Sepsis Management | Septic Shock & ICU Care

48.9M

Global cases/year

11M

Deaths/year worldwide

7.6%

↑ Mortality per hour delay

1 Hour

Target to first antibiotics

Sepsis-3 Definitions (2016)

SEPSIS

Life-threatening organ dysfunction caused by a dysregulated host response to infection.

Clinical Criteria Suspected infection + SOFA score ≥ 2 points (or acute change of ≥ 2)

SEPTIC SHOCK

Subset of sepsis with profound circulatory, cellular, and metabolic abnormalities.

Clinical Criteria Vasopressors required for MAP ≥ 65 mmHg
AND Lactate > 2 mmol/L despite adequate fluid resuscitation

Mortality: 40–60%

qSOFA (Bedside)

Quick screening — ≥ 2 suggests poor outcome:

1 Respiratory Rate ≥ 22/min

1 Altered Mentation (GCS < 15)

1 Systolic BP ≤ 100 mmHg

SOFA Score — Organ Dysfunction Assessment

System	0	1	2	3	4
Respiration PaO₂/FiO₂	≥ 400	< 400	< 300	< 200 + vent	< 100 + vent
Coagulation Platelets (×10³/µL)	≥ 150	< 150	< 100	< 50	< 20
Liver Bilirubin (mg/dL)	< 1.2	1.2–1.9	2.0–5.9	6.0–11.9	≥ 12
Cardiovascular MAP / Vasopressors	MAP ≥70	MAP <70	Dopa ≤5	Dopa >5 Epi ≤0.1	Dopa >15 Epi >0.1
CNS Glasgow Coma Scale	15	13–14	10–12	6–9	< 6
Renal Creatinine / Urine Output	< 1.2	1.2–1.9	2.0–3.4	3.5–4.9 <500mL/d	≥ 5.0 <200mL/d

Common Infection Sources in Sepsis

Pulmonary (35–50%)

• Community-acquired pneumonia (CAP)
• Hospital-acquired / Ventilator-associated
• Lung abscess, Empyema
• COVID-19, Influenza, TB

Urogenital (20–30%)

• Complicated UTI / Pyelonephritis
• Catheter-associated UTI (CAUTI)
• Perinephric abscess
• Prostatic abscess

Abdominal (15–25%)

• Peritonitis (primary, secondary, tertiary)
• Cholangitis / Cholecystitis
• Appendicitis with perforation
• Intra-abdominal abscess

Skin & Soft Tissue

• Necrotizing fasciitis (type I & II)
• Cellulitis with bacteremia
• Surgical site infections
• Diabetic foot infections

CNS Infections

• Bacterial meningitis
• Brain abscess
• Epidural abscess
• Encephalitis (HSV, viral)

Intravascular

• Central line-associated BSI (CLABSI)
• Infective endocarditis
• Suppurative thrombophlebitis
• Mycotic aneurysm

Special Topics

Special Populations

Immunocompromised Patients

• Broader empiric coverage — add antifungals early
• Consider atypical pathogens: PJP, CMV, Aspergillus
• Neutropenic sepsis: anti-pseudomonal β-lactam ± Vancomycin
• G-CSF if ANC < 500 with expected prolonged neutropenia
• Lower threshold for CT imaging (may lack inflammatory signs)

Elderly Patients (>65 years)

• Atypical presentation: confusion may be ONLY sign
• Blunted febrile response (hypothermia common)
• Lower physiologic reserve → rapid decompensation
• Polypharmacy interactions (anticoagulants, antihypertensives)
• Discuss goals of care and advance directives early

Obstetric Sepsis

• Leading cause of maternal mortality worldwide
• Sources: chorioamnionitis, endometritis, pyelonephritis
• Normal pregnancy hemodynamics mask early shock
• Modified SOFA for pregnancy; lower BP thresholds
• Fetal monitoring alongside maternal resuscitation

Burns & Trauma Sepsis

• Baseline SIRS from tissue injury confounds diagnosis
• Burn wound sepsis: quantitative culture >10⁵ organisms/g
• Increased drug clearance → higher antibiotic doses needed
• Aggressive wound care + early excision/grafting
• Higher metabolic demands → enhanced nutritional support

Multidrug-Resistant (MDR) Pathogens

Pathogen	Resistance	Treatment Options
MRSA	mecA gene; all β-lactams	Vancomycin, Linezolid, Daptomycin, TMP-SMX
ESBL-producing Enterobacterales	Extended-spectrum cephalosporins	Meropenem, Ertapenem, Ceftazidime-Avibactam
CRE (KPC/NDM)	Carbapenems	Ceftazidime-Avibactam, Meropenem-Vaborbactam, Cefiderocol
MDR Pseudomonas	Multiple classes	Ceftolozane-Tazobactam, Cefiderocol, Colistin (last resort)
VRE	Vancomycin (vanA/vanB)	Linezolid, Daptomycin, Tigecycline
MDR Acinetobacter	Pan-drug resistance common	Ampicillin-Sulbactam (high dose), Colistin, Cefiderocol

Quality Metrics & Prognosis

Bundle Compliance Impact

• 3-hour bundle compliance: ↓ mortality by 15–20%
• Each hour delay in antibiotics: ↑ mortality ~7.6%
• Complete Hour-1 bundle: NNT = 6 to save one life
• Lactate-guided resuscitation: ↓ mortality by 11%
• Procalcitonin-guided de-escalation: ↓ antibiotic days by 2–3

Prognostic Factors (Poor Outcome)

• Lactate > 4 mmol/L that fails to clear
• Need for ≥ 2 vasopressors
• SOFA score > 11
• Thrombocytopenia (DIC)
• Immunosuppression / Malignancy
• Delay in source control > 12 hours
• MDR pathogen isolation

Post-Sepsis Syndrome & Long-Term Outcomes

Physical

• ICU-acquired weakness (CIM/CIP)
• Chronic pain and fatigue
• Recurrent infections
• Organ dysfunction persistence

Cognitive & Psychological

• Cognitive impairment (30–50%)
• PTSD (up to 44%)
• Depression & anxiety
• Sleep disturbances

Healthcare Utilization

• 40% rehospitalized within 90 days
• 60% mortality within 2 years (elderly)
• Higher cardiovascular event risk
• Need for rehabilitation services

Sepsis-3 Definitions (2016)

SEPSIS

SEPTIC SHOCK

qSOFA (Bedside)

SOFA Score — Organ Dysfunction Assessment

Common Infection Sources in Sepsis

Pathophysiology of Sepsis

The Sepsis Cascade

Infection & PAMP/DAMP Recognition

Cytokine Storm & NF-κB Activation

Endothelial Dysfunction & Coagulopathy

Mitochondrial Dysfunction & Cellular Injury

Multi-Organ Dysfunction Syndrome (MODS)

Key Inflammatory Mediators

Pro-Inflammatory

Anti-Inflammatory / Immunosuppressive

Diagnostic Approach

STAT / Immediate

Biomarkers

Source-Directed

Chest X-ray / CT Chest

CT Abdomen/Pelvis

Point-of-Care Ultrasound

Echocardiography

Management Protocol

HOUR-1 BUNDLE (SSC 2021)

Measure Lactate

Obtain Blood Cultures BEFORE Antibiotics

Administer Broad-Spectrum Antibiotics

Rapid IV Fluid Resuscitation

Vasopressors for Refractory Hypotension

Hemodynamic Targets & Monitoring

Targets

Fluid Responsiveness Assessment

Vasopressor Ladder

Adjunctive & Supportive Therapies

Corticosteroids

Glycemic Control

Lung-Protective Ventilation

Source Control

VTE Prophylaxis

Renal Replacement Therapy

Empiric Antibiotic Selection

Community-Acquired Pneumonia (CAP)

Hospital-Acquired / Ventilator-Associated Pneumonia

Urosepsis / Complicated UTI

Intra-Abdominal Sepsis

Bacterial Meningitis

Necrotizing Soft Tissue Infection