Capillary leak and endothelial permeability in critically ill patients: a current overview

Saravi, B., Goebel, U., Hassenzahl, L.O. et al. Capillary leak and endothelial permeability in critically ill patients: a current overview. ICMx 11, 96 (2023). https://doi.org/10.1186/s40635-023-00582-8

Summary of "Capillary leak and endothelial permeability in critically ill patients: a current overview"

Abstract

Capillary leak syndrome (CLS) results in excessive fluid leakage from the vascular system into the extravascular space, leading to intravascular hypovolemia, edema, and tissue hypoperfusion. This condition, often caused by systemic inflammation, disrupts endothelial cell interactions and damages the endothelial glycocalyx. Though the syndrome is commonly identified by clinical symptoms, there are no established diagnostic criteria. This review discusses the pathophysiology, clinical presentation, and potential treatments for CLS, emphasizing the need for diagnostic standardization and more targeted therapies to improve patient outcomes.

Key Points:

1. Pathophysiology of CLS:

- CLS is characterized by increased endothelial permeability, resulting in fluid extravasation, generalized edema, and hypovolemia.

- Systemic inflammation, infections, and endothelial activation lead to CLS, often through the breakdown of inter-endothelial cell adhesion.

- The shedding of the endothelial glycocalyx and the disruption of the angiopoietin–Tie2 signaling pathway are critical mechanisms in CLS development.

2. Clinical Triggers of CLS:

- CLS can be triggered by various conditions, including sepsis, cardiac surgery, anaphylaxis, and major trauma.

- Drugs such as certain interleukins, monoclonal antibodies, and chemotherapy agents have also been associated with CLS.

3. Endothelial Barrier Breakdown:

- Endothelial dysfunction is a core feature of CLS, leading to increased capillary permeability.

- The endothelium regulates fluid exchange, but during systemic inflammation, this balance is disrupted, causing fluid leakage into tissues.

4. Glycocalyx Shedding:

- The glycocalyx, a protective layer on the endothelial surface, is degraded during inflammation, contributing to capillary leakage.

- The degradation process involves enzymes like heparanase-1 and metalloproteinases, exacerbating vascular permeability and fluid shifts.

5. Fluid Overload and Dynamics:

- The altered fluid dynamics in CLS, including the movement of protein-rich fluid into the interstitial space, increase the risk of pulmonary and intestinal edema.

- Fluid overload in critically ill patients is associated with worsened outcomes, such as prolonged mechanical ventilation, acute kidney injury, and increased mortality.

6. Diagnosis:

- CLS diagnosis is challenging due to the lack of standardized criteria.

- Diagnostic methods include bioelectrical impedance analysis (BIA) to measure fluid shifts and serum biomarkers like Angiopoietin-2 and Syndecan-1.

- The Vascular Leak Index and invasive techniques, such as transpulmonary thermodilution, help assess vascular leak and fluid status in critically ill patients.

7. Therapeutic Approaches:

- Currently, treatment focuses on managing fluid balance and minimizing the harmful effects of fluid overload.

- New experimental approaches target endothelial stabilization through agents like phosphodiesterase inhibitors and albumin infusion to preserve the endothelial surface layer (ESL).

- Preserving the glycocalyx and maintaining endothelial integrity are emerging therapeutic goals.

Conclusion

CLS is a complex condition with significant implications for critically ill patients. The lack of uniform diagnostic criteria and specific treatments necessitates further research into its pathophysiology and the development of more targeted therapeutic strategies.

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Discussion Questions:

1. What are the key challenges in diagnosing CLS, and how can emerging biomarkers improve diagnostic accuracy?

2. How can fluid management in CLS patients be optimized to prevent fluid overload while maintaining organ perfusion?

3. What role do emerging therapies, such as endothelial stabilization, play in managing CLS, and how can they be integrated into current clinical practice?

Javier Amador-Casta?eda, BHS, RRT, FCCM

Interprofessional Critical Care Network (ICCN)

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