Extracorporeal Membrane Oxygenation and Neonatal Respiratory Failure: Experience From the Extracorporeal Life Support Organization By Charles

J.H. Stolar,

Sandy

M. Snedecor,

and Robert

H. Bartlett

Ann Arbor, Michigan 0 Extracorporeal membrane oxygenation (ECMO) has rescued moribund infants with respiratory failure from a variety of causes. We report the experience from 58 United States and 7 overseas ECMO centers between 1980 and 1989. Voluntarily submitted data forms provided details of diagnosis, clinical condition, ECMO indications, morbidity, and mortality. Df 3,528 infants with a predicted mortality > 80% treated with ECMO, 83% survived. Entry diagnoses and aggregate survival were: meconium aspiration syndrome (MAS) 1,358 (93%). persistent pulmonary hypertension of the newborn (PPHN) 480 (83%); congenital diaphragmatic hernia (CDH) 585 (62%); hyaline membrane disease (HMD) 532 (84%); sepsis 416 (77%); and other 185 (77%). ECMO indications were a-Ado, > 600 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 9 years except for CDH, which decreased from 70% (1987) to 56% (1989)P < .Ol). Survivors differed from non-survivors (P < .05) by birth weight (> 2 kg), gestational age (>37 weeks), entry diagnosis (MA8 PPHN, HMD, sepsis v CDH), inborn versus outborn, preECMO pH. and ECMO duration. Technical complications in 25% of patients and medical complications in 75% adversely affected survival. Annual sepsis survival improved to 75% (1989) but had significantly greater complication rates (P < .05) than other diagnoses. Multicenter data yield information not available from single institution experience. Although entry criteria and conventional therapy continue to evolve, ECMO currently improves survival from an estimated 20% to 83% overall. Individual prognosis depends on entry diagnosis, clinical condition, and complications. Cop yrighf o 199 1 by W. B. Saunders Company INDEX

WORDS:

Extracorporeal

(ECMO); neonatal respiratory

membrane

oxygenation

failure.

A

LTHOUGH EXTRACORPOREAL membrane oxygenation (ECMO) has been used since 1975,‘,’ systematic collection of information concerning its use was not begun until 1980. In its original format as the Neonatal ECMO Registry, information was collected concerning patient demographics, pre-ECMO clinical features, ECMO indications, medical and technical complications, and short-term outcome. Between 1980 and 1987,715 patients were registered from a small number of ECMO centers.3 Eighty-one percent of treated infants survived despite a predicted 80% mortality. The most frequent indications were persistent pulmonary hypertension of the newborn (PPHN), meconium aspiration syndrome (MAS), and congenital diaphragmatic hernia (CDH). Less common were neonatal sepsis and respiratory distress syndrome (RDS). Technical complications occurred in 23% and physiologic complications occurred in Journal of Pediatric Surgery, Vol26, No 5

(May), 1991:

pp 563-571

65%. Survival rates for the first 10 patients at any one center were significantly worse than for the subsequent 10 patients (74% v 84%, P < .Ol), reflecting a learning curve. Since that report, the number of ECMO centers and infants treated has increased. This report will review the demographics, clinical features, and shortterm outcome of the infants in what is now called the Neonatal ECMO Registry of the Extracorporeal Life Support Organization (incorporated 1989, Ann Arbor, MI). We speculate that if a new therapy gains acceptance and is refined, its effect will be reflected by changing trends in diagnosis, selection criteria, outcome, complications, and diagnosis-related specific features. Because ECMO is specifically for moribund infants refractory to conventional therapy, standard randomized clinical trials have been problematic. Innovative study design and statistical methods,“.5 although controversial, suggest many advantages for ECMO compared with conventional therapy. Although Registry data are not trials of one therapy versus another, we hypothesized that if ECMO is a successful method of treatment, then cumulative and annual data should show a steady increase in survival, with decreasing morbidity and mortality despite any learning curve effects. Further, morbidity and mortality outcome for a specific ECMO entry diagnosis that differed significantly from the aggregate total might reflect pathophysiologic problems unique to that diagnosis rather than an inherent weakness in the ECMO therapy. MATERIALS

AND

METHODS

Registry data were collected from 58 domestic and 7 international ECMO centers (appendix). Data were abstracted from patient records and ECMO flow charts and submitted at the

From The Extracorporeal Life Support Organization, Ann Arbor, Ml. Presented at the 37th Annual International Congress of the British Association of Paediatric Surgeons, Glasgow. Scotland, July 25-27, 1990. Supported in part by The William Randolph Hearst Foundation, Inc, New York, NY,; The Charles Edison Fund, Orange, NJ: and The Anya Fund, Annonk, NY Address reprint requests to Charles J.H. Stolar. MD, Division of Pediatric Surgery The Babies Hospital, Room 203N, 3959 Broadway, New York, NY 10032. Copyright o 1991 by WB. Saunders Company 0022-346819112605-0015$03.00/0 563

STOLAR, SNEDECOR, AND BARTLETT

564

ECMO Center:

Date Completed: -I-

Form Completed by:

Phone:(

i-

)

Patient ldentihcation Hosprtal ID*:

Name: Sex: 1-I

M

/_I

F

Comptiition

Birthdate: _

* 1-l-J

Birthweight: 1-I

/ _

/ _

Mom?

/_I

Yes

/_I

No

Gsstatrcnal Age: I-1-I

Apgar Score: I_/_/

kg.

(weeks)

(1 mm) ~-1-l

(5 min)

of pregnancy (Describe): Pre-ECMO Course Secondary Respiratory Diagnose (Circle as many as necessary) RDS CDH Sepsis (Pneumonia) MAS PPHN (PFC) Cardrac Pneumothorax other

Primary Respiratory Diagnosis (clrde one only) MAS RDS Sepsis (Pneumonra) CDH PPHN (PFC) Pneumothcfax Cardiac other: Non-Respiratory Pre-ECMO

or Congenital Anomolies:

serzures: I-1

Yes

/_I

Renal Farlure: 1-I (Creatrnrne 2 1.5)

No

Yes

/_I

No

Other Abnormakttes: Vasoactrve Drugs Trted: I-1

None

I-I

Dopamrne

/_I

Tolazotine

l-1

Other

Last

Arteriaf Blood Gas Pnoc to ECMO: pH l-1 * l_l_l PO2 ~-l_I_~ mmHg Ventilator Setting Prior to ECMO: Fi021-I. l_l_l Rate l_/_l_l Jet/Oscrllatory Ventilations

1-I

PC02 /_l_/_I

Peak Pressure l-I-1

Yes

I-1

HCOJ l-l-l-l

mmlig

PEEP I-I-

No

Criteria for going on ECMO (check only one): 1-I AaCQ > /_/_l_t for l_l_l hours 1-l Oxygenation Index Score /_I_1 (Fi02 x MAP/PO*) 1-1 Acute Deterioration: PaO, < l_/_L mmHg for l_l_l hours Elevated MAP Emphysema 1-I Barotrauma: (circle one) PIE PT I-1 Failure to respond to maximum treatment l-l Cardiac Arrest

1-I

other: ECMO Course

Age starting ECMO: ~_~__I--I ~cde:

I_/

V-A

Cannula srze: PDA ligation whrle on ECMO:I_I

1-I

V-V

(hours of kfe) 1-l

VV-VA

Venous l-l-I

Yes

I_/

French

No

Hours on ECMO:

l-l-l-l

hours

(reason) Arterial ~-1-I

Other Surgery: /_I Fig 1.

French

Yes

I-1

No

(Describe)

Neonatal ECMO Registry forms.

conclusion of the infant’s hospitalization using data capture forms (Figs 1A and 1B). Although all infants requiring ECMO had pulmonary hypertension to some degree, a central primary diagnosis was assigned to each patient, namely MAS, CDH, neonatal sepsis, RDS, or other. RDS included classical hyaline membrane disease, perinatal asphyxia, “shock lung,” cardiac arrest, maternal drug dependency, and miscellaneous conditions. If the etiology of the pulmonary hypertension was truly idiopathic the diagnosis of PPHN was assigned. A secondary associated diagnosis of MAS, PPHN, sepsis or air leak syndrome was assigned if appropriate. Each participating center developed ECMO selection criteria estimated to represent a predicted mortality of at least 80% using maximal conventional therapy at that institution. Details of specific therapy were not a defined part of the Registry information: most institutions practiced a respiratory therapy strategy based on muscle paralysis and induced alkalosis. Failure of maximal therapy

was determined by clinical judgment, duration of alveolar-arterial oxygen gradient >600 mm Hg beyond 6 to 8 hours ([a-Ado, = [FiO, x (760 to 47 mm Hg) - [pCOJ.S) - pa02]) or oxygenation index >40 beyond 4 hours (01 = [FiO, x MAP/paO,] x 100. Other infants were entered because of acute deterioration before meeting the defined time requirements of a-Ado, or 01. ECMO therapy was administered as venoarterial bypass. Less than 2% were supported by venovenous bypass. Extrathoracic cannulation was accomplished through the right neck. The extracorporeal circuit has been previously described.6 The details of ECMO patient management are well described elsewhere.’ Physiological complications are defined on the ECMO Registry form (Figs 1A and 1B) and are characterized as either infectious, hematologic, renal, neurological, or cardiopulmonary. Technical complications are compiled on an occurrence basis and are also listed on the Registry

Form.

REGISTRY REPORT OF NEONATAL ECMO

565

Ventilator setting at 24 hours on ECMO: Rate l-l-1 FiO2 I-1. I-1-1

Peak Ressure I-1-1

PEEP I-I-I

Compkcations on ECMO (see codes below): Mechamcal:

A

B

C

D

E

F

Pabent.

1 13 25

2 14 26

3 15 27

4 16 28

5 17 29

6 18 30

7 19 31

8 20 32

9 21 33

10 22 34

11 23 35

12 24 36

Descriptions:

I-1

outcome

SUrvlVed

Hours to Extubatlon /_I_/-_ Date of Discharge Home _ Total Hospital Days l_l_/_l Pre-Discharge Morbidity (Describe)

Late Death: _

/ _

-----_---_I_

I-1 /_

hours / _

Died

Date of Death: _ I_ / ECMO Electivefy Terminated /_I Cause(s) of Death:

Yes

/_I

No

f_

----------

Mechanica/ A. oxygenator failure 0. tubing rupture, circuit disrupbon C. pump malfunction D. heat exchanger malfunctii E. cannula placement or removal problems (specify above) F. other (specify above)

Hemorrhagfc -&nonWqeby 1. Intracranial cranial ultrasound (specify) 2. lntracranlal hemorrhage by CT scan (specify above) 3. sgnifkzant GI hemonbags 4. sgnlficant surgical site bleeding 5. 25 units platelet transfuuons/ 24 hours 6. serumhgbr100 7 other (specify above)

Codes for Complitiis

Neurologic 8. brain death (no spent movement,pupils fixed and dilated) 9. probable or definite seozure 10. excessive jitteriness 11. other (specify above)

Renal 12. 13. 14. 15.

~-

on ECMO

aeatinine > 1.5. ~3.0 creatinine 2 3.0 dialysis or hemofiltratii other (specify above)

Cardiovascular 16. cardiopulmonary resuscitation required 17. cardiac arrhythmia 10. tolazoline (cu other puWxmaq vasodilator) given 19. other (specify above)

infectious 22. culture proven mfecbon (specifv _ above) 23. WBCS1500 24. other (specify above)

Metabolic 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36

K (_ 2.5 K 2 7.5 Na 5 120 Naz160 Ca < 6.0 Ca t 14.0 gkmm? 5 20 glucose 2 350 pti 5 7.05 pH t 7.75 Hypertensive: Systdi BP z 90 mmHg for 4 hours Other (specify above)

fulmonary 20. pneumothorax requiring chest tube @acement 21. other (specify above)

Return Form To: ECMO Data Registry Phone: (313) 9365822 2920 Taubman Center University of Michigan Medical Center Ann Arbor, Michigan 48109-0331 ___---_--

(Rev. l/29/87) Fig 1. (Cont’d).

Survival was defined as being decannulated from ECMO and extubated from all mechanical ventilator support for at least 24 hours.

Statistical

tics by blood gas values and ventilator settings. Logistic regression analysis was used for diagnosis specific medical complications. All statistical instruments were applied within the Statistical Analysis System @AS) and SYSTAT.

Analysis

Registry data were analysed in two ways. The xZ test (MantelHaenzel) examined the association between outcome and preECMO characteristics, technical, and medical complications. The two-sample r test identified survivor and nonsurvivor characteris-

RESULTS

Between 1980 and 1989, 3,528 infants reported from 58 centers in the United States and 7 interna-

566

STOLAR,

tional centers were registered in the Neonatal ECMO Registry of the Extracorporeal Life Support Organization. This represents a further 2,813 patients from an additional 47 centers since the first Registry report of 715 patients from 18 centers.3 During the last 3 years, 1987 through 1989, there was a 261% increase in the number of ECMO centers and a 393% increase in treated infants (Figs 2 and 3). Although there was a rapid increase in the aggregate and annual numbers of infants treated through 1988, the annual totals for 1988 and 1989 are the same. Similarly, the annual rate at which new ECMO centers have opened was greatest in 1987 and is less for 1988 and 1989 (Fig 2). The number of infants treated annually at any one ECMO center ranged from 2 to 53, with an average of 20 ECMO patients per center per year. Ninety-three percent of the patients were outborn and only 7% were inborn, indicating that almost all infants were referred to a level III neonatal intensive care unit specifically for ECMO therapy. ECMO Patient Description The primary diagnoses for the aggregate group were MAS (39%), CDH (16%), hyaline membrane disease (15%), PPHN (13%) sepsis (12%), cardiac support (2%), and other (2%). Figure 4 shows the annual total of cases by primary diagnosis. Although MAS predominates in all years, it has decreased from 47% of all ECMO cases in 1985 to 37% in 1989 (P < .05). Over the same period of time the number of patients being treated for sepsis increased from 7% to 15%. The most common secondary diagnoses were PPHN (64%) and air leak syndrome (19%). Table 1 summarizes other features of the patients. ECMO Entry Criteria Criteria for instituting ECMO changed and evolved during the 10 years of this report. The goal of all entry

0

AND

BARTLETT

‘75 ‘76 ‘77 ‘78 ‘79 ‘80 ‘81 ‘82 ‘83 ‘84 ‘85 ‘86 ‘87 ‘88 ‘89

0

Year Fig 3. Annual ECMO patient survival rates and annual total numbers of patients treated through 1989.

criteria was to identify infants with a greater than 80% likelihood of dying. The criteria recognized by the Registry and the incidence in this study were alveolar-arterial oxygen gradient > 600 mm Hg for 6 to 8 hours or more (22%), oxygenation index > 40 for 4 hours (18%), acute deterioration (14%), failure of maximal therapy (34%), barotrauma (l%), cardiac arrest (1%) and others 10%. Arterial blood gas measurements and ventilator settings just prior to ECMO (preductal or postductal not specified) are detailed in Table 1. If one considers the last arterial pre-ECMO blood gas analysis on an annual basis for 1981, 1985, and 1989 (Table 2) there is no significant change in the pH and pC0,. However, the last p0, and its variability may reflect greater consistency and more rigorous application of ECMO therapy. If one considers the last pre-ECMO arterial blood gas analysis by entry diagnosis (Table 2), the following observations can be made. The pOZ for hyaline membrane disease (45 2 23 mmHg) is significantly higher than for other entry 400

20

SNEDECOR,

n MAS n HMD

70

W CDH 300

Ed PPHN

2 3 0 ‘0 t

0

Sepsis

200

f z

0

‘82

‘83

‘84

‘85

‘86

‘87

‘88

‘89

0

1oc

C

73-‘83

‘84

‘85

‘86

‘87

‘88

‘89

Year Fig 2. centers.

ECMO centers opening each year and cumulative

active

Fig 4. sis.

Annual total number of ECMO patients treated, by diagno-

REGISTRY REPORT OF NEONATAL

ECMO

567

Table 1. Patient Characteristics

Table 3. Characteristics of Survivors Versus Nonsurvivors

Male/female (%) Apgar scores

Birthweight (kg)

l-minute

5.2 + 3.8

5-minute

7.2 -t 3.5

Birthweight (kg)

3.2 2 0.6

Gestational age (wk)

39 + 2

Age at ECMO initiation (h)

51.7 t 48.8

ECMO duration (h)

128?

111.6

Last pre-ECMO ABG

3.0 _’ 0.7