BACKGROUND: The optimal timing for post traumatic Chest Wall Reconstruction (CWR) in severely injured / polytraumatized patients with severe chest wall instability remains a subject of debate. While early surgery within...BACKGROUND: The optimal timing for post traumatic Chest Wall Reconstruction (CWR) in severely injured / polytraumatized patients with severe chest wall instability remains a subject of debate. While early surgery within 72 h is associated with improved outcomes, the efficacy and safety of an even earlier "rapid sequence" approach on the day of admission are unclear. This study aims to compare outcomes of severely injured patients undergoing rapid sequence surgery (Day 0) versus early surgery (Days 1-3). METHODS: A retrospective analysis was conducted using data from the TraumaRegister DGU (2015-2023). Patients with serious chest wall injuries (AIS ≥3), an Injury Severity Score (ISS) ≥ 9, who survived the first 48 h and underwent CWR were included. Patients were stratified into a "Rapid Sequence" group (surgery on Day 0) and an "Early" group (surgery on Days 1-3). Propensity score matching (PSM) was performed to balance baseline characteristics, including injury patterns, demographics, and initial physiological status. Primary outcome was in-hospital mortality. Secondary outcomes included sepsis, multi-organ failure (MOF), and length of stay. RESULTS: From an initial cohort of 34,659 patients with severe chest wall injuries, 2,498 operatively treated patients with a known date of surgery were analyzed. 1,168 (46.8%) underwent rapid sequence surgery (Day 0) and 567 (22.7%) underwent early surgery (Days 1-3). Before matching, the Rapid Sequence group had a higher ISS (27.7 vs. 26.0), a higher incidence of severe head trauma (14.4% vs. 9.2%), and significantly higher mortality (8.4% vs. 4.1%). PSM yielded 500 matched pairs. Despite matching, the Rapid Sequence group retained a higher baseline injury burden (mean ISS: 28.1 vs. 26.2; mortality prognosis (Revised Injury Severity Classification, Version III (RISC III) Score): 16.2% vs. 10.7%). The primary outcome showed a nearly threefold higher mortality rate in the Rapid Sequence group (10.6% vs. 3.6%; p < .001). Rates of sepsis (14.6% vs. 12.0%) and MOF (33.6% vs. 28.3%) were also higher in the rapid group, though not statistically significant. CONCLUSION: In this large registry analysis, rapid sequence CWR on the day of admission identified a distinct subgroup of patients with more severe concomitant injuries and higher baseline risk. The higher mortality in this group likely reflects residual confounding by indication and survivorship bias, rather than a detrimental effect of rapid surgery per se. This suggests that the decision for immediate surgery is likely driven by life-threatening concomitant injuries not fully captured in the matching model, identifying a patient population with an intrinsically higher risk of death. Our findings therefore do not justify a blanket Day-0-for-all strategy, but are consistent with the broader literature suggesting that CWR performed within 72 h is beneficial when timing is individualized to overall injury severity and physiological stability.
Microcirculatory dysfunction is a defining feature of septic shock and is strongly associated with mortality, yet its relationship to macrocirculatory haemodynamics remains poorly understood. In particular, the persisten...Microcirculatory dysfunction is a defining feature of septic shock and is strongly associated with mortality, yet its relationship to macrocirculatory haemodynamics remains poorly understood. In particular, the persistence of heterogeneous capillary perfusion despite restoration of blood pressure and cardiac output (termed haemodynamic incoherence) lacks a coherent mechanistic explanation. I developed a conceptual and computational model of the microcirculation in which network behaviour is constrained by three interacting variables: cardiac output, vasomotor state, and shear stress regulation. A network of one million parallel arterioles was simulated using physiologically plausible distributions of vessel radius. For each vessel, flow requirements were determined by an apparent shear target, reflecting endothelial sensing of shear rather than absolute physical values. Total cardiac output required to maintain network-wide shear was calculated as the sum of individual vessel demands. The model demonstrates that, for a given shear target, total flow requirements increase in proportion to the sum of vessel radii cubed, such that even modest global vasodilation produces a substantial increase in required cardiac output. Increasing the apparent shear target further amplifies this demand. When cardiac output is insufficient to meet these requirements, vessels experience low shear and undergo functional derecruitment, reducing total flow demand but resulting in marked heterogeneity and reduced functional capillary density. These behaviours reproduce key features of septic physiology, including the hyperdynamic circulation and microvascular shunting observed in severe sepsis. The model provides a unifying framework in which microcirculatory dysfunction emerges as an inevitable consequence of the interaction between vasodilation, flow limitation, and shear regulation, rather than as an independent pathological process. It further predicts that therapies which reduce global vasodilation or lower the apparent shear target may restore microvascular coherence without requiring supranormal cardiac output. This framework generates testable hypotheses and offers a physiologically grounded basis for reinterpreting haemodynamic management in septic shock.
BACKGROUND: Patients recovering from cardiac surgery in the intensive care unit (ICU) do not sleep well. Commonly used sedative-hypnotic medications can disrupt sleep architecture and increase the risk of delirium in cri...BACKGROUND: Patients recovering from cardiac surgery in the intensive care unit (ICU) do not sleep well. Commonly used sedative-hypnotic medications can disrupt sleep architecture and increase the risk of delirium in critically ill patients after surgery. The orexin receptor antagonist suvorexant, improves sleep onset and duration in patients with chronic insomnia. We hypothesized that suvorexant improves sleep onset and duration while also reducing the incidence of delirium after cardiac surgery. METHODS: This multicentric, double-blind, randomized controlled trial was conducted at two university-based cardiac ICUs. One hundred adult patients were enrolled after admission to the ICU following cardiac surgery. Enrollment occurred between March 2020 and February 2025. Participants were randomized to receive either a once daily oral dose of suvorexant 20 mg or placebo. Treatment began on the first night after extubation and continued until hospital discharge or for a maximum of seven days, whichever occurred first. Sleep was recorded using an electroencephalography (EEG) monitor (SedLine, Masimo Corp., California, USA) on the first night after extubation and was scored blindly by an experienced registered polysomnographic technologist. The primary outcome was wakefulness after persistent sleep onset (WASO). Sleep onset was defined as the first 30-second epoch classified by rapid eye movement (REM) or non-REM stages 1, 2, 3 after lights off. Wakefulness was defined as an awake period of 30s or longer. Sleep questionnaires were administered and delirium screenings were conducted every morning until hospital discharge. RESULTS: One hundred patients were randomized to receive suvorexant (n = 49) or placebo (n = 51). EEG analysis indicated that neither the median [inter-quartile range] nighttime WASO (200.7 [112.1, 328.4] minutes vs. 184.2 [80.4, 304.2] minutes; p = 0.33) nor total sleep time (224.0 [112.0, 379.0] minutes vs. 253.0 [68.0, 420.0] minutes; p = 0.92) differed significantly between the groups. There was no significant difference in rescue medication (melatonin, dexmedetomidine, benzodiazepine) utilization between the groups. Subjective sleep quality, incidence of delirium, and delirium-free days did not differ between the two groups. TRIAL REGISTRATION NUMBER: Clinical Trials Registry no. NCT04092894, Registration Date 09/17/2019. CONCLUSIONS: Among patients recovering in the ICU who underwent cardiac surgery with cardiopulmonary bypass, the suvorexant treatment did not affect wakefulness after sleep onset or post-operative delirium.
BACKGROUND: Red blood cell (RBC) transfusion decisions after cardiovascular surgery require integration of hemoglobin (Hb), hemodynamics, bleeding status, and oxygen supply-demand balance. Mixed venous oxygen saturation...BACKGROUND: Red blood cell (RBC) transfusion decisions after cardiovascular surgery require integration of hemoglobin (Hb), hemodynamics, bleeding status, and oxygen supply-demand balance. Mixed venous oxygen saturation (SvO₂) reflects the global relationship between oxygen delivery and oxygen consumption, but an increase in SvO₂ does not necessarily indicate improved tissue oxygenation or clinical benefit. We evaluated acute SvO₂ changes after RBC transfusion in cardiovascular surgical ICU patients. METHODS: We conducted a single-center retrospective cohort study of adult cardiovascular surgical ICU patients who received one RBC-equivalent transfusion with pre-transfusion Hb ≥ 7.5 g/dL and paired pre- and post-transfusion SvO₂ measurements. The primary outcome was an individual-level SvO₂ response, defined a priori as ΔSvO₂ ≥5% points from baseline to approximately 60 min after transfusion initiation. Multivariable regression was used to evaluate predictors selected a priori based on physiologic relevance to oxygen delivery and consumption. Receiver operating characteristic analysis was used to evaluate the discriminative ability of pre-transfusion SvO₂. RESULTS: 1,352 unique patients met the final inclusion criteria. Mean Hb increased from 9.82 ± 0.92 to 10.24 ± 0.98 g/dL, corresponding to a paired mean difference of 0.42 g/dL (95% CI, 0.38 to 0.46; P < 0.001). Mean SvO₂ changed minimally at the cohort level, from 73.79 ± 9.91% to 73.86 ± 9.37%, corresponding to a paired mean difference of 0.08% points (95% CI, -0.28 to 0.43; P = 0.671). Lower pre-transfusion SvO₂ was associated with a higher probability of an individual-level SvO₂ response. In multivariable logistic regression, pre-transfusion SvO₂ was associated with SvO₂ response (adjusted odds ratio, 0.89 per 1% increase; 95% confidence interval, 0.86-0.91; P < 0.001). Pre-transfusion SvO₂ showed moderate discrimination for SvO₂ response, with an area under the curve of 0.778 (95% confidence interval, 0.740-0.816). The Youden-derived cutoff was 69%, which should be interpreted as an exploratory predictor of acute SvO₂ rise rather than a transfusion trigger. CONCLUSIONS: Lower pre-transfusion SvO₂ was associated with acute individual-level SvO₂ increase after transfusion, but mean SvO₂ change was minimal. The association did not establish tissue oxygenation or clinical benefit and does not support using SvO₂, including the 69% cutoff, as a transfusion indication or trigger.
BACKGROUND: To compare whether fat-free mass (FFM)-adjusted protein dosing is associated with different clinical and metabolic outcomes compared with total body weight (TBW)-based dosing in critically ill patients in the...BACKGROUND: To compare whether fat-free mass (FFM)-adjusted protein dosing is associated with different clinical and metabolic outcomes compared with total body weight (TBW)-based dosing in critically ill patients in the intensive care unit (ICU). METHODS: Adult ICU patients (April 2020-October 2025) with serial bioelectrical impedance analysis were included in the PROGRESS-ICU observational cohort study. Patients received either TBW-based protein dosing (1.5 g/kg/day; April 2020-June 2023) or FFM-based dosing after protocol revision (1.85 g/kg/day dry FFM, corrected for fluid overload; July 2023 onward). The primary outcome was 90-day all-cause mortality. Secondary outcomes included 30-day mortality, ICU and hospital length of stay, invasive mechanical ventilation (IMV) duration, and longitudinal changes in FFM and urea-to-creatinine ratio (UCR). Survival was analysed using multivariable Cox regression and inverse probability of treatment weighting; longitudinal outcomes were assessed using mixed-effects models. RESULTS: Among 620 patients (310 per cohort), median age was 69 years, and ~ 60% were male. Notable baseline differences included a higher proportion of COVID-19 admissions in the TBW cohort (40% vs. 1%), which may have influenced outcomes. Ninety-day mortality did not differ significantly between groups (adjusted hazard ratio [HR] 0.78, 95% CI 0.56-1.09). FFM-based dosing was associated with shorter ICU stay (HR 0.79, 95% CI 0.69-0.91) and fewer IMV days (HR 0.79, 95% CI 0.65-0.96); hospital length of stay was similar (HR 0.86, 95% CI 0.67-1.10). TBW-based dosing was associated with higher UCR trajectories and greater FFM loss. These associations should be interpreted cautiously due to the observational design, substantial baseline imbalances, and potential residual confounding. CONCLUSIONS: In this observational before-after study, FFM-based protein dosing was not associated with differences in mortality compared with TBW-based dosing. Associations with ICU stay, IMV duration, and metabolic markers were observed but may reflect residual confounding and temporal changes. The study was underpowered to detect modest differences in mortality, and confidence intervals include the possibility of clinically relevant benefit or harm. These findings are exploratory and require confirmation in adequately powered randomised controlled trials. TRIAL REGISTRATION: The study was approved by the local ethics committee (protocol number 2403-017; 11 April 2024) and registered prior to data analysis on ClinicalTrials.gov (NCT07312708; 5 December 2025), the Open Science Framework (https://doi.org/10.17605/OSF.IO/3SU49; 4 December 2025), and the Dutch Central Committee on Research Involving Human Subjects (NL-010953; 26 October 2025). Patients admitted before ethics approval were retrospectively included under a waiver of informed consent, and from April 2024 an opt-out consent procedure was implemented for all new admissions. Data were collected as part of routine clinical care. The study protocol, including prespecified analyses, was finalised and registered before the research team accessed the data.
BACKGROUND: Prolonged infusion (extended [EI, 2-4 h] or continuous [CI, 24 h] extended) of beta-lactam antibiotics is considered to have advantages for patients with severe infection compared with intermittent bolus (IB)...BACKGROUND: Prolonged infusion (extended [EI, 2-4 h] or continuous [CI, 24 h] extended) of beta-lactam antibiotics is considered to have advantages for patients with severe infection compared with intermittent bolus (IB). However, the choice of EI and CI is unclear due to the lack of direct comparison. We aimed to compare the EI and CI of beta-lactams in patients with severe infections using a network meta-analysis method. METHODS: We systematically searched PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang Database, and Weipu Database for randomized controlled trials (RCTs) comparing EI, CI, or IB with beta-lactams in adults with severe infections. The primary outcome was all-cause mortality. A frequentist network meta-analysis with a random-effects model was performed. Risk of bias was assessed using the Cochrane RoB 2 tool. FINDINGS: Thirty-five RCTs (10,627 patients) were included. Risk of bias was moderate to high in most studies. For mortality, EI ranked highest (SUCRA 74.20%) with numerically lower rates versus IB (EI: OR 0.80, 95% CI 0.55-1.17; CI: OR 0.86, 95% CI 0.62-1.02). Both EI and CI significantly improved clinical cure rates versus IB (EI: OR 1.58, 95% CI 1.13-2.23; CI: OR 1.35, 95% CI 1.05-1.85), and EI ranked first (SUCRA 87.72%). For microbiological success, CI ranked highest (SUCRA 83.03%), followed by EI (SUCRA 42.98%) and IB (SUCRA 23.99%), but no significant difference was found. For hospital stay, EI was associated with a reduction of borderline statistical significance (MD -3.49 days, 95% CI -6.79 - -0.08), whereas CI did not show a significant reduction (MD 1.11 days, 95% CI -1.24 - 3.63), and EI ranked best (SUCRA 98.09%). No significant adverse event differences were observed. Subgroup analyses showed variable treatment rankings across categories, with no statistically significant subgroup effects. CONCLUSION: In patients with severe infections, both EI and CI improved clinical cure versus IB, whereas mortality did not differ significantly. Indirect evidence suggests EI may be more effective than CI in most outcomes except microbiological response. EI trended to shorten hospital stay but the difference was of borderline significance. Considering its practical feasibility, EI appears to be a favorable option based on current evidence. However, this finding is based on indirect evidence and requires confirmation in head-to-head trials. REGISTRATION: PROSPERO CRD420251242437.
Sadjadi M, Marcello M, Köhler A
… +17 more, Perschinka F, Schauflinger S, Joannidis M, Vadász I, Husain-Syed F, Klop-Riehl M, Pickkers P, Villa G, Nagel T, Bormann E, Booke H, Schöne LM, von Groote T, Mertes MJ, Kellum JA, Strauß C, Zarbock A
BACKGROUND: The international Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend the implementation of a kidney protection strategy (KPS) in patients at high risk of and with Acute Kidney Injury (AKI)...BACKGROUND: The international Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend the implementation of a kidney protection strategy (KPS) in patients at high risk of and with Acute Kidney Injury (AKI). However, real-world implementation of this strategy in critically ill patients with AKI is unclear. We quantified timely and sustained adherence to KPS in critically ill adults with moderate-to-severe (KDIGO stage 2 or 3) AKI and explored associations with clinical outcomes. METHODS: This was a multicenter, prospective cohort study enrolling adult patients with moderate or severe AKI requiring vasopressors and/or mechanical ventilation across five centers in Europe. The primary endpoint was adherence to the KPS, which included hemodynamic monitoring, sustained optimization of mean arterial pressure (MAP) > 65 mmHg, monitoring of serum creatinine and urine output, and avoidance of hyperglycemia, radiocontrast agents and nephrotoxins when possible, within 12 h after AKI diagnosis for 48 h or until ICU discharge. Exploratory analyses examined associations between adherence and renal outcomes. RESULTS: A total of 258 patients were enrolled (median age 69 years [IQR 62-75]; 65% male; median SOFA 10 [IQR 8-13]). The complete KPS was implemented in 80 patients (31%; 95% CI, 25.5-37.2%). Adherence to individual components of the KPS varied widely with optimization of MAP showing the lowest implementation rate (33%). In exploratory analyses accounting for death as a competing risk, KPS adherence was associated with a lower incidence of AKD beyond day 7 (subdistribution hazard ratio [SHR] 0.64; 95% CI, 0.41-0.99; p = 0.046), a higher incidence of renal recovery at hospital discharge (SHR 6.02; 95% CI, 4.00-9.05; p < 0.0001), and a lower incidence of RRT within 30 days (SHR 0.12; 95% CI, 0.02-0.91; p = 0.04). After multivariable adjustment, the association with renal recovery remained robust (adjusted SHR 6.29; 95% CI, 3.08-12.85; p < 0.0001). A clear dose-response relationship was observed between the number of implemented KPS components and renal outcomes. CONCLUSIONS: In critically ill patients with moderate-to-severe AKI, the complete KDIGO-recommended kidney protection strategy was implemented in approximately one-third of patients, and full KPS adherence was associated with a higher rate of renal recovery at hospital discharge.
BACKGROUND: Delirium is a common and serious complication in critically ill patients, and family-centered care has emerged as a promising non-pharmacological strategy. However, evidence on structured, nurse-led family pa...BACKGROUND: Delirium is a common and serious complication in critically ill patients, and family-centered care has emerged as a promising non-pharmacological strategy. However, evidence on structured, nurse-led family participatory support (NFPS) intervention remains limited. AIM: To evaluate the effectiveness and safety of NFPS in critically ill adult patients. METHODS: Adult patients admitted to intensive care units (ICU) from three tertiary hospitals in Gansu Province were allocated to either the NFPS group or a usual care group without family participation (non-NFPS). In the NFPS group, trained family members participated in care under the guidance of ICU nurses. The primary outcome was the incidence of delirium. RESULTS: After 1:1 propensity score matching, 365 patients were included in each group. The NFPS group demonstrated significant reductions in incidence of delirium [26.85% vs. 34.25%, p = 0.03]. Compared with the control group, the NFPS group also had significantly shorter hospital length of stay (HLOS) (25 [17-34] vs. 30 [22-38] days, P < 0.001), ICU-LOS (13 [7-17] vs. 14 [10-18] days, P < 0.001), duration of mechanical ventilation (10 [6-15] vs. 11 [8-17] days, P < 0.001) and lower hospitalization cost (193,931.99 [117,616.64-294,201.02] vs. 199,330.72 [138,636.05-300,993.88] CNY, P = 0.032). No significant differences were observed in 6-month mortality (6.03% vs. 7.67%, P = 0.380), 1-year mortality (9.32% vs. 11.51%, P = 0.330), ICU-acquired weakness (26.58% vs. 29.59%, P = 0.270), ICU-acquired infection (19.45% vs. 19.73%, P = 0.930), or adverse events (2.19% vs. 3.84%, P = 0.190). CONCLUSION: The NFPS significantly reduced the incidence of delirium and was associated with shorter durations of mechanical ventilation, ICU-LOS, HLOS, lower hospitalization costs, without increasing the risks of ICU-AW, ICU-acquired infection, or adverse events. No significant differences were observed in long-term mortality between the two groups.
BACKGROUND: Sex differences in intensive care treatment and mortality are well documented, but the timing of decisions to limit treatment remains unclear. We investigated whether sex differences in decisions to limit tre...BACKGROUND: Sex differences in intensive care treatment and mortality are well documented, but the timing of decisions to limit treatment remains unclear. We investigated whether sex differences in decisions to limit treatment arise at ICU admission or during the ICU stay. METHODS: Nationwide cohort study using the Swiss Minimal Dataset for Intensive Care Units, including adult (≥ 18 years) ICU admissions between 2016 and 2024. Two adjusted logistic regression models assessed treatment limitations documented at ICU admission and those occurring later among patients admitted without limitations. RESULTS: Among 654,660 ICU stays, treatment limitations at admission were more common in women than men (12.0% vs. 8.6%), whereas rates during the ICU stay were similar (5.5% vs. 5.5%). Female sex was independently associated with limitations at admission (aOR 1.26, 95% CI 1.24-1.28) but only weakly associated with later limitations (aOR 1.10, 95% CI 1.08-1.13). Differences at admission varied by diagnosis and were most pronounced in trauma and cardiovascular conditions. Women more often had ceiling-of-care decisions and documented patient wishes, whereas men more frequently underwent withdrawal of life-sustaining therapies and physician-driven decisions. Mortality was highest with limitations at ICU admission and lowest without limitations, with minimal sex differences within categories. CONCLUSIONS: In Switzerland, sex differences in treatment limitations occur mainly at ICU admission and vary across diagnoses. These findings suggest that differences may reflect early triage heuristics, societal norms influencing advance care planning, and potential implicit biases under prognostic uncertainty. Structured goal-of-care discussions at ICU admission may help promote consistent and equitable decision-making.
Melatonin (MEL) modulates the circadian rhythm and has been studied as a preventive measure against delirium, especially in intensive care unit (ICU) patients, but the current findings are conflicting. We performed a pai...Melatonin (MEL) modulates the circadian rhythm and has been studied as a preventive measure against delirium, especially in intensive care unit (ICU) patients, but the current findings are conflicting. We performed a pairwise dose‒response meta-analysis of randomized controlled trials (RCTs) followed by meta-regression and trial sequential analysis to assess the ability of MEL or ramelteon (RAL) to prevent delirium in the ICU. We evaluated the certainty of the evidence via GRADE and the credibility of the subgroup analysis via the ICEMAN tool. We identified 24 studies that included 3680 participants. Compared with placebo, melatoninergic agonists reduce the incidence of delirium (0.77 [0.62,0.94], primary analysis of 18 studies), with superior effects in the MEL group (RR 0.77 [0.62, 0.97]) and in surgical-type ICU (RR 0.64 [0.48, 0.87]). We found a nonlinear dose‒response relationship between the cumulative dose of MEL and the RR of delirium, suggesting an optimal cumulative dose of 22 mg of MEL (RR 0.732 [0.599, 0.895]). Subgroup and meta-regression analyses revealed a significant effect of intervention duration on the risk of delirium, with a superior effect in the subgroup with ≥ 7 days of intervention (RR 0.73 [0.60, 0.90]). Melatoninergic agonists did not affect 28-30-day or ICU mortality or the incidence of adverse effects. Melatoninergic agonists showed a clinically relevant trend based on the minimal clinically important difference (MCID) to reduce the ICU length of stay (LOS) (MD:-0.74 [-1.60, 0.12], MCDI -0.113 [1.846, -2.073]), hospital LOS (MD -0.33 [-1.91, 1.25], MCID -0.134 [1.833, -2.108]) and length of mechanical ventilation (MV) (MD -0.50 [-1.16, 0.16], MCID -0.2146 [1.744, -2.173]). Compared with placebo, they may increase the time to the onset of delirium (MD 0.76 [0.43, 1.09]), but with very-low certainty. Our findings indicate that melatoninergic agonists probably reduce the risk of delirium in ICU patients, especially those treated with MEL, in surgical-type ICUs and for durations equal to or longer than 7 days, with an optimal cumulative dose of 22 mg. Additionally, they appear to be safe while offering potential benefits in reducing ICU length of stay and duration of mechanical ventilation. However, the magnitude of effect was modest, with low-certainty evidence and moderate heterogeneity, and these findings should therefore be interpreted with caution.