Other bulletins in this series include:

Breast Surgery

Thursday, 13 November 2025

 

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.


 

 

Tuesday, 14 October 2025

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.