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. 2024 Jan 19;165(6):1421–1430. doi: 10.1016/j.chest.2024.01.028

Hospital-Onset Sepsis Warrants Expanded Investigation and Consideration as a Unique Clinical Entity

Jennifer C Ginestra a, Angel O Coz Yataco b, Siddharth P Dugar b, Matthew R Dettmer b,c,∗
PMCID: PMC11177099  PMID: 38246522

Abstract

Sepsis causes more than a quarter million deaths among hospitalized adults in the United States each year. Although most cases of sepsis are present on admission, up to one-quarter of patients with sepsis develop this highly morbid and mortal condition while hospitalized. Compared with patients with community-onset sepsis (COS), patients with hospital-onset sepsis (HOS) are twice as likely to require mechanical ventilation and ICU admission, have more than two times longer ICU and hospital length of stay, accrue five times higher hospital costs, and are twice as likely to die. Patients with HOS differ from those with COS with respect to underlying comorbidities, admitting diagnosis, clinical manifestations of infection, and severity of illness. Despite the differences between these patient populations, patients with HOS sepsis are understudied and warrant expanded investigation. Here, we outline important knowledge gaps in the recognition and management of HOS in adults and propose associated research priorities for investigators. Of particular importance are questions regarding standardization of research and clinical case identification, understanding of clinical heterogeneity among patients with HOS, development of tailored management recommendations, identification of impactful prevention strategies, optimization of care delivery and quality metrics, identification and correction of disparities in care and outcomes, and how to ensure goal-concordant care for patients with HOS.

Sepsis, a state of life-threatening organ dysfunction caused by a dysregulated host response to infection, is a common syndrome associated with high morbidity, mortality, and health care costs.1 In the United States, more than 1.7 million adults develop sepsis annually, resulting in approximately 270,000 deaths and ultimately contributing to one in every three deaths among hospitalized patients.2 Sepsis is the most expensive of all inpatient disease states, with aggregate costs in the United States exceeding $57 billion annually.3

Although most sepsis episodes are caused by an infection beginning before presentation to the hospital, up to one-quarter of sepsis cases develop during hospitalization.2,4 Patients with sepsis present on admission, often diagnosed in the ED, are referred to as having community-onset sepsis (COS), whereas those who develop sepsis more than 48 h after admission have hospital-onset sepsis (HOS).5,6 Although these designations may have some overlap in practice, as patients with infection present on admission may ultimately be labeled with sepsis after 48 h in the hospital because of progression of illness or delayed diagnosis, herein we refer to HOS according to Centers for Disease Control criteria, defined by both infection and organ dysfunction developing more than 48 h after admission.

Improved recognition and timely intervention for COS have led to significant improvement in mortality over the last 2 decades.7 However, outcomes for patients with HOS remain comparatively poor.5 In-hospital mortality among patients with HOS is 35%—and as high as 52% among those with shock—compared with 25% among patients with COS.4,8 Even after adjusting for baseline factors, developing HOS confers threefold increased odds of mortality compared with patients who never develop an infection leading to sepsis while hospitalized, and twofold greater odds of mortality than COS.5,9 Moreover, HOS is associated with greater resource utilization, with longer ICU length of stay (7 vs 3 days), longer hospital length of stay (17 vs 6 days), and fivefold higher hospital costs compared with COS.10

Although these poor outcomes may be explained in part by nonmodifiable baseline factors including differences in chronic and acute comorbidities (ie, underlying chronic conditions, acute pre-HOS admission illness, and related complications), some risk factors may be modifiable. For example, patients with HOS are less likely to receive timely infectious workup and treatment than their COS counterparts.9,11, 12, 13 In propensity-matched cohorts, differences in initial sepsis management including antimicrobial timing and fluid resuscitation accounted for 23% of observed greater mortality risk among HOS patients compared with COS, suggesting that nearly one in four excess deaths from HOS may not be explained by baseline differences in the populations.5 Most sepsis research, including the largest clinical trials, has focused on management of COS, to the exclusion of patients with HOS.14, 15, 16, 17 Data from these studies have been incorporated into society guidelines for sepsis management and quality metrics administered by the National Quality Forum and adopted by the Centers for Medicare and Medicare Services (CMS).18,19 Whether and how these data should be applied to patients with HOS is unclear.

Here, we argue for a concerted research effort focused on this high-risk yet understudied group of patients. We first describe how HOS differs from COS in adults, and why it may represent a distinct clinical condition. We then outline eight important domains of current knowledge gaps in the field and propose associated research priorities for investigators.

A Unique Clinical Entity

Baseline Factors

Patients who develop infections while hospitalized that lead to HOS tend to have a greater number of and different chronic comorbidities than patients with COS.5,20 Heart failure, renal failure, active cancer, stroke, and myocardial infarction have been reported more frequently in patients with HOS.9,20 Some of these comorbidities are associated with significant mortality risk. Moderate to severe liver disease and congestive heart failure in particular are shown to be associated with 27-fold and nearly sixfold increased odds of in-hospital mortality from HOS, respectively.21

Although nearly two-thirds of HOS cases occur during medical as opposed to surgical admissions, episodes of HOS are three times more likely to involve surgical conditions than COS.10 Although surgical admissions complicated by HOS are associated with longer lengths of stay and costs of hospitalization, medical patients who develop HOS have the highest mortality: 50% higher than for surgical patients with HOS.10 Common nonsurgical admitting diagnoses among patients with HOS include stroke, congestive heart failure, acute respiratory failure, acute kidney injury, trauma, and myocardial infarction.21

Illness Presentation

Patients with HOS and COS also differ in source of infection and causal organisms. Bacteremia and intraabdominal infections are more common in HOS, whereas pneumonia, urinary tract infections, and skin and soft tissue infections are more common in COS.5,9,10,22 Although Staphylococcus aureus causes nearly one-quarter of bloodstream infections for both COS and HOS, Enterococcus, Candida, and Pseudomonas species are two times more common in HOS bacteremia, and Escherichia and Streptococcus species are two times more common in COS.5

Compared with COS, patients with HOS less frequently present with typical systemic inflammatory response syndrome (SIRS) symptoms of infection such as tachypnea, tachycardia, fever, and elevated WBC count.9,21 In contrast, hypotension, impaired gas exchange, and normothermia or hypothermia are more common in patients with HOS.9,21 Severity of illness is generally higher in patients with HOS, with a greater number of dysfunctional organ systems and higher Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment (SOFA) scores than those with COS.5,22 Because HOS is more commonly complicated by neurologic, cardiovascular, respiratory, and renal dysfunction, these patients require vasopressors, mechanical ventilation, and renal replacement therapy nearly twice as often as those with COS.5,9 As a result, patients with HOS have higher rates of ICU admissions.5,9,10,21,22

One-Size-Fits-Some

Although there is overlap in the populations of patients affected by HOS and COS, these epidemiologic data demonstrate important differences signaling distinct patterns of comorbid disease and related underlying risk, complications, and prognosis. Observed differences in clinical presentation and manifestations of sepsis further suggest unique microbial risk profiles, immune response, and physiology among patients with HOS. This group thus may merit a more tailored diagnosis and treatment framework than the traditionally one-size-fits-all approach to sepsis management. Whether COS and HOS are best distinguished as different physiologic phenotypes of sepsis, as populations with different prevalence of the same subphenotypes of sepsis, or as entirely distinct clinical entities remains to be determined. Because most sepsis research has thus far focused on COS, expanded investigation focused on HOS is warranted.

Research Priorities

We have identified eight domains of important knowledge gaps and associated research priorities in HOS: clinical case identification, research case identification, clinical heterogeneity, management recommendations, prevention, care delivery, disparities, and goal-concordant care (Table 1).

Table 1.

Knowledge Gaps and Associated Proposed Research Priories for HOS

Knowledge Gaps Research Priorities
Clinical Case Identification
Diagnostic uncertainty
  • •

    Identify clinical presentations with greater risk of diagnostic uncertainty and delayed recognition.

  • •

    Develop diagnostic frameworks and tools to facilitate recognition and expedite management.
Early warning systems
  • •

    Incorporate HOS-specific clinical presentation and risk assessments into model development.

  • •

    Tailor implementation to patients and times at highest risk for delayed care.

  • •

    Determine evidence-based treatment goals for HOS to guide clinically meaningful lead time and clinically impactful interventions deployed with alert implementation.
ResearchCaseIdentification
EHR definition implementation
  • •

    Develop a standard approach to quantification of baseline organ dysfunction.

  • •

    Clearly describe implementation methods in publications to optimize replicability and generalizability.
“Time zero” for HOS research
  • •

    Develop and evaluate different approaches to demarcating sepsis onset in EHR data.

  • •

    Clearly describe and justify time zero approaches in publications.
Inpatient care delivery measures
  • •

    Identify the most appropriate time zero approaches for different care delivery questions.

  • •

    Clearly describe methods used to measure process-of-care timing in publications.
Heterogeneity
Patient population heterogeneity
  • •

    Develop diagnosis and risk assessment frameworks informed by acute and chronic comorbidities.
Physiologic heterogeneity
  • •

    Identify latent clinical HOS phenotypes and evaluate differences from COS phenotypes.

  • •

    Determine phenotype relevance for risk stratification and treatment decisions.
Management Recommendations
Treatment effectiveness
  • •

    Evaluate treatment effect among patients with HOS for key interventions and treatment strategies.

  • •

    Evaluate heterogeneity of treatment effect among HOS subgroups.
Balancing speed with uncertainty
  • •

    Identify patients at risk of poor outcomes from delays and evaluate optimal treatment timing.

  • •

    Develop clinical decision frameworks to guide risk evaluation and urgency of empiric treatment.
Modifiable risk factors
  • •

    Evaluate the impact of HAI prevention efforts on HOS incidence and outcomes.

  • •

    Develop strategies for risk mitigation and prevention of other inpatient infectious etiologies.
Prevention
Hospital-acquired infections
  • •

    Optimize delivery of and adherence to evidence-based interventions to prevent reportable HAIs.

  • •

    Evaluate the impact of reportable HAI prevention efforts on HOS incidence and outcomes.

  • •

    Examine epidemiology of infectious sources in HOS beyond reportable HAIs.
Pneumonia and aspiration
  • •

    Optimize delivery of and adherence to evidence-based interventions to prevent aspiration and ventilator-associated pneumonia.

  • •

    Evaluate the impact of pneumonia risk reduction efforts on HOS incidence and outcomes.
Care Delivery
Mechanisms of care gaps
  • •

    Identify times, places, care organization models, and patients most at risk for delays in care.

  • •

    Identify mechanisms underlying observed care quality gaps.
Improving care delivery
  • •

    Develop interventions targeting hospital-, provider-, and process-specific care delay mechanisms.
Measuring care quality
  • •

    Identify performance metrics that address HOS-specific risk factors and account for the realities of diagnostic uncertainty and inpatient workflow.
Disparities
Disparities in care and outcomes
  • •

    Evaluate quality of care and outcomes across sex, race, ethnicity, income, primary language, insurance status, region, and other social determinants of health.
Correcting disparities
  • •

    Evaluate impact of hospital-level variation in care quality on HOS disparities.

  • •

    Identify pre-hospital and in-hospital mechanisms underlying any identified HOS disparities.
Goal-concordant Care
Goal-concordant care
  • •

    Assess patients’ goals and priorities in the setting of life-limiting illness complicated by HOS.

  • •

    Include patient-centered outcomes such as hospital-free-days in HOS studies.
Palliative care services
  • •

    Develop frameworks to identify patients most likely to benefit from palliative care services.

  • •

    Evaluate the impact of targeted palliative care consult programs for patients with HOS.
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COS, community-onset sepsis; EHR, electronic health record; HAI, hospital-acquired infections; HOS, hospital-onset sepsis.

Clinical Case Identification

Clinical recognition of an episode of HOS is often challenging, because there may be considerable diagnostic uncertainty in the early hours of a new infection. First, patients who develop a new infection leading to sepsis while hospitalized often have persistent physiologic derangements before sepsis onset that are attributable to the initial acute illness that prompted hospitalization. Recognizing and untangling new signs and symptoms among multiple active pathologic conditions can be difficult. Second, the cause of a clinical change may be unclear, because patients are at risk for not only hospital-acquired infections (HAIs), but also progression of noninfectious processes, exacerbations of chronic disease, and iatrogenic complications. Consider for example a 78-year-old patient admitted after a hip replacement who develops new encephalopathy, dyspnea, hypoxia, and pulmonary opacities on imaging. It may be unclear initially whether the patient has developed hospital-onset pneumonia and sepsis, a heart failure exacerbation and hospital-exacerbated dementia, or iatrogenic volume overload and pain medication-induced delirium. Moreover, patients with HOS may be less likely to present with typical signs of infection, which can contribute to diagnostic uncertainty and lead to delays in recognition and management.9,21,23 Research is needed to identify patients and clinical presentations that present greater diagnostic challenges and may benefit from diagnostic and decision support tools.

Improved understanding of HOS clinical presentations and the complexity of diagnostic uncertainty is critical to ensure clinical validity and utility of decision support tools. As of 2022, nearly two-thirds of US hospitals employ alerts based on older SIRS-based sepsis criteria to facilitate rapid sepsis recognition.25 Given that nearly one-half of ward patients meet at least two SIRS criteria at least once during admission, this nonspecific approach is likely impractical and does not align with modern definitions of sepsis.1,24 Correspondingly, one-third of hospitals have begun to employ more advanced predictive models, including machine-learning model-guided alerts, although with mixed impact on patient outcomes.25,26 Notably, the most commonly used predictive tool has been shown to miss sepsis in two-thirds of cases, infrequently identify septic patients not receiving timely care, and generate a high degree of false positives.27 Tailoring the development and implementation of inpatient sepsis alerts to the clinical presentations, diagnostic vulnerabilities, and evidence-based treatment goals for HOS may help target resources to the highest-risk patients. The wealth of clinical electronic health record (EHR) data available before, during, and after an episode of HOS makes this area of research ripe with opportunity.

Research Case Identification

Accurate HOS case identification for research is also no easy feat. Two approaches using retrospective EHR data are well described: (1) the Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3) criteria and (2) the Centers for Disease Control and Prevention Adult Sepsis Event criteria.1,6,28,29 Although each has been validated for both community- and hospital-onset case identification, there is little published guidance regarding optimal practical implementation for HOS cases, resulting in variable approaches across studies. For example, although the Sepsis-3 authors recommend assuming a baseline SOFA score of zero “unless the patient is known to have preexisting (acute or chronic) organ dysfunction before the onset of infection,” they do not detail their approach to determining the degree of preexisting organ dysfunction.1,28 Investigators must report implementation methods clearly to facilitate replicability and promote standard research practices.

Defining and identifying “time zero” of sepsis onset in hospital-onset cases also requires special consideration. Even with the advantage of a retrospective lens and at least 48 h of inpatient data before sepsis onset available for all patients, demarcating the start of a HOS episode remains difficult. In the absence of a gold standard clinical definition, the time of ED triage is often used to represent time zero for COS.30 Such a proxy cannot be applied to patients who develop a new infection leading to sepsis while hospitalized. Although the first EHR indication of a hospital-onset infection may be signaled by a blood culture being collected, if the associated acute kidney injury is not picked up until the next morning’s routine laboratory tests, when did sepsis “start”? Additional research is needed to identify time zero approaches that are most appropriate for different clinical and research questions.

Moreover, because adult sepsis event and Sepsis-3 criteria were designed for epidemiologic surveillance, they are based on calendar-day measures.1,6,28,29 Expert guidance is still needed to standardize their application to evaluate the timing of inpatient processes and delivery of care for patients with HOS. With early antimicrobial initiation having emerged as potentially the only treatment in our sepsis arsenal showing survival benefit for the sickest patients, our ability to accurately estimate treatment timing in the inpatient setting is increasingly important for quality assessments and observational causal inference studies in which logistical and ethical limitations preclude randomized trials. Hospital-quality metrics intended to ensure safety and effectiveness of inpatient care delivery would be strengthened by HOS-specific case criteria and care delivery measures that balance evidence-based goals for this population with the realities of diagnostic uncertainty and the realities of inpatient care.

Heterogeneity

There is growing recognition of heterogeneity in the sepsis syndrome and increasing research interest in describing subgroups that may benefit from tailored approaches to treatment.31

Risk stratification for patients with HOS must take into account heterogeneity in baseline chronic comorbidities, acute comorbid illness, and the effects of hospitalization itself. For example, patients with cirrhosis are particularly susceptible to infection and sepsis; infection is associated with a fourfold increase in mortality for cirrhotic patients and is an independent risk factor for acute-on-chronic liver failure.32 Patients with solid tumors who develop sepsis have a 28-day mortality of almost 70%.33 Patients with these and other conditions associated with a higher risk of death from HOS may benefit from population-specific approaches to diagnosis and triage. Disease-specific organ dysfunction scores such as the Chronic Liver Failure Sequential Organ Failure Assessment (CLIF-SOFA) may have better predictive accuracy for sepsis and mortality than conventional scores such as the SOFA score, SIRS, or National Early Warning Score.34,35 Incorporating important comorbidities in sepsis screening algorithms for hospitalized patients also may improve electronic sepsis detection.36 Collaboration between critical care and subspecialties that care for high-risk patient populations (eg, oncologic, cirrhotic, otherwise immunosuppressed) is vital to incorporate valuable research conducted on HAI in these populations, better understand disease-specific physiologic phenotypes and complications, align diagnostic and therapeutic recommendations, and appropriately risk stratify these patients as they develop sepsis.

In addition to observed differences in comorbidities, clinical presentation, complications, and outcomes compared with COS patients, patients who have been hospitalized are susceptible to changes in microbiome, vascular permeability, and immune function that may be important determinants of unique physiologic HOS phenotypes.37, 38, 39 Comprehensive latent clinical phenotypes associated with patterns of organ dysfunction, inflammatory profiles, patient outcomes, and related treatment implications have been described in COS, but equivalent research has lagged for HOS.40, 41, 42 In light of data suggesting heterogeneity of treatment effect across sepsis phenotypes and molecular endotypes—with variable benefit, and at times even harm, from interventions such as aggressive fluid resuscitation and corticosteroids—the identification of clinically important HOS phenotypes and subgroups will be vital to inform strategic enrollment into clinical trials, targeted quality improvement initiatives, and the development of precision treatment approaches.31,41, 42, 43, 44

Management Recommendations

International consensus guidelines for the management of severe sepsis and septic shock published by the Surviving Sepsis Campaign reference studies primarily conducted among patients with COS.18 Surviving Sepsis Campaign recommendations inform the CMS sepsis metric (SEP-1), to which adherence is publicly reported as a quality metric for acute care hospitals in the United States.19 However, whether and how these recommendations should be applied to patients with HOS has not been established. As such, the research priorities identified here have significant implications for quality improvement initiatives directed toward patients with HOS, including potential modifications of current sepsis guidelines.

Given clinical differences between the groups, and the fact that patients with HOS have largely been excluded from sepsis clinical trials, whether some recommendations confer the same benefits for patients with HOS as for those with COS is unclear. Although administration of IV fluids has been associated with reduced duration of shock among patients with COS, the same effect has not been demonstrated among patients with HOS.45 Particularly given increasing equipoise regarding the benefits of aggressive IV fluid resuscitation for sepsis, concerns about the potential harms of overresuscitation, and data suggesting heterogeneity of treatment effect across subgroups, additional research is needed to understand how current sepsis resuscitation recommendations and practices impact outcomes in HOS.42,46

Although rapid antimicrobial administration has been shown to be associated with improved mortality rates in patients with HOS,45 the optimal timing for treatment initiation and microbial coverage has not been established. Recommendations must balance the need for prompt treatment and appropriately broad coverage in this high-risk group with the realities of diagnostic uncertainty and need for appropriate risk assessment and infectious workup to guide therapy in the face of higher prevalence of fungal and multi-drug-resistant organisms in HOS.47

Identification of clinical phenotypes may be helpful to examine the risks and benefits of resuscitation and treatment strategies among subgroups of patients with HOS, informing targeted enrollment in clinical trials enriched for patients most likely to benefit from given treatment arms.31

Prevention

Research is needed to identify and understand modifiable risk factors to guide HOS-specific management recommendations. Because one in four patients with reportable HAIs—including more than one in two of those with central line-associated bloodstream infections—will develop HOS, studies examining the impact of HAI prevention recommendations including removal of indwelling catheters and other source control efforts on HOS incidence and outcomes are warranted.48 However, reportable HAIs account for only 14% of infections in HOS, so existing HAI prevention targets are likely insufficient.48 Given that 43% of the HOS cases not attributable to a reportable HAI are caused by pneumonia, 35% of these ventilator-associated, more work is needed to understand and mitigate risk factors such as aspiration.48 Guidelines and programs to reduce HAIs may need to be expanded to address more common HOS sources of infection.

Care Delivery

Although the rapidity of antimicrobial administration for COS has improved over time, there remains significant hospital-level and patient-level variation, particularly in HOS, for which care delivery is less often adherent to standard quality metrics.9,11, 12, 13,49 Patients with HOS are less likely than those with COS to receive CMS SEP-1-compliant care, including timeliness of blood culture collection, initial and repeat lactate testing, and fluid resuscitation.9,11, 12, 13 This group is also less likely to receive broad-spectrum antimicrobials within recommended timeframes, despite this being the SEP-1 element most associated with reduced mortality in HOS.9,11, 12, 13

Notably, patients who develop new infections leading to sepsis on non-ICU nursing wards are at higher risk of receiving SEP-1 noncompliant care than those developing sepsis in critical care areas.12,13 Although EDs are designed to triage and deliver rapid care for life-threatening conditions, hospital wards often lack the resources needed to frequently monitor vital signs or laboratory tests.10 Higher unit census also may contribute to delays in antibiotic administration among ward patients with new sepsis.50 Among hospitalized patients, sepsis onset during night shift and at change of shift is associated with longer time to antibiotic administration.51 Dedicated sepsis response teams have been associated with improved sepsis process of care metrics as well as mortality, although most patients included in these studies had COS and received initial care in the ED.52, 53, 54 Further studies to quantify the benefit of sepsis response teams on outcomes among HOS patients are indicated.

Faced with consistent findings of suboptimal care delivery for HOS, quality improvement personnel and clinical researchers should prioritize efforts to identify mechanisms underlying delays and quality gaps and develop interventions to address them. Moreover, unique performance and quality metrics may be indicated in this population, given the role of HAIs in HOS, patterns of infectious source, and microbial resistance specific to HOS, and differing workflow on inpatient units than in the ED.

Disparities

Higher rates of HAI and HOS are observed in patients who identify as belonging to racial and ethnic minority groups compared with White patients, which may be explained by socioeconomic and structural inequities that contribute to both prehospital and in-hospital risk factors.5,55 Sepsis mortality is higher among patients from socioeconomically disadvantaged populations and those who identify as belonging to racial and ethnic minority groups, although literature describing HOS-specific outcomes across these groups is lacking.56,57 Studies primarily conducted among patients with COS report conflicting associations between race and sepsis risk, with some reporting higher adjusted sepsis incidence and mortality among Black compared with White patients, and others reporting no difference, or even lower risk.58,59

Black patients and patients living in areas of socioeconomic disadvantage disproportionately receive care in urban teaching hospitals and so-called safety-net hospitals, which have higher patient-to-staff ratios and higher levels of capacity strain.56,60, 61, 62 These safety-net hospitals that primarily serve patients from racial and ethnic minority groups have been shown to have higher rates of HAIs, worse uptake and adherence to mandated sepsis protocols and quality metrics, longer times to antimicrobial initiation, and worse outcomes for sepsis.60,61,63, 64, 65, 66 However, disparities in care received and patient outcomes across social groups have not been comprehensively explored among patients with HOS, nor has the role of hospital factors in such disparities.

Patients with both COS and HOS are more likely to be men than not. Studies in COS report conflicting results regarding the presence of disparities in care delivery or patient outcomes by gender.58,67 Literature describing gender-based disparities among patients with HOS are lacking and warranted.

Goal-Concordant Care

Although the identification of modifiable causes of mortality in patients with HOS is an important research objective, defining nonmodifiable clinical factors also has considerable implications for clinical practice. Patients with HOS frequently have severe comorbidities, including active malignancy, so a subset of HOS-related deaths may not be preventable. Moreover, those who survive to hospital discharge experience high rates of postdischarge mortality; in one study, 28% of patients discharged to home health care from a sepsis admission died in the following year.68 Despite poor outcomes for patients hospitalized with sepsis, goals of care are not consistently documented, and these patients are at risk for receiving goal-discordant care after their sepsis admission.69 With epidemiologic overlap between malignancy and HOS, this group may share the quality-of-life benefits seen by patients with advanced cancer receiving early palliative intervention.70

Palliative medicine consultation for patients admitted with sepsis has the potential to decrease inpatient procedures, length of stay, and overall health care utilization and costs.71,72 Electronic screening tools have shown utility in identifying patients who might benefit from palliative care and may be of benefit in HOS.73 Given the high mortality risk from developing sepsis while hospitalized, and high rates of life-limiting underlying comorbidities in this population, early and patient-centered approaches to goals of care discussions and triage may help limit medically futile ICU admissions. Notably, continuation of antimicrobial therapy for patients with HOS sepsis may be consistent with patient-centered palliative goals, because it has been demonstrated to improve symptom burden and prolong meaningful survival in terminally ill patients, particularly in those with urinary tract infections.74,75

Conclusions

HOS is a high-risk clinical entity that differs substantially from COS and is associated with high morbidity, mortality, and health care costs, yet it remains understudied. Initial studies suggest that beyond baseline differences between the patient populations at risk for COS and HOS, differences in care received may explain some of these worse outcomes. As such, HOS warrants expanded investigation and consideration as a unique clinical entity. Areas of priority for future research should include optimizing HOS case identification at the bedside and in research, understanding clinical and risk heterogeneity in HOS, tailoring of management recommendations to the unique risks and needs of patients with HOS, optimizing HOS prevention measures, improving care delivery for HOS, identifying and eliminating disparities in care and outcomes for patients with HOS, and promoting goal-concordant care.

Financial/Nonfinancial Disclosures

None declared

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