A Randomized Trial of Intravenous Amino Acids for Kidney Protection.

BACKGROUND: Acute kidney injury (AKI) is a serious and common complication of cardiac surgery, for which reduced kidney perfusion is a key contributing factor. Intravenous amino acids increase kidney perfusion and recruit renal functional reserve. However, the efficacy of amino acids in reducing the occurrence of AKI after cardiac surgery is uncertain. METHODS: In a multinational, double-blind trial, we randomly assigned adult patients who were scheduled to undergo cardiac surgery with cardiopulmonary bypass to receive an intravenous infusion of either a balanced mixture of amino acids, at a dose of 2 g per kilogram of ideal body weight per day, or placebo (Ringer's solution) for up to 3 days. The primary outcome was the occurrence of AKI, defined according to the Kidney Disease: Improving Global Outcomes creatinine criteria. Secondary outcomes included the severity of AKI, the use and duration of kidney-replacement therapy, and all-cause 30-day mortality. RESULTS: We recruited 3511 patients at 22 centers in three countries and assigned 1759 patients to the amino acid group and 1752 to the placebo group. AKI occurred in 474 patients (26.9%) in the amino acid group and in 555 (31.7%) in the placebo group (relative risk, 0.85; 95% confidence interval [CI], 0.77 to 0.94; P = 0.002). Stage 3 AKI occurred in 29 patients (1.6%) and 52 patients (3.0%), respectively (relative risk, 0.56; 95% CI, 0.35 to 0.87). Kidney-replacement therapy was used in 24 patients (1.4%) in the amino acid group and in 33 patients (1.9%) in the placebo group. There were no substantial differences between the two groups in other secondary outcomes or in adverse events. CONCLUSIONS: Among adult patients undergoing cardiac surgery, infusion of amino acids reduced the occurrence of AKI. (Funded by the Italian Ministry of Health; PROTECTION ClinicalTrials.gov number, NCT03709264.).

Low Versus High Blood Pressure Targets in Critically Ill and Surgical Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: Hypotension is associated with adverse outcomes in critically ill and perioperative patients. However, these assumptions are supported by observational studies. This meta-analysis of randomized controlled trials aims to compare the impact of lower versus higher blood pressure targets on mortality. DATA SOURCES: We searched PubMed, Cochrane, and Scholar from inception to February 10, 2024. STUDY SELECTION: Randomized trials comparing lower versus higher blood pressure targets in the management of critically ill and perioperative settings. DATA EXTRACTION: The primary outcome was all-cause mortality at the longest follow-up available. This review was registered in the Prospective International Register of Systematic Reviews, CRD42023452928. DATA SYNTHESIS: Of 2940 studies identified by the search string, 28 (12 in critically ill and 16 in perioperative settings) were included totaling 15,672 patients. Patients in the low blood pressure target group had lower mortality (23 studies included: 1019/7679 [13.3%] vs. 1103/7649 [14.4%]; relative risk 0.93; 95% CI, 0.87-0.99; p = 0.03; I2 = 0%). This corresponded to a 97.4% probability of any increase in mortality with a Bayesian approach. These findings were mainly driven by studies performed in the ICU setting and with treatment lasting more than 24 hours; however, the magnitude and direction of the results were similar in the majority of sensitivity analyses including the analysis restricted to low risk of bias studies. We also observed a lower rate of atrial fibrillation and fewer patients requiring transfusion in low-pressure target groups. No differences were found in the other secondary outcomes. CONCLUSIONS: Based on pooled randomized trial evidence, a lower compared with a higher blood pressure target results in a reduction of mortality, atrial fibrillation, and transfusion requirements. Lower blood pressure targets may be beneficial but there is ongoing uncertainty. However, the present meta-analysis does not confirm previous findings and recommendations. These results might inform future guidelines and promote the study of the concept of protective hemodynamics.

Stroke outcomes following durable left ventricular assist device implant in patients bridged with micro-axial flow pump: Insights from a large registry.

BACKGROUND: Stroke after durable left ventricular assist device (d-LVAD) implantation portends high mortality. The incidence of ischemic and hemorrhagic stroke and the impact on stroke outcomes of temporary mechanical circulatory support (tMCS) management among patients requiring bridge to d-LVAD with micro-axial flow-pump (mAFP, Abiomed) is unsettled. METHODS: Consecutive patients, who underwent d-LVAD implantation after being bridged with mAFP at 19 institutions, were retrospectively included. The incidence of early ischemic and hemorrhagic stroke after d-LVAD implantation (<60 days) and association of pre-d-LVAD characteristics and peri-procedural management with a specific focus on tMCS strategies were studied. RESULTS: Among 341 patients, who underwent d-LVAD implantation after mAFP implantation (male gender 83.6%, age 58 [48-65] years, mAFP 5.0/5.5 72.4%), the early ischemic stroke incidence was 10.8% and early hemorrhagic stroke 2.9%. The tMCS characteristics (type of mAFP device and access, support duration, upgrade from intra-aortic balloon pump, ECMELLA, ECMELLA at d-LVAD implantation, hemolysis, and bleeding) were not associated with ischemic stroke after d-LVAD implant. Conversely, the device model (mAFP 2.5/CP vs. mAFP 5.0/5.5: HR 5.6, 95%CI 1.4-22.7, p = 0.015), hemolysis on mAFP support (HR 10.5, 95% CI 1.3-85.3, p = 0.028) and ECMELLA at d-LVAD implantation (HR 5.0, 95% CI 1.4-18.7, p = 0.016) were associated with increased risk of hemorrhagic stroke after d-LVAD implantation. Both early ischemic (HR 2.7, 95% CI 1.9-4.5, p < 0.001) and hemorrhagic (HR 3.43, 95% CI 1.49-7.88, p = 0.004) stroke were associated with increased 1-year mortality. CONCLUSIONS: Among patients undergoing d-LVAD implantation following mAFP support, tMCS characteristics do not impact ischemic stroke occurrence, while several factors are associated with hemorrhagic stroke suggesting a proactive treatment target to reduce this complication.

Extracorporeal Membrane Oxygenation Without Invasive Ventilation for Respiratory Failure in Adults: A Systematic Review.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) is an advanced treatment for acute severe respiratory failure. Patients on ECMO are frequently maintained sedated and immobilized until weaning from ECMO, first, and then from mechanical ventilation. Avoidance of sedation and invasive ventilation during ECMO may have potential advantages. We performed a systematic literature review to assess efficacy and safety of awake ECMO without invasive ventilation in patients with respiratory failure. DATA SOURCES: PubMed, Web of Science, and Scopus were searched for studies reporting outcome of awake ECMO for adult patients with respiratory failure. STUDY SELECTION: We included all studies reporting outcome of awake ECMO in patients with respiratory failure. Studies on ECMO for cardiovascular failure, cardiac arrest, or perioperative support and studies on pediatric patients were excluded. Two investigators independently screened and selected studies for inclusion. DATA EXTRACTION: Two investigators abstracted data on study characteristics, rate of awake ECMO failure, and mortality. Primary outcome was rate of awake ECMO failure (need for intubation). Pooled estimates with corresponding 95% CIs were calculated. Subgroup analyses by setting were performed. DATA SYNTHESIS: A total of 57 studies (28 case reports) included data from 467 awake ECMO patients. The subgroup of patients with acute respiratory distress syndrome showed a pooled estimate for awake ECMO failure of 39.3% (95% CI, 24.0-54.7%), while in patients bridged to lung transplantation, pooled estimate was 23.4% (95% CI, 13.3-33.5%). Longest follow-up mortality was 121 of 439 (pooled estimate, 28%; 95% CI, 22.3-33.6%). Mortality in patients who failed awake ECMO strategy was 43 of 74 (pooled estimate, 57.2%; 95% CI, 40.2-74.3%). Two cases of cannula self-removal were reported. CONCLUSIONS: Awake ECMO is feasible in selected patients, although the effect on outcome remains to be demonstrated. Mortality is almost 60% in patients who failed awake ECMO strategy.

Extrinsic outflow graft flow obstruction in patients with HeartMate3 LVAD.

Blood flow obstruction at the level of the outflow graft is a rare but severe complication of LVAD support. We present a series of five patients supported with HeartMate3 LVAD (Abbott Labs, Chicago, IL) that developed an outflow graft obstruction after 607-1250 days of support, during prolonged antithrombotic therapy. Three patients presented with severe symptoms of heart failure, were treated with endovascular stenting and experienced full recovery. Preoperative computed tomography angiography and intraoperative angiography together with intravascular ultrasound provided diagnosis and guided treatment. In two patients, outflow obstruction was an occasional finding at imaging without heart failure symptoms and a "watchful waiting" approach was adopted: delayed treatment in one of them was futile. This late adverse event is peculiar for its pathophysiology and not yet discussed among the mechanical circulatory support community.

Refractory out-of-hospital cardiac arrest and extracorporeal cardiopulmonary resuscitation: A meta-analysis of randomized trials.

BACKGROUND: In adults with refractory out-of-hospital cardiac arrest, when conventional cardiopulmonary resuscitation (CPR) alone does not achieve return of spontaneous circulation, extracorporeal CPR is attempted to restore perfusion and improve outcomes. Considering the contrasting findings of recent studies, we conducted a meta-analysis of randomized controlled trials to ascertain the effect of extracorporeal CPR on survival and neurological outcome. METHODS: Pubmed via MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched up to February 3, 2023, for randomized controlled trials comparing extracorporeal CPR versus conventional CPR in adults with refractory out-of-hospital cardiac arrest. Survival with a favorable neurological outcome at the longest follow-up available was the primary outcome. RESULTS: Among four randomized controlled trials included, extracorporeal CPR compared with conventional CPR increased survival with favorable neurological outcome at the longest follow-up available for all rhythms (59/220 [27%] vs. 39/213 [18%]; OR = 1.72; 95% CI, 1.09-2.70; p = 0.02; I2  = 26%; number needed to treat of 9), for initial shockable rhythms only (55/164 [34%] vs. 38/165 [23%]; OR = 1.90; 95% CI, 1.16-3.13; p = 0.01; I2  = 23%; number needed to treat of 7), and at hospital discharge or 30 days (55/220 [25%] vs. 34/212 [16%]; OR = 1.82; 95% CI, 1.13-2.92; p = 0.01; I2  = 0.0%). Overall survival at the longest follow-up available was similar (61/220 [25%] vs. 34/212 [16%]; OR = 1.82; 95% CI, 1.13-2.92; p = 0.59; I2  = 58%). CONCLUSIONS: Extracorporeal CPR compared with conventional CPR increased survival with favorable neurological outcome in adults with refractory out-of-hospital cardiac arrest, especially when the initial rhythm was shockable. REVIEW REGISTRATION: PROSPERO CRD42023396482.

Extracorporeal CPR after the INCEPTION trial: No one steps twice into the same river.

The use of veno-arterial extracorporeal membrane oxygenation as extracorporeal cardiopulmonary resuscitation in patients suffering out-of-hospital cardiac arrest, largely increased in the last decade despite evidence supporting this practice being limited to non-randomized studies. However, between 2020 and 2023, four randomized studies were published comparing extracorporeal cardiopulmonary resuscitation to conventional cardiopulmonary resuscitation with controversial findings that triggered great debates. In this controversy, we discuss merits and pitfalls, and provide a critical interpretation of the available evidence from randomized trials on the use of extracorporeal cardiopulmonary resuscitation, with a particular focus on the recent multi-center INCEPTION trial.

Monitoring MCS patients on the intensive care unit: integrating haemodynamic assessment, laboratory data, and imaging techniques for timely detection of deterioration and recovery.

Monitoring of the patient supported with a temporary mechanical circulatory support (tMCS) is crucial in achieving the best possible outcome. Monitoring is a continuous and labour-intensive process, as cardiogenic shock (CS) patients can rapidly deteriorate and may require new interventions within a short time period. Echocardiography and invasive haemodynamic monitoring form the cornerstone of successful tMCS support. During monitoring, it is particularly important to ensure that adequate end-organ perfusion is achieved and maintained. Here, we provide a comprehensive overview of best practices for monitoring the CS patient supported by a micro-axial flow pump, veno-arterial extracorporeal membrane oxygenation, and both devices simultaneously (ECMELLA approach). It is a complex process that encompasses device control, haemodynamic control and stabilization, monitoring of interventions, and assessment of end-organ function. The combined, continuous, and preferably protocol-based approach of echocardiography, evaluation of biomarkers, end-organ assessment, and haemodynamic parameters is crucial in assessing this critically ill CS patient population.

Continuous vs Intermittent Meropenem Administration in Critically Ill Patients With Sepsis: The MERCY Randomized Clinical Trial.

Importance: Meropenem is a widely prescribed ß-lactam antibiotic. Meropenem exhibits maximum pharmacodynamic efficacy when given by continuous infusion to deliver constant drug levels above the minimal inhibitory concentration. Compared with intermittent administration, continuous administration of meropenem may improve clinical outcomes. Objective: To determine whether continuous administration of meropenem reduces a composite of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria compared with intermittent administration in critically ill patients with sepsis. Design, Setting, and Participants: A double-blind, randomized clinical trial enrolling critically ill patients with sepsis or septic shock who had been prescribed meropenem by their treating clinicians at 31 intensive care units of 26 hospitals in 4 countries (Croatia, Italy, Kazakhstan, and Russia). Patients were enrolled between June 5, 2018, and August 9, 2022, and the final 90-day follow-up was completed in November 2022. Interventions: Patients were randomized to receive an equal dose of the antibiotic meropenem by either continuous administration (n = 303) or intermittent administration (n = 304). Main Outcomes and Measures: The primary outcome was a composite of all-cause mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. There were 4 secondary outcomes, including days alive and free from antibiotics at day 28, days alive and free from the intensive care unit at day 28, and all-cause mortality at day 90. Seizures, allergic reactions, and mortality were recorded as adverse events. Results: All 607 patients (mean age, 64 [SD, 15] years; 203 were women [33%]) were included in the measurement of the 28-day primary outcome and completed the 90-day mortality follow-up. The majority (369 patients, 61%) had septic shock. The median time from hospital admission to randomization was 9 days (IQR, 3-17 days) and the median duration of meropenem therapy was 11 days (IQR, 6-17 days). Only 1 crossover event was recorded. The primary outcome occurred in 142 patients (47%) in the continuous administration group and in 149 patients (49%) in the intermittent administration group (relative risk, 0.96 [95% CI, 0.81-1.13], P = .60). Of the 4 secondary outcomes, none was statistically significant. No adverse events of seizures or allergic reactions related to the study drug were reported. At 90 days, mortality was 42% both in the continuous administration group (127 of 303 patients) and in the intermittent administration group (127 of 304 patients). Conclusions and Relevance: In critically ill patients with sepsis, compared with intermittent administration, the continuous administration of meropenem did not improve the composite outcome of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. Trial Registration: ClinicalTrials.gov Identifier: NCT03452839.

Selection criteria and triage in extracorporeal membrane oxygenation during coronavirus disease 2019.

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) pandemic changed the way we had to approach hospital- and intensive care unit (ICU)-related resource management, especially for demanding techniques required for advanced support, including extracorporeal membrane oxygenation (ECMO). RECENT FINDINGS: Availability of ICU beds and ECMO machines widely varies around the world. In critical conditions, such a global pandemic, the establishment of contingency capacity tiers might help in defining to which conditions and subjects ECMO can be offered. A frequent reassessment of the resource saturation, possibly integrated within a regional healthcare coordination system, may be of help to triage the patients who most likely will benefit from advanced techniques, especially when capacities are limited. SUMMARY: Indications to ECMO during the pandemic should be fluid and may be adjusted over time. Candidacy of patients should follow the same prepandemic rules, taking into account the acute disease, the burden of any eventual comorbidity and the chances of a good quality of life after recovery; but the current capacity of healthcare system should also be considered, and frequently reassessed, possibly within a wide hub-and-spoke healthcare system. VIDEO ABSTRACT: http://links.lww.com/COCC/A43.

Extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest: A systematic review and meta-analysis of randomized and propensity score-matched studies.

BACKGROUND: In selected patients with refractory out-of-hospital cardiac arrest, extracorporeal cardiopulmonary resuscitation represents a promising approach when conventional cardiopulmonary resuscitation fails to achieve return of spontaneous circulation. This systematic review and meta-analysis aimed to compare extracorporeal cardiopulmonary resuscitation to conventional cardiopulmonary resuscitation. METHODS: We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials up to November 28, 2021, for randomized trials and observational studies reporting propensity score-matched data and comparing adults with out-of-hospital cardiac arrest treated with extracorporeal cardiopulmonary resuscitation with those treated with conventional cardiopulmonary resuscitation. The primary outcome was survival with favorable neurological outcome at the longest follow-up available. Secondary outcomes were survival at the longest follow-up available and survival at hospital discharge/30 days. RESULTS: We included six studies, two randomized and four propensity score-matched studies. Patients treated with extracorporeal cardiopulmonary resuscitation had higher rates of survival with favorable neurological outcome (81/584 [14%] vs. 46/593 [7.8%]; OR = 2.11; 95% CI, 1.41-3.15; p < 0.001, number needed to treat 16) and of survival (131/584 [22%] vs. 102/593 [17%]; OR = 1.40; 95% CI, 1.05-1.87; p = 0.02) at the longest follow-up available compared with conventional cardiopulmonary resuscitation. Survival at hospital discharge/30 days was similar between the two groups (142/584 [24%] vs. 122/593 [21%]; OR = 1.26; 95% CI, 0.95-1.66; p = 0.10). CONCLUSIONS: Evidence from randomized trials and propensity score-matched studies suggests increased survival and favorable neurological outcome in patients with refractory out-of-hospital cardiac arrest treated with extracorporeal cardiopulmonary resuscitation. Large, multicentre randomized studies are still ongoing to confirm these findings.

Clinical characteristics and outcomes of patients with ventricular arrhythmias after continuous-flow left ventricular assist device implant.

BACKGROUND: Ventricular arrhythmias (VAs) are observed in 25%-50% of continuous-flow left ventricular assist device (CF-LVAD) recipients, but their role on mortality is debated. METHODS: Sixty-nine consecutive patients with a CF-LVAD were retrospectively analyzed. Study endpoints were death and occurrence of first episode of VAs post CF-LVAD implantation. Early VAs were defined as VAs in the first month after CF-LVAD implantation. RESULTS: During a median follow-up of 29.0 months, 19 patients (27.5%) died and 18 patients (26.1%) experienced VAs. Three patients experienced early VAs, and one of them died. Patients with cardiac resynchronization therapy (CRT-D) showed a trend toward more VAs (p = 0.076), compared to patients without CRT-D; no significant difference in mortality was found between patients with and without CRT-D (p = 0.63). Patients with biventricular (BiV) pacing ≥98% experienced more frequently VAs (p = 0.046), with no difference in mortality (p = 0.56), compared to patients experiencing BiV pacing <98%. There was no difference in mortality among patients with or without VAs after CF-LVAD [5 patients (27.8%) vs. 14 patients (27.5%), p = 0.18)], and patients with or without previous history of VAs (p = 0.95). Also, there was no difference in mortality among patients with a different timing of implant of implantable cardioverter-defibrillator (ICD), before and after CF-LVAD (p = 0.11). CONCLUSIONS: VAs in CF-LVAD are a common clinical problem, but they do not impact mortality. Timing of ICD implantation does not have a significant impact on patients' survival. Patients with BiV pacing ≥98% experienced more frequently VAs.

Trend and Pattern of 100 Acute Respiratory Distress Syndrome Patients Referred for Venovenous Extracorporeal Membrane Oxygenation Treatment in a National Referral Center in North Italy During the Last Decade.

OBJECTIVE: Current evidence supports centralization of patients with refractory acute respiratory distress syndrome (ARDS) to institutions with a high level of expertise and with extracorporeal membrane oxygenation (ECMO) capabilities. The aim of this study was to analyze and report the data of transferred refractory ARDS patients managed with venovenous (VV) ECMO at a national referral center over the last 11 years. DESIGN: Observational study. SETTING: Referral center in Italy. PARTICIPANTS: The study comprised 100 patients treated from May 2009-November 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The mean age was 54 ± 14 years, and 65% of patients were male. Patients were treated throughout the year, with seasonal peaks in the winter months. The majority of patients were referred from hospitals within the Lombardia region (81%), mainly from the city of Milan and surrounding area (36% of the total). The most common etiology of refractory ARDS was H1N1 influenza A (42 patients [42%]), followed by bacterial pneumonia (35 patients [35%]), and severe acute respiratory syndrome due to Sars-CoV-2 infection (five patients [5%]). All patients were severely hypoxic at the time of VV ECMO treatment. No transport-related complication was recorded. The most common configuration used in the authors' clinical practice was a bicaval dual-lumen configuration (61 patients [61%]), followed by a femoro-jugular configuration (38 patients [38%]). The intensive care unit survival rate was 55%. CONCLUSIONS: Referral to a specialized center for VV ECMO treatment should be considered expeditiously in case of refractory ARDS, which often is lethal. Transport of patients with an unstable condition, although challenging, is feasible, and centralization of patient care is associated with good outcomes.

Eleven Years of Venovenous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: From H1N1 to SARS-CoV-2. Experience and Perspectives of a National Referral Center.

OBJECTIVE: Despite growing expertise and wide application of venovenous extracorporeal membrane oxygenation (VV ECMO) treatment for acute respiratory distress syndrome (ARDS) of different origin and during pandemics (H1N1 Influenza A virus and SARS-CoV-2), large reports are few and pertain mostly to multicenter registries, and randomized trials are difficult to perform. The aim of this study was to report outcomes, trends, and innovations of VV ECMO treatment over the last 11 years. DESIGN, SETTING, AND PARTICIPANTS: Observational study on 142 patients treated at the IRCCS San Raffaele Hospital in Milan from June 2009 (year of the H1N1 pandemic) to May 2020 (SARS-CoV-2 pandemic). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main causes of ARDS were H1N1 pneumonia in 36% of patients, bacterial pneumonia in 17%, and SARS-CoV-2 in 9%. Seventy-two percent of patients were centralized from remote hospitals, of whom 33% had implanted VV ECMO before transport. The most common cannulation strategy was the dual-lumen catheter cannulation system (55%), and anticoagulation was performed with bivalirudin in most patients (79%). Refractory hypoxia was treated with intravenous beta-blockers (64%), nitric oxide (20%), and pronation (8%). Almost one-third of patients (32%) were extubated while on ECMO. Forty-nine percent of patients were discharged from the intensive care unit, and hospital discharge was 46%; survival was lower in patients requiring VV ECMO for more than three weeks compared with shorter support duration (23% v 56%, p = 0.007). Anticoagulation with bivalirudin was associated with higher survival, compared with heparin (55% v 31%, p = 0.03), and lower thrombocytopenia incidence (69% v 35%, p = 0.003). CONCLUSION: VV ECMO is the pivotal rescue treatment for refractory ARDS-timely treatment and optimal care are needed to optimize therapy, as duration of support is associated with outcome. Anticoagulation with bivalirudin may improve outcome.

Anticoagulation Strategies in Critically Ill Patients With SARS-CoV-2 Infection: The Role of Direct Thrombin Inhibitors.

OBJECTIVES: To compare heparin-based anticoagulation and bivalirudin-based anticoagulation within the context of critically ill patients with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN: An observational study. SETTING: At the intensive care unit of a university hospital. PARTICIPANTS AND INTERVENTIONS: Critically ill patients with a SARS-CoV-2 infection receiving full anticoagulation with heparin or bivalirudin. MEASUREMENTS AND MAIN RESULTS: Twenty-three patients received full anticoagulation with bivalirudin and 60 with heparin. Despite patients in the bivalirudin group having higher mortality risk scores (SAPS II 60 ± 16 v 39 ±7, p < 0.001) and a higher need for extracorporeal support compared to the heparin group, hospital mortality was comparable (57% v 45, p = 0.3). No difference in thromboembolic complications was observed, and bleeding events were more frequent in patients treated with bivalirudin (65% v 40%, p = 0.01). Similar results were confirmed in the subgroup analysis of patients undergoing intravenous anticoagulation; in addition to comparable thrombotic complications occurrence and thrombocytopenia rate, however, no difference in the bleeding rate was observed (65% v 35%, p = 0.08). CONCLUSIONS: Although heparin is the most used anticoagulant in the intensive care setting, bivalirudin-based anticoagulation was safe and effective in a cohort of critically ill patients with SARS-CoV-2. Bivalirudin may be given full consideration as an anticoagulation strategy for critically ill patients with SARS-CoV-2, especially in those with thrombocytopenia and on extracorporeal support.

Effect of Volatile Anesthetics on Myocardial Infarction After Coronary Artery Surgery: A Post Hoc Analysis of a Randomized Trial.

OBJECTIVE: To investigate the effect of volatile anesthetics on the rates of postoperative myocardial infarction (MI) and cardiac death after coronary artery bypass graft (CABG). DESIGN: A post hoc analysis of a randomized trial. SETTING: Cardiac surgical operating rooms. PARTICIPANTS: Patients undergoing elective, isolated CABG. INTERVENTIONS: Patients were randomized to receive a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or total intravenous anesthesia (TIVA). The primary outcome was hemodynamically relevant MI (MI requiring high-dose inotropic support or prolonged intensive care unit stay) occurring within 48 hours from surgery. The secondary outcome was 1-year death due to cardiac causes. MEASUREMENTS AND MAIN RESULTS: A total of 5,400 patients were enrolled between April 2014 and September 2017 (2,709 patients randomized to the volatile anesthetics group and 2,691 to TIVA). The mean age was 62 ± 8.4 years, and the median baseline ejection fraction was 57% (50-67), without differences between the 2 groups. Patients in the volatile group had a lower incidence of MI with hemodynamic complications both in the per-protocol (14 of 2,530 [0.6%] v 27 of 2,501 [1.1%] in the TIVA group; p = 0.038) and as-treated analyses (16 of 2,708 [0.6%] v 29 of 2,617 [1.1%] in the TIVA group; p = 0.039), but not in the intention-to-treat analysis (17 of 2,663 [0.6%] v 28 of 2,667 [1.0%] in the TIVA group; p = 0.10). Overall, deaths due to cardiac causes were lower in the volatile group (23 of 2,685 [0.9%] v 40 of 2,668 [1.5%] than in the TIVA group; p = 0.03). CONCLUSIONS: An anesthetic regimen, including volatile agents, may be associated with a lower rate of postoperative MI with hemodynamic complication in patients undergoing CABG. Furthermore, it may reduce long-term cardiac mortality.

Self-expanding transcatheter aortic valve infolding: Current evidence, diagnosis, and management.

BACKGROUND: Prosthetic valve infolding is a rare but severe complication of transcatheter aortic valve implantation (TAVI) with self-expanding valves. However, currently available clinical data are limited and fragmented. OBJECTIVES: This report aims to provide a comprehensive overview of this complication focusing on predisposing factors, clinical presentation, diagnostic findings, treatment and clinical outcomes. METHODS: A systematic review of the literature was performed to identify cases of infolding occurring during TAVI with self-expanding valves published until August 2020. These data were pooled with all the retrospectively identified infolding cases occurred at San Raffaele Scientific Institute between December 2014 and August 2020. RESULTS: A total of 34 cases were included. Among patients with available data, 38% received a first-generation CoreValve, and 62% a second-generation Evolut R (82%) or Evolut PRO (18%). Infolding occurred mostly with ≥29-mm valves (94%). Predisposing factors included resheathing of a second-generation valve (82%), heavy calcification of the native valve (65%), lack of predilatation (16%), Sievers type-1 bicuspid aortic valve (11%), and improper valve loading (5%). Infolding resulted in severe PVL causing hemodynamic instability (29%) or cardiac arrest (12%). Postdilatation was the treatment strategy in 68%, while prosthesis replacement with a new device in 23% of cases. Device success rate was 82%. Death and stroke occurred in 3% and 12% of cases. CONCLUSIONS: Prosthetic valve infolding is typically observed after resheathing of a large-size self-expanding TAVI. When infolding is timely diagnosed, prosthesis removal and replacement should be pursued. Further studies are required to precisely define predisposing factors to prevent this complication.

Two-months quality of life of COVID-19 invasively ventilated survivors; an Italian single-center study.

BACKGROUND: COVID-19 disease can lead to severe functional impairments after discharge. We assessed the quality of life of invasively ventilated COVID-19 ARDS survivors. METHODS: We carried out a prospective follow-up study of the patients admitted to the Intensive Care Units (ICUs) of a teaching hospital. Patients affected by COVID-19 ARDS who required invasive ventilation and were successfully discharged home were assessed through the telephone administration of validated tests. We explored survival, functional outcomes, return to work, quality of life, cognitive and psychological sequelae. The main variables of interest were the following: demographics, severity scores, laboratory values, comorbidities, schooling, working status, treatments received during ICU stay, complications, and psychological, cognitive, functional outcomes. RESULTS: Out of 116 consecutive invasively ventilated patients, overall survival was 65/116 (56%) with no death occurring after hospital discharge. Forty-two patients were already discharged home with a median follow-up time of 61 (51-71) days after ICU discharge and 39 of them accepted to be interviewed. Only one patient (1/39) experienced cognitive decline. The vast majority of patients reported no difficulty in walking (32/35:82%), self-care (33/39:85%), and usual activities (30/39:78%). All patients were either malnourished (15/39:38%) or at risk for malnutrition (24/39:62%). Exertional dyspnea was present in 20/39 (51%) patients. 19/39 (49%) reported alterations in senses of smell and/or taste either before or after hospitalization. CONCLUSIONS: Invasively ventilated COVID-19 ARDS survivors have an overall good recovery at a 2-months follow-up which is better than what was previously reported in non-COVID-19 ARDS patients.

Impact of CytoSorb on kinetics of vancomycin and bivalirudin in critically ill patients.

CytoSorb is a promising tool to treat severe inflammatory status with multiple mechanisms in the acute care setting. Its effect on drugs is, however, poorly documented in vivo, although removal of small molecules might translate into decreased blood levels of life-saving medications. The aim of this study was to assess the impact of CytoSorb on vancomycin and bivalirudin clearance in a large population of critically ill patients. We performed a single-center analysis of CytoSorb treatments performed between January 2018 and March 2019 in critically ill patients admitted to our intensive care unit. A total of 109 CytoSorb treatments were performed in 89 patients. A decrease in lactate dehydrogenase (P = .007), troponin T (P = .022), and creatine phosphokinase (P = .013) was reported during treatment. Vancomycin dose required significant adjustments during treatment (P < .001), but no significant change was necessary after the first 3 days. Similarly, the requirements of bivalirudin significantly changed over days (P < .001), but no dose adjustment was needed after the first 3 days of treatment. No differences in terms of vancomycin and bivalirudin dose need was observed between patients on extracorporeal membrane oxygenation and those who were not (P = .6 and P = .6, respectively), between patients with and without continuous veno-venous hemofiltration (P = .9 and P = .9, respectively), and between CytoSorb responders or not (P = .4 and P = .7, respectively). CytoSorb is effective in mitigating the systemic inflammatory response and safe with respect to vancomycin and bivalirudin administration. These preliminary data further support the use of CytoSorb as adjunct therapy in critically ill patients.