Effects of rescue inhaled nitric oxide on right ventricle and pulmonary circulation in severe COVID-related acute respiratory distress syndrome.

PURPOSES: To assess the effects of inhaled Nitric Oxide (iNO) on right ventricle dimension and function and systolic pulmonary arterial pressures in severe Acute Respiratory Distress (ARDS) due to Sars-Cov2 (COVID) infection. MATERIALS AND METHODS: We assessed the effects of iNO on right ventricle dimension and function and systolic pulmonary arterial pressures in 12 consecutive COVID-related ARDS patients by means of serial echocardiographic exams (baseline, 12 and 24 h since iNO start). RESULTS: Inhaled NO administration did not influence systolic pulmonary arterial pressures nor RV dimension and function. No changes were detectable in ventilatory data with iNO administration. Considering the negligible effect on oxygenation, iNO use was discontinued in all cases. CONCLUSIONS: In COVID-related severe ARDS iNO administrated as rescue therapy is not able to ameliorate oxygenation nor pulmonary hypertension, as assessed by serial echocardiograms. This finding may be explained by the diffuse loss of hypoxic pulmonary vasoconstriction with increased perfusion around alveolar consolidations which characterizes COVID-related severe ARDS.

Hemodynamic management in brain dead donors.

Donor management is the key in the complex donation process, since up to 20% of organs of brain death donors (DBD) are lost due to hemodynamic instability. This challenge is made more difficult due to the lack of strong recommendations on therapies for hemodynamic management in DBDs and more importantly to the epidemiologic changes in these donors who are becoming older and with more comorbidities (marginal donors). In the present manuscript we aimed at summarizing the available evidence on therapeutic strategies for hemodynamic management (focusing on vasoactive drugs) and monitoring (therapeutic goals). Evidence on management in elderly DBDs is also summarized. Donor management continues critical care but with different and specific therapeutic goals since the number of donor goals met is related to the number of organs retrieved and transplanted. Careful monitoring of selected parameters (possibly including serial echocardiography) is the clinical tool able to guarantee the achievement and maintaining of therapeutic goals. Despide worldwide differences, norepinephrine is the vasoactive of choice in most countries but, whenever higher doses (> 0.2 mcg/kg/min) are needed, a second vasoactive drug (vasopressin) is advisable. Hormonal therapy (desmopressin, corticosteroid and thyroid hormone) are suggested in all DBDs independently of hemodynamic instability. In the single patient, therapeutic regimen (imprimis vasoactive drugs) should be chosen also according to the potential organs retrievable (i.e. heart vs liver and kidneys).

Delayed graft function and perfusion parameters of kidneys from uncontrolled donors after circulatory death.

Better preservation and evaluation of kidneys from donors after circulatory death serve to increase the number of kidneys available for transplantation and hypothermic machine perfusion has been shown to decrease ischemia reperfusion injury and delayed graft function. Data on relation between hemodynamic parameters during hypothermic machine perfusion and delayed graft function in kidneys from donors after circulatory death are so far scarce and not univocal. We aimed at assessing whether hemodynamic parameters measured during hypothermic machine perfusion (flow, mean perfusion pressure, and renal resistance) are associated with delayed graft function in 26 kidneys retrieved from uncontrolled donors after circulatory death. In our series, the incidence of delayed graft function was 57.7% (15/26). Recipients who developed delayed graft function had a longer warm ischemic time (p = 0.04). All hemodynamic parameters measured during hypothermic machine perfusion were comparable between recipients with delayed graft function and those without. According to our data, in kidneys from uncontrolled donors after circulatory death, a longer warm ischemic time (that is the overall time of no flow, as the sum of the no-flow and the no-touch period) is associated with delayed graft function. This finding underscores the pivotal role of ischemic injury in terms of absence of flow in affecting graft function. No association was detectable between hemodynamic parameters during hypothermic machine perfusion and the development of delayed graft function in our series.

Cardiac Involvment in COVID-19-Related Acute Respiratory Distress Syndrome.

The cardiac involvement in Coronavirus disease (COVID-19) is still under evaluation, especially in severe COVID-19-related Acute Respiratory Distress Syndrome (ARDS). The cardiac involvement was assessed by serial troponin levels and echocardiograms in 28 consecutive patients with COVID-19 ARDS consecutively admitted to our Intensive Care Unit from March 1 to March 31. Twenty-eight COVID-19 patients (aged 61.7 ± 10 years, males 79%). The majority was mechanically ventilated (86%) and 4 patients (14%) required veno-venous extracorporeal membrane oxygenation. As of March 31, the Intensive Care Unit mortality rate was 7%, whereas 7 patients were discharged (25%) with a length of stay of 8.2 ±5 days. At echocardiographic assessment on admission, acute core pulmonale was detected in 2 patients who required extracorporeal membrane oxygenation support. Increased systolic arterial pressure was detected in all patients. Increased Troponin T levels were detectable in 11 patients (39%) on admission. At linear regression analysis, troponin T showed a direct relationship with C-reactive Protein (R square: 0.082, F: 5.95, p = 0.017). In conclusions, in COVID-19-related ARDS, increased in Tn levels was common but not associated with alterations in wall motion kinesis, thus suggesting that troponin T elevation is likely to be multifactorial, mainly linked to disease severely (as inferred by the relation between Tn and C-reactive Protein). The increase in systolic pulmonary arterial pressures observed in all patients may be related to hypoxic vasoconstriction. Further studies are needed to confirm our findings in larger cohorts.

Utilization rate of uncontrolled donors after circulatory death-a 3-year single-center investigation.

BACKGROUND: Effectiveness of uncontrolled donation after circulatory death (uDCD) has been recently reported to be 75% according to data coming from some European countries in 2016, but few data are to date available on this topic. METHODS: We assessed the utilization rate (as the percentage of donors who were converted into actual donors) in 37 uDCDs consecutively enrolled at our Center (Careggi Teaching Hospital) from June 2016 to June 2019. RESULTS: In three cases, the family did not give consent for donation (3/37, 8.1%). Among the 37 potential uDCDs, 22 became actual donors (22/37, 59%), with 10 livers and 38 kidneys being transplanted, respectively. Fifteen livers were recovered (15/37, 68%), and 10 livers were transplanted (10/15, 67%). Forty-two kidneys were procured and 38 organs transplanted. The overall effectiveness was 78%. CONCLUSIONS: According to our 3-year experience, uncontrolled DCDs do represent an additional means of increasing the number of transplanted organs (kidneys and livers) with an acceptable utilization rate. Research on organ viability assessment (for both livers and kidneys from uDCDs) is still in its infancy, and there is probably space for a further wider use of organs from uDCDs.

Right Ventricular Hypertrophy in Refractory Acute Respiratory Distress Syndrome Treated With Venovenous Extracorporeal Membrane Oxygenation Support.

OBJECTIVE: In severe acute respiratory distress syndrome (ARDS) treated with extracorporeal membrane oxygenation (ECMO), right ventricular (RV failure) and dilation have been investigated with the use of echocardiography, whereas RV hypertrophy has not been addressed in the literature. The present study assessed the incidence of RV hypertrophy using echocardiography before ECMO treatment and at intensive care unit (ICU) discharge in severe ARDS patients. DESIGN: Observational, retrospective, single-center study. SETTING: A single ECMO center. PARTICIPANTS: The study comprised 46 consecutive patients with severe ARDS. INTERVENTION: Echocardiographic evaluation and ECMO support. MEASUREMENTS AND MAIN RESULTS: A dual-lumen cannula was implanted in most patients (38/46 [82.6%]). Before the start of ECMO, RV hypertrophy was present in 28 patients (60.8%) with no significant differences in baseline characteristics between the 2 subgroups. The ICU mortality rate was 30.4% (14/46), with no difference between patients with RV hypertrophy and those without. At ICU discharge, all patients showed RV hypertrophy. CONCLUSIONS: In severe ARDS treated with ECMO support, RV hypertrophy is a common finding and patients with normal RV wall thickness developed RV hypertrophy after ECMO support. The latter finding may suggest that during ECMO support, the right ventricle still may be subjected to increased afterload. However, additional research should be performed to elucidate the spectrum of mechanism(s) involved in the genesis of RV hypertrophy.

Out of hospital cardiac arrest and uncontrolled donation after circulatory death in a tertiary cardiac arrest center.

OBJECTIVES: Out of hospital cardiac arrest (OHCA) is worldwide quite a common disease, whose mortality still remains high. We aimed at assessing the number of potential donors after OHCA in a tertiary cardiac arrest center with extracorporeal membrane oxygenation (ECPR) and uncontrolled donation after circulatory death (uDCD) programs. METHODS: In our single center, prospective, observational study (June 2016 to December 2018), we included all OHCA consecutive patients aged or less 65 years. RESULTS: Our series included 134 OHCA patients. The percentage of patients with return of spontaneous circulation (ROSC) was 36% (48/134). Among patients with no ROSC, ECPR was implanted in 26 patients (26/86, 30%). Among patients without ROSC, 25 patients were eligible for uDCD (25/86, 29%), while 35 patients died at the emergency department. Among patients with ROSC, 15 patients died (15/48, 31%), among whom seven became donors after brain death (7/15, 49%), a percentage which did not vary during the study period. In the subgroup of the 26 patients treated with ECPR, 24 patients died (24/26, 92%) among whom eight were potential donors (33%, 8/34), and only two patients survived (7.7%, 2/26) though with good neurological outcome. CONCLUSIONS: The implementation of ECPR and uDCD programs in a tertiary cardiac center is feasible and increased the number of donors, because despite organizational and technical challenges, the uDCD donor pool was 62.5% of all potential donors (25/40).

A metabolic approach during normothermic regional perfusion in uncontrolled donors after circulatory death-A pilot study.

The use of donation after circulatory death (DCD) has increased significantly to face the persistent mismatch between supply and demand of organs for transplantation. While controlled (c) DCDs have warm ischemic time (WIT) that can be estimated, the WIT is often inexact and extended in uncontrolled DCD (uDCD), making assessment of injury difficult. We aimed at investigating the effects of cold ischemia on potential donor organ damage in the course of nRP by assessing the dynamic variations of transaminases and creatinine values in 17 uDCD donors. In our series, lactate values did not show significant changes during the study period (P = 0.147). Creatinine values did not significantly changed while transaminases progressive increased throughout the study period, even if it was significant only for AST (P = 0.035). According to our data, nRP duration affects splanchnic organs, being the liver sensitive to hypoperfusion, and serial biochemical measurements could help in detecting organ functional status.

Bilirubin in the early course of venovenous extracorporeal membrane oxygenation support for refractory ARDS.

Bilirubin is known as a marker of hepatic dysfunction and is incorporated in scoring algorithms to assess prognosis in critically ill patients. No data are so far available on the prognostic role of hepatic dysfunction in patients with severe ARDS on venovenous extracorporeal membrane oxygenation (VV-ECMO) support. In 112 consecutive patients with severe ARDS treated with VV-ECMO, we aimed at assessing whether increased bilirubin during the first 72 h could affect early death. Increased serum bilirubin (≥1.2 mg/dl) was detectable in 29 patients (25.9%) who were older (p = 0.031), exhibited a higher SOFA score (p = 0.006), were more frequently given pre-ECMO muscular blockers (p = 0.001) and supported with ECMO for a longer period (p = 0.024), when compared to patients with normal bilirubin. No difference in in-ICU mortality rate was observed between the two subgroups. In survivors, bilirubin showed a progressive and significant decrease (p = 0.032) during the first 72 h of ECMO support, while it increased in dead patients (p = 0.007).The mortality rate was higher in patients with increased bilirubin at 24, 48 and 72 h after ECMO start in respect to that of patients with normal values. Pre-ECMO increased bilirubin values (≥1.2 mg/dl), being detectable in about one-fourth of the entire population, is not associated with increased in-ICU mortality, while the persistence of increased bilirubin values after 24 h of ECMO start and within the first 3 days identified a subgroup of patients at higher risk of death.