Understanding North-South Syndrome and Its Impact on VA ECMO

North-South Syndrome, also known as Harlequin Syndrome or Differential Hypoxia, is a critical condition that can occur in patients on peripheral Veno-Arterial Extracorporeal Membrane Oxygenation (VA ECMO). This phenomenon primarily affects the upper body, including the heart and brain, leading to significant complications if not promptly recognized and addressed. Let's explore what North-South Syndrome is, how it affects patients on VA ECMO, and strategies to correct this issue.

What is North-South Syndrome?

North-South Syndrome arises when there is differential oxygenation between the upper and lower parts of the body. In VA ECMO, blood is typically drained from a large vein and returned to a large artery. This process supports both cardiac and respiratory function by oxygenating the blood and assisting with circulation. However, in some cases, the blood returning from the ECMO circuit may not adequately mix with the blood being ejected from the heart. This results in well-oxygenated blood being delivered to the lower body while the upper body receives poorly oxygenated blood.

Causes of North-South Syndrome

The syndrome occurs due to the following mechanisms:

1. Poor Mixing of Oxygenated and Native Blood: In peripheral VA ECMO, the oxygenated blood is returned to the femoral artery, which travels in a retrograde direction (against the natural flow of blood). If the heart continues to pump poorly oxygenated blood from the lungs, the upper body (perfused by the left ventricle) may receive less oxygenated blood.

2. LV Ejection: The left ventricle may still eject some of the poorly oxygenated blood from the native circulation into the aorta, leading to differential oxygenation.

3. High Cardiac Output States: Conditions such as sepsis or significant agitation can increase the cardiac output, exacerbating the mixing problem.

Fig 1: Illustration of mixing cloud evolution in North South Syndrome. Retrieved from Ruiz, A., Ghadimi, K., et al. (2019). Journal of Cardiothoracic and Vascular Anesthesia. 33(5), S1053-0770.

Impact on Patients

North-South Syndrome can lead to severe hypoxia in critical organs such as the brain and heart, causing:

- Neurological Complications: Altered mental status, seizures, or stroke due to inadequate oxygenation of the brain.

- Cardiac Complications: Myocardial ischemia or infarction due to poor oxygen delivery to the heart muscle.

- Overall Organ Dysfunction: Multiple organ dysfunction syndrome (MODS) if the hypoxia is not corrected promptly.

Recognizing North-South Syndrome

Early recognition is crucial for effective management. Indicators include:

- Differential Oxygen Saturation: Notable differences in oxygen saturation between the upper and lower extremities. For instance, low right radial artery oxygen saturation compared to femoral artery saturation/left radial artery saturation.

- Clinical Symptoms: Signs of hypoxia in the upper body, such as cyanosis (bluish discoloration of the skin), confusion, or chest pain.

Strategies to Correct North-South Syndrome

Addressing North-South Syndrome involves several strategies:

1. Optimize ECMO Flow: Ensuring that the ECMO circuit provides adequate flow to support oxygenation needs.

2. Adjust Cannula Positioning: 

 - Central Cannulation: Switching from peripheral to central cannulation can help as it allows for better mixing of oxygenated blood. Blood is typically returned to the aortic root or ascending aorta, closer to the heart, ensuring more effective distribution.

 - Cannulation Strategy: Placing or switching to an additional arterial cannula to the right axillary or subclavian artery can help deliver oxygenated blood directly to the upper body. Adding another return cannula to the RIJ and converting to VAV ECMO can be utilized as well in situations where the pulmonary system needs additional support. 

3. Adjust Native Cardiac Output:

 - Using inotropes or other supportive measures to enhance the left ventricular ejection fraction, promoting better mixing.

4. Adjust Ventilator Settings: Improving the native lung function to enhance the oxygen content of the blood ejected by the heart.

5. Atrial Septostomy: In severe cases, creating a shunt between the right and left atria can help mix oxygenated and deoxygenated blood, improving systemic oxygenation.

Case Study

Patient Background:

A 58-year-old male patient with cardiogenic shock secondary to acute myocardial infarction was initiated on VA ECMO due to refractory hemodynamic instability despite maximal medical therapy. Initial cannulation was performed with a drainage cannula placed in the femoral vein and a return cannula in the femoral artery.

Phase 1: Identifying North-South Syndrome

- Symptoms: Differential cyanosis was observed, with cyanosis of the upper body (head, neck, arms) and well-perfused lower body.

- Diagnostic Measures: Blood gas analysis revealed significant differences between ABGs from the right radial artery (PaO2 55 mmHg) and femoral artery (PaO2 150 mmHg).

- Hemodynamics: Mean arterial pressure (MAP) was 60 mmHg, central venous pressure (CVP) 15 mmHg, and mixed venous oxygen saturation (SvO2) 50%.

Phase 2: Correcting North-South Syndrome

1. Repositioning Cannulas: Conversion to veno-veno-arterial (VVA) ECMO with an additional venous return cannula in the internal jugular vein to improve upper body oxygenation.

2. Adjusting Flow Rates: Optimized ECMO flow rates to enhance oxygen delivery.

3. Inotropic Support: Adjusted inotropic support to balance the native cardiac output with ECMO flow.

4. Ventilation Adjustments: Increased ventilatory support with higher FiO2 and PEEP settings to improve overall oxygenation.

Phase 3: Outcomes

- Hemodynamics Post-Correction: 

 - Right Radial Artery ABG: PaO2 100 mmHg, PaCO2 40 mmHg, pH 7.35

 - Femoral Artery ABG: PaO2 150 mmHg, PaCO2 38 mmHg, pH 7.38

 - Vitals: BP 95/65 mmHg, HR 85 bpm, SpO2 95% on 50% FiO2

 - Hemodynamics: MAP 75 mmHg, CVP 12 mmHg, SvO2 65%

- Clinical Improvement: The patient's overall condition stabilized with improved systemic oxygenation, allowing for gradual weaning from ECMO support.

Conclusion

North-South Syndrome presents a significant challenge in VA ECMO management, but with prompt recognition and targeted interventions, its impact can be mitigated. Understanding the mechanisms, early indicators, and corrective strategies is crucial for healthcare professionals managing patients on VA ECMO. Effective management not only improves patient outcomes but also enhances the overall success of ECMO therapy.

References

1. Frontiers in Cardiovascular Medicine. (n.d.). Overview of Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO) support for the management of cardiogenic shock. Retrieved from https://www.frontiersin.org/articles/10.3389/fcvm.2020.594972/full

2. Journal of Clinical Medicine. (n.d.). Extracorporeal Membrane Oxygenation (VA-ECMO) in management of cardiogenic shock. Retrieved from https://www.mdpi.com/2077-0383/8/10/1602

3. Alfred ECMO Guideline. (n.d.). Differential hypoxia – Alfred ECMO guideline. Retrieved from https://ecmo.icu/

4. Critical Care Notes. (2022, August 26). Harlequin syndrome in ECMO. Retrieved from https://criticalcarenotes.com/2022/08/26/harlequin-syndrome-in-ecmo/

5. RK.MD. (n.d.). What is VA-ECMO? Retrieved from https://rk.md/2021/va-ecmo/

6. Ruiz, A., Ghadimi, K., et al. (2019). Hypoxia and Complications of Oxygenation in Extracorporeal Membrane Oxygenation. Journal of Cardiothoracic and Vascular Anesthesia, 33(5). https://doi.org/10.1053/j.jvca.2018.11.016