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 Effects of Corticosteroids on Survival in Pediatric and Nonelderly Adult Patients Undergoing Cardiac Surgery: A Meta-analysis of Randomized Studies.

OBJECTIVE: Cardiac surgery can be complicated by the development of a systemic inflammatory response syndrome related to cardiopulmonary bypass. This potentially contributes to the occurrence of postoperative morbidity and mortality. Corticosteroids can be used to reduce such inflammation, but the overall balance between potential harm and benefit is unknown and may be age-dependent. The present meta-analysis aims to evaluate the effects of prophylactic corticosteroids in pediatric and non-elderly adult cardiac surgery patients. DESIGN: Systematic review and meta-analysis of randomized trials. SETTING: Cardiac surgery with cardiopulmonary bypass. PARTICIPANTS: Patients younger than 65 years old (pediatric and non-elderly adults). INTERVENTIONS: Perioperative use of corticosteroids versus placebo or standard care. MEASUREMENTS AND MAIN RESULTS: Two independent investigators searched PubMed, EMBASE and the Cochrane Library from inception to January 20, 2024. The primary outcome was mortality at the longest follow-up available. Secondary outcomes included acute kidney injury, atrial fibrillation, myocardial injury, cerebrovascular events, and infections. Our search strategy identified a total of 17 randomized trials involving 6,598 patients. Mortality was significantly reduced in the corticosteroid group (78/3321 [2.3%] vs. 116/3277 [3.5%]; risk ratio = 0.69; 95% confidence interval, 0.52 to 0.92; P = 0.01; I2 = 0%; NNT = 91). Moreover, the highest postoperative vasoactive inotropic score (VIS) was significantly lower in corticosteroid group (MD: -2.07, 95% CI -3.69 to -0.45, P = 0.01, I2 = 0%). No significant differences in secondary outcomes between the two treatment groups were recorded. CONCLUSIONS: This meta-analysis of randomized trials highlights the potential benefits of corticosteroids on survival in cardiac surgery for patients younger than 65 years old.

Amino Acid Infusion for Perioperative Functional Renal Protection: A Meta-analysis.

OBJECTIVES: Acute kidney injury (AKI) is a common perioperative complication. To date, no single intervention has been proven effective for AKI prevention in this setting. However, intravenous amino acids (AA) administration may recruit renal functional reserve and, thereby, attenuate the perioperative loss of the glomerular filtration rate. DESIGN: We performed a meta-analysis to assess the efficacy of AA infusion for perioperative renal functional protection. SETTING AND PARTICIPANTS: We performed a meta-analysis of controlled studies in perioperative patients evaluating intravenous AA infusion versus any comparator. MEASUREMENTS: The primary outcome was AKI at longest follow-up. We performed a random effects meta-analysis on the relative risk (RR) scale to assess the effect of AA infusion. We used a Bayesian approach to estimate the probability of benefit (RR < 1) for the primary outcome. Secondary outcomes included renal replacement therapy, serum creatinine, and estimated glomerular filtration rate. Tertiary outcomes included mechanical ventilation duration, intensive care unit and hospital length of stay and mortality (PROSPERO: CRD42024547225). RESULTS: We identified 15 studies (14 randomized controlled trials and 1 prospective before-after study) reporting at least one outcome of interest (4,544 patients), with 6 studies (4,084 patients) reporting the primary outcome. AKI occurred 504 of 2,041 (24.7%) in AA patients versus 614 of 2,041 (30.1%) in controls (RR, 0.66; 95% confidence interval, 0.47-0.94; I2 = 50%; p = 0.02), which corresponded with a 99.1% probability of AKI reduction with AA. Moreover, consistent with these findings, AA decreased serum creatinine and hospital length of stay and increased the estimated glomerular filtration rate. CONCLUSIONS: This meta-analysis suggests that AA administration likely decreased the perioperative incidence of AKI.

Minimal invasive extracorporeal circulation: A bibliometric network analysis of the global scientific output.

INTRODUCTION: Minimal Invasive Extracorporeal Circulation (MiECC) has recently emerged as a more 'physiologic' alternative to conventional extracorporeal circulation. However, its adoption is still limited due to lack of robust scientific evidence and ongoing debate about its potential benefits. This bibliometric analysis aims to analyze the scientific articles on MiECC and identify current research domains and existing gaps to be addressed in future studies. METHODS: Pertinent articles were retrieved from the Web of Science (WOS) database. The search string included 'minimal invasive extracorporeal circulation' and its synonyms. The VOSviewer (version 1.6.17) software was used to conduct comprehensive analyses. Semantic and research networks, bibliographic coupling and journal analysis were performed. RESULTS: Of the 1777 articles identified in WOS, 292 were retrieved. The trend in publications increased from 1991 to date. Most articles focused on transfusion requirements, acute kidney injury, inflammatory markers and cytokines, inflammation and delirium, though the impact of intraoperative optimal fluid and hemodynamic management as far as the occurrence of postoperative complications were poorly addressed. The semantic network analysis found inter-connections between the terms "cardiopulmonary bypass", "inflammatory response", and "cardiac surgery". Perfusion contributed the highest number of published documents. The most extensive research partnerships were between Germany, Greece, Italy, and England. CONCLUSIONS: Notwithstanding the scientific community's growing interest in MiECC, crucial topics (i.e., the best anesthetic management and intraoperative need for inotropes, vasopressors and fluids) still require more comprehensive exploration. This investigation may prove to be a useful tool for clinicians, scientists, and students concerning global publication output and for the use of MiECC in cardiac surgery.

Remimazolam for anesthesia and sedation in pediatric patients: a scoping review.

Anesthetic management of pediatric patients poses several challenges and the optimal anesthetic agent for use in this population is still a matter of debate. We systematically searched PubMed/MEDLINE and Google Scholar from their inception for studies that investigated the role and potential applications of remimazolam, a novel ultra-short-acting benzodiazepine, in pediatric patients. Furthermore, in March 2024, an update of the literature search along with an additional post-hoc search on the EMBASE database were performed. A total of fourteen pertinent studies which spanned the 2021-2023 period explored remimazolam as either the primary or adjuvant hypnotic agent for inducing and/or maintaining general anesthesia or sedation. Preliminary evidence derived from these studies highlighted that remimazolam is a safe and effective option for both sedation and general anesthesia in pediatric patients, particularly those with concurrent mitochondrial disorders, myopathic diseases, or at risk for malignant hyperthermia. Moreover, the current evidence suggested that remimazolam may contribute to reducing preoperative anxiety and postoperative delirium in children. Its favorable pharmacodynamic and pharmacokinetic profile demonstrated potential safety, effectiveness, and ease-of-use in various perioperative pediatric contexts, making it suitable for integration into specific protocols, such as intraoperative monitoring of evoked potentials and management of difficult intubation. Notwithstanding these promising findings, further research is essential to determine optimal dosages, establish conclusive evidence of its superiority over other benzodiazepines, and elucidate the impact of genetic factors on drug metabolism.

Non-Invasive Ventilation in the Prehospital Emergency Setting: A Systematic Review and Meta-Analysis.

INTRODUCTION: Noninvasive ventilation is a well-established treatment for acute respiratory failure, being increasingly applied in the prehospital setting. This systematic review and meta-analysis aims to investigate whether early prehospital initiation of noninvasive ventilation reduces mortality compared to standard oxygen therapy. METHODS: We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to February 7th, 2022, for studies comparing prehospital noninvasive ventilation performed by emergency medical services versus standard oxygen therapy in patients with acute respiratory failure. The primary outcome was mortality at the longest follow-up available. RESULTS: We included ten randomized studies and two quasi-randomized studies for a total of 1485 patients. Prehospital treatment with noninvasive ventilation compared with standard oxygen therapy did not significantly reduce mortality at the longest follow-up available (107/810 [13%] vs 114/772 [15%]; RR = 0.89; 95% CI, 0.70-1.13; P = 0.34; I2=24%). The endotracheal intubation rate was reduced when receiving prehospital noninvasive ventilation (38/776 [4.9%] vs 81/743 [11%]; RR = 0.44; 95% CI, 0.31-0.63; P < 0.001; I2=0%; number needed to treat 17). The intensive care admission rate (114/532 [21%] vs 129/507 [25%]; RR = 0.85; 95% CI, 0.69-1.04; P = 0.11; I2=0%) and length of hospital stay (mean difference=-1.29 days; 95% CI, -3.35-0.77; P = 0.21; I2=82%) were similar between groups. CONCLUSIONS: Adults with acute respiratory failure treated in the prehospital setting with noninvasive ventilation had a lower risk of intubation than those managed with standard oxygen therapy, with similar risk of death, intensive care admission, and length of hospital stay. REVIEW REGISTRATION: PROSPERO CRD42021284947.

Barotrauma in Coronavirus Disease 2019 Patients Undergoing Invasive Mechanical Ventilation: A Systematic Literature Review.

OBJECTIVE: There are concerns of a high barotrauma rate in coronavirus disease 2019 patients with acute respiratory distress syndrome receiving invasive mechanical ventilation. However, a few studies were published, and reported rates were highly variable. We performed a systematic literature review to identify rates of barotrauma, pneumothorax, and pneumomediastinum in coronavirus disease 2019 acute respiratory distress syndrome patients receiving invasive mechanical ventilation. DATA SOURCE: PubMed and Scopus were searched for studies reporting barotrauma event rate in adult coronavirus disease 2019 patients receiving invasive mechanical ventilation. STUDY SELECTION: We included all studies investigating adult patients with coronavirus disease 2019 acute respiratory distress syndrome requiring mechanical ventilation. Case reports, studies performed outside ICU setting, and pediatric studies were excluded. Two investigators independently screened and selected studies for inclusion. DATA EXTRACTION: Two investigators abstracted data on study characteristics, rate of pneumothorax, pneumomediastinum and overall barotrauma events, and mortality. When available, data from noncoronavirus disease 2019 acute respiratory distress syndrome patients were also collected. Pooled estimates for barotrauma, pneumothorax, and pneumomediastinum were calculated. DATA SYNTHESIS: A total of 13 studies with 1,814 invasively ventilated coronavirus disease 2019 patients and 493 noncoronavirus disease 2019 patients were included. A total of 266/1,814 patients (14.7%) had at least one barotrauma event (pooled estimates, 16.1% [95% CI, 11.8-20.4%]). Pneumothorax occurred in 132/1,435 patients (pooled estimates, 10.7%; 95% CI, 6.7-14.7%), whereas pneumomediastinum occurred in 162/1,432 patients (pooled estimates, 11.2%; 95% CI, 8.0-14.3%). Mortality in coronavirus disease 2019 patients who developed barotrauma was 111/198 patients (pooled estimates, 61.6%; 95% CI, 50.2-73.0%). In noncoronavirus disease 2019 acute respiratory distress syndrome patients, barotrauma occurred in 31/493 patients (6.3%; pooled estimates, 5.7%; 95% CI, -2.1% to 13.5%). CONCLUSIONS: Barotrauma occurs in one out of six coronavirus disease 2019 acute respiratory distress syndrome patients receiving invasive mechanical ventilation and is associated with a mortality rate of about 60%. Barotrauma rate may be higher than noncoronavirus disease 2019 controls.

Characteristics of Out-of-Hospital Cardiac Arrest Trials Registered in ClinicalTrials.gov.

Background/Objective: Out-of-hospital cardiac arrest (OHCA) poses a substantial public health concern. A collective evaluation of clinical trials is crucial for understanding systemic trends and progress within a specific research area of interest, ultimately shaping future directions. We performed a comprehensive analysis of the characteristics of trials in the adult OHCA population registered on ClinicalTrials.gov. Methods: Aided by medical subject headings (MeSH), we systematically searched the ClinicalTrials.gov database. Trends over time were assessed with the Cochran-Mantel-Haenszel test. The association between publication year and annual number was assessed with the Pearson correlation coefficient. Results: Out of 152 trials spanning the 2003-2023 period, 29.6% were observational and 70.4% were interventional. Compared with the observational trials, interventional trials were more often randomized (RCT) and achieved full publication status in 84% of cases (p = 0.03). The primary focus of interventional trials was "procedures" (43%), "devices" (23%), and "drugs" (21%). Observational studies focused on "biomarkers" (16%) and "diagnostic test" (13%) (p < 0.001). A decrement in the number of interventional trials with a sample size ≥100 patients across three temporal study points was observed. Nevertheless, published studies predominantly had a sample size ≥100 patients (76%), in contrast to unpublished trials (p ≤ 0.001). An increase in the number of interventional studies funded by the "academic/university" sector was also recorded. Conclusions: Clinical trials on OHCA primarily involved interventions aimed at treatment and were more often randomized, single-center, with small (<100) sample sizes, and funded by the "academic/university" sector.

Remimazolam for anesthesia and sedation in cardiac surgery and for cardiac patients undergoing non-cardiac surgery: a systematic-narrative hybrid review.

INTRODUCTION: Remimazolam, an ultra-short-acting benzodiazepine recognized and approved as an anesthetic and sedative in multiple countries, offers a distinctive pharmacokinetic profile, boasting advantages such as rapid onset, short action duration, and rapid recovery. These attributes may contribute to enhanced hemodynamic stability and a diminished risk of respiratory depression compared to other sedatives. EVIDENCE ACQUISITION: We conducted the first comprehensive systematically structured narrative review to evaluate the role and potential application of remimazolam in cardiac surgery. Twenty-one studies published from 2021 to 2023 delved into remimazolam's application in open cardiac surgery, cardiac catheterization or electrophysiology laboratories, and high-risk cardiovascular patients undergoing non-cardiac surgery. EVIDENCE SYNTHESIS: Overall, remimazolam usage was apparently linked to potentially superior hemodynamic stability compared to other hypnotic drugs. However, findings regarding the reduction in postoperative delirium incidence with remimazolam and the doses of remimazolam for anesthesia induction and maintenance were inconsistent across the studies. CONCLUSIONS: Though remimazolam has demonstrated potential safety, efficacy, and ease-of-use for both anesthesia induction and maintenance in cardiac surgery patients and high-risk cardiovascular patients undergoing non-cardiac surgery, further research is imperative to delve into specific patient subgroups (e.g., the elderly or emergent procedures) so as to ascertain optimal dose ranges to suit diverse clinical scenarios.

Perioperative Mechanical Circulatory Support for Cardiac Assistance in Thoracic Surgery: A Scoping Review Protocol.

Background and Aims: Over the past decades, the number of cardiac patients (e.g., with advanced heart failure or existing cardiovascular comorbidities that expose them to a heightened risk of acute cardiovascular decompensation) requiring noncardiac surgery is rising. For this patient population, potentially curative surgical treatments may be denied due to their prohibitive perioperative risk. Around 30% of patients undergoing general thoracic surgery experience cardiovascular complications of varying severity that may ultimately result in refractory heart failure and/or hemodynamic instability. In both these scenarios, perioperative implantation of temporary mechanical circulatory support (tMCS) may improve patient outcomes by both expanding preoperative surgical eligibility criteria and enabling safer management of unexpected periprocedural complications. This scoping review seeks to summarize the current existing evidence on the role of tMCS for cardiac assistance in thoracic surgery and provide a thorough overview. Methods: We will perform a scoping review adhering to the Joanna Briggs Institute (JBI) methodology and the extension for Scoping Reviews of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis checklist (PRISMA). We will carry out a comprehensive search of several online databases to identify studies on the perioperative implantation of tMCS in patients undergoing thoracic surgery to provide cardiac assistance either due to their heightened preoperative cardiac risk (pre-emptive tMCS) or for acute cardiac failure due to inherent surgical complications (bail-out tMCS). Standardized forms will be employed to perform data charting and extraction. Results: Retrieved studies will be presented through a narrative synthesis following initial categorization, supplemented by descriptive statistical analyses of quantitative data if adequate inter-study homogeneity is observed and further complemented by figures and tables. Conclusion: The planned scoping review aims to assess the safety and feasibility of perioperative implantation of tMCS in patients undergoing thoracic surgery either to mitigate their heightened cardiovascular risk or as a rescue strategy in the event of life-threatening surgical complications. It will identify knowledge gaps, offer direction for future research, and improve clinical practices within the field.

Spiritual Care in Palliative Medicine and End of Life: A Bibliometric Network Analysis.

Background and Objectives: Spiritual care is an essential component of care for the terminally ill, because of its potential to positively impact patient perception of quality of life and dignity. However, it continues to be the least cultivated or even most overlooked aspect of palliative care and end of life. We performed a methodological review using bibliometric analysis to provide a holistic view of the scientific output published on this topic in the literature at the same time outlining present perspectives and research trends. Methods: In accordance with the BIBLIO checklist for reporting the bibliometric reviews of the biomedical literature, pertinent articles were retrieved from the Web of Science (WOS) database. The search string included "spiritual care," "end of life," and their synonyms. The VOSviewer (version 1.6.17) software was used to conduct comprehensive analyses. Semantic and research networks, bibliographic coupling, and journal analysis were examined. Results: A total of 924 articles were identified in WOS, and 842 were retrieved. An increasing trend in the number of publications is observed from 1981 to date, with a peak in the 2019-2021 timeframe. Most articles focused on palliative care, spirituality, spiritual care, religion, end of life, and cancer. The Journal of Pain and Symptom Management contributed the highest number of published documents, while the Journal of Palliative Medicine was the top-cited journal. The highest number of publications originated from collaborations of authors from the United Kingdom, the United States, and Australia. Conclusion: The remarkable increase in the number of publications on spiritual care observed in the years of the COVID-19 pandemic likely reflected global concerns, reasserting the importance of prioritizing spiritual care for whole-person palliation. Spiritual care is integrated with palliative care, in line with the latter's holistic nature and the recognition of spirituality as a fundamental aspect of end-of-life care. Nurses and chaplains exhibited more involvement in palliative-spiritual care than physicians reflecting the belief that chaplains are perceived as specialized providers, and nurses, owing to their direct exposure to spiritual suffering and ethos, are deemed suitable for providing spiritual care.

Interventions reducing mortality in COVID-19 patients: a systematic review of randomized evidence.

INTRODUCTION: COVID-19 pandemic changed the way medical research is published, possibly forever. As the need for rapidity led to the rise of preprint servers, the undeniable drop in the overall quality of scientific publications requires an in-depth review of all available evidence. The present manuscript aims to identify and summarize all treatments which have been reported to reduce mortality in randomized trials in hospitalized COVID-19 patients. EVIDENCE ACQUISITION: Independent investigators searched MEDLINE/PubMed, Scopus, and Embase databases to identify all randomized trials of any intervention influencing mortality in hospitalized COVID-19 patients up to August 18th, 2022. Articles were selected only when they fulfilled all the following: randomized trial design; dealing with any kind of interventions in adult hospitalized COVID-19 patients; and statistically significant reduction in mortality. EVIDENCE SYNTHESIS: We identified 28 interventions (42 manuscripts) reducing mortality in hospitalized COVID-19 patients. About 60% of the studies (26/42) were multicentric, for a total of 1140 centers involved worldwide. Several of these studies were published in high-ranked, peer-reviewed journals. Interventions with randomized evidence of mortality reduction in hospitalized COVID-19 patients belonged to 5 domains: corticosteroids, immunomodulators, antimicrobials, supportive therapies, and other drugs. CONCLUSIONS: Many interventions have the potential to reduce mortality in COVID-19 hospitalized patients. The correct treatment of future pandemics relies on large, multicentric randomized clinical trials for further evaluation of these promising strategies.

Incidence, characteristics, and outcome of out-of-hospital cardiac arrest in Italy: A systematic review and meta-analysis.

Introduction: Data on out-of-hospital cardiac arrest (OHCA) is limited in Italy, and there has never been a comprehensive systematic appraisal of the available evidence. Therefore, this review aims to explore the incidence, characteristics, and outcome of OHCA in Italy. Methods: We systematically searched PubMed, Embase, Google Scholar, ResearchGate, and conference proceedings up to September 23, 2022. Studies investigating OHCA in Italy and reporting at least one outcome related to cardiac arrest were considered eligible. The primary outcome was survival at the longest follow-up available. Risk of bias was assessed using the Joanna Briggs Institute critical appraisal tool. A random-effects model proportion meta-analysis was performed to calculate the pooled outcomes with 95% confidence interval (CI). Results: We included 42 studies (43,042 patients) from 13 of the 20 Italian regions published between 1995 and 2022. Only five studies were deemed to be at low risk of bias. The overall average incidences of OHCA attended by emergency medical services and with resuscitation attempted were 86 (range: 10-190) and 55 (range: 6-108) per 100,000 populations per year, respectively. Survival at the longest follow-up available was 9.0% (95% CI, 6.7-12%; 30 studies and 15,195 patients) in the overall population, 25% (95% CI, 21-30%; 16 studies and 2,863 patients) among patients with shockable rhythms, 28% (95% CI, 20-37%; 8 studies and 1,292 patients) among the Utstein comparator group. Favourable neurological outcome was 5.0% (95% CI, 3.6-6.6%; 16 studies and 9,675 patients). Return of spontaneous circulation was achieved in 19% (95% CI, 16-23%; 40 studies and 30,875 patients) of cases. Bystanders initiated cardiopulmonary resuscitation in 26% (95% CI, 21-32%; 33 studies and 23,491 patients) of cases but only in 3.2% (95% CI, 1.9-4.9%; 9 studies and 8,508 patients) with an automated external defibrillator. The mean response time was 10.2 (95% CI, 8.9-11.4; 25 studies and 23,997 patients) minutes. Conclusions: Survival after OHCA in Italy occurred in one of every ten patients. Bystanders initiated cardiopulmonary resuscitation in only one-third of cases, rarely with a defibrillator. Different areas of the country collected data, but an essential part of the population was not included. There was high heterogeneity and large variation in outcomes results and reporting, limiting the confidence in the estimates of incidence and outcome. Creating and maintaining a nationwide registry is a priority.