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.).

The Use of Pulmonary Artery Catheters and Echocardiography in the Cardiac Surgery Setting: A Nationwide Italian Survey.

OBJECTIVE: Wide variations exist in the use of pulmonary artery catheters (PACs) and echocardiography in the field of cardiac surgery. DESIGN: A national survey promoted by the Italian Association of Cardio-Thoracic Anesthesiologists and Intensive Care was conducted. SETTING: The study occurred in Italian cardiac surgery centers (n = 71). PARTICIPANTS: Anesthesiologists-intensivists were enrolled. INTERVENTIONS: Anonymous questionnaires were used to investigate the use of PACs and echocardiography in the operating room (OR) and intensive care unit (ICU). MEASUREMENTS AND MAIN RESULTS: A total of 257 respondents (32.2% response rate) from 59 centers (83.1% response rate) participated. Use of PACs seems less common in ORs (median insertion in 20% [5-70] of patients), with slightly higher use in ICUs; in about half of cases, it was the continuous cardiac output monitoring system of choice. Almost two-thirds of respondents recently inserted at least one PAC within a few hours of ICU admission, despite its need being largely preoperatively predictable. Protocols regulating PAC insertion were reported by 25.3% and 28% of respondents (OR and ICU, respectively). Transesophageal echocardiography (TEE) was performed intraoperatively in >75% of patients by 86.4% of respondents; only 23.7% stated that intraoperative TEE relied on anesthesiologists. Tissue Doppler and/or 3D imaging were widely available (87.4% and 82%, respectively), but only 37.8% and 24.3% of respondents self-declared skills in these modalities, respectively; 77.1% of respondents had no echocardiography certification, nor were pursuing certification (various reasons); 40.9% had not attended recent echocardiography courses. Lower PAC use was associated with university hospitals (OR: p = 0.014, ICU: p = 0.032) and with lower interventions/year (OR: p = 0.023). Higher independence in performing TEE was reported in university hospitals (OR: p < 0.001; ICU: p = 0.006), centers with higher interventions/year (OR: p = 0.019), and by respondents with less experience in cardiology (ICU: p = 0.046). CONCLUSION: Variability in the use of PACs and echocardiography was found. Protocols regulating the use of PACs seem infrequent. University centers use PACs less and have greater skills in TEE. Training and certifications in echocardiography should be encouraged.

Comparative Effectiveness of Combined IgM-Enriched Immunoglobulin and Extracorporeal Blood Purification Plus Standard Care Versus Standard Care for Sepsis and Septic Shock after Cardiac Surgery.

Background: The combination of surgery, bacterial spread-out, and artificial cardiopulmonary bypass surfaces results in a release of key inflammatory mediators leading to an overshooting systemic hyper-inflammatory condition frequently associated with compromised hemodynamics and organ dysfunction. A promising approach could be extracorporeal blood purification therapies in combination with IgM enriched immunoglobulin. This approach might perform a balanced control of both hyper and hypo-inflammatory phases as an immune-modulating intervention. Methods: We performed a retrospective observational study of patients with proven infection after cardiac surgery between January 2020 and December 2021. Patients were divided into two groups: (1) the first group (Control Group) followed a standard care approach as recommended by the Surviving Sepsis Campaign Guidelines; The second group (Active Group) underwent extracorporeal blood purification therapy (EBPT) in combination with intravenous administration of IgM enriched immunoglobulin 5 mL/kg die for at least three consecutive days, in conjunction with the standard approach (SSC Guidelines). In addition, ventriculo-arterial (V/A) coupling, Interleukin 6 (IL-6), Endotoxin Activity Assay (EAA), Procalcitonin, White Blood Cells (WBC) counts, Sequential Organ Failure Assessment (SOFA) Score and Inotropic Score were assessed in both two groups at different time points. Results: Fifty-four patients were recruited; 25 were in the Control Group, while 29 participants were in the Active Group. SOFA score significantly improved from baseline [12 (9-16)] until at T 3 [8 (3-13)] in the active group; it was associated with a median EAA reduction from 1.03 (0.39-1.20) at T 0 to 0.41 (0.2-0.9) at T 3 in the active group compared with control group 0.70 (0.50-1.00) at T 0 to 0.70 (0.50-1.00) at T 3 (p < 0.001). V/A coupling tended to be lower in patients of the active arm ranging from 1.9 (1.2-2.7) at T 0 to 0.8 (0.8-2.2) at T 3 than in those of the control arm ranging from 2.1 (1.4-2.2) at T0 to 1.75 (1.45-2.1) at T 3 (p = 0.099). The hemodynamic improvement over time was associated with evident but no significant decrease in inotropic score in the active group compared with the control group. Changes in EAA value from T 0 to T 4 were directly and significantly related (r = 0.39, p = 0.006) to those of V/A coupling. Conclusions: EBPT, in combination with IgM enriched immunoglobulin, was associated with a mitigated postoperative response of key cytokines with a significant decrease in IL-6, Procalcitonin, and EAA and was associated with improvement of clinical and metabolic parameters.

The use of angiotensin II for the management of distributive shock: expert consensus statements.

BACKGROUND: Despite the growing body of evidence supporting the use of angiotensin II (ATII) in distributive shock, its integration into existing treatment algorithms requires careful consideration of factors related to patient comorbidities, hemodynamic parameters, cost-effectiveness, and risk-benefit balance. Moreover, several questions regarding its use in clinical practice warrant further investigations. To address these challenges, a group of Italian intensive care specialists (the panel) developed a consensus process using a modified Delphi technique. METHODS: The panel defined five clinical questions during an online scoping workshop and then provided a short list of statements related to each clinical question based on literature review and clinical experience. A total of 20 statements were collected. Two coordinators screened and selected the final list of statements to be included in the online survey, which consisted of 17 statements. The consensus was reached when ≥ 75% of respondents assigned a score within the 3-point range of 1-3 (disagreement) or 7-9 (agreement). RESULTS: Overall, a consensus on agreement was reached on 13 statements defining the existing gaps in scientific evidence, the possibility of evaluating the addition of drugs with different mechanisms of action for the treatment of refractory shock, the utility of ATII in reducing the catecholamine requirements in the treatment of vasopressor-resistant septic shock, and the effectiveness of ATII in treating patients in whom angiotensin-converting enzyme activity is reduced or pharmacologically blocked. It was widely shared that renin concentration can be used to identify patients who most likely benefit from ATII to restore vascular tone. Thus, the patients who might benefit most from using ATII were defined. Lastly, some potential barriers to the use of ATII were described. CONCLUSIONS: ATII was recognized as a useful treatment to reduce catecholamine requirements in treating vasopressor-resistant septic shock. At the same time, the need for additional clinical trials to further elucidate the efficacy and safety of ATII, as well as investigations into potential mechanisms of action and optimization of treatment protocols in patients with refractory distributive shock, emerged.

Cryoglobulinemia: the "cold" problem in cardiac surgery, a single-center experience and a literature review.

Cardiac surgery with cardiopulmonary bypass (CBP) is essential for different cardiac procedures in order to perform surgery with a clear sight field.To safely perform surgery with CPB and preserve brain, kidney, and patient tissue from ischemic damage, cold cardioplegia, and mild to deep hypothermia are induced during the operation.Cryoglobulinemia is a hematological/infective-related disease (in certain cases idiopathic) in which temperature-dependent antibodies tend to aggregate and form emboli in the vascular system causing tissue damage if exposed to low temperature.The patient with cryoglobulinemia (known and unknown) can be at risk of a major ischemic event during CPB and induced hypothermia.This article's aim is to evaluate the present scientific literature in order to understand how, in years, the therapeutic or preventive approach, is evolving, and to analyze and make improvements to the management of a cryoglobulinemic patient who must undergo elective or emergency cardiac surgery.In the last part of our article, we expose our single-center experience during a 32-month-long period of survey.In all cases, our medical team (anesthesiologists, perfusionists, and cardiac surgeons) opted for a normothermic cardiopulmonary bypass to lower the risk of cryoglobulin-associated complications.In our experience, along with therapeutic intervention to lower the cryoglobulin titer, normothermic management of cardiopulmonary bypass is as safe as hypothermic management.Notwithstanding our results, further studies with a larger population are needed to confirm this perioperative management in a cardiac surgery setting.

The use of extracorporeal blood purification therapies and sequential extracorporeal support in patients with septic shock (EROICASS): a study protocol for a national, non-interventional, observational multicenter, prospective study.

BACKGROUND: Septic shock, a critical condition characterized by organ failure, presents a substantial mortality risk in intensive care units (ICUs), with the 28-day mortality rate possibly reaching 40%. Conventional management of septic shock typically involves the administration of antibiotics, supportive care for organ dysfunction, and, if necessary, surgical intervention to address the source of infection. In recent decades, extracorporeal blood purification therapies (EBPT) have emerged as potential interventions aimed at modulating the inflammatory response and restoring homeostasis in patients with sepsis. Likewise, sequential extracorporeal therapy in sepsis (SETS) interventions offer comprehensive organ support in the setting of multiple organ dysfunction syndrome (MODS). The EROICASS study will assess and describe the utilization of EBPT in patients with septic shock. Additionally, we will evaluate the potential association between EBPT treatment utilization and 90-day mortality in septic shock cases in Italy. METHODS: The EROICASS study is a national, non-interventional, multicenter observational prospective cohort study. All consecutive patients with septic shock at participating centers will be prospectively enrolled, with data collection extending from intensive care unit (ICU) admission to hospital discharge. Variables including patient demographics, clinical parameters, EBPT/SETS utilization, and outcomes will be recorded using a web-based data capture system. Statistical analyses will encompass descriptive statistics, hypothesis testing, multivariable regression models, and survival analysis to elucidate the associations between EBPT/SETS utilization and patient outcomes. CONCLUSIONS: The EROICASS study provides valuable insights into the utilization and outcomes of EBPT and SETS in septic shock management. Through analysis of usage patterns and clinical data, this study aims to guide treatment decisions and enhance patient care. The implications of these findings may impact clinical guidelines, potentially improving survival rates and patient outcomes in septic shock cases.

Acute normovolemic hemodilution in cardiac surgery: Rationale and design of a multicenter randomized trial.

BACKGROUND: Minimizing the use of blood component can reduce known and unknown blood transfusion risks, preserve blood bank resources, and decrease healthcare costs. Red Blood Cell (RBC) transfusion is common after cardiac surgery and associated with adverse perioperative outcomes, including mortality. Acute normovolemic hemodilution (ANH) may reduce bleeding and the need for blood product transfusion after cardiac surgery. However, its blood-saving effect and impact on major outcomes remain uncertain. METHODS: This is a single-blinded, multinational, pragmatic, randomized controlled trial with a 1:1 allocation ratio conducted in Tertiary and University hospitals. The study is designed to enroll patients scheduled for elective cardiac surgery with planned cardiopulmonary bypass (CPB). Patients are randomized to receive ANH before CPB or the best available treatment without ANH. We identified an ANH volume of at least 650 ml as the critical threshold for clinically relevant benefits. Larger ANH volumes, however, are allowed and tailored to the patient's characteristics and clinical conditions. RESULTS: The primary outcome is the percentage of patients receiving RBCs transfusion from randomization until hospital discharge, which we hypothesize will be reduced from 35% to 28% with ANH. Secondary outcomes are all-cause 30-day mortality, acute kidney injury, bleeding complications, and ischemic complications. CONCLUSION: The trial is designed to determine whether ANH can safely reduce RBC transfusion after elective cardiac surgery with CPB. STUDY REGISTRATION: This trial was registered on ClinicalTrials.gov in April 2019 with the trial identification number NCT03913481.