Multisystem Processes & Disorders

Septic shock: vasopressor selection and resuscitation goals

Clinical Overview and When to Suspect Septic Shock

— Fever or hypothermia (<36°C is worse prognosis in elderly)

— Tachycardia, tachypnea, altered mentation, oliguria

— qSOFA ≥2 (RR ≥22, SBP ≤100, altered mental status) — screening tool only, not diagnostic

— Unexplained lactate >2, new AKI, new coagulopathy, ileus, mottling

— Vasoplegia from NO/prostacyclin → needs vasoconstrictors

— Capillary leak + venodilation → needs fluids early, but not unlimited (lung/gut edema worsens outcomes)

— Mitochondrial dysfunction → tissue hypoxia despite normal SaO₂; lactate is the surrogate

— Measure lactate, repeat if >2

— Obtain blood cultures before antibiotics (do not delay abx >45 min)

— Broad-spectrum antibiotics within 1 hour of recognition

— 30 mL/kg balanced crystalloid for hypotension or lactate ≥4

— Start vasopressors if MAP <65 during/after fluids to keep MAP ≥65

Board pearl: Septic shock requires BOTH vasopressor dependence AND lactate >2 after fluids — hypotension alone that responds to fluids is sepsis with hypotension, not septic shock. The distinction matters because shock physiology mandates earlier norepinephrine, central access planning, and ICU disposition.

Definition (Sepsis-3): Sepsis = life-threatening organ dysfunction from dysregulated host response to infection, operationalized as SOFA score ↑≥2. Septic shock = sepsis + persistent hypotension requiring vasopressors to keep MAP ≥65 AND lactate >2 mmol/L despite adequate volume resuscitation.

Epidemiology: ~1.7 million US sepsis cases/year, ~270,000 deaths. Mortality in septic shock 30–40% even with optimal care. Most common sources: pulmonary (≈40%), abdominal (≈20%), GU (≈10%), bloodstream/line, skin/soft tissue.

When to suspect on the wards or ED:

Pathophysiology pearls driving therapy:

Hour-1 Surviving Sepsis bundle (memorize):

Presentation Patterns and Key History

— Pneumonia: cough, pleuritic pain, recent influenza, nursing home resident, post-stroke aspiration risk

— Pyelonephritis/urosepsis: flank pain, dysuria, indwelling Foley, recent stent or stone, pregnancy

— Intra-abdominal: post-op day 3–7 fever + ileus, diverticulitis with peritonitis, cholangitis (Charcot triad/Reynolds pentad), perforated viscus

— Skin/soft tissue: rapidly spreading erythema, pain out of proportion → necrotizing fasciitis, IVDU with injection sites

— CNS: fever + headache + neck stiffness, recent neurosurgery, ventricular shunt

— Catheter-related BSI: rigors with line flush, tunneled catheter, dialysis access

— Recent hospitalization or IV abx within 90 days → MDR/Pseudomonas risk

— Neutropenia (chemo within 2 weeks) → febrile neutropenia protocol

— Asplenia (surgical, sickle cell) → encapsulated organisms, dramatic fulminant course

— Cirrhosis → SBP risk, Vibrio if raw oysters/seawater

— Immunosuppression (steroids, biologics, transplant, HIV CD4<200) → fungal, PJP, atypical

— Recent travel, animal/tick exposure, IVDU

Step 3 management: On any hypotensive febrile patient, your first three history questions should drive empiric antibiotic choice: (1) Where do you think the infection is? (2) Has the patient had antibiotics or been hospitalized in 90 days? (3) Are they immunocompromised? Missing any of these is the most common reason an exam vignette punishes you for "inadequate empiric coverage" downstream.

Classic presentation: febrile, tachycardic, hypotensive patient with a localizing infectious source. But up to 15% are afebrile or hypothermic — especially elderly, immunosuppressed, ESRD, cirrhotic.

High-yield source-specific stems:

Risk factor history (alters empiric coverage):

Time course matters: Fulminant <24 h with purpura → think meningococcemia, capnocytophaga (post-splenectomy + dog bite), toxic shock.

Physical Exam Findings and Hemodynamic Assessment

— Hypotension with wide pulse pressure (low diastolic from vasodilation)

— Tachycardia (blunted in β-blocked patients — beware false reassurance)

— Warm, flushed extremities early ("warm shock") → progresses to cold/mottled as cardiac output falls

— Capillary refill >3 sec — ANDROMEDA-SHOCK showed CRT-guided resuscitation is non-inferior to lactate-guided and reduced organ failure

— Mottling score (knees), cold extremities, weak distal pulses

— Mental status — agitation, somnolence, delirium

— Urine output <0.5 mL/kg/hr for 2 hours

— Lung crackles/bronchial breath sounds, dullness

— CVA tenderness, suprapubic tenderness

— Peritoneal signs, surgical wound erythema/drainage

— Crepitus, bullae, dusky skin → necrotizing soft tissue infection — surgical emergency

— Murmur + peripheral stigmata (Janeway, Osler, Roth) → endocarditis

— Indwelling devices: line site erythema, pacemaker pocket

— POCUS: IVC collapsibility >50% suggests fluid responsiveness; hyperdynamic LV with small chamber = vasodilated/volume-depleted; look for B-lines (pulmonary edema) before more fluid

— Passive leg raise + stroke volume change ≥10% = fluid responsive

— Pulse pressure variation >13% on mechanical ventilation = fluid responsive

— Mixed/central venous O₂ sat (ScvO₂) — historically >70% goal; no longer mandated but useful trend

Key distinction: Septic shock is distributive (warm, wide pulse pressure, low SVR, high CO early) vs cardiogenic (cold, narrow pulse pressure, JVD, crackles, low CO). Misclassifying cardiogenic as septic and giving 30 mL/kg crystalloid is a classic exam trap producing flash pulmonary edema.

Vital sign triad of distributive shock:

Perfusion exam (drives resuscitation endpoints):

Source-localizing exam:

Bedside hemodynamic assessment (Step 3 favorite):

Diagnostic Workup — Initial Labs, Imaging, Cultures

— CBC with diff — leukocytosis, bandemia, leukopenia (worse), thrombocytopenia (DIC, severity marker)

— CMP — AKI (creatinine ↑), transaminitis, hyperbilirubinemia (cholestasis of sepsis), hypoglycemia (late, ominous)

— Lactate — initial AND repeat at 2–4 hr; failure to clear (<10% drop) predicts mortality

— VBG/ABG — anion gap metabolic acidosis, respiratory compensation

— Coags (PT/INR, PTT, fibrinogen, D-dimer) — screen for DIC

— Procalcitonin — can support bacterial etiology and guide antibiotic de-escalation; not for initiation decisions

— Troponin (demand ischemia common), BNP if CHF overlap

— Two sets of blood cultures from separate sites (peripheral + line if present, paired DTP for CLABSI)

— Urinalysis + urine culture on everyone

— Sputum gram stain/culture if pneumonia

— Wound, CSF, peritoneal fluid as source dictates

— CXR universal

— CT abdomen/pelvis with contrast if abdominal source suspected and renal function permits (don't withhold for AKI when source control is urgent)

— CT head before LP if focal deficit, immunocompromise, papilledema, altered mentation — but start empiric abx + dexamethasone first for suspected meningitis

— POCUS for cardiac function, IVC, lung, gallbladder, hydronephrosis

CCS pearl: On a CCS septic shock case, the high-yield order set in the first simulated 30 minutes is: large-bore IV ×2, NS or LR 30 mL/kg, blood cultures ×2, UA + Ucx, lactate, CBC, CMP, coags, VBG, CXR, broad-spectrum antibiotics, acetaminophen if febrile, and move location to ICU. Forgetting to move location is a common point loss.

Initial lab panel (within first hour):

Cultures before antibiotics — but don't delay abx >45 min:

Imaging:

Pregnancy test in any woman of reproductive age before imaging/medications

Diagnostic Workup — Advanced and Source-Specific Studies

— Repeat exam q2–4 h focusing on skin folds, perineum, back (decubitus), joints

— CT chest/abdomen/pelvis with contrast — high yield for occult abscess, perforation, pyelonephritis, mesenteric ischemia

— TTE → TEE if endocarditis suspected (persistent bacteremia, new murmur, embolic phenomena, S. aureus bacteremia, prosthetic valve)

— LP if meningismus, altered mentation without alternative explanation

— Joint aspiration if monoarticular effusion

— Paracentesis in any cirrhotic with ascites and shock (SBP if PMN ≥250)

— Fungal blood cultures, (1,3)-β-D-glucan, galactomannan in immunocompromised

— MRSA nares PCR — high NPV allows early vancomycin de-escalation in pneumonia

— Respiratory viral PCR, influenza, SARS-CoV-2

— C. difficile PCR/toxin if diarrhea

— HIV testing if not recent

— SOFA — organ dysfunction trajectory; ↑≥2 from baseline defines sepsis

— APACHE II — ICU prognostication

— MEWS/NEWS — ward early warning

— MAP ≥65 mmHg (higher 80–85 considered in chronic HTN if AKI worsens at 65)

— Lactate clearance — repeat q2–4 h until normalized

— Urine output ≥0.5 mL/kg/hr

— Capillary refill ≤3 sec, mental status improvement

— Resolving vasopressor requirement

Board pearl: S. aureus bacteremia mandates TTE (TEE if prosthetic, persistent bacteremia >72 h, or pacemaker), repeat blood cultures every 48 h until negative, ID consult, and a minimum 14-day IV course even without identified endocarditis — this is one of the most tested longitudinal management items.

When initial workup doesn't localize a source ("occult sepsis"):

Specialized cultures/molecular:

Severity and risk scores:

Endpoints of resuscitation to track:

Resuscitation Logic — Fluids First, Then Pressors

— 30 mL/kg balanced crystalloid (LR or Plasma-Lyte preferred over NS) within first 3 hours for hypotension or lactate ≥4

— SMART and BaSICS trials: balanced solutions reduce major adverse kidney events vs 0.9% saline (NS causes hyperchloremic acidosis, worsens AKI)

— In CHF/ESRD/cirrhosis with overt volume overload, smaller boluses (250–500 mL) with reassessment are acceptable — do not blindly give 30 mL/kg if it will cause harm, but document the reasoning

— Dynamic measures preferred over CVP: passive leg raise, pulse pressure variation, stroke volume variation, IVC ultrasound, lung B-lines

— Static CVP is not a reliable predictor (FENICE, multiple meta-analyses)

— Do not wait for full 30 mL/kg before starting norepinephrine if patient remains hypotensive — early NE (within first 1–6 h) is associated with reduced mortality (CENSER trial signal)

— Norepinephrine can be initiated through a large peripheral IV (proximal to antecubital, well-running) for up to 6 hours while obtaining central access — current consensus, reduces delay

— SEPSISPAM trial: higher MAP target (80–85) showed no overall mortality benefit but reduced AKI in chronic hypertensives — individualize

Step 3 management: If a patient remains hypotensive after 30 mL/kg, the answer is norepinephrine, not more fluid. Over-resuscitation (>5 L positive on day 1) independently predicts mortality, prolonged ventilation, and AKI.

Step 1 — Initial crystalloid bolus:

Step 2 — Reassess fluid responsiveness before more fluid:

Step 3 — Start vasopressors early if MAP <65 during or after initial fluids:

Step 4 — Target MAP ≥65 mmHg:

Step 5 — Source control within 6–12 h for drainable/removable foci (abscess drainage, line removal, necrotic tissue debridement, decompression of obstructed urinary tract). No amount of antibiotics replaces source control.

Pharmacotherapy — Vasopressor Selection

— α1 > β1; raises MAP via vasoconstriction with modest inotropy, minimal reflex bradycardia

— Start 0.05 μg/kg/min, titrate to MAP ≥65; no ceiling dose but >0.5 μg/kg/min indicates refractory shock — add second agent

— Fixed dose 0.03 units/min (do not titrate, do not exceed 0.04)

— V1 receptor → pure vasoconstriction; corrects relative vasopressin deficiency in sepsis

— VASST trial: no overall mortality benefit but catecholamine-sparing, signal toward benefit in less severe shock

— Bonus: may reduce new-onset AFib and AKI progression vs escalating NE

— Add when MAP still inadequate on NE + vasopressin, or as alternative if NE unavailable

— Causes lactate elevation via β2 effect — don't misinterpret as worsening perfusion

— Risk: tachyarrhythmia, splanchnic ischemia

Board pearl: Memorize the ladder: NE → add vasopressin → add epinephrine → add hydrocortisone (if not already started) → consider angiotensin II. Dopamine has essentially no role.

Norepinephrine — FIRST-LINE for septic shock (Grade 1B):

Vasopressin — SECOND-LINE (add when NE 0.25–0.5 μg/kg/min):

Epinephrine — THIRD-LINE or if cardiac dysfunction:

Phenylephrine: pure α1, useful when tachyarrhythmia limits NE (rapid AFib with RVR); generally avoided as monotherapy

Dopamine: NOT recommended in septic shock (SOAP II — more arrhythmias, possibly worse mortality vs NE). Reserve for symptomatic bradycardia.

Angiotensin II (Giapreza): rescue for refractory vasodilatory shock on NE + vasopressin (ATHOS-3); raises MAP, increases thrombosis risk — give VTE prophylaxis

Inotrope — dobutamine added if persistent hypoperfusion despite adequate MAP and volume with evidence of low CO/myocardial dysfunction on echo (septic cardiomyopathy)

Corticosteroids: hydrocortisone 200 mg/day IV (50 mg q6h or infusion) when pressor requirement persists (typically NE >0.25 μg/kg/min for >4 h) — APROCCHSS showed mortality benefit; ADRENAL showed faster shock resolution. Do not perform cosyntropin stim test.

Antibiotics, Source Control, and Adjuncts

— Empiric pillars: anti-MRSA (vancomycin or linezolid) + antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, meropenem) for most undifferentiated septic shock

— Pneumonia (CAP severe): ceftriaxone + azithromycin (or respiratory FQ); add anti-MRSA + antipseudomonal if HCAP risks, structural lung disease, recent abx

— Intra-abdominal: piperacillin-tazobactam OR ceftriaxone + metronidazole; add antifungal if perforation with prior abx exposure

— Urosepsis: ceftriaxone or piperacillin-tazobactam; carbapenem if recent ESBL

— Skin/soft tissue: vancomycin; add piperacillin-tazobactam + clindamycin for necrotizing (clinda for toxin suppression) → emergent surgical debridement

— Neutropenic fever: cefepime or piperacillin-tazobactam monotherapy; add vancomycin only if line infection, MRSA risk, mucositis, hypotension

— Meningitis (community): ceftriaxone + vancomycin + dexamethasone before/with first abx; add ampicillin if >50 or immunocompromised (Listeria)

— Asplenic/post-splenectomy fulminant: ceftriaxone (covers encapsulated)

— Drain abscess, decompress obstructed urinary tract, ERCP for cholangitis, cholecystostomy/cholecystectomy, debride necrotic tissue, remove infected lines and prosthetics

— Target source control within 6–12 hours

— Glycemic control 140–180 mg/dL with insulin infusion (avoid <110, hypoglycemia kills)

— Lung-protective ventilation if intubated: Vt 6 mL/kg IBW, plateau <30, PEEP titrated

— VTE prophylaxis (LMWH preferred unless contraindicated)

— Stress ulcer prophylaxis (PPI) if mechanically ventilated or coagulopathic

— Transfuse pRBC at Hgb <7 (TRISS); higher threshold only if active ACS/bleeding

CCS pearl: Don't forget to order central line, arterial line, Foley, NG if ileus and to advance the clock — failing to recheck lactate at 2–4 h or to repeat blood cultures at 48 h for S. aureus are classic point losses.

Antibiotics within 1 hour — broad, then de-escalate:

De-escalation: narrow within 48–72 h based on cultures/sensitivities; stop MRSA coverage if nares PCR negative and no growth; use procalcitonin trend to support stopping abx; typical course 7 days for most sources (longer for endocarditis, osteo, undrained collections, S. aureus bacteremia).

Source control (often more important than the antibiotic):

Adjuncts:

Special Populations — Elderly and Renal/Hepatic Impairment

— Present afebrile, hypothermic, or only with delirium or falls — low threshold to work up sepsis in any acute mental status change

— Blunted tachycardic response (β-blockers, conduction disease) — MAP and lactate trends matter more than HR

— Polypharmacy — review ACEi/ARB, diuretics, β-blockers that may need holding

— Higher risk of AKI, delirium, deconditioning — early mobilization, sleep-wake cycle, avoid benzos

— Goals-of-care conversation early (chunk 17)

— Adjust antibiotic doses: piperacillin-tazobactam, cefepime, meropenem, vancomycin all renally dosed; loading dose is unchanged — never under-load vancomycin in shock (give 25–30 mg/kg loading)

— Avoid nephrotoxins when possible (aminoglycosides, IV contrast if alternatives exist; balance against need for source localization)

— Balanced crystalloid still preferred; LR's modest K⁺ load (4 mEq/L) is not a contraindication in most ESRD

— Dialysis patients: vancomycin 15–20 mg/kg after HD; consider catheter as source

— High SBP risk — paracentesis any cirrhotic admitted with shock

— Albumin 1.5 g/kg day 1, 1 g/kg day 3 in SBP reduces hepatorenal syndrome

— Avoid hepatically cleared sedatives (midazolam → use propofol); avoid NSAIDs, aminoglycosides

— Coagulopathy is not truly anticoagulant — give VTE prophylaxis

— β-blocker controversy: hold nonselective β-blockers in shock or SBP — associated with worse outcomes

— Broaden empirically: include antifungal (echinocandin) if prolonged neutropenia, TPN, recent broad abx, candida colonization

— Consider PJP (TMP-SMX), CMV, atypical mycobacteria based on host

Step 3 management: In any cirrhotic with shock, your first 5 orders include diagnostic paracentesis + albumin + ceftriaxone (or piperacillin-tazobactam if nosocomial) — don't wait for the cell count.

Elderly (>65):

Chronic kidney disease / ESRD:

Hepatic impairment / cirrhosis:

Immunocompromised:

Special Populations — Pregnancy and Pediatrics

— Maternal physiology: baseline HR 80–100, SBP 10 mmHg lower, WBC up to 15K — normal "vitals" can mask shock; MAP <65 is still abnormal

— Sources unique to pregnancy: chorioamnionitis, endometritis (post-partum), septic abortion, pyelonephritis (most common non-obstetric cause), retained products

— Antibiotic safety:

— Safe: β-lactams (penicillins, cephalosporins, carbapenems), azithromycin, clindamycin, vancomycin, metronidazole (after first trimester preferred but use in shock)

— Avoid: tetracyclines, fluoroquinolones, aminoglycosides (relative — use if needed), TMP-SMX (term, first trimester)

— Position: left lateral tilt if >20 weeks to relieve aortocaval compression

— Delivery may be needed for source control (chorioamnionitis, septic uterus)

— Fetal monitoring; resuscitating mother is best fetal resuscitation

— Different definitions (age-adjusted vitals, SIRS-based historically; Phoenix criteria emerging)

— Fluids: 10–20 mL/kg boluses, reassess — FEAST trial in resource-limited settings showed harm with large boluses; in US ICU, push-pull boluses with reassessment

— Epinephrine is first-line vasopressor in cold shock (low CO physiology more common in kids); norepinephrine in warm shock

— Cover empirically: ceftriaxone ± vancomycin; add ampicillin in neonates (Listeria, GBS) and acyclovir if HSV suspected

Board pearl: In any pregnant woman with sepsis, avoid aminoglycosides as first line, give early antibiotics regardless of trimester (untreated sepsis is far more teratogenic than abx), and consider delivery for intrauterine source control. Norepinephrine remains first-line vasopressor.

Pregnancy/peripartum sepsis:

Pediatric septic shock (brief — primarily Step 2 but appears on Step 3 ED/FM):

Postpartum considerations: retained products → D&C; mastitis with abscess → drainage; GAS puerperal sepsis is fulminant — high suspicion.

Complications and Adverse Outcomes

— AKI (50% of septic shock) — ATN from hypoperfusion + inflammation; RRT indications: refractory hyperkalemia, acidosis, volume overload, uremia (AEIOU)

— ARDS — bilateral infiltrates, PaO₂/FiO₂ ≤300, not from cardiac failure; manage with low-tidal-volume ventilation, prone positioning if P/F <150

— Septic cardiomyopathy — reversible LV dysfunction with depressed EF; usually resolves within 7–10 days; add dobutamine if low CO with adequate MAP

— DIC — bleeding + thrombosis simultaneously; ↑PT/PTT, ↓fibrinogen, ↓platelets, ↑D-dimer, schistocytes; treat underlying cause; transfuse for bleeding (not numbers alone)

— Hepatic dysfunction — cholestasis of sepsis, shock liver (transaminases >1000 then rapid fall)

— Adrenal insufficiency / critical illness-related corticosteroid insufficiency — relative; treat with hydrocortisone if pressor-dependent

— Stress hyperglycemia, hypoglycemia in late shock

— Fluid overload — pulmonary edema, abdominal compartment syndrome, prolonged ventilation

— Peripheral vasopressor extravasation — local tissue ischemia/necrosis; antidote: phentolamine 5–10 mg in 10 mL NS infiltrated locally within 12 h; topical nitroglycerin alternative

— CLABSI from central line itself

— VAP, C. difficile from broad-spectrum abx

— Pressure injuries, ICU-acquired weakness, delirium

— Post-Sepsis Syndrome (PICS): cognitive impairment, depression, PTSD, physical weakness; 40% of survivors hospitalized again within 90 days

— Increased 1-year mortality beyond hospital discharge

— Higher cardiovascular event risk (MI, stroke) in months after sepsis

Key distinction: Lactate ↑ after starting epinephrine is often pharmacologic (β2-mediated glycolysis) — recheck with downtrend in pressor dose before assuming worsening shock. Don't reflexively bolus more fluid.

Acute organ failures (define SOFA progression):

Iatrogenic and procedural:

Late and post-discharge:

Escalation — ICU, Consults, and Disposition

— Vasopressor requirement

— Mechanical ventilation or high FiO₂ requirement

— Lactate >4 or rising despite resuscitation

— Need for invasive monitoring (arterial line, central line)

— Source requiring close monitoring (necrotizing infection, severe pancreatitis)

— Surgery / IR for any drainable or debridable source — page before imaging confirms if clinical suspicion is high (necrotizing fasciitis, perforation)

— Infectious Disease for complex hosts, multidrug-resistant organisms, fungemia, endocarditis, persistent bacteremia

— Nephrology if AKI with RRT indications

— GI/hepatology for cirrhotic, cholangitis (ERCP)

— OB for any pregnant patient

— Palliative care for poor-prognosis patients or unclear goals

— Community ED → tertiary center for ECMO candidacy (refractory ARDS, refractory shock in selected patients), advanced source control (interventional radiology, hepatobiliary surgery), transplant evaluation

— Stabilize before transfer when possible: secure airway if marginal, two vasopressors on infusion pumps, broad-spectrum abx initiated, blood products available

— Move location: ED → ICU when starting pressors

— Order central line + arterial line + Foley

— Schedule lactate q2–4 h, CBC/BMP q6h initially, daily cultures if persistent bacteremia

— Reassess vasopressor, ventilator settings, and antibiotic appropriateness every 24 h

Step 3 management: A "stable on norepinephrine" patient is not stable — they belong in the ICU. Common test scenario: floor patient on low-dose NE deteriorates because monitoring was inadequate. The correct prior step was ICU transfer when pressors started.

ICU admission criteria (essentially all septic shock):

Early consults:

Transfer considerations:

CCS workflow reminders:

Key Differentials — Other Distributive/Vasodilatory Shocks

— Acute onset, urticaria, angioedema, wheeze, exposure history (food, sting, drug, IV contrast)

— First-line: IM epinephrine 0.3–0.5 mg (0.01 mg/kg) lateral thigh, repeat q5–15 min; adjuncts: IVF, H1/H2 blockers, steroids, nebulized albuterol

— Distinction: rapid onset, mucocutaneous signs, trigger

— Spinal cord injury above T6 — loss of sympathetic tone

— Hypotension + BRADYCARDIA + warm dry skin (unlike sepsis with tachycardia and sweating)

— Treat: fluids, norepinephrine or phenylephrine; atropine for bradycardia

— Fever, diffuse macular rash → desquamation, multi-organ failure

— Tampon use, packing, surgical wound (Staph); preceding skin/soft tissue infection (Strep)

— Treat: clindamycin + β-lactam (vancomycin if MRSA risk), source control (remove tampon, debride), IVIG in severe Strep TSS

— Known/unknown adrenal insufficiency, recent steroid withdrawal, etomidate exposure

— Hyponatremia, hyperkalemia, hypoglycemia, refractory hypotension

— Treat: hydrocortisone 100 mg IV bolus then 50 mg q6h, fluids, dextrose

— Profound vasodilation; treat with NE, vasopressin, methylene blue, hydroxocobalamin

Key distinction: Bradycardia + hypotension + warm skin = neurogenic; bradycardia + hypotension + cold skin + JVD = consider β-blocker/CCB toxicity, MI with RV involvement, or hypothermia; tachycardia + hypotension + warm skin + fever = septic/distributive.

Anaphylactic shock:

Neurogenic shock:

Toxic shock syndrome (Staph or Strep):

Adrenal crisis:

Vasoplegic syndrome post-cardiac surgery / post-bypass:

Drug-induced: dihydropyridines, sedative overdose, β-blocker/CCB toxicity (CCB → calcium, glucagon, high-dose insulin)

Pancreatitis with SIRS — looks septic but cultures negative; treat supportively; abx only for infected necrosis

Key Differentials — Non-Distributive Shocks

— Cold, clammy, narrow pulse pressure, JVD, crackles, S3, low CO/CI <2.2

— Causes: large MI (anterior), acute valve failure, fulminant myocarditis, decompensated HF, tamponade

— Workup: ECG, troponin, echo, lactate

— Treat: revascularize if MI; vasopressors (norepinephrine first), inotropes (dobutamine, milrinone), mechanical support (IABP, Impella, VA-ECMO)

— Avoid large-volume fluid resuscitation — will precipitate pulmonary edema

— GI bleed, trauma, ruptured AAA, ectopic pregnancy, retroperitoneal bleed (anticoagulation)

— Cold, narrow pulse pressure, flat neck veins, falling Hgb

— Treat: blood products in balanced ratio (1:1:1 pRBC:FFP:plt) for hemorrhagic shock, TXA if trauma <3 h, source control (endoscopy, IR, OR)

— Tamponade — Beck triad (hypotension, muffled heart sounds, JVD), pulsus paradoxus >10; pericardiocentesis

— Tension pneumothorax — absent breath sounds, tracheal deviation, JVD; needle decompression at 4th–5th ICS midaxillary (adults) before CXR

— Massive PE — RV strain on ECG/echo, JVD, hypoxia; systemic tPA or catheter-directed thrombolysis if hemodynamically unstable

— Cirrhotic with GI bleed AND SBP — distributive + hemorrhagic

— MI with secondary infection

— Septic cardiomyopathy producing combined distributive + cardiogenic — needs NE + dobutamine

— Mesenteric ischemia (out-of-proportion pain, lactate ↑), DKA, thiamine deficiency, metformin toxicity (MALA), seizure (transient lactate ↑)

Board pearl: Use bedside POCUS in 60 seconds — RUSH exam (Rapid Ultrasound in Shock): heart (function, effusion, RV strain), IVC, lungs (B-lines, pneumothorax, effusion), abdomen (free fluid, AAA). Distinguishes shock category faster than labs.

Cardiogenic shock:

Hypovolemic / hemorrhagic shock:

Obstructive shock:

Mixed pictures:

Mimics with hypotension and lactate elevation:

Recovery Phase, Discharge, and Long-Term Plan

— Day 1–3: stabilize hemodynamics, source control, broad abx

— Day 3–5: wean pressors, narrow antibiotics based on cultures, extubate if possible, begin enteral nutrition

— Day 5–7: transfer out of ICU when off pressors, stable oxygenation

— Day 7–10+: complete antibiotic course, rehabilitate, plan discharge

— Confirm total course is appropriate (CAP 5–7 days, pyelonephritis 7–10 days, complicated intra-abdominal 4–7 days post-source control, S. aureus bacteremia 14–42 days IV, endocarditis 4–6 weeks)

— OPAT (outpatient parenteral antibiotic therapy) if extended IV needed — requires reliable access, ID follow-up, weekly labs

— Oral step-down when bioavailability allows (FQs, linezolid, TMP-SMX, doxycycline) and source controlled

— Resume home antihypertensives gradually as BP normalizes — do not auto-restart full doses on discharge

— Statins, antiplatelets — continue

— Hold or dose-reduce metformin during AKI; restart when Cr normalizes

— Avoid NSAIDs in recent AKI

— Update vaccines before discharge — pneumococcal (PCV20 or PCV15+PPSV23), influenza, COVID, especially in asplenic, COPD, CKD, post-sepsis cohort

— Physical/occupational therapy referral — ICU-acquired weakness affects 25–50%

— Cognitive and mood screening at 2–4 weeks (PHQ-9, MoCA) — high rates of depression, PTSD, cognitive impairment (Post-Sepsis Syndrome)

— Address advance care planning before discharge

Step 3 management: Sepsis survivors have 40% 90-day readmission risk. The discharge order set should include: PCP follow-up within 7–14 days, ID follow-up if on OPAT, PT/OT referral, depression screening at 2 weeks, vaccine update, clear medication reconciliation explaining held/restarted home meds.

De-escalation timeline (typical septic shock survivor):

Discharge antibiotic plan:

Medication reconciliation:

Functional recovery:

Follow-Up, Monitoring, and Counseling

— Within 7 days: PCP visit — review hospital course, med rec, screen for delirium/cognitive issues, check BMP if on diuretics/ACEi restarted, wound check

— Within 14 days: ID clinic if completing parenteral antibiotics or with complex infection

— At 30 days: comprehensive review — PHQ-9, MoCA, functional status; review readmissions, ensure home services adequate

— 3 and 6 months: screen for Post-Sepsis Syndrome, evaluate need for ongoing rehab

— Weekly CBC, BMP, LFTs on OPAT

— Vancomycin trough or AUC monitoring; serial creatinine (vanc nephrotoxicity)

— Repeat cultures if persistent fevers or suspected relapse

— Echocardiogram at end of therapy for endocarditis to document resolution

— Expect prolonged fatigue, weakness, poor concentration ("brain fog") for weeks to months

— Sleep disturbance, nightmares, anxiety — normal, seek help if persistent

— Recognize relapse: fever, rigors, return of original symptoms → ED, not wait for clinic

— Vaccination importance — sepsis prevention starts with pneumococcal, influenza, COVID, Tdap

— Smoking cessation, alcohol reduction, diabetes control, dental hygiene (bacteremia source)

— Patients with S. aureus bacteremia or endocarditis: dental prophylaxis as indicated, lifetime awareness

— Asplenic patients: lifelong vaccination, on-demand abx, MedicAlert bracelet

— Recurrent UTI/urosepsis: urology workup for anatomic/functional cause

— Recurrent pneumonia: consider immunodeficiency, structural lung disease, aspiration evaluation

Board pearl: Post-sepsis cardiovascular risk is elevated for ≥1 year. Reinforce statin adherence, BP control, and screen for new arrhythmias (AFib often emerges during sepsis and recurs). Sepsis is now considered a cardiovascular risk modifier.

Post-discharge follow-up cadence:

Lab monitoring:

Counseling points for patient and family:

Special long-term considerations:

Ethical, Legal, and Patient Safety Considerations

— Address code status on admission, not when patient deteriorates. In septic shock with high baseline frailty or terminal illness, an early palliative care consult is appropriate

— DNR ≠ "do not treat" — patients can be full ICU care, antibiotics, pressors, but DNR for cardiac arrest

— Surrogate decision-making hierarchy (varies by state but typically: spouse → adult children → parents → siblings); document

— Time-limited trials of aggressive care (e.g., "72 hours of full support; if no improvement, transition to comfort") are ethically robust and well-supported

— Septic, encephalopathic patients usually lack capacity; obtain surrogate consent for central line, intubation, blood transfusion

— Emergent procedures (intubation, central line for vasopressor) can proceed under implied consent if life-threatening and surrogate unavailable — document

— Jehovah's Witness: respect refusal of blood products if previously documented; use cell-saver, iron, EPO, hemostatic adjuncts

— Meningococcal disease, certain forms of meningitis — report to health department; prophylax close contacts (rifampin, ciprofloxacin, ceftriaxone)

— Suspected bioterrorism (anthrax, plague, tularemia) — notify public health

— Healthcare-associated infections (CLABSI, CAUTI, VAP) — reportable, drive hospital quality metrics

— Handoff at ICU transfer is highest-risk moment — explicit communication of active issues, pending cultures, antibiotic stop dates, allergies, code status. Use structured tools (I-PASS, SBAR)

— Vasopressor extravasation — peripheral norepinephrine should be in proximal large vein with hourly site checks

— Sepsis bundle compliance is a CMS-reportable quality measure (SEP-1); failure to meet bundle has financial and quality implications

— Medication errors during transitions (renally dosed abx, anticoagulation) — pharmacist-led reconciliation reduces errors

Step 3 management: A reasonable, written time-limited trial with explicit reassessment points satisfies both family expectations and ethical principles when prognosis is uncertain — and is a frequent correct answer in ethics vignettes.

Goals-of-care and code status:

Informed consent edge cases:

Mandatory reporting and public health:

Patient safety / transitions of care:

Disclosure of error: if a delayed antibiotic, missed source, or extravasation injury occurs, transparent disclosure with patient/family is the ethical and legally protective standard.

High-Yield Associations and Rapid-Fire Facts

Board pearl: If a vignette describes a hypotensive patient who responded to 2 L of fluid with normalized MAP and clearing lactate, that's sepsis, not septic shock — admit, antibiotics, monitor, but don't start vasopressors. Conversely, persistent MAP <65 after fluid → norepinephrine + ICU.

Norepinephrine = first-line vasopressor in septic shock. Period.

Vasopressin = second, fixed dose 0.03 units/min, catecholamine-sparing.

Dopamine — more arrhythmias (SOAP II), not used.

30 mL/kg balanced crystalloid in first 3 hours; reassess fluid responsiveness with dynamic measures (PLR, PPV, IVC, lung US).

MAP target ≥65; consider 80–85 in chronic HTN with AKI.

Hydrocortisone 200 mg/day if persistent vasopressor requirement; no stim test.

Lactate >2 + pressor requirement = septic shock (Sepsis-3).

Source control within 6–12 h — most important determinant of mortality after timely antibiotics.

Antibiotics within 1 hour of recognition; each hour of delay ↑ mortality ~7%.

Balanced crystalloid (LR) > 0.9% saline (SMART, BaSICS) — fewer MAKE events.

Procalcitonin — guides de-escalation, not initiation.

Peripheral norepinephrine is acceptable bridge for up to 6 hours.

Phentolamine for NE extravasation; topical nitroglycerin alternative.

Endocarditis prophylaxis (procedure-related) — only for highest-risk lesions: prosthetic valve, prior IE, unrepaired cyanotic CHD, recent repair with material, transplant valvulopathy.

S. aureus bacteremia → TTE, ID consult, repeat cultures q48h, 14+ day IV course minimum.

Cirrhotic + shock → paracentesis + albumin (1.5 g/kg → 1 g/kg day 3) + ceftriaxone.

Asplenic fulminant sepsis → encapsulated organisms (S. pneumoniae #1) → ceftriaxone.

Neutropenic fever → cefepime or piperacillin-tazobactam monotherapy; vancomycin only with specific indications.

Toxic shock → clindamycin + β-lactam, IVIG for Strep TSS, source removal (tampon, packing).

CCS sequence: location ICU → IVF → cultures → abx → vasopressors → reassess lactate → source control → consults.

Sepsis-3 SOFA: respiration, coagulation, liver, cardiovascular, CNS (GCS), renal.

Glucose target 140–180; hypoglycemia kills more than mild hyperglycemia.

Lung-protective ventilation: Vt 6 mL/kg IBW, plateau <30.

VTE prophylaxis in all unless active bleeding.

Board Question Stem Patterns

Key distinction: The exam frequently tests timing — antibiotics within 1 hour, source control within 6–12 hours, lactate recheck within 2–4 hours, ID consult for S. aureus bacteremia within 24 hours. Memorize these intervals; they are the substrate of most "what is the next best step" stems.

Stem 1 — "Which vasopressor next?" Hypotensive patient on norepinephrine titrated to 0.4 μg/kg/min with MAP 60. Answer: add vasopressin 0.03 units/min. Distractors: dopamine, phenylephrine, increase NE further alone.

Stem 2 — "Best initial fluid?" Septic shock patient with AKI. Answer: balanced crystalloid (LR or Plasma-Lyte). Distractor: 0.9% NS (worse MAKE outcomes), albumin (not first-line), hydroxyethyl starch (harmful, never).

Stem 3 — "When to start corticosteroids?" Septic shock on NE + vasopressin, MAP 62. Answer: hydrocortisone 200 mg/day IV. Do not perform cosyntropin test.

Stem 4 — "Cirrhotic with hypotension and ascites" — Answer: diagnostic paracentesis + IV albumin + ceftriaxone. Distractor: TIPS, beta-blocker, more fluids alone.

Stem 5 — "Persistent S. aureus bacteremia at 48 hours" — Next step: TEE (especially if prosthetic valve or pacemaker), ID consult, repeat blood cultures, search for occult source. Distractor: switch antibiotic blindly.

Stem 6 — "Hypotensive post-op patient with peripheral norepinephrine for 8 hours, site cold and dusky" — Answer: stop infusion, infiltrate phentolamine, consider topical nitroglycerin, establish new access.

Stem 7 — "Pregnant woman with pyelonephritis and septic shock" — Answer: ceftriaxone, IV fluids, norepinephrine if needed, left lateral tilt, fetal monitoring; avoid aminoglycosides/FQs as first line.

Stem 8 — "Septic shock with rising lactate after starting epinephrine" — Answer: expected pharmacologic effect (β2); reassess clinical perfusion, do not bolus fluids reflexively.

Stem 9 — "Neutropenic fever, hypotensive" — Answer: cefepime or piperacillin-tazobactam within 1 hour; add vancomycin if line, MRSA risk, or persistent hypotension.

Stem 10 — "When to escalate to ICU?" Floor patient newly on low-dose NE. Answer: transfer to ICU now, not later.

Stem 11 — "Discharge planning for sepsis survivor" — Answer: PCP within 7 days, PT/OT, depression screening, vaccine update, med rec.

Stem 12 — "Ethics: time-limited trial" — frail elderly with septic shock, family wants "everything" — Answer: agree to time-limited trial (e.g., 72 h) with explicit reassessment, palliative care involvement.

One-Line Recap

Septic shock is sepsis with persistent hypotension requiring vasopressors to keep MAP ≥65 plus lactate >2 despite adequate fluids — treat with hour-1 broad-spectrum antibiotics after cultures, 30 mL/kg balanced crystalloid, norepinephrine first then vasopressin then hydrocortisone, and source control within 6–12 hours.

Resuscitation sequence: balanced crystalloid 30 mL/kg → reassess with dynamic measures → norepinephrine to MAP ≥65 → add vasopressin at NE 0.25–0.5 μg/kg/min → add epinephrine and/or hydrocortisone for refractory shock → consider angiotensin II as rescue. Dopamine has essentially no role.

Antibiotics and source control: Broad empiric coverage within 1 hour after 2 sets of blood cultures and source-directed cultures; de-escalate at 48–72 hours based on data and procalcitonin trend; drainable/removable sources (abscess, infected line, obstructed urinary tract, necrotic tissue) take surgical/IR priority within 6–12 hours — antibiotics never substitute for source control.

Endpoints and pitfalls: Track MAP ≥65, lactate clearance, urine output ≥0.5 mL/kg/hr, mental status, capillary refill. Avoid over-resuscitation (>5 L positive day 1 worsens outcomes); avoid 0.9% saline when balanced crystalloid is available; avoid dopamine; recognize epinephrine-induced lactate rise as pharmacologic; remember peripheral norepinephrine is acceptable for up to 6 hours through a proximal large vein.

Longitudinal Step 3 layer: Septic shock survivors face 40% 90-day readmission and persistent cardiovascular, cognitive, and functional sequelae — discharge planning must include PCP follow-up within 7 days, ID follow-up for ongoing antibiotics, PT/OT, depression and cognitive screening at 2–4 weeks, vaccine updates (pneumococcal, influenza, COVID), and goals-of-care reassessment for high-risk patients.