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/1jvnwmb7jnkpz.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:T75e5,## Summary **Sepsis** is life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis-3 operationalizes organ dysfunction as an acute **SOFA increase ≥2 points** attributable to infection. **Septic shock** is the high-risk subset in which vasopressors are required to maintain **MAP ≥65 mm Hg** and serum lactate remains **>2 mmol/L (18 mg/dL)** despite adequate volume resuscitation and in the absence of unresolved hypovolemia.[1] Sepsis is a time-critical syndrome, but treatment must remain physiology- and source-directed. The first bedside questions are: **Is infection likely? Is there organ dysfunction? Is perfusion threatened? Where is the source? What must be done now to reverse shock and control the infection?**[1,2] The **2026 Surviving Sepsis Campaign (SSC)** is the current international adult guideline. It recommends prompt cultures when this does not delay treatment, source-directed antimicrobials, balanced crystalloid as the preferred initial fluid, norepinephrine as first-line vasopressor, dynamic reassessment of fluid responsiveness, and timely source control. For sepsis-induced hypoperfusion or septic shock, SSC suggests at least **30 mL/kg IV crystalloid during the first 3 hours**, while emphasizing individualization and repeated reassessment rather than automatic repeated fixed-volume boluses.[2] Antimicrobial timing depends on shock and diagnostic probability. For **possible, probable, or definite septic shock**, give antimicrobials immediately, ideally within **1 hour**. For **probable or definite sepsis without shock**, 2026 SSC also recommends immediate treatment, ideally within **1 hour**. When sepsis is only possible and shock is absent, perform a rapid investigation; if concern for infection persists, administer antimicrobials within **3 hours**. If infection is unlikely and shock is absent, close monitoring while deferring antimicrobials is reasonable.[2] Start **norepinephrine** for persistent hypotension; it may be initiated through a well-sited peripheral IV rather than waiting for central access. For escalating norepinephrine requirements, add **vasopressin**; add epinephrine when MAP remains inadequate despite norepinephrine plus vasopressin. The usual initial MAP target is **65 mm Hg**; 2026 SSC suggests **60-65 mm Hg** as an initial target in adults aged 65 years or older when clinically appropriate.[2] For septic shock with an ongoing vasopressor requirement, SSC suggests IV corticosteroids. A widely studied regimen is **hydrocortisone 200 mg/day IV**, given as 50 mg every 6 hours or by continuous infusion. The 2026 guideline no longer anchors steroid initiation to the older rigid norepinephrine-dose/time threshold; use the persistence and severity of vasopressor-dependent shock to guide initiation.[2] > **Clinical pearl:** Sepsis care is serial reassessment. Every fluid bolus, vasopressor change, antimicrobial choice, lactate result, and source-control decision must be interpreted in the patient's evolving physiology. ## Definitions ### Sepsis Sepsis is **life-threatening organ dysfunction caused by a dysregulated host response to infection**.[1] Operationally: - suspected or confirmed infection; - acute SOFA increase **≥2 points** attributable to infection.[1] The older term “severe sepsis” is redundant under Sepsis-3 because infection-associated organ dysfunction is already sepsis. ### Septic shock Septic shock is identified by:[1] - vasopressor requirement to maintain MAP **≥65 mm Hg**; - lactate **>2 mmol/L**; - after adequate volume resuscitation / without unresolved hypovolemia. Do not wait for all formal criteria to be documented before treating a patient with clear shock physiology. ### Infection without sepsis Pneumonia, pyelonephritis, cellulitis, cholangitis, or another infection is not automatically sepsis. Infection becomes sepsis when it produces life-threatening organ dysfunction. ## Pathophysiology Sepsis combines dysregulated immune signaling with endothelial injury, vasodilation, capillary leak, coagulation activation, microvascular heterogeneity, myocardial dysfunction, mitochondrial/metabolic stress, and organ-specific injury.[1] A simplified sequence is: ```text Infection ↓ Dysregulated host response ↓ Vasodilation + endothelial leak + coagulation/microvascular dysfunction ↓ Relative intravascular depletion + maldistributed flow ↓ Cellular/metabolic stress ↓ Organ dysfunction ↓ Shock / multiorgan failure in severe disease ``` ### Lactate interpretation Lactate can rise from impaired perfusion, adrenergic-driven glycolysis, reduced hepatic clearance, seizures, epinephrine, and other mechanisms. It is a severity and trend marker, not a direct meter of tissue hypoxia.[2] A persistently high or rising lactate should trigger reassessment for: - ongoing shock; - inadequate source control; - mesenteric or limb ischemia; - seizures; - severe liver dysfunction; - epinephrine effect; - an alternative diagnosis. ## Common sources and source-control threats | Source | Typical clues | Urgent procedural issue | |---|---|---| | Lung | Cough, hypoxemia, infiltrate | Empyema, abscess, obstructed airway | | Urinary tract | Pyuria, flank pain, bacteremia | Infected obstructed collecting system | | Biliary | RUQ pain, jaundice, cholestatic profile | Cholangitis requiring biliary drainage | | Intra-abdominal | Pain, ileus, peritoneal signs | Perforation, ischemia, abscess | | Skin/soft tissue | Severe pain, erythema, bullae, crepitus | Necrotizing infection or drainable abscess | | Vascular catheter | Rigors, line inflammation, no alternate source | Remove infected catheter when appropriate | | CNS | Headache, neck stiffness, altered consciousness | Meningitis/encephalitis pathway; abscess | | Bone/joint | Focal pain, prosthesis, effusion | Drainage/debridement | | Endocardium | Murmur, embolic findings, prosthetic valve/device | Echocardiography, surgery/device management | ## Clinical features Sepsis can present with: - fever or hypothermia; - tachycardia; - tachypnea; - altered mentation; - hypotension; - oliguria; - hypoxemia; - mottling or delayed capillary refill; - thrombocytopenia; - hyperbilirubinemia; - acidosis; - elevated lactate. Older, immunocompromised, or medication-treated patients may have little fever or tachycardia despite severe illness. ### Immediate escalation features - airway compromise; - severe hypoxemia or respiratory fatigue; - persistent hypotension or mottled/cold shock physiology; - rapidly rising lactate with poor perfusion; - severe oliguria/anuria; - purpura or rapidly progressive soft-tissue pain; - peritoneal signs; - meningitis syndrome with altered consciousness; - infected urinary obstruction; - acute cholangitis with organ dysfunction; - suspected necrotizing soft-tissue infection; - rapidly progressive multiorgan dysfunction. ## Recognition and risk stratification ### SOFA SOFA assesses respiratory, coagulation, hepatic, cardiovascular, neurologic, and renal function. An acute rise ≥2 points in a patient with infection operationalizes Sepsis-3 organ dysfunction.[1] Do not delay treatment while waiting for every SOFA variable when infection-associated organ failure is clinically clear. ### qSOFA qSOFA uses: - respiratory rate ≥22/min; - altered mentation; - systolic BP ≤100 mm Hg. It can identify higher-risk patients but lacks sufficient sensitivity to be a sole screening strategy. The 2026 SSC recommends using **NEWS/NEWS2, MEWS, or SIRS rather than qSOFA alone** for hospital screening.[2] ### NEWS2 and the UK pathway NICE guideline NG253, published in 2025, uses **NEWS2 plus clinical judgment** for adult sepsis risk assessment in relevant settings.[3] This is an operational recognition/escalation pathway and is not interchangeable with SOFA, which describes organ dysfunction. > **Current practice:** International SSC and UK NICE pathways differ in operational details, especially initial fluid-bolus size. Institutions should implement one coherent local pathway rather than combining incompatible pieces from different protocols. ## First minutes: stabilization and parallel diagnosis | Domain | Assess | Immediate action | |---|---|---| | Airway | Patency, secretions, consciousness | Position/suction; definitive airway if protection or ventilation is failing | | Breathing | RR, SpO₂, work of breathing, gas when indicated | Oxygen to appropriate target; HFNC or ventilatory support when needed | | Circulation | HR, BP/MAP, capillary refill, skin, urine, lactate | IV/IO access; crystalloid for hypoperfusion; early norepinephrine for persistent hypotension | | Neurologic | Consciousness, glucose, focal deficit | Correct glucose/oxygen/perfusion; assess alternate causes | | Source | Skin, wounds, devices, chest, abdomen, back, urinary/biliary clues | Cultures, imaging, and procedural consultation without delaying resuscitation | Diagnostic work and stabilization should occur in parallel. ## Diagnostic work-up No single laboratory test confirms sepsis. Testing should establish organ dysfunction, identify the source, guide antimicrobials, and detect competing diagnoses. ### Common initial studies - CBC with differential; - sodium, potassium, bicarbonate, urea/BUN, creatinine; - liver profile and bilirubin; - glucose; - lactate; - venous or arterial blood gas when respiratory or metabolic failure is possible; - coagulation studies in significant illness; - blood cultures; - urinalysis and urine culture when urinary infection is plausible; - pregnancy testing when relevant to imaging/drug/procedure choices; - source-specific microbiology. ### Blood cultures Obtain appropriate blood cultures **before antimicrobials when this can be accomplished promptly without a clinically important treatment delay**.[2] Adequate blood volume matters. If endocarditis is plausible and the patient is stable enough, obtain the recommended multi-set culture strategy before antibiotics. ### Imaging Use the fastest study likely to identify a treatable source or complication: - chest radiography or lung ultrasound; - CT chest for complications or alternate diagnoses; - renal ultrasound or CT for obstruction; - CT abdomen/pelvis for intra-abdominal infection; - RUQ ultrasound and targeted biliary imaging; - echocardiography for suspected endocarditis or mixed shock; - brain imaging and lumbar-puncture pathway for CNS infection when appropriate. > **Caution:** In suspected necrotizing infection, perforated viscus, ischemic bowel, or another surgical catastrophe, do not let low-value imaging delay definitive source control. ## Sepsis mimics | Mimic | Clues | Useful discriminator | |---|---|---| | Hemorrhagic shock | Trauma, GI bleeding, postoperative bleeding | Focused imaging/procedure; hemoglobin can fall late | | Cardiogenic shock | Pulmonary edema, infarction, severe valve disease | ECG, troponin, bedside echo | | Obstructive shock | PE, tamponade, tension pneumothorax | Ultrasound/CT according to stability | | Adrenal crisis | Steroid dependence, hyponatremia, hyperkalemia | Clinical context; treat promptly when suspected | | Anaphylaxis | Exposure, urticaria, bronchospasm | Clinical syndrome and response to epinephrine | | DKA/HHS | Hyperglycemia, ketones, osmotic symptoms | Glucose, ketones, acid-base status | | Thyrotoxic crisis | Hyperthermia, marked adrenergic state | Thyroid studies and clinical context | | Drug toxicity | Exposure history, toxidrome | ECG and targeted toxicology testing | | Pancreatitis | Epigastric pain | Lipase and imaging when needed | | Hyperinflammatory syndromes | Cytopenias, extreme ferritin, organomegaly | Specialist diagnostic work-up | If a convincing noninfectious diagnosis emerges, de-escalate or stop empiric antimicrobials when safe.[2] ## Antimicrobial therapy ### Timing: 2026 SSC | Clinical state | Antimicrobial timing | |---|---| | Possible/probable/definite septic shock | Immediately, ideally within **1 hour** | | Probable/definite sepsis without shock | Immediately, ideally within **1 hour** | | Possible sepsis without shock | Rapid investigation; treat within **3 hours** if infection concern persists | | Low likelihood of infection, no shock | Close monitoring while deferring therapy can be reasonable | ### Empiric selection Choose therapy from: - likely anatomic source; - community versus healthcare acquisition; - local antibiogram; - prior cultures/colonization; - recent antibiotics; - MRSA risk; - resistant gram-negative risk; - immune status; - organ function; - allergy history; - source-specific local guidance. There is no universal “sepsis antibiotic.” Meningitis, cholangitis, obstructed pyelonephritis, pneumonia, neutropenic sepsis, and necrotizing soft-tissue infection require different regimens. ### Resistant organisms and combination therapy Broaden empirically when the probability and consequence of resistant infection justify it. The 2026 SSC supports MDR-risk-based coverage rather than routine duplicate gram-negative therapy for every patient.[2] Routine empiric antifungal therapy is not recommended for low-risk patients; consider it only when invasive fungal infection risk is substantial. Add anaerobic coverage when the source has a plausible anaerobic component rather than automatically.[2] ### Beta-lactam administration For patients with sepsis/septic shock receiving a beta-lactam, 2026 SSC recommends a **loading dose followed by prolonged infusion for maintenance dosing** when operationally feasible and pharmacologically appropriate.[2] Dose for the infection, site, renal function, body size, extracorporeal support, and local susceptibility data. In early shock, augmented renal clearance can coexist with increased volume of distribution, while later AKI can sharply reduce clearance. ### Daily antimicrobial reassessment At least daily, ask: - Is infection still the leading diagnosis? - Are cultures or molecular tests actionable? - Can spectrum be narrowed? - Has source control been achieved? - Is the current dose correct for organ function? - What is the shortest effective duration? SSC recommends de-escalation when microbiology permits and favors shorter effective courses after adequate source control. Procalcitonin plus clinical assessment can help decide when to stop antimicrobials when optimal duration remains uncertain.[2] ## Source control Source control can be as important as the antimicrobial. Targets include: - drainage of abscess or empyema; - decompression of obstructed infected urinary tract; - biliary drainage for severe cholangitis; - debridement of necrotizing soft-tissue infection; - surgery for perforation or ischemic bowel; - removal of infected devices when indicated; - drainage of septic arthritis. The 2026 SSC suggests implementing necessary source-control intervention **as soon as medically and logistically practical, ideally within 6 hours** when a source requiring intervention has been identified.[2] Do not use prolonged stabilization attempts as a reason to defer source control when the uncontrolled source is driving shock. ## Fluid resuscitation ### Initial fluid SSC 2026 suggests at least **30 mL/kg IV crystalloid within the first 3 hours** for sepsis-induced hypoperfusion or septic shock.[2] Key qualifiers: - individualize to age, heart failure, kidney disease, cirrhosis, obesity, and current congestion; - reassess frequently; - stop automatic bolusing when further fluid is unlikely to increase stroke volume or when congestion is developing; - in marked instability, vasopressors can begin concurrently rather than waiting until the entire fluid volume is complete.[2] SSC allows actual or adjusted/ideal body-weight approaches in patients with BMI >30 kg/m² according to clinical context and local implementation.[2] ### Fluid choice **Crystalloids** are first line. SSC favors **balanced crystalloids over 0.9% saline** for initial resuscitation.[2] Albumin is not routine first-line fluid; it can be considered in selected patients who require large crystalloid volumes and in selected cirrhosis contexts. Avoid hydroxyethyl starch and gelatin solutions.[2] ### Reassessment after initial resuscitation Use dynamic assessment where possible: - passive leg raise with stroke-volume/cardiac-output response; - stroke-volume change after a small fluid challenge; - pulse-pressure variation or stroke-volume variation in carefully selected ventilated patients; - capillary refill; - skin perfusion; - urine output; - serial lactate interpreted in context; - bedside ultrasound for ventricular function and congestion. Static filling pressures alone are poor predictors of fluid responsiveness.[2] ### SSC versus NICE fluid strategy NICE 2025 uses smaller sequential boluses in its adult pathway—typically **250 mL isotonic crystalloid over 10-15 minutes with reassessment**, repeated when indicated, generally up to an initial total of 1 L before senior review and further individualized management.[3] This differs from the SSC 30 mL/kg suggestion. The common principle is repeated reassessment and avoidance of blind fluid accumulation. ## Vasopressors ### Norepinephrine **Norepinephrine is first-line vasopressor therapy**.[2] Start it when hypotension persists despite an appropriate initial fluid trial, or concurrently with fluid in profoundly unstable vasodilatory shock. Do not wait for central venous access: a proximal, well-monitored peripheral IV is acceptable for initiation while central access is arranged when ongoing infusion is needed.[2] Titrate to perfusion and MAP rather than to a fixed dose. ### MAP target The usual initial target is **65 mm Hg**.[2] For adults **≥65 years**, SSC 2026 suggests an initial target of **60-65 mm Hg**, recognizing that lower pressure may reduce vasopressor exposure without compromising outcomes in selected older patients.[2] Use a higher individualized target when organ perfusion clearly requires it, such as selected patients with chronic severe hypertension and persistent renal hypoperfusion, but avoid reflexively driving MAP high with escalating catecholamines. ### Vasopressin Add vasopressin when norepinephrine requirements are escalating rather than continuing large increases in norepinephrine alone.[2] A commonly used fixed dose in adult septic shock is **0.03 units/min**; local protocols may use a narrow 0.03-0.04 units/min range. Vasopressin is not titrated like norepinephrine in most protocols. ### Epinephrine Add epinephrine when MAP remains inadequate despite norepinephrine plus vasopressin, or use it as an alternative in selected circumstances.[2] Epinephrine can raise lactate through beta-adrenergic effects; interpret a lactate rise in the full perfusion context. ### Cardiac dysfunction and persistent hypoperfusion When septic shock includes cardiac dysfunction with persistent hypoperfusion despite adequate volume status and arterial pressure, SSC supports either: - **dobutamine added to norepinephrine**, or - **epinephrine alone** as an inotropic/vasopressor strategy.[2] Bedside echocardiography helps distinguish vasoplegia from septic cardiomyopathy, RV failure, tamponade, severe valve disease, or another mixed-shock state. ## Corticosteroids For adults with septic shock and an ongoing vasopressor requirement, SSC 2026 suggests IV corticosteroids.[2] A standard evidence-based regimen is: - **hydrocortisone 200 mg/day IV**, given as **50 mg every 6 hours** or continuous infusion. The largest modern trials used total hydrocortisone exposure around 200 mg/day.[4,5] APROCCHSS used hydrocortisone plus fludrocortisone, while ADRENAL used hydrocortisone alone.[4,5] Monitor: - glucose; - sodium and potassium; - secondary infection risk; - delirium/weakness in the broader critical-care context. There is no requirement to perform adrenal testing before starting hydrocortisone for vasopressor-dependent septic shock. ## Respiratory support ### Oxygen and high-flow nasal oxygen For sepsis-associated acute hypoxemic respiratory failure, SSC 2026 favors **high-flow nasal oxygen** over conventional low-flow oxygen when higher support is required, and often over noninvasive ventilation in appropriate patients.[2] Escalate to intubation when there is: - worsening hypoxemia despite noninvasive support; - excessive work of breathing; - inability to protect the airway; - severe encephalopathy; - hemodynamic instability incompatible with continued noninvasive support. ### ARDS ventilation For sepsis-associated ARDS: - use low tidal volume ventilation around **6 mL/kg predicted body weight**; - target plateau pressure **≤30 cm H₂O**; - consider higher PEEP strategies in moderate/severe ARDS; - use prolonged prone positioning, generally **>12 hours/day**, in moderate/severe ARDS when criteria are met; - consider venovenous ECMO at experienced centers for refractory severe hypoxemia despite optimal conventional management.[2] See [Mechanical Ventilation in Adults](mechanical-ventilation-in-adults.md). ## Acute kidney injury and acid-base management ### Kidney support Prevent additional kidney injury by avoiding nephrotoxins when alternatives exist, optimizing perfusion, and adjusting drug doses. Renal-replacement therapy is initiated for standard indications such as refractory hyperkalemia, severe acidosis, pulmonary edema/volume overload, or major uremic complications rather than creatinine alone. ### Sodium bicarbonate SSC recommends against sodium bicarbonate solely to improve hemodynamics or reduce vasopressor needs in hypoperfusion-induced lactic acidemia. It suggests bicarbonate in selected patients with **pH ≤7.2 and AKI stage 2 or 3**.[2] Treat the cause of acidosis rather than targeting the serum bicarbonate number alone. ## Glucose, transfusion, and thromboprophylaxis ### Glucose SSC recommends starting insulin therapy when blood glucose is **≥180 mg/dL (10 mmol/L)**, then avoiding overly tight control that increases hypoglycemia risk.[2] ### Red-cell transfusion Use a restrictive transfusion strategy in most stable adults, with clinical context modifying the threshold for active hemorrhage, severe hypoxemia, acute myocardial ischemia, or another special circumstance.[2] ### Venous thromboembolism prevention Provide pharmacologic VTE prophylaxis unless contraindicated. Low-molecular-weight heparin is generally preferred over unfractionated heparin when renal function and bleeding risk allow.[2] ## Nutrition and fluid removal after stabilization Initiate enteral nutrition early when the gastrointestinal tract is usable; SSC 2026 supports enteral nutrition within **72 hours** in patients who cannot eat normally.[2] After the acute resuscitation phase, actively address fluid accumulation. Once shock is stabilizing, diuretics or renal-replacement–based fluid removal can be appropriate when edema, pulmonary congestion, or cumulative positive balance is clinically harmful.[2] ## Treatments not recommended routinely SSC 2026 recommends against routine use of: - IV vitamin C for sepsis; - IV immunoglobulin solely for sepsis; - blood-purification devices outside specific established indications; - beta-blockers as treatment for septic shock; - antipyretic drugs solely to improve sepsis outcomes.[2] These recommendations do not prevent standard use of a drug for another valid indication. ## Special populations ### Heart failure Do not withhold all initial fluid solely because heart failure is present, but use smaller reassessed increments when congestion risk is high. Start vasopressors early when vasoplegia persists rather than forcing additional fluid after responsiveness is lost. ### Advanced kidney disease Fluid accumulation can become dangerous rapidly. Use dynamic response, lung/venous-congestion assessment, and early vasopressor support. Adjust antimicrobials to the relevant renal function and dialysis modality. ### Cirrhosis Baseline vasodilation, low albumin, ascites, thrombocytopenia, and altered creatinine production complicate assessment. Search specifically for spontaneous bacterial peritonitis, cholangitis, pneumonia, urinary infection, and bloodstream infection. Albumin has disease-specific indications in cirrhosis that are separate from general sepsis fluid guidance. ### Neutropenia and major immune suppression Fever may be absent and infection can progress rapidly. Follow neutropenic-sepsis pathways for immediate antipseudomonal therapy, culture strategy, and source evaluation. Fungal risk depends on duration/type of immune suppression and prior antimicrobial exposure. ### Pregnancy and postpartum Physiologic heart rate, blood pressure, respiratory, and laboratory values differ during pregnancy. Manage with obstetric, maternal-medicine, critical-care, and source-specific specialists. Early source control and appropriate antimicrobials remain central. ## Monitoring shock response Track trends rather than isolated values: - MAP and vasopressor dose; - capillary refill and skin temperature/mottling; - mental status; - urine output; - lactate trajectory; - oxygen requirement and ventilation; - creatinine, bilirubin, platelet count, and coagulation; - cumulative fluid balance and signs of congestion; - source-control status; - antimicrobial susceptibility results. ### Refractory shock checklist If vasopressor requirements continue to rise: 1. Reconfirm the diagnosis and source. 2. Reassess intravascular volume and fluid responsiveness. 3. Look for ongoing hemorrhage. 4. Perform focused cardiac ultrasound for LV/RV failure, tamponade, severe valve disease, or dynamic obstruction. 5. Check for tension pneumothorax or massive pulmonary embolism. 6. Verify antimicrobial adequacy and source control. 7. Correct severe hypoxemia, acidosis, hypocalcemia, and other major physiologic derangements. 8. Ensure vasopressor delivery and vascular access are reliable. 9. Add vasopressin/epinephrine or inotropic support according to physiology. 10. Use hydrocortisone when vasopressor-dependent septic shock persists. ## Disposition ### ICU care Strongly indicated for: - vasopressor-dependent shock; - invasive or escalating noninvasive respiratory support; - rapidly progressive organ dysfunction; - severe lactic acidosis with poor perfusion; - major source-control procedures; - severe encephalopathy; - need for close hemodynamic monitoring. ### Step-down or ward care Appropriate only after hemodynamics are stable without escalating support, respiratory needs are manageable, source control is complete or clearly planned, and monitoring intensity matches the residual risk. ### Before discharge Address: - completion/de-escalation of antimicrobial therapy; - removal or management of temporary devices; - medication reconciliation; - rehabilitation and mobility; - new kidney, cardiac, pulmonary, cognitive, or functional impairment; - follow-up for unresolved source issues; - patient/family education about recurrent infection and post-sepsis symptoms. ## Prognosis and post-sepsis care Sepsis survivors have increased risk of: - recurrent infection and readmission; - new or worsened physical disability; - cognitive impairment; - anxiety, depression, and post-traumatic stress symptoms; - chronic kidney disease; - cardiovascular events; - persistent fatigue and reduced quality of life. Discharge planning should identify new organ dysfunction and provide appropriate primary-care, specialty, rehabilitation, and mental-health follow-up rather than treating hospital survival as the endpoint of care.[2] ## Acute management checklist - Confirm infection is plausible; identify organ dysfunction. - Obtain blood cultures promptly if this will not delay antimicrobial treatment. - Measure lactate and trend it in context. - Give immediate source-directed antimicrobials according to shock/probability timing. - Give balanced crystalloid for hypoperfusion; target at least 30 mL/kg over the first 3 hours when appropriate under SSC, with repeated reassessment. - Start norepinephrine early for persistent hypotension; peripheral initiation is acceptable. - Target MAP around 65 mm Hg; consider 60-65 mm Hg initially in adults ≥65 years when appropriate. - Use dynamic fluid-responsiveness measures before additional boluses. - Identify and control a drainable/removable/obstructed/ischemic source, ideally within 6 hours when intervention is needed. - Add vasopressin, then epinephrine according to escalating vasopressor needs and physiology. - Consider hydrocortisone 200 mg/day IV for ongoing vasopressor-dependent shock. - Use lung-protective ventilation for ARDS. - Reassess antimicrobials, dose, spectrum, and source control daily. - Transition from resuscitation to active decongestion when fluid accumulation becomes harmful and shock is stabilizing. ## References 1. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). *JAMA*. 2016;315:801-810. PMID: 26903338. DOI: 10.1001/jama.2016.0287. https://pubmed.ncbi.nlm.nih.gov/26903338/ 2. Prescott HC, Antonelli M, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026. *Crit Care Med*. 2026;54(4):725-812. DOI: 10.1097/CCM.0000000000007075. https://doi.org/10.1097/CCM.0000000000007075 3. National Institute for Health and Care Excellence. Suspected sepsis in people aged 16 or over: recognition, assessment and early management. NICE guideline NG253. 2025. https://www.nice.org.uk/guidance/ng253 4. Venkatesh B, Finfer S, Cohen J, et al. Adjunctive Glucocorticoid Therapy in Patients with Septic Shock. *N Engl J Med*. 2018;378:797-808. PMID: 29347874. DOI: 10.1056/NEJMoa1705835. https://pubmed.ncbi.nlm.nih.gov/29347874/ 5. Annane D, Renault A, Brun-Buisson C, et al. Hydrocortisone plus Fludrocortisone for Adults with Septic Shock. *N Engl J Med*. 2018;378:809-818. PMID: 29490185. DOI: 10.1056/NEJMoa1705716. https://pubmed.ncbi.nlm.nih.gov/29490185/19:T75e5,## Summary **Sepsis** is life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis-3 operationalizes organ dysfunction as an acute **SOFA increase ≥2 points** attributable to infection. **Septic shock** is the high-risk subset in which vasopressors are required to maintain **MAP ≥65 mm Hg** and serum lactate remains **>2 mmol/L (18 mg/dL)** despite adequate volume resuscitation and in the absence of unresolved hypovolemia.[1] Sepsis is a time-critical syndrome, but treatment must remain physiology- and source-directed. The first bedside questions are: **Is infection likely? Is there organ dysfunction? Is perfusion threatened? Where is the source? What must be done now to reverse shock and control the infection?**[1,2] The **2026 Surviving Sepsis Campaign (SSC)** is the current international adult guideline. It recommends prompt cultures when this does not delay treatment, source-directed antimicrobials, balanced crystalloid as the preferred initial fluid, norepinephrine as first-line vasopressor, dynamic reassessment of fluid responsiveness, and timely source control. For sepsis-induced hypoperfusion or septic shock, SSC suggests at least **30 mL/kg IV crystalloid during the first 3 hours**, while emphasizing individualization and repeated reassessment rather than automatic repeated fixed-volume boluses.[2] Antimicrobial timing depends on shock and diagnostic probability. For **possible, probable, or definite septic shock**, give antimicrobials immediately, ideally within **1 hour**. For **probable or definite sepsis without shock**, 2026 SSC also recommends immediate treatment, ideally within **1 hour**. When sepsis is only possible and shock is absent, perform a rapid investigation; if concern for infection persists, administer antimicrobials within **3 hours**. If infection is unlikely and shock is absent, close monitoring while deferring antimicrobials is reasonable.[2] Start **norepinephrine** for persistent hypotension; it may be initiated through a well-sited peripheral IV rather than waiting for central access. For escalating norepinephrine requirements, add **vasopressin**; add epinephrine when MAP remains inadequate despite norepinephrine plus vasopressin. The usual initial MAP target is **65 mm Hg**; 2026 SSC suggests **60-65 mm Hg** as an initial target in adults aged 65 years or older when clinically appropriate.[2] For septic shock with an ongoing vasopressor requirement, SSC suggests IV corticosteroids. A widely studied regimen is **hydrocortisone 200 mg/day IV**, given as 50 mg every 6 hours or by continuous infusion. The 2026 guideline no longer anchors steroid initiation to the older rigid norepinephrine-dose/time threshold; use the persistence and severity of vasopressor-dependent shock to guide initiation.[2] > **Clinical pearl:** Sepsis care is serial reassessment. Every fluid bolus, vasopressor change, antimicrobial choice, lactate result, and source-control decision must be interpreted in the patient's evolving physiology. ## Definitions ### Sepsis Sepsis is **life-threatening organ dysfunction caused by a dysregulated host response to infection**.[1] Operationally: - suspected or confirmed infection; - acute SOFA increase **≥2 points** attributable to infection.[1] The older term “severe sepsis” is redundant under Sepsis-3 because infection-associated organ dysfunction is already sepsis. ### Septic shock Septic shock is identified by:[1] - vasopressor requirement to maintain MAP **≥65 mm Hg**; - lactate **>2 mmol/L**; - after adequate volume resuscitation / without unresolved hypovolemia. Do not wait for all formal criteria to be documented before treating a patient with clear shock physiology. ### Infection without sepsis Pneumonia, pyelonephritis, cellulitis, cholangitis, or another infection is not automatically sepsis. Infection becomes sepsis when it produces life-threatening organ dysfunction. ## Pathophysiology Sepsis combines dysregulated immune signaling with endothelial injury, vasodilation, capillary leak, coagulation activation, microvascular heterogeneity, myocardial dysfunction, mitochondrial/metabolic stress, and organ-specific injury.[1] A simplified sequence is: ```text Infection ↓ Dysregulated host response ↓ Vasodilation + endothelial leak + coagulation/microvascular dysfunction ↓ Relative intravascular depletion + maldistributed flow ↓ Cellular/metabolic stress ↓ Organ dysfunction ↓ Shock / multiorgan failure in severe disease ``` ### Lactate interpretation Lactate can rise from impaired perfusion, adrenergic-driven glycolysis, reduced hepatic clearance, seizures, epinephrine, and other mechanisms. It is a severity and trend marker, not a direct meter of tissue hypoxia.[2] A persistently high or rising lactate should trigger reassessment for: - ongoing shock; - inadequate source control; - mesenteric or limb ischemia; - seizures; - severe liver dysfunction; - epinephrine effect; - an alternative diagnosis. ## Common sources and source-control threats | Source | Typical clues | Urgent procedural issue | |---|---|---| | Lung | Cough, hypoxemia, infiltrate | Empyema, abscess, obstructed airway | | Urinary tract | Pyuria, flank pain, bacteremia | Infected obstructed collecting system | | Biliary | RUQ pain, jaundice, cholestatic profile | Cholangitis requiring biliary drainage | | Intra-abdominal | Pain, ileus, peritoneal signs | Perforation, ischemia, abscess | | Skin/soft tissue | Severe pain, erythema, bullae, crepitus | Necrotizing infection or drainable abscess | | Vascular catheter | Rigors, line inflammation, no alternate source | Remove infected catheter when appropriate | | CNS | Headache, neck stiffness, altered consciousness | Meningitis/encephalitis pathway; abscess | | Bone/joint | Focal pain, prosthesis, effusion | Drainage/debridement | | Endocardium | Murmur, embolic findings, prosthetic valve/device | Echocardiography, surgery/device management | ## Clinical features Sepsis can present with: - fever or hypothermia; - tachycardia; - tachypnea; - altered mentation; - hypotension; - oliguria; - hypoxemia; - mottling or delayed capillary refill; - thrombocytopenia; - hyperbilirubinemia; - acidosis; - elevated lactate. Older, immunocompromised, or medication-treated patients may have little fever or tachycardia despite severe illness. ### Immediate escalation features - airway compromise; - severe hypoxemia or respiratory fatigue; - persistent hypotension or mottled/cold shock physiology; - rapidly rising lactate with poor perfusion; - severe oliguria/anuria; - purpura or rapidly progressive soft-tissue pain; - peritoneal signs; - meningitis syndrome with altered consciousness; - infected urinary obstruction; - acute cholangitis with organ dysfunction; - suspected necrotizing soft-tissue infection; - rapidly progressive multiorgan dysfunction. ## Recognition and risk stratification ### SOFA SOFA assesses respiratory, coagulation, hepatic, cardiovascular, neurologic, and renal function. An acute rise ≥2 points in a patient with infection operationalizes Sepsis-3 organ dysfunction.[1] Do not delay treatment while waiting for every SOFA variable when infection-associated organ failure is clinically clear. ### qSOFA qSOFA uses: - respiratory rate ≥22/min; - altered mentation; - systolic BP ≤100 mm Hg. It can identify higher-risk patients but lacks sufficient sensitivity to be a sole screening strategy. The 2026 SSC recommends using **NEWS/NEWS2, MEWS, or SIRS rather than qSOFA alone** for hospital screening.[2] ### NEWS2 and the UK pathway NICE guideline NG253, published in 2025, uses **NEWS2 plus clinical judgment** for adult sepsis risk assessment in relevant settings.[3] This is an operational recognition/escalation pathway and is not interchangeable with SOFA, which describes organ dysfunction. > **Current practice:** International SSC and UK NICE pathways differ in operational details, especially initial fluid-bolus size. Institutions should implement one coherent local pathway rather than combining incompatible pieces from different protocols. ## First minutes: stabilization and parallel diagnosis | Domain | Assess | Immediate action | |---|---|---| | Airway | Patency, secretions, consciousness | Position/suction; definitive airway if protection or ventilation is failing | | Breathing | RR, SpO₂, work of breathing, gas when indicated | Oxygen to appropriate target; HFNC or ventilatory support when needed | | Circulation | HR, BP/MAP, capillary refill, skin, urine, lactate | IV/IO access; crystalloid for hypoperfusion; early norepinephrine for persistent hypotension | | Neurologic | Consciousness, glucose, focal deficit | Correct glucose/oxygen/perfusion; assess alternate causes | | Source | Skin, wounds, devices, chest, abdomen, back, urinary/biliary clues | Cultures, imaging, and procedural consultation without delaying resuscitation | Diagnostic work and stabilization should occur in parallel. ## Diagnostic work-up No single laboratory test confirms sepsis. Testing should establish organ dysfunction, identify the source, guide antimicrobials, and detect competing diagnoses. ### Common initial studies - CBC with differential; - sodium, potassium, bicarbonate, urea/BUN, creatinine; - liver profile and bilirubin; - glucose; - lactate; - venous or arterial blood gas when respiratory or metabolic failure is possible; - coagulation studies in significant illness; - blood cultures; - urinalysis and urine culture when urinary infection is plausible; - pregnancy testing when relevant to imaging/drug/procedure choices; - source-specific microbiology. ### Blood cultures Obtain appropriate blood cultures **before antimicrobials when this can be accomplished promptly without a clinically important treatment delay**.[2] Adequate blood volume matters. If endocarditis is plausible and the patient is stable enough, obtain the recommended multi-set culture strategy before antibiotics. ### Imaging Use the fastest study likely to identify a treatable source or complication: - chest radiography or lung ultrasound; - CT chest for complications or alternate diagnoses; - renal ultrasound or CT for obstruction; - CT abdomen/pelvis for intra-abdominal infection; - RUQ ultrasound and targeted biliary imaging; - echocardiography for suspected endocarditis or mixed shock; - brain imaging and lumbar-puncture pathway for CNS infection when appropriate. > **Caution:** In suspected necrotizing infection, perforated viscus, ischemic bowel, or another surgical catastrophe, do not let low-value imaging delay definitive source control. ## Sepsis mimics | Mimic | Clues | Useful discriminator | |---|---|---| | Hemorrhagic shock | Trauma, GI bleeding, postoperative bleeding | Focused imaging/procedure; hemoglobin can fall late | | Cardiogenic shock | Pulmonary edema, infarction, severe valve disease | ECG, troponin, bedside echo | | Obstructive shock | PE, tamponade, tension pneumothorax | Ultrasound/CT according to stability | | Adrenal crisis | Steroid dependence, hyponatremia, hyperkalemia | Clinical context; treat promptly when suspected | | Anaphylaxis | Exposure, urticaria, bronchospasm | Clinical syndrome and response to epinephrine | | DKA/HHS | Hyperglycemia, ketones, osmotic symptoms | Glucose, ketones, acid-base status | | Thyrotoxic crisis | Hyperthermia, marked adrenergic state | Thyroid studies and clinical context | | Drug toxicity | Exposure history, toxidrome | ECG and targeted toxicology testing | | Pancreatitis | Epigastric pain | Lipase and imaging when needed | | Hyperinflammatory syndromes | Cytopenias, extreme ferritin, organomegaly | Specialist diagnostic work-up | If a convincing noninfectious diagnosis emerges, de-escalate or stop empiric antimicrobials when safe.[2] ## Antimicrobial therapy ### Timing: 2026 SSC | Clinical state | Antimicrobial timing | |---|---| | Possible/probable/definite septic shock | Immediately, ideally within **1 hour** | | Probable/definite sepsis without shock | Immediately, ideally within **1 hour** | | Possible sepsis without shock | Rapid investigation; treat within **3 hours** if infection concern persists | | Low likelihood of infection, no shock | Close monitoring while deferring therapy can be reasonable | ### Empiric selection Choose therapy from: - likely anatomic source; - community versus healthcare acquisition; - local antibiogram; - prior cultures/colonization; - recent antibiotics; - MRSA risk; - resistant gram-negative risk; - immune status; - organ function; - allergy history; - source-specific local guidance. There is no universal “sepsis antibiotic.” Meningitis, cholangitis, obstructed pyelonephritis, pneumonia, neutropenic sepsis, and necrotizing soft-tissue infection require different regimens. ### Resistant organisms and combination therapy Broaden empirically when the probability and consequence of resistant infection justify it. The 2026 SSC supports MDR-risk-based coverage rather than routine duplicate gram-negative therapy for every patient.[2] Routine empiric antifungal therapy is not recommended for low-risk patients; consider it only when invasive fungal infection risk is substantial. Add anaerobic coverage when the source has a plausible anaerobic component rather than automatically.[2] ### Beta-lactam administration For patients with sepsis/septic shock receiving a beta-lactam, 2026 SSC recommends a **loading dose followed by prolonged infusion for maintenance dosing** when operationally feasible and pharmacologically appropriate.[2] Dose for the infection, site, renal function, body size, extracorporeal support, and local susceptibility data. In early shock, augmented renal clearance can coexist with increased volume of distribution, while later AKI can sharply reduce clearance. ### Daily antimicrobial reassessment At least daily, ask: - Is infection still the leading diagnosis? - Are cultures or molecular tests actionable? - Can spectrum be narrowed? - Has source control been achieved? - Is the current dose correct for organ function? - What is the shortest effective duration? SSC recommends de-escalation when microbiology permits and favors shorter effective courses after adequate source control. Procalcitonin plus clinical assessment can help decide when to stop antimicrobials when optimal duration remains uncertain.[2] ## Source control Source control can be as important as the antimicrobial. Targets include: - drainage of abscess or empyema; - decompression of obstructed infected urinary tract; - biliary drainage for severe cholangitis; - debridement of necrotizing soft-tissue infection; - surgery for perforation or ischemic bowel; - removal of infected devices when indicated; - drainage of septic arthritis. The 2026 SSC suggests implementing necessary source-control intervention **as soon as medically and logistically practical, ideally within 6 hours** when a source requiring intervention has been identified.[2] Do not use prolonged stabilization attempts as a reason to defer source control when the uncontrolled source is driving shock. ## Fluid resuscitation ### Initial fluid SSC 2026 suggests at least **30 mL/kg IV crystalloid within the first 3 hours** for sepsis-induced hypoperfusion or septic shock.[2] Key qualifiers: - individualize to age, heart failure, kidney disease, cirrhosis, obesity, and current congestion; - reassess frequently; - stop automatic bolusing when further fluid is unlikely to increase stroke volume or when congestion is developing; - in marked instability, vasopressors can begin concurrently rather than waiting until the entire fluid volume is complete.[2] SSC allows actual or adjusted/ideal body-weight approaches in patients with BMI >30 kg/m² according to clinical context and local implementation.[2] ### Fluid choice **Crystalloids** are first line. SSC favors **balanced crystalloids over 0.9% saline** for initial resuscitation.[2] Albumin is not routine first-line fluid; it can be considered in selected patients who require large crystalloid volumes and in selected cirrhosis contexts. Avoid hydroxyethyl starch and gelatin solutions.[2] ### Reassessment after initial resuscitation Use dynamic assessment where possible: - passive leg raise with stroke-volume/cardiac-output response; - stroke-volume change after a small fluid challenge; - pulse-pressure variation or stroke-volume variation in carefully selected ventilated patients; - capillary refill; - skin perfusion; - urine output; - serial lactate interpreted in context; - bedside ultrasound for ventricular function and congestion. Static filling pressures alone are poor predictors of fluid responsiveness.[2] ### SSC versus NICE fluid strategy NICE 2025 uses smaller sequential boluses in its adult pathway—typically **250 mL isotonic crystalloid over 10-15 minutes with reassessment**, repeated when indicated, generally up to an initial total of 1 L before senior review and further individualized management.[3] This differs from the SSC 30 mL/kg suggestion. The common principle is repeated reassessment and avoidance of blind fluid accumulation. ## Vasopressors ### Norepinephrine **Norepinephrine is first-line vasopressor therapy**.[2] Start it when hypotension persists despite an appropriate initial fluid trial, or concurrently with fluid in profoundly unstable vasodilatory shock. Do not wait for central venous access: a proximal, well-monitored peripheral IV is acceptable for initiation while central access is arranged when ongoing infusion is needed.[2] Titrate to perfusion and MAP rather than to a fixed dose. ### MAP target The usual initial target is **65 mm Hg**.[2] For adults **≥65 years**, SSC 2026 suggests an initial target of **60-65 mm Hg**, recognizing that lower pressure may reduce vasopressor exposure without compromising outcomes in selected older patients.[2] Use a higher individualized target when organ perfusion clearly requires it, such as selected patients with chronic severe hypertension and persistent renal hypoperfusion, but avoid reflexively driving MAP high with escalating catecholamines. ### Vasopressin Add vasopressin when norepinephrine requirements are escalating rather than continuing large increases in norepinephrine alone.[2] A commonly used fixed dose in adult septic shock is **0.03 units/min**; local protocols may use a narrow 0.03-0.04 units/min range. Vasopressin is not titrated like norepinephrine in most protocols. ### Epinephrine Add epinephrine when MAP remains inadequate despite norepinephrine plus vasopressin, or use it as an alternative in selected circumstances.[2] Epinephrine can raise lactate through beta-adrenergic effects; interpret a lactate rise in the full perfusion context. ### Cardiac dysfunction and persistent hypoperfusion When septic shock includes cardiac dysfunction with persistent hypoperfusion despite adequate volume status and arterial pressure, SSC supports either: - **dobutamine added to norepinephrine**, or - **epinephrine alone** as an inotropic/vasopressor strategy.[2] Bedside echocardiography helps distinguish vasoplegia from septic cardiomyopathy, RV failure, tamponade, severe valve disease, or another mixed-shock state. ## Corticosteroids For adults with septic shock and an ongoing vasopressor requirement, SSC 2026 suggests IV corticosteroids.[2] A standard evidence-based regimen is: - **hydrocortisone 200 mg/day IV**, given as **50 mg every 6 hours** or continuous infusion. The largest modern trials used total hydrocortisone exposure around 200 mg/day.[4,5] APROCCHSS used hydrocortisone plus fludrocortisone, while ADRENAL used hydrocortisone alone.[4,5] Monitor: - glucose; - sodium and potassium; - secondary infection risk; - delirium/weakness in the broader critical-care context. There is no requirement to perform adrenal testing before starting hydrocortisone for vasopressor-dependent septic shock. ## Respiratory support ### Oxygen and high-flow nasal oxygen For sepsis-associated acute hypoxemic respiratory failure, SSC 2026 favors **high-flow nasal oxygen** over conventional low-flow oxygen when higher support is required, and often over noninvasive ventilation in appropriate patients.[2] Escalate to intubation when there is: - worsening hypoxemia despite noninvasive support; - excessive work of breathing; - inability to protect the airway; - severe encephalopathy; - hemodynamic instability incompatible with continued noninvasive support. ### ARDS ventilation For sepsis-associated ARDS: - use low tidal volume ventilation around **6 mL/kg predicted body weight**; - target plateau pressure **≤30 cm H₂O**; - consider higher PEEP strategies in moderate/severe ARDS; - use prolonged prone positioning, generally **>12 hours/day**, in moderate/severe ARDS when criteria are met; - consider venovenous ECMO at experienced centers for refractory severe hypoxemia despite optimal conventional management.[2] See [Mechanical Ventilation in Adults](mechanical-ventilation-in-adults.md). ## Acute kidney injury and acid-base management ### Kidney support Prevent additional kidney injury by avoiding nephrotoxins when alternatives exist, optimizing perfusion, and adjusting drug doses. Renal-replacement therapy is initiated for standard indications such as refractory hyperkalemia, severe acidosis, pulmonary edema/volume overload, or major uremic complications rather than creatinine alone. ### Sodium bicarbonate SSC recommends against sodium bicarbonate solely to improve hemodynamics or reduce vasopressor needs in hypoperfusion-induced lactic acidemia. It suggests bicarbonate in selected patients with **pH ≤7.2 and AKI stage 2 or 3**.[2] Treat the cause of acidosis rather than targeting the serum bicarbonate number alone. ## Glucose, transfusion, and thromboprophylaxis ### Glucose SSC recommends starting insulin therapy when blood glucose is **≥180 mg/dL (10 mmol/L)**, then avoiding overly tight control that increases hypoglycemia risk.[2] ### Red-cell transfusion Use a restrictive transfusion strategy in most stable adults, with clinical context modifying the threshold for active hemorrhage, severe hypoxemia, acute myocardial ischemia, or another special circumstance.[2] ### Venous thromboembolism prevention Provide pharmacologic VTE prophylaxis unless contraindicated. Low-molecular-weight heparin is generally preferred over unfractionated heparin when renal function and bleeding risk allow.[2] ## Nutrition and fluid removal after stabilization Initiate enteral nutrition early when the gastrointestinal tract is usable; SSC 2026 supports enteral nutrition within **72 hours** in patients who cannot eat normally.[2] After the acute resuscitation phase, actively address fluid accumulation. Once shock is stabilizing, diuretics or renal-replacement–based fluid removal can be appropriate when edema, pulmonary congestion, or cumulative positive balance is clinically harmful.[2] ## Treatments not recommended routinely SSC 2026 recommends against routine use of: - IV vitamin C for sepsis; - IV immunoglobulin solely for sepsis; - blood-purification devices outside specific established indications; - beta-blockers as treatment for septic shock; - antipyretic drugs solely to improve sepsis outcomes.[2] These recommendations do not prevent standard use of a drug for another valid indication. ## Special populations ### Heart failure Do not withhold all initial fluid solely because heart failure is present, but use smaller reassessed increments when congestion risk is high. Start vasopressors early when vasoplegia persists rather than forcing additional fluid after responsiveness is lost. ### Advanced kidney disease Fluid accumulation can become dangerous rapidly. Use dynamic response, lung/venous-congestion assessment, and early vasopressor support. Adjust antimicrobials to the relevant renal function and dialysis modality. ### Cirrhosis Baseline vasodilation, low albumin, ascites, thrombocytopenia, and altered creatinine production complicate assessment. Search specifically for spontaneous bacterial peritonitis, cholangitis, pneumonia, urinary infection, and bloodstream infection. Albumin has disease-specific indications in cirrhosis that are separate from general sepsis fluid guidance. ### Neutropenia and major immune suppression Fever may be absent and infection can progress rapidly. Follow neutropenic-sepsis pathways for immediate antipseudomonal therapy, culture strategy, and source evaluation. Fungal risk depends on duration/type of immune suppression and prior antimicrobial exposure. ### Pregnancy and postpartum Physiologic heart rate, blood pressure, respiratory, and laboratory values differ during pregnancy. Manage with obstetric, maternal-medicine, critical-care, and source-specific specialists. Early source control and appropriate antimicrobials remain central. ## Monitoring shock response Track trends rather than isolated values: - MAP and vasopressor dose; - capillary refill and skin temperature/mottling; - mental status; - urine output; - lactate trajectory; - oxygen requirement and ventilation; - creatinine, bilirubin, platelet count, and coagulation; - cumulative fluid balance and signs of congestion; - source-control status; - antimicrobial susceptibility results. ### Refractory shock checklist If vasopressor requirements continue to rise: 1. Reconfirm the diagnosis and source. 2. Reassess intravascular volume and fluid responsiveness. 3. Look for ongoing hemorrhage. 4. Perform focused cardiac ultrasound for LV/RV failure, tamponade, severe valve disease, or dynamic obstruction. 5. Check for tension pneumothorax or massive pulmonary embolism. 6. Verify antimicrobial adequacy and source control. 7. Correct severe hypoxemia, acidosis, hypocalcemia, and other major physiologic derangements. 8. Ensure vasopressor delivery and vascular access are reliable. 9. Add vasopressin/epinephrine or inotropic support according to physiology. 10. Use hydrocortisone when vasopressor-dependent septic shock persists. ## Disposition ### ICU care Strongly indicated for: - vasopressor-dependent shock; - invasive or escalating noninvasive respiratory support; - rapidly progressive organ dysfunction; - severe lactic acidosis with poor perfusion; - major source-control procedures; - severe encephalopathy; - need for close hemodynamic monitoring. ### Step-down or ward care Appropriate only after hemodynamics are stable without escalating support, respiratory needs are manageable, source control is complete or clearly planned, and monitoring intensity matches the residual risk. ### Before discharge Address: - completion/de-escalation of antimicrobial therapy; - removal or management of temporary devices; - medication reconciliation; - rehabilitation and mobility; - new kidney, cardiac, pulmonary, cognitive, or functional impairment; - follow-up for unresolved source issues; - patient/family education about recurrent infection and post-sepsis symptoms. ## Prognosis and post-sepsis care Sepsis survivors have increased risk of: - recurrent infection and readmission; - new or worsened physical disability; - cognitive impairment; - anxiety, depression, and post-traumatic stress symptoms; - chronic kidney disease; - cardiovascular events; - persistent fatigue and reduced quality of life. Discharge planning should identify new organ dysfunction and provide appropriate primary-care, specialty, rehabilitation, and mental-health follow-up rather than treating hospital survival as the endpoint of care.[2] ## Acute management checklist - Confirm infection is plausible; identify organ dysfunction. - Obtain blood cultures promptly if this will not delay antimicrobial treatment. - Measure lactate and trend it in context. - Give immediate source-directed antimicrobials according to shock/probability timing. - Give balanced crystalloid for hypoperfusion; target at least 30 mL/kg over the first 3 hours when appropriate under SSC, with repeated reassessment. - Start norepinephrine early for persistent hypotension; peripheral initiation is acceptable. - Target MAP around 65 mm Hg; consider 60-65 mm Hg initially in adults ≥65 years when appropriate. - Use dynamic fluid-responsiveness measures before additional boluses. - Identify and control a drainable/removable/obstructed/ischemic source, ideally within 6 hours when intervention is needed. - Add vasopressin, then epinephrine according to escalating vasopressor needs and physiology. - Consider hydrocortisone 200 mg/day IV for ongoing vasopressor-dependent shock. - Use lung-protective ventilation for ARDS. - Reassess antimicrobials, dose, spectrum, and source control daily. - Transition from resuscitation to active decongestion when fluid accumulation becomes harmful and shock is stabilizing. ## References 1. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). *JAMA*. 2016;315:801-810. PMID: 26903338. DOI: 10.1001/jama.2016.0287. https://pubmed.ncbi.nlm.nih.gov/26903338/ 2. Prescott HC, Antonelli M, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026. *Crit Care Med*. 2026;54(4):725-812. DOI: 10.1097/CCM.0000000000007075. https://doi.org/10.1097/CCM.0000000000007075 3. National Institute for Health and Care Excellence. Suspected sepsis in people aged 16 or over: recognition, assessment and early management. NICE guideline NG253. 2025. https://www.nice.org.uk/guidance/ng253 4. Venkatesh B, Finfer S, Cohen J, et al. Adjunctive Glucocorticoid Therapy in Patients with Septic Shock. *N Engl J Med*. 2018;378:797-808. PMID: 29347874. DOI: 10.1056/NEJMoa1705835. https://pubmed.ncbi.nlm.nih.gov/29347874/ 5. Annane D, Renault A, Brun-Buisson C, et al. Hydrocortisone plus Fludrocortisone for Adults with Septic Shock. *N Engl J Med*. 2018;378:809-818. PMID: 29490185. DOI: 10.1056/NEJMoa1705716. https://pubmed.ncbi.nlm.nih.gov/29490185/1a:T8da2,## One-minute summary The **ABCDE approach** is a structured method for the immediate assessment and treatment of a deteriorating or critically ill patient: **A**irway, **B**reathing, **C**irculation, **D**isability, **E**xposure. The central rule is **treat life-threatening abnormalities as soon as they are found, then reassess from A**.[1,2] ABCDE is designed for **physiologic stabilization before diagnostic completeness**. It is useful in emergency departments, wards, critical care, perioperative settings, clinics, and prehospital care. The 2025 Resuscitation Council UK (RCUK) First Aid Guidelines explicitly endorse a structured ABCDE assessment for people who appear ill, injured, or in shock.[2] **Do not continue a routine ABCDE survey in a patient who is unresponsive and not breathing normally:** activate the cardiac-arrest pathway and start CPR according to current resuscitation guidance.[1,3] ### Core sequence ```text Safety → responsiveness → call for help ↓ A Airway: patent and protected? ↓ B Breathing: oxygenation and ventilation adequate? ↓ C Circulation: perfusion adequate? bleeding? shock? ↓ D Disability: consciousness, pupils, glucose, focal deficit? ↓ E Exposure: hidden clues, temperature, environment? ↓ REASSESS A → B → C → D → E after every important intervention ``` ★ **HIGH YIELD:** ABCDE is a **treat-as-you-find** framework, not “finish the examination, then begin treatment.” --- ## General principles 1. **Treat the greatest immediate threat first.** 2. **Call for help early** if the patient is critically ill or deterioration is likely.[1] 3. **Use the team in parallel:** monitoring, IV access, blood sampling, medication preparation, airway equipment, documentation, and escalation can occur simultaneously.[1] 4. **Reassess after interventions** because the response to treatment determines the next step.[1] 5. **Do not delay lifesaving treatment for a definitive diagnosis.** 6. **Trend physiology**, not isolated numbers: respiratory rate, work of breathing, SpO₂, pulse, blood pressure, mental status, perfusion, urine output, lactate, and response to therapy. 7. **Escalate early** when the patient may require airway expertise, critical care, surgery, interventional radiology, cardiology, neurology, obstetrics, pediatrics, toxicology, or transfer. The ABCDE concept is broadly applicable because airway obstruction, respiratory failure, shock, and neurologic compromise can kill more quickly than many definitive diagnoses can be established.[4] --- ## Clinical applications Use ABCDE for any patient who is **potentially unstable**, including: - sudden deterioration on a ward - severe dyspnea or hypoxemia - shock or suspected sepsis - major bleeding - altered mental status - anaphylaxis - poisoning/overdose - major trauma - peri-arrest states - acute neurologic deterioration - postoperative deterioration - obstetric or pediatric emergencies, with population-specific modifications ### When ABCDE is not the primary pathway If the patient is **unresponsive and not breathing normally**, manage as possible cardiac arrest rather than spending time completing a conventional ABCDE survey.[1,3] ⚠ **COMMON TRAP:** Agonal gasps are abnormal breathing and may occur during cardiac arrest. --- ## First 30 seconds — before A A rapid global impression can reveal critical illness before detailed examination. | Step | What to do | Why it matters | |---|---|---| | Safety | Confirm scene/personal safety; use appropriate PPE | Protects patient and team | | Responsiveness | Speak to the patient; assess response | A coherent answer suggests current airway patency, ventilation, cerebral perfusion, and neurologic function | | Help | Call emergency/resuscitation/senior help early | Complex stabilization is a team task | | Monitoring | Apply pulse oximetry, ECG monitoring, and noninvasive BP early when feasible | Establishes trends and detects deterioration | | Access | Obtain IV access and blood samples when indicated | Enables treatment and diagnostics | | Arrest check | If unresponsive and not breathing normally, activate cardiac-arrest response | CPR/defibrillation take priority | RCUK emphasizes early monitoring, IV access, teamwork, structured communication, and repeated reassessment in critically ill patients.[1] --- ## A — Airway ### Goal Determine whether the airway is **patent, maintainable, and protectable**, and correct life-threatening obstruction immediately. ### Why airway comes first Complete airway obstruction rapidly prevents oxygen delivery. Even partial obstruction can worsen suddenly because of edema, blood, vomitus, secretions, foreign material, trauma, reduced consciousness, or progressive upper-airway pathology.[1,4] ### Airway assessment and immediate management | Component | Assessment | Concerning findings | Immediate action | Anticipate deterioration when… | |---|---|---|---|---| | Speech | Ask patient to speak | Hoarse voice, weak voice, inability to speak | Call for help; prepare airway support | voice is changing, swelling progressing | | Sounds | Listen without a stethoscope first | Stridor, snoring, gurgling, silence | Airway maneuvers, suction, adjuncts, expert help | stridor, swelling, reduced consciousness | | Mouth/oropharynx | Inspect if safe | Blood, vomit, secretions, foreign body, edema | Suction/remove visible obstruction as appropriate | bleeding or secretions continue | | Consciousness | AVPU/GCS trend | Reduced airway protection | Position, adjunct, ventilation; consider definitive airway | GCS/alertness falling | | Neck/face | Trauma, swelling, burns, hematoma | Distortion, rapidly progressive edema | Early anesthetic/ENT/critical-care involvement | expanding neck hematoma, angioedema, inhalation injury | | Air movement | Look/listen/feel | Minimal or absent airflow | Immediate airway opening + ventilation support | fatigue or obstruction worsening | ### Immediate airway interventions Depending on cause, setting, and expertise: - call for expert airway help early - open the airway with appropriate maneuvers - suction blood, vomit, or secretions - remove visible foreign material when appropriate - insert an oropharyngeal or nasopharyngeal airway when indicated - provide bag-mask ventilation if ventilation is inadequate - use a supraglottic airway as a rescue/bridge when appropriate - proceed to tracheal intubation when a definitive airway is required and expertise is available - prepare for emergency front-of-neck access if oxygenation/ventilation cannot be achieved by conventional means RCUK notes that simple airway-opening measures and adjuncts are sufficient in many cases, while tracheal intubation may be required when these fail.[1] #### Causes of threatened airway - reduced consciousness - foreign-body obstruction - blood/vomit/secretions - anaphylaxis/angioedema - inhalational or facial burns - neck hematoma or penetrating injury - upper-airway infection or mass - facial/maxillofacial trauma - seizures - intoxication/sedation #### Trauma note If cervical-spine injury is possible, minimize unnecessary neck movement, but **do not allow spinal precautions to prevent airway opening or oxygenation**. ⚠ **RED FLAGS** - stridor - rapidly progressive facial/tongue/neck swelling - inability to handle secretions - falling level of consciousness - silent airway with respiratory effort - severe facial/neck trauma - smoke inhalation with evolving airway edema ★ **EXAM PEARL:** A patient who can speak normally has a patent airway **at that moment**; it does not guarantee continued patency. --- ## B — Breathing ### Goal Determine whether oxygenation and ventilation are adequate, recognize immediately life-threatening thoracic/respiratory disorders, and support breathing while treating the cause. ### Breathing assessment | Component | Assess | Key abnormal patterns | Immediate implications | |---|---|---|---| | General appearance | agitation, confusion, fatigue, cyanosis | agitation may be early hypoxemia; somnolence may signal hypercapnia/fatigue | escalate monitoring and support | | Respiratory rate | rate and trend | tachypnea, bradypnea, apnea | severe abnormalities can precede arrest | | Speech | full sentences vs words only | short phrases suggest marked respiratory distress | urgent support/treatment | | Work of breathing | accessory muscles, recession, paradoxical movement | increased effort or exhaustion | impending respiratory failure | | Chest movement | symmetry and depth | unilateral reduction | pneumothorax, hemothorax, effusion, obstruction | | Auscultation | bilateral air entry, wheeze, crackles | silent chest, unilateral absent sounds, diffuse wheeze, crackles | targeted emergency therapy | | Percussion | hyperresonance/dullness when useful | hyperresonance vs dullness | pneumothorax vs fluid/consolidation | | SpO₂ | saturation and trend | hypoxemia | oxygen and cause-specific therapy | | CO₂ assessment | capnography/blood gas when indicated | hypercapnia or hypocapnia | assesses ventilation and severity | ### Immediately dangerous breathing problems Think especially about: - tension pneumothorax - severe asthma/bronchospasm - pulmonary edema - massive hemothorax - severe pneumonia - pulmonary embolism - respiratory muscle failure - opioid/sedative respiratory depression - airway obstruction causing secondary ventilatory failure #### Oxygen RCUK’s ABCDE guidance recommends high-concentration oxygen initially for critically ill patients, followed by titration once reliable monitoring is available. For acute respiratory failure, typical targets are **94–98% for most patients** and **88–92% for patients at risk of hypercapnic respiratory failure**, unless an individualized target is documented.[1] #### Ventilatory support If spontaneous ventilation is inadequate: 1. open/secure the airway 2. assist ventilation, commonly beginning with bag-mask ventilation 3. add airway adjuncts when needed 4. escalate to noninvasive or invasive ventilation when appropriate 5. treat the underlying reversible cause #### Bedside tests and monitoring Depending on severity: - continuous pulse oximetry - respiratory-rate monitoring - arterial or venous blood gas - capnography/capnometry - portable chest radiography - lung/pleural point-of-care ultrasound ⚠ **COMMON TRAP:** A normal SpO₂ does **not** prove adequate ventilation. A patient can retain dangerous amounts of CO₂ while oxygen saturation appears acceptable, especially while receiving supplemental oxygen. ✓ **NEXT BEST STEP:** In obvious severe respiratory failure, support oxygenation/ventilation **before** sending the patient for nonessential imaging. --- ## C — Circulation ### Goal Recognize shock, hemorrhage, dysrhythmia, or other circulatory failure and restore adequate tissue perfusion while treating the cause. ### Circulation assessment | Component | What to assess | Concerning findings | What they suggest | |---|---|---|---| | Mental status | confusion, agitation, drowsiness | deterioration | cerebral hypoperfusion, hypoxemia, metabolic cause | | Skin | color, temperature, mottling, diaphoresis | cool/mottled or markedly flushed | shock pattern varies by etiology | | Pulse | rate, rhythm, volume, symmetry | tachycardia, bradycardia, weak pulse, asymmetry | shock, dysrhythmia, vascular emergency | | BP | repeated/trended measurements | hypotension or severe hypertension | shock or hypertensive emergency | | Capillary refill | trend in context | prolonged refill | possible poor peripheral perfusion | | JVP/volume clues | neck veins, edema, mucosa | low vs high filling signs | helps distinguish hypovolemia from obstructive/cardiogenic states | | Bleeding survey | external, GI, thoracic, abdominal, pelvic, retroperitoneal | ongoing blood loss | hemorrhagic shock | | Urine output | trend when catheterization indicated | oliguria | possible renal hypoperfusion | ★ **HIGH YIELD:** **Normal blood pressure does not exclude shock.** Compensatory vasoconstriction may preserve blood pressure despite inadequate tissue perfusion.[1] ### Initial circulatory actions - control obvious external hemorrhage immediately - establish IV access; use IO access when necessary and appropriate - obtain blood samples while access is established - apply continuous cardiac monitoring when indicated - obtain a 12-lead ECG for suspected ischemia/dysrhythmia - use blood gas/lactate and other tests according to context - consider point-of-care ultrasound to help identify shock physiology - begin cause-specific resuscitation without waiting for diagnostic perfection ### Shock framework | Shock type | Typical clues | Immediate priorities | |---|---|---| | Hypovolemic/hemorrhagic | bleeding, low filling signs, tachycardia, cool skin | hemorrhage control, blood products when indicated, cautious crystalloid where appropriate | | Distributive | sepsis/anaphylaxis; may have warm peripheries early | cause-specific treatment, fluids when appropriate, vasopressors when indicated | | Cardiogenic | pulmonary edema, ischemia, high JVP, cool peripheries | cautious fluids, reperfusion/arrhythmia management, vasoactive support, specialist care | | Obstructive | tamponade, tension pneumothorax, massive PE | immediate relief/treatment of obstruction | #### Fluids are not one-size-fits-all Use the suspected cause, comorbidities, dynamic response, and disease-specific guidance to determine fluid strategy. Reassess after each intervention. Excess fluid can worsen cardiogenic shock, pulmonary edema, and some other states. #### Major hemorrhage Priorities may include: - hemorrhage control - major hemorrhage/massive transfusion protocol activation - balanced blood-component or whole-blood strategies according to local protocol - correction of coagulopathy and hypothermia - urgent surgery/interventional radiology - anticoagulant reversal when indicated #### Obstructive emergencies - **tension pneumothorax:** emergency decompression followed by definitive pleural drainage according to trauma/emergency protocol - **cardiac tamponade:** urgent drainage in the appropriate clinical context - **high-risk pulmonary embolism with hemodynamic collapse:** reperfusion strategy according to PE guidance #### Distributive emergencies - **anaphylaxis:** intramuscular epinephrine/adrenaline is first-line - **sepsis/septic shock:** rapid antimicrobials, source control, hemodynamic support according to current sepsis guidance - **adrenal crisis:** glucocorticoid replacement and supportive therapy ### Useful rapid investigations - ECG - CBC - electrolytes/renal function - glucose - blood gas and lactate - coagulation tests - type and screen/crossmatch - troponin when ACS suspected - cultures when infection suspected and they do not delay treatment - POCUS when expertise is available ⚠ **COMMON TRAP:** Treating “hypotension” with repeated fluid boluses without considering cardiogenic or obstructive shock. --- ## D — Disability ### Goal Rapidly assess neurologic function and correct immediately reversible causes of impaired consciousness. ### Disability assessment | Component | What to check | Why | |---|---|---| | Level of consciousness | AVPU/ACVPU and/or GCS | detects deterioration and airway-protection risk | | Pupils | size, symmetry, reactivity | clues to structural neurologic disease or toxins | | Glucose | bedside capillary/POC glucose | hypoglycemia is rapidly reversible | | Focal deficits | face, speech, limbs, gaze as appropriate | stroke/intracranial pathology | | Seizure activity | ongoing or recent | requires urgent treatment and airway consideration | | Toxidrome clues | pupils, skin, secretions, respiratory pattern | directs antidote/supportive therapy | #### First principle: revisit ABC causes Before attributing altered consciousness to a primary brain disorder, reconsider: - hypoxemia - hypercapnia - shock/cerebral hypoperfusion - hypoglycemia - sedatives/opioids/toxins Then consider stroke, intracranial hemorrhage, seizures, meningitis/encephalitis, traumatic brain injury, raised intracranial pressure, electrolyte disorders, and other causes. #### Immediate reversible conditions - hypoglycemia → glucose according to local protocol - opioid toxicity with respiratory depression → airway/ventilation support and naloxone when indicated - ongoing convulsive status epilepticus → benzodiazepine-based emergency seizure treatment followed by protocolized escalation - suspected bacterial meningitis → prompt empiric antimicrobial therapy once appropriate initial steps are taken; do not allow nonessential imaging to create dangerous delay - suspected raised ICP/herniation → urgent neurocritical/neurosurgical pathway and neuroprotective measures ⚠ **COMMON TRAP:** Sending an unstable obtunded patient straight to CT before correcting hypoxia, hypotension, hypoglycemia, or active seizures. #### Airway and consciousness Reduced consciousness may compromise airway protection, but **a single GCS threshold should not be used mechanically without clinical context**. Consider trajectory, airway reflexes, ventilation, oxygenation, aspiration risk, anticipated course, and available expertise. --- ## E — Exposure / Environment ### Goal Perform a sufficiently complete examination to identify hidden pathology while preserving dignity and preventing environmental harm. ### Exposure assessment Look for: - trauma, burns, wounds, bruising - rashes, petechiae, purpura - cellulitis, gangrene, infected surgical sites - bleeding or occult sources of blood loss - edema - abdominal distention or peritonism - limb ischemia - track marks, transdermal patches, toxic exposures - devices, drains, catheters, stomas - bites/stings or retained foreign material - pregnancy-related clues when relevant Measure temperature and manage hypothermia or hyperthermia appropriately. #### Environmental control - replace wet or contaminated clothing - remove ongoing allergen/toxin exposure where safe - begin rewarming or cooling as indicated - re-cover the patient after examination - preserve privacy and dignity ★ **HIGH YIELD:** Exposure means **look thoroughly, then protect the patient from heat loss and environmental harm**. --- ## Reassessment — the essential sixth step ABCDE is **cyclical**, not linear. After every meaningful intervention, ask: - **A:** Is the airway now patent and likely to remain so? - **B:** Has oxygenation, ventilation, respiratory rate, or work of breathing improved? - **C:** Has perfusion improved? What happened to pulse, BP, capillary refill, mental status, urine output, lactate? - **D:** Has consciousness or glucose improved? Any new focal deficit? - **E:** Has a hidden cause or environmental problem been identified? RCUK specifically emphasizes reassessing the patient and evaluating the effect of treatment.[1] ⚠ **RED FLAG:** Any deterioration during later assessment or secondary survey should trigger an immediate return to **A**. --- ## Anticipation of deterioration A high-quality ABCDE assessment does not only ask “what is wrong now?” It asks **“what may fail next?”** | Domain | High-risk features | Prepare for | |---|---|---| | Airway | angioedema, inhalation injury, expanding neck hematoma, worsening consciousness | advanced airway equipment, expert airway team, rescue airway plan | | Breathing | escalating O₂ need, exhaustion, silent chest, rising CO₂ | assisted ventilation, NIV/intubation, critical care | | Circulation | ongoing bleeding, rising lactate, worsening perfusion, escalating vasopressor need | major hemorrhage response, invasive monitoring, definitive source control | | Disability | declining GCS, recurrent seizures, focal deterioration, signs of herniation | airway protection, urgent imaging when stable enough, neurocritical/neurosurgical care | | Exposure | hypothermia, toxin contamination, spreading infection, concealed hemorrhage | rewarming/decontamination/source control | ★ **BOARD-LEVEL POINT:** Deterioration often becomes obvious first as a **trend**—rising respiratory rate, increasing oxygen requirement, narrowing pulse pressure, altered mentation, or increasing support needs—before a single dramatic threshold is crossed. --- ## Crisis resource management and team performance The ABCDE method works best when the team functions deliberately. ### Key principles - establish a clear team leader - allocate tasks explicitly - use **closed-loop communication** - announce important findings and changes - avoid fixation on a single diagnosis - anticipate next steps and prepare equipment early - call additional expertise before crisis becomes irreversible - use structured handover, such as **SBAR** #### Closed-loop communication A task is assigned to a named person, repeated back, completed, and completion is announced. This reduces ambiguity during emergencies. #### Cognitive forcing question At intervals, the team leader should ask: > “What is the immediate threat now, what have we treated, and what could deteriorate next?” --- ## Adjuncts to the ABCDE assessment Adjuncts depend on presentation and should **support rather than delay stabilization**. ### Monitoring - continuous ECG monitoring - pulse oximetry - frequent or continuous blood pressure measurement - capnography where indicated - temperature - urine output in selected critically ill patients ### Access - peripheral IV access - IO access if vascular access is urgently needed and IV access cannot be established promptly - arterial/central access when clinically indicated after initial stabilization ### Point-of-care and laboratory testing Possible tests include: - bedside glucose - ABG/VBG - lactate - CBC - electrolytes and renal function - liver chemistry - coagulation studies - troponin - pregnancy testing when relevant - type and screen/crossmatch - cultures and microbiology when infection is suspected - targeted toxicology testing rather than indiscriminate screening ### Imaging For unstable patients, prioritize tests that can be performed **at the bedside or without delaying treatment**, including: - point-of-care ultrasound - portable chest radiograph - focused trauma ultrasound where appropriate CT and other advanced imaging generally follow once the patient can be transported safely, unless an immediately necessary diagnostic pathway requires otherwise. --- ## Secondary survey and definitive phase Once immediate life threats are controlled: 1. obtain a fuller history 2. perform a head-to-toe examination appropriate to the presentation 3. review medications, allergies, comorbidities, events, and collateral history 4. complete diagnostic testing 5. establish a working diagnosis and differential 6. arrange definitive therapy 7. determine level of care: ward, high-dependency/step-down, ICU, operating room, catheterization lab, stroke unit, transfer, etc. 8. perform structured handover #### SAMPLE history when useful - **S**igns/symptoms - **A**llergies - **M**edications - **P**ast medical history/pregnancy - **L**ast oral intake - **E**vents leading to illness/injury If the patient deteriorates during the secondary survey, **stop and repeat ABCDE immediately**. --- ## Acute management checklist ### Airway - assess ability to speak and airway sounds - inspect for obstruction, blood, vomit, edema, trauma - suction/open airway as needed - use adjuncts when appropriate - call for difficult-airway expertise early - prepare definitive/rescue airway if deterioration is likely ### Breathing - respiratory rate, SpO₂, work of breathing - chest symmetry and bilateral air entry - oxygen to an appropriate target - assist ventilation if inadequate - treat tension pneumothorax, severe bronchospasm, pulmonary edema, or other immediate cause - use blood gas/capnography/POCUS when indicated ### Circulation - pulse, BP, perfusion, capillary refill - search for bleeding - obtain IV/IO access - ECG and blood sampling - cause-specific shock management - reassess after fluids/blood/vasoactive therapy ### Disability - AVPU/ACVPU or GCS - pupils - bedside glucose - focal neurologic signs - seizure/toxin assessment - correct reversible causes promptly ### Exposure - whole-body inspection as appropriate - temperature - remove wet/contaminated clothing or ongoing triggers - prevent heat loss ### Then - reassess A–E - obtain fuller history and examination - pursue definitive diagnosis and treatment - arrange disposition and handover --- ## Diagnostic and management algorithm ```text Acutely unwell / deteriorating patient ↓ Safety + responsiveness + summon help ↓ Unresponsive AND not breathing normally? ├── YES → Cardiac-arrest pathway / CPR / AED-defibrillation as indicated └── NO ↓ A — Airway patent and maintainable? ├── NO → Airway opening/suction/adjunct/ventilation/expert airway help │ ↓ reassess A └── YES ↓ B — Oxygenation and ventilation adequate? ├── NO → Oxygen/ventilatory support + treat immediate respiratory cause │ ↓ reassess A-B └── YES ↓ C — Perfusion adequate? bleeding/shock/arrhythmia? ├── NO → Hemorrhage control + access + cause-specific resuscitation │ ↓ reassess A-C └── YES ↓ D — Neurologic impairment / hypoglycemia / seizure / toxin? ├── YES → Correct reversible cause + urgent neurologic/toxicologic pathway └── NO ↓ E — Expose, inspect, temperature/environment control ↓ REPEAT ABCDE ↓ Secondary survey + diagnostics + definitive care + disposition ``` --- ## Common pitfalls | Pitfall | Why dangerous | Better practice | |---|---|---| | Long history before stabilization | delays treatment of immediate threats | ABCDE first, fuller history later | | Completing all of A–E before treating | allows reversible deterioration to progress | treat abnormalities as found | | Focusing on diagnosis rather than physiology | may delay oxygenation/perfusion support | stabilize first, diagnose in parallel | | Normal BP = no shock | compensated shock may preserve BP | assess global perfusion and trends | | Normal SpO₂ = adequate ventilation | hypercapnia may be missed | assess respiratory effort and CO₂ when indicated | | Repeated fluid boluses for every hypotensive patient | may worsen cardiogenic/obstructive states | use cause-specific resuscitation | | Missing bedside glucose | overlooks a reversible cause of altered consciousness | check early in D | | Failure to expose | hidden rash, bleeding, trauma, devices, infection missed | perform adequate whole-body inspection | | Failure to re-cover | promotes hypothermia and loss of dignity | exposure + environmental control | | No reassessment | treatment may fail or patient may deteriorate | repeat ABCDE after interventions | | Poor task allocation | delays parallel care | leadership + closed-loop communication | --- ## Special populations ### Trauma Trauma systems may use **ABCDE** or **XABCDE**, placing catastrophic external hemorrhage control before airway when exsanguinating bleeding is immediately apparent. Follow the trauma protocol in use locally. Cervical-spine precautions modify airway technique but must not prevent oxygenation or ventilation. ### Pediatrics The same physiologic priorities apply, but airway anatomy, normal vital-sign ranges, fluid therapy, drug dosing, shock patterns, and deterioration differ substantially by age. Use current pediatric life-support guidance. ### Pregnancy Apply ABCDE with pregnancy physiology in mind. Maternal oxygenation and perfusion are the primary determinants of fetal oxygen delivery. Advanced pregnancy may require positioning strategies to reduce aortocaval compression during resuscitative care. ### Older adults Older patients may have limited physiologic reserve, atypical presentations, beta-blocker use that blunts tachycardia, renal vulnerability, and high risk from both under- and over-resuscitation. ### Toxicology Airway, ventilation, ECG, glucose, temperature, and toxidrome recognition are especially important. Use targeted antidotes when indicated, but supportive ABC care remains fundamental. --- ## Evidence and current guidance ### ESTABLISHED STANDARD OF CARE - Structured ABCDE assessment for acutely unwell patients is longstanding and internationally used.[1,4] - Treat life-threatening abnormalities as they are identified and reassess frequently.[1] - If the patient is unresponsive and not breathing normally, switch immediately to cardiac-arrest management.[1,3] - Early teamwork, monitoring, vascular access, and structured communication improve the efficiency of emergency assessment.[1] ### NEW / UPDATED GUIDANCE The **2025 RCUK First Aid Guidelines** introduced first aid as a dedicated guideline chapter and explicitly recommend structured ABCDE assessment for a person who appears ill, injured, or in shock.[2] The **2025 AHA Adult Basic Life Support Guidelines** supersede the prior full 2020 BLS set and update adult cardiac-arrest, respiratory-arrest, and foreign-body-airway-obstruction guidance.[3] ### EMERGING EVIDENCE ABCDE itself is primarily a structured clinical framework rather than a single therapeutic intervention. Evidence evaluating its effect on outcomes is less extensive than evidence for individual treatments embedded within the framework. Its enduring value is in prioritization, communication, repeated reassessment, and early correction of physiologic threats.[4] --- ## Exam-focused review ### USMLE Step 1 — mechanisms Know the physiology behind: - airway obstruction → alveolar hypoventilation/hypoxemia - respiratory failure → hypoxemia and/or hypercapnia - shock → reduced tissue perfusion → anaerobic metabolism/lactate - sympathetic compensation → tachycardia and vasoconstriction - hypoglycemia → neuroglycopenia ### USMLE Step 2 CK — next best step Common pattern: > **Unstable patient + possible diagnosis → stabilize first.** Examples: - airway compromise before CT - severe respiratory failure before definitive imaging - active major hemorrhage before prolonged diagnostic workup - hypoglycemia correction before broad neurologic testing ### Step 3 / Resident Expect decisions about: - when to escalate to airway/critical care - shock subtype and resuscitation strategy - reassessment after interventions - disposition and transfer - complications of treatment ### MRCP / ABIM / Board level High-yield nuances: - normal BP does not exclude shock - oxygenation and ventilation are distinct - a single GCS number does not automatically determine airway management - fluid strategy depends on shock phenotype and comorbidity - trends and response to treatment often matter more than single measurements - cognitive errors such as fixation and premature closure are important in deteriorating patients --- ## Original MCQs ### Question 1 — next best step A 67-year-old patient becomes drowsy and tachypneic on the ward. SpO₂ is 82% on room air, BP is 118/70 mmHg, and the patient can answer only one-word questions. What is the best immediate approach? A. Obtain CT pulmonary angiography B. Complete a full neurologic examination C. Begin ABCDE stabilization with immediate respiratory support D. Wait for arterial blood gas results before treatment E. Obtain a detailed medication history **Answer: C.** **Explanation:** The patient is unstable with severe hypoxemia and respiratory distress. Stabilization of airway/breathing takes priority over definitive diagnosis. Imaging and detailed history follow once immediate physiologic threats are addressed.[1] **Tested concept:** next-best-step prioritization **Difficulty:** Step 2 CK / MRCP --- ### Question 2 — shock A trauma patient is tachycardic, cool, clammy, and confused. BP is 112/74 mmHg. Which statement is most accurate? A. Shock is excluded because systolic BP is >100 mmHg B. The patient may have compensated shock despite normal BP C. Lactate must be elevated before shock can be diagnosed D. Hypotension is required before hemorrhage control E. CT should precede resuscitation **Answer: B.** **Explanation:** Compensatory vasoconstriction can preserve blood pressure despite reduced perfusion. Clinical perfusion and trends matter.[1] **Tested concept:** compensated shock **Difficulty:** Step 2 CK / Step 3 --- ### Question 3 — ventilation A patient with COPD is somnolent on supplemental oxygen with SpO₂ 95%. Which statement is most important? A. Normal SpO₂ excludes respiratory failure B. Pulse oximetry directly measures PaCO₂ C. Hypercapnia may still be present despite acceptable SpO₂ D. Oxygen should always be stopped immediately E. Respiratory rate is not useful **Answer: C.** **Explanation:** Pulse oximetry assesses oxygen saturation, not ventilation or CO₂ clearance. Blood gas and clinical assessment may reveal hypercapnic respiratory failure. **Tested concept:** oxygenation vs ventilation **Difficulty:** MRCP / ABIM --- ### Question 4 — disability An obtunded patient arrives after an unwitnessed collapse. Which bedside test belongs early in the disability assessment because it identifies a rapidly reversible cause? A. EEG B. Lumbar puncture C. Blood glucose D. MRI brain E. Carotid Doppler **Answer: C.** **Explanation:** Hypoglycemia is a rapidly reversible cause of altered mental status and should be checked promptly during D.[1] **Tested concept:** reversible causes of altered consciousness **Difficulty:** Step 2 CK --- ### Question 5 — reassessment After airway suction and bag-mask ventilation, the patient's oxygen saturation improves. What is the best next action? A. Proceed directly to discharge planning B. Continue to C without checking the airway again C. Reassess from A, then continue through ABCDE D. Wait 30 minutes before reassessment E. Perform only a neurologic examination **Answer: C.** **Explanation:** ABCDE is iterative. After an important intervention, reassess the effect of treatment and return to the beginning of the sequence.[1] **Tested concept:** reassessment **Difficulty:** Foundation / Step 2 CK --- ## Cross-links for the library Future linked articles should include: - Airway management - Oxygen therapy - Respiratory failure - Shock - Sepsis and septic shock - Anaphylaxis - Altered mental status and coma - Trauma primary and secondary survey - Cardiac arrest and CPR - Point-of-care ultrasound in shock --- ## References 1. **Resuscitation Council UK.** *The ABCDE Approach.* Updated July 2024. Official clinical guidance. https://www.resus.org.uk/library/abcde-approach 2. **Resuscitation Council UK.** *First Aid Guidelines — 2025 Resuscitation Guidelines.* Published October 27, 2025. Based on European Resuscitation Council Guidelines 2025 First Aid. https://www.resus.org.uk/professional-library/2025-resuscitation-guidelines/first-aid-guidelines 3. **Kleinman ME, Buick JE, Huber N, et al.** Part 7: Adult Basic Life Support: 2025 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. *Circulation.* 2025;152(Suppl 2):S448-S478. doi:10.1161/CIR.0000000000001369. 4. **Thim T, Krarup NHV, Grove EL, Rohde CV, Løfgren B.** Initial assessment and treatment with the Airway, Breathing, Circulation, Disability, Exposure (ABCDE) approach. *International Journal of General Medicine.* 2012;5:117-121. doi:10.2147/IJGM.S28478. PMID:22319249. --- ### Editorial note This article is an original synthesis for Dr Note Library. It is designed to provide layered learning from foundational physiology through clinical stabilization and board-level reasoning. It should be updated whenever major resuscitation, airway, oxygen, trauma, or critical-care guidance changes.1b: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 AKI1c: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.1d: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-sepsis-and-septic-shock","title":"Sepsis and Septic Shock","slug":"sepsis-and-septic-shock","description":"Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis-3 operationalizes organ dysfunction as an acute SOFA increase ≥2 points attributable to infection. 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