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.