Amino acids and the kidney; friends or foes?

PURPOSE OF REVIEW: Acute kidney injury (AKI) is common in hospitalized patients and is independently associated with morbidity and mortality. Moreover, AKI increases the risk of chronic kidney disease, which is a major healthcare problem. Currently, no single therapy has been proven to be effective in preventing AKI. The role of amino acids in the context of kidney function and AKI prevention has been controversial and most of the evidence is available from nutritional studies. However, knowledge of amino acids in recruiting renal functional reserve and their potential role to protect renal function under stress has recently expanded. RECENT FINDINGS: The nephroprotective effects of amino acids were first postulated in 1973. Recently, this strategy gained renewed interest and has been more extensively studied, reintroducing their use in clinical situations characterized by a high incidence of AKI. Intravenous amino acids administration for kidney protection is now supported by a large multinational randomized double-blind controlled trial in cardiac surgery and by experimental and observational data. All such data support the rationale for a biologically and clinically important nephroprotective effect. SUMMARY: The infusion of amino acids was recently found to reduce the incidence of AKI in cardiac surgery patients and surgical patients. This strategy for the protection of renal function is supported by a multicenter, international, double-blind randomized trial, with a huge potential for additional application in several clinical fields. Several mechanisms of action support the robustness of these findings and are summarized in this manuscript.

Predictors and outcomes of delirium in the emergency department during the first wave of the COVID-19 pandemic in Milan.

BACKGROUND: Respiratory infections can be complicated by acute brain failure. We assessed delirium prevalence, predictors and outcomes in COVID-19 ED patients. METHODS: This was a retrospective observational study conducted at the San Raffaele ED (Italy). Patients age >18 years attending the ED between 26 February 2020 and 30 May 2020 and who had a positive molecular nasopharyngeal swab for SARS-CoV-2 were included. The Chart-Based Delirium Identification Instrument (CHART-DEL) was used to retrospectively assess delirium. Univariable and multivariable logistic regression analyses were used to evaluate delirium predictors. Univariable binary logistic regression analyses, linear regression analyses and Cox regression analyses were used to assess the association between delirium and clinical outcomes. Age-adjusted and sex-adjusted models were then run for the significant predictors of the univariable models. RESULTS: Among the 826 included patients, 123 cases (14.9%) of delirium were retrospectively detected through the CHART-DEL method. Patients with delirium were older (76.9±13.15 vs 61.3±14.27 years, p<0.001) and more frequently living in a long-term health facility (32 (26%) vs 22 (3.1%), p<0.001). Age (OR 1.06, 95% CI 1.04 to 1.09, p<0.001), dementia (OR 17.5, 95% CI 7.27 to 42.16, p<0.001), epilepsy (OR 6.96, 95% CI 2.48 to 19.51, p<0.001) and the number of chronic medications (OR 1.09, 95% CI 1.01 to 1.17, p=0.03) were significant predictors of delirium in multivariable analyses. Delirium was associated with increased in-hospital mortality (adjusted HR 2.16, 95% CI 1.55 to 3.03, p<0.001) and with a reduced probability of being discharged home compared with being institutionalised (adjusted OR 0.39, 95% CI 0.25 to 0.61, p<0.001). CONCLUSIONS: Chart review frequently identified ED delirium in patients with COVID-19. Age, dementia, epilepsy and polypharmacy were significant predictors of ED delirium. Delirium was associated with an increased in-hospital mortality and with a reduced probability of being discharged home after hospitalisation. The findings of this single-centre retrospective study require validation in future studies.

Gas-exchange deficit and systemic hypoperfusion in COVID-19 and non-COVID-19 young adult patients with pneumonia.

BACKGROUND: Lung damage leading to gas-exchange deficit and sepsis leading to systemic hypoperfusion are well-known features of severe pneumonia. Although frequently described in COVID-19, their prognostic impact in COVID-19-related pneumonia vs COVID-19-urelated pneumonia has never been compared. This study assesses fundamental gas-exchange and hemodynamic parameters and explores their prognostic impact in COVID-19 pneumonia and non-COVID-19 pneumonia. METHODS: We prospectively evaluated arterial pO2/FiO2, alveolar to arterial O2 gradient, shock index, and serum lactate in 126 COVID-19 pneumonia patients, aged 18- 65, presenting to the emergency department with acute, non-hypercapnic respiratory failure. As a control group we identified 1:1 age-, sex-, and pO2/FiO2-matched COVID-19-urelated pneumonia patients. Univariate and multivariable predictors of 30-day survival were identified in both groups. RESULTS: COVID-19 patients showed lower arterial serum lactate concentration (p<0.001) and shock index (p<0.001) values as compared to non-COVID-19 patients. While we did not observe differences in lactate concentration or in shock index values in deceased vs surviving COVID-19 patients (respectively, p=0.7 and p=0.6), non-COVID-19 deceased patients showed significantly higher lactate and shock index than non-COVID-19 survivors (p<0.001 and p=0.03). The pO2/FiO2 was the most powerful determinant of survival by Cox regression multivariate analysis in COVID-19 patients (p=0.006), while it was lactate in non-COVID-19 patients (p=0.001). CONCLUSIONS: As compared to COVID19-unrelated pneumonia, COVID-19 pneumonia outcome seems more strictly correlated to the extent of lung damage, rather than to the systemic circulatory and metabolic derangements typical of sepsis.

Early predictors of clinical outcomes of COVID-19 outbreak in Milan, Italy.

BACKGROUND: National health-system hospitals of Lombardy faced a heavy burden of admissions for acute respiratory distress syndromes associated with coronavirus disease (COVID-19). Data on patients of European origin affected by COVID-19 are limited. METHODS: All consecutive patients aged ≥18 years, coming from North-East of Milan's province and admitted at San Raffaele Hospital with COVID-19, between February 25th and March 24th, were reported, all patients were followed for at least one month. Clinical and radiological features at admission and predictors of clinical outcomes were evaluated. RESULTS: Of the 500 patients admitted to the Emergency Unit, 410 patients were hospitalized and analyzed: median age was 65 (IQR 56-75) years, and the majority of patients were males (72.9%). Median (IQR) days from COVID-19 symptoms onset was 8 (5-11) days. At hospital admission, fever (≥ 37.5 °C) was present in 67.5% of patients. Median oxygen saturation (SpO2) was 93% (range 60-99), with median PaO2/FiO2 ratio, 267 (IQR 184-314). Median Radiographic Assessment of Lung Edema (RALE) score was 9 (IQR 4-16). More than half of the patients (56.3%) had comorbidities, with hypertension, coronary heart disease, diabetes and chronic kidney failure being the most common. The probability of overall survival at day 28 was 66%. Multivariable analysis showed older age, coronary artery disease, cancer, low lymphocyte count and high RALE score as factors independently associated with an increased risk of mortality. CONCLUSION: In a large cohort of COVID-19 patients of European origin, main risk factors for mortality were older age, comorbidities, low lymphocyte count and high RALE.

Fast reshaping of intensive care unit facilities in a large metropolitan hospital in Milan, Italy: facing the COVID-19 pandemic emergency

At the end of 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak spread from China all around the world, causing thousands of deaths. In Italy, the hardest hit region was Lombardy, with the first reported case on 20 February 2020. San Raffaele Scientific Institute ­ a large tertiary hospital and research centre in Milan, Italy ­ was immediately involved in the management of the public health emergency. Since the beginning of the outbreak, the elective surgical activity of the hospital was rapidly reduced and large areas of the hospital were simultaneously reorganised to admit and assist patients with coronavirus disease 2019 (COVID-19). In addition, the hospital became the regional referral hub for cardiovascular emergencies in order to keep ensuring a high level of health care to non-COVID-19 patients in northern Italy. In a few days, a COVID-19 emergency department was created, improving the general ward capacity to a total number of 279 beds dedicated to patients with COVID-19. Moreover, the number of intensive care unit (ICU) beds was increased from 28 to 72 (54 of them dedicated to patients with COVID-19, and 18 to cardiology and cardiac surgery hub emergencies), both converting pre-existing areas and creating new high technology spaces. All the involved health care personnel were rapidly trained to use personal protection equipment and to manage this particular category of patients both in general wards and ICUs. Furthermore, besides clinical activities, continuously important research projects were carried out in order to find new strategies and more effective therapies to better face an unprecedented health emergency in Italy.

Noninvasive Ventilation After Thoracoabdominal Aortic Surgery: A Pilot Randomized Controlled Trial.

OBJECTIVE: To assess the beneficial effects of noninvasive ventilation in treating postoperative pulmonary complications in patients undergoing thoracoabdominal aortic aneurysm (TAAA) open repair surgery. DESIGN: Randomized controlled trial. SETTING: University tertiary-care hospital. PARTICIPANTS: Forty patients who underwent elective TAAA open repair. INTERVENTIONS: Patients were randomized to the "noninvasive ventilation" group, receiving 2-hour cycles of noninvasive ventilation every 8 hours for at least 3 days in addition to the best available postoperative treatment currently in use at the authors' institution versus the "standard" group, not receiving noninvasive ventilation treatment MEASUREMENTS AND MAIN RESULTS: The primary outcome of clinical worsening, described as a composite outcome of need for therapeutic noninvasive ventilation, need for mechanical ventilation owing to respiratory causes, need for intensive care unit admission owing to respiratory causes, and in-hospital mortality, occurred in 2 (11%) patients in the noninvasive ventilation group versus 12 (57%) in the standard group (p = 0.002; relative risk 0.18; 95% confidence interval 0.047-0.72). CONCLUSION: Noninvasive ventilation is a promising, affordable, and easy-to-use tool to prevent postoperative respiratory complications after TAAA open surgical repair.

The Brachiocephalic Vein as a Safe and Viable Alternative to Internal Jugular Vein for Central Venous Cannulation.

BACKGROUND: Although many studies have compared success and complication rates for central line insertion sites with and without ultrasound, few have examined the use of the brachiocephalic vein for central venous access. The aim of this study was to describe the brachiocephalic vein as an alternative site for elective ultrasound vascular cannulation in adults, and to compare it with the more commonly used internal jugular vein site in terms of procedural difficulties, first pass failure rate, overall failure rate, and safety. METHODS: In this single-center, retrospective cohort study, clinical data from consecutive adult patients undergoing elective ultrasound-guided central venous catheterization of upper body were retrieved from the department database. All of these central venous catheters were requested by department team, none was positioned for surgery. Seven hundred nine patients underwent central venous catheterization via the internal jugular approach and 285 patients via the brachiocephalic route. Patients catheterized via the brachiocephalic vein approach were then compared with those catheterized via the internal jugular vein in terms of ease of catheterization, success rate, and complications. Differences between approaches were assessed by univariate analyses and multivariable analysis. RESULTS: Overall, 994 patients underwent central venous catheterization. A total of 87% had a successful catheter implantation at the first attempt, 6.7% of insertions were difficult, 5.7% were complicated, and 3.4% failed. Procedural difficulty was more frequent with the internal jugular than with the brachiocephalic approach (odds ratio, 0.38; 95% confidence interval, 0.19-0.76; P = .007) after correction for potential confounders. Differences between groups in complication rate (6.3% vs 4.1%) or failure rate (3.4% vs 3.5%) were not significant. CONCLUSIONS: Brachiocephalic cannulation is a reasonable alternative to ultrasound-guided internal jugular vein catheterization.

Nonsurgical Strategies to Reduce Mortality in Patients Undergoing Cardiac Surgery: An Updated Consensus Process.

OBJECTIVE: A careful choice of perioperative care strategies is pivotal to improve survival in cardiac surgery. However, there is no general agreement or particular attention to which nonsurgical interventions can reduce mortality in this setting. The authors sought to address this issue with a consensus-based approach. DESIGN: A systematic review of the literature followed by a consensus-based voting process. SETTING: A web-based international consensus conference. PARTICIPANTS: More than 400 physicians from 52 countries participated in this web-based consensus conference. INTERVENTIONS: The authors identified all studies published in peer-reviewed journals that reported on interventions with a statistically significant effect on mortality in the setting of cardiac surgery through a systematic Medline/PubMed search and contacts with experts. These studies were discussed during a consensus meeting and those considered eligible for inclusion in this study were voted on by clinicians worldwide. MEASUREMENTS AND MAIN RESULTS: Eleven interventions finally were selected: 10 were shown to reduce mortality (aspirin, glycemic control, high-volume surgeons, prophylactic intra-aortic balloon pump, levosimendan, leuko-depleted red blood cells transfusion, noninvasive ventilation, tranexamic acid, vacuum-assisted closure, and volatile agents), whereas 1 (aprotinin) increased mortality. A significant difference in the percentages of agreement among different countries and a variable gap between agreement and clinical practice were found for most of the interventions. CONCLUSIONS: This updated consensus process identified 11 nonsurgical interventions with possible survival implications for patients undergoing cardiac surgery. This list of interventions may help cardiac anesthesiologists and intensivists worldwide in their daily clinical practice and can contribute to direct future research in the field.

Outcome of cardiac surgery in patients with low preoperative ejection fraction.

BACKGROUND: In patients undergoing cardiac surgery, a reduced preoperative left ventricular ejection fraction (LVEF) is common and is associated with a worse outcome. Available outcome data for these patients address specific surgical procedures, mainly coronary artery bypass graft (CABG). Aim of our study was to investigate perioperative outcome of surgery on patients with low pre-operative LVEF undergoing a broad range of cardiac surgical procedures. METHODS: Data from patients with pre-operative LVEF ≤40 % undergoing cardiac surgery at a university hospital were reviewed and analyzed. A subgroup analysis on patients with pre-operative LVEF ≤30 % was also performed. RESULTS: A total of 7313 patients underwent cardiac surgery during the study period. Out of these, 781 patients (11 %) had a pre-operative LVEF ≤40 % and were included in the analysis. Mean pre-operative LVEF was 33.9 ± 6.1 % and in 290 patients (37 %) LVEF was ≤30 %. The most frequently performed operation was CABG (31 % of procedures), followed by mitral valve surgery (22 %) and aortic valve surgery (19 %). Overall perioperative mortality was 5.6 %. Mitral valve surgery was more frequent among patients who did not survive, while survivors underwent more frequently CABG. Post-operative myocardial infarction occurred in 19 (2.4 %) of patients, low cardiac output syndrome in 271 (35 %). Acute kidney injury occurred in 195 (25 %) of patients. Duration of mechanical ventilation was 18 (12-48) hours. Incidence of complications was higher in patients with LVEF ≤30 %. Stepwise multivariate analysis identified chronic obstructive pulmonary disease, pre-operative insertion of intra-aortic balloon pump, and pre-operative need for inotropes as independent predictors of mortality among patients with LVEF ≤40 %. CONCLUSIONS: We confirmed that patients with low pre-operative LVEF undergoing cardiac surgery are at higher risk of post-operative complications. Cardiac surgery can be performed with acceptable mortality rates; however, mitral valve surgery, was found to be associated with higher mortality rates in this population. Accurate selection of patients, risk/benefit evaluation, and planning of surgical and anesthesiological management are mandatory to improve outcome.

Long-Term Survival Rate in Patients With Acute Respiratory Failure Treated With Noninvasive Ventilation in Ordinary Wards.

OBJECTIVE: Noninvasive ventilation is a life-saving technique increasingly used to treat acute respiratory failure. Noninvasive ventilation has been applied mostly in ICUs, but several reasons brought to an increasing application of noninvasive ventilation in ordinary wards. Few articles evaluated the outcomes of patients receiving noninvasive ventilation including long-term follow-up. The aim of the present study was to assess 1-year survival rate of patients treated with noninvasive ventilation outside the ICU for acute respiratory failure of heterogeneous causes and to identify the predictors of long-term mortality. DESIGN: Prospective, observational, pragmatic study. SETTING: Ordinary wards of a teaching hospital. PATIENTS: Consecutive patients treated with noninvasive ventilation for acute respiratory failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two-hundred and twenty-patients were enrolled. Mortality rates at 30-day, 90-days, and 1-year follow-up were 20%, 26%, and 34%. When excluding patients with "do-not-resuscitate" status, mortality rates were 13%, 19%, and 28%. The multivariate analyses identified solid cancer, pneumonia in hematologic patients, and do-not-resuscitate status as independent predictors of mortality with postoperative acute respiratory failure associated with improved survival. The same predictors were confirmed when excluding do-not-resuscitate patients from the analyses. CONCLUSIONS: Noninvasive ventilation applied in ordinary wards was effective, with long-term outcomes not different from those reported for ICU settings. Solid cancer, pneumonia in hematologic malignancies, and do-not-resuscitate status predicted mortality, whereas patients with postoperative acute respiratory failure had the best survival rate. Additional studies are required to evaluate noninvasive ventilation efficacy in the wards compared with ICU.

Levosimendan: new indications and evidence for reduction in perioperative mortality?

PURPOSE OF REVIEW: In the last years, the perioperative use of levosimendan in cardiac surgery patients is spreading. Moreover, newer indications have been suggested such as the treatment of sepsis-associated myocardial dysfunction. In the present review, we discuss the most recent evidences in these settings. RECENT FINDINGS: Levosimendan has been seemingly confirmed to reduce mortality in patients undergoing cardiac surgery. In particular, it appears to be the only inotropic drug to have a favorable effect on survival in any clinical setting. Moreover, levosimendan has been shown to exert a cardioprotective action and to reduce acute kidney injury, renal replacement therapy, and ICU stay in cardiac surgery patients. Finally, levosimendan has been suggested to reduce mortality in patients with severe sepsis and to improve renal outcomes in critically ill patients. SUMMARY: Although a strong rationale likely exists to use levosimendan in the setting of perioperative and critical care medicine, evidence mainly comes from small and often poor-quality randomized clinical trials, whose results acquire significance only when pooled in meta-analyses. Moreover, some aspects related to which subgroups of patients may derive the most benefits from receiving levosimendan, to the optimal timing of administration, and to the potential adverse effects need to be further clarified. Important insights will be hopefully provided soon by the several large multicenter investigations which are currently ongoing.

Spinal analgesia in cardiac surgery: a meta-analysis of randomized controlled trials.

OBJECTIVE: Controversial results exist on the effects of spinal analgesia in cardiac surgery. The authors conducted a review of randomized studies to show whether there are any advantages in clinically relevant outcomes using spinal analgesia in patients undergoing cardiac surgery. DESIGN: Meta-analysis. SETTING: Multiple hospitals. PARTICIPANTS: A total of 1,106 patients from 25 randomized trials. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULT: PubMed, BioMedCentral, CENTRAL, EMBASE, Cochrane Central Register of Controlled Trials, and conference proceedings were searched (updated January 2009) for randomized trials that compared general anesthesia with an anesthetic plan including spinal analgesia in cardiac surgery. Four independent reviewers performed data extraction, with divergences resolved by consensus. A total of 1,106 patients from 25 randomized studies were included in the analysis. Overall analysis showed that there were no differences in terms of mortality (2/562 [0.4%] in the spinal group v 2/514 [0.4%] in the control arm [risk difference (RD) = 0.00 [-0.02, +0.02], p = 1.0), perioperative myocardial infarction (9/421 [2.1%] in the spinal group v 11/407 [2.7%] in the control arm [RD = 0.00, -(0.03, +0.02), p = 0.77), and the length of hospital stay (WMD = -0.28 days [-0.68, -0.13], p = 0.18, with 419 included patients). CONCLUSIONS: This analysis indicated that spinal analgesia does not improve clinically relevant outcomes in patients undergoing cardiac surgery, discouraging further randomized controlled trials on this topic even if changes in techniques, devices, and drugs could modify the outlook of the comparison between spinal and standard anesthesia in this setting.