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Annals of Intensive Care
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The critically ill older patient with sepsis: a narrative review

Annals of Intensive Care volume 14, Article number: 6 (2024) Cite this article

Abstract

Sepsis is a significant public health concern, particularly affecting individuals above 70 years in developed countries. This is a crucial fact due to the increasing aging population, their heightened vulnerability to sepsis, and the associated high mortality rates. However, the morbidity and long-term outcomes are even more notable. While many patients respond well to timely and appropriate interventions, it is imperative to enhance efforts in identifying, documenting, preventing, and treating sepsis. Managing sepsis in older patients poses greater challenges and necessitates a comprehensive understanding of predisposing factors and a heightened suspicion for diagnosing infections and assessing the risk of sudden deterioration into sepsis. Despite age often being considered an independent risk factor for mortality and morbidity, recent research emphasizes the pivotal roles of frailty, disease severity, and comorbid conditions in influencing health outcomes. In addition, it is important to inquire about the patient's preferences and establish a personalized treatment plan that considers their potential for recovery with quality of life and functional outcomes. This review provides a summary of the most crucial aspects to consider when dealing with an old critically ill patient with sepsis.

Background

Despite advances in modern medicine, sepsis remains a major cause of morbidity and mortality. Sepsis accounts for 20% of global deaths [1], and survivors often endure long-term physical, psychological, and cognitive impairments.

Reporting sepsis epidemiology accurately is challenging due to evolving definitions, variations in reporting, demographic disparities, and discrepancies in healthcare resources [2, 3]. Estimates of sepsis cases range widely, from 19 to 48.9 million yearly [3, 4].

According to the Centers for Disease Control and Prevention, at least 1.7 million adults in the U.S. develop sepsis each year, resulting in nearly 270,000 deaths. Global sepsis data analysis [1] indicates a significant rise in sepsis cases, reaching 11 million deaths and 48.9 million incident cases in 2017 (Figs. 1, 2). While age-standardized sepsis incidence dropped by 37.0% and mortality by 52.8% between 1990 and 2017, substantial regional differences persist. The study highlights a decrease in global sepsis burden but emphasizes the urgent need for intervention, particularly in areas with the lowest Socio-Demographic Index.

Fig. 1
figure 1

Incident sepsis cases by age group and underlying cause category, both sexes, all locations, 2017. Bars represent 95% uncertainty intervals. Reproduced from (1). Published under the CC BY 4.0 license

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Fig. 2
figure 2

Percentage of all sepsis-related deaths in each underlying cause category, by age group and for both sexes, in 2017. Bars represent 95% uncertainty intervals. Reproduced from (1). Published under the CC BY 4.0 license

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In 2021–22, England and Wales reported over 100,000 emergency admissions with sepsis, with a mean patient age of 71 years [5]. In England, sepsis represented one-third of admissions to adult ICUs [6] and in China sepsis affected a fifth of patients admitted to the ICU [7].

Sepsis affects all age groups, but its incidence and mortality notably increase with advancing age, particularly in older adults who face elevated risks [8, 9]. In a Taiwanese nationwide study on sepsis, the incidence of sepsis in the oldest old (≥ 85 years) was 31-fold greater than the adult incidence (18–64 years) and threefold greater than the old (65–84 years) [10].

Due to an aging population, sepsis incidences are expected to rise. By 2050, about 16% of the global population will be aged 65 and above [11]. The most rapid increases in older populations are happening in developed countries, with a projected 140% rise in individuals aged 65 years and older by 2030, and those aged 85 years and above being the fastest-growing group [11,12,13].

Today, three key factors stand out: a global increase in sepsis cases [1, 14], significant healthcare challenges from sepsis-related mortality and morbidity [2, 15] and a notably rise in very old patients with sepsis due to the aging of population [16, 17]. Addressing these challenges requires standardized definitions, improved data collection, and better healthcare access.

In this review we will underscore the factors that contribute to the increased susceptibility to sepsis and higher mortality risk in older patients. The focus advocates for a comprehensive strategy in sepsis management, emphasizing a holistic approach and personalized care that considers individual factors, such as frailty, comorbidities, and patient values. We consider "older adults" as those surpassing 65 years with 'very old' individuals being those over 85 years.

Risk factors for sepsis

Older individuals are particularly vulnerable to developing sepsis due to pre-existing comorbidities, compromised immune function, sarcopenia, diminished physiological reserves associated with aging, malnutrition, and polypharmacy (Fig. 3). In the subsequent discussion, we will focus on the key factors, with additional details available in a recent review [18].

Fig. 3
figure 3

Risk factors for sepsis in older adults. Older adults face an elevated risk of sepsis due to several factors, including aging itself, comorbidities, and a weakened immunity. The interplay between their general health and sepsis severity significantly influences both short- and long-term outcomes, emphasizing the need for comprehensive assessment and personalized treatment strategies

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Immunosenescence and inflammaging play a crucial role in making the older individuals more susceptible to sepsis [19, 20]. Immunosenescence involves a gradual decline in the immune system, especially T-cell function and inflammaging is characterized by persistent low-grade inflammation. Both processes are interconnected, forming a cycle that heightens susceptibility [19, 21,22,23]. The immune system’s interaction with other systems, such as the neural or endocrine system, links declining immune function to frailty, sarcopenia, and malnutrition [19, 20]. Reduced insulation and lower metabolism compromise the immune system, making older individuals more vulnerable to infections and illnesses.

Geriatric syndromes arising from impairments in multiple systems, result from a combination of age-related changes, underlying medical conditions, and environmental influences and significantly impact quality of life and increase susceptibility to infection.

Frailty, a clinically recognizable state of increased vulnerability resulting from aging-associated decline, becomes more prevalent with age, impacting 25% of those over 65 and over 50% of patients over 80. It affects approximately 40% of older ICU patients and significantly impacts mortality and morbidity [24,25,26,27,28,29,30]. Incorporating frailty assessment into risk stratification can identify a vulnerable population that may benefit from targeted interventions.

Sarcopenia, characterized by muscle decline, has a prevalence rate ranging from 11 to 50% in those aged 80 years and above [31]. Aging disrupts muscle balance, triggering mechanisms, such as anabolic resistance, reduced IGF-1 signalling, mitochondrial dysfunction, inflammation, and oxidative stress, leading to muscle loss. Anabolic resistance diminishes muscle responsiveness to stimuli, causing reduced protein synthesis and muscle wasting. Immobilization in hospitalized older individuals results in a daily muscle mass reduction (0.5%) and strength decline (0.3–4.2%), impacting functional status and quality of life [32]. Sepsis worsens sarcopenia by promoting inflammation, muscle wasting, and potential mitochondrial dysfunction [33, 34]. Sarcopenia is linked to various pathophysiological processes, increasing mortality risk, especially in critical illness [33].

Malnutrition and dehydration are widespread in older people, and obesity is an increasing problem [35]. Malnutrition, linked to reduced food intake, underlying health issues, and nutrient absorption problems, contributes to functional decline, sarcopenia, slow wound healing, and adverse outcomes, such as increased infection rates and prolonged hospital stays [36]. Prevalence rates vary but can exceed two-thirds in hospitalized patients [35]. Dehydration prevalence can rise to over one-third in more vulnerable individuals [35]. Preventive measures, ensuring adequate nutrition and hydration, are essential. In hospital settings interventions such as a protein-rich diet, nutritional supplements, sedation protocols with short-acting drugs and early mobilization can improve outcomes. Routine screenings for prompt identification of potential malnutrition risks in geriatrics patients are recommended [35].

Cognitive impairment, is associated with brain changes, including reduced grey and white matter volume, impaired blood flow, altered neurotransmitter activity, and a more permeable blood–brain barrier [37]. It involves memory, attention, and cognitive deterioration potentially progressing to dementia at a rate of 10–15% per year. Critical illness often induces psychological symptoms, sleep disturbances, delirium, and cognitive impairment, all associated with higher mortality rates [38]. Delirium independently increases mechanical ventilation duration, ICU and hospital stays, health care costs, long-term cognitive impairment, and mortality risk. Non-pharmacological measures for delirium prevention are recommended [39].

The impact of comorbidities on septic patients is substantial. Malignancies, diabetes mellitus, and dysfunctions in cardiac, renal, liver, or pulmonary systems contribute to poorer outcomes. Notably, 78% of septic patients have at least one comorbidity [40], and 60% exhibit three or more [41]. On average, patients aged 65 to 84 have 2.6 ± 2.2 comorbidities, while those aged 85 or over have 3.6 ± 2.3 [42].

Moreover, older individuals face other vulnerabilities, including altered vaginal flora in women due to reduced estrogen levels, urinary issues from prostatic hypertrophy in men, compromised skin integrity, diminished cough reflex, and swallowing difficulties, all contributing to increased infection susceptibility. The use of medical instruments and institutionalization further heightens sepsis risk particularly due to the prevalence of multidrug-resistant (MDR) pathogens in healthcare settings.

Finally, aging shows significant individual heterogeneity, with some maintaining resilience and an active lifestyle, while others face higher susceptibility to diseases and disabilities. Understanding resilience, the ability to withstand and recover from stressors, is crucial for addressing chronic diseases and promoting healthy aging [43]. Lifestyle interventions, such as personalized exercise, and nutrition may help older individuals better adapt to the biological changes associated with aging and potentially reduce their susceptibility to infections [32, 44].

Diagnosis of sepsis

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection [45]. Organ dysfunction is defined as an acute increase of two or more points in the Sequential Organ Failure Assessment (SOFA) score [46]. Septic shock, a severe form of sepsis with circulatory, cellular, and metabolic dysfunction, carries a higher risk of mortality compared to sepsis alone [45, 47].

Diagnosing sepsis in older individuals can be challenging due to atypical presentations and subtle symptoms [48,49,50] (Fig. 4). Timely recognition is crucial for proper management and prevention of adverse outcomes. Therefore, a comprehensive evaluation, including a detailed history, thorough physical examination, and a heightened suspicion for infections is necessary. Biomarkers can provide fast and accurate early diagnosis compared to traditional microbiology tests, reducing the risk of negative results due to prior antibiotic treatment.

Fig. 4
figure 4

Clinical picture in older patients may be ambiguous

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In older individuals, potentially life-threatening infections may manifest through various behavioural changes, including sudden confusion, perception disorders, psychomotor agitation, or lethargy. Physical symptoms such as loss of appetite, dehydration, dizziness, falls, and incontinence can serve as sole indicators. Notably, fever, a common sign of infection, is absent in 30–50% of older adults, who may exhibit a reduced febrile response to infections, such as bacteraemia, pneumonia, endocarditis, and meningitis [51,52,53]. The conventional definition of fever may not apply due to the lower baseline body temperature in older adults, influenced by diminished cytokine production, reduced hypothalamic receptor sensitivity, and impaired adaptation of peripheral thermoregulation [51, 54]. The use of medications, such as non-steroidal anti-inflammatory drugs, corticosteroids, beta-receptor blockers, antihistamines, and ranitidine, further dampens the inflammatory response. Therefore, assessing temperature changes from their baseline proves more useful than relying on absolute values.

Regarding organ dysfunction related to sepsis, the SOFA score serves as a tool to assess organ failure and functions both diagnostically and prognostically [45]. It is crucial to consider the interplay between pre-existing comorbidities and acute organ dysfunction when evaluating organ failure.

Biomarkers contribute to antibiotic stewardship by minimizing unnecessary prescriptions. However, their performance may differ in older patients due to comorbidities and chronic inflammation. Clinical judgment and comprehensive assessment are necessary when using biomarkers in this population [55].

Lactate measurements indicate tissue hypoperfusion and sepsis severity. Levels of 2 mmol/L and higher predict mortality regardless of age, but factors such as dehydration and anaemia, common in older individuals, can also increase lactic acid levels [56, 57]. Comorbidities, such as heart, liver, renal or respiratory dysfunction, may contribute to increased lactate levels due to factors, such as reduced cardiac output, impaired liver function, compromised kidney clearance, and inadequate tissue oxygenation elevating the risk of developing type B lactic acidosis or hinder lactate clearance.

C-reactive protein (CRP) has low specificity in this population. There is growing evidence suggesting that CRP is not only an inflammatory biomarker but is also associated with age-related conditions, such as cardiovascular disease, hypertension, diabetes mellitus, and kidney disease [58].

Serum procalcitonin (PCT) is a valuable biomarker for bacterial infections and sepsis prognosis [59,60,61,62]. It can be applied in older patients using similar cutoff values as in younger patients [63] demonstrating comparable performance and higher diagnostic accuracy than other markers [55]. Serial PCT measurements can guide antibiotic therapy duration, reducing exposure without compromising recovery. However, clinical and microbiological assessments should complement PCT levels due to potential false results [64].

An ideal biomarker with high clinical accuracy for sepsis diagnosis is still needed. Novel biomarkers, such as Pancreatic Stone Protein (PSP) [65,66,67], Presepsin, and Mid-regional Pro-adrenomedullin (MR-proADM) [68], showing early elevation in response to sepsis, are under study. Future clinical trials are necessary to further verify their utility in clinical practice.

Sources of infection

Infections are more prevalent in older individuals correlating with increased hospitalization and mortality, particularly in those over 85 years [69]. Lower respiratory tract and urinary tract infections (UTIs) are predominant both in community and health care associated infections (HAI) [49, 70]. Among 308 elderly individuals, respiratory tract infections represented 49.7%, urinary tract infections (UTIs) 33.8%, blood stream infections (BSIs) 21.1%, and surgical site infections 4.9% [9].

Pneumonia, a severe respiratory tract infection, can be challenging to diagnose because of atypical symptoms and difficulty in obtaining accurate chest radiographs due to physical limitations. Lung ultrasound and CT scanner can aid in the diagnosis, while bronchoscopy and BAL are recommended for immunocompromised and more critical patients. Aspiration pneumonia, with a higher mortality rate, is prevalent among older adults especially if impaired swallowing, intubation or in general anaesthesia’s postoperative phase. About 76% of aspiration pneumonia-related deaths occur in patients aged 75 years or older [71]. Common microorganisms include Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Enterobacteriaceae. In case of poor dental health, anaerobic microorganisms should also be considered [72]. In HAI the pathogens involved are mainly gram-negative bacteria (many of which are MDR) [70]. COVID-19 was a major complication in the older population, leading to high mortality rates, particularly among those requiring invasive ventilation [73].

UTI diagnosis is challenging due to overlapping symptoms, the presence of asymptomatic bacteriuria (ASB) and difficulties in obtaining uncontaminated urine. Approximately 15–50% of patients aged 80 and older have ASB, and over 50% of antibiotic treatments for ASB are unnecessary [74,75,76]. In urinary sepsis, E. coli is the most common microorganism, but catheter-associated infections are polymicrobial, including Proteus spp., Klebsiella spp., E. faecalis and Pseudomonas spp. [77].

BSIs are common and fatal in older patients, with around half of all cases occurring in this age group. Case fatality rates peak at 50–60% for individuals over 85 years. Older people face increased risks for Gram-negative infections, urinary source infections, and antimicrobial resistance, frequently healthcare-associated [78,79,80]. MDR microorganisms, pose significant challenges and may lead to treatment failures. In a Spanish cohort with healthcare-associated bacteremic UTIs, over 61% had MDR microorganisms, and over 75% were elderly [81]. Removing unnecessary urinary catheters could reduce a significant portion of these BSIs.

Skin and soft tissue infections (SSTIs) are prevalent in older adults, exhibiting a wide clinical spectrum from mild infections to life-threatening diseases. Prognosis worsens with comorbidities, such as heart failure, diabetes mellitus, and malnutrition. SSTIs pose a notable challenge in treatment, especially in acute care hospitals and long-term care facilities, where their prevalence is significant (10.9% and 17%, respectively) [70, 82, 83]. Common bacteria associated with SSTIs in this demographic include Streptococcus spp., Staphylococcus spp., and Pseudomonas aeruginosa. Screening for risk factors associated with methicillin-resistant Staphylococcus aureus (MRSA) is crucial.

Hospital-acquired infections (HAIs) pose serious health risks to the older population, resulting in longer hospital stays, extended antibiotic therapy, significant mortality, and higher healthcare costs. HAIs are the primary cause of death in one-third of individuals aged 65 and over. MDR microorganisms make infection prevention and control measures crucial [70].

Management of sepsis

Treatment of older individuals with sepsis/septic shock should adhere to the Surviving Sepsis Campaign (SSC) International Guidelines [84], but the following items require special attention.

Antibiotic therapy

Empirical antibiotic should consider common pathogens, their susceptibility to antimicrobials and resistance patterns. The risk of infections by MDR microorganisms is notable in this demographic due to frequent healthcare exposure [70]. In addition, older individuals face an elevated risk of fungal infections due to age-related changes, compromised immune status, catheter use, prolonged antibiotic use, and treatments, such as corticosteroids and chemotherapy [85, 86].

Selecting and dosing antibiotics is challenging due to factors, such as comorbidities, drug pharmacokinetics (PK) and pharmacodynamics (PD), polypharmacy and risk of drug interactions [87, 88]. Age-related changes in organ function, body composition, renal clearance, hepatic metabolism, and drug distribution significantly influence antibiotic PK and PD [49, 89, 90]. With aging, the decrease in body water percentage reduces the distribution volume for hydrophilic drugs (e.g., β-lactams, glycopeptides, aminoglycosides, azoles), leading to a faster increase in plasma concentrations. Conversely, a relative increase in adipose tissue raises the distribution volume for lipophilic drugs (e.g., macrolides, fluoroquinolones), prolonging their half-life and leading to lower tissue concentrations [90]. Age-related liver and renal declines affect drug half-life and elimination [87, 91,92,93,94]. Adjustments for antibiotics in reduced renal function involve considering bacterial killing type. For concentration-dependent antibiotics, increase dosing intervals to prevent overdosing; for time-dependent ones, reduce the dose while maintaining the interval.

Morphological and functional changes such as delayed gastric emptying, reduced splanchnic blood flow and altered gastric pH can affect the bioavailability of orally administered drugs [87, 89, 90, 92].

Resuscitation

In fluid resuscitation and hemodynamic support, careful fluid management is crucial, considering comorbidities and age-related changes in autoregulation. While guidelines propose a target mean arterial pressure (MAP) of ≥ 65 mm Hg, older patients with chronic hypertension may require higher MAP targets to prevent acute kidney injury [95, 96]. Dehydration is common in older adults, often necessitating an initial 500 mL crystalloid bolus. However, protocolized resuscitation, such as 30 mL/kg of intravenous crystalloid within 3 h, may be detrimental in patients with cardiac impairment or chronic kidney disease [5]. Excessive fluid therapy can lead to impaired outcomes, emphasizing the need for a dynamic evaluation of fluid response. Customized assessment of perfusion indicators, including mental status, diuresis, circulatory assessment, pulse rate, blood pressure, capillary refill, and point-of-care echocardiography, is crucial for monitoring and treatment decisions. Initiating de-resuscitation promptly with diuretics is essential.

The ideal hemoglobin transfusion threshold in older septic patients is undefined and may differ from that in young adults. Anemia is increasingly prevalent in the aging population, affecting over 10% of those aged 65 and older, with nearly two-thirds of critically ill patients in ICUs experiencing anemia. In sepsis, anemia's multifactorial causes include reduced red blood cell production, stress-induced bleeding, hemodilution, recurrent blood withdrawal, impaired iron metabolism and hemolysis. A study of 815 older septic patients revealed over 20% had hemoglobin levels below 10 g/dL on admission, doubling during the first week. Although initial hemoglobin strongly correlated with in-hospital mortality, blood transfusions, administered to 8.3% of patients, were not an independent predictor of mortality [97] A recent meta-analysis focusing on older adults suggests higher hemoglobin thresholds result in lower mortality and fewer cardiac complications, considering age-related declines in cardiac output affecting oxygen delivery [98]. Ongoing debates and trials explore anemia management, transfusion thresholds, and frequency.

Additional factors

Individualized sedation protocols, short-acting drugs, and nonpharmacologic approaches for managing pain, agitation and delirium significantly enhance outcomes in critically ill adults [39]. The PADIS guidelines, crucial for all patients, are especially important for older individuals. They advocate for shorter mechanical ventilation (MV), early mobilization, and notably contribute to reducing sarcopenia and delirium incidence in older patients. Delirium rates can reach 80% in ventilated older patients, compared to 33% in general medical units, significantly increasing the risk of persistent cognitive impairment post-discharge. Up to 70% may experience prolonged cognitive impairment within a year post-hospitalization, with around 10% developing dementia [99, 100]. Ventilated patients face a 30% higher likelihood of needing assistance with activities of daily living (ADLs) compared to non-ventilated individuals.

Non-invasive ventilation (NIV) reduces risks associated with mechanical ventilation and eases discomfort in critically ill older patients. While guidelines primarily recommend NIV for acute COPD exacerbation with hypercapnia and acute respiratory failure due to pulmonary oedema, it is not the preferred initial therapy for hypoxemic respiratory failure from pneumonia, because the potential need for intubation post-NIV failure carries severe clinical implications and a high risk of death. An analysis [101] compared NIV as the primary mode of respiratory support in two large observational studies with 1986 patients aged ≥ 80 (1292 from the VIP2 study, pre-pandemic era and 694 from the COVIP study, during pandemic). Those with COVID-19 ARDS treated primarily with NIV were less likely to survive 30 days after ICU admission, despite being less frail. This discrepancy may be linked to the study population, as VIP2 included patients with respiratory failure from COPD or pulmonary oedema. In addition, the risk of NIV failure quadrupled during the COVID-19 pandemic.

Steroid use in sepsis is a subject of debate due to conflicting evidence regarding its impact on mortality [102,103,104]. The SSC guidelines recommend intravenous hydrocortisone at a dose of 200 mg per day if adequate fluid resuscitation and vasopressor therapy fail to restore hemodynamic stability or if adrenal impairment is suspected. Gradual reduction is advised when vasopressor support is no longer needed. The decision to use steroids in septic older patients should be individualized, considering the patient's overall health, comorbidities, and the specific circumstances of their sepsis.

Finally, Impaired glucose control, thrombotic events and stress ulcers are more frequent in the older population. Therefore, glucose control should be monitored, and insulin therapy should be initiated promptly if hyperglycaemia is detected, although optimal target levels are not well-defined. Pharmacologic thromboembolic prophylaxis with LMWH, considering renal function and bleeding risks, as well as stress ulcer prophylaxis [105], is recommended for older patients with sepsis.

In addition to specific sepsis treatments, incorporating multidisciplinary interventions is crucial [106,107,108]. Utilizing a comprehensive geriatric assessment to understand an older patient’s medical, psychosocial, and functional capabilities can enhance their functional status, prevent institutionalization, and reduce mortality for those admitted to the hospital. High-quality geriatric nursing, including falls prevention, nutrition, and physiotherapy, remains important beyond the acute illness phase.

Outcomes

Sepsis has a profound impact on the senior population, leading to significant morbidity and mortality [41, 77, 109]. The financial strain on healthcare systems is significant, with extensive healthcare resource utilization both before and after ICU admission [110,111,112,113,114,115].

In patients aged ≥ 65, in-hospital mortality ranges from 30 to 60%, escalating to 40–80% in those aged 80 and above [49]. A systematic review of very old septic patients in the ICU reports mortality rates of 43% in the ICU, 47% in the hospital, and 68% one year after ICU admission [116]

An analysis of the Intensive Care Over Nations (ICON) database, focusing on patients above 50 years, reveals age-related differences in sepsis outcomes. Hospital mortality increases with age, doubling in patients over 80 compared to those under 50 years (49.3% vs. 25.2%, p < 0.05). Mortality sees a maximum rate increase of about 0.75% per year between the ages of 71 and 77 years. Multilevel analysis confirms age > 70 years as an independent risk factor for mortality [117].

Despite age often being considered an independent risk factor for mortality and morbidity [118,119,120], emerging research underscores the crucial roles of other factors, such as frailty, disease severity, and comorbid conditions [26, 121,122,123,124,125]. Post-hoc analyses of the VIP-1 and VIP-2 studies, examining patients aged 80 and over admitted to the ICU with sepsis, show ICU mortality rates of 31% and 41%, with 30-day and 6-month mortality rates of 45% and 54%, respectively [121, 122] (Table 1). Sepsis as admission diagnosis did not maintain an independent link to mortality after adjusting for organ dysfunction. Frailty, advanced age, and SOFA score emerged as key independent prognostic factors for adverse outcomes (Table 2).

Table 1 Characteristics of older patients (≥ 80 years) admitted to the ICU with sepsis diagnosis in VIP-1 and VIP-2 studies
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Table 2 Multivariate analysis (Cox). Predictors of 30-day mortality (VIP-1 study) and 6-month mortality (VIP-2 study) in older patients (≥ 80 years), admitted to the ICU with sepsis
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Advancements in sepsis management have led to a reduction in sepsis-associated mortality. [2, 10, 126,127,128,129,130,131], even among the older population [132]. However, older sepsis survivors face worse long-term outcomes, including greater cognitive and functional decline, an increase risk of hospital readmission, and a higher likelihood of discharge to long-term care facilities [18, 115, 133,134,135].

Post-intensive care syndrome (PICS) symptoms, prevalent among older sepsis survivors, include muscle weakness, fatigue, cognitive decline, sleep disturbances, emotional distress, and swallowing problems [125, 136, 137]. Another term, possibly more specific, is post-sepsis syndrome (PSS) [138]. Factors such as pre-existing co-morbidity and frailty, polypharmacy, delirium during hospitalization and injury induced by sepsis [134, 138] can exacerbate outcomes.

Ongoing efforts to improve sepsis management, including early recognition, prompt source control, and timely antibiotic administration are crucial. In addition, adopting a multi-faceted approach to improve long-term outcomes for survivors is essential.

Goals of care

Predicting survival or future quality of life for older individuals poses challenges due to the substantial biological and functional heterogeneity in this demographic. Ethical and legal frameworks vary globally, influencing diverse management approaches among healthcare professionals shaped by geographical locations and cultures. In the absence of robust evidence guiding patient management, decisions regarding the proportionality of intensive care often stem from personal preferences and experience [139].

Key criteria for ICU admission include the condition's reversibility, emphasizing both survival and maintaining a similar quality of life. Medical treatment should align with the patient's wishes and prioritize their well-being, considering the burden vs. the chance of recovery. Recognizing the patient’s perspective on aging, health, and disease is crucial, as some prioritize quality of dying over life-prolonging measures [122, 127, 132]. In uncertain cases, a therapeutic trial is recommended, with its duration remaining undefined and contingent on the patient’s response. If irreversibility becomes clear, discussions with the patient, surrogates, and colleagues guide decisions on excluding treatments causing suffering. Divergent opinions require additional time for clarity.

Decisions to limit life-sustaining treatment (LST) should account for baseline status, quality of life, survival potential, functional outcomes, and treatment burden. Mousai et al. [140] illustrate that integrating clinical phenotypes with cultural factors and information about critical care course enhances predictive discrimination accuracy for LST in very old ICU patients. Clinicians can make these decisions either before ICU admission or as the patient’s condition evolves. Family involvement and regular discussions about the patient’s condition are essential. A framework encompassing physical and cognitive status, quality of life, survival likelihood, functional performance, preferences, and treatment burden guides decisions for intensive care in older patients (Fig. 5) [18, 84, 134].

Fig. 5
figure 5

Triage considerations for the older septic patient. HRQoL Health-Related Quality of Life, TLT Time Limited (ICU) Trial

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Conclusions

Sepsis poses a significant threat to the senior population. However, current research on this demographic remains insufficient. It is imperative to raise awareness, educate healthcare professionals, implement preventive measures, and deliver timely and appropriate care to improve outcomes.

The insights from the VIP-1 and VIP-2 studies prompt a reassessment of sepsis as a standalone contributor to mortality, emphasizing the importance of understanding and addressing comorbid geriatric conditions to enhance patient resilience and overall prognosis. In addition, it is crucial to inquire about the patient's preferences and establish a personalized treatment plan that considers their potential for recovery with an acceptable HRQoL and functional outcomes.

The aim ahead is to recognize the gaps and limitations in current research while determining short- and long-term priorities. These priorities should extend beyond merely reducing sepsis mortality to gaining insights into, and enhancing, the HRQoL of sepsis survivors.

Availability of data and materials

Not applicable.

Abbreviations

ASB:

Asymptomatic bacteriuria

COPD:

Chronic obstructive pulmonary disease

CFS:

Clinical Frailty Scale

HRQoL:

Health-related quality of life

ICU:

Intensive care unit

IMV:

Invasive mechanical ventilation

LOS:

Length of stay

LST:

Life sustaining treatment

MDR:

Multi-drug resistant

NIV:

Non-invasive ventilation

PCT:

Procalcitonin

PICS:

Post-intensive care syndrome

RRT:

Renal replacement therapy

SOFA:

Sequential Organ Failure Assessment

TLT:

Time Limited (ICU) Trial

UTI:

Urinary tract infection

VIPs:

Very Old Intensive Care Patients

References

  1. Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study. Lancet Lond Engl. 2020;395:200–11.

    Article  Google Scholar 

  2. Fleischmann C, Scherag A, Adhikari NKJ, Hartog CS, Tsaganos T, Schlattmann P, et al. Assessment of global incidence and mortality of hospital-treated sepsis. Current estimates and limitations. Am J Respir Crit Care Med. 2016;193:259–72.

    Article  CAS  PubMed  Google Scholar 

  3. Chiu C, Legrand M. Epidemiology of sepsis and septic shock. Curr Opin Anaesthesiol. 2021;34:71–6.

    Article  PubMed  Google Scholar 

  4. Labib A. Sepsis care pathway 2019. Qatar Med J. 2019;2019(2019):4.

    PubMed  PubMed Central  Google Scholar 

  5. Goodacre S, Fuller G, Conroy S, Hendrikse C. Diagnosis and management of sepsis in the older adult. BMJ. 2023;382: e075585.

    Article  PubMed  Google Scholar 

  6. Shankar-Hari M, Harrison DA, Rubenfeld GD, Rowan K. Epidemiology of sepsis and septic shock in critical care units: comparison between sepsis-2 and sepsis-3 populations using a national critical care database. Br J Anaesth. 2017;119:626–36.

    Article  CAS  PubMed  Google Scholar 

  7. Xie J, Wang H, Kang Y, Zhou L, Liu Z, Qin B, et al. The epidemiology of sepsis in Chinese ICUs: a national cross-sectional survey. Crit Care Med. 2020;48:e209–18.

    Article  PubMed  Google Scholar 

  8. Knoop ST, Skrede S, Langeland N, Flaatten HK. Epidemiology and impact on all-cause mortality of sepsis in Norwegian hospitals: a national retrospective study. PLoS ONE. 2017;12: e0187990.

    Article  PubMed  PubMed Central  Google Scholar 

  9. de Sousa ÁFL, Queiroz AAFLN, de Oliveira LB, Moura LKB, de Andrade D, Watanabe E, et al. Deaths among the elderly with ICU infections. Rev Bras Enferm. 2017;70:733–9.

    Article  PubMed  Google Scholar 

  10. Lee S-H, Hsu T-C, Lee MTG, Chao CCT, Lee W-C, Lai C-C, et al. Nationwide trend of sepsis: a comparison among octogenarians, elderly, and young adults. Crit Care Med. 2018;46:926–34.

    Article  PubMed  Google Scholar 

  11. Nations U. World Population Prospects 2019: Highlights|Naciones Unidas. U. N. United Nations. https://www.un.org/es/desa/world-population-prospects-2019-highlights. Accessed 22 Aug 2023.

  12. Dobriansky PJ, Suzman RM, Hodes RJ. Why population aging matters—a global perspective. Natl Institutes Heal US Dep Heal Hum Serv US Dep State; 2007.

    Google Scholar 

  13. Leblanc G, Boumendil A, Guidet B. Ten things to know about critically ill elderly patients. Intensive Care Med. 2017;43:217–9.

    Article  PubMed  Google Scholar 

  14. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303–10.

    Article  CAS  PubMed  Google Scholar 

  15. Dugani S, Veillard J, Kissoon N. Reducing the global burden of sepsis. CMAJ Can Med Assoc J J Assoc Medicale Can. 2017;189:E2-3.

    Article  Google Scholar 

  16. Flaatten H, de Lange DW, Artigas A, Bin D, Moreno R, Christensen S, et al. The status of intensive care medicine research and a future agenda for very old patients in the ICU. Intensive Care Med. 2017;43:1319–28.

    Article  CAS  PubMed  Google Scholar 

  17. Fernando SM, McIsaac DI, Perry JJ, Rochwerg B, Bagshaw SM, Thavorn K, et al. Frailty and associated outcomes and resource utilization among older ICU patients with suspected infection. Crit Care Med. 2019;47:e669–76.

    Article  PubMed  Google Scholar 

  18. Vallet H, Guidet B, Boumendil A, De Lange DW, Leaver S, Szczeklik W, et al. The impact of age-related syndromes on ICU process and outcomes in very old patients. Ann Intensive Care. 2023;13:68.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Soysal P, Stubbs B, Lucato P, Luchini C, Solmi M, Peluso R, et al. Inflammation and frailty in the elderly: a systematic review and meta-analysis. Ageing Res Rev. 2016;31:1–8.

    Article  CAS  PubMed  Google Scholar 

  20. Sieber CC. Malnutrition and sarcopenia. Aging Clin Exp Res. 2019;31:793–8.

    Article  PubMed  Google Scholar 

  21. Fulop T, Larbi A, Dupuis G, Le Page A, Frost EH, Cohen AA, et al. Immunosenescence and inflamm-aging as two sides of the same coin: friends or foes? Front Immunol. 2017;8:1960.

    Article  PubMed  Google Scholar 

  22. Pangrazzi L, Weinberger B. T cells, aging and senescence. Exp Gerontol. 2020;134: 110887.

    Article  CAS  PubMed  Google Scholar 

  23. Aiello A, Farzaneh F, Candore G, Caruso C, Davinelli S, Gambino CM, et al. Immunosenescence and its hallmarks: how to oppose aging strategically? A review of potential options for therapeutic intervention. Front Immunol. 2019;10:2247.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Darvall JN, Bellomo R, Bailey M, Young PJ, Rockwood K, Pilcher D. Impact of frailty on persistent critical illness: a population-based cohort study. Intensive Care Med. 2022;48:343–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Flaatten H, Jung C, Vallet H. How does frailty afects outcome? Curr Anesthesiol Rep. 2019;9:144.

    Article  Google Scholar 

  26. Flaatten H, De Lange DW, Morandi A, Andersen FH, Artigas A, Bertolini G, et al. The impact of frailty on ICU and 30-day mortality and the level of care in very elderly patients (≥ 80 years). Intensive Care Med. 2017;43:1820–8.

    Article  PubMed  Google Scholar 

  27. Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet Lond Engl. 2013;381:752–62.

    Article  Google Scholar 

  28. Patrizio E, Zambon A, Mazzola P, Massariello F, Galeazzi M, Cavalieri d’Oro L, et al. Assessing the mortality risk in older patients hospitalized with a diagnosis of sepsis: the role of frailty and acute organ dysfunction. Aging Clin Exp Res. 2022;34:2335–43.

    Article  PubMed  Google Scholar 

  29. Hoogendijk EO, Afilalo J, Ensrud KE, Kowal P, Onder G, Fried LP. Frailty: implications for clinical practice and public health. Lancet Lond Engl. 2019;394:1365–75.

    Article  Google Scholar 

  30. De Biasio JC, Mittel AM, Mueller AL, Ferrante LE, Kim DH, Shaefi S. Frailty in critical care medicine: a review. Anesth Analg. 2020;130:1462–73.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Cruz-Jentoft AJ, Landi F, Schneider SM, Zúñiga C, Arai H, Boirie Y, et al. Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS). Age Ageing. 2014;43:748–59.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Angulo J, El Assar M, Álvarez-Bustos A, Rodríguez-Mañas L. Physical activity and exercise: Strategies to manage frailty. Redox Biol. 2020;35: 101513.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Cho M-R, Lee S, Song S-K. A review of sarcopenia pathophysiology, diagnosis, treatment and future direction. J Korean Med Sci. 2022;37: e146.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Zhang X-M, Chen D, Xie X-H, Zhang J-E, Zeng Y, Cheng AS. Sarcopenia as a predictor of mortality among the critically ill in an intensive care unit: a systematic review and meta-analysis. BMC Geriatr. 2021;21:339.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Volkert D, Beck AM, Cederholm T, Cruz-Jentoft A, Hooper L, Kiesswetter E, et al. ESPEN practical guideline: clinical nutrition and hydration in geriatrics. Clin Nutr Edinb Scotl. 2022;41:958–89.

    Article  CAS  Google Scholar 

  36. Neloska L, Damevska K, Nikolchev A, Pavleska L, Petreska-Zovic B, Kostov M. The association between malnutrition and pressure ulcers in elderly in long-term care facility. Open Access Maced J Med Sci. 2016;4:423–7.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Maldonado JR. Delirium pathophysiology: an updated hypothesis of the etiology of acute brain failure. Int J Geriatr Psychiatry. 2018;33:1428–57.

    Article  PubMed  Google Scholar 

  38. Trompeo AC, Vidi Y, Locane MD, Braghiroli A, Mascia L, Bosma K, et al. Sleep disturbances in the critically ill patients: role of delirium and sedative agents. Minerva Anestesiol. 2011;77:604–12.

    CAS  PubMed  Google Scholar 

  39. Devlin JW, Skrobik Y, Gélinas C, Needham DM, Slooter AJC, Pandharipande PP, et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med. 2018;46:e825–73.

    Article  PubMed  Google Scholar 

  40. Mellhammar L, Wollter E, Dahlberg J, Donovan B, Olséen C-J, Wiking PO, et al. Estimating sepsis incidence using administrative data and clinical medical record review. JAMA Netw Open. 2023;6: e2331168.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Mankowski RT, Anton SD, Ghita GL, Brumback B, Cox MC, Mohr AM, et al. Older sepsis survivors suffer persistent disability burden and poor long-term survival. J Am Geriatr Soc. 2020;68:1962–9.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Barnett K, Mercer SW, Norbury M, Watt G, Wyke S, Guthrie B. Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study. Lancet. 2012;380:37–43.

    Article  PubMed  Google Scholar 

  43. Zampino M, Polidori MC, Ferrucci L, O’Neill D, Pilotto A, Gogol M, et al. Biomarkers of aging in real life: three questions on aging and the comprehensive geriatric assessment. GeroScience. 2022;44:2611–22.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Lee S-Y, Tung H-H, Liu C-Y, Chen L-K. Physical activity and sarcopenia in the geriatric population: a systematic review. J Am Med Dir Assoc. 2018;19:378–83.

    Article  PubMed  Google Scholar 

  45. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315:801–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22:707–10.

    Article  CAS  PubMed  Google Scholar 

  47. Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, et al. Assessment of clinical criteria for sepsis: for the third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315:762–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Chester JG, Rudolph JL. Vital signs in older patients: age-related changes. J Am Med Dir Assoc. 2011;12:337–43.

    Article  PubMed  Google Scholar 

  49. Rowe TA, McKoy JM. Sepsis in older adults. Infect Dis Clin North Am. 2017;31:731–42.

    Article  PubMed  Google Scholar 

  50. van Duin D. Diagnostic challenges and opportunities in older adults with infectious diseases. Clin Infect Dis Off Publ Infect Dis Soc Am. 2012;54:973–8.

    Article  Google Scholar 

  51. Shimazui T, Nakada T-A, Walley KR, Oshima T, Abe T, Ogura H, et al. Significance of body temperature in elderly patients with sepsis. Crit Care Lond Engl. 2020;24:387.

    Article  Google Scholar 

  52. Ewig S, Klapdor B, Pletz MW, Rohde G, Schütte H, Schaberg T, et al. Nursing-home-acquired pneumonia in Germany: an 8-year prospective multicentre study. Thorax. 2012;67:132–8.

    Article  PubMed  Google Scholar 

  53. Dhawan VK. Infective endocarditis in elderly patients. Clin Infect Dis Off Publ Infect Dis Soc Am. 2002;34:806–12.

    Article  Google Scholar 

  54. Norman DC. Fever in the elderly. Clin Infect Dis Off Publ Infect Dis Soc Am. 2000;31:148–51.

    Article  CAS  Google Scholar 

  55. Falcone M, Bauer M, Ferrer R, Gavazzi G, Gonzalez Del Castillo J, Pilotto A, et al. Biomarkers for risk stratification and antibiotic stewardship in elderly patients. Aging Clin Exp Res. 2023;35:925–35.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Chen H, Xu J, Wang X, Wang Y, Tong F. Early lactate-guided resuscitation of elderly septic patients. J Intensive Care Med. 2022;37:686–92.

    Article  PubMed  Google Scholar 

  57. Cheng H-H, Chen F-C, Change M-W, Kung C-T, Cheng C-Y, Tsai T-C, et al. Difference between elderly and non-elderly patients in using serum lactate level to predict mortality caused by sepsis in the emergency department. Medicine (Baltimore). 2018;97: e0209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Tang Y, Fung E, Xu A, Lan H-Y. C-reactive protein and ageing. Clin Exp Pharmacol Physiol. 2017;44(Suppl 1):9–14.

    Article  CAS  PubMed  Google Scholar 

  59. Gavazzi G, Drevet S, Debray M, Bosson JL, Tidadini F, Paccalin M, et al. Procalcitonin to reduce exposure to antibiotics and individualise treatment in hospitalised old patients with pneumonia: a randomised study. BMC Geriatr. 2022;22:965.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Gavazzi G, Meyrignac L, Zerhouni N, Bioteau C, Lopez C, François P, et al. Intrinsic values of procalcitonin in bacterial bloodstream infections in people aged 75 years and over: a retrospective study. Diagn Microbiol Infect Dis. 2023;105: 115887.

    Article  CAS  PubMed  Google Scholar 

  61. Lee S-H, Chan R-C, Wu J-Y, Chen H-W, Chang S-S, Lee C-C. Diagnostic value of procalcitonin for bacterial infection in elderly patients - a systemic review and meta-analysis. Int J Clin Pract. 2013;67:1350–7.

    Article  PubMed  Google Scholar 

  62. Gregoriano C, Heilmann E, Molitor A, Schuetz P. Role of procalcitonin use in the management of sepsis. J Thorac Dis. 2020;12:S5-15.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Heilmann E, Gregoriano C, Annane D, Reinhart K, Bouadma L, Wolff M, et al. Duration of antibiotic treatment using procalcitonin-guided treatment algorithms in older patients: a patient-level meta-analysis from randomized controlled trials. Age Ageing. 2021;50:1546–56.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Heilmann E, Gregoriano C, Wirz Y, Luyt C-E, Wolff M, Chastre J, et al. Association of kidney function with effectiveness of procalcitonin-guided antibiotic treatment: a patient-level meta-analysis from randomized controlled trials. Clin Chem Lab Med. 2020;59:441–53.

    Article  PubMed  Google Scholar 

  65. Pugin J, Daix T, Pagani J-L, Morri D, Giacomucci A, Dequin P-F, et al. Serial measurement of pancreatic stone protein for the early detection of sepsis in intensive care unit patients: a prospective multicentric study. Crit Care. 2021;25:151.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Fidalgo P, Nora D, Coelho L, Povoa P. Pancreatic stone protein: review of a new biomarker in sepsis. J Clin Med. 2022;11:1085.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Prazak J, Irincheeva I, Llewelyn MJ, Stolz D, García de Guadiana Romualdo L, Graf R, et al. Accuracy of pancreatic stone protein for the diagnosis of infection in hospitalized adults: a systematic review and individual patient level meta-analysis. Crit Care Lond Engl. 2021;25:182.

    Article  Google Scholar 

  68. Liang J, Cai Y, Shao Y. Comparison of presepsin and Mid-regional pro-adrenomedullin in the diagnosis of sepsis or septic shock: a systematic review and meta-analysis. BMC Infect Dis. 2023;23:288.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Vincent JL. EPIC II: sepsis around the world. Minerva Anestesiol. 2008;74:293–6.

    CAS  PubMed  Google Scholar 

  70. Cristina ML, Spagnolo AM, Giribone L, Demartini A, Sartini M. Epidemiology and prevention of healthcare-associated infections in geriatric patients: a narrative review. Int J Environ Res Public Health. 2021;18:5333.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Gupte T, Knack A, Cramer JD. Mortality from aspiration pneumonia: incidence, trends, and risk factors. Dysphagia. 2022;37:1493–500.

    Article  PubMed  Google Scholar 

  72. Niederman MS, Cilloniz C. Aspiration pneumonia. Rev Espanola Quimioter Publicacion Of Soc Espanola Quimioter. 2022;35(Suppl 1):73–7.

    Google Scholar 

  73. Hussien H, Nastasa A, Apetrii M, Nistor I, Petrovic M, Covic A. Different aspects of frailty and COVID-19: points to consider in the current pandemic and future ones. BMC Geriatr. 2021;21:389.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Gavazzi G, Krause K-H. Ageing and infection. Lancet Infect Dis. 2002;2:659–66.

    Article  PubMed  Google Scholar 

  75. Nicolle LE, Gupta K, Bradley SF, Colgan R, DeMuri GP, Drekonja D, et al. Clinical practice guideline for the management of asymptomatic bacteriuria: 2019 update by the infectious diseases society of America. Clin Infect Dis Off Publ Infect Dis Soc Am. 2019;68:e83-110.

    Article  Google Scholar 

  76. Froom P, Shimoni Z. The uncertainties of the diagnosis and treatment of a suspected urinary tract infection in elderly hospitalized patients. Expert Rev Anti Infect Ther. 2018;16:763–70.

    Article  CAS  PubMed  Google Scholar 

  77. Artero A, López-Cruz I, Alberola J, Eiros JM, Resa E, Piles L, et al. Influence of sepsis on the middle-term outcomes for urinary tract infections in elderly people. Microorganisms. 2023;11:1959.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Yahav D, Eliakim-Raz N, Leibovici L, Paul M. Bloodstream infections in older patients. Virulence. 2016;7:341–52.

    Article  PubMed  Google Scholar 

  79. Leibovici-Weissman Y, Tau N, Yahav D. Bloodstream infections in the elderly: what is the real goal? Aging Clin Exp Res. 2021;33:1101–12.

    Article  PubMed  Google Scholar 

  80. Laupland KB, Pasquill K, Steele L, Parfitt EC. Burden of bloodstream infection in older persons: a population-based study. BMC Geriatr. 2021;21:31.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Gómez-Zorrilla S, Becerra-Aparicio F, López Montesinos I, Ruiz de Gopegui E, Grau I, Pintado V, et al. A large multicenter prospective study of community-onset healthcare associated bacteremic urinary tract infections in the era of multidrug resistance: even worse than hospital acquired infections? Infect Dis Ther. 2021;10:2677–99.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Falcone M, Meier JJ, Marini MG, Caccialanza R, Aguado JM, Del Prato S, et al. Diabetes and acute bacterial skin and skin structure infections. Diabetes Res Clin Pract. 2021;174: 108732.

    Article  CAS  PubMed  Google Scholar 

  83. Falcone M, Tiseo G. Skin and soft tissue infections in the elderly. Curr Opin Infect Dis. 2023;36:102–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021;47:1181–247.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Flevari A, Theodorakopoulou M, Velegraki A, Armaganidis A, Dimopoulos G. Treatment of invasive candidiasis in the elderly: a review. Clin Interv Aging. 2013;8:1199–208.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Matthaiou DK, Dimopoulos G, Taccone FS, Bulpa P, Van den Abeele AM, Misset B, et al. Elderly versus nonelderly patients with invasive aspergillosis in the ICU: a comparison and risk factor analysis for mortality from the AspICU cohort. Med Mycol. 2018;56:668–78.

    Article  CAS  PubMed  Google Scholar 

  87. Falcone M, Paul M, Tiseo G, Yahav D, Prendki V, Friberg LE, et al. Considerations for the optimal management of antibiotic therapy in elderly patients. J Glob Antimicrob Resist. 2020;22:325–33.

    Article  PubMed  Google Scholar 

  88. Psarrakis C, Giamarellos-Bourboulis EJ. Advancements in the pharmacological management of sepsis in the elderly. Expert Opin Pharmacother. 2023;24:1171–87.

    Article  CAS  PubMed  Google Scholar 

  89. Herring AR, Williamson JC. Principles of antimicrobial use in older adults. Clin Geriatr Med. 2007;23(481–97):v.

    PubMed  Google Scholar 

  90. Soraci L, Cherubini A, Paoletti L, Filippelli G, Luciani F, Laganà P, et al. Safety and tolerability of antimicrobial agents in the older patient. Drugs Aging. 2023;40:499–526.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Noreddin AM, El-Khatib W, Haynes V. Optimal dosing design for antibiotic therapy in the elderly: a pharmacokinetic and pharmacodynamic perspective. Recent Patents Anti-Infect Drug Disc. 2008;3:45–52.

    Article  CAS  Google Scholar 

  92. Weber S, Mawdsley E, Kaye D. Antibacterial agents in the elderly. Infect Dis Clin North Am. 2009;23:881–98, viii.

  93. Bellmann-Weiler R, Weiss G. Pitfalls in the diagnosis and therapy of infections in elderly patients–a mini-review. Gerontology. 2009;55:241–9.

    Article  PubMed  Google Scholar 

  94. Clifford KM, Dy-Boarman EA, Haase KK, Maxvill K, Pass SE, Alvarez CA. Challenges with diagnosing and managing sepsis in older adults. Expert Rev Anti Infect Ther. 2016;14:231–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Asfar P, Meziani F, Hamel J-F, Grelon F, Megarbane B, Anguel N, et al. High versus low blood-pressure target in patients with septic shock. N Engl J Med. 2014;370:1583–93.

    Article  CAS  PubMed  Google Scholar 

  96. Moman RN, Ostby SA, Akhoundi A, Kashyap R, Kashani K. Impact of individualized target mean arterial pressure for septic shock resuscitation on the incidence of acute kidney injury: a retrospective cohort study. Ann Intensive Care. 2018;8:124.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Muady GF, Bitterman H, Laor A, Vardi M, Urin V, Ghanem-Zoubi N. Hemoglobin levels and blood transfusion in patients with sepsis in Internal Medicine Departments. BMC Infect Dis. 2016;16:569.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Simon GI, Craswell A, Thom O, Chew MS, Anstey CM, Fung YL. Impacts of aging on anemia tolerance, transfusion thresholds, and patient blood management. Transfus Med Rev. 2019;33:154–61.

    Article  PubMed  Google Scholar 

  99. Serrano P, Kheir YNP, Wang S, Khan S, Scheunemann L, Khan B. Aging and postintensive care syndrome-family: a critical need for geriatric psychiatry. Am J Geriatr Psychiatry Off J Am Assoc Geriatr Psychiatry. 2019;27:446–54.

    Article  Google Scholar 

  100. Ferrante LE, Pisani MA, Murphy TE, Gahbauer EA, Leo-Summers LS, Gill TM. Functional trajectories among older persons before and after critical illness. JAMA Intern Med. 2015;175:523–9.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Polok K, Fronczek J, Guidet B, Artigas A, De Lange DW, Fjølner J, et al. Outcomes of patients aged ≥80 years with respiratory failure initially treated with non-invasive ventilation in European intensive care units before and during COVID-19 pandemic. Ann Intensive Care. 2023;13:82.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Annane D, Bellissant E, Bollaert PE, Briegel J, Keh D, Kupfer Y, et al. Corticosteroids for treating sepsis in children and adults. Cochrane Database Syst Rev. 2019;12:CD002243.

    PubMed  Google Scholar 

  103. Gibbison B, López-López JA, Higgins JPT, Miller T, Angelini GD, Lightman SL, et al. Corticosteroids in septic shock: a systematic review and network meta-analysis. Crit Care Lond Engl. 2017;21:78.

    Article  Google Scholar 

  104. Fang F, Zhang Y, Tang J, Lunsford LD, Li T, Tang R, et al. Association of corticosteroid treatment with outcomes in adult patients with sepsis: a systematic review and meta-analysis. JAMA Intern Med. 2019;179:213–23.

    Article  PubMed  Google Scholar 

  105. Young PJ, Bagshaw SM, Forbes AB, Nichol AD, Wright SE, et al. Effect of stress ulcer prophylaxis with proton pump inhibitors vs histamine-2 receptor blockers on in-hospital mortality among ICU patients receiving invasive mechanical ventilation: the PEPTIC randomized clinical trial. JAMA. 2020;323:616–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. van Haastregt JCM, Everink IHJ, Schols JMGA, Grund S, Gordon AL, Poot EP, et al. Management of post-acute COVID-19 patients in geriatric rehabilitation: EuGMS guidance. Eur Geriatr Med. 2022;13:291–304.

    Article  PubMed  Google Scholar 

  107. Niemöller U, Arnold A, Stein T, Juenemann M, Farzat M, Erkapic D, et al. Comprehensive geriatric care in older hospitalized patients with depressive symptoms. Geriatrics. 2023;8:37.

    Article  PubMed  PubMed Central  Google Scholar 

  108. Gagliano M, Bula CJ, Seematter-Bagnoud L, Michalski-Monnerat C, Nguyen S, Carron P-N, et al. Older patients referred for geriatric consultation in the emergency department: characteristics and healthcare utilization. BMC Geriatr. 2023;23:642.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Rowe T, Araujo KLB, Van Ness PH, Pisani MA, Juthani-Mehta M. Outcomes of older adults with sepsis at admission to an intensive care unit. Open Forum Infect Dis. 2016;3:ofw010.

    Article  PubMed  PubMed Central  Google Scholar 

  110. Lagu T, Rothberg MB, Shieh M-S, Pekow PS, Steingrub JS, Lindenauer PK. Hospitalizations, costs, and outcomes of severe sepsis in the United States 2003 to 2007. Crit Care Med. 2012;40:754–61.

    Article  PubMed  Google Scholar 

  111. Kumar G, Kumar N, Taneja A, Kaleekal T, Tarima S, McGinley E, et al. Nationwide trends of severe sepsis in the 21st century (2000–2007). Chest. 2011;140:1223–31.

    Article  PubMed  Google Scholar 

  112. Stoller J, Halpin L, Weis M, Aplin B, Qu W, Georgescu C, et al. Epidemiology of severe sepsis: 2008–2012. J Crit Care. 2016;31:58–62.

    Article  PubMed  Google Scholar 

  113. Liang L, Moore B, Soni A. National inpatient hospital costs: the most expensive conditions by payer, 2017. Healthc Cost Util Proj HCUP Stat Briefs. Rockville (MD): Agency for Healthcare Research and Quality (US); 2006. http://www.ncbi.nlm.nih.gov/books/NBK561141/.

  114. van Beusekom I, Bakhshi-Raiez F, de Keizer NF, van der Schaaf M, Busschers WB, Dongelmans DA. Healthcare costs of ICU survivors are higher before and after ICU admission compared to a population based control group: a descriptive study combining healthcare insurance data and data from a Dutch national quality registry. J Crit Care. 2018;44:345–51.

    Article  PubMed  Google Scholar 

  115. Mayr FB, Talisa VB, Balakumar V, Chang CCH, Fine M, Yende S. Proportion and cost of unplanned 30-day readmissions after sepsis compared with other medical conditions. JAMA. 2017;317:530–1.

    Article  PubMed  Google Scholar 

  116. Haas LEM, van Dillen LS, de Lange DW, van Dijk D, Hamaker ME. Outcome of very old patients admitted to the ICU for sepsis: a systematic review. Eur Geriatr Med. 2017;8:446–53.

    Article  Google Scholar 

  117. Kotfis K, Wittebole X, Jaschinski U, Solé-Violán J, Kashyap R, Leone M, et al. A worldwide perspective of sepsis epidemiology and survival according to age: observational data from the ICON audit. J Crit Care. 2019;51:122–32.

    Article  PubMed  Google Scholar 

  118. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003;348:1546–54.

    Article  PubMed  Google Scholar 

  119. Yang Y, Yang KS, Hsann YM, Lim V, Ong BC. The effect of comorbidity and age on hospital mortality and length of stay in patients with sepsis. J Crit Care. 2010;25:398–405.

    Article  PubMed  Google Scholar 

  120. Nasa P, Juneja D, Singh O, Dang R, Arora V. Severe sepsis and its impact on outcome in elderly and very elderly patients admitted in intensive care unit. J Intensive Care Med. 2012;27:179–83.

    Article  PubMed  Google Scholar 

  121. Haas LEM, Boumendil A, Flaatten H, Guidet B, Ibarz M, Jung C, et al. Frailty is associated with long-term outcome in patients with sepsis who are over 80 years old: results from an observational study in 241 European ICUs. Age Ageing. 2021;50:1719–27.

    Article  PubMed  Google Scholar 

  122. Ibarz M, Boumendil A, Haas LEM, Irazabal M, Flaatten H, de Lange DW, et al. Sepsis at ICU admission does not decrease 30-day survival in very old patients: a post-hoc analysis of the VIP1 multinational cohort study. Ann Intensive Care. 2020;10:56.

    Article  PubMed  PubMed Central  Google Scholar 

  123. Hall MJ, Levant S, DeFrances CJ. Trends in inpatient hospital deaths: National Hospital Discharge Survey, 2000–2010. NCHS Data Brief. 2013;1–8.

  124. Guidet B, de Lange DW, Boumendil A, Leaver S, Watson X, Boulanger C, et al. The contribution of frailty, cognition, activity of daily life and comorbidities on outcome in acutely admitted patients over 80 years in European ICUs: the VIP2 study. Intensive Care Med. 2020;46:57–69.

    Article  CAS  PubMed  Google Scholar 

  125. Akinosoglou K, Schinas G, Almyroudi MP, Gogos C, Dimopoulos G. The impact of age on intensive care. Ageing Res Rev. 2023;84: 101832.

    Article  PubMed  Google Scholar 

  126. Ferrer R, Artigas A, Levy MM, Blanco J, González-Díaz G, Garnacho-Montero J, et al. Improvement in process of care and outcome after a multicenter severe sepsis educational program in Spain. JAMA. 2008;299:2294–303.

    Article  CAS  PubMed  Google Scholar 

  127. Esteban E, Belda S, García-Soler P, Rodríguez-Núñez A, Calvo C, Gil-Anton J, et al. A multifaceted educational intervention shortened time to antibiotic administration in children with severe sepsis and septic shock: ABISS Edusepsis pediatric study. Intensive Care Med. 2017;43:1916–8.

    Article  PubMed  Google Scholar 

  128. Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34:1589–96.

    Article  PubMed  Google Scholar 

  129. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368–77.

    Article  CAS  PubMed  Google Scholar 

  130. ARISE Investigators, ANZICS Clinical Trials Group, Peake SL, Delaney A, Bailey M, Bellomo R, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014;371:1496–506.

  131. Fabbri A, Marchesini G, Benazzi B, Morelli A, Montesi D, Bini C, et al. Old subjects with sepsis in the emergency department: trend analysis of case fatality rate. BMC Geriatr. 2019;19:372.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Skei NV, Nilsen TIL, Mohus RM, Prescott HC, Lydersen S, Solligård E, et al. Trends in mortality after a sepsis hospitalization: a nationwide prospective registry study from 2008 to 2021. Infection. 2023;51:1773–86.

    Article  PubMed  PubMed Central  Google Scholar 

  133. Philippart F, Vesin A, Bruel C, Kpodji A, Durand-Gasselin B, Garçon P, et al. The ETHICA study (part I): elderly’s thoughts about intensive care unit admission for life-sustaining treatments. Intensive Care Med. 2013;39:1565–73.

    Article  CAS  PubMed  Google Scholar 

  134. Guidet B, Vallet H, Boddaert J, de Lange DW, Morandi A, Leblanc G, et al. Caring for the critically ill patients over 80: a narrative review. Ann Intensive Care. 2018;8:114.

    Article  PubMed  PubMed Central  Google Scholar 

  135. Prescott HC, Angus DC. Enhancing recovery from sepsis: a review. JAMA. 2018;319:62–75.

    Article  PubMed  PubMed Central  Google Scholar 

  136. Wang S, Allen D, Kheir YN, Campbell N, Khan B. Aging and post-intensive care syndrome: a critical need for geriatric psychiatry. Am J Geriatr Psychiatry Off J Am Assoc Geriatr Psychiatry. 2018;26:212–21.

    Article  Google Scholar 

  137. Lee M, Kang J, Jeong YJ. Risk factors for post-intensive care syndrome: a systematic review and meta-analysis. Aust Crit Care Off J Confed Aust Crit Care Nurses. 2020;33:287–94.

    Google Scholar 

  138. van der Slikke EC, Beumeler LFE, Holmqvist M, Linder A, Mankowski RT, Bouma HR. Understanding post-sepsis syndrome: how can clinicians help? Infect Drug Resist. 2023;16:6493–511.

    Article  PubMed  PubMed Central  Google Scholar 

  139. Beil M, van Heerden PV, Joynt GM, Lapinsky S, Flaatten H, Guidet B, et al. Limiting life-sustaining treatment for very old ICU patients: cultural challenges and diverse practices. Ann Intensive Care. 2023;13:107.

    Article  PubMed  PubMed Central  Google Scholar 

  140. Mousai O, Tafoureau L, Yovell T, Flaatten H, Guidet B, Beil M, et al. The role of clinical phenotypes in decisions to limit life-sustaining treatment for very old patients in the ICU. Ann Intensive Care. 2023;13:40.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank all the researchers who have dedicated their time to the older population.

Funding

AC acknowledges receiving financial support from Instituto de Salud Carlos III (ISCIII; Sara Borrell 2021: CD21/00087).

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Authors and Affiliations

  1. Department of Intensive Care Medicine, Hospital Universitari Sagrat Cor, Quirón Salud, Viladomat 288, 08029, Barcelona, Spain

    Mercedes Ibarz & Adrián Ceccato

  2. Department of Intensive Care Medicine, Diakonessenhuis Utrecht, Utrecht, the Netherlands

    Lenneke E. M. Haas

  3. Department of Intensive Care Medicine, CIBER Enfermedades Respiratorias, Corporación Sanitaria Universitaria Parc Tauli, Autonomous University of Barcelona, Sabadell, Spain

    Adrián Ceccato & Antonio Artigas

  4. Institut d’investigació i innovació Parc Tauli (I3PT-CERCA), Sabadell, Spain

    Antonio Artigas

Authors
  1. Mercedes Ibarz
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  2. Lenneke E. M. Haas
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  3. Adrián Ceccato
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  4. Antonio Artigas
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MI, AC and LH together drafted, wrote, and revised the manuscript. AA contributed to the writing. All authors read and approved the final manuscript.

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Correspondence to Mercedes Ibarz.

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None of the authors have conflicts of interest; both authors have read the current “Instructions to authors” and accept the conditions posed therein. This manuscript is original and has not been and will not be simultaneously submitted elsewhere for publication. None of the material from this study is included in another manuscript, has been published previously, or has been posted on the internet.

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Ibarz, M., Haas, L.E.M., Ceccato, A. et al. The critically ill older patient with sepsis: a narrative review. Ann. Intensive Care 14, 6 (2024). https://doi.org/10.1186/s13613-023-01233-7

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