Blood flow and emboli transport patterns during venoarterial extracorporeal membrane oxygenation: A computational fluid dynamics study.

PROBLEM: Despite advances in Venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO), a significant mortality rate persists due to complications. The non-physiological blood flow dynamics of VA-ECMO may lead to neurological complications and organ ischemia. Continuous retrograde high-flow oxygenated blood enters through a return cannula placed in the femoral artery which opposes the pulsatile deoxygenated blood ejected by the left ventricle (LV), which impacts upper body oxygenation and subsequent hyperoxemia. The complications underscore the critical need to comprehend the impact of VA-ECMO support level and return cannula size, as mortality remains a significant concern. AIM: The aim of this study is to predict and provide insights into the complications associated with VA-ECMO using computational fluid dynamics (CFD) simulations. These complications will be assessed by characterising blood flow and emboli transport patterns through a comprehensive analysis of the influence of VA-ECMO support levels and arterial return cannula sizes. METHODS: Patient-specific 3D aortic and major branch models, derived from a male patient's CT scan during VA-ECMO undergoing respiratory dysfunction, were analyzed using CFD. The investigation employed species transport and discrete particle tracking models to study ECMO blood (oxygenated) mixing with LV blood (deoxygenated) and to trace emboli transport patterns from potential sources (circuit, LV, and aorta wall). Two cannula sizes (15 Fr and 19 Fr) were tested alongside varying ECMO pump flow rates (50%, 70%, and 90% of the total cardiac output). RESULTS: Cannula size did not significantly affect oxygen transport. At 90% VA-ECMO support, all arteries distal to the aortic arch achieved 100% oxygen saturation. As support level decreased, oxygen transport to the upper body also decreased to a minimum saturation of 73%. Emboli transport varied substantially between emboli origin and VAECMO support level, with the highest risk of cerebral emboli coming from the LV with a 15 Fr cannula at 90% support. CONCLUSION: Arterial return cannula sizing minimally impacted blood oxygen distribution; however, it did influence the distribution of emboli released from the circuit and aortic wall. Notably, it was the support level alone that significantly affected the mixing zone of VA-ECMO and cardiac blood, subsequently influencing the risk of embolization of the cardiogenic source and oxygenation levels across various arterial branches.

Brain death determination in patients with veno-arterial extracorporeal membrane oxygenation: A systematic study to address the Harlequin syndrome.

PURPOSE: The Harlequin syndrome may occur in patients treated with venoarterial extracorporal membrane oxygenation (VA-ECMO), in whom blood from the left ventricle and the ECMO system supply different parts of the body with different paCO2-levels. The purpose of this study was to compare two variants of paCO2-analysis to account for the Harlequin syndrome during apnea testing (AT) in brain death (BD) determination. MATERIALS AND METHODS: Twenty-seven patients (median age 48 years, 26-76 years; male n = 19) with VA-ECMO treatment were included who underwent BD determination. In variant 1, simultaneous arterial blood gas (ABG) samples were drawn from the right and the left radial artery. In variant 2, simultaneous ABG samples were drawn from the right radial artery and the postoxygenator ECMO circuit. Differences in paCO2-levels were analysed for both variants. RESULTS: At the start of AT, median paCO2-difference between right and left radial artery (variant 1) was 0.90 mmHg (95%-confidence intervall [CI]: 0.7-1.3 mmHg). Median paCO2-difference between right radial artery and postoxygenator ECMO circuit (variant 2) was 3.3 mmHg (95%-CI: 1.5-6.0 mmHg) and thereby significantly higher compared to variant 1 (p = 0.001). At the end of AT, paCO2-difference according to variant 1 remained unchanged with 1.1 mmHg (95%-CI: 0.9-1.8 mmHg). In contrast, paCO2-difference according to variant 2 increased to 9.9 mmHg (95%-CI: 3.5-19.2 mmHg; p = 0.002). CONCLUSIONS: Simultaneous paCO2-analysis from right and left distal arterial lines is the method of choice to reduce the risk of adverse effects (e.g. severe respiratory acidosis) while performing AT in VA-ECMO patients during BD determination.

Sarcoidosis-Associated Sensory Ganglionopathy and Harlequin Syndrome: A Case Report.

Background and Objectives: Sensory ganglionopathy is a rare neurological disorder caused by degeneration of the neurons composing the dorsal root ganglia. It manifests as various sensory disturbances in the trunk, proximal limbs, face, or mouth in a patchy and asymmetrical pattern. Harlequin syndrome is characterized by unilateral flushing and sweating of the face, neck, and upper chest, concurrent with contralateral anhidrosis. Here, we present and discuss a clinical case of sarcoidosis-associated ganglionopathy and Harlequin syndrome. Case presentation: A 31-year-old woman complained of burning pain in the right side of the upper chest and the feet. She also experienced episodes of intense flushing and sweating on the right side of her face, neck, and upper chest. Three years before these symptoms began, the patient was diagnosed with pulmonary sarcoidosis. On neurological examination, sensory disturbances were present. In the trunk, the patient reported pronounced hyperalgesia and allodynia in the upper part of the right chest and some patches on the right side of the upper back. In the extremities, hypoalgesia in the tips of the fingers and hyperalgesia in the feet were noted. An extensive diagnostic workup was performed to eliminate other possible causes of these disorders. A broad range of possible metabolic, immunological, and structural causes were ruled out. Thus, the final clinical diagnosis of sarcoidosis-induced sensory ganglionopathy, small-fiber neuropathy, and Harlequin syndrome was made. Initially, the patient was treated with pregabalin and amitriptyline, but the effect was inadequate for the ganglionopathy-induced pain. Therefore, therapeutic plasma exchange as an immune-modulating treatment was selected, leading to partial pain relief. Conclusions: This case report demonstrates the possible autoimmune origin of both sensory ganglionopathy and Harlequin syndrome. It suggests that an autoimmune etiology for these disorders should be considered and the diagnostic workup should include screening for the most common autoimmune conditions.

Idiopathic Harlequin Syndrome in a Patient from Ethiopia: A Case Report.

Background: Harlequin syndrome is a rare disorder caused by autonomic nervous system dysfunction. It manifests as asymmetric facial flashing and sweating with contralateral anhidrosis. It may be primary (idiopathic) with a benign course or can occur secondary to structural abnormalities or iatrogenic factors. To our knowledge, there has been no report of idiopathic Harlequin syndrome published from Ethiopia. We are reporting this case since it signifies the existence of idiopathic Harlequin syndrome in our setting and the need to properly diagnose this condition. Case Presentation: We are reporting a 29-year-old female from Addis Ababa, Ethiopia, who presented with a complaint of left hemifacial hyperhidrosis of 8 years which worsen after routine household activities and exercise. Physical examination revealed left hemifacial hyperhidrosis with right-side anhidrosis. She was diagnosed with idiopathic Harlequin syndrome after an appropriate investigation revealed a nonremarkable finding. Symptomatic treatment showed no significant improvement and the patient was also counseled on the disease entity. Conclusions: The patient described here signifies an idiopathic Harlequin syndrome in an Ethiopian woman. This case highlights the existence of idiopathic Harlequin syndrome within our setting and the need to properly diagnose this condition.

Harlequin syndrome during peripheral cardiopulmonary bypass in a patient with an obstructing tracheal schwannoma: A case report.

Surgical resection of obstructive tracheal tumors can be challenging to cardiothoracic surgeons and anesthesiologists. It is often difficult in these cases to maintain oxygenation by face mask ventilation during induction of general anesthesia. Also, the extent and location of these tracheal tumors can preclude conventional induction of general anesthesia and subsequent successful endotracheal intubation. Peripheral cardiopulmonary bypass (CPB) under local anesthesia and mild intravenous sedation may be safe to support the patient until securing a definitive airway. We describe a case of a 19-year-old female with a tracheal schwannoma, who developed differential hypoxemia (Harlequin, or North-South, syndrome) after institution of awake peripheral femorofemoral venoarterial (VA) partial CBP.

Harlequin syndrome.

A 56-year-old man presented to the clinic with episodic headaches for several years which had been worsening over a few months prior to the presentation. He described headache as sharp, stabbing pain around the left eye associated with nausea, vomiting, photophobia, and phonophobia lasting for hours associated with flushing on the left side of the face. The picture of his face during these episodes showed flushing of the left side of the face, ptosis of the right eyelid, and miosis (panel A). Flushing in his face would resolve with the abortion of the headache. At the time of presentation to the clinic, his neurological exam was only significant for mild left eye ptosis and miosis (panels B and C). Extensive workup including MRI brain, cervical spine, thoracic spine, lumbar spine, CTA head and neck, and CT maxillofacial was unremarkable. He had tried several medications in the past including valproic acid, nortriptyline, and verapamil without significant benefit. He was started on erenumab for migraine prophylaxis and was given sumatriptan for abortive therapy following which his headaches improved. The patient was diagnosed with idiopathic left Horner's syndrome and his migraines with autonomic dysfunction would present with unilateral flushing opposite to the site of Horner's presenting as Harlequin syndrome [1, 2].

Management of harlequin syndrome under ECPELLA support: A report of two cases and a proposed approach.

The use of ECPELLA in patients with severe lung disease may result in an unfavorable phenomenon of differential hypoxia. The simultaneous evaluation of three arterial blood samples from different arterial line (right radial artery, left radial artery, ECMO arterial line) in patients at risk of Harlequin syndrome (also called differential hypoxemia (DH)) can localize the "mixing cloud" along the aorta. Focusing the attention on the "mixing cloud" position instead of on isolated flows of Veno-Arterial Extracorporeal Membrane Oxygenation (VA ECMO) and Impella CP makes the decision making easier about how to modify MCSs flows according to the clinical context. Herein, we present two cases in which ECPELLA configuration was used to treat a cardiogenic shock condition and how the ECPELLA-induced hypoxia was managed.

Harlequin color change in a newborn who was positive for COVID-19: report of a case

Harlequin color change is a benign, idiopathic, self-limiting disorder characterized by the appearance of skin divided into two distinctly colored areas. Its etiology is unknown but thought to be caused by immaturity of hypothalamic regulation of peripheral vascular tone. COVID-19 infection in neonates is infrequent and rarely symptomatic, with only a few cases described in the literature. In isolation, both conditions have a low incidence. It is the first case reported in the world literature of harlequin color change in a newborn who tested positive for COVID-19. There isn't a single publication that links harlequin color change to COVID-19.

El cambio de color arlequín es un trastorno benigno, idiopático y autolimitado que se caracteriza por una apariencia de la piel dividida en dos zonas de color distinto. Su etiología es desconocida, pero se cree que está causada por una inmadurez hipotalámica del tono vascular periférico. La infección por COVID-19 en neonatos es infrecuente y raramente sintomática, con sólo unos pocos casos descritos en la literatura. De forma aislada, ambas afecciones tienen una baja incidencia. Este es el primer caso descrito en la literatura mundial de cambio de coloración arlequín en un recién nacido que dio positivo a COVID-19. Aun no existe ninguna publicación que relacione el cambio de color arlequín con COVID-19.

Video-assisted thoracoscopic sympathectomy for Harlequin syndrome.

Harlequin syndrome is an exceedingly rare condition, characterized by unilateral facial flushing and hyperhidrosis. Postulated to be dysregulated sympathetic nervous system stimulation of the dermal vasculature and blood vessels of the face. There is no clear unifying pathological cause. Due to its heterogeneity and rarity, very little is known about the treatment of it. Hereafter, we describe our experience in successfully curing right-sided Harlequin syndrome through video-assisted thoracoscopic sympathectomy.

The effect of arterial cannula tip position on differential hypoxemia during venoarterial extracorporeal membrane oxygenation.

Interaction between native ventricular output and venoarterial extracorporeal membrane oxygenation (VA ECMO) flow may hinder oxygenated blood flow to the aortic arch branches, resulting in differential hypoxemia. Typically, the arterial cannula tip is placed in the iliac artery or abdominal aorta. However, the hemodynamics of a more proximal arterial cannula tip have not been studied before. This study investigated the effect of arterial cannula tip position on VA ECMO blood flow to the upper extremities using computational fluid dynamics simulations. Four arterial cannula tip positions (P1. common iliac, P2. abdominal aorta, P3. descending aorta and P4. aortic arch) were compared with different degrees of cardiac dysfunction and VA ECMO support (50%, 80% and 90% support). P4 was able to supply oxygenated blood to the arch vessels at all support levels, while P1 to P3 only supplied the arch vessels during the highest level (90%) of VA ECMO support. Even during the highest level of support, P1 to P3 could only provide oxygenated VA-ECMO flow at 0.11 L/min to the brachiocephalic artery, compared with 0.5 L/min at P4. This study suggests that cerebral perfusion of VA ECMO flow can be increased by advancing the arterial cannula tip towards the aortic arch.

Harlequin Syndrome Following Regional Liposomal Bupivacaine Use in a Partial Sternectomy.

Harlequin syndrome is a condition in which disruption of the autonomic nervous system results in ipsilateral anhidrosis and pallor of the face. We report the first documented case of Harlequin syndrome following the use of liposomal bupivacaine, in which a patient developed symptoms five hours after a bilateral erector spinae plane (ESP) block with liposomal bupivacaine before partial sternectomy. It is additionally unique as the first report of delayed onset of symptoms. The proposed mechanism is the diffusion of the anesthetic into the paravertebral space with cephalad migration to the T2-T3 level, where facial vasomotor fibers exit the spinal cord.

Harlequin syndrome induced by intraspinal analgesia in patients with advanced cancer: a case report.

Background: The Harlequin syndrome is an idiopathic, autonomic disorder. It typically presents with unilateral sweating and flushing of the face. It could be caused not only by autonomic dysfunction or space-occupying central neuropathy, but by some clinical interventions as well. Although iatrogenic Harlequin syndrome is rare, clinicians should be aware of this condition to diagnose correctly and provide suitable assistance. Case Description: Here we report a case of iatrogenic Harlequin syndrome. The unique part of this case is that this patient presented with successive presentations of Harlequin syndrome on different sides of the body. The patient was a 30-40-year-old woman who had flushing and sweating on one side of the face after intraspinal analgesia. This symptom disappeared on its own after a period of persistence, and reappeared several days later after increasing the dose of the drug injected into the epidural cavity. Interestingly, the second blush appeared on the other side of the patient's face. Conclusions: Triggered by intraspinal analgesia and manifested in different body parts, Harlequin syndrome is proven here to be derived from iatrogenic stimuli. We believe that the different distribution states of analgesic drugs after entering the spinal canal can promote Harlequin syndrome to manifest in different body parts.

Mini-Review on the Harlequin Syndrome-A Rare Dysautonomic Manifestation Requiring Attention.

Harlequin syndrome (HS) is a rare autonomic disorder. The causes and risk factors of the disease are not fully understood. Some cases of HS are associated with traumatic injuries, tumors, or vascular impairments of the head. Symptoms of HS can also occur in some autoimmune disorders, ophthalmic disorders, sleep disorders, and with certain organic lesions. In this context, a thorough review of the pathophysiology of HS in relation to neurological, ophthalmological, and dermatological conditions is necessary. In this mini-review, we aim to review the pathophysiological changes and underlying mechanisms in primary and secondary HS. Additionally, we discuss possible management approaches for patients with HS in light of the discussed pathological mechanisms. The main symptoms of HS that are correlated with autonomic nervous system impairments include sudden unilateral flushing of the face, neck, chest, and rarely arm, with concurrent contralateral anhidrosis. Despite reported co-occurring syndromes (such as cluster headaches), several studies have shown that HS could frequently overlap with other syndromes that are disruptive to the idiopathic nerve pathways. HS usually does not require any medical treatment. In some severe cases, symptomatic treatments could be needed. However, total symptomatic relief may not be achieved in many cases of HS. We therefore suggest an approach to comprehensive management of HS, which may lead to better long-term control of HS.

Harlequin syndrome: An asymmetric face.

Harlequin syndrome corresponds to unilateral dysfunction of the sympathetic system, characterized by flush and unilateral hyperhidrosis associated with hypo or anhidrosis and paleness of the opposite side. It is, usually, idiopathic. Rarely, it may be associated with compressive organic processes, iatrogenic causes, and general diseases. It is a real therapeutic challenge.

Managing Harlequin Syndrome in VA-ECMO - do not forget the right ventricle.

Harlequin Syndrome (also known as North-South Syndrome) is a complication of veno-arterial extracorporeal membrane oxygenation (V-A ECMO) that can occur when left ventricular function starts to recover. While most commonly due to continued impaired gas exchange in the lungs, we present a case caused by right ventricular dysfunction, successfully managed by conversion of the ECMO circuit to a veno-veno-arterial (VV-A) configuration.

Harlequin syndrome in a young girl: An opportunity to rethink the terminology.

Harlequin syndrome is a rare disorder of the autonomic nervous system, presenting as unilateral reduced flushing and sweating of the face induced by exercise, stress, or heat. It is caused by a cervical sympathetic deficit located at the preganglionic or postganglionic level on the non-flushing side. We present a case of an 8 year old with harlequin syndrome and review the other dermatological conditions for which the term "harlequin" is part of the nomenclature.

Case Report: Left Ventricular Unloading Using a Mechanical CPR Device in a Prolonged Accidental Hypothermic Cardiac Arrest Treated by VA-ECMO - a Novel Approach.

We recently treated a 36-year-old previously healthy male with a prolonged hypothermic (lowest temperature 22.3°C) cardiac arrest after an alcohol intoxication with a return of spontaneous circulation after 230min of mechanical cardiopulmonary resuscitation and rewarming by veno-arterial ECMO with femoral cannulation and retrograde perfusion of the aortic arch. Despite functional veno-arterial ECMO, we continued mechanical cardiopulmonary resuscitation (Auto Pulse™ device, ZOLL Medical Corporation, Chelmsford, USA) until return of spontaneous circulation to prevent left ventricular distention from persistent ventricular fibrillation. The case was further complicated by extensive trauma caused by mechanical cardiopulmonary resuscitation (multiple rib fractures, significant hemothorax, and a liver laceration requiring massive transfusion), lung failure necessitating a secondary switch to veno-venous ECMO, and acute kidney injury with the need for renal replacement therapy. Shortly after return of spontaneous circulation, the patient was already following commands and could be discharged 3 weeks later without neurologic, cardiac, or renal sequelae and being entirely well. Prolonged accidental hypothermic cardiac arrest might present with excellent outcomes when supported with veno-arterial ECMO. Until return of spontaneous circulation, one might consider continuing with mechanical cardiopulmonary resuscitation in addition to ECMO to allow some left ventricular unloading. However, the clinician should keep in mind that prolonged mechanical cardiopulmonary resuscitation may cause severe injuries.

Successful treatment of idiopathic Harlequin Syndrome with oxybutynin and propranolol.

Harlequin syndrome (HS) is a rare entity derived from the dysfunction of the sympathetic nervous system. It is characterised by unilateral facial flushing and sweating induced by exercise, heat and emotion. Most cases are primary with an unknown pathogenic mechanism. In these cases, the prognosis is favourable. Medical or surgical treatments are not usually required for idiopathic HS. However, symptomatic treatment may be indicated when symptoms affect the quality of life of patients. We present the case of a patient with idiopathic HS successfully treated with oxybutynin and propranolol. In this patient, a marked improvement in both hyperhidrosis and facial erythema was noted with this combined therapy. We consider it of interest to highlight the response of our patient to the treatment employed, which may be advantageous in future cases of this rare disorder.