Relatively Increased CO2 Delivered to the Brain From the Descending Aorta Leading to an Elevated Respiratory Rate Causing Differential Hypocapnia (RIDDLER or East-West Syndrome): New Pitfalls in Awake Peripheral V-A ECMO

Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is a critical support system for patients with severe cardiac failure, often used in cases of cardiogenic shock or cardiac arrest. While it serves as a life-saving intervention, its use introduces complex physiological challenges. One such challenge, newly described in this article, is the phenomenon termed RIDDLER (Relatively Increased CO2 Delivered to the Brain from the Descending Aorta Leading to an Elevated Respiratory Rate) Syndrome, also referred to as East-West Syndrome.

The authors highlight that, in peripheral V-A ECMO, oxygenated blood is delivered in a retrograde fashion via the femoral artery, creating a competing flow dynamic between native cardiac output and ECMO support. When the heart begins to recover before the lungs, the circulation can become imbalanced, leading to regional hypoxia and hypocapnia. The most well-known manifestation of this imbalance is Harlequin syndrome (North-South Syndrome), where the upper body remains hypoxic while the lower body receives well-oxygenated ECMO blood. However, the focus of this study is a related but distinct issue—differential hypocapnia, which has been overlooked until now.

Case Study and Physiological Explanation:

A 39-year-old patient with fulminant myocarditis on peripheral ECMO and Impella 5.5 was extubated to facilitate early mobilization. Initially, the patient showed stable oxygen and CO2 levels, but shortly after, he developed tachypnea and delirium. Blood gas analysis from the right radial artery suggested hypocapnia, leading clinicians to reduce the ECMO sweep gas flow in an attempt to normalize CO2 levels. Instead of improving, the patient’s respiratory distress worsened, culminating in sedation, reintubation, and an alarming postoxygenator PaCO2 of 60 mmHg (hypercapnia).

The authors provide a step-by-step breakdown of the pathophysiology of RIDDLER syndrome:

1. Tachypnea is triggered by exertion, pain, or sepsis, causing the patient to breathe faster and expel more CO2.
2. The deoxygenated blood from the lungs, now CO2-depleted, enters the right brachiocephalic trunk but may not reach the entire cerebral circulation.
3. The ECMO clinician interprets the right radial blood gas values as global hypocapnia and mistakenly reduces ECMO CO2 clearance.
4. This leads to hypercapnic blood being delivered retrogradely to the aortic arch, where it preferentially perfuses the left common carotid artery, including respiratory control centers in the brain.
5. Cerebral hypercapnia triggers further increases in respiratory rate, creating a paradox: the radial blood gases continue to show low PaCO2 despite worsening hypercapnia elsewhere.
6. Clinicians continue to adjust the ECMO settings incorrectly, exacerbating the problem and leading to a dangerous cycle of respiratory exhaustion.

Clinical Implications and Management:

The authors emphasize the importance of early recognition of RIDDLER syndrome to prevent respiratory decompensation and neurological injury. Unlike Harlequin syndrome, which primarily involves oxygenation discrepancies, RIDDLER syndrome involves CO2 imbalances affecting cerebral function.

To diagnose and manage RIDDLER syndrome, the following strategies are recommended:

• Use postoxygenator CO2/pH measurements rather than relying solely on right radial blood gases.
• Monitor central, mixed venous, and left radial arterial blood gases to get a more comprehensive view of CO2 kinetics.
• Use echocardiography to locate the watershed area where antegrade and retrograde blood flows meet.
• Adjust ECMO sweep gas flow cautiously, matching the sweep gas to blood flow in a 1:1 ratio once in maintenance mode.
• Treat underlying causes of tachypnea (e.g., pain, anxiety, sepsis) before making ECMO adjustments.
• In severe cases, consider reintubation and neuromuscular blockade if differential hypoxia is also present.

Conclusion:

RIDDLER syndrome is a newly described iatrogenic complication of awake peripheral V-A ECMO that results in differential hypocapnia and paradoxical respiratory distress. It differs from Harlequin syndrome and requires a distinct management approach to prevent unnecessary interventions and worsening patient outcomes. Clinicians should remain vigilant for both syndromes and implement proper CO2 monitoring techniques to ensure optimal ECMO management.

Study Ranking: 3,5 (High Quality, Expert Opinion/Case Report Based on Strong Physiological Evidence) While this article introduces a novel physiological phenomenon, it is not yet backed by large-scale studies or randomized trials. The case study and mechanistic insights are compelling, but further research is needed to validate its clinical impact.