Annals of Intensive Care最新文献

Background: The cytokine IFNγ is released primarily by lymphocytes to initiate and orchestrate immune responses in a broad range of target cells. Whereas immune cells release inflammatory mediators and initiate antimicrobial responses when stimulated by IFNγ, parenchymal cells frequently display increased immunogenicity and incidental cell death. In addition to these well-characterized effects of IFNγ, recent studies disclose a key role of the cytokine in sepsis and organ dysfunction. MAIN: This review summarizes current knowledge on the IFNγ response to infection and attempts to relate the IFNγ response to endophenotypes of sepsis in the human host. Both, excessive pro-inflammatory responses with high IFNγ and downstream mediators, such as chemokines (CXCL9), as well as immunosuppression with low IFNγ levels are associated with unfavorable outcomes in sepsis. Pilot studies suggested beneficial effects of recombinant IFNγ in counteracting immunosuppression associated with low IFNγ levels. On the other hand, IFNγ may induce macrophages to release chemokines CXCL9, 10, and 11 to attract B and T lymphocytes to the sites of infection. Downstream induction of CXCL9 (but not of CXCL10 and 11) occurring in a subset of patients with high IFNγ levels has been shown to correlate with the hyper-inflammatory phenotype of sepsis. Both, high- and low-expressing IFNγ phenotypes of sepsis, might be related to nucleotide polymorphisms of the human IFNγ gene.

Conclusion: Association of IFNγ activity states with sepsis outcome renders this key regulatory protein of immunity a top candidate for theranostic interventions in a "personalized medicine approach" to infection and sepsis, especially when combined with additional biomarkers, such as CXCL9, reflecting or even mediating maladaptive downstream actions.

Purpose: The optimal ventilation strategy in acute respiratory distress syndrome (ARDS) patients with veno-venous extracorporeal membrane oxygenation (VV-ECMO) remains unknown. We aimed to compare the effects of two ultra-protective ventilatory strategies applied to patients with ARDS and VV-ECMO.

Methods: Our study was an observational, retrospective, single-center study with a before-and-after design. All consecutive patients treated with VV-ECMO for severe ARDS between 2016 and 2023 were included. Before 2021, patients received a quasi-apneic ventilation strategy in assist-controlled volume mode with a tidal volume (V_T) of 1 ml.kg^-1 predicted body weight (PBW), a respiratory rate (RR) of 5 min^-1 and a PEEP set to keep plateau pressure (P_PLAT) between 20 and 25 cmH₂O. From 2021 onwards, the protocolized ventilatory strategy consisted in pressure-controlled mode with a PEEP of 14 cmH₂O, a driving pressure (∆P) of 8 cmH₂O and a RR of 10 min^-1. We evaluated the impact of strategies on longitudinal respiratory mechanics and on the time to successful ECMO weaning at day-90 after VV-ECMO canulation.

Results: 121 patients were enrolled, with 69 receiving the VT1 strategy, and 52 the ∆P8 strategy. Over the first 7 days of ECMO, the ∆P8 strategy was associated with significantly higher ∆P and RR, lower PaCO₂, and higher static elastic mechanical power, compared with the VT1 strategy. The day-90 survival rate was 30% with the VT1 strategy, and 42% with the ∆P8 strategy (P = 0.19). Time to successful VV-ECMO weaning was 7 [4-13] days in day-90 survivors, with no significant difference between groups. The adjusted subdistribution hazard ratio associated with the ∆P8 strategy was 0.99 (95% confidence interval: 0.53-1.84), as compared to the VT1 strategy (P > 0.9).

Conclusions: In the context of our center, a ventilatory strategy targeting a PEEP of 14 cmH₂O, a ∆P of 8 cmH₂O and a RR of 10 min^-1 led to the application of ∆P, RR and static elastic mechanical power and improved decarboxylation, compared to a strategy in volumetric mode with a V_T of 1 ml.kg^-1 PBW and a RR of 5 min^-1, in patients with ARDS and VV-ECMO. No significant difference on clinical outcomes was observed between both strategies.

Background: Acutely infected critically ill patients develop coagulopathies and perturbations to the fibrinolysis system that manifest as immunothrombosis. Whole blood viscoelastic testing, using an exogenous fibrinolytic agent to enhance fibrinolysis (FE-VET) can assess both processes of coagulation and fibrinolysis at the bedside. This scoping review aimed to illustrate clinical applicability, knowledge gaps and unmet needs for this emerging technology.

Methods: A systematic search of bibliographic databases and the grey literature was performed between the 10th October 2024 and the 14th January 2025 using a pre-published protocol and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline for scoping reviews (PRISMA-ScR). Studies reporting FE-VET to investigate fibrinolysis in acutely infected patients admitted to the intensive care unit were assessed, including associations with disease severity and clinical outcomes.

Results: The search identified 297 studies with 24 included in this review. Fifteen studies were observational (12 prospective, 3 retrospective), 4 case reports and series, 2 validation studies, 2 letters, and 1 poster abstract. No randomised controlled trials were identified. Most studies used varying concentrations of tissue plasminogen activator (tPA) to enhance fibrinolysis, with FE-VET performed at a single time point and the lysis time to achieve 50% reduction of maximum clot firmness being the most frequently reported variable. Fibrinolysis resistance was the prevailing state reported in acute sepsis or COVID-19 infections and associated with increased disease severity and worse clinical outcomes.

Conclusion: Viscoelastic testing using a fibrinolysis enhancing agent demonstrated a spectrum of fibrinolysis resistance in acutely infected critically ill patients, associated with increased disease severity and mortality. Standardisation of the concentrations of fibrinolysis enhancing agents and the reporting of clot lysis parameters across testing devices are needed to establish reference values. This would improve future clinical studies of fibrinolysis, including trials of fibrinolytic therapies using a personalised medicine approach.

Background: Shock, encompassing septic and cardiogenic etiologies, is a life-threatening condition associated with systemic inflammation, metabolic dysregulation, and high mortality in intensive care units. Traditional clinical markers often fail to capture the complexity of this syndrome, limiting personalized therapeutic approaches. Advances in metabolomics enable comprehensive analysis of metabolic disruptions, providing novel insights into shock pathophysiology. This study aimed to cluster critically ill patients with shock into metabolic phenotypes and investigate their associations with clinical severity.

Results: We analyzed metabolomic profiles from 60 critically ill patients with shock at ICU admission using Uniform Manifold Approximation and Projection (UMAP) for dimensionality reduction and Density-Based Spatial Clustering of Applications with Noise (DBSCAN) for clustering. Three distinct clusters were identified: Cluster 1 (n = 13) exhibited the highest severity (median APACHE II: 29) and mortality (54%), with elevated biogenic amines, sugars, and sphingolipids, reflecting intense metabolic activation. Cluster 2 (n = 24), despite having low initial severity (median APACHE II: 25), demonstrated high mortality (38%) and was characterized by elevated glycerophospholipids and sphingolipids as in cluster 1, without enhanced biogenic amines and sugars, indicating inadaptive metabolic responses. Cluster 3 (n = 23) showed the lowest severity (median APACHE II: 22) and mortality (9%), with uniformly reduced metabolite levels, suggesting an adaptive metabolic profile.

Conclusions: Shock patients exhibit distinct metabolic phenotypes associated with clinical severity and outcomes. Metabolomic profiling offers a promising avenue for precision medicine in critical care by uncovering pathophysiological insights. Future research should validate these findings, identify practical biomarkers, and explore therapeutic interventions tailored to specific metabolic profiles.

Objectives: To provide a comprehensive overview of current research on intensive care providers' awareness, knowledge, and practices regarding IAP/IAH/ACS, as well as barriers to IAP measurement.

Methods: This scoping review was guided by the framework of Arksey and Malley. Eight databases were searched to identify research published after 2007, including MEDLINE Complete, EMBASE, Web of Science, Cochrane Library, CINAHL Complete, ProQuest Health & Medical Complete, CNKI, and WANFANG. Two researchers reviewed and screened potentially relevant studies based on title and abstract. Full-text articles were independently assessed for eligibility based on predefined inclusion criteria.

Results: Nineteen articles were included. Overall, pediatric intensive care providers demonstrated a lower awareness and knowledge of IAH/ACS compared to adult intensive care providers, particularly regarding the consensus definitions of IAH/ACS in critically ill children. IAP measurement has not been adequately integrated into clinical practice, with 18.0-73.0% of intensive care providers reporting they have never measured it. The frequency of IAP measurements and the criteria for determining which patients necessitate such measurements exhibited significant variability across different hospitals. The most frequently mentioned barriers to IAP measurement include a lack of knowledge regarding IAP measurement among adult intensivists, an overreliance on physical examination among pediatric intensivists, uncertainty in interpreting IAP data among adult intensive care nurses, and challenges in identifying populations at high risk of IAH among pediatric intensive care nurses. Diuretics were mentioned most often in the management of IAH/ACS, followed by administration of vasopressors and inotropes, decompressive laparotomy, and judicious administration of fluids and blood products. 37.0-66.3% of adult intensivists would choose a decompressive laparotomy in cases of ACS, whereas pediatric intensivists were less inclined to opt for the same approach.

Conclusions: Since the publication of the WSACS consensus in 2007, there has been an improvement in awareness and knowledge regarding IAP/IAH/ACS among intensive care providers. Nevertheless, the understanding of the consensus definitions regarding IAH/ACS remains inadequate, particularly among pediatric intensive care providers. It is imperative to advocate for the implementation of WSACS guidelines in hospitals through targeted training programs and to promote the routine practice of IAP measurement in clinical settings.

Background: Angiotensin II (Ang II) is typically used in addition to adrenergic agents and vasopressin (conventional therapy) in patients with shock, but whether its use improves outcomes is unknown.

Research question: We evaluated whether Ang II, when added to conventional therapy at different norepinephrine equivalent (NE) doses, was associated with mortality.

Methods: We performed a retrospective analysis of 811 patients admitted to four centers in a single healthcare system who received vasopressors for shock, including 275 who received Ang II plus conventional therapy and 536 who received only conventional therapy. Age, gender, sequential organ failure assessment score, serum lactate, background NE dose, corticosteroid use, pre-morbid angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, and Charlson Comorbidity Index were calculated at initiation of Ang II or at an equivalent point of acuity in the conventional therapy cohort. We used propensity scores with inverse probability of treatment weighting (IPTW) to achieve covariate balance and multivariable logistic regression to compare 30-day mortality, further stratifying patients by 0.10 mcg/kg/min NE increments.

Results: Overall 30-day mortality was 56.4%. Groups statistically differed by all baseline variables. In multivariable logistic regression, Ang II treatment was associated with lower 30-day mortality compared to conventional therapy alone (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.45-0.95, p = 0.025). After IPTW, Ang II use was independently associated with lower mortality (OR 0.74, 95% CI 0.55-0.99, p = 0.040). When stratifying by increments of background NE dose, Ang II initiation was associated with lower 30-day mortality compared to conventional therapy alone in patients on background NE doses > 0.4, > 0.5, and ≤ 0.6 mcg/kg/min. Ang II use in patients on background NE dose > 0.6 was not significantly associated with mortality.

Conclusions: Ang II administration was associated with a lower risk of death in unadjusted and adjusted analyses. This effect was preserved only with patients receiving NE at doses ranging from 0.4 to 0.6 mcg/kg/min. Though additional prospective studies are required, these findings suggest that Ang II may be beneficial across a specific range of background vasopressor doses.

Background: Venous congestion is associated with adverse clinical outcomes in critically ill patients, yet its assessment remains challenging. Recently, the Venous Excess Ultrasound (VExUS) score has shown great potential as a non-invasive tool for assessing venous congestion in cardiac patients. However, the relationship between VExUS and clinical outcomes in patients with sepsis remains understudied. This study aims to evaluate the incidence of venous congestion based on VExUS assessment within the first 5 days of intensive care unit (ICU) admission in critically ill patients with sepsis, and to investigate the association between VExUS and clinical outcomes.

Methods: We conducted a prospective, observational study in four ICUs, enrolling adult patients with sepsis who stayed in the ICU for at least 24 h. VExUS assessments were performed on days 1 (within 24 h), 3 (48-72 h), and 5 (96-120 h) following ICU admission. Patients were classified according to VExUS score ≥ 2 or < 2. The primary outcome was the prevalence of acute kidney injury (AKI) during ICU stay, while secondary outcomes included 30-day mortality, ICU mortality, and requirement for renal replacement therapy (RRT).

Results: Among the 108 patients included, 18% (19 patients) showed VExUS score ≥ 2 on day 1 of ICU admission, and the prevalence progressively decreased to 15% (15 patients) by day 3 and 6% (6 patients) by day 5. The VExUS score ≥ 2 was not associated with AKI (OR 1.82, 95% CI 0.62-5.31, p = 0.274), 30-day mortality (OR 0.82, 95% CI 0.28-2.4, p = 0.711), ICU mortality (OR 1.12, 95% CI 0.41-3.04, p = 0.82), or requirement for RRT (OR 2.29, 95% CI 0.68-7.64, p = 0.179). There was no significant correlation between VExUS and central venous pressure (coefficient: - 0.019, 95% CI -0.01 to 0.05, p = 0.204).

Conclusion: In critically ill patients with sepsis, approximately 20% exhibit early (within 24 h of ICU admission) venous congestion, with the prevalence progressively decreasing over the subsequent 5 days. Venous congestion assessed by VExUS was not associated with the occurrence of AKI or with mortality.

Trial registration: Chinese Clinical Trial Registry, ChiCTR2200066987. Registered 22 December 2022, https://www.chictr.org.cn/.