316

Extracorporeal Membrane Oxygenation (EeMO) for Neonatal Respiratory Failure J. B. Zw ischenberger and C. S. Cox, Jr.

Summary

Beha ndlung der neo na la ien respl ra tort sch en Ins uffizien z

tionskriterien sind ane rkannt: Versagen der maximalen Th era pie, Oxygenationsindex (mittl. Beatmungsdruck x in spirierter Oz-Anteil x 100 dividiert durch den postduktalen Pa02) ' A· aD02 , akute Verschlechteru ng und Barotraum a. Als Kontraindlkationen werden die intrakranielle Blutung oder ein anderer Hirnschaden. multiple kongen itale AnomaHen und ein irreversib ler Lunge nsc hade n anges ehen . Unter den 5863 Pattenten fande n sich folgende Diagncsen in der Reihenfolge der Haufi gkeit: Mekoni um-Aspirations-Syndrc rn, Hyallne-M embran-Kran kh eit, kongenitale Zwerchfellhernie, Sepsis und persistiere nder pulmonaler Hochdruck des Neuge borenen. Es wird die Techni k der ECMO·Therapi e beschrieben, es we rden die beobachteten KompHkatio nen aufgeflihrt und es we rden follow-up-Daten vorgelegt.

Es wird tiber den gegenwarttgen Stand der Beha ndlung der respira torischen Insuffizienz von Neuge borene n mit EC MO be-

Key w ords

richtet. Weltwei t worden hi s Januar 199 2 in 83 Zentren (devo n 13 auBerhalb der USA) 5863 Neuge borene mit ECMO behan delt mit eine r Ober lebensquote von 82 % . Folgend e Indika-

Extracorporeal oxygenation - Membrane oxygenation - Indications - Complications - Extraco rporea l Life Support Organization

Extraccrporea l membran e oxyge nation (EeMO) has been a successful treatment (82 % survival) in over 5000 neonates w ith seve re respi rato ry failure (80 % pred icted mortality wi thout ECM O) . ECMO is prolonged extracorporeaJ ca rdtopulmonary bypass achieve d by ext r a tho racic vasc ular cannulation using a modified hea rt-lung machine . EeM O is currently the treatment of choice for full-te rm new borns with seve re respiratory failure. The report summarizes indications. resu lting co mplicatio ns . and future applications of neonatal ECMO. Extrakorpora le Membran -Dxygen ierung (ECMO) zur

In troduction

technique (5, I S, 28 , 29). As of January 1992, ECMO, prolonged extra corp ore a l cardiopulmonary byp a ss a ch iev ed

Gibbon began developing the heart-lung ma chine in 1937 (13) an d began th e er a of open cardia c surgery in 1954. The use of an artificial pump a nd lung, however, was limited to 1 or 2 hours, not becau se of th e pump, but because th e oxygena tor severely altered blood cells an d pro-

by extratho racic vasc ular cannulation (16, 30), has been used in th e managem ent of 586 3 n eonates in 8 3 centers

worldwide (13 outsid e the US) with an overall survival rate of 82 % (12). This observation alone is sufficient to establish ECMO as therapeutically effective , since infan ts in

tein s . The first m embrane oxyge nator built and us ed clini-

th e s e cen te rs ar e treated o n ly after th ey m eet crite ria pr e-

cally was reported in 1956 by Clowes and his coworkers (10). With the introduction of silicone r ubber as a membran e for gas tran sfer, the memb ran e oxygenato r becam e pra ctical for long-term car diopulmonary bypa ss (18). Extra corp or eal cir cul ati on for re sp iratory failure w a s first at-

dicting an 80 % mortality. Bartlett and associates con ducte d th e first prosp ective randomi zed study of ECMO in newborn infants (6). The statistical meth od used in this study (randomized play-th ewinner) (11), whi ch for ethical cons iderations pr ogr essive-

tempted in newb orn s by Rashkind and associates (23).

ly w ei g hts th e more successful treatm ent, dir ect ed 11 p a -

After a s e rie s oflabo rato ry s tud ies , Bartlett a nd cowo rkers

tients to the ECMO gr oup (all survived) and 1 pati ent to the

began clinica l trials of extracorporeal me mbrane oxygena tion mCMO) in 1972 , and rep orte d the first success ful use of ECMO in newborn respiratory failur e in 1976 (4). Sub-

co ntro l group (d ie d). O'Rourke and a ssociat e s lik ewis e con duct e d a pr ospective randomi zed s tud y co m paring ECMO to co nven tio n al mech an ical ventilator therap y ; s ix o f te n s u rvivors w e re in th e conventional tr eatm ent gro u p a n d 2 8

sequen tly, severa l gro up s were succ e s sful u sing Bartlett's

of 29 survivors were in the ECMO group (21). These studies helped to confirm th at ECMO is th e treatment of choice for Presented in part at the 21st Annual Meeting of the German Society for Thoracic and Cardiovascular Surgery February 19-22 . 1992 . Bonn

Thorac. cardlovasc . Surgeon 40 (1992) 316-322 © Georg Thieme Verlag Stuttgart New York

full-term n ewborns with s e vere re spiratory failure .

Although ECMO has been used since 1975 , systema tic co llec tion of informati on co ncern ing its u s e w a s not begun

Received for Publication: April 12. 1992

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Division ofC ardiothoracic Surgery. Univers ity of Te xas Medical Branch. Galveston , Texas. USA

Extraco rpo rea l Membra ne Oxygenation (ECMO)for Neona tal Resp ira tory Failur e

Patient selection Th e indi cati on for ECMO support is acute reversible respiratory or cardiac failure unresponsive to optimal ventilator and pharmacological management, but from which recovery can be expected within a reas onable period (10 -14 days) of extra corporea l support. The requirement for systemi c heparinizati on limits th e population for wh om ECMO is appropriate to patients without bleeding complications or wh o are a t high risk for intracranial hem orrhag e. th er eby excluding pr em ature infants (less th an 34 weeks gestation) (9). Criteria for instituting E C~ IO cha nge d a nd evolved durin g th e 12 years of this rep ort. Th e goa l was to ide ntify infants with a gre a ter than 80 % likelih ood of dying. Included a re neona tes wh o. desp ite optim um medi cal man agement dem onstrate: acute deterioration, failure to improve, uncontrolled tension pneumo thoraces or pneumomediasti num, or deterioration following diaphragmatic hernia repair. Excessive alveolar to arterial oxygen gradients a lso have been proposed as an indi cati on for ECMO (15). In a retrospective review by Krummel and associates, an alveolar to arterial oxygen gradie nt greater tha n 620 mmHg for 12 cons ec utive hours correlated with over 90 % mortality (19). Many program s curre ntly use th e oxygena tion index: mean airway pressure x 100 divided by postductal arterial oxygen partial pressure (Pa02)' In most hos-

317

Table 1 Cnteriaand Outcomefor Neonatal ECMO

%Total

Survival

26 %

80 %

A·a 0",

18 %

Oxygenation Index Acute Deterioration Barotrauma

27 % 21 %

87 % 85 % 77 % 89 %

Failure to Respond to Maximum treatment

2%

Table 2 Aggregate survival by diagnosis (5863 cases) Meconium Aspiration Syndrome Hyaline Membrane Disease Congenital Diaphragmatic Hernia Sepsis Persistent Pulmonary Hypertension of the Newborn Other

93 % 12058/22121 85 %(688/813) 61 %(668/109 11 77 %(619/805) 87 %1642/739) 79 %(\ 52/2031

pitals, an oxygenation index cons istently over 40 after optimal conventional therapy defines greater than 80 % morta lity. Th e criteria recognized by the Registry and the in cidence in this report were : failure to respond to maximum treatm ent (26 %), oxygenation ind ex (27 %), A-aDo, (18 %). acut e deterioration (21 %) and barotra uma (2 %). Oth er criteria have been used but are now obsolete or represent less th an 6 % (Tabl e 1). Contraindications to ECMO include evidence of intracranial hemorrhage (grade I is controversial) or other brain damage , multiple congenital anomalies, and irreversible lung damage. Mechanica l ventilatio n beyond 10 days is considered a relative contraindication and beyond 14 days abso lute although exceptions have been noted. In congenital diaphragmatic hernia one cannot distinguish between persis tent fetal circulation and pulmonary hypoplasia, th er efore, most centers tr ea t a ll pa tients with dia phragmatic hernia who otherwis e meet local ECMO criteria. Some centers require a Paoz > 70 torr at som e time in the neonate's life as evidence of pulmonary parenchyma capable of gas excha nge. This is to avoid using ECMO to treat infants with fa tal pulmonary hyp op lasi a . Possible ECMO ca ndidates are evaluated with cranial ultrasound to rule out intracranial hemorrhage, and with cardiac ultrasound to rule out congenital anomalies . Because of regional differences in patient populations and treatment protocols, entry criteria a re evalua ted at eac h hospital before a n ECMO program is initiated. The primary diagnosis for the entire series were meconium aspiration syndrome (38 'Yo), congenital diaphragma tic hernia (19 %), hyalin e membrane dis ease (14 %J, se psis (14 %) persistent pulmonary hypertension of th e newborn (13 'Yo), and oth er (3 %) (Table 2).

Techniques and management Th e average duration of ECMO is 135 ± 85 hour s. Although there are some differences in management, most centers practice similar techniques . Us ing local anesthesia , an operating room team performs the dissection and cannulation of the internal jugular and commo n carotid artery in the int ensive ca re un il. The infant is give n a 100 -uni Vkg bolus of heparin as a loading dose. The vesse ls are ligated distally and cannulas are inserted in a proximal direction from the ligation site. The venous cannula is threaded

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until 1980 . In its origina l form at as th e Neonatal ECMO Registry, information was collected concerning patient dem ograph ics . pr e-ECMO clinica l featur es , ECMO indica tions , medical and technica l complications , and shortterm out com e. Betw een 1980 and 1987. 715 patients were registered from a small number of E C ~I O centers (27) . Eighty-one percent of tr eated infants survived despite a predicted 80 % mo rtality. Technical com plications occurred in 23 % and physiological complications occurred in 65 %. Survival rates for the first 10 patients at any one center were significantly worse than for the sub se que nt 10 pati ents (74 % v 84 %, p < 0. 0 1), reflectin g a learning curve. Since th at rep ort. th e number of ECMO centers and infants treated has greatly increased (see Figs . 1 and 2). In 1991 St olar, Sn edecor a nd Bartlett reviewed the demographics, clinical features , and shorttenn outcome of the infants in what is now called the Neonatal ECMO Registry of th e Extra corporeal Life Support Orga ni zati on (ELSO) (incorp or ated 1989. Ann Arb or. Mil (26) . Of 352 8 infants with a pr ed icted mortality > 80% trea ted with ECMO. 83 % survived . Entry diagnoses and aggregate survival were: meconium aspiration syndrome (MAS) 93 %. persistent pulmon a ry hype rte nsion of th e newborn (PPIIN) 83 %; congenital diaphragmatic hernia (CDH) 62 %; hya line membran e disease (liMO) 84 %: sepsis 77 %; and other 77 %. ECMO indications were A-aDoz > 600 m mll g for 6 to 8 hours (22 %), oxygenation index > 40 for 4 hours (18 %). acute deterioration (14 %), maximal therapy failure (34 % ), and barotrauma (1 % ). Annual survival improved over Y years exce pt for CDH, which decreased from 70 % (19 87) to 56 % (1989). p < 0.01. Surv ivors differed from non -su rvivors (p < 0.05) by birth weight (> 2 kg), gestatio nal age [> 37 weeks), entry diagnosis (MAS. I'PHN, HMD. sepsis v COli) , inbo rn vers us outborn, pre-ECMO pll, a nd ECMO duration . Technical complications in 25 % of patients and medical complications in 75 % adversely affected survival.

Thorne. eardiov as e. Surgeo fl 40 (1 992)

J. B. Zwischenberger and C. S. Cox. Jr.

Thome . eardiovas e. Surgeon 40 (199 2)

through the right int ernal jugular vein into the right atrium and th e arteri al can nula is th readed into the common carotid so that its tip rests at the entrance to the aortic arch. The common carotid artery in a neonate can be successfully ligat ed with a relati vely low complication rate, pre sumahly because of abundant collateral flow (8, 24), Once extracorporeal support is established, ventilator settings are reduced to minimize the barotrauma and oxygen toxicity (peak inspiratory pressure to 20 cm H20; rate 10/mi n; fra ctional inspired oxygen 0.3.) ECMO flow is maintained at a level that achie ves full respiratory support until lung improvem ent occurs (80 to 120 ml/kg/min usually is 300- 400 ml/min). Adequate support is defined as the level of extracorporeal flow that results in normal arterial and mixed venous oxygenation, mean arterial pressure, and organ function. Anticoagulation must be maintained during the entire course of treatment. As the lungs beginn to recov er, extracor poreai blood flow is reduc ed in a stepwise fashion until only 10 % to 20 % of the infan t's cardiac output (usually 40 - 80 ml/min) is diverted through the cir cuit. After an idling peri od of 8 to 12 hours to ensure continued lung function, the circuit is disconnected . the cannulas rem oved , and th e vessels ligated pro ximally. Initially following decannulation the infan t is maintain ed with mechanica l ventilation, but is usually weaned to an oxygen hood within 48 to 72 hours. Termination of ECMO is indicated whe n th ere are signs of irrever sible hr ain damage, uncon tr ollable bleeding. or irreversible lung damage. Some programs will continue ECMO indefinitely if progressive improvement is seen or if open lung biopsy demonstrates a reversible condition.

Complications The medi cal managem ent of the ECMO patient, includ ing mechanical and patient-related complications, spans the entir e field of critical ca re (31). The following ha ve been re ported in the latest ELSO re gistr y update. There wer e 1039 mechani cal complications reported in 3528 ECMO cases , or an average of 0 .31 mechanical complications per case . Mechanical complic ations as rep orted in the ELSO Registry include: clots in the circuit, cannula placement, oxygena tion failure, air in the circuit, cracks in pigtails/conne ctors, pump malfunction, hea t-exchanger malfunction, racewa y rupture, and mechani cal "other" (Table 3). Surv ivors reported 0.31 ± 0.5 complications per case while non-survivors r eported 0.45 ± 0.6 complications per case (p < 0.1). There we re 5054 patient complications in 35 28 cases or an average of 1.50 ± 1.9 complications per case. Of the registered ECMO patients, 37 % had no medical complica tions . There was a 95 % survival in patients with no medical complications. Survival decreased to 76 % with 1 or more medical complications (p 150 Na' > 125 Ca'" > 12 Ca++ < 6

CHO > 240 CHO < 40 pf-i > 7.60 pH < 7.20 Other

72

32 72

Outcome From January 1980 to January 1990, more than 3528 newborn infants were treated with ECMO at 83 cent ers (13 cent er s are outside the United States) (Addendum). Fig. 1 sho ws the number of ECMO centers opening each year and cumulative active centers. The survival rate for the entire series , including all of the early cas es, is 83 % (Fig. 2) (12). Outcome by prim ary respiratory diagnosis (Tabl e 2) in decreasing percentage of survivors on ECMO include: meconium aspiration 93 %; primary pulmonary hypertensian/persistent fetal circulation 87 %; respiratory distress

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318

Extracorporeal Membrane Oxygenation (HeMOJ/o r Neonatal Respiratory Failure

8

90 80 70

15

1500

"E

1250

ss •• •m

UJ

1000

'0

> ~ "5

750

0

0

0

60

o UJ

50

" ""

• "••

10

40

c c m

30 5

"o

0

• E

"

500

0

20

25

~3

'~

~

•

~7

•

W

•

~1

0

year

.8E c" ~

250

10 ~

319

o

73-'79 '80 '81 '82 '83 '84 '85 '86 '87 '88 '89 '90 year

a

Fig. 1 ECMO centers opening each year and cumulative active centers.

Fig.2 Annual ECMO patient survival rates and annual total numbers of

syndrome 85 % ; beta streptococcal pneumonia/sepsis 77 %, and congen ital diaphragmatic hern ia 61 %. Table 1 documents survival as a function of se lection criteria. oxygena tion index (85 % ) a nd A-aDo, (87 %) yield a similar ly good survival rate. Patients entered because of acute deterioration had a 77 % survival, reflecting the eme rgent initia tion of ECMO in this gr oup. As previously noted by S tolar et al. (26), th e 26 % of patients who entered becau se of failure of maxima l therapy (clinical judgement) might be criticize d for lack of rigorously defined entry criteria. This group, however, had only 70 % survival, suggesting they were either more desperately ill or ECMO entry was accomplished mor e, not less, stringently than in the othe r en trycriteria groups . The quality of life for survivors appears the same as or better than that reported for conventional respiratory care and the cost may be less . Short and Pearson evaluated the effect of ECMO the ra py on hos pital charges (25). By decreasing average length of stay and esse ntially eliminating bronchop ulmonary dysplasia and other chronic lung damage secon dary to maximum ventilator support, ECMO therapy redu ced total hospital and physicia n charges considsera bly. The length of hospitalization for survivors of routin e th erap y and ECMO therapy were 75.8 and 25.0 da ys, respectively. Total charges were 43 % lower for ECMO patients. Follow-up on 72 survivors from Bartlett ran ges from 3 mo nths to 11 years (3). Of these 72 infants , 45 (63 %) are normal or near normaLThere have been seve n late deaths. Twelve patient s (17 %) ha d major ne urological dysfunction and developm ental delay. Eight ha d pulmonary dysfunction (needed suppleme ntal oxygen at the time of hospital dis charge). Glass and associates (14) reported the outcome in 42 patients at 1 year of age . Using the Bayley Scales with a score greater than 90 considere d normal. they found that 25 of 42 patients (60 %) we re normal an d eight infants (19 %) generally had a mild motor delay with nor ma l scores on the mental scale. The researchers also identified three factors that were associated with a poor outcome of 1 yea r of age : pre-ECMO diagnosis of se psis, chronic lung disease, and abnormal cranial ultrasound or CT scan. Adolph an d others (I ) rep orted res ults consis tent with the previous reports of outcome in neonata l ECMO. Based on the Bayley Scales, the McCart hy Scales, and the Gessel!,

74 % of 57 patients were norm al. Only one patient (2 %) was profoundly delayed. Results are thought to be poor in infants ofless th an 35 weeks gestation. Only 4 of 16 pati ents in this group survived in an early series . Almost all the deat hs were due to intracranial hemorrhage or cere bral edema. Intracranial bleeding is often a terminal event in critically ill premature infants and may be aggravated by thr ombo cytopenia and anticoagulation during ECMO. Bui et al. (7) reviewed these patients and concluded that survival of moribund prema ture infan ts might be 50 % or greater with ECMO usin g improved indications and technology. Differentiation between preexisting deficits and those seco ndary to ECMO remains difficult; however, some infants at high risk for brain damage (low Apgar scores, perinatal cardiac arrest, prolonged or profound hypoxia, prolonged fetal distress) ha ve normal mental function, so definitive predictors of outcome have yet to be determin ed. Norma l function and developm ent (up to 90 %) at follow up of ECMO survivors is encouraging an d suggests that ECMOsupport can be accomplished sa fely and that subsequent norm al de velopment is frequent. The ELSO par ticipan ts continue ta bulation of mu lticenter early res ults and are organizing a long term follow-up st udy.

patients treated through 1990.

Ven ovenous ECMO Total support of gas exchange with venovenous perfusion returning perfusate blood into the venous circulation through the femoral vein or a modified jugular venous drainage catheter has the advantage of avoiding carotid artery ligation in the neonate. As we treat patients earlier in this course of respirat ory failure, the need for total support will be less , with some gas excha nge still pers isting in the native lung. Although jugulo-femor al venoveno us bypass is feasible and was used in 16 patients, the advantages do not outweigh the disad van tages in neonates (17). The occa siona l nee d for better cardiopulmonary support, and the extra complexity ofven ovenous bypass leads us to favor venoarteri al bypass for unstabl e neonates. Bartlett 's gro up has developed a polyur ethan e dou ble-lumen cath eter for sing le-site cannulation of the intern al jugu lar vein (22 , 32). Venovenous life support for seve re respiratory failure was successfu l in 15 of 17 neonates with 2 of 17 converted to

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20

ss "• "E

Thorae. eardiovase. Surgeon 40(1992)

Thome. cardiovas c. Surgeon 40 (1992)

venoarte ria l bypass beca use of ina de qua te support (2). A tidal flow venove nous system with a single-lumen catheter (32) as well as an intr aven ous gas exchange device (20) have also been developed to aid venous gas excha nge. Single-site-cannulation veno venous bypass may soo n become the method of choice for most newborn patients. Developme nt an d refinement of ECMO technology are not limited to newborns with respiratory failure. Vascular access techniques , methods of clotting-time measurement, and long term use of membrane oxygenators are utilized in cardiopulmonary bypass for cardiac surgery. The servocontrol mechanism, heparin-coated circuits, and perfusion techn ology gained from the ECMO experience also have applica tion in ca rdiac and tra nsplant surgery. Similarly, measurements of whole blood activated clotting time and techniques of prolonged continuous perfusion are useful in hemod ialysis, hypert hermic perfusion, and hemofiltration. Comment

Between 19 8 0 an d 19 91 , 5 863 ECMO cases wer e registered with an overall survival of 82 % in a population expected to have at lea st an 8 0 % mortality. Although a previous Registry report (27 ) descri bed a learning cur ve for th e first 10 patients , with subsequent experience and additional new ECMO centers the overall survival rate has been unaffected and remains close to 9 0 % for all entry diagnoses except CDH. Diagnosis-specific outcome analysis suggests more about the pa rticular diagnosis than ECMOitself (26 ). Specifically, CDH had significa ntly more hem orrhagic complications and poorer survival than other diagnoses. Of all the ECMO entry diagn oses, CDH is th e only situation in which the patient has less than two completely developed lun gs and requires an operation. The hemo rrhagic complications can be attributed to the major operation necessary to repair the diaphragmatic hernia, either imme diately before or during ECMO. The poorer surviva l can be related, in part , to the hemorrh agic comp lications, but also to pulmon ary hypoplasia to a degr ee that is incompatible with life. With the incre ase d availability of ECMO, more infants with CDH, pa rt icularly the most despera tely ill, will receive ECMO. Sepsis is characte rized by mu ltiple orga n failur e, which may acco unt for the increased morbidity. Selection criteria remain problematic for a variety of reason s. They cannot be viewe d as absolute because of variability between centers. What represents likely 80 % mortality in one center may not apply to another. Historical contro ls are mislead ing becau se cha nging respirator y therapy strategies make histor ical populations difficult to compare, Also, once an ECMO center becomes esta blishe d, a more cha llen ging group of patients will be at tracted than previously was the case . Further, a single entry criteria cannot be generalize d for all entry diagnoses. It is misleading to sugges t that criteria for an 8 0 % predicted mortality is the sa me for MAS, CDH, PPHN, and sepsis. Subse quent pati ents r egistered in the Neon ata l ECMO registry of the Extracorporea l Life Support Organization will address these issues more thoroughly, as specific details of the preECMO condition and thera pe utic str at egies are collected,

1. B. Zwischenberger and C. S. Cox, Jr.

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with extr acorporea l memb rane oxygena tion. J. Pediatr. Surg. 25 (1990) 43-46 Anderson. I/. L.. Ill. T. Otsu. R. A. Chapman, and R. H. Bartlett: Venovenous extracorporeal life support in neonates using a double lumen cathe ter. ASAIO Trans . 35 ( 989) 650 - 653 Andrews, A. F. C A. Nixon. R. E. Cilley. D. W Roloff. and R. tt. Bartlett: One-to-three-year outcome for 14 survivors of extracorporeal me mbrane oxygenation. Pediatrics . 78 (9 86) 692 698 Bartlett, R. 1I.. A. B. Gazza niga. M. R. Jefferies. R. F Huxtable. N. 1. Ilaiduc, and S. W Fond: Extracorporeal mem brane oxygenat ion mCMO) cardiopulmonary support in infancy. Trans. Am. Soc. Artif. Intern. Organs. 22 (19 76) 80- 9 3 Bartlett. R. l l., A. B. Gazzaniga, and J. Toomasian et al.: Extracorporeal mem brane oxygenation (ECMO) in neonatal res piratory failure, 100 cases. Ann. Snrg. 204 (1986) 236 -245 Bartlett. R. D. W Roloff. R. G. Cornell. A. E Andrews. P W Dillon, and J. B. Zwischenberger: Extracorporeal circulation in neonatal respiratory failure: a prospective randomized study. Pediatrics. 76 (1985) 479 - 487 Bui. K. C. P LaClair. 1. Vanderkerhove. and R. fI. Bart lett: ECMO in Premature Infants. Review of Factor's Associated with Mortality. ASAIOTrans 37 (1991) 54 -59 Campbell, L. R.. C. Bunyapen, G. L. Holmes, C G. Howell, Jr , and W P Kanto. Jr. : Right commo n carotid artery ligation in extracorporeal me mbrane oxygenation . J. Pediatr. 113 (1988) 110 - 113 Cilley. R. E.. 1. B. Zwischenberger. A. F Andrews. R. A. Bowerman. D. W Roloff. and R. H. Bartlet t: Intracranial hemorrhage during extracorp oreal membrane oxygenation in neo nates . Pediatrics. 78 (1986) 699-704 Clowes. G. II., Jr., A. L. Ilopkins, and W E. Neville: An artificial lung depend ent upon diffusion of oxyge n and carbon dioxide through plastic mem branes . J. Thorac. Cardiovasc . Surg. 32 (1956) 6 30 -637 Cornell, R. G., B. D. Landenberger. and R. If. Bartlett: Randomized play-the -winn er clinical trials. Comm Statistics Theory Methods. 1 (1986) 159 -178

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Hxtracorporeal Membrane Oxygenation (/;,CMO)fo r Neonata l Respiratcrq Failure 21 O'Rourke. P T . R. K. Crone. 1. P: Vacanti et al.: Extracorpo real m em bra ne oxygena tion (ECMO) an d conve ntiona l me dical therapy in ne onates with persistent pulmo nary hypertension of th e newborn : a pros pecti ve ran dom ized stu dy. Pediatrics. 84 (1989 ) 957 -967 22 OISll. T, II. Anderson. H. Cha p numn, and H. II. Bartle tt: Veno ven ous extra corp creal life s uppo rt in neona tes us ing a do ub le lume n ca thete r. A5AIO Abst racts . 18 (1989) 6 1 23 Rashklnd. ~v 1.. A. l-r eeman. IJ. Klein. and H. W ToJL Evalua tion of a disposable plastic. 10...... volume, pumplcss oxyge nator as a lun g subs titute. J. Ped iat r, 66 (196 5) 94 - 102 24 Schuma cher; H. E., J. D. Barks. an d M. V. Johnston c t al.: Hightsided b rain lesions in in fan ts following extracorpo rea l membrane oxygenation . Ped ia tric s. 82 ( 988) 155 - 161 25 Sh ort; B. 1... and G. D. Pearson: Neona ta l cxtrucorpore a l me mbrane oxygenatio n : A review. J . lntens. Ca re Med . 1 (19 86) 47

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29 Weber. T. R., D. G. Penning ton. R. Connors et al.: Extracorpo real mem brane oxygenation for new born respiratory failur e. Ann . Th orac. Su rg. 42 ( 986) 529 -535 30 Ztolschenberqer; 1. B., and R. I/. Bartl ett: Extracorporeal circ ula tion and oxyge nation. In: Civetta , J . M.. Taylor, H. W.. an d Kirb y, H. H. eds. Critical Care. Lippin cott Pubs (1988) 1629 1637 3 1 Ztoischenberqer. J. B.. C. S. Cox: Complica tio ns During Ext racorporeal Mem brane Oxygen ation (ECMOl, In : Are ns ma n . R., Corn ish , D. cd s. for th e Extracor poreal Life Support Orga nization . ECMO. In Press. 32 Zunschenberqer; 1. B., J. M. Toomasian. K. Drake. A. F Andr ews. T. Kolobow, and R. 11. Bartlett: Total respiratory support w ith single ca nnu la ve novenous ECMO: double lum en cont in uous flow vs single lum e n tidal flow. Tr an s Am . Soc Arti f Intern Organs. 3 1 (19 85 ) 6 10 -6 15

1. B. Z toisc henberce r, M. D. Division of Card iothoracic Surgery 6 .120 John Sealy University of Texas Medical Bra nch Ga lveston, Texas 775 55-0528

USA

Addendum: Cont r ib ut ing I:C.\IO Ce n ters or t he Ex t r aco r por c a l Life Suppor t Or g an ization Univers ity of Michi gan Ann Arbor, Michiga n Child ren 's Hos pital Pittsbu r gh, PA Medica l College of Virgin ia Hic hm ond, Virginia Ochsn er Clinic New Orleans, LA Colu mbia Pres byter ia n Ilospital New York, NY Children 's Hos pital of Michigan Detr oit, Michi gan Childre n' s Nationa l Med ical Cente r Washington , D. C Ca r dina l Glen non Childr en 's Hospi ta l 51. Louis , MO Georgetown Un ivers ity ll ospita l Washington , D. C. Kosa ir Children 's lIospita l Lou isville, KY Miami Valley Hos pital Da yton , Oh io Medical Colle ge of Georgi a Augusta , Georgia Tho mas J effer so n Unive r sity Hosp ital Ph iladelp hia , PA Childre n's Hosp ital Medical Cent er Cinci nnati. Ohio Child ren 's Hos pital of Ora nge County Orange, CA Chi ldre n 's Hosp ital of Wiscon sin Milwa ukee, WI Childre n's Hos pital of Bost on Bosto n, Mass Wilfor d lI a ll Medical Cen ter Lack land AFB, Texas Huntington Memorial Hospita l Pasadena , CA

St. Fr ancis Medical Center Peoria , IL Un ive rs ity of Texa s Medica l Branch Galveston, TX Caroli na s Medica l Cente r Charlotte , NC Prim a ry Children's Medica l Center Salt Lake City. UT Children 's Hospital of Los Angeles Los Angeles, CA Emanue l Hospital a nd Hea lth Center Portla nd , Oregon Childr e n's Memorial Hospita l Chicago , IL Children's Mer cy Hospita l Kans as City, MO Un ive rsity Medical Center - Texa s Tech Lubbock, Texa s Phoen ix Childre n's Hosp ita l Phoenix . Arizona St. Luke 's Hospital Boise, ID 51. J oseph 's Hospita l & Medica l Center Pho enix , Arizona St. Louis Children 's Hos pital St. Louis , MO Minnesota Hegiona l ECMO Pr ogra m Minneapolis, MN Cook County Hospital (Inactive) Chicago . ILL Sutter Memo ria l Hospital Sacr amento , CA San Diego Regiona l ECMO Progra m Sa n Diego, CA UCLA Medical Cente r (Inactive) Los Angeles, CA Ch ildre n's Hosp ita l of Denve r Den ver, CO

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- 54 26 Stolar. C. 1.. S . J\1. Snedecor; and R. II. Bartlett : Extracor porea l me m bran e oxyge na tio n an d neon a tal r es pira tory failure: experience from the Extracor por eal Life Suppo rt Organ iza tion . J. Ped iatr Surg . 26 (199 1) 56 3 - 571 2i Toomasiun. J. At.. S. M. S nedecor: n. G. Cornell, R. E. Cilh>y. and R. II. Bartlett : Nationa l ex pe rie nce vvIth newborn respi rato ry failure: data from 7 15 cas es . Tra ns . Am . Soc. Artif. Intern. Organs. 34 (1988) 140 - 147 2M Trento , A. . B. P. GrijJith. an d n. t: Ilardesty: Extracor po real me m brane oxygena tio n ex pe rien ce a t the Un iversi ty of Pittsbu r gh. An n. T hcrac. Surg . 42 (1986) 529 -53 5

Thorae. eardiovase. Surgeon 40 (1992)

Sta nford Univers ity Hospi tal Sta nford . CA James Whitco mb Riley Hospita l Ind ia napolis, IN Luther an General Hosp ital Park Ridge. IL Massach use tts General Hospital Boston, MASS Rainb ow Bab ies and Childre n's Hospital Cleveland . OH University of Nebraska Medica l Center Omaha , Nebraska Childre n's Hospital of Alabama Birmingham , AJab am a Eas tern Oklah oma Perinatal Cente r Tulsa, Oklahoma Medical University of South Caro lina Cha rleston, SC Child ren's Hos pitalHichland Memorial Columbia, SC Miami Childre n's Hos pital Miami , Flori da Children's Hosp ital of Oak land Oakland , California John s Hop kins Hosp ita l Baltimor e, Ma ryla nd Arka nsas Child ren's Hospital Little Rock, Arkansas AJab am a Neonat Assoc-St. Vince nt's (Inactive) Birmingham , AL University of Californ iaSan Francisco San Francisco, CA Presbyterian Hospi tal of DalJas Dallas, Texa s Arno ld Palme r Hosp . for Wome n/Childre n Orlando , Florida Children's Hospita l of Columbus Columb us, Ohio Vanderbilt Univer sity Hosp ita l Nashville, Tenn Children's Hos pital an d Medica l Center Seattle, Washing ton LeBonheur Children 's Medica l Center Memp his, Tenn Children 's Hosp ita l of Philad elphia Philad elph ia . PA

J. B. ZWischenberger and C. S. Cox, Jr.

Duke Univers ity Medi cal Cente r Durh am , CA Children's Hospital of Da llas Da llas, Texas Sha nds Hosp italUniversity of Flor ida Gainesv ille, Florid a Sha rp Mem ori al Hospital San Diego, Ca liforn ia University of Chicago Medical Cente r Chicago, ILL Sa nta Rosa Medical Center San Anton io, Texas Long Beach Mem ori al Hospi tal Long Beach , CA Chris t Hospital and Medical Center Oak Lawn , ILL Egleston Childre n's Hosp ital Atla nta, Georgia Hospital for Sick Children Toro nto, Cana da Montreal Children's Hospi ta l Montr eal. Canada Central Hospital Kasu gai, Japan Univers itats -Kinde rkIin ik-Mann heim Ma nnheim . Germany Hosp ital Hobert-D ebra Pari s, Fra nce Karolinska Institutet Stockholm, Swede n Royal Alexandra Childre n's Pav. Edmo nton, Cana da Groby Road Hospital Leicest er, England Prince of Wales Children's Hospital Randwick, Australi a Salesi Childre n's Hospi tal Ancona , Italy S1. Radoud Ilospital Nijmegen , The Netherla nds Nationa l Childre n's Hospital Tokyo,Japa n Royal Children's Hosp ital Par kville, Austra lia

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