Regional citrate anticoagulation (RCA) is now recommended over systemic heparin for continuous renal replacement therapy in patients without contraindications. Its use is likely to increase ...throughout the world. However, in the absence of citrate blood level monitoring, the diagnosis of citrate accumulation, the most feared complication of RCA, remains relatively complex. It is therefore commonly mistaken with other conditions. This review aims at providing clarifications on RCA-associated acid-base disturbances and their management at the bedside. In particular, the authors wish to propose a clear distinction between citrate accumulation and net citrate overload.
Sepsis-associated acute kidney injury (SA-AKI) is common in critically ill patients and is strongly associated with adverse outcomes, including an increased risk of chronic kidney disease, ...cardiovascular events and death. The pathophysiology of SA-AKI remains elusive, although microcirculatory dysfunction, cellular metabolic reprogramming and dysregulated inflammatory responses have been implicated in preclinical studies. SA-AKI is best defined as the occurrence of AKI within 7 days of sepsis onset (diagnosed according to Kidney Disease Improving Global Outcome criteria and Sepsis 3 criteria, respectively). Improving outcomes in SA-AKI is challenging, as patients can present with either clinical or subclinical AKI. Early identification of patients at risk of AKI, or at risk of progressing to severe and/or persistent AKI, is crucial to the timely initiation of adequate supportive measures, including limiting further insults to the kidney. Accordingly, the discovery of biomarkers associated with AKI that can aid in early diagnosis is an area of intensive investigation. Additionally, high-quality evidence on best-practice care of patients with AKI, sepsis and SA-AKI has continued to accrue. Although specific therapeutic options are limited, several clinical trials have evaluated the use of care bundles and extracorporeal techniques as potential therapeutic approaches. Here we provide graded recommendations for managing SA-AKI and highlight priorities for future research.
Decreased monocytic (m)HLA-DR expression is the most studied biomarker of sepsis-induced immunosuppression. To date, little is known about the relationship between sepsis characteristics, such as the ...site of infection, causative pathogen, or severity of disease, and mHLA-DR expression kinetics.
We evaluated mHLA-DR expression kinetics in 241 septic shock patients with different primary sites of infection and pathogens. Furthermore, we used unsupervised clustering analysis to identify mHLA-DR trajectories and evaluated their association with outcome parameters.
No differences in mHLA-DR expression kinetics were found between groups of patients with different sites of infection (abdominal vs. respiratory, p = 0.13; abdominal vs. urinary tract, p = 0.53) and between pathogen categories (Gram-positive vs. Gram-negative, p = 0.54; Gram-positive vs. negative cultures, p = 0.84). The mHLA-DR expression kinetics differed between survivors and non-survivors (p < 0.001), with an increase over time in survivors only. Furthermore, we identified three mHLA-DR trajectories ('early improvers', 'delayed or non-improvers' and 'decliners'). The probability for adverse outcome (secondary infection or death) was higher in the delayed or non-improvers and decliners vs. the early improvers (delayed or non-improvers log-rank p = 0.03, adjusted hazard ratio 2.0 95% CI 1.0-4.0, p = 0.057 and decliners log-rank p = 0.01, adjusted hazard ratio 2.8 95% CI 1.1-7.1, p = 0.03).
Sites of primary infection or causative pathogens are not associated with mHLA-DR expression kinetics in septic shock patients. However, patients showing delayed or no improvement in or a declining mHLA-DR expression have a higher risk for adverse outcome compared with patients exhibiting a swift increase in mHLA-DR expression. Our study signifies that changes in mHLA-DR expression over time, and not absolute values or static measurements, are of clinical importance in septic shock patients.
T lymphocyte alterations are central to sepsis pathophysiology, whereas related mechanisms remain poorly understood. We hypothesized that metabolic alterations could play a role in sepsis-induced T ...lymphocyte dysfunction. Samples from septic shock patients were obtained at day 3 and compared with those from healthy donors. T cell metabolic status was evaluated in the basal condition and after T cell stimulation. We observed that basal metabolic content measured in lymphocytes by nuclear magnetic resonance spectroscopy was altered in septic patients. Basal ATP concentration, oxidative phosphorylation (OXPHOS), and glycolysis pathways in T cells were decreased as well. After stimulation, T lymphocytes from patients failed to induce glycolysis, OXPHOS, ATP production, GLUT1 expression, glucose entry, and proliferation to similar levels as controls. This was associated with significantly altered mTOR, but not Akt or HIF-1α, activation and only minor AMPKα phosphorylation dysfunction. IL-7 treatment improved mTOR activation, GLUT1 expression, and glucose entry in septic patients' T lymphocytes, leading to their enhanced proliferation. mTOR activation was central to this process, because rapamycin systematically inhibited the beneficial effect of recombinant human IL-7. We demonstrate the central role of immunometabolism and, in particular, mTOR alterations in the pathophysiology of sepsis-induced T cell alterations. Our results support the rationale for targeting metabolism in sepsis with recombinant human IL-7 as a treatment option.
Prone position is used in acute respiratory distress syndrome and in coronavirus disease 2019 acute respiratory distress syndrome. However, it is unclear how responders may be identified and whether ...an oxygenation response improves outcome. The objective of this study was to quantify the response to prone position, describe the differences between coronavirus disease 2019 acute respiratory distress syndrome and acute respiratory distress syndrome, and explore variables associated with survival.
Retrospective, observational, multicenter, international cohort study.
Seven ICUs in Italy, United Kingdom, and France.
Three hundred seventy-six adults (220 coronavirus disease 2019 acute respiratory distress syndrome and 156 acute respiratory distress syndrome).
None.
Preproning, a greater proportion of coronavirus disease 2019 acute respiratory distress syndrome patients had severe disease (53% vs 40%), worse Pao2/Fio2 (13.0 kPa interquartile range, 10.5-15.5 kPa vs 14.1 kPa interquartile range, 10.5-18.6 kPa; p = 0.017) but greater compliance (38 mL/cm H2O interquartile range, 27-53 mL/cm H2O vs 31 mL/cm H2O interquartile range, 21-37 mL/cm H2O; p < 0.001). Patients with coronavirus disease 2019 acute respiratory distress syndrome had a longer median time from intubation to prone position (2.0 d interquartile range, 0.7-5.0 d vs 1.0 d interquartile range, 0.5-2.9 d; p = 0.03). The proportion of responders, defined by an increase in Pao2/Fio2 greater than or equal to 2.67 kPa (20 mm Hg), upon proning, was similar between acute respiratory distress syndrome and coronavirus disease 2019 acute respiratory distress syndrome (79% vs 76%; p = 0.5). Responders had earlier prone position (1.4 d interquartile range, 0.7-4.2 d vs 2.5 d interquartile range, 0.8-6.2 d; p = 0.06). Prone position less than 24 hours from intubation achieved greater improvement in oxygenation (11 kPa interquartile range, 4-21 kPa vs 7 kPa interquartile range, 2-13 kPa; p = 0.002). The variables independently associated with the "responder" category were Pao2/Fio2 preproning (odds ratio, 0.89 kPa-1 95% CI, 0.85-0.93 kPa-1; p < 0.001) and interval between intubation and proning (odds ratio, 0.94 d-1 95% CI, 0.89-0.99 d-1; p = 0.019). The overall mortality was 45%, with no significant difference observed between acute respiratory distress syndrome and coronavirus disease 2019 acute respiratory distress syndrome. Variables independently associated with mortality included age (odds ratio, 1.03 yr-1 95% CI, 1.01-1.05 yr-1; p < 0.001); interval between hospital admission and proning (odds ratio, 1.04 d-1 95% CI, 1.002-1.084 d-1; p = 0.047); and change in Pao2/Fio2 on proning (odds ratio, 0.97 kPa-1 95% CI, 0.95-0.99 kPa-1; p = 0.002).
Prone position, particularly when delivered early, achieved a significant oxygenation response in ~80% of coronavirus disease 2019 acute respiratory distress syndrome, similar to acute respiratory distress syndrome. This response was independently associated with improved survival.
Objective structured clinical examination (OSCE) is a valid method to evaluate medical students' competencies. The present cross-sectional study aimed at determining how students' coping and ...health-related behaviors are associated with their psychological well-being and performance on the day of the OSCE. Fourth-year medical students answered a set of standardized questionnaires assessing their coping (BCI) and health-related behaviors before the examination (sleep PSQI, physical activity GPAQ). Immediately before the OSCE, they reported their level of instant psychological well-being on multi-dimensional visual analogue scales. OSCE performance was assessed by examiners blinded to the study. Associations were explored using multivariable linear regression models. A total of 482 students were included. Instant psychological well-being was positively associated with the level of positive thinking and of physical activity. It was negatively associated with the level of avoidance and of sleep disturbance. Furthermore, performance was negatively associated with the level of avoidance. Positive thinking, good sleep quality, and higher level of physical activity were all associated with improved well-being before the OSCE. Conversely, avoidance coping behaviors seem to be detrimental to both well-being and OSCE performance. The recommendation is to pay special attention to students who engage in avoidance and to consider implementing stress management programs.Clinical trial: The study protocol was registered on clinicaltrial.gov NCT05393206, date of registration: 11 June 2022.
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