Congenital Diaphragmatic Hernia

The Shift to Physiological Stability

As neonatal intensive care matured, the management paradigm shifted toward achieving physiological stabilization before surgery. Reports in the 1960s showed that implementing planned pre-operative resuscitation strategies—including intubation, ventilation, central line placement, monitoring blood gases, correcting acidosis, and ensuring warmth—resulted in improved survival, with mortality falling from 76% to 28%. Further studies in the 1980s reinforced the idea that early repair in the face of labile respiratory and hemodynamic function may be harmful. The conclusion was that repair should be deferred until the patient had been satisfactorily stabilized, specifically achieving respiratory and hemodynamic stabilization. This philosophy was supported by the only randomized controlled trial (RCT) in non-ECMO CDH patients (1996), which showed a trend toward improved survival in the delayed surgery group (median repair age 48 hours) compared to the early group (mean repair age 6 hours), although this trend was not statistically significant. This delayed approach, based on physiological parameters, has persisted and is incorporated into current consensus guidelines, such as the 2016 Euro consortium guideline. This guideline recommends surgery after clinical stabilization defined by specific criteria:

• Mean arterial blood pressure (MAP) normal for gestation.

• Preductal saturations 85–90%.

• Fraction of inspired oxygen (FiO2) less than 50%.

• Lactate below 3.

• Urine output less than 1.

However, this recommendation carries a low grade of evidence (D), often based on expert opinion and non-analytic studies. Practically, this approach means the majority of babies are now repaired somewhere between day two and day seven of life. More recently, there has been publications of the Canadian CDH Guidelines - outlined below. 

Precision Medicine: Incorporating Haemodynamics

More recently, efforts have focused on developing more objective and precise criteria for defining physiological stability, particularly through the incorporation of pulmonary artery pressure (PAP) and cardiac function assessment.

Pulmonary Artery Pressure (PAP) Assessment: Pulmonary hypertension (PH) is a highly variable and pathognomonic finding in CDH pathophysiology. Studies show that PH tends to improve over the first 48 hours of life, suggesting that waiting for this improvement can help guide optimal surgical timing. Pulmonary pressure is a function of pulmonary vascular resistance, pulmonary blood flow and distal draining pressure (pulmonary capillary wedge). All these elements may be influenced in CDH, since there may be a component of decreased pulmonary vascular surface area, pulmonary vascular reactivity, abnormal pulmonary vasculature, pulmonary collapse/atelectasis, high mean airway pressure leading to increased pulmonary vascular resistance by compression, pulmonary venous congestion due to low pulmonary venous surface area and/or left ventricular hypoplasia/dysfunction.

Investigators have used objective measures to track improvement in the relationship between pulmonary and systemic afterload:

1. Ductal Shunting Direction: Some groups defined their criteria for repair based on the pattern of ductal shunting, waiting for the appearance of a left-to-right shunt, which indicates that PVR has fallen below systemic vascular resistance.

2. LR Ratio: A specific Japanese study calculated the LR ratio (percentage of left-to-right flow in the patent ductus arteriosus, PDA) and aimed to operate when this ratio was less than 50%.

3. PAP Threshold: A Denver group implemented criteria requiring PAP to be less than 80% of systemic blood pressure for repair. This assessment typically utilized Doppler measurements, such as flow across the PDA via the Bernoulli equation (although imprecise since the PDA does not satisfy Bernouilli's assumptions), TR velocity jet estimation of right ventricle systolic pressure, or flow velocity in a VSD. The implementation of this hemodynamically focused approach correlated with a significant improvement in 30-day survival (rising from 80% to 94%).

4. The contemporary Canadian guidelines reflect this movement, incorporating estimated PAPs less than systemic pressure alongside traditional stability markers.

Cardiac Dysfunction and Cardiovascular Phenotypes

Further precision involves assessing cardiac function, as cardiovascular instability is fundamental to early CDH pathogenesis.

• Mechanisms of Dysfunction

  • Elevated PAP increases the afterload on the right ventricle (RV), quickly leading to RV dysfunction, characterized by dilation and hypertrophy. This impacts pulmonary blood flow and, coupled with septal displacement, can cause secondary dysfunction in the left ventricle (LV). It may also lead to decreased LV preload by underfilling and compression due to adverse RV-LV interactions. 

  • Importantly, primary left ventricular dysfunction (LVD) is common, occurring in 40% to 60% of CDH cases, especially severe ones. LVD is a crucial mechanism of post-capillary pulmonary venous hypertension (PVH). The resulting PVH contributes to pulmonary edema and impairs gas exchange, driving the clinical instability (hypoxia, hypercarbia, hypotension, metabolic acidosis) traditionally used to determine surgical timing.

Identifying Phenotypes

Understanding these mechanisms allows clinicians to categorize patients into distinct cardiovascular phenotypes:

1. Good Cardiac Function: Ventricles coupled normally.

2. Right Ventricular (RV) Dysfunction: Predominantly pre-capillary PH driven by resistance.

3. Left Ventricular (LV) Dysfunction: Pulmonary venous hypertension phenotype.

4. Biventricular or Mixed Dysfunction: Often the most severe patients.

In severe CDH, LVD may be profound initially but often improves rapidly within the first 72 hours. Following this period, ongoing pulmonary arterial hypertension and RV dysfunction often persist.

Timing Repair Based on Optimized Cardiac Function

The operation itself can affect cardiac function. Limited data indicates a risk of deterioration in cardiac function (in both ventricles) after repair, especially in more severe patients. For instance, RV function might temporarily improve pre-op (as clinicians wait for stability) but then deteriorate post-op, potentially due to an exacerbation of PAP. Based on this knowledge, the strong rationale for timing surgery within a precision approach is to operate when the patient’s function is optimized. This ensures the patient is not going into surgery with existing compromise and allows for maximum "headroom" to tolerate post-operative deterioration. The proposed optimal point of repair is when LV function has improved and RV function has optimized. Objective data supports this approach, showing that repair is performed earlier in patients with normal function or isolated RV dysfunction, and is delayed in those with LV or biventricular dysfunction. This approach emphasizes achieving stability in hemodynamic and clinical factors prior to repair.

Practical Haemodynamic Management and Respiratory Support

The application of hemodynamic precision has significantly impacted patient management, often leading to a reduction in the requirement for ECMO. Hemodynamic understanding provides confidence to maintain lung protective, low-pressure ventilation strategies. Impaired gas exchange (hypoxia, hypercarbia) in these patients is frequently a circulatory issue stemming from reduced pulmonary blood flow, and sometimes secondary pulmonary edema, rather than solely a ventilator issue. By focusing on optimizing cardiac function and pulmonary hypertension, gas exchange often improves without necessitating higher ventilation settings.

Revisiting Early Repair

There is recent interest in revisiting an early repair approach, which warrants further exploration. A maximum lung protection strategy, including early repair (within the first 24 hours), has been argued to prevent exposing the patient to higher ventilation pressures and minimize early lung injury. Data from Japan suggests that immediate repair (median 2.8 hours) may mechanically improve left ventricular performance by removing the compressive effect of the herniated contents. The current dilemma is balancing the benefits of minimizing early lung injury and removing the hernia with the risk of operating during peak cardiac dysfunction.

Exceptional Cases

In rare instances, early repair may be indicated regardless of hemodynamic stability if the patient experiences gastric intestinal compromise, such as volvulus or ischemia, especially in patients with small defects. Clinical signs suggesting this complication include bilious aspirates, thrombocytopenia, excessively high lactates, and, critically, disproportionate hypotension or hemodynamic compromise.

Conclusion

The management of CDH requires multidisciplinary decision-making, particularly involving intensive care and surgical teams. While delayed repair strategies based on clinical stability have been traditional, improved understanding of the cardiovascular transition and the use of functional echocardiography allow for a more objective, precision-based approach. This approach emphasizes optimizing ventricular function (especially waiting for LV recovery) before repair, ensuring the patient is maximally stable for surgery. The current evolution in CDH care is akin to a complex docking procedure: instead of simply waiting for the largest vessel to appear stable, precision hemodynamics allows caregivers to measure the velocity and stability of all the engine components (the ventricles) to determine the exact moment when the system is operating optimally, providing the maximum chance for a smooth and successful transition.