ECPR and Harlequin Syndrome

CASE PRESENTATION: 57 year old male presented in ER with chest pain and diaphoresis since 1 hour. ECG showed acute anterior wall myocardial infarction. Loading dose was given. Patient was being taken for primary angioplasty (PAMI) but had episode of Ventricular Fibrillation (VF), hence defibrillated. Rhythm changed to Pulseless Electrical Activity (PEA) and Cardio-Pulmonary Resuscitation (CPR) was started as per ACLS protocol. Patient was simultaneously intubated and mechanically ventilated. As patient fulfilled criteria for Extra-Corporeal Cardio-Pulmonary resuscitation (ECPR) he was put on V-A ECMO support through femoro-femoral route (Fig. 1) and taken to Cath lab where PAMI to LAD stenting done. As patient was unstable he was also put on Impella 2.5 device support (Fig. 2). Patient was shifted to ICU from Cath lab on Noradrenaline, Vasopressin and Adrenaline support. On Day 2 patient had episode of malena and oozing from cannulation site. TEG was done and appropriate products were transfused. In view of decreased urine output and persistent metabolic acidosis patient was started on CRRT support. Neurological assessments done regularly by giving sedation breaks showed good response. On Day 3 SpO2 of right arm dropped to 86% and arterial blood gas showed PaO2 of 45 mm of Hg. The SpO2 and PaO2 values from other extremities were normal with similar ventilator and ECMO flow rate settings. When the ECMO flow rate was reduced from 2.8 litres/min to 0.8 litres/min there was return of pulsatile flow as seen on arterial waveform but decrease in saturation from 100% to 88% with settings on mechanical ventilator unchanged (Figs 3, 4, 5, 6 and 7). Echocardiogram showed improvement of LV systolic function with Impella Support. So Harlequin syndrome was diagnosed as patient had differential hypoxia. Chest X-ray also demonstrated bilateral lower lobes atelectasis. Bronchoscopy was done and broncho alveolar lavage was given to remove thick purulent secretions. High PEEP of 10–12 was given to treat atelectasis. Negative fluid balance was maintained. Patient improved on Day 5 with normal oxygenation in all extremities. ECMO support was successfully removed on Day 6. Impella was removed on day 7. Patient recovered and was discharged on day 14. DISCUSSION: Extracorporeal cardiopulmonary resuscitation (ECPR)(1,2) is a salvage procedure in which veno- arterial extracorporeal membrane oxygenation (V-A ECMO) is initiated on patients who have had cardiac arrest and on whom the conventional cardiopulmonary resuscitation (CCPR) has failed. In V-A ECMO, blood is drained from a central vein, pumped through a membrane lung, and returned through an artery, providing both gas exchange and circulatory support(3). The aim of ECPR is to provide adequate perfusion to the end-organs and has certain inclusion criteria like witnessed cardiac arrest, no flow time <5 minutes, VF/VT rhythm, age 18–65 years and ability to initiate ECPR within 60 minutes of collapse. CCPR can provide only 25 to 30% of cardiac output(4) but adequate end-organ perfusion (especially brain and heart) can be achieved with ECPR and low flow duration can be reduced(5). Harlequin syndrome (also known as North-South syndrome or Differential Hypoxia) is a known complication of peripheral VA-ECMO with an incidence around 8.8%(6,7). It occurs when the heart function is preserved or recovering but the lungs are still poorly functioning. Hence the native cardiac output flows against the pumped blood usually in the aortic arch region. Depending on the amount of native cardiac function the location of the interface between antegrade and retrograde flow may vary. With poor gas exchange and improved cardiac output a significant amount of poorly oxygenated blood is ejected from the left ventricle. The oxygenated reinfused blood from peripheral V-A ECMO may not reach the aortic arch and the coronary arteries, thus supra-aortic vessel are pumped with hypoxic blood leading to inadequate perfusion of heart and brain(3). As the right radial artery is a branch of the brachiocephalic trunk which is originating from aortic arch, so the blood oxygen content of the right radial artery is monitored to detect the development of Harlequin syndrome. Also with reducing flow rate on V-A ECMO if there is increasing pulsatility as seen on multi-para monitor, this implies improved native cardiac function. Also this can be confirmed by echocardiogram. Thus poor oxygenation of right arm with improved cardiac function and inadequate pulmonary function leads to differential hypoxia. Early recognition of Harlequin syndrome is crucial as it may prevent damage of vital organs due to hypoxia. Troubleshooting options include improving pulmonary function by Bronchoscopic removal of mucus plug, fluid removal and maintaining negative fluid balance, High PEEP to manage atelectasis. Other methods include increasing ECMO blood flow to full cardiac output, beta blockers to reduce native cardiac output till improvement in pulmonary function, relocation of the arterial cannula into the right subclavian artery or aorta(6), or converting to central VA-ECMO. It can also be solved by converting to a VA-V setting, where an additional return cannula may be added to the configuration with a “Y” connection off the femoral arterial reinfusion cannula or additional return canula insertion into an internal jugular vein. If the cardiac function is adequate can switch to V-V ECMO also. CONCLUSION: This case highlights early identification of Harlequin Syndrome in patient on peripheral V-A ECMO which is a known complication and measures taken to prevent development of hypoxia. We identified lung pathology causing differential hypoxia and used bronchoscopic removal of thick secretions, High PEEP and negative fluid balance to improve lung function. Other options included switching to V-V ECMO support with improving cardiac function or V-A-V ECMO with additional inflow cannula to jugular vein if cardiac function is not adequate. Our patient's successful outcome was due to timely ECPR support followed by primary angioplasty, use of Impella 2.5 device, CRRT and also troubleshooting of various other complications like Harlequin Syndrome by multidisciplinary approach. Early recognition and appropriate therapeutic strategies, which are case specific, are essential to improve patient outcomes in such complex clinical scenarios.