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.).

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.

Continuous vs intermittent Non-Invasive blood pressure MONitoring in preventing postoperative organ failure (niMON): study protocol for an open-label, multicenter randomized trial.

BACKGROUND: Blood pressure has become one of the most important vital signs to monitor in the perioperative setting. Recently, the Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care (SIAARTI) recommended, with low level of evidence, continuous monitoring of blood pressure during the intraoperative period. Continuous monitoring allows for early detection of hypotension, which may potentially lead to a timely treatment. Whether the ability to detect more hypotension events by continuous noninvasive blood pressure (C-NiBP) monitoring can improve patient outcomes is still unclear. Here, we report the rationale, study design, and statistical analysis plan of the niMON trial, which aims to evaluate the effect of intraoperative C-NiBP compared with intermittent (I-NiBP) monitoring on postoperative myocardial and renal injury. METHODS: The niMon trial is an investigator-initiated, multicenter, international, open-label, parallel-group, randomized clinical trial. Eligible patients will be randomized in a 1:1 ratio to receive C-NiBP or I-NiBP as an intraoperative monitoring strategy. The proportion of patients who develop myocardial injury in the first postoperative week is the primary outcome; the secondary outcomes are the proportions of patients who develop postoperative AKI, in-hospital mortality rate, and 30 and 90 postoperative days events. A sample size of 1265 patients will provide a power of 80% to detect a 4% absolute reduction in the rate of the primary outcome. CONCLUSIONS: The niMON data will provide evidence to guide the choice of the most appropriate intraoperative blood pressure monitoring strategy. CLINICAL TRIAL REGISTRATION: Clinical Trial Registration: NCT05496322, registered on the 5th of August 2023.

Sequential Normothermic Regional Perfusion and End-ischemic Ex Situ Machine Perfusion Allow the Safe Use of Very Old DCD Donors in Liver Transplantation.

BACKGROUND: In Italy, 20 min of continuous, flat-line electrocardiogram are required for death declaration. Despite prolonged warm ischemia time, Italian centers reported good outcomes in controlled donation after circulatory death (cDCD) liver transplantation by combining normothermic regional and end-ischemic machine perfusion (MP). The aim of this study was to evaluate the safety and feasibility of the use of septuagenarian and octogenarian cDCD donors with this approach. METHODS: All cDCD older than 70 y were evaluated during normothermic regional perfusion and then randomly assigned to dual hypothermic or normothermic MP. RESULTS: In the period from April 2021 to December 2022, 17 cDCD older than 70 y were considered. In 6 cases (35%), the graft was not considered suitable for liver transplantation, whereas 11 (65%) were evaluated and eventually transplanted. The median donor age was 82 y, being 8 (73%) older than 80. Median functional warm ischemia and no-flow time were 36 and 28 min, respectively. Grafts were randomly assigned to ex situ dual hypothermic oxygenated MP in 6 cases (55%) and normothermic MP in 5 (45%). None was discarded during MP. There were no cases of primary nonfunction, 1 case of postreperfusion syndrome (9%) and 2 cases (18%) of early allograft dysfunction. At a median follow-up of 8 mo, no vascular complications or ischemic cholangiopathy were reported. No major differences were found in terms of postoperative hospitalization or complications based on the type of MP. CONCLUSIONS: The implementation of sequential normothermic regional and end-ischemic MP allows the safe use of very old donation after circulatory death donors.

A Multi-Country Survey on the Availability of Intraoperative Use of Echocardiography for Noncardiac Surgery.

BACKGROUND: This survey aimed to explore the availability and accessibility of echocardiography during noncardiac surgery worldwide. METHODS: An internet-based 45-item survey was sent, followed by reminders from August 30, 2021, to August 20, 2022. RESULTS: 1189 responses were received from 62 countries. Nearly seventy-one percent of respondents had intraoperatively used transesophageal or transthoracic echocardiography (TEE and TTE, respectively) for monitoring or examination. The unavailability of echocardiography machines (30.3%), lack of trained personnel (30.2%), and absence of clinical indications (22.6%) were the top 3 reasons for not using intraoperative echocardiography in noncardiac surgery. About 61.5% of participants had access to at least one echocardiography machine. About 41% had access to at least 1 TEE probe, and 62.2% had access to at least 1 TTE probe. Seventy-four percent of centers had a procedure to request intraoperative echocardiography if needed for noncardiac cases. Intraoperative echocardiography service was immediately available in 58% of centers. CONCLUSIONS: Echocardiography machines and skilled echocardiographers are still unavailable at many centers worldwide. National societies should aim to train a critical mass of certified TEE/TTE anesthesiologists and provide all anesthesiologists access to perioperative TEE/TTE machines in anesthesiology departments, considering the increasing number of older and sicker surgical patients scheduled for noncardiac surgery.

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.

Percutaneous Tracheostomy in COVID-19 Critically Ill Patients: Experience from 30 Consecutive Procedures

Abstract Introduction Percutaneous tracheostomy (PT) in the intensive care unit (ICU) is a well-established practice that shows a reduced risk of wound infection compared with surgical tracheostomy, thus facilitating mechanical ventilation, nursing procedures, reduction in sedation and early mobilization. Objective This is an observational case-control study that compares the results of PT in ICU patients with coronavirus disease 2019 (COVID-19) prospectively enrolled to a similar group of subjects, retrospectively recruited, without COVID-19. Methods Ninety-eight consecutive COVID-19 patients admitted to the ICU at Pisa Azienda Ospedaliero Universitaria Pisana between March 11th and May 20th, 2020 were prospectively studied. Thirty of them underwent PT using different techniques. Another 30 non-COVID-19 ICU patients were used as a control-group. The main outcome was to evaluate the safety and feasibility of PT in COVID-19 patients. We measured the rate of complications. Results Percutaneous tracheostomy was performed with different techniques in 30 of the 98 COVID-19 ICU patients admitted to the ICU. Tracheostomy was performed on day 10 (mean 10 ± 3.3) from the time of intubation. Major tracheal complications occurred in 5 patients during the procedure. In the control group of 30 ICU patients, no differences were found with regards to the timing of the tracheostomy, whereas a statistically significant difference was observed regarding complications with only one tracheal ring rupture reported. Conclusion Percutaneous tracheostomy in COVID-19 patients showed a higher rate of complications compared with controls even though the same precautions and the same expertise were applied. Larger studies are needed to understand whether the coronavirus disease itself carries an increased risk of tracheal damage.