What is the diagnosis and treatment for Sepsis (Systemic Inflammatory Response Syndrome)?

From the Guidelines

Sepsis should be treated with immediate administration of broad-spectrum antibiotics, fluid resuscitation with crystalloids, and vasopressors as needed, with the goal of eliminating the infection and supporting organ function until the body can recover. The standard treatment involves administration of broad-spectrum antibiotics within one hour of recognition, with common regimens including combinations like piperacillin-tazobactam, ceftriaxone plus metronidazole, or meropenem for more severe cases 1. Fluid resuscitation with crystalloids, typically 30ml/kg within the first 3 hours, is essential to maintain blood pressure and organ perfusion 1. Vasopressors, particularly norepinephrine, should be initiated if hypotension persists despite fluid resuscitation, with a goal of maintaining a mean arterial pressure of 65 mmHg 1. Source control through procedures like abscess drainage or removal of infected devices is necessary when applicable 1. Continuous monitoring of vital signs, urine output, lactate levels, and organ function helps guide ongoing treatment 1.

Some key points to consider in the treatment of sepsis include:

• Early recognition and treatment are crucial for survival 1
• Broad-spectrum antibiotics should be administered within one hour of recognition 1
• Fluid resuscitation with crystalloids is essential to maintain blood pressure and organ perfusion 1
• Vasopressors, particularly norepinephrine, should be initiated if hypotension persists despite fluid resuscitation 1
• Source control is necessary when applicable 1
• Continuous monitoring of vital signs, urine output, lactate levels, and organ function helps guide ongoing treatment 1

It's also important to note that the treatment of sepsis should be individualized based on the patient's specific needs and circumstances, and that the goal of treatment is to eliminate the infection while supporting organ function until the body can recover 1.

The diagnosis of sepsis is based on the presence of a suspected or documented infection, and signs of organ dysfunction, such as an increase in the SOFA score of 2 points or more 1. The quick SOFA (qSOFA) score, which includes variables such as Glasgow Coma Scale score, systolic blood pressure, and respiratory rate, can be used to quickly identify patients who are at risk of sepsis 1.

In terms of morbidity, mortality, and quality of life, the treatment of sepsis should prioritize the elimination of the infection, support of organ function, and prevention of long-term complications 1. The use of broad-spectrum antibiotics, fluid resuscitation, and vasopressors as needed, can help to reduce morbidity and mortality, and improve quality of life for patients with sepsis 1.

From the Research

Diagnosis of Sepsis

• Sepsis is a medical emergency and life-threatening condition due to a dysregulated host response to infection, which is time-dependent and associated with unacceptably high mortality 2
• The clinical presentation of sepsis is highly variable depending on the etiology, with the most common sites of infection being the respiratory, genitourinary, and gastrointestinal systems, as well as the skin and soft tissue 3
• Fever is often the first manifestation of sepsis, with pneumonia being the most common presentation leading to sepsis 3

Treatment of Sepsis

• Broad-spectrum antimicrobials should be initiated within the first hour of diagnosis, and optimizing antibiotic use is essential to ensure successful outcomes and to reduce adverse antibiotic effects, as well as preventing drug resistance 2
• The loading dose is an initial higher dose of an antibiotic for all patients, yet an individualized treatment approach for further doses should be implemented according to pharmacokinetics (PK)/pharmacodynamics (PD) and the presence of renal/liver dysfunction 2
• Extended or continuous infusion of beta-lactams and therapeutic drug monitoring (TDM) can help to achieve therapeutic levels of antimicrobials, and reevaluation of duration and appropriateness of treatment at regular intervals are also necessary 2
• Early goal-directed therapy completed within the first six hours of sepsis recognition significantly decreases in-hospital mortality, and initial management includes respiratory stabilization followed by aggressive fluid resuscitation 3
• Vasopressor therapy is indicated when fluid resuscitation fails to restore adequate mean arterial pressure and organ perfusion, and early antibiotic therapy can improve clinical outcomes, and should be given within one hour of suspected sepsis 3
• Insulin therapy may be required to maintain serum glucose levels less than 180 mg per dL, and initiation of low-dose corticosteroids may further improve survival in patients with septic shock that does not respond to vasopressor therapy 3
• For fluid treatment, if hypoperfusion is present, the first (approximately) 2L (30 ml/kg BW) of crystalloid solution is usually safe and indicated, and after that, the rule is: less is more, and any further fluid administration should be carefully weighed up with the help of dynamic parameters, the patient's clinical condition and echo(cardio)graphy 4
• Resuscitation targets include mean arterial pressure ≥ 65 mmHg, mental status, capillary refill time, lactate, and urine output, and intravenous fluid resuscitation plays an integral role in those who are fluid responsive 5
• Balanced crystalloids and normal saline are both reasonable options for resuscitation, and early vasopressors should be initiated in those who are not fluid-responsive, with norepinephrine being the recommended first-line vasopressor 5
• Steroids such as hydrocortisone and fludrocortisone should be considered in those with refractory septic shock 5

Antibiotic Administration

• The Surviving Sepsis Campaign recommends immediate antibiotics for all patients with suspected sepsis and septic shock, ideally within 1 hour of recognition 6
• Immediate antibiotic treatment is lifesaving for some patients, but a substantial fraction of patients initially diagnosed with sepsis have noninfectious conditions, and aggressive time-to-antibiotic targets risk promoting antibiotic overuse and antibiotic-associated harms for this subset of the population 6
• Administer beta-lactam antibiotics as a prolonged (or if therapeutic drug monitoring is available, continuous) infusion after an initial loading dose 4
• Combination treatment with two agents for one pathogen group should remain the exception (e.g. multidrug-resistant gram-negative pathogens) 4
• In the case of doubt, the duration of anti-infective treatment should rather be shorter than longer, and procalcitonin can support the clinical decision to stop (not to start!) antibiotic treatment 4