Sepsis and Septic Shock: Definition, Symptoms, and Treatment

Sepsis is a life-threatening condition characterized by organ dysfunction due to a dysregulated host response to infection. Septic shock is a severe subset of sepsis, defined by persistent hypotension that requires vasopressors to maintain a mean arterial pressure (MAP) of 65 mmHg or higher, along with a serum lactate level greater than 2 mmol/L, despite adequate fluid resuscitation.

In the Sepsis-3 definition, the requirement for systemic inflammatory response syndrome (SIRS) criteria to define sepsis has been removed.

Clinical Signs and Symptoms

Sepsis presents with nonspecific signs and symptoms, which can vary depending on the underlying infection. Common clinical manifestations include:

• Fever: >38°C
• Neurological: Anxiety, confusion
• Respiratory: Difficulty breathing (dyspnea)
• Gastrointestinal: Nausea, vomiting
• Renal: Oliguria
• Integumentary: Cyanosis

Neonatal Sepsis

Neonatal sepsis, defined as a bloodstream infection in infants less than 28 days old, is associated with high morbidity and mortality, requiring immediate intervention. Risk factors include chorioamnionitis and prematurity, and clinical features can vary from asymptomatic presentations to hemodynamic collapse. Common signs include poor feeding, irritability, and lethargy, but relying solely on vital signs is not recommended, as they may not reliably indicate sepsis in neonates. Diagnosis is based on laboratory findings, with hypoglycemia, hyperbilirubinemia, and acidosis being key indicators. Blood cultures (with at least 1 mL sample), complete blood analysis, and C-reactive protein (CRP) levels are essential for diagnosis. Empirical antibiotics should be started promptly, even before lab results are available, to ensure timely treatment and improve outcomes.

Identifying the Source of Infection

• Chest infections: Cough, pleuritic chest pain, shortness of breath
• Cardiac infections: New-onset cardiac murmur
• Abdominal infections: Abdominal pain, diarrhea, distention, rebound tenderness
• Bone and soft tissue infections: Localized limb pain, edema, painful and swollen joints, joint effusion
• Skin infections: Purpura, erythema, petechial rash, ulceration

Sepsis vs. Septic Shock vs. bacteremia

• Sepsis: As mentioned, it is an exaggerated immune response to infection, leading to organ dysfunction.
• Septic Shock: A severe subset of sepsis where circulatory and cellular/metabolic abnormalities increase mortality risk. It’s characterized by persistent low blood pressure despite adequate fluid resuscitation, requiring vasopressors and typically presenting with elevated lactate levels.
• Bacteremia: This term is sometimes used interchangeably with sepsis but technically refers to the presence of bacteria in the bloodstream (bacteremia) that can lead to sepsis.

Sepsis vs SIRS (Systemic Inflammatory Response Syndrome)

The earlier SIRS criteria used to identify sepsis involved at least two of the following:

• Temperature >38°C or <36°C
• Heart rate >90 beats/min
• Respiratory rate >20 breaths/min
• White blood cell count >12,000/mm3 or <4,000/mm3

Sepsis Diagnosis

Diagnosing involves mainly the clinical suspicion combined with laboratory tests. Key diagnostic tools include:

• Blood cultures: To identify the infectious agent.
• Complete blood count (CBC): To check for elevated or decreased white blood cell count, indicating infection.
• Lactate levels: Elevated lactate levels (above 2 mmol/L) are indicative of tissue hypoperfusion.
• Procalcitonin: Elevated levels may help differentiate bacterial infections.
• Urinalysis, imaging (X-ray, CT scan): To locate the source of infection.
• qSOFA: A bedside tool for quickly assessing risk. It includes:
  • Respiratory rate ≥ 22/min
  • Altered mentation
  • Systolic blood pressure ≤ 100 mmHg

Treatment: The Sepsis Bundle Approach

Early intervention is key to improving outcomes. The main components of the bundle include:

1. Measure lactate levels: Re-measure if initial levels > 2 mmol/L.
2. Obtain blood cultures: Before administering antibiotics.
3. Administer broad-spectrum antibiotics: Timely administration of the correct antibiotics significantly reduces mortality.
4. Fluid resuscitation: Administer 30 ml/kg of crystalloid for hypotension or lactate ≥ 4 mmol/L.
5. Vasopressors: If hypotension persists after fluids, to maintain a mean arterial pressure (MAP) of ≥ 65 mmHg.

The Surviving Sepsis Campaign guidelines emphasize initiating these steps within the first hour of recognition to reduce mortality risk significantly.

Empirical antibiotics should be started as early as possible and adjusted based on culture results. Common antibiotics used in the initial management include:

The choice of antibiotics should be tailored to the suspected source of infection, the patient’s clinical condition, and local antimicrobial resistance patterns.

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References

1. Srzić, I., Nesek Adam, V., & Tunjić Pejak, D. (2022). SEPSIS DEFINITION: WHAT’S NEW 
IN THE TREATMENT GUIDELINES. Acta clinica Croatica, 61(Suppl 1), 67–72. https://doi.org/10.20471/acc.2022.61.s1.11
2. Singh M, Alsaleem M, Gray CP. Neonatal Sepsis. [Updated 2022 Sep 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK531478/
3. Dellinger, R. P., Levy, M. M., Carlet, J. M., Bion, J., Parker, M. M., Jaeschke, R., Reinhart, K., Angus, D. C., Brun-Buisson, C., Beale, R., Calandra, T., Dhainaut, J. F., Gerlach, H., Harvey, M., Marini, J. J., Marshall, J., Ranieri, M., Ramsay, G., Sevransky, J., Thompson, B. T., … World Federation of Societies of Intensive and Critical Care Medicine (2008). Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Critical care medicine, 36(1), 296–327. https://doi.org/10.1097/01.CCM.0000298158.12101.41