creation date: 2026-06-23 23:39
tags: Pathologies
Sepsis
Background
Definitions
Sepsis is a clinical syndrome caused by a dysregulated host response to infection. Sepsis can lead to deadly complications and requires prompt evaluation and treatment.
Septic shock is a type of distributive shock that is characterized by persistent hypotension despite resuscitation efforts while the criteria for sepsis is fulfilled.
Systemic inflammatory response syndrome (SIRS) refers to a clinical syndrome similar to sepsis but classically with noninfectious etiology.
Etiology & Risk Factors
Common sources of sepsis include:
- Upper respiratory tract
- Lower respiratory tract
- Urinary tract
- Vascular, indwelling pleural, or peritoneal dialysis catheters
- Wound or burn
- Skin/soft tissue
- Central nervous system
- Gastrointestinal
- Intra-abdominal
- Genital tract
- Bone and joint
Risk factors for sepsis include:
- ICU admission
- Bacteremia
- Advanced age (≥65)
- Immunosuppression
- Diabetes and obesity
- Cancer
- Community-acquired pneumonia
- Previous hospitalization
- Genetics (eg. lack of T cells, antibody production abnormalities)
- SES factors (eg. poverty, low hygiene, limited access to clean water and health care)
Pathogenesis
The pathogenesis of sepsis classically begins with systemic infection. Bacteremia activates inflammatory mediators throughout the body, dilating blood vessels and release of proinflammatory cytokines.
Dilation of blood vessels reduces ventricular preload and afterload, requiring an increase in cardiac output for compensation through heart rate.
Endothelial disruption also results in capillary leak and generalized edema as intravascular fluid and albumin move into tissue, further worsening hypovolemia.
Sepsis is also associated iwth activation of the clotting cascade with tissue factor, causing microvascular thrombosis. Thrombus formation worsen tissue hypoperfusion.
These elements in combination impairs tissue oxygenation, leading to hyperlactatemia and tissue ischemia. At its most severe form, multiple organ failure can ensue.
Clinical Presentation
Signs & Symptoms
Sepsis presents with both nonspecific findings and signs specific to the source of infection.
Findings specific to source of sepsis:
| Suspected site | Symptoms/signs |
|---|---|
| Upper respiratory tract | Pharyngeal inflammation plus exudate ± swelling and lymphadenopathy |
| Lower respiratory tract | Productive cough, pleuritic chest pain, consolidative auscultatory findings |
| Urinary tract | Urgency, dysuria, loin, or back pain |
| Vascular catheters, indwelling pleural catheter | Redness or drainage at insertion site |
| PD catheter | Cloudy PD fluid, abdominal pain |
| Wound or burn | Inflammation, edema, erythema, discharge of pus |
| Skin/soft tissue | Erythema, edema, lymphangitis |
| Central nervous system | Signs of meningeal irritation |
| Gastrointestinal | Abdominal pain, distension, diarrhea, and vomiting |
| Intra-abdominal | Specific abdominal symptoms/signs |
| Genital tract | Female: Low abdominal pain, vaginal discharge Male: Dysuria, frequency, urgency, urge incontinence, cloudy urine, prostatic tenderness |
| Bone, joint | Pain, warmth, swelling, decreased use/ROM |
Additionally, findings include:
- Arterial hypotension
- Fever (>38.3ºC)
- Tachycardia (>90)
- Tachypnea
In more severe states, signs of end-organ perfusion may be present:
- Warm, flushed skin (especially early) which transitions to cool (as blood is redirected to core organs)
- Decreased capillary refill, cyanosis, mottling
- Altered mental status, obtundation or restlessness
- Oliguria or anuria
- Ileus or absent bowel sounds
History & Physical Exam
Evaluate for source of infection.
Diagnosis
Criteria
Diagnosis of sepsis and septic shock is made definitively with a constellation of clinical, laboratory, and investigation findings. However, an empiric diagnosis is often made upon presentation.
Sepsis is evidenced by:
- Organ dysfunction (SOFA ≥2 or increase of ≥2 over baseline)
- Presence of infection
Septic shock criteria includes those of sepsis and, despite adequate fluid resuscitation, have:
- Requirement of vasopressors to maintain a MAP ≥65 mmHg
- Lactate >2 mmol/L
Work-up
Initial investigations
Routine laboratory studies:
- CBC with differential
- Electrolytes and eGFR
- Liver function tests
- Coagulation studies
Other studies:
- Serum lactate
- Peripheral blood cultures
- Urinalysis
- Microbiologic cultures from suspected source if accessible
- Blood gas analysis
- Imaging for source of infection
Note that investigations should not delay fluids and antibiotics.
Focused workup
Within the first 6 hours, focused history and physical should be completed to identify and control the source(s) of infection. Additionally,
- CT, ultrasound
- Further diagnostic cultures
Differential
Other diagnoses include:
- Non-infectious SIRS (eg. severe trauma/burns, acute pancreatitis, major surgery, autoimmune flares)
- Other shock types
- Other causes of hypotension (eg. tension pneumothorax)
Red Flags / Complications
Management
Immediate Management
Initial management consist of:
- Securing the airway if indicated
- Stabilizing respiration (oxygen targeted to 90-96%)
- Establish IV (two large bore IV)
Initial investigations are also ordered (see above).
Initial Therapy
Early goal-directed therapy is the mainstay of the first 1-3 hours of treatment. This consist of:
Crystalloid IV fluids given at 30 mL/kg (started within 1 hour, completed within 3 hours)
- Lactated Ringer’s or Normal saline
- Administered in well-defined (eg. 500 mL boluses)
Empiric antibiotic therapy (within the first hour)
- Tailor to suspected pathogens and comorbidities
- If pseudomonas unlikely: vancomycin PLUS ceftriaxone or pip-tazo
- If pseudomonas likely: vancomycin PLUS two antipseudomonal antibiotic classes based on antibiogram (eg. ceftazidine/cefepime, imipenem/meropenem, pip-tazo, ciprofloxacin/levofloxacin, )
Monitoring should be done via a central venous catheter (or arterial if placed). Targets are:
- ScvO2 ≥ 70%
- CVP 8–12 mmHg
- MAP ≥65 mmHg
- Urine output ≥0.5 mL/kg/hr
Vitals should also be monitored including capillary refill time and mental status.
Source control should be focused to eliminate further infection. Ideally this should be done within 6-12 hours after diagnosis.
Further Therapy
In patients with persistent hypoperfusion despite adequate fluid resuscitation, further treatment is indicated.
Ensure above treatment has been optimized and all sources of infection are considered. If persistent, further options are used to treat hypoperfusion.
Vasopressors:
- Norepinephrine
- Vaspressin
- Epinephrine (phenylephrine)
For patients with low cardiac output, addition of an inotropic agent may be helpful:
- Dobutamine
- Epinephrine
References
Tools / Guidelines
MDCalc - SIRS/Sepsis/Septic Shock Criteria