BACKGROUND: β-lactam antibiotics are the most commonly used antibiotics to treat infection in critically-ill patients. The modalities of antibiotics reconstitution/preparation for continuous infusion are elaborated accor...BACKGROUND: β-lactam antibiotics are the most commonly used antibiotics to treat infection in critically-ill patients. The modalities of antibiotics reconstitution/preparation for continuous infusion are elaborated according to drug stability. In between 2 periods, a sustainable protocol for 4 common β-lactam antibiotics administration was implemented, consisting of preparing the highest stable concentration for continuous administration through a 50 mL syringe. RESULTS: Overall, 418 patients were treated (202 in 2024 and 216 in 2025), age, and SAPSII did not differed between both periods. A sustainable protocol implementation reduced the greenhouse gas emission (GHG) by 52% from 2760 [1380-4968]g to 1380 [552-2208]g/treatment, p < 0.0001. The global reduction of plastic consumed (syringes, tubing, solution bags, blister packs) was - 48% (-61 kg), and treatment cost was also reduced by 48% (-1324 €). The total nursing time for preparation was 145 h shorter during the second 6 months period. DISCUSSION: These results showed that implementation of a sustainable protocol for continuous β-lactam antibiotics can significantly reduce the environmental impact of antibiotic administration. CONCLUSION: A careful prescription of drug dilution, if continuous infusion of β-lactam antibiotics is used, can be efficient in reducing GHG emissions, consumables, waste, and costs.
BACKGROUND AND OBJECTIVES: Secretion retention is common in invasively mechanically ventilated ICU patients. Airway clearance techniques (ACTs) are widely used, although their physiological and clinical effects remains u...BACKGROUND AND OBJECTIVES: Secretion retention is common in invasively mechanically ventilated ICU patients. Airway clearance techniques (ACTs) are widely used, although their physiological and clinical effects remains uncertain. We aimed to evaluate the physiological and clinical effects of selected ACTs in invasively mechanically ventilated adult ICU patients. METHODS: This systematic review was registered in PROSPERO (CRD42025631124) and conducted according to PRISMA guidelines. We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and PEDro up to 20 March 2025. Studies evaluating ventilator hyperinflation, PEEP-ZEEP technique, expiratory rib-cage compression (ERCC), or mechanical insufflation-exsufflation (MI-E) in mechanically ventilated adults were included. We assessed risk of bias using the Cochrane Risk of Bias tool for randomized studies and Joanna Briggs Institute tools for observational studies and case series. The primary outcome was secretion clearance (e.g., sputum weight or volume). Secondary outcomes included clinical outcomes (mortality, duration of invasive mechanical ventilation, ICU length of stay), safety (adverse events during ACTs), and respiratory complications related to impaired airway clearance (gas-exchange impairment, increased work of breathing, and ventilator-associated pneumonia). RESULTS: Forty-six studies including 1,884 patients were analysed. Secretion clearance was the most frequently reported outcome. Several studies reported greater secretion clearance with ACTs compared with standard care or suctioning alone, although findings varied across techniques, comparisons, and outcome definitions. ERCC, MI-E, and hyperinflation techniques were associated with increased secretion clearance in some studies, whereas results for PEEP-ZEEP technique were inconsistent. Effects on respiratory mechanics, oxygenation, and clinical outcomes were variable and predominantly short-term. Clinically relevant respiratory complications and patient-centred outcomes were inconsistently reported. No clear effect was observed on mortality, duration of mechanical ventilation, or ICU length of stay. No major adverse events were reported. CONCLUSION: Selected ACTs may improve short-term secretion clearance in invasively ventilated ICU patients. However, the evidence is largely limited to surrogate physiological outcomes and is of low certainty for clinically meaningful outcomes, whose effects remain uncertain. Further high-quality studies using standardized outcome definitions and robust safety reporting are required.
BACKGROUND: Light is a key regulator of circadian rhythms, sleep, and neuroendocrine function. Abnormal light exposure has been associated with delirium and adverse outcomes in critically ill patients. While previous ICU...BACKGROUND: Light is a key regulator of circadian rhythms, sleep, and neuroendocrine function. Abnormal light exposure has been associated with delirium and adverse outcomes in critically ill patients. While previous ICU studies have generally reported low daytime illuminance and intermittent nocturnal light exposure, most relied on averaged measurements or low temporal resolution monitoring, potentially obscuring clinically relevant exposure patterns. In routine ICU care, light exposure often occurs as brief but frequent events related to necessary interventions, yet the extent and temporal structure of such light fragmentation remain poorly characterized. This study therefore aimed to characterize high-resolution 24-hour light exposure patterns and nocturnal fragmentation in ICU patients. METHODS: In this observational study, ambient illuminance was continuously recorded every 5 s in adult ICU patients over a one-year period. A total of 222 patients were monitored for up to 7 consecutive days, yielding more than 14 million individual measurements. Light exposure was analysed across complete 24-hour cycles and stratified into daytime (07:00-20:59) and nighttime (21:00-06:59) periods. Outcomes included median illuminance, frequency of light events, extreme illuminance (99th percentile), and duration of uninterrupted nocturnal darkness. Mixed-effects models and negative binomial regression were used to account for repeated measurements and to assess associations with room configuration. RESULTS: Across the 24-hour cycle, median illuminance demonstrated a flattened diurnal pattern, with daytime light levels remaining markedly below those typically encountered in indoor working environments and limited sustained darkness at night. Nighttime exposure was dominated by frequent short-duration light events, resulting in pronounced fragmentation of nocturnal darkness. Fragmentation patterns were largely independent of room configuration and treatment intensity, as ambient illuminance did not differ according to organ support modality once time of day was considered. Extreme illuminance values occurred intermittently, predominantly during daytime, and varied according to room type. CONCLUSIONS: ICU light exposure is characterized primarily by temporal fragmentation rather than sustained brightness. Repeated interruptions of darkness may represent a plausible environmental mechanism contributing to circadian dysregulation. These findings highlight care processes as a key target for interventions and support the use of fragmentation-based metrics in future circadian research in critical care.
BACKGROUND: Myocardial injury is common in sepsis and associated with increased mortality, but its underlying mechanisms remain incompletely understood. Coronary microvascular dysfunction (CMD) has been proposed as a con...BACKGROUND: Myocardial injury is common in sepsis and associated with increased mortality, but its underlying mechanisms remain incompletely understood. Coronary microvascular dysfunction (CMD) has been proposed as a contributor, although in vivo evidence is limited. We characterised coronary microvascular function in patients with sepsis and myocardial injury and its relationship with cardiac troponin release. METHODS: Consecutive adults with sepsis (Sepsis-3 criteria) and myocardial injury (hs-cTnT ≥ 15 ng/L) were prospectively enrolled between June 2019 and December 2024. Patients underwent coronary angiography, invasive thermodilution-based assessment of coronary microvascular function, and transthoracic echocardiography after clinical stabilisation. CMD was defined as an index of microcirculatory resistance (IMR) > 25 and/or microvascular resistance reserve (MRR) ≤ 3. Associations between hs-cTnT concentrations and coronary microvascular indices, obstructive coronary artery disease (CAD), and echocardiographic variables were assessed using regression analyses. Coronary microvascular indices were compared with those of age-, sex-, and CAD-matched patients with chronic coronary syndrome (CCS) using mixed-effects models. RESULTS: Fifty-five patients underwent coronary angiography and 49 completed invasive coronary microvascular assessment. Obstructive CAD was identified in 12/55 (22%). CMD was present in 30/49 (61%). Among these, 8/49 (16%) had elevated IMR only, 9/49 (18%) had functional CMD (MRR ≤ 3 and IMR ≤ 25), and 13/49 (27%) had structural CMD (MRR ≤ 3 and IMR > 25). Restricted cubic spline analyses demonstrated no evidence of associations between hs-cTnT and IMR (overall P = 0.899; non-linearity P = 0.687) or MRR (overall P = 0.987; non-linearity P = 0.954). CMD was associated with a higher prevalence of ventriculo-arterial uncoupling, right ventricular systolic dysfunction, and impaired right ventricular-pulmonary arterial coupling. Patients with sepsis demonstrated reduced coronary microvascular vasodilatory capacity compared with matched CCS controls (MRR 3.2 [IQR 2.4-4.5] vs. 4.0 [2.7-6.2]). IMR was similar between groups. CONCLUSIONS: CMD was common and heterogeneous and exhibited distinct phenotypes in patients with sepsis and myocardial injury. Measures of coronary microvascular function were not associated with troponin release. Previously unrecognised obstructive CAD was identified in 22% of patients, supporting consideration of underlying CAD in patients with sepsis and myocardial injury. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT06294730.
BACKGROUND: Hyper-inflammation is common to multiple critical care syndromes, including acute respiratory distress syndrome (ARDS) and sepsis, and is associated with worse outcomes. A signature of hyper-inflammatory ARDS...BACKGROUND: Hyper-inflammation is common to multiple critical care syndromes, including acute respiratory distress syndrome (ARDS) and sepsis, and is associated with worse outcomes. A signature of hyper-inflammatory ARDS has been described in adults using IL-6, TNFR1, and bicarbonate, and has prognostic utility. We investigated the application of this traditional parsimonious signature to pediatric ARDS patients and tested whether we could improve prognostic enrichment using other cytokines. METHODS: We leveraged a prospective multicenter cohort study of 500 children with ARDS (Linking Endotypes and Outcomes in Pediatric Acute Respiratory Distress Syndrome [LEOPARDS]; NCT04113434) study. Plasma samples were obtained within 24 h of ARDS. Cytokines were measured using microfluidic immunoassay (Ella™). RESULTS: The traditional 3-term (IL-6, TNFR1, and bicarbonate) hyper-/hypo-inflammatory phenotype model demonstrated modest utility for 90-day mortality (AUC 0.62, sensitivity 26%, positive predictive value [PPV] 24%) in LEOPARDS (14% hyper-inflammatory, 13.4% 90-day mortality). Of the additional cytokine biomarkers tested, CCL7 (MCP-3) demonstrated the most significant association with 90-day mortality (p < 0.0001). Parsimonious two-term (CCL7, IL-18) and three-term models (CCL7, IL-18, TNFR1) demonstrated mortality discrimination in both training (n = 300) (AUROCs 0.72-0.73) and validation (n = 200) (AUROCs 0.66) sets, with improved net reclassification (~ 40% improved classification). Immune compromised status was independently associated with 90-day mortality (p < 0.0001) with evidence that the optimal prognostic model may vary by immunocompromised status. CONCLUSIONS: Cytokine-based prognostic enrichment strategies show promise for children with ARDS. In addition to models based primarily on IL-6 and TNFR1, models including CCL7 and IL-18 may be of utility for assessing the full spectrum of inflammation. Future studies should focus on identifying whether cytokine-based enrichment can identify specific pathways to inform immunomodulatory interventions. TRIAL REGISTRATION: Clinical Trial NCT04113434 was registered 2019-10-02.
BACKGROUND: The Intensive Care Unit (ICU) is an environment where multiple factors that predispose to the transmission of Antimicrobial Resistance (AMR) coexist. Genomic sequencing is a technology that enables a better u...BACKGROUND: The Intensive Care Unit (ICU) is an environment where multiple factors that predispose to the transmission of Antimicrobial Resistance (AMR) coexist. Genomic sequencing is a technology that enables a better understanding of how AMR genes are transmitted within the ICU environment. OBJECTIVE: To evaluate the genomic dynamics of the transmission of antimicrobial resistance genes between bacteria from ICU surfaces and bacteria from critically ill patients. METHODS: A cross-sectional analytical study. Surface swab samples were collected from the ICU, including suction units, infusion pumps, stethoscopes, dialysis machines, monitors, ventilators and gas valves, as well as samples from critically ill patients with infections. Species were identified using microbiological microplate panels; antibiotic susceptibility testing was carried out to assess AMR; and whole-genome sequencing was performed on isolates that were multidrug-resistant (MDR). The sequencing was carried out using a nanopore long-read sequencer and the results were analysed using specialised bioinformatics tools. RESULTS: A total of 130 positive isolates were identified, of which 96 (73.85%) were from environmental samples and 34 (26.15%) from patient samples. Forty (30.76%) MDR species were identified. The most common MDR species were Klebsiella pneumoniae and Acinetobacter baumannii. The most frequently detected AMR genes were blaNDM-5 and blaOXA-23. The most common plasmids were IncFIB(K)_1_Kpn3, Col440I and IncL/M(pMU407)_1_pMU407. A clonal outbreak of Acinetobacter baumannii ST 2 was detected on the dialysis machine, stethoscopes and patient samples. Evidence of horizontal transfer of resistance genes via plasmids conjugation was found in samples taken from suction units, oxygen valves and tracheal secretion in three cases. CONCLUSION: The findings of this research show that antimicrobial resistance genes are transferred between bacteria on surfaces and bacteria in critically ill patients, and that this transfer occurs in both directions.
BACKGROUND: Infection is a major complication after trauma and is associated with worse clinical outcomes. Although red blood cell (RBC) transfusion is an essential component of resuscitation in trauma patients, its rela...BACKGROUND: Infection is a major complication after trauma and is associated with worse clinical outcomes. Although red blood cell (RBC) transfusion is an essential component of resuscitation in trauma patients, its relationship with infection risk remains controversial. Furthermore, the dose-response relationship has not been fully elucidated. METHODS: We conducted a retrospective observational study using a nationwide trauma registry in Japan. Trauma patients registered between 2019 and 2021 were included. Patients were categorized into four groups according to RBC transfusion volume within the first 24 h after admission: None (0 units), Low (1-4 units), Moderate (5-9 units), and High (≥ 10 units). The primary outcome was in-hospital infection. Multivariable modified Poisson regression analyses were performed to estimate adjusted risk ratios (RRs) with 95% confidence intervals (CIs). Furthermore, we performed multivariable-adjusted restricted cubic spline analyses with four knots to assess the adjusted dose-response relationship between RBC transfusion volume and the risk of in-hospital infection. RESULTS: A total of 55,807 patients were analyzed. The incidence of in-hospital infection increased across transfusion categories: 4,399/48,308 (9.1%) in the None group, 618/3,724 (16.6%) in the Low group, 396/1,733 (22.8%) in the Moderate group, and 548/2,042 (26.8%) in the High group. In multivariable analysis, compared with the None group, Low (adjusted RR 1.85, 95% CI 1.62-2.10), Moderate (adjusted RR 1.95, 95% CI 1.69-2.26) and High (adjusted RR 2.07, 95% CI 1.76-2.43) transfusion volumes were associated with significantly increased risks of infection, respectively. Restricted cubic spline analyses showed an increase in infection risk at lower transfusion volumes, followed by a plateau at higher transfusion volumes. CONCLUSIONS: RBC transfusion volume within the first 24 h after trauma was associated with in-hospital infection risk. The association was generally linear at lower transfusion volumes, whereas a plateau was observed at higher transfusion volumes. Given the observational nature of this study, these findings should be interpreted cautiously.
BACKGROUND: Critical illness induces a catabolic state, associated with profound muscle wasting and functional disability in survivors. Based on evidence at the time of development, international critical care nutrition...BACKGROUND: Critical illness induces a catabolic state, associated with profound muscle wasting and functional disability in survivors. Based on evidence at the time of development, international critical care nutrition guidelines recommend providing higher protein doses than in healthy populations. MAIN BODY: Three recent international multi-centre randomised trials (total n = 5633 patients) have compared higher protein doses to usual protein doses in critically ill patients. Based on the primary outcomes, these trials concluded that higher protein doses did not improve time-to-discharge alive or number of days free of the index hospital and alive at day 90, with worse functional recovery using the EQ-5D-5L health utility score over 180 days. Supported by evidence from recent trials, it appears preferable to commence protein delivery at low doses once patients are haemodynamically stable and increase progressively over the first 5 days to deliver a maximum of 1.2 g/kg/day. Based on current trial data, this upper limit may represent a safer alternative to doses >1.2 g/kg/day, acknowledging that the optimal dose may be lower. Subgroup analyses suggest that patients with an acute kidney injury may be particularly vulnerable to higher protein. There are no data to indicate the minimum protein dose that can be safely delivered to critically ill patients over their entire ICU stay. While existing trials included patients with a prolonged ICU stay, no trial identifying this cohort pre-randomisation has been conducted. It cannot be excluded that higher protein doses may provide benefit later in recovery, when the anabolic resistance to dietary protein observed early in the ICU admission has subsided. Evidence is also lacking on optimal protein targets for patients after ICU discharge. CONCLUSION: In critically ill adults, we suggest that protein doses be commenced at a low dose and increased progressively to a maximum of 1.2 g/kg/day based on recent randomised trials.
BACKGROUND: Survivors of critical illness commonly experience post-intensive care syndrome (PICS), including cognitive, mental health, physical, quality-of-life, and social impairments after discharge. Telemedicine may i...BACKGROUND: Survivors of critical illness commonly experience post-intensive care syndrome (PICS), including cognitive, mental health, physical, quality-of-life, and social impairments after discharge. Telemedicine may improve access to post-ICU recovery clinic care, but its feasibility and effect on recovery outcomes remain unclear. We evaluated the feasibility of a multidisciplinary telemedicine post-ICU recovery clinic and collecting 6-month outcome data. METHODS: We conducted a two-site pilot feasibility randomized controlled trial at an academic medical center and regional community medical center in the southeastern United States. Adults admitted to medical or surgical ICUs with sepsis and/or acute respiratory distress syndrome were randomized 1:1 to telemedicine ICU recovery clinic visits or standard care. The intervention included two multidisciplinary visits at 3 weeks and 3 months after hospital discharge; participants accessed visits via a secure web-based personal health portal, where they videoconferenced simultaneously with an ICU clinician, pharmacist, and psychologist. Participants in the standard of care group received usual post-discharge care. Feasibility outcomes included enrollment, retention, attendance, clinician fidelity, and participant ratings of acceptability, appropriateness, and feasibility. Exploratory outcomes included cognitive, mental health (i.e., depression, anxiety, PTSD), and physical health (i.e., activities of daily living, independent activities of daily living) composite scores measured at 1 week and 6 months after hospital discharge. RESULTS: Of 1,108 screened patients, 91 were randomized (telemedicine, n = 46; standard care, n = 45). Among 83 participants completing the 1-week assessment, median age was 56 years, 51% were male, and 91% were White. In the telemedicine arm, 23 participants (57.5%) attended at least one visit; attendance was 55% at 3 weeks and 42.5% at 3 months among eligible participants. Primary 6-month outcome assessment was completed by 31 participants in each group (67%). Clinician participation fidelity was high, and telemedicine attendees reported favorable acceptability, appropriateness, and feasibility ratings. Exploratory analyses of PICS composite outcomes did not differ significantly between groups. CONCLUSION: A multidisciplinary telemedicine post-ICU recovery clinic and associated trial procedures were feasible, with high clinician fidelity and favorable participant ratings. Larger trials are needed to explore engagement strategies and evaluate effectiveness on long-term recovery outcomes, prioritizing inclusion of more diverse and historically underrepresented populations. TRIAL REGISTRATION: NCT03926533 (posted 4/24/2019).
Reizine F, Henry J, Desmedt L
… +31 more, Camus C, Coirier V, Arrive F, Burban E, Eustache G, Belleville T, Marc A, Malherbe J, Bouju P, Jaubert P, Lesieur O, Leclerc M, Fillâtre P, Frérou A, Prével R, Mainguy N, Cady A, Morio F, Le Gal S, Perraud E, Delhaes L, Imbert S, Guegan H, Bonhomme J, Pihet M, Dupin C, Delbove A, Du Cheyron D, Launey Y, Aubron C, Gangneux JP
BACKGROUND: Candidemia displays significant clinical heterogeneity in critically ill patients. This study aimed to identify distinct clinical phenotypes and to assess their association with 90-day mortality. METHODS: We...BACKGROUND: Candidemia displays significant clinical heterogeneity in critically ill patients. This study aimed to identify distinct clinical phenotypes and to assess their association with 90-day mortality. METHODS: We conducted a multicenter retrospective cohort study of 492 intensive care unit (ICU) patients with candidemia from 16 French ICUs (2015-2023). We performed a factor analysis of mixed data (FAMD) incorporating both categorical and continuous baseline variables, followed by hierarchical clustering on principal components (HCPC). Survival analysis was performed with Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Overall, 90-day mortality for the 492 patients (median age: 64 years, 69.1% male) with candidemia was 62.6%. Three different phenotypes emerged from FAMD followed by HCPC: Phenotype 1 (n = 70, 14.2%) comprised patients with severe immunosuppression, mostly due to hematological malignancies (82.9%), and high severity scores (SAPS II:70); Phenotype 2 (n = 223, 45.3%) corresponded to elderly cirrhotic patients (19.3%) with early-onset digestive candidemia; Phenotype 3 (n = 199, 40.5%) comprised younger patients with lower severity scores and catheter-related candidemia. Mortality differed significantly between phenotypes: 72.9% (Phenotype 1), 70.4% (Phenotype 2), and 50.3% (Phenotype 3) (p < 0.001). Independent predictors of mortality included age (aHR: 1.01, 95% CI: 1.00-1.02; p = 0.003), cirrhosis (aHR: 1.90, 95% CI: 1.39-2.60; p < 0.001), SAPS II (aHR: 1.01, 95% CI: 1.01-1.02; p < 0.001), echinocandin use (aHR = 0.49, 95% CI: 0.39-0.63; p < 0.001) and proven catheter-related candidemia (protective; aHR: 0.48, 95% CI: 0.33-0.69; p < 0.001). Immunodepression was not associated with mortality. CONCLUSION: Unsupervised clustering identified three clinically different candidemia phenotypes with different outcomes. Cirrhosis, higher age and illness severity were associated with mortality, whereas a catheter-related source of infection was protective.