Fluid management in the perioperative setting: mind the kidney

Acute kidney injury (AKI) is one of the most frequent complications in critically ill patients and in the perioperative setting. The anatomical structure and the microvasculature of the kidney makes it highly vulnerable to hypoxia. Although fluid therapy is considered crucial in situations where improvement of cardiac output is needed, it can also contribute to AKI development when administered inappropriately. Hemodilution and anemia during cardio-pulmonary bypass have been demonstrated to be risk factors for AKI and they are likely to be a consequence of fluid administration. In order to assess the perfusion of the kidneys it is necessary to investigate the determinants of delivery of oxygen at the microcirculatory level. Indeed, fluids can decrease the capillary hematocrit and the functional capillary density, affecting the renal oxygenation and increasing the risk of AKI. Monitoring sublingual microcirculation can be a reliable tool to guide fluid administration, aiming to prevent or improve perioperative AKI

Acute Kidney Injury and Fluid Resuscitation in Septic Patients: Are We Protecting the Kidney?

Acute kidney injury (AKI) is a common complication in critically ill patients, especially among septic patients. Sepsis and hypovolemia are the 2 most frequent etiologies of AKI in intensive care units and frequently coexist in critically ill patients. Effective fluid resuscitation is crucial for the stabilization of sepsis-induced tissue hypoperfusion or septic shock. However, the lack of a goal-directed therapy targeting kidney oxygenation prevents from optimization of the fluid therapy with regard to improvement of renal oxygen delivery and extraction. Similarly, fluid administration as all therapeutic actions carries adverse effects such as the activation of cytokines, disruption of the capillary glycocalyx, and adverse effects on kidney metabolism and oxygenation. Moreover, a positive fluid balance is associated with an increased risk of AKI and is a negative predictor for recovery of renal function. The role of fluid resuscitation on kidney injury stems from the high renal vulnerability to hypoxemic injury. Indeed, fluids have a poor oxygen solubility and hemodilution decreases blood viscosity both promoting intrarenal shunting and heterogeneity with a decreased capillary density and enhanced intrarenal cortex and medullary hypoxia. The development of physiological biomarkers that are able to detect the early development of AKI specifically aimed at the identification of renal microcirculatory dysfunctions should form a valuable contribution to monitoring therapeutic modalities

Prognostic factors associated with mortality risk and disease progression in 639 critically ill patients with COVID-19 in Europe: Initial report of the international RISC-19-ICU prospective observational cohort

Background: Coronavirus disease 2019 (COVID-19) is associated with a high disease burden with 10% of confirmed cases progressing towards critical illness. Nevertheless, the disease course and predictors of mortality in critically ill patients are poorly understood. Methods: Following the critical developments in ICUs in regions experiencing early inception of the pandemic, the European-based, international RIsk Stratification in COVID-19 patients in the Intensive Care Unit (RISC-19-ICU) registry was created to provide near real-time assessment of patients developing critical illness due to COVID-19. Findings: As of April 22, 2020, 639 critically ill patients with confirmed SARS-CoV-2 infection were included in the RISC-19-ICU registry. Of these, 398 had deceased or been discharged from the ICU. ICU-mortality was 24%, median length of stay 12 (IQR, 5–21) days. ARDS was diagnosed in 74%, with a minimum P/F-ratio of 110 (IQR, 80–148). Prone positioning, ECCO2R, or ECMO were applied in 57%. Off-label therapies were prescribed in 265 (67%) patients, and 89% of all bloodstream infections were observed in this subgroup (n = 66; RR=3·2, 95% CI [1·7–6·0]). While PCT and IL-6 levels remained similar in ICU survivors and non-survivors throughout the ICU stay (p = 0·35, 0·34), CRP, creatinine, troponin, D-dimer, lactate, neutrophil count, P/F-ratio diverged within the first seven days (p<0·01). On a multivariable Cox proportional-hazard regression model at admission, creatinine, D-dimer, lactate, potassium, P/F-ratio, alveolar-arterial gradient, and ischemic heart disease were independently associated with ICU-mortality. Interpretation: The European RISC-19-ICU cohort demonstrates a moderate mortality of 24% in critically ill patients with COVID-19. Despite high ARDS severity, mechanical ventilation incidence was low and associated with more rescue therapies. In contrast to risk factors in hospitalized patients reported in other studies, the main mortality predictors in these critically ill patients were markers of oxygenation deficit, renal and microvascular dysfunction, and coagulatory activation. Elevated risk of bloodstream infections underscores the need to exercise caution with off-label therapies

Dynamics of disease characteristics and clinical management of critically ill COVID-19 patients over the time course of the pandemic: an analysis of the prospective, international, multicentre RISC-19-ICU registry.

BACKGROUND It remains elusive how the characteristics, the course of disease, the clinical management and the outcomes of critically ill COVID-19 patients admitted to intensive care units (ICU) worldwide have changed over the course of the pandemic. METHODS Prospective, observational registry constituted by 90 ICUs across 22 countries worldwide including patients with a laboratory-confirmed, critical presentation of COVID-19 requiring advanced organ support. Hierarchical, generalized linear mixed-effect models accounting for hospital and country variability were employed to analyse the continuous evolution of the studied variables over the pandemic. RESULTS Four thousand forty-one patients were included from March 2020 to September 2021. Over this period, the age of the admitted patients (62 [95% CI 60-63] years vs 64 [62-66] years, p < 0.001) and the severity of organ dysfunction at ICU admission decreased (Sequential Organ Failure Assessment 8.2 [7.6-9.0] vs 5.8 [5.3-6.4], p < 0.001) and increased, while more female patients (26 [23-29]% vs 41 [35-48]%, p < 0.001) were admitted. The time span between symptom onset and hospitalization as well as ICU admission became longer later in the pandemic (6.7 [6.2-7.2| days vs 9.7 [8.9-10.5] days, p < 0.001). The PaO2/FiO2 at admission was lower (132 [123-141] mmHg vs 101 [91-113] mmHg, p < 0.001) but showed faster improvements over the initial 5 days of ICU stay in late 2021 compared to early 2020 (34 [20-48] mmHg vs 70 [41-100] mmHg, p = 0.05). The number of patients treated with steroids and tocilizumab increased, while the use of therapeutic anticoagulation presented an inverse U-shaped behaviour over the course of the pandemic. The proportion of patients treated with high-flow oxygen (5 [4-7]% vs 20 [14-29], p < 0.001) and non-invasive mechanical ventilation (14 [11-18]% vs 24 [17-33]%, p < 0.001) throughout the pandemic increased concomitant to a decrease in invasive mechanical ventilation (82 [76-86]% vs 74 [64-82]%, p < 0.001). The ICU mortality (23 [19-26]% vs 17 [12-25]%, p < 0.001) and length of stay (14 [13-16] days vs 11 [10-13] days, p < 0.001) decreased over 19 months of the pandemic. CONCLUSION Characteristics and disease course of critically ill COVID-19 patients have continuously evolved, concomitant to the clinical management, throughout the pandemic leading to a younger, less severely ill ICU population with distinctly different clinical, pulmonary and inflammatory presentations than at the onset of the pandemic

Influenza vaccination for immunocompromised patients: systematic review and meta-analysis from a public health policy perspective.

Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events

GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment