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Sepsis is a medical emergency caused by organ dysfunction resulting from a dysregulated host response to an infection. Early identification and treatment of sepsis and septic shock are essential for improving outcomes. Timely initiation of antimicrobial therapy is one of the most effective interventions to reduce sepsis-related morbidity and mortality. Identifying sepsis and septic shock can be difficult due to their variable clinical presentation. Patients with suspected sepsis or septic shock are evaluated with various laboratory studies, including different biomarkers essential for diagnosis, early recognition of severity, risk stratification, and prognosis. The results of these studies and various clinical criteria can be used to effectively screen patients for sepsis and gauge the severity of the disease. This activity reviews the laboratory evaluation of patients with suspected sepsis or septic shock and highlights the role of the interprofessional team in improving care for patients with this life-threatening condition. Objectives: Identify the most common sources of infection in patients with sepsis. Correlate the pathophysiology of sepsis and septic shock with the common presenting clinical symptoms. Employ laboratory testing to determine the etiology and severity of sepsis or septic shock. Develop and implement interprofessional team protocols to improve outcomes in patients with sepsis or septic shock. Access free multiple choice questions on this topic.

Sepsis, defined by the Society of Critical Care Medicine (SCCM) Sepsis-3 criteria, is life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis and septic shock are high causes of mortality worldwide, resulting in the death of 1 in 3 to 1 in 6 patients in whom sepsis is identified.[1] Sepsis and septic shock are considered medical emergencies requiring time-sensitive evaluation and management; early identification and treatment initiation improve outcomes in sepsis patients. Specifically, early treatment with antimicrobial therapy is one of the most effective interventions that decreases in-hospital mortality in patients with sepsis.[2][3] Identifying sepsis and septic shock can prove problematic on initial presentation. The clinical presentation of sepsis is highly variable, the differential diagnosis of sepsis is exceedingly broad, and the underlying etiology of the presenting symptoms may not be immediately evident. This is particularly true for patients presenting with suggestive signs and symptoms in the emergency department.[4] Various screening tools for sepsis are used depending on the location of the evaluation. Most of these tools utilize criteria incorporating clinical evaluation, vital signs, and laboratory data to screen for sepsis and predict mortality. Some tools commonly used to screen for sepsis include the Systemic Inflammatory Response Syndrome (SIRS) criteria, quick Sequential Organ Failure Score (qSOFA), Sequential Organ Failure Assessment (SOFA) criteria, National Early Warning Score (NEWS), and Modified Early Warning Score (MEWS).[1] Sepsis is evaluated with various laboratory studies, including different biomarkers essential for diagnosis, early recognition of severity, risk stratification, and prognosis. These studies also have a role in dictating management and antibiotic stewardship. The initial management of a patient with suspected sepsis includes evaluation for the source of infection, severity assessment, treatment and prevention of hypotension, intravenous fluids, vasopressors, antibiotics, and infection source control. The severity of sepsis is determined through physical examination and laboratory evaluation.[4]

Sepsis is evaluated with various laboratory studies, including different biomarkers essential for diagnosis, early recognition of severity, risk stratification, and prognosis. These studies also have a role in dictating management and antibiotic stewardship. The initial management of a patient with suspected sepsis includes evaluation for the source of infection, severity assessment, treatment and prevention of hypotension, intravenous fluids, vasopressors, antibiotics, and infection source control. The severity of sepsis is determined through physical examination and laboratory evaluation.[4] The laboratory workup for patients with suspected sepsis includes blood lactate, complete blood count with differential (CBC), chemistry panel, and liver function tests (LFTs). Using this laboratory data, along with clinical findings, is essential in stratifying the severity of the disease. The SOFA score is used to define sepsis and has prognostic and therapeutic value. This scoring system allows clinicians to assess organ dysfunction, the characterizing feature of sepsis and septic shock, and evaluates the respiratory, cardiovascular, hepatic, renal, hematologic, and central nervous systems. The scores range from 0 to 4, with high scores signifying higher predicted mortality and the likelihood of requiring intensive care.[4][5]

In healthy hosts, infection causes an inflammatory response that is ideally localized and controlled. This host response is protective against microbial proliferation and dissemination. Certain microorganisms contain molecular constituents, such as gram-negative bacterial lipopolysaccharide and fungal beta-D-glucan, termed pathogen-associated molecular patterns (PAMPs). These PAMPs are recognized by pattern recognition receptors (PRRs), including but not limited to Toll-like receptors (TLRs), which initiate an inflammatory response. Additionally, the release of intracellular contents into the circulation by damaged host cells, termed damage-associated molecular patterns (DAMPs), potentiates the host inflammatory response. These molecules activate the TLRs of antigen-presenting cells (APCs) and monocytes, increasing the expression of various transcription factors, including nuclear factor-κB and AP-1. This subsequently results in the release of proinflammatory interleukins (IL), tumor necrosis factor-alpha (TNF-α), cytokines, interferons (IFNs), and chemokines.[12][13][14] Severe infection stimulates the release of both mature and immature neutrophils via emergency granulocyte maturation. Immature neutrophils have decreased phagocytic abilities and a reduced capacity for oxidative burst. Elevated levels of immature neutrophils and increased production of neutrophil extracellular traps (NETs) are directly linked to clinical deterioration. NETs are designed to trap various microbial pathogens, including bacteria, viruses, fungi, protozoa, and parasites. Chemokines, cytokines, and platelet agonists trigger the production and release of NETs. Increased NETs are associated with hypercoagulability and endothelial dysfunction.[14]

Severe infection stimulates the release of both mature and immature neutrophils via emergency granulocyte maturation. Immature neutrophils have decreased phagocytic abilities and a reduced capacity for oxidative burst. Elevated levels of immature neutrophils and increased production of neutrophil extracellular traps (NETs) are directly linked to clinical deterioration. NETs are designed to trap various microbial pathogens, including bacteria, viruses, fungi, protozoa, and parasites. Chemokines, cytokines, and platelet agonists trigger the production and release of NETs. Increased NETs are associated with hypercoagulability and endothelial dysfunction.[14] The immune response to infection includes cellular and chemical mediators that lead to the activation of other components, and inactivation occurs via counterregulatory processes to restore homeostasis after the resolution of the acute phase of infection. Derangement of this process results in organ dysfunction and sepsis. Multifactorial systemic derangements, including increased vascular permeability, decreased organ perfusion, and hypercoagulability secondary to increased leukocyte adhesion and endothelial and platelet dysfunction cause organ dysfunction in sepsis. Decreased tissue perfusion leads to tissue hypoxia and cellular and mitochondrial dysfunction, which can persist even after restoring adequate tissue perfusion.[15]

Managing sepsis and septic shock requires the collaborative effort of healthcare professionals such as physicians, nurses, patient care technicians, and pharmacists, among others, to enhance patient-centered care and improve outcomes. Early identification of sepsis and treatment with antimicrobial therapy is the most effective intervention that decreases in-hospital mortality in patients with sepsis. The diagnosis of sepsis can be complex due to the broad differential diagnosis, which requires a combination of clinical evaluation, vital signs, and laboratory data using various screening tools such as SIRS, qSOFA, SOFA, NEWS, and MEWS. A laboratory workup, including CBC, chemistry panel, LFTs, and biomarkers such as blood lactate, is essential for diagnosis, risk stratification, and prognosis of sepsis. The SOFA score is used to define sepsis and has diagnostic and prognostic value. Evaluation for the source of infection, severity assessment, treatment and prevention of hypotension, intravenous fluids, vasopressors, antibiotics, and infection source control are essential in managing patients with suspected sepsis. Healthcare professionals should be aware of the complexity and potential outcomes involved in caring for septic patients. They should engage in interprofessional communication and care coordination to enhance team performance and patient safety. Thorough understanding of laboratory evaluations of sepsis can better aid the healthcare team in delivering patient care promptly and improving patient outcomes.