01Approach to the Critical Patient/attcp49

Immediate resuscitation priorities

›Airway and oxygenation

›Supplemental oxygen targeting SpO2 >= 94%

›High-flow nasal cannula for hypoxemia not meeting intubation threshold

›Early intubation planning if respiratory failure or severe encephalopathy

›Intubation indications

›GCS <= 8 with inability to protect airway

›Refractory hypoxemia despite high-flow oxygen

›Respiratory muscle fatigue with rising PaCO2

›Hemodynamic stabilization

›MAP target >= 65 mmHg

›Higher target 70-80 mmHg may benefit chronic hypertension patients

›Norepinephrine first-line vasopressor; do not delay for central line

›IV access and fluid resuscitation

›Two large-bore peripheral IVs or intraosseous access

›Crystalloid 30 mL/kg within 3 hours of recognition (strong recommendation)

›Lactate clearance target

›Initial lactate >= 2 mmol/L confirms tissue hypoperfusion

›Repeat lactate within 2 hours to confirm downward trend

›Antimicrobials within 1 hour

›Septic shock: antibiotics within 1 hour of recognition (Surviving Sepsis Campaign 2026, strong recommendation)

›Delay in antibiotics increases mortality by 7-10% per hour

›Broad-spectrum empiric coverage before cultures finalize

›Blood cultures x2 sets before antibiotics when feasible without delay

Monitoring and escalation targets

›Continuous monitoring bundle

›Continuous cardiac monitoring and pulse oximetry

›Arterial line for vasopressor-dependent patients

02History/hx75

Presenting complaint and source identification

›Infectious source symptoms

›Pneumonia source

›Cough with purulent sputum

›Dyspnea and pleuritic chest pain

›Urinary source

›Dysuria, frequency, flank pain

›Catheter or instrumentation history

›Abdominal source

›Abdominal pain, nausea, vomiting

›Recent abdominal surgery or perforation concern

›Skin and soft tissue source

›Wound erythema, swelling, drainage

›Crepitus suggesting gas-forming organism

›Constitutional symptoms

›Fever or rigors

›Antipyretic use masking temperature

›Hypothermia in elderly or immunocompromised

›Confusion or altered mentation

›Baseline cognitive status for comparison

›Acute delirium as sole sepsis presentation in elderly

›Decreased urine output

›Duration before presentation

›Last normal urine output

Risk factors and predisposing conditions

›Host susceptibility factors

›Age extremes

›Infants under 1 year

03Physical Exam/exam65

Vital signs and general appearance

›Hemodynamic profile

›Blood pressure

›SBP < 90 mmHg or MAP < 65 mmHg defining hypotension

›Pulse pressure narrowing suggesting low cardiac output state

›Heart rate

›Tachycardia HR > 90 bpm

›Relative bradycardia in beta-blocker use or high vagal tone

›Respiratory rate

›RR > 22 per minute as qSOFA criterion

›Rising RR as fatigue and deterioration marker

›Temperature

›Fever > 38.3 C

›Hypothermia < 36 C as severity marker in elderly and immunocompromised

›Oxygen saturation

›Room air SpO2 as baseline

›Escalating oxygen requirement trend

›General appearance

›Diaphoresis and toxic appearance

›Altered mental status

›GCS score and orientation

›Agitation or obtundation

Source-directed physical examination

›Skin and extremities

›Mottling

›Especially over knees and lower extremities

›Livedo reticularis pattern

›Capillary refill time

04Differential Diagnosis/ddx58

Life-threatening shock states

›Distributive shock mimics

›Anaphylaxis

›ICD-10 T78.2 (anaphylactic shock)

›Urticaria, angioedema, allergen exposure history

›Adrenal crisis

›ICD-10 E27.1

›Hypotension refractory to fluids, hyperkalemia, hyponatremia

›Corticosteroid history or primary adrenal insufficiency

›Toxic shock syndrome

›Staphylococcal vs streptococcal distinction

›Diffuse erythroderma, desquamation

›Thyroid storm

›ICD-10 E05.5

›Tachycardia disproportionate to temperature, thyroid history

›Non-distributive shock

›Cardiogenic shock

›ICD-10 R57.0

›Cold extremities, elevated JVP, pulmonary edema, reduced EF on echo

›Septic cardiomyopathy overlap requiring echocardiography

›Pulmonary embolism

›ICD-10 I26.0 (with acute cor pulmonale)

›Pleuritic chest pain, RV strain on echo or ECG, CT-PA findings

›Tension pneumothorax

›Tracheal deviation, absent breath sounds

›Pulseless electrical activity cardiac arrest

›Hemorrhagic shock

›Trauma history, GI bleeding

05Laboratory Tests/lt61

Core infection and organ function labs

›Complete blood count with differential

›Leukocytosis > 12 x 10^9/L

›Left shift with bands as bacterial infection marker

›Leukopenia < 4 x 10^9/L as severe sepsis/immunosuppression marker

›Thrombocytopenia as DIC or bone marrow suppression marker

›Platelet < 100 x 10^9/L warrants coagulation panel

›Platelet trend more informative than single value

›Comprehensive metabolic panel

›Creatinine and BUN for acute kidney injury staging

›KDIGO AKI criteria application

›Renal dose adjustment for antibiotics

›Liver function tests

›Hyperbilirubinemia as organ dysfunction criterion

›Transaminase elevation in hepatic hypoperfusion

›Glucose

›Hyperglycemia as stress response marker

›Hypoglycemia in hepatic failure or adrenal insufficiency

›Electrolytes

›Hyponatremia in SIADH or adrenal crisis

›Hyperkalemia in AKI or adrenal insufficiency

Perfusion and sepsis biomarkers

›Lactate

›Venous or arterial lactate >= 2 mmol/L defines tissue hypoperfusion

›Lactate >= 4 mmol/L associated with > 40% mortality

›Serial lactate q2-4h to confirm clearance

›Lactate clearance >= 10% at 2 hours associated with improved survival

›SSC 2026 recommends lactate-guided resuscitation

06Diagnostic Tests/dt94

Scoring Systems

›SOFA score (Sequential Organ Failure Assessment)

›Six organ systems scored 0-4 each

›Respiratory: PaO2/FiO2 ratio

›Coagulation: platelet count

›Liver: bilirubin

›Cardiovascular: vasopressor requirement

›CNS: GCS

›Renal: creatinine or urine output

›Sepsis-3 definition: acute SOFA increase >= 2 with suspected infection

›Mortality increases with SOFA score

›SOFA > 11 associated with > 50% hospital mortality

›SOFA outperforms SIRS and qSOFA for ICU mortality prediction (JAMA 2017, AUROC 0.74 vs 0.64 for qSOFA)

›qSOFA (Quick SOFA)

›Three criteria, 1 point each

›Respiratory rate >= 22 per minute

›SBP <= 100 mmHg

›Altered mental status (any GCS < 15)

›qSOFA >= 2 associated with prolonged ICU stay and in-hospital mortality

›Sensitivity 70%, specificity 79% for in-hospital mortality outside ICU

›Screening tool only; not sufficient for diagnosis

›Limitations

›Lower sensitivity than SIRS for early sepsis detection in ED

›Not recommended to replace clinical judgment

›SIRS criteria (historical)

›Temperature > 38 C or < 36 C

›HR > 90 bpm

›RR > 20 per minute or PaCO2 < 32 mmHg

›WBC > 12 x 10^9/L or < 4 x 10^9/L or > 10% bands

›SIRS >= 2 sensitive but non-specific

›Present in many non-infectious conditions

›Sepsis-3 does not use SIRS for definition

›Septic shock definition criteria

›Vasopressor requirement to maintain MAP >= 65 mmHg

›Persistent hypotension despite adequate fluid resuscitation

›Serum lactate > 2 mmol/L

›Hospital mortality approximately 40-50% when both criteria met (Sepsis-3, JAMA 2016)

MRI

›MRI indications in septic shock

›Limited acute utility in hemodynamically unstable patients

›Contraindicated in patients requiring continuous vasopressor monitoring

›Magnet environment incompatible with many ICU devices

›Brain MRI when CNS source suspected

›Brain abscess characterization

›Cerebral venous sinus thrombosis

›Spinal MRI for epidural abscess

›Midline spinal tenderness with fever

›Neurological deficits suggesting cord compression

›Contraindications

›Hemodynamic instability requiring active vasopressor titration

›Non-MRI compatible implants or devices

CT

›CT chest

›Pneumonia source evaluation

›Consolidation pattern and distribution

›Pleural effusion and empyema detection

›ARDS pattern recognition

›Bilateral ground-glass opacities

›Dependent consolidation

›CT abdomen and pelvis with contrast

›Intra-abdominal source identification

›Abscess localization for drainage planning

›Bowel perforation with free air

›Appendicitis, cholecystitis, diverticulitis

›Sensitivity for intra-abdominal abscess approximately 80-90%

›IV contrast required for optimal evaluation

›Oral contrast optional per institutional protocol

›CT-PA (pulmonary angiography)

›PE exclusion when clinical suspicion high

›Wells score or PERC rule application before CT-PA

›RV strain pattern suggestive of massive PE

›Soft tissue CT for necrotizing fasciitis

›Gas in soft tissue planes as diagnostic finding

›Sensitivity 80%, specificity 94% for gas on CT

›CT should not delay surgical exploration when high clinical suspicion

›Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score adjunct

Ultrasound

›Point-of-care ultrasound protocol

›Cardiac POCUS

›LV function and global contractility estimate

›Septic cardiomyopathy: new LV dysfunction in 20-50% of septic shock patients

›RV strain pattern suggesting PE or ARDS

›Pericardial effusion and tamponade screen

›IVC assessment

›IVC collapsibility index for fluid responsiveness (limited reliability)

›IVC > 2 cm non-collapsible suggests fluid overload

›Dynamic measures (passive leg raise) preferred over static IVC

›Lung ultrasound

›B-lines suggesting pulmonary edema or consolidation

›A-lines pattern in pneumothorax

›Pleural effusion identification and thoracentesis guidance

›Source identification

›Biliary ultrasound for cholecystitis or biliary obstruction

›Gallbladder wall thickening > 3 mm, pericholecystic fluid

›Common bile duct dilation > 6 mm

›Renal and bladder ultrasound for hydronephrosis

›Obstructive uropathy as reversible AKI cause

›Perinephric abscess identification

07Disposition/dispo37

ICU admission criteria

›All septic shock patients require ICU admission

›Vasopressor requirement mandates ICU-level monitoring

›Arterial line and central venous access preferably in ICU

›Transfer within 6 hours of recognition; delay increases mortality (SSC 2026)

›Continuous hemodynamic monitoring required

›Arterial line for all vasopressor-dependent patients

›Central venous catheter for vasopressor infusions

›Step-down or intermediate care eligibility

›Sepsis without shock responsive to initial resuscitation

›Lactate < 2 mmol/L after resuscitation

›No vasopressor requirement after fluid challenge

›Close monitoring for deterioration

›Frequent vital sign reassessment

›Repeat lactate within 6 hours

Source control timing

›Surgical source control

›Necrotizing fasciitis: immediate operative debridement

›Do not delay surgery for CT when clinical diagnosis clear

›Mortality increases significantly with each hour of delay

›Abscess: drainage within 6-12 hours of identification

›Percutaneous image-guided drainage when accessible

›Open surgical drainage for inaccessible or complex collections

›Infected prosthetic material: removal when feasible

›Infected central lines removed as source control

›Infected urinary catheters replaced or removed

Post-ICU and discharge planning

›Transfer criteria

08Treatment/t125

Initial resuscitation

›Fluid resuscitation

›Crystalloid 30 mL/kg within 3 hours (strong recommendation, SSC 2026)

›Normal saline 0.9% or balanced crystalloids (lactated Ringer's)

›Balanced crystalloids preferred; lower chloride load, less hyperchloremic acidosis

›Avoid colloids as initial resuscitation fluid

›Hydroxyethyl starch associated with increased mortality and AKI; contraindicated

›Albumin 4-5% may be considered for ongoing resuscitation after crystalloid

›Dynamic fluid responsiveness assessment after initial bolus

›Passive leg raise: increase in SV or CO >= 10% predicts fluid responsiveness

›Pulse pressure variation >= 13% in ventilated patients predicts responsiveness

›CVP unreliable as static fluid responsiveness marker

›Avoid fluid overload

›Cumulative positive balance > 10% body weight associated with worse outcomes

›Restrictive fluid strategy after initial resuscitation

Vasopressors

›Norepinephrine (first-line vasopressor)

›Starting dose 0.01-0.1 mcg/kg/min IV infusion

›Titrate to MAP >= 65 mmHg

›Doses up to 1-2 mcg/kg/min may be required in refractory shock

›Can be initiated via peripheral IV (18-20 gauge) safely without central access

›Peripheral norepinephrine safe for up to 24 hours in large bore PIV

›ACEP supports peripheral vasopressor use to avoid central line delays

›Alpha-adrenergic dominant with mild beta-1 effect

›Increases SVR without excessive tachycardia

›Preferred over dopamine; lower mortality and arrhythmia risk

›Vasopressin (second-line addition)

›Fixed dose 0.03 U/min IV infusion (not titrated)

›Add when norepinephrine dose >= 0.25-0.5 mcg/kg/min

›V1 receptor-mediated vasoconstriction independent of catecholamine pathway

›Vasopressin spares norepinephrine dose

›VASST trial: similar overall mortality but benefit in less severe shock subgroup

›SSC 2021/2026: vasopressin addition recommended at threshold dose

›Epinephrine (third-line)

›Dose 0.01-0.5 mcg/kg/min IV infusion

›Add or substitute if MAP target not met with norepinephrine + vasopressin

›Strong alpha and beta agonism

›Caution

›Tachycardia and arrhythmia risk

›Elevated lactate via beta-2 stimulation (may confound lactate monitoring)

›Dopamine (use limited)

›Second-line only in highly selected patients with bradycardia

›Higher risk of tachyarrhythmia versus norepinephrine

›SSC: norepinephrine preferred over dopamine in most patients

›Phenylephrine (avoid as primary agent)

›Pure alpha-1 agonist; reduces cardiac output

›May be used when tachyarrhythmias limit norepinephrine

›Not recommended as primary vasopressor in septic shock

Empiric antimicrobials

›Timing and culture strategy

›Antibiotics within 1 hour of recognition for septic shock (strong recommendation)

›Each hour delay increases mortality approximately 7%

›Do not delay antibiotics to obtain cultures if it prolongs time

›Blood cultures x2 sets before antibiotics when feasible

›Source-directed cultures: urine, sputum, wound as clinically indicated

›Broad-spectrum empiric coverage

›Piperacillin-tazobactam 4.5 g IV every 6 hours (extended infusion preferred)

›Extended infusion over 4 hours improves pharmacodynamic target attainment

›Covers gram-positive, gram-negative, anaerobes

›Alternative: meropenem 1-2 g IV every 8 hours for healthcare-associated or MDR risk

›2 g every 8 hours as extended infusion for severe illness

›Carbapenem choice for ESBL-producing organisms

›Add MRSA coverage when high risk

›Vancomycin IV: 15-20 mg/kg every 8-12 hours; target AUC/MIC 400-600

›Renal dose adjustment required

›AUC-guided monitoring preferred over trough-only monitoring

›Linezolid 600 mg IV/PO every 12 hours as alternative

›Platelet monitoring with use > 2 weeks

›Serotonin syndrome risk with concurrent serotonergic drugs

›Source-directed modification

›Urinary source without ESBL risk

›Ceftriaxone 2 g IV daily

›Or ciprofloxacin 400 mg IV every 8-12 hours if susceptible

›Community-acquired pneumonia source

›Beta-lactam plus atypical coverage (azithromycin or respiratory fluoroquinolone)

›Add MRSA coverage if severe community-acquired pneumonia with risk factors

›Suspected fungal infection

›Prolonged ICU stay, TPN, immunosuppression, prior antibiotics, Candida colonization

›Micafungin 100 mg IV daily or caspofungin 70 mg loading then 50 mg daily

›Antiviral coverage

›Influenza season or clinical suspicion: oseltamivir 75 mg PO/NG every 12 hours

›HSV or CMV in immunocompromised: acyclovir or ganciclovir per specialist guidance

›De-escalation strategy

›Narrow spectrum based on culture and sensitivity results

›Serial procalcitonin to guide de-escalation

›Antibiotic stewardship consultation in complex cases

›Duration 7-10 days typical for most sources

›Shorter courses when rapid clinical improvement and culture guidance

›Longer courses for specific sources: endocarditis, osteomyelitis, fungal infection

Corticosteroids

›Hydrocortisone for refractory vasopressor requirements

›Hydrocortisone 200 mg/day IV

›50 mg IV every 6 hours or 200 mg continuous infusion daily

›Add fludrocortisone 50 mcg daily enterally (optional per SSC 2026)

›Indications

›Norepinephrine or epinephrine >= 0.25 mcg/kg/min to maintain MAP

›Conditional recommendation (SSC 2026)

›Mechanism and evidence

›Accelerates shock reversal; uncertain 28-day mortality benefit

›APROCCHSS trial: hydrocortisone + fludrocortisone reduced 90-day mortality

›ADRENAL trial: faster vasopressor weaning but no mortality difference

›Monitoring

›Hyperglycemia: glucose monitoring every 1-2 hours

›Hypernatremia risk

›Avoid prolonged use beyond shock resolution

›Taper when vasopressors weaned

›Abrupt discontinuation after > 3 days may cause rebound vasodilation

›Wean over 24-48 hours when hemodynamically stable

Ventilatory support

›Lung-protective ventilation if intubated

›Tidal volume 6 mL/kg ideal body weight

›Maximum plateau pressure < 30 cmH2O

›Driving pressure <= 15 cmH2O associated with reduced ARDS mortality

›PEEP titration

›Higher PEEP for moderate-severe ARDS (PEEP >= 5 cmH2O minimum)

›PEEP/FiO2 table per ARDSNet protocol

›Prone positioning

›For moderate-severe ARDS with PaO2/FiO2 < 150 mmHg

›16+ hours per session; Class I recommendation based on PROSEVA trial

›Glucose management

›Target glucose 7.8-10 mmol/L (140-180 mg/dL equivalent)

›Insulin infusion protocol for ICU glucose management

›Hypoglycemia prevention: glucose < 3.9 mmol/L associated with mortality

›Tight glucose control (< 6.1 mmol/L) avoided

›NICE-SUGAR trial: intensive insulin therapy increased mortality

›VTE and stress ulcer prophylaxis

›LMWH preferred over UFH for VTE prophylaxis when feasible

›Mechanical prophylaxis when anticoagulation contraindicated

›Proton pump inhibitor or H2 blocker for stress ulcer prophylaxis

›Risk-benefit balance; PPI may increase C difficile risk

09Special Populations/sp87

Pregnancy

›Physiologic considerations in pregnancy

›Baseline physiologic changes alter sepsis recognition

›Physiologic tachycardia and lower blood pressure in pregnancy

›WBC 6-16 x 10^9/L normal in pregnancy; leukocytosis less specific

›Common septic shock sources in pregnancy

›Chorioamnionitis and postpartum endometritis

›Urinary tract infection (more common due to anatomic changes)

›Group A Streptococcus postpartum sepsis

›Management modifications

›Vasopressor selection

›Norepinephrine: preferred; limited data but increasingly used in pregnancy

›Phenylephrine: used in obstetric anesthesia; preserves uteroplacental flow

›Avoid pure vasoconstrictors without cardiac output monitoring

›Antibiotic selection

›Beta-lactams safe throughout pregnancy

›Avoid aminoglycosides (ototoxicity), fluoroquinolones (cartilage effects in animal studies)

›Metronidazole considered safe after first trimester

›Fluid resuscitation standard approach

›30 mL/kg crystalloid; left lateral positioning to relieve aorto-caval compression

›Fetal heart rate monitoring when viable gestation

›Corticosteroids

›Hydrocortisone acceptable; consider betamethasone if < 34 weeks for fetal lung maturity

›Obstetric team involvement

›Immediate obstetrics consultation for all pregnant septic shock patients

›Delivery may be source control in peripartum sepsis

›Neonatology involvement for premature gestation

Geriatric

›Atypical presentation

›Absence of fever in up to 30-40% of elderly sepsis patients

›Hypothermia as presenting sign

›Delirium or acute confusion as primary or only symptom

›Blunted heart rate response

›Beta-blocker or pacemaker masking tachycardia

›Relative bradycardia with severe infection possible

›Lower baseline blood pressure

›MAP target may need individualization

›Chronically hypertensive patients may be hypoperfused at MAP 65 mmHg

›Frailty and functional status

›Pre-morbid functional status guides resuscitation goals

›Clinical Frailty Scale assessment

›Goals of care discussion with patient and family early

›Polypharmacy interactions

›Renal dose adjustment for antibiotics and vasopressors

›Drug-drug interactions in complex medication regimens

›Cognitive baseline critical for delirium recognition

›Informant history for baseline mental status

›CAM-ICU or ICDSC for delirium monitoring in ICU

›Resuscitation modifications

›Fluid resuscitation with careful monitoring

›Diastolic dysfunction increases pulmonary edema risk with aggressive fluids

›Serial lung ultrasound for fluid status monitoring

›Vasopressor targets

›Higher MAP target 70-80 mmHg in chronic hypertension patients

›More frequent reassessment for vasopressor tolerance

Pediatrics

›Pediatric septic shock differences

›Pediatric Sepsis definitions (PICU-specific)

›Age-specific vital sign thresholds for tachycardia and hypotension

›IPSCC 2024 pediatric sepsis criteria differ from Sepsis-3

›Compensated vs decompensated shock in pediatrics

›Children maintain blood pressure until late decompensation

›Tachycardia and capillary refill > 2 seconds as early warning signs

›Cold shock vs warm shock

›Cold shock (high SVR): cool extremities, delayed cap refill, narrow pulse pressure

›Warm shock (low SVR): warm extremities, bounding pulses, wide pulse pressure

›Fluid resuscitation in pediatrics

›Initial fluid bolus 10-20 mL/kg IV/IO over 5-10 minutes

›Repeat boluses every 5-10 minutes titrated to clinical response

›Total initial resuscitation up to 40-60 mL/kg in first hour if needed

›FEAST trial implications

›Aggressive bolus fluids in African malaria/non-malaria sepsis increased mortality

›Reassessment after each bolus mandatory

›Vasopressor selection in pediatrics

›Epinephrine preferred for cold shock

›0.05-2 mcg/kg/min IV infusion

›Improves cardiac contractility in low cardiac output state

›Norepinephrine preferred for warm shock

›0.05-2 mcg/kg/min IV infusion

›Increases SVR in vasodilatory shock

›Dopamine historical first-line; norepinephrine increasingly preferred

›Antibiotic dosing (weight-based)

›Ceftriaxone 100 mg/kg IV daily (max 4 g/day)

›For community-acquired sources

›Piperacillin-tazobactam 100 mg/kg piperacillin component IV every 6-8 hours

›Max 4.5 g per dose; healthcare-associated or broad coverage needed

›Vancomycin 15 mg/kg IV every 6 hours (neonates) to 10-15 mg/kg every 6 hours (older children)

›AUC-guided monitoring where available

›Hydrocortisone 50 mg/m2/day for catecholamine-resistant shock

›Divided every 6-8 hours

10Background/b90

Epidemiology

›Global burden

›Approximately 49 million sepsis cases worldwide annually

›11 million sepsis-related deaths per year

›Septic shock mortality 40-50%

›Incidence increasing as population ages and immunosuppressed populations grow

›Incidence approximately 300 per 100,000 population in high-income countries

›Sub-Saharan Africa disproportionately affected

›Demographic risk

›Age: bimodal distribution in infants and elderly >= 65 years

›Incidence increases 13-fold per decade after age 65

›Elderly account for > 60% of all sepsis cases

›Sex: male sex associated with higher incidence

›Black race associated with higher incidence and mortality

›Socioeconomic factors contribute to disparity

›Prognostic factors

›Cirrhosis independently associated with mortality (adjusted OR 1.85, Lancet Respir Med 2026 meta-analysis)

›Malignancy, CKD, heart failure as additional independent predictors

›Source matters: intra-abdominal and fungal sources carry higher mortality

›Post-sepsis syndrome affects majority of survivors

›Rehospitalization within 12 months in > 40% of survivors

›Cognitive impairment and functional disability persist in 30-50%

Pathophysiology

›Dysregulated host response

›Innate immune activation

›Pattern recognition receptors (TLR4, TLR2) detect PAMPs

›Cytokine storm: TNF-alpha, IL-1, IL-6, IL-8 release

›Complement activation and coagulation cascade engagement

›Endothelial dysfunction

›Loss of endothelial barrier integrity

›Capillary leak syndrome causing distributive physiology

›Vasodilation via excess nitric oxide production

›Mitochondrial dysfunction

›Cellular oxygen utilization failure independent of delivery

›Cytopathic hypoxia contribution to organ failure

›Organ dysfunction cascade

›Cardiovascular

›Septic cardiomyopathy in 20-50% of patients

›Biventricular diastolic and systolic dysfunction

›Autonomic dysregulation with new-onset atrial fibrillation

›Renal

›AKI in up to 50% of septic shock patients

›Multifactorial: hypoperfusion, microvascular thrombosis, direct tubular injury

›Renal replacement therapy required in 5-10%

›Coagulation

›DIC via thrombin generation and fibrinolysis impairment

›Microvascular thrombosis contributes to organ injury

›Neurological

›Septic encephalopathy in > 70% of ICU sepsis patients

›Blood-brain barrier disruption, neuroinflammation, neurotransmitter changes

›Microbiology

›Gram-negative organisms most common overall

›E coli, Klebsiella, Pseudomonas, Acinetobacter

›Endotoxin (LPS) dominant PAMP

›Gram-positive organisms

›Staphylococcus aureus (including MRSA)

›Streptococcus pneumoniae, Group A Streptococcus

›Enterococcus especially in healthcare-associated sepsis

›Fungal sepsis

›Candida most common in ICU setting

›Invasive aspergillosis in immunocompromised

›Polymicrobial bacteremia in 5-10% of cases

Therapeutic Considerations

›Resuscitation strategy evolution

›Early Goal-Directed Therapy (EGDT) historical basis

›Rivers trial 2001: ScvO2 targeting improved survival

›ProCESS, ARISE, ProMISe trials: protocolized EGDT not superior to usual care

›Current approach: individualized resuscitation targets with dynamic monitoring

›Lactate-guided resuscitation

›SSC 2026 recommends targeting lactate clearance

›Lactate normalization associated with reduced mortality

›Lactate-guided therapy reduces fluid overload risk compared to static targets

›Antibiotic stewardship in sepsis

›De-escalation guided by culture data reduces resistance and C difficile

›Serial procalcitonin reduction guides antibiotic duration

›7-10 day courses appropriate for most sources

›Prolonged beta-lactam infusions

›Extended infusion improves PK/PD target attainment

›Most relevant for MIC-elevated organisms and severe infections

›Source control principles

›Source identification mandatory for optimal outcomes

›CT imaging for occult intra-abdominal sources

›Echocardiography when endocarditis suspected

›Timing of source control

›Necrotizing fasciitis: immediate; cholecystitis: within 24-72 hours

›Delay beyond 12 hours for other sources associated with mortality increase

›Monitoring targets

›MAP >= 65 mmHg as minimum target

›Higher targets (70-80 mmHg) for known chronic hypertension

›SEPSISPAM trial: MAP 80-85 mmHg did not improve overall mortality but reduced RRT

›Capillary refill time normalization <= 3 seconds

›ANDROMEDA-SHOCK trial: cap refill-guided resuscitation non-inferior to lactate-guided

›Peripheral perfusion markers complementary to lactate

11Patient Discharge Instructions/pdi32

copy discharge instructions

›Septic shock recovery information

›Serious infection required ICU-level care

›Full recovery may take weeks to months

›Fatigue, weakness, and cognitive difficulty are common after critical illness

›Antibiotics instructions

›Complete the full antibiotic course as prescribed

›Do not stop antibiotics early even if feeling better

›Take with food if stomach upset occurs

›Warning signs requiring immediate return to ER

›Fever above 38.5 C or shaking chills

›New confusion or difficulty thinking clearly

›Dizziness or feeling faint when standing

›Decreased urination less than usual

›Worsening redness, swelling, or drainage from wound or IV site

›Difficulty breathing or rapid breathing

›New or worsening pain at site of original infection

›Feeling significantly worse than at hospital discharge

›Post-sepsis recovery expectations

›Fatigue and weakness are common and may persist weeks to months

›Gradual return to activity as tolerated

›Physical therapy referral may be needed for deconditioning

›Cognitive changes including memory and concentration difficulty

›Brain fog can persist for months; seek assessment if concerning

›Psychological effects including anxiety, depression, and PTSD are common

›Follow-up appointment within 1-2 weeks is essential

›Antibiotic course completion review

›Blood tests to check kidney function and infection markers if recommended

12References/r33

Guidelines and key sources

›Surviving Sepsis Campaign guidelines

›Prescott HC, Antonelli M, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026. Critical Care Medicine. 2026

›Current gold standard guideline with strong and conditional recommendations

›Available at doi.org/10.1097/CCM.0000000000007075

›Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign 2021 guidelines. Critical Care Medicine. 2021

›Predecessor guideline with landmark vasopressor and antibiotic recommendations

›Sepsis-3 definition references

›Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016

›Current operational definition: SOFA-based criteria with vasopressor/lactate threshold

›Shankar-Hari M, Phillips GS, Levy ML, et al. Developing a New Definition for Septic Shock (Sepsis-3). JAMA. 2016

›Companion paper defining septic shock subpopulation

›Emergency medicine key references

›Long B, Gottlieb M. Emergency Medicine Updates: Evaluation and Diagnosis of Sepsis and Septic Shock. Am J Emerg Med. 2025

›Long B, Gottlieb M. Emergency Medicine Updates: Management of Sepsis and Septic Shock. Am J Emerg Med. 2025

›Yealy DM, Mohr NM, Shapiro NI, et al. Early Care of Adults With Suspected Sepsis in The ED. Annals of Emergency Medicine. 2021

Landmark trials and systematic reviews

›Resuscitation trials

›Meyer NJ, Prescott HC. Sepsis and Septic Shock. NEJM. 2024

›Comprehensive review of pathophysiology, diagnosis, and management

›Delaney A, Borges-Sa M, Chew MS, et al. Current Standard of Care for Septic Shock. Intensive Care Medicine. 2025

›Contemporary review of standard-of-care evidence

›Vasopressor trials

›VASST trial: vasopressin versus norepinephrine in septic shock

›No overall mortality difference; possible benefit in less severe shock

›ANDROMEDA-SHOCK trial: capillary refill vs lactate-guided resuscitation

›Non-inferior outcomes; peripheral perfusion viable resuscitation endpoint

›Corticosteroid trials

Evidence & Review