17:I[462708,["/_next/static/chunks/3yo3kiro3bmlp.js","/_next/static/chunks/3vr2wvd8f2efb.js","/_next/static/chunks/2vtmb68_vu-9t.js","/_next/static/chunks/2s8mt6_8wrpfo.js","/_next/static/chunks/3vkulz2i3l61y.js","/_next/static/chunks/1cqw2i1silz0i.js","/_next/static/chunks/14dbm3lm_t629.js","/_next/static/chunks/335_v2mb569ld.js","/_next/static/chunks/3ykn5ops9bft5.js","/_next/static/chunks/3cmavum774kjt.js","/_next/static/chunks/3th-0-a2xf9qs.js","/_next/static/chunks/0p0xpwde6kzmv.js","/_next/static/chunks/401-sxxnzbtf_.js","/_next/static/chunks/0wywtv698a1v0.js","/_next/static/chunks/2botzqwpnrzyj.js"],"ArticleReader"] 18:Tb3af,## One-minute summary **Acute kidney injury (AKI)** is an abrupt decline in kidney function identified by a rise in serum creatinine and/or reduced urine output. The current established international definition remains the **KDIGO 2012 definition**: an increase in serum creatinine by **≥0.3 mg/dL (≥26.5 µmol/L) within 48 hours**, an increase to **≥1.5 times baseline within 7 days**, or urine output **<0.5 mL/kg/hour for 6 hours**.[1] NICE uses equivalent criteria in UK practice.[2] AKI is a **syndrome, not a diagnosis**. Immediate priorities are to identify reversible threats, determine the cause, restore adequate perfusion when appropriate, relieve urinary obstruction, stop or adjust nephrotoxins and renally cleared drugs, manage electrolyte/acid-base/volume complications, and recognize patients who need urgent nephrology or kidney replacement therapy (KRT).[1,2] The classic “prerenal / intrinsic / postrenal” framework is useful, but many patients—especially those with sepsis, heart failure, cirrhosis, major surgery, or shock—have mixed mechanisms. A low fractional excretion of sodium or a bland urine sediment should never override the clinical picture. **Do not dialyze because the creatinine is high.** Initiate KRT urgently for life-threatening complications such as refractory hyperkalemia, severe acid-base disturbance, pulmonary edema/volume overload, or uremic complications; otherwise use the overall clinical trajectory rather than a single creatinine or BUN threshold.[1,6] **Current practice point (2026):** KDIGO has released a **2026 AKI/acute kidney disease (AKD) public-review draft**, but the final guideline has not yet replaced the 2012 standard. New draft concepts—biomarkers, risk models, AKD continuum, updated fluid and KRT guidance—should be considered **emerging until final publication**.[8] --- ## Core concepts ### What AKI represents physiologically Kidney function depends on adequate renal perfusion, intact glomerular filtration, functioning tubular/interstitial tissue, and unobstructed urine flow. AKI can arise from failure at any of these levels and often evolves through several mechanisms at once. A creatinine rise is a **delayed functional marker**: serum creatinine may not increase immediately after injury, and its concentration is influenced by muscle mass, fluid balance, creatinine production, medications that alter tubular secretion, and the baseline kidney reserve. Urine output can change earlier, but oliguria is neither perfectly sensitive nor specific for structural kidney injury.[1] The clinical objective is therefore not merely to “normalize creatinine.” It is to: 1. prevent ongoing injury; 2. preserve oxygen delivery and perfusion; 3. identify treatable causes; 4. prevent lethal electrolyte/volume/acid-base complications; 5. minimize avoidable drug toxicity; 6. recognize transition to persistent AKI/AKD and later CKD. --- ## Definition and KDIGO staging ### Diagnostic criteria AKI is present if **any** of the following occur:[1,2] - serum creatinine rises by **≥0.3 mg/dL (≥26.5 µmol/L) within 48 hours**; - serum creatinine rises to **≥1.5 × baseline**, known or presumed to have occurred within the prior 7 days; - urine output falls to **<0.5 mL/kg/hour for at least 6 hours**. #### KDIGO staging | Stage | Serum creatinine criterion | Urine-output criterion | |---|---|---| | **1** | 1.5–1.9 × baseline **or** rise ≥0.3 mg/dL (≥26.5 µmol/L) | <0.5 mL/kg/h for 6–12 h | | **2** | 2.0–2.9 × baseline | <0.5 mL/kg/h for ≥12 h | | **3** | 3.0 × baseline **or** creatinine ≥4.0 mg/dL (≥353.6 µmol/L) with an acute rise **or** initiation of KRT | <0.3 mL/kg/h for ≥24 h **or** anuria ≥12 h | **Board pearl:** Stage by the **worst criterion** met. A patient can be stage 3 by urine output even if the creatinine rise appears modest. #### Baseline creatinine problems Baseline creatinine may be unknown. Options include: - the most recent reliable pre-illness creatinine; - a stable outpatient value from the preceding months; - adjudication based on prior records and clinical context. Back-calculating a creatinine from an assumed normal eGFR can misclassify patients and should not be treated as a precise substitute for a known baseline. --- ## AKI, AKD, and CKD continuum AKI describes abrupt kidney dysfunction over **≤7 days**. The ADQI framework introduced **acute kidney disease (AKD)** for kidney disease persisting **7–90 days** after an acute initiating event; disease persisting beyond 90 days meets a chronic kidney disease time criterion.[4] This continuum matters because apparent “recovery” from creatinine-defined AKI does not eliminate future risk. AKI survivors have increased risk of recurrent AKI, CKD, cardiovascular events, and death. Post-discharge kidney follow-up is part of AKI care, not an optional afterthought.[1,4] --- ## Epidemiology and prognosis AKI is common across hospital medicine. A large meta-analysis using KDIGO-equivalent definitions found a pooled adult AKI incidence of about **21.6%** during hospital episodes and an associated mortality of about **23.9%**, although rates vary greatly by case mix, geography, and illness severity.[3] ICU cohorts are substantially higher risk; the ADQI consensus summarizes AKI rates around 50% in critical care populations.[4] Severity, duration, recurrence, multiorgan failure, and incomplete recovery all worsen prognosis. Stage 1 AKI is not benign, and repeated “small” creatinine rises can carry meaningful long-term risk. --- ## Risk factors Important risk factors include:[2] - pre-existing CKD, especially eGFR <60 mL/min/1.73 m²; - older age; - diabetes mellitus; - heart failure; - liver disease/cirrhosis; - previous AKI; - sepsis or systemic inflammatory illness; - hypovolemia or hemorrhage; - major or emergency surgery; - urinary tract obstruction or urologic disease; - nephrotoxins or drugs that worsen hemodynamics during acute illness; - recent iodinated contrast exposure in susceptible patients; - hematologic malignancy, tumor lysis, myeloma, or hemolysis/rhabdomyolysis in selected contexts. #### Common medication/exposure contributors | Exposure | Mechanism / concern | Practical response | |---|---|---| | NSAIDs | Afferent arteriolar vasoconstriction; interstitial nephritis | Stop when AKI suspected unless a compelling reason exists | | ACE inhibitor / ARB | Reduces efferent arteriolar tone; can worsen GFR in hypoperfusion, bilateral renal artery stenosis | Review/temporarily hold during significant hypovolemia, shock, vomiting/diarrhea or sepsis; reassess indication when stable | | Diuretics | Can aggravate effective volume depletion; useful for congestion | Do not reflexively stop if patient is markedly congested; treat the physiology | | Aminoglycosides | Tubular toxicity | Avoid if alternatives exist; therapeutic drug monitoring if required | | Vancomycin | AKI risk increases with excessive exposure and other nephrotoxins | Use current AUC/local monitoring strategy; reassess co-nephrotoxins | | Iodinated contrast | Risk is concentrated in selected high-risk patients; causal risk historically overestimated | Do not delay clinically important emergency imaging; use risk-based hydration strategy | | Calcineurin inhibitors | Vasoconstriction and chronic/acute toxicity | Check level/interactions; transplant-nephrology input | | Chemotherapy / targeted agents | Multiple mechanisms: TLS, TMA, interstitial nephritis, tubular injury | Drug-specific evaluation, oncology/nephrology collaboration | **Clinical trap:** “ACE inhibitor + diuretic + NSAID” can be particularly hazardous during dehydration because renal autoregulation and circulating volume are impaired simultaneously. --- ## Etiology: practical classification ### 1. Reduced renal perfusion / hemodynamic AKI Common causes: - hypovolemia: vomiting, diarrhea, hemorrhage, diuresis, burns; - distributive shock/sepsis; - cardiogenic shock or severe low-output heart failure; - advanced cirrhosis with low effective arterial volume; - medications that impair autoregulation in a susceptible patient; - renal artery compromise. Early hemodynamic AKI may be rapidly reversible, but persistent hypoperfusion can progress to tubular injury. ### 2. Intrinsic renal parenchymal injury #### Acute tubular injury (ATI) Common triggers: - ischemia/shock; - sepsis; - major surgery; - nephrotoxins; - pigments (myoglobin/hemoglobin); - prolonged hemodynamic insult. Urine sediment may show **granular “muddy brown” casts** and renal tubular epithelial cells, but their absence does not exclude ATI. #### Acute interstitial nephritis (AIN) Potential causes include: - antibiotics (e.g., beta-lactams, sulfonamides); - proton-pump inhibitors; - NSAIDs; - immune-checkpoint inhibitors; - infections and systemic disease. The classic triad of **fever, rash, eosinophilia** is uncommon; do not require it for diagnosis. #### Glomerular disease Think urgently about glomerulonephritis when AKI is accompanied by: - hematuria; - proteinuria; - red-cell casts/dysmorphic red cells; - hypertension/edema; - systemic inflammatory features (purpura, pulmonary hemorrhage, sinus disease, arthritis, low complement, etc.). #### Vascular causes - thrombotic microangiopathy; - malignant hypertension; - renal infarction/embolism; - atheroembolic disease; - renal vein thrombosis in selected settings. ### 3. Postrenal / obstructive AKI Causes include: - benign prostatic obstruction; - stones; - pelvic/retroperitoneal malignancy; - blood clots; - neurogenic bladder; - urethral obstruction; - bilateral ureteric obstruction; - obstruction of a solitary functioning kidney. Obstruction can occur **without hydronephrosis early** or in dehydration/retroperitoneal fibrosis, so imaging is not infallible. --- ## Initial clinical assessment ### Immediate questions 1. Is the patient unstable? 2. Is there severe hyperkalemia, pulmonary edema, severe acidosis, pericarditis/encephalopathy, or another KRT-level complication? 3. Is the patient volume depleted, congested, or in shock? 4. Could there be urinary obstruction? 5. Is there a nephrotoxin or recent medication change? 6. Does urine/clinical context suggest glomerulonephritis, interstitial nephritis, TMA, myeloma, rhabdomyolysis, or another intrinsic process? --- ## History Focus on: #### Volume and hemodynamic history - oral intake; - vomiting/diarrhea; - fever/sepsis symptoms; - bleeding; - diuretic escalation; - hypotension/syncope; - heart failure symptoms; - cirrhosis/ascites. #### Urinary history - reduced urine volume or anuria; - hesitancy, poor stream, retention; - flank pain/colic; - hematuria; - recent urologic procedure; - pelvic cancer. #### Drug/exposure history - NSAIDs, ACEi/ARB, diuretics; - antibiotics and recent hospitalization; - contrast exposure; - herbal/supplement use; - chemotherapy or immune-checkpoint therapy; - recreational drugs/toxins; - creatine supplements or drugs affecting creatinine secretion. #### Systemic clues - rash/purpura; - arthralgia; - hemoptysis; - sinus disease; - neuropathy; - fever; - weight loss; - muscle pain/immobility/seizure (rhabdomyolysis); - diarrhea followed by anemia/thrombocytopenia (TMA/HUS context). --- ## Examination Assess both **volume depletion and congestion**—they can coexist. #### General and hemodynamic - blood pressure and trend; - heart rate; - capillary refill/peripheral temperature; - mental status; - orthostatic features when safe and relevant. #### Volume status - mucous membranes; - jugular venous pressure; - peripheral edema; - lung crackles; - ascites; - daily weight trend; - bedside ultrasound where expertise exists. #### Cause-specific signs - bladder distention; - flank tenderness; - rash/purpura; - signs of endocarditis; - pulmonary hemorrhage; - severe hypertension with end-organ injury. **Pitfall:** JVP, IVC ultrasound, urine sodium, and physical signs each have limitations. Use converging evidence rather than one “volume status” variable. --- ## Diagnostic workup ### Minimum initial tests in most hospitalized AKI - repeat serum creatinine/urea; - sodium, potassium, bicarbonate; - calcium, phosphate, magnesium as appropriate; - CBC; - urinalysis/dipstick; - urine microscopy when intrinsic disease is possible; - glucose; - ECG if hyperkalemia or arrhythmia risk; - strict urine-output measurement when clinically important. NICE recommends urine dipstick for **blood, protein, leukocytes, nitrites, and glucose** as soon as AKI is suspected or detected.[2] ### Additional tests guided by context | Suspicion | Useful tests | |---|---| | Sepsis | cultures, lactate, source evaluation | | Rhabdomyolysis | CK, phosphate, calcium, urinalysis with heme but few/no RBCs | | Hemolysis/TMA | smear, LDH, haptoglobin, bilirubin, platelets, ADAMTS13 when indicated | | Glomerulonephritis | urine microscopy, urine protein quantification, C3/C4, ANA, ANCA, anti-GBM, hepatitis/HIV tests as context dictates | | Myeloma | serum free light chains, serum/urine electrophoresis/immunofixation | | AIN | medication timeline; eosinophils are nonspecific; biopsy if diagnosis will alter therapy | | Obstruction | bladder scan; renal tract ultrasound or CT depending on suspected level/cause | --- ## Urinalysis and urine microscopy Urine sediment can be one of the highest-yield bedside “kidney biopsies.” | Finding | Suggests | Caveat | |---|---|---| | Muddy brown granular casts / tubular epithelial cells | Acute tubular injury | Sensitivity varies; absence does not exclude ATI | | RBC casts / dysmorphic RBCs | Glomerulonephritis | Urgent nephrology workup | | WBC casts | Interstitial nephritis or pyelonephritis | Not specific | | Heavy proteinuria | Glomerular disease, paraprotein disease | Dipstick underdetects some light chains | | Heme-positive dipstick with few RBCs | Myoglobinuria/hemoglobinuria | Correlate with CK/hemolysis | | Crystals | Drug/crystal nephropathy, uric acid, oxalate | Context determines significance | NICE specifically advises considering acute nephritis and nephrology referral when AKI has no obvious cause and urinalysis shows **hematuria plus proteinuria** without UTI or catheter trauma.[2] --- ## Fractional excretion indices: use cautiously #### FeNa \[ FeNa(\%) = \frac{Urine\ Na \times Plasma\ Cr}{Plasma\ Na \times Urine\ Cr}\times 100 \] A low FeNa can occur in reduced effective circulating volume, but also in: - early sepsis; - contrast-associated AKI; - pigment nephropathy; - glomerulonephritis; - hepatorenal physiology; - some obstructive states. A high FeNa can occur with diuretics, CKD, or established tubular injury. #### FeUrea Sometimes used when diuretics confound FeNa, but FeUrea is also imperfect and should not be treated as a diagnostic truth test. **Board pearl:** The distinction between “prerenal azotemia” and “ATN” is not reliably made by one urine index. --- ## Imaging ### Renal tract ultrasound Use when obstruction is possible or the cause is unclear. NICE advises **immediate ultrasound (within 6 hours)** when pyonephrosis/infected obstruction is suspected.[2] Do not routinely order ultrasound if the cause is already clear and obstruction is not clinically plausible.[2] ### CT Useful when stone disease, retroperitoneal pathology, vascular disease, trauma, or another abdominal cause is suspected. **Do not withhold or delay emergency contrast imaging when delay is likely to be clinically harmful.** NICE’s 2024 update emphasizes that contrast-associated AKI risk is small but increased when eGFR is <30 mL/min/1.73 m² and specifically advises not delaying emergency iodinated contrast when the clinical cost of delay is significant.[2] --- ## Differential diagnosis by pattern | Pattern | Leading possibilities | Clues that shift probability | |---|---|---| | Oliguria after vomiting/diarrhea | Hypovolemia, ATI if prolonged | Orthostasis, low JVP, hemoconcentration, response to cautious fluid | | AKI + edema + pulmonary congestion | Cardiorenal syndrome, GN, renal failure with volume overload | JVP, BNP context, echo, urine sediment, proteinuria | | AKI + hematuria + proteinuria | GN, vasculitis, anti-GBM, infection-related GN | RBC casts, systemic features, complement/serologies | | AKI + thrombocytopenia + hemolysis | TMA/TTP/HUS, malignant HTN | Schistocytes, LDH, haptoglobin, BP, ADAMTS13 context | | AKI + very high CK | Rhabdomyolysis | Muscle injury, dark urine, heme-positive dipstick without RBCs | | AKI + eosinophilia/rash after new drug | AIN | Often lacks classic triad; biopsy may be needed | | AKI + anuria/retention | Obstruction until proven otherwise | Bladder scan, ultrasound/CT | | AKI in cirrhosis | Volume depletion, sepsis, ATI, hepatorenal syndrome, drugs | Diagnose HRS only after excluding/treating competing causes | --- ## Management: stepwise approach ### STEP 1 — Stabilize life-threatening complications Address ABC problems first. In AKI, immediate threats include: - severe hyperkalemia; - pulmonary edema with respiratory compromise; - severe metabolic acidosis; - uremic pericarditis/encephalopathy; - severe symptomatic sodium disturbance; - toxin accumulation where extracorporeal removal is indicated. ### STEP 2 — Treat the cause Examples: - hypovolemia → judicious isotonic crystalloid/blood as appropriate; - hemorrhage → hemorrhage control + blood-product strategy; - sepsis → prompt infection/source control and hemodynamic management; - obstruction → catheterization, nephrostomy, stent, or urologic decompression according to level/cause; - GN/vasculitis/TMA → urgent disease-specific specialist pathway; - rhabdomyolysis → early fluids when appropriate, treat cause, monitor potassium/calcium/phosphate; - drug toxicity → stop culprit, adjust doses, antidote/extracorporeal therapy when indicated. ### STEP 3 — Stop ongoing kidney insults - stop nonessential nephrotoxins; - review ACEi/ARB, NSAIDs, diuretics and SGLT2 inhibitors in context rather than by rote; - adjust doses of renally cleared drugs; - avoid duplicate contrast/nephrotoxin exposure where clinically unnecessary; - check drug interactions and levels where relevant. ### STEP 4 — Optimize volume and perfusion KDIGO favors **isotonic crystalloids rather than colloids** for initial intravascular volume expansion in patients at risk of or with AKI when hemorrhagic shock is absent.[1] #### Balanced crystalloid vs 0.9% saline In the SMART trial, balanced crystalloids modestly reduced the composite of death, new KRT, or persistent renal dysfunction compared with saline in critically ill adults (14.3% vs 15.4%).[5] This supports frequent use of balanced crystalloid in many critically ill patients, but fluid choice must account for the indication, electrolyte/acid-base context, neurologic disease, and local protocol. **Do not give fluid merely because creatinine rose.** If the patient is congested or has cardiogenic physiology, repeated boluses can worsen pulmonary edema and renal venous congestion. ### STEP 5 — Monitor dynamically - urine output; - daily or more frequent creatinine/electrolytes according to severity; - potassium and bicarbonate; - fluid input/output; - daily weight in significant volume disturbance; - hemodynamics; - drug concentrations when indicated; - clinical response to interventions. NICE notes that daily creatinine measurement is typical for hospitalized patients with or at risk of AKI, adjusted to clinical need.[2] --- ## Pharmacotherapy principles ### Diuretics **STANDARD OF CARE:** Do **not** use loop diuretics to prevent AKI or to “convert” oliguric AKI to non-oliguric AKI. They are appropriate for **fluid overload/congestion** when there is a reasonable chance of diuretic response.[1,2] A rise in creatinine during effective decongestion in heart failure does not automatically mean diuretics should be stopped; interpret renal function alongside congestion, perfusion, blood pressure, and overall trajectory. ### Low-dose dopamine Do **not** use low-dose “renal-dose” dopamine to prevent or treat AKI.[1,2] ### ACE inhibitors and ARBs During significant acute volume depletion, vomiting/diarrhea, hypotension, or sepsis, temporary withholding may be reasonable and is specifically suggested by NICE in relevant acute illness.[2] However, once the acute process resolves, **reassess and restart evidence-based indications** rather than allowing accidental permanent discontinuation. --- ## Emergency hyperkalemia in AKI Hyperkalemia is one of the most important immediately reversible causes of death in severe AKI. #### First actions - confirm the result rapidly if pseudohyperkalemia is plausible, **without delaying treatment** when the patient is unstable or ECG changes are present; - obtain a 12-lead ECG and continuous monitoring for severe hyperkalemia; - stop exogenous potassium and contributing drugs; - stabilize the myocardium when ECG toxicity is present; - shift potassium intracellularly; - remove potassium from the body; - repeat potassium and glucose because rebound and hypoglycemia are common. #### UK Kidney Association 2023 adult emergency doses | Purpose | Treatment | Adult dose / note | |---|---|---| | **Protect the heart** | 10% calcium chloride | **10 mL IV over 5 min** in peri-arrest/cardiac arrest or according to local resuscitation protocol | | **Protect the heart** | 10% calcium gluconate | **30 mL IV over 10 min** for other patients with hyperkalemic ECG changes | | **Shift K into cells** | Soluble insulin + glucose | **10 units soluble insulin in 25 g glucose IV** for severe K ≥6.5 mmol/L; consider in moderate K 6.0–6.4 mmol/L | | Prevent post-insulin hypoglycemia | 10% glucose infusion | If pretreatment glucose <7 mmol/L, UKKA recommends **10% glucose 50 mL/hour for 5 h** after insulin-glucose | | **Adjunct shift** | Nebulized salbutamol | **10–20 mg nebulized** as adjunct in severe hyperkalemia; do not use as sole therapy | These doses are from UKKA guidance and may differ by jurisdiction/local resuscitation policy.[7] **Calcium does not lower serum potassium.** It temporarily reduces myocardial excitability risk while potassium-lowering therapy is initiated. **KRT should not be delayed** when severe hyperkalemia is refractory or expected to recur rapidly because of advanced renal failure, ongoing tissue breakdown, or inability to remove potassium medically.[1,7] --- ## Metabolic acidosis Treat the cause first: shock, sepsis, ketoacidosis, toxin, renal failure, etc. Sodium bicarbonate is **not a universal AKI therapy**. Consider it selectively when severe acidemia itself is harmful and bicarbonate therapy is physiologically appropriate, while avoiding sodium/volume overload and recognizing that severe refractory acidosis may require KRT. --- ## Kidney replacement therapy (KRT) ### Indications KDIGO recommends emergency KRT when there are **life-threatening changes in fluid, electrolyte, or acid-base balance**.[1] Common practical indications include: - refractory severe hyperkalemia; - refractory severe metabolic acidosis; - refractory pulmonary edema/volume overload causing hypoxemia; - uremic pericarditis; - uremic encephalopathy or severe symptomatic uremia; - selected dialyzable intoxications; - progressive complications when medical management is failing. #### What should NOT determine KRT alone - one creatinine value; - one BUN/urea value; - oliguria in isolation; - “stage 3 AKI” without clinical context. ### Timing when no emergency indication exists The **STARRT-AKI** trial randomized critically ill patients with severe AKI to accelerated vs standard KRT initiation. Accelerated initiation **did not reduce 90-day mortality** and was associated with more adverse events and greater dialysis dependence among survivors.[6] **STANDARD OF CARE implication:** In a patient without an urgent indication, do not start KRT solely because severe AKI has developed. Watch the clinical trajectory closely and start when complications, worsening physiology, or failure of conservative management justify it. ### Modality - **Intermittent hemodialysis:** efficient solute/volume removal; may be poorly tolerated in unstable patients. - **Continuous KRT (CKRT/CRRT):** often favored in severe hemodynamic instability or some neurocritical-care situations. - **Prolonged intermittent therapies (SLED/PIRRT):** hybrid option depending on local resources. Modality should reflect hemodynamics, neurologic status, solute-removal needs, staffing/resources, and local expertise—not an assumption that one modality is universally superior. --- ## Contrast-associated AKI: 2024 practice update NICE updated its iodinated-contrast recommendations in **October 2024**.[2] #### Key points - An **eGFR <30 mL/min/1.73 m²** is associated with a small but increased risk of AKI from iodinated contrast exposure. - **Do not delay emergency contrast imaging** if delaying contrast is likely to cause clinically significant harm. - For increased-risk patients, encourage **oral hydration** before and after IV iodinated contrast when appropriate. - For particularly high-risk inpatients (e.g., eGFR <30, kidney transplant, high contrast volume/repeat dose, first-pass intra-arterial exposure), consider IV volume expansion with **0.9% saline or isotonic sodium bicarbonate**. - NICE suggests considering temporary ACEi/ARB withholding in CKD with eGFR <30 around iodinated contrast. **Guideline conflict / nuance:** Contrast protocols differ among radiology, nephrology, and national guidance. Modern evidence has reduced previous estimates of contrast-caused AKI, especially for routine IV CT. The clinical harm of missing or delaying a time-critical diagnosis can exceed the renal risk. Use local radiology policy and patient-specific risk rather than a blanket “no contrast in AKI” rule. --- ## When to involve nephrology urgently NICE recommends discussion with nephrology within 24 hours when there is, among other situations:[2] - stage 3 AKI; - AKI with no clear cause; - inadequate response to treatment; - complications of AKI; - suspected vasculitis, glomerulonephritis, interstitial nephritis, or myeloma requiring specialist therapy; - kidney transplant; - advanced CKD (stage 4–5). **Immediate** nephrology/critical-care discussion is needed for potential KRT indications or severe rapidly evolving complications. --- ## Special clinical contexts ### Sepsis-associated AKI Mechanisms extend beyond simple “renal hypoperfusion” and include inflammatory, endothelial, microcirculatory, venous-congestion, and tubular-metabolic changes. Management centers on: - source control and antimicrobials; - hemodynamic resuscitation; - avoiding both under-resuscitation and fluid overload; - dose-adjusting renally cleared antimicrobials; - KRT when indicated. ### Heart failure / cardiorenal syndrome Creatinine can worsen from low forward flow, high venous pressure, neurohormonal activation, or treatment-related hemodynamic changes. In a clearly congested patient, blindly giving fluid because of AKI can be dangerous. Decongestion often remains necessary. ### Cirrhosis Consider: - hypovolemia/bleeding; - sepsis; - acute tubular injury; - nephrotoxins; - abdominal compartment physiology; - hepatorenal syndrome (HRS-AKI). HRS is a diagnosis requiring appropriate exclusion/treatment of competing causes; early hepatology/nephrology involvement is appropriate. ### Rhabdomyolysis - treat the cause; - give isotonic fluid early when appropriate and not volume-overloaded; - monitor potassium, calcium, phosphate, bicarbonate, CK and urine output; - do not use bicarbonate or mannitol routinely solely to prevent AKI without a specific indication; - dialyze for standard complications, not CK level alone. ### Pregnancy AKI requires obstetric-nephrology evaluation. Important causes include hemorrhage, sepsis, hyperemesis, preeclampsia/HELLP, acute fatty liver of pregnancy, TMA, cortical necrosis, and obstruction. Normal pregnancy creatinine is lower than in nonpregnant adults, so a “normal-range” creatinine may already represent significant renal dysfunction. ### Kidney transplant AKI differentials include rejection, obstruction, vascular complications, infection, volume/hemodynamic causes, calcineurin-inhibitor toxicity, and drug interactions. Involve the transplant team early. --- ## Prevention ### General prevention bundle For high-risk patients: - identify CKD and previous AKI; - monitor creatinine and urine output appropriately; - maintain adequate perfusion and avoid unnecessary hypotension; - avoid or minimize nephrotoxins; - use drug-dose adjustment and therapeutic monitoring; - avoid unnecessary contrast repetition; - prevent/treat sepsis promptly; - prevent severe dehydration; - use protocolized perioperative risk management when indicated. NICE recommends active AKI risk assessment in acutely ill adults with CKD, heart failure, liver disease, diabetes, prior AKI, oliguria, hypovolemia, sepsis, recent nephrotoxin exposure, obstruction risk, deteriorating early-warning scores, or age ≥65 years.[2] --- ## Monitoring and reassessment ### In-hospital Track: - urine output hourly when severe/unstable; - creatinine and electrolytes at a frequency dictated by trajectory; - potassium more frequently after emergency therapy; - bicarbonate/pH when acid-base disturbance is important; - daily weights and fluid balance in major volume disturbance; - drug levels where required; - nutritional status; - recovery vs persistent AKI. ### After discharge KDIGO recommends evaluating patients **3 months after AKI** for resolution, new CKD, or worsening pre-existing CKD.[1] NICE advises post-AKI creatinine monitoring based on stability at discharge and considering nephrology referral when eGFR is **≤30 mL/min/1.73 m²** after recovery.[2] Practical follow-up should also address: - blood pressure; - albuminuria/proteinuria where appropriate; - medication reconciliation and restart of indicated drugs; - recurrent AKI prevention; - avoidance of unnecessary NSAIDs; - cardiovascular/CKD risk management. --- ## Anticipating deterioration | Warning sign | Why it matters | Immediate response | |---|---|---| | Rapidly rising K or ECG changes | Arrhythmic death | Cardiac protection + K shift/removal + nephrology/KRT planning | | Falling urine output → anuria | Severe AKI or obstruction | Check catheter/bladder, hemodynamics, imaging, obstruction | | Rising O2 requirement + edema | Pulmonary edema/volume overload | Respiratory support, diuresis if responsive, KRT if refractory | | New confusion, pericarditic pain/rub | Uremic complication | Urgent nephrology/KRT assessment | | Hematuria + proteinuria + systemic features | Rapidly progressive GN | Serologies + urgent nephrology; biopsy/immunotherapy pathway | | Thrombocytopenia + hemolysis | TMA | Immediate hematology/nephrology pathway | | Severe hypertension + AKI | Malignant HTN/TMA | Controlled BP reduction, end-organ assessment | | Persistent AKI >7 days | AKD transition | Reassess diagnosis, nephrotoxins, obstruction, biopsy need, follow-up plan | --- ## Common pitfalls | Pitfall | Why it fails | Better approach | |---|---|---| | Calling every creatinine rise “dehydration” | Misses congestion, GN, obstruction, TMA, ATI | Establish physiology and cause | | Giving repeated fluids without reassessment | Can worsen pulmonary edema and venous congestion | Give fluid only for a plausible fluid-responsive state and reassess | | Relying on FeNa alone | Many false-low and false-high states | Integrate history, exam, urine sediment, hemodynamics | | Using diuretics to “treat the creatinine” | Does not reverse renal injury | Use for clinically important volume overload | | Waiting for severe creatinine before checking urine | Delays GN/obstruction clues | Early urinalysis and sediment | | Refusing emergency contrast because of AKI | Can delay diagnosis of PE, aortic catastrophe, bleeding, stroke pathway, etc. | Weigh diagnostic harm vs renal risk; emergency imaging often proceeds | | Dialyzing by BUN/creatinine threshold | Ignores actual indication and trial evidence | Dialyze for physiology/complications/trajectory | | Forgetting medication restart after recovery | Permanent loss of beneficial ACEi/ARB/other therapy | Reconcile and restart when safe | | Discharging without follow-up | Misses AKD/CKD and recurrence risk | Define post-AKI kidney monitoring | --- ## Diagnostic and management algorithm ```text Creatinine rise and/or oliguria meets AKI criteria ↓ 1. Confirm trend + assess severity - K, bicarbonate/pH, oxygenation, volume status, urine output ↓ 2. Any immediate life threat? - severe hyperK / pulmonary edema / severe acidosis / uremic complication ├─ YES → emergency treatment + nephrology/critical care + consider KRT └─ NO ↓ 3. Search for reversible cause - hypovolemia/shock? - congestion/heart failure? - obstruction? - nephrotoxin/drug? - sepsis? - GN/AIN/TMA/rhabdo/myeloma? ↓ 4. Core tests - urinalysis + sediment - electrolytes/CBC - bladder scan/ultrasound if obstruction plausible - targeted serology/CK/hemolysis tests as indicated ↓ 5. Treat cause + optimize perfusion/volume - fluid only if appropriate - decongest if overloaded - relieve obstruction - stop/adjust nephrotoxins ↓ 6. Reassess repeatedly - creatinine trend, urine output, K, acid-base, volume status ↓ 7. Persistent/worsening AKI, stage 3, unclear cause, or complications? ├─ YES → nephrology; consider biopsy/KRT └─ NO → continue cause-directed management ↓ 8. Discharge only with recovery trajectory + medication plan + kidney follow-up ``` --- ## STANDARD OF CARE vs EMERGING EVIDENCE vs EXPERIMENTAL ### STANDARD OF CARE - KDIGO creatinine/urine-output diagnosis and staging.[1] - Cause-directed treatment and repeated clinical reassessment. - Isotonic crystalloid for true intravascular volume depletion, avoiding indiscriminate fluid loading.[1] - Stop/adjust nephrotoxins and renally cleared drugs. - Do not use low-dose dopamine.[1,2] - Do not use loop diuretics to prevent/treat AKI except to manage volume overload.[1,2] - Urgent KRT for life-threatening electrolyte, acid-base, volume, or uremic complications.[1] - Do not start KRT solely because a creatinine/BUN threshold has been reached.[1,6] - Post-AKI follow-up for CKD/AKD risk.[1,4] ### EMERGING EVIDENCE / ACTIVE IMPLEMENTATION - Biomarker-supported risk stratification (e.g., tubular-stress/injury biomarkers) in selected settings. - Electronic AKI prediction and decision-support systems. - More formal AKI-to-AKD transition pathways and structured post-discharge clinics. - Precision fluid/hemodynamic strategies using dynamic responsiveness and congestion measures. - Broader integration of nephrotoxin stewardship programs. ### EXPERIMENTAL / NOT ROUTINE FOR GENERAL AKI - Using a novel biomarker alone to diagnose the cause of AKI or decide KRT. - “Renal-protective” pharmacologic agents without proven patient-centered benefit. - Routine extracorporeal therapy solely to remove inflammatory mediators in sepsis-associated AKI outside established indications/trials. --- ## Current guideline changes and conflicts (2024–2026) ### 1. Contrast-associated AKI risk has been reframed NICE 2024 now emphasizes an increased risk mainly at **eGFR <30**, uses updated terminology “contrast-associated AKI,” and explicitly warns against delaying clinically important emergency contrast imaging.[2] ### 2. KDIGO AKI update is imminent but not final KDIGO released a **2026 public-review draft** covering AKI and AKD, expanded biomarkers/risk prediction, fluids/hemodynamics, nephrotoxin stewardship, contrast-associated AKI, KRT timing/modality/dose/discontinuation, and follow-up.[8] Until final publication, the 2012 guideline remains the formal KDIGO standard. ### 3. Early routine KRT has lost momentum STARRT-AKI provides strong evidence against automatic accelerated KRT in severe AKI without urgent complications.[6] ### 4. Balanced crystalloids increasingly favored in many acute-care pathways SMART demonstrated a modest kidney-centered composite benefit compared with saline in critically ill adults.[5] Fluid composition remains context-dependent rather than absolute. --- ## Landmark and practice-shaping evidence ### SMART (2018) 15,802 critically ill adults were randomized in a pragmatic cluster-crossover design. Major adverse kidney events within 30 days occurred in **14.3%** with balanced crystalloids vs **15.4%** with saline (P=0.04).[5] **Takeaway:** A small absolute benefit supports balanced crystalloid as a reasonable default in many critically ill adults, but effect size is modest and context matters. ### STARRT-AKI (2020) Nearly 3000 critically ill patients with severe AKI were assigned to accelerated or standard KRT initiation. Accelerated KRT did **not** reduce 90-day mortality; adverse events were more frequent, and KRT dependence among survivors was higher.[6] **Takeaway:** In the absence of emergency indications, clinical watchfulness is often preferable to automatic early dialysis. ### AKI–AKD continuum (ADQI) The ADQI consensus formalized AKD as kidney disease persisting 7–90 days after an acute event, emphasizing that kidney recovery is a trajectory, not a binary discharge diagnosis.[4] --- ## Exam-focused review ### USMLE Step 1 Know: - afferent vs efferent arteriolar physiology; - how NSAIDs and ACEi/ARB can reduce GFR under vulnerable hemodynamic conditions; - tubular injury and muddy brown casts; - glomerular hematuria/RBC casts; - obstruction physiology; - why creatinine lags behind true GFR decline. ### USMLE Step 2 CK Prioritize: - volume status and cause; - urinalysis/sediment; - ultrasound when obstruction is possible; - stopping nephrotoxins; - treating hyperkalemia and pulmonary edema before “workup completion.” ### Step 3 / Resident Focus on: - mixed hemodynamic + structural AKI; - drug dosing and restart plans; - when fluid is harmful; - nephrology referral; - KRT indications vs timing; - post-AKI follow-up. ### MRCP / ABIM / Boards High-yield discriminators: - low FeNa is not synonymous with prerenal AKI; - loop diuretics do not improve AKI recovery; - stage can be determined by urine output; - emergency contrast should not be reflexively withheld; - dialysis is based on complications/trajectory, not a creatinine number; - hematuria + proteinuria + AKI should trigger GN thinking; - thrombocytopenia + hemolysis + AKI should trigger TMA thinking. --- ## Original MCQs ### Question 1 A 72-year-old man with vomiting and diarrhea has a creatinine rise from 1.0 to 1.4 mg/dL within 36 hours. Urine output is preserved. Which statement is most accurate? A. He does not have AKI because creatinine is <2 mg/dL B. He has KDIGO stage 1 AKI C. He has stage 2 AKI D. AKI requires oliguria E. AKI can only be diagnosed after 7 days **Answer: B.** A rise ≥0.3 mg/dL within 48 hours meets AKI criteria and stage 1 severity.[1] --- ### Question 2 A patient with severe decompensated heart failure, pulmonary edema, high JVP, and worsening creatinine receives repeated 1-L saline boluses because the creatinine is rising. Which is the best critique? A. All AKI should receive at least 3 L crystalloid B. Rising creatinine proves intravascular depletion C. Fluid can worsen venous congestion and pulmonary edema; volume therapy should follow physiology D. Diuretics are contraindicated in all AKI E. Dialysis should be started based on creatinine alone **Answer: C.** AKI in heart failure may reflect congestion and low effective perfusion; indiscriminate fluid can worsen both respiratory status and renal venous pressure. --- ### Question 3 A patient with AKI has potassium 7.0 mmol/L, a widened QRS, and no dialysis catheter. What is the immediate priority? A. Wait for repeat potassium before treatment B. Give IV calcium to stabilize the myocardium while initiating potassium-lowering therapy C. Give furosemide only D. Start oral sodium bicarbonate and review tomorrow E. Obtain renal biopsy **Answer: B.** Hyperkalemic ECG toxicity is immediately life-threatening. Calcium protects the myocardium but does not lower K; simultaneous shift/removal therapy and urgent nephrology/KRT planning are required.[7] --- ### Question 4 A critically ill patient has KDIGO stage 3 AKI but potassium, pH, oxygenation, and volume status are controlled. Which statement best reflects modern evidence? A. Stage 3 AKI mandates immediate dialysis in all patients B. Creatinine >3× baseline mandates dialysis C. Accelerated KRT improves 90-day mortality D. In the absence of urgent indications, KRT timing should be individualized and close monitoring is appropriate E. KRT should be withheld even if refractory hyperkalemia develops **Answer: D.** STARRT-AKI found no mortality benefit from accelerated KRT in severe AKI without urgent indications.[6] --- ### Question 5 A 69-year-old with AKI has hematuria, proteinuria, pulmonary infiltrates, and falling hemoglobin. What should be prioritized? A. Diagnose prerenal AKI from FeNa alone B. Assume contrast nephropathy C. Urgent evaluation for pulmonary-renal vasculitis/anti-GBM disease with nephrology involvement D. Give NSAIDs for pleuritic pain E. Wait for spontaneous recovery **Answer: C.** AKI with an active urine sediment and pulmonary hemorrhage features is a nephrologic emergency. --- ### Question 6 A hemodynamically stable patient with suspected aortic dissection has AKI and eGFR 24 mL/min/1.73 m². CT angiography is urgently needed. Which is the best approach? A. Delay contrast for several days until creatinine normalizes B. Cancel definitive imaging because eGFR is <30 C. Proceed with time-critical contrast imaging while using appropriate renal-risk mitigation D. Give N-acetylcysteine and postpone imaging E. Dialyze prophylactically before CT **Answer: C.** NICE 2024 explicitly states not to delay emergency iodinated contrast when the risk of delay is clinically significant.[2] --- ## Acute management checklist ### Recognition - [ ] Compare creatinine with baseline and stage AKI. - [ ] Measure and trend urine output. - [ ] Check K, bicarbonate/pH, volume status, oxygenation. - [ ] Obtain urinalysis early. ### Immediate threats - [ ] ECG if hyperkalemia suspected/severe. - [ ] Treat hyperkalemic ECG toxicity immediately. - [ ] Treat pulmonary edema and severe acidosis. - [ ] Call nephrology/critical care early for KRT-level complications. ### Cause - [ ] Assess hypovolemia vs congestion vs shock. - [ ] Review all medications and recent exposures. - [ ] Check for urinary obstruction. - [ ] Screen for GN/AIN/TMA/rhabdo/myeloma when context suggests. ### Management - [ ] Give isotonic crystalloid only when a fluid-responsive state is plausible. - [ ] Stop/adjust nephrotoxins and renally cleared drugs. - [ ] Treat infection/bleeding/obstruction/cardiac cause. - [ ] Use diuretics for congestion, not to “cure AKI.” - [ ] Reassess after every major intervention. ### Discharge - [ ] Document AKI episode and peak stage. - [ ] Define creatinine/electrolyte follow-up. - [ ] Reconcile temporarily held medications. - [ ] Assess CKD/albuminuria/BP risk. - [ ] Educate regarding dehydration and NSAID/nephrotoxin risk. --- ## References 1. **Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group.** KDIGO Clinical Practice Guideline for Acute Kidney Injury. *Kidney Int Suppl.* 2012;2:1-138. Official guideline: https://kdigo.org/guidelines/acute-kidney-injury/ 2. **National Institute for Health and Care Excellence (NICE).** Acute kidney injury: prevention, detection and management. NG148. Published 2019; updated 16 October 2024. https://www.nice.org.uk/guidance/ng148 3. **Susantitaphong P, Cruz DN, Cerda J, et al.** World incidence of AKI: a meta-analysis. *Clin J Am Soc Nephrol.* 2013;8(9):1482-1493. PMID: 23744003. doi:10.2215/CJN.00710113 4. **Chawla LS, Bellomo R, Bihorac A, et al.; ADQI 16 Workgroup.** Acute kidney disease and renal recovery: consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup. *Nat Rev Nephrol.* 2017;13:241-257. doi:10.1038/nrneph.2017.2 5. **Semler MW, Self WH, Wanderer JP, et al.; SMART Investigators.** Balanced Crystalloids versus Saline in Critically Ill Adults. *N Engl J Med.* 2018;378:829-839. doi:10.1056/NEJMoa1711584 6. **STARRT-AKI Investigators.** Timing of Initiation of Renal-Replacement Therapy in Acute Kidney Injury. *N Engl J Med.* 2020;383:240-251. doi:10.1056/NEJMoa2000741 7. **Alfonzo A, Harrison A, Baines R, Chu A, Mann S, MacRury M.** UK Kidney Association Clinical Practice Guideline: Management of Hyperkalaemia in Adults. Published 19 December 2023. https://www.ukkidney.org/health-professionals/guidelines/treatment-acute-hyperkalaemia-adults-0 8. **Kidney Disease: Improving Global Outcomes (KDIGO).** Acute Kidney Injury (AKI) and Acute Kidney Disease (AKD): 2026 Guideline Public Review information. Public review closed 11 May 2026; final guideline pending at time of review. https://kdigo.org/guidelines/acute-kidney-injury/ --- ### NEXT-TOPIC LEDGER **Completed today:** Acute Kidney Injury **Do not repeat normalized title:** `acute-kidney-injury` **Suggested future linked topics:** Acute kidney disease; Chronic kidney disease; Hyperkalemia; Glomerulonephritis; Acute interstitial nephritis; Rhabdomyolysis; Kidney replacement therapy; Contrast-associated AKI19:Tb3af,## One-minute summary **Acute kidney injury (AKI)** is an abrupt decline in kidney function identified by a rise in serum creatinine and/or reduced urine output. The current established international definition remains the **KDIGO 2012 definition**: an increase in serum creatinine by **≥0.3 mg/dL (≥26.5 µmol/L) within 48 hours**, an increase to **≥1.5 times baseline within 7 days**, or urine output **<0.5 mL/kg/hour for 6 hours**.[1] NICE uses equivalent criteria in UK practice.[2] AKI is a **syndrome, not a diagnosis**. Immediate priorities are to identify reversible threats, determine the cause, restore adequate perfusion when appropriate, relieve urinary obstruction, stop or adjust nephrotoxins and renally cleared drugs, manage electrolyte/acid-base/volume complications, and recognize patients who need urgent nephrology or kidney replacement therapy (KRT).[1,2] The classic “prerenal / intrinsic / postrenal” framework is useful, but many patients—especially those with sepsis, heart failure, cirrhosis, major surgery, or shock—have mixed mechanisms. A low fractional excretion of sodium or a bland urine sediment should never override the clinical picture. **Do not dialyze because the creatinine is high.** Initiate KRT urgently for life-threatening complications such as refractory hyperkalemia, severe acid-base disturbance, pulmonary edema/volume overload, or uremic complications; otherwise use the overall clinical trajectory rather than a single creatinine or BUN threshold.[1,6] **Current practice point (2026):** KDIGO has released a **2026 AKI/acute kidney disease (AKD) public-review draft**, but the final guideline has not yet replaced the 2012 standard. New draft concepts—biomarkers, risk models, AKD continuum, updated fluid and KRT guidance—should be considered **emerging until final publication**.[8] --- ## Core concepts ### What AKI represents physiologically Kidney function depends on adequate renal perfusion, intact glomerular filtration, functioning tubular/interstitial tissue, and unobstructed urine flow. AKI can arise from failure at any of these levels and often evolves through several mechanisms at once. A creatinine rise is a **delayed functional marker**: serum creatinine may not increase immediately after injury, and its concentration is influenced by muscle mass, fluid balance, creatinine production, medications that alter tubular secretion, and the baseline kidney reserve. Urine output can change earlier, but oliguria is neither perfectly sensitive nor specific for structural kidney injury.[1] The clinical objective is therefore not merely to “normalize creatinine.” It is to: 1. prevent ongoing injury; 2. preserve oxygen delivery and perfusion; 3. identify treatable causes; 4. prevent lethal electrolyte/volume/acid-base complications; 5. minimize avoidable drug toxicity; 6. recognize transition to persistent AKI/AKD and later CKD. --- ## Definition and KDIGO staging ### Diagnostic criteria AKI is present if **any** of the following occur:[1,2] - serum creatinine rises by **≥0.3 mg/dL (≥26.5 µmol/L) within 48 hours**; - serum creatinine rises to **≥1.5 × baseline**, known or presumed to have occurred within the prior 7 days; - urine output falls to **<0.5 mL/kg/hour for at least 6 hours**. #### KDIGO staging | Stage | Serum creatinine criterion | Urine-output criterion | |---|---|---| | **1** | 1.5–1.9 × baseline **or** rise ≥0.3 mg/dL (≥26.5 µmol/L) | <0.5 mL/kg/h for 6–12 h | | **2** | 2.0–2.9 × baseline | <0.5 mL/kg/h for ≥12 h | | **3** | 3.0 × baseline **or** creatinine ≥4.0 mg/dL (≥353.6 µmol/L) with an acute rise **or** initiation of KRT | <0.3 mL/kg/h for ≥24 h **or** anuria ≥12 h | **Board pearl:** Stage by the **worst criterion** met. A patient can be stage 3 by urine output even if the creatinine rise appears modest. #### Baseline creatinine problems Baseline creatinine may be unknown. Options include: - the most recent reliable pre-illness creatinine; - a stable outpatient value from the preceding months; - adjudication based on prior records and clinical context. Back-calculating a creatinine from an assumed normal eGFR can misclassify patients and should not be treated as a precise substitute for a known baseline. --- ## AKI, AKD, and CKD continuum AKI describes abrupt kidney dysfunction over **≤7 days**. The ADQI framework introduced **acute kidney disease (AKD)** for kidney disease persisting **7–90 days** after an acute initiating event; disease persisting beyond 90 days meets a chronic kidney disease time criterion.[4] This continuum matters because apparent “recovery” from creatinine-defined AKI does not eliminate future risk. AKI survivors have increased risk of recurrent AKI, CKD, cardiovascular events, and death. Post-discharge kidney follow-up is part of AKI care, not an optional afterthought.[1,4] --- ## Epidemiology and prognosis AKI is common across hospital medicine. A large meta-analysis using KDIGO-equivalent definitions found a pooled adult AKI incidence of about **21.6%** during hospital episodes and an associated mortality of about **23.9%**, although rates vary greatly by case mix, geography, and illness severity.[3] ICU cohorts are substantially higher risk; the ADQI consensus summarizes AKI rates around 50% in critical care populations.[4] Severity, duration, recurrence, multiorgan failure, and incomplete recovery all worsen prognosis. Stage 1 AKI is not benign, and repeated “small” creatinine rises can carry meaningful long-term risk. --- ## Risk factors Important risk factors include:[2] - pre-existing CKD, especially eGFR <60 mL/min/1.73 m²; - older age; - diabetes mellitus; - heart failure; - liver disease/cirrhosis; - previous AKI; - sepsis or systemic inflammatory illness; - hypovolemia or hemorrhage; - major or emergency surgery; - urinary tract obstruction or urologic disease; - nephrotoxins or drugs that worsen hemodynamics during acute illness; - recent iodinated contrast exposure in susceptible patients; - hematologic malignancy, tumor lysis, myeloma, or hemolysis/rhabdomyolysis in selected contexts. #### Common medication/exposure contributors | Exposure | Mechanism / concern | Practical response | |---|---|---| | NSAIDs | Afferent arteriolar vasoconstriction; interstitial nephritis | Stop when AKI suspected unless a compelling reason exists | | ACE inhibitor / ARB | Reduces efferent arteriolar tone; can worsen GFR in hypoperfusion, bilateral renal artery stenosis | Review/temporarily hold during significant hypovolemia, shock, vomiting/diarrhea or sepsis; reassess indication when stable | | Diuretics | Can aggravate effective volume depletion; useful for congestion | Do not reflexively stop if patient is markedly congested; treat the physiology | | Aminoglycosides | Tubular toxicity | Avoid if alternatives exist; therapeutic drug monitoring if required | | Vancomycin | AKI risk increases with excessive exposure and other nephrotoxins | Use current AUC/local monitoring strategy; reassess co-nephrotoxins | | Iodinated contrast | Risk is concentrated in selected high-risk patients; causal risk historically overestimated | Do not delay clinically important emergency imaging; use risk-based hydration strategy | | Calcineurin inhibitors | Vasoconstriction and chronic/acute toxicity | Check level/interactions; transplant-nephrology input | | Chemotherapy / targeted agents | Multiple mechanisms: TLS, TMA, interstitial nephritis, tubular injury | Drug-specific evaluation, oncology/nephrology collaboration | **Clinical trap:** “ACE inhibitor + diuretic + NSAID” can be particularly hazardous during dehydration because renal autoregulation and circulating volume are impaired simultaneously. --- ## Etiology: practical classification ### 1. Reduced renal perfusion / hemodynamic AKI Common causes: - hypovolemia: vomiting, diarrhea, hemorrhage, diuresis, burns; - distributive shock/sepsis; - cardiogenic shock or severe low-output heart failure; - advanced cirrhosis with low effective arterial volume; - medications that impair autoregulation in a susceptible patient; - renal artery compromise. Early hemodynamic AKI may be rapidly reversible, but persistent hypoperfusion can progress to tubular injury. ### 2. Intrinsic renal parenchymal injury #### Acute tubular injury (ATI) Common triggers: - ischemia/shock; - sepsis; - major surgery; - nephrotoxins; - pigments (myoglobin/hemoglobin); - prolonged hemodynamic insult. Urine sediment may show **granular “muddy brown” casts** and renal tubular epithelial cells, but their absence does not exclude ATI. #### Acute interstitial nephritis (AIN) Potential causes include: - antibiotics (e.g., beta-lactams, sulfonamides); - proton-pump inhibitors; - NSAIDs; - immune-checkpoint inhibitors; - infections and systemic disease. The classic triad of **fever, rash, eosinophilia** is uncommon; do not require it for diagnosis. #### Glomerular disease Think urgently about glomerulonephritis when AKI is accompanied by: - hematuria; - proteinuria; - red-cell casts/dysmorphic red cells; - hypertension/edema; - systemic inflammatory features (purpura, pulmonary hemorrhage, sinus disease, arthritis, low complement, etc.). #### Vascular causes - thrombotic microangiopathy; - malignant hypertension; - renal infarction/embolism; - atheroembolic disease; - renal vein thrombosis in selected settings. ### 3. Postrenal / obstructive AKI Causes include: - benign prostatic obstruction; - stones; - pelvic/retroperitoneal malignancy; - blood clots; - neurogenic bladder; - urethral obstruction; - bilateral ureteric obstruction; - obstruction of a solitary functioning kidney. Obstruction can occur **without hydronephrosis early** or in dehydration/retroperitoneal fibrosis, so imaging is not infallible. --- ## Initial clinical assessment ### Immediate questions 1. Is the patient unstable? 2. Is there severe hyperkalemia, pulmonary edema, severe acidosis, pericarditis/encephalopathy, or another KRT-level complication? 3. Is the patient volume depleted, congested, or in shock? 4. Could there be urinary obstruction? 5. Is there a nephrotoxin or recent medication change? 6. Does urine/clinical context suggest glomerulonephritis, interstitial nephritis, TMA, myeloma, rhabdomyolysis, or another intrinsic process? --- ## History Focus on: #### Volume and hemodynamic history - oral intake; - vomiting/diarrhea; - fever/sepsis symptoms; - bleeding; - diuretic escalation; - hypotension/syncope; - heart failure symptoms; - cirrhosis/ascites. #### Urinary history - reduced urine volume or anuria; - hesitancy, poor stream, retention; - flank pain/colic; - hematuria; - recent urologic procedure; - pelvic cancer. #### Drug/exposure history - NSAIDs, ACEi/ARB, diuretics; - antibiotics and recent hospitalization; - contrast exposure; - herbal/supplement use; - chemotherapy or immune-checkpoint therapy; - recreational drugs/toxins; - creatine supplements or drugs affecting creatinine secretion. #### Systemic clues - rash/purpura; - arthralgia; - hemoptysis; - sinus disease; - neuropathy; - fever; - weight loss; - muscle pain/immobility/seizure (rhabdomyolysis); - diarrhea followed by anemia/thrombocytopenia (TMA/HUS context). --- ## Examination Assess both **volume depletion and congestion**—they can coexist. #### General and hemodynamic - blood pressure and trend; - heart rate; - capillary refill/peripheral temperature; - mental status; - orthostatic features when safe and relevant. #### Volume status - mucous membranes; - jugular venous pressure; - peripheral edema; - lung crackles; - ascites; - daily weight trend; - bedside ultrasound where expertise exists. #### Cause-specific signs - bladder distention; - flank tenderness; - rash/purpura; - signs of endocarditis; - pulmonary hemorrhage; - severe hypertension with end-organ injury. **Pitfall:** JVP, IVC ultrasound, urine sodium, and physical signs each have limitations. Use converging evidence rather than one “volume status” variable. --- ## Diagnostic workup ### Minimum initial tests in most hospitalized AKI - repeat serum creatinine/urea; - sodium, potassium, bicarbonate; - calcium, phosphate, magnesium as appropriate; - CBC; - urinalysis/dipstick; - urine microscopy when intrinsic disease is possible; - glucose; - ECG if hyperkalemia or arrhythmia risk; - strict urine-output measurement when clinically important. NICE recommends urine dipstick for **blood, protein, leukocytes, nitrites, and glucose** as soon as AKI is suspected or detected.[2] ### Additional tests guided by context | Suspicion | Useful tests | |---|---| | Sepsis | cultures, lactate, source evaluation | | Rhabdomyolysis | CK, phosphate, calcium, urinalysis with heme but few/no RBCs | | Hemolysis/TMA | smear, LDH, haptoglobin, bilirubin, platelets, ADAMTS13 when indicated | | Glomerulonephritis | urine microscopy, urine protein quantification, C3/C4, ANA, ANCA, anti-GBM, hepatitis/HIV tests as context dictates | | Myeloma | serum free light chains, serum/urine electrophoresis/immunofixation | | AIN | medication timeline; eosinophils are nonspecific; biopsy if diagnosis will alter therapy | | Obstruction | bladder scan; renal tract ultrasound or CT depending on suspected level/cause | --- ## Urinalysis and urine microscopy Urine sediment can be one of the highest-yield bedside “kidney biopsies.” | Finding | Suggests | Caveat | |---|---|---| | Muddy brown granular casts / tubular epithelial cells | Acute tubular injury | Sensitivity varies; absence does not exclude ATI | | RBC casts / dysmorphic RBCs | Glomerulonephritis | Urgent nephrology workup | | WBC casts | Interstitial nephritis or pyelonephritis | Not specific | | Heavy proteinuria | Glomerular disease, paraprotein disease | Dipstick underdetects some light chains | | Heme-positive dipstick with few RBCs | Myoglobinuria/hemoglobinuria | Correlate with CK/hemolysis | | Crystals | Drug/crystal nephropathy, uric acid, oxalate | Context determines significance | NICE specifically advises considering acute nephritis and nephrology referral when AKI has no obvious cause and urinalysis shows **hematuria plus proteinuria** without UTI or catheter trauma.[2] --- ## Fractional excretion indices: use cautiously #### FeNa \[ FeNa(\%) = \frac{Urine\ Na \times Plasma\ Cr}{Plasma\ Na \times Urine\ Cr}\times 100 \] A low FeNa can occur in reduced effective circulating volume, but also in: - early sepsis; - contrast-associated AKI; - pigment nephropathy; - glomerulonephritis; - hepatorenal physiology; - some obstructive states. A high FeNa can occur with diuretics, CKD, or established tubular injury. #### FeUrea Sometimes used when diuretics confound FeNa, but FeUrea is also imperfect and should not be treated as a diagnostic truth test. **Board pearl:** The distinction between “prerenal azotemia” and “ATN” is not reliably made by one urine index. --- ## Imaging ### Renal tract ultrasound Use when obstruction is possible or the cause is unclear. NICE advises **immediate ultrasound (within 6 hours)** when pyonephrosis/infected obstruction is suspected.[2] Do not routinely order ultrasound if the cause is already clear and obstruction is not clinically plausible.[2] ### CT Useful when stone disease, retroperitoneal pathology, vascular disease, trauma, or another abdominal cause is suspected. **Do not withhold or delay emergency contrast imaging when delay is likely to be clinically harmful.** NICE’s 2024 update emphasizes that contrast-associated AKI risk is small but increased when eGFR is <30 mL/min/1.73 m² and specifically advises not delaying emergency iodinated contrast when the clinical cost of delay is significant.[2] --- ## Differential diagnosis by pattern | Pattern | Leading possibilities | Clues that shift probability | |---|---|---| | Oliguria after vomiting/diarrhea | Hypovolemia, ATI if prolonged | Orthostasis, low JVP, hemoconcentration, response to cautious fluid | | AKI + edema + pulmonary congestion | Cardiorenal syndrome, GN, renal failure with volume overload | JVP, BNP context, echo, urine sediment, proteinuria | | AKI + hematuria + proteinuria | GN, vasculitis, anti-GBM, infection-related GN | RBC casts, systemic features, complement/serologies | | AKI + thrombocytopenia + hemolysis | TMA/TTP/HUS, malignant HTN | Schistocytes, LDH, haptoglobin, BP, ADAMTS13 context | | AKI + very high CK | Rhabdomyolysis | Muscle injury, dark urine, heme-positive dipstick without RBCs | | AKI + eosinophilia/rash after new drug | AIN | Often lacks classic triad; biopsy may be needed | | AKI + anuria/retention | Obstruction until proven otherwise | Bladder scan, ultrasound/CT | | AKI in cirrhosis | Volume depletion, sepsis, ATI, hepatorenal syndrome, drugs | Diagnose HRS only after excluding/treating competing causes | --- ## Management: stepwise approach ### STEP 1 — Stabilize life-threatening complications Address ABC problems first. In AKI, immediate threats include: - severe hyperkalemia; - pulmonary edema with respiratory compromise; - severe metabolic acidosis; - uremic pericarditis/encephalopathy; - severe symptomatic sodium disturbance; - toxin accumulation where extracorporeal removal is indicated. ### STEP 2 — Treat the cause Examples: - hypovolemia → judicious isotonic crystalloid/blood as appropriate; - hemorrhage → hemorrhage control + blood-product strategy; - sepsis → prompt infection/source control and hemodynamic management; - obstruction → catheterization, nephrostomy, stent, or urologic decompression according to level/cause; - GN/vasculitis/TMA → urgent disease-specific specialist pathway; - rhabdomyolysis → early fluids when appropriate, treat cause, monitor potassium/calcium/phosphate; - drug toxicity → stop culprit, adjust doses, antidote/extracorporeal therapy when indicated. ### STEP 3 — Stop ongoing kidney insults - stop nonessential nephrotoxins; - review ACEi/ARB, NSAIDs, diuretics and SGLT2 inhibitors in context rather than by rote; - adjust doses of renally cleared drugs; - avoid duplicate contrast/nephrotoxin exposure where clinically unnecessary; - check drug interactions and levels where relevant. ### STEP 4 — Optimize volume and perfusion KDIGO favors **isotonic crystalloids rather than colloids** for initial intravascular volume expansion in patients at risk of or with AKI when hemorrhagic shock is absent.[1] #### Balanced crystalloid vs 0.9% saline In the SMART trial, balanced crystalloids modestly reduced the composite of death, new KRT, or persistent renal dysfunction compared with saline in critically ill adults (14.3% vs 15.4%).[5] This supports frequent use of balanced crystalloid in many critically ill patients, but fluid choice must account for the indication, electrolyte/acid-base context, neurologic disease, and local protocol. **Do not give fluid merely because creatinine rose.** If the patient is congested or has cardiogenic physiology, repeated boluses can worsen pulmonary edema and renal venous congestion. ### STEP 5 — Monitor dynamically - urine output; - daily or more frequent creatinine/electrolytes according to severity; - potassium and bicarbonate; - fluid input/output; - daily weight in significant volume disturbance; - hemodynamics; - drug concentrations when indicated; - clinical response to interventions. NICE notes that daily creatinine measurement is typical for hospitalized patients with or at risk of AKI, adjusted to clinical need.[2] --- ## Pharmacotherapy principles ### Diuretics **STANDARD OF CARE:** Do **not** use loop diuretics to prevent AKI or to “convert” oliguric AKI to non-oliguric AKI. They are appropriate for **fluid overload/congestion** when there is a reasonable chance of diuretic response.[1,2] A rise in creatinine during effective decongestion in heart failure does not automatically mean diuretics should be stopped; interpret renal function alongside congestion, perfusion, blood pressure, and overall trajectory. ### Low-dose dopamine Do **not** use low-dose “renal-dose” dopamine to prevent or treat AKI.[1,2] ### ACE inhibitors and ARBs During significant acute volume depletion, vomiting/diarrhea, hypotension, or sepsis, temporary withholding may be reasonable and is specifically suggested by NICE in relevant acute illness.[2] However, once the acute process resolves, **reassess and restart evidence-based indications** rather than allowing accidental permanent discontinuation. --- ## Emergency hyperkalemia in AKI Hyperkalemia is one of the most important immediately reversible causes of death in severe AKI. #### First actions - confirm the result rapidly if pseudohyperkalemia is plausible, **without delaying treatment** when the patient is unstable or ECG changes are present; - obtain a 12-lead ECG and continuous monitoring for severe hyperkalemia; - stop exogenous potassium and contributing drugs; - stabilize the myocardium when ECG toxicity is present; - shift potassium intracellularly; - remove potassium from the body; - repeat potassium and glucose because rebound and hypoglycemia are common. #### UK Kidney Association 2023 adult emergency doses | Purpose | Treatment | Adult dose / note | |---|---|---| | **Protect the heart** | 10% calcium chloride | **10 mL IV over 5 min** in peri-arrest/cardiac arrest or according to local resuscitation protocol | | **Protect the heart** | 10% calcium gluconate | **30 mL IV over 10 min** for other patients with hyperkalemic ECG changes | | **Shift K into cells** | Soluble insulin + glucose | **10 units soluble insulin in 25 g glucose IV** for severe K ≥6.5 mmol/L; consider in moderate K 6.0–6.4 mmol/L | | Prevent post-insulin hypoglycemia | 10% glucose infusion | If pretreatment glucose <7 mmol/L, UKKA recommends **10% glucose 50 mL/hour for 5 h** after insulin-glucose | | **Adjunct shift** | Nebulized salbutamol | **10–20 mg nebulized** as adjunct in severe hyperkalemia; do not use as sole therapy | These doses are from UKKA guidance and may differ by jurisdiction/local resuscitation policy.[7] **Calcium does not lower serum potassium.** It temporarily reduces myocardial excitability risk while potassium-lowering therapy is initiated. **KRT should not be delayed** when severe hyperkalemia is refractory or expected to recur rapidly because of advanced renal failure, ongoing tissue breakdown, or inability to remove potassium medically.[1,7] --- ## Metabolic acidosis Treat the cause first: shock, sepsis, ketoacidosis, toxin, renal failure, etc. Sodium bicarbonate is **not a universal AKI therapy**. Consider it selectively when severe acidemia itself is harmful and bicarbonate therapy is physiologically appropriate, while avoiding sodium/volume overload and recognizing that severe refractory acidosis may require KRT. --- ## Kidney replacement therapy (KRT) ### Indications KDIGO recommends emergency KRT when there are **life-threatening changes in fluid, electrolyte, or acid-base balance**.[1] Common practical indications include: - refractory severe hyperkalemia; - refractory severe metabolic acidosis; - refractory pulmonary edema/volume overload causing hypoxemia; - uremic pericarditis; - uremic encephalopathy or severe symptomatic uremia; - selected dialyzable intoxications; - progressive complications when medical management is failing. #### What should NOT determine KRT alone - one creatinine value; - one BUN/urea value; - oliguria in isolation; - “stage 3 AKI” without clinical context. ### Timing when no emergency indication exists The **STARRT-AKI** trial randomized critically ill patients with severe AKI to accelerated vs standard KRT initiation. Accelerated initiation **did not reduce 90-day mortality** and was associated with more adverse events and greater dialysis dependence among survivors.[6] **STANDARD OF CARE implication:** In a patient without an urgent indication, do not start KRT solely because severe AKI has developed. Watch the clinical trajectory closely and start when complications, worsening physiology, or failure of conservative management justify it. ### Modality - **Intermittent hemodialysis:** efficient solute/volume removal; may be poorly tolerated in unstable patients. - **Continuous KRT (CKRT/CRRT):** often favored in severe hemodynamic instability or some neurocritical-care situations. - **Prolonged intermittent therapies (SLED/PIRRT):** hybrid option depending on local resources. Modality should reflect hemodynamics, neurologic status, solute-removal needs, staffing/resources, and local expertise—not an assumption that one modality is universally superior. --- ## Contrast-associated AKI: 2024 practice update NICE updated its iodinated-contrast recommendations in **October 2024**.[2] #### Key points - An **eGFR <30 mL/min/1.73 m²** is associated with a small but increased risk of AKI from iodinated contrast exposure. - **Do not delay emergency contrast imaging** if delaying contrast is likely to cause clinically significant harm. - For increased-risk patients, encourage **oral hydration** before and after IV iodinated contrast when appropriate. - For particularly high-risk inpatients (e.g., eGFR <30, kidney transplant, high contrast volume/repeat dose, first-pass intra-arterial exposure), consider IV volume expansion with **0.9% saline or isotonic sodium bicarbonate**. - NICE suggests considering temporary ACEi/ARB withholding in CKD with eGFR <30 around iodinated contrast. **Guideline conflict / nuance:** Contrast protocols differ among radiology, nephrology, and national guidance. Modern evidence has reduced previous estimates of contrast-caused AKI, especially for routine IV CT. The clinical harm of missing or delaying a time-critical diagnosis can exceed the renal risk. Use local radiology policy and patient-specific risk rather than a blanket “no contrast in AKI” rule. --- ## When to involve nephrology urgently NICE recommends discussion with nephrology within 24 hours when there is, among other situations:[2] - stage 3 AKI; - AKI with no clear cause; - inadequate response to treatment; - complications of AKI; - suspected vasculitis, glomerulonephritis, interstitial nephritis, or myeloma requiring specialist therapy; - kidney transplant; - advanced CKD (stage 4–5). **Immediate** nephrology/critical-care discussion is needed for potential KRT indications or severe rapidly evolving complications. --- ## Special clinical contexts ### Sepsis-associated AKI Mechanisms extend beyond simple “renal hypoperfusion” and include inflammatory, endothelial, microcirculatory, venous-congestion, and tubular-metabolic changes. Management centers on: - source control and antimicrobials; - hemodynamic resuscitation; - avoiding both under-resuscitation and fluid overload; - dose-adjusting renally cleared antimicrobials; - KRT when indicated. ### Heart failure / cardiorenal syndrome Creatinine can worsen from low forward flow, high venous pressure, neurohormonal activation, or treatment-related hemodynamic changes. In a clearly congested patient, blindly giving fluid because of AKI can be dangerous. Decongestion often remains necessary. ### Cirrhosis Consider: - hypovolemia/bleeding; - sepsis; - acute tubular injury; - nephrotoxins; - abdominal compartment physiology; - hepatorenal syndrome (HRS-AKI). HRS is a diagnosis requiring appropriate exclusion/treatment of competing causes; early hepatology/nephrology involvement is appropriate. ### Rhabdomyolysis - treat the cause; - give isotonic fluid early when appropriate and not volume-overloaded; - monitor potassium, calcium, phosphate, bicarbonate, CK and urine output; - do not use bicarbonate or mannitol routinely solely to prevent AKI without a specific indication; - dialyze for standard complications, not CK level alone. ### Pregnancy AKI requires obstetric-nephrology evaluation. Important causes include hemorrhage, sepsis, hyperemesis, preeclampsia/HELLP, acute fatty liver of pregnancy, TMA, cortical necrosis, and obstruction. Normal pregnancy creatinine is lower than in nonpregnant adults, so a “normal-range” creatinine may already represent significant renal dysfunction. ### Kidney transplant AKI differentials include rejection, obstruction, vascular complications, infection, volume/hemodynamic causes, calcineurin-inhibitor toxicity, and drug interactions. Involve the transplant team early. --- ## Prevention ### General prevention bundle For high-risk patients: - identify CKD and previous AKI; - monitor creatinine and urine output appropriately; - maintain adequate perfusion and avoid unnecessary hypotension; - avoid or minimize nephrotoxins; - use drug-dose adjustment and therapeutic monitoring; - avoid unnecessary contrast repetition; - prevent/treat sepsis promptly; - prevent severe dehydration; - use protocolized perioperative risk management when indicated. NICE recommends active AKI risk assessment in acutely ill adults with CKD, heart failure, liver disease, diabetes, prior AKI, oliguria, hypovolemia, sepsis, recent nephrotoxin exposure, obstruction risk, deteriorating early-warning scores, or age ≥65 years.[2] --- ## Monitoring and reassessment ### In-hospital Track: - urine output hourly when severe/unstable; - creatinine and electrolytes at a frequency dictated by trajectory; - potassium more frequently after emergency therapy; - bicarbonate/pH when acid-base disturbance is important; - daily weights and fluid balance in major volume disturbance; - drug levels where required; - nutritional status; - recovery vs persistent AKI. ### After discharge KDIGO recommends evaluating patients **3 months after AKI** for resolution, new CKD, or worsening pre-existing CKD.[1] NICE advises post-AKI creatinine monitoring based on stability at discharge and considering nephrology referral when eGFR is **≤30 mL/min/1.73 m²** after recovery.[2] Practical follow-up should also address: - blood pressure; - albuminuria/proteinuria where appropriate; - medication reconciliation and restart of indicated drugs; - recurrent AKI prevention; - avoidance of unnecessary NSAIDs; - cardiovascular/CKD risk management. --- ## Anticipating deterioration | Warning sign | Why it matters | Immediate response | |---|---|---| | Rapidly rising K or ECG changes | Arrhythmic death | Cardiac protection + K shift/removal + nephrology/KRT planning | | Falling urine output → anuria | Severe AKI or obstruction | Check catheter/bladder, hemodynamics, imaging, obstruction | | Rising O2 requirement + edema | Pulmonary edema/volume overload | Respiratory support, diuresis if responsive, KRT if refractory | | New confusion, pericarditic pain/rub | Uremic complication | Urgent nephrology/KRT assessment | | Hematuria + proteinuria + systemic features | Rapidly progressive GN | Serologies + urgent nephrology; biopsy/immunotherapy pathway | | Thrombocytopenia + hemolysis | TMA | Immediate hematology/nephrology pathway | | Severe hypertension + AKI | Malignant HTN/TMA | Controlled BP reduction, end-organ assessment | | Persistent AKI >7 days | AKD transition | Reassess diagnosis, nephrotoxins, obstruction, biopsy need, follow-up plan | --- ## Common pitfalls | Pitfall | Why it fails | Better approach | |---|---|---| | Calling every creatinine rise “dehydration” | Misses congestion, GN, obstruction, TMA, ATI | Establish physiology and cause | | Giving repeated fluids without reassessment | Can worsen pulmonary edema and venous congestion | Give fluid only for a plausible fluid-responsive state and reassess | | Relying on FeNa alone | Many false-low and false-high states | Integrate history, exam, urine sediment, hemodynamics | | Using diuretics to “treat the creatinine” | Does not reverse renal injury | Use for clinically important volume overload | | Waiting for severe creatinine before checking urine | Delays GN/obstruction clues | Early urinalysis and sediment | | Refusing emergency contrast because of AKI | Can delay diagnosis of PE, aortic catastrophe, bleeding, stroke pathway, etc. | Weigh diagnostic harm vs renal risk; emergency imaging often proceeds | | Dialyzing by BUN/creatinine threshold | Ignores actual indication and trial evidence | Dialyze for physiology/complications/trajectory | | Forgetting medication restart after recovery | Permanent loss of beneficial ACEi/ARB/other therapy | Reconcile and restart when safe | | Discharging without follow-up | Misses AKD/CKD and recurrence risk | Define post-AKI kidney monitoring | --- ## Diagnostic and management algorithm ```text Creatinine rise and/or oliguria meets AKI criteria ↓ 1. Confirm trend + assess severity - K, bicarbonate/pH, oxygenation, volume status, urine output ↓ 2. Any immediate life threat? - severe hyperK / pulmonary edema / severe acidosis / uremic complication ├─ YES → emergency treatment + nephrology/critical care + consider KRT └─ NO ↓ 3. Search for reversible cause - hypovolemia/shock? - congestion/heart failure? - obstruction? - nephrotoxin/drug? - sepsis? - GN/AIN/TMA/rhabdo/myeloma? ↓ 4. Core tests - urinalysis + sediment - electrolytes/CBC - bladder scan/ultrasound if obstruction plausible - targeted serology/CK/hemolysis tests as indicated ↓ 5. Treat cause + optimize perfusion/volume - fluid only if appropriate - decongest if overloaded - relieve obstruction - stop/adjust nephrotoxins ↓ 6. Reassess repeatedly - creatinine trend, urine output, K, acid-base, volume status ↓ 7. Persistent/worsening AKI, stage 3, unclear cause, or complications? ├─ YES → nephrology; consider biopsy/KRT └─ NO → continue cause-directed management ↓ 8. Discharge only with recovery trajectory + medication plan + kidney follow-up ``` --- ## STANDARD OF CARE vs EMERGING EVIDENCE vs EXPERIMENTAL ### STANDARD OF CARE - KDIGO creatinine/urine-output diagnosis and staging.[1] - Cause-directed treatment and repeated clinical reassessment. - Isotonic crystalloid for true intravascular volume depletion, avoiding indiscriminate fluid loading.[1] - Stop/adjust nephrotoxins and renally cleared drugs. - Do not use low-dose dopamine.[1,2] - Do not use loop diuretics to prevent/treat AKI except to manage volume overload.[1,2] - Urgent KRT for life-threatening electrolyte, acid-base, volume, or uremic complications.[1] - Do not start KRT solely because a creatinine/BUN threshold has been reached.[1,6] - Post-AKI follow-up for CKD/AKD risk.[1,4] ### EMERGING EVIDENCE / ACTIVE IMPLEMENTATION - Biomarker-supported risk stratification (e.g., tubular-stress/injury biomarkers) in selected settings. - Electronic AKI prediction and decision-support systems. - More formal AKI-to-AKD transition pathways and structured post-discharge clinics. - Precision fluid/hemodynamic strategies using dynamic responsiveness and congestion measures. - Broader integration of nephrotoxin stewardship programs. ### EXPERIMENTAL / NOT ROUTINE FOR GENERAL AKI - Using a novel biomarker alone to diagnose the cause of AKI or decide KRT. - “Renal-protective” pharmacologic agents without proven patient-centered benefit. - Routine extracorporeal therapy solely to remove inflammatory mediators in sepsis-associated AKI outside established indications/trials. --- ## Current guideline changes and conflicts (2024–2026) ### 1. Contrast-associated AKI risk has been reframed NICE 2024 now emphasizes an increased risk mainly at **eGFR <30**, uses updated terminology “contrast-associated AKI,” and explicitly warns against delaying clinically important emergency contrast imaging.[2] ### 2. KDIGO AKI update is imminent but not final KDIGO released a **2026 public-review draft** covering AKI and AKD, expanded biomarkers/risk prediction, fluids/hemodynamics, nephrotoxin stewardship, contrast-associated AKI, KRT timing/modality/dose/discontinuation, and follow-up.[8] Until final publication, the 2012 guideline remains the formal KDIGO standard. ### 3. Early routine KRT has lost momentum STARRT-AKI provides strong evidence against automatic accelerated KRT in severe AKI without urgent complications.[6] ### 4. Balanced crystalloids increasingly favored in many acute-care pathways SMART demonstrated a modest kidney-centered composite benefit compared with saline in critically ill adults.[5] Fluid composition remains context-dependent rather than absolute. --- ## Landmark and practice-shaping evidence ### SMART (2018) 15,802 critically ill adults were randomized in a pragmatic cluster-crossover design. Major adverse kidney events within 30 days occurred in **14.3%** with balanced crystalloids vs **15.4%** with saline (P=0.04).[5] **Takeaway:** A small absolute benefit supports balanced crystalloid as a reasonable default in many critically ill adults, but effect size is modest and context matters. ### STARRT-AKI (2020) Nearly 3000 critically ill patients with severe AKI were assigned to accelerated or standard KRT initiation. Accelerated KRT did **not** reduce 90-day mortality; adverse events were more frequent, and KRT dependence among survivors was higher.[6] **Takeaway:** In the absence of emergency indications, clinical watchfulness is often preferable to automatic early dialysis. ### AKI–AKD continuum (ADQI) The ADQI consensus formalized AKD as kidney disease persisting 7–90 days after an acute event, emphasizing that kidney recovery is a trajectory, not a binary discharge diagnosis.[4] --- ## Exam-focused review ### USMLE Step 1 Know: - afferent vs efferent arteriolar physiology; - how NSAIDs and ACEi/ARB can reduce GFR under vulnerable hemodynamic conditions; - tubular injury and muddy brown casts; - glomerular hematuria/RBC casts; - obstruction physiology; - why creatinine lags behind true GFR decline. ### USMLE Step 2 CK Prioritize: - volume status and cause; - urinalysis/sediment; - ultrasound when obstruction is possible; - stopping nephrotoxins; - treating hyperkalemia and pulmonary edema before “workup completion.” ### Step 3 / Resident Focus on: - mixed hemodynamic + structural AKI; - drug dosing and restart plans; - when fluid is harmful; - nephrology referral; - KRT indications vs timing; - post-AKI follow-up. ### MRCP / ABIM / Boards High-yield discriminators: - low FeNa is not synonymous with prerenal AKI; - loop diuretics do not improve AKI recovery; - stage can be determined by urine output; - emergency contrast should not be reflexively withheld; - dialysis is based on complications/trajectory, not a creatinine number; - hematuria + proteinuria + AKI should trigger GN thinking; - thrombocytopenia + hemolysis + AKI should trigger TMA thinking. --- ## Original MCQs ### Question 1 A 72-year-old man with vomiting and diarrhea has a creatinine rise from 1.0 to 1.4 mg/dL within 36 hours. Urine output is preserved. Which statement is most accurate? A. He does not have AKI because creatinine is <2 mg/dL B. He has KDIGO stage 1 AKI C. He has stage 2 AKI D. AKI requires oliguria E. AKI can only be diagnosed after 7 days **Answer: B.** A rise ≥0.3 mg/dL within 48 hours meets AKI criteria and stage 1 severity.[1] --- ### Question 2 A patient with severe decompensated heart failure, pulmonary edema, high JVP, and worsening creatinine receives repeated 1-L saline boluses because the creatinine is rising. Which is the best critique? A. All AKI should receive at least 3 L crystalloid B. Rising creatinine proves intravascular depletion C. Fluid can worsen venous congestion and pulmonary edema; volume therapy should follow physiology D. Diuretics are contraindicated in all AKI E. Dialysis should be started based on creatinine alone **Answer: C.** AKI in heart failure may reflect congestion and low effective perfusion; indiscriminate fluid can worsen both respiratory status and renal venous pressure. --- ### Question 3 A patient with AKI has potassium 7.0 mmol/L, a widened QRS, and no dialysis catheter. What is the immediate priority? A. Wait for repeat potassium before treatment B. Give IV calcium to stabilize the myocardium while initiating potassium-lowering therapy C. Give furosemide only D. Start oral sodium bicarbonate and review tomorrow E. Obtain renal biopsy **Answer: B.** Hyperkalemic ECG toxicity is immediately life-threatening. Calcium protects the myocardium but does not lower K; simultaneous shift/removal therapy and urgent nephrology/KRT planning are required.[7] --- ### Question 4 A critically ill patient has KDIGO stage 3 AKI but potassium, pH, oxygenation, and volume status are controlled. Which statement best reflects modern evidence? A. Stage 3 AKI mandates immediate dialysis in all patients B. Creatinine >3× baseline mandates dialysis C. Accelerated KRT improves 90-day mortality D. In the absence of urgent indications, KRT timing should be individualized and close monitoring is appropriate E. KRT should be withheld even if refractory hyperkalemia develops **Answer: D.** STARRT-AKI found no mortality benefit from accelerated KRT in severe AKI without urgent indications.[6] --- ### Question 5 A 69-year-old with AKI has hematuria, proteinuria, pulmonary infiltrates, and falling hemoglobin. What should be prioritized? A. Diagnose prerenal AKI from FeNa alone B. Assume contrast nephropathy C. Urgent evaluation for pulmonary-renal vasculitis/anti-GBM disease with nephrology involvement D. Give NSAIDs for pleuritic pain E. Wait for spontaneous recovery **Answer: C.** AKI with an active urine sediment and pulmonary hemorrhage features is a nephrologic emergency. --- ### Question 6 A hemodynamically stable patient with suspected aortic dissection has AKI and eGFR 24 mL/min/1.73 m². CT angiography is urgently needed. Which is the best approach? A. Delay contrast for several days until creatinine normalizes B. Cancel definitive imaging because eGFR is <30 C. Proceed with time-critical contrast imaging while using appropriate renal-risk mitigation D. Give N-acetylcysteine and postpone imaging E. Dialyze prophylactically before CT **Answer: C.** NICE 2024 explicitly states not to delay emergency iodinated contrast when the risk of delay is clinically significant.[2] --- ## Acute management checklist ### Recognition - [ ] Compare creatinine with baseline and stage AKI. - [ ] Measure and trend urine output. - [ ] Check K, bicarbonate/pH, volume status, oxygenation. - [ ] Obtain urinalysis early. ### Immediate threats - [ ] ECG if hyperkalemia suspected/severe. - [ ] Treat hyperkalemic ECG toxicity immediately. - [ ] Treat pulmonary edema and severe acidosis. - [ ] Call nephrology/critical care early for KRT-level complications. ### Cause - [ ] Assess hypovolemia vs congestion vs shock. - [ ] Review all medications and recent exposures. - [ ] Check for urinary obstruction. - [ ] Screen for GN/AIN/TMA/rhabdo/myeloma when context suggests. ### Management - [ ] Give isotonic crystalloid only when a fluid-responsive state is plausible. - [ ] Stop/adjust nephrotoxins and renally cleared drugs. - [ ] Treat infection/bleeding/obstruction/cardiac cause. - [ ] Use diuretics for congestion, not to “cure AKI.” - [ ] Reassess after every major intervention. ### Discharge - [ ] Document AKI episode and peak stage. - [ ] Define creatinine/electrolyte follow-up. - [ ] Reconcile temporarily held medications. - [ ] Assess CKD/albuminuria/BP risk. - [ ] Educate regarding dehydration and NSAID/nephrotoxin risk. --- ## References 1. **Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group.** KDIGO Clinical Practice Guideline for Acute Kidney Injury. *Kidney Int Suppl.* 2012;2:1-138. Official guideline: https://kdigo.org/guidelines/acute-kidney-injury/ 2. **National Institute for Health and Care Excellence (NICE).** Acute kidney injury: prevention, detection and management. NG148. Published 2019; updated 16 October 2024. https://www.nice.org.uk/guidance/ng148 3. **Susantitaphong P, Cruz DN, Cerda J, et al.** World incidence of AKI: a meta-analysis. *Clin J Am Soc Nephrol.* 2013;8(9):1482-1493. PMID: 23744003. doi:10.2215/CJN.00710113 4. **Chawla LS, Bellomo R, Bihorac A, et al.; ADQI 16 Workgroup.** Acute kidney disease and renal recovery: consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup. *Nat Rev Nephrol.* 2017;13:241-257. doi:10.1038/nrneph.2017.2 5. **Semler MW, Self WH, Wanderer JP, et al.; SMART Investigators.** Balanced Crystalloids versus Saline in Critically Ill Adults. *N Engl J Med.* 2018;378:829-839. doi:10.1056/NEJMoa1711584 6. **STARRT-AKI Investigators.** Timing of Initiation of Renal-Replacement Therapy in Acute Kidney Injury. *N Engl J Med.* 2020;383:240-251. doi:10.1056/NEJMoa2000741 7. **Alfonzo A, Harrison A, Baines R, Chu A, Mann S, MacRury M.** UK Kidney Association Clinical Practice Guideline: Management of Hyperkalaemia in Adults. Published 19 December 2023. https://www.ukkidney.org/health-professionals/guidelines/treatment-acute-hyperkalaemia-adults-0 8. **Kidney Disease: Improving Global Outcomes (KDIGO).** Acute Kidney Injury (AKI) and Acute Kidney Disease (AKD): 2026 Guideline Public Review information. Public review closed 11 May 2026; final guideline pending at time of review. https://kdigo.org/guidelines/acute-kidney-injury/ --- ### NEXT-TOPIC LEDGER **Completed today:** Acute Kidney Injury **Do not repeat normalized title:** `acute-kidney-injury` **Suggested future linked topics:** Acute kidney disease; Chronic kidney disease; Hyperkalemia; Glomerulonephritis; Acute interstitial nephritis; Rhabdomyolysis; Kidney replacement therapy; Contrast-associated AKI1a:T7b05,## One-minute summary **Acute bacterial meningitis** is infection-driven inflammation of the leptomeninges and cerebrospinal fluid (CSF). It can progress over hours to **sepsis, shock, cerebral edema, seizures, raised intracranial pressure, herniation, hearing loss, neurologic disability, and death**. WHO's first global meningitis diagnosis/treatment guideline was released in 2025, followed by a practical implementation manual in May 2026.[1,2] WHO estimates bacterial meningitis causes death in roughly **1 in 6 affected people**, and about **1 in 5 survivors** develops long-term complications.[1] ### The core emergency sequence 1. **Recognize the syndrome**: fever, headache, neck stiffness, altered mental status, photophobia, vomiting, seizure, focal deficit, non-blanching rash, or sepsis; not every patient has the classic triad. 2. **Stabilize ABCs** and treat shock/seizures immediately. 3. Obtain **blood cultures and key blood tests**, but never allow diagnostics to cause a clinically significant antibiotic delay. 4. Perform **lumbar puncture before antibiotics if safe and immediately feasible**. 5. **Do not routinely obtain CT before LP.** Image first only when specific features suggest a space-occupying lesion or dangerous raised intracranial pressure. 6. Start **IV antibiotics as soon as meningitis is suspected**; NICE specifies within **1 hour of hospital arrival**.[3] 7. Give **IV dexamethasone with or before the first antibiotic dose if possible** in strongly suspected bacterial meningitis (age >3 months in NICE guidance); never delay antibiotics for dexamethasone.[3] 8. Narrow therapy once Gram stain, PCR, culture, and susceptibility data return. 9. Assess for **hearing and neurologic sequelae** and involve public health for meningococcal disease. ★ **High-yield principle:** If CT is needed before LP, **take bloods and start antibiotics first**. Imaging must not become a treatment-delay ritual.[3] --- ## Definition Meningitis is inflammation of the meninges and CSF, usually infectious. **Bacterial meningitis** refers to acute meningitis caused by bacteria, most often acquired in the community but sometimes related to neurosurgery, skull defects, penetrating trauma, CSF devices, or bacteremia. This article focuses primarily on **acute community-acquired bacterial meningitis in children beyond the neonatal period and adults**, with emphasis on adult clinical reasoning. Neonatal, post-neurosurgical, TB, cryptococcal, and chronic meningitis require specialized protocols. --- ## Epidemiology and major pathogens The pathogen distribution varies with age, vaccination, immune status, geography, and healthcare exposure. | Population / risk state | Important organisms | Practical implication | |---|---|---| | Adolescents / younger adults | *Neisseria meningitidis*, *Streptococcus pneumoniae* | Consider meningococcal sepsis/rash; droplet precautions and public-health actions | | General adults | *S. pneumoniae*, *N. meningitidis* | Pneumococcus is a major cause of severe adult disease | | Older adults / cell-mediated immune impairment | Above + *Listeria monocytogenes* | Add anti-Listeria therapy | | Asplenia / complement deficiency | Encapsulated organisms, especially meningococcus/pneumococcus | Higher invasive-disease risk | | Cochlear implant / CSF leak | Pneumococcus | Recurrent meningitis risk; vaccination/prevention critical | | Neurosurgery / CSF shunt | Staphylococci, resistant gram-negative bacilli | Not a standard community-acquired regimen; use healthcare-associated CNS infection guidance | #### Risk factors - Extremes of age - Asplenia or hyposplenia - Complement deficiency or complement-inhibitor therapy - HIV or other immunocompromise - Alcohol use disorder - Diabetes and chronic disease - Otitis, mastoiditis, sinusitis, pneumonia - Basilar skull fracture or CSF leak - Cochlear implant - Recent neurosurgery or CSF device - Crowded living environments for meningococcal transmission - Under-immunization --- ## Pathophysiology The disease usually follows: **nasopharyngeal colonization or local infection → mucosal invasion/bacteremia → crossing of the blood–brain/CSF barriers → bacterial replication in CSF → intense host inflammatory response → endothelial injury and blood–brain barrier disruption → vasogenic/cytotoxic/interstitial edema + impaired CSF flow + vasculitis/thrombosis → increased intracranial pressure and reduced cerebral perfusion.** Bacterial cell-wall products trigger cytokines and neutrophilic inflammation. Complications arise not only from bacterial burden but also from the inflammatory response, which is why appropriately timed corticosteroids can reduce selected neurologic sequelae. --- ## Clinical presentation ### Classic adult features - Fever - Severe headache - Neck stiffness - Altered mental status - Photophobia - Nausea/vomiting The “classic triad” of fever, neck stiffness, and altered consciousness is **not sensitive enough to rule out disease when incomplete**. #### Additional features - Seizure - Focal neurologic deficit - Cranial nerve palsy - Reduced GCS - Petechial or purpuric rash - Shock/DIC - Limb pain or rapidly progressive sepsis in meningococcal disease #### Infants and children Presentation may be nonspecific: irritability, poor feeding, lethargy, high-pitched cry, fever or hypothermia, vomiting, seizures, bulging fontanelle, abnormal tone. #### Older or immunocompromised adults Fever and meningeal signs may be muted. New delirium, sepsis, seizure, or unexplained decline may dominate. --- ## Red flags requiring immediate resuscitation / ICU-level concern - GCS ≤9 or rapidly declining consciousness - Recurrent/prolonged seizure - Abnormal pupils or posturing - Focal neurologic deficit - Shock, rising lactate, DIC - Purpura fulminans / rapidly spreading non-blanching rash - Respiratory failure - Signs of impending herniation - Severe hyponatremia or other metabolic complication --- ## Initial assessment and “what to do next” | Component | Assessment | Interpretation | Immediate action | Anticipate deterioration | |---|---|---|---|---| | A — Airway | GCS, protective reflexes, vomiting | Airway loss risk | Airway support/intubation when indicated | Aspiration, herniation physiology | | B — Breathing | RR, SpO₂, work of breathing | Sepsis, aspiration, pulmonary complication | Oxygen/ventilation as needed | Fatigue, ARDS | | C — Circulation | HR, BP, perfusion, rash, lactate | Septic shock/DIC | IV/IO access, sepsis resuscitation | Refractory shock, adrenal hemorrhage | | D — Disability | GCS, pupils, focal deficit, seizure, glucose | Raised ICP, stroke mimic, hypoglycemia | Treat seizure/glucose; decide LP safety | Herniation, status epilepticus | | E — Exposure | Rash, infection source, trauma/CSF leak | Meningococcus, source clue | Droplet precautions if suspected meningococcus; source management | Rapid purpura/DIC | --- ## Diagnostic strategy ### Blood tests before antibiotics when feasible NICE recommends the following in suspected bacterial meningitis:[3] - Blood culture - WBC with neutrophils - CRP, or procalcitonin if CRP unavailable - Blood glucose - Whole-blood diagnostic PCR including meningococcal and pneumococcal targets where available - HIV testing according to local policy Do **not** rule out meningitis because WBC, CRP, or procalcitonin is normal.[3] Additional tests often include electrolytes, renal/liver profile, lactate, coagulation studies, and type/screen if severe DIC or critical illness is present. --- ## Lumbar puncture: do it early, but safely NICE states that LP should be performed before antibiotics **unless it is unsafe or would cause a clinically significant delay**. If antibiotics have already been started, perform LP as soon as safely possible.[3] ### Stabilize before LP Treat/stabilize these first:[3] - Unprotected airway - Respiratory compromise - Shock - Uncontrolled seizures - Bleeding risk ### Do not perform immediate LP when there is - Extensive/rapidly spreading purpura - Infection at the LP site - Risk factors for an evolving intracranial space-occupying lesion - Clinical signs suggesting dangerous raised ICP requiring imaging first --- ## CT before lumbar puncture: NOT routine NICE explicitly advises **against routine neuroimaging before LP**.[3,4] #### Image before LP when there is - Risk of an evolving space-occupying lesion - New focal neurologic features, including seizure or posturing - Abnormal pupillary reactions - **GCS ≤9** - Progressive sustained or rapid fall in consciousness[3] #### Critical sequence when imaging is required **Bloods → antibiotics (and dexamethasone when indicated) → stabilization → neuroimaging → LP when safe.** ⚠ **Common trap:** “Possible meningitis = CT first.” This delays antibiotics and is not recommended for most patients. --- ## CSF investigations NICE recommends:[3] - RBC and WBC count with differential - Total protein - CSF glucose **with paired blood glucose** to calculate CSF:blood glucose ratio - Gram stain - Culture and antimicrobial susceptibility - PCR for relevant pathogens Store remaining CSF for additional testing if needed.[3] ### Typical CSF patterns | Feature | Bacterial | Viral | TB/fungal (typical) | |---|---|---|---| | Opening pressure | Often high | Normal or mildly high | Often high | | WBC | High, usually neutrophilic | Lymphocytic | Lymphocytic/mononuclear | | Protein | High | Mild–moderately high | High | | Glucose | Low | Usually normal | Low | | CSF:blood glucose ratio | Reduced | Usually preserved | Reduced | | Gram stain/culture | May identify organism | Negative for bacteria | Specialized stains/culture/PCR | **Exceptions are common.** Early bacterial disease can be less neutrophilic; partially treated bacterial meningitis can have altered CSF findings; immunocompromised patients can have weak pleocytosis. --- ## Empiric antibiotics ### STANDARD OF CARE: treatment must not wait NICE recommends IV antibiotics as soon as bacterial meningitis is suspected, **within 1 hour of hospital arrival**.[3] #### UK/NICE approach Before the organism is known:[3] - **Ceftriaxone** at the highest meningitis dose recommended by formulary/local guidance - If ceftriaxone is contraindicated, consider **cefotaxime** - Add **IV amoxicillin** when there are risk factors for *Listeria monocytogenes* NICE does **not** recommend routine aciclovir unless herpes simplex encephalitis is strongly suspected.[3] #### Common adult meningitis doses used internationally These are common adult regimens; always verify local guidance, renal function, body size, allergy and resistance patterns: | Drug | Common adult meningitis dosing | Role | |---|---:|---| | Ceftriaxone | **2 g IV every 12 h** (or total 4 g/day in some protocols) | Core empiric agent / pneumococcus, meningococcus, Hib coverage | | Ampicillin / amoxicillin | **2 g IV every 4 h** (local protocols may vary) | *Listeria* coverage | | Vancomycin | Weight- and renal-function based; dose/monitor to local AUC or trough protocol | Added in many North American regimens for resistant pneumococcus | | Dexamethasone | **10 mg IV every 6 h** in adults | Adjunct, ideally before/with first antibiotic | #### U.S./North American vs UK/WHO nuance Many North American empiric adult protocols use **vancomycin + a third-generation cephalosporin**, adding ampicillin when Listeria risk is present because of concern for cephalosporin-resistant pneumococci. NICE uses ceftriaxone (or cefotaxime) as its core empiric regimen and recommends specialist input for resistance risks.[3] **Do not blindly merge regimens.** Use the guideline adopted in your jurisdiction and local pneumococcal susceptibility data. --- ## Dexamethasone NICE recommends IV dexamethasone for people **over 3 months** with strongly suspected or confirmed bacterial meningitis.[3] #### Timing - Give **with or before the first antibiotic dose if possible**. - Do **not** delay antibiotics to administer dexamethasone. - If delayed by <12 hours after antibiotics, NICE advises giving it as soon as possible; if >12 hours late, obtain infection-specialist advice.[3] #### Adult dose A widely used adult regimen, supported by the landmark randomized trial and common clinical guidance, is **dexamethasone 10 mg IV every 6 hours for 4 days**.[5] #### Continue or stop when organism known NICE recommends:[3] - **Continue** if *S. pneumoniae* or *H. influenzae* type b - **Stop** for other identified organisms - If no organism is identified, seek infection-specialist advice #### Why timing matters Antibiotic-induced bacterial lysis can amplify meningeal inflammation. Steroids are most useful when present before or at the onset of this inflammatory burst. --- ## Pathogen-specific treatment and duration Exact definitive therapy depends on susceptibility and jurisdiction. | Organism | Typical targeted approach | NICE duration concept | |---|---|---| | *N. meningitidis* | Ceftriaxone/cefotaxime; penicillin/ampicillin if susceptibility proven in some systems | **5 days** if recovered[3] | | *S. pneumoniae* | Ceftriaxone/cefotaxime ± vancomycin depending susceptibility/local resistance | **10 days** if recovered[3] | | Hib | Ceftriaxone/cefotaxime | **7 days**, extend to 10 if not recovered[3] | | Group B streptococcus | Ceftriaxone/cefotaxime; specialist input | **14 days** if recovered[3] | | *Listeria monocytogenes* | Ampicillin/amoxicillin-based therapy; specialist guidance | Often prolonged, commonly ~21 days depending disease/response | | Gram-negative bacilli | Susceptibility-guided 3rd/4th-gen cephalosporin or other agent | Often ~21 days; specialist management | NICE states that when CSF suggests bacterial meningitis but blood culture/PCR are negative, initial antibiotics can be continued for **10 days**, stopping if recovered or seeking specialist advice if not.[3] --- ## Meningococcal disease Meningococcal infection may present as meningitis, meningococcemia, or both. ### Clues - Rapidly progressive sepsis - Petechiae/purpura - Limb pain - Shock - DIC - Meningism may be absent in bloodstream-predominant disease #### Infection control Use appropriate **droplet precautions** for suspected meningococcal disease according to local infection-prevention policy. #### Treatment CDC guidance updated in 2026 states empiric treatment should include an extended-spectrum cephalosporin such as **ceftriaxone or cefotaxime**. Once susceptibility is known, penicillin or ampicillin may be used when susceptible.[6] #### Public-health actions Urgently notify public health according to jurisdiction. Close contacts may require chemoprophylaxis, and vaccination may be required depending on serogroup/outbreak context. ★ **Important:** Ceftriaxone treatment effectively clears carriage after a dose; if treatment used cefotaxime or penicillin/ampicillin, additional eradication therapy may be required before discharge according to CDC guidance.[6] --- ## Supportive and critical care ### Sepsis / shock Treat according to current sepsis principles: - Rapid IV/IO access - Lactate when indicated - Appropriate fluids with repeated reassessment - Norepinephrine for persistent vasodilatory shock when indicated - Source-directed antimicrobial therapy - Organ support ### Fluids NICE advises **not routinely restricting fluids below maintenance needs** in bacterial meningitis.[3] ⚠ **Common trap:** Historic reflex fluid restriction can worsen perfusion. Correct true SIADH/hyponatremia thoughtfully, but do not impose routine dehydration. ### Intracranial pressure NICE advises against routine glycerol and against routine use of osmotic agents such as mannitol or hypertonic saline for all meningitis patients.[3] Osmotherapy is reserved for selected patients with suspected impending herniation/raised ICP under critical-care/neurospecialist guidance. General neuroprotective principles include: - Avoid hypoxemia - Avoid hypotension - Treat fever and seizures - Elevate head of bed in selected patients - Maintain appropriate ventilation; avoid unnecessary prolonged hyperventilation - Urgent neurocritical care when herniation is suspected ### Seizures Treat status epilepticus promptly with standard protocols. Persistent altered consciousness may require EEG to detect nonconvulsive seizures. --- ## Complications ### Acute neurologic - Raised ICP / cerebral edema - Brain herniation - Seizures/status epilepticus - Ischemic stroke from vasculitis/thrombosis - Cerebral venous thrombosis - Hydrocephalus - Subdural effusion/empyema - Cranial neuropathies ### Systemic - Septic shock - DIC - Purpura fulminans - Acute kidney injury - ARDS - Waterhouse–Friderichsen syndrome in fulminant meningococcemia ### Long-term WHO highlights long-term complications in approximately **20%** of bacterial meningitis survivors.[1] Important sequelae: - Sensorineural hearing loss - Cognitive impairment - Epilepsy - Motor deficits - Visual/cranial nerve deficits - Learning/behavioral problems in children - Psychological sequelae and reduced quality of life --- ## Hearing and follow-up All survivors require structured assessment for neurologic and functional sequelae. Hearing evaluation is especially important after pneumococcal/Hib disease and in children, because hearing loss can be clinically silent initially but profoundly affect development. Follow-up should address: - Audiology - Cognitive and neurologic function - Seizure recurrence - Rehabilitation needs - Vaccination status - Evaluation for predisposing CSF leak, asplenia, complement deficiency, cochlear implant issues, or immune deficiency when clinically indicated --- ## Prevention ### Vaccination Major prevention tools include: - Pneumococcal vaccination - Hib vaccination - Meningococcal ACWY vaccination - Meningococcal B vaccination in indicated populations Schedules vary by age, country, risk group, and evolving public-health recommendations. ### Meningococcal contact prophylaxis Close contacts and people exposed directly to oral/respiratory secretions can require antibiotic prophylaxis. CDC options include rifampin, ciprofloxacin, or ceftriaxone, with selection based on age, pregnancy, resistance, and local public-health advice.[6] --- ## Special populations ### Immunocompromised / older adult Have a lower threshold for *Listeria* coverage and for atypical presentation. Consider broader differential: cryptococcal, TB, fungal, viral, malignant, and drug-related meningitis. ### Pregnancy *Listeria* risk is important. Antibiotic and prophylaxis choices should be coordinated with infectious disease and obstetrics. ### Asplenia / complement inhibitor therapy High risk of invasive encapsulated organisms. Prevention with vaccination and education about urgent fever management is essential. ### Cochlear implants / CSF leak Recurrent pneumococcal meningitis risk may be elevated. Investigate anatomical predisposition and ensure appropriate vaccination. ### Neurosurgical patients Do not use a routine community-acquired pathway. Post-craniotomy, shunts, drains, and penetrating trauma raise concern for staphylococci and resistant gram-negative bacilli; use healthcare-associated ventriculitis/meningitis guidance. --- ## Important mimics and alternative diagnoses | Condition | Clues | Key discriminator | |---|---|---| | Viral meningitis | Often less toxic, normal glucose | PCR; clinical course | | HSV encephalitis | Altered behavior, focal seizures, temporal signs | Brain MRI + CSF HSV PCR; empiric aciclovir when strongly suspected | | TB meningitis | Subacute course, cranial neuropathies, low glucose | TB testing, imaging, epidemiology | | Cryptococcal meningitis | HIV/immunocompromise, high opening pressure | CSF cryptococcal antigen | | Subarachnoid hemorrhage | Thunderclap headache | CT ± LP for blood/xanthochromia | | Brain abscess | Focal deficit, seizures, source infection | MRI/CT; LP may be unsafe/unhelpful | | Autoimmune encephalitis | Psychiatric symptoms, seizures, dyskinesia | CSF/serology/EEG/MRI | | Drug-induced aseptic meningitis | Temporal medication relationship | Exclusion + history | --- ## Diagnostic / management algorithm ```text Fever/headache/neck stiffness/AMS/seizure/rash → suspect meningitis ↓ ABC stabilization ↓ Blood cultures + CBC/CRP(or PCT) + glucose + chemistries ± PCR ↓ Is immediate LP safe, and can it occur without significant antibiotic delay? ├── YES → LP: cells/diff, protein, CSF glucose + paired blood glucose, │ Gram stain, culture/susceptibility, PCR │ ↓ │ IV antibiotics immediately + dexamethasone with/before first dose │ └── NO → IV antibiotics immediately + dexamethasone when indicated ↓ Does patient meet imaging-before-LP criteria? ├── YES → stabilize + CT/MRI → LP when safe └── NO → LP as soon as safely feasible Then: Gram stain/PCR/culture + susceptibility → narrow therapy Assess seizures/ICP/shock continuously Meningococcus? → droplet precautions + public health + contact management Recovery → hearing + neurologic follow-up + prevention evaluation ``` --- ## Acute management checklist - [ ] ABCs; treat hypoxemia, shock, uncontrolled seizures - [ ] Droplet precautions if meningococcal disease suspected - [ ] Blood cultures before antibiotics if this does not delay therapy - [ ] CBC, CRP/PCT, blood glucose, chemistries; lactate/coagulation if ill - [ ] LP immediately if safe and feasible - [ ] **No routine CT before LP** - [ ] If focal signs, abnormal pupils, GCS ≤9, rapid consciousness decline, or mass-lesion risk → image first, but **antibiotics first** - [ ] IV ceftriaxone-based empiric therapy per local guideline - [ ] Add Listeria coverage when risk factors present - [ ] Add vancomycin when required by local pneumococcal-resistance policy (common North American practice) - [ ] Dexamethasone with/before first antibiotic dose if indicated; never delay antibiotics - [ ] CSF cell count/diff, protein, glucose + paired serum glucose, Gram stain, culture, PCR - [ ] Narrow regimen and define duration once organism/susceptibility known - [ ] Monitor sodium, renal function, neurologic status, seizures, perfusion - [ ] Public-health notification/contact prophylaxis if meningococcus - [ ] Arrange hearing and neurologic follow-up --- ## Common pitfalls | Pitfall | Why dangerous | Better approach | |---|---|---| | Waiting for the classic triad | Triad is insensitive | Use overall syndrome and risk state | | CT on every suspected case | Delays LP and antibiotics | CT only for defined risk features | | Delaying antibiotics until after imaging/LP | Mortality/neurologic harm | Treat within 1 hour; diagnostics only if they do not delay | | Normal CRP/WBC “rules out” disease | False reassurance | NICE explicitly warns against this | | No paired serum glucose with CSF | Loses useful CSF:blood ratio | Draw blood glucose with LP | | Forgetting Listeria in older/immunocompromised patient | Cephalosporins do not reliably cover Listeria | Add ampicillin/amoxicillin when risk present | | Routine aciclovir for all meningitis | Unnecessary treatment | Use when HSV encephalitis is strongly suspected | | Giving dexamethasone hours later without thought | Benefit depends on timing/pathogen | Give with/before antibiotics; follow guideline if delayed | | Routine fluid restriction | May worsen perfusion | Maintain appropriate fluids; treat specific sodium disorder | | Missing meningococcal public-health actions | Preventable secondary cases | Isolation + urgent notification + contact prophylaxis | --- ## Current guideline changes ### WHO 2025 guideline + 2026 practical manual WHO issued its **first global guideline on meningitis diagnosis, treatment and care on 10 April 2025**, covering community-acquired acute meningitis across ages >1 month and including diagnostics, antibiotics, adjunctive therapy, supportive care, and long-term effects.[1] On **26 May 2026**, WHO released a practical manual with job aids and decision algorithms to operationalize these recommendations.[2] **STANDARD OF CARE implications:** rapid recognition, prompt effective antibiotics, rational LP/imaging, supportive care, and active management of sequelae. ### NICE NG240 (2024) Important UK practice points include:[3] - Antibiotics within 1 hour of hospital arrival - Ceftriaxone as core empiric therapy; add amoxicillin for Listeria risk - No routine CT before LP - Explicit criteria for imaging-first cases - Dexamethasone for strongly suspected/confirmed bacterial meningitis >3 months, with/before antibiotics if possible - Pathogen-specific durations including 5 days for meningococcus and 10 days for pneumococcus if recovered - No routine fluid restriction - No routine osmotic therapy ### Jurisdiction differences The major difference clinicians encounter is empiric pneumococcal resistance coverage: **many U.S. protocols add vancomycin**, whereas NICE does not use routine vancomycin in its baseline community-acquired regimen. This reflects antimicrobial-resistance assumptions and local epidemiology, not a fundamental disagreement that therapy should be broad enough to cover likely resistant pathogens. --- ## Evidence classification ### STANDARD OF CARE - Immediate IV antibiotics once bacterial meningitis is suspected - LP as early as safely possible - Selective, not routine, neuroimaging before LP - Dexamethasone given before/with first antibiotic dose in appropriate patients - Pathogen-directed narrowing - Public-health intervention for meningococcal disease - Hearing/neurologic follow-up ### EMERGING EVIDENCE - Faster multiplex molecular diagnostics and metagenomic testing - Biomarker-assisted bacterial-vs-viral differentiation - Improved neurocritical-care phenotyping and individualized ICP management - Better long-term neurocognitive rehabilitation strategies ### EXPERIMENTAL / INVESTIGATIONAL Novel host-directed anti-inflammatory strategies, precision diagnostics, and new adjunctive therapies should not replace immediate antibiotics, dexamethasone when indicated, and basic neurocritical/sepsis care outside trials. --- ## Exam-focused review ### Step 1 / Foundations Know: - Bacterial entry into CSF and inflammatory BBB injury - Neutrophilic CSF response - Low CSF glucose from bacterial/leukocyte metabolism and impaired transport - Raised protein from BBB disruption - Encapsulated organisms and splenic/complement defense ### Step 2 CK Classic next-best-step questions: - Suspected meningitis, stable, no focal deficit/ICP sign → **LP promptly**, then immediate antibiotics; do not order routine CT. - Focal deficit or GCS ≤9 → **blood cultures + antibiotics first**, image, then LP when safe. - Older/immunocompromised adult → add **Listeria coverage**. - Meningococcal rash/sepsis → antibiotics immediately + droplet precautions + public health. ### Step 3 / Resident Add: - Empiric regimen selection by age/immunity/resistance - Dexamethasone timing - Interpretation of partially treated CSF - Sepsis/ICP/seizure management - Contact prophylaxis - De-escalation and duration ### MRCP / ABIM / boards Expect nuance on: - CT-before-LP criteria - Pneumococcal vs meningococcal durations - Dexamethasone continuation by organism - Listeria risk - CSF patterns and exceptions - Public-health management --- ## Original MCQs #### 1. A 23-year-old has fever, headache, photophobia and neck stiffness. GCS 15, no focal deficits, normal pupils, stable vital signs. Best next step? A. CT head before any other test B. Lumbar puncture promptly if immediately available and safe, without delaying antibiotics C. MRI brain D. Discharge with oral antibiotics **Answer: B.** Routine neuroimaging before LP is not recommended. LP should precede antibiotics only when safe and when it will not cause clinically significant delay. #### 2. A 67-year-old with suspected meningitis has a new right arm weakness and GCS 8. Best sequence? A. LP first, then antibiotics B. CT first, then blood cultures, then antibiotics C. Blood cultures + immediate antibiotics/dexamethasone as indicated + stabilization, then imaging, then LP when safe D. EEG only **Answer: C.** Focal deficit/GCS ≤9 are imaging-before-LP criteria, but antibiotics must not wait for the scan. #### 3. Which additional empiric coverage is especially important in an older or cell-mediated immunocompromised adult? A. Metronidazole for *C. difficile* B. Ampicillin/amoxicillin for *Listeria monocytogenes* C. Oseltamivir D. Doxycycline for Lyme disease in every case **Answer: B.** Listeria is not reliably covered by third-generation cephalosporins. #### 4. When should dexamethasone ideally be administered? A. Only after culture confirms pneumococcus B. 24 hours after antibiotics C. Before or with the first antibiotic dose D. Only at discharge **Answer: C.** Benefit is linked to blunting the inflammatory response triggered by bacterial lysis. #### 5. CSF shows 2,400 WBC/µL (90% neutrophils), high protein, low glucose, and a low CSF:serum glucose ratio. Most likely diagnosis? A. Typical bacterial meningitis B. Migraine C. Normal CSF D. Isolated peripheral neuropathy **Answer: A.** This is the classic bacterial pattern, although real cases can vary. --- ## References 1. World Health Organization. **WHO guidelines on meningitis diagnosis, treatment and care.** 10 April 2025. ISBN **978-92-4-010804-2**. https://www.who.int/publications/i/item/9789240108042 2. World Health Organization. **WHO practical manual on meningitis diagnosis, treatment and care.** 26 May 2026. ISBN **978-92-4-012102-7**. https://www.who.int/publications/i/item/9789240121027 3. National Institute for Health and Care Excellence (NICE). **Meningitis (bacterial) and meningococcal disease: recognition, diagnosis and management. NG240.** Published March 2024. https://www.nice.org.uk/guidance/ng240 4. NICE. **Rationale and impact: neuroimaging and lumbar puncture, NG240.** 2024. https://www.nice.org.uk/guidance/ng240/chapter/rationale-and-impact 5. de Gans J, van de Beek D; European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators. **Dexamethasone in adults with bacterial meningitis.** *N Engl J Med.* 2002;347:1549–1556. doi: **10.1056/NEJMoa021334**. 6. Centers for Disease Control and Prevention. **Clinical Guidance for Meningococcal Disease.** Updated 2026. https://www.cdc.gov/meningococcal/hcp/clinical-guidance/index.html 7. Médecins Sans Frontières. **Bacterial meningitis — Medical Guidelines.** Current online edition. https://medicalguidelines.msf.org/en/viewport/CG/english/bacterial-meningitis-16689907.html 8. World Health Organization. **Defeating meningitis by 2030: a global road map.** Geneva: WHO; 2021. https://www.who.int/initiatives/defeating-meningitis-by-2030 --- **Review trigger:** Re-review when WHO, NICE, CDC, IDSA/ESCMID, or national antimicrobial guidance changes empiric regimens, dexamethasone recommendations, LP/imaging criteria, meningococcal prophylaxis, or vaccine schedules.1b:Tc5b9,## One-minute summary **Acute pulmonary embolism (PE)** is obstruction of the pulmonary arterial circulation by thrombus, usually arising from deep veins of the legs or pelvis. The immediate threat is **acute right-ventricular (RV) pressure overload**, which may progress from compensated RV strain to reduced left-ventricular preload, systemic hypotension, obstructive shock, and cardiac arrest. The 2026 multisociety AHA/ACC guideline introduces a new **A–E Acute PE Clinical Category system** that moves beyond the older low/intermediate/high-risk labels. [1,3] - **A:** incidental/asymptomatic PE. - **B:** symptomatic PE with a low clinical severity score. - **C:** symptomatic PE with an elevated clinical severity score, stratified by RV dysfunction and cardiac biomarkers. - **D:** incipient cardiopulmonary failure, such as transient hypotension or normotensive shock/end-organ hypoperfusion. - **E:** established cardiopulmonary failure, including persistent hypotension with shock or cardiac arrest. [1,3] The core clinical pathway is: **Estimate pretest probability → use PERC only in truly very-low-risk patients → use D-dimer when appropriate → CTPA (or V/Q when needed) → confirm PE → immediately risk-stratify → anticoagulate unless contraindicated → identify who is safe for outpatient care vs who needs monitored hospitalization or advanced reperfusion.** High-yield 2026 practice points: [1] - A negative **age-adjusted D-dimer** can avoid imaging in appropriate low/intermediate-probability patients over age 50. - **CTPA** is the usual first-line definitive test; V/Q scanning is valuable when iodinated contrast is unsuitable. - **LMWH is preferred over UFH** when initial parenteral anticoagulation is required in most C1–E1 patients. - **DOACs are preferred over vitamin K antagonists** for most eligible adults. - Advanced reperfusion therapies are **reasonable in Category E1** and may be considered in **D1–D2**; routine systemic thrombolysis is harmful in A–C2. - **PERT assessment is recommended** for higher-risk categories to improve care delivery. - Follow-up should include anticoagulation review and screening for persistent dyspnea/functional limitation and chronic thromboembolic pulmonary disease (CTEPD). Two major randomized trials published after the guideline evidence cutoff—**HI-PEITHO** and **PRAGUE-26**—showed fewer early clinical deterioration events with catheter-directed thrombolysis in selected intermediate-risk/intermediate-high-risk patients. These are important **emerging evidence**, but they do not yet justify indiscriminate catheter treatment of all normotensive PE. [15,16] --- ## 1. Definition and core concepts ### 1.1 Definition Acute PE is partial or complete obstruction of one or more pulmonary arteries by embolic material, overwhelmingly thrombus. Most thrombi originate from lower-extremity or pelvic deep venous thrombosis (DVT), although upper-extremity catheter-associated thrombosis and other sources occur. #### Anatomical terms - **Subsegmental PE:** clot limited to subsegmental pulmonary arteries. - **Segmental PE:** segmental branch involvement. - **Lobar/proximal PE:** lobar or main pulmonary artery involvement. - **Saddle PE:** thrombus straddling the pulmonary artery bifurcation. This is an anatomical description, **not a severity category**; a saddle embolus can be hemodynamically stable, while a smaller clot burden can be fatal in a patient with limited cardiopulmonary reserve. ### 1.2 The main physiological problem is RV afterload Abrupt obstruction plus vasoconstriction increases pulmonary vascular resistance. The RV, a thin-walled chamber adapted to a low-pressure system, dilates under acute pressure load. RV wall tension and oxygen demand rise while coronary perfusion can fall. The interventricular septum shifts toward the LV, impairing LV filling. Cardiac output declines; systemic hypotension further reduces RV coronary perfusion, creating a vicious cycle. #### Hemodynamic spiral ```text Pulmonary arterial obstruction ↓ ↑ Pulmonary vascular resistance ↓ RV dilation + ↑ wall stress ↓ Tricuspid regurgitation + septal shift ↓ ↓ LV preload and cardiac output ↓ Hypotension / systemic hypoperfusion ↓ ↓ RV coronary perfusion ↓ RV ischemia → worsening RV failure ↓ Obstructive shock / cardiac arrest ``` This explains why **blood pressure alone is insufficient** for risk assessment: a patient may be normotensive while already developing low cardiac output, lactate elevation, acute kidney injury, oliguria, or altered mental status. --- ## 2. Epidemiology and risk factors PE is a major manifestation of venous thromboembolism (VTE). Risk follows **Virchow’s triad**: venous stasis, endothelial injury, and hypercoagulability. ### 2.1 Major provoking factors #### Strong transient factors - Major surgery, especially orthopedic/pelvic surgery - Major trauma or fracture - Prolonged hospitalization or severe acute illness - Marked immobilization - Pregnancy and postpartum state #### Persistent factors - Active cancer - Chronic inflammatory or autoimmune disease - Persistent immobility - Antiphospholipid syndrome (APS) - Selected inherited thrombophilias #### Common acquired risk factors - Prior VTE - Increasing age - Obesity - Estrogen-containing hormonal therapy - Heart failure - Chronic lung disease - Nephrotic syndrome - Central venous catheters - Myeloproliferative neoplasms ### 2.2 Provoked vs unprovoked is clinically useful—but imperfect The traditional binary distinction helps estimate recurrence risk, but risk is a continuum. A PE after major surgery is very different from a PE after a minor transient trigger in a patient with obesity, inflammatory disease, and previous VTE. Modern duration decisions increasingly incorporate **persistent risk, recurrence risk, bleeding risk, and patient preference**, rather than relying on a single label. [1,17] --- ## 3. Clinical presentation PE ranges from asymptomatic incidental imaging findings to sudden cardiac arrest. ### 3.1 Common symptoms - Acute or progressive dyspnea - Pleuritic chest pain - Nonpleuritic chest pressure - Cough - Hemoptysis - Syncope or presyncope - Palpitations - Unilateral leg pain/swelling ### 3.2 Common signs - Tachycardia - Tachypnea - Hypoxemia - Fever (usually low grade if present) - Unilateral leg swelling/tenderness - Elevated JVP - RV heave - Loud P2 - New tricuspid regurgitation murmur - Hypotension, cool extremities, altered mental status, oliguria in advanced disease ### 3.3 Red flags for impending deterioration - Syncope with persistent tachycardia or borderline BP - SBP near 90–110 mm Hg or a meaningful fall from baseline - Rising lactate - Increasing oxygen requirement - RR ≥30/min - New confusion - Oliguria/acute kidney injury - Marked RV dilation or reduced RV function - Elevated troponin with RV dysfunction - Free-floating right-heart clot-in-transit A normotensive patient with several of these features may be in **incipient cardiopulmonary failure**, not “stable PE.” [1] --- ## 4. Differential diagnosis | Condition | Features that overlap | Clues favoring alternative diagnosis | |---|---|---| | Acute coronary syndrome | Chest pain, dyspnea, troponin elevation | Ischemic ECG pattern/coronary syndrome; remember PE can also elevate troponin | | Pneumonia | Dyspnea, pleuritic pain, fever, hypoxemia | Focal infiltrate, infectious prodrome; PE and pneumonia can coexist | | Pneumothorax | Sudden dyspnea/pleuritic pain | Unilateral absent breath sounds, pleural line on ultrasound, CXR findings | | Acute aortic syndrome | Chest/back pain, syncope | Pulse/BP differential, aortic imaging findings | | Acute heart failure | Dyspnea, hypoxemia, elevated BNP | Pulmonary edema, LV dysfunction; PE can precipitate RV-predominant failure | | Pericarditis | Pleuritic pain | Positional pain, diffuse ST elevation/PR depression | | COPD/asthma exacerbation | Dyspnea, tachycardia | Wheeze/known disease; PE remains possible if unexplained deterioration | | Panic/hyperventilation | Dyspnea, chest discomfort | Diagnosis of exclusion when PE probability is nontrivial | | Sepsis | Tachycardia, hypotension, lactate elevation | Infection source; PE can coexist with systemic illness | --- ## 5. Diagnostic strategy: probability before testing The biggest diagnostic error is ordering tests without first considering **pretest probability**. D-dimer is useful when disease probability is low enough that a negative result safely rules out PE; it is inefficient in high-probability patients and frequently positive in hospitalized, elderly, pregnant, inflammatory, postoperative, and cancer populations. ### 5.1 Step 1 — Is the patient unstable? If the patient has shock or cardiac arrest and PE is strongly suspected: - Resuscitate immediately. - Obtain bedside echocardiography/POCUS if it can be performed without delaying treatment. - Obtain CTPA if the patient can safely reach CT. - Activate PERT/critical care/interventional/surgical resources early. Echocardiography is **not recommended to confirm or exclude PE in a stable suspected case**, because RV findings are not sufficiently specific; its major value is risk stratification and bedside assessment in unstable patients. [1] ### 5.2 Step 2 — Estimate clinical probability Validated tools include: - Wells score - Revised Geneva score - Clinical gestalt in experienced hands The practical purpose is to classify the patient into a pathway where PE is: - very unlikely, - low/intermediate probability, or - high probability. ### 5.3 PERC — only for very-low-risk patients The **Pulmonary Embolism Rule-out Criteria (PERC)** may allow no further testing when clinician-estimated pretest probability is very low (commonly <15%) and **all 8 criteria are absent**: 1. Age ≥50 years 2. Pulse ≥100/min 3. SpO₂ <95% 4. Unilateral leg swelling 5. Hemoptysis 6. Estrogen use 7. Prior DVT/PE 8. Recent surgery or trauma requiring hospitalization If any PERC criterion is positive, PERC does not rule out PE—move to a D-dimer or imaging strategy depending on pretest probability. [1] **Pitfall:** PERC is not a “PE score” to apply indiscriminately to every patient with chest pain. ### 5.4 D-dimer #### Standard threshold A highly sensitive D-dimer below the assay cutoff (often 500 µg/L FEU) excludes PE in appropriately selected low/intermediate-probability patients. #### Age-adjusted D-dimer For patients older than 50 years, a commonly validated threshold is: **Age × 10 µg/L FEU** Example: age 72 → negative threshold <720 µg/L FEU, assuming the assay uses compatible FEU units. [1,5] Always confirm laboratory units and assay convention; D-dimer units are not interchangeable. ### 5.5 YEARS strategy The YEARS algorithm assesses three items: - Clinical signs of DVT - Hemoptysis - PE judged the most likely diagnosis Typical thresholds: [6] - **No YEARS items:** D-dimer <1000 µg/L FEU can exclude PE. - **≥1 YEARS item:** D-dimer <500 µg/L FEU can exclude PE. A pregnancy-adapted YEARS pathway is an evidence-based option in selected pregnant patients and can reduce unnecessary chest imaging when applied correctly. [1] --- ## 6. Imaging and bedside tests ### 6.1 CTPA **CT pulmonary angiography (CTPA)** is the standard definitive imaging test in most adults. It provides: - direct visualization of emboli; - clot location/burden; - alternative diagnoses; - RV/LV ratio for risk stratification; - signs of chronic thromboembolic disease. The 2026 guideline recommends **numerical RV/LV ratio reporting** rather than subjective RV enlargement when CTPA is performed. [1] ### 6.2 Ventilation-perfusion (V/Q) scanning V/Q scanning is especially useful when: - iodinated contrast is contraindicated; - severe contrast allergy exists; - renal function makes CTPA undesirable in the individual context; - radiation distribution is a concern, including selected pregnancy pathways; - chest radiograph is relatively normal, improving interpretability. ### 6.3 Compression ultrasonography Finding a proximal DVT can establish VTE and may support treatment when chest imaging is impossible or undesirable, but a negative leg ultrasound does **not** exclude PE. ### 6.4 Echocardiography In confirmed PE, echo assists risk assessment by evaluating RV size/function and pulmonary pressures. The August 11, 2026 correction to the AHA/ACC guideline clarified right-heart echocardiographic parameters. [2] | Parameter | Abnormal / concerning threshold or finding | |---|---| | RV/LV end-diastolic ratio | >0.9 abnormal in the guideline framework | | RV end-diastolic dimension | ≥30 mm in an RV-focused parasternal long-axis view, or basal RV EDD ≥41 mm in an apical RV-focused view | | TAPSE | ≤1.7 cm abnormal | | TDI S′ velocity | ≤9.5 cm/s abnormal | | TR velocity | ≥2.9 m/s suggests pulmonary hypertension | | Other findings | McConnell sign, paradoxical septal motion, reduced IVC respirophasic collapse, elevated estimated RV systolic pressure | No single echo sign proves PE; interpret the overall pattern and clinical context. ### 6.5 ECG Possible findings: - Sinus tachycardia (most common) - Right bundle-branch block - Right-axis deviation - Anterior T-wave inversion - S1Q3T3 pattern - Atrial arrhythmias **S1Q3T3 is neither sensitive nor specific** and should never be used to rule in or rule out PE. ### 6.6 Laboratory biomarkers #### Troponin Elevation reflects RV myocardial injury and is prognostic in confirmed PE; it is not specific for PE. #### BNP/NT-proBNP Reflects RV wall stress and helps risk stratification. #### Lactate Elevated lactate can reveal low-output physiology/end-organ hypoperfusion despite preserved blood pressure. In the 2026 framework it is important for identifying **normotensive shock / Category D2 physiology**. [1,3] --- ## 7. 2026 AHA/ACC Acute PE Clinical Categories The new classification is designed to connect bedside severity directly to disposition and therapy. [1,3] | Category | Clinical picture | Key objective features | Typical disposition/implication | |---|---|---|---| | **A** | Subclinical/incidental, asymptomatic PE | No PE symptoms | Usually outpatient if no separate reason for admission | | **B** | Symptomatic, low clinical severity | Low PESI/sPESI/Hestia profile | Early discharge/outpatient treatment often appropriate | | **C1** | Symptomatic, elevated clinical severity | Normal RV and normal cardiac biomarkers | Hospitalization; anticoagulation | | **C2** | Symptomatic, elevated severity | RV abnormality **or** ≥1 abnormal cardiac biomarker | Hospitalization; closer monitoring | | **C3** | Symptomatic, elevated severity | RV abnormality **and** ≥1 abnormal cardiac biomarker | Higher deterioration risk; monitored care/PERT consideration | | **D1** | Incipient cardiopulmonary failure | Transient/recurrent hypotension or relative hypotension without established end-organ hypoperfusion | High-acuity monitored care; advanced therapy may be considered | | **D2** | Incipient failure with hypoperfusion | Transient/relative hypotension plus end-organ hypoperfusion such as lactate >2 mmol/L, AKI, oliguria, mental-status change, low cardiac index/MAP | Critical-care level; PERT; advanced reperfusion consideration | | **E1** | Cardiopulmonary failure | Persistent/recurrent hypotension with cardiogenic shock | Advanced therapy is generally reasonable if feasible | | **E2** | Refractory failure / arrest | Refractory shock or cardiac arrest | Resuscitation, systemic lysis when appropriate, ECMO/advanced rescue in expert centers | #### Respiratory modifier “R” The 2026 system adds an **R modifier** when significant respiratory compromise is present. In Category C this includes features such as SpO₂ <90%, RR ≥30/min, or supplemental oxygen requirement; more advanced categories use higher oxygen/ventilatory support thresholds. [1,3] #### Why this is better than “massive/submassive” The older terminology can hide important gradients. A normotensive patient with RV dysfunction, positive troponin, lactate 4 mmol/L, oliguria, and escalating oxygen needs is much sicker than another normotensive patient with mild RV dilation alone. The A–E framework explicitly identifies that difference. --- ## 8. PESI, sPESI, and Hestia ### 8.1 PESI/sPESI These scores estimate short-term mortality and are most helpful when considering outpatient management. A **sPESI of 0** identifies a low-risk group when other outpatient criteria are satisfied. ### 8.2 Hestia criteria Hestia is a pragmatic exclusion checklist for outpatient treatment, incorporating hemodynamic instability, oxygen requirement, bleeding risk, severe pain needing IV medication, renal/liver failure, pregnancy, social barriers, and other practical concerns. **Important:** A low PESI/sPESI does not override clinical judgment, RV dysfunction, active bleeding, inability to obtain medication, severe comorbidity, or inadequate follow-up. --- ## 9. Acute management algorithm ```text Suspected PE ↓ Is patient in shock / peri-arrest? ├─ Yes → ABC resuscitation + bedside echo if useful + urgent CTPA if feasible │ → therapeutic anticoagulation if not contraindicated │ → PERT / ICU / interventional / surgical activation │ → consider immediate reperfusion strategy └─ No ↓ Estimate pretest probability ↓ Very low risk + all PERC negative? ├─ Yes → PE ruled out without D-dimer └─ No ↓ Low/intermediate probability → D-dimer strategy ├─ Negative → PE excluded └─ Positive → CTPA (or V/Q) High probability → proceed directly to imaging ↓ PE confirmed ↓ Anticoagulate unless contraindicated ↓ Risk stratify: PESI/sPESI/Hestia + RV + troponin/BNP + lactate + BP/perfusion + oxygen ↓ A/B → outpatient/early discharge when safe C → hospitalize; monitor intensity by C1/C2/C3 + R D → critical/step-down care + PERT; consider advanced reperfusion E → shock/arrest pathway; advanced reperfusion ± VA-ECMO in expert center ``` --- ## 10. Anticoagulation — STANDARD OF CARE Unless there is an absolute contraindication, **therapeutic anticoagulation should be initiated for acute PE** to reduce recurrence and death. [1] ### 10.1 Initial parenteral anticoagulation When parenteral therapy is required, the 2026 guideline recommends **LMWH over UFH** for most patients in Categories C1–E1 because LMWH reduces recurrent VTE and major bleeding. [1] #### When UFH can still be advantageous UFH is often selected when: - an immediate invasive procedure or thrombolysis is likely and rapid titration/reversal is desired; - severe renal dysfunction limits LMWH use; - extremely unstable physiology requires a highly controllable infusion; - local advanced-therapy protocols specify UFH. Do not treat “UFH for every high-risk PE” as a universal rule; the 2026 guideline explicitly prefers LMWH when parenteral therapy is required in most eligible patients. [1] ### 10.2 DOACs For eligible adults, **DOACs are recommended over vitamin K antagonists**. [1] Common evidence-based VTE regimens: [4] | Drug | Initial phase | Primary treatment | |---|---|---| | **Apixaban** | 10 mg PO twice daily for 7 days | 5 mg PO twice daily | | **Rivaroxaban** | 15 mg PO twice daily with food for 21 days | 20 mg PO once daily with food | | **Dabigatran** | Requires ≥5 days of parenteral anticoagulation first | 150 mg PO twice daily | | **Edoxaban** | Requires ≥5 days of parenteral anticoagulation first | 60 mg PO once daily in standard eligible patients | **Safety note:** renal function, hepatic function, age, weight, drug interactions, bleeding risk, and product-specific labeling must be checked before prescribing. Edoxaban and other agents have label-defined dose modifications that should not be guessed from memory. #### 2026 comparative evidence The COBRRA randomized trial compared apixaban with rivaroxaban for acute VTE and found clinically relevant bleeding at 3 months in **3.3% vs 7.1%**, respectively, with similar VTE efficacy. The 2026 ACC scientific statement therefore suggests apixaban may be preferred for many patients when either agent is otherwise suitable. This is an evolving comparative-practice consideration rather than a declaration that rivaroxaban is inappropriate. [4,18] ### 10.3 Empiric anticoagulation before imaging If PE is strongly suspected, imaging is delayed, and bleeding risk is low, the 2026 guideline states that therapeutic anticoagulation may be beneficial in patients with a clinical picture equivalent to **Category C2 or higher**. [1] This is not an excuse to anticoagulate every low-probability patient before diagnosis. --- ## 11. Reperfusion and advanced therapies The central decision is whether anticoagulation alone is sufficient or whether clot removal/lysis is needed because the RV is failing or likely to fail. ### 11.1 Systemic thrombolysis #### Standard regimen The most commonly used FDA-approved alteplase regimen for PE is: **Alteplase 100 mg IV over 2 hours.** [1] Lower-dose systemic regimens may be considered in selected circumstances to reduce bleeding, but evidence is less robust and protocols vary. [1] #### Who should receive systemic thrombolysis? | 2026 category | Systemic lysis position | |---|---| | A–C1 | **Harm / do not use routinely** | | C2 | **Harm / do not use routinely** | | C3 | Benefit uncertain; highly individualized if advanced therapy is contemplated | | D1–D2 | May be considered with acceptable bleeding risk | | E1–E2 | Reasonable when advanced reperfusion is indicated and bleeding risk is acceptable | This explains a classic board principle: **routine fibrinolysis for a normotensive intermediate-risk PE is not standard care**. The PEITHO trial reduced hemodynamic decompensation but increased major extracranial bleeding and hemorrhagic stroke with systemic tenecteplase, without a mortality advantage sufficient to justify routine use. [7] ### 11.2 Catheter-directed thrombolysis (CDT) The 2026 guideline position, based largely on pre-2025 evidence, is: [1,3] - **E1:** CDT + anticoagulation is reasonable. - **D1–D2:** may be considered when advanced therapy is being considered. - **C2–C3:** benefit vs anticoagulation alone was considered uncertain. - **A–C1:** routine catheter intervention has no benefit. This field changed materially after the evidence cutoff; see HI-PEITHO and PRAGUE-26 below. ### 11.3 Mechanical thrombectomy For catheter-based mechanical thrombectomy (MT): [1] - **E1:** reasonable compared with anticoagulation alone. - **D1–D2:** may be considered. - **C2–C3:** benefit remains uncertain for routine use. - A–C1: not routinely beneficial. A major attraction is avoiding or minimizing thrombolytic exposure, but access-site bleeding, pulmonary-artery injury, blood loss, procedural deterioration, and device-specific complications remain possible. ### 11.4 Surgical embolectomy Surgical embolectomy is reasonable in **E1** and may be considered in selected **D1–D2** patients, especially when thrombolysis is contraindicated or has failed and surgical expertise is immediately available. [1] It can also be attractive for: - central clot burden with shock; - right-heart clot-in-transit; - selected patients with a patent foramen ovale and systemic embolic risk; - situations where catheter options are unsuitable. ### 11.5 Right-heart clot-in-transit A free-floating right-atrial/RV thrombus is uncommon but high risk. In Categories C3–E2, the 2026 guideline considers advanced therapy reasonable over anticoagulation alone to reduce deterioration, although randomized comparative evidence is limited. [1] ### 11.6 VA-ECMO **Venoarterial extracorporeal membrane oxygenation (VA-ECMO)** can provide circulatory/oxygenation support in refractory cardiogenic shock or arrest from PE in expert centers. It is usually a bridge to recovery or definitive reperfusion, not treatment of the clot itself. [1] --- ## 12. Hemodynamic and respiratory support ### 12.1 Oxygen and ventilation Correct hypoxemia while avoiding interventions that precipitate RV collapse. Positive-pressure ventilation can reduce venous return and increase RV afterload. In a tenuous PE patient, deep sedation and intubation may trigger sudden cardiovascular collapse. If intubation is unavoidable: - involve experienced airway/critical-care staff; - optimize preload and vasopressor support before induction; - use hemodynamically cautious induction; - minimize excessive PEEP/airway pressures while maintaining adequate oxygenation. ### 12.2 Fluids The failing RV is preload-sensitive but easily overdistended. Large indiscriminate fluid boluses can worsen septal shift and cardiac output. Use **small, reassessed fluid challenges** only when true preload deficiency is plausible. Stop if JVP/RV dilation worsens without improved perfusion. ### 12.3 Vasopressors/inotropes In obstructive shock, vasopressor support is often required to restore systemic pressure and RV coronary perfusion while definitive reperfusion is arranged. Norepinephrine is commonly favored in shock physiology; inotropes may be added for severe low-output RV failure under critical-care guidance. The goal is not simply a numeric blood pressure—it is restoration of **organ perfusion** without excessive tachycardia or RV oxygen demand. --- ## 13. Disposition ### Category A The 2026 guideline states that asymptomatic Category A patients can generally be discharged rather than hospitalized, assuming no competing reason for admission and a safe treatment/follow-up plan. [1,3] ### Category B Early discharge/outpatient treatment is generally recommended if: - low PESI/sPESI/Hestia risk; - no oxygen/hemodynamic instability; - no major bleeding risk; - reliable access to anticoagulation; - adequate home support and follow-up. ### Categories C–E Hospitalization is recommended because of increasing deterioration risk. Level of care escalates with: - C3 physiology; - respiratory modifier; - lactate/end-organ hypoperfusion; - transient hypotension; - escalating oxygen; - shock/arrest. --- ## 14. Duration of anticoagulation The 2026 guideline defines: - **Initial treatment phase:** first **3–6 months**. - **Extended phase:** beyond 6 months. [1] ### 14.1 Major reversible provoking factor If a first PE occurred because of a **major reversible risk factor** and that factor has resolved, stopping anticoagulation after the initial treatment phase is generally recommended when recurrence risk is low and there is no other indication for continued therapy. [1] ### 14.2 No major reversible factor / unprovoked PE Extended anticoagulation is recommended for many patients after a first PE without a major reversible risk factor, assuming bleeding risk is acceptable. [1] ### 14.3 Persistent risk factor Continued anticoagulation is generally recommended while a clinically important persistent risk factor remains, with periodic reassessment. ### 14.4 Extended-dose options Evidence-supported extended regimens include: [4] - **Apixaban 2.5 mg twice daily** after completion of primary therapy in selected patients. - **Rivaroxaban 10 mg once daily** in selected patients. - Full-dose regimens remain appropriate in patients with higher recurrence risk. Duration is a shared decision balancing recurrence risk, bleeding risk, comorbidity, preference, cost, adherence, and changing life circumstances. --- ## 15. Special populations ### 15.1 Pregnancy Pregnancy changes both diagnostic and treatment decisions. - Pregnancy-adapted YEARS can reduce imaging in appropriate patients. - **LMWH is generally preferred** for treatment during pregnancy. - UFH may be useful close to delivery or when rapid reversibility is needed. - DOACs should not be used routinely in pregnancy and are generally avoided during breastfeeding because of insufficient safety data. - Warfarin is teratogenic and is generally avoided during pregnancy, although there are narrow specialist-managed exceptions in mechanical-valve care unrelated to routine PE treatment. A pregnant patient with shock from PE requires immediate multidisciplinary maternal resuscitation; maternal survival is the priority. ### 15.2 Cancer-associated PE DOACs or LMWH are effective. Choice depends on: - bleeding risk, particularly GI/GU mucosal tumors; - thrombocytopenia; - drug interactions; - vomiting/malabsorption; - renal function; - planned procedures; - patient preference. The 2026 ACC statement notes a strong evidence base for apixaban in cancer-associated thrombosis, while LMWH remains valuable in high-bleeding-risk or interaction-heavy situations. [4] ### 15.3 Antiphospholipid syndrome For thrombotic APS—especially high-risk/triple-positive APS—**vitamin K antagonist therapy is generally preferred over DOACs** because DOACs have been associated with excess recurrent arterial/thrombotic events in high-risk APS. ### 15.4 Severe renal disease Renal clearance differs substantially among DOACs. Severe CKD/dialysis requires drug-specific labeling and specialist judgment; do not apply standard VTE doses automatically. UFH or carefully selected anticoagulant strategies may be preferable in some patients. ### 15.5 Liver disease Hepatic dysfunction affects both coagulation and DOAC metabolism. The 2026 ACC statement supports individualized use by Child-Pugh class and notes that evidence becomes very limited in severe hepatic disease. [4] ### 15.6 Isolated subsegmental PE Management is individualized. Important questions include: - Is the diagnosis radiographically certain? - Is there proximal DVT? - Is the patient pregnant, has active cancer, prior VTE, impaired cardiopulmonary reserve, or persistent provoking risk? - Is the patient symptomatic? - Can reliable surveillance be performed? Selected low-risk patients with isolated subsegmental PE and no DVT may be candidates for surveillance in some guidelines, but many patients have enough recurrence risk to favor anticoagulation. This requires careful shared decision-making rather than an automatic rule. [17] --- ## 16. Complications | Complication | Clinical clues | Management principle | |---|---|---| | Obstructive shock | Hypotension, cool skin, oliguria, lactate rise, confusion | Vasopressor support + urgent reperfusion strategy | | Cardiac arrest | Often PEA | CPR + high suspicion; systemic lysis/ECMO/advanced reperfusion as appropriate | | Recurrent PE | New dyspnea/chest pain/syncope while treated | Verify adherence/dose/interactions; repeat imaging; consider alternate anticoagulant class | | Major bleeding | GI, intracranial, retroperitoneal, access-site | Stop/reverse anticoagulation as appropriate; hemostasis; reassess thrombosis risk | | Chronic thromboembolic pulmonary disease | Persistent dyspnea/exercise intolerance ≥3 months | Structured evaluation; V/Q often central to CTEPD workup; refer expert center | | CTEPH | Persistent pulmonary hypertension from chronic organized thrombi | Expert-center evaluation for endarterectomy/BPA/medical therapy | | Post-PE syndrome | Dyspnea, reduced exercise capacity despite no CTEPH | Exclude CTEPD, cardiac/pulmonary disease; rehabilitation and targeted management | --- ## 17. Follow-up after acute PE The acute event is not over at discharge. The 2026 guideline recommends: [1,3] - early post-discharge contact/assessment can be helpful, often within the first week; - a clinical visit **by about 3 months** to assess symptoms, bleeding, adherence, provoking factors, and anticoagulation duration; - asking about **dyspnea and functional limitation for at least 1 year** after PE; - evaluating persistent symptoms after ≥3 months of anticoagulation for CTEPD/CTEPH or other causes. #### Follow-up checklist - Confirm anticoagulant and correct dose. - Check renal/hepatic function when relevant. - Review bleeding and interacting medications. - Clarify whether the PE was major-provoked, minor-provoked, persistent-risk, or unprovoked. - Decide initial vs extended anticoagulation plan. - Encourage safe early ambulation. - Review cancer screening based on age/standard indications rather than indiscriminate extensive testing. - Ask about exertional dyspnea, exercise intolerance, chest pain, syncope, edema. --- ## 18. Common pitfalls | Pitfall | Why it is dangerous | Better approach | |---|---|---| | Ordering D-dimer in a high-probability patient | Delays definitive imaging and is likely positive | Proceed directly to imaging | | Using PERC in moderate-risk patients | PERC was designed for very-low pretest probability | Estimate probability first | | Treating saddle location as synonymous with “massive PE” | Anatomy ≠ physiology | Risk-stratify by BP, perfusion, RV function, biomarkers, respiratory status | | Calling a normotensive patient “stable” despite lactate/AKI | Misses normotensive shock | Assess end-organ perfusion and Category D physiology | | Giving liters of crystalloid for RV shock | Can overdistend RV and reduce LV filling | Small, reassessed bolus only if preload-responsive; vasopressors/reperfusion early | | Intubating a tenuous PE patient without hemodynamic preparation | Induction/positive pressure can precipitate arrest | Optimize pressors/preload; expert airway strategy | | Routine systemic lysis in intermediate-risk PE | Major bleeding/ICH risk | Anticoagulation + monitoring; select advanced therapy by deterioration risk | | Assuming all catheter devices have equal RCT evidence | Devices/mechanisms differ | Apply trial data only to comparable technology/populations | | Stopping anticoagulation automatically at 3 months | Recurrence risk may remain high | Reassess provoking/persistent factors and bleeding risk | | Ignoring persistent dyspnea after PE | Misses CTEPD/CTEPH | Structured follow-up for at least a year | --- ## 19. Acute management checklist ### First 10–30 minutes - [ ] ABC assessment; identify shock/arrest. - [ ] Oxygen as needed; avoid unplanned deep sedation/intubation in RV failure. - [ ] IV access, ECG, continuous monitoring. - [ ] Determine pretest probability if diagnosis is not established. - [ ] PERC only if truly very low risk. - [ ] D-dimer if low/intermediate probability and appropriate. - [ ] CTPA or V/Q when indicated. - [ ] If confirmed: assess BP trend, oxygen requirement, RV, troponin/BNP, lactate, renal perfusion/mental status. - [ ] Start therapeutic anticoagulation unless contraindicated. ### After confirmation - [ ] Assign AHA/ACC category A–E ± respiratory modifier. - [ ] A/B: assess outpatient safety using PESI/sPESI/Hestia and social/bleeding factors. - [ ] C–E: hospitalize. - [ ] C3/D/E: early PERT/critical-care discussion. - [ ] D/E: prepare reperfusion strategy before deterioration becomes arrest. ### Shock pathway - [ ] Avoid excessive fluids. - [ ] Vasopressor support as needed. - [ ] Activate PERT/interventional/surgical teams. - [ ] Choose systemic thrombolysis vs CDT vs MT vs surgery based on category, bleeding risk, anatomy, timing, expertise. - [ ] Consider VA-ECMO in refractory shock/arrest in an experienced system. --- ## 20. Exam-focused review ### Foundation / Step 1 Know the physiology: **PE → ↑ pulmonary vascular resistance → RV dilation/failure → septal shift → ↓ LV preload → ↓ cardiac output → obstructive shock.** Understand Virchow’s triad and why tachycardia/hypoxemia arise. ### Step 2 CK High-yield sequence: - very-low probability + PERC negative → no testing; - low/intermediate probability → D-dimer; - high probability or positive D-dimer → imaging; - confirmed PE → anticoagulate and risk-stratify; - shock → reperfusion, not anticoagulation alone. ### Step 3 / resident Know: - age-adjusted D-dimer = age × 10 µg/L FEU after age 50 in validated pathways; - apixaban 10 mg BID ×7 days → 5 mg BID; - rivaroxaban 15 mg BID ×21 days → 20 mg daily; - dabigatran/edoxaban require ≥5 days initial parenteral anticoagulation; - systemic alteplase regimen commonly 100 mg over 2 hours; - LMWH is now guideline-preferred over UFH when initial parenteral therapy is needed in most eligible patients; - hemodynamic status plus RV/biomarkers/perfusion determines treatment—not clot size alone. ### MRCP/ABIM/board level Be able to distinguish: - low-risk PE vs C3 PE vs D2 normotensive shock; - thrombolysis indications vs contraindications; - outpatient eligibility vs admission; - recurrence-risk decisions for anticoagulation duration; - CTEPD/CTEPH follow-up; - guideline-standard advanced therapy vs post-guideline emerging CDT evidence. --- ## 21. Original MCQs #### Question 1 A 34-year-old woman with pleuritic chest pain has clinician-estimated PE probability <10%. HR 82, SpO₂ 98%, no hemoptysis, no estrogen use, no prior VTE, no unilateral swelling, no recent surgery/trauma. What is the best next step? A. CTPA B. D-dimer in all cases C. Apply PERC; if all negative, no further PE testing D. Start apixaban empirically **Answer: C.** PERC can exclude PE without D-dimer in genuinely very-low-risk patients when all criteria are negative. [1] #### Question 2 A 74-year-old low/intermediate-probability patient has D-dimer 650 µg/L FEU. Using a validated age-adjusted strategy, which statement is most accurate? A. The result is automatically positive because it exceeds 500 B. The age-adjusted cutoff is approximately 740 µg/L FEU C. The age-adjusted cutoff is 74 µg/L D. Age adjustment is used only below age 50 **Answer: B.** For age >50, a commonly validated FEU cutoff is age ×10 µg/L, here approximately 740. [1,5] #### Question 3 A patient has confirmed PE, normal BP, elevated sPESI, RV dilation, positive troponin, lactate 4 mmol/L, oliguria, and cool extremities. Which concept is most important? A. Normal BP proves low-risk PE B. This can represent normotensive shock/incipient cardiopulmonary failure C. Troponin proves acute MI rather than PE D. The patient should be discharged on a DOAC **Answer: B.** End-organ hypoperfusion can precede persistent hypotension; this is the rationale for Category D2 physiology in the 2026 scheme. [1,3] #### Question 4 Which anticoagulation statement is correct in the 2026 guideline? A. UFH is always preferred to LMWH in acute PE B. LMWH is recommended over UFH when initial parenteral therapy is required in most C1–E1 patients C. Warfarin is preferred over DOACs for most eligible adults D. Anticoagulation should wait until all thrombophilia tests return **Answer: B.** LMWH is guideline-preferred over UFH for most patients requiring initial parenteral therapy, and DOACs are preferred over VKAs when eligible. [1] #### Question 5 Which apixaban regimen is evidence-based for acute VTE in a standard eligible adult? A. 2.5 mg BID from day 1 B. 5 mg daily C. 10 mg BID for 7 days, then 5 mg BID D. 10 mg daily after 5 days of heparin **Answer: C.** [4,9] #### Question 6 A normotensive patient has elevated clinical severity score but normal RV function and normal cardiac biomarkers. Which 2026 category best fits? A. A B. B C. C1 D. E1 **Answer: C.** C1 is symptomatic PE with elevated clinical severity but normal RV and biomarkers. [1,3] #### Question 7 Which statement about systemic thrombolysis is most accurate? A. It is routine for all RV-strain PE B. It should be used for all C2 patients C. It is reasonable in cardiopulmonary failure when bleeding risk is acceptable, but routine use in A–C2 is discouraged because of bleeding/ICH D. It is contraindicated in cardiac arrest from PE **Answer: C.** The benefit-risk balance changes sharply as the patient progresses toward D/E physiology. [1] #### Question 8 Which statement best reflects the 2026 catheter-directed thrombolysis evidence? A. The February guideline already incorporated PRAGUE-26 B. HI-PEITHO and PRAGUE-26 were published after the guideline evidence cutoff and suggest reduced early deterioration in selected intermediate-risk patients C. Catheter treatment is now mandatory for every C3 patient D. All catheter devices are clinically interchangeable **Answer: B.** The trials are important emerging evidence but require careful population/device-specific interpretation. [1,15,16] --- ## 22. Current guideline changes and recent research ### STANDARD OF CARE — 2026 multisociety guideline #### New A–E severity categories The 2026 guideline’s most visible conceptual change is replacement of broad low/intermediate/high-risk terminology with categories that integrate symptoms, clinical severity scores, RV function, biomarkers, respiratory compromise, transient hypotension, and end-organ perfusion. [1,3] #### PERT Multidisciplinary PERT assessment is recommended for patients at increased risk of adverse outcomes (Categories C–E) to improve care delivery. [1,3] #### Anticoagulation - LMWH over UFH when parenteral therapy is required in most eligible patients. - DOAC over VKA for most eligible patients. - Extended anticoagulation for first PE without a major reversible factor and for persistent risk factors when bleeding risk permits. [1] #### Advanced therapy - **E1:** systemic thrombolysis, CDT, MT, and surgical embolectomy are reasonable options depending on patient/center factors. - **D1–D2:** these therapies may be considered. - **A–C2:** routine systemic thrombolysis is harmful; routine advanced catheter/surgical treatment is not supported. - **C3:** evidence for routine advanced reperfusion remained uncertain in the guideline. [1,3] #### Follow-up Screen for post-PE symptoms and functional limitation for at least one year; evaluate persistent dyspnea for CTEPD/CTEPH. [1,3] --- ### EMERGING EVIDENCE — HI-PEITHO (2026) HI-PEITHO randomized **544** selected intermediate-risk PE patients with RV/LV ratio ≥1.0, elevated troponin, and at least two indicators of cardiorespiratory distress to ultrasound-facilitated catheter-directed fibrinolysis plus anticoagulation or anticoagulation alone. [15] The primary composite of PE-related death, cardiorespiratory decompensation/collapse, or symptomatic recurrent PE occurred in **4.0% vs 10.3%**. The benefit was driven mainly by less clinical deterioration; major bleeding was numerically higher but not statistically different, and no intracranial hemorrhage occurred in either group. [15] #### Interpretation This trial lowers the threshold for discussing CDT in **carefully selected higher-severity normotensive PE**, but it does not prove that every patient with RV strain should undergo an intervention. The population was highly selected, and results should not be generalized to every catheter device or lower-risk PE. [15] --- ### EMERGING EVIDENCE — PRAGUE-26 (published August 31, 2026) PRAGUE-26 randomized **558** patients with intermediate-high-risk PE to catheter-directed alteplase thrombolysis plus anticoagulation or anticoagulation alone. [16] The 7-day composite of death, recurrent PE, or cardiorespiratory decompensation/collapse occurred in: - **0.7%** with catheter-directed thrombolysis - **6.8%** with standard care - RR **0.10** (95% CI 0.02–0.44; P<0.001). [16] The difference was again driven largely by prevention of decompensation. Clinically relevant bleeding was similar (**4.6% vs 5.0%**); major bleeding was **1.4% vs 2.2%**; intracranial hemorrhage occurred in **0.7% vs 0%**. [16] #### Why this matters PRAGUE-26 was published **after** the February 2026 guideline and therefore is not incorporated into its formal recommendations. Along with HI-PEITHO, it substantially strengthens the clinical-outcome evidence for selected catheter-directed thrombolysis in intermediate-high-risk PE. #### What it does not prove - It does not establish catheter treatment as mandatory for all intermediate-risk PE. - It does not establish equivalence across all devices, lytic doses, or center expertise. - It does not eliminate intracranial or major bleeding risk. - Mortality benefit remains less certain than reduction in deterioration. A future guideline update may change the formal category-C recommendations. --- ### EXPERIMENTAL / INVESTIGATIONAL Areas still requiring stronger evidence include: - selecting the exact C2/C3 phenotype that gains net benefit from early catheter intervention; - head-to-head CDT vs mechanical thrombectomy; - optimal lytic dose and device strategy; - validated biomarkers of impending RV collapse; - long-term effects of acute catheter therapy on post-PE syndrome/CTEPH; - artificial-intelligence–assisted CT triage without compromising clinical judgment. --- ## 23. Guideline differences: 2019 ESC vs 2026 AHA/ACC The 2019 ESC guideline stratifies PE as low risk, intermediate-low, intermediate-high, or high risk using hemodynamic status, PESI/sPESI, RV dysfunction, and troponin. [8] The 2026 AHA/ACC system maps broadly as follows: [3] | 2019 ESC concept | Approximate 2026 AHA/ACC counterpart | |---|---| | Low risk | B (and some A) | | Intermediate-low | C1–C2 | | Intermediate-high | C3 | | Hemodynamic instability/high risk | D–E, with greater granularity for transient hypotension, normotensive shock, established shock, and arrest | They are not perfectly interchangeable. The 2026 model explicitly emphasizes **end-organ perfusion and respiratory modifiers**, allowing earlier recognition of impending failure. --- ## 24. References 1. Creager MA, Barnes GD, Giri J, et al. **2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults.** *J Am Coll Cardiol*. 2026;87(13):1626-1710. doi: **10.1016/j.jacc.2025.11.005**. https://www.jacc.org/doi/10.1016/j.jacc.2025.11.005 2. **Correction: 2026 Acute Pulmonary Embolism Guideline.** *J Am Coll Cardiol*. 2026;88(6):713. Published August 11, 2026. doi: **10.1016/j.jacc.2026.06.033**. https://www.jacc.org/doi/10.1016/j.jacc.2026.06.033 3. Dudzinski DM, Cibotti-Sun M, Moore MM. **2026 Acute Pulmonary Embolism Guideline-at-a-Glance.** *J Am Coll Cardiol*. 2026;87(13):1620-1625. doi: **10.1016/j.jacc.2025.12.023**. 4. Kumbhani DJ, Armbruster AL, Cheng RK, et al. **Direct Oral Anticoagulants in Primary and Secondary Prevention of Thrombotic Events: 2026 ACC Scientific Statement.** *J Am Coll Cardiol*. 2026. doi: **10.1016/j.jacc.2026.05.033**. 5. Righini M, Van Es J, Den Exter PL, et al. **Age-Adjusted D-Dimer Cutoff Levels to Rule Out Pulmonary Embolism: The ADJUST-UNLIKELY/ADJUST-PE strategy evidence.** *JAMA*. 2014;311:1117-1124. doi: **10.1001/jama.2014.2135**. 6. van der Hulle T, Cheung WY, Kooij S, et al. **Simplified diagnostic management of suspected pulmonary embolism (the YEARS study).** *Lancet*. 2017;390:289-297. doi: **10.1016/S0140-6736(17)30885-1**. 7. Meyer G, Vicaut E, Danays T, et al. **Fibrinolysis for Patients with Intermediate-Risk Pulmonary Embolism (PEITHO).** *N Engl J Med*. 2014;370:1402-1411. doi: **10.1056/NEJMoa1302097**. 8. Konstantinides SV, Meyer G, Becattini C, et al. **2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the ERS.** *Eur Heart J*. 2020;41:543-603. doi: **10.1093/eurheartj/ehz405**. 9. Agnelli G, Buller HR, Cohen A, et al. **Oral Apixaban for the Treatment of Acute Venous Thromboembolism (AMPLIFY).** *N Engl J Med*. 2013;369:799-808. doi: **10.1056/NEJMoa1302507**. 10. EINSTEIN–PE Investigators. **Oral Rivaroxaban for the Treatment of Symptomatic Pulmonary Embolism.** *N Engl J Med*. 2012;366:1287-1297. doi: **10.1056/NEJMoa1113572**. 11. Schulman S, Kearon C, Kakkar AK, et al. **Dabigatran versus Warfarin in the Treatment of Acute Venous Thromboembolism.** *N Engl J Med*. 2009;361:2342-2352. doi: **10.1056/NEJMoa0906598**. 12. Hokusai-VTE Investigators. **Edoxaban versus Warfarin for the Treatment of Symptomatic Venous Thromboembolism.** *N Engl J Med*. 2013;369:1406-1415. doi: **10.1056/NEJMoa1306638**. 13. Stevens SM, Woller SC, Kreuziger LB, et al. **Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report.** *Chest*. 2021;160:e545-e608. doi: **10.1016/j.chest.2021.07.055**. 14. Kearon C, Akl EA, Ornelas J, et al. **Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report.** *Chest*. 2016;149:315-352. doi: **10.1016/j.chest.2015.11.026**. 15. Rosenfield K, Klok FA, Piazza G, et al; HI-PEITHO Investigators. **Ultrasound-Facilitated, Catheter-Directed Fibrinolysis for Acute Pulmonary Embolism.** *N Engl J Med*. 2026;394(20):1979-1990. doi: **10.1056/NEJMoa2516567**. PMID: **41910345**. 16. Clarençon F, et al. **Catheter-Directed Thrombolysis in Intermediate-High-Risk Pulmonary Embolism (PRAGUE-26).** *N Engl J Med*. Published August 31, 2026. doi: **10.1056/NEJMoa2608012**. 17. Piazza G, et al. **Extended-Duration Low-Intensity Apixaban to Prevent Recurrence in High-Risk Patients With Provoked Venous Thromboembolism (HI-PRO).** *N Engl J Med*. 2025. See ACC ESC 2025 report for trial details. 18. Castellucci LA, Chen VM, Kovacs MJ, et al. **Bleeding Risk with Apixaban vs Rivaroxaban in Acute Venous Thromboembolism (COBRRA).** *N Engl J Med*. 2026;394(11):1051-1060. doi: **10.1056/NEJMoa2510703**. 19. Piazza G, Cushman M. **AHA/ACC Acute Pulmonary Embolism Clinical Categories: Perspectives on Development and Application.** *J Am Coll Cardiol*. 2026;87(13):1554-1557. doi: **10.1016/j.jacc.2025.11.053**. --- ### Bottom line The modern approach to PE is not “diagnose clot and give anticoagulation.” It is a sequence of **probability-based diagnosis, immediate anticoagulation when appropriate, and rapid physiologic risk stratification of the right ventricle and systemic perfusion**. The 2026 AHA/ACC categories make a critical distinction between compensated RV strain and **incipient cardiopulmonary failure**, where early escalation may prevent arrest. Anticoagulation remains the foundation of treatment; advanced reperfusion is standard in shock-level disease and increasingly evidence-supported in carefully selected higher-risk normotensive patients, but treatment must remain individualized to bleeding risk, physiology, anatomy, and local expertise.1c:T9ea4,## One-minute summary **Sepsis** is life-threatening organ dysfunction caused by a dysregulated host response to infection. Operationally, Sepsis-3 identifies organ dysfunction as an acute increase in **SOFA score ≥2 points** attributable to infection.[1] **Septic shock** is a high-risk subset in which, despite adequate volume resuscitation, the patient requires vasopressors to maintain **MAP ≥65 mm Hg** and has **lactate >2 mmol/L**; this phenotype carries very high mortality.[1] The bedside priority is not to “prove sepsis” before acting. In a patient with suspected infection and organ dysfunction, **recognize physiologic threat, stabilize ABCs, obtain cultures without materially delaying therapy, give appropriate antimicrobials when infection is sufficiently likely, restore perfusion, identify the source, and obtain source control early**.[2,3] ### Core treatment sequence 1. **Recognize possible infection + organ dysfunction.** 2. **Assess airway, breathing, circulation and perfusion immediately.** 3. **Measure lactate** when sepsis is suspected; interpret in context.[2] 4. **Obtain appropriate cultures** before antibiotics if this does not cause a clinically important delay. 5. **Antimicrobials:** immediately, ideally within 1 hour for septic shock or high-likelihood sepsis; in possible sepsis without shock, perform rapid diagnostic assessment and treat within 3 hours if concern persists.[2] 6. **Fluids:** crystalloids are first line; balanced crystalloids are generally preferred. For sepsis-induced hypoperfusion/septic shock, SSC suggests at least **30 mL/kg IV crystalloid within the first 3 hours**, followed by frequent reassessment rather than automatic repeated boluses.[2] 7. **Vasopressor:** **norepinephrine** is first line; initial MAP target is usually **65 mm Hg**.[2] 8. **Source control:** drain, debride, remove infected hardware/device, or operate as soon as medically and logistically practical when indicated.[2] 9. **Reassess repeatedly** using mentation, capillary refill, urine output, lactate trend, hemodynamics, dynamic fluid-responsiveness measures and organ function.[2] ★ **High yield:** qSOFA is **not recommended as a stand-alone screening test** for sepsis or septic shock.[2] --- ## Definition and classification ### Sepsis Sepsis-3 defines sepsis as **life-threatening organ dysfunction caused by a dysregulated host response to infection**.[1] Operationally: - Suspected or confirmed infection **plus** - Acute increase in **SOFA ≥2 points** attributable to the infection.[1] The old term **“severe sepsis”** is redundant under Sepsis-3; once organ dysfunction is present, the patient has sepsis.[1] ### Septic shock Septic shock is a subset of sepsis with profound circulatory, cellular and metabolic abnormalities. Sepsis-3 clinical criteria are:[1] - Vasopressor requirement to maintain **MAP ≥65 mm Hg**, **and** - Serum lactate **>2 mmol/L (18 mg/dL)**, - Despite adequate volume resuscitation. ### Infection without sepsis A patient can have pneumonia, pyelonephritis, cellulitis or another infection without meeting criteria for sepsis if there is no infection-related life-threatening organ dysfunction. Conversely, organ dysfunction may be the first clue to an occult infection. --- ## Epidemiology and risk factors Sepsis is among the leading causes of critical illness and infection-related death worldwide. Risk rises substantially with age, frailty, chronic disease and impaired host defense.[1,2] Important risk factors include: - Age extremes and advanced age - Immunosuppression: neutropenia, hematologic malignancy, solid-organ or stem-cell transplantation, high-dose corticosteroids, biologic immunomodulators, advanced HIV - Diabetes mellitus - Chronic kidney disease and dialysis - Cirrhosis - Chronic lung disease - Cancer - Recent surgery or invasive procedures - Indwelling vascular, urinary or biliary devices - Recent hospitalization or antimicrobial exposure - Prior colonization/infection with multidrug-resistant organisms - Functional impairment, frailty, nursing-home residence - Pregnancy/postpartum state (with different physiologic thresholds and dedicated pathways) ### Common infection sources | Source | Typical clues | Important source-control question | |---|---|---| | Lung | Cough, hypoxemia, infiltrate, focal crackles | Empyema? Obstructed airway? Abscess? | | Urinary tract | Dysuria, flank pain, pyuria, hydronephrosis | Obstructed infected collecting system? | | Abdomen | Pain, ileus, peritonism, free air/fluid | Perforation, ischemia, abscess, cholangitis? | | Skin/soft tissue | Cellulitis, wound, pain, crepitus | Necrotizing infection or abscess needing surgery? | | Bloodstream/catheter | Rigors, line tenderness, no other focus | Remove infected line/device after alternate access? | | CNS | Meningism, altered consciousness, seizures | Need immediate meningitis/encephalitis pathway? | | Bone/joint | Focal pain, prosthesis, effusion | Drainage, debridement, prosthetic infection? | | Endocardium | Murmur, emboli, prosthetic valve/device | Echo, surgery/device management? | --- ## Pathophysiology Sepsis is not simply “too much inflammation.” It is a dysregulated host-pathogen interaction involving simultaneous inflammatory and immunosuppressive pathways, endothelial injury, microvascular dysfunction, coagulation abnormalities, altered cellular metabolism and organ-specific responses.[1] ### Mechanistic chain ```text Infection / pathogen products ↓ Innate immune recognition + cytokine signaling ↓ Endothelial activation and injury ↓ Vasodilation + capillary leak + altered vascular tone ↓ Relative/absolute intravascular volume deficit ↓ Microcirculatory heterogeneity + coagulation activation ↓ Impaired tissue oxygen delivery/utilization ↓ Cellular/metabolic dysfunction ↓ Organ dysfunction ± shock ``` ### Why lactate rises Elevated lactate can reflect tissue hypoperfusion and adrenergic-driven glycolysis, but it is **not a pure measure of anaerobic metabolism**. Liver dysfunction, seizures, beta-agonists, epinephrine and impaired clearance can elevate lactate. Therefore a falling lactate may support improving physiology, but a single value should never be interpreted in isolation.[2] ### Why hypotension may be late Compensatory vasoconstriction and tachycardia may preserve blood pressure early. A patient can have clinically important hypoperfusion with apparently acceptable BP; examine mentation, skin perfusion, urine output, capillary refill, lactate and trajectory. --- ## Clinical presentation There is no single sepsis phenotype. Presentation depends on source, age, comorbidity, medications and stage of illness. ### Symptoms and signs suggesting infection - Fever or hypothermia - Rigors - Cough, sputum, pleuritic pain - Dysuria, frequency, flank pain - Abdominal pain, vomiting, diarrhea - Skin/wound pain or erythema - Headache, photophobia, neck stiffness - Device-related pain or discharge - New confusion, weakness or functional decline ### Features of organ dysfunction | Organ/system | Concerning findings | |---|---| | Neurologic | Confusion, reduced GCS, delirium | | Respiratory | Tachypnea, hypoxemia, increased work of breathing, ARDS | | Cardiovascular | Hypotension, prolonged capillary refill, mottling, cool or abnormally warm peripheries | | Renal | Oliguria, rising creatinine | | Hematologic | Thrombocytopenia, DIC pattern | | Hepatic | Rising bilirubin, coagulopathy | | Metabolic | Elevated lactate, worsening acidosis | ### Red flags for immediate escalation - Airway compromise or rapidly falling consciousness - Severe hypoxemia or impending ventilatory failure - Persistent hypotension or signs of shock - Marked mottling, prolonged capillary refill, cold peripheries - Lactate significantly elevated or rising despite treatment - New oliguria/anuria - Purpura, rapidly progressive soft-tissue pain, crepitus - Meningism with altered mental state - Suspected neutropenic sepsis - Suspected obstructed infected urinary or biliary system - Severe abdominal pain/peritonism - Rapidly progressive organ dysfunction --- ## Recognition and screening ### SOFA SOFA evaluates six systems: respiratory, coagulation, liver, cardiovascular, CNS and renal function. An acute rise by **≥2 points** in the context of infection operationalizes sepsis in Sepsis-3.[1] ### qSOFA qSOFA assigns one point each for: - Respiratory rate **≥22/min** - Altered mentation - Systolic BP **≤100 mm Hg** It identifies higher-risk patients but has insufficient sensitivity as a sole screening strategy. SSC recommends **against qSOFA as the single screening tool** compared with SIRS, NEWS or MEWS.[2] ### NEWS2 and the UK approach NICE NG253, published **19 November 2025**, uses **NEWS2 plus clinical judgment** for adults aged 16 years and older who are not currently/recently pregnant. In acute hospital settings, suspected/confirmed infection with NEWS2 ≥7 is high risk; a lower total can still be high risk when a single parameter scores 3 or there are other clinical reasons for concern.[3] **Guideline difference:** Sepsis-3/SCCM use SOFA conceptually for organ dysfunction and advise against qSOFA alone; NICE emphasizes NEWS2-based risk stratification in its UK recognition pathway. These approaches are complementary rather than interchangeable. --- ## Initial assessment: a practical first 10 minutes | Component | Assess | Interpret | Immediate action | Anticipate deterioration | |---|---|---|---|---| | Airway | Patency, voice, secretions, consciousness | Loss of airway reflexes, obstruction | Suction, adjunct, airway team, definitive airway when indicated | Fatigue, encephalopathy, aspiration | | Breathing | RR, SpO₂, work, chest exam, blood gas if needed | Pneumonia, ARDS, pulmonary edema, fatigue | Oxygen to appropriate target; ventilatory support if failing | Rapid ARDS progression | | Circulation | HR, BP/MAP, cap refill, skin, urine, lactate | Shock/hypoperfusion | IV/IO access, cultures/labs, crystalloid if indicated, vasopressor if hypotension persists | Fluid overload, refractory vasoplegia | | Disability | GCS/AVPU, glucose, pupils | Sepsis encephalopathy vs mimics | Correct glucose/oxygen/perfusion; consider CNS infection/stroke/toxin | Seizures, coma | | Exposure/source | Full examination, wounds, lines, abdomen, back | Hidden source, necrotizing infection, device infection | Source-specific imaging/consult; remove triggers/devices when indicated | Need for emergency operation/drainage | --- ## Diagnostic work-up ### Core tests The exact panel is source- and severity-dependent. Common initial tests include: - CBC with differential - Electrolytes, urea/BUN, creatinine - Liver panel and bilirubin - Venous or arterial blood gas when clinically indicated - **Lactate** - Glucose - Coagulation studies - Blood cultures - Urinalysis and urine culture where relevant - Source-specific microbiology: sputum, CSF, wound, joint fluid, stool, respiratory viral PCR, etc. ### Blood cultures Obtain blood cultures before antimicrobials **when this can be done promptly and does not materially delay treatment**. Draw adequate volume and appropriate sets according to local laboratory policy. If endocarditis is suspected, follow a dedicated multi-set culture strategy. ### Imaging Use the fastest test that will meaningfully identify source or complication: - Chest radiograph or lung ultrasound - Renal ultrasound/CT for obstruction - CT abdomen/pelvis for intra-abdominal source - RUQ ultrasound or MRCP/CT for biliary source - Echocardiography for suspected endocarditis or shock phenotype - CT brain/LP pathway for CNS infection as appropriate - Soft-tissue imaging only if it will not delay surgery in suspected necrotizing infection ★ **High yield:** In suspected necrotizing fasciitis or another source requiring emergency surgery, **do not delay definitive source control for low-value imaging** when the clinical diagnosis is sufficiently concerning. --- ## Differential diagnosis: sepsis mimics | Mimic | Clues | Discriminator | |---|---|---| | Hemorrhagic shock | Bleeding, trauma, GI loss | Imaging/exam, falling Hb may lag | | Cardiogenic shock | ACS, pulmonary edema, low EF | ECG, troponin, echo | | Pulmonary embolism | Sudden dyspnea, RV strain | CTPA/echo, risk factors | | Adrenal crisis | Steroid dependence, hyponatremia/hyperkalemia | Cortisol if feasible; do not delay steroids in crisis | | Anaphylaxis | Urticaria, bronchospasm, exposure | Rapid response to IM epinephrine | | Thyroid storm | Hyperthermia, tachyarrhythmia, thyrotoxic features | Thyroid testing, clinical score | | DKA/HHS | Hyperglycemia, ketones, osmotic symptoms | Glucose/ketones/acid-base | | Drug toxicity | Exposure, toxidrome | ECG, drug levels selectively | | Malignant hyperthermia/NMS/serotonin syndrome | Drug trigger, rigidity/clonus | Medication history, neuromuscular findings | | Pancreatitis | Epigastric pain | Lipase, imaging | | HLH/cytokine syndromes | Cytopenias, extreme ferritin, organomegaly | Specialist work-up | **STANDARD OF CARE:** Continuously reassess whether infection remains the most likely diagnosis; SSC recommends stopping empiric antimicrobials if a convincing alternative diagnosis is established.[2] --- ## Management ### 1. Immediate resuscitation Sepsis and septic shock are medical emergencies; treatment and resuscitation should begin immediately.[2] #### Oxygen and ventilation Treat hypoxemia and respiratory failure according to usual critical-care principles. Sepsis-induced ARDS should receive lung-protective ventilation; prone positioning is recommended for moderate-to-severe ARDS when appropriate.[2] #### Access and monitoring - Peripheral IV access; IO if IV access is not rapidly obtainable in shock - Continuous ECG and pulse oximetry in unstable patients - Frequent or continuous BP monitoring; arterial catheter when practical in septic shock - Urine output monitoring - Serial perfusion reassessment --- ### 2. Antimicrobial therapy #### Timing SSC 2021 recommends:[2] - **Possible septic shock or high likelihood of sepsis:** give antimicrobials immediately, ideally **within 1 hour** of recognition. - **Possible sepsis without shock:** rapidly assess infectious vs noninfectious causes; if concern for infection persists, give antimicrobials **within 3 hours** of recognition. - **Low likelihood of infection without shock:** it is reasonable to defer antimicrobials while monitoring closely. NICE 2025 similarly prioritizes urgent assessment and antibiotic treatment within 1 hour for adults at high risk of severe illness or death from sepsis.[3] #### Empiric selection Choose empiric therapy according to: - Likely anatomic source - Community vs healthcare exposure - Local antibiogram - Prior microbiology/colonization - Recent antibiotics - Risk of MRSA or resistant gram-negative organisms - Immune status - Organ function and drug allergy history Do **not** use a universal “sepsis antibiotic.” The correct regimen for community-acquired pneumonia differs from obstructive pyelonephritis, cholangitis, meningitis, neutropenic sepsis or necrotizing soft-tissue infection. #### Resistant organisms SSC recommends MRSA coverage when risk is high, against routine MRSA coverage when risk is low, and against routine double gram-negative coverage in low-MDR-risk patients. Two gram-negative agents may be considered empirically when MDR risk is high, but double coverage should generally stop once susceptibilities are known.[2] #### Pharmacokinetics Critical illness changes drug volume of distribution and clearance. Use appropriate loading doses, renal/hepatic adjustment after the initial strategy as appropriate, and therapeutic drug monitoring when available. SSC favors prolonged infusion of beta-lactams for maintenance after an initial bolus.[2] #### De-escalation and duration - Review cultures and diagnosis daily. - Narrow spectrum when possible. - Shorter effective durations are generally preferred after adequate source control. - Procalcitonin may support **discontinuation** decisions when duration is uncertain, but SSC advises against using procalcitonin plus clinical evaluation to decide whether to **start** antibiotics.[2] --- ### 3. Fluid resuscitation #### Initial fluid For sepsis-induced hypoperfusion or septic shock, SSC suggests **at least 30 mL/kg IV crystalloid in the first 3 hours**.[2] This is a weak recommendation based on low-quality evidence and should not be interpreted as permission for repeated blind boluses. #### Fluid type - **Crystalloids:** first line.[2] - **Balanced crystalloids:** suggested over 0.9% saline.[2] - **Albumin:** may be considered when very large crystalloid volumes have already been required.[2] - **Hydroxyethyl starch:** avoid.[2] #### Reassessment after initial fluid Use **dynamic measures** when possible rather than static measures alone:[2] - Passive leg raise with stroke-volume/cardiac-output response - Small fluid challenge with objective response - Pulse-pressure or stroke-volume variation in appropriate ventilated patients - Bedside echocardiography Also reassess: - Capillary refill - MAP and pulse pressure - Mental status - Urine output - Mottling/skin temperature - Lung ultrasound/B-lines and respiratory status - Lactate trend #### What recent trials changed The **CLASSIC** trial in ICU septic shock found no 90-day mortality difference between restrictive and standard IV-fluid strategies after initial resuscitation.[5] The **CLOVERS** trial found no significant 90-day mortality difference between an early restrictive strategy emphasizing vasopressors and a liberal-fluid strategy in sepsis-induced hypotension.[4] **Practical interpretation:** after initial stabilization, there is no evidence that either indiscriminately liberal fluid or rigidly restrictive fluid is superior for all patients. Give fluid when there is evidence of hypoperfusion and likely fluid responsiveness; stop when benefit is unlikely or congestion emerges. --- ### 4. Vasopressors and hemodynamic targets #### First line **Norepinephrine** is first-line vasopressor therapy for septic shock.[2] A common starting infusion range is institution-specific; titrate rapidly to perfusion goals rather than waiting for central access. SSC supports short-term administration through a well-sited proximal peripheral vein when necessary rather than delaying vasopressor initiation.[2] #### MAP target Initial target **MAP 65 mm Hg** for most adults on vasopressors.[2] Individualize upward when clinically justified, for example selected patients with chronic severe hypertension and ongoing renal or neurologic hypoperfusion, while recognizing that higher targets can increase vasopressor exposure and arrhythmias. #### Second-line strategy - If MAP remains inadequate on norepinephrine, SSC suggests **adding vasopressin** rather than simply escalating norepinephrine indefinitely; guideline practice commonly adds vasopressin when norepinephrine is around **0.25–0.5 micrograms/kg/min**.[2] - If MAP is still inadequate despite norepinephrine + vasopressin, consider **epinephrine**.[2] - For cardiac dysfunction with persistent hypoperfusion despite adequate volume and BP, consider **dobutamine added to norepinephrine** or epinephrine alone.[2] #### Peripheral perfusion Capillary refill is a useful adjunct to other resuscitation endpoints. The ANDROMEDA-SHOCK trial did not show a statistically significant reduction in 28-day mortality with a capillary-refill-targeted strategy versus lactate-targeted resuscitation, but its findings supported renewed emphasis on bedside peripheral perfusion assessment.[6] --- ### 5. Source control **Source control is definitive therapy when infection persists because of an anatomic focus.** SSC recommends identifying/excluding sources requiring emergent intervention and performing required source control as soon as medically and logistically practical.[2] Examples: - Drain intra-abdominal abscess - ERCP/biliary drainage for obstructed cholangitis - Urgent decompression for infected obstructed urinary tract - Debridement for necrotizing soft-tissue infection - Remove infected vascular catheter after alternate access - Drain empyema - Operate for perforated viscus or ischemic bowel - Manage infected prosthetic material/device with specialists ★ **Board pearl:** Antibiotics cannot sterilize a closed abscess, obstructed infected system or necrotic tissue reliably without source control. --- ### 6. Corticosteroids For septic shock with an ongoing vasopressor requirement, SSC suggests IV corticosteroids. Typical regimen:[2] - **Hydrocortisone 200 mg/day IV**, either - 50 mg every 6 hours, or - continuous infusion. SSC remarks that treatment is often started when norepinephrine/epinephrine is **≥0.25 micrograms/kg/min for at least 4 hours**.[2] #### Evidence - **ADRENAL:** hydrocortisone 200 mg/day shortened time to shock resolution but did not reduce 90-day mortality compared with placebo.[7] - **APROCCHSS:** hydrocortisone plus fludrocortisone reduced 90-day mortality compared with placebo in a more severely shocked population.[8] **Guideline interpretation:** steroids are standard adjunctive therapy for vasopressor-dependent septic shock, not routine therapy for uncomplicated sepsis without shock. --- ### 7. Other organ support and adjuncts #### Red blood cell transfusion SSC recommends a restrictive strategy; a typical trigger is **hemoglobin 7 g/dL (70 g/L)**, but transfusion should reflect the whole clinical context, including active hemorrhage, severe hypoxemia or myocardial ischemia.[2] #### Glucose Start insulin for glucose **≥180 mg/dL (10 mmol/L)**; typical post-initiation target is approximately **144–180 mg/dL (8–10 mmol/L)**.[2] #### Bicarbonate - Do **not** use sodium bicarbonate simply to improve hemodynamics in hypoperfusion-induced lactic acidosis.[2] - Consider it in septic shock with **pH ≤7.2 plus AKI stage 2–3**, where SSC gives a weak recommendation.[2] #### Renal replacement therapy Use standard indications such as refractory hyperkalemia, severe acidemia, volume overload or uremic complications. Do not start RRT solely because AKI is present without a definitive indication.[2] #### VTE and stress-ulcer prophylaxis Use pharmacologic VTE prophylaxis unless contraindicated; LMWH is generally preferred over UFH. Stress-ulcer prophylaxis is for patients with GI-bleeding risk factors, not automatically for every sepsis admission.[2] #### Vitamin C and extracorporeal “blood purification” SSC suggests **against IV vitamin C** and against polymyxin-B hemoperfusion; evidence for other blood purification techniques remains insufficient.[2] --- ### Reassessment and monitoring #### Perfusion endpoints No single number defines successful resuscitation. Reassess the pattern: - Mental status - Capillary refill and mottling - Peripheral temperature - MAP - Heart rate - Urine output - Lactate trend - Acid-base status - Bedside echo/dynamic fluid responsiveness - Respiratory status and signs of fluid accumulation #### Urine output Oliguria is a marker of possible renal hypoperfusion or AKI, but urine output also changes with CKD, obstruction, medications and hormonal response. Persistent oliguria warrants evaluation rather than automatic fluid boluses. #### Lactate SSC suggests guiding resuscitation toward decreasing lactate when lactate is elevated, while explicitly noting that lactate must be interpreted in context.[2] --- ### Anticipation of deterioration | Pattern | What it may mean | Next actions | |---|---|---| | Rising vasopressor requirement | Ongoing vasoplegia, missed source, cardiogenic/obstructive component, bleeding | Reassess volume, echo, source control, diagnosis, steroids | | Persistent lactate elevation | Ongoing hypoperfusion or non-hypoxic lactate production | Re-examine perfusion; do not chase lactate with fluid blindly | | Worsening oxygenation after fluids | ARDS or hydrostatic pulmonary edema | Stop indiscriminate fluid, lung ultrasound/echo, ventilatory strategy | | New oliguria | AKI, hypoperfusion, obstruction | Hemodynamics, urinalysis, bladder scan/renal imaging as indicated | | New thrombocytopenia/coagulopathy | DIC, marrow suppression, liver dysfunction, drug effect | Coags/fibrinogen, bleeding assessment, source control | | Persistent fever/hypothermia | Uncontrolled source, resistant organism, noninfectious mimic | Repeat source search and microbiology review | --- ### Complications - Septic shock - ARDS - Acute kidney injury - Disseminated intravascular coagulation - Acute liver dysfunction - Myocardial dysfunction and arrhythmia - Delirium/encephalopathy - Critical illness polyneuropathy/myopathy - Pressure injury and deconditioning - Secondary/nosocomial infections - Malnutrition - Thromboembolism #### Post-sepsis syndrome Survivors may experience persistent weakness, exercise limitation, cognitive impairment, anxiety, depression, PTSD, sleep disturbance and recurrent hospitalization. Discharge planning should include medication reconciliation, rehabilitation needs, recovery education and follow-up for physical, cognitive and emotional sequelae.[2] --- ### Special populations #### Neutropenic sepsis Treat fever/instability in neutropenia as an emergency. Antipseudomonal empiric coverage and local neutropenic-sepsis protocols take priority; do not wait for neutrophil recovery or culture confirmation. #### Pregnancy and postpartum Normal pregnancy physiology changes heart rate, respiratory rate, BP and laboratory reference ranges. Use obstetric sepsis pathways and involve obstetrics early; maternal stabilization remains the priority. #### Cirrhosis Patients may have baseline vasodilation, thrombocytopenia, renal vulnerability and unusual infections. Consider spontaneous bacterial peritonitis, bacteremia and hepatorenal physiology; fluid and vasopressor decisions need particular caution. #### Advanced CKD/heart failure Initial shock treatment is still urgent, but repeated fluid boluses should be guided by dynamic responsiveness, congestion and bedside echo rather than fear of all fluid or routine large-volume administration. #### Immunosuppression Broaden the differential for opportunistic and fungal infection and involve infectious-diseases/microbiology expertise early when appropriate. --- ### Acute management checklist #### First hour: suspected septic shock / high-likelihood sepsis - [ ] ABCDE assessment and immediate stabilization - [ ] Call senior/critical-care help early - [ ] Continuous monitoring; IV/IO access - [ ] Lactate - [ ] Blood cultures and source cultures if they will not delay treatment - [ ] Appropriate empiric antimicrobials immediately, ideally within 1 hour - [ ] Crystalloid for hypoperfusion; balanced crystalloid preferred - [ ] Reassess after each bolus using dynamic/perfusion markers - [ ] Norepinephrine promptly if hypotension persists; do not delay for central line - [ ] Initial MAP target about 65 mm Hg - [ ] Identify source and emergency source-control need - [ ] Glucose, CBC, renal/liver profile, coagulation, blood gas as appropriate - [ ] Imaging focused on source without delaying life-saving intervention #### Following hours - [ ] Repeat lactate if elevated and clinically useful - [ ] Trend capillary refill, urine output, mentation and hemodynamics - [ ] Add vasopressin if norepinephrine requirement rises and MAP remains inadequate - [ ] Consider hydrocortisone for ongoing vasopressor-dependent shock - [ ] De-escalate/target antibiotics when microbiology returns - [ ] Reassess for ARDS, AKI, DIC and occult source - [ ] Re-evaluate diagnosis if response is atypical --- ### Diagnostic and management algorithm ```text Suspected infection ↓ Any acute organ dysfunction / concerning physiology? ├─ No → treat infection; monitor for deterioration └─ Yes ↓ Immediate ABCDE + lactate + cultures/labs + source assessment ↓ Shock / high likelihood of sepsis? ├─ Yes → antimicrobials immediately (ideally ≤1 h) │ + crystalloid if hypoperfusion │ + norepinephrine if hypotension persists │ + urgent source control └─ No → rapid infectious vs noninfectious assessment if concern persists → antimicrobials within 3 h ↓ Reassess perfusion dynamically ↓ Fluid responsive? ├─ Yes + hypoperfused → cautious additional fluid └─ No / congested → avoid further routine bolus ↓ MAP still inadequate? → norepinephrine → add vasopressin → consider epinephrine ↓ Persistent vasopressor-dependent shock? → hydrocortisone 200 mg/day ↓ Repeat source search + organ support + de-escalation + recovery planning ``` --- ### Common pitfalls | Pitfall | Why it is dangerous | Better approach | |---|---|---| | Treating qSOFA as a rule-out test | Misses sepsis | Use broad clinical assessment/NEWS or local screening plus organ dysfunction evaluation | | Waiting for hypotension before recognizing shock | BP can be preserved early | Assess perfusion and trajectory | | Delaying antibiotics in septic shock for “perfect cultures” | Time-sensitive mortality risk | Cultures quickly, then treat; do not materially delay | | Giving repeated automatic 30 mL/kg boluses | Fluid accumulation may worsen outcomes | Initial resuscitation + dynamic reassessment | | Chasing lactate with fluid alone | Lactate has non-hypoperfusion causes | Integrate cap refill, echo, urine, MAP and clinical context | | Delaying vasopressors until central line placement | Prolongs hypotension | Use appropriate proximal peripheral access short-term | | Ignoring source control | Antibiotics alone may fail | Drain/debride/decompress/remove source early | | Continuing broad-spectrum antibiotics indefinitely | Resistance/toxicity/C. difficile | Daily de-escalation and shortest effective duration | --- ### Guideline conflicts and practice variation #### Fluid volume SSC retains a suggestion for at least 30 mL/kg within 3 hours for sepsis-induced hypoperfusion/septic shock.[2] However, CLASSIC and CLOVERS show that after initial resuscitation, restrictive and liberal strategies produce similar major outcomes in broad trial populations.[4,5] Contemporary practice is therefore shifting toward **individualized, physiology-guided fluid** after the initial phase. #### Screening - **SSC:** do not use qSOFA alone; institutional screening and performance-improvement programs are recommended.[2] - **NICE 2025:** uses NEWS2 thresholds plus clinical judgment to stratify risk in adults.[3] #### Antibiotic timing Both SSC and NICE prioritize the fastest treatment in shock/high-risk sepsis. SSC is more explicit about allowing a short diagnostic window (up to 3 hours) for possible sepsis **without shock** when the likelihood of infection is uncertain.[2,3] --- ### STANDARD OF CARE vs emerging vs experimental #### STANDARD OF CARE - Early recognition and organ-supportive resuscitation - Appropriate cultures without clinically important antibiotic delay - Timely empiric antimicrobials based on source and resistance risk - Crystalloids for hypoperfusion, with reassessment - Norepinephrine first-line vasopressor - Initial MAP target around 65 mm Hg - Early source control when indicated - Hydrocortisone for persistent vasopressor-dependent septic shock - De-escalation and shorter appropriate antimicrobial courses #### EMERGING / EVOLVING PRACTICE - Earlier vasopressor initiation with less routine fluid after initial resuscitation - Greater use of capillary refill, bedside echo and dynamic fluid-responsiveness testing - Precision resuscitation based on shock phenotype rather than a fixed fluid recipe - Biomarker- and rapid-diagnostic-guided antimicrobial stewardship #### EXPERIMENTAL / INVESTIGATIONAL - Routine extracorporeal cytokine adsorption/blood purification - Immune-phenotype-directed immunomodulation - Broad metabolomic/genomic sepsis endotyping for bedside treatment selection These should not displace proven infection control, antimicrobials, source control and organ support outside trials or specialist protocols. --- ### Exam-focused review #### USMLE Step 1 Understand: - Vasodilation + capillary leak → decreased effective circulating volume - Endothelial and microcirculatory dysfunction - Why lactate can rise - DIC and organ dysfunction mechanisms #### Step 2 CK / Step 3 Prioritize: - Unstable patient → resuscitate before extensive diagnostics - Septic shock → antibiotics + perfusion support immediately - Persistent hypotension after appropriate fluid → norepinephrine - Obstructed infected system → decompression/source control #### MRCP / ABIM / boards Know: - Sepsis-3 definition and septic shock criteria - SOFA vs qSOFA role - 30 mL/kg recommendation is a **weak initial-resuscitation recommendation**, not a maintenance strategy - Norepinephrine first line; vasopressin add-on - Hydrocortisone 200 mg/day for ongoing vasopressor need - Hb 7 g/dL is a typical restrictive transfusion threshold, modified by clinical context --- ### Original MCQs #### Question 1 A 68-year-old man with pyelonephritis has MAP 56 mm Hg, lactate 4.2 mmol/L, mottled extremities and worsening confusion. He has received an appropriate initial crystalloid resuscitation. What is the best next hemodynamic treatment? A. Dopamine as first-line vasopressor B. Norepinephrine infusion C. Additional 2 L saline without reassessment D. Sodium bicarbonate for the lactate E. Wait for central venous access before starting a vasopressor **Answer: B. Norepinephrine infusion.** **Explanation:** Norepinephrine is first-line vasopressor therapy for septic shock. Vasopressor treatment should not be delayed solely to obtain central access; a suitable proximal peripheral IV can be used briefly with monitoring.[2] #### Question 2 A patient with suspected infection has RR 26/min, SBP 98 mm Hg and normal mentation. Which statement about qSOFA is most accurate? A. qSOFA ≥2 confirms sepsis B. qSOFA <2 excludes sepsis C. qSOFA should be the sole screening test D. qSOFA can identify risk but is not recommended as the sole screening test E. qSOFA replaces SOFA for defining organ dysfunction **Answer: D.** **Explanation:** qSOFA is a prognostic bedside signal, not a definitive diagnostic test. SSC advises against qSOFA as the single screening tool.[2] #### Question 3 A patient with septic shock remains hypotensive despite norepinephrine and appropriate reassessment of volume status. What vasopressor strategy is favored next by SSC? A. Add vasopressin B. Switch to phenylephrine routinely C. Stop norepinephrine and use dopamine D. Give repeated fluid regardless of fluid responsiveness E. Start terlipressin **Answer: A. Add vasopressin.** **Explanation:** For inadequate MAP on norepinephrine, SSC suggests adding vasopressin rather than simply escalating norepinephrine indefinitely.[2] #### Question 4 Which patient most clearly requires urgent source control in addition to antimicrobials? A. Uncomplicated cellulitis without abscess B. Viral bronchitis C. Obstructed infected ureter with hydronephrosis and shock D. Asymptomatic bacteriuria E. Mild cystitis **Answer: C.** **Explanation:** An infected obstructed urinary system is a source-control emergency; decompression is essential because antimicrobials alone may not control infection. #### Question 5 A patient with septic shock is receiving norepinephrine 0.35 micrograms/kg/min for several hours with persistent vasopressor requirement. Which adjunct is guideline-supported? A. Routine IV vitamin C B. Hydrocortisone 200 mg/day IV C. Polymyxin-B hemoperfusion D. Hydroxyethyl starch E. Routine bicarbonate regardless of pH **Answer: B.** **Explanation:** SSC suggests IV corticosteroids for septic shock with ongoing vasopressor need; hydrocortisone 200 mg/day is the typical regimen.[2] --- ### Recent guideline and practice updates - **19 November 2025:** NICE published NG253 for suspected sepsis in people aged 16 or over, replacing the prior all-age structure and emphasizing NEWS2 plus clinical judgment and rapid antibiotics for high-risk patients.[3] - Contemporary post-SSC evidence from **CLASSIC (2022)** and **CLOVERS (2023)** supports a move away from automatic repeated fluid boluses after initial resuscitation toward individualized fluid/vasopressor decisions.[4,5] - As of this review date, the **Surviving Sepsis Campaign 2021 adult guideline remains the principal international comprehensive management guideline** listed by SCCM; local institutions may have more recent operational pathways.[2] --- ### Landmark and influential research - **Sepsis-3 (2016):** modern definition centered on infection-related organ dysfunction and defined septic shock phenotype.[1] - **ProCESS, ARISE, ProMISe (2014–2015):** showed no benefit from mandatory early goal-directed therapy protocols compared with contemporary usual care, helping shift practice toward early recognition/resuscitation without fixed invasive targets.[9-11] - **ADRENAL and APROCCHSS (2018):** clarified the role of corticosteroids in vasopressor-dependent septic shock.[7,8] - **ANDROMEDA-SHOCK (2019):** brought peripheral perfusion/capillary refill back into resuscitation discussions.[6] - **CLASSIC (2022) and CLOVERS (2023):** challenged the assumption that more fluid is inherently better after initial resuscitation.[4,5] --- ### References 1. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). *JAMA*. 2016;315(8):801-810. doi:10.1001/jama.2016.0287. https://jamanetwork.com/journals/jama/fullarticle/2492881 2. Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. *Intensive Care Med*. 2021;47:1181-1247. doi:10.1007/s00134-021-06506-y. SCCM recommendations: https://www.sccm.org/clinical-resources/guidelines/guidelines/surviving-sepsis-guidelines-2021 3. National Institute for Health and Care Excellence. Suspected sepsis in people aged 16 or over: recognition, assessment and early management. NICE guideline NG253. Published 19 November 2025. https://www.nice.org.uk/guidance/NG253 4. National Heart, Lung, and Blood Institute PETAL Clinical Trials Network. Early Restrictive or Liberal Fluid Management for Sepsis-Induced Hypotension (CLOVERS). *N Engl J Med*. 2023;388:499-510. doi:10.1056/NEJMoa2212663. 5. Meyhoff TS, Hjortrup PB, Wetterslev J, et al. Restriction of Intravenous Fluid in ICU Patients with Septic Shock (CLASSIC). *N Engl J Med*. 2022;386:2459-2470. doi:10.1056/NEJMoa2202707. 6. Hernández G, Ospina-Tascón GA, Damiani LP, et al. Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock: ANDROMEDA-SHOCK. *JAMA*. 2019;321(7):654-664. doi:10.1001/jama.2019.0071. 7. Venkatesh B, Finfer S, Cohen J, et al. Adjunctive Glucocorticoid Therapy in Patients with Septic Shock (ADRENAL). *N Engl J Med*. 2018;378:797-808. doi:10.1056/NEJMoa1705835. 8. Annane D, Renault A, Brun-Buisson C, et al. Hydrocortisone plus Fludrocortisone for Adults with Septic Shock (APROCCHSS). *N Engl J Med*. 2018;378:809-818. doi:10.1056/NEJMoa1705716. 9. ProCESS Investigators. A Randomized Trial of Protocol-Based Care for Early Septic Shock. *N Engl J Med*. 2014;370:1683-1693. doi:10.1056/NEJMoa1401602. 10. ARISE Investigators; ANZICS Clinical Trials Group. Goal-Directed Resuscitation for Patients with Early Septic Shock. *N Engl J Med*. 2014;371:1496-1506. doi:10.1056/NEJMoa1404380. 11. Mouncey PR, Osborn TM, Power GS, et al. Trial of Early, Goal-Directed Resuscitation for Septic Shock (ProMISe). *N Engl J Med*. 2015;372:1301-1311. doi:10.1056/NEJMoa1500896. --- ### Related topics to build next - Shock: classification and hemodynamic approach - Community-acquired pneumonia - Neutropenic sepsis - Acute respiratory distress syndrome - Disseminated intravascular coagulation - Vasopressors and inotropes - Source control in severe infection1d:T76cc,## One-minute summary **Acute coronary syndrome (ACS)** is the clinical spectrum caused most often by acute coronary atherothrombosis after plaque rupture or erosion and includes **ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), and unstable angina (UA)**. Modern care is built around five simultaneous priorities: **recognize ischemia, obtain/interpret a 12-lead ECG rapidly, use high-sensitivity cardiac troponin serially, start evidence-based antithrombotic/anti-ischemic therapy, and choose the correct revascularization strategy without delay**.[1–4] The 2025 ACC/AHA/ACEP/NAEMSP/SCAI ACS guideline emphasizes DAPT, radial access for PCI, intravascular imaging for PCI guidance, complete revascularization in appropriate multivessel disease, prompt revascularization in cardiogenic shock, intensive lipid lowering, and cardiac rehabilitation.[1,2] The 2023 ESC ACS guideline similarly integrates STEMI and NSTE-ACS in one pathway and stresses high-sensitivity troponin algorithms and time-sensitive invasive care.[3] ### Immediate priorities 1. **ABCs + monitor + IV access**; treat shock, malignant arrhythmia, pulmonary edema, or cardiac arrest first. 2. **12-lead ECG promptly** and repeat if symptoms continue or the first tracing is nondiagnostic. 3. **High-sensitivity troponin** with an assay-specific accelerated serial algorithm; do not use a single universal numeric cutoff across assays. 4. **Aspirin immediately** unless true contraindication. 5. Determine whether this is **STEMI/occlusion requiring immediate reperfusion** versus **NSTE-ACS requiring risk-stratified invasive management**. 6. Add a **P2Y12 inhibitor + parenteral anticoagulation** according to the reperfusion/invasive strategy and bleeding risk. 7. Start **high-intensity statin** and secondary prevention early. ★ **High-yield principle:** In suspected ACS, the ECG determines the urgent reperfusion pathway; troponin helps diagnose myocardial injury/infarction but should **not delay reperfusion** for a clear STEMI pattern with an appropriate clinical presentation. --- ## Definition and classification ACS describes acute myocardial ischemia caused predominantly by an unstable atherosclerotic coronary lesion and thrombosis. The 2025 U.S. guideline focuses mainly on **type 1 ACS**, where plaque disruption and coronary thrombosis are the mechanism.[1] | Syndrome | ECG pattern | Troponin | Core concept | |---|---|---|---| | STEMI | Persistent ST elevation or an accepted STEMI-equivalent/occlusion pattern in the right context | Usually rises, but may initially be normal | Acute coronary occlusion or near-occlusion requiring immediate reperfusion | | NSTEMI | No persistent ST elevation; may show ST depression, T-wave inversion, transient elevation, or a nondiagnostic ECG | Rise/fall with ≥1 value above assay-specific 99th percentile plus evidence of ischemia | Myocardial infarction without classic persistent ST elevation | | Unstable angina | No persistent ST elevation | No biomarker evidence meeting MI criteria | Ischemic symptoms without detectable acute myocardial necrosis; less common in the high-sensitivity troponin era | ### Myocardial injury is not automatically myocardial infarction Troponin elevation means **myocardial injury**, not necessarily ACS. MI requires acute myocardial injury plus evidence of ischemia. Important alternative causes include sepsis, tachyarrhythmia, myocarditis, pulmonary embolism, acute heart failure, severe anemia, renal disease with dynamic injury, and supply-demand mismatch (type 2 MI). --- ## Pathophysiology The usual sequence is: **lipid-rich atherosclerotic plaque → plaque rupture or endothelial erosion → platelet adhesion/activation → thrombin generation → fibrin-rich thrombus → abrupt reduction in coronary blood flow → myocardial ischemia → myocyte necrosis if ischemia persists.** Ischemia begins subendocardially because wall stress and perfusion vulnerability are highest there. With sustained complete occlusion, necrosis can progress toward the epicardium. Infarct size is influenced by occlusion duration, collateral supply, myocardial oxygen demand, ischemic preconditioning, reperfusion timing, and microvascular obstruction. ### STEMI vs NSTEMI is an ECG phenotype, not a complete anatomy report Some acute coronary occlusions do not produce classic ST elevation. Conversely, ST elevation can be caused by pericarditis, early repolarization, left ventricular aneurysm, Takotsubo syndrome, electrolyte disorders, and other mimics. Clinical reasoning and serial ECGs matter. --- ## Risk factors Major atherosclerotic risk factors include: - Age and family history of premature ASCVD - Cigarette smoking - Hypertension - Diabetes mellitus - Dyslipidemia - Chronic kidney disease - Obesity and physical inactivity - Established coronary, cerebrovascular, or peripheral arterial disease - Chronic inflammatory disease Additional precipitants or modifiers include cocaine/amphetamine exposure, severe emotional or physiologic stress, acute infection, anemia, uncontrolled hypertension, and perioperative stress. --- ## Clinical presentation ### Typical ischemic symptoms - Retrosternal pressure, heaviness, squeezing, burning, or tightness - Radiation to arm(s), shoulder, neck, jaw, back, or epigastrium - Dyspnea - Diaphoresis - Nausea/vomiting - Sense of impending doom - Symptoms provoked by exertion and persistent at rest in acute presentations ### Atypical or less obvious presentations Older adults, women, and patients with diabetes or CKD may present with: - Dyspnea without prominent pain - Weakness or fatigue - Syncope/presyncope - Nausea or epigastric discomfort - Acute heart failure - Confusion Do not dismiss ACS because pain is described as “burning,” “indigestion,” or is not left-sided. ### Red flags for immediate instability - Hypotension, cool extremities, altered mentation - Ongoing severe chest pain despite initial therapy - Ventricular tachycardia/fibrillation - High-grade AV block or severe bradycardia - Acute pulmonary edema - Mechanical complication murmur - Recurrent dynamic ST changes - Cardiac arrest --- ## Initial assessment: first 10 minutes ### Core workflow | Component | Assessment | Interpretation | Immediate action | Anticipate deterioration | |---|---|---|---|---| | Airway/Breathing | Work of breathing, SpO₂, lung exam | Pulmonary edema, hypoxemia, alternative diagnosis | Oxygen only when clinically indicated; ventilatory support if needed | Acute LV failure, respiratory fatigue | | Circulation | HR, BP, perfusion, pulses, JVP | Shock, RV infarction, mechanical complication, arrhythmia | Monitor, IV access, cautious fluids if appropriate, shock pathway | Cardiogenic shock, VT/VF, AV block | | ECG | 12-lead ECG; right/posterior leads when indicated | STEMI/occlusion, ischemia, alternate diagnosis | Activate reperfusion pathway when indicated | Dynamic evolution; repeat ECG | | Biomarkers | hs-cTn serially | Acute myocardial injury pattern | Use validated assay-specific algorithm | Early presenters may have initially normal value | | History | Onset, quality, duration, bleeding history, anticoagulants, PDE5 inhibitors, prior stroke/TIA, allergy | Determines differential and treatment safety | Do not delay reperfusion for exhaustive history | Bleeding, medication contraindications | #### ECG Obtain a 12-lead ECG as early as possible in suspected ACS. Repeat ECGs if symptoms persist or recur, and consider: - **Right-sided leads (especially V4R)** for inferior MI with possible RV involvement - **Posterior leads V7–V9** when posterior MI is suspected, e.g., ST depression V1–V3 with a compatible presentation #### High-sensitivity troponin Use the laboratory's validated **high-sensitivity cardiac troponin (hs-cTn)** assay and accelerated serial algorithm. ESC guidance supports 0/1-hour or 0/2-hour pathways with assay-specific thresholds.[3,4] Interpretation requires: - Absolute concentration relative to the assay's 99th percentile - Rise/fall (delta) - Time since symptom onset - Renal function and chronic structural heart disease - Clinical/ECG evidence of ischemia ⚠ **Common trap:** A chronically elevated troponin in CKD does not prove NSTEMI. Look for a dynamic change and ischemic context. --- ### Differential diagnosis of acute chest pain | Diagnosis | Clues favoring diagnosis | Distinguishing test/findings | Immediate hazard | |---|---|---|---| | ACS | Pressure, diaphoresis, dynamic ECG/troponin | Serial ECG + hs-cTn | Arrhythmia, infarction, shock | | Aortic dissection | Abrupt tearing pain, pulse/BP differential, neuro deficit | CT angiography/TEE | Rupture; anticoagulation can be catastrophic | | Pulmonary embolism | Pleuritic pain, dyspnea, tachycardia, VTE risk | CT pulmonary angiography or V/Q | Obstructive shock | | Pericarditis | Pleuritic/positional pain, diffuse ST elevation/PR depression | ECG, echo | Tamponade if effusion | | Myocarditis | Viral prodrome, variable ECG, troponin, noncoronary pattern | CMR, echo, selective biopsy | Ventricular arrhythmia/shock | | Tension pneumothorax | Sudden dyspnea, unilateral absent breath sounds, shock | Clinical diagnosis | Immediate death without decompression | | Esophageal rupture | Severe pain after vomiting, systemic toxicity | CT/esophagram | Mediastinitis/sepsis | | GI/musculoskeletal pain | Reproducible or meal-related features may occur | Diagnosis of exclusion in high-risk cases | Risk is missed ACS | ★ **Exam pearl:** Do not give antithrombotics reflexively to undifferentiated tearing chest pain before considering dissection. --- ## STEMI and acute coronary occlusion ### Primary PCI is preferred when timely Primary PCI is the preferred reperfusion strategy when it can be performed within an appropriate system delay. ESC guidance recommends primary PCI when achievable within **120 minutes from STEMI diagnosis**; if timely PCI cannot be achieved and symptom onset is within 12 hours with no contraindication, fibrinolysis is indicated, followed by immediate transfer to a PCI-capable center.[3,5] #### STEMI network principles - Activate the cath lab early. - EMS should preferentially transport to a PCI-capable center when system targets can be met. - Do not wait for troponin when the clinical/ECG diagnosis is clear. - After fibrinolysis, transfer to PCI capability even if symptoms improve. - Rescue PCI is required for failed fibrinolysis or ongoing instability/ischemia. #### Cardiogenic shock Prompt revascularization remains a **Class 1** principle in ACS-related cardiogenic shock.[1,2] Shock management requires a multidisciplinary approach: airway/ventilation when necessary, invasive hemodynamic assessment in selected cases, vasopressor/inotrope support, and mechanical circulatory support only in carefully selected patients because benefit and complications vary by device and phenotype. --- ## NSTE-ACS: risk-stratified invasive management NSTE-ACS includes NSTEMI and unstable angina. An invasive strategy is recommended for ACS, but timing depends on risk.[3] #### Very high-risk features: immediate invasive evaluation Examples include: - Hemodynamic instability/cardiogenic shock - Recurrent or refractory chest pain despite medical treatment - Life-threatening arrhythmia or cardiac arrest attributed to ischemia - Mechanical complication - Acute heart failure clearly driven by ongoing ischemia - Recurrent dynamic ST-segment changes, particularly intermittent ST elevation #### High-risk features Features supporting early/inpatient invasive care include confirmed NSTEMI, significant dynamic ST/T changes, and high clinical risk (e.g., elevated GRACE risk). ESC guidance states an early invasive strategy (<24 h) should be considered in high-risk NSTE-ACS.[3] #### GRACE risk score The GRACE score estimates mortality using age, heart rate, systolic BP, creatinine, Killip class, cardiac arrest, ST deviation, and biomarkers. It is useful for prognosis and invasive-timing decisions, but it does not replace clinical judgment. --- ## Acute pharmacotherapy ### STANDARD OF CARE #### Aspirin The 2025 ACC/AHA guideline dosing table recommends:[1] - **Loading:** **162–325 mg orally**, non-enteric coated; chew when possible for faster effect. - **Maintenance:** **75–100 mg orally daily**. Aspirin is generally continued long term unless contraindicated or a specific antithrombotic strategy modifies it. #### P2Y12 inhibitors For patients undergoing PCI, **ticagrelor or prasugrel is preferred over clopidogrel** when not contraindicated.[1,2] | Agent | Loading | Maintenance | Key cautions | |---|---:|---:|---| | Ticagrelor | 180 mg PO | 90 mg PO twice daily | Dyspnea, bleeding; keep aspirin maintenance ≤100 mg/day | | Prasugrel | 60 mg PO | 10 mg daily if ≥60 kg and <75 y; 5 mg daily if <60 kg or age ≥75 y with caution | **Contraindicated with prior stroke/TIA**; higher bleeding risk | | Clopidogrel | 300 or 600 mg PO without fibrinolysis | 75 mg daily | Variable response; used when potent agents unsuitable | | Clopidogrel with fibrinolysis | 300 mg if age ≤75 y; 75 mg initial dose if >75 y | 75 mg daily | Standard P2Y12 option with fibrinolysis | #### DAPT duration For ACS patients **without high bleeding risk**, aspirin plus an oral P2Y12 inhibitor for **at least 12 months** is the default.[1,2] Bleeding-reduction strategies include: - PPI in patients at GI bleeding risk - In selected patients tolerating ticagrelor-based DAPT after PCI, transition to ticagrelor monotherapy ≥1 month after PCI - If chronic oral anticoagulation is required, discontinue aspirin 1–4 weeks after PCI and continue a P2Y12 inhibitor (preferably clopidogrel) with anticoagulation, individualized to ischemic and bleeding risk.[2] #### Anticoagulation Parenteral anticoagulation is part of acute ACS management, selected according to strategy and renal function (e.g., UFH, enoxaparin, or bivalirudin in appropriate settings). Dosing should follow the local PCI/fibrinolysis protocol because the required dose depends on whether the patient is proceeding to PCI, has already received anticoagulant, renal function, and activated clotting time targets. #### Nitrates For ischemic discomfort or hypertensive pulmonary congestion, sublingual nitroglycerin is commonly used if hemodynamically appropriate. The 2025 guideline cautions against nitrates when: - SBP <90 mmHg or >30 mmHg below baseline - Suspected RV infarction - Recent PDE5 inhibitor exposure: approximately **12 h after avanafil, 24 h after sildenafil/vardenafil, 48 h after tadalafil**.[1] Nitrates improve symptoms; they are **not a substitute for reperfusion** and have not been shown to reduce mortality in modern ACS care. #### Analgesia Opioids are reserved for persistent severe pain despite other anti-ischemic therapy. The 2025 guideline notes morphine **2–4 mg IV**, repeat every 5–15 minutes if needed, with careful monitoring; opioids can delay absorption/effect of oral P2Y12 inhibitors.[1] #### Oxygen Do **not** use routine oxygen solely because ACS is suspected when oxygenation is adequate. Give supplemental oxygen for hypoxemia or respiratory distress and titrate according to the patient's condition and local protocol. #### Beta-blocker In ACS without contraindications, the 2025 guideline recommends **early oral beta-blocker initiation within 24 hours** to reduce reinfarction and ventricular arrhythmias.[1] Delay/avoid in cardiogenic shock, decompensated acute HF, severe bradycardia, high-grade AV block without pacing, or other contraindications. #### High-intensity statin High-intensity statin therapy is recommended for all ACS patients unless contraindicated.[2] Common high-intensity regimens include: - **Atorvastatin 40–80 mg daily** - **Rosuvastatin 20–40 mg daily** The 2025 guideline recommends adding a nonstatin lipid-lowering agent when LDL-C remains **≥70 mg/dL (≥1.8 mmol/L)** on maximally tolerated statin; adding a nonstatin is also reasonable at **55–69 mg/dL** in selected patients.[2] #### ACE inhibitor / ARB and mineralocorticoid receptor antagonist ACEi/ARB is indicated particularly in higher-risk ACS patients (e.g., LVEF ≤40%, hypertension, diabetes, or anterior STEMI). An MRA is indicated for LVEF ≤40% with HF symptoms and/or diabetes when renal function and potassium permit.[1] --- ## PCI and revascularization ### Access and imaging The 2025 guideline recommends **radial access over femoral access** for PCI in ACS to reduce bleeding, vascular complications, and death.[1,2] **Intravascular imaging-guided PCI** is now a **Class 1, Level A** recommendation in the 2025 U.S. guideline.[2] ### Complete revascularization For appropriate STEMI and NSTE-ACS patients with multivessel disease, a strategy of complete revascularization is recommended/strongly favored, with timing and method determined by anatomy, comorbidities, shock status, renal function, lesion complexity, and surgical candidacy.[1,2] ⚠ **Shock exception:** Immediate multivessel PCI in cardiogenic shock is not automatically beneficial; culprit-vessel revascularization remains the immediate priority in many cases, with staged treatment of nonculprit disease according to anatomy and stability. --- ## Complications ### Electrical - Ventricular tachycardia/fibrillation - Accelerated idioventricular rhythm after reperfusion - Sinus bradycardia - AV block, especially inferior MI - Atrial fibrillation Treat unstable arrhythmias according to ACLS while correcting ischemia, hypoxia, potassium, magnesium, and acid-base abnormalities. ### Mechanical — think days after MI, sudden collapse or new murmur | Complication | Typical clue | Hemodynamics / echo | Action | |---|---|---|---| | Papillary muscle rupture → acute MR | Sudden pulmonary edema, shock, new systolic murmur | Severe eccentric MR | Emergency surgery; stabilize with afterload reduction/mechanical support when appropriate | | Ventricular septal rupture | New harsh holosystolic murmur, shock | Left-to-right shunt | Urgent surgical/interventional consultation | | Free-wall rupture | Sudden PEA, tamponade | Pericardial blood/effusion | Emergency surgical management | | LV aneurysm/pseudoaneurysm | Persistent ST changes, HF/embolism | Structural abnormality on echo/CT/CMR | Specialist management; pseudoaneurysm has rupture risk | ### Pump failure - Acute LV failure/pulmonary edema - RV infarction with preload sensitivity - Cardiogenic shock #### RV infarction pearl Suspect with inferior MI, hypotension, elevated JVP, and clear lungs. Obtain right-sided leads. Avoid aggressive nitrates/diuresis if preload dependent; give cautious fluid only if clinically appropriate and reassess frequently. --- ## Special populations ### Older adults and frailty Do not withhold evidence-based ACS care based solely on age. Balance invasive benefit against frailty, cognition, bleeding risk, kidney disease, goals of care, and functional status. ### Chronic kidney disease - hs-cTn may be chronically elevated; rely on dynamic change and clinical context. - Adjust renally cleared drugs. - Minimize contrast burden while avoiding harmful delays in indicated revascularization. ### Patients requiring oral anticoagulation Triple therapy markedly increases bleeding. The 2025 guideline favors early aspirin discontinuation (1–4 weeks after PCI) with continuation of oral anticoagulation plus a P2Y12 inhibitor, usually clopidogrel, when long-term anticoagulation is required.[2] ### Prior stroke/TIA **Prasugrel is contraindicated.** Choose another P2Y12 inhibitor when indicated. ### Pregnancy ACS in pregnancy is uncommon and more likely to involve mechanisms such as spontaneous coronary artery dissection. Management requires a pregnancy-heart team; maternal stabilization and indicated reperfusion take priority, while medication and radiation choices are individualized. --- ## Secondary prevention after ACS ### Before discharge - Smoking cessation treatment - Blood pressure optimization - Diabetes management - High-intensity statin ± nonstatin therapy - Antiplatelet plan documented with duration and bleeding strategy - Echocardiographic assessment of LVEF when appropriate - Cardiac rehabilitation referral - Exercise, weight, diet, and adherence counseling - Review driving/work restrictions per jurisdiction The 2025 guideline recommends a fasting lipid panel **4–8 weeks** after starting or adjusting lipid-lowering therapy and recommends referral to cardiac rehabilitation before discharge.[2] #### Cardiac rehabilitation Cardiac rehabilitation reduces recurrent events, improves functional status and quality of life, and is a Class 1 component of contemporary ACS secondary prevention.[2] --- ## Current guideline changes and areas of nuance ### 2025 ACC/AHA/ACEP/NAEMSP/SCAI — major practical updates **STANDARD OF CARE** - DAPT remains foundational. - Ticagrelor/prasugrel preferred over clopidogrel for PCI when appropriate. - Default DAPT ~12 months when bleeding risk is not high. - Radial PCI access favored. - Intravascular imaging-guided PCI elevated to Class 1. - Complete revascularization emphasized. - High-intensity statin for all ACS. - More aggressive nonstatin lipid-lowering thresholds. - Cardiac rehab referral before discharge.[1,2] ### 2023 ESC vs 2025 U.S. guideline Both support rapid hs-cTn pathways, invasive management for high-risk ACS, potent antiplatelet therapy, radial access, and complete revascularization in appropriate patients. Important practical differences may arise in preferred P2Y12 timing, exact invasive-timing categories, local fibrinolysis systems, and antithrombotic de-escalation strategies. Follow the locally adopted guideline and cath-lab protocol. ### EMERGING EVIDENCE - Individualized antiplatelet de-escalation and monotherapy strategies continue to evolve. - Mechanical circulatory support for selected AMI cardiogenic shock remains an area of active patient-selection research. - Physiology- and imaging-guided complete revascularization strategies continue to be refined. ### EXPERIMENTAL / INVESTIGATIONAL No investigational therapy should replace timely reperfusion, guideline antithrombotic treatment, and secondary prevention outside a trial or specialist protocol. --- ## Acute management checklist ### Suspected ACS - [ ] ABCs; identify shock, pulmonary edema, arrhythmia, cardiac arrest - [ ] Cardiac monitor + defibrillator availability - [ ] IV access - [ ] 12-lead ECG promptly; repeat if nondiagnostic - [ ] Right/posterior leads if indicated - [ ] hs-cTn serial algorithm - [ ] CBC, electrolytes, creatinine, glucose; coagulation studies when relevant - [ ] Aspirin 162–325 mg chewed unless contraindicated - [ ] Determine STEMI/occlusion vs NSTE-ACS pathway - [ ] P2Y12 inhibitor based on strategy and bleeding risk - [ ] Parenteral anticoagulation based on strategy - [ ] Nitrate only if appropriate; check BP/RV infarct/PDE5 exposure - [ ] Oxygen only if indicated - [ ] High-intensity statin - [ ] Early beta-blocker if stable and no contraindication - [ ] Echocardiography for LV function/complications as indicated - [ ] Document DAPT duration and bleeding mitigation - [ ] Cardiac rehab + secondary prevention plan --- ## Diagnostic / management algorithm ```text Acute chest discomfort / dyspnea / ischemic equivalent ↓ ABCs + monitor + IV + 12-lead ECG + hs-cTn ↓ Persistent ST elevation / occlusion pattern with compatible syndrome? ├── YES → STEMI reperfusion pathway │ ├─ Primary PCI achievable within system target → PCI │ └─ PCI not achievable within ~120 min, onset ≤12 h, │ no contraindication → fibrinolysis + transfer to PCI center │ └── NO → NSTE-ACS pathway ↓ Serial hs-cTn + repeat ECG + risk assessment ↓ Very high risk / instability? → Immediate invasive strategy High risk? → Early/inpatient invasive strategy Low risk / ACS ruled out? → Evaluate alternative diagnosis / safe disposition At all stages: Aspirin + strategy-appropriate P2Y12 + anticoagulation + high-intensity statin Treat shock/arrhythmia/HF immediately; reassess continuously ``` --- ## Common pitfalls | Pitfall | Why it is dangerous | Better approach | |---|---|---| | Waiting for troponin before activating clear STEMI | Delays reperfusion | Treat ECG + clinical syndrome as time-critical | | Treating every troponin elevation as type 1 NSTEMI | Causes diagnostic anchoring/bleeding risk | Distinguish injury, type 1 MI, type 2 MI, myocarditis, PE, etc. | | One normal ECG ends the workup | ACS can be dynamic | Repeat ECG during symptoms and use posterior/right leads when indicated | | Routine oxygen in normoxemia | No benefit; potential harm | Give for hypoxemia/respiratory distress | | Nitrates in RV infarction or after PDE5 inhibitor | Severe hypotension | Check hemodynamics and medication history | | Prasugrel in prior stroke/TIA | Major bleeding risk | Use alternative P2Y12 agent | | Ignoring bleeding risk when planning DAPT | Preventable hemorrhage | Use PPI, shortened/modified strategies when appropriate | | Discharge without rehab/lipid plan | Misses high-value prevention | Document secondary prevention before discharge | --- ## Exam-focused review ### Foundation / Step 1 Know plaque rupture/erosion, platelet activation, thrombin/fibrin, subendocardial vulnerability, transmural progression, and the physiologic consequences of reduced coronary blood flow. ### Step 2 CK Priority questions usually ask: **What must happen next?** - STEMI ECG → reperfusion, not stress testing. - Ongoing ischemia with instability → invasive management. - Troponin rise/fall + ischemic evidence without ST elevation → NSTEMI. - Inferior MI + hypotension + clear lungs → consider RV infarction; obtain right-sided leads and avoid nitrates. - New murmur + shock days after MI → mechanical complication. ### Step 3 / Resident Add strategy details: reperfusion timing, fibrinolysis contraindications, antithrombotic selection, bleeding mitigation, shock phenotype, mechanical complications, secondary prevention. ### MRCP / ABIM / boards Expect nuance around: - Type 1 vs type 2 MI - Dynamic hs-cTn interpretation - GRACE risk - Antiplatelet contraindications - DAPT duration in bleeding risk / anticoagulation - Post-MI LV dysfunction therapy - Mechanical complications --- ## Original MCQs #### 1. A 61-year-old man has 90 minutes of crushing chest pain. ECG shows 3 mm ST elevation in V2–V5. Initial hs-cTn is within the reference range. What is the best next step? A. Repeat troponin in 3 hours before treatment B. Exercise stress testing C. Activate immediate reperfusion/primary PCI pathway D. CT coronary angiography first **Answer: C.** Early troponin can be normal. A diagnostic STEMI pattern with an appropriate syndrome requires immediate reperfusion; biomarkers must not delay treatment. #### 2. A patient with inferior STEMI becomes hypotensive after sublingual nitroglycerin. Lungs are clear and JVP is elevated. Best next diagnostic step? A. V4R right-sided ECG lead B. D-dimer C. CT pulmonary angiography D. Stress echocardiography **Answer: A.** The pattern strongly suggests RV infarction with preload dependence. #### 3. Which P2Y12 inhibitor is contraindicated in a patient with prior ischemic stroke? A. Clopidogrel B. Ticagrelor C. Prasugrel D. Cangrelor **Answer: C.** Prasugrel is contraindicated after prior stroke/TIA because of bleeding risk. #### 4. A stable ACS patient undergoes PCI and has no high bleeding risk. What is the contemporary default DAPT duration? A. 48 hours B. 1 month C. 6 weeks D. At least 12 months **Answer: D.** The 2025 ACC/AHA guideline uses at least 12 months as the default in patients without high bleeding risk. #### 5. A patient with NSTEMI has shock, ongoing ischemic pain, and recurrent VT despite initial therapy. What invasive strategy is appropriate? A. Outpatient angiography B. Immediate invasive evaluation C. Stress testing before angiography D. Coronary calcium score **Answer: B.** Very high-risk NSTE-ACS features require immediate invasive care. --- ## References 1. Rao SV, O'Donoghue ML, Ruel M, et al. **2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes.** *J Am Coll Cardiol.* 2025;85(22):2135–2237. doi: **10.1016/j.jacc.2024.11.009**. https://www.jacc.org/doi/10.1016/j.jacc.2024.11.009 2. American College of Cardiology / American Heart Association. **Top Things to Know: 2025 Guideline for Acute Coronary Syndromes.** Updated February 27, 2025. https://professional.heart.org/en/science-news/2025-guideline-for-the-management-of-patients-with-acute-coronary-syndromes/top-things-to-know 3. Byrne RA, Rossello X, Coughlan JJ, et al. **2023 ESC Guidelines for the management of acute coronary syndromes.** *Eur Heart J.* 2023;44(38):3720–3826. doi: **10.1093/eurheartj/ehad191**. PMID: **37622654**. https://www.escardio.org/guidelines/clinical-practice-guidelines/all-esc-practice-guidelines/acute-coronary-syndromes/ 4. Thygesen K, Alpert JS, Jaffe AS, et al. **Fourth Universal Definition of Myocardial Infarction (2018).** *Circulation.* 2018;138:e618–e651. doi: 10.1161/CIR.0000000000000617. 5. European Society of Cardiology. **Essential Messages from the 2023 ESC Guidelines for the Management of Acute Coronary Syndromes.** 2023. https://www.escardio.org/ 6. Kumbhani DJ, Cibotti-Sun M, Moore MM. **2025 Acute Coronary Syndromes Guideline-at-a-Glance.** *J Am Coll Cardiol.* 2025;85(22):2128–2134. doi: **10.1016/j.jacc.2025.01.018**. 7. Bikdeli B, Ujueta F, Rashedi S, et al. **Antiplatelet and Anticoagulant Therapy in the 2025 ACC/AHA Guideline for Acute Coronary Syndromes: Key Recommendations.** *J Am Coll Cardiol.* 2025. doi: **10.1016/j.jacc.2025.04.002**. --- **Review trigger:** Re-review whenever ACC/AHA or ESC ACS guidance changes, or when major trials alter PCI strategy, cardiogenic-shock support, antiplatelet duration/de-escalation, or lipid-lowering recommendations.7:["$","$L17",null,{"article":{"id":"medical-0002","title":"Acute Kidney Injury","slug":"acute-kidney-injury","description":"Acute kidney injury (AKI) is an abrupt decline in kidney function identified by a rise in serum creatinine and/or reduced urine output. 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