A 47-year-old woman with a history of cirrhosis is admitted with an acute kidney injury and altered mental status. On the initial workup, there are no signs of infection, and dehydration is determined to be the cause of the kidney injury. There are signs of improvement in the kidney injury with hydration. On hospital day 3, the patient develops a fever (101.9 oF) with accompanying leukocytosis to 14,000. Concerned for infection, the team starts empiric broad spectrum antibiotics for presumed spontaneous bacterial peritonitis. The next day (hospital day 4), a rapid response evaluation is activated as the patient is demonstrating increasing confusion, hypotension with a systolic blood pressure of 70 mm Hg, and elevated lactic acid. The patient receives 1 L of normal saline and transfers to the ICU. The new critical care fellow, who has just read up on sepsis early management bundles, and specifically the Severe Sepsis and Septic Shock Management Bundle (SEP-1), is reviewing the chart and notices a history of multidrug-resistant organisms in her urine cultures from an admission 2 months ago. They ask of the transferring team, “When was time zero, and was the 3-hour bundle completed?”
Sepsis is recognized as a medical emergency, which, without a prompt response, causes significant morbidity and mortality. In the United States alone, more than 1.7 million adults develop sepsis, with approximately 270,000 deaths and $57 billion in aggregate costs annually. 1 The excessive cost, both of human life and monetary, has led to the commitment of significant resources to sepsis care. Improved recognition and timely intervention for sepsis have led to noteworthy improvement in mortality. Most of this effort has been directed toward patients with sepsis diagnosed in the emergency department (ED) who are presenting with community-onset sepsis (COS). A new entity, called hospital-onset sepsis (HOS), has been described recently, defined by the Centers for Disease Control and Prevention (CDC) as both infection and organ dysfunction developing more than 48 hours after hospital admission.2
A systematic review of 51 studies found approximately 23.6% of all sepsis cases are HOS. The proportion of HOS is even higher (more than 45%) in patients admitted to the ICU with sepsis.3 The outcome for this group remains comparatively poor. The hospital mortality among patients with HOS is 35%, which increases to 52% with progression to septic shock compared with 25% with COS.3 Even after adjusting for baseline factors that make one prone to developing infection in the hospital, a patient developing HOS has three-times a higher risk of dying compared with a patient who never developed sepsis and two-times a higher risk of dying compared with patients with COS.4 Furthermore, HOS utilizes more resources with significantly longer ICU and hospital stays and has five-times the hospital cost compared with COS.4
The two most crucial factors in improving sepsis outcomes, as identified by the Surviving Sepsis Campaign guidelines, are: 1) prompt identification and treatment within the first few hours of onset and 2) regular reevaluation of the patient’s response to treatment.
Prompt identification
Diagnosing sepsis in the patient who is hospitalized is challenging. Patients admitted to the hospital often have competing comorbidities, have existing organ failure, or are in a postoperative/intervention state that clouds the application and interpretation of vital sign triggers customarily used to identify sepsis. The positive predictive value for all existing sepsis definitions and diagnostic criteria is dismally low. 5 And while automated electronic sepsis alerts may improve processes of care, they still have poor positive predictive value and have not impacted patient-centered outcomes (mortality or length of stay). Furthermore, the causative microorganisms often associated with hospital-acquired infections are complex, are drug-resistant, and can have courses which further delay identification. Finally, cognitive errors, such as anchoring biases or premature diagnosis closure, can contribute to provider-level identification delays that are only further exacerbated by system issues, such as capacity constraints, staffing issues, and differing paces between wards that tend to impede time-sensitive evaluations and interventions. 4 6 7
Management
The SEP-1 core measure uses a framework of early recognition of infection and completion of the sepsis bundles in a timely manner to improve outcomes. Patients with HOS are less likely than those with COS to receive Centers for Medicare & Medicaid Services SEP-1-compliant care, including timely blood culture collection, initial and repeat lactate testing, and fluid resuscitation.8 The Surviving Sepsis Campaign has explored barriers to managing HOS. Among caregivers, these include delay in recognition, poor communication regarding change in patient status, not prioritizing treatment for sepsis, failure to measure lactate, delayed or no antimicrobial administration, and inadequate fluid resuscitation. In one study, the adherence to SEP-1 for HOS was reported at 13% compared with 39.9% in COS. The differences in initial sepsis management included timing of antimicrobials and fluid resuscitation, which accounted for 23% of observed greater mortality risk among patients with HOS compared with COS.6 8 It remains unclear how these recommendations should be applied and whether some of these recommendations confer the same benefits for patients with HOS as for those with COS. For example, administration of fluids conferred no additional benefit to patients with HOS, while rapid antimicrobial administration was shown to be associated with improved mortality in patients with HOS. Although, the optimal timing for treatment initiation and microbial coverage has not been established.
The path forward
Effective HOS management requires both individual and systematic approaches. How clinicians identify a patient with sepsis must be context-dependent. Although standard criteria exist for defining sepsis, the approach to a patient presenting to the ED from home should differ from that of a patient who has been hospitalized for several days, is postoperative, or is in the ICU on multiple forms of life support. Clinical medicine is context-dependent, and the same principles apply to sepsis management. To address the diagnostic uncertainty of the syndrome, providers must remain vigilant and maintain a clinical “iterative urgency” in diagnosing and managing sepsis. While machine learning algorithms have potential, they still rely on human intervention and interaction to navigate the complexities of HOS diagnosis.
At the system level, survival from sepsis is determined by the speed with which complex medical care is delivered and the effectiveness with which resources and personnel are mobilized and coordinated. The Hospital Sepsis Program Core Elements, released by the CDC, serves as an initial playbook to aid hospitals in establishing comprehensive sepsis improvement programs.
A second invaluable resource for hospitals in sepsis management is the rapid response team (RRT). Studies have shown that resolute RRTs can enhance patient outcomes and compliance with sepsis bundles; though, the composition and scope of these teams are crucial to their effectiveness. Responding to in-hospital emergencies and urgencies without conflicting responsibilities is an essential feature of a successful RRT. Often, they are familiar with bundles, protocols, and documentation, and members of these teams can offer clinical and/or technical expertise as well as support active participation and reengagement with bedside staff, which fosters trust and collaboration. This partnership is key, as these interactions instill a common mission and foster a culture of sepsis improvement that is required to achieve sustained success and improved patient outcomes.
Dr. Dugar is Director, Point-of-Care Ultrasound, Department of Critical Care, Respiratory Institute, Assistant Professor, Cleveland Clinic Lerner College of Medicine, Cleveland, OH. Dr. Jayaprakash is Associate Medical Director, Quality, Emergency Medicine, Physician Lead, Henry Ford Health Sepsis Program. Dr. Reilkoff is Executive Medical Director of Critical Care, M Health Fairview Intensive Care Units, Director of Acting Internship in Critical Care, University of Minnesota Medical School, Associate Professor of Medicine and Surgery, University of Minnesota. Dr. Duggal is Vice-Chair, Department of Critical Care, Respiratory Institute, Director, Critical Care Clinical Research, Associate Professor, Cleveland Clinic Lerner College of Medicine, Cleveland, OH
References
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3. Markwart R, Saito H, Harder T, et al. Epidemiology and burden of sepsis acquired in hospitals and intensive care units: a systematic review and meta-analysis. Intensive Care Med. 2020;46(8):1536-1551.
4. Rhee C, Wang R, Zhang Z, et al. Epidemiology of hospital-onset versus community-onset sepsis in U.S. hospitals and association with mortality: a retrospective analysis using electronic clinical data. Crit Care Med. 2019;47(9):1169-1176.
5. Wong A, Otles E, Donnelly JP, et al. External validation of a widely implemented proprietary sepsis prediction model in hospitalized patients. JAMA Intern Med. 2021;181(8):1065-1070.
6. Baghdadi JD, Brook RH, Uslan DZ, et al. Association of a care bundle for early sepsis management with mortality among patients with hospital-onset or community-onset sepsis. JAMA Intern Med. 2020;180(5):707-716.
7. Baghdadi JD, Wong MD, Uslan DZ, et al. Adherence to the SEP-1 sepsis bundle in hospital-onset v. community-onset sepsis: a multicenter retrospective cohort study. J Gen Intern Med. 2020;35(4):1153-1160.
8. Basheer A. Patients with hospital-onset sepsis are less likely to receive sepsis bundle care than those with community-onset sepsis. Evid Based Nurs. 2021;24(3):99.