Sepsis is an acute life-threatening condition characterized by organ dysfunction due to a dysregulated immune response to infection. Without prompt intervention, patients frequently progress to and . The precipitating infection is often bacterial, typically originating in the respiratory, genitourinary, or gastrointestinal systems or in the skin or soft tissue. Clinical features include fever, tachycardia, confusion, and signs of the primary infection. Sepsis screening tools incorporating common clinical variables and laboratory values are used to facilitate early identification of sepsis. Favorable patient outcomes rely on early detection, effective resuscitation measures (e.g., aggressive fluid therapy and appropriate use of vasopressors), and early administration of antibiotics. The diagnostic workup of sepsis should occur in parallel with resuscitation efforts and focuses on identifying the site of infection and causative pathogen for definitive treatment.
Definitions and criteria in this section apply to adult patients.
Third International Consensus Definitions for Sepsis and Septic Shock 
- Sepsis: a severe, life-threatening condition that results from a dysregulation of the patient's response to an infection, causing tissue and organ damage and subsequent organ dysfunction 
- Septic shock: a sepsis syndrome accompanied by circulatory and metabolic abnormalities that can significantly increase mortality 
Organ dysfunction secondary to sepsis is defined as an acute increase of ≥ 2 in the total due to the infection.
Other definitions of sepsis syndromes 
- Systemic inflammatory response syndrome (SIRS) : a group of physiological and immune-mediated reactions that are triggered in response to an infectious or noninfectious insult (e.g., an acute inflammatory process or trauma) 
- Sepsis: ≥ 2 SIRS criteria PLUS a suspected or confirmed underlying infection 
- Severe sepsis: sepsis PLUS dysfunction of at least one organ or system 
Multiple organ dysfunction syndrome (MODS) : 
- Progressive, but potentially reversible, dysfunction of several organs and/or systems 
- The more organs that are affected, the greater the mortality risk.
- : the presence of viable bacteria in the bloodstream, with or without clinical signs of infection 
Sequential organ failure assessment score (SOFA score) 
- Used in critical care settings as a tool to identify organ failure and predict mortality
- The score should be calculated after 24 hours of ICU admission and then every 48 hours.
- Should not be used to diagnose sepsis
|SOFA score |
|System||0 points||1 point||2 points||3 points||4 points|
| || || || || |
Platelets x 103/mm3
| || || || || |
| || || || || |
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Glasgow Coma Scale
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The SOFA score is not designed to diagnose sepsis.
See also “.”
- Common sources of sepsis: 
- Bacterial: gram-positive bacteria (most common in the US); gram-negative bacteria
- Fungal, viral, or parasitic infection (rare)
Common risk factors
- Age: < 1 year or > 75 years
- Primary comorbidities (diabetes mellitus, cirrhosis, community acquired pneumonia, bacteremia, )
- Immunosuppression (neutropenia, corticosteroid treatment)
- Intensive care or prolonged admission (nosocomial infections)
- Recent antibiotic or corticosteroid treatment
- Invasive medical devices (e.g., endotracheal tubes, intravenous lines, urinary catheters)
Implanted devices are an important risk factor and a common source of infection. 
Sepsis is a hyperinflammatory systemic reaction.
- Local activation of inflammatory mediators (complement system, mast cells, macrophages) results in vessel dilation and further release of proinflammatory cytokines (esp. TNFα, IL-1).
- Generalized endothelial disruption → capillary leak → generalized edema due to a shift of intravascular fluid and albumin into the surrounding tissue
- Intravascular hypovolemia; → excessive triggering of the extrinsic coagulation cascade → disseminated intravascular coagulation (DIC) and microvascular thrombosis
- Decreased oxygen utilization and tissue ischemia; → widespread cellular injury → organ dysfunction (commonly multisystem)
An adequate immune response requires a balance between proinflammatory (antiinfectious) and antiinflammatory signals!
- General features
- Features of organ dysfunction (see )
- Features of septic shock
- Features of the primary infection: e.g., , , , ,
The following recommendations are consistent with the 2021 Surviving Sepsis Campaign guidelines and the American College of Emergency Physicians (ACEP) task force consensus statement for adults with suspected sepsis in the emergency department. 
Perform diagnostics and treatment simultaneously in patients with suspected sepsis.
- Use a to identify at-risk patients following local protocols.
- Consider empiric management of high-risk patients even if screening tools are negative. 
- Perform a clinical evaluation using the .
- Establish IV access, pulse oximetry, and continuous .
- Obtain the following initial studies immediately:
- Initial management: Provide and respiratory support for unstable patients without delay.
- Continuous reassessment of
- Begin .
Hour-1 bundle for sepsis 
- Definition: a group of critical measures that should be performed within 60 minutes of recognizing patients with septic shock or a high (PTP) of sepsis. 
- Five essential elements
- Admit unstable patients with sepsis to the ICU within 6 hours.
- If available, consider using a ICU to other hospital settings after stabilization. for patients discharged from
- Consider transfer to a rehabilitation program upon hospital discharge for patients with the following:
The main goals of the diagnostic workup in a patient with suspected sepsis are to determine the presence and severity of organ dysfunction and to identify the source of infection. See the “Definitions” section for diagnostic criteria. 
Positive cultures are not mandatory for the diagnosis of sepsis.
Sepsis screening tools 
- Goal: early identification of patients with sepsis to reduce mortality 
- Commonly used tools 
- Limitations: Accuracy is low and can vary. 
- CBC: variable findings
- CRP, procalcitonin: typically elevated 
- BMP and electrolytes
- Liver chemistry and synthetic function tests: hyperbilirubinemia, ↑ INR, ↑ ALT, ↑ AST
- Coagulation panel, D dimer: ↑ prothrombin time, ↑ activated partial thromboplastin time, ↓ antithrombin III, ↑ D dimer may be present (see “Disseminated intravascular coagulation”)
- Consider amylase, lipase (if pancreatitis is suspected)
- Blood gas: to identify possible acid-base disturbances and assess oxygenation
Identifying the source of infection
- In addition to blood cultures, consider additional cultures guided by clinical judgment (see “Etiology”).
- Diagnostic procedures as indicated to obtain samples for cultures (e.g., lumbar puncture, thoracentesis, paracentesis, arthrocentesis)
- Pan cultures are discouraged unless the source of infection is unclear. 
Direct decisions based on clinical suspicion. Examples of commonly performed imaging include:
- Chest x-ray: if pneumonia is suspected and/or to determine if ARDS is present as a complication (see “Diagnosis of pneumonia”)
- Abdominal x-ray: if a perforation or obstruction is suspected (pneumoperitoneum, air-fluid levels)
- CT scan: for a more detailed assessment of thoracic and abdominal/pelvic pathology
- Echocardiography: to identify valve vegetations (see “Infective endocarditis”)
Resuscitation and reassessment
- Initial : rapid infusion of 30 mL/kg crystalloid fluid 
- Ongoing management 
Vasopressors for septic shock 
- Indication: persistent hypotension during or after fluid resuscitation
- Target: MAP ≥ 65 mm Hg 
- First line: norepinephrine 
- Second line: Consider adding vasopressin if hypotension persists with moderate doses of norepinephrine. 
- Third line: Consider adding epinephrine if hypotension persists despite norepinephrine AND vasopressin. 
- Refractory tissue hypoperfusion : Consider adding dobutamine OR switching to epinephrine alone. 
Consider starting vasopressor infusion through a peripheral IV to avoid delays while awaiting . 
Hemodynamic reassessment in sepsis 
- Consider adding . 
Consider protocolized resuscitation targets.
- Protocols targeting ≤ 3 seconds 
If possible, use to facilitate continuous reassessment. 
Respiratory support 
- Start  as needed.
- Secure the airway and assess for .
- Consider screening for 
to ensure early identification.
- See “ .”
- See “ .”
- Begin broad-spectrum antibiotics as soon as possible after sepsis is identified, ideally after blood cultures have been drawn. 
- Follow local guidelines.
- Ensure as early as possible.
Empiric antibiotic therapy for sepsis 
Evident source of infection 
If the source of infection is clear, follow local hospital protocols to administer antibiotics that cover the most common causative pathogens.
|Common sources of infective pathogens and their treatment|
|Respiratory tract||S. pneumoniae, H. influenzae, M. pneumoniae, S. aureus, C. pneumoniae ||See “.”|
|Urinary tract||E. coli, Proteus spp., Klebsiella spp., Pseudomonas spp. ||See “” and “ .”|
|Intraabdominal||E. coli, other Enterobacteriaceae (e.g., K. pneumoniae), Pseudomonas spp., Streptococcus spp., anaerobes (e.g., Bacteroides spp.) ||See “.”|
|Bone or soft tissue||Streptococcus spp. (including MRSA), Staphylococcus spp., P. aeruginosa, Enterobacteriaceae, anaerobes ||See “” and “ .”|
|Cardiovascular||Staphylococcus spp., Streptococcus spp., Enterococcus spp., ||See “.”|
|Hospital-acquired infections (HAIs)||See “Overview of the most common causative pathogens in HAIs” and “Multidrug-resistant organisms.”||See “.”|
Unclear source of infection 
The following regimens are examples commonly mentioned in the literature; follow local hospital protocols when available.
|Empiric antibiotic regimens for sepsis with unclear source|
|Patient characteristics||Commonly used regimens|
Unknown risk factors
At risk for specific pathogens
Antifungal therapy 
- Risk factors for include:
- Consider empiric antifungals (in consultation with an ID specialist) for high-risk patients only, e.g., those with: 
- Treatment options
Source control for sepsis 
Identify and eliminate sources of infection that cannot be adequately treated with antimicrobials as soon as possible (e.g., within 6–12 hours). 
- or devices after replacement with an alternative.
- Arrange drainage of contained infections (e.g., abscesses, cholangitis) and/or surgical resection of infected tissue
- Consult the appropriate specialty for definitive treatment of the infectious source, e.g.:
- Surgery for:
- Interventional radiology for:
- Fluids, nutrition, and electrolytes 
Transfusions: Consider as needed. 
- pRBCs for the following hemoglobin thresholds:
Platelets for the following platelet count thresholds:
- < 10,000/mm3 in all patients
- < 20,000/mm3 in patients with a high risk of bleeding
- < 50,000/mm3 in patients with active bleeding or planned surgery or invasive procedure
- FFP to correct coagulopathy in patients with active bleeding or a planned invasive procedure
Other supportive measures 
- Normoglycemia: insulin as needed for target glucose of 140–180 mg/dL (see “Inpatient management of hyperglycemia”)
- VTE prophylaxis with LMWH if there are no contraindications 
- Stress ulcer prophylaxis in patients with risk factors for GI bleeding 
- Renal replacement therapy (RRT) in patients with absolute 
- Use a sepsis screening tool (e.g., SIRS criteria) in at-risk patients.
- Obtain IV access and blood samples including 2 sets of blood cultures and serum lactate.
- Begin continuous cardiac and respiratory monitoring.
- Consider and insertion if is present.
- Initiate fluid resuscitation with 30 mL/kg of crystalloid fluid.
- Add vasopressors if shock persists despite adequate fluid resuscitation.
- Provide respiratory support as needed.
- Start empiric broad-spectrum antibiotic therapy (within 1 hour for or high of sepsis).
- Conduct frequent reassessments, e.g., lactate, , serial serum
- Consult ICU early.
- Complete evaluation for organ dysfunction, e.g., CBC, BMP, liver chemistries, blood gas, coagulation panel
- Consider additional imaging and cultures (urine, wound, sputum) based on clinical suspicion.
- Arrange surgery for acute abdomen , e.g., , consult
- Start supportive care, e.g., maintenance of normoglycemia, nutritional support, VTE prophylaxis
- Identify and treat complications, e.g., DIC, ARDS, AKI
- Admit to critical care unit.
The following is a list of noninfectious conditions that may mimic sepsis. 
- Other causes of hypotension/shock
- Cardiovascular diagnoses
- Respiratory diagnoses
- Common complications 
Critical illness polyneuropathy 
- Definition: axonal injury, particularly to the motor neurons, as a sequela of sepsis and multiple organ dysfunction
- Clinical features
- Predominantly distal, symmetrical, flaccid paralysis of the extremities with muscle atrophy; may affect the diaphragm
- Absent or reduced reflexes
- Dysesthesias in a glove-and-stocking distribution may be present
- Preservation of cranial nerve function
- May be associated with critical illness myopathy : flaccid quadriparesis (proximal > distal); facial muscle weakness, sensation normal, tendon reflexes normal or ↑
- Diagnosis: typical clinical features, sepsis, and electrophysiological evidence of motor and sensory neuropathy
- Treatment: no specific treatment available, usually gradual spontaneous resolution (weeks to months)
We list the most important complications. The selection is not exhaustive.
- One-Minute Telegram 8-2020-2/3: Should a cocktail of vitamin C, thiamine, and hydrocortisone be given to all patients with septic shock?
- One-Minute Telegram 3-2020-2/3: If they’re septic and you know it … raise their legs?
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