What are the guidelines for managing sepsis in a patient with suspected infection?

Sepsis Management Guidelines

Immediate Actions (Within 1 Hour)

Administer broad-spectrum IV antibiotics within 1 hour of recognizing sepsis or septic shock—this is the single most critical intervention to reduce mortality. 1, 2, 3

Antimicrobial Therapy

• Start empiric broad-spectrum antibiotics immediately covering all likely pathogens (bacterial, and consider fungal/viral if indicated) that penetrate adequately into the presumed infection source 1, 2, 3
• Use maximum recommended dosages during the initial phase, administered intravenously for optimal bioavailability 1
• For septic shock specifically, use combination therapy with at least two different antimicrobial classes targeting the most likely pathogens 1, 3
• For neutropenic patients, initiate meropenem, imipenem/cilastatin, or piperacillin/tazobactam monotherapy as first-line treatment 1
• Add aminoglycoside combination therapy in severe sepsis/shock, particularly for suspected Pseudomonas or multidrug-resistant organisms 1
• Adjust empiric therapy based on local resistance patterns and patient-specific risk factors for resistant organisms 1

Fluid Resuscitation

• Administer 30 mL/kg IV crystalloid solution rapidly within the first 3 hours for patients with hypotension or lactate ≥4 mmol/L 2, 3, 4
• Target mean arterial pressure (MAP) ≥65 mmHg as the primary hemodynamic goal 1, 2, 4
• Continue aggressive fluid resuscitation with more than 4 L potentially required in the first 24 hours for adults 1
• Use crystalloids as first-line fluids—avoid albumin and use colloids cautiously due to increased risk of renal failure and mortality 1
• Stop fluid administration when tissue perfusion fails to improve or pulmonary crepitations develop indicating fluid overload 1

Diagnostic Workup (Do Not Delay Antibiotics)

• Obtain at least two sets of blood cultures before antibiotics if this causes no significant delay (<45 minutes)—one percutaneous and one through each vascular access device 1, 2
• Measure serum lactate immediately; if elevated (>2 mmol/L), remeasure within 2-4 hours to guide resuscitation 2, 3
• Perform imaging studies promptly (X-ray, ultrasound, CT) to identify infection source requiring drainage 1
• Sample fluid or tissue from suspected infection site for Gram stain, culture, and susceptibility testing when feasible 1

Early Resuscitation Goals (First 6 Hours)

Target these specific endpoints within 6 hours of recognizing sepsis: 1

• Central venous pressure 8-12 mmHg 1
• Mean arterial pressure ≥65 mmHg 1, 2
• Urine output ≥0.5 mL/kg/hr 1, 2, 3
• Central venous oxygen saturation (ScvO2) ≥70% or mixed venous ≥65% 1, 4
• Normalize lactate as rapidly as possible in patients with elevated levels 1, 2, 4

Use dynamic measures of fluid responsiveness (passive leg raise, pulse pressure variation) rather than static measures like CVP when available, as CVP has only 50% positive predictive value 4

Vasopressor Support

• Initiate norepinephrine as first-line vasopressor if hypotension persists despite adequate fluid resuscitation 2, 3
• Target MAP ≥65 mmHg with vasopressor titration 2, 3, 4
• Consider adding epinephrine if inadequate response to norepinephrine alone 2
• For epinephrine dosing in septic shock: start at 0.05 mcg/kg/min and titrate up to 2 mcg/kg/min in increments of 0.05-0.2 mcg/kg/min every 10-15 minutes to achieve desired MAP 5
• Add low-dose corticosteroids if no response to norepinephrine or epinephrine ≥0.25 mcg/kg/min for at least 4 hours 2

Source Control

Implement source control measures as soon as possible after initial resuscitation, ideally within 12 hours: 1

• Drain or debride abscesses, necrotizing soft tissue infections, gastrointestinal perforations, cholangitis, obstructive urinary infections, and deep space infections (empyema, septic arthritis) 1
• Remove infected intravascular devices promptly after establishing alternative vascular access 1, 3
• Use the least invasive technique available (percutaneous/endoscopic drainage preferred over surgical when feasible) 1

Ongoing Monitoring and Reassessment

• Monitor vital signs continuously with meaningful alarm limits set appropriately 1
• Calculate Sequential Organ Failure Assessment (SOFA) score to assess organ dysfunction 2, 3
• Use NEWS2 score for risk stratification: Score ≥7 = high risk (reassess every 30 minutes); Score 5-6 = moderate risk (reassess hourly); Score 1-4 = low risk (reassess every 4-6 hours) 2, 3
• Monitor for tissue hypoperfusion signs: mottled skin, decreased capillary refill, peripheral cyanosis, altered mental status 3
• Measure serial lactate levels to guide resuscitation and assess treatment response 2, 3

De-escalation and Duration (After 24-48 Hours)

• Reassess antimicrobial regimen daily for potential de-escalation based on culture results and clinical improvement 1, 2, 3
• Narrow to targeted therapy once pathogen identification and susceptibilities are available 1, 3
• Discontinue combination therapy within 3-5 days in patients showing clinical improvement 1, 3
• Typical treatment duration is 7-10 days; longer courses may be necessary for slow clinical response, undrainable infection foci, S. aureus bacteremia, or immunocompromised patients 1, 3
• Consider using procalcitonin levels to guide antibiotic discontinuation (not initiation) in patients initially suspected of sepsis 1, 3

Critical Pitfalls to Avoid

• Never delay antibiotics for diagnostic testing—each hour of delay in the first 6 hours decreases survival by 7.6% 1
• Do not use sustained antimicrobial prophylaxis in severe inflammatory states of noninfectious origin (severe pancreatitis, burns) 3
• In African children with profound anemia and suspected malaria, administer fluid boluses cautiously and consider blood transfusion instead of aggressive crystalloid resuscitation 1
• Avoid aminoglycoside monotherapy—while combination therapy increases renal toxicity, it may be justified in severe sepsis/shock 1
• Do not rely solely on CVP for fluid responsiveness assessment due to poor predictive value 4
• Avoid leg veins for infusions in elderly patients or those with occlusive vascular disease 5