What are the recommended evidence-based treatments for sepsis management in high-risk patients, such as the elderly or those with compromised immune systems?

Evidence-Based Sepsis Management in High-Risk Populations

Key Randomized Controlled Trials in Sepsis Management

The most impactful RCTs in sepsis management have established the foundation for current evidence-based care, with five major lactate-guided resuscitation trials (647 patients total) demonstrating significant mortality reduction (RR 0.67; 95% CI 0.53–0.84). 1

Major RCT Categories and Findings

Lactate-Guided Resuscitation Trials

• Five RCTs (n=647 patients) compared lactate-guided resuscitation versus standard care, showing moderate evidence for mortality reduction when early lactate clearance strategies were employed 1
• These trials demonstrated no significant difference in ICU length of stay (mean difference −1.51 days; 95% CI −3.65 to 0.62) 1
• Two meta-analyses of these 647 patients confirmed moderate evidence for mortality reduction with lactate normalization strategies compared to either usual care or ScvO2 normalization 1

MAP Target Trials

• A pilot RCT of 118 septic shock patients suggested that in the subgroup of patients older than 75 years, mortality was reduced when targeting MAP of 60–65 mmHg versus 75–80 mmHg 1
• This led to the strong recommendation for an initial MAP target of 65 mmHg, with lower risk of atrial fibrillation and lower vasopressor doses 1

Febrile Neutropenic Patient Trials

• Two multicenter RCTs (n=317 evaluable patients) compared cefepime monotherapy (2g IV q8h) versus ceftazidime monotherapy (2g IV q8h) for empiric treatment of febrile neutropenia 2
• Cefepime demonstrated therapeutic equivalence to ceftazidime, with survival rates of 93% versus 97% respectively 2
• Primary episode resolution with no treatment modification occurred in 62% versus 67% of patients 2

Complicated Intra-abdominal Infection Trials

• One randomized, double-blind, multicenter trial compared cefepime (2g q12h) plus metronidazole (500mg q6h) versus imipenem/cilastatin (500mg q6h) for up to 14 days 2
• Clinical cure rate was 81% (51/63) in the cefepime plus metronidazole group versus 66% (62/94) in the imipenem/cilastatin group 2

Evidence-Based Treatment Recommendations for High-Risk Patients

Immediate Resuscitation (First Hour)

Administer 30 mL/kg of IV crystalloid fluid within the first 3 hours for sepsis-induced hypoperfusion (strong recommendation, low quality evidence). 1

• Obtain at least two sets of blood cultures before starting antimicrobials, as long as this doesn't delay treatment >45 minutes 3, 4
• Measure serum lactate levels immediately as a marker of tissue hypoperfusion, and remeasure within 2-4 hours if initially elevated 3, 4
• Administer broad-spectrum IV antimicrobials within one hour of recognizing sepsis or septic shock 3, 4, 5
• Each hour of delay in antibiotic administration is associated with a 7.6% decrease in survival—this is critical in elderly and immunocompromised patients 3, 5

Hemodynamic Management for High-Risk Populations

Use norepinephrine as the first-choice vasopressor to maintain MAP ≥65 mmHg (strong recommendation). 3, 4, 5

• In patients older than 75 years, consider targeting MAP of 60-65 mmHg rather than higher targets to reduce atrial fibrillation risk and vasopressor requirements 1
• Add epinephrine when an additional agent is needed to maintain adequate blood pressure 3, 4, 5
• Consider vasopressin (0.03 U/min or 0.01-0.04 units/min) as rescue therapy in refractory shock 3, 4, 5
• Avoid dopamine except in highly selected circumstances due to increased arrhythmia risk 5
• Consider dobutamine infusion in the presence of myocardial dysfunction or ongoing signs of hypoperfusion despite adequate volume and MAP 5

Corticosteroid Therapy in Immunocompromised Patients

Consider intravenous hydrocortisone (200 mg/day or up to 300 mg/day) only in patients with septic shock requiring escalating vasopressor doses after adequate fluid resuscitation. 1, 5

• Do not use the ACTH stimulation test to identify patients who should receive hydrocortisone 1
• Taper hydrocortisone when vasopressors are no longer required 1
• Do not administer corticosteroids for sepsis in the absence of shock 1
• Use continuous infusion rather than bolus dosing when hydrocortisone is given 1

Respiratory Support in Elderly and High-Risk Patients

Apply oxygen to achieve oxygen saturation >90%, and position patients semi-recumbent with head of bed elevated 30-45 degrees. 3, 4, 5

• For sepsis-induced ARDS, use low tidal volume ventilation (6 mL/kg predicted body weight) (strong recommendation, high quality evidence) 1, 3, 5
• Target an upper limit for plateau pressures of 30 cm H2O in patients with severe ARDS (strong recommendation, moderate quality evidence) 1
• Use higher PEEP over lower PEEP in moderate to severe ARDS (weak recommendation, moderate quality evidence) 1
• Use prone positioning in patients with ARDS and PaO2/FIO2 ratio <150 (strong recommendation, moderate quality evidence) 1
• Consider neuromuscular blocking agents for ≤48 hours in severe ARDS with PaO2/FIO2 ratio <150 mm Hg (weak recommendation, moderate quality evidence) 1, 5

Source Control

Identify and control the source of infection as rapidly as possible, implementing interventions as soon as possible after diagnosis. 3, 4, 5

• Drain or debride infected sites whenever feasible, balancing risks and benefits of the chosen method 3, 4, 5
• Remove foreign bodies or devices that may be the source of infection 3, 4, 5
• Failure to identify and control the infection source leads to persistent sepsis—this is a critical pitfall 3, 5

Antimicrobial Management in Immunocompromised Patients

Administer broad-spectrum antimicrobials with activity against all likely pathogens within one hour. 4, 5

• For febrile neutropenic patients, cefepime 2g IV every 8 hours is therapeutically equivalent to ceftazidime based on RCT evidence 2
• Consider combination empirical therapy for neutropenic patients and for difficult-to-treat, multidrug-resistant pathogens 4, 5
• Limit empiric combination therapy to no more than 3-5 days 5
• Reassess antimicrobial regimen daily for potential de-escalation 4, 5
• Typical duration of therapy is 7-10 days, guided by clinical response 5
• Overlooking daily antimicrobial reassessment contributes to antimicrobial resistance—this is a common pitfall 3

Nutritional Support in High-Risk Patients

Initiate early enteral feeding rather than parenteral nutrition alone or in combination with enteral feeds (strong recommendation, moderate quality evidence). 1

• Do not administer early parenteral nutrition alone or in combination with enteral feeding in critically ill patients who can be fed enterally 1
• Do not administer parenteral nutrition in the first 7 days for patients for whom early enteral feeding is not feasible; instead initiate IV glucose and advance enteral feeds as tolerated 1
• Consider either early trophic/hypocaloric or early full enteral feeding; if trophic feeding is initial strategy, advance feeds according to patient tolerance (weak recommendation, moderate quality evidence) 1
• Do not use omega-3 fatty acids as an immune supplement (strong recommendation, low quality evidence) 1
• Do not use IV selenium to treat sepsis and septic shock (strong recommendation, moderate quality evidence) 1
• Do not use glutamine to treat sepsis and septic shock (strong recommendation, moderate quality evidence) 1

Stress Ulcer Prophylaxis

Provide stress ulcer prophylaxis to patients with sepsis or septic shock who have risk factors for GI bleeding (strong recommendation, low quality evidence). 1

• Use either proton pump inhibitors or histamine-2 receptor antagonists when stress ulcer prophylaxis is indicated (weak recommendation, low quality evidence) 1
• Do not provide stress ulcer prophylaxis in patients without risk factors for GI bleeding 1

Glucose Control in Elderly Patients

Use a protocolized approach to blood glucose management, targeting an upper blood glucose level ≤180 mg/dL (strong recommendation, high quality evidence). 1, 4, 5

• Monitor blood glucose every 1-2 hours until glucose values and insulin infusion rates are stable, then every 4 hours 1, 4, 5
• Avoid hypoglycemia, particularly in elderly patients who are at higher risk 4
• Do not target blood glucose ≤110 mg/dL due to increased hypoglycemia risk 1

Blood Product Therapy

Transfuse RBCs only when hemoglobin decreases to <7.0 g/dL, targeting hemoglobin of 7.0–9.0 g/dL in adults once tissue hypoperfusion has resolved (strong recommendation, high quality evidence). 1

• Consider different hemoglobin targets based on clinical tolerance or presence of myocardial ischemia, severe hypoxemia, acute hemorrhage, or ischemic heart disease 1, 4
• Do not use fresh frozen plasma to correct laboratory clotting abnormalities in the absence of bleeding or planned invasive procedures 1
• Administer platelets prophylactically when counts are <10,000/mm³ in the absence of apparent bleeding 1
• Consider prophylactic platelet transfusion when counts are <20,000/mm³ if significant bleeding risk exists 1

Performance Improvement and Screening

Hospitals should have a performance improvement program for sepsis, including sepsis screening for acutely ill, high-risk patients (best practice statement). 1

• Sepsis screening is associated with decreased mortality in several studies 1
• Implementation of a core set of recommendations (bundle) has been a cornerstone of sepsis performance improvement programs 1
• Having a protocol champion and sepsis education program is crucial to success, with studies showing in-hospital mortality of 23% in protocol patients versus 44% in non-protocol patients 6

Goals of Care in Elderly and High-Risk Patients

Discuss goals of care and prognosis with patients and families (best practice statement). 1

• Incorporate goals of care into treatment and end-of-life care planning, utilizing palliative care principles where appropriate (strong recommendation, moderate quality evidence) 1
• Address goals of care as early as feasible, but no later than within 72 hours of ICU admission (weak recommendation, low quality evidence) 1

Critical Pitfalls to Avoid in High-Risk Populations

• Never leave septic patients unattended—ensure continuous observation and clinical examinations several times per day 3, 4
• Excessive fluid administration without frequent reassessment can cause fluid overload, particularly dangerous in elderly patients with cardiac dysfunction 3
• In elderly patients >75 years, targeting MAP >75 mmHg may increase atrial fibrillation risk without mortality benefit 1
• Insufficient data exist to support cefepime monotherapy in patients at high risk for severe infection, including those with recent bone marrow transplantation, hypotension at presentation, underlying hematologic malignancy, or severe/prolonged neutropenia 2