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: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.19:T850a,## 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](/library/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.1a: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.1b:T7b05,## One-minute summary **Acute bacterial meningitis** is infection-driven inflammation of the leptomeninges and cerebrospinal fluid (CSF). It can progress over hours to **sepsis, shock, cerebral edema, seizures, raised intracranial pressure, herniation, hearing loss, neurologic disability, and death**. WHO's first global meningitis diagnosis/treatment guideline was released in 2025, followed by a practical implementation manual in May 2026.[1,2] WHO estimates bacterial meningitis causes death in roughly **1 in 6 affected people**, and about **1 in 5 survivors** develops long-term complications.[1] ### The core emergency sequence 1. **Recognize the syndrome**: fever, headache, neck stiffness, altered mental status, photophobia, vomiting, seizure, focal deficit, non-blanching rash, or sepsis; not every patient has the classic triad. 2. **Stabilize ABCs** and treat shock/seizures immediately. 3. Obtain **blood cultures and key blood tests**, but never allow diagnostics to cause a clinically significant antibiotic delay. 4. Perform **lumbar puncture before antibiotics if safe and immediately feasible**. 5. **Do not routinely obtain CT before LP.** Image first only when specific features suggest a space-occupying lesion or dangerous raised intracranial pressure. 6. Start **IV antibiotics as soon as meningitis is suspected**; NICE specifies within **1 hour of hospital arrival**.[3] 7. Give **IV dexamethasone with or before the first antibiotic dose if possible** in strongly suspected bacterial meningitis (age >3 months in NICE guidance); never delay antibiotics for dexamethasone.[3] 8. Narrow therapy once Gram stain, PCR, culture, and susceptibility data return. 9. Assess for **hearing and neurologic sequelae** and involve public health for meningococcal disease. ★ **High-yield principle:** If CT is needed before LP, **take bloods and start antibiotics first**. Imaging must not become a treatment-delay ritual.[3] --- ## Definition Meningitis is inflammation of the meninges and CSF, usually infectious. **Bacterial meningitis** refers to acute meningitis caused by bacteria, most often acquired in the community but sometimes related to neurosurgery, skull defects, penetrating trauma, CSF devices, or bacteremia. This article focuses primarily on **acute community-acquired bacterial meningitis in children beyond the neonatal period and adults**, with emphasis on adult clinical reasoning. Neonatal, post-neurosurgical, TB, cryptococcal, and chronic meningitis require specialized protocols. --- ## Epidemiology and major pathogens The pathogen distribution varies with age, vaccination, immune status, geography, and healthcare exposure. | Population / risk state | Important organisms | Practical implication | |---|---|---| | Adolescents / younger adults | *Neisseria meningitidis*, *Streptococcus pneumoniae* | Consider meningococcal sepsis/rash; droplet precautions and public-health actions | | General adults | *S. pneumoniae*, *N. meningitidis* | Pneumococcus is a major cause of severe adult disease | | Older adults / cell-mediated immune impairment | Above + *Listeria monocytogenes* | Add anti-Listeria therapy | | Asplenia / complement deficiency | Encapsulated organisms, especially meningococcus/pneumococcus | Higher invasive-disease risk | | Cochlear implant / CSF leak | Pneumococcus | Recurrent meningitis risk; vaccination/prevention critical | | Neurosurgery / CSF shunt | Staphylococci, resistant gram-negative bacilli | Not a standard community-acquired regimen; use healthcare-associated CNS infection guidance | #### Risk factors - Extremes of age - Asplenia or hyposplenia - Complement deficiency or complement-inhibitor therapy - HIV or other immunocompromise - Alcohol use disorder - Diabetes and chronic disease - Otitis, mastoiditis, sinusitis, pneumonia - Basilar skull fracture or CSF leak - Cochlear implant - Recent neurosurgery or CSF device - Crowded living environments for meningococcal transmission - Under-immunization --- ## Pathophysiology The disease usually follows: **nasopharyngeal colonization or local infection → mucosal invasion/bacteremia → crossing of the blood–brain/CSF barriers → bacterial replication in CSF → intense host inflammatory response → endothelial injury and blood–brain barrier disruption → vasogenic/cytotoxic/interstitial edema + impaired CSF flow + vasculitis/thrombosis → increased intracranial pressure and reduced cerebral perfusion.** Bacterial cell-wall products trigger cytokines and neutrophilic inflammation. Complications arise not only from bacterial burden but also from the inflammatory response, which is why appropriately timed corticosteroids can reduce selected neurologic sequelae. --- ## Clinical presentation ### Classic adult features - Fever - Severe headache - Neck stiffness - Altered mental status - Photophobia - Nausea/vomiting The “classic triad” of fever, neck stiffness, and altered consciousness is **not sensitive enough to rule out disease when incomplete**. #### Additional features - Seizure - Focal neurologic deficit - Cranial nerve palsy - Reduced GCS - Petechial or purpuric rash - Shock/DIC - Limb pain or rapidly progressive sepsis in meningococcal disease #### Infants and children Presentation may be nonspecific: irritability, poor feeding, lethargy, high-pitched cry, fever or hypothermia, vomiting, seizures, bulging fontanelle, abnormal tone. #### Older or immunocompromised adults Fever and meningeal signs may be muted. New delirium, sepsis, seizure, or unexplained decline may dominate. --- ## Red flags requiring immediate resuscitation / ICU-level concern - GCS ≤9 or rapidly declining consciousness - Recurrent/prolonged seizure - Abnormal pupils or posturing - Focal neurologic deficit - Shock, rising lactate, DIC - Purpura fulminans / rapidly spreading non-blanching rash - Respiratory failure - Signs of impending herniation - Severe hyponatremia or other metabolic complication --- ## Initial assessment and “what to do next” | Component | Assessment | Interpretation | Immediate action | Anticipate deterioration | |---|---|---|---|---| | A — Airway | GCS, protective reflexes, vomiting | Airway loss risk | Airway support/intubation when indicated | Aspiration, herniation physiology | | B — Breathing | RR, SpO₂, work of breathing | Sepsis, aspiration, pulmonary complication | Oxygen/ventilation as needed | Fatigue, ARDS | | C — Circulation | HR, BP, perfusion, rash, lactate | Septic shock/DIC | IV/IO access, sepsis resuscitation | Refractory shock, adrenal hemorrhage | | D — Disability | GCS, pupils, focal deficit, seizure, glucose | Raised ICP, stroke mimic, hypoglycemia | Treat seizure/glucose; decide LP safety | Herniation, status epilepticus | | E — Exposure | Rash, infection source, trauma/CSF leak | Meningococcus, source clue | Droplet precautions if suspected meningococcus; source management | Rapid purpura/DIC | --- ## Diagnostic strategy ### Blood tests before antibiotics when feasible NICE recommends the following in suspected bacterial meningitis:[3] - Blood culture - WBC with neutrophils - CRP, or procalcitonin if CRP unavailable - Blood glucose - Whole-blood diagnostic PCR including meningococcal and pneumococcal targets where available - HIV testing according to local policy Do **not** rule out meningitis because WBC, CRP, or procalcitonin is normal.[3] Additional tests often include electrolytes, renal/liver profile, lactate, coagulation studies, and type/screen if severe DIC or critical illness is present. --- ## Lumbar puncture: do it early, but safely NICE states that LP should be performed before antibiotics **unless it is unsafe or would cause a clinically significant delay**. If antibiotics have already been started, perform LP as soon as safely possible.[3] ### Stabilize before LP Treat/stabilize these first:[3] - Unprotected airway - Respiratory compromise - Shock - Uncontrolled seizures - Bleeding risk ### Do not perform immediate LP when there is - Extensive/rapidly spreading purpura - Infection at the LP site - Risk factors for an evolving intracranial space-occupying lesion - Clinical signs suggesting dangerous raised ICP requiring imaging first --- ## CT before lumbar puncture: NOT routine NICE explicitly advises **against routine neuroimaging before LP**.[3,4] #### Image before LP when there is - Risk of an evolving space-occupying lesion - New focal neurologic features, including seizure or posturing - Abnormal pupillary reactions - **GCS ≤9** - Progressive sustained or rapid fall in consciousness[3] #### Critical sequence when imaging is required **Bloods → antibiotics (and dexamethasone when indicated) → stabilization → neuroimaging → LP when safe.** ⚠ **Common trap:** “Possible meningitis = CT first.” This delays antibiotics and is not recommended for most patients. --- ## CSF investigations NICE recommends:[3] - RBC and WBC count with differential - Total protein - CSF glucose **with paired blood glucose** to calculate CSF:blood glucose ratio - Gram stain - Culture and antimicrobial susceptibility - PCR for relevant pathogens Store remaining CSF for additional testing if needed.[3] ### Typical CSF patterns | Feature | Bacterial | Viral | TB/fungal (typical) | |---|---|---|---| | Opening pressure | Often high | Normal or mildly high | Often high | | WBC | High, usually neutrophilic | Lymphocytic | Lymphocytic/mononuclear | | Protein | High | Mild–moderately high | High | | Glucose | Low | Usually normal | Low | | CSF:blood glucose ratio | Reduced | Usually preserved | Reduced | | Gram stain/culture | May identify organism | Negative for bacteria | Specialized stains/culture/PCR | **Exceptions are common.** Early bacterial disease can be less neutrophilic; partially treated bacterial meningitis can have altered CSF findings; immunocompromised patients can have weak pleocytosis. --- ## Empiric antibiotics ### STANDARD OF CARE: treatment must not wait NICE recommends IV antibiotics as soon as bacterial meningitis is suspected, **within 1 hour of hospital arrival**.[3] #### UK/NICE approach Before the organism is known:[3] - **Ceftriaxone** at the highest meningitis dose recommended by formulary/local guidance - If ceftriaxone is contraindicated, consider **cefotaxime** - Add **IV amoxicillin** when there are risk factors for *Listeria monocytogenes* NICE does **not** recommend routine aciclovir unless herpes simplex encephalitis is strongly suspected.[3] #### Common adult meningitis doses used internationally These are common adult regimens; always verify local guidance, renal function, body size, allergy and resistance patterns: | Drug | Common adult meningitis dosing | Role | |---|---:|---| | Ceftriaxone | **2 g IV every 12 h** (or total 4 g/day in some protocols) | Core empiric agent / pneumococcus, meningococcus, Hib coverage | | Ampicillin / amoxicillin | **2 g IV every 4 h** (local protocols may vary) | *Listeria* coverage | | Vancomycin | Weight- and renal-function based; dose/monitor to local AUC or trough protocol | Added in many North American regimens for resistant pneumococcus | | Dexamethasone | **10 mg IV every 6 h** in adults | Adjunct, ideally before/with first antibiotic | #### U.S./North American vs UK/WHO nuance Many North American empiric adult protocols use **vancomycin + a third-generation cephalosporin**, adding ampicillin when Listeria risk is present because of concern for cephalosporin-resistant pneumococci. NICE uses ceftriaxone (or cefotaxime) as its core empiric regimen and recommends specialist input for resistance risks.[3] **Do not blindly merge regimens.** Use the guideline adopted in your jurisdiction and local pneumococcal susceptibility data. --- ## Dexamethasone NICE recommends IV dexamethasone for people **over 3 months** with strongly suspected or confirmed bacterial meningitis.[3] #### Timing - Give **with or before the first antibiotic dose if possible**. - Do **not** delay antibiotics to administer dexamethasone. - If delayed by <12 hours after antibiotics, NICE advises giving it as soon as possible; if >12 hours late, obtain infection-specialist advice.[3] #### Adult dose A widely used adult regimen, supported by the landmark randomized trial and common clinical guidance, is **dexamethasone 10 mg IV every 6 hours for 4 days**.[5] #### Continue or stop when organism known NICE recommends:[3] - **Continue** if *S. pneumoniae* or *H. influenzae* type b - **Stop** for other identified organisms - If no organism is identified, seek infection-specialist advice #### Why timing matters Antibiotic-induced bacterial lysis can amplify meningeal inflammation. Steroids are most useful when present before or at the onset of this inflammatory burst. --- ## Pathogen-specific treatment and duration Exact definitive therapy depends on susceptibility and jurisdiction. | Organism | Typical targeted approach | NICE duration concept | |---|---|---| | *N. meningitidis* | Ceftriaxone/cefotaxime; penicillin/ampicillin if susceptibility proven in some systems | **5 days** if recovered[3] | | *S. pneumoniae* | Ceftriaxone/cefotaxime ± vancomycin depending susceptibility/local resistance | **10 days** if recovered[3] | | Hib | Ceftriaxone/cefotaxime | **7 days**, extend to 10 if not recovered[3] | | Group B streptococcus | Ceftriaxone/cefotaxime; specialist input | **14 days** if recovered[3] | | *Listeria monocytogenes* | Ampicillin/amoxicillin-based therapy; specialist guidance | Often prolonged, commonly ~21 days depending disease/response | | Gram-negative bacilli | Susceptibility-guided 3rd/4th-gen cephalosporin or other agent | Often ~21 days; specialist management | NICE states that when CSF suggests bacterial meningitis but blood culture/PCR are negative, initial antibiotics can be continued for **10 days**, stopping if recovered or seeking specialist advice if not.[3] --- ## Meningococcal disease Meningococcal infection may present as meningitis, meningococcemia, or both. ### Clues - Rapidly progressive sepsis - Petechiae/purpura - Limb pain - Shock - DIC - Meningism may be absent in bloodstream-predominant disease #### Infection control Use appropriate **droplet precautions** for suspected meningococcal disease according to local infection-prevention policy. #### Treatment CDC guidance updated in 2026 states empiric treatment should include an extended-spectrum cephalosporin such as **ceftriaxone or cefotaxime**. Once susceptibility is known, penicillin or ampicillin may be used when susceptible.[6] #### Public-health actions Urgently notify public health according to jurisdiction. Close contacts may require chemoprophylaxis, and vaccination may be required depending on serogroup/outbreak context. ★ **Important:** Ceftriaxone treatment effectively clears carriage after a dose; if treatment used cefotaxime or penicillin/ampicillin, additional eradication therapy may be required before discharge according to CDC guidance.[6] --- ## Supportive and critical care ### Sepsis / shock Treat according to current sepsis principles: - Rapid IV/IO access - Lactate when indicated - Appropriate fluids with repeated reassessment - Norepinephrine for persistent vasodilatory shock when indicated - Source-directed antimicrobial therapy - Organ support ### Fluids NICE advises **not routinely restricting fluids below maintenance needs** in bacterial meningitis.[3] ⚠ **Common trap:** Historic reflex fluid restriction can worsen perfusion. Correct true SIADH/hyponatremia thoughtfully, but do not impose routine dehydration. ### Intracranial pressure NICE advises against routine glycerol and against routine use of osmotic agents such as mannitol or hypertonic saline for all meningitis patients.[3] Osmotherapy is reserved for selected patients with suspected impending herniation/raised ICP under critical-care/neurospecialist guidance. General neuroprotective principles include: - Avoid hypoxemia - Avoid hypotension - Treat fever and seizures - Elevate head of bed in selected patients - Maintain appropriate ventilation; avoid unnecessary prolonged hyperventilation - Urgent neurocritical care when herniation is suspected ### Seizures Treat status epilepticus promptly with standard protocols. Persistent altered consciousness may require EEG to detect nonconvulsive seizures. --- ## Complications ### Acute neurologic - Raised ICP / cerebral edema - Brain herniation - Seizures/status epilepticus - Ischemic stroke from vasculitis/thrombosis - Cerebral venous thrombosis - Hydrocephalus - Subdural effusion/empyema - Cranial neuropathies ### Systemic - Septic shock - DIC - Purpura fulminans - Acute kidney injury - ARDS - Waterhouse–Friderichsen syndrome in fulminant meningococcemia ### Long-term WHO highlights long-term complications in approximately **20%** of bacterial meningitis survivors.[1] Important sequelae: - Sensorineural hearing loss - Cognitive impairment - Epilepsy - Motor deficits - Visual/cranial nerve deficits - Learning/behavioral problems in children - Psychological sequelae and reduced quality of life --- ## Hearing and follow-up All survivors require structured assessment for neurologic and functional sequelae. Hearing evaluation is especially important after pneumococcal/Hib disease and in children, because hearing loss can be clinically silent initially but profoundly affect development. Follow-up should address: - Audiology - Cognitive and neurologic function - Seizure recurrence - Rehabilitation needs - Vaccination status - Evaluation for predisposing CSF leak, asplenia, complement deficiency, cochlear implant issues, or immune deficiency when clinically indicated --- ## Prevention ### Vaccination Major prevention tools include: - Pneumococcal vaccination - Hib vaccination - Meningococcal ACWY vaccination - Meningococcal B vaccination in indicated populations Schedules vary by age, country, risk group, and evolving public-health recommendations. ### Meningococcal contact prophylaxis Close contacts and people exposed directly to oral/respiratory secretions can require antibiotic prophylaxis. CDC options include rifampin, ciprofloxacin, or ceftriaxone, with selection based on age, pregnancy, resistance, and local public-health advice.[6] --- ## Special populations ### Immunocompromised / older adult Have a lower threshold for *Listeria* coverage and for atypical presentation. Consider broader differential: cryptococcal, TB, fungal, viral, malignant, and drug-related meningitis. ### Pregnancy *Listeria* risk is important. Antibiotic and prophylaxis choices should be coordinated with infectious disease and obstetrics. ### Asplenia / complement inhibitor therapy High risk of invasive encapsulated organisms. Prevention with vaccination and education about urgent fever management is essential. ### Cochlear implants / CSF leak Recurrent pneumococcal meningitis risk may be elevated. Investigate anatomical predisposition and ensure appropriate vaccination. ### Neurosurgical patients Do not use a routine community-acquired pathway. Post-craniotomy, shunts, drains, and penetrating trauma raise concern for staphylococci and resistant gram-negative bacilli; use healthcare-associated ventriculitis/meningitis guidance. --- ## Important mimics and alternative diagnoses | Condition | Clues | Key discriminator | |---|---|---| | Viral meningitis | Often less toxic, normal glucose | PCR; clinical course | | HSV encephalitis | Altered behavior, focal seizures, temporal signs | Brain MRI + CSF HSV PCR; empiric aciclovir when strongly suspected | | TB meningitis | Subacute course, cranial neuropathies, low glucose | TB testing, imaging, epidemiology | | Cryptococcal meningitis | HIV/immunocompromise, high opening pressure | CSF cryptococcal antigen | | Subarachnoid hemorrhage | Thunderclap headache | CT ± LP for blood/xanthochromia | | Brain abscess | Focal deficit, seizures, source infection | MRI/CT; LP may be unsafe/unhelpful | | Autoimmune encephalitis | Psychiatric symptoms, seizures, dyskinesia | CSF/serology/EEG/MRI | | Drug-induced aseptic meningitis | Temporal medication relationship | Exclusion + history | --- ## Diagnostic / management algorithm ```text Fever/headache/neck stiffness/AMS/seizure/rash → suspect meningitis ↓ ABC stabilization ↓ Blood cultures + CBC/CRP(or PCT) + glucose + chemistries ± PCR ↓ Is immediate LP safe, and can it occur without significant antibiotic delay? ├── YES → LP: cells/diff, protein, CSF glucose + paired blood glucose, │ Gram stain, culture/susceptibility, PCR │ ↓ │ IV antibiotics immediately + dexamethasone with/before first dose │ └── NO → IV antibiotics immediately + dexamethasone when indicated ↓ Does patient meet imaging-before-LP criteria? ├── YES → stabilize + CT/MRI → LP when safe └── NO → LP as soon as safely feasible Then: Gram stain/PCR/culture + susceptibility → narrow therapy Assess seizures/ICP/shock continuously Meningococcus? → droplet precautions + public health + contact management Recovery → hearing + neurologic follow-up + prevention evaluation ``` --- ## Acute management checklist - [ ] ABCs; treat hypoxemia, shock, uncontrolled seizures - [ ] Droplet precautions if meningococcal disease suspected - [ ] Blood cultures before antibiotics if this does not delay therapy - [ ] CBC, CRP/PCT, blood glucose, chemistries; lactate/coagulation if ill - [ ] LP immediately if safe and feasible - [ ] **No routine CT before LP** - [ ] If focal signs, abnormal pupils, GCS ≤9, rapid consciousness decline, or mass-lesion risk → image first, but **antibiotics first** - [ ] IV ceftriaxone-based empiric therapy per local guideline - [ ] Add Listeria coverage when risk factors present - [ ] Add vancomycin when required by local pneumococcal-resistance policy (common North American practice) - [ ] Dexamethasone with/before first antibiotic dose if indicated; never delay antibiotics - [ ] CSF cell count/diff, protein, glucose + paired serum glucose, Gram stain, culture, PCR - [ ] Narrow regimen and define duration once organism/susceptibility known - [ ] Monitor sodium, renal function, neurologic status, seizures, perfusion - [ ] Public-health notification/contact prophylaxis if meningococcus - [ ] Arrange hearing and neurologic follow-up --- ## Common pitfalls | Pitfall | Why dangerous | Better approach | |---|---|---| | Waiting for the classic triad | Triad is insensitive | Use overall syndrome and risk state | | CT on every suspected case | Delays LP and antibiotics | CT only for defined risk features | | Delaying antibiotics until after imaging/LP | Mortality/neurologic harm | Treat within 1 hour; diagnostics only if they do not delay | | Normal CRP/WBC “rules out” disease | False reassurance | NICE explicitly warns against this | | No paired serum glucose with CSF | Loses useful CSF:blood ratio | Draw blood glucose with LP | | Forgetting Listeria in older/immunocompromised patient | Cephalosporins do not reliably cover Listeria | Add ampicillin/amoxicillin when risk present | | Routine aciclovir for all meningitis | Unnecessary treatment | Use when HSV encephalitis is strongly suspected | | Giving dexamethasone hours later without thought | Benefit depends on timing/pathogen | Give with/before antibiotics; follow guideline if delayed | | Routine fluid restriction | May worsen perfusion | Maintain appropriate fluids; treat specific sodium disorder | | Missing meningococcal public-health actions | Preventable secondary cases | Isolation + urgent notification + contact prophylaxis | --- ## Current guideline changes ### WHO 2025 guideline + 2026 practical manual WHO issued its **first global guideline on meningitis diagnosis, treatment and care on 10 April 2025**, covering community-acquired acute meningitis across ages >1 month and including diagnostics, antibiotics, adjunctive therapy, supportive care, and long-term effects.[1] On **26 May 2026**, WHO released a practical manual with job aids and decision algorithms to operationalize these recommendations.[2] **STANDARD OF CARE implications:** rapid recognition, prompt effective antibiotics, rational LP/imaging, supportive care, and active management of sequelae. ### NICE NG240 (2024) Important UK practice points include:[3] - Antibiotics within 1 hour of hospital arrival - Ceftriaxone as core empiric therapy; add amoxicillin for Listeria risk - No routine CT before LP - Explicit criteria for imaging-first cases - Dexamethasone for strongly suspected/confirmed bacterial meningitis >3 months, with/before antibiotics if possible - Pathogen-specific durations including 5 days for meningococcus and 10 days for pneumococcus if recovered - No routine fluid restriction - No routine osmotic therapy ### Jurisdiction differences The major difference clinicians encounter is empiric pneumococcal resistance coverage: **many U.S. protocols add vancomycin**, whereas NICE does not use routine vancomycin in its baseline community-acquired regimen. This reflects antimicrobial-resistance assumptions and local epidemiology, not a fundamental disagreement that therapy should be broad enough to cover likely resistant pathogens. --- ## Evidence classification ### STANDARD OF CARE - Immediate IV antibiotics once bacterial meningitis is suspected - LP as early as safely possible - Selective, not routine, neuroimaging before LP - Dexamethasone given before/with first antibiotic dose in appropriate patients - Pathogen-directed narrowing - Public-health intervention for meningococcal disease - Hearing/neurologic follow-up ### EMERGING EVIDENCE - Faster multiplex molecular diagnostics and metagenomic testing - Biomarker-assisted bacterial-vs-viral differentiation - Improved neurocritical-care phenotyping and individualized ICP management - Better long-term neurocognitive rehabilitation strategies ### EXPERIMENTAL / INVESTIGATIONAL Novel host-directed anti-inflammatory strategies, precision diagnostics, and new adjunctive therapies should not replace immediate antibiotics, dexamethasone when indicated, and basic neurocritical/sepsis care outside trials. --- ## Exam-focused review ### Step 1 / Foundations Know: - Bacterial entry into CSF and inflammatory BBB injury - Neutrophilic CSF response - Low CSF glucose from bacterial/leukocyte metabolism and impaired transport - Raised protein from BBB disruption - Encapsulated organisms and splenic/complement defense ### Step 2 CK Classic next-best-step questions: - Suspected meningitis, stable, no focal deficit/ICP sign → **LP promptly**, then immediate antibiotics; do not order routine CT. - Focal deficit or GCS ≤9 → **blood cultures + antibiotics first**, image, then LP when safe. - Older/immunocompromised adult → add **Listeria coverage**. - Meningococcal rash/sepsis → antibiotics immediately + droplet precautions + public health. ### Step 3 / Resident Add: - Empiric regimen selection by age/immunity/resistance - Dexamethasone timing - Interpretation of partially treated CSF - Sepsis/ICP/seizure management - Contact prophylaxis - De-escalation and duration ### MRCP / ABIM / boards Expect nuance on: - CT-before-LP criteria - Pneumococcal vs meningococcal durations - Dexamethasone continuation by organism - Listeria risk - CSF patterns and exceptions - Public-health management --- ## Original MCQs #### 1. A 23-year-old has fever, headache, photophobia and neck stiffness. GCS 15, no focal deficits, normal pupils, stable vital signs. Best next step? A. CT head before any other test B. Lumbar puncture promptly if immediately available and safe, without delaying antibiotics C. MRI brain D. Discharge with oral antibiotics **Answer: B.** Routine neuroimaging before LP is not recommended. LP should precede antibiotics only when safe and when it will not cause clinically significant delay. #### 2. A 67-year-old with suspected meningitis has a new right arm weakness and GCS 8. Best sequence? A. LP first, then antibiotics B. CT first, then blood cultures, then antibiotics C. Blood cultures + immediate antibiotics/dexamethasone as indicated + stabilization, then imaging, then LP when safe D. EEG only **Answer: C.** Focal deficit/GCS ≤9 are imaging-before-LP criteria, but antibiotics must not wait for the scan. #### 3. Which additional empiric coverage is especially important in an older or cell-mediated immunocompromised adult? A. Metronidazole for *C. difficile* B. Ampicillin/amoxicillin for *Listeria monocytogenes* C. Oseltamivir D. Doxycycline for Lyme disease in every case **Answer: B.** Listeria is not reliably covered by third-generation cephalosporins. #### 4. When should dexamethasone ideally be administered? A. Only after culture confirms pneumococcus B. 24 hours after antibiotics C. Before or with the first antibiotic dose D. Only at discharge **Answer: C.** Benefit is linked to blunting the inflammatory response triggered by bacterial lysis. #### 5. CSF shows 2,400 WBC/µL (90% neutrophils), high protein, low glucose, and a low CSF:serum glucose ratio. Most likely diagnosis? A. Typical bacterial meningitis B. Migraine C. Normal CSF D. Isolated peripheral neuropathy **Answer: A.** This is the classic bacterial pattern, although real cases can vary. --- ## References 1. World Health Organization. **WHO guidelines on meningitis diagnosis, treatment and care.** 10 April 2025. ISBN **978-92-4-010804-2**. https://www.who.int/publications/i/item/9789240108042 2. World Health Organization. **WHO practical manual on meningitis diagnosis, treatment and care.** 26 May 2026. ISBN **978-92-4-012102-7**. https://www.who.int/publications/i/item/9789240121027 3. National Institute for Health and Care Excellence (NICE). **Meningitis (bacterial) and meningococcal disease: recognition, diagnosis and management. NG240.** Published March 2024. https://www.nice.org.uk/guidance/ng240 4. NICE. **Rationale and impact: neuroimaging and lumbar puncture, NG240.** 2024. https://www.nice.org.uk/guidance/ng240/chapter/rationale-and-impact 5. de Gans J, van de Beek D; European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators. **Dexamethasone in adults with bacterial meningitis.** *N Engl J Med.* 2002;347:1549–1556. doi: **10.1056/NEJMoa021334**. 6. Centers for Disease Control and Prevention. **Clinical Guidance for Meningococcal Disease.** Updated 2026. https://www.cdc.gov/meningococcal/hcp/clinical-guidance/index.html 7. Médecins Sans Frontières. **Bacterial meningitis — Medical Guidelines.** Current online edition. https://medicalguidelines.msf.org/en/viewport/CG/english/bacterial-meningitis-16689907.html 8. World Health Organization. **Defeating meningitis by 2030: a global road map.** Geneva: WHO; 2021. https://www.who.int/initiatives/defeating-meningitis-by-2030 --- **Review trigger:** Re-review when WHO, NICE, CDC, IDSA/ESCMID, or national antimicrobial guidance changes empiric regimens, dexamethasone recommendations, LP/imaging criteria, meningococcal prophylaxis, or vaccine schedules.1c:T9ea4,## One-minute summary **Sepsis** is life-threatening organ dysfunction caused by a dysregulated host response to infection. Operationally, Sepsis-3 identifies organ dysfunction as an acute increase in **SOFA score ≥2 points** attributable to infection.[1] **Septic shock** is a high-risk subset in which, despite adequate volume resuscitation, the patient requires vasopressors to maintain **MAP ≥65 mm Hg** and has **lactate >2 mmol/L**; this phenotype carries very high mortality.[1] The bedside priority is not to “prove sepsis” before acting. In a patient with suspected infection and organ dysfunction, **recognize physiologic threat, stabilize ABCs, obtain cultures without materially delaying therapy, give appropriate antimicrobials when infection is sufficiently likely, restore perfusion, identify the source, and obtain source control early**.[2,3] ### Core treatment sequence 1. **Recognize possible infection + organ dysfunction.** 2. **Assess airway, breathing, circulation and perfusion immediately.** 3. **Measure lactate** when sepsis is suspected; interpret in context.[2] 4. **Obtain appropriate cultures** before antibiotics if this does not cause a clinically important delay. 5. **Antimicrobials:** immediately, ideally within 1 hour for septic shock or high-likelihood sepsis; in possible sepsis without shock, perform rapid diagnostic assessment and treat within 3 hours if concern persists.[2] 6. **Fluids:** crystalloids are first line; balanced crystalloids are generally preferred. For sepsis-induced hypoperfusion/septic shock, SSC suggests at least **30 mL/kg IV crystalloid within the first 3 hours**, followed by frequent reassessment rather than automatic repeated boluses.[2] 7. **Vasopressor:** **norepinephrine** is first line; initial MAP target is usually **65 mm Hg**.[2] 8. **Source control:** drain, debride, remove infected hardware/device, or operate as soon as medically and logistically practical when indicated.[2] 9. **Reassess repeatedly** using mentation, capillary refill, urine output, lactate trend, hemodynamics, dynamic fluid-responsiveness measures and organ function.[2] ★ **High yield:** qSOFA is **not recommended as a stand-alone screening test** for sepsis or septic shock.[2] --- ## Definition and classification ### Sepsis Sepsis-3 defines sepsis as **life-threatening organ dysfunction caused by a dysregulated host response to infection**.[1] Operationally: - Suspected or confirmed infection **plus** - Acute increase in **SOFA ≥2 points** attributable to the infection.[1] The old term **“severe sepsis”** is redundant under Sepsis-3; once organ dysfunction is present, the patient has sepsis.[1] ### Septic shock Septic shock is a subset of sepsis with profound circulatory, cellular and metabolic abnormalities. Sepsis-3 clinical criteria are:[1] - Vasopressor requirement to maintain **MAP ≥65 mm Hg**, **and** - Serum lactate **>2 mmol/L (18 mg/dL)**, - Despite adequate volume resuscitation. ### Infection without sepsis A patient can have pneumonia, pyelonephritis, cellulitis or another infection without meeting criteria for sepsis if there is no infection-related life-threatening organ dysfunction. Conversely, organ dysfunction may be the first clue to an occult infection. --- ## Epidemiology and risk factors Sepsis is among the leading causes of critical illness and infection-related death worldwide. Risk rises substantially with age, frailty, chronic disease and impaired host defense.[1,2] Important risk factors include: - Age extremes and advanced age - Immunosuppression: neutropenia, hematologic malignancy, solid-organ or stem-cell transplantation, high-dose corticosteroids, biologic immunomodulators, advanced HIV - Diabetes mellitus - Chronic kidney disease and dialysis - Cirrhosis - Chronic lung disease - Cancer - Recent surgery or invasive procedures - Indwelling vascular, urinary or biliary devices - Recent hospitalization or antimicrobial exposure - Prior colonization/infection with multidrug-resistant organisms - Functional impairment, frailty, nursing-home residence - Pregnancy/postpartum state (with different physiologic thresholds and dedicated pathways) ### Common infection sources | Source | Typical clues | Important source-control question | |---|---|---| | Lung | Cough, hypoxemia, infiltrate, focal crackles | Empyema? Obstructed airway? Abscess? | | Urinary tract | Dysuria, flank pain, pyuria, hydronephrosis | Obstructed infected collecting system? | | Abdomen | Pain, ileus, peritonism, free air/fluid | Perforation, ischemia, abscess, cholangitis? | | Skin/soft tissue | Cellulitis, wound, pain, crepitus | Necrotizing infection or abscess needing surgery? | | Bloodstream/catheter | Rigors, line tenderness, no other focus | Remove infected line/device after alternate access? | | CNS | Meningism, altered consciousness, seizures | Need immediate meningitis/encephalitis pathway? | | Bone/joint | Focal pain, prosthesis, effusion | Drainage, debridement, prosthetic infection? | | Endocardium | Murmur, emboli, prosthetic valve/device | Echo, surgery/device management? | --- ## Pathophysiology Sepsis is not simply “too much inflammation.” It is a dysregulated host-pathogen interaction involving simultaneous inflammatory and immunosuppressive pathways, endothelial injury, microvascular dysfunction, coagulation abnormalities, altered cellular metabolism and organ-specific responses.[1] ### Mechanistic chain ```text Infection / pathogen products ↓ Innate immune recognition + cytokine signaling ↓ Endothelial activation and injury ↓ Vasodilation + capillary leak + altered vascular tone ↓ Relative/absolute intravascular volume deficit ↓ Microcirculatory heterogeneity + coagulation activation ↓ Impaired tissue oxygen delivery/utilization ↓ Cellular/metabolic dysfunction ↓ Organ dysfunction ± shock ``` ### Why lactate rises Elevated lactate can reflect tissue hypoperfusion and adrenergic-driven glycolysis, but it is **not a pure measure of anaerobic metabolism**. Liver dysfunction, seizures, beta-agonists, epinephrine and impaired clearance can elevate lactate. Therefore a falling lactate may support improving physiology, but a single value should never be interpreted in isolation.[2] ### Why hypotension may be late Compensatory vasoconstriction and tachycardia may preserve blood pressure early. A patient can have clinically important hypoperfusion with apparently acceptable BP; examine mentation, skin perfusion, urine output, capillary refill, lactate and trajectory. --- ## Clinical presentation There is no single sepsis phenotype. Presentation depends on source, age, comorbidity, medications and stage of illness. ### Symptoms and signs suggesting infection - Fever or hypothermia - Rigors - Cough, sputum, pleuritic pain - Dysuria, frequency, flank pain - Abdominal pain, vomiting, diarrhea - Skin/wound pain or erythema - Headache, photophobia, neck stiffness - Device-related pain or discharge - New confusion, weakness or functional decline ### Features of organ dysfunction | Organ/system | Concerning findings | |---|---| | Neurologic | Confusion, reduced GCS, delirium | | Respiratory | Tachypnea, hypoxemia, increased work of breathing, ARDS | | Cardiovascular | Hypotension, prolonged capillary refill, mottling, cool or abnormally warm peripheries | | Renal | Oliguria, rising creatinine | | Hematologic | Thrombocytopenia, DIC pattern | | Hepatic | Rising bilirubin, coagulopathy | | Metabolic | Elevated lactate, worsening acidosis | ### Red flags for immediate escalation - Airway compromise or rapidly falling consciousness - Severe hypoxemia or impending ventilatory failure - Persistent hypotension or signs of shock - Marked mottling, prolonged capillary refill, cold peripheries - Lactate significantly elevated or rising despite treatment - New oliguria/anuria - Purpura, rapidly progressive soft-tissue pain, crepitus - Meningism with altered mental state - Suspected neutropenic sepsis - Suspected obstructed infected urinary or biliary system - Severe abdominal pain/peritonism - Rapidly progressive organ dysfunction --- ## Recognition and screening ### SOFA SOFA evaluates six systems: respiratory, coagulation, liver, cardiovascular, CNS and renal function. An acute rise by **≥2 points** in the context of infection operationalizes sepsis in Sepsis-3.[1] ### qSOFA qSOFA assigns one point each for: - Respiratory rate **≥22/min** - Altered mentation - Systolic BP **≤100 mm Hg** It identifies higher-risk patients but has insufficient sensitivity as a sole screening strategy. SSC recommends **against qSOFA as the single screening tool** compared with SIRS, NEWS or MEWS.[2] ### NEWS2 and the UK approach NICE NG253, published **19 November 2025**, uses **NEWS2 plus clinical judgment** for adults aged 16 years and older who are not currently/recently pregnant. In acute hospital settings, suspected/confirmed infection with NEWS2 ≥7 is high risk; a lower total can still be high risk when a single parameter scores 3 or there are other clinical reasons for concern.[3] **Guideline difference:** Sepsis-3/SCCM use SOFA conceptually for organ dysfunction and advise against qSOFA alone; NICE emphasizes NEWS2-based risk stratification in its UK recognition pathway. These approaches are complementary rather than interchangeable. --- ## Initial assessment: a practical first 10 minutes | Component | Assess | Interpret | Immediate action | Anticipate deterioration | |---|---|---|---|---| | Airway | Patency, voice, secretions, consciousness | Loss of airway reflexes, obstruction | Suction, adjunct, airway team, definitive airway when indicated | Fatigue, encephalopathy, aspiration | | Breathing | RR, SpO₂, work, chest exam, blood gas if needed | Pneumonia, ARDS, pulmonary edema, fatigue | Oxygen to appropriate target; ventilatory support if failing | Rapid ARDS progression | | Circulation | HR, BP/MAP, cap refill, skin, urine, lactate | Shock/hypoperfusion | IV/IO access, cultures/labs, crystalloid if indicated, vasopressor if hypotension persists | Fluid overload, refractory vasoplegia | | Disability | GCS/AVPU, glucose, pupils | Sepsis encephalopathy vs mimics | Correct glucose/oxygen/perfusion; consider CNS infection/stroke/toxin | Seizures, coma | | Exposure/source | Full examination, wounds, lines, abdomen, back | Hidden source, necrotizing infection, device infection | Source-specific imaging/consult; remove triggers/devices when indicated | Need for emergency operation/drainage | --- ## Diagnostic work-up ### Core tests The exact panel is source- and severity-dependent. Common initial tests include: - CBC with differential - Electrolytes, urea/BUN, creatinine - Liver panel and bilirubin - Venous or arterial blood gas when clinically indicated - **Lactate** - Glucose - Coagulation studies - Blood cultures - Urinalysis and urine culture where relevant - Source-specific microbiology: sputum, CSF, wound, joint fluid, stool, respiratory viral PCR, etc. ### Blood cultures Obtain blood cultures before antimicrobials **when this can be done promptly and does not materially delay treatment**. Draw adequate volume and appropriate sets according to local laboratory policy. If endocarditis is suspected, follow a dedicated multi-set culture strategy. ### Imaging Use the fastest test that will meaningfully identify source or complication: - Chest radiograph or lung ultrasound - Renal ultrasound/CT for obstruction - CT abdomen/pelvis for intra-abdominal source - RUQ ultrasound or MRCP/CT for biliary source - Echocardiography for suspected endocarditis or shock phenotype - CT brain/LP pathway for CNS infection as appropriate - Soft-tissue imaging only if it will not delay surgery in suspected necrotizing infection ★ **High yield:** In suspected necrotizing fasciitis or another source requiring emergency surgery, **do not delay definitive source control for low-value imaging** when the clinical diagnosis is sufficiently concerning. --- ## Differential diagnosis: sepsis mimics | Mimic | Clues | Discriminator | |---|---|---| | Hemorrhagic shock | Bleeding, trauma, GI loss | Imaging/exam, falling Hb may lag | | Cardiogenic shock | ACS, pulmonary edema, low EF | ECG, troponin, echo | | Pulmonary embolism | Sudden dyspnea, RV strain | CTPA/echo, risk factors | | Adrenal crisis | Steroid dependence, hyponatremia/hyperkalemia | Cortisol if feasible; do not delay steroids in crisis | | Anaphylaxis | Urticaria, bronchospasm, exposure | Rapid response to IM epinephrine | | Thyroid storm | Hyperthermia, tachyarrhythmia, thyrotoxic features | Thyroid testing, clinical score | | DKA/HHS | Hyperglycemia, ketones, osmotic symptoms | Glucose/ketones/acid-base | | Drug toxicity | Exposure, toxidrome | ECG, drug levels selectively | | Malignant hyperthermia/NMS/serotonin syndrome | Drug trigger, rigidity/clonus | Medication history, neuromuscular findings | | Pancreatitis | Epigastric pain | Lipase, imaging | | HLH/cytokine syndromes | Cytopenias, extreme ferritin, organomegaly | Specialist work-up | **STANDARD OF CARE:** Continuously reassess whether infection remains the most likely diagnosis; SSC recommends stopping empiric antimicrobials if a convincing alternative diagnosis is established.[2] --- ## Management ### 1. Immediate resuscitation Sepsis and septic shock are medical emergencies; treatment and resuscitation should begin immediately.[2] #### Oxygen and ventilation Treat hypoxemia and respiratory failure according to usual critical-care principles. Sepsis-induced ARDS should receive lung-protective ventilation; prone positioning is recommended for moderate-to-severe ARDS when appropriate.[2] #### Access and monitoring - Peripheral IV access; IO if IV access is not rapidly obtainable in shock - Continuous ECG and pulse oximetry in unstable patients - Frequent or continuous BP monitoring; arterial catheter when practical in septic shock - Urine output monitoring - Serial perfusion reassessment --- ### 2. Antimicrobial therapy #### Timing SSC 2021 recommends:[2] - **Possible septic shock or high likelihood of sepsis:** give antimicrobials immediately, ideally **within 1 hour** of recognition. - **Possible sepsis without shock:** rapidly assess infectious vs noninfectious causes; if concern for infection persists, give antimicrobials **within 3 hours** of recognition. - **Low likelihood of infection without shock:** it is reasonable to defer antimicrobials while monitoring closely. NICE 2025 similarly prioritizes urgent assessment and antibiotic treatment within 1 hour for adults at high risk of severe illness or death from sepsis.[3] #### Empiric selection Choose empiric therapy according to: - Likely anatomic source - Community vs healthcare exposure - Local antibiogram - Prior microbiology/colonization - Recent antibiotics - Risk of MRSA or resistant gram-negative organisms - Immune status - Organ function and drug allergy history Do **not** use a universal “sepsis antibiotic.” The correct regimen for community-acquired pneumonia differs from obstructive pyelonephritis, cholangitis, meningitis, neutropenic sepsis or necrotizing soft-tissue infection. #### Resistant organisms SSC recommends MRSA coverage when risk is high, against routine MRSA coverage when risk is low, and against routine double gram-negative coverage in low-MDR-risk patients. Two gram-negative agents may be considered empirically when MDR risk is high, but double coverage should generally stop once susceptibilities are known.[2] #### Pharmacokinetics Critical illness changes drug volume of distribution and clearance. Use appropriate loading doses, renal/hepatic adjustment after the initial strategy as appropriate, and therapeutic drug monitoring when available. SSC favors prolonged infusion of beta-lactams for maintenance after an initial bolus.[2] #### De-escalation and duration - Review cultures and diagnosis daily. - Narrow spectrum when possible. - Shorter effective durations are generally preferred after adequate source control. - Procalcitonin may support **discontinuation** decisions when duration is uncertain, but SSC advises against using procalcitonin plus clinical evaluation to decide whether to **start** antibiotics.[2] --- ### 3. Fluid resuscitation #### Initial fluid For sepsis-induced hypoperfusion or septic shock, SSC suggests **at least 30 mL/kg IV crystalloid in the first 3 hours**.[2] This is a weak recommendation based on low-quality evidence and should not be interpreted as permission for repeated blind boluses. #### Fluid type - **Crystalloids:** first line.[2] - **Balanced crystalloids:** suggested over 0.9% saline.[2] - **Albumin:** may be considered when very large crystalloid volumes have already been required.[2] - **Hydroxyethyl starch:** avoid.[2] #### Reassessment after initial fluid Use **dynamic measures** when possible rather than static measures alone:[2] - Passive leg raise with stroke-volume/cardiac-output response - Small fluid challenge with objective response - Pulse-pressure or stroke-volume variation in appropriate ventilated patients - Bedside echocardiography Also reassess: - Capillary refill - MAP and pulse pressure - Mental status - Urine output - Mottling/skin temperature - Lung ultrasound/B-lines and respiratory status - Lactate trend #### What recent trials changed The **CLASSIC** trial in ICU septic shock found no 90-day mortality difference between restrictive and standard IV-fluid strategies after initial resuscitation.[5] The **CLOVERS** trial found no significant 90-day mortality difference between an early restrictive strategy emphasizing vasopressors and a liberal-fluid strategy in sepsis-induced hypotension.[4] **Practical interpretation:** after initial stabilization, there is no evidence that either indiscriminately liberal fluid or rigidly restrictive fluid is superior for all patients. Give fluid when there is evidence of hypoperfusion and likely fluid responsiveness; stop when benefit is unlikely or congestion emerges. --- ### 4. Vasopressors and hemodynamic targets #### First line **Norepinephrine** is first-line vasopressor therapy for septic shock.[2] A common starting infusion range is institution-specific; titrate rapidly to perfusion goals rather than waiting for central access. SSC supports short-term administration through a well-sited proximal peripheral vein when necessary rather than delaying vasopressor initiation.[2] #### MAP target Initial target **MAP 65 mm Hg** for most adults on vasopressors.[2] Individualize upward when clinically justified, for example selected patients with chronic severe hypertension and ongoing renal or neurologic hypoperfusion, while recognizing that higher targets can increase vasopressor exposure and arrhythmias. #### Second-line strategy - If MAP remains inadequate on norepinephrine, SSC suggests **adding vasopressin** rather than simply escalating norepinephrine indefinitely; guideline practice commonly adds vasopressin when norepinephrine is around **0.25–0.5 micrograms/kg/min**.[2] - If MAP is still inadequate despite norepinephrine + vasopressin, consider **epinephrine**.[2] - For cardiac dysfunction with persistent hypoperfusion despite adequate volume and BP, consider **dobutamine added to norepinephrine** or epinephrine alone.[2] #### Peripheral perfusion Capillary refill is a useful adjunct to other resuscitation endpoints. The ANDROMEDA-SHOCK trial did not show a statistically significant reduction in 28-day mortality with a capillary-refill-targeted strategy versus lactate-targeted resuscitation, but its findings supported renewed emphasis on bedside peripheral perfusion assessment.[6] --- ### 5. Source control **Source control is definitive therapy when infection persists because of an anatomic focus.** SSC recommends identifying/excluding sources requiring emergent intervention and performing required source control as soon as medically and logistically practical.[2] Examples: - Drain intra-abdominal abscess - ERCP/biliary drainage for obstructed cholangitis - Urgent decompression for infected obstructed urinary tract - Debridement for necrotizing soft-tissue infection - Remove infected vascular catheter after alternate access - Drain empyema - Operate for perforated viscus or ischemic bowel - Manage infected prosthetic material/device with specialists ★ **Board pearl:** Antibiotics cannot sterilize a closed abscess, obstructed infected system or necrotic tissue reliably without source control. --- ### 6. Corticosteroids For septic shock with an ongoing vasopressor requirement, SSC suggests IV corticosteroids. Typical regimen:[2] - **Hydrocortisone 200 mg/day IV**, either - 50 mg every 6 hours, or - continuous infusion. SSC remarks that treatment is often started when norepinephrine/epinephrine is **≥0.25 micrograms/kg/min for at least 4 hours**.[2] #### Evidence - **ADRENAL:** hydrocortisone 200 mg/day shortened time to shock resolution but did not reduce 90-day mortality compared with placebo.[7] - **APROCCHSS:** hydrocortisone plus fludrocortisone reduced 90-day mortality compared with placebo in a more severely shocked population.[8] **Guideline interpretation:** steroids are standard adjunctive therapy for vasopressor-dependent septic shock, not routine therapy for uncomplicated sepsis without shock. --- ### 7. Other organ support and adjuncts #### Red blood cell transfusion SSC recommends a restrictive strategy; a typical trigger is **hemoglobin 7 g/dL (70 g/L)**, but transfusion should reflect the whole clinical context, including active hemorrhage, severe hypoxemia or myocardial ischemia.[2] #### Glucose Start insulin for glucose **≥180 mg/dL (10 mmol/L)**; typical post-initiation target is approximately **144–180 mg/dL (8–10 mmol/L)**.[2] #### Bicarbonate - Do **not** use sodium bicarbonate simply to improve hemodynamics in hypoperfusion-induced lactic acidosis.[2] - Consider it in septic shock with **pH ≤7.2 plus AKI stage 2–3**, where SSC gives a weak recommendation.[2] #### Renal replacement therapy Use standard indications such as refractory hyperkalemia, severe acidemia, volume overload or uremic complications. Do not start RRT solely because AKI is present without a definitive indication.[2] #### VTE and stress-ulcer prophylaxis Use pharmacologic VTE prophylaxis unless contraindicated; LMWH is generally preferred over UFH. Stress-ulcer prophylaxis is for patients with GI-bleeding risk factors, not automatically for every sepsis admission.[2] #### Vitamin C and extracorporeal “blood purification” SSC suggests **against IV vitamin C** and against polymyxin-B hemoperfusion; evidence for other blood purification techniques remains insufficient.[2] --- ### Reassessment and monitoring #### Perfusion endpoints No single number defines successful resuscitation. Reassess the pattern: - Mental status - Capillary refill and mottling - Peripheral temperature - MAP - Heart rate - Urine output - Lactate trend - Acid-base status - Bedside echo/dynamic fluid responsiveness - Respiratory status and signs of fluid accumulation #### Urine output Oliguria is a marker of possible renal hypoperfusion or AKI, but urine output also changes with CKD, obstruction, medications and hormonal response. Persistent oliguria warrants evaluation rather than automatic fluid boluses. #### Lactate SSC suggests guiding resuscitation toward decreasing lactate when lactate is elevated, while explicitly noting that lactate must be interpreted in context.[2] --- ### Anticipation of deterioration | Pattern | What it may mean | Next actions | |---|---|---| | Rising vasopressor requirement | Ongoing vasoplegia, missed source, cardiogenic/obstructive component, bleeding | Reassess volume, echo, source control, diagnosis, steroids | | Persistent lactate elevation | Ongoing hypoperfusion or non-hypoxic lactate production | Re-examine perfusion; do not chase lactate with fluid blindly | | Worsening oxygenation after fluids | ARDS or hydrostatic pulmonary edema | Stop indiscriminate fluid, lung ultrasound/echo, ventilatory strategy | | New oliguria | AKI, hypoperfusion, obstruction | Hemodynamics, urinalysis, bladder scan/renal imaging as indicated | | New thrombocytopenia/coagulopathy | DIC, marrow suppression, liver dysfunction, drug effect | Coags/fibrinogen, bleeding assessment, source control | | Persistent fever/hypothermia | Uncontrolled source, resistant organism, noninfectious mimic | Repeat source search and microbiology review | --- ### Complications - Septic shock - ARDS - Acute kidney injury - Disseminated intravascular coagulation - Acute liver dysfunction - Myocardial dysfunction and arrhythmia - Delirium/encephalopathy - Critical illness polyneuropathy/myopathy - Pressure injury and deconditioning - Secondary/nosocomial infections - Malnutrition - Thromboembolism #### Post-sepsis syndrome Survivors may experience persistent weakness, exercise limitation, cognitive impairment, anxiety, depression, PTSD, sleep disturbance and recurrent hospitalization. Discharge planning should include medication reconciliation, rehabilitation needs, recovery education and follow-up for physical, cognitive and emotional sequelae.[2] --- ### Special populations #### Neutropenic sepsis Treat fever/instability in neutropenia as an emergency. Antipseudomonal empiric coverage and local neutropenic-sepsis protocols take priority; do not wait for neutrophil recovery or culture confirmation. #### Pregnancy and postpartum Normal pregnancy physiology changes heart rate, respiratory rate, BP and laboratory reference ranges. Use obstetric sepsis pathways and involve obstetrics early; maternal stabilization remains the priority. #### Cirrhosis Patients may have baseline vasodilation, thrombocytopenia, renal vulnerability and unusual infections. Consider spontaneous bacterial peritonitis, bacteremia and hepatorenal physiology; fluid and vasopressor decisions need particular caution. #### Advanced CKD/heart failure Initial shock treatment is still urgent, but repeated fluid boluses should be guided by dynamic responsiveness, congestion and bedside echo rather than fear of all fluid or routine large-volume administration. #### Immunosuppression Broaden the differential for opportunistic and fungal infection and involve infectious-diseases/microbiology expertise early when appropriate. --- ### Acute management checklist #### First hour: suspected septic shock / high-likelihood sepsis - [ ] ABCDE assessment and immediate stabilization - [ ] Call senior/critical-care help early - [ ] Continuous monitoring; IV/IO access - [ ] Lactate - [ ] Blood cultures and source cultures if they will not delay treatment - [ ] Appropriate empiric antimicrobials immediately, ideally within 1 hour - [ ] Crystalloid for hypoperfusion; balanced crystalloid preferred - [ ] Reassess after each bolus using dynamic/perfusion markers - [ ] Norepinephrine promptly if hypotension persists; do not delay for central line - [ ] Initial MAP target about 65 mm Hg - [ ] Identify source and emergency source-control need - [ ] Glucose, CBC, renal/liver profile, coagulation, blood gas as appropriate - [ ] Imaging focused on source without delaying life-saving intervention #### Following hours - [ ] Repeat lactate if elevated and clinically useful - [ ] Trend capillary refill, urine output, mentation and hemodynamics - [ ] Add vasopressin if norepinephrine requirement rises and MAP remains inadequate - [ ] Consider hydrocortisone for ongoing vasopressor-dependent shock - [ ] De-escalate/target antibiotics when microbiology returns - [ ] Reassess for ARDS, AKI, DIC and occult source - [ ] Re-evaluate diagnosis if response is atypical --- ### Diagnostic and management algorithm ```text Suspected infection ↓ Any acute organ dysfunction / concerning physiology? ├─ No → treat infection; monitor for deterioration └─ Yes ↓ Immediate ABCDE + lactate + cultures/labs + source assessment ↓ Shock / high likelihood of sepsis? ├─ Yes → antimicrobials immediately (ideally ≤1 h) │ + crystalloid if hypoperfusion │ + norepinephrine if hypotension persists │ + urgent source control └─ No → rapid infectious vs noninfectious assessment if concern persists → antimicrobials within 3 h ↓ Reassess perfusion dynamically ↓ Fluid responsive? ├─ Yes + hypoperfused → cautious additional fluid └─ No / congested → avoid further routine bolus ↓ MAP still inadequate? → norepinephrine → add vasopressin → consider epinephrine ↓ Persistent vasopressor-dependent shock? → hydrocortisone 200 mg/day ↓ Repeat source search + organ support + de-escalation + recovery planning ``` --- ### Common pitfalls | Pitfall | Why it is dangerous | Better approach | |---|---|---| | Treating qSOFA as a rule-out test | Misses sepsis | Use broad clinical assessment/NEWS or local screening plus organ dysfunction evaluation | | Waiting for hypotension before recognizing shock | BP can be preserved early | Assess perfusion and trajectory | | Delaying antibiotics in septic shock for “perfect cultures” | Time-sensitive mortality risk | Cultures quickly, then treat; do not materially delay | | Giving repeated automatic 30 mL/kg boluses | Fluid accumulation may worsen outcomes | Initial resuscitation + dynamic reassessment | | Chasing lactate with fluid alone | Lactate has non-hypoperfusion causes | Integrate cap refill, echo, urine, MAP and clinical context | | Delaying vasopressors until central line placement | Prolongs hypotension | Use appropriate proximal peripheral access short-term | | Ignoring source control | Antibiotics alone may fail | Drain/debride/decompress/remove source early | | Continuing broad-spectrum antibiotics indefinitely | Resistance/toxicity/C. difficile | Daily de-escalation and shortest effective duration | --- ### Guideline conflicts and practice variation #### Fluid volume SSC retains a suggestion for at least 30 mL/kg within 3 hours for sepsis-induced hypoperfusion/septic shock.[2] However, CLASSIC and CLOVERS show that after initial resuscitation, restrictive and liberal strategies produce similar major outcomes in broad trial populations.[4,5] Contemporary practice is therefore shifting toward **individualized, physiology-guided fluid** after the initial phase. #### Screening - **SSC:** do not use qSOFA alone; institutional screening and performance-improvement programs are recommended.[2] - **NICE 2025:** uses NEWS2 thresholds plus clinical judgment to stratify risk in adults.[3] #### Antibiotic timing Both SSC and NICE prioritize the fastest treatment in shock/high-risk sepsis. SSC is more explicit about allowing a short diagnostic window (up to 3 hours) for possible sepsis **without shock** when the likelihood of infection is uncertain.[2,3] --- ### STANDARD OF CARE vs emerging vs experimental #### STANDARD OF CARE - Early recognition and organ-supportive resuscitation - Appropriate cultures without clinically important antibiotic delay - Timely empiric antimicrobials based on source and resistance risk - Crystalloids for hypoperfusion, with reassessment - Norepinephrine first-line vasopressor - Initial MAP target around 65 mm Hg - Early source control when indicated - Hydrocortisone for persistent vasopressor-dependent septic shock - De-escalation and shorter appropriate antimicrobial courses #### EMERGING / EVOLVING PRACTICE - Earlier vasopressor initiation with less routine fluid after initial resuscitation - Greater use of capillary refill, bedside echo and dynamic fluid-responsiveness testing - Precision resuscitation based on shock phenotype rather than a fixed fluid recipe - Biomarker- and rapid-diagnostic-guided antimicrobial stewardship #### EXPERIMENTAL / INVESTIGATIONAL - Routine extracorporeal cytokine adsorption/blood purification - Immune-phenotype-directed immunomodulation - Broad metabolomic/genomic sepsis endotyping for bedside treatment selection These should not displace proven infection control, antimicrobials, source control and organ support outside trials or specialist protocols. --- ### Exam-focused review #### USMLE Step 1 Understand: - Vasodilation + capillary leak → decreased effective circulating volume - Endothelial and microcirculatory dysfunction - Why lactate can rise - DIC and organ dysfunction mechanisms #### Step 2 CK / Step 3 Prioritize: - Unstable patient → resuscitate before extensive diagnostics - Septic shock → antibiotics + perfusion support immediately - Persistent hypotension after appropriate fluid → norepinephrine - Obstructed infected system → decompression/source control #### MRCP / ABIM / boards Know: - Sepsis-3 definition and septic shock criteria - SOFA vs qSOFA role - 30 mL/kg recommendation is a **weak initial-resuscitation recommendation**, not a maintenance strategy - Norepinephrine first line; vasopressin add-on - Hydrocortisone 200 mg/day for ongoing vasopressor need - Hb 7 g/dL is a typical restrictive transfusion threshold, modified by clinical context --- ### Original MCQs #### Question 1 A 68-year-old man with pyelonephritis has MAP 56 mm Hg, lactate 4.2 mmol/L, mottled extremities and worsening confusion. He has received an appropriate initial crystalloid resuscitation. What is the best next hemodynamic treatment? A. Dopamine as first-line vasopressor B. Norepinephrine infusion C. Additional 2 L saline without reassessment D. Sodium bicarbonate for the lactate E. Wait for central venous access before starting a vasopressor **Answer: B. Norepinephrine infusion.** **Explanation:** Norepinephrine is first-line vasopressor therapy for septic shock. Vasopressor treatment should not be delayed solely to obtain central access; a suitable proximal peripheral IV can be used briefly with monitoring.[2] #### Question 2 A patient with suspected infection has RR 26/min, SBP 98 mm Hg and normal mentation. Which statement about qSOFA is most accurate? A. qSOFA ≥2 confirms sepsis B. qSOFA <2 excludes sepsis C. qSOFA should be the sole screening test D. qSOFA can identify risk but is not recommended as the sole screening test E. qSOFA replaces SOFA for defining organ dysfunction **Answer: D.** **Explanation:** qSOFA is a prognostic bedside signal, not a definitive diagnostic test. SSC advises against qSOFA as the single screening tool.[2] #### Question 3 A patient with septic shock remains hypotensive despite norepinephrine and appropriate reassessment of volume status. What vasopressor strategy is favored next by SSC? A. Add vasopressin B. Switch to phenylephrine routinely C. Stop norepinephrine and use dopamine D. Give repeated fluid regardless of fluid responsiveness E. Start terlipressin **Answer: A. Add vasopressin.** **Explanation:** For inadequate MAP on norepinephrine, SSC suggests adding vasopressin rather than simply escalating norepinephrine indefinitely.[2] #### Question 4 Which patient most clearly requires urgent source control in addition to antimicrobials? A. Uncomplicated cellulitis without abscess B. Viral bronchitis C. Obstructed infected ureter with hydronephrosis and shock D. Asymptomatic bacteriuria E. Mild cystitis **Answer: C.** **Explanation:** An infected obstructed urinary system is a source-control emergency; decompression is essential because antimicrobials alone may not control infection. #### Question 5 A patient with septic shock is receiving norepinephrine 0.35 micrograms/kg/min for several hours with persistent vasopressor requirement. Which adjunct is guideline-supported? A. Routine IV vitamin C B. Hydrocortisone 200 mg/day IV C. Polymyxin-B hemoperfusion D. Hydroxyethyl starch E. Routine bicarbonate regardless of pH **Answer: B.** **Explanation:** SSC suggests IV corticosteroids for septic shock with ongoing vasopressor need; hydrocortisone 200 mg/day is the typical regimen.[2] --- ### Recent guideline and practice updates - **19 November 2025:** NICE published NG253 for suspected sepsis in people aged 16 or over, replacing the prior all-age structure and emphasizing NEWS2 plus clinical judgment and rapid antibiotics for high-risk patients.[3] - Contemporary post-SSC evidence from **CLASSIC (2022)** and **CLOVERS (2023)** supports a move away from automatic repeated fluid boluses after initial resuscitation toward individualized fluid/vasopressor decisions.[4,5] - As of this review date, the **Surviving Sepsis Campaign 2021 adult guideline remains the principal international comprehensive management guideline** listed by SCCM; local institutions may have more recent operational pathways.[2] --- ### Landmark and influential research - **Sepsis-3 (2016):** modern definition centered on infection-related organ dysfunction and defined septic shock phenotype.[1] - **ProCESS, ARISE, ProMISe (2014–2015):** showed no benefit from mandatory early goal-directed therapy protocols compared with contemporary usual care, helping shift practice toward early recognition/resuscitation without fixed invasive targets.[9-11] - **ADRENAL and APROCCHSS (2018):** clarified the role of corticosteroids in vasopressor-dependent septic shock.[7,8] - **ANDROMEDA-SHOCK (2019):** brought peripheral perfusion/capillary refill back into resuscitation discussions.[6] - **CLASSIC (2022) and CLOVERS (2023):** challenged the assumption that more fluid is inherently better after initial resuscitation.[4,5] --- ### References 1. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). *JAMA*. 2016;315(8):801-810. doi:10.1001/jama.2016.0287. https://jamanetwork.com/journals/jama/fullarticle/2492881 2. Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. *Intensive Care Med*. 2021;47:1181-1247. doi:10.1007/s00134-021-06506-y. SCCM recommendations: https://www.sccm.org/clinical-resources/guidelines/guidelines/surviving-sepsis-guidelines-2021 3. National Institute for Health and Care Excellence. Suspected sepsis in people aged 16 or over: recognition, assessment and early management. NICE guideline NG253. Published 19 November 2025. https://www.nice.org.uk/guidance/NG253 4. National Heart, Lung, and Blood Institute PETAL Clinical Trials Network. Early Restrictive or Liberal Fluid Management for Sepsis-Induced Hypotension (CLOVERS). *N Engl J Med*. 2023;388:499-510. doi:10.1056/NEJMoa2212663. 5. Meyhoff TS, Hjortrup PB, Wetterslev J, et al. Restriction of Intravenous Fluid in ICU Patients with Septic Shock (CLASSIC). *N Engl J Med*. 2022;386:2459-2470. doi:10.1056/NEJMoa2202707. 6. Hernández G, Ospina-Tascón GA, Damiani LP, et al. Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock: ANDROMEDA-SHOCK. *JAMA*. 2019;321(7):654-664. doi:10.1001/jama.2019.0071. 7. Venkatesh B, Finfer S, Cohen J, et al. Adjunctive Glucocorticoid Therapy in Patients with Septic Shock (ADRENAL). *N Engl J Med*. 2018;378:797-808. doi:10.1056/NEJMoa1705835. 8. Annane D, Renault A, Brun-Buisson C, et al. Hydrocortisone plus Fludrocortisone for Adults with Septic Shock (APROCCHSS). *N Engl J Med*. 2018;378:809-818. doi:10.1056/NEJMoa1705716. 9. ProCESS Investigators. A Randomized Trial of Protocol-Based Care for Early Septic Shock. *N Engl J Med*. 2014;370:1683-1693. doi:10.1056/NEJMoa1401602. 10. ARISE Investigators; ANZICS Clinical Trials Group. Goal-Directed Resuscitation for Patients with Early Septic Shock. *N Engl J Med*. 2014;371:1496-1506. doi:10.1056/NEJMoa1404380. 11. Mouncey PR, Osborn TM, Power GS, et al. Trial of Early, Goal-Directed Resuscitation for Septic Shock (ProMISe). *N Engl J Med*. 2015;372:1301-1311. doi:10.1056/NEJMoa1500896. --- ### Related topics to build next - Shock: classification and hemodynamic approach - Community-acquired pneumonia - Neutropenic sepsis - Acute respiratory distress syndrome - Disseminated intravascular coagulation - Vasopressors and inotropes - Source control in severe infection1d:T8eb2,## One-minute summary **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 instability**. Major etiologies include **peptic ulcer disease, erosive disease, varices, portal hypertensive gastropathy, Mallory-Weiss tears, malignancy, and vascular lesions**. Management begins with **resuscitation and risk stratification before definitive diagnosis**. For most hemodynamically stable adults without a special indication for a higher threshold, a **restrictive red-cell transfusion strategy around hemoglobin 7 g/dL** is recommended by major guidelines.[1,2] The **Glasgow-Blatchford Score (GBS)** is the preferred pre-endoscopy score; a score of **0–1** identifies many very-low-risk patients who can be considered for outpatient management if clinically appropriate.[1] For **nonvariceal bleeding**, endoscopy is generally performed **within 24 hours after resuscitation**. The 2026 ESGE peptic-ulcer bleeding update specifically discourages routine emergent (≤6 h) or urgent (≤12 h) endoscopy in resuscitated patients unless instability persists despite adequate resuscitation, reinforcing that stabilization matters more than racing to the endoscopy suite.[2] High-risk peptic ulcers—Forrest **Ia, Ib, IIa**, and selected **IIb**—require endoscopic hemostasis.[2] For **suspected variceal bleeding**, treat before endoscopic confirmation: start a vasoactive drug, give antibiotic prophylaxis, resuscitate restrictively, and perform endoscopy **within 12 hours once safely resuscitated**.[3,4] Baveno VIII, published August 2026, emphasizes **pre-emptive TIPS within 72 hours (ideally <24 h)** for high-risk esophageal/GOV1 bleeds: Child-Pugh **C 10–13**, Child-Pugh **B >7 with active bleeding**, or **HVPG ≥20 mmHg**.[3] --- ## Definition and classification UGIB is hemorrhage originating from the esophagus, stomach, or duodenum proximal to the ligament of Treitz. ### Clinical presentations - **Hematemesis:** red blood or clots vomited; suggests active/recent UGIB. - **Coffee-ground emesis:** blood exposed to gastric acid; does not guarantee low risk. - **Melena:** black, tarry, typically foul-smelling stool; usually upper GI source but can arise from small bowel/right colon. - **Hematochezia:** classically lower GI, but a **brisk UGIB can produce red/maroon stool**, particularly with shock. - **Occult/slow bleeding:** iron-deficiency anemia, fatigue, positive fecal testing. ### Etiologic categories | Category | Important causes | Clues | |---|---|---| | **Peptic ulcer** | H. pylori, NSAIDs, aspirin, critical illness | Epigastric history, antiplatelets/NSAIDs, prior ulcer | | **Portal hypertensive** | Esophageal/gastric varices, portal hypertensive gastropathy | Cirrhosis, splenomegaly, thrombocytopenia, ascites | | **Mucosal** | Erosive gastritis/duodenitis/esophagitis | Alcohol, NSAIDs, reflux, critical illness | | **Mechanical tear** | Mallory-Weiss | Retching/vomiting before hematemesis | | **Vascular** | Dieulafoy lesion, angioectasia, GAVE | Recurrent/obscure bleeding | | **Malignancy** | Esophageal/gastric cancer | Weight loss, dysphagia, persistent anemia | | **Aortoenteric fistula** | Especially after aortic graft | Sentinel bleed + catastrophic rebleed; surgical emergency | --- ## Epidemiology and prognosis UGIB remains a major emergency with significant hospitalization and mortality. Contemporary nonvariceal UGIB reviews still report mortality in the range of roughly **5–10%**, depending heavily on age, comorbidity, shock, recurrent bleeding, and etiology.[5] Variceal hemorrhage carries particularly high short-term mortality in cirrhosis; modern portal-hypertension care has improved outcomes but 6-week mortality remains clinically important.[3,6] Outcome is driven less by the visible amount of blood than by: - age/frailty - hemodynamic instability - comorbid cardiovascular/renal/liver disease - ongoing bleeding - coagulopathy/antithrombotic therapy - endoscopic stigmata - failure of initial hemostasis - hepatic reserve in variceal bleeding --- ## Pathophysiology ### Peptic ulcer bleeding Ulceration erodes through mucosa/submucosa into an arterial vessel. Posterior duodenal ulcers can involve the gastroduodenal artery; high lesser-curvature gastric ulcers can involve branches of the left gastric artery. Rebleeding risk depends strongly on endoscopic stigma, vessel caliber, ulcer size/location, and hemodynamic presentation. ### Variceal bleeding Portal hypertension produces portosystemic collaterals. Variceal rupture reflects the interaction of: - portal pressure - varix size - wall tension - mucosal injury - liver disease severity Portal pressure can rise further with overtransfusion, which is one reason restrictive transfusion is important. --- ## Initial assessment and stabilization ### First priorities | Component | Assessment | Interpretation | Immediate action | Anticipate deterioration | |---|---|---|---|---| | **Airway** | Mental status, active hematemesis, aspiration risk | Blood-filled airway can rapidly become unsafe | Suction, oxygen if needed, early anesthesia/airway help | Intubation may be required for altered consciousness or uncontrolled active hematemesis before endoscopy | | **Breathing** | RR, SpO₂, aspiration signs | Tachypnea may reflect shock/acidosis | Oxygen if hypoxemic; evaluate aspiration | Pneumonitis/pneumonia after large hematemesis | | **Circulation** | HR, BP, cap refill, skin temp, orthostasis, mental status | Shock can precede hemoglobin fall | Two large-bore IVs, labs, crystalloid judiciously, blood if indicated | Rebleeding, myocardial ischemia, AKI | | **Disability** | Confusion, encephalopathy | Hypoperfusion, hepatic encephalopathy, alcohol withdrawal, CNS disease | Correct perfusion; treat cause | Worsening consciousness may mandate airway control | | **Exposure** | Cirrhosis signs, abdominal exam, melena, bleeding elsewhere | Helps classify source and severity | Focused exam; avoid delaying resuscitation | Hidden alternative source / aortic catastrophe | #### Key principle: hemoglobin can initially be misleading In acute whole-blood loss, hemoglobin may remain near baseline before plasma volume equilibrates. **Do not wait for anemia to diagnose hemorrhagic shock.** Use physiology, bleeding history, serial hemoglobin, and response to resuscitation. --- ### Laboratory and bedside testing #### Initial tests - CBC - type and screen; crossmatch if substantial bleeding - urea/BUN and creatinine - electrolytes - liver profile - PT/INR, aPTT as context—not as complete measures of hemostasis in cirrhosis - lactate / venous blood gas if shocked - ECG and troponin if ischemia possible - pregnancy test when relevant #### BUN/creatinine ratio A disproportionate BUN rise supports an upper GI source because digested blood increases urea generation and hypovolemia increases urea reabsorption, but renal function, catabolism, and steroids limit specificity. --- ### Risk stratification #### Glasgow-Blatchford Score GBS uses pre-endoscopy variables including hemoglobin, BUN, BP, HR, melena, syncope, and hepatic/cardiac disease. Major guidelines recommend it for initial risk stratification.[1,7] **GBS 0–1** identifies a very-low-risk group who may be considered for discharge with outpatient follow-up/endoscopy when: - hemodynamically stable - no ongoing major bleeding - reliable follow-up - no competing reason for admission #### Rockall score The complete Rockall score incorporates endoscopic findings and helps predict rebleeding/mortality. It is less useful than GBS for the initial “admit vs potentially discharge” decision. #### AIMS65 Uses albumin, INR, mental status, systolic BP, and age; more useful for mortality prediction than deciding need for intervention. --- ## Resuscitation ### Fluids Use isotonic crystalloid to restore perfusion while arranging blood products and definitive hemostasis. Avoid unlimited crystalloid in ongoing major bleeding; excessive dilution and volume overload can worsen outcomes. ### Red-cell transfusion #### STANDARD OF CARE For most hospitalized UGIB patients, a **restrictive transfusion threshold near hemoglobin 7 g/dL** is recommended.[1] In variceal hemorrhage, portal-hypertension guidance generally targets approximately **7–8 or 7–9 g/dL**, individualized for: - active shock - ongoing exsanguination - ischemic heart disease - severe hypoxemia - age/comorbidity Do not apply a static threshold to an actively exsanguinating patient whose hemoglobin has not yet equilibrated. #### Massive bleeding Activate local massive transfusion protocols when physiology and blood loss warrant it. Balance RBCs, plasma, platelets, fibrinogen, calcium, temperature, and coagulation using local trauma/hemorrhage principles rather than waiting for laboratory collapse. --- ### Antithrombotic medications and coagulopathy Management depends on the drug, bleeding severity, indication, thrombotic risk, and availability of reversal agents. #### General principles - Stop the causative antithrombotic temporarily in major active bleeding unless a compelling reason exists not to. - Use **specific reversal** for life-threatening bleeding when indicated by drug class and timing. - In cirrhosis, **INR does not accurately represent global hemostasis**; routine FFP simply to “normalize INR” is not recommended and can worsen portal pressure/volume status.[3,8] - Platelet/fibrinogen replacement in variceal bleeding should be individualized rather than driven by INR alone. #### Aspirin For aspirin used for **secondary cardiovascular prevention**, prolonged interruption increases cardiovascular risk. Older ESGE guidance recommends rapid resumption after endoscopic hemostasis; the exact timing depends on ulcer stigma and bleeding control.[7] #### Anticoagulation After nonvariceal UGIB is controlled, anticoagulation should generally be resumed once safe because permanent discontinuation increases thromboembolism and mortality; ESGE 2021 suggested resumption **within or soon after 7 days** for many patients, individualized to thrombotic risk and DOAC pharmacokinetics.[9] --- ## Pre-endoscopy management ### Proton pump inhibitor before endoscopy #### Nonvariceal/undifferentiated UGIB The **2026 ESGE peptic-ulcer bleeding update** suggests considering **high-dose IV PPI before endoscopy**, but it **must not delay endoscopy**.[2] Pre-endoscopy PPI may downstage endoscopic stigmata and reduce need for endoscopic treatment, but it is not a substitute for resuscitation or definitive hemostasis. ### Prokinetic before endoscopy For severe or ongoing bleeding with likely blood/clot in the stomach: - **erythromycin 250 mg IV 30–120 minutes before endoscopy** is supported by major guidance to improve visualization.[7,10] - the 2026 ESGE update suggests **IV metoclopramide as an alternative in selected patients if erythromycin is unavailable**.[2] Check QT/drug-interaction issues where relevant. ### Nasogastric lavage Routine NG/OG aspiration or lavage is **not recommended** simply to diagnose UGIB.[7] --- ## Timing of endoscopy ### Nonvariceal bleeding **Endoscopy within 24 hours after presentation and resuscitation** is the standard target for most admitted patients.[1] #### 2026 ESGE update ESGE now explicitly advises against routine **emergent (≤6 h) or urgent (≤12 h)** endoscopy in peptic-ulcer bleeding unless the patient remains **hemodynamically unstable despite adequate resuscitation**.[2] **Why this matters:** earlier is not automatically better if the patient is not resuscitated, the stomach is full of blood, the airway is unsafe, or skilled endoscopy/support is not ready. ### Suspected variceal bleeding Perform endoscopy **within 12 hours** once hemodynamic resuscitation has made the procedure reasonably safe.[3,4] --- ## Nonvariceal UGIB: endoscopic diagnosis and treatment ### Forrest classification for peptic ulcer bleeding | Forrest class | Finding | Rebleeding risk | Management | |---|---|---|---| | **Ia** | Spurting arterial bleeding | Very high | Endoscopic hemostasis | | **Ib** | Oozing bleeding | High | Endoscopic hemostasis | | **IIa** | Nonbleeding visible vessel | High | Endoscopic hemostasis | | **IIb** | Adherent clot | Intermediate/high | 2026 ESGE suggests clot removal and therapy if operator can manage conversion to active bleeding[2] | | **IIc** | Flat pigmented spot | Low | No endoscopic hemostasis; PPI | | **III** | Clean base | Low | No endoscopic hemostasis; PPI | --- ### Endoscopic modalities #### Active bleeding (Forrest Ia/Ib) Use a durable hemostatic modality, commonly: - thermal contact therapy - through-the-scope clips - over-the-scope (OTS) clip - combination therapy including epinephrine **plus** a second modality **Epinephrine injection should not be used alone** because tamponade/vasoconstriction is temporary and rebleeding is higher without definitive therapy.[7] #### 2026 ESGE advances The 2026 ESGE update adds several practical changes:[2] - **OTS clips can be used as first-line monotherapy** for high-risk spurting/oozing ulcers as an alternative to standard combination therapy. - **Hemostatic forceps with soft coagulation** can be used as monotherapy for Forrest Ia, Ib, and IIa lesions. - **Topical hemostatic agents should not be routine first-line monotherapy** for high-risk ulcer stigmata. - If standard therapy fails, use a **topical hemostatic agent or OTS clip** as rescue. - If all endoscopic modalities fail, proceed to **transcatheter angiographic embolization (TAE)**; surgery if TAE is unavailable or unsuccessful. #### Nonbleeding visible vessel (IIa) Acceptable therapies include: - contact or noncontact thermal treatment - mechanical therapy (TTS/OTS clips) - sclerosant injection - combinations with epinephrine #### Adherent clot (IIb) The 2026 ESGE update leans more toward active management: remove the clot and treat the underlying lesion **when the endoscopist has the skill and rescue capability** to manage provoked bleeding.[2] --- ## Post-endoscopic PPI After successful hemostasis of a high-risk ulcer, give **high-dose PPI for 72 hours**.[1,9] A classic regimen is: - IV bolus **80 mg**, then - infusion **8 mg/hour for 72 hours** Intermittent high-dose IV or oral regimens can be acceptable alternatives depending on guideline/local protocol and patient factors.[9] After the initial 72-hour high-risk period, ACG recommends **twice-daily oral PPI for 2 weeks**, then once daily for a duration based on ulcer etiology/healing needs.[1] --- ## Recurrent or refractory nonvariceal bleeding ### Clinical evidence of rebleeding Suspect when there is: - recurrent hematemesis/melena with instability - new tachycardia/hypotension - substantial hemoglobin drop after stabilization - increasing transfusion requirement #### Stepwise response 1. Resuscitate again. 2. **Repeat endoscopy** and re-treat. 3. 2026 ESGE favors **OTS clip** for recurrent peptic-ulcer bleeding when feasible.[2] 4. If repeat endoscopic hemostasis fails → **TAE**. 5. Surgery if TAE unavailable or unsuccessful. #### Prophylactic TAE — emerging/selective The 2026 ESGE guideline suggests considering prophylactic TAE after endoscopic hemostasis in **selected very-high-risk cases**, such as:[2] - hemodynamic instability at presentation - posterior duodenal wall ulcer - ulcer >2 cm - uncertain durability of endoscopic hemostasis This is **not routine for all ulcers**. --- ## H. pylori and ulcer recurrence prevention Every bleeding peptic ulcer should be assessed for **Helicobacter pylori**.[7] - Test during the acute episode. - If positive → eradicate. - If negative during acute bleeding/PPI exposure → **retest later**, because false negatives occur. - Confirm successful eradication. - Avoid NSAIDs where possible. - If NSAID is essential, use the lowest-risk strategy plus PPI gastroprotection as appropriate. --- ## Suspected variceal bleeding: treat before endoscopy A patient with cirrhosis/portal hypertension and UGIB should be managed as **suspected variceal hemorrhage until proven otherwise**. ### STANDARD OF CARE bundle 1. Restrictive resuscitation/transfusion. 2. Start a **vasoactive drug immediately**. 3. Give **antibiotic prophylaxis at presentation**. 4. Airway protection if altered consciousness or active uncontrolled hematemesis. 5. Endoscopy within **12 hours after resuscitation**. 6. Endoscopic variceal ligation for esophageal/GOV1 bleeding. 7. Identify high-risk patients for **pre-emptive TIPS**. --- ### Vasoactive drugs Accepted options include: - **octreotide** - **terlipressin** - **somatostatin** These reduce portal inflow and should begin as soon as variceal hemorrhage is suspected—before endoscopy.[3,4] Common octreotide protocols use an IV bolus followed by continuous infusion; exact dosing follows local hepatology/endoscopy protocol. #### Baveno VIII 2026 update Baveno VIII recommends vasoactive therapy as soon as possible and generally for **2–5 days or until TIPS if indicated**; it also allows consideration of shorter courses after successful endoscopic hemostasis in selected lower-risk patients when NSBB therapy is initiated thereafter.[3] Terlipressin can cause **hyponatremia**, so sodium should be monitored.[3] --- ### Antibiotic prophylaxis Bacterial infection increases failure of hemostasis and mortality in cirrhotic UGIB. Give prophylaxis from presentation.[3,4] A widely used regimen is **ceftriaxone 1 g IV daily**, historically for up to **7 days**, adjusted for allergies and local resistance patterns.[4,11] #### Baveno VIII nuance Baveno VIII maintains preventive antibiotics as standard but suggests duration/need may be individualized by infection risk and cirrhosis severity; lower-risk Child-Pugh A patients may ultimately need shorter therapy or possibly none, but this remains an area for prospective study.[3] --- ## Endoscopic variceal therapy ### Esophageal varices and GOV1 **Endoscopic variceal ligation (EVL)** is first-line hemostatic therapy.[3,4] ### Gastric fundal varices (GOV2 / IGV1) Management is anatomy- and expertise-dependent. Options include: - cyanoacrylate/tissue adhesive injection where used - EUS-guided coil + glue therapy in expert centers - TIPS, often with embolization - retrograde transvenous obliteration (RTO/BRTO variants) when a suitable shunt anatomy exists Contemporary AASLD educational guidance emphasizes that gastric variceal bleeding is often more severe and requires specialized endoscopic/interventional planning.[6,12] --- ## Pre-emptive TIPS: major 2026 practice update Baveno VIII (published August 2026) recommends **PTFE-covered pre-emptive TIPS within 72 hours, ideally <24 hours**, for esophageal or GOV1 variceal bleeding when any of the following are present:[3] - **Child-Pugh C 10–13** - **Child-Pugh B >7 with active bleeding at initial endoscopy** - **HVPG ≥20 mmHg** at the acute bleed This is not “rescue after failure”; the point is to identify high-risk patients **early** and decompress portal pressure before rebleeding occurs. #### New Baveno VIII timing nuance If the preferred 72-hour window is missed, Baveno VIII states that TIPS may still provide benefit: - within **2 weeks** for Child-Pugh C 10–13 - within **1 week** for Child-Pugh B >7 with active bleeding[3] #### Imaging after acute variceal bleeding Baveno VIII recommends **contrast-enhanced CT or MRI** after AVB to: - exclude portal/splanchnic vein thrombosis - assess HCC - map portosystemic collaterals - guide TIPS/obliteration strategy[3] --- ## Failure to control variceal bleeding ### Rescue sequence - continue vasoactive therapy - urgent expert endoscopy if appropriate - **salvage TIPS** for persistent/recurrent uncontrolled bleeding - temporary bridge: covered self-expanding esophageal metal stent or balloon tamponade in selected cases while arranging definitive therapy Balloon tamponade is a **bridge only**, with major aspiration, necrosis, and rebleeding risks; use in ICU/expert settings for the shortest possible time. --- ### Post-variceal bleed secondary prophylaxis For patients not treated with definitive portal decompression where standard secondary prevention applies: - **nonselective beta blocker (NSBB)** plus - serial **EVL** until eradication If bleeding recurs despite adequate secondary prophylaxis, evaluate for TIPS.[3] Do not start/titrate NSBB aggressively during uncontrolled shock; initiate after stabilization according to hepatology guidance. --- ## Differential diagnosis by presentation | Presentation | High-priority diagnoses | |---|---| | Hematemesis after repeated retching | Mallory-Weiss tear, peptic ulcer, varix | | Massive painless hematemesis | Varix, Dieulafoy lesion, large ulcer | | Melena + NSAID use | Peptic ulcer | | Cirrhosis + hematemesis | Variceal bleed until proven otherwise | | “Sentinel” GI bleed after aortic graft | **Aortoenteric fistula**—vascular surgical emergency | | Dysphagia/weight loss + bleeding | Esophageal/gastric malignancy | | Recurrent obscure bleeding | Angioectasia, Dieulafoy, small bowel source | | Hematochezia + shock | Brisk UGIB should be considered alongside lower GI hemorrhage | --- ## Special populations ### Cirrhosis - Avoid interpreting elevated INR as simple anticoagulation deficiency. - Avoid routine plasma solely to normalize INR. - Start antibiotics and vasoactive therapy early if variceal bleeding suspected. - Assess Child-Pugh/MELD and pre-emptive TIPS eligibility immediately. - Evaluate for encephalopathy, AKI, infection, ascites/SBP, and transplant candidacy. ### Ischemic heart disease A restrictive strategy still usually applies, but transfusion threshold and hemodynamic targets may need upward individualization if there is active myocardial ischemia or severe coronary disease. ### CKD BUN is less diagnostically useful; volume overload risk is higher; platelet dysfunction may complicate bleeding. ### Pregnancy Stabilize mother first. Endoscopy can be performed when clinically necessary with obstetric/anesthesia coordination and pregnancy-appropriate medication choices. ### Older/frail patients Lower physiologic reserve, greater transfusion/aspiration risk, and more anticoagulant exposure; disposition decisions should not rely solely on a low bleeding score. --- ## Secondary survey after initial stabilization Once immediate threats are controlled: #### History - onset and number of hematemesis/melena episodes - syncope/presyncope - NSAIDs/aspirin - anticoagulants and last dose - alcohol use - prior ulcers/H. pylori - cirrhosis/portal hypertension - prior variceal bleed/banding/TIPS - prior aortic surgery - weight loss/dysphagia #### Examination - volume status - stigmata of chronic liver disease - abdominal tenderness/mass - rectal exam if it changes management - encephalopathy - cardiac ischemia signs --- ## Current evidence and guideline differences ### STANDARD OF CARE - GBS for pre-endoscopic risk stratification; GBS 0–1 identifies many low-risk patients.[1] - Restrictive RBC transfusion around 7 g/dL for most stable patients.[1] - Endoscopy within 24 h for most nonvariceal UGIB after stabilization.[1] - Endoscopic hemostasis for Forrest Ia/Ib/IIa and selected IIb lesions.[2] - High-dose PPI for 72 h after high-risk ulcer hemostasis.[1,9] - Suspected variceal bleed: vasoactive drug + antibiotic + endoscopy within 12 h.[3,4] - EVL for esophageal/GOV1 variceal bleeding.[3] ### RECENT PRACTICE CHANGES — 2026 #### ESGE peptic ulcer bleeding update - Do **not** routinely rush all patients to ≤6 h or ≤12 h endoscopy; prioritize resuscitation, reserving very urgent endoscopy for persistent instability.[2] - OTS clips move earlier in the algorithm and may be used as first-line monotherapy for selected high-risk ulcers.[2] - Consider prophylactic TAE in selected very-high-risk ulcers after endoscopic control.[2] - Potassium-competitive acid blockers remain insufficiently established for routine post-hemostasis replacement of PPI therapy.[2] #### Baveno VIII portal hypertension update - Expanded/highlighted p-TIPS criteria: Child C 10–13, Child B >7 with active bleeding, or HVPG ≥20 mmHg.[3] - Preferred p-TIPS timing remains within 72 h, ideally <24 h, but benefit may persist beyond the classic window in selected patients.[3] - Cross-sectional portal-venous imaging after AVB is specifically emphasized.[3] - Antibiotic and vasoactive duration may become more individualized in lower-risk patients.[3] ### EMERGING EVIDENCE - EUS-guided coil/glue for gastric varices - prophylactic TAE for selected high-risk peptic ulcers - Doppler-guided endoscopic hemostasis (2026 ESGE could not reach consensus for routine use)[2] ### EXPERIMENTAL / INVESTIGATIONAL - telemetric blood-sensing capsules for routine UGIB triage: **not recommended routinely by 2026 ESGE**[2] - broader algorithmic prediction using AI/endoscopy imaging - expanded p-TIPS indications beyond established high-risk groups --- ## Acute management checklists ### Undifferentiated UGIB - [ ] ABC stabilization; airway plan if active hematemesis/altered consciousness - [ ] Two large-bore IVs - [ ] CBC, chemistry, liver tests, INR/aPTT, type & cross - [ ] GBS - [ ] Restrictive RBC strategy unless active exsanguination/special indication - [ ] Review/reverse antithrombotics when indicated - [ ] IV PPI reasonable for suspected nonvariceal bleed - [ ] Erythromycin 250 mg IV pre-endoscopy for severe/ongoing blood burden when appropriate - [ ] Endoscopy within 24 h after resuscitation ### Suspected variceal bleed - [ ] Restrictive resuscitation - [ ] Vasoactive drug immediately - [ ] Antibiotic prophylaxis immediately - [ ] Airway protection if indicated - [ ] Endoscopy within 12 h after safe resuscitation - [ ] EVL for esophageal/GOV1 varices - [ ] Calculate Child-Pugh/MELD - [ ] Assess p-TIPS criteria before leaving the acute pathway - [ ] Contrast CT/MRI for PVT/HCC/collateral mapping after stabilization ### High-risk peptic ulcer after hemostasis - [ ] High-dose PPI 72 h - [ ] H. pylori test/eradicate/retest if initially negative - [ ] Avoid culprit NSAID or provide gastroprotection if essential - [ ] Plan antithrombotic resumption - [ ] Watch for rebleeding - [ ] Repeat endoscopy → OTS clip → TAE if recurrent/refractory --- ## Diagnostic/management algorithm ```text Hematemesis / melena / suspected brisk UGIB ↓ ABC + IV access + labs + type/cross + resuscitation ↓ High-risk airway or shock? ├─ Yes → airway/critical-care + blood/resuscitation + urgent specialist input └─ No → risk-stratify (GBS) ↓ Cirrhosis/portal HTN strongly suspected? ├─ Yes → vasoactive drug + antibiotic NOW │ ↓ │ EGD within 12 h after resuscitation │ ↓ │ EVL (esophageal/GOV1) / expert gastric-varix therapy │ ↓ │ Assess p-TIPS: Child C 10–13 OR Child B>7 active bleed OR HVPG≥20 │ └─ No/uncertain → IV PPI reasonable ± erythromycin if severe ↓ EGD within 24 h ↓ Peptic ulcer Forrest class ├─ Ia/Ib/IIa → endoscopic hemostasis ├─ IIb → clot removal + therapy if capable └─ IIc/III → PPI, no endoscopic hemostasis ↓ High-risk lesion → high-dose PPI 72 h ↓ Rebleed → repeat EGD (consider OTS clip) → TAE → surgery if needed ``` --- ## Common pitfalls | Pitfall | Why dangerous | Better approach | |---|---|---| | Waiting for hemoglobin to fall before treating shock | Hb may initially be normal | Treat physiology and ongoing blood loss | | Transfusing every patient to Hb >10 | Can increase complications and portal pressure | Restrictive strategy for most patients | | Sending an unstable, unresuscitated patient straight to endoscopy | Sedation/procedure may worsen shock/aspiration | Resuscitate and secure airway first | | Using epinephrine injection alone for ulcer bleeding | Temporary hemostasis, higher rebleeding | Add mechanical/thermal definitive therapy | | Assuming all UGIB needs endoscopy within 6 hours | 2026 ESGE discourages routine emergent scope after adequate resuscitation | ≤24 h for most nonvariceal cases; earlier only for selected persistent instability | | Giving PPI alone for suspected variceal bleeding | Does not reduce portal pressure or prevent infection | Vasoactive drug + antibiotics + endoscopy | | “Correcting” cirrhotic INR with routine FFP | INR is not global hemostasis; FFP adds volume/portal pressure | Individualized coagulation strategy | | Forgetting early TIPS candidacy | High-risk patients can rebleed despite successful banding | Assess Child-Pugh/endoscopic activity/HVPG early | | Assuming hematochezia rules out UGIB | Brisk UGIB can present with red stool | Consider upper source when unstable | --- ## Exam-focused review ### USMLE Step 1 Know anatomy: - posterior duodenal ulcer → gastroduodenal artery - lesser-curvature gastric ulcer → left gastric artery branches - portal hypertension → variceal collaterals ### Step 2 CK Typical next-best-step decisions: - Cirrhosis + hematemesis → **octreotide/terlipressin + ceftriaxone + urgent endoscopy**, not PPI alone. - Stable nonvariceal UGIB → resuscitate, risk-stratify, endoscopy within 24 h. - Peptic ulcer + visible vessel → endoscopic hemostasis. - Rebleeding after prior hemostasis → repeat endoscopy before surgery/embolization in most cases. ### Step 3 / Resident Think beyond the scope: - massive hemorrhage activation - airway protection - antithrombotic reversal/resumption - H. pylori eradication verification - early IR discussion for refractory/high-risk ulcer - p-TIPS decision before the patient leaves the acute phase ### MRCP / ABIM High-yield distinctions: - GBS = pre-endoscopy risk score - Forrest classification = endoscopic ulcer rebleeding risk - Child-Pugh/MELD/HVPG = variceal prognosis/TIPS selection - high-dose PPI follows high-risk **nonvariceal** endoscopic hemostasis - vasoactive drugs + antibiotics are core treatment for **variceal** hemorrhage --- ## Original MCQs #### Question 1 A 54-year-old man with melena is hemodynamically stable after initial fluids. Hemoglobin is 6.8 g/dL. He has no known coronary disease. What is the best transfusion strategy? A. No transfusion until Hb <5 g/dL B. Transfuse RBCs using a restrictive threshold around 7 g/dL C. Transfuse to Hb >12 g/dL D. Give FFP instead of RBCs E. Platelets only **Answer: B.** Major UGIB guidelines support a restrictive RBC strategy around 7 g/dL for most hospitalized stable adults.[1] #### Question 2 A patient with cirrhosis presents with large-volume hematemesis. BP is 98/60 after initial resuscitation. Which treatment should begin before endoscopy? A. Oral PPI only B. Vasoactive therapy and antibiotic prophylaxis C. Beta blocker loading immediately despite active bleeding D. Routine FFP to normalize INR E. Colonoscopy prep **Answer: B.** Suspected variceal hemorrhage requires early vasoactive therapy and antibiotics before endoscopic confirmation.[3,4] #### Question 3 Endoscopy shows a duodenal ulcer with a nonbleeding visible vessel. What is the best management? A. No treatment because bleeding has stopped B. Endoscopic hemostasis followed by high-dose PPI C. Oral antacid only D. Immediate colectomy E. Routine thrombolysis **Answer: B.** Forrest IIa lesions have high rebleeding risk and require endoscopic treatment plus intensive acid suppression.[1,2] #### Question 4 A patient with esophageal variceal bleeding is successfully banded. Child-Pugh score is 11. Which next decision is most important during the first day? A. Discharge immediately B. Stop all vasoactive therapy and antibiotics regardless of course C. Assess for pre-emptive TIPS, ideally within 24 h and within 72 h D. Schedule colonoscopy in 5 years E. Begin aspirin **Answer: C.** Child-Pugh C 10–13 is a Baveno VIII criterion for p-TIPS after esophageal/GOV1 bleeding.[3] #### Question 5 A resuscitated patient with suspected peptic-ulcer bleeding is stable and has no ongoing shock. Which statement best reflects the 2026 ESGE update? A. Every patient requires endoscopy within 1 hour B. Routine ≤6-hour endoscopy is superior for all patients C. Routine emergent/urgent endoscopy is not recommended after adequate resuscitation unless instability persists D. Endoscopy should always be delayed 7 days E. Video capsule endoscopy is routine first-line therapy **Answer: C.** The 2026 ESGE update emphasizes resuscitation and generally avoids routine emergent (≤6 h) or urgent (≤12 h) endoscopy in stabilized peptic-ulcer bleeding.[2] #### Question 6 A patient rebleeds 24 hours after successful endoscopic therapy for a high-risk peptic ulcer. What is the preferred next strategy? A. Immediate elective discharge B. Repeat endoscopy, with OTS clip considered; if unsuccessful proceed to TAE C. Oral iron only D. Routine platelet transfusion regardless of count E. Start anticoagulation immediately **Answer: B.** Repeat endoscopic hemostasis remains first-line for recurrent ulcer bleeding; 2026 ESGE specifically highlights OTS clips, followed by TAE if repeat endoscopy fails.[2] --- ### References 1. Laine L, Barkun AN, Saltzman JR, Martel M, Leontiadis GI. **ACG Clinical Guideline: Upper Gastrointestinal and Ulcer Bleeding.** *Am J Gastroenterol.* 2021;116:899-917. PMID:33929377. https://pubmed.ncbi.nlm.nih.gov/33929377/ 2. Gralnek IM, et al. **Endoscopic diagnosis and management of peptic ulcer bleeding: European Society of Gastrointestinal Endoscopy (ESGE) Guideline — Update 2026.** *Endoscopy.* 2026;58(8):899-924. doi:10.1055/a-2863-8314. PMID:42127996. https://pubmed.ncbi.nlm.nih.gov/42127996/ 3. Baveno VIII Faculty. **Baveno VIII — Advancing Consensus in Portal Hypertension.** *J Hepatol.* 2026. doi:10.1016/j.jhep.2026.07.030. PMID:42624290. Published online 2026-08-19. https://pubmed.ncbi.nlm.nih.gov/42624290/ 4. Gralnek IM, et al. **Endoscopic diagnosis and management of esophagogastric variceal hemorrhage: ESGE Guideline.** *Endoscopy.* 2022. PMID:36174643. https://pubmed.ncbi.nlm.nih.gov/36174643/ 5. Lim H. **Management of Non-Variceal Upper Gastrointestinal Bleeding.** *Korean J Helicobacter Up Gastrointest Res.* 2026;26(1):37-41. doi:10.7704/kjhugr.2025.0083. PMID:41846443. 6. American Association for the Study of Liver Diseases. **Why is retrograde transvenous obliteration used to treat gastrofundal variceal bleeding?** 2026. https://www.aasld.org/liver-fellow-network/core-series/why-series/why-retrograde-transvenous-obliteration-used-treat 7. Gralnek IM, et al. **Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: ESGE Guideline.** *Endoscopy.* 2015;47. https://www.esge.com/diagnosis-and-management-of-nonvariceal-upper-gastrointestinal-hemorrhage 8. Garcia-Tsao G, Abraldes JG, Berzigotti A, Bosch J. **Portal Hypertensive Bleeding in Cirrhosis: Risk Stratification, Diagnosis, and Management.** *Hepatology.* 2017;65(1). AASLD Practice Guidance. 9. Gralnek IM, Stanley AJ, Morris AJ, et al. **Endoscopic diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: ESGE Guideline — Update 2021.** *Endoscopy.* 2021;53. PMID:33567467. 10. Hatta W, Ogata Y, Chiba T, et al. **Non-variceal upper gastrointestinal bleeding: advances and future directions in management.** *Clin Endosc.* 2026;59(4):510-522. doi:10.5946/ce.2025.202. PMID:41409024. 11. AASLD Liver Fellow Network. **Endoscopic Management of Gastric Varices.** 2026. https://www.aasld.org/liver-fellow-network/core-series/clinical-pearls/endoscopic-management-gastric-varices 12. AASLD educational review of gastric variceal hemorrhage and retrograde transvenous obliteration, 2026. https://www.aasld.org/liver-fellow-network/core-series/why-series/why-retrograde-transvenous-obliteration-used-treat --- **Next linked topics:** Peptic ulcer disease; H. pylori infection; portal hypertension; esophageal and gastric varices; cirrhosis; anticoagulant reversal; lower GI bleeding; iron-deficiency anemia.7:["$","$L17",null,{"article":{"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":"$18","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. 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