Annals of Intensive Care最新文献

Background: Septic myocardial dysfunction is a frequent complication of sepsis, commonly defined by impaired cardiac contractility. Despite its clinical significance, its pathophysiology remains poorly understood and no targeted therapy is currently available. Pro-inflammatory cytokines have been implicated in experimental models, but their causal role and therapeutic relevance in septic myocardial dysfunction remain uncertain. We aimed to systematically review and meta-analyze the impact of cytokine addition or blockade on myocardial function in sepsis across in vitro, in vivo, and human studies.

Methods: We performed a systematic search of MEDLINE, Embase, Cochrane, and PubMed databases up to December 2024. We included all cellular, animal, and human studies (descriptive or interventional) assessing the effect of cytokine modulation on myocardial contractility in sepsis. Studies lacking contractility assessment were excluded from the meta-analysis but retained in the systematic review. Standardized mean differences (SMDs) were pooled using a random-effects model. Risk of bias was assessed using dedicated tools adapted to each study design.

Results: A total of 39 studies were included in the systematic review, and 21 in the meta-analysis. Eleven in vitro or ex vivo studies showed that cardiomyocyte contractility was significantly reduced after exposure to IL-1 (SMD 5.62 [5.01;6.23]), IL-6 (4.24 [1.49;6.99]) and TNF-α (4.45 [3.17;5.72]); all were included in the meta-analysis. Seventeen in vivo animal studies were reviewed, of which six were eligible for meta-analysis: TNF-α (5.06 [1.46;8.65]) and IL-18 (1.56 [0.77;2.36]) were associated with significant cardiac depression, whereas IL-1 showed a non-significant effect (2.58 [-0.90;6.07]). Among eleven human studies, four were included in the meta-analysis. Patients with septic myocardial dysfunction had higher circulating levels of IL-6 (SMD 0.51 [0.06;0.97]), IL-1 (0.67 [0.11;1.23]), IL-8 (0.59 [0.35;0.83]) and IL-10 (0.57 [0.34;0.80]) than controls, while the difference for TNF-α was not significant (0.63 [-0.02;1.28]). Two small interventional studies suggested potential benefits from cytokine-targeting therapies.

Conclusions: This translational review supports a cytokine-mediated contribution to septic myocardial dysfunction. While mechanistic evidence is strong in preclinical models, clinical data remain observational. These findings justify further interventional studies targeting cytokines in septic myocardial dysfunction.

Background: The diagnosis of acute mesenteric ischemia (AMI) is challenging, especially in the intensive care unit (ICU), where non-occlusive mesenteric ischemia (NOMI) predominates. In ICU patients, contrast-enhanced computed tomography (CT) provides limited diagnostic accuracy, and no single biomarker is sufficiently reliable. Transmural digestive necrosis, revealed as necrotic bowel (NB) during surgical exploration, is irreversible and requires bowel resection. We proposed an approach combining several clinical, biological, and therapeutic parameters to predict the presence of NB in ICU patients with high suspicion of AMI.

Methods: We conducted a prospective observational study in three ICUs. All consecutive patients with suspected AMI were enrolled. Patients with NB identified during surgical exploration were compared with those without NB. Patients who survived without undergoing surgery were considered not to have NB. Multivariable logistic regression analysis was used to identify parameters independently associated with NB.

Results: A total of 202 patients were included. Among them, 74 (37%) had NB (including 70 with NOMI and 4 with occlusive AMI), while 128 (63%) did not. In the multivariable analysis, age (OR 1.068, 95% CI 1.027-1.111, p = 0.001), active fluid removal (OR 3.148 (1.19-8.33), p = 0.021), signs of gastrointestinal injury (3.432 (1.082-10.885), p = 0.036), need for renal replacement therapy (OR 3.834 (1.457-10.01), p = 0.006), and lactate dehydrogenase (log) at the time of AMI suspicion (OR 7.135 (2.1-24.235) p = 0.002) were independently associated with NB. Among biomarkers, lactate dehydrogenase, showed the highest area under the ROC curve.

Conclusions: This is the first study to propose a combined approach for predicting NB in ICU patients with suspected AMI. When AMI is highly suspected, surgical exploration should be considered in patients presenting with signs of gastrointestinal injury in a context of fluid removal or renal replacement therapy, as these findings are strongly suggestive of necrotic bowel.

Objective: The French Society of Emergency Medicine (SFMU) and the French Intensive Care Society (SRLF) present formalized expert recommendations from a multidisciplinary panel on the initial assessment of respiratory distress in adult patients presenting to the Emergency Department.

Design: A group of 30 French experts from the SFMU and FICS was assembled. Any potential conflicts of interest were officially declared at the start of the guidelines development process, which was conducted independently of any industry funding. The authors followed the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology to assess the level of evidence from the literature.

Methods: The aim of this expert panel was to define evidence-based recommendations for the initial assessment of respiratory distress in the emergency setting. Three key areas were defined: (1) assessment of severity in respiratory distress; (2) initial assessment and triage in respiratory distress; (3) diagnostic approach for respiratory distress. For each area, the goal of the recommendations was to address a set of questions formulated by the experts following the PICO model ("Population, Intervention, Comparison, Outcome"). Based on these questions, a comprehensive literature search was conducted for the last 20 years using predefined keywords according to PRISMA guidelines. The quality of the data was analyzed using the GRADE method. The recommendations were formulated using the GRADE methodology, and then voted on by all experts using the GRADE Grid method.

Results: The expert consensus process, based on the GRADE methodology, resulted in 13 clinical questions yielding 20 recommendations. For three of these questions, however, no recommendation could be issued due to insufficient evidence. After two rounds of voting and several amendments, a strong consensus was reached on the recommendations. Among these, two were supported by high-quality evidence and resulted in a strong recommendation (GRADE 1); six were based on moderate-quality evidence and led to a conditional recommendation (GRADE 2); and twelve were based on expert opinion, reflecting a low level of evidence. Finally, for 3 questions, no recommendation could be formulated.

Conclusion: A strong consensus was reached among the experts on 20 of the recommendations. This work provides updated recommendations for the initial assessment of respiratory distress in adult patients presenting to the Emergency Department.

Sepsis-induced coagulopathy is a severe complication of sepsis and septic shock, contributing significantly to organ dysfunction and increased mortality. Currently, there is no effective treatment for coagulopathy, highlighting a critical need for new therapeutic options to improve patient outcomes. This review explores the potential use of nucleic acid aptamers for septic-induced coagulopathy. Aptamers are short single-stranded oligonucleotides, known for their high affinity and specificity towards targets. They offer several advantages over antibodies, including smaller size, synthetic production, lower immunogenicity, and greater flexibility in targeting a wide range of molecules and cells. Due to these properties, aptamers have emerged as promising tools for the diagnosis and treatment of various diseases, with several currently ongoing clinical trials and others already available on the pharmaceutical market. This illustrated and thoroughly documented review provides a comprehensive overview of the key aspects of sepsis pathophysiology, emphasizing the significant roles aptamers can play, including: the targeting of endothelial dysfunction where aptamers could protect vascular integrity and inhibit leukocyte adhesion to the endothelium thereby limiting local inflammation; the targeting of dysregulated coagulation pathways by preventing platelet adhesion and aggregation, as well as blocking coagulation factors, helping to limit thrombus formation; the restoration of fibrinolytic function by targeting direct inhibitors of plasmin generation; the targeting of neutrophil extracellular traps to decrease excessive coagulation activation and restore fibrinolysis; the inhibition of complement system in sepsis-induced disseminated intravascular coagulation. This review also includes a chapter on the use of aptamers as diagnostic and prognostic tools for sepsis-induced coagulopathy.

Background: Adequate intraoperative fluid therapy is essential, as both uncorrected fluid loss and excessive fluid administration are associated with increased complications. However, current practice varies widely. In this narrative review, we examine current concepts of intraoperative fluid therapy in adults having non-cardiac surgery, focusing on fluid type, volume of fluid, and fluid administration strategy.

Results: Balanced crystalloids, compared to unbalanced crystalloids, more closely resemble the body's natural electrolyte composition. However, moderate intraoperative volumes of 0.9% saline do not seem to increase complications. Colloid fluids additionally contain larger molecules exerting colloid osmotic pressure and can be divided into synthetic and natural colloids. While concerns about synthetic colloids, especially hydroxyethyl starch, persist in intensive care medicine, intraoperative trials suggest that giving moderate volumes of hydroxyethyl starch is safe. The natural colloid human albumin theoretically offers a more favorable safety profile than synthetic colloids, but large randomized trials justifying the increased costs through improved outcomes are missing. Fluid administration strategies include calculation-based strategies, the concept of fluid responsiveness, and goal-directed fluid therapy. Calculation-based strategies rely on formulas to estimate fluid requirements. For patients having elective major non-cardiac surgery, a mildly positive intraoperative fluid balance (1-2 liters at the end of the procedure) is generally recommended. The concept of fluid responsiveness aims to assess the current hemodynamic status and evaluate whether a patient's cardiac output increases after fluid administration. However, even if fluid responsive, fluids should only be administered if there are additional clinical or metabolic signs of hypovolemia or tissue hypoperfusion. Goal-directed fluid therapy aims to optimize hemodynamics via treatment strategies by titrating fluids, vasoactive drugs, and inotropes to predefined hemodynamic target variables. Yet, goal-directed fluid therapy did not reduce complications compared to routine care in patients having non-cardiac surgery in recent multicenter trials.

Conclusion: The optimal type of fluid for intraoperative fluid therapy remains uncertain and limited volumes of unbalanced crystalloids and hydroxyethyl starch appear to be safe in surgical patients. A mildly positive intraoperative fluid balance is generally recommended for patients having major non-cardiac surgery. Fluid responsiveness can help guide fluid administration, but should not be the only factor leading to fluid administration.

Septic shock represents the most severe form of an infection, marked by a dysregulated host response that can lead to multiple organ failure and death. Among these patients, 30-40% develop disseminated intravascular coagulation (DIC), a life-threatening complication associated with a 60% increase in mortality. DIC is characterized by widespread activation of the coagulation cascade, resulting in disseminated microthrombi and a hypercoagulable state. This prothrombotic profile arises from the upregulated expression of tissue factor by endothelial cells, monocytes, and neutrophils, combined with insufficient regulation by endogenous anticoagulant pathways. In addition, a profound impairment of fibrinolysis further contributes to this imbalance. Initially, this fibrinolytic insufficiency was attributed to elevated plasma levels of plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor. More recently, it has been shown that DIC-associated fibrinolytic insufficiency during septic shock involves plasminogen degradation driven by neutrophil elastase carried by neutrophil extracellular traps circulating in patients' plasma. The failure to resolve this hypercoagulable state and restore hemostatic balance has emerged as a key determinant of poor outcomes in DIC. Therefore, elucidating the mechanisms underlying fibrinolytic insufficiency is very important both to identify at-risk patients and to treat DIC. This review provides an overview of the most recent advances in our understanding of fibrinolytic dysregulation in sepsis-induced DIC, with a particular focus on emerging molecular mechanisms and their implications for the identification of novel pharmacological targets.

Background: Septic shock triggers a complex immune response characterized by the coexistence of hyperinflammation and immunosuppression, the latter being a major driver of ICU-acquired infections and increased mortality. Currently, the most established biomarkers for assessing sepsis-induced immunosuppression rely on flow cytometry-a technique not universally available in clinical practice. In contrast, soluble biomarkers are, in principle, easier to measure. Although assays for soluble PD-L1 (sPD-L1) are not yet standardized, sPD-L1 concentrations may represent a pragmatic alternative, given the putative role of PD-1/PD-L1 signaling in immunosuppressive pathways during sepsis. In this study, we investigated sPD-L1 in relation to established cellular markers of immunosuppression in a cohort of 161 patients with septic shock. sPD-L1 levels were measured using the ELLA microfluidic platform during the first week of ICU admission. We assessed their association with clinical outcomes and explored the relationship between sPD-L1 and immunosuppressive profiles defined by low monocytic HLA-DR expression (mHLA-DR) and absolute lymphocyte count.

Results: Upon admission, patients exhibited elevated sPD-L1 levels compared to healthy controls (medians: 179 vs. 54 pg/mL, p < 0.001). No correlation was observed between sPD-L1 levels and severity scores (SOFA, SAPS II). Elevated sPD-L1 was independently and significantly associated with increased mortality at both 28 and 90 days. Longitudinal analysis using K-means clustering revealed that the cluster with consistently highest sPD-L1 levels was associated with unfavorable outcomes. Overall, and at any single time point, sPD-L1 concentrations did not correlate with mHLA-DR expression or lymphopenia. However, the combined presence of high sPD-L1 and low mHLA-DR levels at the end of the first week identified a subgroup of patients with particularly poor clinical outcomes.

Conclusions: These findings highlight the potential of sPD-L1 as a clinically relevant biomarker in the context of sepsis immunopathology. Further studies are warranted to elucidate its role in the mechanisms underlying sepsis-induced immunosuppression. Such insights could support the integration of sPD-L1 into multimodal biomarker panels for immune monitoring and risk stratification in patients with septic shock.