Rapid-Response Extracorporeal Membrane Oxygenation to Support

Cardiopulmonary Resuscitation in Children With Cardiac Disease

David A. Kane, Ravi R. Thiagarajan, David Wypij, Mark A. Scheurer, Francis
Fynn-Thompson, Sitaram Emani, Pedro J. del Nido, Peter Betit and Peter C. Laussen
Circulation 2010, 122:S241-S248
doi: 10.1161/CIRCULATIONAHA.109.928390
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Rapid-Response Extracorporeal Membrane Oxygenation to

Support Cardiopulmonary Resuscitation in Children With
Cardiac Disease
David A. Kane, MD; Ravi R. Thiagarajan, MBBS, MPH; David Wypij, PhD;
Mark A. Scheurer, MD; Francis Fynn-Thompson, MD; Sitaram Emani, MD; Pedro J. del Nido, MD;
Peter Betit, RRT; Peter C. Laussen, MBBS
BackgroundSurvival of children with in-hospital cardiac arrest that does not respond to conventional cardiopulmonary
resuscitation (CPR) is poor. We report on survival and early neurological outcomes of children with heart disease
supported with rapid-response extracorporeal membrane oxygenation (ECMO) to aid cardiopulmonary resuscitation
(ECPR).
Methods and ResultsChildren with heart disease supported with ECPR were identified from our ECMO database.
Demographic, CPR, and ECMO details associated with mortality were evaluated using multivariable logistic regression.
Pediatric overall performance category and pediatric cerebral performance category scores were assigned to ECPR
survivors to assess neurological outcomes. There were 180 ECPR runs in 172 patients. Eighty-eight patients (51%)
survived to discharge. Survival in patients who underwent ECPR after cardiac surgery (54%) did not differ from
nonsurgical patients (46%). Survival did not vary by cardiac diagnosis and CPR duration did not differ between
survivors and nonsurvivors. Factors associated with mortality included noncardiac structural or chromosomal
abnormalities (OR, 3.2; 95% CI, 1.37.9), use of blood-primed ECMO circuit (OR, 7.1; 95% CI, 1.4 36), and arterial
pH 7.00 after ECMO deployment (OR, 6.0; 95% CI, 2.117.4). Development of end-organ injury on ECMO and
longer ECMO duration were associated with increased mortality. Of pediatric overall performance category/pediatric
cerebral performance category scores assigned to survivors, 75% had scores 2, indicating no to mild neurological
injury.
ConclusionsECPR may promote survival in children with cardiac disease experiencing cardiac arrest unresponsive to
conventional CPR with favorable early neurological outcomes. CPR duration was not associated with mortality, whereas
patients with metabolic acidosis and noncardiac structural or chromosomal anomalies had higher mortality. (Circulation.
2010;122[suppl 1]:S241S248.)
Key Words: cardiopulmonary resuscitation congenital heart defects extracorporeal circulation pediatrics

urvival with conventional cardiopulmonary resuscitation

(CPR) after in-hospital cardiac arrest (CA) is poor in the
pediatric population.1,2 The use of extracorporeal membrane
oxygenation (ECMO) to support failed conventional CPR
(ECPR) has been shown to rescue some patients who would
face imminent mortality without this intervention.37 The
American Heart Association 2005 Pediatric Advanced Life
Support guidelines recommend the consideration of ECPR in
patients when the conditions leading to the arrest are thought
to be potentially reversible or amenable to heart transplantation. The use of ECPR has been increasing in adult and
pediatric populations.8
Recent series report survival to hospital discharge for
patients supported with ECPR to be variable, with a range of

33% to 55%.4 7 This variability in survival outcomes may be

related to differences in ECPR deployment systems, variability in indications for ECPR, and postdeployment care among
reporting institutions. A clear population of patients who are
best suited for ECPR has not been identified. In addition,
neurological outcomes in ECPR survivors are rarely reported.
Given the interest and recommendation for the use of ECPR
and the considerable institutional resources needed to run and
sustain an ECPR program, it is important to critically review
outcomes and try to identify factors associated with mortality
to help guide patient selection for ECPR.
In this large, single institution study, we report on the
survival to hospital discharge after ECPR used to support
children with cardiac disease at Childrens Hospital Boston.

From Department of Cardiology (D.A.K., R.R.T., D.W., M.A.S., P.B., P.C.L.), Childrens Hospital Boston and Department of Pediatrics, Harvard
Medical School, Boston, Mass; Department of Biostatistics (D.W.), Harvard School of Public Health, Boston, Mass; Department of Cardiac Surgery
(F.F.-T., S.E., P.J.d.N.), Childrens Hospital Boston, Boston, Mass and Department of Surgery, Harvard Medical School, Boston, Mass.
Presented at the 2009 American Heart Association meeting in Orlando, Fla, November 14 18, 2009.
Correspondence to David Kane, MD, Childrens Hospital Boston, Department of Cardiology, 300 Longwood Avenue, Boston, MA 02115. E-mail
david.kane@cardio.chboston.org
2010 American Heart Association, Inc.
Circulation is available at http://circ.ahajournals.org

DOI: 10.1161/CIRCULATIONAHA.109.928390

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September 14, 2010

We also describe the structure of our ECPR program, report

on predictors of mortality in our ECPR patients, and describe
early neurological outcomes for ECPR survivors.

Subjects and Methods

We conducted a retrospective review of the Childrens Hospital
Boston ECMO database during 1995 to 2008 and selected all patients
with cardiac disease (congenital and acquired) supported with
ECMO for CA after failed conventional CPR therapies. Review of
patient medical records was approved by the Childrens Hospital
Committee on Clinical Investigation and the need for informed
consent was waived. For purposes of this study, we defined ECPR as
ECMO instituted during active CPR with chest compressions.
Patients (n8) who had return of spontaneous circulation during
resuscitation but were deemed to be unstable and requiring ECMO
support immediately (30 minutes) after return of spontaneous
circulation were also included in this cohort.

Rapid Response ECPR Program at Childrens

Hospital Boston
Children with cardiac disease who experience an in-hospital CA that
does not respond to conventional CPR techniques are eligible for
ECMO support. The decision to deploy ECPR is made by the
patients primary bedside physician based on the patients diagnosis,
etiology of the event, and likely response to resuscitation, and it is
usually initiated if there is failure of return of spontaneous circulation
after 2 rounds of resuscitation drugs. Contraindications for ECPR
include existing irreversible neurological injury and multi-organ
failure before CA, irreversible or nonoperable primary disease,
extreme prematurity (32 weeks gestation), and previous parental
refusal for the use of mechanical support. The ECPR team consists
of an in-house cardiac intensive care physician (pool of 13), a cardiac
surgery resident or fellow (pool of 5), ECMO specialists, and the
bedside nursing staff. Two crystalloid-primed (Plasma Lyte A;
Baxter) ECMO circuits (1 for use in children 15 kg and 1 for those
15 kg) and ECMO equipment carts with necessary surgical
instruments and ECMO cannulae are available at all times in the
cardiac intensive care unit. The cardiac intensive care unit attending
is the event manager responsible for overseeing all aspects of CPR
and ensuring resource availability, whereas the surgical team cannulates the patient for ECMO. Cannulation sites may be peripheral
(neck or femoral vessels) or intrathoracic, via the right atrium and
aorta, depending on patient site, anatomy, and postoperative status.
All ECPR patients are supported with veno-arterial ECMO at our
institution and a mandatory time-out is completed before starting
ECMO flow to insure that cannulae are connected properly. After
initiation, ECMO flow is increased to achieve a goal of 100 to 150
mL/kg per minute. Sweep gases for the membrane oxygenator are
adjusted to contain fraction of inspired oxygen concentration of 0.21.
Controlled hypothermia is maintained at 34C to 35C for 48 hours
to lower metabolic demands and to provide central nervous system
(CNS) protection. Cannulae position are confirmed using chest
x-rays and echocardiography. Anticoagulation is provided using
heparin infusion to maintain an activated clotting time of 180 to 240
seconds. Decisions regarding the care of the patient administered
ECMO, investigating the cause of CA, and weaning from ECMO are
patient-specific. In general, patients who are unable to be weaned
from ECMO because of persistent myocardial dysfunction and who
have no major end-organ injury are typically evaluated by our
transplant team to determine candidacy for heart transplantation. All
ECMO patients receive daily consultation with a pediatric neurologist, and evaluations for neurological injury may include a combination of serial head ultrasounds, electroencephalography, and portable head computerized tomography scans. All ECPR deployment
events are debriefed within 24 hours to identify issues with personnel, equipment, and the conduct of CPR to identify factors that are
modifiable, to improve the quality and safety of ECPR deployment,
and to decrease deployment times. ECPR survivors are referred
routinely for neuro-developmental follow-up. The ECPR team at

Childrens Hospital Boston is available to deploy ECMO 24 hours

per day and is staffed with 9 full-time-equivalent ECMO specialists.

Data Collection and Categorization

Data collected for the purposes of this study include patient demographic information, CPR details, ECMO details, course, and complications. The primary outcome variable used for purposes of this
study is survival to discharge from our institution to either home or
another facility.
Patients were divided into 1 of 4 diagnostic categories, including single
ventricle lesions (including any patient with only 1 pumping chamber),
2 ventricle lesions, primary myocardial disease (including cardiomyopathy and patients who have undergone transplantation), and
primary pulmonary hypertension. Patients were designated as postoperative if they had undergone a cardiac surgery during the
admission before CA. Noncardiac structural malformations were
defined as major anomalies that were present in other organ systems
that may have significantly influenced the course of the patient (eg,
tracheo-esophageal fistula). The presence of a known genetic syndrome was noted. Post-ECMO blood gases represent the first arterial
sample that was sent after ECMO was deployed.
Information on complications or end-organ injury that became
evident during the ECMO run was also collected. Bleeding was
defined as cannulation site or surgical bleeding requiring surgical
exploration. Mechanical circuit complications included air emboli,
thrombus formation in the circuit, breaks or leaks developing in any
part or component of the ECMO circuit, and circuit or oxygenator
change. Renal injury was categorized based on peak serum creatinine
values 1.5 mg/dL (for all age groups) after deployment of ECPR or
use of renal replacement therapy, including peritoneal dialysis,
continuous veno-venous hemodialysis, or hemodialysis. CNS injury
was defined by the presence of clinical injury (eg, seizures, hypoxicischemic encephalopathy, movement disorder) or an abnormal neurological imaging study result. Patients with hepatic injury were
defined as those with a peak aspartate aminotransferase or alanine
aminotransferase 500 IU/dL that developed in the period after
deployment of ECPR. The presence of a positive blood culture was
used to define infection during ECMO use. Respiratory complications included ventilator associated pneumonia, acute respiratory
distress syndrome, pneumothorax, and pulmonary hemorrhage.
To assess global neurological status, we used pediatric overall
performance category (POPC) and pediatric cerebral performance
category (PCPC) scores.9 These scores were assigned to survivors
older than age 2 months at discharge and at follow-up if there was
adequate neurological information available in the medical record.

Statistical Analysis
For the patients who underwent multiple ECPR runs during the same
admission (n7), only the first ECPR run was included in this
analysis. Demographics, CPR variables, pre-ECMO data, ECMO
support details, and ECMO complications were compared between
survivors and nonsurvivors. Pearson 2 tests were used to compare
categorical data and Fisher exact tests were used when the expected
count in any category was 5. Continuous data were compared
using the Mann-Whitney test. For patients with multiple ECPR runs,
cumulative duration of ECMO based on all ECMO runs was used.
Data are shown as median values with the interquartile range or as
numbers with proportion (%).
Three separate multivariable logistic regression models were
developed in an effort to identify factors independently associated
with mortality after ECPR. The first model explored the influence of
pre-ECMO and ECMO variables, whereas the second model evaluated the association of ECMO duration and complications on
mortality. Because our patient cohort spanned over the course of 13
years, and because some variables (eg, blood lactate levels) were
only collected for patients in the recent cohort, we developed a third
model exploring the association of pre-ECMO and ECMO factors at
the time of deployment using data from patients treated with ECPR
during 2000 to 2008. Variables with a univariate P0.1 were
selected for consideration in the model. A forward selection procedure was used for variable entry into the multivariable model.

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Kane et al

ECMO for Pediatric Cardiopulmonary Resuscitation

Figure 1. Outcomes of patients with cardiac disease supported

with use of extracorporeal membrane oxygenation to support
failed conventional cardiopulmonary resuscitation (ECPR). VAD,
ventricular assist device; OHT, orthotopic heart transplant.

Variables were retained in the multivariable model if adjusted

P0.05. Continuous variables (eg, post-ECMO arterial blood pH)
retained in the multivariable model were refitted as categorical
variables based on quartile or quintiles values of their distribution to
test the presence of a linear association with the outcome variable. If
a linear increase in the odds ratio across categories could not be
demonstrated, then linearity assumptions were considered violated
and the variable was retained as a categorical variable.

Results
Study Population
From 1995 to 2008, 172 patients with cardiac disease underwent 180 ECPR runs (41% of all ECMO runs) at Childrens
Hospital Boston (Figure 1). The median age (interquartile
range) of the study population was 5.7 months (0.4, 43.6) and
the median weight was 6.0 kg (3.2, 14.0). Eight patients with
congenital heart disease were older than 18 years (5%).
Seventy patients (41%) had single-ventricle congenital heart
disease, 65 (38%) had 2-ventricle congenital heart disease, 31
patients (18%) had primary myocardial disease, and 6 (3%)
had primary pulmonary hypertension. A total of 103 (60%)
patients underwent ECPR after cardiac surgery. Median
duration of CPR before ECMO flow for the entire cohort was
33 minutes (23, 44) and the trend decreased significantly over
time (P0.001; Figure 2). Twenty-seven of 172 patients
(16%) were deemed eligible and, subsequently, were listed
for transplantation, with 6 of these patients transitioned to a
ventricular assist device and 13 ultimately undergoing transplantation (12 patients underwent orthotopic heart transplantation and 1 received a lung transplant for primary pulmonary
hypertension). The patients listed for transplantation who did
not receive an organ died (n14). Overall, 88 patients (51%)
survived to hospital discharge.

S243

Figure 2. Trends of cardiopulmonary resuscitation (CPR) duration are displayed with box plots. The median CPR duration is
represented by the line in the center of the box, whereas the
first and third quartiles are the ends of the boxes. The whiskers
extend to the 5th and 95th percentiles. The line graph represents
the average number of uses of extracorporeal membrane oxygenation to support failed conventional cardiopulmonary resuscitation (ECPR) cases per year in the listed time intervals.

cardiac diagnosis, and year of ECPR. Details of the resuscitation and pre-ECMO deployment are outlined in Table 2.
There was a significant difference in survivors and nonsurvivors when the location of CA was compared between the 2
groups. In this cohort, 129 (75%) of the CA occurred in the
cardiac intensive care unit with 49% (n63) of the patients
surviving to discharge, patients who required ECPR in our
catheterization laboratory (n27) had a survival to discharge
rate of 73%, and patients whose CA occurred in other
locations (inpatient ward, emergency department, and operating room) had a survival to discharge rate of 35%. Duration
of CPR, initial rhythm, and medications used during CPR
Table 1. Demographic Features of ECPR Survivors
and Nonsurvivors
Variable

Survivors
(n88)

Age, mo

4 (0, 33)

Nonsurvivors
(n84)

9 (0, 105)

0.20

Weight, kg

5.3 (3.3, 12.0)

6.3 (2.8, 19.5)

0.93

Female

46 (52)

31 (37)

0.04

Single-ventricle circulation

36 (41)

34 (40)

Two-ventricle circulation

31 (35)

34 (40)

Primary myocardial disease

19 (22)

12 (14)

Diagnosis

Pulmonary hypertension
Noncardiac structural and
chromosomal anomalies
Cardiac surgery before ECPR

0.53

2 (2)

4 (5)

9 (10)

21 (25)

56 (64)

47 (56)

Year of ECPR

0.24
0.53

19951998

13 (15)

14 (17)

19992002

32 (36)

22 (26)

Pre-ECMO Factors

20032005

18 (20)

22 (26)

Table 1 illustrates the demographic details of survivors

compared to nonsurvivors after ECPR use. There were more
females and fewer children with noncardiac structural malformations among survivors compared to nonsurvivors. Notably, survivors and nonsurvivors did not differ by age,

20062008

25 (28)

26 (31)

36 (21, 59)

17 (8, 28)

Hospital length of stay, d

0.01

0.001

Data are presented as median (IQR) or n (%).

ECPR indicates use of extracorporeal membrane oxygenation to support
failed conventional cardiopulmonary resuscitation.

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Table 2. Cardiopulmonary Resuscitation Details of ECPR

Survivors and Nonsurvivors
Survivors
(n88)

Variable

Nonsurvivors
(n84)

Cause of arrest
Hypoxemia

21 (24)

14 (17)

Arrhythmia

24 (27)

16 (19)

Hypotension (bleeding)

9 (10)

8 (10)

32 (36)

41 (49)

2 (2)

5 (6)

CICU

63 (72)

66 (79)

Catheterization laboratory

19 (22)

7 (8)

6 (7)

11 (13)

Hypotension (cardiogenic shock)

Pulmonary hypertension
Location of arrest

Other

P
0.26

0.03

lactate level after ECMO deployment was lower in survivors

compared to nonsurvivors.
Eighty-three (48%) patients underwent an interventional
procedure either in the operating room or in the catheterization laboratory after deployment of ECPR. The most common
intervention performed after ECPR was manipulation of the
systemic to pulmonary shunt (n20) for either presumed
thrombosis or pulmonary overcirculation. The performance
of an additional procedure after ECPR deployment did not
vary between survivors and nonsurvivors. The duration of
ECMO was shorter in survivors compared to nonsurvivors.
The survival rate of 29% for the 7 patients who needed 1
ECPR run was lower but not significantly different than the
52% survival rate for patients supported with 1 ECPR run
(Fisher exact P0.29).

Duration of CPR, min

32 (25, 41)

36 (21, 45)

0.51

ECMO Complications

Open chest massage

50 (57)

40 (48)

0.23

5 (6)

3 (4)

0.24

The incidence of complications occurring during the ECMO

run in survivors and nonsurvivors are shown in Table 4. The
incidence of ECMO circuit complications, respiratory complications, sepsis, CNS complications, and end-organ dysfunction were significantly higher in nonsurvivors compared
to survivors. Eighty-nine patients in the cohort (52%) had
clinical or radiological evidence of CNS injury.

ROSC during cannulation

Initial rhythm*
Bradycardia

0.35
54 (63)

44 (57)

Asystole

2 (2)

3 (4)

Ventricular tachycardia

9 (10)

4 (5)

Ventricular fibrillation

8 (9)

6 (8)

13 (15)

20 (26)

39 (45)

34 (44)

02

23 (30)

17 (22)

34

21 (28)

24 (31)

32 (42)

37 (47)

Bicarbonate use

70 (92)

70 (90)

0.61

Calcium use

57 (75)

60 (77)

0.78

PEA and other

Defibrillation or cardioversion use*
N of epinephrine doses

0.77
0.49

Data are presented as median (IQR) or n (%).

CICU indicates cardiac intensive care unit; CPR, cardiopulmonary resuscitation; ECPR, use of extracorporeal membrane oxygenation to support failed
conventional cardiopulmonary resuscitation; PEA, pulseless electrical activity;
ROSC, return of spontaneous circulation.
*Missing (n9).
Missing (n18).

were not significantly different between survivors and

nonsurvivors.

ECMO and Factors After CA

Table 3 outlines the differences between survivors and
nonsurvivors of factors after CA and ECMO management.
There was no survival difference between patients who were
cannulated in the neck as compared to those who underwent
chest cannulation. There were more survivors among patients
who underwent decompression of the left atrium compared to
those who did not. A smaller number of patients went on to
ECMO with a blood prime (n11) compared to crystalloid
(n161), and 82% (n9) of these patients died compared to
only 47% (n75) of patients with a crystalloid-primed
ECMO circuit (P0.03). Arterial blood pH and standardized
bicarbonate levels obtained after establishing ECMO flows
were higher in survivors than in nonsurvivors. In the cohort of
patients supported with ECPR after January 1, 2000, peak

Multivariable Logistic Regression Models

Predicting Mortality for ECPR Patients
Multiple models were constructed to evaluate predictors of
in-hospital mortality in ECPR users as shown in Table 5. The
first model shows the association of mortality with demographic variables and ECMO factors. Noncardiac structural
anomalies, use of blood-primed ECMO circuit for ECPR
deployment, and post-ECPR deployment arterial blood pH
7.00 compared to a pH 7.380 were significantly associated with higher mortality. The second model evaluated the
association of ECMO duration and complications and mortality. Longer ECMO duration and injury to the CNS, liver, or
kidney were significantly associated with increased mortality.
The need for longer ECMO support was associated with
increased mortality odds compared to ECMO duration of
49 hours. The third multivariable model using data from the
most recent cohort of patients showed that higher peak lactate
levels (13 mmol/L) after ECPR deployment was significantly associated with higher mortality. Arterial blood pH
was not retained in the model.

Neurological Outcomes Among Survivors

POPC/PCPC scores were assigned to 87 of 88 survivors at
hospital discharge or at follow-up after discharge. Sixty-five
survivors (75%) had POPC scores 2, and 69 (79%) had
PCPC scores 2, indicating no to mild neurological injury.
Neurological scores for single-ventricle patients were similar
to the remaining survivors with 2-ventricle circulation.
Seventy-one percent (26/35) of the single-ventricle patients
had POPC scores 2 compared to 77% (40/52) of the
remaining survivors with 2-ventricle circulations. Among
ECPR survivors who had a cavopulmonary connection
(n7), 4 (57%) had moderate to severe CNS impairment
(POPC/PCPC score 3). The patients assigned scores in

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Kane et al
Table 3.

ECMO for Pediatric Cardiopulmonary Resuscitation

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ECMO Support Details of ECPR Survivors and Nonsurvivors

Variable

Survivors (n88)

Nonsurvivors (n84)

Primary arterial cannulation site

Aorta

0.12
51 (58)

41 (49)

Right carotid artery

25 (28)

21 (25)

Other

12 (14)

22 (26)

50 (57)

41 (49)

Primary venous cannulation site

Right atrium

0.39

Right internal jugular vein

24 (27)

23 (27)

Other

14 (16)

20 (24)

Second arterial cannulation site

2 (2)

7 (8)

0.10

Second venous cannulation site

11 (13)

16 (19)

0.25

Thoracic cannulation

52 (59)

44 (52)

0.33

Left atrial vent use

22 (25)

10 (12)

0.03

6 (7)

0.32

Limb reperfuser use

3 (3)

ECMO flow at hour 4, mL/kg/min

101 (77, 138)

110 (71, 166)

0.50

ECMO flow at hour 24, mL/kg/min

104 (80, 140)

114 (81, 168)

0.22

ECMO circuit prime

Blood
Crystalloid

0.03*
2 (2)

9 (11)

86 (98)

75 (89)

75 (85)

68 (81)

Oxygenator used
Silicone membrane
Hollow fiber or Quadrox
Post-ECMO arterial pH

0.45
13 (15)

16 (19)

7.26 (7.14, 7.39)

7.17 (6.96, 7.28)

0.001

Post-ECMO arterial pH quintiles

7.002

0.03
10 (11)

24 (29)
15 (18)

7.0027.159

15 (17)

7.1607.259

18 (20)

18 (21)

7.2607.379

21 (24)

16 (19)

7.38
Post-ECMO HCO3, mmol/L
Peak post-ECMO lactate, mmol/L

24 (27)

11 (13)

17 (12, 21)

14 (9, 19)

11.2 (7.3, 14.9)

0.02

14.9 (10.6, 21.9)

0.001

Post-ECMO lactate, mmol/L

9

0.001
24 (34)

10 (14)

912.9

20 (29)

15 (21)

1317.9

18 (26)

18 (26)

8 (11)

27 (39)

Hours to peak lactate level

2 (1, 4)

2.5 (1, 4)

0.49

Admission to ECMO use, d

3 (1, 6)

4 (1, 8)

0.26

Surgery to ECMO use, d

1 (1, 3)

1 (0, 4)

0.34

18

ECMO duration, hr
Use of ventricular assist device

84 (52, 118)
1 (1)

119 (57, 183)

0.005

5 (6)

0.11

Data are presented as median (IQR) or n (%).

ECMO indicates extracorporeal membrane oxygenation; ECPR, use of extracorporeal membrane oxygenation to
support failed conventional cardiopulmonary resuscitation.
*Fisher exact test.
Missing (n32).
Cumulative duration.

follow-up (n63) compared to those assigned scores at

discharge (n24) were similar in baseline characteristics and
in their median POPC (P0.67) and PCPC (P0.77). Based
on the patients seen in follow-up at a median duration of 25
months (11, 62), 80% of our ECPR survivors to hospital
discharge are alive at 5 years.

Discussion
The use of rapid-response ECMO to support failed conventional CPR in our institution rescued 51% of the patients who
would have most likely died, and 75% of these survivors had
no or mild early neurological impairment. Despite a heterogeneous compilation of cardiac disease ranging from single-

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Table 4. ECMO Complications of ECPR Survivors and Nonsurvivors

Survivors
(n88)

Variable

Nonsurvivors
(n84)

Table 5. Multivariable Models of Factors Associated With

In-Hospital Mortality in ECPR Users
Variable

OR

95% CI

P
0.01

ECMO circuit complications

21 (24)

38 (45)

0.003

Surgical or cannulation site

bleeding

31 (35)

34 (40)

0.48

Noncardiac structural and

chromosomal anomalies

3.2

1.37.9

0.002

ECMO blood prime

7.1

1.436

Respiratory complications

Model 1: Pre-ECMO, CPR, and ECMO

8 (9)

23 (27)

Pneumonia, ARDS

5 (6)

17 (20)

Pleural effusion or pneumothorax

3 (3)

7 (8)

7.380

Pulmonary hemorrhage

2 (2)

2 (2)

7.2607.379

1.1

0.54.0

0.49
0.10

Post-ECMO arterial pH

0.02
0.02

Reference

Sepsis

14 (16)

24 (29)

0.05

7.1607.259

2.3

0.96.4

CNS injury

31 (35)

58 (69)

0.001

7.0027.159

2.3

0.86.6

0.12

Seizures

17 (19)

19 (23)

7.001

6.0

2.117.4

0.001

Radiological evidence of CNS

injury

24 (27)

32 (38)

0 (0)

10 (12)

CNS injury

4.1

1.98.6

0.001

16 (18)

37 (44)

Renal failure

3.3

1.47.7

0.007

4.2

1.215.3

Brain death
Renal failure
Serum creatinine 1.5 mg/dL
Dialysis use (PD or CVVHD)
Liver injury (ALT/AST 500 IU/dL)

Model 2: ECMO duration and

complications
0.001

15 (17)

36 (43)

Liver injury

5 (6)

13 (15)

ECMO duration, hr*

4 (5)

16 (19)

0.002

Data are presented as n (%).

ALT indicates alanine aminotransferase; ARDS, acute respiratory distress
syndrome; AST, aspartate aminotransferase; CNS, central nervous system;
CVVHD, continuous veno-venous hemodialysis; ECMO, extracorporeal membrane
oxygenation; ECPR, use of extracorporeal membrane oxygenation to support failed
conventional cardiopulmonary resuscitation; PD, peritoneal dialysis.

ventricle physiology to primary myocardial disease, there

were no significant differences in mortality based on the
underlying cardiac diagnosis. Children with significant chromosomal or noncardiac structural anomalies and patients who
have severe metabolic acidosis based on arterial blood gas pH
or blood lactate levels immediately after ECMO deployment
had increased mortality. Another factor that was predictive of
increased mortality in our cohort was the use of a bloodprimed ECMO circuit. We believe that use of a blood-primed
circuit may indicate severity of patient illness before ECPR
deployment and that an ECMO circuit was being prepared for
deployment to support significant refractory cardiorespiratory
dysfunction before the CA. Conversely, it may also be a
surrogate for a complicated and prolonged cannulation procedure. As reported in previous studies, need for longer
duration of ECMO support and evidence of end-organ injury
with ECMO were associated with increased mortality.4
The overall survival rate of 51% for ECPR compares
favorably to the overall survival for pediatric cardiac patients
administered ECMO as reported by the Extracorporeal Life
Support Organization (42%)10 and by other smaller singlecenter studies.5,6 Optimizing CPR, early deployment of
ECPR, and refining a system for rapid deployment that
includes immediate staff and resource availability are important factors contributing to our improved survival and outcomes. This is evidenced by the continued reduction in the
duration of CPR from the onset of CA to the establishment of
ECMO flows as our experience has grown over the years
(Figure 2). However, despite decreases in CPR duration, our
survival rates have not improved with time. Our analysis, as

49

0.03
0.002

Reference

5082

0.6

0.22.0

0.40

83116

0.6

0.21.9

0.41

117173

1.6

0.54.9

0.41

174

5.6

1.817.6

0.003

3.8

1.212.2

0.03

Model 3: Pre-ECMO, CPR, and

ECMO in patients during
2000 to 2008
Noncardiac structural and
chromosomal anomalies
Peak post-ECMO lactate, mmol/L
9

0.002
Reference

912.9

2.2

0.76.5

1317.9

3.1

1.09.2

0.04

10.0

2.933.5

0.001

18

0.17

Model 1: N172; area under receiver-operating characteristic curve

(AUC)0.70. Model 2: N163; AUC0.82. Model 3: N130; AUC0.72.
CNS indicates central nervous system; CPR, cardiopulmonary resuscitation;
ECMO, extracorporeal membrane oxygenation; ECPR, use of extracorporeal membrane oxygenation to support failed conventional cardiopulmonary resuscitation.
*Cumulative duration.

well as those of others, has shown that CPR duration may not
influence eventual survival.5 We showed that arterial blood
pH after ECPR deployment and peak lactate levels within 72
hours after ECMO are strongly associated with increased
mortality. This association may reflect those patients who had
severely compromised circulation before CA and thus may
have benefited from earlier introduction of ECMO support
before CA, those who did not receive adequate CPR, and
those who were not adequately supported with ECMO soon
after their CA. Although speculative, it appears that patient
selection for ECPR and the quality of CPR are more likely to
influence mortality than CPR duration. In our study, the
efficacy of CPR could not be evaluated because of the
heterogeneity of locations, personnel, and monitoring equipment present, but it should be an important focus of future
research to improve outcomes for ECPR users.

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Kane et al

ECMO for Pediatric Cardiopulmonary Resuscitation

The Extracorporeal Life Support Organization study of

pediatric cardiac patients requiring ECPR found that singleventricle physiology, history of stage 1-type palliation, and
arterial pH 7.01 were associated with increased mortality,
whereas right carotid artery cannulation was associated with
improved survival.7 We found similar results in regard to
metabolic acidosis after the initiation of ECMO, but cannulation site did not predict mortality. Chest cannulation allows
for easier access to the vasculature, but open cardiac massage
is frequently interrupted, reducing the effectiveness of CPR.
We speculate that it is this conflict between administering
ECMO quickly and delivering uninterrupted CPR that creates
similar mortality rates between patients who undergo chest
and neck cannulation. There have been a number of studies
with contrary survival outcomes regarding single-ventricle
patients supported with ECPR. Chan et al7 found lower
survival rates for single-ventricle patients, whereas a smaller
case series found single-ventricle patients had a 47% survival
rate compared to 27% of 2-ventricle lesions.6 Our data show
similar survival rates between single-ventricle and 2-ventricle
lesions of 51% and 48%, respectively. The subset of singleventricle patients with cavopulmonary anastomoses on
ECMO has not been well-studied in the literature. Booth et
al11 evaluated 20 patients from Childrens Hospital Boston
with either bidirectional Glenn or Fontan circulation who
were supported by ECMO and found that the survival rate
was 30%. Seven of our 16 patients (44%) with cavopulmonary anastomoses survived to hospital discharge, with a
tendency to have more severe neurological injury than
shunted single-ventricle patients in this cohort. Passive systemic venous return as a source of pulmonary blood flow is
vulnerable to conventional CPR because the increased intrathoracic pressure with chest compressions can actually
restrict pulmonary blood flow and increase systemic venous
pressure. Thus, we suggest the presence of single-ventricle
lesions alone may not be used as a contraindication for ECPR
deployment. These patients are at higher risk for CA because
of their physiology and are less likely to respond to conventional CPR therapies.
Location of the CA was not predictive of mortality in our
series despite our belief that the cardiac catheterization
laboratory is often an ideal location for ECPR because of a
higher level of invasive patient monitoring that can help
detect deterioration quickly and the presence of invasive
vascular access that can be used to rapidly place percutaneous
ECMO cannulae. The finding that a similar number of
survivors and nonsurvivors underwent a procedure after CA
demonstrates that CA in these patients may be related to
unrecoverable myocardial dysfunction despite the perception
that a correctable anatomic lesion may be present. Early
listing for cardiac transplantation must be considered in some
of these patients as an optimal rescue strategy.
Neurological injury has been well-documented as a complication of ECMO and has been reported to be higher in
patients undergoing ECPR.12 Studies from the Extracorporeal
Life Support Organization registry have used the incidence of
brain death, brain infarction, and hemorrhage to define the
frequency of CNS injury, but they lack functional assessments and follow-up evaluation of neurological impair-

S247

ment.1213 Utilizing the Extracorporeal Life Support Organization registry, Barrett et al13 reported a 22% incidence of
CNS injury in ECPR patients. Patients with less severe
metabolic acidosis before ECMO and an uncomplicated
ECMO course were more likely to avoid neurological injury.13
Our series had a higher incidence of CNS injury (52%). This
may have resulted from the use of broader clinical and
radiological criteria to define neurological injury, because we
wanted to capture all neurological insults to determine if they
predicted functional impairment during follow-up. Our use of
POPC/PCPC metric of functional status is limited because it
lacks a detailed objective assessment of the patients true
neurological status. However, it has been shown to accurately
predict performance in more rigorous psychometric testing.9
This study has several limitations. The retrospective observational design precluded collection of important predictors
that may have influenced our outcome. In addition, the
generalizability of these findings is limited because of the
heterogeneity of our study population and the report of a
single-center experience with ECPR. Neurological assessment would have been more robust if our survivors were
evaluated by standardized neuro-developmental testing rather
than POPC/PCPC categorization. Furthermore, 28% of our
survivors were lost to follow-up, and assignment of POPC/
PCPC scores at discharge limits our ability to truly assess
functional impairment and overall capability. However, the
similar baseline characteristics and median POPC/PCPC
scores between the patients assigned scores in follow-up and
at discharge suggest that there is likely little or no bias in this
distribution. The POPC/PCPC measures also tend to not capture
the behavioral and attention issues that these patients may be at
severe risk for. Our neurological outcomes are only descriptive,
and there needs to be a primary outcome variable in future
studies to determine predictors of favorable outcomes.

Conclusion
The 51% overall survival and the preserved long-term survival without severe early neurological impairment demonstrate that ECPR is a useful modality to rescue children with
cardiac disease who experience an in-hospital CA that does
not respond to conventional CPR therapies. The presence of
a structured ECPR program with continuous quality improvement can help decrease deployment times. Patients with
noncardiac structural and chromosomal anomalies may not be
suitable for ECPR because their risk of mortality is higher.
The presence of significant metabolic acidosis increases risk
of mortality and future studies on ECPR should focus on
methods to improve quality of CPR and early management
after ECPR to help provide adequate support to these patients.
Although early crude indicators suggest preserved neurological function in ECPR survivors, CNS injury remains high
and future studies should also focus on reducing the burden of
neurological injury in these patients. An active transplant and
mechanical support program is necessary because 11% of our
survivors underwent successful heart and lung transplantation. A pediatric cardiovascular program that performs surgical and interventional catheterization procedures should
consider developing ECPR capabilities to best serve their
patients.

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S248

Circulation

September 14, 2010

Disclosure
Ravi R. Thiagarajan received an honorarium from Seattle Childrens
Hospital for a lecture on ECPR and served as a consultant to the
ECMO program at Childrens National Medical Center.

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