Critical Care最新文献

Fluid overload is common after resuscitation in critically ill patients and is independently associated with unfavorable outcomes. Ultrafiltration (UF) during renal replacement therapy is a common strategy to reverse this condition. Nevertheless, the optimal timing, dose, and safety limits remain unclear. Observational studies suggest a U-shaped relationship between net UF rate and mortality, highlighting a narrow therapeutic window. Insufficient UF prolongs exposure to congestion, whereas excessive UF may precipitate hemodynamic instability and tissue hypoperfusion. This phenomenon, often labeled "UF intolerance", lacks a standardized definition and is frequently attributed to intravascular volume depletion alone, overlooking broader cardiovascular and autonomic mechanisms. This perspective synthesizes the physiological effects and cardiovascular response to ultrafiltration and reframes "ultrafiltration intolerance" as a multidimensional construct determined by four compensatory axes: vascular refilling, cardiac response, venoconstriction/venous capacitance, and systemic arteriolar resistance. We delineate how renal replacement therapy-related factors interact with underlying critical illness to impair these axes and precipitate tissue hypoperfusion. Building on this framework, we (i) argue for proactive, individualized ultrafiltration prescriptions; (ii) propose dynamic predictors that emulate fluid removal to reveal physiologic reserve (iii) outline pragmatic, bedside endotypes of ultrafiltration intolerance: preload dependence, cardiac dysfunction, decreased vascular tone, autonomic dysfunction, and impaired vascular refilling. We propose a holistic framework that emphasizes prevention over rescue and guides tailored ultrafiltration prescription based on endotypes. Ultrafiltration intolerance in critically ill patients is multifactorial and not solely a problem of volume depletion. A physiology-based, preventive, and personalized ultrafiltration strategy (anchored in dynamic testing, ultrasound-based congestion profiling, and perfusion monitoring) may improve hemodynamic tolerance, decongestion efficacy, and patient-centered outcomes. Prospective studies should validate these concepts to establish evidence-based protocols for personalized ultrafiltration in critical care.

Background: Optimal pain and sedation management in intensive care unit (ICU) remains challenging. While opioids and benzodiazepines are widely used, their adverse effects highlight the need for alternative or adjunctive strategies. Ketamine, with its analgesic and opioid-sparing has been proposed as an adjuvant. However, current evidence regarding its efficacy in ICU patients, particularly within the surgical population, remains inconclusive. We evaluated whether continuous low-dose ketamine infusion in postoperative surgical ICU patients reduces opioid consumption and improves pain intensity, and whether it affects opioid-related adverse events and key ICU recovery outcomes.

Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing continuous postoperative ketamine infusion versus non-ketamine based infusion for analgesia & sedation in patients admitted to the surgical ICU. Literature searches were performed in PubMed, Cochrane Central, and ClinicalTrials.gov from inception until July 2025. The primary endpoints were cumulative opioid consumption in the first 24-48 h (standardized to IV morphine equivalents where applicable) and rest pain intensity at prespecified early postoperative timepoints. Secondary endpoints included PONV, psychotomimetic events (e.g., hallucinations), and ICU recovery outcomes (e.g., ICU length of stay and duration of mechanical ventilation) when reported. We performed random-effects meta-analyses and assessed certainty using GRADE.

Results: Nine RCTs comprising 666 patients were included. Ketamine significantly reduced opioid consumption at 24 h in adults (mean difference [MD] - 5.77 mg morphine equivalents; 95% CI - 6.32 to - 5.23; p < 0.0001), although the reduction at 48 h and in pediatric subgroups was not statistically significant. Pain scores at 12, 24, and 48 h were comparable between the groups. Ketamine did not significantly shorten the mechanical ventilation time (MD - 0.84 h; 95% CI - 1.93 to 0.24) or ICU length of stay (MD - 0.97 h; 95% CI - 1.95 to 0.02). However, ketamine use was associated with a lower incidence of PONV (RR 0.59; 95% CI 0.36-0.98; p = 0.0399). Psychotomimetic adverse events were infrequent and not significantly increased. GRADE evidence was moderate for opioids in adults at 24 h and low to very low for the remaining outcomes.

Conclusions: In postoperative surgical ICU patients, continuous low-dose ketamine infusion provides modest opioid sparing and is associated with lower PONV, without clear improvements in pain scores or ICU recovery outcomes. Large-scale trials with different dosing protocols are needed to explore the optimal role of ketamine beyond analgesia and PONV reduction.

Background: The relationship between fluid responsiveness and right-and left-sided congestion remains underexplored. This study aimed to delineate the dynamic behaviour of venous congestion and extravascular lung water index (EVLWI) during a fluid challenge depending on the concomitant changes in cardiac index (CI).

Methods: In patients from three intensive care units, for whom a 500-mL fluid challenge was administered, we retrospectively analysed CI, central venous pressure (CVP), venous excess ultrasound (VExUS), and EVLWI, which had been prospectively recorded. A VExUS congestion point was calculated from 0 to 7 by assigning 1 point to each degree of abnormality for the 4 investigated veins. A subgroup analysis was planned in patients with acute respiratory distress syndrome (ARDS).

Results: We analysed 64 patients, of whom 42 (66%) were fluid responders (FR+) defined by a CI increase ≥ 15% with fluid infusion. Before the fluid challenge, CVP was lower in FR + than in fluid non-responders (FR-) (7.3 [2.9-10.3] vs. 10.6 [8.2-13.0] mmHg,respectively, p = 0.002). VExUS grades and congestion points were not different between FR + and FR- (Grade 0: 62% vs. 55%, respectively, p = 0.601; congestion points: 1.0 [0.0-2.3] vs. 2.0 [1.0-3.0], respectively, p = 0.053). EVLWI was also similar between groups. Following fluid administration, VExUS grade deterioration occurred in 5% of FR + versus 73% of FR- (p < 0.001). After the fluid challenge, abnormal VExUS grades were more prevalent in FR - than in FR+ (91% vs. 43%, respectively, p < 0.001), and congestion points were higher (4.0 [3.0-5.0] vs. 1.5 [1.0-3.0], respectively, p < 0.001). CVP increased by 1.4 [0.4-2.4] mmHg in FR + and 2.0 [1.1-3.5] mmHg in FR- (p = 0.064). Among 25 patients with ARDS, EVLWI increased more than in patients without ARDS, in both FR- (by 1.7 [0.9-3.3] vs. 0.7 [0-1.4] mL/kg, respectively, p = 0.046) and FR+ (by 1.0 [-0.6-2.5] vs. 0 [-0.7-0.4] mL/kg, respectively, p = 0.009).

Conclusion: A fluid challenge worsened venous congestion, assessed by VExUS as well as CVP, in fluid non-responders, while it was not in fluid responders.

Background: Carnitine deficiency affects mitochondrial and muscle function, but its relevance during critical illness remains unknown. Our aim was to investigate the relationship between plasma free carnitine concentrations and outcome in prolonged critical illness.

Methods: In this secondary analysis of the EPaNIC randomised controlled trial, abnormal plasma free carnitine concentrations, measured on ICU-day-6 (N = 1600), were defined by their association with a lower likelihood of an earlier alive ICU discharge (the primary endpoint) in a Cox proportional hazards model. Subsequently, they were binned based on their distribution and partial residuals in the Cox-model. Adjusted multivariable Cox-model and logistic regression analysed both association of abnormal carnitinemia with acute and long-term morbidity and mortality, and predictive risk factors.

Results: The median plasma free carnitine concentration on ICU-day-6 was 34.8 (IQR 24.4-49.8 µmol/L). Surprisingly, higher concentrations associated with a lower likelihood of an earlier alive ICU discharge (HR [95% CI] (per 10 µmol/L increase): 0.97 [0.95-0.99]). Yet, the partial residuals plot revealed this likelihood to be lower for patients with concentrations corresponding to the lowest (< 24 µmol/L; N = 374) and highest quartiles (> 50 µmol/L; N = 395) as compared to intermediate quartiles (24-50 µmol/L; N = 831). Both low and high carnitine concentrations were associated with a prolonged ICU and hospital dependency, a prolonged need for life-supporting therapies, and increased mortality at 90-days. Carnitine concentrations above 50 µmol/L also associated with muscle weakness and increased two and five year-mortality.

Conclusion: On ICU-day-6, both low and high free carnitine concentrations associated with delayed ICU-recovery, and excess morbidity and mortality, suggesting a U-shaped relationship.