What is the treatment for sepsis?

Treatment for Sepsis

The treatment of sepsis requires immediate intervention with early administration of broad-spectrum antibiotics within one hour of recognition, aggressive fluid resuscitation, and hemodynamic support to reduce mortality and improve outcomes. 1, 2

Definition and Diagnosis

• Sepsis is a life-threatening syndrome characterized by organ dysfunction caused by a dysregulated host response to infection, with a sepsis-related organ failure assessment (SOFA) score of ≥2 in patients with infections 3
• Worldwide, approximately 30 million people are hospitalized with sepsis annually, with up to 6 million deaths 3
• Septic shock is the most severe form of sepsis, characterized by profound circulatory, metabolic, and cellular abnormalities requiring vasopressors to maintain perfusion pressure despite adequate fluid repletion 3

Initial Management

Antimicrobial Therapy

• Administer intravenous antimicrobials within one hour of sepsis recognition to reduce mortality 1, 4
• Obtain appropriate microbiological cultures, including at least two sets of blood cultures, before starting antimicrobial therapy (as long as this doesn't significantly delay treatment) 1
• Use empiric broad-spectrum therapy covering all likely pathogens (bacterial, fungal, or viral) 1, 4
• For septic shock, use combination therapy with at least two antibiotics of different classes targeting the most likely pathogens 1

Fluid Resuscitation

• Infuse fluids aggressively in patients with tissue hypoperfusion and continue liberal infusions for 24-48 hours (more than 4L during the first 24 hours may be required) 3, 1
• Administer at least 30 ml/kg of intravenous crystalloid fluid within the first 3 hours for sepsis-induced hypoperfusion 1, 2
• Use crystalloids and/or colloids for fluid resuscitation (colloid solutions are preferred for children with severe Dengue shock syndrome) 3

Hemodynamic Support

Vasopressors

• If despite adequate intravascular filling a mean arterial pressure (MAP) of at least 65 mmHg cannot be achieved, vasopressors must be used 3, 1
• Norepinephrine (noradrenaline) is recommended as the first-line vasopressor 3, 2
• Early use of vasopressors is recommended as it reduces the incidence of organ failure 3
• Vasopressin (0.01-0.04 units/min) or terlipressin (boluses of 1-2 mg) are rescue therapies in cases of refractory shock 3

Inotropic Support

• Routine use of inotropes is not recommended 3
• Consider inotropes when a low cardiac output is accompanied by a central venous oxygen saturation (ScvO2) below 70% 3
• The combination of dobutamine and noradrenaline is recommended as first-line treatment when inotropic support is needed 3

Corticosteroid Therapy

• Administer intravenous hydrocortisone (up to 300 mg/day) or prednisolone (up to 75 mg/day) to adult patients requiring escalating dosages of epinephrine or dopamine 3
• For children with severe shock, consider equivalent hydrocortisone or prednisolone doses 3
• The recommended dose of hydrocortisone is 200-300 mg/day for at least 5 days, followed by a tapering dose 3
• In pediatric patients, the recommended dose of hydrocortisone is 1 mg/kg every 6 hours 3
• Corticosteroids may reduce the risk of death by a small amount and increase recovery in people with sepsis or septic shock 3

Respiratory Support

• Apply oxygen to achieve an oxygen saturation >90% 3
• If no pulse oximeter is available, administer oxygen empirically in patients with severe sepsis or septic shock 3
• Place patients in a semi-recumbent position (head of the bed raised to 30-45°) 3, 1
• Place unconscious patients in the lateral position and keep the airway clear 3
• If available and medical staff is adequately trained, use non-invasive ventilation in patients with dyspnea and/or persistent hypoxemia despite oxygen therapy 3

Monitoring Parameters

• Monitor SpO2 (target ≥95%), mean arterial pressure (target ≥65 mmHg), fluid loading (500 ml/30 min), and diuresis (≥0.5 ml/kg/h) 3
• Never leave the septic patient alone; ensure continuous observation 3
• Perform clinical examinations several times per day 3
• Whenever available, use a continuous patient monitor and set meaningful alarm limits 3

Special Considerations

Pediatric Patients

• Sepsis in children is more often characterized by cardiac failure and hypovolemia, which responds well to fluid loading 3
• Diagnosis may be more difficult as hypotension develops later than in adults 3
• Prognosis depends on prompt diagnosis and intervention with aggressive fluid therapy and early use of antibiotics 3
• Mortality rate in children is lower than in adults, although fulminant purpuric sepsis warrants consideration as a separate entity 3

Common Pitfalls and Caveats

• Delays in antimicrobial administration significantly increase mortality - aim for administration within the first hour of sepsis recognition 1, 2
• Excessive fluid administration can be harmful - tailor fluid therapy to individual patient response 2, 5
• Inadequate source control is a common reason for treatment failure - identify and address the source of infection promptly 1, 5
• Underdosing of antimicrobials can result in treatment failure, while overdosing leads to toxicity and risk of developing multi-drug resistant organisms 4
• Both steroids and no steroids are reasonable management options - fully informed patients who value avoiding death over quality of life and function would likely choose corticosteroids 3