Congenital diaphragmatic hernia

Key points

1:5000 live births

20% have sac, 20% right side

Pulmonary dysplasia consists of:

1. Lung hypoplasia

2. Vascular Dysplasia

3. Abnormal lung fluid distribution

Normally pulmonary vascular remodelling should take place, with the lumen widening and the wall thinning. This does not happen in CDH and it causes pulmonry hypertension. The vessels are prone to vasospasm with mild insults

Four key embryological structures develop between weeks 3-10:

• Somites - contribute to the muscular components of the diaphragm

• Pleuroperitoneal folds (PPFs) - bilateral mesodermal structures forming the dorsolateral edges, potentially crucial for multiple diaphragm components according to recent research

• Posthepatic mesenchymal plate (PHMP) - develops in close association with the peritoneal organs

• Septum transversum - may be the origin of the separation between the thoracic and abdominal cavities and a potential embryologic source of the central tendon

This development process impacts the cannalicular phase of lung development

Genetics

Possible links with GATA4, WT1, SLIT3

Future siblings have 1-2% chance of having CDH

Antenatal features

Lung head ratio (LHR)

On USS at level of 4 chamber view of heart: Measure 2 longest perpendicular diameters of CONTRALATERAL lung in mm and multiply them

Divide by head circumference in mm

If >1.35 = 100% survival

If 0.6-1.35 = 60%

If <0.6% = 0%

Observed/Expected LHR

Compare LHR to what normal foetal measurements should be

If in left sided defects O/E = <25%, then 20% survival

If >45% then >90% survival

Quantitive lung index

Lung area/(Head circumference/10)^2

Not validated

Foetal intervention can be tracheal occlusion (FETO)

Criteria for FETO:

• Diagnosis before 26 weeks gestation

• Lung-to-head ratio (LHR) less than 1

• Liver up (intrathoracic liver position)

• No associated abnormalities

• Normal karyotype

No particular mode of delivery needed

Deliver in a surgical centre to avoid the stress of transfer

For the same reason, there should be minimal handling and no unnecessary examinations

FETO Trials:

• 2003: 24 cases, no survival benefit, did not meet criteria for severe congenital diaphragmatic hernia (CDH)

• 2009: 41 severe cases, 50% survival in FETO group versus 5% with standard treatment, included right CDH, not adjusted for gestation

• 2021/22: TOTAL trial, FETO for moderate left CDH at 30-32 weeks, 196 patients, 63% survival in FETO group versus 50% in the expectant group, 44% preterm birth rate in FETO group versus 12% in expectant group, 1 death from balloon retention

• TOTAL trial, severe left CDH, 80 patients, 36% survival in FETO group versus 14% in expectant group, 1 death from balloon retention, 1 death from placental laceration during balloon removal

FETO should only be used for most high risk patients

EXIT to ECMO procedure can be used for high risk

Associations

20% associated abnormalities - these must be actively looked for, as they affect prognosis

Decision for foetal intervention or termination: 15% Trisomy 13 and 18, 5% genitourinary anomalies, 30% cardiac abnormalities

Fryns’ syndrome, Donnai-Barrow syndrome, Denys-Drash syndrome, Pallister-Killian, Cornelia de Lange, foetal alcohol syndrome, CHARGE syndrome, Wolf-Hirschhorn, Goldenhar syndrome, Noonan syndrome

Pentalogy of Cantrell

18% have cardiac defect - associated with LV hypoplasia

Postnatal Management

PIP 20, PEEP 5

Give 100% O2

Maintain preductal sats >85%

Avoid muscle relaxants

Permissive hypercapnia

ECMO

Types:

VA, 2 cannula VV, double lumen VV (DLVV), Veno-veno-arterial (VVA)

VA:

Open neck and sling carotids and IJV

Arterial cannula 10Fr for neonates - tip in ascending aorta

Venous cannula 12-14Fr for neonates - tip in distal right atrium

Ligate proximal IJV

Or can cannulate femoral vein (tip always in proximal RA) and artery (tip in common iliac artery)

VV: Cannulate IJV and Femoral

VV and DLVV do not provide cardiac support

VV is not used in neonates as small femoral. DLVV instead

DLVV: Avalon catheter - openings in SVC, IVC and middle one in RA

VVA: IJV, Femoral vein and artery - tip in common iliac artery

Flow: 100-150ml/kg/min

Elevated protein requirements

On heparin, monitor clotting and check for DIC

Cranial USS for first 3 days in neonates

Can have a CXR 'white out' early on ECMO

To decannulate: Wean flow, can clamp cannulas, stop sweep gas

26% risk of neurological complications - 6% long term

Evidence in CDH:

Morini Meta Analysis 2006

Pooled CDH data from 2 ECMO trials - Early survival benefit but no effect on late mortality

Non-randomised studies show benefit - Approximately 60% overall survival - but poor quality evidence

Usually VA ECMO in CDH

Best to repair early if on ECMO

Ventilation index = (RRxPCO2xPIP)/1000

Oxygenation index (OI) = MAP × FiO2 × 100 / PaO2

OI is a measure of the diffusion barrier in the lungs, and how well inspired O2 is being used in the tissues

The higher the OI, the worse the oxygenation

VI and OI >40 associated with 77% mortality, so can be used as an indication for ECMO

ECMO Criteria

Reversible cardiopulmonary disorder

0I index >40

Pre ductal saturations <85%

Combined metabolic and respiratory acidosis suggestive of poor perfusion - pH <7.15, lactate of 4/5

ECMO Indications:

VI and OI >40 associated with 77% mortality, so can be used as an indication for ECMO

ECMO Relative contraindications:

Gestation <34 weeks due to risk of Intracranial haemorrhage

<2kg

Intracranial haemorrhage >Grade 2

Bleeding

Prolonged ventilation (>14 days) due to irreversible lung damage

When to operate on CDH

The practice of emergency early CDH closure is largely historical, as it has been found to worsen outcomes

This is due to the fact that pulmonary hypertension is due to pulmonary hypoplasia and resultant vascular dysplasia, rather than any compression of the lungs by the bowel

In general, surgery should wait until the patient is on conventional ventilation and off inotropes

APSA targets for surgery:

FiO2 <50%

Lactate <3

Urine output >1ml/kg/h

Normal BP

Pulmonary artery pressures lower than systemic

Operation

Open approach:

Upper quadrant transverse incision

Carefully reduce contents

Resect sac if present

Check for width of mesentery - perform Ladd's procedure if needed

Define edges of diaphragm

Techniques for deficient posterior wall:

Transversalis muscle flap

Suturing around/through rib

Use patch if unable to close primarily

Consider using patch/staged closure of abdominal wall

Goretex/Marlex combined patches have lowest recurrence rate - goretex on abdo side + prolene on lung side

Goretex pores need to be 30um or there will be no ingrowth of tissue

Extra lobar sequestrations are often found at level of diaphragm - resect if found

Thoracoscopic Repair:

Relative Indications:

• Stable haemodynamics before surgery

• Minimal and consistent respiratory support (CO2 levels below 55, pH above 7.3)

• Late presentation of the condition

Relative Contraindications:

• Haemodynamic instability prior to surgery

• Requirement for significant respiratory support, including extracorporeal life support (ECLS)

• Presence of other congenital anomalies, especially cardiac

• Prematurity

• Low birth weight (under 2.5 kg)

• Persistent right-to-left shunt with moderate pulmonary hypertension

Thoracoscopy transiently worsens hypercarbia

Higher recurrence rate with thoracoscopic - likely due to learning curve

Complications

10-20% recurrence rate - likely within first 2 years

Reflux - think fundoplication/GJ

Chronic lung disease + Increased respiratory infections

Growth impairment - think PEG

20% small bowel obstruction

Spinal and chest wall deformities 10-15% in patch repair

50% Neurodevelopmental delay

3% Sensorineural hearing loss - related to drugs used in NICU

Outcome

Predictors of poor outcome

LHR <1

Liver herniation

Predictors of positive outcome pre ECMO

pCO2 <6.6kPa and preductal sats >90% for 1 hour at any time = Survival 75%

Standard scenario

Antenatal diagnosis of CDH

Important information:

Liver in thorax

Stomach in thorax

LHR

Cardiac anomalies

Chromosomal diagnosis

Eligible for FETO?

Discuss trials

FETO should only be used for most high risk patients

Plan for birth in Tertiary centre

At birth - resuscitation by NICU

Must be intubated - low pressures

Must have NG

Examination:

Scaphoid abdomen

Dysmorphic features

Eye abnormalities (Fryn's syndrome - poor prognosis)

Investigations:

CXR to confirm diagnosis

Management:

If severe chromosomal abnormalities - discuss with NICU - palliation may be more appropriate

Is ECMO required?

Wait for patient to stabilise from pulmonary hypertension - 48-72h

Procedure of choice

Follow up - Chronic lung disease + Increased respiratory infections

MDT with respiratory team

Warn about recurrence - 10-20% recurrence rate - likely within first 2 years

References

Holcomb and Ashcraft’s Pediatric Surgery, 7th edition, 2020, Chapter 24 Congential Diaphragmatic Hernia and Eventration

Bhatia, Manisha, et al. "Congenital Diaphragmatic Hernia." Pediatric Surgery NaT, American Pediatric Surgical Association, 2022. Pediatric Surgery Library, www.pedsurglibrary.com/apsa/view/Pediatric-Surgery-NaT/829067/all/Congenital_Diaphragmatic_Hernia.

Harrison MR, Keller RL, Hawgood SB, Kitterman JA, Sandberg PL, Farmer DL, Lee H, Filly RA, Farrell JA, Albanese CT. A randomized trial of fetal endoscopic tracheal occlusion for severe fetal congenital diaphragmatic hernia. N Engl J Med. 2003 Nov 13;349(20):1916-24. doi: 10.1056/NEJMoa035005. PMID: 14614166.

Ruano R, Yoshisaki CT, da Silva MM, Ceccon ME, Grasi MS, Tannuri U, Zugaib M. A randomized controlled trial of fetal endoscopic tracheal occlusion versus postnatal management of severe isolated congenital diaphragmatic hernia. Ultrasound Obstet Gynecol. 2012 Jan;39(1):20-7. doi: 10.1002/uog.10142. Epub 2011 Dec 14. PMID: 22170862.

Deprest JA, Benachi A, Gratacos E, Nicolaides KH, Berg C, Persico N, Belfort M, Gardener GJ, Ville Y, Johnson A, Morini F, Wielgoś M, Van Calster B, DeKoninck PLJ; TOTAL Trial for Moderate Hypoplasia Investigators. Randomized Trial of Fetal Surgery for Moderate Left Diaphragmatic Hernia. N Engl J Med. 2021 Jul 8;385(2):119-129. doi: 10.1056/NEJMoa2026983. Epub 2021 Jun 8. PMID: 34106555; PMCID: PMC7613454.

Deprest JA, Nicolaides KH, Benachi A, Gratacos E, Ryan G, Persico N, Sago H, Johnson A, Wielgoś M, Berg C, Van Calster B, Russo FM; TOTAL Trial for Severe Hypoplasia Investigators. Randomized Trial of Fetal Surgery for Severe Left Diaphragmatic Hernia. N Engl J Med. 2021 Jul 8;385(2):107-118. doi: 10.1056/NEJMoa2027030. Epub 2021 Jun 8. PMID: 34106556; PMCID: PMC7613453.

Morini F, Goldman A, Pierro A. Extracorporeal membrane oxygenation in infants with congenital diaphragmatic hernia: a systematic review of the evidence. Eur J Pediatr Surg. 2006 Dec;16(6):385-91. doi: 10.1055/s-2006-924751. PMID: 17211783.