Critical Care Bulletin: November 2025

 

Epidemiology of pain, delirium, psychiatric disorders, discomfort and sedation-analgesia management in the intensive care unit: a one-day nationwide study

Critical Care volume 29, Article number: 483 (2025) Published: 11 November 2025

Background

The administration of sedatives and analgesics in intensive care units (ICUs) has evolved significantly over the past 20 years, shifting from deep to light sedation strategies to minimize adverse effects. Despite this shift, substantial variability persists in sedation-analgesia practices. This study aimed to provide an updated national overview of sedation-analgesia management with a focus on discomfort assessment practices, including pain, delirium, anxiety, thirst, mood, and sleep disorders.

Methods

This was a one-day, multicenter, cross-sectional study conducted in French ICUs. Data were collected from all adult patients hospitalized in the ICU on the study day. A Unit-level survey documented ICU characteristics and sedation-analgesia protocols. Patient-level data included sedation levels, pain scores, and assessments of discomfort conditions. Statistical analyses were performed using descriptive methods and multilevel logistic regression.

Results

Among 258 French ICUs contacted, 128 units (50%) participated, enrolling 2,063 patients. Most ICUs were university-affiliated (54%) and mixed medical-surgical (58%); 63% had a written protocol for sedation-analgesia. Sedation and pain were assessed in 96% and 91% of ICUs, respectively. Light or no sedation was observed in 84% of patients, while 15% were deeply sedated – 63% of whom were misaligned with usual indications. Pain assessment was performed at rest in 90% of patients and during care in 62%. Pain prevalence increased with lighter sedation levels and during care. Hypnotics were used in 31% of patients, Mainly propofol and midazolam. Discomfort was reported in 44% of patients, mainly anxiety, sleep disorders, and thirst. Written protocols for sedation and analgesia were not associated with sedation depth, drug use, or delirium screening, but were linked to more frequent pain assessment at rest. Multivariable analyses showed that higher SOFA scores were associated with deep or misaligned deep sedation. The presence of a written protocol for sedation and analgesia reduced the risk of unassessed pain but was not associated with deep or misaligned deep sedation.

Conclusion

The shift toward lighter sedation has been successfully achieved; however, a broad spectrum of stressful symptoms persists, including pain, anxiety, thirst, and sleep disruption. These findings underscore the need for more effective strategies to optimize pain and overall patient comfort in non-deeply sedated ICU patients.

 

Association between controlled mechanical ventilation and systemic inflammation in acute hypoxemic respiratory failure: an observational cohort study

Critical Care volume 29, Article number: 482 (2025) Published: 11 November 2025

Background

In patients with acute hypoxemic respiratory failure, spontaneous breathing efforts may contribute to patient self-inflicted lung injury through increased ventilation inhomogeneity and systemic inflammation. Whether early transition to controlled mechanical ventilation (CMV) mitigates these effects remains uncertain.

Methods

This observational, prospective cohort study included 40 ICU patients with acute hypoxemic respiratory failure who initially breathed spontaneously. Based on clinical decisions, patients were managed with either continued spontaneous breathing (SB group, n = 12) or transitioned to CMV (CMV group, n = 28). Arterial blood gases, hemodynamics, plasma cytokines (IL-6 and IL-8), and ventilation distribution via electrical impedance tomography (EIT) were recorded at baseline and after 24 h. In the CMV group, intermediate time points (T2, T6, T12) were also assessed after intubation. The trial was registered in ClinicalTrials.gov (NCT03513809).

Results

In the CMV group, respiratory rate and heart rate decreased significantly over time. IL-6 levels dropped markedly from 305 ± 938 pg/mL at baseline to 27 ± 58 pg/mL at 24 h (p = 0.0195), accompanied by a significant improvement in oxygenation (PaO₂/FiO₂ from 140 ± 51 to 199 ± 67, p = 0.0004). EIT data showed improved ventilation distribution with increased end-expiratory lung impedance, decreased global inhomogeneity, and a shift in the center of ventilation toward dorsal regions. In contrast, the SB group showed no significant changes over 24 h in gas exchange, systemic inflammation, or EIT-derived parameters.

Conclusions

In patients with acute hypoxemic respiratory failure initially breathing spontaneously, transition to CMV was associated with reduced IL-6 levels and improved ventilatory homogeneity over 24 h. These exploratory findings indicate that connection to controlled mechanical ventilation was associated with reduced systemic inflammation, a relationship that warrants confirmation in larger prospective studies.

 

 

Toward optimal mechanical ventilation of the injured lung: the role of expiratory duration

Critical Care volume 29, Article number: 481 (2025) Published: 10 November 2025

Abstract

Positive pressure mechanical ventilation is a life-saving intervention for patients with acute respiratory distress syndrome (ARDS), but it can also increase mortality by causing ventilator-induced lung injury (VILI) if applied inappropriately. Although strategies like low-tidal volume ventilation and prone positioning have been shown to reduce mortality, the optimal patient-specific approach to mechanical ventilation in ARDS has yet to be identified. The worst manifestations of acute lung injury arise when fluid and proteins from the blood leak through a damaged blood-gas barrier, accumulating in the airspaces and impairing the ability of pulmonary surfactant to lower surface tension. This amplifies the ventilatory stresses in the lung tissues, which further damages the blood-gas barrier, leading to a vicious cycle of worsening injury. Studies suggest that VILI may be most effectively avoided by preventing the atelectrauma caused during inspiration by the forced reopening of lung units that close during each expiration. Atelectrauma is conventionally mitigated with positive end-expiratory pressure (PEEP), but it remains unclear if the algorithmic selection of PEEP leads to mortality reductions in ARDS. Animal studies, however, support the efficacy of exploiting the time-dependent nature of recruitment and derecruitment, for example through the use of brief expiratory durations that continually adapt to changing lung mechanics. Despite decades of research, it remains unclear how to minimize VILI in any given ARDS patient. Animal studies coupled with energy dissipation analysis indicate that the prevention of VILI requires, above all, avoidance of the atelectrauma caused by cyclic recruitment and derecruitment in the lung. In addition, the path to optimal mechanical ventilation in ARDS must be based not only on the amplitudes of the pressures applied to the lung but also on their temporal natures.

 

Intermediate Care Unit performance being properly assessed?

Critical Care volume 29, Article number: 480 (2025) Published: 10 November 2025

Abstract

Intermediate Care Units (ImCU) are worldwide considered as an intermediate setting of care between standard wards and intensive care units (ICU), specifically addressed to critically ill patients admitted from Emergency Departments, stepping down from ICUs or stepping up from general wards. ImCU formats vary considerably between institutions, missing univocal criteria of where they should be placed, how be formatted and staffed, what monitoring and treatments delivered, which patients admitted, and when discharged. Many published studies focused primarily on mortality as the main variable of interest, while the effects of ImCU implementations on healthcare costs, hospital governance and comprehensive inpatient outcomes remain controversial. A consensus on which measures should be most accurate and based on evidence is still lacking. Appropriate quality-of-care key indicators should concern structures, processes, outcomes and their relationships. The development of a multi-level framework to assess ImCU performance, tailored on resources and management of each specific reality, should consider their functional role on hospital macro-systems, warranting both by patient-level and system-level objectives to ensure effective benchmarking and to provide a substantial support to clinical practice.

 

Impact of frailty on mortality, functional outcome, and health status after out-of-hospital cardiac arrest: insights from the TTM2-trial

Intensive Care Medicine Published: 10 November 2025

Purpose

To explore the association of frailty with mortality, functional outcome, and health status after out-of-hospital cardiac arrest.

Methods

This is a cohort-based secondary analysis of the Targeted Hypothermia versus Targeted Normothermia after out-of-hospital cardiac arrest (TTM2) trial, an international, prospective, multicentre study. Frailty was assessed using the Clinical Frailty Scale (1–9): fit (1–3), prefrail (4), frail (5), and severely frail (6–9). Main outcomes were mortality and poor functional outcome (modified Rankin Scale 4–6) at 6 and 24 months. Additional outcomes included neuroprognostication, withdrawal-of-life-sustaining-therapies (WLST), functional decline (retrospectively reported pre-arrest versus 6 month Glasgow Outcome Scale Extended score), health status (EQ-5D-5L, EQ-VAS), and life satisfaction at 6 and 24 months.

Results

Of 1861 participants, 240 (13%) were prefrail, and 188 (10%) were frail or severely frail. Mortality and poor functional outcome increased significantly with greater frailty. Compared to fit participants, adjusted ORs (95% CI) for 6 month mortality were: prefrail 2.7 (1.8–3.8), frail 3.7 (1.9–7.1), and severely frail 8.9 (4.2–18.7); and poor functional outcome: prefrail 2.9 (1.9–4.2), frail 3.9 (1.9–8.1), and severely frail 35.4 (8.4–148.8). Severely frail participants underwent neuroprognostication less often (p < 0.001), while WLST was more common in the prefrail, frail and severely frail (p < 0.001). Prefrail and frail survivors tended to report more frequent functional decline and lower health status, though with individual variation.

Conclusion

Frailty was associated with a significantly increased risk of mortality and poor functional outcome after out-of-hospital cardiac arrest. Findings suggest more frequent functional decline and lower overall health status in frail survivors.

 

Handgrip strength association with weaning outcome in mechanically ventilated ICU patients: a systematic review and meta-analysis

Critical Care volume 29, Article number: 478 (2025) Published: 07 November 2025

Abstract

Weaning from mechanical ventilation is a critical process in the intensive care unit (ICU), and extubation failure remains associated with poor outcomes. ICU-acquired weakness has been identified as a risk factor for delayed weaning. Maximal handgrip strength (HGS) is a simple bedside measure proposed as a surrogate marker of global muscle strength. This systematic review and meta-analysis aimed to assess the association between HGS and weaning outcomes in ICU patients. A systematic search of MEDLINE, EMBASE, CINAHL, and Cochrane Library was conducted up to December 2024. We included prospective cohort studies assessing maximal HGS prior to extubation in mechanically ventilated adults, and its association with extubation failure, spontaneous breathing trial (SBT) failure, or weaning classification (simple, difficult, or prolonged). Meta-analyses pooled mean differences in HGS between outcome groups, and diagnostic accuracy was evaluated using a hierarchical summary ROC model. Risk of bias was assessed using the QUIPS tool. Seven studies were included in the review (n = 707 patients), and six in the meta-analysis. No significant difference in HGS was found between extubation failure and success (mean difference: − 3.62 kg; 95% CI: − 7.92 to 0.62). However, significantly lower HGS was associated with SBT failure (–3.00 kg; 95% CI: − 4.64 to − 1.36) and non-simple weaning (–3.94 kg; 95% CI: − 5.31 to − 2.58). Pooled sensitivity and specificity of HGS were 72% and 60% respectively, in predicting either extubation failure or non-simple weaning. Negative predictive values ranged from 90% to 95%, for 10% and 20% pre-test probability. Maximal HGS does not appear to significantly differentiate extubation success from failure Given the limited number of studies and their heterogeneity, further high-quality research is needed to clarify its prognostic value across different patient subgroups and timeframes.

 

Persistent inspiratory muscle weakness among extubated patients after prolonged intubation is frequent and can be predicted early by maximal inspiratory pressure measured 12 days after its initial diagnosis: a prospective observational study

Critical Care volume 29, Article number: 477 (2025) Published: 07 November 2025

Background

Prolonged mechanical ventilation (MV) frequently results in inspiratory and peripheral muscle weakness, impairing recovery. These conditions can be identified at the bedside using respectively Maximal Inspiratory Pressure (MIP) measurement and Medical Research Council (MRC) score. This study investigated the evolution over the acute-care hospital stay of MIP and MRC score in patients with documented post-extubation inspiratory muscle weakness (IMW), defined as MIP ≤ 30 cmH2O, and looked for the factors associated with persistent IMW at the end of the acute care hospital stay.

Method

This exploratory prospective observational study was conducted across five Swiss hospitals. Patients in the Intensive Care Unit (ICU) who were extubated after ≥ 7 days of MV, with IMW diagnosed within 48 h post planned extubation, were included. Patients’ characteristics and ICU-related factors were recorded throughout the acute care stay as were MIP and MRC score. ICU-acquired weakness (ICU-AW) recorded in the medical file, ICU readmission, reintubation, and hospital mortality were also documented. Descriptive statistics and linear interpolation for missing MIP data were applied, and associations with persistent IMW (MIP ≤ 30 cmH2O) at study completion were explored using univariable logistic regression. The optimal timepoint for predicting persistent IMW using MIP was identified using a random forest model.

Results

Sixty-nine patients (48 men, 21 women) completed the study. At study completion, persistent IMW was observed in 30 patients (43%), with a median MIP of 22 [13–24] cmH2O. MIP was of 44 [36–64] in patients without persistent IMW. Persistent IMW was positively associated in univariable logistic regression with female sex, duration of catecholamine use until inclusion, MIP at day 12, MRC score at day 12 and changes in MIP from inclusion to day 12. The presence of respiratory comorbidities was negatively associated with persistent IMW.

Conclusion

Persistent IMW following prolonged MV is frequent throughout the acute care stay and until acute care hospital discharge. The MIP measured at day 12 after inclusion, as well as its change from inclusion to day 12, were strongly associated with persistent IMW.

 

Use of rescue noninvasive ventilation for post-extubation respiratory failure

Critical Care volume 29, Article number: 470 (2025) Published: 04 November 2025

Background

Robust evidence supports the use of preemptive non-invasive ventilation (NIV) after extubation in selected high-risk patient cohorts. In contrast, current guidelines discourage the use of NIV as a rescue therapy for respiratory failure that develops later after extubation, based on earlier studies indicating a potential increase in hospital mortality due to delayed reintubation. Nonetheless, NIV continues to be employed in this setting. We conducted a post-hoc analysis of a randomized trial to assess the clinical outcomes of rescue NIV for post-extubation respiratory failure.

Methods

In this post-hoc analysis of a randomized trial comparing high-flow with Venturi mask oxygen in hypoxemic patients after extubation, we included those who developed post-extubation respiratory failure according to prespecified criteria; patients who received rescue NIV per physician’s decision were compared to those who received direct re-intubation. Criteria for re-intubation during NIV were prespecified. Odds ratio after inverse probability of treatment weighting and posterior probabilities by Bayesian regression are reported.

Results

Among 494 extubated patients, 147 developed respiratory failure while receiving oxygen therapy, occurring at a median of 37 h [IQR 13–85] after extubation: 83 (57%) were treated with rescue NIV and 64 (43%) received immediate re-intubation. The rate of NIV failure was 58%, without differences between patients with hypoxemic respiratory failure and those with hypercapnia and/or respiratory distress (60% vs. 56%, p = 0.82). In the weighted cohort, the use of rescue NIV, compared to direct re-intubation, was associated with lower intensive care unit mortality (adjusted odds ratio = 0.31 [95%CI: 0.12–0.82], p = 0.019) and similar hospital mortality (adjusted odds ratio = 1.01 [95%CI: 0.43–2.33], p = 0.99). The posterior probability that NIV reduced intensive care unit mortality was > 90% across all priors. The posterior probability that NIV did not increase hospital mortality was 44% under a noninformative prior, 47% under a skeptical prior, and 39% under a pessimistic prior.

Conclusion

Rescue NIV for post-extubation respiratory failure is associated with high failure rates; however, when applied with well-defined criteria for reintubation, it does not appear to be clearly associated with increases in hospital mortality. A randomized trial to re-evaluate the efficacy of rescue NIV for post-extubation respiratory failure is warranted.

 

 

ICU predictive factors of fibrotic changes following COVID-19 related ARDS: a RECOVIDS substudy

Annals of Intensive Care volume 15, Article number: 177 (2025) Published: 04 November 2025

Background

Pulmonary fibrotic changes (FC) following COVID-19-related ARDS represent a significant concern due to the potential respiratory complications. The identification of early predictive factors for FC and the development of predictive tools are needed to optimize patient management and outcomes.

Methods

This observational prospective multicentre study is a substudy of the RECOVIDS study and included 32 centres in France and Belgium. COVID-19 ARDS survivors were included if they met the Berlin ARDS criteria or if they received high flow oxygen therapy (flow ≥ 50 L/min and FiO2 ≥ 50%). Exclusion criteria were non-attendance at follow-up 6 ± 1 months after ICU discharge, lack of baseline or follow-up chest CT, and history of interstitial lung disease. The primary endpoint was presence of FC at follow-up CT. The secondary outcome was to identify predominant radiological patterns.

Results

Among 555 patients included in the RECOVIDS study, 440 were analysed, of whom 162 (36.8%) had FC at follow-up. Predictive factors for FC included older age, body mass index < 30, Charlson comorbidity index ≥ 1, invasive mechanical ventilation, early signs of FC, and greater lung involvement on baseline CT. The nomogram for predicting pulmonary FC yielded an AUC of 80.6% (95%CI (76.4–84.8)). Late organizing pneumonia was the most common pattern overall and 30 (18.5%) of the 162 patients with FC presented mainly anterior fibrosis compatible with post ventilatory changes.

Conclusion

In this large cohort of COVID-19 ARDS survivors, 36.8% exhibited FC at 6 months post-ICU discharge. The key predictors identified here could guide therapeutic and follow-up strategies.

 

 

 

 

New persistent opioid use among ICU survivors after discharge: incidence, predictors, and nationwide cohort analysis

Critical Care volume 29, Article number: 469 (2025) Published: 03 November 2025

Background

Long-term opioid dependence after critical illness is an emerging concern, yet the incidence and predictors of persistent opioid use among intensive care unit (ICU) survivors remain incompletely characterized. We aimed to estimate the six-month incidence of new persistent opioid use in opioid-naïve ICU survivors and to identify associated risk factors.

Methods

We conducted a retrospective, nationwide cohort study using South Korea’s National Health Insurance Service database. Adults admitted to any ICU between January 1, 2020, and December 31, 2022, were included if they survived to hospital discharge and remained alive for at least six months, with no opioid prescription in the 12 months preceding admission. New persistent opioid use was defined as at least one outpatient opioid prescription within 90 days after discharge and at least one additional prescription between 91 and 180 days. We performed multivariable logistic regression to identify independent predictors.

Results

Among 567,260 opioid-naïve ICU survivors, 23,945 (4.2%) developed new persistent opioid use within six months. Across the cohort, 22,643 (4.0%) received less-potent opioids (tramadol, dihydrocodeine) and 1,643 (0.3%) received potent opioids (morphine, fentanyl, oxycodone, hydromorphone, methadone). Independent predictors included older age (odds ratio [OR] 1.01 per year; 95% confidence interval [CI], 1.01–1.02; P < 0.001), female sex (OR 1.13; 95% CI, 1.09–1.16; P < 0.001), socioeconomic disadvantage (Medical Aid, OR 1.30; 95% CI, 1.23–1.38; P < 0.001), malignancy (OR 1.05; 95% CI, 1.01–1.09; P = 0.017), metastatic tumor (OR 1.24; 95% CI, 1.15–1.35; P < 0.001), extracorporeal membrane oxygenation (OR 1.80; 95% CI, 1.75–1.89; P < 0.001), and continuous renal replacement therapy (OR 1.24; 95% CI, 1.11–1.37; P < 0.001). The strongest predictor was an early opioid prescription within 30 days of discharge (OR 19.7; 95% CI, 19.1–20.3; P < 0.001). Potency-specific analysis showed potent opioid persistence was largely driven by cancer, while less-potent use was shaped more by demographic and socioeconomic factors.

Conclusions

Approximately one in 25 ICU survivors developed new persistent opioid use by six months. Early post-discharge opioid prescription was the dominant risk factor. Risk profiles differed by opioid potency, underscoring the need for early tapering strategies, multimodal non-opioid analgesia, and stewardship programs tailored to patient subgroups and opioid type.

 

Incidence, severity, and predictors of citrate accumulation during continuous kidney replacement therapy in the critically ill

Critical Care volume 29, Article number: 468 (2025) Published: 03 November 2025

Background

Regional citrate anticoagulation (RCA) is the recommended anticoagulation strategy for continuous kidney replacement therapy (CKRT). However, the safety of RCA in patients with liver dysfunction and/or shock remains controversial due to the risk of citrate accumulation. This study assesses the associations of citrate accumulation with liver dysfunction, circulatory shock, and mortality, and investigates lactate and the vasoactive inotropic score (VIS) as early predictors.

Methods

This retrospective cohort study included critically ill patients requiring RCA-based CKRT between January 2018 and March 2022. Lactate, VIS and parameters of organ failure were investigated as predictors of citrate accumulation. An albumin-corrected total calcium to ionized calcium ratio ≥ 2.5 was used to define citrate accumulation. Regression models were employed to investigate the association of predictors with outcomes.

Results

Nine hundred eleven patients were included, citrate accumulation was observed in 159 individuals (17%). Factors related to liver dysfunction, but not circulatory shock, were attributed to citrate accumulation. After multivariable adjustment, citrate accumulation was not associated with mortality. Lactate measured before onset of CKRT showed an improved discriminative performance compared to the VIS. The odds of citrate accumulation increased by 2.34 (CI 1.94–2.85, p < 0.001) for each one-unit increase in lactate on the logarithmic scale (log mmol/L). The probability for citrate accumulation ranged from 3.3 (CI 2.06–5.28) % at lactate levels of 0.3 mmol/L to 59.8 (CI 48.88–69.78) % at levels of 25 mmol/L.

Conclusion

Lactate is a reliable predictor for assessing the risk of citrate accumulation in patients undergoing CKRT. Further research is needed to develop and validate predictive algorithms for various anticoagulation strategies to offer reliable support for personalized decision-making in clinical practice.

 

Therapeutic plasma exchange in amatoxin associated acute liver failure–results from the multi-center Amanita-PEX study

Critical Care volume 29, Article number: 458 (2025) Published: 30 October 2025

Background

Amatoxin-related acute liver failure (AT-ALF) carries high mortality without liver transplantation (LTX). While therapeutic plasma exchange (PEX) might improve LTX-free survival in other ALF cases, its role in AT-ALF is unclear. Clinical practice varies, and, given the rarity of this ALF entity, the feasibility of conducting a randomized controlled trial to investigate PEX in AT-ALF is more or less impossible.

Methods

The Amanita-PEX study is a multi-center, international, retrospective study analyzing patients with AT-ALF from 2013 to 2024. The primary outcome was 28-day LTX-free survival (composite endpoint: death or LTX) after ALF diagnosis.

Results

The study included 111 patients from 25 centers: 82 received standard-of-care (SOC), and 29 received at least one PEX-session. PEX and SOC-groups were comparable at baseline, but 76% of PEX- vs. 58% of SOC-patients developed hepatic-encephalopathy (HE) grade ≥ 2 (p = 0.021). While the primary outcome of 28-day LTX-free survival in all patients was not different between the SOC and PEX-groups, in the subgroup of patients with maximal HE grade ≥ 2, LTX-free survival was 19.1% (n = 8/42) in the SOC group, while it was 36.4% (n = 8/22) in patients receiving adjunctive PEX (Gehan-Breslow-Wilcoxon-p = 0.041, Log-Rank-p = 0.060). PEX was independently associated with reduced risk of the combined endpoint death or liver transplantation within 28 days from inclusion in patients with HE grade ≥ 2 (HR 0.37, 95%-CI 0.19–0.73, p = 0.004). After propensity-score-matching, LTX-free survival was 28% in the SOC- and 52% in the PEX group (Gehan-Breslow-p = 0.036; Log-Rank-p = 0.035).

Conclusions

In this real-world study, adjunctive use of PEX was associated with increased LTX-free-survival in patients with AT-ALF and HE grade ≥ 2.

 

 

Positive communication for decreasing burnout in intensive-care-unit staff: a cluster-randomized trial

Intensive Care Medicine Published: 30 October 2025

Purpose

Occupational burnout is common among intensive-care-unit (ICU) staff and adversely affects staff well-being and patient care. We hypothesized that a multicomponent intervention based on organizational support and workplace climate improvement would reduce burnout.

Methods

The 1:1 cluster-randomized Hello trial involved 370 ICUs from sixty countries allocated to either the intervention or usual care. The four-week intervention designed to promote a positive workplace culture and within-team support used posters, email nudges, greetings during morning meetings, role modeling, and positive messages in boxes and on noticeboards. The primary endpoint was burnout prevalence, measured using the Maslach Burnout Inventory. Secondary outcomes included MBI subscale scores, well-being, job satisfaction, ethical climate, intention to leave, work safety, and professional conflicts.

Results

Before the intervention, burnout prevalence was 59.4% (95% CI, 58.6–60.5), with no difference between arms. After the intervention, 4966 intervention-arm and 4602 control-arm healthcare professionals completed the MBI. Burnout prevalence was significantly lower in the intervention arm relative to controls (52.2% vs. 63.3%; adjusted odds ratio, 0.56; 95%CI 0.46–0.68; P < 0.001). Among MBI sub-scales scores, emotional exhaustion and depersonalization were lower, and personal accomplishment was higher in the intervention arm. Staff in the intervention arm reported better job satisfaction, workplace safety, ethical climate, and patient- and family-centered care; they were less often considering a job change.

Conclusions

The Hello intervention reduced burnout and improved workplace culture among ICU staff. Given the pragmatic design, the intervention tested may have broad applicability.

 

 

 

 

Towards optimised nutrition therapy after critical illness: a position statement and research framework by the global research initiative on post-intensive care nutrition (GRIP) consortium

Critical Care volume 29, Article number: 460 (2025) Published: 29 October 2025

Background

While mortality for critically ill patients has decreased, many survivors face persistent physical, cognitive, and psychological impairments, collectively known as post-intensive care syndrome, which significantly reduce health-related quality of life (HRQoL). Nutrition is a crucial component of recovery, yet evidence-based strategies for post-intensive care unit (ICU) nutritional management remain underdeveloped.

Methods

The Global Research Initiative on Post-ICU Nutrition (GRIP) was established to address this gap by advancing research, education, and clinical practice in post-ICU nutrition. International experts in the field of critical care nutrition were invited to a diagnostic matrix meeting, to develop a definition of post-ICU patients relevant to GRIP, discuss emerging evidence regarding post-ICU nutritional management, and identify core research domains to guide future research.

Results

The consortium consensus was achieved. A post-ICU patient is defined as any adult patient who has been admitted to an ICU for more than 48 h and is in the post-ICU recovery phase, which begins after the first ICU discharge and continues for up to one year, regardless of hospital length of stay, readmissions, or discharge destination. Ten core nutrition research domains were identified, including: (1) pathophysiology of post-ICU recovery, (2) phenotyping and personalised nutrition strategies, (3) timing and delivery of nutrition, (4) nutritional intake monitoring and optimisation, (5) nutrition interventions and effectiveness, (6) long-term functional and health-related quality of life outcomes, (7) digital tools and remote monitoring, (8) education and healthcare professional engagement, (9) implementation science and system integration, and (10) patient and family involvement.

Conclusion

GRIP envisions a future in which patients post-ICU receive personalised, timely, and effective nutritional care to enhance recovery, reduce complications, and improve long-term HRQoL. By identifying knowledge gaps, initiating targeted research projects, and supporting global educational efforts, GRIP aims to generate robust evidence, foster international collaboration, and strengthen clinical capacity to improve global post-ICU nutritional care.

 

Respiratory effects of trunk inclination in obese and non-obese patients mechanically ventilated for ARDS

Critical Care volume 29, Article number: 457 (2025) Published: 28 October 2025

Background

Adjusting trunk inclination in patients with acute respiratory distress syndrome directly affects physiological variables such as respiratory mechanics and PaCO2 levels. These effects may vary according to the body mass index (BMI) due to differences in lung and chest wall mechanics, highlighting the need for further investigation to clarify the clinical relevance of body position across patient subgroups.

Methods

A secondary analysis compared the physiological effects of increasing trunk inclination angles between mechanically ventilated patients with obesity (BMI ≥ 30 kg/m2) and those without obesity (BMI < 30 kg/m2).

Results

Data from 159 patients collected across seven individual studies were analyzed. The following physiological changes were observed in response to increased trunk inclination: Sixty-five patients with obesity presented a greater decrease in respiratory system compliance (-7.5 [-10; -5] mL/cmH2O; p < 0.001) compared to ninety-four patients without obesity (-3.5 [-7; -0.08] mL/cmH2O; p = 0.045). Lung compliance decreased in obese patients (-7.8 [-12.4; -3.3] mL/cmH2O; p < 0.001), whereas no significant changes were observed in patients without obesity (-5.9 [-14.2; 2.3] mL/cmH2O; p = 0.160). Chest wall compliance decreased by -42.9 [-63.2; -22.6] mL/cmH2O (p < 0.001) in obese patients and by -47.7 [-95.3; -0.15] mL/cmH2O in non-obese patients (p = 0.049). PaCO2 increased in obese patients by 4.6 [1.4; 7.8] mmHg (p = 0.004) but not in patients without obesity (2.5 [-0.6; 5.6] (p = 0.113). No significant differences were observed in PaO2/FIO2 between phases.

Conclusions

Increasing the trunk inclination angle during passive ventilation reduces respiratory system, lung, and chest wall compliance. This effect was more pronounced in obese patients. Moreover, only this population exhibited an increase in PaCO2. We acknowledge the methodological heterogeneity across the included studies, which may have influenced the results. Overall, our results highlight the importance of considering BMI as a significant variable that influences individual physiological responses to changes in bed inclination.

 

Development of a gene panel for immune status assessment in sepsis

Annals of Intensive Care volume 15, Article number: 170 (2025) Published: 27 October 2025

Background

Sepsis is characterized by a dysregulated immune response to infection, with a balance between hyperinflammation and immunosuppression, which determines the patient's immune status. Real-time monitoring of the immune status in sepsis is crucial for guiding immunotherapy. However, reliable biomarkers are lacking. This study aims to identify a panel of biomarkers for rapid bedside assessment of immune status in sepsis to guide immunotherapy decisions.

Results

TBX21, GNLY, PRF1, and IL2RB represent the immune status in sepsis. These genes demonstrated discriminatory power in the external validation, with area under the curve values ranging from 0.891 to 0.909 across several machine learning models. 99 double-blind randomized patients with sepsis were clustered into two endotypes on the basis of the expression of the four-gene panel. Higher 90-day mortality was observed in patients with sepsis treated with hydrocortisone (Odds ratio 12.46, 95% confidence intervals 3.11 to 65.72) or thymosin (Odds ratio 4.17, 95% confidence intervals 1.13 to 16.51) within the high-expression 4-gene panel endotype, but not in another endotype.

Conclusions

The results support the potential utility of a four-gene panel to assess immune status and guide immunotherapy; further prospective validation and translational studies are warranted.

Trial registration National Medical Research Registration and Filing Information of China, 2022ZDSYLL196-P01. Registered 26 May 2023, https://www.medicalresearch.org.cn/login

 

Do diabetes and poor control of acute stress-related hyperglycemia increase the risk of ICU-acquired infections? A retrospective assessment in patients with septic shock

Annals of Intensive Care volume 15, Article number: 168 (2025) Published: 22 October 2025

Background

Patients with septic shock who survive the early resuscitation phase are prone to ICU-acquired infections. Although hyperglycemia harbors potent immunomodulatory properties, the impact of preexisting diabetes and the control of acute stress-induced hyperglycemia on the risk of further infections remains unclear.

Materials and methods

We conducted a retrospective (2008–2023) single-center study in patients with septic shock who remained alive in the ICU after 72 h. Glycemic control was assessed during the first 72 h. Mild and severe hyperglycemia were defined by blood glucose levels > 8 mmol/L and > 10 mmol/L, respectively. Poor glycemic control was defined when blood glucose levels were above 8 mmol/L for more than 20% of time. The primary outcome was ICU-acquired infections.

Results

The study involved 901 patients, with preexisting diabetes present in 22% of them. Most patients (71%) experienced hyperglycemic episodes > 8 mmol/L, prompting fast-acting insulin treatment. ICU-acquired infections developed in 243 patients (26.9%), with median time from ICU admission to diagnosis of 9 days, interquartile range [6–13]. There was no association between preexisting diabetes and ICU-acquired infections. Patients with further ICU-acquired infections displayed poorer control of stress-induced hyperglycemia, with longer exposure to hyperglycemia (78% with mild or severe hyperglycemia for more than 20% of time compared to 68% of patients without subsequent infections (p = 0.005)). Poor glycemic control was independently associated with the development of ICU-acquired infections.

Conclusion

72-hour poor glycemic control, but not preexisting diabetes, was independently associated with an increased risk of ICU-acquired infections in septic shock patients and may therefore contribute to the post-aggressive immunosuppressive response. This argues for effective glycemic management to improve outcomes in this setting.

 

Does obesity impact on weaning from invasive ventilation: a secondary analysis of the WEAN SAFE study

Annals of Intensive Care volume 15, Article number: 164 (2025) Published: 21 October 2025

Objective

To understand the impact of obesity on outcomes of weaning from invasive mechanical ventilation (MV).

Methods

The study population consisted of patients enrolled in the WEAN SAFE study. We defined 4 groups based on body mass index (BMI), namely: Normal weight (BMI 18.5–24.9 kg/m²), Overweight (BMI 25–29.9 kg/m²), Obesity Class I (BMI 30–34.9 kg/m²), and obesity classes II and III (BMI ≥ 35 kg/m²). The primary outcome was the rate of successful extubation in patients in each BMI group. Secondary outcomes included the ICU and hospital survival, and PEEP levels at time of weaning eligibility in patients in each BMI group.

Results

In the study population, 1728 (38.2%) were of normal weight, 1395 (30.8%) were overweight, 590 (13.1%) were class I Obesity, and 431 (9.5%) were obesity classes II and III. Patients with obesity were more likely to be female, to be a medical admission, and to have comorbidities. Patients with grade II-III obesity had lower levels of sedation, later timing of the first separation attempt, longer time to weaning success, they received more noninvasive ventilation post extubation, and they had a longer ICU stay. In contrast, weaning success, and ICU and hospital mortality rates were not different in obese patients. There was no independent relationship between obesity and weaning delay, weaning success, or with overall survival outcomes. Higher PEEP at weaning eligibility was associated with weaning failure in normal and overweight patients but not in patients with obesity.

Conclusions

Patients with obesity had a more complex and longer weaning process, but obesity per se was not independently associated with adverse weaning outcomes.

 

 

Critical Care Bulletin: October 2025

 

Antibiotic therapy in necrotizing soft tissue infections: a narrative review of the greater Paris SURFAST consortium

Critical Care volume 29, Article number: 431 (2025)  Published: 10 October 2025

Abstract

Necrotizing soft tissue infections (NSTIs) are uncommon, yet rapidly progressive and potentially fatal conditions. However, evidence-based guidance on antibiotic therapy remains limited. Current recommendations emphasize the need for broad-spectrum empirical coverage, including gram-positive, gram-negative, anaerobes, and Streptococcus pyogenes when clinically indicated. We aimed at developing a practical, evidence-based framework for empirical antibiotic therapy in NSTIs. This narrative review is informed by a comprehensive literature search of PubMed, without date restrictions. We propose a structured decision-making algorithm for empirical antibiotic selection in NSTIs, integrating key clinical parameters: infection site, healthcare-associated versus community-acquired origin, risk factors for extended-spectrum β-lactamase-producing Enterobacterales and methicillin-resistant Staphylococcus aureus, and signs of sepsis or septic shock. Alternative regimens are provided for patients with severe β-lactam allergies. Special considerations for immunocompromised and other vulnerable host populations are also addressed. This review offers clinicians a pragmatic, stepwise approach to antibiotic therapy in NSTIs, while identifying critical knowledge gaps and priorities for future research.

 

Potential therapeutic benefit of exogenous ketone ester administration in delirium: a narrative review

Critical Care volume 29, Article number: 424 (2025) Published: 07 October 2025

Abstract

Delirium is a prevalent neuropsychiatric syndrome during critical illness and is associated with prolonged hospitalization, increased mortality, and post-ICU cognitive decline. It is hypothesized to result from systemic inflammation, disrupted neurotransmission, and failure of cerebral energy metabolism. This narrative review highlights the key role of altered neurometabolism and neuroinflammation, which occurs due to peripheral inflammation, compromised blood-brain barrier integrity, and increased microglial glycolysis. These changes limit neuronal glucose uptake, leading to a brain energy crisis and consequently amplifying oxidative and inflammatory stress. We focus on studies of ICU delirium in the setting of acute critical illness with an emphasis on sepsis-associated encephalopathy, where mechanistic data derived from murine models are most robust. Ketones bypass the glycolytic bottleneck and enter the tricarboxylic acid cycle directly, activating signaling pathways that enhance mitochondrial biogenesis, bolster antioxidant defenses, modulate neurotransmission, and reduce inflammation. In models of neurodegenerative diseases and traumatic brain injury, ketosis restores cerebral metabolism, reduces neuroinflammation, and enhances cognitive function. Additionally, preliminary human studies have demonstrated cognitive benefits and patient tolerance of ketone supplementation. Although data in the critically ill are limited, pilot studies suggest that enteral ketone supplementation can safely achieve therapeutic serum concentrations without worsening acidosis or hemodynamic instability. We hypothesize that exogenous ketone ester supplementation may support brain energy production by providing an alternative substrate for energy production, reducing microglial substrate competition, and mitigating the neuronal stress that precipitates delirium. In conclusion, exogenous ketone esters are a biologically plausible, rapidly acting metabolic intervention that warrants rigorous clinical evaluation as a novel strategy to prevent or treat delirium in those who are critically ill. However, randomized controlled trials are essential for verifying safety, determining optimal dosing, and assessing clinical effectiveness in the intensive care setting.

 

Beyond diabetes: harnessing the power of metformin in burn care

Critical Care volume 29, Article number: 423 (2025) Published: 07 October 2025

Abstract

Burn injuries are complex and devastating traumas that trigger a profound systemic metabolic response, characterized by hyperglycemia, insulin resistance, and a hypermetabolic state. Notably, hyperglycemia is a critical determinant of worse prognoses in burn patients. While insulin has long been the gold standard for managing post-burn hyperglycemia, its therapy is associated with a risk of hypoglycemic events, which can exacerbate morbidity and compromise patient outcomes. As such, investigation of alternative therapeutics is warranted to improve glycemic control while mitigating associated risks. Recently, metformin, a first-line therapy for the treatment of type II diabetes, has emerged as a potential therapeutic agent for the management of post-burn hyperglycemia as well as other burn injury sequelae. This review examines the mechanistic underpinnings of metformin, its potential application in managing post-burn hyperglycemia, and its comparative advantages over other hypoglycemic agents. Additionally, we examine the broad spectrum of metformin’s pleiotropic effects in the context of burn injury–extending beyond glycemic control to include attenuation of muscle catabolism, suppression of lipolysis, regulation of non-shivering thermogenesis, support of mitochondrial and immune function, enhanced wound healing, and its potential role in addressing burn-induced acceleration of biological aging. Taken together, we discuss how metformin represents a paradigm shift in burn care, with the potential to substantially improve patient outcomes.

 

Tidal volume and mortality during extracorporeal membrane oxygenation for acute respiratory distress syndrome: a multicenter observational cohort study

Annals of Intensive Care volume 15, Article number: 151 (2025) Published: 06 October 2025

Background

Approximately half of the patients with acute respiratory distress syndrome (ARDS) receiving extracorporeal membrane oxygenation (ECMO) remain ECMO-dependent beyond 14 days after ECMO initiation. The identification of factors associated with mortality during an ECMO run may update prognostic assessment and focus clinical interventions.

Methods

In this observational study, data from 1137 patients with COVID-19 ARDS receiving ECMO support in 29 German centers between January 1st 2020 and July 31st 2021 were analyzed. Multivariable stepwise logistic regression analyses were performed to build survival prediction models with day-by-day data during the first 14 days of an ECMO run. The primary endpoint was all-cause mortality in the intensive care unit.

Results

Mortality in this cohort was high (75%). Patients who remained ECMO-dependent on day 14 of their ECMO run showed comparable mortality to all patients receiving ECMO support on day 1. Yet, factors associated with mortality changed during the first 14 days of ECMO support. On day 1 of ECMO support, only patient age and lactate remained in the final mortality prediction model. On day 14 of an ECMO run, tidal volume was independently associated with mortality (adjusted Odds Ratio 0.693 (95%CI 0.564–0.851), p < 0.001 for 1 mL/kg increase in tidal volume per predicted body weight). The adjusted mortality for patients with a tidal volume below 2 mL/kg on day 14 of their ECMO run was above 80% (lower limit of the 95%CI interval). Higher tidal volume was mainly based on higher respiratory system compliance. Yet, the benefit of higher compliance was not observed in some patients who were still ventilated with very low driving pressures despite remaining ECMO-dependent on day 14 of ECMO support.

Conclusions

Mortality predictors change during the course of an ECMO run. In a cohort with high mortality, on day 14 of ECMO support for ARDS, tidal volume may be an independent predictor of mortality. Further analyses on ventilation strategies in patients who remain ECMO-dependent are needed.

 

Post-intensive care unit clinics: models and implementation - a systematic review

Critical Care volume 29, Article number: 421 (2025) Published: 06 October 2025

Background

Advances in critical care have shifted the focus from survival alone to addressing Post-Intensive Care Syndrome (PICS), which includes persistent physical, cognitive, and psychological challenges after discharge from the intensive care unit (ICU). While post-ICU clinics have been established in high-income countries (HICs), their adoption in low- and middle-income countries (LMICs) remains limited, with structured follow-up care still under development.

Objective

To systematically review models of post-ICU clinics, examine barriers and facilitators to their implementation, and explore their potential applicability in LMICs.

Methods

This review was prospectively registered with PROSPERO (CRD42024536147) and conducted according to PRISMA guidelines. A comprehensive search of Medline, Embase, and CINAHL was completed on April 24, 2024. Studies published after 2000 describing adult post-ICU clinic models addressing PICS were included. Nineteen studies—comprising randomized controlled trials, observational studies, and quasi-experimental designs—met inclusion criteria. Risk of bias was assessed using the Joanna Briggs Institute checklists. Thematic synthesis was guided by the Consolidated Framework for Implementation Research (CFIR).

Results

Three primary models emerged: (1) hospital-based physical interviews (2), hybrid models incorporating both in-person and telehealth consultations, and (3) fully remote models using telehealth or home visits. Telehealth/home-visit models reported the highest mean attendance (88.7%), followed by hybrid (59%) and physical interview models (51.9%). Common barriers included resource constraints, transportation difficulties, limited awareness, inadequate insurance coverage, and poor interdisciplinary coordination. Facilitators included flexible scheduling, early stakeholder engagement, multidisciplinary team involvement, and use of telehealth technologies. While hybrid models appeared promising for LMICs due to their balance of accessibility and comprehensiveness, the evidence for clinical outcome benefit remains inconclusive, and questions about cost-effectiveness and sustainability persist.

Conclusion

Hybrid post-ICU clinic models may offer a feasible pathway for improving follow-up care in LMICs, especially when tailored to local constraints. However, their implementation must consider significant barriers, particularly related to funding and infrastructure, and be guided by emerging but still limited evidence on long-term patient outcomes. These findings aim to inform cautious, context-specific development of post-ICU care strategies in resource-limited settings.

 

Optimal cerebrovascular reactivity thresholds for the determination of individualized intracranial pressure thresholds in traumatic brain injury: a CAHR-TBI cohort study

Critical Care volume 29, Article number: 420 (2025) Published: 06 October 2025

Abstract

It has been demonstrated that patient-specific intracranial pressure (ICP) thresholds are possible to derive using the function intersectionality between ICP and cerebrovascular reactivity (CVR). Such individualized ICP (iICP) thresholds represent a potential personalized medicine approach to neurocritical care management. However, it is currently unknown how various CVR thresholds compare in regard to deriving iICP. Here we attempt to identify the CVR thresholds that are best suited for iICP derivation. Leveraging 365 patient data sets from the CAnadian High-Resolution TBI (CAHR-TBI) Research Collaborative, iICP was derived using three ICP-based CVR indices: the pressure reactivity index (PRx); the pulse amplitude index (PAx); and the RAC index, and thresholds ranging from − 1 to + 1, in 0.05 increments. Patients were dichotomized based on 6-month outcome scores into Alive vs. Dead and Favorable vs. Unfavorable outcome. 2 × 2 tables were created for each threshold, grouping patients by outcome and whether their mean ICP was greater or less than their calculated iICP. Chi-squares were calculated for each table and subsequently plotted. The thresholds that produced the largest Chi-square values were identified as those able to derive the iICP with the greatest ability to predict outcomes. Next, Spearman rank correlation testing was used to evaluate associations between iICP, for each threshold, and measures of cerebral physiologic insult burden. With consideration of yield data, ability to predict outcome, and association with cerebral physiologic insult burden, a threshold of + 0.05 was identified for PRx. No optimal threshold could be identified for PAx or RAC.

 

Melatonin and delirium in the intensive care units: a systematic review and meta-analysis of randomized controlled trials

 

Intensive Care Medicine Published: 06 October 2025

Background

Delirium is frequent in critically ill patients and is associated with increased mortality. Discrepancies were found in the results of recent randomized controlled trials (RCTs) regarding the effect of melatonin to prevent delirium onset in critically ill patients.

Methods

We searched MEDLINE, Embase, and Web of Science from inception to 5 July 2025 for RCTs evaluating melatonin in critically ill patients. The primary outcome was the incidence of delirium. The main secondary outcome was mortality. We generated pooled risk ratios (RR). To base our conclusions on the highest quality of evidence, our primary analysis was based only on the trials with low to moderate risk of bias for each outcome. A secondary analysis was conducted, including all the trials.

The study was registered with PROSPERO (CRD420251041661).

Findings

Our primary analysis was based on six RCTs with 2209 patients and did not show any difference in the incidence of delirium attributable to the treatment with melatonin (RR 0.89, [95% confidence interval (CI) 0.73—1.09]). This result was consistent with the secondary analysis including thirteen RCTs with 2830 patients (RR 0.86, [95% CI 0.70–1.04]). No association was found between mortality and melatonin in the primary (seven RCTs, 2165 patients, RR 0.87, [95% CI 0.73–1.02]) and secondary (8 RCTs, 2396 patients, RR 0.92, [95% CI 0.79–1.06]) analyses.

Interpretation

The results suggest that compared to placebo, melatonin does not reduce delirium incidence in critically ill patients. Similarly, no effect was observed on mortality.

 

Determinants of ICU memories and the impact on the development and trajectory of post-traumatic stress symptoms: a multicenter longitudinal cohort study

Intensive Care Medicine Published: 06 October 2025

 Purpose

To identify demographic and clinical determinants of memory formation in intensive care unit (ICU) patients, and determine the relationship between ICU memories and the development and trajectory of post-traumatic stress disorder (PTSD) symptoms.

Methods

Adult patients (n = 426) from two Dutch University ICUs underwent a structured telephone interview using the validated ICU-Memory Tool (ICU-MT) 3 months post-ICU and were assessed for symptoms of PTSD using the Impact of Event Scale (IES-6) at 3 and 12 months post-ICU.

Results

Factual memories without delusional memories were present in 47.7% (n = 203), complete ICU amnesia in 13.8% (n = 59), and delusional memories in 38.5% (n = 164) of patients. Delirium was present in 41% (n = 68) of patients with delusional memories. Using multinomial logistic regression, female sex and number of days with deep sedation were associated with ICU amnesia (aOR 1.99, 95% CI 1.04–3.81, and aOR 1.34, 95% CI 1.09–1.65, respectively), whereas delirium and length of ICU stay were associated with delusional memories (aOR 1.94, 95% CI 1.04–3.61, and aOR 1.11, 95% CI 1.02–1.21, respectively). Of 250 patients assessed at both time points, the prevalence of PTSD symptoms increased significantly over time (4.5 to 10.0%, p < 0.01), driven by a significant increase among those with delusional memories (6.7 to 18.1%, p < 0.01). In a linear mixed-effects model, delusional memories were independently linked to both 3- and 12-month symptoms of PTSD (vs. factuals, adjusted %-difference in mean IES score, 12.9%, 95% CI 2.6–24.1%, and 18.1%, 95% CI 5.2–32.5%, respectively).

Conclusions

Female sex and prolonged deep sedation were associated with complete ICU amnesia, whereas a longer ICU stay and delirium were associated with delusional memories, although these memories were also common in those without delirium. Delusional memories were independently linked to the development and persistence of PTSD symptoms. Targeted interventions to mitigate memory disturbances, both during and after the ICU, may help alleviate the psychological impact of critical illness.