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.).

"Inhibitory immune checkpoints predict 7-day, in-hospital and 1-year mortality of internal medicine patients admitted with bacterial sepsis".

BACKGROUND: Sepsis is a life-threatening syndrome with complex pathophysiology and great clinical heterogeneity which complicates the delivery of personalized therapies. Our goals were to demonstrate that some biomarkers identified as regulatory immune checkpoints in preclinical studies could 1)improve sepsis prognostication based on clinical variables and 2)guide the stratification of septic patients in subgroups with shared characteristics of immune response or survival outcomes. METHODS: We assayed the soluble counterparts of 12 biomarkers of immune response in 113 internal medicine patients with bacterial sepsis. RESULTS: IL-1 receptor-associated kinase M (IRAK-M) exhibited the highest hazard ratios (HRs) for increased 7-day (1.94 [1.17-3.20]) and 30-day mortality (1.61 [1.14-2.28]). HRs of IRAK-M and Galectin-1 for predicting 1-year mortality were 1.52 (1.20-1.92) and 1.64 (1.13-2.36), respectively. A prognostic model including IRAK-M, Galectin-1, and clinical variables (Charlson Comorbidty Index, multiple source of sepsis, and SOFA score) had high discrimination for death at 7 days and 30 days (area under the curve 0.90 [0.82-0.99]) and 0.86 [0.79-0.94], respectively). Patients with elevated serum levels of IRAK-M and Galectin-1 had clinical traits of immune suppression and low survival rates. None of the 12 biomarkers were independent predictors of 2-year mortality. CONCLUSIONS: Two inhibitory immune checkpoint biomarkers (IRAK-M and Galectin-1) helped identify 3 distinct sepsis phenotypes with distinct prognoses. These biomarkers shed light on the interplay between immune dysfunction and prognosis in patients with bacterial sepsis and may prove to be useful prognostic markers, therapeutic targets, and biochemical markers for targeted enrollment in targeted therapeutic trials.

Andexanet alpha versus four-factor prothrombin complex concentrate in DOACs anticoagulation reversal: an updated systematic review and meta-analysis.

BACKGROUND: There is currently a lack of evidence for the comparative effectiveness of Andexanet alpha and four-factor prothrombin complex concentrate (4F-PCC) in anticoagulation reversal of direct oral anticoagulants (DOACs). The primary aim of our systematic review was to verify which drug is more effective in reducing short-term all-cause mortality. The secondary aim was to determine which of the two reverting strategies is less affected by thromboembolic events. METHODS: A systematic review and meta-analysis was performed. RESULTS: Twenty-two studies were analysed in the systematic review and quantitative synthesis. In all-cause short-term mortality, Andexanet alpha showed a risk ratio (RR) of 0.71(95% CI 0.37-1.34) in RCTs and PSMs, compared to 4F-PCC (I2 = 81%). Considering the retrospective studies, the pooled RR resulted in 0.84 (95% CI 0.69-1.01) for the common effects model and 0.82 (95% CI 0.63-1.07) for the random effects model (I2 = 34.2%). Regarding the incidence of thromboembolic events, for RCTs and PSMs, the common and the random effects model exhibited a RR of 1.74 (95% CI 1.09-2.77), and 1.71 (95% CI 1.01-2.89), respectively, for Andexanet alpha compared to 4F-PCC (I2 = 0%). Considering the retrospective studies, the pooled RR resulted in 1.21 (95% CI 0.87-1.69) for the common effects model and 1.18 (95% CI 0.86-1.62) for the random effects model (I2 = 0%). CONCLUSION: Considering a large group of both retrospective and controlled studies, Andexanet alpha did not show a statistically significant advantage over 4F-PCC in terms of mortality. In the analysis of the controlled studies alone, Andexanet alpha is associated with an increased risk of thromboembolic events. CLINICAL TRIAL REGISTRATION: PROSPERO: International prospective register of systematic reviews, 2024, CRD42024548768.

Lidocaine spray vs mepivacaine local infiltration for suturing 1st/2nd grade perineal lacerations: a randomised controlled non-inferiority trial.

BACKGROUND: Perineal lacerations are a very common complication of post-partum. Usually, the repair of 1st and 2nd-grade lacerations is performed after the administration of local anesthesia. Despite the great relevance of the problem, there are only a few studies about the best choice of local anesthetic to use during suturing. We performed a randomised controlled trial to evaluate the efficacy and safety of the use of a local anesthetic spray during the suturing of perineal lacerations in the post-partum. METHODS: We compared the spray with the standard technique, which involves the infiltration of lacerated tissues, using the NRS scale. 136 eligible women who had given birth at University Hospital of Udine were enrolled and randomly assigned to receive nebulization of Lidocaine hydrochloride 10% spray (experimental group) or subcutaneous/submucosal infiltration of mepivacaine hydrochloride (control group) during suturing of perineal laceration. RESULTS: The lacerations included 84 1st-grade perineal traumas (61.7%) and 52 2nd-grade perineal traumas (38.2%). All the procedures were successfully completed without severe complications or serious adverse reactions. There were no statistically significant differences between the two groups in terms of blood losses or total procedure time. Moreover, there were no statistically significant differences in terms of NRS to none of the intervals considered. Regarding the application of the spray in the B group, in 36 cases (52.9%) it was necessary to improve the number of puffs previously supposed to be sufficient (5 puffs). Just in 3 cases, an additional injection was necessary (4.4%). CONCLUSIONS: Our study demonstrates that lidocaine spray alone can be used as a first line of local anesthetic during the closure of I-II-grade perineal lacerations, as it has comparable efficacy to mepivacaine infiltration. TRIAL REGISTRATION: The trial was recorded on https://clinicaltrials.gov . Identification number: NCT05201313. First registration date: 21/01/2022. Unique Protocol ID: 0042698/P/GEN/ARCS.

Diaphragmatic morphological post-mortem findings in critically ill COVID-19 patients: an observational study.

Our study investigates the post-mortem findings of the diaphragm's muscular structural changes in mechanically ventilated COVID-19 patients. Diaphragm samples of the right side from 42 COVID-19 critically ill patients were analyzed and correlated with the type and length of mechanical ventilation (MV), ventilatory parameters, prone positioning, and use of sedative drugs. The mean number of fibers was 550±626. The cross-sectional area was 4120±3280 µm2, while the muscular fraction was 0.607±0.126. The overall population was clustered into two distinct populations (clusters 1 and 2). Cluster 1 showed a lower percentage of slow myosin fiber and higher fast fiber content than cluster 2, 68% versus 82%, p<0.00001, and 29.8% versus 18.8%, p=0.00045 respectively. The median duration of MV was 180 (41-346) hours. In cluster 1, a relationship between assisted ventilation and fast myosin fiber percentage (R2=-0.355, p=0.014) was found. In cluster 2, fast fiber content increased with increasing the length of the controlled MV (R2=0.446, p=0.006). A high grade of fibrosis was reported. Cluster 1 was characterized by fibers' atrophy and cluster 2 by hypertrophy, supposing different effects of ventilation on the diaphragm but without excluding a possible direct viral effect on diaphragmatic fibers.

Hemodynamic goals in sepsis and septic shock resuscitation: An umbrella review of systematic reviews and meta-analyses with trial sequential analysis.

OBJECTIVE: The objective of this study was to verify whether any parameter among those used as the target for haemodynamic optimisation (e.g., mean arterial pressure, central venous oxygen saturation, systolic or diastolic dysfunction, CO2 gap, lactates, right ventricular dysfunction, and PvaCO2/CavO2 ratio) is correlated with mortality in an undifferentiated population with sepsis or septic shock. METHODS: An umbrella review, searching MEDLINE, the Cochrane Database of Systematic Reviews, Health Technology Assessment Database, and the JBI Database of Systematic Reviews and Implementation Reports, was performed. We included systematic reviews and meta-analyses enrolling a population of unselected patients with sepsis or septic shock. The main outcome was mortality. Two authors conducted data extraction and risk-of-bias assessments independently. We used a random-effects model to pool binary and continuous data and summarised estimates of effect using equivalent odds ratios (eORs). We used the ROBIS tool to assess risk of bias and the assessment of multiple systematic reviews 2 score to assess global quality. DATA SYNTHESIS: 17 systematic reviews and meta-analyses (15 828 patients) were included in the quantitative analysis. Diastolic dysfunction (eOR: 1.42; 95% confidence interval [CI]: 1.14-1.76), PvaCO2/CavO2 ratio (eOR: 2.15; 95% CI: 1.37-3.37), and CO2 gap (eOR: 1.86; 95% CI: 1.07-3.25) showed a significant correlation with mortality. Lactates were the parameter with highest inconsistency (I2 = 92%). Central venous oxygen saturation and right ventricle dysfunction showed significant statistical excess test of significance (p-value = 0.009 and 0.005, respectively). None of the considered parameters showed statistically significant publication bias. CONCLUSIONS: According to this umbrella review, diastolic dysfunction is the haemodynamic variable that is most closely linked to the prognosis of septic patients. The PvaCO2/CavO2 ratio and the CO2gap are significantly related to the mortality of septic patients, but the poor quality of evidence or the low number of cases, studied so far, limit their clinical applicability. CLINICAL TRIAL REGISTRATION: PROSPERO: International prospective register of systematic reviews, 2023, CRD42023432813 (Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023432813).

Association between artificial nutrition in brain dead donors and early allograft function in liver transplant recipients: an observational study.

BACKGROUND: The role of nutrition in donor after brain deaths (DBDs) has yet to be adequately discussed. The primary aim of this study was to investigate whether the nutritional intake in the 48 h before organ retrieval may play a role on the graft functional recovery assessed with Model for Early Allograft Function (MEAF) Score. METHODS: Single-center retrospective study evaluating all liver transplants performed at the University Hospital of Udine from January 2010 to August 2020. Patients receiving grafts from DBD donors fed with artificial enteral nutrition in the 48 h prior to organ procurement (EN-group) or who did not (No-EN-group). Caloric debt was calculated using the difference between the calculated caloric needs and the effective calories delivered through enteral nutrition. RESULTS: Livers from EN-group presented a lower mean MEAF score compared to the no-EN-group: 3.39 ± 1.46 versus 4.15 ± 1.51, respectively (p = .04). A positive correlation between caloric debt and the MEAF score was found within the overall population (r = .227, p = .043) as well as in EN-group (r = .306, p = .049). CONCLUSIONS: Donor's nutritional intake in the final 48 h before organ procurement correlates with MEAF score, and nutrition probably plays a positive role on the functional recovery of the graft. Large future randomized controlled trials are needed to confirm this preliminary results.

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.

Volatile Anesthetics versus Total Intravenous Anesthesia for Cardiac Surgery.

BACKGROUND: Volatile (inhaled) anesthetic agents have cardioprotective effects, which might improve clinical outcomes in patients undergoing coronary-artery bypass grafting (CABG). METHODS: We conducted a pragmatic, multicenter, single-blind, controlled trial at 36 centers in 13 countries. Patients scheduled to undergo elective CABG were randomly assigned to an intraoperative anesthetic regimen that included a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or to total intravenous anesthesia. The primary outcome was death from any cause at 1 year. RESULTS: A total of 5400 patients were randomly assigned: 2709 to the volatile anesthetics group and 2691 to the total intravenous anesthesia group. On-pump CABG was performed in 64% of patients, with a mean duration of cardiopulmonary bypass of 79 minutes. The two groups were similar with respect to demographic and clinical characteristics at baseline, the duration of cardiopulmonary bypass, and the number of grafts. At the time of the second interim analysis, the data and safety monitoring board advised that the trial should be stopped for futility. No significant difference between the groups with respect to deaths from any cause was seen at 1 year (2.8% in the volatile anesthetics group and 3.0% in the total intravenous anesthesia group; relative risk, 0.94; 95% confidence interval [CI], 0.69 to 1.29; P = 0.71), with data available for 5353 patients (99.1%), or at 30 days (1.4% and 1.3%, respectively; relative risk, 1.11; 95% CI, 0.70 to 1.76), with data available for 5398 patients (99.9%). There were no significant differences between the groups in any of the secondary outcomes or in the incidence of prespecified adverse events, including myocardial infarction. CONCLUSIONS: Among patients undergoing elective CABG, anesthesia with a volatile agent did not result in significantly fewer deaths at 1 year than total intravenous anesthesia. (Funded by the Italian Ministry of Health; MYRIAD ClinicalTrials.gov number, NCT02105610.).

Diaphragm ultrasound evaluation during weaning from mechanical ventilation in COVID-19 patients: a pragmatic, cross-section, multicenter study.

BACKGROUND: Diaphragmatic dysfunction is a major factor responsible for weaning failure in patients that underwent prolonged invasive mechanical ventilation for acute severe respiratory failure from COVID-19. This study hypothesizes that ultrasound measured diaphragmatic thickening fraction (DTF) could provide corroborating information for weaning COVID-19 patients from mechanical ventilation. METHODS: This was an observational, pragmatic, cross-section, multicenter study in 6 Italian intensive care units. DTF was assessed in COVID-19 patients undergoing weaning from mechanical ventilation from 1st March 2020 to 30th June 2021. Primary aim was to evaluate whether DTF is a predictive factor for weaning failure. RESULTS: Fifty-seven patients were enrolled, 25 patients failed spontaneous breathing trial (44%). Median length of invasive ventilation was 14 days (IQR 7-22). Median DTF within 24 h since the start of weaning was 28% (IQR 22-39%), RASS score (- 2 vs - 2; p = 0.031); Kelly-Matthay score (2 vs 1; p = 0.002); inspiratory oxygen fraction (0.45 vs 0.40; p = 0.033). PaO2/FiO2 ratio was lower (176 vs 241; p = 0.032) and length of intensive care stay was longer (27 vs 16.5 days; p = 0.025) in patients who failed weaning. The generalized linear regression model did not select any variables that could predict weaning failure. DTF was correlated with pH (RR 1.56 × 1027; p = 0.002); Kelly-Matthay score (RR 353; p < 0.001); RASS (RR 2.11; p = 0.003); PaO2/FiO2 ratio (RR 1.03; p = 0.05); SAPS2 (RR 0.71; p = 0.005); hospital and ICU length of stay (RR 1.22 and 0.79, respectively; p < 0.001 and p = 0.004). CONCLUSIONS: DTF in COVID-19 patients was not predictive of weaning failure from mechanical ventilation, and larger studies are needed to evaluate it in clinical practice further. Registered: ClinicalTrial.gov (NCT05019313, 24 August 2021).

Association between preoperative diastolic dysfunction and early allograft dysfunction after orthotopic liver transplantation: An observational study.

OBJECTIVES: To investigate the association between the grade of diastolic dysfunction (DD) and the occurrence of early allograft dysfunction (EAD) in liver transplant patients following the new 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) guidelines. METHODS: From January 2015 to December 2019, we retrospectively analyzed 83 patients who underwent orthotopic liver transplantation (OLTx) and their susceptibility to develop EAD according to the grade of preoperative DD. EAD was defined according to the criteria proposed by Olfhoff et al.; DD was defined with four parameters: E/A, e/e', Left Atrium volume, and Tricuspid Regurgitation velocity. RESULTS: According to the ASE/EACVI guidelines grade II DD was detected in 20 patients (24.1%) undergoing OLTx. A statistically significant association was found between grade II DD and the occurrence of EAD (p-value < 0.003). The Kaplan-Meier analysis failed to find any significant difference between the survival probability, nevertheless at the end of a 90-day follow-up period, mortality showed a different trend in classes with more severe diastolic dysfunction. CONCLUSION: According to the ASE/EACVI guidelines from 2016, patients with grade II DD seem to have a higher propensity to develop early allograft dysfunction EAD after OLTx. Our study advises a need for an urgent prospective multicenter study to elucidate the long-term outcomes of liver transplants patients with diastolic dysfunction.

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.

Level of Diffusion and Training of Lung Ultrasound during the COVID-19 Pandemic - A National Online Italian Survey (ITALUS) from the Lung Ultrasound Working Group of the Italian Society of Anesthesia, Analgesia, Resuscitation, and Intensive Care (SIAARTI).

PURPOSE: The goal of this survey was to describe the use and diffusion of lung ultrasound (LUS), the level of training received before and during the COVID-19 pandemic, and the clinical impact LUS has had on COVID-19 cases in intensive care units (ICU) from February 2020 to May 2020. MATERIALS AND METHODS: The Italian Lung Ultrasound Survey (ITALUS) was a nationwide online survey proposed to Italian anesthesiologists and intensive care physicians carried out after the first wave of the COVID-19 pandemic. It consisted of 27 questions, both quantitative and qualitative. RESULTS: 807 responded to the survey. The median previous LUS experience was 3 years (IQR 1.0-6.0). 473 (60.9 %) reported having attended at least one training course on LUS before the COVID-19 pandemic. 519 (73.9 %) reported knowing how to use the LUS score. 404 (52 %) reported being able to use LUS without any supervision. 479 (68.2 %) said that LUS influenced their clinical decision-making, mostly with respect to patient monitoring. During the pandemic, the median of patients daily evaluated with LUS increased 3-fold (p < 0.001), daily use of general LUS increased from 10.4 % to 28.9 % (p < 0.001), and the daily use of LUS score in particular increased from 1.6 % to 9.0 % (p < 0.001). CONCLUSION: This survey showed that LUS was already extensively used during the first wave of the COVID-19 pandemic by anesthesiologists and intensive care physicians in Italy, and then its adoption increased further. Residency programs are already progressively implementing LUS teaching. However, 76.7 % of the sample did not undertake any LUS certification.

Evaluation of Drug Wastage in the Operating Rooms and Intensive Care Units of a Regional Health Service.

BACKGROUND: Pharmacological treatments for critical processes in patients need to be initiated as rapidly as possible; for this reason, it is a standard of care to prepare the main anesthesia and emergency drugs in advance. As a result, 20%-50% of the prepared drugs remain unused and are then discarded. Decreasing waste by optimizing drug use is an attractive strategy for meeting both cost containment and environmental sustainability. The primary end point of this study was to measure the actual amount of drug wastage in the operating rooms (ORs) and intensive care units (ICUs) of a Regional Health Service (RHS). The secondary end point was to analyze and estimate the economic implications of this waste for the Health Service and to suggest possible measures to reduce it. METHODS: This prospective observational multicenter study was conducted across 12 hospitals, all of which belong to the same RHS in the north-east of Italy. Data collection took place in March 2018 and included patients admitted to ICUs, emergency areas, and ORs of the participating hospitals. Data concerning drug preparation and administration were collected for all consecutive patients, independent of case types and of whether operations were scheduled or unscheduled. Drug wastage was defined as follows: drugs prepared in ready-to-use syringes but not administered at all and discarded untouched. We then estimated the costs of wasted drugs for a 1-year period using the data from this study and the yearly regional pharmacy orders of drugs provided to the ORs and ICUs. We also performed a sensitivity analysis to validate the robustness of our assumptions and qualitative conclusions. RESULTS: We collected data for a total of 13,078 prepared drug syringes. Drug wastage varied from 7.8% (Urapidil, an alpha-1 antagonist antihypertensive) to 85.7% (epinephrine) of prepared syringes, with an overall mean wastage rate of 38%. The estimated yearly waste was 139,531 syringes, for a total estimated financial cost of €78,060 ($92,569), and an additional quantity of medical waste amounting to 4968 kg per year. The total provider time dedicated to the preparation of unused drugs was predicted to be 1512 working hours per year. CONCLUSIONS: The overall extent of drug wastage in ORs and ICUs is concerning. Interventions aimed at minimizing waste-related costs and improving the environmental sustainability of our practice are paramount. Effort should be put into designing a more efficient workflow that reduces this waste while providing for the emergency availability of these medications in the OR and ICU.

Classification and analysis of outcome predictors in non-critically ill COVID-19 patients.

BACKGROUND: Early detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients who could develop a severe form of COVID-19 must be considered of great importance to carry out adequate care and optimise the use of limited resources. AIMS: To use several machine learning classification models to analyse a series of non-critically ill COVID-19 patients admitted to a general medicine ward to verify if any clinical variables recorded could predict the clinical outcome. METHODS: We retrospectively analysed non-critically ill patients with COVID-19 admitted to the general ward of the hospital in Pordenone from 1 March 2020 to 30 April 2020. Patients' characteristics were compared based on clinical outcomes. Through several machine learning classification models, some predictors for clinical outcome were detected. RESULTS: In the considered period, we analysed 176 consecutive patients admitted: 119 (67.6%) were discharged, 35 (19.9%) dead and 22 (12.5%) were transferred to intensive care unit. The most accurate models were a random forest model (M2) and a conditional inference tree model (M5) (accuracy = 0.79; 95% confidence interval 0.64-0.90, for both). For M2, glomerular filtration rate and creatinine were the most accurate predictors for the outcome, followed by age and fraction-inspired oxygen. For M5, serum sodium, body temperature and arterial pressure of oxygen and inspiratory fraction of oxygen ratio were the most reliable predictors. CONCLUSIONS: In non-critically ill COVID-19 patients admitted to a medical ward, glomerular filtration rate, creatinine and serum sodium were promising predictors for the clinical outcome. Some factors not determined by COVID-19, such as age or dementia, influence clinical outcomes.

The COVID-19 Worsening Score (COWS)-a predictive bedside tool for critical illness.

OBJECTIVES: To evaluate the accuracy of a new COVID-19 prognostic score based on lung ultrasound (LUS) and previously validated variables in predicting critical illness. METHODS: We conducted a single-center retrospective cohort development and internal validation study of the COVID-19 Worsening Score (COWS), based on a combination of the previously validated COVID-GRAM score (GRAM) variables and LUS. Adult COVID-19 patients admitted to the emergency department (ED) were enrolled. Ten variables previously identified by GRAM, days from symptom onset, LUS findings, and peripheral oxygen saturation/fraction of inspired oxygen (P/F) ratio were analyzed. LUS score as a single predictor was assessed. We evaluated GRAM model's performance, the impact of adding LUS, and then developed a new model based on the most predictive variables. RESULTS: Among 274 COVID-19 patients enrolled, 174 developed critical illness. The GRAM score identified 51 patients at high risk of developing critical illness and 132 at low risk. LUS score over 15 (range 0 to 36) was associated with a higher risk ratio of critical illness (RR, 2.05; 95% confidence interval [CI], 1.52-2.77; area under the curve [AUC], 0.63; 95% CI 0.676-0.634). The newly developed COVID-19 Worsening Score relies on five variables to classify high- and low-risk patients with an overall accuracy of 80% and negative predictive value of 93% (95% CI, 87%-98%). Patients scoring more than 0.183 on COWS showed a RR of developing critical illness of 8.07 (95% CI, 4.97-11.1). CONCLUSIONS: COWS accurately identify patients who are unlikely to need intensive care unit (ICU) admission, preserving resources for the remaining high-risk patients.

Lung, Heart, Vascular, and Diaphragm Ultrasound Examination of COVID-19 Patients: A Comprehensive Approach.

Lung ultrasound (LU) has a multitude of features and capacities that make it a useful medical tool to assist physicians contending with the pandemic spread of novel coronavirus disease-2019 (COVID-19) caused by coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus, an LU approach to patients with suspected COVID-19 is being implemented worldwide. In noncritical COVID-19 patients, 2 new LU signs have been described and proposed, the "waterfall" and the "light beam" signs. Both signs have been hypothesized to increase the diagnostic accuracy of LU for COVID-19 interstitial pneumonia. In critically ill patients, a distinct pattern of LU changes seems to follow the disease's progression, and this information can be used to guide decisions about when a patient needs to be ventilated, as occurs in other disease states similar to COVID-19. Furthermore, a new algorithm has been published, which enables the automatic detection of B-lines as well as quantification of the percentage of the pleural line associated with lung disease. In COVID-19 patients, a direct involvement of cardiac function has been demonstrated, and ventilator-induced diaphragm dysfunction might be present due to the prolonged mechanical ventilation often involved, as reported for similar diseases. For this reason, cardiac and diaphragm ultrasound evaluation are highly important. Last but not least, due to the thrombotic tendency of COVID-19 patients, particular attention also should be paid to vascular ultrasound. This review is primarily devoted to the study of LU in COVID-19 patients. The authors explain the significance of its "light and shadows," bearing in mind the context in which LU is being used-the emergency department and the intensive care setting. The use of cardiac, vascular, and diaphragm ultrasound is also discussed, as a comprehensive approach to patient care.

Indocyanine green dye clearance test: early graft (dys)-function and long-term mortality after liver transplant. Should we continue to use it? An observational study.

Early allograft dysfunction (EAD) can be a serious complication in the immediate postoperative period following liver transplantation. Our aim was to study the prognostic role of the indocyanine green plasma disappearance rate (ICG-PDR) in predicting early and late EAD and mortality at 3 and 12 months and 5 years after liver transplantation. ICG-PDR values were also assessed for association with the Donor Risk Index (DRI). 220 patients underwent orthotopic liver transplantation. In 77 patients, ICG-PDR was assessed on the 1st post-operative (PO) day. ICG, a water-soluble dye almost entirely excreted into the bile, was measured by spectrophotometry to evaluate graft (dys)-function. DRI was calculated in all patients. The primary study outcomes were the presence (or absence) of EAD after transplant and the results of mortality risk factor analysis. EAD occurred in 18 patients. 1st PO day ICG-PDR was significantly associated with EAD (p < 0.005). A threshold ICG-PDR value < 16%/min on the 1st PO day was also associated with patient probability to survive at 3 and 12 months and 5 years. The sensitivity and specificity of the AUC was good in predicting EAD, being 83% and 56%, respectively, for a 1st PO day ICG-PDR cut-off value < 16%/min. In this study, ICG-PDR on the 1st PO day following OLT can reliably predict EAD and survival at 3 and 12 months and 5 years. ICG-PDR should, therefore, be routinely performed on the 1st PO day following OLTx in all patients in light of its important prognostic role.

Association between indocyanine green clearance test and ischemic type biliary lesions within one year after orthotopic liver transplantation.

BACKGROUND: Ischemic type biliary lesions (ITBLs), a particular subset of non-anastomotic biliary strictures (NAS), are characterized by intra and extrahepatic strictures that occur in the absence of either hepatic artery thrombosis or stenosis. When they occur within the first year after liver transplantation their development is mostly related to ischemia-reperfusion injury (IRI). The indocyanine green plasma disappearance rate (ICG-PDR) might be able to predict the probability of IRI-induced graft damage after liver transplantation. OBJECTIVE: Our aim was to evaluate the association between ICG-PDR and the occurrence of ITBLs. Secondly, we searched for evidence of IRI in patients presenting ITBLs. METHODS: This retrospective single-center observational study assessed a cohort of 60 liver transplant patients. Each patient underwent ICG-PDR on the 1st postoperative day. ITBLs were identified by means of either cholangiography or magnetic resonance imaging evidence of a deformity and narrowing of the biliary tree in the absence of hepatic artery thrombosis/stenosis. RESULTS: ITBLs were discovered in 10 patients out of 60 liver recipients (16.67%) within one year after transplantation. A low ICG-PDR value was found to be a significant predictive factor for ITBL development, with an OR of 0.87 and a 95% CI of 0.77-0.97. Liver biopsies were performed in 56 patients presenting unexplained abnormal liver function test results. A statistically significant association was found between the development of ITBLs and anatomopathological evidence of IRI. LIMITATIONS: Retrospective, single-center study. CONCLUSIONS: The findings from this study show a relationship between low ICG-PDR values on first post-operative-day and the occurrence of ITBLs within 1 year after transplantation.

Levosimendan for Hemodynamic Support after Cardiac Surgery.

BACKGROUND: Acute left ventricular dysfunction is a major complication of cardiac surgery and is associated with increased mortality. Meta-analyses of small trials suggest that levosimendan may result in a higher rate of survival among patients undergoing cardiac surgery. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial involving patients in whom perioperative hemodynamic support was indicated after cardiac surgery, according to prespecified criteria. Patients were randomly assigned to receive levosimendan (in a continuous infusion at a dose of 0.025 to 0.2 µg per kilogram of body weight per minute) or placebo, for up to 48 hours or until discharge from the intensive care unit (ICU), in addition to standard care. The primary outcome was 30-day mortality. RESULTS: The trial was stopped for futility after 506 patients were enrolled. A total of 248 patients were assigned to receive levosimendan and 258 to receive placebo. There was no significant difference in 30-day mortality between the levosimendan group and the placebo group (32 patients [12.9%] and 33 patients [12.8%], respectively; absolute risk difference, 0.1 percentage points; 95% confidence interval [CI], -5.7 to 5.9; P=0.97). There were no significant differences between the levosimendan group and the placebo group in the durations of mechanical ventilation (median, 19 hours and 21 hours, respectively; median difference, -2 hours; 95% CI, -5 to 1; P=0.48), ICU stay (median, 72 hours and 84 hours, respectively; median difference, -12 hours; 95% CI, -21 to 2; P=0.09), and hospital stay (median, 14 days and 14 days, respectively; median difference, 0 days; 95% CI, -1 to 2; P=0.39). There was no significant difference between the levosimendan group and the placebo group in rates of hypotension or cardiac arrhythmias. CONCLUSIONS: In patients who required perioperative hemodynamic support after cardiac surgery, low-dose levosimendan in addition to standard care did not result in lower 30-day mortality than placebo. (Funded by the Italian Ministry of Health; CHEETAH ClinicalTrials.gov number, NCT00994825 .).