Hereditary angioedema in cardiac surgery: Perioperative management considerations for a rare disease.

INTRODUCTION: Hereditary Angioedema is a rare disease caused by C1 esterase inhibitor deficiency leading to diffuse and potentially life-threatening oedema formation. Preventing attacks is critical, particularly for patients undergoing cardiac surgery. CASE REPORT: We report a case of a 71-years-old woman with a history of Hereditary Angioedema scheduled for open-heart surgery on Cardiopulmonary Bypass. Multidisciplinar teamwork and patient-targeted strategy were crucial to obtain a favorable outcome. DISCUSSION: Cardiac surgery is a major stressor for Angioedema attacks because of Complement cascade and inflammatory response activation leading to potential life-threatening oedema formation. In literature only few cases of complex open heart surgery under Cardiopulmonary Bypass are described. CONCLUSION: Continuous updating and multidisciplinarity are key elements to manage patients with Hereditary Angioedema in cardiac surgery in order to reduce morbidity and mortality.

International survey of neuromonitoring and neurodevelopmental outcome in children and adults supported on extracorporeal membrane oxygenation in Europe.

BACKGROUND: Adverse neurological events during extracorporeal membrane oxygenation (ECMO) are common and may be associated with devastating consequences. Close monitoring, early identification and prompt intervention can mitigate early and late neurological morbidity. Neuromonitoring and neurocognitive/neurodevelopmental follow-up are critically important to optimize outcomes in both adults and children. OBJECTIVE: To assess current practice of neuromonitoring during ECMO and neurocognitive/neurodevelopmental follow-up after ECMO across Europe and to inform the development of neuromonitoring and follow-up guidelines. METHODS: The EuroELSO Neurological Monitoring and Outcome Working Group conducted an electronic, web-based, multi-institutional, multinational survey in Europe. RESULTS: Of the 211 European ECMO centres (including non-ELSO centres) identified and approached in 23 countries, 133 (63%) responded. Of these, 43% reported routine neuromonitoring during ECMO for all patients, 35% indicated selective use, and 22% practiced bedside clinical examination alone. The reported neuromonitoring modalities were NIRS (n = 88, 66.2%), electroencephalography (n = 52, 39.1%), transcranial Doppler (n = 38, 28.5%) and brain injury biomarkers (n = 33, 24.8%). Paediatric centres (67%) reported using cranial ultrasound, though the frequency of monitoring varied widely. Before hospital discharge following ECMO, 50 (37.6%) reported routine neurological assessment and 22 (16.5%) routinely performed neuroimaging with more paediatric centres offering neurological assessment (65%) as compared to adult centres (20%). Only 15 (11.2%) had a structured longitudinal follow-up pathway (defined followup at regular intervals), while 99 (74.4%) had no follow-up programme. The majority (n = 96, 72.2%) agreed that there should be a longitudinal structured follow-up for ECMO survivors. CONCLUSIONS: This survey demonstrated significant variability in the use of different neuromonitoring modalities during and after ECMO. The perceived importance of neuromonitoring and follow-up was noted to be very high with agreement for a longitudinal structured follow-up programme, particularly in paediatric patients. Scientific society endorsed guidelines and minimum standards should be developed to inform local protocols.

Risk Factors of Ischemic and Hemorrhagic Strokes During Venovenous Extracorporeal Membrane Oxygenation: Analysis of Data From the Extracorporeal Life Support Organization Registry.

OBJECTIVES: Stroke is commonly reported in patients receiving venovenous extracorporeal membrane oxygenation, but risk factors are not well described. We sought to determine preextracorporeal membrane oxygenation and on-extracorporeal membrane oxygenation risk factors for both ischemic and hemorrhagic strokes in patients with venovenous extracorporeal membrane oxygenation support. DESIGN: Retrospective analysis. SETTING: Data reported to the Extracorporeal Life Support Organization by 366 extracorporeal membrane oxygenation centers from 2013 to 2019. PATIENTS: Patients older than 18 years supported with a single run of venovenous extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 15,872 venovenous extracorporeal membrane oxygenation patients, 812 (5.1%) had at least one type of acute brain injury, defined as ischemic stroke, hemorrhagic stroke, or brain death. Overall, 215 (1.4%) experienced ischemic stroke and 484 (3.1%) experienced hemorrhagic stroke. Overall inhospital mortality was 36%, but rates were higher in those with ischemic or hemorrhagic stroke (68% and 73%, respectively). In multivariable analysis, preextracorporeal membrane oxygenation pH (adjusted odds ratio = 0.10; 95% CI, 0.03-0.35; p < 0.001), hemolysis (adjusted odds ratio = 2.27; 95% CI, 1.22-4.24; p = 0.010), gastrointestinal hemorrhage (adjusted odds ratio = 2.01; 95% CI 1.12-3.59; p = 0.019), and disseminated intravascular coagulation (adjusted odds ratio = 3.61; 95% CI, 1.51-8.66; p = 0.004) were independently associated with ischemic stroke. Pre-extracorporeal membrane oxygenation pH (adjusted odds ratio = 0.28; 95% CI, 0.12-0.65; p = 0.003), preextracorporeal membrane oxygenation Po2 (adjusted odds ratio = 0.96; 95% CI, 0.93-0.99; p = 0.021), gastrointestinal hemorrhage (adjusted odds ratio = 1.70; 95% CI, 1.15-2.51; p = 0.008), and renal replacement therapy (adjusted odds ratio=1.57; 95% CI, 1.22-2.02; p < 0.001) were independently associated with hemorrhagic stroke. CONCLUSIONS: Among venovenous extracorporeal membrane oxygenation patients in the Extracorporeal Life Support Organization registry, approximately 5% had acute brain injury. Mortality rates increased two-fold when ischemic or hemorrhagic strokes occurred. Risk factors such as lower pH and hypoxemia during the pericannulation period and markers of coagulation disturbances were associated with acute brain injury. Further research on understanding preextracorporeal membrane oxygenation and on-extracorporeal membrane oxygenation risk factors and the timing of acute brain injury is necessary to develop appropriate prevention and management strategies.

Mortality Predictors in Elderly Patients With Cardiogenic Shock on Venoarterial Extracorporeal Life Support. Analysis From the Extracorporeal Life Support Organization Registry.

OBJECTIVES: Because significantly higher mortality is observed in elderly patients undergoing venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock, decision-making in this setting is challenging. We aimed to elucidate predictors of unfavorable outcomes in these elderly (≥ 70 yr) patients. DESIGN: Analysis of international worldwide extracorporeal life support organization registry. SETTING: Refractory cardiogenic shock due to various etiologies (cardiac arrest excluded). PATIENTS: Elderly patients (≥ 70 yr). INTERVENTIONS: Venoarterial extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: Three age groups (70-74, 75-79, ≥80 yr) were in-depth analyzed. Uni- and multivariable analysis were performed. From January 1997 to December 2018, 2,644 patients greater than or equal to 70 years (1,395 [52.8%] 70-74 yr old, 858 [32.5%] 75-79 yr, and 391 [14.8%] ≥ 80 yr old) were submitted to venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock with marked increase in the most recent years. Peripheral access was applied in majority of patients. Median extracorporeal membrane oxygenation support duration was 3.5 days (interquartile range: 1.6-6.1 d), (3.9 d [3.7-4.6 d] in patients ≥ 80 yr) (p < 0.001). Weaning from extracorporeal membrane oxygenation was possible in 1,236 patients (46.7%). Overall in-hospital mortality was estimated at 68.3% with highest crude mortality rates observed in 75-79 years old subgroup (70.1%). Complications were mostly cardiovascular and bleeding, without apparent differences between subgroups. Airway pressures, 24-hour pH after extracorporeal membrane oxygenation start, extracorporeal membrane oxygenation duration, and renal replacement therapy were predictive of higher mortality. In-hospital mortality was lower in heart transplantation recipients, posttranscatheter aortic valve replacement, and pulmonary embolism; conversely, higher mortality followed extracorporeal membrane oxygenation institution after coronary artery bypass + valve and in decompensated chronic heart failure, and nearly 100% mortality followed in extracorporeal membrane oxygenation for sepsis. CONCLUSIONS: This study confirmed the remarkable increase of venoarterial extracorporeal membrane oxygenation use in elderly affected by refractory cardiogenic shock. Despite in-hospital mortality remains high, venoarterial extracorporeal membrane oxygenation should still be considered in such setting even in elderly patients, since increasing age itself was not linked to increased mortality, whereas several predictors may guide indication and management.

Brain Injury in Extracorporeal Membrane Oxygenation: A Multidisciplinary Approach.

Extracorporeal membrane oxygenation (ECMO) represents an established technique to provide temporary cardiac and/or pulmonary support. ECMO, in veno-venous, veno-arterial or in extracorporeal carbon dioxide removal modality, is associated with a high rate of brain injuries. These complications have been reported in 7 to 15% of adults and 20% of neonates, and are associated with poor survival. Thromboembolic events, loss of cerebral autoregulation, alteration of the blood-brain barrier, and hemorrhage related to anticoagulation represent the main causes of severe brain injury during ECMO. The most frequent forms of acute neurological injuries in ECMO patients are intracranial hemorrhage (2-21%), ischemic stroke (2-10%), seizures (2-6%), and hypoxic-ischemic brain injury; brain death may also occur in this population. Other frequent complications are infarction (1-8%) and cerebral edema (2-10%), as well as neuropsychological and psychiatric sequelae, including posttraumatic stress disorder.

Dynamic extracorporeal life support: A novel management modality in temporary cardio-circulatory assistance.

Extracorporeal life support (ECLS) is a temporary mechanical assistance method employed in acute respiratory, cardiocirculatory, and cardio-respiratory failure, refractory to conventional treatments. Patient's hemodynamic, respiratory and metabolic condition, or situations related to ECLS support or performance, may change during ECLS treatment. Provision of an additional drainage or perfusion cannula, or even of an additional associated device, for example, transaortic suction device or intra-aortic balloon pump (IABP), may be required to improve the ECLS/patient interaction and effects. Besides such a modified ECLS mode, however, a potential asset is represented by the "dynamic ECLS," which is the change of the flow direction (drainage or perfusion) in the already implanted cannula during the ECLS run. This particular management may be achieved in venous femoral or jugular cannulation, but it finds an even more appealing potential with the pulmonary artery (PA) cannulation. The PA allows the institution of a multitasking ECLS circuit, ranging from enhanced left ventricle (LV) unloading (drainage from the PA) to a right ventricular support or "central" veno-venous ECLS (perfusing the PA), tailored according to the patient hemodynamic, gas exchange, metabolic state, underlying cardiac involvement, and ECLS performance. Dynamic ECLS may, therefore, represent an additional option in ECLS management, particularly including the PA cannulation. Based on this new dynamic management of ECLS mode, we propose the Extracorporeal Life Support Organization nomenclature update.

Modifiable Risk Factors and Mortality From Ischemic and Hemorrhagic Strokes in Patients Receiving Venoarterial Extracorporeal Membrane Oxygenation: Results From the Extracorporeal Life Support Organization Registry.

OBJECTIVES: Although acute brain injury is common in patients receiving extracorporeal membrane oxygenation, little is known regarding the mechanism and predictors of ischemic and hemorrhagic stroke. We aimed to determine the risk factors and outcomes of each ischemic and hemorrhagic stroke in patients with venoarterial extracorporeal membrane oxygenation support. DESIGN: Retrospective analysis. SETTING: Data reported to the Extracorporeal Life Support Organization by 310 extracorporeal membrane oxygenation centers from 2013 to 2017. PATIENTS: Patients more than 18 years old supported with a single run of venoarterial extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 10,342 venoarterial extracorporeal membrane oxygenation patients, 401 (3.9%) experienced ischemic stroke and 229 (2.2%) experienced hemorrhagic stroke. Reported acute brain injury during venoarterial extracorporeal membrane oxygenation decreased from 10% to 6% in 5 years. Overall in-hospital mortality was 56%, but rates were higher when ischemic stroke and hemorrhagic stroke were present (76% and 86%, respectively). In multivariable analysis, lower pre-extracorporeal membrane oxygenation pH (adjusted odds ratio, 0.21; 95% CI, 0.09-0.49; p < 0.001), higher PO2 on first day of extracorporeal membrane oxygenation (adjusted odds ratio, 1.01; 95% CI, 1.00-1.02; p = 0.009), higher rates of extracorporeal membrane oxygenation circuit mechanical failure (adjusted odds ratio, 1.33; 95% CI, 1.02-1.74; p = 0.03), and renal replacement therapy (adjusted odds ratio, 1.49; 95% CI, 1.14-1.94; p = 0.004) were independently associated with ischemic stroke. Female sex (adjusted odds ratio, 1.61; 95% CI, 1.16-2.22; p = 0.004), extracorporeal membrane oxygenation duration (adjusted odds ratio, 1.01; 95% CI, 1.00-1.03; p = 0.02), renal replacement therapy (adjusted odds ratio, 1.81; 95% CI, 1.30-2.52; p < 0.001), and hemolysis (adjusted odds ratio, 1.87; 95% CI, 1.11-3.16; p = 0.02) were independently associated with hemorrhagic stroke. CONCLUSIONS: Despite a decrease in the prevalence of acute brain injury in recent years, mortality rates remain high when ischemic and hemorrhagic strokes are present. Future research is necessary on understanding the timing of associated risk factors to promote prevention and management strategy.

The IN-PANCIA Study: Clinical Evaluation of Gastrointestinal Dysfunction and Failure, Multiple Organ Failure, and Levels of Citrulline in Critically Ill Patients.

PURPOSE: Gastrointestinal dysfunction and failure (GID and GIF) in critically ill patients are a common, relevant, and underestimated complications in ICU patients. The aims of this study were (1) to determine plasmatic levels of citrulline, glutamine, and arginine as markers of GID/GIF in critically ill patients with or without GID/GIF with or without multiple organ failure (MOF) and (2) to assess the role of intra-abdominal hypertension in these patient groups. MATERIALS AND METHODS: This is a 1-year, monocentric (Italian hospital), prospective observational study. Inclusion criteria were adult patients with GID/GIF, with or without MOF. The GIF score was daily evaluated in 39 critically ill patients. Amino acids were measured at the time of GID or GIF. RESULTS: We enrolled 39 patients. Nine patients developed GID and 7 GIF; 6 of patients with GID/GIF developed MOF. Citrulline was lower (P < .001) in patients with GID/GIF (11.3 [4.4] µmol/L), compared to patients without GID/GIF (22.4 [6.8] µmol/L); likewise, glutamine was lower in patients with GID/GIF, whereas arginine was nonstatistically different between the 2 groups. Intra-abdominal pressure was higher in patients affected by MOF (13.0 [2.2] mm Hg) than in patients with GIF/GID without MOF (9.6 [2.6] mm Hg) and compared to patients without GID/GIF (7.2 [2.1] mm Hg). CONCLUSIONS: Both GID and GIF in critically ill patients are associated with low levels of citrulline and glutamine, which could be considered as markers of small bowel dysfunction. The higher the GIF score, the lower the citrulline levels. Patients affected by MOF had higher levels of intra-abdominal pressure.

Electroencephalographic monitoring of brain activity during cardiac arrest: a narrative review.

BACKGROUND: To date cardiac arrest (CA) remains a frequent cause of morbidity and mortality: despite advances in cardiopulmonary resuscitation (CPR), survival is still burdened by hypoxic-ischemic brain injury (HIBI), and poor neurological outcome, eventually leading to withdrawal of life sustaining treatment (WLST). The aim of CPR is cardiac pump support to preserve organ perfusion, until normal cardiac function is restored. However, clinical parameters of target organ end-perfusion during CPR, particularly brain perfusion, are still to be identified. In this context, electroencephalography (EEG) and its derivatives, such as processed EEG, could be used to assess brain function during CA. OBJECTIVES: We aimed to review literature regarding the feasibility of EEG and processed or raw EEG monitoring during CPR. METHODS: A review of the available literature was performed and consisted of mostly case reports and observational studies in both humans and animals, for a total number of 22 relevant studies. RESULTS: The research strategy identified 22 unique articles. 4 observational studies were included and 6 animal testing studies in swine models. The remaining studies were case reports. Literature regarding this topic consists of conflicting results, containing studies where the feasibility of EEG during CPR was positive, and others where the authors reached opposite conclusions. Furthermore, the level of evidence, in general, remains low. DISCUSSION: EEG may represent a useful tool to assess CPR effectiveness. A multimodal approach including other non-invasive tools such as, quantitative infrared pupillometry and transcranial Doppler, could help to optimize the quality of resuscitation maneuvers.

Operative strategies for acute mitral regurgitation as a mechanical complication of myocardial infarction.

Severe mitral regurgitation secondary to papillary muscle rupture is one of the mechanical complications after an acute myocardial infarction. Surgical strategies represent the cornerstone of treatment in this disease; in addition to surgical valve replacement, approaches involving surgical valve repair have been reported over time in different clinical scenarios to restore valve competency, improve cardiac function and reduce mechanical prosthesis-related risks. Moreover, in recent years, percutaneous trans-catheter procedures have emerged as an important alternative in high risk or inoperable patients.

Right ventricular failure after left ventricular assist device implantation: a review of the literature.

Right ventricular failure (RVF) following left ventricular assist device (LVAD) implantation remains a major complication which may significantly impair patient outcome. The genesis of RVF is, however, multifactorial, and the mechanisms underlying such a condition have not been fully elucidated, making its prevention challenging and the course not always predictable. Although preoperative risks factors can be associated with RV impairment, the physiologic changes after the LV support, can still hamper the function of the RV. Current medical treatment options are limited and sometimes, patients with a severe post-LVAD RVF may be unresponsive to pharmacological therapy and require more aggressive treatment, such as temporary RV support. We retrieved 11 publications which we assessed and divided in groups based on the RV support [extracorporeal membrane oxygenation (ECMO), right ventricular assist device (RVAD), TandemHeart with ProtekDuo cannula]. The current review comprehensively summarizes the main studies of the literature with particular attention to the RV physiology and its changes after the LVAD implantation, the predictors and prognostic score as well as the different modalities of temporary mechanical cardio-circulatory support, and its effects on patient prognosis for RVF in such a setting. In addition, it provides a decision making of the pre-, intra and post-operative management in high- and moderate- risk patients.