definition: Infection causing persistent hypotension, despite fluid resuscitation. needing vasopressor requirement to maintain a MAP > 65 mm plus a serum lactate >2 mM.

Evidence of physiological stress (endogenous cortisol & epinephrine release) hyperlactatemia; hypo-/hyperglycemia (incl. DKA/HHS); ↑ NLR; tachycardia with hypotension or ↑ shock index (HR/SBP); tachypnea with ↓ pCO₂ (respiratory compensation for acidosis).

signs of End-organ failure (compact): AKI (↓ UOP), delirium/AMS, hypotension requiring vasopressors/inotropes, DIC; bedside echo helps differentiate shock type—abnormal findings suggest cardiogenic/obstructive/hypovolemic causes (RV/LV dysfunction, tamponade, hypovolemia), whereas a normal echo in persistent shock favors distributive shock (most commonly septic).

possible source of infection: Pneumonia (CXR), Urosepsis (Dysuria, frequency, flank pain, Abnormal UA, positive urine culture) Ascending cholangitis — (RUQ/epigastric pain, jaundice, rigors, GNR bacteremia) → ↑ bilirubin, dilated CBD on US/CT) C. difficile colitis — (Recent antibiotics, diarrhea, abdominal tenderness) → Stool testing;) intra-abdominal source (appendicitis/diverticulitis/perforation/obstruction) — (Abdominal pain, distension, N/V, recent surgery) → CT abdomen/pelvis), Cellulitis/Toxic shock — (Cellulitis with systemic toxicity ± erythroderma) → Blood cultures ± clinical diagnosis.) Necrotizing fasciitis — (Pain out of proportion, bullae, necrosis) → CT and urgent surgical exploration.) Line infection — (Erythema/warmth at catheter site, dysfunctional line) → Paired central and peripheral blood cultures) Endocarditis — (Murmur, embolic phenomena, valvular disease history) → Echocardiogram + blood cultures), source of infection unknown at this time

These tests are ordered together in sepsis to (1) confirm systemic inflammation and organ dysfunction, (2) gauge severity, and (3) find the infection source and right antibiotic: lactate assesses tissue hypoperfusion and shock; CBC w/diff (WBC, neutrophil‑to‑lymphocyte ratio, platelets) reflects inflammatory response and early DIC risk; CMP (Cr, BUN, LFTs, glucose, anion gap, calcium) evaluates kidney and liver injury, metabolic derangements, and shock severity; ABG/VBG with low pCO₂ shows hyperventilation and lets you assess acid–base status; coagulation panel (INR/PTT) screens for DIC and hepatic dysfunction; urine output trends indicate renal perfusion and AKI; CXR/CT/ultrasound look for pneumonia, abscess, cholecystitis, or other focal sources; blood cultures ×2, sputum culture, line cultures (>48 h in place), urine studies, and other site‑specific cultures (CSF, ascitic fluid, etc.) are essential to identify the causative organism and tailor or de‑escalate antibiotics.

After 30 mL/kg IV LR within the first 3 hours, remember the vast majority redistributes into the interstitial space; for most patients 1–2 L total is reasonable, but adjust clinically — patients with HF, respiratory failure, ARDS, or baseline congestion often need less, while those who are profoundly volume depleted (eg, DKA, severe N/V, poor PO intake) may require 2–4 L initially. After initial resuscitation, stop reflexive fluids and reassess — ongoing ICU meds, antibiotics, infusions, and nutrition already provide 1–2 L/day. Avoid fluid creep. Monitor closely for pulmonary edema; instead of overloading and later intubating/diuresing, aim to maintain euvolemia from the start. Use LR or Plasma-Lyte as preferred balanced crystalloids; consider isotonic bicarbonate for significant AGMA, and normal saline for metabolic alkalosis. If hypernatremia develops, correct with free water rather than more isotonic fluid.

Sepsis Mimics (Ultra-Compact): Infectious — Endocarditis (murmur, emboli) → echo + blood cultures; Tick-borne illness / Anaplasmosis (exposure, thrombocytopenia, rash) → PCR ± smear; Candida septicemia (critical illness, lines, TPN) → blood cultures + β-D-glucan; Invasive Aspergillus (neutropenia, malignancy, steroids) → β-D-glucan + galactomannan; PJP (diffuse infiltrates, HIV/steroids) → β-D-glucan + PCR. Endocrine — Adrenal crisis (steroid withdrawal, eosinophilia, pressor-refractory shock) → cortisol before steroids; Thyroid storm (tremor, tachycardia, encephalopathy) → TSH + free T4; DKA (hyperglycemia, AG metabolic acidosis) → β-hydroxybutyrate. GI — Mesenteric ischemia (AFib, pain out of proportion) → CTA; Bowel obstruction (distension, vomiting) → CT A/P; Pancreatitis (epigastric pain, N/V) → lipase ± CT; Fulminant hepatic failure (jaundice, encephalopathy) → LFTs; Decompensated cirrhosis (↑INR, thrombocytopenia) → LFTs + US. Toxicologic — Salicylates (tachypnea, AG acidosis) → level; BB/CCB toxicity (bradycardia, hypotension) → clinical ± levels; CO poisoning (winter exposure) → carboxyhemoglobin; Metformin toxicity (severe lactic acidosis) → lactate + med review. Misc — Anaphylaxis (rapid trigger, hives, bronchospasm) → immediate treatment response; HLH (cytopenias, very high ferritin) → ferritin; DRESS/AGEP (rash, new meds) → derm consult + biopsy; Aspiration pneumonitis (sudden event, rapid improvement) → clinical course.

Plan

Initiate norepinephrine early targeting MAP ≥65 mmHg (≈60 mmHg in cirrhosis, chronic hypotension, dialysis, elderly). Add vasopressin as fixed-dose second-line, then epinephrine if needed. Avoid dopamine (↑ mortality in sepsis); avoid piling up ineffective agents—add thoughtfully and discontinue non-beneficial pressors. Epinephrine may raise lactate (do not panic if perfusion improving). Do not use dobutamine to target MAP (risk hypotension; consider only if clear low cardiac output). Follow blood cultures and start with a broad beta-lactam backbone such as piperacillin-tazobactam, cefepime, or meropenem, selected based on suspected source, resistance risk, and severity of illness. Add MRSA coverage only in high-risk patients, including those with soft-tissue or abscess infections, line infections (especially hemodialysis patients), selected community-acquired pneumonia cases, nosocomial infections (e.g., surgical-site infections), or IV drug use; options include vancomycin, linezolid, or daptomycin, chosen based on site of infection and patient factors. For community-acquired pneumonia, add atypical coverage—typically doxycycline (preferred) or azithromycin. If tick-borne illness is suspected, initiate doxycycline at minimum. For C. difficile infection, treat with oral vancomycin, adding IV metronidazole Review prior cultures, recent antibiotics, allergies, and likely source. Trend lactate q4h initially (interpret cautiously on epinephrine; rising levels → reassess source control, adequacy of antibiotics, ischemia, or missed diagnosis). Prioritize early source control (remove lines, drain abscess, imaging as needed). In patients with septic shock, first assess for known or probable adrenal insufficiency (e.g., Addison’s disease or chronic steroid use); if present, initiate stress-dose steroids with hydrocortisone 50 mg IV every 6 hours (or methylprednisolone 40 mg IV daily if hydrocortisone is unavailable). If adrenal insufficiency is not present, evaluate for relative contraindications to steroids such as brittle diabetes, delirium, fungal or mycobacterial infection, or severe immunocompromise; if these exist, avoid steroids unless shock becomes refractory. If there are no contraindications, determine whether the patient is refractory to low–moderate dose vasopressors; if refractory, start stress-dose steroids as above. If not refractory, withhold steroids and continue close hemodynamic monitoring, but initiate steroids if refractory shock subsequently develops. taper once off pressors.steroids reduce the time on vasopressors, the duration of intubation, and the length of ICU stay. HAT therapy (hydrocortisone, vitamin C, thiamine) remains controversial. Maintain CBG <180 mg/dL, monitor electrolytes, provide DVT prophylaxis (LMWH), and strict I/O with daily weights.

Resuscitation targets & reassessment: Aim MAP ≥65 (or 60 in select patients), HR 90–120, urine output ≥0.5 cc/kg/hr (consider diuretics, osmotic diuresis, hypothermia, intrinsic renal failure, venous congestion, or low cardiac output in oliguria). Capillary refill and skin temperature are more reliable than CVP/mixed venous O₂. Avoid excessive vasoconstriction (cold extremities—consider adjusting norepinephrine/epinephrine balance). Monitor cumulative fluid balance; if markedly positive (e.g., +4 L), consider de-resuscitation. In refractory shock: ensure central access, optimize sedation (avoid propofol/dexmedetomidine if hypotensive; consider fentanyl/ketamine), escalate vasopressors appropriately (no strict norepinephrine ceiling), consider IV calcium (transient effect) or methylene blue (NO inhibition, last resort), and reassess MAP target. Once stabilized, reassess for mimics, medication effects, and confirm goals (MAP, UOP, HR).