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.