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.

Optical, flow, and thermal analysis of a phototherapy extracorporeal membrane oxygenator for treating carbon monoxide poisoning.

BACKGROUND: Extracorporeal membrane oxygenators (ECMO) are currently utilized to mechanically ventilate blood when lung or lung and heart function are impaired, like in cases of acute respiratory distress syndrome (ARDS). ARDS can be caused by severe cases of carbon monoxide (CO) inhalation, which is the leading cause of poison-related deaths in the United States. ECMOs can be further optimized for severe CO inhalation using visible light to photo-dissociate CO from hemoglobin (Hb). In previous studies, we combined phototherapy with an ECMO to design a photo-ECMO device, which significantly increased CO elimination and improved survival in CO-poisoned animal models using light at 460, 523, and 620 nm wavelengths. Light at 620 nm was the most effective in removing CO. OBJECTIVE: The aim of this study is to analyze the light propagation at 460, 523, and 620 nm wavelengths and the 3D blood flow and heating distribution within the photo-ECMO device that increased CO elimination in CO-poisoned animal models. METHODS: Light propagation, blood flow dynamics, and heat diffusion were modeled using the Monte Carlo method and the laminar Navier-Stokes and heat diffusion equations, respectively. RESULTS: Light at 620 nm propagated through the device blood compartment (4 mm), while light at 460 and 523 nm only penetrated 48% to 50% (~2 mm). The blood flow velocity in the blood compartment varied with regions of high (5 mm/s) and low (1 mm/s) velocity, including stagnant flow. The blood temperatures at the device outlet for 460, 523, and 620 nm wavelengths were approximately 26.7°C, 27.4°C, and 20°C, respectively. However, the maximum temperatures within the blood treatment compartment rose to approximately 71°C, 77°C, and 21°C, respectively. CONCLUSIONS: As the extent of light propagation correlates with efficiency in photodissociation, the light at 620 nm is the optimal wavelength for removing CO from Hb while maintaining blood temperatures below thermal damage. Measuring the inlet and outlet blood temperatures is not enough to avoid unintentional thermal damage by light irradiation. Computational models can help eliminate risks of excessive heating and improve device development by analyzing design modifications that improve blood flow, like suppressing stagnant flow, further increasing the rate of CO elimination.

Medical nutrition therapy in patients receiving ECMO: Evidence-based guidance for clinical practice.

Patients receiving extracorporeal membrane oxygenation (ECMO) inherit substantial disease-associated metabolic, endocrinologic, and immunologic modifications. Along with the technical components of ECMO, the aforementioned alterations may affect patients' needs and feasibility of adequate macronutrient and micronutrient supply and intake. Thus, patients receiving ECMO are at increased risk for iatrogenic malnutrition and require targeted individual medical nutrition therapy (MNT). However, specific recommendations for MNT in patients receiving ECMO are limited and, with some exceptions, based on an evidence base encompassing general patients who are critically ill. Consequently, clinician decision-making for MNT in patients receiving ECMO is unguided, which may further increase nutrition risk, culminating in iatrogenic malnutrition and ultimately affecting patient outcomes. The purpose of this article is to provide educational background and highlight specific points for MNT in adult patients receiving ECMO, which might serve as evidence-based guidance to develop institutional standard operating procedures and nutrition protocols for daily clinical practice.

The evolution of cardiopulmonary resuscitation: Global productivity and publication trends.

BACKGROUND/OBJECTIVE: There is still no comprehensive bibliometric study in the literature on cardiopulmonary resuscitation (CPR), an important topic in emergency medicine, the number of global studies on which is increasing day by day. In this study, it was aimed to analyze the scientific articles on CPR published between 1980 and 2020 by statistical methods and to evaluate the subject holistically. METHODS: Articles on CPR published between 1980 and 2020 were downloaded from the Web of Science (WoS) database and analyzed using statistical methods. Network visualization maps were used to identify trending topics. Nonlinear regression analysis (exponential model) was used to estimate the number of articles in the coming years. Correlation studies were conducted using the Spearman correlation coefficient. RESULTS: A total of 21,623 publications were found. Of these publications, 14,818 (68.5%) were articles. The top 3 contributing countries to the literature were the United States (5281, 35.6%), Germany (1458, 9.8%), and the United Kingdom (1152, 7.7%). The 3 most active institutions were the University of Washington (417), University of Pittsburgh (361), and University of Arizona (240). The 3 journals with the most publications were Resuscitation (2822), Critical Care Medicine (522), and the American Journal of Emergency Medicine (421). CONCLUSION: In this comprehensive study, a summary of 14,818 articles was presented. The trending topics in CPR research in recent years are out-of-hospital cardiac arrest, extracorporeal membrane oxygenation, cardio, simulation, in-hospital cardiac arrest, extracorporeal life support, extracorporeal cardiopulmonary resuscitation, targeted management temperature, and outcome. This article may be a useful resource on CPR global outcomes for clinicians and scientists.

Targeted high volume hemofiltration could avoid extracorporeal membrane oxygenation in some patients with severe Hantavirus cardiopulmonary syndrome.

BACKGROUND: Hantavirus cardiopulmonary syndrome (HCPS) has a high lethality. Severe cases may be rescued by venoarterial extracorporeal membrane oxygenation (VA ECMO), alongside substantial complications. High volume hemofiltration (HVHF) is a depurative technique that provides homeostatic balance allowing hemodynamic stabilization in some critically ill patients. METHODS: We implemented HVHF before VA ECMO consideration in the last five severe HCPS patients requiring mechanical ventilation and vasoactive drugs admitted to our intensive care unit. Patients were considered HVHF-responders if VA ECMO was avoided and HVHF-nonresponders if VA ECMO support was needed despite HVHF. A targeted-HVHF strategy compounded by aggressive hyperoncotic albumin, sodium bicarbonate, and calcium supplementation plus ultrafiltration to avoid fluid overload was implemented on three patients. RESULTS: Patients had maximum serum lactate of 8.8 (8.7-12.8) mmol/L and a lowest cardiac index of 1.8 (1.8-1.9) L/min/m2 . The first two required VA ECMO. They were connected later to HVHF, displayed progressive tachycardia and declining stroke volume. The opposite was true for HVHF-responders who received targeted-HVHF. All patients survived, but one of the VA ECMO patients suffered a vascular complication. CONCLUSION: HVHF may contribute to support severe HCPS patients avoiding the need for VA ECMO in some. Early connection and targeted-HVHF may increase the chance of success.

Phototherapy and extracorporeal membrane oxygenation facilitate removal of carbon monoxide in rats.

Inhaled carbon monoxide (CO) displaces oxygen from hemoglobin, reducing the capacity of blood to carry oxygen. Current treatments for CO-poisoned patients involve administration of 100% oxygen; however, when CO poisoning is associated with acute lung injury secondary to smoke inhalation, burns, or trauma, breathing 100% oxygen may be ineffective. Visible light dissociates CO from hemoglobin. We hypothesized that the exposure of blood to visible light while passing through a membrane oxygenator would increase the rate of CO elimination in vivo. We developed a membrane oxygenator with optimal characteristics to facilitate exposure of blood to visible light and tested the device in a rat model of CO poisoning, with or without concomitant lung injury. Compared to ventilation with 100% oxygen, the addition of extracorporeal removal of CO with phototherapy (ECCOR-P) doubled the rate of CO elimination in CO-poisoned rats with normal lungs. In CO-poisoned rats with acute lung injury, treatment with ECCOR-P increased the rate of CO removal by threefold compared to ventilation with 100% oxygen alone and was associated with improved survival. Further development and adaptation of this extracorporeal CO photo-removal device for clinical use may provide additional benefits for CO-poisoned patients, especially for those with concurrent acute lung injury.

Antithrombin supplementation during extracorporeal membrane oxygenation: study protocol for a pilot randomized clinical trial.

BACKGROUND: Normal levels of plasma antithrombin (AT) activity might decrease heparin requirements to achieve an adequate level of anticoagulation during treatment with extracorporeal membrane oxygenation (ECMO). Acquired AT deficiency during ECMO is common, but formal recommendations on target, timing, and rate of AT supplementation are lacking. Thus, we conceived a pilot trial to evaluate the feasibility and safety of prolonged AT supplementation in patients requiring veno-venous ECMO for respiratory failure. METHODS: Grifols Antithrombin Research Awards (GATRA) is a prospective, randomized, single blinded, multicenter, controlled two-arm trial. Patients undergoing veno-venous ECMO will be randomized to either receive AT supplementation to maintain a functional AT level between 80 and 120% (AT supplementation group) or not (control group) for the entire ECMO course. In both study groups, anticoagulation will be provided with unfractionated heparin following a standardized protocol. The primary endpoint will be the dose of heparin required to maintain the ratio of activated partial thromboplastin time between 1.5 and 2. Secondary endpoints will be the adequacy of anticoagulation and the incidence of hemorrhagic and thrombotic complications. DISCUSSION: GATRA is a pilot trial that will test the efficacy of a protocol of AT supplementation in decreasing the heparin dose and improving anticoagulation adequacy during ECMO. If positive, it might provide the basis for a future larger trial aimed at verifying the impact of AT supplementation on a composite outcome endpoint including hemorrhagic events, transfusion requirements, and mortality. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03208270 . Registered on 5 July 2017.

Utilization of therapeutic plasma exchange for hyperbilirubinemia in a premature newborn on extracorporeal membrane oxygenation.

BACKGROUND: We report a case of a premature newborn girl with a hospital course complicated by suspected respiratory syncytial virus pneumonitis for which she was placed on veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Despite phototherapy, her total bilirubin steadily increased to a peak of 50.4 mg/dL with concern for bilirubin-induced neurologic dysfunction, kernicterus. STUDY DESIGN AND METHODS: Therapeutic plasma exchange (TPE) was achieved via connection with the VA-ECMO circuit. Our institution's standard apheresis procedural parameters were adjusted to account for the small body weight and thus the low blood volume of the neonate while on ECMO. These included calculating the total blood volume to include the patient as well as the ECMO circuit, priming of the apheresis instrument with packed red blood cells to limit the extracorporeal volume, using a lower inlet flow rate, the connection setup of the inlet and return line, and monitoring of ionized calcium and anticoagulation throughout the procedure. RESULTS: A total of three TPE procedures were performed over three consecutive days. This resulted in improvement and stabilization of the patient's bilirubin. CONCLUSION: This case emphasizes that TPE is feasible on a neonate with a suboptimal body weight and thus a low blood volume due to the increased blood volume provided while on ECMO. In the absence of ECMO, whole blood manual exchange transfusion is recommended as TPE would be unsafe due to significant extracorporeal volume that would occur during TPE in a pediatric patient with low body weight.

Effects of Nutritional Intervention on the Survival of Patients with Cardiopulmonary Failure Undergoing Extracorporeal Membrane Oxygenation Therapy.

BACKGROUND/AIM: This study aimed to examine the effects of nutritional intervention on the prognosis of patients with cardiopulmonary failure undergoing extracorporeal membrane oxygenation (ECMO) therapy in Taiwan. MATERIALS AND METHODS: An institutional review board-approved retrospective study was conducted on patients receiving ECMO therapy in the intensive care unit of the China Medical University Hospital, Taiwan, from January 2013 to December 2013. The study included 102 patients with cardiopulmonary failure receiving ECMO therapy. RESULTS: The data indicated that higher survival rates were closely related to lower age and APACHE II scores among the patients. In addition, compared to patients who deceased, those who survived had a higher total calorie intake. Most patients could tolerate bolus feeding and polymeric formulas. Furthermore, patients who underwent nutritional therapy with nutritional goals greater than 80% achieved a better outcome and lower mortality than other patients. CONCLUSION: Early nutritional intervention could benefit patients undergoing ECMO, and those who reached the delivery goal of 80% had significantly better outcomes than other patients. Enteral feeding can begin early and was well tolerated by patients receiving ECMO therapy. Following individual nutrition goals is critical for better outcomes, and this analysis might be useful in establishing individualized nutrition goals for oriental population when caring for critically ill 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.

Population Pharmacokinetics of Meropenem in Plasma and Subcutis from Patients on Extracorporeal Membrane Oxygenation Treatment.

The objectives of this study were to describe meropenem pharmacokinetics (PK) in plasma and/or subcutaneous adipose tissue (SCT) in critically ill patients receiving extracorporeal membrane oxygenation (ECMO) treatment and to develop a population PK model to simulate alternative dosing regimens and modes of administration. We conducted a prospective observational study. Ten patients on ECMO treatment received meropenem (1 or 2 g) intravenously over 5 min every 8 h. Serial SCT concentrations were determined using microdialysis and compared with plasma concentrations. A population PK model of SCT and plasma data was developed using NONMEM. Time above clinical breakpoint MIC for Pseudomonas aeruginosa (8 mg/liter) was predicted for each patient. The following targets were evaluated: time for which the free (unbound) concentration is maintained above the MIC of at least 40% (40% fT>MIC), 100% fT>MIC, and 100% fT>4×MIC. For all dosing regimens simulated in both plasma and SCT, 40% fT>MIC was attained. However, prolonged meropenem infusion would be needed for 100% fT>MIC and 100% fT>4×MIC to be obtained. Meropenem plasma and SCT concentrations were associated with estimated creatinine clearance (eCLCr). Simulations showed that in patients with increased eCLCr, dose increment or continuous infusion may be needed to obtain therapeutic meropenem concentrations. In conclusion, our results show that using traditional targets of 40% fT>MIC for standard meropenem dosing of 1 g intravenously every 8 h is likely to provide sufficient meropenem concentration to treat the problematic pathogen P. aeruginosa for patients receiving ECMO treatment. However, for patients with an increased eCLCr, or if more aggressive targets, like 100% fT>MIC or 100% fT>4×MIC, are adopted, incremental dosing or continuous infusion may be needed.

Reducing hospital-acquired pressure ulcers using bundle methodology in pediatric and neonatal patients receiving extracorporeal membrane oxygenation therapy: An integrative review and call to action.

PURPOSE: This review focuses on identifying (1) evidence of the effectiveness of care bundle methodology to reduce hospital-acquired pressure ulcers (HAPUs) in pediatric and neonatal patients receiving extracorporeal membrane oxygenation (ECMO) therapy and (2) barriers to implementing HAPU care bundles in this at-risk population. DESIGN AND METHODS: An integrative review was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A search of the scientific literature was performed. Studies included were published between January 2011 and February 2016. A total of seven articles met inclusion criteria. Data were extracted from each published article and analyzed to identify common themes, specifically bundle methodology and barriers to implementing HAPU bundles, in this population. RESULTS: There is limited research on effectiveness of care bundle methodology in reducing HAPUs in children, and no research specific to its effectiveness in pediatric or neonatal ECMO patients. No research was identified studying barriers to implementation of HAPU care bundles in this population. PRACTICE IMPLICATIONS: Nurses are well poised to test innovative strategies to prevent HAPUs. Nurses should consider implementing and testing bundle methodology to reduce HAPU in this at-risk population, and conduct research to identify any barriers to implementing this strategy. There is literature to support the use of nurses as unit-based skin care champions to facilitate teamwork and reliable use of the bundle, both critical components to the success of bundle methodology.

Extracorporeal life support and digoxin-specific Fab fragments for successful management of Taxus baccata intoxication with low output and ventricular arrhythmia.

INTRODUCTION: Yew plants are evergreen shrubs which are widely spread throughout the northern hemisphere. Taxane alkaloid derivatives, mainly taxine B, represent the main toxins of Taxus baccata and are highly cardiotoxic. Due to the lack of randomized clinical trials, case reports on accidental or suicidal yew intoxications build the only source of knowledge of clinical treatment options. CASE REPORT: We report the case of a suicidal yew ingestion admitted to our hospital under prolonged cardiopulmonary resuscitation due to pulseless electrical activity. Extra-corporeal life support (ECLS) was established to maintain adequate organ perfusion. Repeated administration of digoxin-specific Fab antibody fragments, which cross-react with taxine, was associated with an immediate conversion from asystole to broad-complex bradycardia and a gradual normalization of the electrocardiogram (ECG). This was paralleled by a recovery of the cardiac function and weaning from the ECLS. The taxine metabolite 3,5-dimethoxyphenol could be detected by mass spectrometry before but not after the first Fab-fragment treatment. In contrast, the total amount of taxine (including the neutralized, Fab fragment-bound fraction) was increased after each Fab fragment administration, suggesting an accumulation of neutralized, since antibody-bound taxine in the blood by anti-digoxin Fab fragments. DISCUSSION: In conclusion, the successful clinical course of this case suggests a benefit of an early anti-digoxin Fab-fragment administration for the treatment of yew intoxication.

Massive diltiazem and metoprolol overdose rescued with extracorporeal life support.

The management of overdoses of cardioactive medications in the emergency department can be challenging. The reversal of severe toxicity from one or more types of cardioactive medication may fail maximal medical therapies and require extreme invasive measures such as transvenous cardiac pacing and extracorporeal life support. We present a case of massive diltiazem and metoprolol overdose refractory to maximal medical therapy, including intravenous calcium, glucagon, vasopressors, high dose insulin, and lipid emulsion. The patient experienced refractory bradydysrhythmia that responded only to transvenous pacing. Extracorporeal life support was initiated and resulted in successful organ perfusion and complete recovery of the patient. This case highlights the potential utility of extracorporeal life support in cases of severe toxicity due to multiple cardioactive medications.

Severe hypoxemia: which strategy to choose.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is characterized by a noncardiogenic pulmonary edema with bilateral chest X-ray opacities and reduction in lung compliance, and the hallmark of the syndrome is hypoxemia refractory to oxygen therapy. Severe hypoxemia (PaO2/FiO2 < 100 mmHg), which defines severe ARDS, can be found in 20-30 % of the patients and is associated with the highest mortality rate. Although the standard supportive treatment remains mechanical ventilation (noninvasive and invasive), possible adjuvant therapies can be considered. We performed an up-to-date clinical review of the possible available strategies for ARDS patients with severe hypoxemia. MAIN RESULTS: In summary, in moderate-to-severe ARDS or in the presence of other organ failure, noninvasive ventilatory support presents a high risk of failure: in those cases the risk/benefit of delayed mechanical ventilation should be evaluated carefully. Tailoring mechanical ventilation to the individual patient is fundamental to reduce the risk of ventilation-induced lung injury (VILI): it is mandatory to apply a low tidal volume, while the optimal level of positive end-expiratory pressure should be selected after a stratification of the severity of the disease, also taking into account lung recruitability; monitoring transpulmonary pressure or airway driving pressure can help to avoid lung overstress. Targeting oxygenation of 88-92 % and tolerating a moderate level of hypercapnia are a safe choice. Neuromuscular blocking agents (NMBAs) are useful to maintain patient-ventilation synchrony in the first hours; prone positioning improves oxygenation in most cases and promotes a more homogeneous distribution of ventilation, reducing the risk of VILI; both treatments, also in combination, are associated with an improvement in outcome if applied in the acute phase in the most severe cases. The use of extracorporeal membrane oxygenation (ECMO) in severe ARDS is increasing worldwide, but because of a lack of randomized trials is still considered a rescue therapy. CONCLUSION: Severe ARDS patients should receive a holistic framework of respiratory and hemodynamic support aimed to ensure adequate gas exchange while minimizing the risk of VILI, by promoting lung recruitment and setting protective mechanical ventilation. In the most severe cases, NMBAs, prone positioning, and ECMO should be considered.