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

From the Guidelines

Sepsis management should prioritize early recognition, prompt administration of broad-spectrum antibiotics within one hour, and fluid resuscitation with crystalloids, as these interventions are crucial for reducing morbidity, mortality, and improving quality of life. The standard treatment involves immediate administration of broad-spectrum antibiotics, with common regimens including combinations like vancomycin plus piperacillin-tazobactam or cefepime for empiric coverage, as recommended by the Surviving Sepsis Campaign guidelines 1. Fluid resuscitation with crystalloids (typically 30 ml/kg) should be given within the first three hours to improve microvascular blood flow and increase cardiac output, as suggested by the 2016 SCC guidelines 1.

Key Interventions

• Broad-spectrum antibiotics: Administer within one hour of recognition, with common regimens including combinations like vancomycin plus piperacillin-tazobactam or cefepime for empiric coverage 1.
• Fluid resuscitation: Use crystalloids (typically 30 ml/kg) within the first three hours to improve microvascular blood flow and increase cardiac output 1.
• Vasopressors: Use norepinephrine as the first choice (starting at 0.05-0.1 mcg/kg/min) if hypotension persists despite fluid resuscitation, as recommended by the Surviving Sepsis Campaign guidelines 1.
• Source control: Implement source control measures, such as draining abscesses or removing infected devices, as soon as medically and logistically practical after diagnosis, as recommended by the Surviving Sepsis Campaign guidelines 1.

Monitoring and Assessment

• Frequent vital signs
• Lactate levels
• Urine output
• Organ function assessments

The pathophysiology of sepsis involves an overwhelming inflammatory response triggered by pathogens, leading to endothelial damage, microvascular dysfunction, and ultimately organ failure. Mortality increases significantly with each hour delay in appropriate antibiotic administration, making rapid intervention the cornerstone of management. The 2016 SCC guidelines suggest that initial hemodynamic resuscitation should be achieved within 3 h, and fluid therapy should be used to improve microvascular blood flow through an increased cardiac output as an essential part of the treatment of sepsis 1.

From the Research

Definition and Overview of Sepsis

• Sepsis is a common consequence of infection, associated with a mortality rate > 25% 2
• It is a life-threatening syndrome that requires rapid diagnosis and management 3
• Sepsis can be due to bacterial, fungal, or viral pathogens, with gram-negative sepsis being more common than gram-positive infection 2

Diagnosis and Management of Sepsis

• Early recognition of sepsis and appropriate treatment with antibiotics, fluids, and vasopressors is essential to reducing organ system injury and mortality 4
• Antimicrobials should be administered as soon as possible, as delays are associated with increased mortality 3
• The choice of empirical antimicrobial therapy should be based on host characteristics, site of infection, local ecology, and the pharmacokinetics and pharmacodynamics of the antibiotics 5
• Resuscitation targets include mean arterial pressure ≥ 65 mmHg, mental status, capillary refill time, lactate, and urine output 3

Antibiotic Therapy in Sepsis

• Broad-spectrum antibiotics must be selected with one or more agents active against likely bacterial or fungal pathogens and with good penetration into the presumed source 6
• Combination therapy should be considered in Pseudomonas infections, and combination empiric therapy in neutropenic patients 6
• Antimicrobial therapy should be reevaluated daily to optimize efficacy, prevent resistance, avoid toxicity, and minimize costs 6
• The duration of antibiotic therapy typically is limited to 7 to 10 days; longer duration is considered if response is slow, if there is inadequate surgical source control, or in the case of immunologic deficiencies 6

Supportive Care in Sepsis

• Intravenous fluid resuscitation plays an integral role in those who are fluid responsive 3
• Balanced crystalloids and normal saline are both reasonable options for resuscitation 3
• Early vasopressors should be initiated in those who are not fluid-responsive, with norepinephrine being the recommended first-line vasopressor 3
• Steroids such as hydrocortisone and fludrocortisone should be considered in those with refractory septic shock 3