Left Ventricular Unloading in Extracorporeal Membrane Oxygenation: A Clinical Perspective Derived from Basic Cardiovascular Physiology.

PURPOSE OF REVIEW: To present an abridged overview of the literature and pathophysiological background of adjunct interventional left ventricular unloading strategies during veno-arterial extracorporeal membrane oxygenation (V-A ECMO). From a clinical perspective, the mechanistic complexity of such combined mechanical circulatory support often requires in-depth physiological reasoning at the bedside, which remains a cornerstone of daily practice for optimal patient-specific V-A ECMO care. RECENT FINDINGS: Recent conventional clinical trials have not convincingly shown the superiority of V-A ECMO in acute myocardial infarction complicated by cardiogenic shock as compared with medical therapy alone. Though, it has repeatedly been reported that the addition of interventional left ventricular unloading to V-A ECMO may improve clinical outcome. Novel approaches such as registry-based adaptive platform trials and computational physiological modeling are now introduced to inform clinicians by aiming to better account for patient-specific variation and complexity inherent to V-A ECMO and have raised a widespread interest. To provide modern high-quality V-A ECMO care, it remains essential to understand the patient's pathophysiology and the intricate interaction of an individual patient with extracorporeal circulatory support devices. Innovative clinical trial design and computational modeling approaches carry great potential towards advanced clinical decision support in ECMO and related critical care.

Clinical decision making for VA ECMO weaning in patients with cardiogenic shock A formative qualitative study.

Weaning and liberation from VA ECMO in cardiogenic shock patients comprises a complex process requiring a continuous trade off between multiple clinical parameters. In the absence of dedicated international guidelines, we hypothesized a great heterogeneity in weaning practices among ECMO centers due to a variety in local preferences, logistics, case load and individual professional experience. This qualitative study focused on the appraisal of clinicians' preferences in decision processes towards liberation from VA ECMO after cardiogenic shock while using focus group interviews in 4 large hospitals. The goal was to provide novel and unique insights in daily clinical weaning practices. As expected, we found we a great heterogeneity of weaning strategies among centers and professionals, although participants appeared to find common ground in a clinically straightforward approach to assess the feasibility of ECMO liberation at the bedside. This was shown in a preference for robust, easily accessible parameters such as arterial pulse pressure, stable cardiac index ≥2.1 L/min, VTI LVOT and 'eyeballing' LVEF.

Computational physiological models for individualised mechanical ventilation: a systematic literature review focussing on quality, availability, and clinical readiness.

BACKGROUND: Individualised optimisation of mechanical ventilation (MV) remains cumbersome in modern intensive care medicine. Computerised, model-based support systems could help in tailoring MV settings to the complex interactions between MV and the individual patient's pathophysiology. Therefore, we critically appraised the current literature on computational physiological models (CPMs) for individualised MV in the ICU with a focus on quality, availability, and clinical readiness. METHODS: A systematic literature search was conducted on 13 February 2023 in MEDLINE ALL, Embase, Scopus and Web of Science to identify original research articles describing CPMs for individualised MV in the ICU. The modelled physiological phenomena, clinical applications, and level of readiness were extracted. The quality of model design reporting and validation was assessed based on American Society of Mechanical Engineers (ASME) standards. RESULTS: Out of 6,333 unique publications, 149 publications were included. CPMs emerged since the 1970s with increasing levels of readiness. A total of 131 articles (88%) modelled lung mechanics, mainly for lung-protective ventilation. Gas exchange (n = 38, 26%) and gas homeostasis (n = 36, 24%) models had mainly applications in controlling oxygenation and ventilation. Respiratory muscle function models for diaphragm-protective ventilation emerged recently (n = 3, 2%). Three randomised controlled trials were initiated, applying the Beacon and CURE Soft models for gas exchange and PEEP optimisation. Overall, model design and quality were reported unsatisfactory in 93% and 21% of the articles, respectively. CONCLUSION: CPMs are advancing towards clinical application as an explainable tool to optimise individualised MV. To promote clinical application, dedicated standards for quality assessment and model reporting are essential. Trial registration number PROSPERO- CRD42022301715 . Registered 05 February, 2022.

Cardiac tamponade during venoarterial extracorporeal membrane oxygenation: a case report.

BACKGROUND: Cardiac tamponade may present with very different signs and clinical consequences in patients who are supported with venoarterial extracorporeal membrane oxygenation. Failure to recognize cardiac tamponade in this setting can cause failure to wean from venoarterial extracorporeal membrane oxygenation, and even lead to death. CASE PRESENTATION: We present a 44-year-old Caucasian female in whom cardiac tamponade manifested as venoarterial extracorporeal membrane oxygenation weaning failure. After discovering the contribution of cardiac tamponade, it was possible to wean the patient from venoarterial extracorporeal membrane oxygenation support. No clear signs of cardiac tamponade had existed beforehand. CONCLUSIONS: The diagnosis of cardiac tamponade can be very challenging in venoarterial extracorporeal membrane oxygenation supported patients due to (patho)physiological particularities related to the parallel blood flow.

Initiation of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for cardiogenic shock during out of hours versus working hours is not associated with increased mortality.

BACKGROUND: Initiation of veno-arterial (VA) Extracorporeal Membrane Oxygenator (ECMO) is associated with severe complications. It is unknown whether these adverse consequences occur more often after initiations during out of hours service compared to working hours. METHODS: All patients receiving VA-ECMO for cardiogenic shock between 2009 and 2020 were categorized into a working hours group (between 8 am and 5 pm on weekdays) and an out of hours service group (between 5 pm and 8 am, or between Friday 5 pm and Monday 8 am). Primary outcome was all-cause mortality at 30 days. Secondary outcomes included vascular complications (including limb ischemia and/or bleeding), bloodstream infections and length of ICU stay. Propensity scores were used to adjust for potential confounding effects. RESULTS: Among 250 patients (median (IQR) age 56 (42-64) years) receiving VA-ECMO (median duration 3.5 (1.0-9.0) days), 160 (64%) runs were initiated between 5 pm and 8 am whereas the remainder (36%) started during working hours. Characteristic did not differ between the working hours- and out of hours-group. By day 30, 37 (41.1%), and 68 (42.5%) patients in either group had died, respectively (p = 0.831). VA-ECMO support duration and length of stay on the ICU did not differ significantly in both crude and adjusted analyses. More complications occurred during out of hours service (p = 0.039). CONCLUSIONS: Out of hours- versus working hours-initiation of VA-ECMO for cardiogenic shock was not associated with higher mortality, longer VA-ECMO support duration, or longer length of stay on the intensive care. Vascular complications were more common in the out of hours group.

Twelve years of circulatory extracorporeal life support at the University Medical Centre Utrecht.

INTRODUCTION: Circulatory extracorporeal life support (ECLS) has been performed at the University Medical Centre Utrecht for 12 years. During this time, case mix, indications, ECLS set-ups and outcomes seem to have substantially changed. We set out to describe these characteristics and their evolution over time. METHODS: All patients receiving circulatory ECLS between 2007 and 2018 were retrospectively identified and divided into six groups according to a 2-year period of time corresponding to the date of ECLS initiation. General characteristics plus data pertaining to comorbidities, indications and technical details of ECLS commencement as well as in-hospital, 30-day, 1­year and overall mortality were collected. Temporal trends in these characteristics were examined. RESULTS: A total of 347 circulatory ECLS runs were performed in 289 patients. The number of patients and ECLS runs increased from 8 till a maximum of 40 runs a year. The distribution of circulatory ECLS indications shifted from predominantly postcardiotomy to a wider set of indications. The proportion of peripheral insertions with or without application of left ventricular unloading techniques substantially increased, while in-hospital, 30-day, 1­year and overall mortality decreased over time. CONCLUSION: Circulatory ECLS was increasingly applied at the University Medical Centre Utrecht. Over time, indications as well as treatment goals broadened, and cannulation techniques shifted from central to mainly peripheral approaches. Meanwhile, weaning success increased and mortality rates diminished.

Extracorporeal life support in cardiogenic shock: indications and management in current practice.

Veno-arterial extracorporeal life support (VA-ECLS) provides circulatory and respiratory stabilisation in patients with severe refractory cardiogenic shock. Although randomised controlled trials are lacking, the use of VA-ECLS is increasing and observational studies repeatedly have shown treatment benefits in well-selected patients. Current clinical challenges in VA-ECLS relate to optimal management of the individual patient on extracorporeal support given its inherent complexity. In this review article we will discuss indications, daily clinical management and complications of VA-ECLS in cardiogenic shock refractory to conventional treatment strategies.

[Extracorporeal life support for Legionella pneumonia]. / Extracorporele life support bij Legionella-pneumonie.

BACKGROUND: Legionella species cause 5% of all community acquired pneumonias. However, Legionella pneumonia results relatively often in admission to the intensive care unit (ICU). A significant complication is the development of acute respiratory distress syndrome (ARDS). The ICU mortality rate for Legionella pneumonia is > 30% with conventional treatments. CASE DESCRIPTION: A 64-year-old male was admitted to the ICU with respiratory failure due to Legionella pneumonia complicated by ARDS. Despite maximum conventional therapy being given, including lung-protective invasive mechanical ventilation and prone positioning, progressive hypoxaemia persisted. In collaboration with an extracorporeal life support (ECLS) centre, venovenous ECLS was initiated. Pulmonary function recovered and the patient was successfully weaned from VV-ECLS after 17 days. After three months of hospitalisation and rehabilitation, the patient was discharged home and able to perform his activities of daily living without assistance. CONCLUSION: Legionella pneumonia relatively frequently results in ICU admission, and carries a high mortality with conventional treatments. ECLS may offer a solution if conventional therapies are not sufficiently effective.

Practical recommendations for calcium channel antagonist poisoning.

Calcium channel antagonists (CCAs) are widely used for different cardiovascular disorders. At therapeutic doses, CCAs have a favourable side effect profile. However, in overdose, CCAs can cause serious complications, such as severe hypotension and bradycardia. Patients in whom a moderate to severe intoxication is anticipated should be observed in a monitored setting for at least 12 hours if an immediate-release formulation is ingested, and at least 24 hours when a sustained-release formulation (or amlodipine) is involved, even if the patient is asymptomatic. Initial treatment is aimed at gastrointestinal decontamination and general supportive care, i.e., fluid resuscitation and correction of metabolic acidosis and electrolyte disturbances. In moderate to severe CCA poisoning, a combined medical strategy might be indispensable, such as administration of vasopressors, intravenous calcium and hyperinsulinaemia/euglycaemia therapy. Especially hyperinsulinaemia/euglycaemia therapy is an important first-line treatment in CCA-overdosed patients in whom a large ingestion is suspected. High-dose insulin, in combination with glucose, seems to be most effective when used early in the intoxication phase, even when the patient shows hardly any haemodynamic instability. Intravenous lipid emulsion therapy should only be considered in patients with life-threatening cardiovascular toxicity, such as refractory shock, which is unresponsive to conventional therapies. When supportive and specific pharmacological measures fail to adequately reverse refractory conditions in CCA overdose, the use of extracorporeal life support should be considered. The efficacy of these pharmacological and non-pharmacological interventions generally advocated in CCA poisoning needs further in-depth mechanistic foundation, in order to improve individualised treatment of CCA-overdosed patients.

Pharmacokinetics and Toxicity of Tacrolimus Early After Heart and Lung Transplantation.

Annually, about 8000 heart and lung transplantations are successfully performed worldwide. However, morbidity and mortality still pose a major concern. Renal failure in heart and lung transplant recipients is an essential adverse cause of morbidity and mortality, often originating in the early postoperative phase. At this time of clinical instability, the kidneys are exposed to numerous nephrotoxic stimuli. Among these, tacrolimus toxicity plays an important role, and its pharmacokinetics may be significantly altered in this critical phase by fluctuating drug absorption, changed protein metabolism, anemia and (multi-) organ failure. Limited understanding of tacrolimus pharmacokinetics in these circumstances is hampering daily practice. Tacrolimus dose adjustments are generally based on whole blood trough levels, which widely vary early after transplantation. Moreover, whole blood trough levels are difficult to predict and are poorly related to the area under the concentration-time curve. Even within the therapeutic range, toxicity may occur. These shortcomings of tacrolimus monitoring may not hold for the unbound tacrolimus plasma concentrations, which may better reflect tacrolimus toxicity. This review focuses on posttransplant tacrolimus pharmacokinetics, discusses relevant factors influencing the unbound tacrolimus concentrations and tacrolimus (nephro-) toxicity in heart and lung transplantation patients.

Non-intubated recovery from refractory cardiogenic shock on percutaneous VA-extracorporeal membrane oxygenation.

We report on the use of percutaneous femoral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in a fully awake, non-intubated and spontaneously breathing patient suffering from acute, severe and refractory cardiogenic shock due to a (sub)acute anterior myocardial infarction. Intensified heart failure therapy was closely monitored with a pulmonary artery catheter and allowed gradual weaning off the ECMO support without additional invasive measures, notably without mechanical ventilation. Neurological assessment was possible at all times and complete physical mobilisation was straightforward directly after weaning from ECMO. This limited invasive approach may encourage a more widespread use of percutaneous VA-ECMO.

An arterio-venous bridge for gradual weaning from adult veno-arterial extracorporeal life support.

PURPOSE: Weaning from extracorporeal life support (ELS) is particularly challenging when cardiac recovery is slow, largely incomplete and hard to predict. Therefore, we describe an individualized gradual weaning strategy using an arterio-venous (AV) bridge incorporated into the circuit to facilitate weaning. METHODS: Thirty adult patients weaned from veno-arterial ELS using an AV bridge were retrospectively analyzed. Serial echocardiography and hemodynamic monitoring were used to assess cardiac recovery and load responsiveness. Upon early signs of myocardial recovery, an AV bridge with an Hoffman clamp was added to the circuit and weaning was initiated. Support flow was reduced stepwise by 10-15% every 2 to 8 hours while the circuit flow was maintained at 3.5-4.5 L/min. RESULTS: The AV bridge facilitated gradual weaning in all 30 patients (median age: 66 [53-71] years; 21 males) over a median period of 25 [8-32] hours, with a median support duration of 96 [31-181] hours. During weaning, the median left ventricular ejection fraction was 25% [15-32] and the median velocity time integral of the aortic valve was 16 cm [10-23]. Through the weaning period, the mean arterial blood pressure was maintained at 70 mmHg and the activated partial thromboplastin time was 60 ± 10 seconds without additional systemic heparinization. Neither macroscopic thrombus formation in the ELS circuit during and after weaning nor clinically relevant thromboembolism was observed. CONCLUSION: Incorporation of an AV bridge for weaning from veno-arterial ELS is safe and feasible to gradually wean patients with functional cardiac recovery without compromising the circuit integrity.

Towards a proactive therapy utilizing the modern spectrum of extracorporeal life support: a single-centre experience.

BACKGROUND: We describe a single-centre experience of extracorporeal life support (ELS) for patients with severe and refractory cardiogenic shock, refractory cardiac arrest and severe respiratory failure. METHODS: Between September 2007 and September 2012, 56 intra-hospital and 10 inter-hospital adult patients were supported. RESULTS: The median ELS duration was 3 (0.9 - 6) days in venoarterial and 9.2 (7.4 - 24.4) days in venovenous supported patients. At hospital discharge and follow-up (12 and 40 months), survival among the respiratory (venovenous) patients and cardiac (venoarterial) patients was 84% and 38%, respectively. Survival in severe refractory cardiogenic shock patients was related to early initiation of ELS (<8 hours of onset of failure). A delay in initiating venoarterial ELS (>8 hours) and increased pre-ELS pH and lactate levels were associated with death in all cardiomyopathy patients, independent of infarct size. CONCLUSIONS: Our results exemplify the benefits of ELS as a bridge to initial stabilization of critically ill patients. Potentially, the early application of ELS technology can lower mortality and morbidity in patients with a regressive pathology.

Management of prolonged QT interval and torsades de pointes in the intoxicated patient.

Many drugs can significantly influence cardiac repolarisation causing an increased duration of this repolarisation phase, challenging the repolarisation reserve. This may set the stage for life-threatening ventricular arrhythmias such as torsades de pointes (TdP). TdP generally occurs in conjunction with a prolonged QT interval (QT) on the electrocardiogram. The Dutch Poisons Information Centre (NVIC) often receives information requests about drugs that can influence the QT already at therapeutic dosages. Drug-induced QT prolongation is dose dependent and hence can be particularly pronounced in overdose situations. Also, additional risk factors for the development of life-threatening arrhythmias are often present in intoxicated patients. This review focuses on identification and management of drug-intoxicated patients who are at risk for a reduction in their repolarisation reserve, measured by their QT interval. The QT interval is strongly dependent on heart rate, which has led to the introduction of different methods to adjust the QT interval, i.e. the QTc. Bazett's formula, which has been used for decades, lacks accuracy concerning QTc calculation at higher and lower heart rates, situations often relevant when dealing with intoxicated patients. Additionally, we highlight drugs with QT-prolonging potential that are commonly associated with an overdose setting in the Netherlands. Finally, standard treatment options specifically pointed toward the intoxicated patient at risk of QT prolongation and TdP will be discussed.

Preventing LVAD implantation by early short-term mechanical support and prolonged inodilator therapy : A case series with acute refractory cardiogenic shock treated with veno-arterial extracorporeal membrane oxygenation and optimised medical strategy.

Cardiogenic shock continues to be a life-threatening condition carrying a high mortality and morbidity, where the prognosis remains poor despite intensive modern treatment modalities. In recent years, mainly technical improvements have led to a more widespread use of short- and long-term mechanical circulatory support, such as veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and left ventricular assist devices (LVADs). Currently, LVADs are indispensable as 'bridge' to cardiac recovery, heart transplantation (HTX), and/or as destination therapy Importantly, both LVADs and HTX put a vast burden on financial resources, besides significant short- and long-term risks of morbidity and mortality. These considerations underscore the importance of optimal timing and appropriate patient selection for LVAD therapy, avoiding as much as possible an unfortunate and costly clinical path. In this report, we present a series of three cases with acute refractory cardiogenic shock ('crash and burn', INTERMACS profile 1) successfully treated by ECMO and early optimal medical therapy preventing a certain path towards LVAD and/or HTX, for which they were initially referred. This conservative approach in INTERMACS profile one patients warrants very early introduction of adequate medical heart failure therapy under the umbrella of a combination of short-term mechanical circulatory and inotropic support by phosphodiesterase inhibitors. Therefore, this novel combined medical-mechanical approach could have important clinical implications for this extremely challenging patient category, as it may avoid an unnecessary and costly clinical path towards LVAD and/or heart transplantation.