17:I[462708,["/_next/static/chunks/3yo3kiro3bmlp.js","/_next/static/chunks/3vr2wvd8f2efb.js","/_next/static/chunks/2vtmb68_vu-9t.js","/_next/static/chunks/2s8mt6_8wrpfo.js","/_next/static/chunks/3vkulz2i3l61y.js","/_next/static/chunks/1cqw2i1silz0i.js","/_next/static/chunks/14dbm3lm_t629.js","/_next/static/chunks/335_v2mb569ld.js","/_next/static/chunks/3ykn5ops9bft5.js","/_next/static/chunks/3cmavum774kjt.js","/_next/static/chunks/3th-0-a2xf9qs.js","/_next/static/chunks/0p0xpwde6kzmv.js","/_next/static/chunks/401-sxxnzbtf_.js","/_next/static/chunks/0wywtv698a1v0.js","/_next/static/chunks/2botzqwpnrzyj.js"],"ArticleReader"] 18:T6803,## Summary Acute bacterial meningitis is infection of the leptomeninges and cerebrospinal fluid (CSF) that can cause cerebral edema, vasculopathy, seizures, hydrocephalus, hearing loss, septic shock, brain herniation, and death within hours. **Do not require the classic combination of fever, headache, neck stiffness, and altered consciousness before acting.** Older adults, immunocompromised patients, and patients who have already received antimicrobials may present atypically.[1-3] Management is time critical. Stabilization, blood cultures, lumbar puncture (LP), empiric antimicrobials, and adjunctive corticosteroid therapy should proceed in parallel. NICE recommends IV antibiotics **within 1 hour of hospital arrival** for suspected bacterial meningitis. LP should be performed before antibiotics when it is safe and immediately feasible, but **antibiotics must not be delayed for LP or neuroimaging**.[1,3] Do not obtain head CT routinely before LP. Image first when there are clinical features suggesting a mass lesion or dangerous intracranial pressure, such as a new focal neurologic deficit, abnormal pupillary responses, markedly depressed or progressively falling consciousness, or another strong concern for space-occupying pathology. If imaging is needed, obtain blood cultures and start treatment before transport when imaging would delay therapy.[1,3] For community-acquired disease in adults, a third-generation cephalosporin is the usual empiric backbone. A commonly used adult regimen is **ceftriaxone 2 g IV every 12 hours**. Add **ampicillin 2 g IV every 4 hours** or an equivalent anti-*Listeria* regimen when *Listeria monocytogenes* risk is clinically important, including older age, pregnancy, and impaired cell-mediated immunity. WHO 2025 identifies **age >60 years, pregnancy, and immunocompromising conditions** as major *Listeria* risk settings.[1,4] Where cephalosporin-resistant pneumococcus is sufficiently prevalent, add vancomycin using local meningitis dosing and therapeutic drug-monitoring protocols.[1,4] Give **dexamethasone 10 mg IV every 6 hours** with or just before the first antimicrobial dose when possible; never delay antibiotics to administer it. WHO 2025 recommends corticosteroids with the first antibiotic dose in non-epidemic settings when bacterial meningitis is suspected and LP can be performed. Continue for up to **4 days** when CSF remains consistent with bacterial meningitis, especially with *Streptococcus pneumoniae* or *Haemophilus influenzae* type b; discontinue when a different pathogen is established unless another indication exists.[1,3] Once microbiology and susceptibility data are available, narrow therapy. WHO 2025 lists typical total treatment durations of **5–7 days for meningococcal meningitis, 7–10 days for *H. influenzae*, 10–14 days for pneumococcal meningitis, 14–21 days for group B streptococcal meningitis, and 21 days for *Listeria***, with extension for complications, delayed sterilization, resistant organisms, or unusual foci.[1] Suspected meningococcal disease requires **droplet precautions and immediate public-health coordination**. Close contacts should receive chemoprophylaxis as soon as possible regardless of vaccination status. Current CDC adult options include ceftriaxone **250 mg IM once**, rifampin **600 mg orally every 12 hours for 2 days**, or ciprofloxacin **500 mg orally once** only where local susceptibility supports its use; pregnancy and regional resistance alter agent selection.[5] > **Caution:** A normal CT does not make LP safe in every patient, and an abnormal CT is not the only reason to defer LP. Safety depends on the whole clinical picture, including rapidly falling consciousness, focal deficits, cardiorespiratory instability, coagulopathy, thrombocytopenia, and local procedural thresholds.[1,3] ## Immediate priorities ### First 10–60 minutes 1. Assess airway, breathing, circulation, glucose, oxygenation, consciousness, and shock. 2. Establish IV access and obtain blood cultures promptly. 3. Institute droplet precautions if meningococcal disease is plausible. 4. Decide whether LP is immediately safe. 5. If LP is safe and can be performed without meaningful delay, obtain CSF before antimicrobials. 6. If LP is unsafe or delayed, **start empiric antimicrobials immediately**. 7. Give dexamethasone with or just before the first antimicrobial dose when appropriate. 8. Treat shock, seizures, hypoxemia, and raised-intracranial-pressure physiology in parallel. 9. Reassess frequently for deterioration and ICU need.[1-3] The diagnostic sequence is flexible; the antimicrobial deadline is not. ## Etiology and risk pattern | Clinical setting | Important pathogens | Immediate implication | |---|---|---| | Younger and middle-aged adults | *S. pneumoniae*, *N. meningitidis* | Ceftriaxone/cefotaxime backbone; consider resistant pneumococcal coverage locally | | Age >60 years | Above plus *L. monocytogenes* | Add ampicillin/amoxicillin-class *Listeria* coverage | | Pregnancy | *Listeria* risk increased | Include anti-*Listeria* therapy | | Impaired cell-mediated immunity | *Listeria* plus usual pathogens; broader differential | Add anti-*Listeria* therapy and individualize for immune defect | | Asplenia or complement deficiency | Encapsulated bacteria, especially meningococcus and pneumococcus | Low threshold for invasive bacterial disease; review prevention after recovery | | CSF leak or cochlear implant | Particularly pneumococcus | Search for anatomic predisposition; optimize vaccination later | | Recent neurosurgery, penetrating head trauma, ventricular drain/shunt | Staphylococci and resistant gram-negative bacilli | Use a healthcare-associated CNS infection pathway, not the community regimen | This article focuses on **community-acquired** acute bacterial meningitis. Ventriculitis and device-associated infection require different empiric coverage and source-control decisions. ## Pathophysiology Bacteria reach the subarachnoid space through hematogenous spread, direct extension, skull-base or dural defects, or implanted hardware. CSF has limited innate immune defenses, allowing rapid bacterial replication. Recognition of bacterial components triggers an intense inflammatory response with neutrophil recruitment and cytokine release. Consequences include: - blood-brain barrier disruption; - vasogenic and cytotoxic cerebral edema; - impaired CSF resorption and hydrocephalus; - cerebral vasculitis, thrombosis, and infarction; - raised intracranial pressure; - cortical irritation and seizures; - cranial nerve injury, especially auditory pathways; - systemic inflammatory response and septic shock.[4,6] Adjunctive corticosteroids are intended to reduce injury caused by this inflammatory response, particularly around the time bactericidal therapy increases bacterial lysis.[1] ## Clinical features ### Common findings - fever or recent febrile illness; - severe headache; - neck stiffness; - photophobia; - confusion, delirium, lethargy, or reduced consciousness; - nausea or vomiting; - seizure; - focal neurologic deficit; - cranial neuropathy; - petechial or purpuric rash in meningococcal disease; - septic shock.[1-4] No individual symptom reliably excludes disease. Fever is less common in older adults, and neck stiffness can be subtle in frailty, dementia, or cervical arthritis.[3] ### Features of immediately dangerous disease - rapidly falling consciousness; - new focal deficit; - abnormal pupils; - recurrent or prolonged seizures; - shock or escalating vasopressor need; - hypoxemia or respiratory failure; - purpura with systemic toxicity; - signs of herniation; - severe hyponatremia with neurologic deterioration; - disseminated intravascular coagulation. These patients need simultaneous antimicrobial therapy, resuscitation, and critical-care/neurology support rather than a linear diagnostic workup. ## Lumbar puncture ### Perform LP promptly when safe CSF should ideally be obtained before antimicrobials because culture yield falls after treatment. Antibiotic pretreatment does not make LP useless: cell count, glucose, protein, Gram stain, and molecular tests may remain informative.[1,3] ### When to defer LP initially Defer LP and treat first when there is: - cardiorespiratory instability; - signs of impending herniation; - markedly depressed or rapidly worsening consciousness; - new focal neurologic deficit suggesting a mass lesion; - abnormal pupillary responses; - uncontrolled seizure activity before stabilization; - clinically important coagulopathy or thrombocytopenia according to local procedural thresholds; - local infection over the puncture site; - another immediate contraindication identified by the treating team.[1,3] If the contraindication resolves, obtain CSF later if the result can still change management. ### Head imaging before LP Routine CT before LP delays treatment and is not recommended.[1,3] Obtain brain imaging before LP when a space-occupying lesion, obstructive hydrocephalus, major mass effect, or another intracranial process is plausible. When imaging is required: ```text Blood cultures -> dexamethasone + empiric antimicrobials -> brain imaging -> LP when safe ``` Do not wait for imaging to begin treatment. ## CSF interpretation Typical untreated bacterial meningitis produces: | CSF variable | Typical bacterial pattern | Important caveats | |---|---|---| | Opening pressure | Elevated | Can be normal early; avoid delaying therapy for a single measurement | | White cells | Often hundreds to thousands/µL, usually neutrophil predominant | Early disease, immunosuppression, or prior antibiotics can alter the pattern | | Protein | Elevated | Nonspecific | | Glucose | Low | Interpret with a simultaneous serum glucose | | CSF:serum glucose ratio | Often <0.4 | Not perfectly sensitive or specific | | Gram stain | May identify organism rapidly | Sensitivity falls after antibiotics and with low bacterial burden | | Culture | Diagnostic and provides susceptibility | Yield falls after antibiotics | | Bacterial PCR/multiplex molecular test | Can remain positive after antibiotics | Interpret panel results with clinical and CSF findings | Send CSF for cell count/differential, protein, glucose with paired serum glucose, Gram stain, culture, and molecular testing when available. Add targeted tests when tuberculosis, cryptococcosis, viral encephalitis, or another diagnosis is plausible. A CSF lactate can support bacterial meningitis in selected settings, particularly before antibiotics, but it does not replace microbiology or the overall clinical picture.[1,4] ## Blood tests and other investigations Obtain without delaying treatment: - at least two sets of blood cultures when feasible; - CBC and platelet count; - electrolytes, creatinine, liver chemistry; - serum glucose paired with CSF glucose; - coagulation studies when bleeding risk or DIC is plausible; - lactate and blood gas when shock or respiratory failure is present; - HIV testing when status is unknown and testing is appropriate; - other source-directed cultures or imaging. Blood culture can establish the pathogen even when CSF culture becomes sterile after treatment. ## Empiric antimicrobial therapy ### Community-acquired adult meningitis Start therapy immediately after blood cultures if LP will be delayed. | Setting | Empiric approach | Rationale | |---|---|---| | Adult without major *Listeria* risk | Ceftriaxone **2 g IV every 12 h** or equivalent cefotaxime regimen | Covers meningococcus, pneumococcus, and susceptible *H. influenzae* | | Age >60, pregnancy, or impaired cell-mediated immunity | Above **plus ampicillin 2 g IV every 4 h** or equivalent local anti-*Listeria* regimen | Adds *Listeria* coverage | | Clinically important prevalence/risk of cephalosporin-resistant pneumococcus | Add vancomycin using local meningitis dosing and drug monitoring | Prevents inadequate initial pneumococcal coverage | | Severe immediate beta-lactam hypersensitivity | Urgent infectious-disease/pharmacy-directed alternative | Choice depends on organism risk, local resistance, and allergy phenotype | WHO 2025 strongly recommends ceftriaxone or cefotaxime as empiric therapy and recommends adding ampicillin/amoxicillin when *Listeria* risk is present. It advises considering vancomycin where resistant pneumococcus is sufficiently prevalent.[1] > **Current practice:** Empiric regimens are jurisdiction dependent. The need for routine vancomycin differs between regions because pneumococcal cephalosporin resistance differs. Use the local antibiogram and national guidance rather than importing another country's regimen unchanged.[1,3,4] ### Narrowing therapy Once organism and susceptibility are known, use the narrowest CNS-active agent with adequate CSF penetration. | Pathogen | Typical directed therapy principle | WHO 2025 usual duration | |---|---|---:| | *N. meningitidis* | Ceftriaxone/cefotaxime initially; narrow to penicillin-class therapy if fully susceptible and locally supported | 5–7 days | | *S. pneumoniae* | Susceptibility-directed penicillin/ampicillin or cephalosporin; resistant strains may require vancomycin-containing therapy | 10–14 days | | *H. influenzae* | Ampicillin/amoxicillin if beta-lactamase negative and susceptible; otherwise ceftriaxone/cefotaxime | 7–10 days | | Group B streptococcus | Penicillin/ampicillin/amoxicillin-class therapy | 14–21 days | | *L. monocytogenes* | Ampicillin/amoxicillin-class therapy | 21 days | Extend treatment when there is brain abscess, ventriculitis, persistent infection, resistant pathogen, parameningeal focus, or another complication requiring longer therapy.[1] ## Adjunctive dexamethasone ### Indication and timing In non-epidemic settings, WHO 2025 recommends IV corticosteroid with the first antibiotic dose in children and adults with suspected acute bacterial meningitis when LP is feasible; NICE likewise recommends IV dexamethasone for strongly suspected or confirmed bacterial meningitis.[1,3] A standard adult regimen is: - **dexamethasone 10 mg IV every 6 hours for up to 4 days**.[3] Give the first dose before or with the first antimicrobial dose if possible. If antibiotics have already started, administer as soon as possible when still likely to benefit; NICE advises specialist input when initiation is delayed beyond 12 hours.[3] ### When to continue or stop - Continue for up to 4 days when CSF supports bacterial meningitis and pneumococcus or *H. influenzae* type b is identified. - Stop when CSF is inconsistent with bacterial meningitis. - When another bacterial pathogen is identified, WHO and NICE permit or recommend discontinuation rather than completing a fixed course.[1,3] Do not delay effective antimicrobial therapy to obtain or administer dexamethasone. ## Meningococcal disease Meningococcal meningitis may coexist with meningococcemia. Purpura, shock, DIC, myocardial dysfunction, adrenal hemorrhage, limb ischemia, and multiorgan failure can dominate the presentation. ### Infection control Use droplet precautions for suspected invasive meningococcal disease according to local infection-control policy. Effective antimicrobial therapy rapidly reduces carriage, but public-health notification should not wait for final susceptibility data. ### Close-contact chemoprophylaxis CDC defines close contacts to include household members, childcare contacts, and people directly exposed to oral or respiratory secretions during the 7 days before symptom onset. Airway-management exposure can qualify healthcare workers for prophylaxis.[5] Provide prophylaxis **as soon as possible**; benefit is limited when delayed beyond 14 days after the index patient's illness onset.[5] Adult CDC regimens include:[5] | Agent | Adult regimen | Important limitation | |---|---|---| | Ceftriaxone | **250 mg IM once** | Preferred option in pregnancy in many settings | | Rifampin | **600 mg orally every 12 h for 2 days** | Drug interactions; not recommended in pregnancy by CDC | | Ciprofloxacin | **500 mg orally once** | Use only where ciprofloxacin susceptibility supports it; avoid in pregnancy under CDC guidance | Local public-health authorities may recommend an alternative such as azithromycin when ciprofloxacin-resistant meningococci are circulating.[5] Vaccination status does not eliminate the need for chemoprophylaxis after a qualifying exposure.[5] ## Seizures and neurologic deterioration Treat clinical seizures promptly with standard antiseizure therapy. Continuous or repeated EEG monitoring is appropriate when altered consciousness persists and nonconvulsive seizures are possible. New focal deficits or declining consciousness should trigger reassessment for: - cerebral infarction or vasculopathy; - cerebral edema; - hydrocephalus; - venous sinus thrombosis; - subdural empyema; - brain abscess; - ongoing seizures; - metabolic derangement; - medication effect. Urgent neuroimaging and neurology/neurosurgery input are appropriate when a structural complication is suspected. ## Raised intracranial pressure and critical care Supportive care is physiology driven. - Elevate the head of bed when not contraindicated. - Avoid hypoxemia and hypotension. - Treat fever and seizures. - Avoid hypotonic fluid loading. - Correct severe sodium disturbance carefully. - Intubate when airway protection, ventilation, or controlled management of severe intracranial hypertension requires it. - Use hyperosmolar therapy for impending herniation according to neurocritical-care protocols while definitive cause-directed management proceeds. Routine intracranial-pressure monitoring is not required for every patient; consider it in selected severe cases with refractory intracranial hypertension in an experienced critical-care/neurosurgical setting.[1,2] ## Fluids, sodium, and shock Do not use routine fluid restriction solely because meningitis is present. Treat true shock with isotonic crystalloid and vasoactive support according to sepsis physiology, while avoiding fluid overload. Hyponatremia may reflect SIADH, cerebral salt wasting, hypovolemia, kidney dysfunction, or administered fluid. Determine volume status and urine/serum indices before assuming the mechanism. Severe symptomatic hyponatremia requires urgent controlled correction. See [Sepsis and Septic Shock](../critical-care/sepsis-and-septic-shock.md) and [Hyponatremia](../nephrology/hyponatremia.md). ## Differential diagnosis | Alternative | Clues | Key tests/actions | |---|---|---| | Viral meningitis/encephalitis | Lymphocytic CSF, seizures/behavioral change, temporal involvement in HSV | CSF viral PCR; empiric acyclovir when HSV encephalitis is plausible | | Tuberculous meningitis | Subacute course, cranial neuropathies, basilar imaging, low CSF glucose | TB-directed CSF testing and specialist treatment | | Cryptococcal meningitis | Advanced immune suppression, subacute headache, raised opening pressure | CSF cryptococcal antigen/culture; pressure-directed management | | Brain abscess | Focal deficits, seizure, mass lesion | Contrast MRI/CT; avoid LP when mass effect is a concern | | Subarachnoid hemorrhage | Thunderclap headache, blood on CT/CSF | Hemorrhage pathway | | Autoimmune encephalitis | Subacute psychiatric, cognitive, movement, or seizure syndrome | MRI/EEG/CSF/antibody pathway after excluding infection | | Drug/toxin/metabolic encephalopathy | Exposure or metabolic abnormalities | Cause-directed testing | See [Brain Abscess in Adults](brain-abscess-in-adults.md), [Aneurysmal Subarachnoid Hemorrhage](../neurology/aneurysmal-subarachnoid-hemorrhage.md), and [Autoimmune Encephalitis in Adults](../neurology/autoimmune-encephalitis-in-adults.md). ## Monitoring During the acute phase, trend: - consciousness and focal neurologic findings; - temperature, heart rate, blood pressure, oxygenation; - urine output and perfusion; - sodium, potassium, glucose, creatinine; - platelet count and coagulation if meningococcemia/DIC is possible; - culture and molecular results; - antimicrobial dosing with kidney-function adjustment; - vancomycin exposure when used; - hearing and cranial nerve function when the patient can participate. Repeat LP is not routine after clear clinical improvement. Consider it when there is poor response, resistant or unusual organism, persistent fever with neurologic deterioration, uncertainty about sterilization, or a specific pathogen for which repeat CSF guides management.[1,4] ## Disposition ### ICU or equivalent high-acuity care Indications include: - shock or vasopressor requirement; - invasive ventilation or rapidly escalating oxygen need; - severely depressed consciousness; - recurrent seizures/status epilepticus; - signs of raised intracranial pressure; - major electrolyte instability; - DIC or rapidly progressive purpura; - evolving focal neurologic deficits; - multiorgan failure. ### Ward care A stable patient without organ failure may be managed on a closely monitored inpatient service with reliable neurologic reassessment and rapid access to escalation. ### Discharge criteria Do not discharge until: - antimicrobial course is complete or a safe outpatient parenteral plan exists when appropriate; - hemodynamics and neurologic trajectory are stable; - complications have been addressed; - hearing follow-up is arranged; - public-health actions are complete when required; - vaccination and anatomic risk-factor review have been addressed or scheduled. ## Complications ### Neurologic - sensorineural hearing loss; - cognitive impairment; - focal neurologic deficit from infarction; - epilepsy; - cranial neuropathy; - hydrocephalus; - subdural empyema or effusion; - brain abscess; - venous thrombosis. ### Systemic - septic shock; - DIC; - acute kidney injury; - myocardial dysfunction; - limb ischemia in fulminant meningococcemia; - secondary nosocomial complications after prolonged critical illness. A 2024 global systematic review found that bacterial meningitis still carries substantial case fatality despite modern therapy, reinforcing the importance of rapid treatment and prevention.[6] ## Follow-up after recovery ### Hearing Arrange formal audiologic assessment after bacterial meningitis, even when the patient does not report hearing loss. Auditory injury may be clinically subtle and can materially affect function.[1-3] ### Neurologic and cognitive sequelae Assess for: - persistent headache; - seizures; - memory, attention, or executive impairment; - balance problems; - focal weakness; - cranial neuropathy; - mood or functional change. Refer to neurology, rehabilitation, audiology, vestibular services, or neuropsychology according to deficits. ### Predisposition and prevention After pneumococcal or recurrent meningitis, look for: - CSF leak; - skull-base defect; - cochlear implant issues; - asplenia; - complement deficiency; - antibody deficiency or other immune disorder when clinically indicated. Update pneumococcal, meningococcal, and *H. influenzae* type b vaccination according to age, risk condition, prior vaccination, and national policy. ## Acute management checklist - [ ] Recognize suspected bacterial meningitis without waiting for a complete classic symptom set. - [ ] Stabilize airway, breathing, circulation, glucose, and seizures. - [ ] Obtain blood cultures promptly. - [ ] Start droplet precautions if meningococcus is plausible. - [ ] Perform LP immediately if safe and not meaningfully delaying therapy. - [ ] Do not order routine pre-LP CT. - [ ] If LP/imaging is delayed, start antibiotics immediately. - [ ] Give dexamethasone with or before the first antibiotic dose when appropriate. - [ ] Add *Listeria* coverage when risk is present. - [ ] Add resistant-pneumococcal coverage according to local epidemiology. - [ ] Narrow treatment when organism/susceptibility data return. - [ ] Escalate to critical care for shock, respiratory failure, severe consciousness impairment, seizures, or raised intracranial pressure. - [ ] Notify public health and arrange meningococcal contact prophylaxis when indicated. - [ ] Arrange hearing and neurologic follow-up after recovery. ## Recent guideline and public-health updates - **WHO 2025:** first global guideline for meningitis diagnosis, treatment, and care; emphasizes immediate empiric third-generation cephalosporin therapy, targeted *Listeria* coverage, selective vancomycin based on pneumococcal resistance, and corticosteroids with the first antibiotic dose in appropriate non-epidemic settings.[1] - **WHO 2026:** practical manual operationalizes the 2025 recommendations with bedside algorithms for diagnosis, treatment, and sequelae care.[2] - **NICE 2024:** emphasizes antibiotics within 1 hour of hospital arrival, selective rather than routine pre-LP imaging, and dexamethasone before/with antibiotics when possible.[3] - **CDC current meningococcal policy:** chemoprophylaxis remains urgent for close contacts regardless of vaccination status, with agent choice increasingly influenced by local ciprofloxacin resistance.[5] ## References 1. World Health Organization. *WHO guidelines on meningitis diagnosis, treatment and care.* Geneva: WHO; 2025. ISBN 978-92-4-010804-2. https://www.ncbi.nlm.nih.gov/books/NBK614847/ 2. World Health Organization. *WHO practical manual on meningitis diagnosis, treatment and care.* Geneva: WHO; 2026. ISBN 978-92-4-012102-7. https://www.who.int/publications/i/item/9789240121027 3. National Institute for Health and Care Excellence. *Meningitis (bacterial) and meningococcal disease: recognition, diagnosis and management.* NICE guideline NG240. 2024. https://www.nice.org.uk/guidance/ng240 4. van de Beek D, Cabellos C, Dzupova O, et al. ESCMID guideline: diagnosis and treatment of acute bacterial meningitis. *Clin Microbiol Infect.* 2016;22 Suppl 3:S37-S62. doi:10.1016/j.cmi.2016.01.007. PMID:27062097. https://pubmed.ncbi.nlm.nih.gov/27062097/ 5. Centers for Disease Control and Prevention. Chapter 8: Meningococcal Disease. *Manual for the Surveillance of Vaccine-Preventable Diseases.* Current online edition, accessed 2026-09-21. https://www.cdc.gov/surv-manual/php/table-of-contents/chapter-8-meningococcal-disease.html 6. van Ettekoven CN, Liechti FD, Brouwer MC, Bijlsma MW, van de Beek D. Global case fatality of bacterial meningitis during an 80-year period: a systematic review and meta-analysis. *JAMA Netw Open.* 2024;7(8):e2424802. doi:10.1001/jamanetworkopen.2024.24802. PMID:39093565. https://pubmed.ncbi.nlm.nih.gov/39093565/19:T6823,## Summary Acute bacterial meningitis is infection of the leptomeninges and cerebrospinal fluid (CSF) that can cause cerebral edema, vasculopathy, seizures, hydrocephalus, hearing loss, septic shock, brain herniation, and death within hours. **Do not require the classic combination of fever, headache, neck stiffness, and altered consciousness before acting.** Older adults, immunocompromised patients, and patients who have already received antimicrobials may present atypically.[1-3] Management is time critical. Stabilization, blood cultures, lumbar puncture (LP), empiric antimicrobials, and adjunctive corticosteroid therapy should proceed in parallel. NICE recommends IV antibiotics **within 1 hour of hospital arrival** for suspected bacterial meningitis. LP should be performed before antibiotics when it is safe and immediately feasible, but **antibiotics must not be delayed for LP or neuroimaging**.[1,3] Do not obtain head CT routinely before LP. Image first when there are clinical features suggesting a mass lesion or dangerous intracranial pressure, such as a new focal neurologic deficit, abnormal pupillary responses, markedly depressed or progressively falling consciousness, or another strong concern for space-occupying pathology. If imaging is needed, obtain blood cultures and start treatment before transport when imaging would delay therapy.[1,3] For community-acquired disease in adults, a third-generation cephalosporin is the usual empiric backbone. A commonly used adult regimen is **ceftriaxone 2 g IV every 12 hours**. Add **ampicillin 2 g IV every 4 hours** or an equivalent anti-*Listeria* regimen when *Listeria monocytogenes* risk is clinically important, including older age, pregnancy, and impaired cell-mediated immunity. WHO 2025 identifies **age >60 years, pregnancy, and immunocompromising conditions** as major *Listeria* risk settings.[1,4] Where cephalosporin-resistant pneumococcus is sufficiently prevalent, add vancomycin using local meningitis dosing and therapeutic drug-monitoring protocols.[1,4] Give **dexamethasone 10 mg IV every 6 hours** with or just before the first antimicrobial dose when possible; never delay antibiotics to administer it. WHO 2025 recommends corticosteroids with the first antibiotic dose in non-epidemic settings when bacterial meningitis is suspected and LP can be performed. Continue for up to **4 days** when CSF remains consistent with bacterial meningitis, especially with *Streptococcus pneumoniae* or *Haemophilus influenzae* type b; discontinue when a different pathogen is established unless another indication exists.[1,3] Once microbiology and susceptibility data are available, narrow therapy. WHO 2025 lists typical total treatment durations of **5–7 days for meningococcal meningitis, 7–10 days for *H. influenzae*, 10–14 days for pneumococcal meningitis, 14–21 days for group B streptococcal meningitis, and 21 days for *Listeria***, with extension for complications, delayed sterilization, resistant organisms, or unusual foci.[1] Suspected meningococcal disease requires **droplet precautions and immediate public-health coordination**. Close contacts should receive chemoprophylaxis as soon as possible regardless of vaccination status. Current CDC adult options include ceftriaxone **250 mg IM once**, rifampin **600 mg orally every 12 hours for 2 days**, or ciprofloxacin **500 mg orally once** only where local susceptibility supports its use; pregnancy and regional resistance alter agent selection.[5] > **Caution:** A normal CT does not make LP safe in every patient, and an abnormal CT is not the only reason to defer LP. Safety depends on the whole clinical picture, including rapidly falling consciousness, focal deficits, cardiorespiratory instability, coagulopathy, thrombocytopenia, and local procedural thresholds.[1,3] ## Immediate priorities ### First 10–60 minutes 1. Assess airway, breathing, circulation, glucose, oxygenation, consciousness, and shock. 2. Establish IV access and obtain blood cultures promptly. 3. Institute droplet precautions if meningococcal disease is plausible. 4. Decide whether LP is immediately safe. 5. If LP is safe and can be performed without meaningful delay, obtain CSF before antimicrobials. 6. If LP is unsafe or delayed, **start empiric antimicrobials immediately**. 7. Give dexamethasone with or just before the first antimicrobial dose when appropriate. 8. Treat shock, seizures, hypoxemia, and raised-intracranial-pressure physiology in parallel. 9. Reassess frequently for deterioration and ICU need.[1-3] The diagnostic sequence is flexible; the antimicrobial deadline is not. ## Etiology and risk pattern | Clinical setting | Important pathogens | Immediate implication | |---|---|---| | Younger and middle-aged adults | *S. pneumoniae*, *N. meningitidis* | Ceftriaxone/cefotaxime backbone; consider resistant pneumococcal coverage locally | | Age >60 years | Above plus *L. monocytogenes* | Add ampicillin/amoxicillin-class *Listeria* coverage | | Pregnancy | *Listeria* risk increased | Include anti-*Listeria* therapy | | Impaired cell-mediated immunity | *Listeria* plus usual pathogens; broader differential | Add anti-*Listeria* therapy and individualize for immune defect | | Asplenia or complement deficiency | Encapsulated bacteria, especially meningococcus and pneumococcus | Low threshold for invasive bacterial disease; review prevention after recovery | | CSF leak or cochlear implant | Particularly pneumococcus | Search for anatomic predisposition; optimize vaccination later | | Recent neurosurgery, penetrating head trauma, ventricular drain/shunt | Staphylococci and resistant gram-negative bacilli | Use a healthcare-associated CNS infection pathway, not the community regimen | This article focuses on **community-acquired** acute bacterial meningitis. Ventriculitis and device-associated infection require different empiric coverage and source-control decisions. ## Pathophysiology Bacteria reach the subarachnoid space through hematogenous spread, direct extension, skull-base or dural defects, or implanted hardware. CSF has limited innate immune defenses, allowing rapid bacterial replication. Recognition of bacterial components triggers an intense inflammatory response with neutrophil recruitment and cytokine release. Consequences include: - blood-brain barrier disruption; - vasogenic and cytotoxic cerebral edema; - impaired CSF resorption and hydrocephalus; - cerebral vasculitis, thrombosis, and infarction; - raised intracranial pressure; - cortical irritation and seizures; - cranial nerve injury, especially auditory pathways; - systemic inflammatory response and septic shock.[4,6] Adjunctive corticosteroids are intended to reduce injury caused by this inflammatory response, particularly around the time bactericidal therapy increases bacterial lysis.[1] ## Clinical features ### Common findings - fever or recent febrile illness; - severe headache; - neck stiffness; - photophobia; - confusion, delirium, lethargy, or reduced consciousness; - nausea or vomiting; - seizure; - focal neurologic deficit; - cranial neuropathy; - petechial or purpuric rash in meningococcal disease; - septic shock.[1-4] No individual symptom reliably excludes disease. Fever is less common in older adults, and neck stiffness can be subtle in frailty, dementia, or cervical arthritis.[3] ### Features of immediately dangerous disease - rapidly falling consciousness; - new focal deficit; - abnormal pupils; - recurrent or prolonged seizures; - shock or escalating vasopressor need; - hypoxemia or respiratory failure; - purpura with systemic toxicity; - signs of herniation; - severe hyponatremia with neurologic deterioration; - disseminated intravascular coagulation. These patients need simultaneous antimicrobial therapy, resuscitation, and critical-care/neurology support rather than a linear diagnostic workup. ## Lumbar puncture ### Perform LP promptly when safe CSF should ideally be obtained before antimicrobials because culture yield falls after treatment. Antibiotic pretreatment does not make LP useless: cell count, glucose, protein, Gram stain, and molecular tests may remain informative.[1,3] ### When to defer LP initially Defer LP and treat first when there is: - cardiorespiratory instability; - signs of impending herniation; - markedly depressed or rapidly worsening consciousness; - new focal neurologic deficit suggesting a mass lesion; - abnormal pupillary responses; - uncontrolled seizure activity before stabilization; - clinically important coagulopathy or thrombocytopenia according to local procedural thresholds; - local infection over the puncture site; - another immediate contraindication identified by the treating team.[1,3] If the contraindication resolves, obtain CSF later if the result can still change management. ### Head imaging before LP Routine CT before LP delays treatment and is not recommended.[1,3] Obtain brain imaging before LP when a space-occupying lesion, obstructive hydrocephalus, major mass effect, or another intracranial process is plausible. When imaging is required: ```text Blood cultures -> dexamethasone + empiric antimicrobials -> brain imaging -> LP when safe ``` Do not wait for imaging to begin treatment. ## CSF interpretation Typical untreated bacterial meningitis produces: | CSF variable | Typical bacterial pattern | Important caveats | |---|---|---| | Opening pressure | Elevated | Can be normal early; avoid delaying therapy for a single measurement | | White cells | Often hundreds to thousands/µL, usually neutrophil predominant | Early disease, immunosuppression, or prior antibiotics can alter the pattern | | Protein | Elevated | Nonspecific | | Glucose | Low | Interpret with a simultaneous serum glucose | | CSF:serum glucose ratio | Often <0.4 | Not perfectly sensitive or specific | | Gram stain | May identify organism rapidly | Sensitivity falls after antibiotics and with low bacterial burden | | Culture | Diagnostic and provides susceptibility | Yield falls after antibiotics | | Bacterial PCR/multiplex molecular test | Can remain positive after antibiotics | Interpret panel results with clinical and CSF findings | Send CSF for cell count/differential, protein, glucose with paired serum glucose, Gram stain, culture, and molecular testing when available. Add targeted tests when tuberculosis, cryptococcosis, viral encephalitis, or another diagnosis is plausible. A CSF lactate can support bacterial meningitis in selected settings, particularly before antibiotics, but it does not replace microbiology or the overall clinical picture.[1,4] ## Blood tests and other investigations Obtain without delaying treatment: - at least two sets of blood cultures when feasible; - CBC and platelet count; - electrolytes, creatinine, liver chemistry; - serum glucose paired with CSF glucose; - coagulation studies when bleeding risk or DIC is plausible; - lactate and blood gas when shock or respiratory failure is present; - HIV testing when status is unknown and testing is appropriate; - other source-directed cultures or imaging. Blood culture can establish the pathogen even when CSF culture becomes sterile after treatment. ## Empiric antimicrobial therapy ### Community-acquired adult meningitis Start therapy immediately after blood cultures if LP will be delayed. | Setting | Empiric approach | Rationale | |---|---|---| | Adult without major *Listeria* risk | Ceftriaxone **2 g IV every 12 h** or equivalent cefotaxime regimen | Covers meningococcus, pneumococcus, and susceptible *H. influenzae* | | Age >60, pregnancy, or impaired cell-mediated immunity | Above **plus ampicillin 2 g IV every 4 h** or equivalent local anti-*Listeria* regimen | Adds *Listeria* coverage | | Clinically important prevalence/risk of cephalosporin-resistant pneumococcus | Add vancomycin using local meningitis dosing and drug monitoring | Prevents inadequate initial pneumococcal coverage | | Severe immediate beta-lactam hypersensitivity | Urgent infectious-disease/pharmacy-directed alternative | Choice depends on organism risk, local resistance, and allergy phenotype | WHO 2025 strongly recommends ceftriaxone or cefotaxime as empiric therapy and recommends adding ampicillin/amoxicillin when *Listeria* risk is present. It advises considering vancomycin where resistant pneumococcus is sufficiently prevalent.[1] > **Current practice:** Empiric regimens are jurisdiction dependent. The need for routine vancomycin differs between regions because pneumococcal cephalosporin resistance differs. Use the local antibiogram and national guidance rather than importing another country's regimen unchanged.[1,3,4] ### Narrowing therapy Once organism and susceptibility are known, use the narrowest CNS-active agent with adequate CSF penetration. | Pathogen | Typical directed therapy principle | WHO 2025 usual duration | |---|---|---:| | *N. meningitidis* | Ceftriaxone/cefotaxime initially; narrow to penicillin-class therapy if fully susceptible and locally supported | 5–7 days | | *S. pneumoniae* | Susceptibility-directed penicillin/ampicillin or cephalosporin; resistant strains may require vancomycin-containing therapy | 10–14 days | | *H. influenzae* | Ampicillin/amoxicillin if beta-lactamase negative and susceptible; otherwise ceftriaxone/cefotaxime | 7–10 days | | Group B streptococcus | Penicillin/ampicillin/amoxicillin-class therapy | 14–21 days | | *L. monocytogenes* | Ampicillin/amoxicillin-class therapy | 21 days | Extend treatment when there is brain abscess, ventriculitis, persistent infection, resistant pathogen, parameningeal focus, or another complication requiring longer therapy.[1] ## Adjunctive dexamethasone ### Indication and timing In non-epidemic settings, WHO 2025 recommends IV corticosteroid with the first antibiotic dose in children and adults with suspected acute bacterial meningitis when LP is feasible; NICE likewise recommends IV dexamethasone for strongly suspected or confirmed bacterial meningitis.[1,3] A standard adult regimen is: - **dexamethasone 10 mg IV every 6 hours for up to 4 days**.[3] Give the first dose before or with the first antimicrobial dose if possible. If antibiotics have already started, administer as soon as possible when still likely to benefit; NICE advises specialist input when initiation is delayed beyond 12 hours.[3] ### When to continue or stop - Continue for up to 4 days when CSF supports bacterial meningitis and pneumococcus or *H. influenzae* type b is identified. - Stop when CSF is inconsistent with bacterial meningitis. - When another bacterial pathogen is identified, WHO and NICE permit or recommend discontinuation rather than completing a fixed course.[1,3] Do not delay effective antimicrobial therapy to obtain or administer dexamethasone. ## Meningococcal disease Meningococcal meningitis may coexist with meningococcemia. Purpura, shock, DIC, myocardial dysfunction, adrenal hemorrhage, limb ischemia, and multiorgan failure can dominate the presentation. ### Infection control Use droplet precautions for suspected invasive meningococcal disease according to local infection-control policy. Effective antimicrobial therapy rapidly reduces carriage, but public-health notification should not wait for final susceptibility data. ### Close-contact chemoprophylaxis CDC defines close contacts to include household members, childcare contacts, and people directly exposed to oral or respiratory secretions during the 7 days before symptom onset. Airway-management exposure can qualify healthcare workers for prophylaxis.[5] Provide prophylaxis **as soon as possible**; benefit is limited when delayed beyond 14 days after the index patient's illness onset.[5] Adult CDC regimens include:[5] | Agent | Adult regimen | Important limitation | |---|---|---| | Ceftriaxone | **250 mg IM once** | Preferred option in pregnancy in many settings | | Rifampin | **600 mg orally every 12 h for 2 days** | Drug interactions; not recommended in pregnancy by CDC | | Ciprofloxacin | **500 mg orally once** | Use only where ciprofloxacin susceptibility supports it; avoid in pregnancy under CDC guidance | Local public-health authorities may recommend an alternative such as azithromycin when ciprofloxacin-resistant meningococci are circulating.[5] Vaccination status does not eliminate the need for chemoprophylaxis after a qualifying exposure.[5] ## Seizures and neurologic deterioration Treat clinical seizures promptly with standard antiseizure therapy. Continuous or repeated EEG monitoring is appropriate when altered consciousness persists and nonconvulsive seizures are possible. New focal deficits or declining consciousness should trigger reassessment for: - cerebral infarction or vasculopathy; - cerebral edema; - hydrocephalus; - venous sinus thrombosis; - subdural empyema; - brain abscess; - ongoing seizures; - metabolic derangement; - medication effect. Urgent neuroimaging and neurology/neurosurgery input are appropriate when a structural complication is suspected. ## Raised intracranial pressure and critical care Supportive care is physiology driven. - Elevate the head of bed when not contraindicated. - Avoid hypoxemia and hypotension. - Treat fever and seizures. - Avoid hypotonic fluid loading. - Correct severe sodium disturbance carefully. - Intubate when airway protection, ventilation, or controlled management of severe intracranial hypertension requires it. - Use hyperosmolar therapy for impending herniation according to neurocritical-care protocols while definitive cause-directed management proceeds. Routine intracranial-pressure monitoring is not required for every patient; consider it in selected severe cases with refractory intracranial hypertension in an experienced critical-care/neurosurgical setting.[1,2] ## Fluids, sodium, and shock Do not use routine fluid restriction solely because meningitis is present. Treat true shock with isotonic crystalloid and vasoactive support according to sepsis physiology, while avoiding fluid overload. Hyponatremia may reflect SIADH, cerebral salt wasting, hypovolemia, kidney dysfunction, or administered fluid. Determine volume status and urine/serum indices before assuming the mechanism. Severe symptomatic hyponatremia requires urgent controlled correction. See [Sepsis and Septic Shock](../critical-care/sepsis-and-septic-shock.md) and [Hyponatremia](../nephrology/hyponatremia.md). ## Differential diagnosis | Alternative | Clues | Key tests/actions | |---|---|---| | Viral meningitis/encephalitis | Lymphocytic CSF, seizures/behavioral change, temporal involvement in HSV | CSF viral PCR; empiric acyclovir when HSV encephalitis is plausible | | Tuberculous meningitis | Subacute course, cranial neuropathies, basilar imaging, low CSF glucose | TB-directed CSF testing and specialist treatment | | Cryptococcal meningitis | Advanced immune suppression, subacute headache, raised opening pressure | CSF cryptococcal antigen/culture; pressure-directed management | | Brain abscess | Focal deficits, seizure, mass lesion | Contrast MRI/CT; avoid LP when mass effect is a concern | | Subarachnoid hemorrhage | Thunderclap headache, blood on CT/CSF | Hemorrhage pathway | | Autoimmune encephalitis | Subacute psychiatric, cognitive, movement, or seizure syndrome | MRI/EEG/CSF/antibody pathway after excluding infection | | Drug/toxin/metabolic encephalopathy | Exposure or metabolic abnormalities | Cause-directed testing | See [Brain Abscess in Adults](brain-abscess-in-adults.md), [Aneurysmal Subarachnoid Hemorrhage](../neurology/aneurysmal-subarachnoid-hemorrhage.md), and [Autoimmune Encephalitis in Adults](../neurology/autoimmune-encephalitis-in-adults.md). ## Monitoring During the acute phase, trend: - consciousness and focal neurologic findings; - temperature, heart rate, blood pressure, oxygenation; - urine output and perfusion; - sodium, potassium, glucose, creatinine; - platelet count and coagulation if meningococcemia/DIC is possible; - culture and molecular results; - antimicrobial dosing with kidney-function adjustment; - vancomycin exposure when used; - hearing and cranial nerve function when the patient can participate. Repeat LP is not routine after clear clinical improvement. Consider it when there is poor response, resistant or unusual organism, persistent fever with neurologic deterioration, uncertainty about sterilization, or a specific pathogen for which repeat CSF guides management.[1,4] ## Disposition ### ICU or equivalent high-acuity care Indications include: - shock or vasopressor requirement; - invasive ventilation or rapidly escalating oxygen need; - severely depressed consciousness; - recurrent seizures/status epilepticus; - signs of raised intracranial pressure; - major electrolyte instability; - DIC or rapidly progressive purpura; - evolving focal neurologic deficits; - multiorgan failure. ### Ward care A stable patient without organ failure may be managed on a closely monitored inpatient service with reliable neurologic reassessment and rapid access to escalation. ### Discharge criteria Do not discharge until: - antimicrobial course is complete or a safe outpatient parenteral plan exists when appropriate; - hemodynamics and neurologic trajectory are stable; - complications have been addressed; - hearing follow-up is arranged; - public-health actions are complete when required; - vaccination and anatomic risk-factor review have been addressed or scheduled. ## Complications ### Neurologic - sensorineural hearing loss; - cognitive impairment; - focal neurologic deficit from infarction; - epilepsy; - cranial neuropathy; - hydrocephalus; - subdural empyema or effusion; - brain abscess; - venous thrombosis. ### Systemic - septic shock; - DIC; - [acute kidney injury](/library/acute-kidney-injury); - myocardial dysfunction; - limb ischemia in fulminant meningococcemia; - secondary nosocomial complications after prolonged critical illness. A 2024 global systematic review found that bacterial meningitis still carries substantial case fatality despite modern therapy, reinforcing the importance of rapid treatment and prevention.[6] ## Follow-up after recovery ### Hearing Arrange formal audiologic assessment after bacterial meningitis, even when the patient does not report hearing loss. Auditory injury may be clinically subtle and can materially affect function.[1-3] ### Neurologic and cognitive sequelae Assess for: - persistent headache; - seizures; - memory, attention, or executive impairment; - balance problems; - focal weakness; - cranial neuropathy; - mood or functional change. Refer to neurology, rehabilitation, audiology, vestibular services, or neuropsychology according to deficits. ### Predisposition and prevention After pneumococcal or recurrent meningitis, look for: - CSF leak; - skull-base defect; - cochlear implant issues; - asplenia; - complement deficiency; - antibody deficiency or other immune disorder when clinically indicated. Update pneumococcal, meningococcal, and *H. influenzae* type b vaccination according to age, risk condition, prior vaccination, and national policy. ## Acute management checklist - [ ] Recognize suspected bacterial meningitis without waiting for a complete classic symptom set. - [ ] Stabilize airway, breathing, circulation, glucose, and seizures. - [ ] Obtain blood cultures promptly. - [ ] Start droplet precautions if meningococcus is plausible. - [ ] Perform LP immediately if safe and not meaningfully delaying therapy. - [ ] Do not order routine pre-LP CT. - [ ] If LP/imaging is delayed, start antibiotics immediately. - [ ] Give dexamethasone with or before the first antibiotic dose when appropriate. - [ ] Add *Listeria* coverage when risk is present. - [ ] Add resistant-pneumococcal coverage according to local epidemiology. - [ ] Narrow treatment when organism/susceptibility data return. - [ ] Escalate to critical care for shock, respiratory failure, severe consciousness impairment, seizures, or raised intracranial pressure. - [ ] Notify public health and arrange meningococcal contact prophylaxis when indicated. - [ ] Arrange hearing and neurologic follow-up after recovery. ## Recent guideline and public-health updates - **WHO 2025:** first global guideline for meningitis diagnosis, treatment, and care; emphasizes immediate empiric third-generation cephalosporin therapy, targeted *Listeria* coverage, selective vancomycin based on pneumococcal resistance, and corticosteroids with the first antibiotic dose in appropriate non-epidemic settings.[1] - **WHO 2026:** practical manual operationalizes the 2025 recommendations with bedside algorithms for diagnosis, treatment, and sequelae care.[2] - **NICE 2024:** emphasizes antibiotics within 1 hour of hospital arrival, selective rather than routine pre-LP imaging, and dexamethasone before/with antibiotics when possible.[3] - **CDC current meningococcal policy:** chemoprophylaxis remains urgent for close contacts regardless of vaccination status, with agent choice increasingly influenced by local ciprofloxacin resistance.[5] ## References 1. World Health Organization. *WHO guidelines on meningitis diagnosis, treatment and care.* Geneva: WHO; 2025. ISBN 978-92-4-010804-2. https://www.ncbi.nlm.nih.gov/books/NBK614847/ 2. World Health Organization. *WHO practical manual on meningitis diagnosis, treatment and care.* Geneva: WHO; 2026. ISBN 978-92-4-012102-7. https://www.who.int/publications/i/item/9789240121027 3. National Institute for Health and Care Excellence. *Meningitis (bacterial) and meningococcal disease: recognition, diagnosis and management.* NICE guideline NG240. 2024. https://www.nice.org.uk/guidance/ng240 4. van de Beek D, Cabellos C, Dzupova O, et al. ESCMID guideline: diagnosis and treatment of acute bacterial meningitis. *Clin Microbiol Infect.* 2016;22 Suppl 3:S37-S62. doi:10.1016/j.cmi.2016.01.007. PMID:27062097. https://pubmed.ncbi.nlm.nih.gov/27062097/ 5. Centers for Disease Control and Prevention. Chapter 8: Meningococcal Disease. *Manual for the Surveillance of Vaccine-Preventable Diseases.* Current online edition, accessed 2026-09-21. https://www.cdc.gov/surv-manual/php/table-of-contents/chapter-8-meningococcal-disease.html 6. van Ettekoven CN, Liechti FD, Brouwer MC, Bijlsma MW, van de Beek D. Global case fatality of bacterial meningitis during an 80-year period: a systematic review and meta-analysis. *JAMA Netw Open.* 2024;7(8):e2424802. doi:10.1001/jamanetworkopen.2024.24802. PMID:39093565. https://pubmed.ncbi.nlm.nih.gov/39093565/1a: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 AKI1b: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.1c:T9843,## One-minute summary **Acute ischemic stroke (AIS)** is sudden neurological dysfunction caused by focal cerebral, retinal, or spinal cord ischemia, most often from arterial occlusion. The practical emergency question is not simply “is this a stroke?” but **“is there salvageable brain, and can reperfusion be delivered safely now?”** The 2026 AHA/ASA guideline makes several practice-changing points: [1] - **Tenecteplase 0.25 mg/kg IV (maximum 25 mg)** and **alteplase 0.9 mg/kg IV** are both recommended thrombolytic options for eligible adults presenting within **4.5 hours** of symptom onset or last known well. - A **disabling deficit may warrant thrombolysis even when NIHSS is low**; NIHSS alone should not define disability. - In **mild, non-disabling stroke**, routine thrombolysis has not shown benefit; short-course **dual antiplatelet therapy (DAPT)** is generally preferred when appropriate. - Selected patients with **wake-up stroke or 4.5–9-hour presentation** can receive IV thrombolysis when advanced imaging demonstrates a favorable tissue profile. - Endovascular thrombectomy (EVT) remains standard for eligible **large-vessel occlusion (LVO)** and now extends to selected patients with **larger ischemic cores** and to selected **basilar artery occlusion** up to 24 hours. - Intensive post-reperfusion systolic BP lowering to **<140 mm Hg is not recommended** and may be harmful after successful EVT. - New randomized evidence does **not** support routine thrombectomy for medium/distal-vessel occlusion in populations similar to ESCAPE-MeVO and DISCOUNT. [1,13,14] **Core emergency sequence:** **Recognize stroke → establish last-known-well → glucose → NIHSS → noncontrast head CT → vascular imaging when LVO is possible → IV thrombolysis if eligible without avoidable delay → EVT evaluation in parallel → stroke-unit care and complication prevention.** --- ## 1. Core concepts ### 1.1 Time is brain—but tissue matters too An arterial occlusion creates an **infarct core** surrounded by variably salvageable **ischemic penumbra**. Reperfusion benefit declines with time because collateral circulation eventually fails and the core expands. However, individuals progress at different rates; modern CT perfusion and MRI can identify patients who retain salvageable tissue beyond conventional clock-based windows. [1,5,6] The most important operational principle is therefore: > **Do not delay proven reperfusion therapy while performing tests that will not change immediate eligibility.** For most patients within 4.5 hours with a clinically convincing disabling AIS, a noncontrast CT excluding hemorrhage is sufficient to make an IV thrombolysis decision; CTA/CT perfusion should not unnecessarily postpone treatment. [1] ### 1.2 Treat the patient, not the NIHSS number The **NIH Stroke Scale (NIHSS)** is the standard severity instrument, but it underweights some clinically devastating deficits, especially posterior circulation deficits and isolated functions such as gait, hand dexterity, vision, or language needed for a patient’s occupation. A patient with NIHSS 2 can still have a disabling stroke. [1] Examples of potentially disabling low-NIHSS deficits include: - aphasia that prevents meaningful communication; - dominant-hand weakness preventing functional use; - leg weakness preventing independent ambulation; - hemianopia that meaningfully impairs function; - severe dysarthria affecting communication; - disabling ataxia despite a modest NIHSS score. --- ## 2. Definition and classification ### 2.1 Definition AIS is acute neurological injury from insufficient blood flow caused by arterial occlusion or critical hypoperfusion, resulting in focal brain infarction when ischemia is prolonged. ### 2.2 Etiologic classification A useful conceptual framework is the TOAST-style grouping: | Mechanism | Typical clues | Common examples | |---|---|---| | Large-artery atherosclerosis | Cortical syndrome, carotid/intracranial stenosis, artery-to-artery embolism | Carotid plaque, intracranial atherosclerosis | | Cardioembolism | Abrupt maximal deficit, multiple vascular territories, AF, structural heart disease | Atrial fibrillation, LV thrombus, mechanical valve | | Small-vessel occlusion | Classic lacunar syndrome without cortical signs | Lipohyalinosis from hypertension/diabetes | | Other determined cause | Younger age or distinctive systemic/vascular clue | Dissection, vasculitis, thrombophilia, sickle cell disease | | Undetermined/cryptogenic | No clear mechanism after evaluation or >1 plausible cause | ESUS-type presentations | Etiology matters most after immediate reperfusion decisions because it drives secondary prevention. --- ## 3. Epidemiology and risk factors Ischemic strokes account for the majority of strokes globally and in the United States. The 2026 AHA/ASA guideline notes that ischemic events represent >80% of strokes in the United States and >60% globally. [1] #### Major modifiable risk factors - Hypertension - Atrial fibrillation - Diabetes mellitus - Tobacco exposure - Dyslipidemia - Carotid/intracranial atherosclerosis - Obesity and physical inactivity - Obstructive sleep apnea - Cocaine/amphetamine exposure - Poor adherence to antithrombotic or vascular-risk therapy #### Important nonmodifiable or context-specific risks - Increasing age - Prior stroke/TIA - Family/genetic predisposition - Sickle cell disease - Cancer-associated thrombosis - Pregnancy/postpartum state - Autoimmune/vasculitic disease --- ## 4. Pathophysiology ### 4.1 Ischemic cascade Arterial occlusion lowers cerebral blood flow. ATP depletion leads to membrane depolarization, glutamate release, calcium influx, oxidative stress, mitochondrial dysfunction, cytotoxic edema, and eventually irreversible cellular death. #### Core vs penumbra - **Core:** critically hypoperfused tissue with a high probability of irreversible injury. - **Penumbra:** functionally impaired tissue that remains viable if perfusion is restored promptly. - **Collateral circulation:** the major determinant of how quickly penumbra converts to core. This explains why two patients arriving 6 hours after onset can have very different imaging profiles and treatment opportunities. ### 4.2 Reperfusion injury and hemorrhagic transformation Recanalization can restore function but damaged microvasculature may leak, producing hemorrhagic transformation. Risk rises with larger infarcts, severe hyperglycemia, uncontrolled hypertension, delayed reperfusion, advanced age, and anticoagulant exposure. --- ## 5. Clinical presentation ### 5.1 Common focal syndromes | Vascular territory | Typical findings | |---|---| | Left MCA | Aphasia, right face/arm > leg weakness/sensory loss, gaze preference toward lesion | | Right MCA | Left neglect, left face/arm > leg weakness/sensory loss, visuospatial dysfunction | | ACA | Contralateral leg > arm weakness, abulia, urinary incontinence | | PCA | Contralateral homonymous hemianopia, memory disturbance; thalamic sensory syndromes | | Basilar/posterior circulation | Diplopia, dysarthria, dysphagia, vertigo with focal signs, ataxia, crossed findings, quadriparesis, decreased consciousness | | Lacunar | Pure motor, pure sensory, ataxic hemiparesis, dysarthria-clumsy hand; usually no aphasia/neglect/visual field deficit | #### Posterior circulation warning “Dizziness” alone is common and nonspecific, but **acute vestibular syndrome plus focal neurological signs, severe gait/truncal ataxia, new headache/neck pain, direction-changing nystagmus, skew, or vascular risk** should raise concern for posterior circulation ischemia. --- ## 6. Immediate assessment ### 6.1 First minutes | Task | Why it matters | Immediate action | |---|---|---| | Confirm exact **last known well** | Determines time-based eligibility | Ask patient, family, witnesses, EMS; distinguish symptom discovery from last-known-normal | | ABC stabilization | Hypoxia/hypotension worsen ischemia | Secure airway/ventilation as needed; avoid hypotension | | **Point-of-care glucose** | Hypoglycemia is a stroke mimic and harms brain | Correct significant hypoglycemia immediately | | Focused neurological exam/NIHSS | Quantifies severity and change | Document baseline before reperfusion if feasible | | Noncontrast CT | Excludes hemorrhage and identifies major early ischemia | Obtain urgently | | CTA head/neck when LVO possible | Detects thrombectomy target | Acquire rapidly; do not wait for creatinine when delay threatens EVT eligibility [1] | | Labs | Detect coagulopathy/metabolic confounders | CBC, PT/INR/aPTT as indicated, electrolytes, renal function, troponin; do not delay thrombolysis for routine labs if no reason to suspect abnormality | ### 6.2 Do not miss a stroke mimic | Mimic | Clues favoring mimic | Clues favoring stroke | |---|---|---| | Hypoglycemia | Low glucose, autonomic symptoms, diffuse/confusional state | Persistent focal deficit after glucose correction | | Seizure/Todd paresis | Witnessed convulsion, postictal state | Persistent cortical deficit, vascular occlusion on imaging | | Migraine aura | Positive spreading sensory/visual symptoms, prior similar episodes | Sudden negative deficit maximal at onset | | Functional neurological disorder | Inconsistency, incongruent examination | Objective vascular syndrome/imaging lesion | | Peripheral vestibulopathy | No focal deficit, peripheral HINTS pattern in expert hands | Severe truncal ataxia, focal signs, central ocular motor findings | | Bell palsy | Isolated LMN facial weakness incl. forehead | Forehead-sparing facial weakness with limb deficit/aphasia | | Toxic-metabolic encephalopathy | Global dysfunction | Focal cortical or brainstem syndrome | The hemorrhage risk of IV thrombolysis in stroke mimics is very low, and the 2026 guideline emphasizes avoiding unnecessary delays when the syndrome is otherwise convincing. [1] --- ## 7. Imaging ### 7.1 Noncontrast CT (NCCT) Primary purposes: 1. Exclude intracranial hemorrhage. 2. Detect major established infarction/edema. 3. Estimate early ischemic change using **ASPECTS** in anterior circulation stroke. A normal NCCT does **not** exclude early ischemic stroke. ### 7.2 CTA/MRA Use to identify: - ICA terminus, M1, selected M2, basilar and other occlusions; - tandem cervical/intracranial disease; - dissection; - intracranial atherosclerotic stenosis. The 2026 AHA/ASA guideline states that vascular imaging required for EVT selection should not be delayed for kidney-function testing when such delay could cost reperfusion opportunity. [1] ### 7.3 CT perfusion and MRI Useful for selected: - wake-up stroke; - 4.5–9-hour thrombolysis decisions; - 6–24-hour EVT selection; - uncertain diagnosis when MRI is immediately available without harmful delay. #### Tissue-selection concepts - **DWI–FLAIR mismatch:** diffusion restriction without corresponding FLAIR change suggests relatively recent infarction. - **Perfusion mismatch:** hypoperfused tissue substantially exceeds estimated core, suggesting salvageable penumbra. --- ## 8. Severity and imaging scores ### NIHSS Useful for communication, prognostication, serial change, and treatment pathways. It should not replace individualized assessment of disability. [1] ### ASPECTS Ten-region score for early ischemic change in the MCA territory: - 10 = no visible early ischemic change; - lower scores = larger predicted infarct burden. The modern thrombectomy era has moved beyond a rigid “ASPECTS ≥6 only” rule: randomized large-core trials and the 2026 AHA/ASA guideline support EVT in selected patients with ASPECTS 3–5, and in carefully selected early-window patients even ASPECTS 0–2 may be reasonable. [1,9,10] --- ## 9. Acute management algorithm ```text Suspected acute stroke ↓ ABCs + glucose + exact last-known-well + NIHSS ↓ Urgent NCCT ± CTA head/neck ↓ Hemorrhage? ├─ Yes → hemorrhagic-stroke pathway └─ No ↓ Disabling ischemic deficit? ↓ Within 4.5 h and IVT eligible? ├─ Yes → tenecteplase 0.25 mg/kg (max 25 mg) │ OR alteplase 0.9 mg/kg (max 90 mg) │ WITHOUT delaying parallel EVT evaluation └─ No/unknown onset → advanced imaging when appropriate ↓ Favorable mismatch 4.5–9 h / wake-up? ├─ Yes → consider IV thrombolysis └─ No → no IVT At all times: Is there treatable LVO? ↓ EVT eligibility (early or selected late window; large-core criteria now broader) ↓ Stroke unit + BP/glucose/temp/swallow/DVT prevention + etiologic workup ``` --- ## 10. Intravenous thrombolysis ### 10.1 STANDARD OF CARE — treatment within 4.5 hours For eligible adults with disabling AIS within 4.5 hours, the 2026 AHA/ASA guideline recommends either: [1] #### Tenecteplase - **0.25 mg/kg IV as a single bolus** - **Maximum 25 mg** #### Alteplase - **0.9 mg/kg IV (maximum 90 mg)** - Standard administration: 10% as initial bolus, remainder over 60 minutes. Tenecteplase’s single-bolus administration simplifies transfer and workflow. The 2026 guideline formally places 0.25 mg/kg tenecteplase alongside alteplase as a recommended option. Higher-dose tenecteplase **0.40 mg/kg should not be used for routine AIS thrombolysis**. [1,2] ### 10.2 Disabling vs non-disabling deficit #### Disabling deficit Treat rapidly if otherwise eligible, regardless of a deceptively low NIHSS. [1] #### Mild non-disabling deficit Routine thrombolysis is not recommended because trials have not shown net benefit; DAPT is generally preferred when the stroke is noncardioembolic and the patient meets antiplatelet criteria. [1] ### 10.3 Extended-window thrombolysis For selected patients with: - wake-up stroke; or - symptom onset/last-known-well **4.5–9 hours** earlier, IV thrombolysis may be reasonable if advanced imaging shows a favorable DWI–FLAIR or perfusion mismatch profile. [1,5,6] This is **tissue-selected reperfusion**, not blanket extension of the standard 4.5-hour window. ### 10.4 Blood pressure around thrombolysis #### Before IV thrombolysis A practical trial-based threshold remains: - **SBP <185 mm Hg and DBP <110 mm Hg** before treatment. [1] #### After thrombolysis The 2026 guideline reinforces a more liberal post-IVT target rather than intensive reduction: - generally keep **SBP <180 mm Hg**; - avoid routine intensive targeting **<140 mm Hg**, which does not improve functional outcome. [1] The guideline supportive text recommends maintaining SBP roughly **140–180 mm Hg** after thrombolysis when no other indication dictates a different target. [1] ### 10.5 Major contraindication framework Eligibility is nuanced and should use the current local protocol. High-impact reasons to withhold or defer IV thrombolysis commonly include: - intracranial hemorrhage on imaging; - uncontrolled BP above accepted treatment thresholds despite therapy; - active major bleeding; - recent intracranial surgery/serious head trauma when bleeding risk is prohibitive; - clinically significant coagulopathy or anticoagulant effect at unsafe levels; - strong suspicion of infective endocarditis-related stroke in many protocols; - extensive established infarction when hemorrhage risk outweighs benefit. The 2026 AHA/ASA guideline deliberately modernizes several historical exclusions; avoid using outdated “absolute contraindication” lists without checking current criteria. [1] ### 10.6 After thrombolysis - Frequent neurological and BP checks. - Avoid antiplatelet/anticoagulant treatment during the first 24 hours unless a compelling specialist-directed indication exists. - Obtain follow-up CT/MRI at approximately 24 hours or sooner for neurological deterioration before starting routine antithrombotic therapy. - Watch for orolingual angioedema and symptomatic intracranial hemorrhage. #### Suspected post-thrombolysis intracranial hemorrhage Stop thrombolytic infusion if still running; obtain emergent CT, CBC, fibrinogen, coagulation studies, and activate stroke/neurocritical-care/hematology protocols for reversal and hemostatic management. Exact reversal regimen is institution-specific. --- ## 11. Endovascular thrombectomy (EVT) ### 11.1 STANDARD OF CARE — proximal anterior circulation LVO EVT is one of the most effective acute neurological interventions. The 2026 guideline recommends thrombectomy for eligible patients with proximal ICA/M1 occlusion in the early window and expands eligibility for patients with larger predicted cores. [1] #### Early window (0–6 hours) A strong evidence base supports EVT for appropriate ICA/M1 LVO with clinically meaningful deficit. The 2026 guideline explicitly includes selected patients with **ASPECTS 3–10** and NIHSS ≥6 under standard criteria; selected ASPECTS 0–2 patients may also reasonably be considered when other features favor benefit. [1] #### Late window (6–24 hours) Selected patients with proximal anterior-circulation LVO can benefit up to 24 hours based on clinical and imaging selection. Large-core trials such as SELECT2 and ANGEL-ASPECT expanded the treatable population beyond the small-core DAWN/DEFUSE-3 paradigm. [1,7-10] ### 11.2 Basilar artery occlusion The 2026 AHA/ASA guideline gives a strong recommendation for EVT in selected patients with **basilar artery occlusion within 24 hours**, particularly those with: - prestroke mRS 0–1; - **NIHSS ≥10**; - **PC-ASPECTS ≥6**. [1] ATTENTION and BAOCHE were major trials establishing benefit in this previously uncertain population. [11,12] ### 11.3 Do not delay IV thrombolysis for EVT When a patient is eligible for IV thrombolysis and also has an LVO, treatment is generally **bridging therapy**: give IV thrombolysis promptly and proceed to thrombectomy rather than waiting to see whether IV treatment works. [1] ### 11.4 Blood pressure after EVT The 2026 guideline incorporates new randomized data showing that aggressive BP lowering can be harmful after successful recanalization: - routine targeting of **SBP <140 mm Hg after successful EVT is harmful/not recommended** when there is no separate indication for such a low target. [1] Avoid hypotension and maintain adequate cerebral perfusion. ### 11.5 Medium/distal vessel occlusion — not routine standard care **EMERGING/NEGATIVE EVIDENCE:** ESCAPE-MeVO (2025) found no improvement in 90-day outcome with EVT for medium-vessel occlusion and observed higher mortality and more symptomatic intracranial hemorrhage in the intervention group. [13] DISCOUNT, published in 2026, similarly did not show improved good functional outcome and reported more symptomatic hemorrhage with thrombectomy. [14] **Practical implication:** Do not extrapolate the dramatic benefit of ICA/M1 thrombectomy to all M2/M3/ACA/PCA distal occlusions. Individual selected cases may still be discussed with neurointerventional experts, but routine thrombectomy for populations matching these trials is not evidence-based. --- ## 12. General supportive care ### Oxygenation - Maintain adequate oxygenation. - Supplemental oxygen is not routinely required in a nonhypoxemic patient. - Treat airway compromise, aspiration, pneumonia, or respiratory failure promptly. ### Blood pressure if no reperfusion therapy When no IVT/EVT is planned and there is no separate hypertensive emergency, routine early BP lowering does not improve outcome when BP is below approximately **220/120 mm Hg**. In severe hypertension, cautious individualized reduction—often around 15% initially—is used. [1] Urgent BP treatment may still be necessary for aortic dissection, acute coronary syndrome, pulmonary edema, hypertensive encephalopathy, preeclampsia/eclampsia, or another compelling condition. ### Glucose - Correct significant hypoglycemia. - Treat marked hyperglycemia, commonly when persistent glucose is >180 mg/dL, while avoiding hypoglycemia. - **Do not target 80–130 mg/dL intensively**; the SHINE trial and 2026 guideline show no functional benefit and more severe hypoglycemia. [1] ### Temperature - Treat fever and investigate infection. - The 2026 guideline supports protocols maintaining normothermia and treating temperatures >37.5°C. [1] - Therapeutic hypothermia is not routine AIS care. ### Swallowing - Screen for dysphagia before oral food, liquids, and medications when feasible. - Provide oral hygiene and aspiration precautions. - Use enteral support when oral intake is unsafe. ### DVT prevention - Early mobilization when safe. - Intermittent pneumatic compression for immobile patients is evidence-based. - Pharmacologic prophylaxis is individualized to hemorrhagic risk and reperfusion status. --- ## 13. Antiplatelet and anticoagulant therapy ### 13.1 Aspirin and DAPT For noncardioembolic AIS not treated with thrombolysis, antiplatelet therapy is initiated early after hemorrhage is excluded. #### Short-course DAPT The 2026 guideline supports **aspirin + clopidogrel for 21 days** in selected patients with: - minor noncardioembolic AIS (generally NIHSS ≤5 depending on the specific pathway); or - high-risk TIA; - no IV thrombolysis; - low enough bleeding risk. [1] This approach derives from CHANCE/POINT-era evidence and should not be extended indefinitely because bleeding risk rises with prolonged dual therapy. ### 13.2 Atrial fibrillation Cardioembolic stroke usually requires long-term oral anticoagulation, but timing depends on infarct size, hemorrhagic transformation, reperfusion treatment, and bleeding risk. The 2026 AIS guideline states that in carefully selected patients—especially milder strokes—**earlier oral anticoagulation is reasonable and appears low risk** compared with delayed initiation, while acknowledging uncertainty about the efficacy of preventing very early recurrence. [1] This is consistent with modern randomized evidence such as ELAN, which supports individualized early DOAC initiation in many patients rather than rigid long delays. [15] --- ## 14. Etiologic workup after stabilization A complete stroke mechanism evaluation commonly includes: - continuous telemetry/ECG for atrial fibrillation; - vascular imaging of neck and intracranial circulation; - transthoracic echocardiography when cardioembolism is possible; - prolonged rhythm monitoring for cryptogenic embolic stroke; - HbA1c and lipid profile; - selective TEE, thrombophilia, vasculitis, infectious, or genetic testing when indicated; - cervical artery dissection evaluation in compatible presentations. Avoid broad low-yield thrombophilia testing in older patients with a conventional atherosclerotic/cardioembolic explanation unless history suggests otherwise. --- ## 15. Important complications | Complication | Warning signs | Key response | |---|---|---| | Hemorrhagic transformation | New headache, vomiting, hypertension, worsening deficit, reduced consciousness | Emergent CT; stop antithrombotics; reverse relevant agents; neurocritical-care input | | Malignant cerebral edema | Declining consciousness, worsening hemiparesis, gaze changes, pupillary abnormalities | Neurocritical care; osmotherapy as bridge; urgent neurosurgical evaluation | | Aspiration pneumonia | Fever, cough, hypoxemia after dysphagia | Swallow precautions, antibiotics when infection established | | Seizure | Convulsion or unexplained episodic decline | Treat clinical seizures; routine prophylaxis is not standard | | DVT/PE | Leg swelling, unexplained hypoxia/tachycardia | Prophylaxis; diagnostic workup if suspected | | Recurrent stroke | New focal deficit | Repeat acute stroke pathway; reassess eligibility for reperfusion | | Depression/delirium | Mood/cognitive change | Screening, rehabilitation, medication review, supportive care | ### Malignant MCA infarction Large hemispheric infarction can cause life-threatening edema over several days. **Early decompressive hemicraniectomy** reduces mortality and severe disability in appropriately selected patients; benefit is strongest in younger patients but can extend to selected older adults with individualized goals-of-care discussion. --- ## 16. Secondary prevention ### 16.1 Blood pressure Long-term hypertension control is one of the most effective recurrent-stroke prevention interventions. Avoid translating permissive acute-stroke BP management into chronic care. ### 16.2 Lipids High-intensity statin therapy is standard after atherosclerotic ischemic stroke unless contraindicated. For very-high-risk atherosclerotic disease, add-on ezetimibe or PCSK9-directed therapy may be needed to achieve guideline LDL targets. ### 16.3 Carotid disease Symptomatic ipsilateral carotid stenosis can require carotid endarterectomy, with benefit depending on stenosis severity, age/sex, procedural risk, and timing. Early specialist evaluation is essential. ### 16.4 Lifestyle - Smoking cessation - Exercise and rehabilitation - Mediterranean-style dietary pattern - Diabetes management - Weight management - Sleep apnea evaluation where indicated --- ## 17. Special populations ### Pregnancy Stroke in pregnancy requires coordinated neurology, maternal-fetal medicine, anesthesia, and neurointerventional care. Pregnancy is not automatically an exclusion from reperfusion; risks and benefits depend on maternal threat, gestational age, bleeding risk, and treatment modality. ### Children The 2026 AHA/ASA guideline includes pediatric interventional recommendations for the first time. Pediatric AIS requires expert center involvement because causes, vessel caliber, dosing, and evidence differ from adults. [1] ### Sickle cell disease Acute focal deficit in sickle cell disease requires urgent stroke-center and hematology management; transfusion/exchange transfusion is central to disease-specific care. ### Cervical artery dissection Dissection is an important cause in younger adults. The 2026 guideline concludes that either antiplatelet therapy or anticoagulation can be reasonable after AIS due to dissection, reflecting limited comparative evidence. [1] --- ## 18. Acute management checklist ### First 10 minutes - [ ] Activate stroke pathway. - [ ] Establish last-known-well. - [ ] ABCs; avoid hypotension/hypoxemia. - [ ] Point-of-care glucose. - [ ] NIHSS/focused deficit assessment. - [ ] Noncontrast head CT. - [ ] CTA head/neck if LVO suspected. - [ ] Determine whether deficit is **disabling**, not merely whether NIHSS is “low.” ### Reperfusion decision - [ ] Within 4.5 hours and eligible? Give **tenecteplase 0.25 mg/kg (max 25 mg)** or **alteplase 0.9 mg/kg (max 90 mg)**. - [ ] BP <185/110 before IVT. - [ ] Do not delay IVT for unnecessary advanced imaging. - [ ] Evaluate EVT in parallel when LVO is possible. - [ ] For wake-up/4.5–9-hour stroke, use advanced imaging selection. - [ ] For 6–24-hour LVO, evaluate late-window EVT eligibility. ### First 24 hours - [ ] Stroke-unit monitoring. - [ ] Maintain appropriate BP; avoid intensive SBP <140 after reperfusion unless another indication exists. - [ ] Treat fever and significant glucose derangement. - [ ] Swallow screen before oral intake. - [ ] DVT prevention. - [ ] Repeat imaging if deterioration; routine post-IVT imaging before antithrombotics. - [ ] Begin etiologic evaluation. --- ## 19. Common pitfalls | Pitfall | Why it is dangerous | Better approach | |---|---|---| | “NIHSS is only 2, so no thrombolysis” | Low NIHSS can still be disabling | Judge functional disability | | Waiting for MRI in a clear <4.5 h disabling stroke | Loses reperfusion benefit | NCCT is usually enough for IVT decision | | Waiting for creatinine before CTA in suspected LVO | Delays EVT | Proceed rapidly when vascular imaging is required [1] | | Treating BP aggressively to “normal” | Can reduce penumbral perfusion | Use reperfusion-specific targets | | Targeting SBP <140 after successful EVT | RCT evidence suggests harm | Avoid overly intensive reduction [1] | | Assuming wake-up stroke is untreatable | Tissue imaging may identify benefit | DWI-FLAIR/perfusion selection | | Giving routine EVT for distal/medium occlusions | RCTs have not shown benefit and may show harm | Individualize; not routine standard care [13,14] | | Starting oral intake without dysphagia assessment | Aspiration risk | Screen swallowing first | --- ## 20. Exam-focused review ### Foundation / Step 1 Know the ischemic cascade, collateral circulation, infarct core vs penumbra, and why reperfusion must be early. ### Step 2 CK Prioritize **stabilization and reperfusion before definitive etiologic workup**. A patient with sudden aphasia and right weakness who arrives 90 minutes after last-known-well needs glucose and emergent CT—not carotid ultrasound, echocardiography, or MRI first. ### Step 3 / resident Know: - tenecteplase 0.25 mg/kg max 25 mg; - alteplase 0.9 mg/kg max 90 mg; - pre-IVT BP <185/110; - do not intensively lower post-reperfusion SBP <140 without a separate indication; - IVT and EVT are complementary when both are indicated; - selected late-window and large-core patients can benefit from EVT. ### MRCP/ABIM/board level Distinguish: - low NIHSS vs non-disabling deficit; - proximal LVO vs medium/distal occlusion; - clock-based vs tissue-based treatment windows; - cardioembolic vs noncardioembolic secondary prevention; - acute permissive hypertension vs long-term hypertension control. --- ## 21. Original MCQs #### Question 1 A 67-year-old right-handed teacher develops isolated expressive aphasia 90 minutes ago. NIHSS is 2. CT shows no hemorrhage. BP is 168/94 mm Hg. Which principle best guides treatment? A. NIHSS <4 excludes thrombolysis B. Aphasia may be disabling despite a low NIHSS C. MRI is mandatory before thrombolysis D. Wait 24 hours to see whether symptoms resolve **Answer: B.** The 2026 guideline emphasizes disability rather than an NIHSS cutoff alone. Disabling deficits should be treated rapidly if otherwise eligible. [1] #### Question 2 Which IV thrombolytic regimen is recommended by the 2026 AHA/ASA guideline? A. Tenecteplase 0.40 mg/kg B. Tenecteplase 0.25 mg/kg, maximum 25 mg C. Alteplase 1.5 mg/kg D. Streptokinase infusion **Answer: B.** Tenecteplase 0.25 mg/kg (max 25 mg) or alteplase 0.9 mg/kg are recommended options. [1] #### Question 3 A patient with an LVO is eligible for both IV thrombolysis and thrombectomy. What is the best strategy? A. Skip IV therapy and wait for EVT in all cases B. Give IV thrombolysis promptly and proceed with EVT evaluation without delay C. Wait 60 minutes after thrombolysis to assess response before transfer D. Anticoagulate with heparin first **Answer: B.** Eligible IV thrombolysis should not be delayed or withheld simply because EVT is planned. [1] #### Question 4 After successful EVT, which routine BP strategy is specifically discouraged by current evidence? A. Avoiding hypotension B. Treating severe hypertension C. Intensive SBP targeting <140 mm Hg without another indication D. Frequent BP measurement **Answer: C.** Intensive SBP lowering below 140 mm Hg after successful EVT may worsen functional outcomes. [1] #### Question 5 A patient wakes with hemiparesis; last known well was 7 hours ago. CT excludes hemorrhage. Which statement is correct? A. IV thrombolysis is always contraindicated after 4.5 hours B. Advanced imaging can identify selected patients for extended-window thrombolysis C. Only aspirin is possible D. MRI mismatch has no role **Answer: B.** Selected wake-up or 4.5–9-hour strokes may receive thrombolysis based on DWI-FLAIR or perfusion mismatch. [1,5,6] #### Question 6 Which statement about medium/distal vessel occlusion is most accurate as of September 2026? A. EVT is proven routine standard care for all M3 occlusions B. Recent randomized trials failed to demonstrate routine benefit and reported safety concerns C. EVT is contraindicated in every distal occlusion D. All patients should receive systemic heparin **Answer: B.** ESCAPE-MeVO and DISCOUNT did not show routine functional benefit; thrombectomy should not be reflexively extrapolated from proximal LVO evidence. [13,14] #### Question 7 A patient with AIS is not receiving reperfusion therapy, has BP 196/108 mm Hg, and no other hypertensive emergency. Which approach is most appropriate? A. Immediately normalize to 120/80 B. Routine aggressive reduction is not required simply because BP is elevated C. Nitroprusside until SBP <100 D. Mandatory IV labetalol to SBP <140 **Answer: B.** In nonreperfused AIS, routine early lowering below the severe-hypertension threshold does not improve outcome; avoid compromising cerebral perfusion. [1] #### Question 8 Which in-hospital glucose strategy is supported by the 2026 guideline? A. Target 80–130 mg/dL with intensive insulin in all patients B. Ignore glucose after the initial value C. Correct hypoglycemia and marked hyperglycemia, but avoid intensive 80–130 mg/dL targeting D. Maintain glucose >250 mg/dL **Answer: C.** Intensive glucose control to 80–130 mg/dL did not improve outcomes and increased severe hypoglycemia. [1] --- ## 22. Current guideline changes and recent research ### STANDARD OF CARE — 2026 changes 1. **Tenecteplase 0.25 mg/kg is now a fully endorsed alternative to alteplase** within the 4.5-hour window. [1] 2. **Thrombolysis is guided by disability, not an NIHSS threshold alone.** [1] 3. **Extended-window thrombolysis** is supported for selected imaging-defined patients. [1] 4. **Large-core EVT eligibility is broader** based on SELECT2, ANGEL-ASPECT, LASTE and related trials. [1,9,10] 5. **Basilar EVT up to 24 hours** is standard in selected NIHSS ≥10, favorable-PC-ASPECTS patients. [1,11,12] 6. **Intensive SBP <140 after EVT is harmful/not recommended.** [1] 7. Intensive glucose control to **80–130 mg/dL is not recommended**. [1] ### EMERGING/NEGATIVE EVIDENCE #### Medium/distal vessel thrombectomy ESCAPE-MeVO (NEJM 2025) found no 90-day functional benefit from EVT for medium-vessel occlusion; symptomatic ICH and mortality were higher in the EVT arm. [13] DISCOUNT (JAMA 2026) similarly found no improvement in good outcome, with symptomatic hemorrhage 11% vs 3% in thrombectomy vs medical treatment. [14] **Interpretation:** Routine EVT for medium/distal occlusion remains unsupported; future work may identify narrower subgroups. ### EXPERIMENTAL/INVESTIGATIONAL - Neuroprotective drugs as an adjunct to reperfusion - Direct-to-angiosuite pathways outside validated systems - Thrombectomy beyond 24 hours - New devices/selection approaches for distal occlusion - Selective brain cooling These should not replace proven rapid reperfusion pathways. --- ## 23. References 1. Prabhakaran S, Gonzalez NR, Zachrison KS, et al. **2026 Guideline for the Early Management of Patients With Acute Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association.** *Stroke*. Published January 26, 2026. doi: **10.1161/STR.0000000000000513**. https://www.ahajournals.org/doi/10.1161/STR.0000000000000513 2. Alamowitch S, Turc G, Palaiodimou L, et al. **European Stroke Organisation expedited recommendation on tenecteplase for acute ischaemic stroke.** *Eur Stroke J*. 2023;8(1). doi: **10.1177/23969873221150022**. https://journals.sagepub.com/doi/10.1177/23969873221150022 3. NINDS rt-PA Stroke Study Group. **Tissue plasminogen activator for acute ischemic stroke.** *N Engl J Med*. 1995;333:1581-1587. doi: **10.1056/NEJM199512143332401**. 4. Hacke W, Kaste M, Bluhmki E, et al. **Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke.** *N Engl J Med*. 2008;359:1317-1329. doi: **10.1056/NEJMoa0804656**. 5. Thomalla G, Simonsen CZ, Boutitie F, et al. **MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset (WAKE-UP).** *N Engl J Med*. 2018;379:611-622. doi: **10.1056/NEJMoa1804355**. 6. Ma H, Campbell BCV, Parsons MW, et al. **Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke (EXTEND).** *N Engl J Med*. 2019;380:1795-1803. doi: **10.1056/NEJMoa1813046**. 7. Nogueira RG, Jadhav AP, Haussen DC, et al. **Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct (DAWN).** *N Engl J Med*. 2018;378:11-21. doi: **10.1056/NEJMoa1706442**. 8. Albers GW, Marks MP, Kemp S, et al. **Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging (DEFUSE 3).** *N Engl J Med*. 2018;378:708-718. doi: **10.1056/NEJMoa1713973**. 9. Sarraj A, Hassan AE, Abraham MG, et al. **Trial of Endovascular Thrombectomy for Large Ischemic Strokes (SELECT2).** *N Engl J Med*. 2023;388:1259-1271. doi: **10.1056/NEJMoa2214403**. https://www.nejm.org/doi/10.1056/NEJMoa2214403 10. Huo X, Ma G, Tong X, et al. **Trial of Endovascular Therapy for Acute Ischemic Stroke with Large Infarct (ANGEL-ASPECT).** *N Engl J Med*. 2023;388:1272-1283. doi: **10.1056/NEJMoa2213379**. 11. Tao C, Nogueira RG, Zhu Y, et al. **Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion (ATTENTION).** *N Engl J Med*. 2022;387:1361-1372. doi: **10.1056/NEJMoa2206317**. 12. Jovin TG, Li C, Wu L, et al. **Trial of Thrombectomy 6 to 24 Hours after Stroke Due to Basilar-Artery Occlusion (BAOCHE).** *N Engl J Med*. 2022;387:1373-1384. doi: **10.1056/NEJMoa2207576**. 13. Goyal M, Ospel JM, Ganesh A, et al; ESCAPE-MeVO Investigators. **Endovascular Treatment of Stroke Due to Medium-Vessel Occlusion.** *N Engl J Med*. 2025;392:1385-1395. doi: **10.1056/NEJMoa2411668**. https://www.nejm.org/doi/10.1056/NEJMoa2411668 14. Clarençon F, Bala F, Baptiste A, et al. **Mechanical Thrombectomy in Ischemic Stroke With a Medium or Distal Arterial Occlusion: The DISCOUNT Randomized Clinical Trial.** *JAMA*. 2026;336(9):755-764. doi: **10.1001/jama.2026.8977**. PMID: **42485024**. 15. Fischer U, Koga M, Strbian D, et al. **Early versus Later Anticoagulation for Stroke with Atrial Fibrillation (ELAN).** *N Engl J Med*. 2023;388:2411-2421. doi: **10.1056/NEJMoa2303048**. 16. Kleindorfer DO, Towfighi A, Chaturvedi S, et al. **2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack.** *Stroke*. 2021;52:e364-e467. doi: **10.1161/STR.0000000000000375**. --- ### Bottom line Acute ischemic stroke is a **reperfusion emergency**. The highest-yield decisions are to establish last-known-well, identify whether the deficit is disabling, exclude hemorrhage, detect LVO, and deliver IV thrombolysis and/or thrombectomy without avoidable delay. In 2026, the treatable population is broader than it was a decade ago—but treatment remains highly selection-dependent: **large-core and basilar occlusion thrombectomy have moved into standard care for selected patients, while routine medium/distal-vessel thrombectomy has not.**1d:T84e6,## One-minute summary **Diabetic ketoacidosis (DKA)** is an acute metabolic emergency caused by insufficient effective insulin activity together with excess counterregulatory hormones, producing **ketogenesis, metabolic acidosis, osmotic diuresis, dehydration, and total-body electrolyte depletion**. The 2024 international consensus report endorsed by the ADA, EASD, AACE, JBDS, and Diabetes Technology Society modernized the adult diagnostic framework: DKA requires **(1) diabetes or glucose ≥200 mg/dL (11.1 mmol/L), (2) significant ketosis—preferably β-hydroxybutyrate ≥3.0 mmol/L, and (3) metabolic acidosis with pH <7.3 and/or bicarbonate <18 mmol/L**.[1,2] Management is simultaneous rather than sequential: **restore circulating volume, administer insulin, replace potassium and other electrolytes appropriately, add dextrose before ketoacidosis has resolved, identify the precipitant, and monitor closely until ketonemia and acidosis resolve**.[1] Quantitative **β-hydroxybutyrate** is preferred over urine ketones for diagnosis and monitoring because nitroprusside urine testing does not measure β-hydroxybutyrate and may paradoxically appear “worse” as DKA improves.[1,3] A crucial modern concept is **euglycemic DKA**, particularly with SGLT2 inhibitors, pregnancy, prolonged fasting, low-carbohydrate intake, and partial insulin treatment. A near-normal glucose does **not** exclude DKA if ketosis and acidosis are present.[1,4] ### Immediate priorities 1. Confirm DKA and assess severity. 2. Search for shock, infection, ischemia, missed insulin, pump failure, pregnancy, drugs/toxins, and SGLT2 inhibitor exposure. 3. Begin isotonic saline or balanced crystalloid; balanced solutions are increasingly favored when available. 4. Check potassium **before and during insulin therapy**. 5. Start insulin when potassium is safe; severe DKA generally uses IV insulin **0.1 units/kg/hour**.[1,2] 6. Add **5–10% dextrose once glucose falls below 250 mg/dL** so insulin can continue until ketoacidosis resolves.[2] 7. Reassess frequently; do not stop insulin merely because glucose has normalized. --- ## Definition and diagnostic criteria DKA is a syndrome of **diabetes/hyperglycemia, ketonemia, and metabolic acidosis** produced by absolute or relative insulin deficiency. In adults, all three diagnostic domains should be present.[1] | Domain | Current adult criterion | Practical interpretation | |---|---|---| | **D — diabetes/hyperglycemia** | Glucose **≥200 mg/dL (11.1 mmol/L)** **or** established diabetes | The lower glucose threshold recognizes euglycemic/near-euglycemic presentations | | **K — ketosis** | β-hydroxybutyrate **≥3.0 mmol/L** preferred; urine ketones ≥2+ if quantitative testing unavailable | β-hydroxybutyrate is the dominant ketone in DKA and best tracks recovery | | **A — acidosis** | Venous/arterial pH **<7.3** and/or bicarbonate **<18 mmol/L** | Mixed acid-base disorders can partially mask acidemia | The **anion gap is still clinically useful**, especially where β-hydroxybutyrate is unavailable, but it was removed from the primary 2024 diagnostic/severity criteria because vomiting, volume contraction, chloride-rich fluids, and other mixed disorders can alter the relationship between ketone burden and bicarbonate/anion gap.[1,3] ### Euglycemic DKA Euglycemic DKA describes ketoacidosis with glucose that is not markedly elevated. Important triggers include: - SGLT2 inhibitors - pregnancy - prolonged fasting or starvation physiology in a person with diabetes - vomiting and reduced carbohydrate intake - partial insulin treatment before presentation - alcohol use - acute illness with reduced intake **Board pearl:** A patient taking an SGLT2 inhibitor with nausea, tachypnea, abdominal pain, high anion gap, and β-hydroxybutyrate elevation may have DKA even with glucose 120–200 mg/dL. --- ## Epidemiology and outcomes Hyperglycemic crises are increasingly common. The 2024 consensus report notes a marked rise in adult DKA admissions over the preceding decade, particularly in adults younger than 45 years.[1] Most DKA still occurs in type 1 diabetes, but DKA also occurs in type 2 diabetes, ketosis-prone diabetes, pancreatic diabetes, and other insulin-deficient states. Recurrent DKA is common and often signals a preventable systems problem such as insulin access, diabetes distress, psychiatric disease, substance use, inadequate sick-day education, or device failure.[1] With timely modern care, **adult DKA mortality is usually <1%**, but risk rises with advanced age, severe comorbidity, sepsis, myocardial infarction, renal failure, profound acidosis, mixed DKA/HHS, and delayed treatment.[1] --- ## Etiology and precipitants | Precipitant | Clues | Immediate implication | |---|---|---| | **Insulin omission/interruption** | Missed doses, affordability issues, injection problems, pump interruption | Restore basal insulin strategy and address access/education before discharge | | **Infection** | Fever may be absent; UTI and pneumonia are common | Cultures/imaging as indicated; antibiotics only when infection is suspected/confirmed | | **New diabetes** | Weight loss, polyuria, polydipsia | Determine phenotype later; acute stabilization comes first | | **SGLT2 inhibitor** | Disproportionate ketosis with modest glucose | Stop drug; treat as DKA; consider euglycemic DKA | | **Acute coronary syndrome / stroke** | Chest pain, ECG/troponin changes, focal deficits | DKA may be precipitant or consequence; manage both emergencies | | **Pancreatitis** | Epigastric pain, elevated lipase; note DKA itself may mildly raise lipase | Diagnose pancreatitis clinically/imaging when appropriate, not by lipase alone | | **Pregnancy** | Lower glucose threshold, rapid ketosis | Obstetric/endocrine involvement; fetal status after maternal stabilization | | **Drugs** | Glucocorticoids, sympathomimetics, atypical antipsychotics, cocaine | Treat trigger; adjust diabetes plan | | **Pump/infusion-set failure** | Rapid deterioration in pump users because no long-acting insulin depot | Inspect device, tubing, site; give insulin by reliable route | --- ## Pathophysiology ### 1. Insulin deficiency and counterregulatory excess Reduced effective insulin plus increased glucagon, catecholamines, cortisol, and growth hormone causes: - increased hepatic gluconeogenesis and glycogenolysis → hyperglycemia - reduced peripheral glucose utilization - increased lipolysis → free fatty acids - hepatic conversion of free fatty acids to ketone bodies, especially **β-hydroxybutyrate** - accumulation of ketoacids → high-anion-gap metabolic acidosis ### 2. Osmotic diuresis and dehydration Glucosuria and ketonuria cause urinary water and electrolyte losses. Patients can have large deficits of: - water - sodium - potassium - phosphate - magnesium The serum potassium may initially be normal or high because insulin deficiency, hyperosmolality, and acidosis shift potassium extracellularly, even though **total-body potassium is depleted**. ### 3. Acid-base complexity Classic DKA causes high-anion-gap metabolic acidosis with respiratory compensation (Kussmaul breathing). Common concurrent disorders include: - metabolic alkalosis from vomiting - hyperchloremic metabolic acidosis during treatment, especially with large saline volumes - lactic acidosis from hypoperfusion - respiratory alkalosis from sepsis/pregnancy - respiratory acidosis if fatigue or CNS depression develops **Clinical implication:** A pH that is only mildly low—or even normal—does not exclude clinically important ketoacidosis when mixed disorders coexist.[3] --- ## Clinical presentation ### Symptoms - polyuria, polydipsia, thirst - weight loss - nausea and vomiting - abdominal pain - weakness/fatigue - dyspnea - confusion or reduced consciousness in severe disease ### Examination - tachycardia - dehydration: dry mucosa, poor skin turgor, low JVP - hypotension or orthostasis - tachypnea / **Kussmaul respirations** - acetone-like breath odor (not reliably present) - abdominal tenderness without peritonitis - altered mental status in severe DKA, mixed DKA/HHS, sepsis, or another CNS process ### Red flags - shock or persistent hypotension - hypoxemia - severe hypokalemia - pH <7.0 - β-hydroxybutyrate >6 mmol/L - coma/stupor - pregnancy - dialysis or severe renal failure - acute MI/stroke/sepsis - suspected cerebral edema - mixed DKA/HHS --- ## Initial assessment: what to do in the first 15–30 minutes | Component | Assessment | Interpretation | Immediate action | Anticipate deterioration | |---|---|---|---|---| | **Airway/mental status** | Ability to protect airway, GCS/AVPU | Marked depression suggests severe DKA, hyperosmolality, sepsis, stroke, intoxication | Airway support if required; avoid routine intubation solely for low pH | Loss of respiratory compensation after sedation/intubation can abruptly worsen acidemia | | **Breathing** | RR, SpO₂, work, chest exam | Kussmaul breathing is compensatory | Oxygen only if indicated; treat pulmonary precipitant | Fatigue or rising CO₂ is ominous | | **Circulation** | BP, pulse, capillary refill, JVP, urine output | Shock may be hypovolemic, septic, cardiogenic, or mixed | IV access, crystalloid, ECG, cause-specific shock care | Older/renal/cardiac patients are vulnerable to overload | | **Disability** | Glucose, pupils, neurologic exam | Hypoglycemia is not typical before therapy; focal deficits require separate evaluation | Bedside glucose immediately; CT/neurology if indicated after stabilization | Cerebral edema is rare in adults but serious | | **Exposure/cause** | Temperature, infection source, injection/pump sites, pregnancy possibility | Identify precipitant | Cultures/imaging/troponin/pregnancy test when indicated | DKA may coexist with sepsis, MI, pancreatitis | --- ## Diagnostic evaluation ### Essential tests - bedside and laboratory plasma glucose - **quantitative β-hydroxybutyrate** when available - venous blood gas (usually sufficient for pH monitoring) - sodium, potassium, chloride, bicarbonate - urea/BUN, creatinine - magnesium and phosphate - CBC - ECG - urinalysis - pregnancy test when relevant ### Directed tests for precipitant - blood/urine cultures if infection suspected - chest radiograph for respiratory symptoms or suspected pneumonia - troponin/serial ECG if ACS possible - lipase if pancreatitis is clinically suspected - toxicology testing only when clinically indicated - device/pump interrogation where relevant ### Useful calculations **Anion gap:** `Na − (Cl + HCO3)` Albumin-correct if necessary. Use as contextual information, especially when β-hydroxybutyrate is unavailable. **Effective osmolality (mOsm/kg):** `2 × Na (mmol/L) + glucose (mg/dL)/18` A markedly elevated osmolality or HHS-level hyperglycemia suggests a mixed DKA/HHS picture, which carries higher risk. --- ## Severity and level of care The 2024 consensus uses β-hydroxybutyrate, pH/bicarbonate, and mental status to guide severity and location of care.[1,2] | Severity | β-hydroxybutyrate | pH / bicarbonate | Mental status | Typical location | |---|---|---|---|---| | **Mild** | 3–6 mmol/L | pH >7.25; HCO3 ≥15 mmol/L | Alert | Observation/ward if adequate monitoring | | **Moderate** | 3–6 mmol/L | pH 7.0–7.25; HCO3 10 to <15 | Alert/drowsy | Step-down/intermediate care often appropriate | | **Severe** | >6 mmol/L | pH <7.0; HCO3 <10 | Stupor/coma possible | ICU/high-dependency care | Clinical judgment overrides classification. Severe comorbidity, shock, pregnancy, dialysis, HHS overlap, or need for organ support warrants higher-acuity care. --- ## Management ### STANDARD OF CARE — core treatment bundle #### 1. Fluids For adults **without cardiac or renal compromise**, the contemporary consensus recommends **isotonic saline or balanced crystalloid at approximately 500–1,000 mL/hour for the first 2–4 hours**, followed by individualized replacement based on hemodynamics, fluid balance, sodium, urine output, and comorbidity.[2] Balanced crystalloids are increasingly preferred where available because randomized and meta-analytic data suggest less hyperchloremic acidosis and potentially faster DKA resolution compared with saline.[1,2,5,6] ##### Practical fluid approach | Situation | Approach | |---|---| | Shock/severe hypovolemia | Rapid isotonic crystalloid with frequent reassessment; simultaneously look for sepsis/hemorrhage/cardiogenic causes | | Typical adult, no heart/kidney failure | 500–1,000 mL/h initially for 2–4 h, then reduce/individualize | | Older adult, heart failure, advanced kidney disease | Smaller boluses (e.g., **250 mL**) with lung/JVP/POCUS/urine-output reassessment[2] | | Glucose <250 mg/dL but DKA persists | Add **5–10% dextrose** while continuing insulin[2] | **Do not chase glucose alone.** Fluid therapy lowers glucose even before insulin by improving renal perfusion and decreasing counterregulatory stress. --- #### 2. Insulin Insulin suppresses lipolysis and ketogenesis; this is the definitive metabolic treatment. ##### IV insulin For severe DKA or when close titration is needed: - regular insulin infusion typically **0.1 units/kg/hour**[1,2] - a routine IV bolus is not required in many modern protocols - continue insulin after glucose reaches the target range by adding dextrose rather than stopping insulin prematurely When glucose falls below **250 mg/dL**, add dextrose and adjust insulin to keep glucose roughly around 200 mg/dL until ketoacidosis has resolved.[2] ##### Subcutaneous rapid-acting insulin **Uncomplicated mild and selected moderate DKA** can be managed with subcutaneous rapid-acting insulin analogues every 1–2 hours in systems with adequate nursing, protocolization, electrolyte monitoring, and ability to escalate.[1,2] Do **not** use subcutaneous pathways for severe DKA, shock, HHS, pregnancy without a dedicated protocol, major comorbidity, impaired perfusion, or inability to monitor closely. --- #### 3. Potassium: the highest-risk electrolyte issue Total-body potassium is depleted even when the initial serum level is high. | Serum K⁺ | Action | |---|---| | **<3.5 mmol/L** | **Hold insulin.** Begin potassium replacement; the 2024 consensus summary recommends about **10 mmol/hour** until K⁺ >3.5 mmol/L, with ECG/serial monitoring and local infusion-safety rules.[2] | | **3.5 to <5.0 mmol/L** | Start insulin and give potassium in IV fluids; titrate to maintain **4–5 mmol/L** | | **≥5.0 mmol/L** | Do not routinely give potassium initially; monitor closely because it will usually fall rapidly after fluids/insulin | Check potassium at baseline, approximately 2 hours after insulin starts, and at least every 4 hours until resolution; more often when abnormal or replacing aggressively.[2] **Board pearl:** Starting insulin in profound hypokalemia can precipitate malignant arrhythmia and respiratory muscle weakness. --- #### 4. Bicarbonate **Routine bicarbonate is not recommended.** It does not improve routine DKA outcomes and may worsen hypokalemia and cause other adverse effects.[1] Consider bicarbonate only for **severe acidosis (pH <7.0)**. The 2024 consensus describes **100 mmol sodium bicarbonate in 400 mL sterile water**, repeatable every 2 hours until pH >7.0 if indicated.[1] Use local critical-care/endocrine protocols because sodium load, potassium shifts, and volume status matter. --- #### 5. Phosphate and magnesium Routine phosphate replacement is not recommended. Consider replacement when phosphate is markedly low—particularly **<1.0 mmol/L** in the setting of muscle weakness or cardiac/respiratory impairment—using local dosing and calcium monitoring.[2] Magnesium should be measured and replaced when low, especially with arrhythmia or refractory hypokalemia. --- #### 6. Treat the precipitating cause - infection → appropriate antimicrobials/source control when indicated - MI/stroke → activate disease-specific pathway - insulin access/omission → correct access and education barriers - pump failure → reliable subcutaneous/IV insulin first; troubleshoot device later - SGLT2-associated DKA → discontinue drug during the event --- ### Monitoring and reassessment During active treatment, the 2024 consensus recommends:[2] - bedside glucose every **1–2 hours** - electrolytes, creatinine, phosphate, β-hydroxybutyrate, and venous pH approximately every **4 hours** until resolution - continuous/frequent vital signs - strict fluid balance and urine output - ECG monitoring when potassium is abnormal, severe illness is present, or cardiac disease is suspected #### What improvement should look like - decreasing β-hydroxybutyrate - rising bicarbonate/pH - improved perfusion and mental status - controlled fall in glucose - correction of potassium deficit without hypokalemia #### Anticipate treatment complications | Complication | Why it happens | Prevention/response | |---|---|---| | **Hypoglycemia** | Insulin continues while glucose falls | Add dextrose before ketosis resolves; frequent glucose checks | | **Hypokalemia** | Insulin + correction of acidosis shifts K intracellularly | Scheduled potassium monitoring/replacement | | **Hyperchloremic acidosis** | Chloride-rich fluids + urinary ketoanion loss | Prefer balanced crystalloids when appropriate; interpret residual low bicarbonate carefully | | **Fluid overload** | Aggressive resuscitation in HF/CKD/older patients | Smaller boluses; frequent clinical/POCUS reassessment | | **Cerebral edema** | Rare in adults; rapid osmotic shifts are a concern | Avoid overly rapid correction, especially in mixed DKA/HHS; urgent critical-care/neuro treatment if suspected | | **Thrombosis** | Severe dehydration/hyperosmolarity, especially HHS overlap | Standard VTE risk assessment/prophylaxis when appropriate | --- ### Resolution and transition to subcutaneous insulin Do not define resolution by glucose alone. Modern practice emphasizes **suppression of ketonemia**.[2,3] Practical resolution requires clinical recovery plus normalization of the ketoacid state, generally with: - β-hydroxybutyrate falling to the normal/near-normal range (the consensus centers direct ketone measurement), and - pH/bicarbonate recovery Where β-hydroxybutyrate is unavailable, anion gap normalization remains a useful surrogate, but beware hyperchloremic acidosis.[3] #### Transition - Estimate total daily insulin based on preadmission therapy, weight, and in-hospital requirements. - A typical insulin-naïve estimate is approximately **0.3–0.6 units/kg/day**, individualized for frailty, renal function, steroid use, obesity, and hypoglycemia risk.[2] - Use a **basal-bolus** strategy where appropriate. - Give basal insulin **at least 1–2 hours before** stopping IV insulin to prevent rebound hyperglycemia/recurrent ketosis.[2] Continuing an established basal insulin dose during IV DKA therapy is reasonable in many patients and may reduce rebound hyperglycemia.[2] --- ### Differential diagnosis | Condition | Distinguishing features | |---|---| | **HHS** | Glucose ≥600 mg/dL, hyperosmolality, minimal ketonemia/acidosis; overlap is common | | **Starvation ketoacidosis** | Low intake, usually lower glucose and milder ketonemia/acidosis; insulin deficiency is not the primary driver | | **Alcoholic ketoacidosis** | Heavy alcohol use, vomiting, low/normal glucose, elevated β-hydroxybutyrate; thiamine and nutrition are important | | **Lactic acidosis** | Elevated lactate; shock, sepsis, hypoxia, toxins, metformin accumulation among causes | | **Toxic alcohols** | Osmolar gap early, neurologic/visual/renal clues; specific antidotal/toxicology pathway | | **Salicylate toxicity** | Mixed respiratory alkalosis + AG acidosis, tinnitus, hyperventilation | | **Uremic acidosis** | Advanced kidney failure; ketones not diagnostic of DKA unless coexisting | --- ### DKA versus HHS | Feature | DKA | HHS | |---|---|---| | Glucose | ≥200 mg/dL or known diabetes; may be euglycemic | Usually ≥600 mg/dL | | Ketones | β-hydroxybutyrate ≥3 mmol/L | <3 mmol/L by definition | | pH | <7.3 and/or HCO3 <18 | pH ≥7.3 and HCO3 ≥15 | | Osmolality | Variable | Effective >300 or total >320 mOsm/kg | | Dominant pathophysiology | Ketogenesis + acidosis | Profound dehydration + hyperosmolality | | Insulin infusion | Commonly 0.1 U/kg/h severe DKA | Typically 0.05 U/kg/h; **0.1 U/kg/h if mixed DKA/HHS**[2] | One-third of hyperglycemic crises may have overlapping features; treat significant ketosis/acidosis as DKA while also respecting HHS limits on the rate of osmotic correction.[1,2] --- ### Special populations #### SGLT2 inhibitor users SGLT2 inhibitors increase the risk of euglycemic DKA. During severe illness, prolonged fasting, ketonemia/ketonuria, and surgery they should be withheld. ADA 2026 hospital standards recommend stopping SGLT2 inhibitors **3 days before scheduled surgery and 4 days for ertugliflozin**.[4] After an episode, reassess the indication and individual risk before restarting; ensure adequate intake and resolution of precipitating factors. #### Pregnancy Pregnancy increases susceptibility to ketosis and DKA can occur at lower glucose concentrations. Maternal DKA threatens fetal oxygenation and perfusion. Priorities are maternal fluids, insulin, electrolyte correction, trigger treatment, and early obstetric/endocrine involvement. Do not delay maternal stabilization for fetal interventions. #### Advanced CKD/dialysis Volume deficit may be smaller or absent, potassium can be dangerously high, and insulin clearance is reduced. Standard large-volume protocols can cause pulmonary edema. Use individualized fluids, potassium strategy, and nephrology/critical-care input. #### Older adults / heart failure Use smaller aliquots of fluid with frequent reassessment; avoid reflexive “protocol liters.”[2] #### Insulin pumps / automated insulin delivery Pump interruption can produce DKA quickly because many pump users have no long-acting insulin depot. During active DKA, use a reliable protocolized insulin route; inspect the infusion set and device, and re-establish pump therapy only after metabolic stabilization and competency assessment. --- ### Prevention and discharge bundle Every DKA admission should trigger a search for preventable causes.[1] Before discharge: - reconcile insulin regimen and supplies - confirm access to insulin, needles/pens, glucose monitoring, ketone testing - teach sick-day rules - explain when to check blood ketones - never stop basal insulin in type 1 diabetes because of poor appetite alone - provide clear hydration/carbohydrate guidance during illness - review pump failure backup plan - review SGLT2 sick-day/perioperative plan - address mental health, diabetes distress, substance use, food insecurity, or cost barriers - arrange prompt diabetes follow-up, especially after recurrent DKA --- ### Current guideline changes and controversies #### STANDARD OF CARE - β-hydroxybutyrate is the preferred ketone test for diagnosis and monitoring.[1,3] - Diagnostic glucose threshold is now **≥200 mg/dL or established diabetes**, acknowledging euglycemic DKA.[1] - Balanced crystalloids are reasonable and increasingly favored when available.[1,2] - Mild/uncomplicated moderate DKA may be treated with protocolized subcutaneous rapid-acting insulin rather than mandatory ICU IV insulin.[1,2] - Routine bicarbonate/phosphate therapy is not recommended.[1,2] #### EMERGING EVIDENCE - Broader adoption of point-of-care β-hydroxybutyrate may shorten time to resolution and reduce inappropriate reliance on urine ketones.[3] - Continuous ketone monitoring and integration with diabetes technology are active research areas.[1] - Evidence continues to refine which moderate-DKA patients can safely avoid ICU care. #### EXPERIMENTAL / INVESTIGATIONAL - Continuous interstitial ketone sensors - algorithmic integration of CGM + ketones + automated insulin delivery for early DKA prevention - novel fluid/electrolyte protocols in severe renal/cardiac comorbidity --- ### Acute management checklist #### Recognition - [ ] Glucose/known diabetes criterion - [ ] β-hydroxybutyrate ≥3 mmol/L or urine ketones ≥2+ - [ ] pH <7.3 and/or bicarbonate <18 - [ ] Check for HHS overlap / osmolality #### Immediate treatment - [ ] IV access and isotonic/balanced crystalloid - [ ] Baseline potassium before insulin - [ ] IV insulin 0.1 U/kg/h for severe DKA, or validated SC protocol for selected mild/moderate cases - [ ] Add dextrose when glucose <250 mg/dL while insulin continues - [ ] Potassium replacement targeted to 4–5 mmol/L - [ ] No routine bicarbonate or phosphate - [ ] Identify/treat precipitant #### Monitoring - [ ] Glucose every 1–2 h - [ ] Electrolytes, creatinine, β-hydroxybutyrate, pH about every 4 h - [ ] ECG/telemetry if indicated - [ ] Fluid balance/urine output - [ ] Repeat neurologic/respiratory assessment #### Transition - [ ] Ketoacidosis resolved—not just glucose normalized - [ ] Basal insulin given 1–2 h before IV infusion stops - [ ] Prevention plan and supplies arranged --- ### Diagnostic/management algorithm ```text Symptoms compatible with hyperglycemic crisis ↓ Glucose + β-hydroxybutyrate + venous pH/HCO3 + electrolytes ↓ DKA criteria all present? D: glucose ≥200 mg/dL OR known diabetes K: β-hydroxybutyrate ≥3 mmol/L A: pH <7.3 and/or HCO3 <18 ↓ Yes → assess severity + HHS overlap + precipitant ↓ Fluids + potassium strategy + insulin + cause-specific treatment ↓ K <3.5? ├─ Yes → replace K, HOLD insulin until >3.5 └─ No → start insulin ↓ Glucose <250 before ketoacidosis resolves? ├─ Yes → add 5–10% dextrose, CONTINUE insulin └─ No → continue protocol ↓ Serial β-hydroxybutyrate / pH / electrolytes / glucose ↓ Ketoacidosis resolved + patient clinically stable ↓ Basal-bolus insulin overlap → discharge prevention bundle ``` --- ### Common pitfalls | Pitfall | Why it is wrong | Better approach | |---|---|---| | “Glucose is 170, so this cannot be DKA.” | Euglycemic DKA exists, especially with SGLT2 inhibitors | Check β-hydroxybutyrate and acid-base status | | Following urine ketones to resolution | Urine nitroprusside measures acetoacetate, not β-hydroxybutyrate | Prefer quantitative blood β-hydroxybutyrate | | Starting insulin with K⁺ 2.9 mmol/L | Can trigger life-threatening hypokalemia | Replace K first; start insulin after K >3.5 | | Stopping insulin once glucose normalizes | Ketogenesis may persist | Add dextrose and continue insulin until DKA resolves | | Treating every adult with several liters rapidly | HF/CKD/older adults may overload | Individualized boluses and frequent reassessment | | Using anion gap alone to declare persistent DKA | Hyperchloremic acidosis can persist after ketones clear | Track β-hydroxybutyrate when available | | Giving bicarbonate routinely | No routine outcome benefit; potential harm | Reserve for severe acidosis, generally pH <7.0 | --- ## Exam-focused review ### Foundation / USMLE Step 1 Know the biochemical sequence: **↓ insulin + ↑ glucagon → lipolysis → free fatty acids → hepatic ketogenesis → β-hydroxybutyrate/acetoacetate → metabolic acidosis.** Despite total-body potassium depletion, serum potassium may be high initially because insulin deficiency and acidosis shift potassium extracellularly. ### USMLE Step 2 CK Classic next-best-step questions: - DKA + K⁺ 2.9 → **potassium before insulin**. - DKA + glucose falls to 220 while gap/ketones persist → **add dextrose and continue insulin**. - SGLT2 user + acidosis/ketones + glucose 160 → **euglycemic DKA**. - Severe DKA + hypotension → **fluids first while preparing insulin/electrolyte management**. ### Step 3 / Resident Think systems: - determine appropriate level of care - identify and treat precipitant - avoid protocol-induced fluid overload - ensure basal insulin overlap - prevent recurrence through medication access, education, and device troubleshooting ### MRCP / ABIM / Board level High-yield distinctions: - β-hydroxybutyrate is preferred over urine ketones - mixed acid-base disorders can mask acidemia - persistent low bicarbonate after ketone clearance may reflect hyperchloremic acidosis - DKA/HHS overlap should be treated with DKA-level insulin while controlling osmotic correction --- ### Original MCQs #### Question 1 A 32-year-old woman with type 1 diabetes presents with vomiting and abdominal pain. Glucose is 390 mg/dL, pH 7.18, bicarbonate 12 mmol/L, β-hydroxybutyrate 5.8 mmol/L, and potassium 2.9 mmol/L. What is the most appropriate immediate metabolic treatment? A. Start insulin infusion immediately B. Administer sodium bicarbonate C. Begin potassium replacement and fluids; delay insulin until potassium is >3.5 mmol/L D. Give subcutaneous basal insulin only E. Restrict fluids **Answer: C.** Severe hypokalemia makes immediate insulin dangerous because insulin will shift potassium intracellularly and can precipitate arrhythmia or respiratory muscle weakness.[2] #### Question 2 A patient with DKA has received fluids and insulin for 5 hours. Glucose has fallen from 520 to 230 mg/dL, but β-hydroxybutyrate remains 3.8 mmol/L and bicarbonate is 14 mmol/L. What should happen next? A. Stop insulin because glucose is now <250 mg/dL B. Add dextrose-containing fluid and continue insulin C. Give bicarbonate routinely D. Switch to oral metformin E. Give glucagon **Answer: B.** Glucose often normalizes before ketogenesis stops. Dextrose permits ongoing insulin therapy without causing hypoglycemia.[2] #### Question 3 A 66-year-old with type 2 diabetes taking empagliflozin presents after poor oral intake with nausea and tachypnea. Glucose is 178 mg/dL, bicarbonate 13 mmol/L, pH 7.22, and β-hydroxybutyrate 4.7 mmol/L. Which diagnosis is most likely? A. HHS B. Lactic acidosis only C. Euglycemic DKA D. Respiratory alkalosis E. Starvation ketosis without diabetes-related ketoacidosis **Answer: C.** The combination of significant ketonemia and metabolic acidosis in an SGLT2 inhibitor user is classic for euglycemic DKA.[1,4] #### Question 4 Which parameter is preferred for monitoring biochemical resolution of DKA when available? A. Urine ketone color intensity B. Serum chloride alone C. Quantitative blood β-hydroxybutyrate D. HbA1c E. Serum osmolar gap **Answer: C.** β-hydroxybutyrate directly reflects the dominant circulating ketone and avoids misleading urine-ketone behavior during recovery.[1,3] #### Question 5 A 78-year-old with DKA, HFrEF, and CKD is hypotensive but has pulmonary crackles after 1 L crystalloid. What is the best principle for ongoing fluid management? A. Continue 1 L/hour regardless of examination B. Stop all fluid and insulin C. Use smaller boluses with frequent hemodynamic/lung reassessment and individualized shock management D. Give free water only E. Administer bicarbonate instead of fluid **Answer: C.** Contemporary guidance recommends smaller aliquots in older adults and those with heart/kidney failure, with repeated reassessment.[2] --- ### References 1. Umpierrez GE, Davis GM, ElSayed NA, et al. **Hyperglycemic Crises in Adults With Diabetes: A Consensus Report.** *Diabetes Care.* 2024;47(8):1257-1275. doi:10.2337/dci24-0032. PMID:39052901. https://diabetesjournals.org/care/article/47/8/1257/156808/Hyperglycemic-Crises-in-Adults-With-Diabetes-A 2. Morey-Vargas OL, et al. **Hyperglycemic Crises in Adults: The 2024 Consensus Report.** Cleveland Clinic Journal of Medicine/Consult QD summary, 2025. https://consultqd.clevelandclinic.org/hyperglycemic-crises-in-adults-the-2024-consensus-report 3. Cleveland Clinic review of the 2024 consensus criteria and monitoring changes, including β-hydroxybutyrate-based diagnosis/resolution. https://consultqd.clevelandclinic.org/hyperglycemic-crises-in-adults-the-2024-consensus-report 4. American Diabetes Association Professional Practice Committee. **16. Diabetes Care in the Hospital: Standards of Care in Diabetes—2026.** *Diabetes Care.* 2026;49(Suppl 1):S339-. https://diabetesjournals.org/care/article/49/Supplement_1/S339/163925/16-Diabetes-Care-in-the-Hospital-Standards-of-Care 5. Alghamdi NA, Major P, Chaudhuri D, et al. **Saline compared to balanced crystalloid in patients with diabetic ketoacidosis: a systematic review and meta-analysis of randomized controlled trials.** *Crit Care Explor.* 2022;4(1):e0613. 6. Self WH, Evans CS, Jenkins CA, et al. **Clinical effects of balanced crystalloids vs saline in adults with diabetic ketoacidosis: a subgroup analysis of cluster randomized clinical trials.** *JAMA Netw Open.* 2020;3(11):e2024596. doi:10.1001/jamanetworkopen.2020.24596. 7. Kilpatrick ES, Butler AE, Ostlundh L, Atkin SL, Sacks DB. **Controversies around the measurement of blood ketones to diagnose and manage diabetic ketoacidosis.** *Diabetes Care.* 2022;45(2):267-272. 8. Kamel KS, Halperin ML. **Acid-base problems in diabetic ketoacidosis.** *N Engl J Med.* 2015;372:546-554. 9. American Diabetes Association Professional Practice Committee. **9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2026.** *Diabetes Care.* 2026;49(Suppl 1):S183-. https://diabetesjournals.org/care/article/49/Supplement_1/S183/163934/9-Pharmacologic-Approaches-to-Glycemic-Treatment 10. Cao S, Cao S. **Comment on Umpierrez et al. Hyperglycemic Crises in Adults With Diabetes.** *Diabetes Care.* 2025;48(3):e40-e41. doi:10.2337/dc24-2296. PMID:39977634. --- **Next linked topics:** Hyperosmolar hyperglycemic state; hypoglycemia; insulin therapy in hospital; SGLT2 inhibitor adverse effects; acid-base disorders; potassium disorders; diabetes sick-day management.7:["$","$L17",null,{"article":{"id":"medical-bacterial-meningitis","title":"Acute Bacterial Meningitis","slug":"bacterial-meningitis","description":"Acute bacterial meningitis is infection of the leptomeninges and cerebrospinal fluid (CSF) that can cause cerebral edema, vasculopathy, seizures, hydrocephalus, hearing loss, septic shock, brain herniation, and death…","aliases":[],"category":"Infectious Disease","tags":["Infectious Disease"],"updatedAt":"$undefined","body":"$18","headings":[{"id":"summary","text":"Summary","level":2},{"id":"immediate-priorities","text":"Immediate priorities","level":2},{"id":"first-1060-minutes","text":"First 10–60 minutes","level":3},{"id":"etiology-and-risk-pattern","text":"Etiology and risk pattern","level":2},{"id":"pathophysiology","text":"Pathophysiology","level":2},{"id":"clinical-features","text":"Clinical features","level":2},{"id":"common-findings","text":"Common findings","level":3},{"id":"features-of-immediately-dangerous-disease","text":"Features of immediately dangerous disease","level":3},{"id":"lumbar-puncture","text":"Lumbar puncture","level":2},{"id":"perform-lp-promptly-when-safe","text":"Perform LP promptly when safe","level":3},{"id":"when-to-defer-lp-initially","text":"When to defer LP initially","level":3},{"id":"head-imaging-before-lp","text":"Head imaging before LP","level":3},{"id":"csf-interpretation","text":"CSF interpretation","level":2},{"id":"blood-tests-and-other-investigations","text":"Blood tests and other investigations","level":2},{"id":"empiric-antimicrobial-therapy","text":"Empiric antimicrobial therapy","level":2},{"id":"community-acquired-adult-meningitis","text":"Community-acquired adult meningitis","level":3},{"id":"narrowing-therapy","text":"Narrowing therapy","level":3},{"id":"adjunctive-dexamethasone","text":"Adjunctive dexamethasone","level":2},{"id":"indication-and-timing","text":"Indication and timing","level":3},{"id":"when-to-continue-or-stop","text":"When to continue or stop","level":3},{"id":"meningococcal-disease","text":"Meningococcal disease","level":2},{"id":"infection-control","text":"Infection control","level":3},{"id":"close-contact-chemoprophylaxis","text":"Close-contact chemoprophylaxis","level":3},{"id":"seizures-and-neurologic-deterioration","text":"Seizures and neurologic deterioration","level":2},{"id":"raised-intracranial-pressure-and-critical-care","text":"Raised intracranial pressure and critical care","level":2},{"id":"fluids-sodium-and-shock","text":"Fluids, sodium, and shock","level":2},{"id":"differential-diagnosis","text":"Differential diagnosis","level":2},{"id":"monitoring","text":"Monitoring","level":2},{"id":"disposition","text":"Disposition","level":2},{"id":"icu-or-equivalent-high-acuity-care","text":"ICU or equivalent high-acuity care","level":3},{"id":"ward-care","text":"Ward care","level":3},{"id":"discharge-criteria","text":"Discharge criteria","level":3},{"id":"complications","text":"Complications","level":2},{"id":"neurologic","text":"Neurologic","level":3},{"id":"systemic","text":"Systemic","level":3},{"id":"follow-up-after-recovery","text":"Follow-up after recovery","level":2},{"id":"hearing","text":"Hearing","level":3},{"id":"neurologic-and-cognitive-sequelae","text":"Neurologic and cognitive sequelae","level":3},{"id":"predisposition-and-prevention","text":"Predisposition and prevention","level":3},{"id":"acute-management-checklist","text":"Acute management checklist","level":2},{"id":"recent-guideline-and-public-health-updates","text":"Recent guideline and public-health updates","level":2},{"id":"references","text":"References","level":2}],"readingMinutes":16},"linkedMarkdown":"$19","backlinks":[],"related":[{"id":"medical-0002","title":"Acute Kidney Injury","slug":"acute-kidney-injury","description":"Acute kidney injury (AKI) is an abrupt decline in kidney function identified by a rise in serum creatinine and/or reduced urine output. The current established international definition remains the KDIGO 2012 definitio…","aliases":[],"category":"Nephrology","tags":["Nephrology","Internal Medicine","Critical Care"],"updatedAt":"2026-09-08","body":"$1a","headings":[{"id":"one-minute-summary","text":"One-minute summary","level":2},{"id":"core-concepts","text":"Core concepts","level":2},{"id":"what-aki-represents-physiologically","text":"What AKI represents physiologically","level":3},{"id":"definition-and-kdigo-staging","text":"Definition and KDIGO staging","level":2},{"id":"diagnostic-criteria","text":"Diagnostic criteria","level":3},{"id":"aki-akd-and-ckd-continuum","text":"AKI, AKD, and CKD continuum","level":2},{"id":"epidemiology-and-prognosis","text":"Epidemiology and prognosis","level":2},{"id":"risk-factors","text":"Risk factors","level":2},{"id":"etiology-practical-classification","text":"Etiology: practical classification","level":2},{"id":"1-reduced-renal-perfusion-hemodynamic-aki","text":"1. Reduced renal perfusion / hemodynamic AKI","level":3},{"id":"2-intrinsic-renal-parenchymal-injury","text":"2. Intrinsic renal parenchymal injury","level":3},{"id":"3-postrenal-obstructive-aki","text":"3. Postrenal / obstructive AKI","level":3},{"id":"initial-clinical-assessment","text":"Initial clinical assessment","level":2},{"id":"immediate-questions","text":"Immediate questions","level":3},{"id":"history","text":"History","level":2},{"id":"examination","text":"Examination","level":2},{"id":"diagnostic-workup","text":"Diagnostic workup","level":2},{"id":"minimum-initial-tests-in-most-hospitalized-aki","text":"Minimum initial tests in most hospitalized AKI","level":3},{"id":"additional-tests-guided-by-context","text":"Additional tests guided by context","level":3},{"id":"urinalysis-and-urine-microscopy","text":"Urinalysis and urine microscopy","level":2},{"id":"fractional-excretion-indices-use-cautiously","text":"Fractional excretion indices: use cautiously","level":2},{"id":"imaging","text":"Imaging","level":2},{"id":"renal-tract-ultrasound","text":"Renal tract ultrasound","level":3},{"id":"ct","text":"CT","level":3},{"id":"differential-diagnosis-by-pattern","text":"Differential diagnosis by pattern","level":2},{"id":"management-stepwise-approach","text":"Management: stepwise approach","level":2},{"id":"step-1-stabilize-life-threatening-complications","text":"STEP 1 — Stabilize life-threatening complications","level":3},{"id":"step-2-treat-the-cause","text":"STEP 2 — Treat the cause","level":3},{"id":"step-3-stop-ongoing-kidney-insults","text":"STEP 3 — Stop ongoing kidney insults","level":3},{"id":"step-4-optimize-volume-and-perfusion","text":"STEP 4 — Optimize volume and perfusion","level":3},{"id":"step-5-monitor-dynamically","text":"STEP 5 — Monitor dynamically","level":3},{"id":"pharmacotherapy-principles","text":"Pharmacotherapy principles","level":2},{"id":"diuretics","text":"Diuretics","level":3},{"id":"low-dose-dopamine","text":"Low-dose dopamine","level":3},{"id":"ace-inhibitors-and-arbs","text":"ACE inhibitors and ARBs","level":3},{"id":"emergency-hyperkalemia-in-aki","text":"Emergency hyperkalemia in AKI","level":2},{"id":"metabolic-acidosis","text":"Metabolic acidosis","level":2},{"id":"kidney-replacement-therapy-krt","text":"Kidney replacement therapy (KRT)","level":2},{"id":"indications","text":"Indications","level":3},{"id":"timing-when-no-emergency-indication-exists","text":"Timing when no emergency indication exists","level":3},{"id":"modality","text":"Modality","level":3},{"id":"contrast-associated-aki-2024-practice-update","text":"Contrast-associated AKI: 2024 practice update","level":2},{"id":"when-to-involve-nephrology-urgently","text":"When to involve nephrology urgently","level":2},{"id":"special-clinical-contexts","text":"Special clinical contexts","level":2},{"id":"sepsis-associated-aki","text":"Sepsis-associated AKI","level":3},{"id":"heart-failure-cardiorenal-syndrome","text":"Heart failure / cardiorenal syndrome","level":3},{"id":"cirrhosis","text":"Cirrhosis","level":3},{"id":"rhabdomyolysis","text":"Rhabdomyolysis","level":3},{"id":"pregnancy","text":"Pregnancy","level":3},{"id":"kidney-transplant","text":"Kidney transplant","level":3},{"id":"prevention","text":"Prevention","level":2},{"id":"general-prevention-bundle","text":"General prevention bundle","level":3},{"id":"monitoring-and-reassessment","text":"Monitoring and reassessment","level":2},{"id":"in-hospital","text":"In-hospital","level":3},{"id":"after-discharge","text":"After discharge","level":3},{"id":"anticipating-deterioration","text":"Anticipating deterioration","level":2},{"id":"common-pitfalls","text":"Common pitfalls","level":2},{"id":"diagnostic-and-management-algorithm","text":"Diagnostic and management algorithm","level":2},{"id":"standard-of-care-vs-emerging-evidence-vs-experimental","text":"STANDARD OF CARE vs EMERGING EVIDENCE vs EXPERIMENTAL","level":2},{"id":"standard-of-care","text":"STANDARD OF CARE","level":3},{"id":"emerging-evidence-active-implementation","text":"EMERGING EVIDENCE / ACTIVE IMPLEMENTATION","level":3},{"id":"experimental-not-routine-for-general-aki","text":"EXPERIMENTAL / NOT ROUTINE FOR GENERAL AKI","level":3},{"id":"current-guideline-changes-and-conflicts-20242026","text":"Current guideline changes and conflicts (2024–2026)","level":2},{"id":"1-contrast-associated-aki-risk-has-been-reframed","text":"1. Contrast-associated AKI risk has been reframed","level":3},{"id":"2-kdigo-aki-update-is-imminent-but-not-final","text":"2. KDIGO AKI update is imminent but not final","level":3},{"id":"3-early-routine-krt-has-lost-momentum","text":"3. Early routine KRT has lost momentum","level":3},{"id":"4-balanced-crystalloids-increasingly-favored-in-many-acute-care-pathways","text":"4. Balanced crystalloids increasingly favored in many acute-care pathways","level":3},{"id":"landmark-and-practice-shaping-evidence","text":"Landmark and practice-shaping evidence","level":2},{"id":"smart-2018","text":"SMART (2018)","level":3},{"id":"starrt-aki-2020","text":"STARRT-AKI (2020)","level":3},{"id":"akiakd-continuum-adqi","text":"AKI–AKD continuum (ADQI)","level":3},{"id":"exam-focused-review","text":"Exam-focused review","level":2},{"id":"usmle-step-1","text":"USMLE Step 1","level":3},{"id":"usmle-step-2-ck","text":"USMLE Step 2 CK","level":3},{"id":"step-3-resident","text":"Step 3 / Resident","level":3},{"id":"mrcp-abim-boards","text":"MRCP / ABIM / Boards","level":3},{"id":"original-mcqs","text":"Original MCQs","level":2},{"id":"question-1","text":"Question 1","level":3},{"id":"question-2","text":"Question 2","level":3},{"id":"question-3","text":"Question 3","level":3},{"id":"question-4","text":"Question 4","level":3},{"id":"question-5","text":"Question 5","level":3},{"id":"question-6","text":"Question 6","level":3},{"id":"acute-management-checklist","text":"Acute management checklist","level":2},{"id":"recognition","text":"Recognition","level":3},{"id":"immediate-threats","text":"Immediate threats","level":3},{"id":"cause","text":"Cause","level":3},{"id":"management","text":"Management","level":3},{"id":"discharge","text":"Discharge","level":3},{"id":"references","text":"References","level":2},{"id":"next-topic-ledger","text":"NEXT-TOPIC LEDGER","level":3}],"readingMinutes":29},{"id":"medical-0010","title":"Acute Coronary Syndrome","slug":"acute-coronary-syndrome","description":"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 myo…","aliases":[],"category":"Cardiology","tags":["Cardiology","Emergency Medicine","Critical Care"],"updatedAt":"2026-09-08","body":"$1b","headings":[{"id":"one-minute-summary","text":"One-minute summary","level":2},{"id":"immediate-priorities","text":"Immediate priorities","level":3},{"id":"definition-and-classification","text":"Definition and classification","level":2},{"id":"myocardial-injury-is-not-automatically-myocardial-infarction","text":"Myocardial injury is not automatically myocardial infarction","level":3},{"id":"pathophysiology","text":"Pathophysiology","level":2},{"id":"stemi-vs-nstemi-is-an-ecg-phenotype-not-a-complete-anatomy-report","text":"STEMI vs NSTEMI is an ECG phenotype, not a complete anatomy report","level":3},{"id":"risk-factors","text":"Risk factors","level":2},{"id":"clinical-presentation","text":"Clinical presentation","level":2},{"id":"typical-ischemic-symptoms","text":"Typical ischemic symptoms","level":3},{"id":"atypical-or-less-obvious-presentations","text":"Atypical or less obvious presentations","level":3},{"id":"red-flags-for-immediate-instability","text":"Red flags for immediate instability","level":3},{"id":"initial-assessment-first-10-minutes","text":"Initial assessment: first 10 minutes","level":2},{"id":"core-workflow","text":"Core workflow","level":3},{"id":"differential-diagnosis-of-acute-chest-pain","text":"Differential diagnosis of acute chest pain","level":3},{"id":"stemi-and-acute-coronary-occlusion","text":"STEMI and acute coronary occlusion","level":2},{"id":"primary-pci-is-preferred-when-timely","text":"Primary PCI is preferred when timely","level":3},{"id":"nste-acs-risk-stratified-invasive-management","text":"NSTE-ACS: risk-stratified invasive management","level":2},{"id":"acute-pharmacotherapy","text":"Acute pharmacotherapy","level":2},{"id":"standard-of-care","text":"STANDARD OF CARE","level":3},{"id":"pci-and-revascularization","text":"PCI and revascularization","level":2},{"id":"access-and-imaging","text":"Access and imaging","level":3},{"id":"complete-revascularization","text":"Complete revascularization","level":3},{"id":"complications","text":"Complications","level":2},{"id":"electrical","text":"Electrical","level":3},{"id":"mechanical-think-days-after-mi-sudden-collapse-or-new-murmur","text":"Mechanical — think days after MI, sudden collapse or new murmur","level":3},{"id":"pump-failure","text":"Pump failure","level":3},{"id":"special-populations","text":"Special populations","level":2},{"id":"older-adults-and-frailty","text":"Older adults and frailty","level":3},{"id":"chronic-kidney-disease","text":"Chronic kidney disease","level":3},{"id":"patients-requiring-oral-anticoagulation","text":"Patients requiring oral anticoagulation","level":3},{"id":"prior-stroketia","text":"Prior stroke/TIA","level":3},{"id":"pregnancy","text":"Pregnancy","level":3},{"id":"secondary-prevention-after-acs","text":"Secondary prevention after ACS","level":2},{"id":"before-discharge","text":"Before discharge","level":3},{"id":"current-guideline-changes-and-areas-of-nuance","text":"Current guideline changes and areas of nuance","level":2},{"id":"2025-accahaacepnaemspscai-major-practical-updates","text":"2025 ACC/AHA/ACEP/NAEMSP/SCAI — major practical updates","level":3},{"id":"2023-esc-vs-2025-us-guideline","text":"2023 ESC vs 2025 U.S. guideline","level":3},{"id":"emerging-evidence","text":"EMERGING EVIDENCE","level":3},{"id":"experimental-investigational","text":"EXPERIMENTAL / INVESTIGATIONAL","level":3},{"id":"acute-management-checklist","text":"Acute management checklist","level":2},{"id":"suspected-acs","text":"Suspected ACS","level":3},{"id":"diagnostic-management-algorithm","text":"Diagnostic / management algorithm","level":2},{"id":"common-pitfalls","text":"Common pitfalls","level":2},{"id":"exam-focused-review","text":"Exam-focused review","level":2},{"id":"foundation-step-1","text":"Foundation / Step 1","level":3},{"id":"step-2-ck","text":"Step 2 CK","level":3},{"id":"step-3-resident","text":"Step 3 / Resident","level":3},{"id":"mrcp-abim-boards","text":"MRCP / ABIM / boards","level":3},{"id":"original-mcqs","text":"Original MCQs","level":2},{"id":"references","text":"References","level":2}],"readingMinutes":19},{"id":"medical-0008","title":"Acute Ischemic Stroke","slug":"acute-ischemic-stroke","description":"Acute ischemic stroke (AIS) is sudden neurological dysfunction caused by focal cerebral, retinal, or spinal cord ischemia, most often from arterial occlusion. The practical emergency question is not simply “is this a…","aliases":[],"category":"Neurology","tags":["Neurology","Vascular Neurology","Emergency Medicine"],"updatedAt":"2026-09-08","body":"$1c","headings":[{"id":"one-minute-summary","text":"One-minute summary","level":2},{"id":"1-core-concepts","text":"1. Core concepts","level":2},{"id":"11-time-is-brainbut-tissue-matters-too","text":"1.1 Time is brain—but tissue matters too","level":3},{"id":"12-treat-the-patient-not-the-nihss-number","text":"1.2 Treat the patient, not the NIHSS number","level":3},{"id":"2-definition-and-classification","text":"2. Definition and classification","level":2},{"id":"21-definition","text":"2.1 Definition","level":3},{"id":"22-etiologic-classification","text":"2.2 Etiologic classification","level":3},{"id":"3-epidemiology-and-risk-factors","text":"3. Epidemiology and risk factors","level":2},{"id":"4-pathophysiology","text":"4. Pathophysiology","level":2},{"id":"41-ischemic-cascade","text":"4.1 Ischemic cascade","level":3},{"id":"42-reperfusion-injury-and-hemorrhagic-transformation","text":"4.2 Reperfusion injury and hemorrhagic transformation","level":3},{"id":"5-clinical-presentation","text":"5. Clinical presentation","level":2},{"id":"51-common-focal-syndromes","text":"5.1 Common focal syndromes","level":3},{"id":"6-immediate-assessment","text":"6. Immediate assessment","level":2},{"id":"61-first-minutes","text":"6.1 First minutes","level":3},{"id":"62-do-not-miss-a-stroke-mimic","text":"6.2 Do not miss a stroke mimic","level":3},{"id":"7-imaging","text":"7. Imaging","level":2},{"id":"71-noncontrast-ct-ncct","text":"7.1 Noncontrast CT (NCCT)","level":3},{"id":"72-ctamra","text":"7.2 CTA/MRA","level":3},{"id":"73-ct-perfusion-and-mri","text":"7.3 CT perfusion and MRI","level":3},{"id":"8-severity-and-imaging-scores","text":"8. Severity and imaging scores","level":2},{"id":"nihss","text":"NIHSS","level":3},{"id":"aspects","text":"ASPECTS","level":3},{"id":"9-acute-management-algorithm","text":"9. Acute management algorithm","level":2},{"id":"10-intravenous-thrombolysis","text":"10. Intravenous thrombolysis","level":2},{"id":"101-standard-of-care-treatment-within-45-hours","text":"10.1 STANDARD OF CARE — treatment within 4.5 hours","level":3},{"id":"102-disabling-vs-non-disabling-deficit","text":"10.2 Disabling vs non-disabling deficit","level":3},{"id":"103-extended-window-thrombolysis","text":"10.3 Extended-window thrombolysis","level":3},{"id":"104-blood-pressure-around-thrombolysis","text":"10.4 Blood pressure around thrombolysis","level":3},{"id":"105-major-contraindication-framework","text":"10.5 Major contraindication framework","level":3},{"id":"106-after-thrombolysis","text":"10.6 After thrombolysis","level":3},{"id":"11-endovascular-thrombectomy-evt","text":"11. Endovascular thrombectomy (EVT)","level":2},{"id":"111-standard-of-care-proximal-anterior-circulation-lvo","text":"11.1 STANDARD OF CARE — proximal anterior circulation LVO","level":3},{"id":"112-basilar-artery-occlusion","text":"11.2 Basilar artery occlusion","level":3},{"id":"113-do-not-delay-iv-thrombolysis-for-evt","text":"11.3 Do not delay IV thrombolysis for EVT","level":3},{"id":"114-blood-pressure-after-evt","text":"11.4 Blood pressure after EVT","level":3},{"id":"115-mediumdistal-vessel-occlusion-not-routine-standard-care","text":"11.5 Medium/distal vessel occlusion — not routine standard care","level":3},{"id":"12-general-supportive-care","text":"12. General supportive care","level":2},{"id":"oxygenation","text":"Oxygenation","level":3},{"id":"blood-pressure-if-no-reperfusion-therapy","text":"Blood pressure if no reperfusion therapy","level":3},{"id":"glucose","text":"Glucose","level":3},{"id":"temperature","text":"Temperature","level":3},{"id":"swallowing","text":"Swallowing","level":3},{"id":"dvt-prevention","text":"DVT prevention","level":3},{"id":"13-antiplatelet-and-anticoagulant-therapy","text":"13. Antiplatelet and anticoagulant therapy","level":2},{"id":"131-aspirin-and-dapt","text":"13.1 Aspirin and DAPT","level":3},{"id":"132-atrial-fibrillation","text":"13.2 Atrial fibrillation","level":3},{"id":"14-etiologic-workup-after-stabilization","text":"14. Etiologic workup after stabilization","level":2},{"id":"15-important-complications","text":"15. Important complications","level":2},{"id":"malignant-mca-infarction","text":"Malignant MCA infarction","level":3},{"id":"16-secondary-prevention","text":"16. Secondary prevention","level":2},{"id":"161-blood-pressure","text":"16.1 Blood pressure","level":3},{"id":"162-lipids","text":"16.2 Lipids","level":3},{"id":"163-carotid-disease","text":"16.3 Carotid disease","level":3},{"id":"164-lifestyle","text":"16.4 Lifestyle","level":3},{"id":"17-special-populations","text":"17. Special populations","level":2},{"id":"pregnancy","text":"Pregnancy","level":3},{"id":"children","text":"Children","level":3},{"id":"sickle-cell-disease","text":"Sickle cell disease","level":3},{"id":"cervical-artery-dissection","text":"Cervical artery dissection","level":3},{"id":"18-acute-management-checklist","text":"18. Acute management checklist","level":2},{"id":"first-10-minutes","text":"First 10 minutes","level":3},{"id":"reperfusion-decision","text":"Reperfusion decision","level":3},{"id":"first-24-hours","text":"First 24 hours","level":3},{"id":"19-common-pitfalls","text":"19. Common pitfalls","level":2},{"id":"20-exam-focused-review","text":"20. Exam-focused review","level":2},{"id":"foundation-step-1","text":"Foundation / Step 1","level":3},{"id":"step-2-ck","text":"Step 2 CK","level":3},{"id":"step-3-resident","text":"Step 3 / resident","level":3},{"id":"mrcpabimboard-level","text":"MRCP/ABIM/board level","level":3},{"id":"21-original-mcqs","text":"21. Original MCQs","level":2},{"id":"22-current-guideline-changes-and-recent-research","text":"22. Current guideline changes and recent research","level":2},{"id":"standard-of-care-2026-changes","text":"STANDARD OF CARE — 2026 changes","level":3},{"id":"emergingnegative-evidence","text":"EMERGING/NEGATIVE EVIDENCE","level":3},{"id":"experimentalinvestigational","text":"EXPERIMENTAL/INVESTIGATIONAL","level":3},{"id":"23-references","text":"23. References","level":2},{"id":"bottom-line","text":"Bottom line","level":3}],"readingMinutes":24},{"id":"medical-0006","title":"Diabetic Ketoacidosis","slug":"diabetic-ketoacidosis","description":"Diabetic ketoacidosis (DKA) is an acute metabolic emergency caused by insufficient effective insulin activity together with excess counterregulatory hormones, producing ketogenesis, metabolic acidosis, osmotic diuresi…","aliases":[],"category":"Endocrinology","tags":["Endocrinology","Emergency Medicine","Critical Care"],"updatedAt":"2026-09-08","body":"$1d","headings":[{"id":"one-minute-summary","text":"One-minute summary","level":2},{"id":"immediate-priorities","text":"Immediate priorities","level":3},{"id":"definition-and-diagnostic-criteria","text":"Definition and diagnostic criteria","level":2},{"id":"euglycemic-dka","text":"Euglycemic DKA","level":3},{"id":"epidemiology-and-outcomes","text":"Epidemiology and outcomes","level":2},{"id":"etiology-and-precipitants","text":"Etiology and precipitants","level":2},{"id":"pathophysiology","text":"Pathophysiology","level":2},{"id":"1-insulin-deficiency-and-counterregulatory-excess","text":"1. Insulin deficiency and counterregulatory excess","level":3},{"id":"2-osmotic-diuresis-and-dehydration","text":"2. Osmotic diuresis and dehydration","level":3},{"id":"3-acid-base-complexity","text":"3. Acid-base complexity","level":3},{"id":"clinical-presentation","text":"Clinical presentation","level":2},{"id":"symptoms","text":"Symptoms","level":3},{"id":"examination","text":"Examination","level":3},{"id":"red-flags","text":"Red flags","level":3},{"id":"initial-assessment-what-to-do-in-the-first-1530-minutes","text":"Initial assessment: what to do in the first 15–30 minutes","level":2},{"id":"diagnostic-evaluation","text":"Diagnostic evaluation","level":2},{"id":"essential-tests","text":"Essential tests","level":3},{"id":"directed-tests-for-precipitant","text":"Directed tests for precipitant","level":3},{"id":"useful-calculations","text":"Useful calculations","level":3},{"id":"severity-and-level-of-care","text":"Severity and level of care","level":2},{"id":"management","text":"Management","level":2},{"id":"standard-of-care-core-treatment-bundle","text":"STANDARD OF CARE — core treatment bundle","level":3},{"id":"monitoring-and-reassessment","text":"Monitoring and reassessment","level":3},{"id":"resolution-and-transition-to-subcutaneous-insulin","text":"Resolution and transition to subcutaneous insulin","level":3},{"id":"differential-diagnosis","text":"Differential diagnosis","level":3},{"id":"dka-versus-hhs","text":"DKA versus HHS","level":3},{"id":"special-populations","text":"Special populations","level":3},{"id":"prevention-and-discharge-bundle","text":"Prevention and discharge bundle","level":3},{"id":"current-guideline-changes-and-controversies","text":"Current guideline changes and controversies","level":3},{"id":"acute-management-checklist","text":"Acute management checklist","level":3},{"id":"diagnosticmanagement-algorithm","text":"Diagnostic/management algorithm","level":3},{"id":"common-pitfalls","text":"Common pitfalls","level":3},{"id":"exam-focused-review","text":"Exam-focused review","level":2},{"id":"foundation-usmle-step-1","text":"Foundation / USMLE Step 1","level":3},{"id":"usmle-step-2-ck","text":"USMLE Step 2 CK","level":3},{"id":"step-3-resident","text":"Step 3 / Resident","level":3},{"id":"mrcp-abim-board-level","text":"MRCP / ABIM / Board level","level":3},{"id":"original-mcqs","text":"Original MCQs","level":3},{"id":"references","text":"References","level":3}],"readingMinutes":21}],"previewBySlug":{"abcde-approach":{"title":"ABCDE Approach","description":"The ABCDE approach is a structured method for the immediate assessment and treatment of a deteriorating or critically ill patient: Airway, Breathing, Circulation, Disability, Exposure. The central rule is treat life-t…","category":"Emergency Medicine"},"acute-asthma-exacerbation":{"title":"Acute Asthma Exacerbation","description":"An asthma exacerbation is an acute or subacute worsening of dyspnea, wheeze, cough or chest tightness with a fall in expiratory airflow compared with the patient’s usual state. The attack is caused by variable airflow…","category":"Pulmonology"},"bacterial-meningitis":{"title":"Acute Bacterial Meningitis","description":"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, hern…","category":"Infectious Disease"},"acute-coronary-syndrome":{"title":"Acute Coronary Syndrome","description":"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 myo…","category":"Cardiology"},"acute-ischemic-stroke":{"title":"Acute Ischemic Stroke","description":"Acute ischemic stroke (AIS) is sudden neurological dysfunction caused by focal cerebral, retinal, or spinal cord ischemia, most often from arterial occlusion. The practical emergency question is not simply “is this a…","category":"Neurology"},"acute-kidney-injury":{"title":"Acute Kidney Injury","description":"Acute kidney injury (AKI) is an abrupt decline in kidney function identified by a rise in serum creatinine and/or reduced urine output. The current established international definition remains the KDIGO 2012 definitio…","category":"Nephrology"},"acute-pulmonary-embolism":{"title":"Acute Pulmonary Embolism","description":"Acute pulmonary embolism (PE) is obstruction of the pulmonary arterial circulation by thrombus, usually arising from deep veins of the legs or pelvis. The immediate threat is acute right-ventricular (RV) pressure over…","category":"Pulmonology"},"atrial-fibrillation":{"title":"Atrial Fibrillation","description":"Atrial fibrillation (AF) is a supraventricular tachyarrhythmia characterized by chaotic atrial electrical activation and ineffective atrial contraction. On ECG it produces irregularly irregular RR intervals (when AV c…","category":"Cardiology"},"diabetic-ketoacidosis":{"title":"Diabetic Ketoacidosis","description":"Diabetic ketoacidosis (DKA) is an acute metabolic emergency caused by insufficient effective insulin activity together with excess counterregulatory hormones, producing ketogenesis, metabolic acidosis, osmotic diuresi…","category":"Endocrinology"},"dyslipidemia-in-adults":{"title":"Dyslipidemia in Adults","description":"Dyslipidemia is an abnormal concentration or composition of circulating lipoproteins that increases atherosclerotic cardiovascular disease (ASCVD) risk or, when triglycerides are very high, pancreatitis risk. LDL-cont…","category":"Cardiology"},"sepsis-and-septic-shock":{"title":"Sepsis and Septic Shock","description":"Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Operationally, Sepsis-3 identifies organ dysfunction as an acute increase in SOFA score ≥2 points attributable to infec…","category":"Critical Care"},"upper-gastrointestinal-bleeding":{"title":"Upper Gastrointestinal Bleeding","description":"Upper gastrointestinal bleeding (UGIB) is bleeding arising proximal to the ligament of Treitz. It most commonly presents with hematemesis, coffee-ground emesis, melena, or—when brisk—hematochezia with hemodynamic inst…","category":"Gastroenterology"}},"categories":["Cardiology","Critical Care","Emergency Medicine","Endocrinology","Gastroenterology","Infectious Disease","Nephrology","Neurology","Pulmonology"]}]