(Fetal therapy for) Congenital Diaphragmatic Hernia · Prenatal therapy Overview Rationale and...
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06/10/2013 1 Tim Van Mieghem Congenital Diaphragmatic Hernia Prenatal therapy Overview Rationale and history Clinical FETO procedure Ongoing trials
Transcript of (Fetal therapy for) Congenital Diaphragmatic Hernia · Prenatal therapy Overview Rationale and...
06/10/2013
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Tim Van Mieghem
Congenital Diaphragmatic Hernia
Prenatal therapy
Overview
Rationale and history
Clinical FETO procedure
Ongoing trials
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< 15 15-25 26-35 36-45
O/E LHR (%)
0
10
20
30
40
50
60
70
80
90
100
Surv
ival
rat
e (
%)
46 and higher
extreme
liver in abdomen (“down”) liver in thorax (“up”)
severe moderate mild
Outcome prediction
Deprest J et al, Sem Fetal Neonat Med, 2008 - n= 329.
Isolated CDH expectantly managed (n=100)
Jani et al UOG 2008 – Done et al 2013
≤ 25 26-45 >45
Patch rate (%)
0
10
20
30
40
50
60
70
80
90
100
O/E LHR (%)
0
10
20
30
40
50
60
Conventional ventilation
day
s
≤ 25 26-45 >45
O/E LHR (%)
0
10
20
30
40
50
60
Enteral feeding
day
s
<25 26-45 >45
O/E LHR (%)
0
10
20
30
40
50
60
NICU**
day
s
<25 26-45 >45
O/E LHR (%)
0
10
20
30
40
50
60
70
80
90
≤ 25 26-45 >45
O/E LHR (%)
Oxygen O2 at 28d (%)
100
Morbidity
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Fetal surgery for CDH
Clinical Tracheal Occlusion
Harrison 2003
criteria o/e LHR ≤ 37%, liver up
technique general anesthesia
laparotomy, 5 mm tracheoscopy
Several occlusion devices
EXIT delivery
PPROM 100% < 34 wks
GA delivery 30.8 (28-34)
survival
o/e LHR ≤ 37% 77%
o/e LHR ≤ 27% ≤33% (n=3!)
Flake et al, 2001; Harrison et al, 2003
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Clinical FETO procedure
Criteria:
• O/E LHR < 28%
• isolated
• < 29 wks gestation
Procedure:
• 10Fr cannula
• external version
• fetal anesthesia
• admission 2 days
Clinical FETO procedure
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Balloon removal - 34 wks
FETO Experience - 2009
1 University Hospital Gasthuisberg, Leuven, Belgium; 2 King’s College Hospital, London, UK;
3 Hospital Clinic-IDIBAPS and CIBER-ER, Barcelona, Spain
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Analgesia
General 8 (4%) Epidural 160 (76%) Local 42 (20%)
Median 27 wks
Gestation (wks)
N
0
10
20
30
40
50
23 24 25 26 27 28 29 30 31 32 33
Gestation at FETO
0
5
10
15
20
25
30
35
<10 11-20 21-30 31-40 >40
Time (min)
%
Median
10 min
Intervention time
n=210, October 2001 - October 2008.
Placenta
Anterior 100 Posterior 110
Successful FETO 1st attempt 203(97%)
2nd FETO 5%
Severe CDH: o/e LHR equivalent to an LHR <1 and intrathoracic herniation of the liver
FETO Experience - 2009
0
5
10
15
20
25
30
35
40
1-10 11-20 21-30 >30
%
Intervention time (min)
25 26 27 28 29 30 31 32 33 34 35 36
0
2
4
6
8
10
12
14
16
18
20 N
Gestation (wks)
Gestation at PROM
PROM
47%
PROM <3 wks (17%)
• Duration of FETO
• General anesthesia
FETO Experience - 2009
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Prenatal Fetoscopic 106 In-utero puncture 40 Intrapartum EXIT 14 Postnatal puncture 13 Postnatal tracheoscopy 21 Spontaneous 10 Not needed 6
Balloon removal
Elective 44%
Emergency 56%
Cause of neonatal death n=10
FETO Experience - 2009
Type Survival Left sided 175 (49.1%) Isolated 158 (49.4%) Plus cardiac defect 6 (50.0%) Plus CCAM 7 (57.1%) Plus pleural effusion 2 (50.0%) Plus del. chromosome 8 2 (0%) Right sided 34 (35.3%) Isolated right 29 (37.9%) Plus CCAM 1 (0%) Plus pleural effusion 4 (25.0%) Bilateral 1 (0%)
Median 35.3 wks Range: 26-41
Gestation (wks)
N
0
5
10
15
20
25
30
25 27 29 31 33 35 37 39 41
Gestation at delivery
Related to
gestation at FETO and PPROM
FETO Experience - 2009
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N=144 left isolated CDH
no balloon removal problems
Survival
Related to • Observed / expected LHR
• Gestation at delivery
Not related: • Gestation at FETO
• Duration of tracheal occlusion
• Incidence of PPROM
• Operator experience
Observed to expected LHR (%)
<15 15-25 26-45
0
10
20
30
40
50
60
70
Su
rviv
al r
ate
(%
)
0
10
20
30
40
50
60
70
0
10
20
30
40
50
60
70
25-29 30-31 32-33 34-41
Gestation at delivery (wks)
Su
rviv
al r
ate
(%
)
48%
FETO Experience - 2009
Isolated CDH eiter expectantly managed (n=41) or FETO (n=90)
Jani et al UOG 2008, Done et al UOG 2013
≤ 25 26-45 >45
Patch rate (%)
0
10
20
30
40
50
60
70
80
90
100
O/E LHR (%)
0
10
20
30
40
50
60
Pulmonary hypertension
day
s
≤ 25 26-45 >45
O/E LHR (%)
0
10
20
30
40
50
60
Enteral feeding
day
s
<25 26-45 >45
O/E LHR (%)
0
10
20
30
40
50
60
NICU**
day
s
<25 26-45 >45
O/E LHR (%)
0
10
20
30
40
50
60
70
80
90
≤ 25 26-45 >45
O/E LHR (%)
Oxygen O2 at 28d (%)
100
Morbidity after FETO
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Jani
2009
Peralta
2011
Ruano
2012
N 210 28 13 20 21
O/E LHR (%) 20 28 28 18 17
Left sided (%) 83 100 100 75 71
GA @ FETO 27 - - 26-30 -
Operating time 10 20 - 17 -
Balloon removal 34 33 - EXIT -
PPROM (%) 47 36 0 36 24
GA @ del (wks) 35 35 37 36 37
Survival (%) 48 36 0 50 4.8
Follow-up studies
www.TOTAL trial.eu
Tracheal Occlusion To Accelerate Lunggrowth
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< 15 15-25 26-35 36-45
O/E LHR (%)
0
10
20
30
40
50
60
70
80
90
100
Surv
ival
rat
e (%
)
46 and higher
extreme
liver in abdomen (“down”) liver in thorax (“up”)
severe moderate mild
Trials in Europe
From : Sem Neonat Fetl Med, 2008.
RCT FETO
[28 – 30 wks]
vs. expectant
Outcome measure:
Survival
RCT FETO
[30-32 wks]
Vs. expectant
Outcome measure:
Survival w/o BPD
isolated left CDH – normal karyotype
SEVERE (<25%, liver up or down)
MODERATE (26-35%, any liver& 36-45%,
up)
refer to FETO center
measurements
standardized postnatal therapy
counseling and consent
web randomization 1:1
FETO
28-30w
unplug
≤34+6 w
expectant management
RE
FE
RIN
G C
EN
TE
R
FETO
30 - 32+6w
Patient flow
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Postnatal management
Delivery Room no bag masking immediatly intubation peak pressure below 25cm H20 nasogastric tube
NICU adapt ventilation to obtain predutcal saturation between 85%-95% pH > 7.20, lactate 3-5 mmol/L conventional ventilation (CMV) or high frequency oscillation (HFO) maximum peak-pressure 25-28cmH20 in CMV and mean airway pressure 17cmH20 in HFO targeting blood pressure : normal value for gestational age conside of inotropic support
Pulmonary hypertension
perform echocardiograhy Inhaled nitric oxide (iNO) first choice in case of non response stop iNO chronic phase : phosphodiesterase - inhibitors, endothelin-antagonist, tyrosine kinase inhibitors
ECMO (if available) only starting if the patient is able to achieve a preductal saturation > 85% inability to maintain preductal saturation above 85% respiratory acidosis inadequate oxygen delivery (lactate>5mmol/L) therapy resistant hypotension
Surgical repair fraction of inspired oxygen (FiO2) below 0.5 mean blood pressure normal of gestational age urine output > 2ml/kg/hour no signs of persistent pulmonary hypertension
Deprest & Tibboel, Clin Perinatol 2009
Outcome measures
• Primary: – BPD : oxygen dependency @ 28 d (moderate)
– survival or death at discharge (severe)
• Secondary postnatal outcome variables: – Need ECMO in centers offering it;
– days of ventilator
– chronic lung disease
– Postnatal co-morbidity
– days in NICU
– Later: • Pulmonary function and volume
• Neurodevelopmental milestones
• death at 2 yr
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Conclusions
FETO is clinically available
Randomized data are needed
Trials are ongoing
Thank you !
