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.

 

Muscle weakness after critical illness: unravelling biological mechanisms and clinical hurdles

Critical Care volume 29, Article number: 248 (2025)

Abstract

Survivors of intensive care unit (ICU) are increasingly numerous because of better hospital care. However, several consequences of an ICU stay, known as post-intensive care syndrome, worsen long-term prognoses. A predominant feature in survivors is reduced muscle strength, mass, and physical function. This leads to lower exercise capacity, long-lasting physical disability, higher mortality risk, and subsequent health costs. While ICU-acquired muscle weakness has been extensively studied these past decades, underlying mechanisms of post-ICU muscle weakness remain poorly understood, and there is still no evidence-based treatment for improving long-term physical outcomes. One hypothesis, among others, could be that the pathophysiology is dynamic over time, differing between the acute ICU and post-ICU recovery periods. This narrative review aims to address the clinical, physiological and biological determinants of persistent muscle dysfunction in ICU survivors, with particular attention to the molecular, cellular and systemic mechanisms involved. Specifically, pre-ICU health factors such as obesity and sarcopenia, ICU-related complications and treatments, and post-ICU management all influence recovery. Dysfunctions in the neuroendocrine, vascular, neurological, and muscle systems contribute as physiological determinants of the muscle weakness. Complex and multifaceted biological mechanisms drive the post-ICU muscle dysfunction with mitochondrial and autophagy dysfunction, epigenetic modifications, cellular senescence, muscle inflammation with altered cell–cell communication, including dysfunction of immune cells, stem cell exhaustion and extracellular matrix remodelling. The review also sheds light on new and innovative therapeutic approaches and discusses future research directions. Emphasis is placed on the potential for multi-approach treatments that integrate nutritional, physical, and biological interventions. Addressing these aspects in a holistic and dynamic manner, from ICU to post-ICU phases, may provide avenues for mitigating the long-term burden of muscle weakness and physical disability in ICU survivors.

 

Improving management of ARDS: uniting acute management and long-term recovery

 

by Nicola Latronico, M. Eikermann, E. W. Ely and D. M. Needham 

 

Critical Care volume 28, Article number: 58 (2024) Published: 23 February 2024

 

Acute Respiratory Distress Syndrome (ARDS) is an important global health issue with high in-hospital mortality. Importantly, the impact of ARDS extends beyond the acute phase, with increased mortality and disability for months to years after hospitalization. These findings underscore the importance of extended follow-up to assess and address the Post-Intensive Care Syndrome (PICS), characterized by persistent impairments in physical, cognitive, and/or mental health status that impair quality of life over the long-term. Persistent muscle weakness is a common physical problem for ARDS survivors, affecting mobility and activities of daily living. Critical illness and related interventions, including prolonged bed rest and overuse of sedatives and neuromuscular blocking agents during mechanical ventilation, are important risk factors for ICU-acquired weakness. Deep sedation also increases the risk of delirium in the ICU, and long-term cognitive impairment. Corticosteroids also may be used during management of ARDS, particularly in the setting of COVID-19. Corticosteroids can be associated with myopathy and muscle weakness, as well as prolonged delirium that increases the risk of long-term cognitive impairment. The optimal duration and dosage of corticosteroids remain uncertain, and there's limited long-term data on their effects on muscle weakness and cognition in ARDS survivors. In addition to physical and cognitive issues, mental health challenges, such as depression, anxiety, and post-traumatic stress disorder, are common in ARDS survivors. Strategies to address these complications emphasize the need for consistent implementation of the evidence-based ABCDEF bundle, which includes daily management of analgesia in concert with early cessation of sedatives, avoidance of benzodiazepines, daily delirium monitoring and management, early mobilization, and incorporation of family at the bedside. In conclusion, ARDS is a complex global health challenge with consequences extending beyond the acute phase. Understanding the links between critical care management and long-term consequences is vital for developing effective therapeutic strategies and improving the quality of life for ARDS survivors.

Critical Care Bulletin - March 2023

 

Incidence of near-death experiences in patients surviving a prolonged critical illness and their long-term impact: a prospective observational study

 

by Anne-Françoise Rousseau, Laurence Dams, Quentin Massart, Laila Choquer, Héléna Cassol, Steven Laureys, Benoit Misset, Nadia Dardenne, Olivia Gosseries and Charlotte Martial 

 

Critical Care volume 27, Article number: 76 (2023)

 

Background

So far, the few prospective studies on near-death experience (NDE) were carried out only in intensive care unit (ICU) patients with homogeneous aetiologies, such as cardiac arrest or trauma survivors. The aims of this 1-year prospective and monocentric study were to investigate the incidence of NDE in ICU survivors (all aetiologies) as well as factors that may affect its frequency, and to assess quality of life up to 1 year after enrolment.

Methods

We enrolled adults with a prolonged ICU stay (> 7 days). During the first 7 days after discharge, all eligible patients were assessed in a face-to-face interview for NDE using the Greyson NDE scale, dissociative experiences using the Dissociative Experience Scale, and spirituality beliefs using the WHOQOL-SRPB. Medical parameters were prospectively collected. At 1-year after inclusion, patients were contacted by phone to measure quality of life using the EuroQol five-dimensional questionnaire.

Results

Out of the 126 included patients, 19 patients (15%) reported having experienced a NDE as identified by the Greyson NDE scale (i.e. cut-off score ≥ 7/32). In univariate analyses, mechanical ventilation, sedation, analgesia, reason for admission, primary organ dysfunction, dissociative and spiritual propensities were associated with the emergence of NDE. In multivariate logistic regression analysis, only the dissociative and spiritual propensity strongly predicted the emergence of NDE. One year later (n = 61), the NDE was not significantly associated with quality of life.

Conclusions

The recall of NDE is not so rare in the ICU. In our cohort, cognitive and spiritual factors outweighed medical parameters as predictors of the emergence of NDE.

 

Long-term cognitive functioning is impaired in ICU-treated COVID-19 patients: a comprehensive controlled neuropsychological study

 

by Henriikka Ollila, Riikka Pihlaja, Sanna Koskinen, Annamari Tuulio-Henriksson, Viljami Salmela, Marjaana Tiainen, Laura Hokkanen and Johanna Hästbacka 

 

Critical Care volume 26, Article number: 223 (2022) Published: 20 July 2022

 

Background

Cognitive impairment has emerged as a common post-acute sequela of coronavirus disease 2019 (COVID-19). We hypothesised that cognitive impairment exists in patients after COVID-19 and that it is most severe in patients admitted to the intensive care unit (ICU).

Methods

This prospective controlled cohort study of 213 participants performed at the Helsinki University Hospital and the University of Helsinki, Finland, comprised three groups of patients—ICU-treated (n = 72), ward-treated (n = 49), and home-isolated (n = 44)—with confirmed COVID-19 between March 13 and December 31, 2020, participating in a comprehensive neuropsychological evaluation six months after the acute phase. Our study included a control group with no history of COVID-19 (n = 48). Medical and demographic data were collected from electronic patient records and interviews carried out four months after the acute phase. Questionnaires filled six months after the acute phase provided information about change in cognitive functioning observed by a close informant, as well as the presence of self-reported depressive and post-traumatic symptoms.

Results

The groups differed (effect size η2p = 0.065, p = 0.004) in the total cognitive score, calculated from neuropsychological measures in three domains (attention, executive functions, and memory). Both ICU-treated (p = 0.011) and ward-treated patients (p = 0.005) performed worse than home-isolated patients. Among those with more than 12 years of education, ICU-treated patients performed worse in the attention domain than ward-treated patients (p = 0.021) or non-COVID controls (p = 0.045); ICU-treated male patients, in particular, were impaired in executive functions (p = 0.037).

Conclusions

ICU-treated COVID-19 patients, compared to patients with less severe acute COVID-19 or non-COVID controls, showed more severe long-term cognitive impairment. Among those with more than 12 years of education, impairment existed particularly in the domains of attention and for men, of executive functions.