Active Donor Management Goals in Serial Donors After Brain Death.

OBJECTIVES: Management of potential organ donors is crucial in the donation process, considering that hemodynamic instability is quite common. MATERIALS AND METHODS: In the this single-center retrospective observational study, we analyzed 87 utilized brain death donors consecutively admitted to our intensive care unit from January 1, 2019, to December 31, 2022. We assessed the achievement of donor management goals during the observation period, and we also evaluated whether the achieve-ment of donor goals differed between younger and older donors (arbitrary age cutoff of 65 years). RESULTS: In our series, mean age of donors was 67 ± 18 y, and organ-per-donor ratio was 2.3. The number of donor goals significantly increased during the 6-hour observation period (P < .001) and all donor goals were achieved in most donors (84/87) at the end of the observation period with no changes in the use and dose of vasoactive drugs. With respect to age, the number of donor goals was significantly higher in older donors at first evaluation, but goals significantly increased in both age subgroups of donors at the end of the 6-hour observation period. CONCLUSIONS: Our data strongly suggested that a strict hemodynamic monitoring schedule allows the achievement of donor goals both in older and in younger brain death donors. We confirmed our previous findings that hemodynamic management in brain death donors is influenced by age. A strict hemodynamic monitoring schedule of brain death donors is useful to consistently achieve donor goals.

First-in-human liver transplantation from a centenarian deceased donor after brain death.

Liver transplantation from elderly donors is expanding due to demand for liver grafts, aging of recipients and donors, and introduction of machine perfusion. We report on a liver transplant from a 100-year-old deceased donor after brain death. The liver was transplanted after the use of hypothermic machine perfusion to a 60-year-old recipient with advanced hepatocellular carcinoma undergoing neoadjuvant immunotherapy. Nine months after the transplant, the patient is alive with a functioning graft and no evidence of acute rejection or tumor recurrence.

Doubts and concerns about COVID-19 uncertainties on imaging data, clinical score, and outcomes.

BACKGROUND: COVID-19 is a pandemic disease affecting predominantly the respiratory apparatus with clinical manifestations ranging from asymptomatic to respiratory failure. Chest CT is a crucial tool in diagnosing and evaluating the severity of pulmonary involvement through dedicated scoring systems. Nonetheless, many questions regarding the relationship of radiologic and clinical features of the disease have emerged in multidisciplinary meetings. The aim of this retrospective study was to explore such relationship throughout an innovative and alternative approach. MATERIALS AND METHODS: This study included 550 patients (range 25-98 years; 354 males, mean age 66.1; 196 females, mean age 70.9) hospitalized for COVID-19 with available radiological and clinical data between 1 March 2021 and 30 April 2022. Radiological data included CO-RADS, chest CT score, dominant pattern, and typical/atypical findings detected on CT examinations. Clinical data included clinical score and outcome. The relationship between such features was investigated through the development of the main four frequently asked questions summarizing the many issues arisen in multidisciplinary meetings, as follows 1) CO-RADS, chest CT score, clinical score, and outcomes; 2) the involvement of a specific lung lobe and outcomes; 3) dominant pattern/distribution and severity score for the same chest CT score; 4) additional factors and outcomes. RESULTS: 1) If CT was suggestive for COVID, a strong correlation between CT/clinical score and prognosis was found; 2) Middle lobe CT involvement was an unfavorable prognostic criterion; 3) If CT score < 50%, the pattern was not influential, whereas if CT score > 50%, crazy paving as dominant pattern leaded to a 15% increased death rate, stacked up against other patterns, thus almost doubling it; 4) Additional factors usually did not matter, but lymph-nodes and pleural effusion worsened prognosis. CONCLUSIONS: This study outlined those radiological features of COVID-19 most relevant towards disease severity and outcome with an innovative approach.

Uncontrolled Donation after Circulatory Death Only Lung Program: An Urgent Opportunity.

Uncontrolled donation after circulatory death (uDCD) represents a potential source of lungs, and since Steen's 2001 landmark case in Sweden, lungs have been recovered from uDCD donors and transplanted to patients in other European countries (France, the Netherlands, Spain and Italy) with promising results. Disparities still exist among European countries and among regions in Italy due to logistical and organizational factors. The present manuscript focuses on the clinical experiences pertaining to uDCD lungs in North America and European countries and on different lung maintenance methods. Existing experiences (and protocols) are not uniform, especially with respect to the type of lung maintenance, the definition of warm ischemic time (WIT) and, finally, the use of ex vivo perfusion (available in the last several years in most centers). In situ lung cooling may be superior to protective ventilation, but this process may be difficult to perform in the uDCD setting and is also time-consuming. On the other hand, the "protective ventilation technique" is simpler and feasible in every hospital. It may lead to a broader use of uDCD lung donors. To date, the results of lung transplants performed after protective ventilation as a preservation technique are scarce but promising. All the protocols comprise, among the inclusion criteria, a witnessed cardiac arrest. The detectable differences included preservation time (240 vs. 180 min) and donor age (<55 years in Spanish protocols and <65 years in Toronto protocols). Overall, independently of the differences in protocols, lungs from uDCD donors show promising results, and the possibility of optimizing ex vivo lung perfusion may broaden the use of these organs.

Urgent coronary angiography in out-of-hospital cardiac arrest: a retrospective single centre investigation.

AIMS: The role of immediate coronary angiography (CAG) with percutaneous coronary intervention (PCI) in patients who present with ST-segment elevation myocardial infarction (STEMI) and cardiac arrest is well recognized. However, the role of immediate angiography in patients after cardiac arrest without STEMI is less clear. We assessed whether urgent (<6 h) CAG and PCI (whenever needed) was associated with improved early survival in out-of-hospital cardiac arrest (OHCA). METHODS: In our single-centre, retrospective, observational study, we included all consecutive OHCA patients admitted to the A&E of the Careggi University Hospital between 1 June 2016 and 31 July 2020. One hundred and forty-four OHCA patients were submitted to CAG and constituted our study population. RESULTS: Among the 221 consecutive OHCA patients, 69 (31%) had refractory cardiac arrest treated with extracorporeal cardiopulmonary resuscitation (eCPR) in 37 (37/69, 56%) patients. The mortality rate was significantly higher in the no CAG subgroup (P < 0.00001). In the CAG subgroup, coronary artery disease was detected in the 70% (92 patients), among whom the left main coronary artery was involved in 10 patients (10.8%). At multivariable regression analysis (CAG subgroup, outcome ICU survival), witnessed cardiac arrest was independently associated with survival. CONCLUSION: A high incidence of coronary artery disease was observed at CAG in the real-world of OHCA patients. Better planning of revascularization and treatment in patients studied with CAG may explain, at least in part, their lower mortality rate.

Haemodynamic management in brain death donors: Influence of aetiology of brain death.

BACKGROUND: In brain death donors (BDDs), donor management is the key in the complex donation process. Donor management goals, which are standards of care or clinical parameters, have been considered an acceptable barometer of successful donor management. AIM: To test the hypothesis that aetiology of brain death could influence haemody namic management in BDDs. METHODS: Haemodynamic data (blood pressure, heart rate, central venous pressure, lactate, urine output, and vasoactive drugs) of BDDs were recorded on intensive care unit (ICU) admission and during the 6-h observation period (Time 1 at the beginning; Time 2 at the end). RESULTS: The study population was divided into three groups according to the aetiology of brain death: Stroke (n = 71), traumatic brain injury (n = 48), and postanoxic encephalopathy (n = 19). On ICU admission, BDDs with postanoxic encephalopathy showed the lowest values of systolic and diastolic blood pressure associated with higher values of heart rate and lactate and a higher need of norepinephrine and other vasoactive drugs. At the beginning of the 6-h period (Time 1), BDDs with postanoxic encephalopathy showed higher values of heart rate, lactate, and central venous pressure together with a higher need of other vasoactive drugs. CONCLUSION: According to our data, haemodynamic management of BDDs is affected by the aetiology of brain death. BDDs with postanoxic encephalopathy have higher requirements for norepinephrine and other vasoactive drugs.

Right ventricle dysfunction does not predict mortality in patients with SARS-CoV-2-related acute respiratory distress syndrome on extracorporeal membrane oxygenation support.

BACKGROUND: The prognostic role of right ventricle dilatation and dysfunction (RVDD) has not been elucidated in patients with coronavirus disease (COVID)-related respiratory failure refractory to standard treatment needing extracorporeal membrane oxygenation (ECMO) support. AIM: To assess whether pre veno-venous (VV) ECMO RVDD were related to in-intensive care unit (ICU) mortality. METHODS: We enrolled 61 patients with COVID-related acute respiratory distress syndrome refractory to conventional treatment submitted to VV ECMO and consecutively admitted to our ICU (an ECMO referral center) from 31th March 2020 to 31th August 2021. An echocardiographic exam was performed immediately before VV ECMO implantation. RESULTS: Males were prevalent (73.8%) and patients with a body mass index > 30 kg/m2 were the majority (46/61, 75%). The overall in-ICU mortality rate was 54.1% (33/61). RVDD was detectable in more than half of the population (34/61, 55.7%) and associated with higher simplified organ functional assessment (SOFA) values (P = 0.029) and a longer mechanical ventilation duration prior to ECMO support (P = 0.046). Renal replacement therapy was more frequently needed in RVDD patients (P = 0.002). A higher in-ICU mortality (P = 0.024) was observed in RVDD patients. No echo variables were independent predictors of in-ICU death. CONCLUSION: In patients with COVID-related respiratory failure on ECMO support, RVDD (dilatation and dysfunction) is a common finding and identifies a subset of patients characterized by a more severe disease (as indicated by higher SOFA values and need of renal replacement therapy) and by a higher in-ICU mortality. RVDD (also when considered separately) did not result independently associated with in-ICU mortality in these patients.

Echocardiography Before Extracorporeal Membrane Oxygenation in Refractory Respiratory Failure: SARS-CoV-2 Infection Versus Other Etiologies.

OBJECTIVES: The study authors hypothesized that in patients with SARS-CoV-2, COVID-19-related refractory respiratory failure requiring extracorporeal membrane oxygenation (ECMO) support echocardiographic findings (just before ECMO implantation) would be different from those observed in patients with refractory respiratory failure from different etiologies. DESIGN: A single-center observational study. SETTING: At an intensive care unit (ICU). PARTICIPANTS: A total of 61 consecutive patients with refractory COVID-19-related respiratory failure (COVID-19 series) and 74 patients with refractory acute respiratory disease syndrome from other etiologies (no COVID-19 series), all needing ECMO support. INTERVENTIONS: Echocardiogram pre-ECMO. MEASUREMENTS AND MAIN RESULTS: Right ventricle dilatation and dysfunction were defined in the presence of the RV end-diastolic area and/or left ventricle end-diastolic area (LVEDA >0.6 and tricuspid annular plane systolic excursion [TAPSE] <15 mm. Patients in the COVID-19 series showed a higher body mass index (p < 0.001) and a lower Sequential Organ Failure Assessment score (p = 0.002). In-ICU mortality rates were comparable between the 2 subgroups. Echocardiograms performed in all patients before ECMO implantation revealed an incidence of RV dilatation that was higher in patients in the COVID-19 series (p < 0.001), and they also showed higher values of systolic pulmonary artery pressure (sPAP) (p < 0.001) and lower TAPSE and/or sPAP (p < 0.001). The multivariate logistic regression analysis showed that COVID-19-related respiratory failure was not associated with early mortality. The presence of RV dilatation and the uncoupling of RV function and pulmonary circulation were associated independently with COVID-19 respiratory failure. CONCLUSIONS: The presence of RV dilatation and an altered coupling between RVe function and pulmonary vasculature (as indicated by TAPSE and/or sPAP) are associated strictly with COVID-19-related refractory respiratory failure needing ECMO support.

An extensive evaluation of hepatic markers of damage and regeneration in controlled and uncontrolled donation after circulatory death.

Livers from donations after circulatory death (DCDs) are very sensitive to ischemia/reperfusion injury and thus need careful reconditioning, such as normothermic regional perfusion (NRP). So far, its impact on DCDs has not been thoroughly investigated. This pilot cohort study aimed to explore the NRP impact on liver function by evaluating dynamic changes of circulating markers and hepatic gene expression in 9 uncontrolled DCDs (uDCDs) and 10 controlled DCDs. At NRP start, controlled DCDs had lower plasma levels of inflammatory and liver damage markers, including α-glutathione s-transferase, sorbitol-dehydrogenase, malate dehydrogenase 1, liver-type arginase-1, and keratin-18, but higher levels of osteopontin, sFas, flavin mononucleotide, and succinate than uDCDs. During 4-hour NRP, some damage and inflammatory markers increased in both groups, while IL-6, HGF, and osteopontin increased only in uDCDs. At the NRP end, the tissue expression of early transcriptional regulators, apoptosis, and autophagy mediators was higher in uDCDs than in controlled DCDs. In conclusion, despite initial differences in liver damage biomarkers, the uDCD group was characterized by a major gene expression of regenerative and repair factors after the NRP procedure. Correlative analysis among circulating/tissue biomarkers and the tissue congestion/necrosis degree revealed new potential candidate biomarkers.

Outcomes of kidney transplantation from uncontrolled donors after circulatory death vs. expanded-criteria or standard-criteria donors after brain death at an Italian Academic Center: a prospective observational study.

BACKGROUND: The use of kidneys from "expanded criteria" donors after brain death (ECD) and uncontrolled donors after circulatory death (uDCD) has been warranted to increase the pool of donors for kidney transplantation (KT). However, there is lack of evidence on the feasibility and safety of KT from such donors in the Italian setting. METHODS: We queried our prospectively KT database to select patients undergoing KT from deceased donors (uDCDs, ECDs, and standard-criteria donors [SCD] after brain death) from January 2017 to December 2020, comparing the perioperative and mid-term functional outcomes. RESULTS: Overall, 172 KTs were included. The donor's profile was different among the study groups, while recipients' characteristics were similar expect for median age. Grafts from uDCDs and ECDs had longer median cold ischemia times as compared to grafts from SCDs. The proportion of patients experiencing DGF, the median hospitalization, as well as the overall and major complications rate, were significantly higher among recipients from uDCDs. The proportion of patients needing dialysis at last follow-up was significantly higher among recipients from uDCDs (33.3% vs. 8.5% vs. 5.4%, P<0.001). However, the median eGFR at the last follow-up was lower for recipients from ECDs compared to those from uDCDs and SCDs, respectively (P<0.001). CONCLUSIONS: While "marginal" donors represent a relevant source of organs, KTs from uDCDs carry higher risks of major surgical complications, DGF, and worse graft survival as compared to KT from both ECDs and SCDs. As such, the use of grafts from uDCDs should be carefully assessed balancing the potential benefits with the risk of primary no function and the subsequent immunological sensitization.

Clinical Significance of Right Ventricle Echocardiographic Patterns in Critically-Ill COVID-Related Acute Respiratory Distress Syndrome "On Behalf of Protecting the Right Ventricle Network (PRORVnet)".

We assessed whether right ventricle (RV) alterations and their development may have clinical significance in critically-ill Coronavirus Disease (COVID) patients, as detected by serial echocardiograms during Intensive Care Unit (ICU) course. This observational single center study included 98 consecutive patients with COVID-related acute respiratory distress syndrome (ARDS). Three subgroups were considered: RV Dysfunction (Dys) on admission (10/98, 10%), developed RV Dys (17/98, 17%), and no RV Dys (71/98, 73%). Overall mortality at 3 months was 46.9%. The first subgroup was characterized by the highest need for Extracorporeal Membrane Oxygenation (ECMO) support (P < .001) and a systemic inflammatory activation (as indicated by increased D-dimer), the second one by the lowest PaO2/FiO2 (P/F). At multivariate regression analysis, age and Sequential Organ Failure Assessment score were independent predictors for mortality. Different RV echo patterns were observed in critically ill patients presenting with COVID-related ARDS during ICU stay. RV Dys on admission was characterized by a high inflammatory activation while patients who developed RV Dys during ICU stay showed lowest P/F. Both these two subgroups identify patients with a severe COVID disease which in a high percentage of cases was unresponsive to standard treatment and required the use of ECMO.

The role of sequential normothermic regional perfusion and end-ischemic normothermic machine perfusion in liver transplantation from very extended uncontrolled donation after cardiocirculatory death.

The use of pre-procurement normothermic regional perfusion (NRP) allowed us to implement controlled DCD liver transplantation with results comparable to brain death donors, but the use of uncontrolled DCD is declining due to logistic challenges and the high incidence of post-transplant complications. In Italy, the mandatory stand-off period of 20 min for DCD donors has driven the combined use of NRP and ex-situ machine perfusion with the intent to counterbalance the negative impact of prolonged warm ischemia. Organ viability during NRP is based on duration of warm ischemia, regional perfusion flow, lactate, transaminases values and histology, and those used in Italy are the widest worldwide. However, this evaluation can be difficult, especially when the acute damage is particularly severe. The use of ex-situ NRP could provide a safe organ evaluation. In the period from 06/2020 to 06/2022, all DCD grafts exceeding NRP viability criteria at a single center were eventually evaluated using ex-situ normothermic machine perfusion. Machine perfusion viability criteria were based on lactate clearance, irrespectively to bile production, unless 1-h transaminases perfusate level were not exceeding 5000 IU/L. Three cases of uncontrolled DCD grafts in excess of NRP viability criteria underwent ex-situ graft evaluation. Two matched ex-situ normothermic machine perfusion viability criteria and were successfully transplanted. Both recipients are doing well after 26 and 5 months after surgery with no signs of ischemic cholangiopathy. This experience suggests that the sequential use of NRP and normothermic machine perfusion may further expand the boundaries of organ viability in uncontrolled DCD liver transplantation.