Sepsis-3 Definitions
Sepsis
Life-threatening organ dysfunction caused by a dysregulated host response to infection.
Operationalised as: suspected/confirmed infection + SOFA score increase ≥2 points from baseline
- Baseline SOFA assumed 0 in patients without pre-existing organ dysfunction
- Associated with in-hospital mortality >10%
- Replaces prior SIRS-based definition (Sepsis-3, 2016)
Septic Shock
Subset of sepsis with profound circulatory, cellular, and metabolic abnormalities.
Vasopressors to maintain MAP ≥65 mmHg AND Lactate >2 mmol/L despite adequate fluid resuscitation
- Hospital mortality exceeds 40%
- Both criteria must be met simultaneously
- Adequate fluids = 30 mL/kg crystalloid given
qSOFA Bedside Screening
qSOFA — Quick SOFA (Screening Tool)
Score 1 point for each criterion present. Use outside ICU as rapid bedside screen.
RR ≥22
Respiratory Rate
/min
↓ Mentation
Altered Mental Status
GCS <15
qSOFA ≥2: High risk for organ dysfunction — escalate to full SOFA assessment, notify senior, initiate sepsis pathway
qSOFA = 1: Monitor closely, reassess frequently, low threshold to escalate if clinical concern persists
Note: qSOFA has lower sensitivity than NEWS2 — a negative qSOFA does not rule out sepsis. Always use clinical judgement.
SOFA Score Domains
Sequential Organ Failure Assessment (SOFA)
| System | Parameter | Score 1 | Score 2 | Score 3 | Score 4 |
|---|
| Respiratory | PaO₂/FiO₂ (mmHg) | <400 | <300 | <200 + vent | <100 + vent |
| Coagulation | Platelets (×10³/µL) | <150 | <100 | <50 | <20 |
| Liver | Bilirubin (µmol/L) | 20–32 | 33–101 | 102–204 | >204 |
| Cardiovascular | MAP or vasopressors | MAP <70 | Dopa ≤5 or Dobu | Dopa >5 or NA/A ≤0.1 | Dopa >15 or NA/A >0.1 |
| Neurological | GCS | 13–14 | 10–12 | 6–9 | <6 |
| Renal | Creatinine (µmol/L) | 110–170 | 171–299 | 300–440 or UO<500/d | >440 or UO<200/d |
Each domain scored 0–4. SOFA ≥2 points increase = sepsis. Maximum total = 24. Score ≥11 associated with >95% mortality in some cohorts.
Early Warning Score Integration
NEWS2 Triggers
- NEWS2 ≥7 Continuous monitoring, immediate senior review
- NEWS2 5–6 Sepsis screen — qSOFA, lactate, blood cultures
- NEWS2 3–4 Increased monitoring frequency q1–2h
- New confusion (C-scale) adds 3 points — high sensitivity for sepsis
- Supplemental O₂ requirement captures respiratory deterioration
SIRS Criteria (Historical Context)
- Temp >38°C or <36°C
- Heart rate >90 bpm
- RR >20/min or PaCO₂ <32 mmHg
- WCC >12 or <4 (×10⁹/L) or >10% bands
SIRS ≥2 criteria is sensitive but non-specific. No longer defines sepsis but still clinically useful. SIRS without organ dysfunction ≠ sepsis.
Sepsis vs SIRS — Key Distinction
| Feature | SIRS | Sepsis (Sepsis-3) |
|---|
| Trigger | Any insult (infection, trauma, burns, pancreatitis) | Infection specifically |
| Defining feature | Inflammatory response criteria (≥2 of 4) | Organ dysfunction (SOFA ≥2) |
| Organ dysfunction | Not required | Required by definition |
| Lactate | Not defining | Key in septic shock (>2 mmol/L) |
| Clinical implication | Screen, monitor, treat cause | Activate sepsis bundle immediately |
Hour-1 Bundle (SSC 2018)
All 5 elements must be initiated within 1 HOUR of sepsis recognition. Time zero = time of clinical recognition, not time of diagnosis confirmation.
SSC Hour-1 Bundle — 5 Critical Actions
1
Measure Serum Lactate
Obtain stat lactate. If initial lactate >2 mmol/L, re-measure within 2 hours after fluid resuscitation. Lactate ≥4 mmol/L = very high risk, initiate aggressive resuscitation regardless of BP.
2
Blood Cultures Before Antibiotics
Obtain at least 2 sets (peripheral + central line if present) before administering antibiotics. Do not delay antibiotics >45 minutes while waiting for cultures. Each set = 20 mL (10 mL aerobic + 10 mL anaerobic).
3
Administer Broad-Spectrum Antibiotics
Empirical broad-spectrum antibiotics covering likely pathogens based on source. Each hour delay in antibiotic administration increases mortality by ~7%. Document time of administration precisely.
4
Fluid Resuscitation — 30 mL/kg Crystalloid
For hypotension (MAP <65 or SBP <90) OR lactate ≥4 mmol/L. Complete within 3 hours. Reassess after each 500 mL bolus for fluid responsiveness. Use balanced crystalloid (Hartmann's/Plasmalyte) where available.
5
Vasopressors for Persistent Hypotension
If MAP <65 mmHg despite initial fluid resuscitation — start noradrenaline. Target MAP ≥65 mmHg (≥70 in elderly or chronic hypertension). Central access preferred but peripheral vasopressors acceptable short-term.
UK Sepsis-6 (One-Hour Pathway)
GIVE 3 — TAKE 3 (within 1 hour)
GIVE
- High-flow O₂ — titrate to SpO₂ 94–98% (88–92% in COPD/T2RF risk)
- IV antibiotics — broad-spectrum, locally approved, time-documented
- IV fluid challenge — 500 mL crystalloid bolus stat, reassess
TAKE
- Blood cultures — ≥2 sets before antibiotics
- Lactate measurement — venous or arterial
- Urine output monitoring — catheterise, target >0.5 mL/kg/h
Antibiotic Stewardship & De-escalation
De-escalation Protocol
| Timepoint | Action | Rationale |
|---|
| 0–24h | Empirical broad-spectrum coverage | Unknown pathogen, life-threatening |
| 48–72h | Review culture & sensitivity results | De-escalate to narrowest effective agent |
| Day 3–5 | Procalcitonin trending down (>80% fall from peak) | Consider stopping antibiotics |
| Day 7–10 | Standard SSC-recommended duration | Longer if inadequate source control/immunosuppressed |
| Ongoing | Daily antibiotic review ("antibiotic timeout") | Reduce resistance, C. difficile risk, toxicity |
Procalcitonin-guided de-escalation reduces antibiotic duration without increasing mortality. PCT <0.5 ng/mL or >80% reduction = consider stopping.
Bundle Compliance Monitoring
CBAHI / JCIA Core Measures
- Door-to-antibiotic time audit (target <1 hour from recognition)
- Blood culture before antibiotics compliance rate
- Lactate measurement within 1 hour
- 30 mL/kg fluid completion within 3 hours
- Vasopressor initiation documentation
- Bundle compliance dashboard — monthly reporting
Common Documentation Pitfalls
- Failure to record exact time of sepsis recognition
- Antibiotics given but time not documented to the minute
- Cultures drawn after antibiotic administration
- Lactate not repeated after initial elevation
- Fluid bolus given but total volume not tallied
- Vasopressor start time missing from drug chart
Initial Fluid Resuscitation
30 mL/kg Crystalloid Protocol
- Initiate for MAP <65 mmHg OR lactate ≥4 mmol/L
- Complete within 3 hours of sepsis recognition
- Reassess after every 500 mL bolus — not as a continuous infusion
- Stop if signs of fluid overload: SpO₂ ↓, new crackles, rising CVP, worsening CXR
- For 70 kg patient: 2,100 mL total = 4 × 500 mL boluses
Caution: Aggressive fluids can cause pulmonary oedema, abdominal compartment syndrome, and worsened outcomes. Always reassess after each bolus.
SMART/SALT-ED trials: balanced crystalloids (Hartmann's/Plasmalyte) associated with lower MAKE-30 composite endpoint vs 0.9% NaCl.
Fluid Responsiveness Assessment
Dynamic Measures (Preferred Over Static CVP)
| Method | Criteria for Responsiveness | Conditions / Limitations |
|---|
| Passive Leg Raise (PLR) | CO ↑ >10% at 60–90 seconds | Requires CO monitoring; not valid in raised IAP or leg fractures |
| Pulse Pressure Variation (PPV) | PPV >12% | Requires MV, sinus rhythm, TV ≥8 mL/kg, closed chest |
| Stroke Volume Variation (SVV) | SVV >10–13% | Arterial line + CO monitoring needed |
| POCUS/Echo LVOT VTI | VTI ↑ >10% post-PLR or fluid bolus | Operator dependent; increasingly available in GCC ICUs |
| End-Expiratory Occlusion Test | Pulse pressure ↑ >5% | Only valid in ventilated patients |
CVP alone is NOT reliable to predict fluid responsiveness — avoid using CVP as sole guide to fluid administration.
Crystalloid Selection
Balanced Crystalloids (Preferred)
- Hartmann's (Lactated Ringer's): Na 131, K 5, Ca 2, Cl 111, Lactate 29 mmol/L — most physiological
- Plasmalyte-148: Na 140, K 5, Mg 1.5, Cl 98, acetate 27, gluconate 23 mmol/L
- Lower risk of hyperchloraemic acidosis
- Associated with lower AKI rates in RCTs
- Preferred choice in GCC hospitals (MOH/DHA guidance)
0.9% NaCl — Avoid as Primary Resuscitation Fluid
- Na 154, Cl 154 mmol/L — supraphysiological chloride
- Large volumes → hyperchloraemic metabolic acidosis
- Acidosis may mimic or worsen septic shock parameters
- SAFE trial: albumin equivalent to saline — no benefit
- Acceptable short-term if balanced crystalloids unavailable
Vasopressor Selection & Dosing
Vasopressor Algorithm — SSC Recommendations
| Agent | Dose Range | Line | Mechanism | Notes |
|---|
| Noradrenaline | 0.01–3 mcg/kg/min | 1st Line | α1 >> β1 agonist | Preferred vasopressor. Titrate to MAP ≥65 |
| Vasopressin | 0.03–0.04 units/min | 2nd Line | V1 receptor (vasoconstriction) | Add when NA >0.25 mcg/kg/min. Fixed dose — do not titrate |
| Adrenaline | 0.01–1 mcg/kg/min | 3rd Line | α1, β1, β2 agonist | Refractory septic shock. Raises lactate — confounds monitoring |
| Dobutamine | 2–20 mcg/kg/min | Inotrope | β1 > β2 agonist | Only if reduced cardiac output/EF. Vasodilatory — use with vasopressor |
Dopamine | — | Abandoned | DA, β1, α1 (dose-dependent) | Higher arrhythmia risk vs NA. Not recommended by SSC |
MAP Targets
- Standard target: MAP ≥65 mmHg
- Elderly (>70yrs) or chronic hypertension: MAP ≥70–75 mmHg
- Renal/mesenteric ischaemia risk: consider MAP ≥70
- Higher MAP targets (≥80) not associated with improved outcomes (SEPSISPAM trial)
- Monitor urine output response to vasopressor titration
Vasopressor Access & Safety
- Central venous catheter preferred for concentrated vasopressors
- Short-term peripheral administration acceptable (forearm, antecubital) — <6 hours
- Monitor insertion site q1h for extravasation
- Phentolamine readily available for extravasation management
- Never run noradrenaline through peripheral IV without local protocol approval
Empirical Antibiotic Selection
Broad-Spectrum Empirical Regimens
| Source / Risk | Empirical Regimen | MRSA Cover |
|---|
| Community-acquired sepsis | Piperacillin-tazobactam 4.5g q6h IV | Add vancomycin if MRSA risk |
| HAI / ICU sepsis | Meropenem 1–2g q8h IV | Add vancomycin/teicoplanin |
| Abdominal source | Meropenem + metronidazole | Assess MRSA risk individually |
| Urological source | Piperacillin-tazobactam or ceftriaxone | Consider ESBL if healthcare contact |
| Neutropaenic sepsis | Cefepime 2g q8h or meropenem | Add vancomycin for line infection/MRSA |
| MRSA high risk | Vancomycin 25–30 mg/kg loading dose or teicoplanin | Yes — primary indication |
| Invasive candidiasis risk | Add caspofungin 70mg loading → 50mg/day | N/A |
Antifungal Indications
Invasive Candidiasis Risk Factors — Initiate Empirical Antifungal If ≥3 Present
- Immunocompromised (transplant, haematological malignancy, steroids)
- Total parenteral nutrition (TPN) >5 days
- Prolonged broad-spectrum antibiotics >7 days
- Candida colonisation at ≥2 body sites
- Central venous catheter >7 days
- Recent abdominal surgery or GI perforation
- Renal replacement therapy
- ICU stay >7 days with deterioration
First-line: Caspofungin (echinocandin) — less hepatotoxic than fluconazole in critically ill. Switch to fluconazole if susceptible Candida albicans, patient stable.
Blood Culture Technique
Optimising Blood Culture Yield
Collection Protocol
- Minimum 2 sets from separate sites
- Set = 1 aerobic + 1 anaerobic bottle (10 mL each)
- 20 mL total per set — volume critical for yield
- Peripheral site + from central line if present
- Before antibiotics — do not delay >45 minutes
- Chlorhexidine/alcohol skin prep — 30 second contact time
Common Errors Reducing Yield
- Insufficient volume (<8–10 mL per bottle)
- Only one set collected
- Collected after antibiotic administration
- Contamination from hub flush or inadequate skin prep
- Bottles not transported within 2 hours
- Failure to label with time and site
PK/PD Optimisation in Sepsis
Pharmacokinetic Alterations in Sepsis
| Drug Class | Sepsis PK Change | Dosing Strategy |
|---|
| Beta-lactams (PIP-TAZ, meropenem) | ↑ Volume of distribution, ↑ clearance | Extended infusion (3–4h) for time-dependent killing; higher loading doses |
| Vancomycin | Variable — ↑ VD early, ↓ clearance in AKI | TDM-guided AUC/MIC dosing (target AUC 400–600). Loading dose 25–30 mg/kg |
| Aminoglycosides | ↑ VD → lower peaks | Once-daily extended-interval dosing; TDM trough <1 mg/L |
| Fluconazole | ↑ VD in septic shock | Higher loading dose (800mg), maintenance 400mg/day |
| Linezolid | ↓ Protein binding; augmented renal clearance | Consider TDM; CRRT may lower levels significantly |
Source Control
Source Control — Within 12 Hours of Diagnosis
- Drain abscess, empyema, infected collection
- Debride necrotising soft tissue infection (emergency)
- Remove infected foreign body (catheter, prosthesis, CVC)
- Biliary drainage for cholangitis — ERCP or PTC
- Percutaneous drainage preferred over surgery where possible
Inadequate source control is a leading cause of treatment failure in sepsis. A septic patient not improving despite adequate antibiotics and fluids — THINK SOURCE CONTROL.
Respiratory Support
Oxygen Therapy & Ventilation Strategy
O₂ Targets
- SpO₂ 94–98% — standard sepsis patients
- SpO₂ 88–92% — chronic hypercapnia risk (COPD, OSA)
- Avoid hyperoxia — associated with worse outcomes
- High-flow nasal cannula (HFNC) early if increasing O₂ demand
Intubation Criteria
- Increasing FiO₂ requirement with falling SpO₂
- Respiratory fatigue — RR >35, use of accessory muscles
- Altered consciousness — inability to protect airway
- Anticipated deterioration for transport/procedure
Lung Protective Ventilation
- Tidal volume: 6 mL/kg IBW (not actual body weight)
- Plateau pressure: <30 cmH₂O
- Driving pressure: <15 cmH₂O (plateau – PEEP)
- PEEP: titrate to prevent derecruitment (5–15 cmH₂O)
- Prone positioning: consider if PaO₂/FiO₂ <150 despite optimised MV
IBW men: 50 + 2.3 × (height in inches − 60) kg. IBW women: 45.5 + 2.3 × (height in inches − 60) kg.
Renal Support
AKI in Sepsis & RRT Indications
AKI Staging (KDIGO)
| Stage | Creatinine | Urine Output |
|---|
| 1 | ×1.5–1.9 baseline or ↑ ≥26.5 µmol/L | <0.5 mL/kg/h ×6–12h |
| 2 | ×2.0–2.9 baseline | <0.5 mL/kg/h ×12h |
| 3 | ×3 or ≥354 µmol/L or RRT | <0.3 mL/kg/h ×24h or anuria ×12h |
CRRT Indications (AEIOU)
- Acidosis — refractory metabolic acidosis pH <7.1
- Electrolytes — hyperkalaemia K >6.5 refractory to medical treatment
- Ingestion — toxin/drug removal (specific indications)
- Overload — fluid overload >10–15% body weight
- Uraemia — encephalopathy, pericarditis, uraemic bleeding
Timing of RRT initiation remains controversial. STARRT-AKI and IDEAL-ICU trials found no benefit to early vs late strategy for uncomplicated AKI — avoid initiating solely based on creatinine thresholds without clinical indications.
Cardiac Support
Stress Cardiomyopathy (Sepsis-Induced Myocardial Dysfunction)
- Occurs in ~40–50% of septic shock patients
- POCUS/echo: reduced LVEF, global hypokinesis
- Distinguish from vasodilatory shock (normal/high CO)
- Troponin elevation common — does not necessarily indicate ACS
- Usually reversible within 7–10 days with adequate treatment
Dobutamine Indications
- Confirmed reduced EF on echo AND adequate filling pressure
- Signs of tissue hypoperfusion despite adequate MAP
- Start at 2.5–5 mcg/kg/min, titrate to response
- Avoid in isolated vasodilatory shock with normal/high CO
- Stop if tachyarrhythmia or worsening hypotension
Glucose Management
Glycaemic Control in Sepsis
- Target blood glucose: 6–10 mmol/L (SSC recommendation)
- Some guidelines accept up to 10–11.1 mmol/L
- Insulin infusion protocol — nurse-driven titration
- Check BGL every 1–2 hours when on insulin infusion
- Tight control (4.5–6 mmol/L) — AVOID: excess hypoglycaemia risk
Hypoglycaemia is MORE dangerous than hyperglycaemia in sepsis. BGL <4 mmol/L — stop insulin infusion immediately, give 50% dextrose 50 mL IV, recheck in 15 minutes.
Corticosteroids
Hydrocortisone in Vasopressor-Refractory Shock
- Indication: Septic shock requiring vasopressors >0.25 mcg/kg/min noradrenaline for >4 hours
- Dose: Hydrocortisone 200 mg/day (50 mg q6h IV or continuous infusion)
- Improves haemodynamics and reduces vasopressor duration
- APROCCHSS/ADRENAL trials: no mortality benefit in general septic shock population
- Adrenocortical insufficiency screen (SST) before starting where time permits
Do not use high-dose steroids (methylprednisolone 1–2 g). Hydrocortisone 200 mg/day only — for haemodynamic benefit, not immunosuppression.
- Taper when vasopressors weaned — abrupt withdrawal may cause rebound hypotension
- Monitor glucose q2h — steroids worsen hyperglycaemia
- Watch for GI bleeding — consider PPI prophylaxis
GCC Sepsis Epidemiology
Common Sepsis Sources in GCC
- Urological: UTI, obstructive uropathy, urological procedures — leading source
- Biliary: Cholangitis, cholecystitis — common in GCC populations
- Respiratory: Community-acquired pneumonia, ventilator-associated pneumonia
- Abdominal: Secondary peritonitis, surgical site infections
- Gram-negative bacteraemia: E. coli, Klebsiella pneumoniae predominant
- ESBL-producing organisms rising — affects empirical antibiotic choice
Special Population Considerations
- Construction workers: Wound infections, UTI — Gram-negative bacteraemia risk
- Hajj pilgrims: Mass gathering — high sepsis volume in peak periods, meningococcal risk
- Expatriate workers: Delayed presentation, language barriers, inadequate vaccination
- Elderly nationals: Diabetes, CKD as common comorbidities — modifies presentation
- MRSA prevalence lower than Western hospitals but rising — monitor local antibiograms
MERS-CoV Sepsis Syndrome
MERS-CoV in GCC — Sepsis Overlap
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) remains endemic in the Arabian Peninsula. Healthcare workers in contact with camels or patients from known clusters are at risk.
- Can present as severe pneumonia → sepsis/ARDS
- High case fatality rate (>35% in hospitalised cases)
- Droplet + contact precautions; airborne for AGPs
- Report to local health authority immediately
- Supportive care only (no approved antiviral in routine use)
- Corticosteroids: limited evidence, may prolong viral shedding
- Apply standard sepsis bundles for organ support
- Camel exposure history essential in relevant cases
Regulatory & Quality Frameworks
DHA / MOH Sepsis Protocols
- Dubai Health Authority (DHA): mandatory sepsis screening on admission to ED/ICU
- Ministry of Health (MOH) KSA: hospital-level sepsis programme with door-to-antibiotic audit
- Abu Dhabi DOH: sepsis as notifiable condition in critical care settings
- All GCC hospitals: NEWS2 or modified EWS implementation
- Mandatory documentation of sepsis bundle completion times
CBAHI / JCIA Compliance
- CBAHI: Saudi Central Board for Accreditation of Healthcare Institutions
- JCIA: Joint Commission International — Middle East accreditation body
- Sepsis core measures: door-to-antibiotic, lactate measurement, bundle completion
- Monthly dashboard reporting — nursing unit-level compliance
- Root cause analysis for any sepsis bundle deviation
- Annual sepsis education mandatory for all clinical staff
Ramadan & Sepsis Management
Fasting, Dehydration and Sepsis Risk
- Dehydration during Ramadan fasting is a known sepsis precipitant — impairs host defences and promotes bacteraemia (especially UTI)
- Muslim patients with sepsis are exempt from fasting under Islamic jurisprudence (Sharia exemption for illness)
- Engage patient and family — religious consultation available in GCC hospitals
- IV fluid resuscitation must not be withheld for religious reasons
- Oral hydration before Suhoor (pre-dawn meal) — preventive advice for at-risk patients post-discharge
- Ramadan timing of medication — consult pharmacy for adjusted dosing schedules
- Document fasting status on admission — relevant to medication route and glucose monitoring
- Increased sepsis admissions typically seen in peak summer Ramadan (dehydration ×heat stress)
Arabic Language & Cultural Communication
Sepsis Education for Arabic-Speaking Patients & Families
- Use certified medical interpreter — not family member for clinical communication
- Arabic term for sepsis: "تعفن الدم" (ta'affun al-dam) — "blood poisoning"
- Family-centred communication norm in GCC — involve designated family spokesperson
- Explain necessity of blood draws, IV access, catheterisation clearly
- Written Arabic discharge instructions — risk signs to return to ED
- Address concerns about ICU admission (fear, cultural unfamiliarity)
- Spiritual care: Imam/religious advisor accessible in GCC hospitals
- Respect for modesty — same-gender nursing assignment where possible
MENA-SEPSIS Registry
- Regional multi-centre sepsis registry for GCC and wider MENA region
- Collects epidemiological data on sepsis incidence, causative organisms, outcomes
- Enables benchmarking of GCC hospital performance against regional standards
- Contributes to evidence base for regionally-adapted sepsis guidelines
- Nurses can contribute to data collection — ensure accurate, timely documentation