably expanded to optimize atrial filling pressures and cardiac output. After the b e g i n n i n g of ECMO, ultrafiltration (Minifilter Plus; Amicon Corp, Danvers, MA) and diuresis were routinely employed to decrease interstitial edema and to lower filling pressures by reducing the intravascular volume. Ultrafiltration was used in 56 (76.7%) of the 73 ECMO patients in this series. Hemodialysis was used in 3 patients (4.1%) to palliate acute renal insufficiency. WEANING. The patient was generally m a i n t a i n e d on full ECMO support for a m i n i m u m of 72 hours. At that time, the flows were gradually reduced by small increments at hourly intervals over a 12- to 24-hour period. During this period of reduction in flow, the ventilator settings were gradually adjusted upward to maintain 100% arterial saturations, normocarbia, and a normal acid-base status. The left a n d right atrial pressures were allowed to rise to normal levels, a u g m e n t e d by volume boluses as indicated. As the reduction in flow continued, inotropic agents, systemic vasodilators, and pulmonary, vasodilators were added, as necessary, to optimize the cardiac output and to treat mild p u l m o n a r y artery hypertension. As long as the clinical assessment of cardiac output remained satisfactory, the w e a n i n g from the ECMO flow was continued. Arbitrarily, the ECMO flow was not allowed to drop to less than 100 to 200 m L / m i n to avoid thrombosis with embolization. A s s u m i n g a satisfactory cardiac output during the entire wean, the patient was given a 10-minute trial off ECMO and was then decannulated if the trial was well tolerated. The cervical vessels were not reconstructed after ECMO decannulation. Delayed sternal closure [19] was performed at the time of

Ann Thorac Surg 1995;60:329--37

decannulation in patients who were cannulated by the transthoracic route. In patients who were c a n n u l a t e d cervically a n d who also had an open sternum, delayed sternal closure was usually performed the day after ECMO decannulation.

Data Collection and Analysis The data collected for each patient consisted of 189 variables that were sorted on Microsoft Excel for Windows program version 4.0 (Microsoft Corp, Redmond, WA). These data were downloaded into SPSS for Windows release 5.0 (SPSS Inc, Chicago, IL) for statistical analysis. Quantitative variables that approximated a normal distribution were reported as the m e a n ± the standard error of the m e a n a n d were analyzed by Student's unpaired t test. Quantitative variables that did not approximate a normal distribution were reported as the m e d i a n and were analyzed by the M a n n - W h i t n e y U test (Wilcoxon r a n k - s u m test). Nominal variables were analyzed nonparametrically by Fisher's exact test or )(2 test. Fifty-one clinical variables were subjected to an initial univariate analysis to screen for possible predictors of the outcome event hospital death. To detect i n d e p e n d e n t predictors of hospital death, the following nine variables (identified in the univariate analysis with a p value of less than 0.1) were subjected to multivariate analysis: (1) duration of CPB, (2) group 2A membership, (3) serum creatinine and (4) blood urea nitrogen values 48 hours after ECMO cannulation, (5) red blood cells and (6) fresh frozen plasma t r a n s f u s e d ( m L . m 2 " h 1) while on ECMO, (7) serum creatinine value after ECMO d e c a n n u lation, (8) right atrial pressure averaged over the first 8 hours after ECMO decannulation, a n d (9) PAHC as the indication for ECMO. The multivariate analysis employed the stepwise forward Wald multiple logistic regression method to construct a model to predict the probability of hospital death in group 2. Results The overall hospital survival was 42 patients (57.5%).

Group 1 The duration of ECMO in the 7 group 1 patients (placed on ECMO preoperatively) was 100.0 + 17.6 hours. Five (71.4%) of these patients were weaned from ECMO support, and 4 of these 5 survived hospitalization (57.1% group 1 hospital survival). Both patients whose cardiac diagnosis had not been correctly established preoperatively survived and are doing well. The 3 patients who died had (1) severe pulmonary, venous obstruction associated with total anomalous p u l m o n a r y venous connection plus complete atrioventricular canal defect a n d severe preoperative atrioventricular valve insufficiency, (2) cor triatriatum status post cardiac arrest in the cardiac catheterization laboratory, and (3) recurrent p u l m o n a r y venous stenosis 10 weeks after repair of the mixed form of total anomalous p u l m o n a r y venous connection. One (25.0%) of the 4 group 1 survivors experienced two clinically significant complications: a left-hemispheric

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Table 3. Complications in Survivors"-'

Complication Neurologic Bleeding requiring reexploration Infection ~ Renal failure Hepatic failure Upper GI bleed

Group 1 Survivors (n 4)

Group 2 Survivors (n - 38)

Subgroup 2A Survivors (n 4)

Subgroup 2B Survivors (n - 34)

Total Survivors (n = 42)

1 (25.0) 0

9 (23.7) 5 (13.2)

0 1 (25.0)

9 (26.5) 4 (11.8)

10 (23.8) 5 (11.9)

1 (25.0) 0 0 0

4 (10.5) 3 (7.9) 2 (5.3) 2 (5.3)

0 0 0 0

4 (11.8) 3 (8.8) 2 (5.9) 2 (5.9)

5 (11.9) 3 (7.1) 2 (4.8) 2 (4.8)

Numbers in parentheses are percentages, b Eight (21.0%) of total survivors, 1 (25.0%) of group 1 survivors, 7 (18.4%) of group 2 survivors, and 6 (17.6%) of group 2B survivors had multiple complications. ' Four (14.3%) of the 28 group 2 nonsurvivors underwent mediastinal exploration for bleeding, and in 1 patient, the mediastinal hemorrhage was probably the cause of death, d There were no cases of mediastinitis. G1 = gastrointestinal.

stroke a n d g r a m - p o s i t i v e sepsis (Table 3). This p a t i e n t s u r v i v e d a n d r e c o v e r e d full n e u r o l o g i c function.

tinal b l e e d i n g r e q u i r i n g t r a n s f u s i o n e a c h o c c u r r e d in 2 g r o u p 2 s u r v i v o r s (5.3%) (see Table 3).

Survival in Group 2 Of the patients w h o w e r e c a n n u l a t e d at any interval after cardiac r e p a i r (group 2, n 66), 22 (33.3%) c o u l d not be w e a n e d f r o m E C M O s u p p o r t a n d died. The r e m a i n i n g 44 p a t i e n t s (66.7%) w e r e s u c c e s s f u l l y w e a n e d f r o m E C M O . Six of t h e s e p a t i e n t s s u b s e q u e n t l y d i e d at a m e a n i n t e r v a l of 10.2 ± 3.4 days after d e c a n n u l a t i o n , for a total of 38 hospital s u r v i v o r s (57.6%) in g r o u p 2 (p = 1.000 [Fisher's exact test] v e r s u s g r o u p 1). The hospital survival in s u b g r o u p 2B (n = 34, 69.4%) was significantly g r e a t e r (p = 0.001 [)(2 test]) t h a n that in s u b g r o u p 2A (n - 4, 23.5%).

Complications in Group 2 Survivors Sixteen (42.1%) of the 38 g r o u p 2 s u r v i v o r s e x p e r i e n c e d o n e or m o r e clinically significant c o m p l i c a t i o n s , with 7 (18.4%) h a v i n g m u l t i p l e c o m p l i c a t i o n s (see Table 3). N e u r o l o g i c c o m p l i c a t i o n s (n 9, 23.7%) w e r e the m o s t c o m m o n , with 2 s u r v i v o r s (5.3%) e x p e r i e n c i n g m u l t i p l e n e u r o l o g i c events. (Nine (32%) of the 28 g r o u p 2 n o n s u r vivors also s u s t a i n e d n e u r o l o g i c c o m p l i c a t i o n s , w h i c h w e r e the p r o b a b l e cause of d e a t h in 4; the r e m a i n i n g 5 p a t i e n t s h a d seizures.) Intracranial h e m o r r h a g e (n - 4, 10.5%), seizures (n - 3, 7.9%), a n d stroke (n - 2, 5.3%) w e r e the m o s t c o m m o n n e u r o l o g i c events. Five (13.2%) of the g r o u p 2 s u r v i v o r s h a d to u n d e r g o m e d i a s t i n a l reexp l o r a t i o n one or m o r e t i m e s for b l e e d i n g w h i l e on E C M O s u p p o r t . (Four (14.3%) of the 28 g r o u p 2 n o n s u r v i v o r s u n d e r w e n t m e d i a s t i n a l exploration for b l e e d i n g , a n d in 1 patient, the m e d i a s t i n a l h e m o r r h a g e was p r o b a b l y the cause of death.) Infectious c o m p l i c a t i o n s (n 4, 10.5%) i n c l u d e d 2 p a t i e n t s w i t h g r a m - n e g a t i v e sepsis, I with g r a m - p o s i t i v e sepsis, a n d I with a superficial infection at the n e c k c a n n u l a t i o n site. In n o n e of the p a t i e n t s in the total s t u d y p o p u l a t i o n did m e d i a s t i n i t i s d e v e l o p . Alt h o u g h ultrafiltration was u s e d f r e q u e n t l y (n - 50, 75.8%) a l o n g w i t h diuretics to treat anasarca, critical renal failure r e q u i r i n g h e m o d i a l y s i s o c c u r r e d in only 3 (7.9%) of the g r o u p 2 survivors. H e p a t i c failure and u p p e r gastrointes-

Univariate Analysis for Group 2 Survivors Versus Nonsurvivors PRE--ECMO VARIABLES. The basic d e m o g r a p h i c v a r i a b l e s (age at operation, weight, and b o d y surface area) of group 2 survivors versus nonsurvivors w e r e similar, although the difference in the male to female ratio b e t w e e n the two groups did a p p r o a c h significance (p = 0.053). Preoperative indices of cardiac function, including the echocardiographically d e t e r m i n e d shortening fraction and the systolic and diastolic left ventricular dimensions, w e r e also similar w h e n group 2 survivors w e r e c o m p a r e d with nonsurvivors. The duration of CPB was the only intraoperative variable that was significantly different (p = 0.045) b e t w e e n survivors (120.7 ± 8.4 minutes) and nonsurvivors (147.0 ± 9.7 minutes) (Table 4). A l t h o u g h the aortic cross-clamp a n d total circulato D, arrest times w e r e longer in the nonsurvivors, these differences w e r e not significant. A h i g h e r proportion of nonsurvivors (46.4 %) than survivors (10.5 %) w e r e cannulated in the operating r o o m (subgroup 2A m e m b e r s h i p ) (p = 0.001). The proportion of group 2 survivors (89.5%) versus nonsurvivors (96.4%) w h o s e indications for E C M O included LCO was not significantly different (p = 0.385), but the difference in the proportion of survivors (28.9%) versus nonsurvivors (10.7%) w h o s e indication for E C M O was P A H C did a p p r o a c h significance (p - 0.073) (see Table 4). ON--ECMO VARIABLES. The m e a n d u r a t i o n of E C M O in g r o u p 2 patients was 114.8 ÷ 5.9 hours. T h e r e was no significant difference (p 0.421) in d u r a t i o n b e t w e e n g r o u p 2 survivors (106 hours) a n d n o n s u r v i v o r s (128.5 hours) ( r e p o r t e d as m e d i a n v a l u e s b e c a u s e the distribution of v a l u e s did not a p p r o x i m a t e a n o r m a l distribution). The s e r u m c r e a t i n i n e (p - 0.004) a n d b l o o d u r e a n i t r o g e n (p = 0.009) levels d e t e r m i n e d 48 h o u r s after E C M O c a n n u l a t i o n as w e l l as the red b l o o d cells (p = 0.017) a n d fresh frozen p l a s m a (p 0.01) t r a n s f u s e d ( m L - m i . h 1) d u r i n g E C M O w e r e all significantly h i g h e r in the n o n s u r v i v o r s (see Table 4).

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Table 4. Group 2 Univariate Analysis of Possible Risk Factorsfor Hospital Death''~' Survivors (n 38)

Variable Pre-ECMO Membership in group 2A ECMO indication: pulmonary artery hypertensive crisis Duration of CPB (min) On-ECMO Cr 48 hours after ECMO cannulation (mg/dL) BUN 48 hours after ECMO cannulation (mg/dL) Red blood c e l l s ( m L - m 2 . h I) Fresh frozen plasma ( m L . m 2 . h i) f'ost-ECMO Cr 48 hours after ECMO decannulation (mg/dL) RAP averaged over 8 hours after ECMO decannulation (ram Hg)

4 (10.5) 11 (28.9) 120.7 + 8.4 0.6 23.6 24.0 26.7

+ + t *

0.1 2.5 2.6 2.9

0.7 + 0.1; 0.5" 14.3 * 1.1

Nonsurvivors (n - 28) 13 (46.4) 3 (10.7) 147 - 9.7 1.1 36.2 87.7 68.4

--

0.2 4.4 25.0 14.7

1.5 - 0.3; 1.5 ~ 21.9 - 1.5

p Value 0.001 ~ 0.073 ~ 0.045 d

0.004 d

0.009 d

0.017 d 0.010 d

0.014 ~ 0.003 d

" Numbers in parentheses are percentages, h Where applicable, data are shown as the mean :~ the standard error of the mean. ~ Significance determined bv ~2 test. a Significance determined by Student's unpaired t test. " The median value is shown after the semicolon, r Significance determined by Mann-Whitney test iWilcoxon rank-sum test). BUN blood urea nitrogen; CPB cardiopulmonary bypass; Cr serum creatinine; E C M O extracorporeal membrane ox'ygenation; RAI' right atrial pressure. :

POBI ECMO VARIABLES. T h e s e r u m c r e a t i n i n e level (p -0.014) d e t e r m i n e d 48 h o u r s after E C M O d e c a n n u l a t i o n a n d t h e r i g h t atrial p r e s s u r e (p 0.003) a v e r a g e d o v e r t h e initial 8 h o u r s a f t e r E C M O d e c a n n u l a t i o n w e r e signific a n t l y h i g h e r in g r o u p 2 n o n s u r v i v o r s (see T a b l e 4).

Multivariate Analysis for Group 2 Outcome Event--Hospital Death T h e m u l t i v a r i a t e a n a l y s i s i d e n t i f i e d h i g h e r r i g h t atrial p r e s s u r e ( a v e r a g e d o v e r t h e initial 8 h o u r s a f t e r E C M O d e c a n n u l a t i o n ) as a n i n d e p e n d e n t p r e d i c t o r of h o s p i t a l d e a t h (p - 0.049). T h e o n l y o t h e r v a r i a b l e i n c l u d e d in t h e m o d e l b y t h e m u l t i v a r i a t e a n a l y s i s as a p o s s i b l e i n d e p e n d e n t risk factor for h o s p i t a l d e a t h w a s m e m b e r s h i p in s u b g r o u p 2A (p - 0.061).

Comment

Critique of Study T h e basic l i m i t a t i o n s of this s t u d y r e l a t e to its s m a l l n u m b e r s a n d to t h e liabilities of its r e t r o s p e c t i v e d e s i g n . H o w e v e r , n o t s u r p r i s i n g l y , all of t h e p r e v i o u s l y r e p o r t e d p e d i a t r i c p o s t c a r d i o t o m y E C M O series [3-12] s h a r e t h e same retrospective format and comprise small numbers of p a t i e n t s . A p r o s p e c t i v e trial with r a n d o m i z a t i o n of p a t i e n t s to e i t h e r c o n t i n u e d , i n t e n s i v e m e d i c a l t r e a t m e n t or to E C M O s u p p o r t is t h e ideal m e t h o d to d e t e r m i n e t h e t r u e e f f e c t i v e n e s s of p e d i a t r i c p o s t c a r d i o t o m y E C M O . H o w e v e r , s u c h a trial is n o t e t h i c a l g i v e n t h e critical clinical c o n d i t i o n of t h e s e p a t i e n t s a n d t h e p r o m i s i n g r e s u l t s t h a t h a v e a l r e a d y b e e n r e p o r t e d in o t h e r clinical E C M O s e r i e s [20]. T h e q u e s t i o n s t h a t r e m a i n c o n c e r n i n g t h e u s e of t h i s t e c h n i q u e in p e d i a t r i c p a t i e n t s w i t h congenital heart disease must be answered using retros p e c t i v e a n a l y s e s . A l t h o u g h t h e n u m b e r of p a t i e n t s in t h i s s t u d y is l a r g e c o m p a r e d w i t h t h e n u m b e r s in s i m i l a r series, t h e m o d e l g e n e r a t e d by t h e m u l t i v a r i a t e a n a l y s i s would be more reliable with a larger study population.

Frequency of ECMO Use T h e l i t e r a t u r e c o n t a i n s little i n f o r m a t i o n c o n c e r n i n g t h e f r e q u e n c y of t h e u s e of E C M O s u p p o r t in p e d i a t r i c c a r d i a c s u r g i c a l p a t i e n t s . O v e r t h e last 91/2 years, w e h a v e u s e d this t e c h n i q u e in 3.0% of o u r p a t i e n t s w h o u n d e r w e n t o p e n c a r d i o t o m y . D u r i n g t h e last y e a r of t h i s s e r i e s (1994), we u s e d E C M O s u p p o r t in 1.4'% of o u r p a t i e n t s who underwent open procedures. Dalton and colleagues [3] a n d Z i o m e k a n d c o - w o r k e r s [12] r e p o r t e d a f r e q u e n c y of u s a g e in o p e n p r o c e d u r e s of 1.5% a n d 6.5%, r e s p e c tivelv. M a n y c o n f o u n d i n g factors c a n i n f l u e n c e t h e p e d i a t r i c p o s t c a r d i o t o m y E C M O u s a g e r a t e f r o m o n e i n s t i t u t i o n to a n o t h e r . Its u s e in i n s t i t u t i o n s w i t h l i m i t e d a c c e s s to t h i s t e c h n i q u e is, of n e c e s s i t y , v e ~ low. In i n s t i t u t i o n s w i t h efficient a n d w e l l - e s t a b l i s h e d E C M O services, t h e r e a d y a v a i l a b i l i t y of this v a l u a b l e tool m a y b e r e f l e c t e d i n h i g h e r r a t e s of use. T h e s u r g e o n ' s b i a s a n d case s e l e c t i o n also u n d o u b t e d l y affect t h e statistics s u b s t a n t i a l l y . S u r g e o n s w h o b e l i e v e t h a t E C M O h a s little to offer p e d i a t r i c c a r d i a c s u r g i c a l p a t i e n t s r a r e l y u s e it. O n t h e o t h e r h a n d , s u r g e o n s w h o are v e r y f a m i l i a r a n d c o m f o r t a b l e w i t h t h e t e c h n i q u e m a y t e n d to o v e r u s e it. For e x a m p l e , s o m e surgeons may place on ECMO neonates who have refracto N c a r d i o p u l m o n a r y f a i l u r e a f t e r a f i r s t - s t a g e N o r w o o d p r o c e d u r e , w h e r e a s o t h e r s c o n s i d e r t h e p r e s e n c e of a systetnic-pulmonary artery shunt a relative contraindic a t i o n to t h e u s e of t h i s t e c h n i q u e . T h e s e a n d o t h e r c o n f o u n d i n g factors m a k e m e a n i n g f u l c o m p a r i s o n s of t h e f r e q u e n c y of u s a g e of p e d i a t r i c p o s t c a r d i o t o m y E C M O b e t w e e n i n s t i t u t i o n s difficult to i n t e r p r e t .

Group 1 (Cannulated Preoperatively) P e d i a t r i c c a r d i a c s u r g i c a l E C M O is m o s t c o m m o n l y u s e d in p a t i e n t s at s o m e i n t e r v a l a f t e r c a r d i a c r e p a i r , b u t t h e r e a r e v a l i d i n d i c a t i o n s for its u s e in p a t i e n t s p r i o r to t h e s u r g i c a l p r o c e d u r e ( g r o u p 1) [3, 21, 22]. W e e l e c t e d to analyze our experience with preoperative ECMO (group

Ann Thorac Surg 1995;60:329-37

1) separately from postoperative use (group 2) for two reasons. First, group 1, as o p p o s e d to group 2, was generally a neonatal population. Second, the poor clinical condition that p r o m p t e d the institution of ECMO in group 1 patients was related solely to the u n d e r l y i n g congenital cardiac disorder. In group 2 patients, on the other hand, the detrimental effects of the operation itself (CPB, global myocardial ischemia, and total circulatory arrest) contributed to the patients' poor condition prior to ECMO. O u r group 1 hospital survival of 57% c o m p a r e s favorably with the 62% overall survival in the report by H u n k e l e r and associates [21]. If the patient is thought to have a diagnosis of persistent p u l m o n a r y h y p e r t e n s i o n of the n e w b o r n before ECMO a n d the response to ECMO does not a p p e a r to be consistent with that diagnosis, it is i m p o r t a n t to reconsider the possibility of an u n d i a g n o s e d congenital cardiac disorder and to perform a r e p e a t echocardiogram.

Group 2 (Cannulated at Any Interval After Cardiac Repair) INDICATIONS. The decision to p r o c e e d with postcardiotomy ECMO is purely a clinical judgment; no reliable predictors of i m m i n e n t postoperative death have been rigorously established. The decision to cannulate m u s t be m a d e in time for the ECMO team to mobilize and before irreversible e n d - o r g a n d a m a g e occurs. U n d o u b t e d l y some patients are placed on ECMO prematurely, w h e n p e r h a p s medical t h e r a p y alone would suffice. This subjective aspect of postcardiotomy ECMO t h e r a p y hinders retrospective attempts to d e t e r m i n e the true degree of efficacy of this technique in salvaging medically " u n s a l v a g e a b l e " patients. Finally, some pediatric patients with medically refractory postcardiotomy LCO r e s p o n d dramatically to d e l a y e d sternal r e o p e n i n g in the intensive care unit. W e r e c o m m e n d this maneuver, especially in the neonatal p o p u l a t i o n where the response rate is high a n d the m o r b i d i t y is low [19]. Delayed sternal r e o p e n i n g does not preclude later cervical or transthoracic ECMO cannulation. CANNULAT1ON SITE. The majority of patients cannulated in the intensive care unit (subgroup 2B) u n d e r w e n t neck cannulation. This often obviated the n e e d to violate the mediastinum. In our opinion, this accounted, in large part, for the absence of mediastinitis in this series and p r o b a b l y r e d u c e d the incidence of major h e m o r r h a g e requiring mediastinal reexploration. In s u b g r o u p 2B patients, the a d e q u a c y of d e c o m p r e s s i o n by the neck cannulas was d o c u m e n t e d by a significant drop in the m e a n left a n d right atrial pressures (p ~ 0.001 for both) after the start of ECMO. SURVIVAL. O u r group 2 hospital survival of 57.6% has been constant since our previous study (1990) [6] involving the first 36 patients in this series. At that time, we r e p o r t e d a hospital survival of 58.0%. The pediatric ECMO survival rate for cardiac s u p p o r t in the 1994 report of the Extracorporeal Life S u p p o r t Organization [23] was 44%.

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335

UNIVARIATE ANALYSIS (PRE-ECMO VARIABLES). By univariate analysis, three p r e - E C M O variables potentially related to hospital death were identified: (1) longer CPB time, (2) m e m b e r s h i p in s u b g r o u p 2A, a n d (3) possibly, absence of PAHC as an indication for instituting ECMO (see Table 4). A longer CPB time is associated with increased activation of c o m p l e m e n t with its deleterious consequences, increased t r a u m a to the f o r m e d elements of the blood, a n d increased capillary permeability. M e m bership in s u b g r o u p 2A is u n d o u b t e d l y associated with m o r e p r o f o u n d postoperative ventricular dysfunction, as the patient is not able to be w e a n e d from CPB at the end of the repair. Finally, because PAHC is a reversible process, its presence as an indication for ECMO should be positively associated with survival. UNIVARIATE ANALYSIS (ON--ECMO VARIABLES). E l e v a t e d

blood urea nitrogen a n d s e r u m creatinine levels 48 hours after ECMO cannulation were associated with the nonsurvivors in the univariate analysis. This could r e p r e s e n t progression of e n d - o r g a n d a m a g e that b e g a n prior to ECMO cannulation or a lack of a d e q u a t e tissue perfusion during the ECMO run itself. The r e d blood cell a n d fresh frozen p l a s m a transfusions were indexed to the patient's b o d y surface area and also to the duration of the ECMO run. The increased need of red b l o o d cell and fresh frozen p l a s m a transfusions p r o b a b l y correlates with increased blood loss on ECMO. These transfusion variables, therefore, m a y be related to hospital death because of the detrimental effects of persistent h e m o r rhage and the adverse consequences of large transfusion volumes. UNIVARIATE ANALYSIS(POST--ECMO VARIABLES).The association b e t w e e n hospital death a n d an elevated serum creatinine level d e t e r m i n e d 48 hours after ECMO decannulation p r o b a b l y signifies persistent e n d - o r g a n d a m a g e precipitated by LCO prior to ECMO, poor tissue perfusion during ECMO, or other potentially nephrotoxic events. The u n d e r l y i n g adverse factor, such as LCO, that produces the renal insufficiency is p r o b a b l y the variable that, of the two, is most closely related to hospital death. A n elevated right atrial p r e s s u r e averaged over the first 8 hours after ECMO decannulation is p r o b a b l y related to poor cardiac function caused by incomplete myocardial recovery during the ECMO run. This integrates well with renal insufficiency as a possible risk factor for hospital death in the univariate analysis. MULTIVARIATE ANALYSIS. It is not surprising that an elevated right atrial pressure after ECMO decannulation was identified in the multivariate analysis as an indep e n d e n t predictor of hospital death. C o m p a r e d with all of the variables related to hospital death that were isolated by the univariate analysis, an elevated right atrial pressure after ECMO reflects a failure of myocardial recovery during the ECMO run with the most certainty. Similarly, a failure to w e a n from CPB after cardiac repair, t h e r e b y necessitating ECMO cannulation in the operating room (group 2A m e m b e r s h i p ) , p r o b a b l y

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denotes profound myocardial dysfunction from which r e c o v e r y is unlikely. INFERENCES. (1) E x t r a c o r p o r e a l m e m b r a n e o x y g e n a t i o n is m o s t effective in s a l v a g i n g p e d i a t r i c cardiac surgical p a t i e n t s w h o h a v e b e e n w e a n e d f r o m CPB a n d h a v e e x p e r i e n c e d an i n t e r v a l of r e l a t i v e clinical stability b e f o r e r e q u i r i n g E C M O s u p p o r t . (2) A l t h o u g h survival varies w i d e l y d e p e n d i n g on the t i m i n g of E C M O c a n n u l a t i o n relative to the t i m e of the cardiac repair, the results in all of t h e g r o u p s d e f i n e d in this r e p o r t are e n c o u r a g i n g e n o u g h to justify the c o n t i n u e d use of E C M O in a p p r o priate p e d i a t r i c cardiac surgical c a n d i d a t e s w h o h a v e no c o n t r a i n d i c a t i o n s to this t h e r a p y . (3) H i g h e r right atrial p r e s s u r e a v e r a g e d o v e r the initial 8 h o u r s after w e a n i n g f r o m pediatric p o s t c a r d i o t o m y E C M O is an i n d e p e n d e n t p r e d i c t o r of hospital death. (4) C a n n u l a t i o n for E C M O in the o p e r a t i n g r o o m ( s u b g r o u p 2A m e m b e r ship) after u n s u c c e s s f u l a t t e m p t s to w e a n f r o m CPB m a y p o s s i b l y be an i n d e p e n d e n t p r e d i c t o r of hospital death. A m u l t i v a r i a t e analysis w i t h larger n u m b e r s of p a t i e n t s is r e q u i r e d to clarify this assertion a n d to i d e n t i f y o t h e r p o s s i b l e i n d e p e n d e n t p r e d i c t o r s of hospital death. (5) Finally, n e u r o l o g i c c o m p l i c a t i o n s r e m a i n the g r e a t e s t s o u r c e of m o r b i d i t y in p e d i a t r i c p o s t c a r d i o t o m y E C M O survivors.

We acknowledge the important contributions of Art, in I. Philippart, MD, Marc L. Cullen, MD, Linda L. Sell, MD, Steven B. Palder, MD, Marc S. Lessin, MD, and the pediatric general surgery staff, pediatric and cardiac surgical fellows, pediatric cardiology staff, operating room nurses and scrub technicians, pediatric intensive care unit nurses, perfusionists, and ECMO technical specialists at Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, MI.

References

1. Baffes TG, Fridman JL, Bicoff JP, Whitehill JL. Extracorporeal circulation for support of palliative cardiac surgery in infants. Ann Thorac Surg 1970;10:354-63. 2. Bartlett RH, Gazzaniga AB, Fong SW, Jeffries MR, Roohk HV, Haiduc N. Extracorporeal membrane oxygenator support for cardiopulmonary failure. J Thorac Cardiovasc Surg 1977;73: 375-86. 3. Dalton HJ, Siewers RD, Fuhrman BP, et al. Extracorporeal membrane oxygenation for cardiac rescue in children with severe myocardial dysfunction. Crit Care Med 1993;21: 1020- 8. 4. Raithel sC, Pennington DG, Boegner E, Fiore A, Weber TR. Extracorporeal membrane oxygenation in children after cardiac surgeD,. Circulation 1992;86(Suppl 2):305-10.

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5. Anderson HL, Attorri RJ, Custer JR, Chapman RA, Bartlett RH. Extracorporeal membrane oxygenation for pediatric cardiopulmonary failure. J Thorac Cardiovasc Surg 1990;99: 1011-21. 6. Klein MD, Shaheen KW, Whittlesey GC, Pinsky WW, Arciniegas E. Extracorporeal membrane oxygenation for the circulatory support of children after repair of congenital heart disease. J Thorac Cardiovasc Surg 1990;100:498-505. 7. Rogers AJ, Trento A, Siewers RD, et al. Extracorporeal membrane oxygenation for postcardiotomy cardiogenic shock in children. Ann Thorac Surg 1989;47:903-6. 8. Weinhaus L, Canter C, Noetzel M, McAlister W, Spray TL. Extracorporeal membrane oxygenation for circulatory support after repair of congenital heart defects. Ann Thorac Surg 1989;48:206-12. 9. Redmond CR, Graves ED, Falterman KW; Ochsner JL, Arensman RM. Extracorporeal membrane oxygenation for respiratory and cardiac failure in infants and children. J Thorac Cardiovasc Surg 1987;93:199-204. 10. Kanter KR, Pennington DG, Weber TR, Zambie MA, Braun P, Martychenko V. Extracorporeal membrane oxygenation for postoperative cardiac support in children, j Thorac Cardiovasc Surg 1987;93:27-35. 11. Delius RE, Bove EL, Meliones JN, et al. Use of extracorporeal life support in patients with congenital heart disease. Crit Care Med 1992;20:1216-22. 12. Ziomek S, Harrell JE Jr, Fasules JW, et al. Extracorporeal membrane oxygenation for cardiac failure after congenital heart operation. Ann Thorac Surg 1992;54:861-8. 13. Pollock JC, Charlton MC, Williams WG, Edmonds JF, Trusler GA. Intraaortic balloon pumping in children. Ann Thorac Surg 1980;29:522-8. 14. Fukumasu H, Blalock R, Veasy LG, et al. Intraaortic balloon pumping device for infants. Clin Cardiol 1979",2:348-53. 15. Veasy LG, Blalock RC, Orth JL, Boucek MMI Intra-aortic balloon pumping in infants and children. Circulation 1983; 68:1095-1100. 16. Del Nido PJ, Swan PR, Benson LN, et al. Successful use of intraaortic balloon pumping in a 2-kilogram infant. Ann Thorac Surg 1988;46:574-6. 17. Sell LL, Cullen ML, Whittlesey GC, et al. Hemorrhagic complications during extracorporeal membrane oxygenation: prevention and treatment. J Pediatr Surg 1986;21:1087-91. 18. Sell LL, Cullen ML, Lerner GR, Whittlesey GC, Shanley CJ, Klein MD. Hypertension during extracorporeal membrane oxygenation: cause, effect, and management. Surgery 1987; 102:724-30. 19. Hakimi M, Waiters HL, Pinsky WW, Gallagher MJ, Lyons JM. Delayed sternal closure after neonatal cardiac operations. J Thorac Cardiovasc Surg 1994;107:925-33. 20. Pennington DG, Swartz MT. Circulatory support in infants and children. Ann Thorac Surg 1993;55:233-7. 21. Hunkeler NM, Canter CE, Donze A, Spray TL. Extracorporeal life support in cyanotic congenital heart disease before cardiovascular operation. Am J Cardiol 1992;69:790-3. 22. Galantowicz ME, Stolar CJH. Extracorporeal membrane oxygenation for perioperative support in pediatric heart transplantation. J Thorac Cardiovasc Surg 1991;102:148-52. 23. Tracy TF, DeLosh T, Bartlett RH. Extracorporeal Life Support Organization 1994. ASAIO J 1994;40:1017-9.

DISCUSSION DR RALPH E. DELIUS (London, England): Doctor Waiters, I enjoyed your presentation very_ much. I am curious if you have taken these data and defined any indications for extracorporeal membrane oxygenation (ECMO). As you know, the indications for ECMO in cardiac patients are not as well defined as they are in respiratory patients, and in many centers, there is a tendency

to keep on supporting the patients until there is really nothing left to save anymore, DR WALTERS: Doctor Delius, this study was a retrospective analysis, and therefore I cannot honestly say that there were strict criteria for the institution of ECMO during the 91/2-year

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period. W e h a v e n o t yet d e v e l o p e d strict criteria. W h e n we h a v e a p a t i e n t w h o h a s s e v e r e right, left, or b i v e n t r i c u l a r failure or a p a t i e n t with a p u l m o n a r y h y p e r t e n s i v e crisis w h o is u n r e s p o n sive to m e d i c a l therapy, we try to institute E C M O t h e r a p y before a n y m a j o r e n d - o r g a n d a m a g e h a s occurred. It is p u r e l y a n i n d i v i d u a l clinical j u d g m e n t at o u r institution at this time. D R T H O M A S L. SPRAY (Philadelphia, PA): T h a t w a s a very nice series. You n o t e d that s o m e of t h e patients h a d p r o b l e m s with a h i g h e r creatinine level a n d that that w a s a relative predictor of n o n s u r v i v a l . I w o n d e r w h e t h e r t h e r e w a s a n y e v i d e n c e that t h o s e p a t i e n t s w e r e placed on E C M O later in t h e course of their low cardiac o u t p u t s y n d r o m e a n d that w a s w h y y o u h a p p e n e d to see a h i g h e r creatinine value at 48 h o u r s after initiation of ECMO. T h e m e a n t i m e to initiation of E C M O p o s t o p e r a t i v e l y w a s fairly long in y o u r series, m o r e t h a n 30 h o u r s , w h i c h s u g g e s t s that t h e s e p a t i e n t s h a d g o n e a fairly long t i m e after o p e r a t i o n before m o s t of t h e m were p u t on ECMO. M y s e c o n d q u e s t i o n h a s to do with the neurologic p r o b l e m s y o u noted. W e r e t h e neurologic e v e n t s in a n y w a y related to the side of t h e neck c a n n u l a t i o n ? Do y o u t h i n k t h e r e is a n y differe n c e w h e t h e r t h o s e p a t i e n t s are c a n n u l a t e d from t h e neck or the chest, a n d do y o u r e a n a s t o m o s e the v e s s e l s in t h e neck in t h e s e p a t i e n t s after t h e y are w e a n e d from E C M O s u p p o r t ? D R WALTERS: Doctor Spray, in this analysis, I did not specifically look for a correlation b e t w e e n l o n g e r time to t h e institution of E C M O a n d p a t i e n t s w h o h a d an elevated creatinine level. T h e s u b j e c t of future investigation at o u r institution is to look not only at the actuarial survival of E C M O p a t i e n t s b u t also at t h e l o n g - t e r m neurologic o u t c o m e . As you know, that is a veD' difficult t h i n g to do b e c a u s e m a n y of t h e s e patients h a v e D o w n ' s s y n d r o m e a n d o t h e r r e a s o n s b e s i d e s E C M O for neurologic a b n o r m a l i t i e s . To date, we h a v e detected no definite correlation b e t w e e n neck c a n n u l a t i o n a n d neurologic events. D R J. T E R R A N C E D A V I S ( C o l u m b u s , OH): 1 e n j o y e d y o u r report very m u c h . M y colleagues a n d I s t r u g g l e d also with t h e indications on h o w long to wait: w h e n is it t i m e to go a h e a d with E C M O a n d w h e n is it time to try m o r e medical t h e r a p y . O n e indication m a y be the overall p e r c e n t a g e of time that you go to ECMO. Do you h a v e a n y s e n s e over this s a m e 9V2-year period h o w m a n y o p e n h e a r t p r o c e d u r e s were done? C a n y o u tell u s w h a t p e r c e n t a g e of y o u r patients e n d u p getting E C M O s u p port? D R WALTERS: Doctor Davis, o u r overall i n c i d e n c e of the u s e of E C M O in a b o u t 2,500 o p e n p r o c e d u r e s over 91/2 y e a r s is 3%, a n d in the last year, it was 1.4%. In the literature, the incidence r a n g e s from 1.5% to a p p r o x i m a t e l y 8% at o t h e r institutions that report their f r e q u e n c y of E C M O usage. D R P E D R O J. DEL N I D O (Pittsburgh, PA): This is a very nice study. W h e n we looked at o u r series, m y colleagues a n d I did not find c a r d i o p u h n o n a r y b y p a s s time to be a risk factor. After s o m e consideration, we t h o u g h t that p e r h a p s t h e r e a s o n w a s o u r h e s i t a n c y to go to E C M O or at least o u r relatively low t h r e s h o l d to go to E C M O in t h e s e children. T h e r e f o r e we did not m a k e m u l t i p l e a t t e m p t s to w e a n t h e m from b y p a s s before instituting ECMO. C a n you give u s an i n s i g h t as to w h a t criteria y o u n o w u s e to

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decide w h e n a child is n o t g o i n g to c o m e off b y p a s s a n d y o u are g o i n g to try to s u p p o r t h i m or h e r on E C M O ? D R WALTERS: Doctor del Nido, t h e p a t i e n t s w h o n e e d E C M O s u p p o r t in t h e o p e r a t i n g r o o m h a v e s o m e f o r m of left v e n t r i c u l a r failure or biventricular failure. W h e n we are u n a b l e to discontinue c a r d i o p u l m o n a r y b y p a s s d e s p i t e t h e a d m i n i s t r a t i o n of m u l t i p l e p h a r m a c o l o g i c a g e n t s s u c h as d o p a m i n e h y d r o c h l o ride, d o b u t a m i n e hydrochloride, e p i n e p h r i n e , a n d afterload r e d u c e r s , we p u t the p a t i e n t back on b y p a s s for a p r o l o n g e d t i m e to rest t h e heart, a n d t h e n we try a g a i n to w e a n h i m or her. However, I e m p h a s i z e that w h e n we calculated o u r cardiopulm o n a r y b y p a s s times, for t h e p u r p o s e s of t h e analysis of survivors v e r s u s n o n s u r v i v o r s , we calculated t h e c a r d i o p u l m o n a r y b y p a s s t i m e to t h e first time of t e r m i n a t i o n . W e did n o t i n c l u d e the p e r i o d s d u r i n g w h i c h we " r e s t e d " the h e a r t o n cardiopulmonary bypass. D R DEL N I D O : H o w did y o u d e t e r m i n e w h e t h e r r e s i d u a l defects were a r e a s o n for instituting E C M O either i m m e d i a t e l y p o s t o p eratively or in t h e first 24 to 48 h o u r s ? D R WALTERS: D u r i n g the latter part of the s t u d y period, we u s e d t r a n s e s o p h a g e a l e c h o c a r d i o g r a p h y in t h e o p e r a t i n g r o o m w h e n e v e r we s u s p e c t e d that we were g o i n g to h a v e to institute E C M O . O u r e x p r e s s p u r p o s e in d o i n g this w a s to look for residual lesions. In p a t i e n t s in t h e i n t e n s i v e care unit w h o h a d h a d an interval of relative clinical stabiliW, we u s e d either t r a n s e s o p h a g e a l e c h o c a r d i o g r a p h y or transthoracic echocardio g r a p h y . Early in t h e series, t h o u g h , t r a n s e s o p h a g e a l echocard i o g r a p h y w a s n o t available. D R J O H N E. MAYER, JR (Boston, MA): C a n y o u tell u s h o w m a n y patients h a d a residual defect? D R WALTERS: N o n e of t h e p a t i e n t s in this series h a d a r e s i d u a l defect. D R J O H N W. B R O W N (indianapolis, IN): T h a t w a s a very nice series with g o o d survival. C o u l d y o u outline y o u r indications for institution of E C M O in the s u b s e t placed on E C M O several h o u r s to d a y s after cardiac repair. All of u s struggle with this subset, a n d t h e r e will p r o b a b l y be a n u m b e r of institutional variations. In o u r series, o u r g r o u p 2A p a t i e n t s h a v e twice t h e survival of o u r g r o u p 2B patients, w h i c h is t h e opposite of w h a t y o u report. At o u r institution, if a b a b y is h a v i n g difficulty in t h e o p e r a t i n g r o o m a n d the i n t r a o p e r a t i v e e c h o c a r d i o g r a m s h o w s no additional correctable p r o b l e m s , we tell the p e r f u s i o n i s t to set u p an E C M O circuit, a n d we rest the b a b y for 2 or 3 d a y s on ECMO. It is i n t e r e s t i n g that o u r institutions h a v e the opposite r e s u l t s in the 2A a n d 2B g r o u p s . Is nitric oxide u s e d in y o u r institution? If so, d o e s it h a v e a n y effect on t h e i n c i d e n c e of y o u r u s e of E C M O postoperatively? DR WALTERS: Doctor Brown, we h a v e n o t yet u s e d nitric oxide on o u r service. I can tell you, t h o u g h , that t h e n u m b e r of p a t i e n t s we have lately h a d to p u t on E C M O for p u l m o n a r y artery h y p e r t e n s i v e crises is m u c h r e d u c e d . W e s e e m to be treating t h o s e patients better m e d i c a l l y n o w t h a n we did in t h e first 5 y e a r s of t h e series.