Consensus Statement

Neonatology 2016;110:66–74 Received: December 3, 2015

Accepted after revision: January 25, 2016
DOI: 10.1159/000444210
Published online: April 15, 2016

Standardized Postnatal Management of Infants with

Congenital Diaphragmatic Hernia in Europe:
The CDH EURO Consortium Consensus – 2015 Update
Kitty G. Snoek a Irwin K.M. Reiss a Anne Greenough c Irma Capolupo e
       

Berndt Urlesberger f Lucas Wessel g Laurent Storme h Jan Deprest d, i

       

Thomas Schaible g Arno van Heijst b Dick Tibboel a  for the CDH EURO Consortium

     

a
  Erasmus MC – Sophia Children’s Hospital, University Medical Center Rotterdam, Rotterdam, and b Radboud University  

Medical Centre, Nijmegen, The Netherlands; c King’s College and d University College London Hospitals, London, UK;
   

e
 Bambino Gesu Children’s Hospital, Rome, Italy; f Medical University Graz, Graz, Austria; g Universitätsklinikum Mannheim,
   

Mannheim, Germany; h Hôpital Jeanne de Flandre, Lille, France; i University Hospital KU Leuven, Leuven, Belgium
   

Key Words nous sildenafil to be considered in CDH patients with severe

Congenital diaphragmatic hernia · Standardized treatment · pulmonary hypertension. This article represents the current
Consensus opinion of all consortium members in Europe for the optimal
neonatal treatment of CDH. © 2016 The Author(s)
Published by S. Karger AG, Basel

Abstract
In 2010, the congenital diaphragmatic hernia (CDH) EURO
Consortium published a standardized neonatal treatment Introduction
protocol. Five years later, the number of participating cen-
ters has been raised from 13 to 22. In this article the relevant In 2008, the congenital diaphragmatic hernia (CDH)
literature is updated, and consensus has been reached be- EURO Consortium was set up and during a consensus
tween the members of the CDH EURO Consortium. Key up- meeting drafted a standardized neonatal treatment pro-
dated recommendations are: (1) planned delivery after a tocol to improve outcome and permit comparison of
gestational age of 39 weeks in a high-volume tertiary center; outcome data [1]. Since then the number of participat-
(2) neuromuscular blocking agents to be avoided during ini- ing centers has increased from 13 to 22 specialized CDH
tial treatment in the delivery room; (3) adapt treatment to centers from all over Europe, and the guidelines from
reach a preductal saturation of between 80 and 95% and 2010 have been widely cited. Moreover, after the imple-
postductal saturation >70%; (4) target PaCO2 to be between mentation of the protocol, the survival rate has increased
50 and 70 mm Hg; (5) conventional mechanical ventilation from 67 to 88% in 2 centers. This indicates the impact of
to be the optimal initial ventilation strategy, and (6) intrave- the original standardized protocol. After 5 years of ad-
ditional research including a multicenter randomized
clinical trial on initial ventilation strategy (VICI-trial;
The Members of the CDH EURO Consortium Group are listed in the Netherlands Trial Register, NTR 1310), we aimed to up-
UFRJ Universidade Federal do Rio de Janeiro

Appendix. date the standardized neonatal treatment protocol for

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© 2016 The Author(s) Dick Tibboel

Published by S. Karger AG, Basel Intensive Care and Department of Pediatric Surgery
1661–7800/16/1101–0066$39.50/0 Erasmus MC – Sophia Children’s Hospital
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E-Mail [email protected]
This article is licensed under the Creative Commons Attribution- Room Sk-3284, PO Box 3060, NL–3000 CB Rotterdam (The Netherlands)
www.karger.com/neo
NonCommercial-NoDerivatives 4.0 International License (CC BY- E-Mail d.tibboel @ erasmusmc.nl
NC-ND) (http://www.karger.com/Services/OpenAccessLicense).
Usage and distribution for commercial purposes as well as any dis-
tribution of modified material requires written permission.
CDH. All recommendations were summarized and ever, but may ultimately improve the predictive value of
compared with the protocol in 2010 (online suppl. file; prenatal testing.
see www.karger.com/doi/10.1159/000444210 for all on- An experienced tertiary center with a high case volume
line suppl. material). (≥6 CDH patients per year) is the optimal environment
for the delivery and neonatal treatment of prenatally diag-
nosed CDH fetuses [9, 10]. Prenatal intervention by fetal
Methods endoscopic tracheal occlusion (FETO) has been proposed
to promote lung growth [11]. Therefore, FETO is being
The studies were graded according to the Scottish Intercolle-
evaluated in two randomized clinical trials both in moder-
giate Guidelines Network (SIGN) criteria [2]. Five experts individ-
ually primarily determined the levels of evidence on the guidance ate (first interim analysis stage reached; >100 patients ran-
of the SIGN checklist. Differences in opinion were primarily dis- domized) and severe cases (>25 patients randomized) in
cussed between the five experts until full consensus was reached, centers in Europe, Australia and Canada (TOTAL trial
and thereafter consensus was reached between all participating cen- [12]; NCT01240057). Current reported survival rates are
ters. The final consensus statement, therefore, represents the opin-
on average around 50%, yet there is a significant impact of
ion of all participating centers based on the interpretation of the
recent literature from 2010 to 2015 and includes the main findings gestational age at delivery. In the largest cohort study
of the so-called VICI-trial [3]. A consensus meeting, in which neo- where 17.1% of all patients were born under 32 weeks, the
natologists, pediatric intensivists, gynecologists, prenatal physi- survival rate was 49.4% for isolated left CDH and 37.9%
cians, pediatric surgeons, pediatric cardiologists and general pedia- for isolated right CDH [13]. This suggests that FETO in-
tricians from 22 centers participated, was organized to discuss the
troduces a significant risk for prematurity and all its con-
most controversial recommendations. If it was very hard to reach
consensus on a specific issue, the consortium concurred to investi- sequences. It is recommended therefore that – while wait-
gate those issues in future randomized trials. The levels of evidence ing for the results – FETO should not be performed out-
and grades of recommendation according to the SIGN criteria are side the trial [11]. According to the consensus statement
presented in online supplementary tables 1 and 2, respectively. of the National Institutes of Health (NIH), CDH fetuses at
risk for delivery before 34 weeks of gestation should be
given prenatal steroid therapy.
Results
Delivery
Prenatal Management The timing and preferred mode of delivery in CDH
With the increased use of second trimester 2D ultra- pregnancies are still controversial. Hutcheon et al. [14]
sound and/or MRI, CDH has become a prenatal diagno- showed that neonatal and infant mortality significantly
sis. Subsequently, a more detailed expert evaluation decreased with advancing gestation, from 25 and 36% at
should be performed to determine the location of the de- 37 weeks of gestation, respectively, to 17 and 20% at 40
fect, the observed/expected lung-to-head ratio (O/E weeks of gestation, respectively. Moreover, a study from
LHR) and the position of the liver (intra-abdominal or Odibo et al. [15] among 107 CDH cases found that gesta-
intrathoracic), in addition to ruling out additional con- tional age at delivery was inversely correlated to the need
genital anomalies or syndromes [4, 5]. Associated con- for ECMO. However, Safavi et al. [16] found no differ-
genital anomalies, such as chromosomal or genitourinary ence in mortality when dividing gestational age at deliv-
anomalies, are present in about 25% [6] and cardiac ery categorically as under 37 weeks, 37–38 weeks and 39
anomalies in about 20% of cases [7]. Comprehensive as- weeks or beyond. Neither did they find a difference in
sessment will also include invasive sampling for high-res- mortality between vaginal and cesarean delivery [16]. In
olution genetic testing. Only once a comprehensive as- the absence of true convincing data it seems intuitive to
sessment has been made can multidisciplinary prenatal schedule delivery (induced delivery or cesarean section)
counseling by clinicians in tertiary centers be offered to carefully in the best possible conditions also dependent of
inform parents about the estimated prognosis after birth. maternal indications, i.e. at 39 weeks or beyond and in the
Several other additional imaging methods, such as lung presence of the relevant clinicians.
volumetry, 3D ultrasound and Doppler studies of the pul-
monary vascularization, have been shown in individual Recommendations (Prenatal Management and
series to be prognostic for pulmonary hypertension, the Delivery)
need for extracorporeal membrane oxygenation (ECMO) – Following prenatal diagnosis, disease severity should
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and survival [8]. All of these remain research tools, how- be assessed at an experienced center. This will involve
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The CDH EURO Consortium Consensus: Neonatology 2016;110:66–74 67

2015 Update DOI: 10.1159/000444210
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 measurement of the O/E LHR and position of the liver natal assessment (e.g. left-sided defect, O/E LHR >50%, and
(grade of recommendation = D). liver down), spontaneous breathing could be considered
– In case of an anticipated birth prior to 34 weeks of ges- instead to prevent ventilator-induced lung injury. Low peak
tation, antenatal steroids should be given (grade of rec- pressures, preferably <25 cm H2O, are recommended to
ommendation = D). avoid lung damage to the ipsilateral and contralateral lung.
– Delivery after a gestational age of 39 weeks in a high-
volume tertiary center should be planned (grade of Sedation and Analgesia/Paralysis for Intubation
recommendation = D). Carbajal et al. [21] have studied physiological respons-
es of neonates to awake intubation, and they reported sig-
Delivery Room Management and Treatment in the nificant rises in systemic arterial blood pressure and in-
Initial Postnatal Phase tracranial pressure, as well as significant decreases in
Initial treatment and procedures in the delivery room heart rate and transcutaneous oxygen saturations. In 166
are based on the updated Guidelines of the International infants Caldwell and Watterberg [22] found that premed-
Consensus on Cardiopulmonary Resuscitation and ication for intubation significantly attenuated both the
Emergency Cardiovascular Care Science with Treatment clinical pain score and the increase in blood glucose as
Recommendations [17]. markers of acute stress. Moreover, it seems that intuba-
tion success rates progressively improve with premedica-
Monitoring and Goal of Treatment tion, although in some cases this is not possible due to a
Measurements of heart rate, pre- and postductal satu- lack of vascular access [23]. Murthy et al. [24] have shown
rations and intra-arterial blood pressure are recommend- no beneficial effects of administration of neuromuscular
ed. The key principles are the avoidance of high airway blocking agents immediately after intubation; in fact lung
pressures and the establishment of adequate perfusion compliance deteriorated upon administration.
and oxygenation (based on preductal arterial saturation,
SpO2 measurements). In a study from Dawson et al. [18] Naso- or Orogastric Tube
in term and preterm healthy neonates, the overall SpO2 The consortium recommends immediate placing of an
values at 10 min after birth were median 94% (interquar- oro- or nasogastric tube with continuous or intermittent
tile range 91–97%) in preterm infants and median 97% in suctioning in order to prevent bowel distension and any
term infants (interquartile range 92–98%). Based on ex- additional ipsilateral lung compression.
pert opinion, the consortium agreed on preductal SpO2
boundaries in the delivery room of 80–95%. In the first Vascular Access
2 h after birth, preductal SpO2 levels as low as 70% are ac- As preductal PaO2 measurements reflect the level of
ceptable if they are improving without ventilator changes, delivered oxygen to the brain, the arterial line should
if organ perfusion is satisfactory, as indicated by a pH preferably be inserted into the right radial artery – also for
>7.2, and if ventilation is adequate (PaCO2 <65 mm Hg, blood sampling and monitoring of the arterial blood pres-
8.6 kPa). Since there is growing evidence that room air is sure. Alternatively, an umbilical arterial line may be
less harmful than 1.0 fractional inspired oxygen (FiO2) in placed. This is less desirable, however, than a right radial
the resuscitation of term infants [19, 20], it may be better artery line because it reflects the postductal situation, but
for CDH infants to start with FiO2 lower than 1.0. The on the other hand, it may give more secure longer-term
aim for preductal saturation is 80–95% after the first hour arterial access. Each procedure should be performed as
of life. Thus, to avoid hyperoxia, supplemental oxygen soon as possible. It is important, however, to prevent fur-
should be diminished by reducing the oxygen fraction ther agitation from recurrent insertion attempts as this
when preductal saturation exceeds 95%. may impair postnatal adaptation [25].

Intubation and Ventilation Blood Pressure Control

The consortium recommends intubating infants with Measures to increase the systemic blood pressure may
prenatally diagnosed CDH immediately after birth as a minimize the right-to-left shunting. However, there is no
standard of care. The position of the endotracheal tube need to increase blood pressure levels to supranormal val-
should be confirmed by end-tidal CO2 monitoring. How- ues if the preductal saturation remains above 80%. There-
ever, based on expert opinion, in those infants who are pre- fore, the consortium recommends maintaining arterial
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dicted to have good lung development based on their pre- blood pressure at normal levels for gestational age if pre-
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ductal saturations remain between 80 and 95%. In the Ventilation Management in the Intensive Care Unit
case of hypotension and/or poor tissue perfusion, a fluid Permissive hypercapnia and ‘gentle ventilation’ have
bolus of 10–20 ml/kg NaCl 0.9% should be administered, been reported to increase survival in neonates with CDH
although no more than 2 times. If tissue perfusion and [28, 29]. A ventilation strategy aiming for preductal satu-
blood pressure do not improve, inotropic and/or vaso- ration between 80 and 95%, postductal saturation above
pressor medication should be considered according to lo- 70% and arterial CO2 levels between 50 and 70 mm Hg
cal practice. Hydrocortisone may be used in the early (6.9–9.3 kPa, permissive hypercapnia) is well accepted. In
phase for the treatment of hypotension after other treat- the first 2 h after birth, preductal SpO2 levels as low as 70%
ment has failed [26]. are acceptable provided they are slowly improving and
organ perfusion is satisfactory (indicated by a pH >7.2),
Surfactant and if ventilation is adequate (PaCO2 <65 mm Hg, 8.6
There is no rationale for surfactant therapy because in kPa). Thereafter, preductal saturation levels are prefera-
CDH patients surfactant amounts are likely to be appro- bly kept between 85 and 95%. In individual cases, how-
priate to lung size [27]. ever, levels down to 80% may be accepted, providing or-
gans are well perfused, as indicated by a pH >7.2, lactate
Recommendations levels <5 mmol/l and urinary output >1 ml/kg/h. Post-
– After delivery, the infant should be intubated routine- ductal saturations should remain above 70%. Oxygen
ly without bag and mask ventilation (grade of recom- toxicity can be avoided by decreasing FiO2 on the guid-
mendation = D). ance of the saturation levels described above. The optimal
– The goal of treatment in the delivery room is achieving initial ventilation strategy was investigated in a collab-
acceptable preductal saturation targets, i.e. between 80 orative initiative from the CDH EURO Consortium
and 95% (grade of recommendation = D). (VICI-trial, NTR 1310) [30]. Although the primary out-
– Ventilation in the delivery room should be done with come (death/bronchopulmonary dysplasia at day 28) was
a peak pressure as low as possible, preferably with 25 not significantly different between the two groups, it was
cm H2O, or below that (grade of recommendation = found that infants initially ventilated by conventional
D). mechanical ventilation required a significantly shorter
– An oro- or nasogastric tube with continuous or inter- duration of ventilation, had less need for inhaled nitric
mittent suction should be placed (grade of recommen- oxide (iNO) or sildenafil, had a shorter duration of vaso-
dation = D). active medication and were less likely to require ECMO
– Arterial blood pressure has to be maintained at a nor- [3]. Therefore, the CDH EURO Consortium recom-
mal level for gestation. In the case of hypotension and/ mends conventional mechanical ventilation as the initial
or poor tissue perfusion, 10–20 ml/kg NaCl 0.9% ventilation strategy. Recommendations for initial ventila-
should be administered 2 times (grade of recommen- tion settings for pressure-controlled ventilation are sum-
dation = D). marized below. In the case of weaning, the peak pressure
– In cases of persistent hypotension after the adminis- should primarily be reduced. Thereafter, frequency or
tration of NaCl 0.9%, inotropic and vasopressor agents PIP/PEEP may be reduced as long as pCO2 <50 mmHg
should be considered (grade of recommendation = D). (6.7 kPa). In general, the consortium recommends aim-
– In CDH infants who are predicted to have good lung ing for a limitation of peak pressure to 25 cm H2O or less,
development based on their prenatal assessment (e.g. a PEEP of 3–5 cm H2O and adjustment of the ventilator
left-sided defect, O/E LHR >50%, and liver down), rate to obtain PaCO2 between 50 and 70 mm Hg (6.9–9.3
spontaneous breathing could be considered (grade of kPa). If a PIP of >28 cm H2O is necessary to achieve pCO2
recommendation = D). and saturation levels within the target range, other treat-
– Premedication should be given before intubation if ment modalities (such as high-frequency oscillatory ven-
possible (grade of recommendation = D). tilation or ECMO) should be considered.
– Neuromuscular blocking agents should be avoided
during initial treatment in the delivery room (grade of Chest Radiograph
recommendation = D). To assess the patient’s initial condition, a chest radio-
– No routine use of surfactant in either term or preterm graph should be obtained as soon as possible.
infants with CDH (grade of recommendation = D).
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 Recommendations Hemodynamic Management
– Conventional mechanical ventilation is the optimal Hemodynamic management should be aimed at
initial ventilation strategy (grade of recommenda- achieving appropriate end-organ perfusion determined
tion = C). by heart rate, urine output and lactate levels. If the heart
– High-frequency oscillatory ventilation can be used as rate is within the normal range [35], urine output is over
rescue therapy if conventional mechanical ventilation 1.0 ml/kg/h, lactate concentration is <3 mmol/l and there
fails (grade of recommendation = D). are no other symptoms of poor tissue perfusion, inotropic
– Adapt ventilation settings to reach a preductal satura- or vasopressor support is not required. Echocardiogra-
tion between 80 and 95% and a postductal saturation phy is indicated if there are signs of poor perfusion or if
above 70% (grade of recommendation = D). the blood pressure is below the normal level for gestation
– The target PaCO2 should be between 50 and 70 mm with a preductal saturation below 80%. This may show
Hg (6.9–9.3 kPa; grade of recommendation = D). whether the poor perfusion is due to hypovolemia or
– Pressure-controlled ventilation: initial settings are a myocardial dysfunction. If there is hypovolemia, saline
PIP <25 cm H2O and a PEEP of 3–5 cm H2O; ventila- fluid therapy should be given (10–20 ml/kg NaCl 0.9% or
tor rate of 40–60/min (grade of recommendation = D). Ringer lactate up to 2 times during the first 2 h) [36]. If
– After stabilization, reduce FiO2 if the preductal satura- necessary, this should be followed by inotropic and/or va-
tion is above 95% (grade of recommendation = D). sopressor therapy. Hydrocortisone may be used for the
treatment of hypotension after other treatment has failed.
Further Management in the Intensive Care Unit
Sedation and Analgesia Recommendations
A wide range of sedative and analgesic practices has – Infants should be sedated and be monitored using val-
been described [31, 32]. Most centers use opioids such as idated analgesia and sedation scoring systems (grade
morphine sulfate or fentanyl. Although there is no spe- of recommendation = D).
cific evidence in infants with CDH, neuromuscular block- – Neuromuscular blocking agents should be avoided if
ade is associated with side effects such as hypoxemia – possible (grade of recommendation = D).
and thus should be avoided. Infants should remain se- – If symptoms of poor perfusion and/or blood pressure
dated during mechanical ventilation until weaning form below the normal level for gestation occur and are as-
mechanical ventilation is commenced. sociated with preductal saturation below 80%, echo-
cardiographic assessment should be performed (grade
Monitoring of recommendation = D).
Heart rate, invasive blood pressure, pO2 and pCO2, – In case of hypovolemia, fluid therapy (10–20 ml/kg
and pre- and postductal saturation should be monitored NaCl 0.9% or Ringer lactate) up to 2 times during the
routinely. A head ultrasound scan should be performed first two hours may be given and followed if necessary
at a time when there is little danger of arousing the new- by administration of inotropic and/or vasopressor
born. Monitoring the regional cerebral oxygenation satu- agents (grade of recommendation = D).
ration with near infrared spectroscopy and transcutane-
ous saturation measurements may be indicated [33], al- Pulmonary Hypertension
though its additional value in CDH infants is not yet clear. A 2D echocardiography performed within the first
Sedation and analgesia should be started as soon as ve- 24 h after birth remains the best modality to (1) rule out
nous access is established. Careful monitoring of the the presence of cardiac anomalies; (2) assess the right
blood pressure is then warranted because more fluid vol- heart function, and (3) determine the amount of pulmo-
umes or vasoactive drugs may be needed in view of the nary hypertension classified accordingly (less or more
potential adverse hemodynamic effect of sedatives, in than 2/3 systemic blood pressure) [37, 38]. Especially in
particular midazolam. Supportive care such as cocooning severe cases of pulmonary hypertension, a cardiac ultra-
and swaddling is recommended to prevent stress from sound may help to evaluate right ventricular dysfunction
too much noise, light and nociceptive stimulation. The and/or right ventricular overload, which condition can
infant’s condition should be regularly assessed using val- also lead to left ventricular dysfunction [39].
idated analgesia and sedation scoring systems, such as the There is no evidence for the usefulness of increasing
COMFORT behavior score [34]. systemic vascular resistance to treat right-to-left shunting,
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but a number of centers from the consortium suggest us-

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ing inotropic or vasopressor agents such as dopamine, do- of 10–20% of PaO2, or improvement in hemodynamic
butamine and (nor)epinephrine to maintain blood pres- parameters meaning a 10% increase in mean blood
sure at normal levels for gestation [40]. If preductal satu- pressure, or a decrease in lactate levels (grade of rec-
ration falls below 85% and/or if there are signs of poor ommendation = D).
organ perfusion, treatment of pulmonary hypertension – Intravenous sildenafil should be considered in CDH
should be initiated. The first choice would be iNO, which patients with severe pulmonary hypertension (grade
is a pulmonary vasodilator. In neonates with pulmonary of recommendation = D).
hypertension of the newborn (PPHN) or severe hypoxic – In case of suprasystemic pulmonary artery pressure
respiratory failure, iNO improves oxygenation and de- and right-to-left shunting through the foramen ovale,
creases the need for ECMO [41, 42]. At an oxygenation intravenous prostaglandin E1 should be considered
index of 20 or higher and/or a pre- and postductal satura- (grade of recommendation = D).
tion difference of 10% or more, iNO may be given for at
least 1 h. A consistent dose-dependent effect of iNO has Extracorporeal Membrane Oxygenation
not yet been shown [43]. As in one study more infants The benefit of ECMO in the treatment of infants with
treated with NO needed ECMO [43], we recommend CDH remains unclear. The ELSO registry showed a sur-
stopping iNO therapy if no effect is seen after its initiation. vival rate of 51% of patients with CDH who required
If there is no or an insufficient response to iNO, intra- ECMO [49]. The use of ECMO has decreased in recent
venous prostacyclin, intravenous phosphodiesterase type years [50]; it is more used for preoperative stabilization,
5 inhibitor (sildenafil) or medication involving the endo- and the preferred method (venoarterial vs. venovenous)
thelin pathway should be considered. These agents have is still being debated. The VICI-trial showed no difference
been used successfully in treating PPHN in neonates with in survival between patients born in ECMO centers and
and without CDH [44, 45]. The effects of treatment may patients born in non-ECMO centers [3].
be best addressed by repeated cardiac evaluation [46].
This can lead to insufficient filling of the left ventricle and Recommendations
thereby to poor systemic perfusion. Reopening of the – Criteria for ECMO (grade of recommendation = D):
ductus arteriosus with prostaglandin E1 may protect the • Inability to maintain preductal saturations >85% or
right ventricle from excessive overload due to increased postductal saturations >70%.
afterload [47]. Phosphodiesterase-3 inhibitor (Milri- • Increased PaCO2 and respiratory acidosis with pH
none) was investigated in only 6 CDH patients by Patel et <7.15 despite optimization of ventilator management.
al. [48]. Right ventricular function and oxygenation index • Peak inspiratory pressure >28 cm H2O or mean air-
significantly improved. Sildenafil has been used in the way pressure >17 cm H2O is required to achieve sat-
treatment of pulmonary hypertension in infants with uration >85%.
CDH. Intravenous sildenafil has recently become avail- • Inadequate oxygen delivery with metabolic acidosis as
able, but its use has not yet been FDA approved. measured by elevated lactate ≥5 mmol/l and pH <7.15.
• Systemic hypotension, resistant to fluid and inotro-
Recommendations pic therapy, resulting in urine output <0.5 ml/kg/h
– Perform echocardiography within the first 24 h after for at least 12–24 h.
birth to rule out structural cardiac anomalies (grade of • Oxygenation index ≥40 present for at least 3 h.
recommendation = D).
– Blood pressure support should be given to maintain Surgical Repair
arterial blood pressure levels at normal levels for gesta- Surgery should be performed electively. The effect of
tion (grade of recommendation = D). hospital volume on mortality is unclear. While a large study
– iNO administration for at least 1 h in a dose of 10–20 (2,203 infants) concluded that hospitals with a high volume
ppm should be considered if there is evidence of extra- of CDH repair have lower in-hospital mortality [51], a
pulmonary right-to-left shunting and the oxygenation more recent study in 3,738 infants showed no difference in
index is above 20 and/or the saturation difference is mortality between lower and higher surgical volume cen-
more than 10% (grade of recommendation = D). ters [52]. Controversies about the exact timing of the surgi-
– In nonresponders iNO should be stopped. iNO re- cal repair in patients on ECMO remain [53]. A recent study
sponders are defined as follows: a decline of 10–20% in from Partridge et al. [54] showed improved outcomes with
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the pre-postductal saturation difference, or an increase surgical repair after ECMO, i.e. a higher likelihood of sur-
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vival, less surgical bleeding and shorter duration of ECMO. hypotension. Parenteral nutrition only is allowed until
A relative small study (n = 46) from Fallon et al. [55] found surgical repair and until postoperative enteral feeding has
that repair within the first 72 h of ECMO correlated with a been achieved. Gastroesophageal reflux may be treated
shorter duration of ECMO, less circuit complications and both by antireflux medication and by surgical interven-
a trend towards improved survival. tion [61]. Maier et al. [62] did not show evidence for prof-
The routine use of a chest tube postoperatively to drain it beyond the first year of life after prophylactic Thal pro-
the effusion filling the pleural cavity has been abandoned. cedure at primary CDH repair. Diuretics should be given
This does not preclude its use in individual cases to drain in the case of persisting positive fluid balance without hy-
an effusion that is symptomatic, for example due to chy- povolemia, aiming for diuresis of >1 ml/kg/h [63].
lothorax existing before surgery.
The optimal surgical technique also remains under de- Recommendations
bate. Minimal access surgery is gaining ground on the – 40 ml/kg/day saline including medication for the first
open approach (thoracotomy or laparotomy) [56]. Mini- 24 h after birth; increase intake thereafter (grade of
mal access surgery has esthetic advantages and may be recommendation = D).
performed in patients with a left-sided defect and liver – Diuretics should be considered in the case of persisting
down, but carries a significantly higher risk of recurrence positive fluid balance; aim for a diuresis >1 ml/kg/h
[56, 57]. There is also concern about absorption of CO2 (grade of recommendation = D).
used for insufflation in minimal access surgery [58], and – Preventive antireflux therapy should be started in
CO2 insufflation pressures should therefore be mini- combination with enteral feeding (grade of recom-
mized. A meta-analysis from Lansdale et al. [59] showed mendation = D).
that thoracoscopic repair had greater recurrence rates – Preoperatively, patients should only receive parenteral
and operative times but similar survival and patch usage nutrition (grade of recommendation = D).
compared with open surgery. Recently, Costerus et al.
[60] concluded that thoracoscopic primary closure seems
a safe and effective procedure, but efficacy of thoraco- Conclusion
scopic patch repair has not been established. To allow for
better comparison of patient groups between studies it is The European task force for CDH (CDH EURO Con-
recommended to record the diaphragmatic defect size in sortium) has agreed on an updated protocol for standard-
all surgeries [37]. ized postnatal treatment guidelines. Although it is emi-
nence-based medicine and many recommendations are
Recommendations level D, we think that a consensus of many specialized
– Surgical repair of the diaphragmatic defect should be centers on the use of a standardized treatment protocol
performed after clinical stabilization, defined as fol- will contribute to making more valid comparisons of pa-
lows (grade of recommendation = D): tient data in ongoing and future multicenter prospective
• Mean arterial blood pressure normal for gestation. clinical studies.
• Preductal saturation levels of 85–95% on FiO2 below
50%.
• Lactate below 3 mmol/l. Appendix
• Urine output more than 1 ml/kg/h.
– No routine chest tube placement postoperatively Members of the CDH EURO Consortium Group:
(grade of recommendation = D). Austria, Graz, Medical University Graz: B. Urlesberger; Bel-
– Repair can be performed while the patient is on ECMO gium, Leuven, University Hospital KU Leuven: K. Allegaert, A.
Debeer, J. Deprest; Canada, Manitoba, University of Manitoba: R.
(grade of recommendation = D). Keijzer; France, Paris, Hôpital Antoine-Béclère: A. Benachi;
France, Lille, Hôpital Jeanne de Flandre: L. Storme; France, Paris,
Fluid Management, Parenteral Feeding, Entering South Paris University Hospitals: P. Tissieres; Germany, Bonn,
Enteral Feeding and Gastroesophageal Reflux Universitätsklinikum Bonn: F. Kipfmueller; Germany, Mannheim,
Restrictive fluid management in the first 24 h after Universitätsklinikum Mannheim: T. Schaible, L. Wessel; Ireland,
Dublin, Our Lady’s Children’s Hospital: C. Breatnach; Scotland,
birth consists of 40 ml/kg/day of fluids including medica- Glasgow, Royal Hospital for Sick Children: N. Patel; Italy, Milan,
tion, with additional saline volume top-up for intravascu- Fondazione IRCCS Cà Granda, Ospedale maggiore policlinico: E.
UFRJ Universidade Federal do Rio de Janeiro

lar filling in the case of inadequate tissue perfusion or Leva, F. Ciralli; Italy, Rome, Bambino Gesu Children’s Hospital: P.
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Bagolan, I. Capolupo, A. Dotta, F. Morini, A. di Pede; Norway, don, University College London Hospitals: J. Deprest; United
Oslo, Oslo University Hospital: R. Emblem, K. Ertesvag; Poland, Kingdom, London, UCL Institute of Child Health and Great Or-
Warsaw, Centrum Zdrowia Dziecka: M. Migdal, A. Piotrowski; mond Street Hospital for Children: P. De Coppi, S. Eaton; UK,
Sweden, Stockholm, Karolinska Univeristy: B. Frenckner, C. Me- London, King’s College: M. Davenport, A. Greenough.
sas; Spain, Madrid, Hospital University La Paz: D. Elorza, L. Mar-
tinez; The Netherlands, Nijmegen, Radboud University Medical
Centre: A. van Heijst, H. Scharbatke; The Netherlands, Rotterdam,
Erasmus MC-Sophia Children’s Hospital University Medical Cen- Acknowledgment
ter Rotterdam: T. Cohen-Overbeek, A.J. Eggink, U.S. Kraemer,
I.K.M. Reiss, K.G. Snoek, D. Tibboel, R.M.H. Wijnen; UK, Lon- We thank Ko Hagoort for editing.

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