Heart transplant outcomes in patients with mechanical circulatory support: cold storage versus normothermic perfusion organ preservation.

OBJECTIVES: Patients with mechanical circulatory support bridged to a heart transplant (HTx) are at higher risk of postoperative graft dysfunction. In this subset, a mode of graft preservation that shortens graft ischaemia should be beneficial. METHODS: The outcomes of 38 patients on mechanical circulatory support (extracorporeal life support, left ventricular assist device and biventricular assist device) who received a HTx between 2015 and 2020 were analysed according to the method of graft preservation: cold storage (CS) group, 24 (63%) or ex vivo perfusion (EVP) group, 14 (37%). RESULTS: The median age was 57 (range 30-73) vs 64 (35-75) years (P = 0.10); 88% were men (P = 0.28); extracorporeal life support was more frequent in the CS group (54% vs 36%; P = 0.27) versus left ventricular and biventricular assist devices in the EVP group (46% vs 64%; P = 0.27). Clamping time was shorter in the EVP group (P < 0.001) and ischaemic time >4 h was higher in the CS group (P = 0.01). Thirty-day mortality was 13% (0-27%) in the CS group and 0% (P = 0.28) in the EVP group. A significantly lower primary graft failure [7% (0-23%) vs 42% (20-63%); P = 0.03] was observed in the EVP group. Survival at 1 year was 79 ± 8% (63-95%) in the CS group and 84 ± 10% (64-104%) in the EVP group (P = 0.95). CONCLUSIONS: Our results support the use of ex vivo graft perfusion in patients on mechanical circulatory support as a bridge to a HTx. This technique, by shortening graft ischaemic time, seems to improve post-HTx outcomes.

Extracorporeal liver support in patients with liver failure: a systematic review and meta-analysis of randomized trials.

PURPOSE: Acute liver failure (ALF) and acute on chronic liver failure (ACLF) are associated with significant mortality and morbidity. Extracorporeal liver support (ECLS) devices have been used as a bridge to liver transplant; however, the efficacy and safety of ECLS are unclear. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to examine the efficacy and safety of ECLS in liver failure. METHODS: We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from inception through March 13, 2019. RCTs comparing ECLS to usual care in ALF or ACLF were included. We used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty of the evidence. RESULTS: We identified 25 RCTs (1796 patients). ECLS use was associated with reduction in mortality (RR 0.84; 95% CI 0.74, 0.96, moderate certainty) and improvement in hepatic encephalopathy (HE) (RR 0.71; 95% CI 0.60, 0.84, low certainty) in patients with ALF or ACLF. The effect of ECLS on hypotension (RR 1.46; 95% CI 0.98, 2.2, low certainty), bleeding (RR 1.21; 95% CI 0.88, 1.66, moderate certainty), thrombocytopenia (RR 1.62; 95% CI 1.0, 2.64, very low certainty) and line infection (RR 1.92; 95% CI 0.11, 33.44, low certainty) was uncertain. CONCLUSIONS: ECLS may reduce mortality and improve HE in patients with ALF and ACLF. The effect on other outcomes is uncertain. However, the evidence is limited by risk of bias and imprecision, and larger trials are needed to better determine the effect of ECLS on patient-important outcomes.

New Strategies to Expand and Optimize Heart Donor Pool: Ex Vivo Heart Perfusion and Donation After Circulatory Death: A Review of Current Research and Future Trends.

Heart transplantation remains the definitive management for end-stage heart failure refractory to medical therapy. While heart transplantation cases are increasing annually worldwide, there remains a deficiency in organ availability with significant patient mortality while on the waiting list. Attempts have therefore been made to expand the donor pool and improve access to available organs by recruiting donors who may not satisfy the standard criteria for organ donation because of donor pathology, anticipated organ ischemic time, or donation after circulatory death. "Ex vivo" heart perfusion (EVHP) is an emerging technique for the procurement of heart allografts. This technique provides mechanically supported warm circulation to a beating heart once removed from the donor and before implantation into the recipient. EVHP can be sustained for several hours, facilitate extended travel time, and enable administration of pharmacological agents to optimize cardiac recovery and function, as well as allow assessment of allograft function before implantation. In this article, we review recent advances in expanding the donor pool for cardiac transplantation. Current limitations of conventional donor criteria are outlined, including the determinants of organ suitability and assessment, involving transplantation of donation after circulatory death hearts, extended criteria donors, and EVHP-associated assessment, optimization, and transportation. Finally, ongoing research relating to organ optimization and functional ex vivo allograft assessment are reviewed.

Extracorporeal techniques for the treatment of critically ill patients with sepsis beyond conventional blood purification therapy: the promises and the pitfalls.

Sepsis is one of the leading causes of morbidity and mortality worldwide. It is characterized by a dysregulated immune response to infections that results in life-threatening organ dysfunction and even death. Bacterial cell wall components (endotoxin or lipopolysaccharide), known as pathogen-associated molecular patterns (PAMPs), as well as damage-associated molecular patterns (DAMPs) released by host injured cells, are well-recognized triggers resulting in the elevation of both pro-inflammatory and anti-inflammatory cytokines. Understanding this complex pathophysiology has led to the development of therapeutic strategies aimed at restoring a balanced immune response by eliminating/deactivating these inflammatory mediators. Different extracorporeal techniques have been studied in recent years in the hope of maximizing the effect of renal replacement therapy in modulating the exaggerated host inflammatory response, including the use of high volume hemofiltration (HVHF), high cut-off (HCO) membranes, adsorption alone, and coupled plasma filtration adsorption (CPFA). These strategies are not widely utilized in practice, depending on resources and local expertise. The literature examining their use in septic patients is growing, but the evidence to support their use at this stage is considered of low level. Our aim is to provide a comprehensive overview of the technical aspects, clinical applications, and associated side effects of these techniques.

Extracorporeal Perfusion in Vascularized Composite Allotransplantation: Current Concepts and Future Prospects.

Severe injuries of the face and limbs remain a major challenge in today's reconstructive surgery. Vascularized composite allotransplantation (VCA) has emerged as a promising approach to restore these defects. Yet, there are major obstacles preventing VCA from broad clinical application. Two key restrictions are (1) the graft's limited possible ischemia time, keeping the potential donor radius extremely small, and (2) the graft's immunogenicity, making extensive lifelong monitoring and immunosuppressive treatment mandatory. Machine perfusion systems have demonstrated clinical success addressing these issues in solid organ transplantation by extending possible ischemia times and decreasing immunogenicity. Despite many recent promising preclinical trials, machine perfusion has not yet been utilized in clinical VCA. This review presents latest perfusion strategies in clinical solid organ transplantation and experimental VCA in light of the specific requirements by the vascularized composite allograft's unique tissue composition. It discusses optimal settings for temperature, oxygenation, and flow types, as well as perfusion solutions and the most promising additives. Moreover, it highlights the implications for the utility of VCA as therapeutic measure in plastic surgery, if machine perfusion can be successfully introduced in a clinical setting.

Arterial Pulsatility and Circulating von Willebrand Factor in Patients on Mechanical Circulatory Support.

BACKGROUND: The main risk factor for bleeding in patients with continuous-flow mechanical circulatory support (CF-MCS) is the acquired von Willebrand factor (VWF) defect related to the high shear-stress forces developed by these devices. Although a higher bleeding rate has been reported in CF-MCS recipients who had reduced pulsatility, the relation between pulsatility and the VWF defect has never been studied. OBJECTIVES: The purpose of this study was to investigate the relation between pulsatility and VWF under CF-MCS. METHODS: We assessed the effect of 2 CF-MCS on VWF multimer degradation in a mock circulatory loop (model 1). Using these devices, we investigated in a dose-effect model (model 2) 3 levels of pulsatility in 3 groups of swine. In a cross-over model (model 3), we studied the effects of sequential changes of pulsatility on VWF. We reported the evolution of VWF multimerization in a patient undergoing serial CF-MCS and/or pulsatile-MCS. RESULTS: We demonstrated the proteolytic degradation of VWF multimers by high shear CF-MCS in a circulatory loop without pulsatility. We observed both in swine models and in a patient that the magnitude of the VWF degradation is modulated by the pulsatility level in the high shear-stress level condition, and that the restoration of pulsatility is a trigger for the endothelial release of VWF. CONCLUSIONS: We demonstrated that the VWF defect reflects the balance between degradation induced by the shear stress and the endothelial release of new VWF triggered by the pulsatility. This modulation of VWF levels could explain the relationship between pulsatility and bleeding observed in CF-MCS recipients. Preservation of pulsatility may be a new target to improve clinical outcomes of patients.

Past and present role of extracorporeal membrane oxygenation in combat casualty care: How far will we go?

Advanced extracorporeal therapies have been successfully applied in the austere environment of combat casualty care over the previous decade. In this review, we describe the historic underpinnings of extracorporeal membrane oxygenation, review the recent experience with both partial and full lung support during combat operations, and critically assess both the current status of the Department of Defense extracorporeal membrane oxygenation program and the way forward to establish long-range lung rescue therapy as a routine capability for combat casualty care.

Temporal Differences in Outcomes During Long-Term Mechanical Circulatory Support.

BACKGROUND: Device indications have changed for placement of continuous-flow left ventricular assist devices (CF-LVADs). We performed a multicenter analysis evaluating temporal variations in outcomes after CF-LVAD implantation. METHODS & RESULTS: We retrospectively defined 3 time intervals to reflect changes in CF-LVAD technology (period 1, 2004-2009; period 2, 2010-2012; and period 3, 2012-2014). A total of 1,064 patients (Heartmate II [HMII] = 835; Heartware [HVAD] = 229) underwent CF-LVAD implantation from May 2004 to October 2014. Device utilization was different between periods: period 1: HMII = 134 (100%); period 2: HMII = 480 (88%) and HW = 63 (12%); and period 3: HMII = 221 (57%) and HW = 166 (43%); P < .001. Despite few baseline group differences, adjusted survivals were similar among the time periods (P = .96). Adjusted multivariable analysis revealed age (per 10-year increase) and Interagency Registry for Mechanically Assisted Circulatory Support category (1 vs all others) as the only independent predictors of mortality: P < .001 and P = .008, respectively. Furthermore, it also showed the later periods to be at an increased risk of adverse events: 1) pump thrombosis (periods 2 and 3); and 2) gastrointestinal bleeding (period 3). CONCLUSIONS: Despite significant differences in device types, indications, and patient characteristics, post-implantation survivals were similar across time intervals. The most recent cohort seems to be at an increased risk of gastrointestinal bleeding and pump thrombosis.

Fifty Years of Research in ARDS. Is Extracorporeal Circulation the Future of Acute Respiratory Distress Syndrome Management?

Mechanical ventilation (MV) remains the cornerstone of acute respiratory distress syndrome (ARDS) management. It guarantees sufficient alveolar ventilation, high FiO2 concentration, and high positive end-expiratory pressure levels. However, experimental and clinical studies have accumulated, demonstrating that MV also contributes to the high mortality observed in patients with ARDS by creating ventilator-induced lung injury. Under these circumstances, extracorporeal lung support (ECLS) may be beneficial in two distinct clinical settings: to rescue patients from the high risk for death associated with severe hypoxemia, hypercapnia, or both not responding to maximized conventional MV, and to replace MV and minimize/abolish the harmful effects of ventilator-induced lung injury. High extracorporeal blood flow venovenous extracorporeal membrane oxygenation (ECMO) may therefore rescue the sickest patients with ARDS from the high risk for death associated with severe hypoxemia, hypercapnia, or both not responding to maximized conventional MV. Successful venovenous ECMO treatment in patients with extremely severe H1N1-associated ARDS and positive results of the CESAR trial have led to an exponential use of the technology in recent years. Alternatively, lower-flow extracorporeal CO2 removal devices may be used to reduce the intensity of MV (by reducing Vt from 6 to 3-4 ml/kg) and to minimize or even abolish the harmful effects of ventilator-induced lung injury if used as an alternative to conventional MV in nonintubated, nonsedated, and spontaneously breathing patients. Although conceptually very attractive, the use of ECLS in patients with ARDS remains controversial, and high-quality research is needed to further advance our knowledge in the field.

Cardiopulmonary Resuscitation in Adults and Children With Mechanical Circulatory Support: A Scientific Statement From the American Heart Association.

Cardiac arrest in patients on mechanical support is a new phenomenon brought about by the increased use of this therapy in patients with end-stage heart failure. This American Heart Association scientific statement highlights the recognition and treatment of cardiovascular collapse or cardiopulmonary arrest in an adult or pediatric patient who has a ventricular assist device or total artificial heart. Specific, expert consensus recommendations are provided for the role of external chest compressions in such patients.

Predicting the Necessity for Extracorporeal Circulation During Lung Transplantation: A Feasibility Study.

OBJECTIVE: The factors leading to the implementation of unplanned extracorporeal circulation during lung transplantation are poorly defined. Consequently, the authors aimed to identify patients at risk for unplanned extracorporeal circulation during lung transplantation. DESIGN: Retrospective data analysis. SETTING: Single-center university hospital. PARTICIPANTS: A development data set of 170 consecutive patients and an independent validation cohort of 52 patients undergoing lung transplantation. INTERVENTIONS: The authors investigated a cohort of 170 consecutive patients undergoing single or sequential bilateral lung transplantation without a priori indication for extracorporeal circulation and evaluated the predictive capability of distinct preoperative and intraoperative variables by using automated model building techniques at three clinically relevant time points (preoperatively, after endotracheal intubation, and after establishing single-lung ventilation). MEASUREMENTS AND MAIN RESULTS: Preoperative mean pulmonary arterial pressure was the strongest predictor for unplanned extracorporeal circulation. A logistic regression model based on preoperative mean pulmonary arterial pressure and lung allocation score achieved an area under the receiver operating characteristic curve of 0.85. Consequently, the authors developed a novel 3-point scoring system based on preoperative mean pulmonary arterial pressure and lung allocation score, which identified patients at risk for unplanned extracorporeal circulation and validated this score in an independent cohort of 52 patients undergoing lung transplantation. CONCLUSIONS: The authors showed that patients at risk for unplanned extracorporeal circulation during lung transplantation could be identified by their novel 3-point score.

Mechanical circulatory support for end-stage heart failure.

Mechanical circulatory assistance has become a frequent therapeutic option for patients with advanced heart failure. For patients with acute cardiogenic shock and impaired organ function, short-term assistance with venoarterial extracorporeal membrane oxygenation is the leading therapeutic option. It enables a "bridge to decision-making" i.e. withdrawal of the device after myocardial recovery or after recognition of therapeutic futility, or as a bridge-to-transplantation or to long-term mechanical support. For Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) class 2-6 patients, implantation of a long-term ventricular assist-device (VAD) should be considered before progression to multiple organ failure if heart transplantation is not a first-line option. Most patients receive a miniaturized axial or centrifugal fully implantable left VAD as a bridge-to-transplantation or as "destination therapy" in this setting.

Extracorporeal Support for Chronic Obstructive Pulmonary Disease: A Bright Future.

In the past the only option for the treatment of respiratory failure due to acute exacerbation of chronic obstructive pulmonary disease (aeCOPD) was invasive mechanical ventilation. In recent decades, the potential for extracorporeal carbon dioxide (CO2) removal has been realized. We review the various types of extracorporeal CO2 removal, outline the optimal use of these therapies for aeCOPD, and make suggestions for future controlled trials. We also describe the advantages and requirements for an ideal long-term ambulatory CO2 removal system for palliation of COPD.

Extreme liver surgery as treatment of liver tumors involving the hepatocaval confluence

Objective. Analyze the characteristics, surgical technique, morbidity and survival of patients treated with extreme liver surgery. Materials and methods. We present a series of consecutive patients with malignant liver tumors in hepatocaval confluence treated in a single center with extreme liver surgery (April 2008-March 2015). Data were collected prospectively and analyzed with SPSS 21.0. Results. 12 patients were included. 50 % were male and 50 % were female with a mean age of 59 ± 10 years old. The median of comorbidities was 7 according to the Charlson Age Comorbidity Index. The 75 % of the tumors were metastases, most of them from colorectal cancer. Most of the patients received neoadjuvant chemotherapy and in 58 % preoperative portal embolization was performed. Major hepatectomies were performed (66.7 % extended right hepatectomy, 33.3 % left extended hepatectomy). The 83.3 % of the patients needed vascular reconstruction. Postoperative morbidity was more than grade II in 50 % of the patients according to Dindo-Clavien classification. There was no intraoperative mortality. The postoperative mortality rate at 90 days was 33 % due to hepatic failure and biliary fistula. In December 2015, 33 % of the patients are still alive with a mean survival of 19 months (13-23) with an ECOG Performance Status of 0. Conclusion. Extreme liver surgery carries a high rate of morbidity and mortality that seem to increase with age and with higher tumor volumes, according to the literature. It is a therapeutic option to consider in patients with low comorbidity suffering from malignant neoplasms that involve the hepatocaval confluence, when no other treatment with curative intention can be performed (AU)

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Alteraciones microcirculatorias en cirugía cardíaca con circulación extracorpórea / Microcirculatory changes during cardiac surgery with cardiopulmonary bypass

Objetivo. Evaluar la microcirculación en pacientes de riesgo quirúrgico intermedio y alto, sometidos a cirugía cardíaca (CC) con circulación extracorpórea (CEC). Pacientes y métodos. Se estudió a 22 pacientes con Euroscore superior a 3. Se evaluó con la técnica de videomicroscopía Side Stream Dark Field: densidad capilar, proporción de capilares perfundidos (PCP), densidad de capilares perfundidos, índice de flujo microvascular (IFM) e índice de heterogeneidad de flujo microvascular. Se grabaron de 3 a 5 secuencias de vídeo: luego de la inducción anestésica (T1), al inicio de la CEC (T2), antes de finalizar la CEC (T3) y una vez finalizada la misma, previo al traslado del paciente a la Unidad de Terapia Intensiva (T4). La presión arterial media disminuyó mientras que el lactato arterial aumentó de manera significativa al comparar valores basales y finales (p<0,05). El IFM aumentó significativamente en T3 y T4 (p<0,05) respecto del valor inicial. Al comparar a los pacientes con y sin complicaciones postoperatorias, se encontraron diferencias significativas en: Euroscore, fracción de eyección del ventrículo izquierdo preoperatoria e IFM en T3. Conclusiones. En pacientes con riesgo preoperatorio intermedio/elevado, la CC y la CEC determinaron un aumento del IFM y del lactato arterial hacia el final del período de estudio. Estas alteraciones plantean la posibilidad de un shunt microcirculatorio funcional a nivel de la perfusión tisular, secundarios a el traumatismo quirúrgica y la CEC. Es necesario profundizar la investigación a efectos de una mejor comprensión de los mecanismos involucrados (AU)

Objective. To evaluate microcirculation in intermediate and high mortality risk patients undergoing cardiac surgery (CS) with cardiopulmonary bypass (CPB). Patients and methods. The study included 22 patients with a Euroscore >3. Using the Videomicroscopy Side Stream Dark Field system, and evaluation was made of, capillary density, proportion of perfused capillaries, density of perfused capillaries, microcirculatory flow index (MFI), and heterogeneity flow index. Three to five video sequences were recorded: after induction of anaesthesia (T1), at the beginning of the CPB (T2), before finalising CPB (T3), at the end of the surgery, and before the patient was transferred to Intensive Care Unit (T4). Mean arterial pressure decreased, while the blood lactate increased significantly, when comparing the initial and final values (P<.05). MFI increased significantly in T3 and T4 (P<.05) with regards to the initial values. When the patients with and without postoperative complications were compared, significant differences were found in, Euroscore, left ventricular ejection fraction, and MFI in T3. Conclusions. in patients with intermediate/high preoperative risk, CS and CBP can involve an increase in MFI and blood lactate at the end of the study. These alterations suggest the possibility of a functional microcirculatory shunt at tissue perfusion level, secondary to the surgical injury and the CPB. Further investigation is needed to have a better understanding of the mechanisms involved (AU)