Calcium Channel Blocker Overdose: What Role Does Extracorporeal Membrane Oxygenation Have in Support? A Systematic Review of the Literature.

Extracorporeal membrane oxygenation (ECMO) has had increasing prevalence and indications in the last decade. Calcium channel blocker overdose (CCBOD) can lead to significant cardiopulmonary dysfunction and has also increased in recent years. CCBOD results in cardiac depression, vasoplegia, and hyperglycemia. Expert consensus recommends treatment with calcium, high-dose insulin, inotropes, and vasopressors. Our systematic review evaluated when to initiate ECMO in the CCBOD population and the mortality rate associated with use. Electronic literature review identified all relevant studies for CCBOD and ECMO. PRISMA guidelines for systematic review were followed. Three independent authors reviewed abstracts and full texts, and only CCB ingestion without polypharmacy was included. Two authors independently collected data, which included demographics, current medical treatments, ECMO type, and survival. From 314 abstracts, 25 papers were included with a median publication year of 2019. Twenty-six patients were included with an average age of 32.7 years and 42%/58% male/female. Average time on ECMO 4.3 days. VA and VV ECMO use were 92.3% and 7.7%, respectively, and 84.6% of patients survived to hospital discharge. Before ECMO, most patients received 4-5 medical treatments (53.8%). Our systematic review demonstrates ECMO is a newly used, yet valuable therapy for CCBOD when medical treatment fails. Survival to discharge after ECMO for CCBOD is substantially higher than standard VV or VA ECMO. Medical management is still the mainstay therapy for CCBOD, but we show that a persistently unstable patient may benefit from prompt evaluation at an ECMO center for treatment.

Antithrombin III supplementation during neonatal and pediatric extracorporeal membrane oxygenation.

BACKGROUND: Bleeding and thrombosis are common extracorporeal membrane oxygenation (ECMO) complications associated with increased mortality. Heparin is the most commonly used ECMO anticoagulant, employed in 94% of cases. Reduced antithrombin III (AT3) levels could decrease heparin effectiveness. Neonates have inherently lower levels of AT3 than adults, and pediatric patients on ECMO can develop AT3 deficiency. One potential approach for patients on ECMO with AT3 deficiency is exogenous AT3 supplementation. However, there is conflicting data concerning the use of AT3 for pediatric and neonatal patients on ECMO. METHODS: We analyzed the Bleeding and Thrombosis during ECMO database of 514 neonatal and pediatric patients on ECMO. We constructed daily regression models to determine the association between AT3 supplementation and rates of bleeding and thrombosis. Given the physiological differences between pediatric patients and neonates, we constructed separate models for each. RESULTS: AT3 administration was associated with increased rates of daily bleeding among pediatric (adjusted odds ratio [aOR] 1.59, p < 0.01) and neonatal (aOR 1.37, p = 0.04) patients. AT3 supplementation did not reduce the rate of thrombosis for either pediatric or neonatal patients. CONCLUSION: AT3 administration was associated with increased rates of daily bleeding, a hypothesized potential complication of AT3 supplementation. In addition, AT3 supplementation did not result in lower rates of thrombosis. We recommend clinicians utilize caution when considering supplementing patients on ECMO with exogenous AT3.

Standards of Psychological Care for Pediatric Patients Awaiting Heart Transplantation and Those Requiring Mechanical Circulatory Support.

Children waiting for a heart transplant who require mechanical circulatory support often experience many months of hospitalization. This has a significant impact on their mental health and their development. Additional risk factors for these disorders are neurologic complications associated with the used treatment. To counteract developmental dysfunctions (despite successful heart transplantation) and possible disability in the sphere of mental health as well as to improve executive functions of children after a neurologic incident, there is a need for comprehensive care provided by a clinical psychologist who is a member of a multidisciplinary medical team taking care of the patient. Based on our own experience, standards of psychological care were developed for pediatric patients awaiting heart transplantation and those requiring mechanical circulatory support.

A Narrative Review of Nutrition Therapy in Patients Receiving Extracorporeal Membrane Oxygenation.

The use of extracorporeal membrane oxygenation (ECMO) in patients with severe cardiorespiratory failure has seen significant growth in the last decade. Despite this, there is paucity of data surrounding the optimum nutritional management for ECMO patients. This review aimed to describe current nutrition practices in patients receiving ECMO, critically appraise available studies and identify areas for future research. A literature search was conducted in PubMed, MEDLINE, and CINAHL Plus to identify all randomized trials and observational studies published between July 2000 and July 2020 investigating nutrition practices in critically ill adults receiving ECMO. The primary outcomes were nutritional adequacy, gastrointestinal complications, and physical function. Secondary outcomes included mortality, length of stay, and duration on ECMO support. From a total of 31 studies identified, 12 met the inclusion criteria. Nine observational studies were reviewed following eligibility assessment. Early enteral nutrition was deemed safe and feasible for ECMO patients; however, meeting nutritional targets was challenging. Utilizing alternative nutrition routes is an option, although risks and benefits should be taken into consideration. Data on gastrointestinal complications and other clinical outcomes were inconsistent, and no data were identified investigating the effects of nutrition on the physical and functional recovery of ECMO patients. Nutrition therapy in ECMO patients should be provided in line with current guidelines for nutrition in critical illness until further data are available. Further prospective, randomized studies investigating optimum nutrition practices and effects on clinical and functional outcomes are urgently required.

Carnitine deficiency among hospitalized pediatric patients: A retrospective study of critically ill patients receiving extracorporeal membrane oxygenation therapy.

BACKGROUND: The metabolic demands associated with critical illness place patients at risk for nutrition deficits. Carnitine is a small molecule essential for fatty acid oxidation and gluconeogenesis. Secondary carnitine deficiency can have clinically significant complications and has been observed anecdotally in patients receiving extracorporeal membrane oxygenation (ECMO) therapy at our institution. Guidelines for monitoring and supplementing carnitine are lacking. This retrospective study determined whether critically ill pediatric patients receiving ECMO have an increased risk of carnitine deficiency. METHODS: Acylcarnitine analysis was performed on residual specimens from patients who received ECMO therapy. The control data were a convenience sample gathered by chart review of patients who had been tested for carnitine during a hospitalization. RESULTS: Acylcarnitines were measured in 217 non-ECMO patients and 81 ECMO patients. Carnitine deficiency, based on age-specific reference ranges, was observed in 41% of ECMO cases compared with 21% of non-ECMO cases. Multivariable analysis of age-matched patients identified that the odds of carnitine deficiency were significantly lower among patients on the floor compared with ECMO patients (odds ratio, 0.21; 95% CI, 0.10-0.44). Age-specific frequency of qualitative carnitine deficiency ranged from 15% (patients >5 years old) to 56% (patients 1 week to 1 month old) in ECMO patients and 15% (patients >5 years old) to 34% (patients 1-5 years old) in non-ECMO patients. CONCLUSION: In this study, ECMO patients were carnitine deficient more frequently compared with other inpatients, with the highest rates of deficiency among ECMO patients between 1 week and 1 month old.

COVID-19 challenge for modern medicine.

Coronaviruses cause disease in animals and people around the world. Human coronaviruses (HCoV) are mainly known to cause infections of the upper and lower respiratory tract but the symptoms may also involve the nervous and digestive systems. Since the beginning of December 2019, there has been an epidemic of SARS-CoV-2, which was originally referred to as 2019-nCoV. The most common symptoms are fever and cough, fatigue, sputum production, dyspnea, myalgia, arthralgia or sore throat, headache, nausea, vomiting or diarrhea (30%). The best prevention is to avoid exposure. In addition, contact per-sons should be subjected to mandatory quarantine. COVID-19 patients should be treated in specialist centers. A significant number of patients with pneumonia require passive oxygen therapy. Non-invasive ventilation and high-flow nasal oxygen therapy can be applied in mild and moderate non-hypercapnia cases. A lung-saving ventilation strategy must be implemented in acute respiratory distress syndrome and mechanically ventilated patients. Extracorporeal membrane oxygenation is a highly specialized method, available only in selected centers and not applicable to a significant number of cases. Specific pharmacological treatment for COVID-19 is not currently available. Modern medicine is gearing up to fight the new coronavirus pandemic. The key is a holistic approach to the patient including, primar-ily, the use of personal protective equipment to reduce the risk of further virus transmission, as well as patient management, which consists in both quarantine and, in the absence of specific pharmacological therapy, symptomatic treatment.

Myocardial edema in paroxysmal permeability disorders: The paradigm of Clarkson's disease.

PURPOSE: Paroxysmal Permeability Disorders (PPDs) comprise a variety of diseases characterized by recurrent and transitory increase of endothelial permeability. Idiopathic Systemic Capillary Leak Syndrome (ISCLS) is a rare PPD that leads to an abrupt massive shift of fluids and proteins from the intravascular to the interstitial compartment. In some cases, tissue edema may involve the myocardium, but its role in the development of shock has not been elucidated so far. MATERIALS AND METHODS: Assessment of cardiac involvement during ten life-threatening ISCLS episodes admitted to ICU. RESULTS: Transthoracic echocardiographic examination was performed in eight episodes, whereas a poor acoustic window prevented cardiac ultrasound assessment in two episodes. Myocardial edema was detected by echocardiography in eight episodes and marked pericardial effusion in one-episode. Cardiac magnetic resonance showed diffuse myocardial edema in another episode. In one case, myocardial edema caused fulminant left ventricular dysfunction, which required extracorporeal life support. The mean septum thickness was higher during the shock phase compared to the recovery phase [15.5 mm (13.1-21 mm) vs. 9.9 mm (9-11.3 mm), p = .0003]. Myocardial edema resolved within 72 h. CONCLUSIONS: During early phases of ISCLS, myocardial edema commonly occurs and can induce transient myocardial dysfunction, potentially contributing to the pathogenesis of shock.

Extracorporeal membrane oxygenation support in acute circulatory failure: A plea for regulation and better organization.

Emergent implantation of temporary mechanical circulatory support using venoarterial ECMO (ECLS for extracorporeal Life Support) is increasingly adopted in various indications of acute circulatory failure refractory to optimal medical treatment. To implant such devices, but also to provide appropriate daily management, expertise and adapted technical platform are required. Organization, coordination and regulation of such program are not clearly established in our country. We propose a dedicated territorial organization to improve and facilitate management of these specific and most severe patients.

Cardiopulmonary support in patients undergoing catheter ablation of poorly tolerated ventricular arrhythmias and electrical storm.

INTRODUCTION: Catheter ablation is an important treatment option for sustained ventricular arrhythmias (VA) that are refractory to pharmacological treatment; however, patients with fast VA or electrical storm (ES) are at risk for cardiogenic shock. We report our experience using cardiopulmonary support with extracorporeal membrane oxygenation (ECMO) during catheter ablation of VA. METHODS: Nineteen patients (mean age, 62 ± 10 years; 84% male) were referred to our center for CA of ES between January 2017 and April 2018. ES was defined as the occurrence of ≥3 ventricular tachycardia or ventricular fibrillation episodes requiring electrical cardioversion or defibrillation in a 24-hour period. ECMO support was implemented for all patients. RESULTS: CA of ES was completed in all patients. Activation mapping was performed for all VTs and substrate modification was performed by targeting sites identified by late/fragmented abnormal potentials. VTs were not inducible after ablation in 16 of 19 patients (84%). With regard to procedural complications, two patients underwent percutaneous angioplasty with stenting for a femoral artery dissection and one patient was treated for a dislodged ECMO arterial cannula and subsequent hemorrhagic shock. After a median follow-up of 10 months, three patients died from refractory heart failure and one patient died as a result of ES. Overall, the procedural success rate was 68% and the Kaplan-Meier mortality rate was 21%. CONCLUSIONS: ECMO support may be used for ablation procedures in patients with ES.

Interhospital ECMO Transport: Regional Focus.

Utilization of extracorporeal membrane oxygenation (ECMO) has increased dramatically over the last decade. Despite this trend, many medical centers have limited, if any, access to this technology or the resources necessary to manage these complex patients. In an effort to improve the current infrastructure of regional ECMO care, ECMO centers of excellence have an obligation to partner with facilities within their communities and regions to increase access to this potentially life-saving technology. While the need for this infrastructure is widely acknowledged in the ECMO community, few reports describe the actual mechanisms by which a successful interfacility transport program can operate. As such, the purpose of this document is to describe the elements of and methods for providing safe and efficient mobile ECMO services from the perspective of an experienced, high-volume tertiary ECMO center of excellence in the Southeastern United States.

How New Support Devices Change Critical Care Delivery.

Mechanical support devices are used to support failing cardiac, respiratory, or both systems. Since Gibbon developed the cardiopulmonary bypass in 1953, collaborative efforts by medical centers, bioengineers, industry, and the National Institutes of Health have led to development of mechanical devices to support heart, lung, or both. These devices are used as a temporary or long-term measures for acute collapse of circulatory system and/or respiratory failure. Patients are managed on these support devices as a bridge to recovery, bridge to long term devices, or bridge to transplant. The progress in development of these devices has improved mortality and quality of life in select groups of patients. Care of these patients requires a multidisciplinary team approach, which includes cardiac surgeons, critical care physicians, cardiologists, pulmonologists, nursing staff, and perfusionists. Using a team approach improves outcomes in these patients.

Heparin-induced thrombocytopenia complicating extracorporeal membrane oxygenation support in pediatric patients: review of the literature and alternative anticoagulants.

Heparin-induced thrombocytopenia (HIT) is a prothrombotic, immune-mediated complication of unfractionated heparin (UFH) and low molecular weight heparin therapy. HIT is characterized by moderate thrombocytopenia 5-10 days after initial heparin exposure, detection of platelet-activating anti-platelet factor 4/heparin antibodies and an increased risk of venous and arterial thrombosis. Extracorporeal membrane oxygenation (ECMO) is a form of mechanical circulatory support used in critically ill patients with respiratory or cardiac failure. Systemic anticoagulation is used to alleviate the thrombotic complications that may occur when blood is exposed to artificial surfaces within the ECMO circuit. Therefore, when HIT complicates patients on ECMO support, it is associated with a high thrombotic morbidity and mortality. The following article reviews the current knowledge in pediatric HIT, especially in ECMO patients, and the alternative anticoagulation options in the presence of HIT.

Management of pediatric tachyarrhythmias on mechanical support.

BACKGROUND: Pediatric patients with persistent arrhythmias may require mechanical cardiopulmonary support. We sought to classify the population, spectrum, and success of current treatment strategies. METHODS AND RESULTS: A multicenter retrospective chart review was undertaken at 11 sites. Inclusion criteria were (1) patients <21 years, (2) initiation of mechanical support for a primary diagnosis of arrhythmias, and (3) actively treated on mechanical support. A total of 39 patients were identified with a median age of 5.5 months and median weight of 6 kg. A total of 69% of patients were cannulated for supraventricular tachycardia with a median rate of 230 beats per minute. A total of 90% of patients were supported with extracorporeal membrane oxygenation for an average of 5 days. The remaining 10% were supported with ventricular assist devices for an average of 38 (20-60) days. A total of 95% of patients were treated with antiarrhythmics, with 43% requiring >1 antiarrhythmic. Amiodarone was the most frequently used medication alone or in combination. A total of 33% patients underwent electrophysiology study/transcatheter ablation. Radiofrequency ablation was successful in 9 patients on full flow extracorporeal membrane oxygenation with 3 radiofrequency-failures/conversion to cryoablation. One patient underwent primary cryoablation. A total of 15% of complications were related to electrophysiology study/ablation. At follow-up, 23 patients were alive, 8 expired, and 8 transplanted. CONCLUSIONS: Younger patients were more likely to require support in the presented population. Most patients were treated with antiarrhythmics and one third required electrophysiology study/ablation. Radiofrequency ablation is feasible without altering extracorporeal membrane oxygenation flows. There was a low frequency of acute adverse events in patients undergoing electrophysiology study/ablation, while on extracorporeal membrane oxygenation.

Whole body hyperthermia by extracorporeal circulation in spontaneously breathing sarcoma patients: hemodynamics and oxygen metabolism.

PURPOSE: This phase I study was performed to evaluate the feasibility and toxicity of a new method of extracorporeal perfusion-induced whole body hyperthermia (WBHT) in patients with advanced sarcoma avoiding the need of intubation and general anesthesia. METHODS: One double-lumen femoral venous access was inserted by Seldinger's technique to obtain WBHT (41.8°C for 120 minutes) via an extracorporeal circuit. No concomitant chemotherapy was applied. Up to 4 treatments of WBHT were performed under moderate sedation in 6 spontaneously breathing patients. Invasive hemodynamic monitoring was performed by use of a pulmonary artery catheter. RESULTS: After their first WBHT session, 2 patients were excluded from further treatment due to transient liver toxicity or catheter-related complication, so a total of 12 cycles remained for analyses. In all patients, conscious sedation resulted in sufficient spontaneous respiration without the need for mandatory ventilation. Median time to reach the target temperature was 84 minutes (range 60-142). Hemodynamic changes revealed the expected hyperdynamic state: heart rate, cardiac index, and stroke volume index significantly increased (p<0.05), whereas blood pressure and systemic and pulmonary vascular resistance index significantly decreased (p<0.05). A net fluid balance of 5822±1766 mL as well as norepinephrine (mean; 0.062 µg·kg¹·min⁻¹) were necessary to maintain the mean arterial blood pressure >60 mmHg. CONCLUSION: Our data demonstrate the feasibility of this method of extracorporeal WBHT without mandatory ventilation. Hemodynamic side effects in spontaneously breathing patients during perfusion-induced WBHT seem less severe than those observed in radiant heat WBHT.

Effects of centrifugal and roller pumps on survival of autologous red cells in cardiopulmonary bypass surgery.

BACKGROUND: Either a roller pump or a centrifugal pump can be used in the extracorporeal circuit during surgery with cardiopulmonary bypass. In this study, we assessed the effect of these two pumps on the 24-h post-transfusion survival values of autologous red blood cells (RBC). STUDY DESIGN AND METHODS: Fourteen male patients subjected to extracorporeal bypass procedures were studied. In seven patients, the autologous red cells were collected following the cardiopulmonary bypass procedure using the roller pump, and in seven patients, autologous red cells were collected following the cardiopulmonary procedure using the centrifugal pump. The 24-h post-transfusion survival values of the autologous RBC were measured using the 51 disodium chromate/99m technetium double isotope procedure. The effects of the extracorporeal bypass procedures using the roller pump and the centrifugal pump were also assessed by the measurements of hematocrit, platelet count, plasma hemoglobin, and serum lactate dehydrogenase levels. RESULTS: The 51 disodium chromate 24-h post-transfusion survival values of the autologous RBC were similar whether the roller pump or the centrifugal pump was used in the extracorporeal circulation, as were the hematocrit, platelet count, plasma hemoglobin and serum lactate dehydrogenase levels. CONCLUSION: The 24-h post-transfusion survival values of autologous RBC, measured by the 51 disodium chromate/99m technetium double isotope procedure, were not significantly different, whether the roller pump or the centrifugal pump was used in the extracorporeal circuit using membrane oxygenators during cardiopulmonary surgical procedures.

White matter disease in magnetic resonance imaging predicts cerebral complications after coronary artery bypass grafting.

BACKGROUND: The aim of the present study was to assess neurologic and neuropsychologic complications in 104 patients randomized to coronary artery bypass grafting or spinal cord stimulation. An additional objective of the study was to assess whether preoperative white matter disease might predict cerebral complications, as previous studies have shown that there is a relationship between white matter disease and neuropsychologic decline after coronary artery bypass grafting. METHODS: The patients were subjected to neurologic examination before and six months after intervention. The patients underwent a cerebral magnetic resonance imaging before intervention and the presence of white matter disease was related to development of cerebral complications. RESULTS: More patients in the bypass group than in the spinal cord stimulation group developed focal cerebral ischemia (p < 0.05) and astheno-emotional disorder (p < 0.001). More patients with white matter disease undergoing bypass were affected by focal cerebral ischemia (p < 0.01) and astheno-emotional disorder (p < 0.001) after the intervention compared to patients with white matter disease undergoing spinal cord stimulation. In patients with no white matter disease there were no differences between the bypass group and spinal cord stimulation group with regard to cerebral complications. CONCLUSIONS: Patients undergoing bypass had more neurologic and neuropsychologic complications than patients undergoing spinal cord stimulation. Furthermore, patients with white matter disease were affected by cerebral complications in a higher extent after bypass than after spinal cord stimulation. Thus, preoperative assessment of white matter disease before undergoing coronary artery bypass grafting might predict the patient's risk of developing cerebral injury.

Inhaled nitric oxide inhibits the release of matrix metalloproteinase-2, but not platelet activation, during extracorporeal membrane oxygenation in adult rabbits.

BACKGROUND/PURPOSE: In neonates receiving extracorporeal membrane oxygenation (ECMO), platelet activation and dysfunction occur with the release of matrix metalloproteinase (MMP)-2, which stimulates platelet aggregation. Because inhaled nitric oxide (NO) reduces pulmonary hypertension and inhibits platelet aggregation, the authors examined the effects of inhaled NO on platelet activation induced by ECMO. METHODS: Ten adult white New Zealand rabbits were instrumented for ECMO and assigned randomly to receive either inhaled NO at 40 ppm or 30% oxygen for 1 hour before ECMO and continued for 4 hours after starting ECMO. Platelet counts, collagen-induced platelet aggregation ex vivo, plasma MMP-2, and MMP-9 activities were measured. RESULTS: (1) ECMO caused thrombocytopenia, decreased platelet aggregation, and increased plasma MMP-2 and MMP-9 activities in controls. (2) Inhaled NO inhibited platelet aggregation before ECMO but did not affect the ECMO-induced thrombocytopenia and platelet activation. (3) Inhaled NO significantly abolished the ECMO-induced increase in plasma MMP-2 but not MMP-9 activities. CONCLUSIONS: Although inhaled NO did not inhibit the platelet activation during ECMO in adult rabbits, it attenuated the increase in plasma MMP-2 activity that may be important for neonates treated with ECMO.