Perioperative extracorporeal membrane oxygenation in pediatric congenital heart disease: Chinese expert consensus

Abstract

Background
Congenital heart disease (CHD) is one of the main supportive diseases of extracorporeal membrane oxygenation in children. The management of extracorporeal membrane oxygenation (ECMO) for pediatric CHD faces more severe challenges due to the complex anatomical structure of the heart, special pathophysiology, perioperative complications and various concomitant malformations. The survival rate of ECMO for CHD was significantly lower than other classifications of diseases according to the Extracorporeal Life Support Organization database. This expert consensus aims to improve the survival rate and reduce the morbidity of this patient population by standardizing the clinical strategy.

Methods
The editing group of this consensus gathered 11 well-known experts in pediatric cardiac surgery and ECMO field in China to develop clinical recommendations formulated on the basis of existing evidences and expert opinions.

Results
The primary concern of ECMO management in the perioperative period of CHD are patient selection, cannulation strategy, pump flow/ventilator parameters/vasoactive drug dosage setting, anticoagulation management, residual lesion screening, fluid and wound management and weaning or transition strategy. Prevention and treatment of complications of bleeding, thromboembolism and brain injury are emphatically discussed here. Special conditions of ECMO management related to the cardiovascular anatomy, haemodynamics and the surgical procedures of common complex CHD should be considered.

Conclusions
The consensus could provide a reference for patient selection, management and risk identification of perioperative ECMO in children with CHD.

Full text

Vol.:(0123456789)
1 3
World Journal of Pediatrics
https://doi.org/10.1007/s12519-022-00636-z
REVIEW ARTICLE
Perioperative extracorporeal membrane oxygenation inpediatric
congenital heart disease: Chinese expert consensus
RuLin1· WeiWang2· XuWang3· Zhuo‑MingXu2· Jin‑PingLiu4· Cheng‑BinZhou5· Xiao‑YangHong6· Xu‑MingMo7·
Shan‑ShanShi8· Li‑FenYe1· QiangShu9
Received: 24 July 2022 / Accepted: 10 October 2022
© The Author(s) 2022
Abstract
Background Congenital heart disease (CHD) is one of the main supportive diseases of extracorporeal membrane oxygena-
tion in children. The management of extracorporeal membrane oxygenation (ECMO) for pediatric CHD faces more severe
challenges due to the complex anatomical structure of the heart, special pathophysiology, perioperative complications and
various concomitant malformations. The survival rate of ECMO for CHD was significantly lower than other classifica-
tionsofdiseases according to the Extracorporeal Life Support Organization database. This expert consensus aims to improve
the survival rate and reduce the morbidity of this patient population by standardizing the clinical strategy.
Methods The editing group of this consensus gathered 11 well-known experts in pediatric cardiac surgery and ECMO field
in China to develop clinical recommendations formulated on the basis of existing evidences and expert opinions.
Results The primary concern of ECMO management in the perioperative period of CHD are patient selection, cannulation
strategy, pump flow/ventilator parameters/vasoactive drug dosage setting, anticoagulation management, residual lesion
screening, fluid and wound management and weaning or transition strategy. Prevention and treatment of complications of
bleeding, thromboembolism and brain injury are emphatically discussed here. Special conditions of ECMO management
related to the cardiovascular anatomy, haemodynamics and the surgical procedures of commoncomplex CHD should be
considered.
Conclusions The consensus could provide a reference for patient selection, management and risk identification of periop-
erative ECMO in children with CHD.
Keywords Circulatory support· Congenital heart disease· Extracorporeal membrane oxygenation· Pediatric· Respiratory
support
* Qiang Shu
shuqiang@zju.edu.cn
1 Department ofExtracorporeal Life Support, Heart
Institute, National Clinical Research Center forChild
Health, Children’s Hospital, Zhejiang University School
ofMedicine, Hangzhou, China
2 Department ofThoracic andCardiovascular Surgery,
Shanghai Children’s Medical Center, Shanghai Jiao Tong
University School ofMedicine, Shanghai, China
3 Department ofPediatric Intensive Care Unit, National Center
forCardiovascular Disease andFuwai Hospital, Chinese
Academy ofMedical Sciences, Peking Union Medical
College, Beijing, China
4 Department ofCardiopulmonary Bypass, National Center
forCardiovascular Disease andFuwai Hospital, Chinese
Academy ofMedical Sciences, Peking Union Medical
College, Beijing, China
5 Department ofCardiovascular Surgery, Guangdong
Provincial Cardiovascular Institute, Guangdong Provincial
People’s Hospital, Guangdong Academy ofMedical
Sciences, Guangzhou, China
6 Pediatric Intensive Care Unit, Faculty ofPediatrics, Chinese
PLA General Hospital, Beijing, China
7 Department ofCardiothoracic, Children’s Hospital
ofNanjing Medical University, Nanjing, China
8 Department ofCICU, Heart Institute, National Clinical
Research Center forChild Health, Children’s Hospital,
Zhejiang University School ofMedicine, Hangzhou, China
9 Department ofCardiac Surgery, National Clinical Research
Center forChild Health, Children’s Hospital, Zhejiang
University School ofMedicine, Binsheng Road 3333,
Hangzhou310052, China

World Journal of Pediatrics
1 3
Introduction
Until the 1970s, extracorporeal membrane oxygenation
(ECMO) was reported to be successfully used in a neo-
nate with acute respiratory failure [1]. Since the 1980s,
the number of cardiac ECMO cases has increased dra-
matically, though neonatal respiratory failure remains to
be the most common indication for ECMO support [2].
ECMO is used for respiratory support, circulatory support
and cardiopulmonary resuscitation (CPR) in pediatrics.
The most common neonatal diagnosis requiring respira-
tory ECLS(extracorporeal life support) was congenital
diaphragmatic hernia (32%), followed by meconium aspi-
ration syndrome (24%) and persistent pulmonary hyper-
tension (21%) [3]. The most common disease requiring
circulatory ECLS is congenital heart disease (CHD), 80%
in newborns and 52% in children [3].
Veno-arterial ECMO (VA ECMO) is the main support
mode for CHD. According to the data from Extracorpor-
eal Life Support Organization (ELSO) registry, a total
of 19,629 cases with CHD from 350 international cent-
ers worldwide from 1990 to 2019 have been supported
by ECMO [4]. Among them, the most common condition
was hypoplastic left heart syndrome (HLHS) in neonates,
whereas in children conditions requiring complex biven-
tricular repair (such as tetralogy of Fallot, double outlet of
right ventricle, Ebstein's anomaly of the tricuspid valve)
were the most common [4]. The median ECMO running
duration for of pediatric cardiac diseases was 6–7days,
and the survival rate was 46%–55%, which was signifi-
cantly lower than other classificationsofdiseases [4].
In China, ECMO was reported to be successfully used
in a neonate with CHD in 2008 [5].A total of 10,946
patients with CHD underwent cardiopumonary bypass
from January 2017 to June 2020, ECMO cases accounted
for 1.21% and a survival rate was 47% [6].In 2021,
ECMO was used for respiratory support in 126 children
and for circulatory support in 422 children with a survival
rate of 59.5% [7]. A total of 127 children underwent exter-
nal cardiopulmonary resuscitation (ECRP) support with a
survival rate 39.4%, and among them 10 were newborns
with a survival rate of 8.3%. A total of 65 newborns with
CHD underwent ECMO with a survival rate of 43.1% [7].
ECMO support after arterial switch operations (ASOs)
accounted for 21.2% of total ECMO cases with CHD [8].
Children with CHD have more challenges due to complex
heart anatomical structure, special pathophysiology, perio-
perative complications and various concomitant malforma-
tions. This consensus focused on the technical approach of
ECMO support in pediatric CHD. Recommendations on
patient selection, management and risk identification of peri-
operative ECMO support in pediatric CHD were provided.
Patient selection criteria
Indications
Most neonatal cardiac ECMO occurs during the periop-
erative period and particularly the post-procedure period
[9]. Perioperative ECMO in children with CHD is used to
stabilize and recover the respiratory and circulatory func-
tion. ECMO may also be used for recovery from the pri-
mary disease and providing time for follow-up diagnosis
and treatment and for awaiting other therapeutic modalities,
such as ventricular-assist device (VAD) or transplantation
in the following situations: (1) pre-procedural patients with
severe hypoxemia and low cardiac output syndrome (LCOS):
patients with total anomalous pulmonary venous connection
and transposition of the great arteries (TGA) may present
with severe hypoxia, acidosis and LCOS due to insufficient
oxygenation of blood and persistent pulmonary hyperten-
sion; (2) failure to wean off cardiopulmonary bypass (CPB):
ECMO support may be required for patients who fail to
wean off CPB after cardiac surgery for improper myocardial
protection, myocardial ischemia injury or residual anatomi-
cal deformity; (3) severe postoperative LCOS: LCOS occurs
due to myocardial damage or stunning, coronary ischemia,
malignant arrhythmia, residual lesions and sudden obstruc-
tion of the postoperative systemic-pulmonary shunt; (4) car-
diac arrest due to a variant of causes.
ECMO should be initiated as early as possible if with the
following indications [10–16]: (1) cardiac index < 2 L/m2/
minute; (2) persistent tissue hypoperfusion: blood pH < 7.15,
BE < -5mmol/L, lact ate > 7.3mmol/L, urine output < 1mL/
kg/hour, capillary refill time > 3seconds, central venous
oxygen saturation (SVO2) < 60% or arteriovenous oxygen
saturation difference (AVO2) > 30% for cyanotic CHDs; (3)
persistent hypotension: the blood pressure is two standard
deviations lower than that of normal blood pressure at the
same age, such as for systolic blood pressure < 50mmHg
(neonates), < 60mmHg (infants) and < 70mmHg (children);
(4) patients presenting with low blood pressure under two
or more high-dose inotropes and/or vasopressors, such as
epinephrine > 0.3µg/kg/minute, dopamine > 10µg/kg/min-
ute, etc., or vasoactive–inotropic score is over 20 for two
or more times and keeps increasing; (5) severe respiratory
failure: severe hypoxia or respiratory acidosis persists even
after conventional aggressive treatment, such as pH < 7.1,
partial pressure of oxygen/fraction of inspired oxygen (PaO2/
FiO2)< 60–80mmHg or oxygenation index > 40, lasting
3–6hours; (6) malignant arrhythmias: ECMO should be
considered when severe arrhythmias, such as ventricular
fibrillation, cardiac arrest or pulseless electrical activity and
short bursts of ventricular tachycardia occur repeatedly and

World Journal of Pediatrics
1 3
cannot be terminated by antiarrhythmic drugs, inotropes or
temporary cardiac pacemakers.Consideration for early ini-
tiation of ECMO is importantas delayed initiation (beyond
6 hours of cardiogenic shockstate) is associated with worse
outcomes.
Contraindications
ECMO should not be used under the following conditions
[10]: (1) prolonged cardiogenic shock state (more than
6hours) complicated with irreversible multiple organ fail-
ure; (2) premature or low birth weight neonates (< 34weeks
of gestational age or weight < 2.0kg); (3) severe chromo-
somal abnormalities; (4) irreversible brain injury or intrac-
ranial hemorrhage (grade III or IV intraventricular hemor-
rhage); (5) uncontrolled bleeding (unless ECMO cannulation
can help to control bleeding).
Cannulation strategy
VA ECMO was the most commonly used mode for most
congenital heart diseases perioperatively. Cannulation
site and strategy were determined by the patient’s body
size, underlying cardiac anatomy and different surgical
procedures for CHD. The commonly used cannulation strat-
egy is listed in Table1. Central cannulation is commonly
used in failure to wean from CPB or in the presence of
recent sternotomy (less than 10–14days). The right neck or
femoral vessels can be considered as the peripheral cannu-
lation site. Most commonly, the right internal jugular vein
and carotid artery configuration is used in younger patients
(weight < 30kg), while the femoral vein and femoral artery
configuration is used in older patients (weight > 30 kg)
[10]. Each ECMO center selects a peripheral cannulation
site based on technique preference with reference to the
patient’s weight range.
Peripheral vessel cannulation requires usually open sur-
gical access [10]. The tip of the arterial cannula is located
at the junction of the innominate artery and the aortic arch,
preventing access to the ascending aorta. The tip of the
venous cannula is located at the right atrium, preventing
access to the right ventricle or hepatic vein. Single-ventricle
patients with ductal- or shunt-dependent pulmonary blood
flow may require excessive ECMO flow rates to accommo-
date the runoff into the pulmonary vascular bed and to pro-
vide adequate systemic tissue oxygen delivery. When a high
volume of flow can be difficult to achieve from peripheral
cannulation, central cannulation may be necessary [2]. When
patients following the Glenn or Fontan procedure require VA
ECMO, venous drainage cannulas may be possible in both
Table 1 Cannulation strategy in children with cardiac disease
RV-PA right ventricle-to-pulmonary artery, SVC superior vena cava [10]
Anatomy or surgical
palliation
Central cannulation Peripheral cannulation Additional strategies
Venousaccess Arterial access Venous access Arterial access
Two ventricles
Biventricular circulation
or structurally normal
heart
Right atrium Aorta Internal jugular or
femoral
Common carotid or
femoral
Left atrial decompres-
sion may need to be
considered
Single ventricle
Shunted or RV-PA
conduit physiology
(stage 1)
Com-
monatrium
Aorta Internal jugular Common carotid Peripheral: neck access due
to patient size
Care: cannula position
with respect to shunt—
may resultin overcircu-
lation to lungs or shunt
occlusion
Superior cavopulmo-
naryanastomosis
(stage 2)
SVC orcom-
monatrium
Aorta Internal jugular or
femoral
Commoncarotid If femoral approach only
used, passive venous
return must flow through
lungs—ventilation must
be optimized
Additional venous cannula
may be required
Total cavopulmo-
naryanastamosis
(Fontan,stage 3)
Fontan baf-
fleor com-
monatrium
Aorta Internal jugular or
femoral
Commoncarotid orfemo-
ral
Additional venous cannula
often required

World Journal of Pediatrics
1 3
the superior and inferior vena cava to achieve adequate vein
drainage [17].
ECMO pump ow, ventilator parameters
andvasoactive drug dosage setting
During ECMO, mixed venous oxygen saturation (SVO2)
should be continuously monitored. The cardiac index should
be maintained at 2.5–3 L/minute/m2 and the ratio of oxygen
delivery (DO2) to oxygen consumption (VO2) should be set
at least > 3:1 by adjusting pump flow and hemoglobin level
[10]. Reasonable ventilator parameters and vasoactive drugs
help to restore cardiac function and maintain perfusion of
the organs and peripheral microcirculation (Table2).
During the initial period, higher blood flow is required for
early oxygen debt repayment, typically 100–150mL/kg/min-
ute in neonates and 80–120mL/kg/minute in children [10,
18]. Pulmonary blood flow is reduced during VA ECMO,
so the ventilation volume should be reduced proportionally
[19]. Protective lung ventilation strategies with low param-
eter settings, including setting positive end-expiratory pres-
sure (PEEP) 8–10cm H2O and tidal volume < 6–8mL/kg,
peak inspiratory pressure < 18–20cm H2O and frequency
10–15 times/minute can be utilized to reduce pulmonary
complications [13, 19, 20]. High PEEP increases intra-
thoracic pressure, pulmonary vascular resistance and right
ventricular afterload, which adversely affect children with
predominant right heart failure [21]. Conversely, children
with predominant left heart failure often benefit from a high
PEEP [19]. High pump flow will increase left ventricular
afterload and myocardial performance after ECMO implan-
tation; vasopressors should be reduced or discontinued as
soon as possible and vasodilators administered to reduce
afterload, to promote recovery of myocardium and micro-
circulation perfusion and to avoid important organ and
extremity complications. Maintenance of normal rhythm
with drugs or pacemakers improves ventricular emptying.
In children with severe right heart failure and pulmonary
hypertension, inhaled nitric oxide and/or targeted pulmo-
nary arterial vasodilators can be used to reduce right heart
afterload [13]. It is necessary to precisely regulate fluid
balance, ventilator parameters and ECMO pump flow after
ASO and anomalous left coronary artery origin from pul-
monary artery (ALCAPA) repair. The regulation strategy
should be tailored to improve the left ventricle adaptability
to preload and afterload and avoid left ventricular distension.
For children with HLHS, low pulmonary vascular resistance
may lead to reduced systemic circulation and hypotension,
whereas excessive pulmonary vascular resistance may lead
to hypoxia. Children with B-T shunts or aortopulmonary col-
lateral arteries require higher blood flow (150–200mL/kg/
minute) to accommodate the runoff into the pulmonary vas-
cular bed [4, 22]. Additionally, when the flow of the shunt
or the collateral artery is too great, the shunt or the collateral
artery needs to be partially clamped or blocked.
Anticoagulation management
Bleeding is a common complication of ECMO for post-
cardiac surgery patients, most frequently in central cannu-
lation [23].The main causes of bleeding are the immature
coagulation function of neonates and infants, the dilution of
coagulation factors after connection to the ECMO circuit, the
large open wound and the coagulopathy usually associated
with a long duration of CPB. The main methods to reduce
bleeding include reversing partial heparin with limited pro-
tamine administration [24], strict surgical hemostasis, and
correcting coagulopathy and thrombocytopenia by infusing
fibrinogen, fresh frozen plasma and platelets. If excessive
bleeding occurs, particularly in post-cardiotomy patients,
Table 2 Indications of vasoactive drugs for pediatric cardiac
VA ECMO veno-arterial extracorporeal membrane oxygenation [4]
Vasoac-
tivedrugs
Indication, benefits, and specific risks Medication Starting dose range
Inotrope Enhancement of contractility in a patient with severe cardiac dysfunction to facili-
tate aortic valve opening, and prevent stasis of blood in the systemic ventricle and
aortic root
To optimize blood pressure and end-organ perfusion
Not facilitate myocardial rest
Epinephrine
Dobutamine
0.02–0.05μg/kg/min
5μg/kg/min
Vasopressor Peripheral vasoconstriction is indicated in a patient on VA ECMO for distributive
shock, on maximal circuit blood flow with inadequate cardiac output to optimize
blood pressure and end-organ perfusion
Norepinephrine
Vasopressin
0.02–0.05μg/kg/min
0.01–0.06IU/kg/h
Vasodilator Peripheral vasodilation will reduce systemic afterload improving circuit blood flow
and systemic perfusion as well as decreasing left ventricle afterload, promoting
ejection
Sodium nitroprusside
Milrinone
Nitroglycerin
0.5-3μg/kg/min
0.25–1.0μg/kg/min
0.3–0.6μg/kg/min

World Journal of Pediatrics
1 3
delayed infusion of unfractionated heparin (UFH) persis-
tently for 4–6hours is required. Under some circumstances
where bleeding is difficult to control, UFH may be held up for
12hours or longer until bleeding is controlled [25]. Delayed
initiation of anticoagulation will increase the risk of circuit
clots, which will increase the consumption of fibrinogen and
platelet. UFH is currently the most commonly used anticoag-
ulant for ECMO. The effectiveness of heparin can usually be
monitored using activated clotting time (ACT) and activated
partial thromboplastin time (APTT) combined with anti-Xa,
thromboelastometry (ROTEM) and thromboelastography
(TEG) [17]. ROTEM or TEG is currently recommended to
guide the administration of blood products and coagulation
factors in the presence of bleeding [26].
A bolus dose of UFH ranging from 50 to100 units/kg is
given after the exposure of the vessels and before insertion
of the cannulas for ECMO. Patients with severe coagulopa-
thy, or active bleeding can receive a UFH bolus at the lower
end of this range. Nevertheless, in the immediate postopera-
tive transferring from CPB, bolus dosing of UFH may not be
necessary [27]. UFH can be commenced when ACT reaches
300seconds [18] and chest tube drainage is < 3mL/kg/hour
for 2hours [28]. Some ECMO centers set maintenance dose of
UFH infusion rate ranging from a minimum of 10–15 units/kg/
hour to a maximum of 40–60 units/kg/hour [18]. The targeted
ACT 180–220seconds and APTT 1.5 and 2.5 times normal are
needed. Targeted ACT value can be lowered to 160–180sec-
onds when there is a tendency to bleed. Blood production can
be given to maintain platelet counts ≥ 100 × 109/L (bleeding
patient) or ≥ 50–100 × 10 9/L (nonbleeding patient), fibrino-
gen > 1.5g/L (bleeding patient or before surgical interven-
tion) or > 1g/L (nonbleeding patient). If a maximum dose
of UFH cannot achieve the targeted ACT value, fresh frozen
plasma could be infused to maintain antithrombin activity
at > 50%–80% or 0.5–0.8 U/mL [25].
Direct thrombin inhibitors (DTIs) have been used in both
adult and pediatric patients with heparin-induced thrombo-
cytopenia (HIT), heparin resistance and non-HIT thrombo-
cytopenia [29, 30]. The two DTIs most commonly used in
ECMO are bivalirudin and argatroban. APTT is currently the
standard test for monitoring DTIs (target 50–60seconds),
and the reported maintenance dose of bivalirudin and arga-
troban ranges from 0.045 to 0.48mg/kg/hour and 0.1 to
0.7μg/kg/minute, respectively [18]. Currently, experiences
of using DTIs are lacking in pediatric ECMO in China, and
clinicians should be aware of the safety and efficacy of DTIs.
Left ventricle decompression
When severe left ventricle (LV) dysfunction is supported
with VA ECMO, continuous flow increases the pres-
sure of the aortic root and LV afterload [31, 32]. Poor LV
decompression may result in a persistently closed aortic
valve, dilatation of the left heart, increased LV end-diastolic
pressure, reduced sub-endothelial perfusion causing myo-
cardial ischemia and poor LV function recovery, and a risk
of LV stasis and consequent clot formation [33, 34]. It is
important to recognize poor LV decompression early and to
perform effective LV decompression.
After cardiac tamponade was excluded, the implications
of poor LV decompression were reduced arterial pulse pres-
sure (< 10mmHg), increased pulmonary capillary wedge
pressure (PCWP) or left atrium (LA) pressure(> 20mmHg),
pulmonary edema, closed aortic valve, increased LA or LV
end-diastolic diameter and aggravated mitral valve regurgi-
tation [35].
Conservative decompression was the first-line strategy:
(1) titrate the ECMO flow [35] and use a vasodilator to
decrease LV afterload; (2) increase inotrope to improve LV
output; and (3) increase PEEP to decrease LV preload [35].
If conservative methods do not work effectively, invasive
strategies can be utilized: (1) LA venting via the right-upper
pulmonary vein or left atrial appendage (most commonly in
post-cardiac surgery); (2) balloon atrial septostomy or blade
atrial septostomy to allow left-to-right shunting [35, 36]; (3)
a venting cannula via the LV apex or pulmonary artery [37,
38]; and (4) intra-aortic balloon pump or a percutaneous LV-
to-aorta ventricular-assist device, such as impella, could be
used in adolescents or young adults [2, 35, 39].
Residual lesions
Postoperative residual lesions of CHD can significantly
increase the risk of postoperative complications and mortal-
ity rate [40]. Therefore, transesophageal echocardiography
during the operation to detect residual lesions and timely
intervention are conducive to the smooth withdrawal of
CPB [41–43]. If there is no sign of myocardial function
recovery after 48–72hours of ECMO support, it is neces-
sary to positively identify residual anatomical malforma-
tion.Identifying residual lesions and intervening during the
first threedays of ECMO support can significantly shorten
support duration and improve the survival rate of patients
[40, 41].
Common residual lesions include residual ventricular
septal defects, stenosis and dysplasia of the pulmonary
artery branch, stenosis of the left and right ventricular
outflow tracts, pulmonary vein stenosis, B-T/Sano duct
stenosis or too great, severe valvular regurgitation, bulky
pulmonary collateral and coronary artery disease [41, 42].
In the early stage of support, residual lesion can present as
ventricular dilatation and dyskinesia, insufficient systemic
perfusion caused by excessive shunt, suboptimal blood lac-
tate decrease, pulmonary hemorrhage, aberrant increase in

World Journal of Pediatrics
1 3
mixed SvO2, etc. Children with a single ventricle may have
insidious manifestations and may not present a significant
increase in the left atrial or central venous pressure until the
auxiliary flow is reduced to 30%–40%.
The first option for examination to identify residual ana-
tomical malformation is ultrasound [41, 42]. When process-
ing the examination, we can reduce the flow of ECMO or
clamp the circuit temporarily to evaluate the cardiac function
more accurately and identify residual lesions. Many factors,
such as wound dressings, opened sternum, various cannula-
tions and inappropriate size of ultrasound probe, can affect
the acquisition of standard ultrasound views. If necessary,
further examinations, such as cardiac catheterization or com-
puted tomography angiography (CTA), can be recommended
[43–45].
Fluid management andrenal replacement
therapy
Children with VA ECMO during the perioperative period
of CHD need appropriate fluid to maintain cardiac output
and ECMO flow. Dynamic monitoring of central venous
pressure (CVP), PCWP, pre-pump pressure of circuit and
other comprehensive evaluations of volume status are cru-
cial. During the early period of ECMO support, bleeding,
insensible fluid loss or capillary leakage syndrome may be
attributed to insufficient ECMO flow. When the pre-pump
pressure of ECMO becomes more negative (below -40 to
-30mmHg), the venous line vibrates or the inferior vena
cava collapses [46] and colloids and low dose of vasoac-
tive drugs can be given firstly to maintain the intravascular
volume. Once the circulation of children is stable and capil-
lary leakage is improved, fluid intake should be limited and
negative fluid balance is warranted to avoid fluid overload.
Renal replacement therapy should be actively applied in
case of intravascular fluid overload, oliguria or refractory
to diuretics and albumin, elevated creatinine and electrolyte
disorder [10, 47].
About 49%–59% of children on ECMO with CHD devel-
oping acute kidney injury (AKI) and fluid overload require
renal replacement therapy (RRT) [48, 49]. Low cardiac out-
put, hypotension, venous congestion, non-pulsatile perfu-
sion, inflammatory reaction and hemolysis may cause AKI
[50] and fluid overload, prolonging ECMO supporting time
and increasing mortality [51–54]. The commonly used RRT
models in children are continuous renal replacement therapy
(CRRT) [50] and peritoneal dialysis (PD). Although some
researchers reported no improvements in the survival rate by
utilizing ECMO with CRRT and no high-level evidence or
guidelines support routine usage of CRRT during ECMO,
some researchers discovered that the combination of ECMO
and CRRT may be effective [51, 55, 56].
To avoid serious air embolism, we recommend the
input and output interfaces of CRRT be connected to the
post-pump part of the ECMO circuit (Fig.1). Parallel
connection with the CRRT circuit will increase the tur-
bulence and coagulation risk of ECMO circuit interface,
with the need for close monitoring for hemolysis, bleed-
ing and coagulation [50]. If the patient has undergone
CRRT before ECMO support, the original CRRT cath-
eter is recommended to be continued. According to the
KDIGO(Kidney Disease: Improving Global Outcomes)
guidelines [57], for those who have already received sys-
temic anticoagulation with UFH, other anticoagulants are
generally not added. Some researchers [58] have proposed
regional citrate anticoagulation to prolong the life span of
the CRRT filter. Each center can make systematic assess-
ment and decide the individual connection mode and anti-
coagulation schemes.
Fig. 1 The connection of ECMO with continuous renal replacement therapy (CRRT)

World Journal of Pediatrics
1 3
The safety and effect of peritoneal dialysis during ECMO
in children with CHD should be affirmed [59–63]. Because
anticoagulation increases the risk of bleeding during PD
tube placement, the patient’s coagulation status should be
evaluated before placement to prevent bleeding. Ultrasound
guidance can avoid the risk of abdominal complications
(such as intestinal perforation, parenchymal organ puncture
injury).
Wound care
Central cannulation generally requires delayed sternal clo-
sure. The sternal skin should be sutured as much as possible
or covered with sterile dressings [64]. Strict aseptic tech-
niques, keeping the wound surface clean and dry, assess-
ing the hemorrhage and exudation, routine cleaning and
sterilizing the skin around the cannula and incision, and
pericardial mediastinal irrigation are essential to prevent
infections. Topical sealants, such as gelatin sponges or dry
gauze strips, can be used to control oozing and bleeding
[65]. When chest drainage increases or stops with increased
tension of the dressing, accompanied by decreasing blood
pressure and pulse pressure, lower cardiac sound and unsta-
ble pump flow [66], pericardial tamponade should be con-
sidered. Emergency thoracotomy to remove the accumulated
blood is recommended.
Weaning andtransition
When cardiac function recovers after 5–7days of ECMO
support, weaning can be considered. If there is no sign of
improvement in cardiac function for longer than two weeks,
transition to an intermediate- or long-term mechanical car-
diac support device or heart transplant should be considered
[67]. If irreversible multiple organ failure occurs, ECMO
withdrawal should be considered. Before VA ECMO wean-
ing, it is necessary to repeatedly evaluate cardiopulmonary
function, residual lesions and adaptive changes in the cardiac
structure. Reducing the pump flow and temporarily clamping
the circuit are needed for further evaluation.
When the pump flow is gradually reduced to less
than 30% of the full flow for 6–24hours, weaning can
be attempted if the following conditions are met [10,
68–70]: (1) with low levels of vasoactive drugs (epi-
nephrine ≤ 0.02–0.05 μg/kg/minute, dopamine/dobu-
tamine 3–5μg/kg/minute), arterial pressure within the
normal values and pulse pressure difference greater
than 20mmHg, CVP > 5mmHg [10]; (2) left ventric-
ular ejection fraction > 25%, left and right ventricu-
lar motion coordination and aortic valve velocity time
integral ≥ 10cm[69]; (3) with the ventilator parameters
as follows: oxygen concentration ≤ 60%, tidal volume
6–8 mL/kg,peak inspiratory pressure < 30 cmH2O,
PEEP 5–15 cmH2O and PaO2/FiO2 > 200 mmHg after
biventricular correction, PCO2 ≤ 45 mmHg, pH > 7.3,
SvO2 ≥ 65%, blood lactate, electrolyte and hematocrit
(HCT) values within the normal range; (4) in patients
with a single ventricle, it is necessary to adjust the bal-
ance of systemic/pulmonary blood flow according to the
cardiac surgical procedures and the level of peripheral
blood oxygen saturation (SpO2). The oxygenation index
and mechanical ventilation parameters should meet the
targets and all conditions remain stable.
First-aid medicines, equipment and blood availability
should be accessible to address the possible risks during
weaning. The trial off VA ECMO for CHD is similar to the
ELSO guideline [10, 68, 71, 72]. The LV decompression
cannula should be removed first. The sternal incision could
be closed at the same time as decannulation if hemodynam-
ics is stable. If the carotid artery is difficult to repair, ligation
should be considered. It is still necessary to evaluate cardio-
pulmonary function after weaning off. If cardiopulmonary
function is unstable, ECMO should be implanted once again.
Main complications
Bleeding andthromboembolism
Bleeding after cardiac surgery could be caused by surgi-
cal factors or coagulation disorder. The optimal treatment
depends on the cause, amount and site of bleeding. For sur-
gical bleeding, operative hemostasis should be performed.
For light bleeding other than the brain, the anticoagulation
level can be adjusted downward. In cases of intracranial
hemorrhage and/or massive bleeding, anticoagulants should
be suspended until the bleeding is controlled. Hemostatic
and blood products should be given as needed. For refrac-
tory bleeding, anti-fibrinolytic therapy (e.g., tranexamic
acid) should be initiated if necessary.
ECMO-associated thrombosis could occur both in the
ECMO circuit and vessels. Coagulation disorders after
prolonged CPB, high-dose vasopressor infusion, delayed
initiation of heparin and excessive infusion of coagulation
substrate increase the risk of thrombosis. An individual
anticoagulation strategy, careful surgical hemostasis, stable
internal environment, reasonable infusion of coagulation
substrate, appropriate vasopressor usage, effective left heart
decompression [73] and reduction of ventricular blood sta-
sis could contribute to reduce the risk of thrombosis. Small
thrombi in the ECMO circuit should be observed closely by
improving the anticoagulation level. In case of life-threat-
ening thrombotic events, emergency treatment of surgical

World Journal of Pediatrics
1 3
thrombectomy [74] and ECMO circuit replacements should
actively be taken into consideration.
Brain injury
The risk factors for ECMO-related brain injury include
younger age (gestational age <34 weeks),lower body weight
(<3kg), exposure to CPR, acidosis, surgical factors, throm-
boembolism, systemic anticoagulation and cerebral hypoper-
fusion [76].Routine neurological assessment and multimodal
neurological function monitoring [76], such as transcranial
ultrasound, continuous near-infrared spectral oxygen satu-
ration, electroencephalography and bispectral index, should
be performed to monitor possible cerebral dysfunction. A
CT scan is recommended to evaluate the possibility of acute
brain injury in cases with clinical signs. In cases with cer-
ebral edema, slightly lowering the circuit temperature, local
sub-hypothermia therapy, glucocorticoids and dehydrating
agents should be used to control the intracranial pressure. It is
necessary to monitor CO2 levels to avoid the effects of hyper-
ventilation on cerebral vessels. In patients with mild intracra-
nial hemorrhage, close monitoring of neurological function
and optimization anticoagulant strategy are required. ECMO
discontinuation should be considered in cases of severe
intracranial hemorrhage with an expected poor prognosis.
Extracorporeal cardiopulmonary resuscitation
ECPR is the rapid deployment of VA ECMO to provide
reperfusion with oxygenation and cardiac support when
conventional cardiopulmonary resuscitation (CPR) fails to
restore sustained spontaneous circulation [77]. Owing to
the anatomical and physiological characteristics of CHD,
low cardiac output, poor oxygenation and insufficient cer-
ebral perfusion are prone to occur during chest compression.
Therefore, when CPR fails to restore spontaneous circulation
within 15minutes, the ECPR procedure should be started
immediately [70, 77]. Timely application of ECPR can
reduce organ damage and improve the survival of children
with CHD in the hospital [78–81].
According to the anatomical characteristics of CHD and
the speed of rescue, the ECPR cannulation strategy is for-
mulated, central cannulation can be performed in the early
stage within the postoperative 14days, and cervical or femoral
arteriovenous cannulation can be performed in children before
surgery or during the late postoperative period [70, 82].
One of the key factors for the success of ECPR is the
full effectiveness of CRP and the rapid implementation of
ECMO [83, 84]. After ECMO initiation, high pump flow
is given to improve the perfusion, oxygenation and inner
environment of organs as soon as possible to create the con-
ditions for subsequent diagnosis and treatment. Although
effects of mild hypothermia brain protection is controver-
sial, targeted management of mild hypothermia (33–34°C)
for 24–48hours may be considered in children at risk of
serious neurological complications [85]. Carrying out imag-
ing examinations, identifying the primary cause of cardiac
arrest and implementing timely intervention or surgical re-
intervention will help to improve the prognosis [82, 86, 87].
Special considerations forcomplicated CHD
Hypoplastic left heart syndrome
ECMO management differences after Norwood surgery for
HLHS is related to the procedures of Sano or B-T shunt.
After Sano shunt, pulmonary vessels only receive blood sup-
ply in ventricular systolic stage, whereas after B-T shunt,
pulmonary vessels receive continuous blood supply in the
systolic and diastolic stages, and the latter is prone to result-
ing in a greater risk of coronary insufficiency. To provide
sufficient systemic and coronary perfusion during ECMO
running, in addition to strengthening cardiac function and
maintaining higher HCT level, excessive reduction in pul-
monary vascular resistance should be avoided by adjustment
of medicine and ventilator setting.
Single‑ventricular, bidirectional Glenn andFontan
circulation
For uncorrected or stage 1 single ventricle, when patent duc-
tus arteriosus(PDA) (or B-T shunt) closure and/or restricted
atrial septal defect (ASD) occurs, insufficient pulmonary and
systemic blood mixing leads to severe hypoxemia, elevated pul-
monary arterial and venous pressure and finally to circulatory
failure. Under these conditions, ECMO support should be con-
sidered. A high ECMO flow rate (150–200mL/kg/minute) is
usually required to compensate for the flow shunt into the pul-
monary circulation [17]. Emergency atrial septostomy or cor-
responding surgery is required when hemodynamics is stable.
Bidirectional Glenn and Fontan circulations rely on pas-
sive low pulmonary resistance. When central cannulation is
adopted after early surgery, superior vena cava cannulation
should be established first to achieve venous drainage and
reduced intracranial pressure to decrease intracranial bleed-
ing risks. If venous drainage is insufficient, inferior vena
cava cannulation should be added. Excessive ventilation
causing low CO2 blood levels perhaps might lead to insuf-
ficient cerebral blood flow, further resulting in insufficient
venous drainage [10, 17].
When higher pump flow is provided, maintaining pulsa-
tile blood flow by a certain degree of ventricle filling and

World Journal of Pediatrics
1 3
output is needed to avoid blood stasis in Fontan graft [17]. In
patients with chronic cardiac insufficiency, increased after-
load induced by higher pump flow may not be conducive to
myocardial recovery and ECMO withdrawal [17]. Due to the
lack of a sub-pulmonic pumping/capacitance chamber, com-
pressions and recoil by chest outside massage often result in
blood moving back through the venous chamber rather than
antegrade through the lungs and into the systemic ventricle
for coronary artery and cerebral perfusion. Once cardiac
arrest happens in patients after Fontan procedure, ECMO
should be established as soon as possible [17].
Various causes of bidirectional Glenn and Fontan cir-
culation failure should be investigated, such as arrhyth-
mia, anatomic obstruction to flow, pulmonary vascular
remodeling, atrioventricular valve dysfunction, univen-
tricular diastolic dysfunction and chronic under filling
and/or univentricular systolic dysfunction. As one might
imagine, the outcome of extracorporeal support largely
depends upon the underlying physiology and mechanism
for “Fontan failure” [17].
ECMO is effective for early postoperative support of
Fontan circulation failure. However, patients with late-phase
failure usually present with extreme end-organ failure, such
as protein losing enteropathy, plastic bronchitis, cirrhosis,
or renal failure. The middle-to-late phase failure patients
are appropriate transplant candidates and are better suited
for transitioning to more durable mechanical support (ven-
tricular-assist device)via ECMO [17].
Transposition ofthegreat arteries withintact
ventricular septum
Pulmonary hypertension is uncommon in patients with
TGA/IVS). The incidence of TGA/IVS with pulmonary
hypertension was 1%–12% [88, 89]. Increased pulmonary
vascular resistance leads to reduced pulmonary blood flow
and atrial blood does not mix effectively. Coupled with PDA
right-to-left shunt, effective pulmonary blood flow is further
lost. The VV or VA ECMO mode can be adopted. The time
of ECMO supporting should not be too long and both pul-
monary hypertension and left ventricular “deconditioning”
resulting from preoperative use of ECMO are responsible
for left ventricular mass decaying and functional degenera-
tion [89, 90]. ASO should be performed as soon as possible
when the condition is stable. When the uncorrected TGA/
IVS with restricted ASD and without pulmonary hyper-
tension develops severe hypoxemia, it is not suitable to
establish the ECMO, but emergency ASO or atrial septo-
stomy should be given priority because the risk of pulmo-
nary hemorrhage and left heart dramatic expansion owing
to restricted ASD and excessive pulmonary blood coming
from PDA is dramatically increased.
Other conditions
Aortic regurgitation
VA ECMO blood flow may aggravate aortic regurgitation
and increase the risk of left ventricular afterload and left
ventricular dramatic expansion, so aortic regurgitation
should be assessed carefully before ECMO implantation. If
it is found after ECMO implantation, early left ventricular
decompression or surgical correction is required [10].
Aortic arch separation
Careful attention to the anatomy of the head and neck ves-
sels (i.e., location of interruption of arch) is required before
ECMO cannulation to ensure brain perfusion with oxygen-
ated ECMO flow [10].
Anomalous left coronary artery origin frompulmonary
artery
Due to secondary severe myocardial ischemia, most of the
ALCAPA patients had severe cardiac insufficiency, with
high incidence of perioperative adverse events [91, 92].
Planned application of ECMO could be carried out for chil-
dren with severe LV insufficiency. If cardiac function can-
not be improved within a short period postoperation, cen-
tral cannulation can be changed to peripheral cannulation
or converted to VAD, which could be beneficial for chest
closure, prolonging ventricularassisting time and reducing
infection risks.
Conclusions
This consensus provided a comprehensive clinical and
technical approach for ECMO support in CHD in children.
Indications and contraindications should be evaluated care-
fully before ECMO application. The cannulation strategy
is determined based on the patient’s body size, cardiac
anatomy and different surgical procedures of CHD. ECMO
pump flow, ventilator parameters and vasoactive drugs
should be adjusted according to different ECMO support
stages and goals as well as special characteristics of cardiac
function, procedures and hemodynamics, to maintain the
balance of DO2 and VO2 and to promote the recovery of
cardiac function and organ protection. The anticoagula-
tion strategy should be tailored by considering the unique
bleeding and clotting risks. Left ventricular decompression
and pericardial tamponade should be monitored carefully
in the early stage of ECMO. Residual lesions, volume over-
load, bleeding and brain complication should be identified

World Journal of Pediatrics
1 3
and intervened as soon as possible. Special considerations
for complicated CHD should be considered during ECMO
management.
Supplementary Information The online version contains supplemen-
tary material available at https:// doi. org/ 10. 1007/ s12519- 022- 00636-z.
Author contributions LR, WW, WX, XZM, LJP, ZCB, HXY, MXM,
SSS and YLF contributed equally to this paper. LR contributed to con-
ceptualization, data curation, formal analysis, investigation, methodol-
ogy, project administration, writing of the original draft, reviewing and
editing. WW contributed to data curation, investigation, supervision,
validation, writing of the original draft, reviewing and editing. WX
contributed to formal analysis, investigation, validation and writing of
the original draft. XZM contributed to formal analysis, investigation,
supervision, validation and writing of the original draft. LJP contrib-
uted to formal analysis, investigation, supervision, validation, writ-
ing of the original draft, reviewing and editing. ZCB contributed to
formal analysis, investigation, supervision, validation, writing of the
original draft, reviewing and editing. HXY contributed to investigation,
writing of the original draft, reviewing and editing. MXM contributed
to investigation, supervision, validation, reviewing and editing. SSS
contributed to investigation, writing of the original draft, reviewing
and editing. YLF contributed to conceptualization, data curation, for-
mal analysis, investigation, methodology, writing of the original draft,
reviewing and editing. SQ contributed to investigation, supervision,
validation, reviewing and editing. All the authors approved the final
version of the manuscript.
Funding This study wassupported by“the Fundamental Research
Funds for the Central Universities” (No. 226–2022-00060)and
National Key R&D Program of China (No.2021YFC2701700).
Declarations
Ethical approval Not applicable.
Conflict of interest No financial or non-financial benefits have been re-
ceived or will be received from any party related directly or indirectly
to the subject of this article. The authors have no conflict of interest
to declare. Author Qiang Shu is the Chief Editor of World Journal of
Pediatrics. The paper was handled by the other editors and has un-
dergone a rigorous peer-review process. Author Qiang Shu was not
involved in the journal's review or decision making of this manuscript.
Open Access This article is licensed under a Creative Commons Attri-
bution 4.0 International License, which permits use, sharing, adapta-
tion, distribution and reproduction in any medium or format, as long
as you give appropriate credit to the original author(s) and the source,
provide a link to the Creative Commons licence, and indicate if changes
were made. The images or other third party material in this article are
included in the article's Creative Commons licence, unless indicated
otherwise in a credit line to the material. If material is not included in
the article's Creative Commons licence and your intended use is not
permitted by statutory regulation or exceeds the permitted use, you will
need to obtain permission directly from the copyright holder. To view a
copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/.
References
1. Bartlett RH, Gazzaniga AB, Jefferies MR, Huxtable RF, Haiduc
NJ, Fong SW. Extracorporealmembrane oxygenation (ECMO)
cardiopulmonary supportininfancy. Trans Am Soc Artif Intern
Organs. 1976;1976:80–93.
2. Allen KY, Allan CK, Su L, McBride ME. Extracorporeal mem-
brane oxygenation in congenital heart disease. Semin Perinatol.
2018;42:104–10.
3. Barbaro RP, Paden ML, Guner YS, Raman L, Ryerson LM, Alex-
ander P, etal. Pediatric extracorporeal life support organization
registry international report 2016. ASAIO J. 2017;63:456–63.
4. Lorusso R, Raffa GM, Kowalewski M, Alenizy K, Sluijpers N,
Makhoul M, etal. Structured review of post-cardiotomy extra-
corporeal membrane oxygenation: part 2-pediatric patients. J
Heart Lung Transplant. 2019;38:1144–61.
5. Lin R, Tan LH, Zhang ZW, Sun MY. Du LZ. Extracorporeal
membrane oxygenation treatment of a neonate with severe low
cardiac output syndrome following open heart surgery. Zhong-
hua Er Ke Za Zhi. 2008;46:26–9 (in Chinese).
6. Liu ML, Yang YY, Zhang W, Jiang L, Shen J, Guo Z, etal.
ECMO in patients with residual lesions after cardiac surgery. J
Clin Pediatr Surg. 2021;20:518–24 (in Chinese).
7. Chinese Society of Extra Corporeal Life Support. 2022.
8. Jin Y, Feng Z, Zhao J, Hu J, Tong Y, Guo S, etal. Outcomes
and factors associated with early mortality in pediatric postcar-
diotomy veno-arterial extracorporeal membrane oxygenation.
Artif Organs. 2021;45:6–14.
9. Ford MA, Gauvreau K, McMullan DM, Almodovar MC, Cooper
DS, Rycus PT, etal. Factors associated with mortality in neonates
requiring extracorporeal membrane oxygenation for cardiac indi-
cations: analysis of the extracorporeal life support organization
registry data. Pediatr Crit Care Med. 2016;17:860–70.
10. Brown G, Moynihan KM, Deatrick KB, Hoskote A, Sandhu HS,
Aganga D, etal. Extracorporeal life support organization (ELSO):
guidelines for pediatric cardiac failure. ASAIO J. 2021;67:463–75.
11. Valencia E, Staffa SJ, Nathan M, Smith-Parrish M, Kaza AK,
DiNardo JA, etal. Hyperlactataemia as a predictor of adverse
outcomes post-cardiac surgery in neonates with congenital heart
disease. Cardiol Young. 2021;31:1401–6.
12. Gaies MG, Gurney JG, Yen AH, Napoli ML, Gajarski RJ, Ohye
RG, etal. Vasoactive–inotropic score as a predictor of morbidity
and mortality in infants after cardiopulmonary bypass. Pediatr Crit
Care Med. 2010;11:234–8.
13. Maratta C, Potera RM, van Leeuwen G, Castillo Moya A,
Raman L, Annich GM. Extracorporeal life support organization
(ELSO): 2020 pediatric respiratory ELSO guideline. ASAIO J.
2020;66:975–9.
14. Rais-Bahrami K, Van Meurs KP. Venoarterial versus veno-
venous ECMO for neonatal respiratory failure. Semin Perinatol.
2014;38:71–7.
15. Zhao J, Jin ZX. ECMO speciallist training manual. Beijing:
People's Medical Publishing House; 2015.
16. Pediatrics Group of Extracorporeal Life Support Professional
Committee of Chinese Medical Doctor Association, Emergency
Treatment Group of Pediatric Society of Chinese Medical Asso-
ciation, Extracorporeal Life Support Society of Chinese Society
of Cardiovascular Anesthesia, Cardiothoracic Surgery Group
of Pediatric Surgery Society of Chinese Medical Association.
Expert consensus of extracorporeal membrane oxygenation sup-
ports in pediatric fulminant myocarditis. Chin J Emerg Med.
2020;29:36–42.
17. Bacon MK, Gray SB, Schwartz SM, Cooper DS. Extracorpor-
eal membrane oxygenation (ECMO) support in special patient
populations-the bidirectional glenn and fontan circulations.
Front Pediatr. 2018;6:299.
18. Brogan TV, Lequier L, Lorusso R, MacLaren G, Peek G. Extra-
corporeal life support: the ELSO red book. 5th ed. Ann Arbor,
MI: Extracorporeal Life Support Organization; 2017.

World Journal of Pediatrics
1 3
19. Schmidt M, Pellegrino V, Combes A, Scheinkestel C, Cooper DJ,
Hodgson C. Mechanical ventilation during extracorporeal mem-
brane oxygenation. Crit Care. 2014;18:203.
20. Alapati D, Aghai ZH, Hossain MJ, Dirnberger DR, Ogino MT,
Shaffer TH, etal. Lung rest during extracorporeal membrane oxy-
genation for neonatal respiratory failure-practice variations and
outcomes. Pediatr Crit Care Med. 2017;18:667–74.
21. Jardin F, Vieillard-Baron A. Monitoring of right-sided heart func-
tion. Curr Opin Crit Care. 2005;11:271–9.
22. Sherwin ED, Gauvreau K, Scheurer MA, Rycus PT, Salvin JW,
Almodovar MC, etal. Extracorporeal membrane oxygenation after
stage 1 palliation for hypoplastic left heart syndrome. J Thorac
Cardiovasc Surg. 2012;144:1337–43.
23. Sy E, Sklar MC, Lequier L, Fan E, Kanji HD. Anti-coagulation
practices and the prevalence of major bleeding, thromboembolic
events, and mortality in venoarterial extracorporeal membrane
oxygenation: a systematic review and meta-analysis. Crit Care.
2017;39:87–96.
24. Beckmann E, Ismail I, Cebotari S, Busse A, Martens A, Shrestha
M, etal. Right-sided heart failure and extracorporeal life support
in patients undergoing pericardiectomy for constrictive pericardi-
tis: a risk factor analysis for adverse outcome. Thorac Cardiovasc
Surg. 2017;65:662–70.
25. McMichael ABV, Ryerson LM, Ratano D, Fan E, Faraoni D,
Annich GM. 2021 ELSO adult and pediatric anticoagulation
guidelines. ASAIO J. 2022;68:303–10.
26. Task Force on Patient Blood Management for Adult Cardiac
Surgery of the European Association for Cardio-Thoracic Sur-
gery (EACTS) and the European Association of Cardiothoracic
Anaesthesiology (EACTA), Boer C, Meesters MI, Milojevic M,
Benedetto U, Bolliger D, etal. 2017 EACTS/EACTA Guidelines
on patient blood management for adult cardiac surgery. J Cardio-
thorac Vasc Anesth. 2018;32:88–120.
27. Lorusso R, Whitman G, Milojevic M, Raffa G, McMullan DM,
Boeken U, etal. 2020 EACTS/ELSO/STS/AATS expert consensus
on post-cardiotomy extracorporeal life support in adult patients.
Ann Thorac Surg. 2021;111:327–69.
28. Sorabella RA, Padilla L, Byrnes JW, Timpa J, O’Meara C, Buck-
man JR, etal. Outcomes in pediatric post-cardiotomy ecmo sup-
port with modification of systematic support strategy. World J
Pediatr Congenit Heart Surg. 2022;13:46–52.
29. Neunert C, Chitlur M, van Ommen CH. The changing landscape
of anticoagulation in pediatric extracorporeal membrane oxygena-
tion: use of the direct thrombin inhibitors. Front Med (Lausanne).
2022;9:887199.
30. Zhang ZR, Zhou XQ, Fan ZK, Shi Y, Shen YY, Zhu C, etal.
Extracorporeal membrane oxygenation treatment for high-risk
pulmonary embolism with cardiac arrest in a young adult male.
World J Emerg Med. 2021;12:324–6.
31. Burkhoff D, Sayer G, Doshi D, Uriel N. Hemodynam-
ics of mechanical circulatory support. J Am Coll Cardiol.
2015;66:2663–74.
32. Ostadal P, Mlcek M, Kruger A, Hala P, Lacko S, Mates M, etal.
Increasing venoarterial extracorporeal membrane oxygenation
flow negatively affects left ventricular performance in a porcine
model of cardiogenic shock. J Transl Med. 2015;13:266.
33. Hireche-Chikaoui H, Grubler MR, Bloch A, Windecker S, Bloech-
linger S, Hunziker L. Nonejecting hearts on femoral veno-arterial
extracorporeal membrane oxygenation: aortic root blood stasis
and thrombus formation-a case series and review of the literature.
Crit Care Med. 2018;46:e459–64.
34. Williams B, Bernstein W. Review of venoarterial extracorporeal
membrane oxygenation and development of intracardiac throm-
bosis in adult cardiothoracic patients. J Extra Corpor Technol.
2016;48:162–7.
35. Cevasco M, Takayama H, Ando M, Garan AR, Naka Y, Takeda
K. Left ventricular distension and venting strategies for patients
on venoarterial extracorporeal membrane oxygenation. J Thorac
Dis. 2019;11:1676–83.
36. Donker DW, Brodie D, Henriques JPS, Broome M. Left ventricu-
lar unloading during veno-arterial ECMO: a simulation study.
ASAIO J. 2019;65:11–20.
37. Hacking DF, Best D, d’Udekem Y, Brizard CP, Konstantinov
IE, Millar J, etal. Elective decompression of the left ventricle in
pediatric patients may reduce the duration of venoarterial extra-
corporeal membrane oxygenation. Artif Organs. 2015;39:319–26.
38. Kimura M, Kinoshita O, Fujimoto Y, Murakami A, Shindo T,
Kashiwa K, etal. Central extracorporeal membrane oxygenation
requiring pulmonary arterial venting after near-drowning. Am J
Emerg Med. 2014;32:e1–2.
39. Fiedler AG, Dalia A, Axtell AL, Ortoleva J, Thomas SM, Roy N,
etal. Impella placement guided by echocardiography can be used
as a strategy to unload the left ventricle during peripheral venoar-
terial extracorporeal membrane oxygenation. J Cardiothorac Vasc
Anesth. 2018;32:2585–91.
40. Agarwal HS, Hardison DC, Saville BR, Donahue BS, Lamb
FS, Bichell DP, etal. Residual lesions in postoperative
pediatric cardiac surgery patients receiving extracorporeal
membrane oxygenation support. J Thorac Cardiovasc Surg.
2014;147:434–41.
41. Howard TS, Kalish BT, Wigmore D, Nathan M, Kulik TJ, Kaza
AK, etal. Association of extracorporeal membrane oxygenation
support adequacy and residual lesions with outcomes in neo-
nates supported after cardiac surgery. Pediatr Crit Care Med.
2016;17:1045–54.
42. Soynov IA, Kornilov IA, Kulyabin YY, Zubritskiy AV, Ponomarev
DN, Nichay NR, etal. Residual lesion diagnostics in pediatric
postcardiotomy extracorporeal membrane oxygenation and its
outcomes. World J Pediatr Congenit Heart Surg. 2021;12:605–13.
43. Hull NC, Schooler GR, Binkovitz LA, Williamson EE, Araoz
PA, Yu L, etal. Chest computed tomography angiography in chil-
dren on extracorporeal membrane oxygenation (ECMO). Pediatr
Radiol. 2018;48:1021–30.
44. Boscamp NS, Turner ME, Crystal M, Anderson B, Vincent JA,
Torres AJ. Cardiac catheterization in pediatric patients supported
by extracorporeal membrane oxygenation: a 15-year experience.
Pediatr Cardiol. 2017;38:332–7.
45. Booth KL, Roth SJ, Perry SB, del Nido PJ, Wessel DL, Laussen
PC. Cardiac catheterization of patients supported by extracorpor-
eal membrane oxygenation. J Am Coll Cardiol. 2002;40:1681–6.
46. Krishnan S, Schmidt GA. Hemodynamic monitoring in the extra-
corporeal membrane oxygenation patient. Curr Opin Crit Care.
2019;25:285–91.
47. Siddall E, Khatri M, Radhakrishnan J. Capillary leak syndrome:
etiologies, pathophysiology, and management. Kidney Int.
2017;92:37–46.
48. Smith AH, Hardison DC, Worden CR, Fleming GM, Taylor MB.
Acute renal failure during extracorporeal support in the pediatric
cardiac patient. ASAIO J. 2009;55:412–6.
49. Elella RA, Habib E, Mokrusova P, Joseph P, Aldalaty H, Ahmadi
MA, etal. Incidence and outcome of acute kidney injury by the
pRIFLE criteria for children receiving extracorporeal membrane
oxygenation after heart surgery. Ann Saudi Med. 2017;37:201–6.
50. Joannidis M, Forni LG, Klein SJ, Honore PM, Kashani K, Oster-
mann M, etal. Lung-kidney interactions in critically ill patients:
consensus report of the acute disease quality initiative (ADQI) 21
workgroup. Intensive Care Med. 2020;46:654–72.
51. Gorga SM, Sahay RD, Askenazi DJ, Bridges BC, Cooper DS,
Paden ML, etal. Fluid overload and fluid removal in pediatric
patients on extracorporeal membrane oxygenation requiring

World Journal of Pediatrics
1 3
continuous renal replacement therapy: a multicenter retrospec-
tive cohort study. Pediatr Nephrol. 2020;35:871–82.
52. Selewski DT, Askenazi DJ, Bridges BC, Cooper DS, Fleming
GM, Paden ML, etal. The impact of fluid overload on outcomes
in children treated with extracorporeal membrane oxygenation:
a multicenter retrospective cohort study. Pediatr Crit Care Med.
2017;18:1126–35.
53. Blijdorp K, Cransberg K, Wildschut ED, Gischler SJ, Jan Houmes
R, Wolff ED, etal. Haemofiltration in newborns treated with
extracorporeal membrane oxygenation: a case-comparison study.
Crit Care. 2009;13:R48.
54. Schmidt M, Bailey M, Kelly J, Hodgson C, Cooper DJ, Scheink-
estel C, etal. Impact of fluid balance on outcome of adult patients
treated with extracorporeal membrane oxygenation. Intensive
Care Med. 2014;40:1256–66.
55. Zarbock A, Kellum JA, Schmidt C, Van Aken H, Wempe C,
Pavenstadt H, etal. Effect of early vs delayed initiation of renal
replacement therapy on mortality in critically ill patients with
acute kidney injury: the ELAIN randomized clinical trial. JAMA.
2016;315:2190–9.
56. Tan BK, Liew ZH, Kaushik M, Cheah AKW, Tan HK. Early ini-
tiation of renal replacement therapy among burned patients with
acute kidney injury. Ann Plast Surg. 2020;84:375–8.
57. Section5: Dialysis Interventions for Treatment of AKI. Kidney
Int Suppl (2011). 2012;2:89–115.
58. Giani M, Scaravilli V, Stefanini F, Valsecchi G, Rona R, Grasselli
G, etal. Continuous renal replacement therapy in venovenous
extracorporeal membrane oxygenation: a retrospective study on
regional citrate anticoagulation. ASAIO J. 2020;66:332–8.
59. Sasser WC, Robert SM, Askenazi DJ, O’Meara LC, Borasino
S, Alten JA. Peritoneal dialysis: an alternative modality of
fluid removal in neonates requiring extracorporeal membrane
oxygenation after cardiac surgery. J Extra Corpor Technol.
2014;46:157–61.
60. Golej J, Boigner H, Burda G, Hermon M, Kitzmueller E, Trit-
tenwein G. Peritoneal dialysis for continuing renal support after
cardiac ECMO and hemofiltration. Wien Klin Wochenschr.
2002;114:733–8.
61. Li G, Zhang L, Sun Y, Chen J, Zhou C. Co-initiation of con-
tinuous renal replacement therapy, peritoneal dialysis, and extra-
corporeal membrane oxygenation in neonatal life-threatening
hyaline membrane disease: a case report. Medicine (Baltimore).
2019;98:e14194.
62. Bao Q, Hong XY, Liu YY, Zhang XJ, Gao HT, Feng ZC. Outcome
of pediatric extracorporeal membrane oxygenation in a single
center. Zhonghua Er Ke Za Zhi. 2018;56:122–7 (in Chinese).
63. Nourse P, Cullis B, Finkelstein F, Numanoglu A, Warady B, Antwi
S, etal. ISPD guidelines for peritoneal dialysis in acute kidney
injury: 2020 update (paediatrics). Perit Dial Int. 2021;41:139–57.
64. Li XF, Luo DD, Zhu WZ. Application of delayed sternal closure
after neonatal cardiac surgery. Chin J Thorac Cardiovasc Surg.
2016;32:257–60 (in Chinese).
65. Lorusso R, Whitman G, Milojevic M, Raffa G, McMullan DM,
Boeken U, etal. 2020 EACTS/ELSO/STS/AATS expert consensus
on post-cardiotomy extracorporeal life support in adult patients.
Eur J Cardiothorac Surg. 2021;59:12–53.
66. Basilio C, Fontoura A, Fernandes J, Roncon-Albuquerque R Jr,
Paiva JA. Cardiac tamponade complicating extracorporeal mem-
brane oxygenation: a single-centre experience. Heart Lung Circ.
2021;30:1540–4.
67. Lorusso R, Whitman G, Milojevic M, Raffa G, McMullan DM,
Boeken U, etal. 2020 EACTS/ELSO/STS/AATS expert consensus
on post-cardiotomy extracorporeal life support in adult patients. J
Thorac Cardiovasc Surg. 2021;161:1287–331.
68. Extracorporeal Life Support Organization. ELSO guidelines for
cardiopulmonary extracorporeal life support. Version 14. 2017.
http:// www. elso. org/ resou rces/ guide lines. aspx. Accessed 1 Jul
2022.
69. Keebler ME, Haddad EV, Choi CW, McGrane S, Zalawadiya S,
Schlendorf KH, etal. Venoarterial extracorporeal membrane oxy-
genation in cardiogenic shock. JACC Heart Fail. 2018;6:503–16.
70. Perry T, Brown T, Misfeldt A, Lehenbauer D, Cooper DS. Extra-
corporeal membrane oxygenation in congenital heart disease.
Children (Basel). 2022. https:// doi. org/ 10. 3390/ child ren90 30380.
71. Holgren SE, Frede RT, Crumley JP, Patel SS, Moore EA, Turek
JW. Novel utilization of the bridge during weaning off venoar-
terial ECMO: the Hoffman clamp method. Innovations (Phila).
2016;11:229–31.
72. Westrope C, Harvey C, Robinson S, Speggiorin S, Faulkner G,
Peek GJ. Pump controlled retrograde trial off from VA-ECMO.
ASAIO J. 2013;59:517–9.
73. Kumar SR, Scott N, Wells WJ, Starnes VA. Liberal use of delayed
sternal closure in children is not associated with increased morbid-
ity. Ann Thorac Surg. 2018;106:581–6.
74. Said AS, Guilliams KP, Bembea MM. Neurological monitoring
and complications of pediatric extracorporeal membrane oxygena-
tion support. Pediatr Neurol. 2020;108:31–9.
75. Brogan TV. ECMO specialist training manual. Michigan: Extra-
corporeal Life Support Organization; 2018.
76. Cerebral Protection In Cardiac Intensive Care Group Neural
Regeneration And Repair Committee Chinese Research Hospital
Association. Chinese consensus guideline for cerebral protection
in the perioperative period of cardiac surgery (2019). Zhonghua
Wei Zhong Bing Ji Jiu Yi Xue. 2019;31:129–34 (in Chinese).
77. Guerguerian AM, Sano M, Todd M, Honjo O, Alexander P,
Raman L. Pediatric extracorporeal cardiopulmonary resuscita-
tion ELSO guidelines. ASAIO J. 2021;67:229–37.
78. Raymond TT, Cunnyngham CB, Thompson MT, Thomas JA, Dal-
ton HJ, Nadkarni VM, etal. Outcomes among neonates, infants,
and children after extracorporeal cardiopulmonary resuscitation
for refractory in hospital pediatric cardiac arrest: a report from the
National Registry of Cardiopulmonary Resuscitation. Pediatr Crit
Care Med. 2010;11:362–71.
79. Ortmann L, Prodhan P, Gossett J, Schexnayder S, Berg R, Nad-
karni V, etal. Outcomes after in-hospital cardiac arrest in children
with cardiac disease: a report from get with the guidelines-resus-
citation. Circulation. 2011;124:2329–37.
80. Matos RI, Watson RS, Nadkarni VM, Huang HH, Berg RA,
Meaney PA, etal. Duration of cardiopulmonary resuscita-
tion and illness category impact survival and neurologic out-
comes for in-hospital pediatric cardiac arrests. Circulation.
2013;127:442–51.
81. Alsoufi B, Awan A, Manlhiot C, Guechef A, Al-Halees Z, Al-
Ahmadi M, et al. Results of rapid-response extracorporeal
cardiopulmonary resuscitation in children with refractory car-
diac arrest following cardiac surgery. Eur J Cardiothorac Surg.
2014;45:268–75.
82. Ergun S, Yildiz O, Gunes M, Akdeniz HS, Ozturk E, Onan IS,
etal. Use of extracorporeal membrane oxygenation in postcardi-
otomy pediatric patients: parameters affecting survival. Perfusion.
2020;35:608–20.
83. Alsoufi B, Awan A, Manlhiot C, Al-Halees Z, Al-Ahmadi M,
McCrindle BW, etal. Does single ventricle physiology affect sur-
vival of children requiring extracorporeal membrane oxygena-
tion support following cardiac surgery? World J Pediatr Congenit
Heart Surg. 2014;5:7–15.
84. Kane DA, Thiagarajan RR, Wypij D, Scheurer MA, Fynn-Thomp-
son F, Emani S, etal. Rapid-response extracorporeal membrane
oxygenation to support cardiopulmonary resuscitation in children
with cardiac disease. Circulation. 2010;122:S241–8.
85. Cerebral Protection In Cardiac Intensive Care Group Neural
Regeneration And Repair Committee Chinese Research Hospital

World Journal of Pediatrics
1 3
Association, Neural Intensive Nursing And Rehabilitation Group
Neural Regeneration And Repair Committee Chinese Research
Hospital Association. Chinese consensus for mild hypother-
mia brain protection. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue.
2020;32:385–91 (in Chinese).
86. Guo Z, Yang Y, Zhang W, Shen J, Jiang L, Yu X, etal. Extracor-
poreal cardiopulmonary resuscitation in children after open heart
surgery. Artif Organs. 2019;43:633–40.
87. Farhat A, Ling RR, Jenks CL, Poon WH, Yang IX, Li X, etal.
Outcomes of pediatric extracorporeal cardiopulmonary resusci-
tation: a systematic review and meta-analysis. Crit Care Med.
2021;49:682–92.
88. Yam N, Chen RH, Rocha BA, Lun KS, Yung TC, Au TW. Pre-
operative venovenous extracorporal membrane oxygenation for
transposition of great arteries with severe pulmonary hypertension
in a newborn. Ann Thorac Surg. 2020;109:e329–30.
89. Jaillard S, Belli E, Rakza T, Larrue B, Magnenant E, Rey
C, et al. Preoperative ECMO in transposition of the great
arteries with persistent pulmonary hypertension. Ann Thorac
Surg. 2005;79:2155–8.
90. Sarris GECG, Balmer CS, Bonou PG, Comas JVS, da Cruz EU,
Chiara LDI, etal. Clinical guidelines for the management of
patients with transposition of the great arteries with intact ven-
tricular septum. Eur J Cardiothorac Surg. 2017;51:e1–32.
91. Fudulu DP, Dorobantu DM, Azar Sharabiani MT, Angelini
GD, Caputo M, Parry AJ, etal. Outcomes following repair of
anomalous coronary artery from the pulmonary artery in infants:
results from a procedure-based national database. Open Heart.
2015;2:e000277.
92. Cashen K, Kwiatkowski DM, Riley CM, Buckley J, Sassalos P,
Gowda KN, etal. Anomalous origin of the left coronary artery
from the pulmonary artery: a retrospective multicenter study.
Pediatr Crit Care Med. 2021;22:e626–35.
Publisher's Note Springer Nature remains neutral with regard to
jurisdictional claims in published maps and institutional affiliations.