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.

 

 

Beyond the bleed: complications after aneurysmal subarachnoid hemorrhage. Pathophysiology, clinical implications, and management strategies: a review

Critical Care volume 29, Article number: 414 (2025) Published: 30 September 2025

Abstract

Aneurysmal subarachnoid hemorrhage is a critical condition with high case-fatality and lasting impacts on survivors. Acute events that are the direct result of aneurysm rupture, such as acute ischemia, elevated intracranial pressure, cerebral edema, seizures, and hydrocephalus, lead to early brain injury. A delayed cascade of processes, including a prominent systemic inflammatory response, may lead to secondary brain injury and delayed cerebral ischemia, which often further impairs recovery. Systemic complications, including cardiac and pulmonary dysfunction, fever, and electrolyte imbalances, arise in the interplay between early and secondary brain injury and challenge the clinical course. Early management focuses on the prevention of rebleeding mainly through aneurysm securement, amelioration of early brain injury through cerebrospinal fluid drainage, control of intracranial pressure, and organ support to avoid or attenuate secondary brain injury. Nimodipine remains the only pharmacological agent shown to reduce delayed cerebral ischemia, and lumbar drainage of cerebrospinal fluid to reduce subarachnoid blood may improve outcome. Management strategies for hemodynamic interventions, seizures, intracranial pressure control, large artery vasospasm, and electrolytes remain consensus-based and with large variation in practice. Several advances in understanding inflammation and delayed cerebral ischemia, as well as in monitoring and interventions hold promise, but robust trials are needed to refine protocols and improve patient recovery. Understanding and mitigating the cascade of damage from rupture to recovery is essential to reduce the burden of this devastating condition. In this review, we appraise the current understanding of the pathophysiology of post-rupture complications as well as scientific and management data, with a focus on recent advances.

 

Circulating biomarkers of vasoplegia: a systematic review

Annals of Intensive Care volume 15, Article number: 150 (2025) Published: 30 September 2025

 

Background

Vasoplegia is characterised by persistent hypotension and reduced systemic vascular resistance despite preserved cardiac output, commonly arising in sepsis, following major surgery, and within systemic inflammatory responses. Despite its clinical significance and association with poor outcomes, there is no universally accepted definition or standardised biomarker, impeding early diagnosis, stratification, and targeted therapy. While individual studies have examined biomarkers within specific clinical contexts such as septic shock or cardiac surgery, no comprehensive synthesis across all aetiologies of vasoplegia has previously been undertaken.

Objectives

To systematically evaluate and synthesise the current evidence regarding circulating biomarkers associated with the incidence, severity, prediction, and progression of vasoplegia across diverse critical care and perioperative populations. As well as review definitions used across literature.

Methods

This systematic review was conducted in accordance with PRISMA 2020 guidelines and registered on PROSPERO (CRD42024438786). Studies were included if they investigated adult patients in critical care or perioperative settings with vasoplegia defined by reduced vascular resistance and hypotension requiring vasopressors.

Results

A total of 43 studies met inclusion criteria. The included studies examined 39 unique biomarkers, with renin and adrenomedullin being the most frequently studied. Heterogeneity in definitions of vasoplegia, outcome measures, and comparator populations precluded meta-analysis. However, several biomarkers demonstrated potential clinical utility: elevated renin levels correlated with vasopressor requirements and haemodynamic instability, while adrenomedullin levels were predictive of vasoplegia development and duration.

Conclusions

The lack of standardisation in biomarker assay methods and vasoplegia definitions remains a significant barrier to comparative analysis. Whilst this review highlights renin and adrenomedullin as promising candidate biomarkers for vasoplegia, the heterogeneity in study design, biomarker measurement, and diagnostic criteria underscores the urgent need for a consensus definition of vasoplegia, standardised sampling protocols, and unified outcome measures. Future research should focus on biomarker-guided risk stratification and personalised therapies, with an emphasis on validating predictive and mechanistic roles across diverse vasoplegic phenotypes.

 

 

Comparison of two transpulmonary pressure-based positive end-expiratory pressure titration strategies in acute respiratory distress syndrome: a randomized crossover study

Critical Care volume 29, Article number: 409 (2025) Published: 29 September 2025

Background

Esophageal pressure monitoring, which enables the estimation of transpulmonary pressure, has been proposed to personalize ventilator settings, particularly positive end-expiratory pressure (PEEP), in patients with acute respiratory distress syndrome (ARDS). Two conceptually different transpulmonary pressure-based PEEP titration strategies have thus been described but have never been compared. This study aims to compare the PEEP levels obtained with these two distinct strategies and their physiological effects.

Methods

This was a randomized crossover physiological study. Twenty patients with moderate to severe ARDS (PaO2/FiO2 < 150 mmHg) were included in an academic intensive care unit. The two transpulmonary pressure-based PEEP titration strategies were applied for 45 min each in a randomized order, separated by a 45-minute washout period. In the directly measured expiratory transpulmonary pressure (PL, exp) strategy, PEEP was set to target a PL, exp using a PL, exp/FiO2 table. In the calculated inspiratory transpulmonary pressure (PL, insp) strategy, PEEP was set to maintain PL, insp estimated using the lung/respiratory system elastance ratio between 20 and 22 cmH2O. Gas exchange, hemodynamics and partitioned respiratory mechanics were assessed at the end of each PEEP application period.

Results

Median PEEP levels determined by the two strategies were not different; however, individual values were uncorrelated, with a difference of at least 3 cmH2O in 14 (70%) patients. The PL, insp strategy resulted in higher PEEP levels than the PL, exp strategy in the non-obese patients but not in the obese patients. The effects on gas exchange, hemodynamics, and respiratory mechanics did not differ between the two strategies considering the entire study population or the obese and non-obese patients separately. Recruitment with PEEP (assessed by the recruited lung volume from PEEP 5 cmH2O), PL, insp, transpulmonary driving pressure and lung strain did not differ between the two strategies.

Conclusions

The two transpulmonary pressure-based titration strategies result in different PEEP levels in most patients. Neither strategy is associated with higher recruited lung volume or lower estimated Stress and Strain.

 

 

Sex differences in sepsis outcomes across the lifespan: a population-based cohort study in Germany

Critical Care volume 29, Article number: 408 (2025) Published: 26 September 2025

 

Importance

Sepsis is a major global health concern influenced by both biological sex and socially constructed gender roles, which can affect disease susceptibility, progression, treatment and outcomes. Evidence on sex-specific differences in sepsis often lacks age-specific analysis, despite known interactions between sex, age, and immune function.

Objective

We aimed to investigate age-dependent associations between sex and mortality as well as long-term outcomes among sepsis survivors after hospitalization.

Design, setting, and participants

This retrospective, population-based cohort study based on nationwide health claims data from 2009 to 2017 of 23.0 million beneficiaries of a large German health insurance provider. Patients aged 15 years and older with incident hospital-treated sepsis identified by ICD-10-GM codes in 2013 to 2014 were included.

Exposures

Female and male sex.

Main outcomes and measures

Differences in 12-months mortality, medical, psychological and cognitive diagnoses, as well as dependency on nursing care by sex and age were analyzed using generalized additive models including sex*age interaction effects. We report average marginal effects (AME) for sex and age as estimates of the adjusted marginal increase or decrease of the event rate of outcomes.

Results

We included 159,684 sepsis patients in 2013/2014, of which 75,809 (47.5%) were female and 83,875 (52.5%) were male. The average marginal hospital and 12-months mortality over the observed age distribution was AME = − 2.8% (95% CI, − 3.2%, − 2.3%, P < .001) and AME = − 5.4% (95% CI, − 5.9%, − 4.9%, P < .001) lower in females, respectively. Significant female survival benefits were predominantly found beyond age 44 (hospital mortality) and age 47 (12-months mortality). Females were also less often affected by cognitive impairments, but more often experienced psychological and physical impairments as well as nursing care dependency with differential associations observable across the lifespan.

Conclusion and relevance

Sepsis long-term outcomes appear to be influenced by a complex interaction between age and sex. While our study focuses on these factors, it is important to acknowledge that observed associations cannot be attributed to biological sex alone, as numerous additional factors - directly or indirectly related to sex- may also contribute. These findings underscore the importance of incorporating sex-specific considerations into sepsis care and post-acute support strategies to improve long-term outcomes.

 

Use of a molecular syndromic panel for the etiological diagnosis of ventilator-associated bacterial pneumonia: impact on clinical outcomes and antibiotic use from a multicenter, prospective study

Critical Care volume 29, Article number: 403 (2025) Published: 25 September 2025

Background

Ventilator-associated bacterial pneumonia (VABP) is a common infection in critically ill patients in intensive care units (ICU), with attributable mortality of up to 13%, and its etiological diagnosis remains challenging.

Materials and methods

We conducted a multicenter, prospective, observational study within the MULTI-SITA platform to assess the impact on relevant clinical and antimicrobial stewardship outcomes of the use of a molecular syndromic panel (BIOFIRE® FILMARRAY® Pneumonia plus), in addition to a standard approach based on culture. The primary outcome measure was 30-day mortality from VABP onset.

Results

Overall, 237 patients with VABP were included in the study. In multivariable analysis, SOFA score (hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.04–1.22, p = 0.003), previous isolation of carbapenem-resistant Pseudomonas aeruginosa (HR 3.02, 95% CI 1.25–7.32, p = 0.015), and solid neoplasm (HR 2.15, 95% CI 1.12–4.14, p = 0.022) were associated with increased mortality, while no association was registered for the molecular syndromic panel performed (HR 1.07, 95% CI 0.59–1.93, p = 0.825). In secondary analyses, use of the molecular syndromic panel resulted in more events of either de-escalation or initiation of appropriate antibiotic therapy at day 1 from VABP onset in comparison with a standard approach based on culture only (41.3% vs. 27.8%, p = 0.041).

Conclusion

The use of a molecular syndromic panel in patients with VABP was able to impact antibiotic decisions, without an unfavorable effect on mortality. Further study is necessary to assess the long-term effects in terms of antimicrobial stewardship of molecular syndromic panels-based antibiotic treatment decisions.

Critical Care Bulletin: August 2025

 

Immunosuppressive therapy management during sepsis in kidney transplant recipients: a prospective multicenter study

Annals of Intensive Care volume 15, Article number: 116, Published: 10 August 2025

Background

Sepsis is the leading cause of Intensive Care Unit (ICU) admissions in kidney transplant recipients (KTRs). However, the optimal immunosuppressive therapy (IST) management in this context is not well-defined. We aimed to evaluate the impact of IST management in the ICU on mortality rates and kidney graft function 6 months after inclusion in KTRs admitted for sepsis.

Methods

We conducted a multicenter, prospective, observational study over 1 year in 11 French ICUs. Inclusion criteria were all KTRs who have been transplanted for at least 3 months, admitted to the ICU for sepsis. All changes of IST (7 days prior to ICU admission or throughout the ICU stay) were collected. The primary outcome was MAKE 180 (Major Adverse Kidney Event), a composite outcome including mortality, kidney graft dysfunction and dialysis requirement at 180 days after inclusion.

Results

One hundred and twenty-four patients were included. The main cause of ICU admission was respiratory failure for 78 patients (62.9%). Predominant IST management was mycophenolic acid (MPA) discontinuation for 74 patients (59.7%) and calcineurin inhibitor (CNI) continuation for 63 patients (50.8%). By multivariable analysis, after adjustment for age, non-renal SOFA score at admission, kidney function at admission, sex, and history of cellular rejection we did not find any significant association between MAKE 180 and CNI discontinuation (adjusted OR = 1.05, 95% CI 0.87–1.26, p = 0.6). In contrast, MPA discontinuation was significantly associated with MAKE 180 (adjusted OR = 1.45, 95% CI 1.07–1.96, p = 0.018). No significant association was found between IST discontinuation and ICU-acquired infections (adjusted OR = 1.14, 95% CI 0.95–1.36, p = 0.157). Among ICU survivors, only 2 graft rejections occurred during the year following ICU discharge.

Conclusion

This study is the first prospective investigation to suggest an association between MPA discontinuation and adverse outcomes during sepsis in critically-ill KTRs. These findings must be interpreted with caution given the potential confounding introduced by SARS-Cov-2–specific treatment protocols. Further interventional trials are necessary to optimize immunosuppressive drug strategies in KTRs during sepsis.

 

Cost-effectiveness of rapid, ICU-based, syndromic PCR in hospital-acquired pneumonia: analysis of the INHALE WP3 multi-centre RCT

Critical Care volume 29, Article number: 352, Published: 08 August 2025

Background

Hospital-acquired and ventilator-associated pneumonia (HAP and VAP) are pneumonias arising > 48 h after admission or intubation respectively. Conventionally, HAP/VAP patients are given broad-spectrum empiric antibiotics at clinical diagnosis, refined after 48–72 h, once microbiology results become available. Molecular tests offer swifter results, potentially improving patient care. To investigate whether this potential is realisable, we conducted a pragmatic multi-centre RCT (‘INHALE WP3’) of rapid, syndromic polymerase chain reaction (PCR) in ICU HAP/VAP compared with standard of care. As the use of molecular tests impact on hospital resources, it is important to consider their potential value-for-money to make fully informed decisions. Consequently, INHALE WP3 included an economic evaluation, presented here. Its aim was to estimate the cost-effectiveness of an in-ICU PCR (bioMérieux BioFire FilmArray Pneumonia Panel) in HAP/VAP, informing whether to implement such technology in routine NHS care.

Methods

We collected data on patient resource use and costs. These data were combined with INHALE WP3’s two primary outcome measures: antibiotic stewardship at 24 h and clinical cure at 14 days. Cost-effectiveness analyses were carried out using regression models adjusting for site. Sensitivity analyses explored assumptions and sub-group analyses explored differential impacts.

Results

We found lower total ICU costs (including PCR costs) in the intervention (PCR-guided therapy) group. Average costs were £40,951 for standard of care compared with £33,149 for the intervention group, a difference of − £7,802 (95% CI: − £15,696, £92). For antibiotic stewardship, the PCR-guided therapy was both less costly and more effective than routine patient management. For clinical cure, we did not find PCR-guided therapy to be cost-effective due to fewer cases being cured in the intervention group.

Conclusions

We found lower average ICU costs with the Pneumonia Panel. The pneumonia panel was cost-effective in terms of antibiotic stewardship, but not clinical cure.