Learning Objective: Distinguish STEMI vs NSTE-ACS and articulate the time-critical management for each within the first 90 minutes.
Recognize
- Symptoms: pressure-like chest pain >10 min, radiation, diaphoresis, dyspnea. Watch for atypical presentations in women, elderly, diabetics.
- ECG within 10 min: ST-elevation β₯1 mm in 2 contiguous leads (β₯2 mm V2βV3 men <40, β₯1.5 mm women) = STEMI.
- Troponin: high-sensitivity at 0 and 1β3 h. Rising/falling pattern + ischemia = MI (4th Universal Definition).
Stratify
- STEMI: activate cath lab. Goal door-to-balloon β€90 min (β€120 min if transfer).
- NSTE-ACS: use TIMI or GRACE score.
- Early invasive (<24 h): GRACE >140, refractory ischemia, dynamic ECG, hemodynamic instability, VT/VF.
Initial Therapy β "MONA-BASH"
- ASA 162β325 mg chewed (Class I).
- P2Y12 inhibitor: ticagrelor or prasugrel preferred over clopidogrel for PCI.
- Anticoagulation: UFH or enoxaparin; bivalirudin alternative.
- High-intensity statin (atorva 80) early.
- Beta-blocker within 24 h if no shock/HF/heart block.
- Oβ only if SaOβ <90% (DETO2X-AMI). Nitrates for ongoing pain β avoid in RV infarct or recent PDE5i.
Don't Miss
- Posterior MI: ST-depression V1βV3 with tall R waves β get posterior leads (V7βV9).
- RV infarct: inferior STEMI + hypotension on nitrates β V4R, give fluids, avoid nitrates/morphine.
- Aortic dissection mimics ACS β check BP both arms, widened mediastinum.
Clinical Pearls
- Time is muscle: every 30 min of delay in STEMI reperfusion increases 1-year mortality ~7.5%.
- Don't withhold ASA for "possible dissection" without strong evidence β ACS is far more common.
- Type 2 MI (demand ischemia from sepsis, anemia, tachyarrhythmia) is treated by fixing the underlying problem, not by routine cath lab activation.
- After discharge: DAPT 12 months (longer if high ischemic risk per DAPT score), high-intensity statin, ACEi/ARB if EF <40% or DM/HTN, MRA if EF <40% + DM or HF, cardiac rehab (Class I).
- Secondary prevention LDL target <55 mg/dL (ESC) or β₯50% reduction with statin Β± ezetimibe Β± PCSK9i for high-risk.
MONA-BASH
Door-to-balloon β€ 90
Key Trials
PLATONEJM 2009Ticagrelor vs clopidogrel in 18,624 ACS patients β 16% reduction in CV death/MI/stroke (9.8% vs 11.7%) without β major bleeding. Established ticagrelor as preferred P2Y12 in ACS.
DETO2X-AMINEJM 2017Routine supplemental Oβ vs ambient air in 6,629 normoxic MI patients β no difference in 1-year mortality. Basis for "Oβ only if SaOβ <90%."
COMPLETENEJM 2019Complete revascularization vs culprit-only in STEMI with multivessel disease β 26% reduction in CV death/MI (HR 0.74). Drove staged non-culprit PCI recommendation.
ISAR-REACT 5NEJM 2019Prasugrel vs ticagrelor in invasively-managed ACS β prasugrel reduced death/MI/stroke (6.9% vs 9.3%) without more bleeding. Reopened the prasugrel-vs-ticagrelor question.
ISCHEMIANEJM 2020Invasive vs conservative strategy in stable IHD with moderate-severe ischemia β no reduction in death/MI; PCI improved angina. Reinforces medical therapy first in stable CAD (ACS still gets cath).
Learning Objective: Classify the patient by perfusion and volume status, then initiate guideline-directed medical therapy (GDMT) for HFrEF.
Bedside Profile (Stevenson)
- Wet vs Dry: JVD, edema, rales, orthopnea, S3.
- Warm vs Cold: narrow pulse pressure, cool extremities, mottling, AKI, lactate.
- Most ADHF = warm & wet β diurese. Cold & wet β cardiogenic shock, may need inotropes.
Workup
- BNP/NT-proBNP β high NPV for ruling out HF in dyspnea.
- ECG, CXR, troponin, TSH, BMP, Mg, LFTs, iron studies.
- TTE for new HF: defines HFrEF (EF β€40%), HFmrEF (41β49%), HFpEF (β₯50%).
- Identify the trigger β "FAILURE": Forgot meds, Arrhythmia, Ischemia/Infection, Lifestyle/diet, Upregulation (thyroid/pregnancy), Renal failure, Embolism.
Acute Management
- IV loop diuretic: dose β₯ 2Γ home oral dose IV (DOSE trial). Reassess UOP and weight q6β8 h.
- Oxygen / NIPPV for respiratory distress; HOB up.
- Vasodilators (NTG) for hypertensive ADHF, severe MR/AR.
- Restrict Na <2β3 g/d, fluid <1.5β2 L/d if congested or hyponatremic.
HFrEF GDMT β The 4 Pillars
- ARNI (sacubitril-valsartan) > ACEi/ARB β Class I.
- Evidence-based Ξ²-blocker: carvedilol, metoprolol succinate, or bisoprolol.
- MRA (spironolactone/eplerenone) if K <5.0, eGFR >30.
- SGLT2 inhibitor (dapagliflozin/empagliflozin) β benefit across all EFs.
Clinical Pearls
- Start all 4 pillars early and simultaneously when feasible β do not wait to "max out" one before adding another (STRONG-HF).
- Discharge bundle: euvolemic, on oral diuretics, GDMT initiated, follow-up in 7β14 days; reduces 30-day readmission.
- In HFpEF: SGLT2i (Class 2a, EMPEROR-Preserved/DELIVER), diuretics for congestion, treat HTN, AF, obesity, OSA. Finerenone (FINEARTS-HF) Class 2a for HFmrEF/HFpEF.
- Iron deficiency (ferritin <100 or 100β300 with TSAT <20%) β IV iron (FAIR-HF, AFFIRM-AHF) improves functional capacity and reduces HF hospitalization.
- ICD for primary prevention if EF β€35% on optimal GDMT for β₯3 months and life expectancy >1 year (Class I for ischemic; 2a for non-ischemic).
- Cardiogenic shock (cold and wet): inotropes (dobutamine/milrinone) for low CO; consider mechanical support (IABP, Impella, ECMO). Refer to advanced HF center.
Wet/Dry Γ Warm/Cold
ARNI Β· BB Β· MRA Β· SGLT2i
Key Trials
PARADIGM-HFNEJM 2014Sacubitril-valsartan vs enalapril in HFrEF (n=8,442) β 20% reduction in CV death/HF hospitalization (HR 0.80); 16% all-cause mortality reduction. Established ARNI as preferred RAAS blocker.
DAPA-HFNEJM 2019Dapagliflozin vs placebo in HFrEF (n=4,744, with and without DM) β 26% reduction in worsening HF or CV death. SGLT2i benefit independent of diabetes.
EMPEROR-ReducedNEJM 2020Empagliflozin in HFrEF β 25% reduction CV death/HF hospitalization. Class effect of SGLT2i in HFrEF confirmed.
EMPEROR-Preserved & DELIVERNEJM 2021/2022Empagliflozin and dapagliflozin reduced HF hospitalization in HFpEF and HFmrEF β first proven therapies in preserved EF. Drove 2023 AHA focused update.
STRONG-HFLancet 2022Rapid up-titration of GDMT post-discharge (within 2 weeks) vs usual care β 34% reduction in 180-day HF readmission/death. Early high-intensity titration is safe and effective.
DOSENEJM 2011High-dose vs low-dose IV furosemide in ADHF β high-dose led to greater symptomatic relief and weight loss with transient β Cr but no harm. Basis for β₯2Γ home oral dose IV.
Learning Objective: Diagnose DKA, fix the three problems (volume, acid-base/ketones, electrolytes β especially K) in the right order, and avoid the classic transition errors.
Diagnostic Triad
- Hyperglycemia >200 mg/dL (may be lower in euglycemic DKA, e.g., on SGLT2i, pregnancy, fasting).
- Ketosis: Ξ²-hydroxybutyrate β₯3 mmol/L (preferred) or moderate/large urine ketones.
- Metabolic acidosis: pH <7.3 or HCOβ <18, anion gap >10β12.
Find the Trigger β "5 I's"
- Infection (UTI, pneumonia)
- Infarction (MI, stroke, mesenteric)
- Insulin non-compliance / pump failure
- Iatrogenic (steroids, SGLT2i, antipsychotics)
- Initial presentation of T1DM / pregnancy
Step-by-Step Management
| Step | Action | Key Number |
|---|
| 1. Fluids | 0.9% NS 500β1000 mL/h Γ 2β4 h, then switch to 0.45% NS once euvolemic. Add D5 when glucose <250. | Replace ~50% deficit in first 12 h |
| 2. Potassium | Check K before insulin. K <3.3 β hold insulin, give K. K 3.3β5.2 β add 20β30 mEq/L. K >5.2 β no K, recheck q2 h. | Target K 4β5 |
| 3. Insulin | Regular insulin 0.1 U/kg/h IV (skip bolus per 2024 consensus). Goal: glucose β 50β75 mg/dL/h. | Continue until AG closed |
| 4. Bicarbonate | Only if pH <7.0 with hemodynamic instability. Otherwise no benefit. | Rarely needed |
| 5. Transition | Overlap SC long-acting insulin with IV drip for β₯2 h before stopping drip. Patient must be eating/AG closed/HCOβ β₯18. | Don't drop the drip too early |
Clinical Pearls
- Resolution criteria: glucose <200 AND two of: HCOβ β₯15, venous pH >7.3, AG β€12. Ketones lag β track AG, not urine ketones.
- Euglycemic DKA on SGLT2i: hold the SGLT2i, treat with insulin + dextrose ("two-bag" approach with D10 + NS to allow continued insulin while maintaining glucose).
- HHS (mostly T2DM): glucose >600, osm >320, minimal ketosis, pH >7.3 β same fluid/K/insulin principles but slower, prolonged correction; mortality higher.
- Cerebral edema is the major peds concern β avoid overly rapid fluid/glucose correction in children.
- Pseudohyponatremia: corrected Na = measured Na + 1.6 Γ (glucoseβ100)/100. Watch for hypophosphatemia and hypomagnesemia during treatment.
- Mild DKA can often be treated with subcutaneous rapid-acting insulin (lispro/aspart) on the floor β avoids ICU.
Fluids β K β Insulin β Bicarb? β Transition
Close the gap, then taper
Key Trials & Evidence
Umpierrez et al.Diabetes Care 2004 / Am J Med 2004Subcutaneous lispro/aspart q1β2 h on the floor was equivalent to IV regular insulin in the ICU for mild-to-moderate DKA β reduced cost and ICU utilization.
Goyal et al.J Emerg Med 2010Skipping the IV insulin bolus produced equivalent glucose decline and time to AG closure β basis for current ADA recommendation against routine bolus.
ADA/EASD ConsensusDiabetes Care 2024Updated diagnostic thresholds (Ξ²-OHB β₯3.0, pH <7.3, HCOβ <18) and severity grading. Reaffirmed insulin 0.1 U/kg/h without bolus and structured 2-bag protocols.
Chua et al.Crit Care 2011Bicarbonate therapy in DKA with pH 6.9β7.1 did not improve outcomes; routine use abandoned outside extreme acidosis.
SGLT2i euDKA registriesFDA, BMJ Open Diabetes 2020Euglycemic DKA reported across SGLT2i agents, particularly with surgery, illness, low carb intake β informed perioperative SGLT2i hold (β₯3 days) recommendation.
Learning Objective: Decide site of care, choose empiric antibiotics, and know when (and when not) to cover for MRSA/Pseudomonas.
Diagnose
- Cough, fever, sputum, dyspnea, pleuritic pain + new infiltrate on imaging.
- Sputum & blood cultures: in severe CAP, prior MRSA/Pseudomonas, or empirically treating for them.
- Procalcitonin should not be used to decide whether to start antibiotics in CAP.
- No routine "HCAP" category β replaced by risk-factor-based MRSA/Pseudomonas coverage.
Site of Care: CURB-65
- Confusion Β· Urea >19 mg/dL (BUN >7 mmol/L) Β· RR β₯30 Β· BP (SBP <90 / DBP β€60) Β· age β₯65
- 0β1: outpatient Β· 2: consider admission Β· β₯3: admit, consider ICU.
- Use clinical judgment + PSI/SMART-COP for ICU triage.
Empiric Antibiotics (ATS/IDSA 2019)
| Setting | Regimen |
|---|
| Outpatient, healthy | Amoxicillin 1 g TID or doxycycline or macrolide (only if local pneumococcal resistance <25%) |
| Outpatient w/ comorbidities | Ξ²-lactam (amox/clav, cefpodoxime) + macrolide/doxy or respiratory fluoroquinolone |
| Inpatient, non-severe | Ξ²-lactam (ceftriaxone, ampicillin-sulbactam) + macrolide or respiratory FQ monotherapy |
| Inpatient, severe | Ξ²-lactam + macrolide (preferred) or Ξ²-lactam + respiratory FQ |
| Add MRSA cover | Vancomycin or linezolid β only if prior MRSA, recent hospitalization + IV antibiotics, or severe CAP with risk factors |
| Add Pseudomonas cover | Pip-tazo, cefepime, meropenem β same trigger criteria |
Clinical Pearls
- Duration: minimum 5 days; stop when afebrile 48 h and clinically stable. Most uncomplicated CAP = 5 days. Pseudomonas/MRSA: 7 days.
- Steroids in severe CAP: hydrocortisone 200 mg/d Γ 4β8 d significantly reduced mortality in CAPE COD β consider for ICU-level CAP without contraindication (active infection like flu/aspergillus = caution).
- Influenza/COVID coinfection: add oseltamivir during flu season; do not delay antibiotics in bacterial pneumonia.
- Follow-up imaging: only if symptoms persist or in patients at risk for malignancy. Routine repeat CXR not recommended.
- Vaccinate on discharge: pneumococcal (PCV20 or PCV15+PPSV23), influenza, COVID, RSV (β₯60), Tdap.
- Aspiration pneumonia: empiric anaerobic coverage (e.g., amox-clav, ampicillin-sulbactam) not required for most β recent evidence supports standard CAP regimens unless empyema/lung abscess.
CURB-65
No more "HCAP"
Key Trials
CAPE CODNEJM 2023Hydrocortisone 200 mg/d in severe CAP (n=800) β 28-d mortality 6.2% vs 11.9% (HR 0.46). Major shift toward steroid use in severe CAP.
Uranga et al.JAMA IM 20165-day antibiotic course (if afebrile 48 h, clinically stable) was non-inferior to physician-determined duration β underpins minimum 5-day rule.
ProHOSP / ProACTJAMA 2009 / NEJM 2018Procalcitonin-guided antibiotic algorithms safely reduced antibiotic exposure in some settings, but no mortality benefit in US ED population β guidelines don't recommend PCT to start antibiotics.
Aliberti / Webb HCAP studiesClin Infect Dis 2013β2018HCAP definition over-treated patients without improving outcomes; risk-factor-based MRSA/Pseudomonas screening more accurate β eliminated HCAP in 2019 ATS/IDSA.
Postma et al.NEJM 2015Ξ²-lactam monotherapy non-inferior to Ξ²-lactam + macrolide or fluoroquinolone in non-severe inpatient CAP β supports stepwise approach.
Learning Objective: Stage AKI by KDIGO criteria, work through pre-renal / intrinsic / post-renal, and know absolute indications for emergent dialysis.
KDIGO Definition
- β SCr β₯0.3 mg/dL within 48 h, or
- β SCr β₯1.5Γ baseline within 7 days, or
- UOP <0.5 mL/kg/h Γ 6 h.
- Stage 1: 1.5β1.9Γ Β· Stage 2: 2β2.9Γ Β· Stage 3: β₯3Γ or SCr β₯4 or RRT.
Categorize: Pre / Intrinsic / Post
- Pre-renal (60%): hypovolemia, sepsis, HF, cirrhosis, NSAIDs/ACEi. FENa <1%, BUN/Cr >20.
- Intrinsic: ATN (FENa >2%, muddy brown casts), AIN (eos, drug β PPIs, Ξ²-lactams, NSAIDs), GN (RBC casts), vascular.
- Post-renal: obstruction β get a bladder scan and renal ultrasound.
Workup
- UA + microscopy, urine Na/Cr, FENa (FEUrea if on diuretic).
- Bladder scan, renal US (rule out obstruction).
- Med review: hold nephrotoxins (NSAIDs, ACEi/ARB, contrast, aminoglycosides). Renally dose all meds.
- If GN suspected: complement, ANA, ANCA, anti-GBM, SPEP/UPEP, HIV/HCV, biopsy.
Emergent Dialysis β "AEIOU"
- Acidosis (refractory, pH <7.1)
- Electrolytes (refractory hyperkalemia)
- Ingestions (toxic alcohols, salicylates, lithium)
- Overload (refractory pulmonary edema)
- Uremia (pericarditis, encephalopathy, bleeding)
Clinical Pearls
- Hyperkalemia order: stabilize membrane (calcium gluconate 1β2 g) β shift K (insulin 10 U + D50, Ξ²-agonist, bicarb if acidotic) β remove K (loop diuretic, K-binder like patiromer/SZC, dialysis). Calcium does not lower K β get an ECG.
- Contrast-associated AKI risk is lower than historically taught β do not withhold indicated contrast in critical illness; isotonic IVF is preferred prophylaxis (PRESERVE trial).
- STARRT-AKI: no benefit to "early" RRT initiation in absence of urgent indications. Wait for AEIOU.
- Cardiorenal syndrome: diurese aggressively (loop Β± thiazide, "sequential nephron blockade") even with rising Cr β congestion drives the AKI.
- Hepatorenal syndrome looks like pre-renal but doesn't respond to volume β treat with vasoconstrictor + albumin (see Talk 9).
- AKI markedly increases risk of CKD β arrange nephrology follow-up post-discharge; resume renin-angiotensin therapy when stable.
Pre Β· Intrinsic Β· Post
AEIOU for HD
Key Trials
PRESERVENEJM 2018IV bicarbonate vs saline + N-acetylcysteine vs placebo in 5,177 high-risk CKD patients getting angiography β no difference. Killed the routine "renal protection cocktail." Use isotonic crystalloid alone.
STARRT-AKINEJM 2020Accelerated vs standard RRT initiation in severe AKI (n=3,019) β no mortality benefit; accelerated arm had more dialysis dependence at 90 days. Wait for clinical indication.
AKIKINEJM 2016Confirmed STARRT-AKI's finding earlier: early vs delayed RRT showed no mortality difference; nearly half in delayed arm never needed RRT.
SMARTNEJM 2018Balanced crystalloids (LR/Plasma-Lyte) vs 0.9% saline in 15,802 ICU patients β reduced major adverse kidney events (14.3% vs 15.4%). Avoid hyperchloremic acidosis from saline.
BaSICS / PLUSJAMA 2021 / NEJM 2022Confirmed and refined SMART β balanced crystalloids preferred for resuscitation in critical illness, especially in sepsis and TBI subgroups.
EMPA-KIDNEYNEJM 2023Empagliflozin in CKD (with or without DM, with or without albuminuria) β 28% reduction in CKD progression/CV death. SGLT2i now a foundational kidney-protective therapy.
Learning Objective: Recognize sepsis early, execute the Hour-1 bundle, and know when to escalate to vasopressors and steroids.
Definitions (Sepsis-3)
- Sepsis: life-threatening organ dysfunction from dysregulated host response β SOFA β β₯2 with suspected infection.
- Septic shock: sepsis + vasopressor requirement to keep MAP β₯65 AND lactate >2 despite resuscitation.
- Screening: qSOFA (RR β₯22, AMS, SBP β€100) or NEWS β qSOFA is for screening, not diagnosis.
Hour-1 Bundle
- Measure lactate (re-measure if >2).
- Blood cultures Γ 2 before antibiotics (do not delay abx >45 min).
- Broad-spectrum antibiotics within 1 h for septic shock; within 3 h for possible sepsis without shock.
- 30 mL/kg crystalloid for hypotension or lactate β₯4 (balanced crystalloid preferred).
- Vasopressors if MAP <65 after fluids β start norepinephrine first (peripheral access OK to start).
Beyond the First Hour
- Add vasopressin (0.03 U/min) when norepi >0.25β0.5 Β΅g/kg/min.
- Hydrocortisone 200 mg/d if persistent shock on pressors (Class 2b).
- Source control ASAP (drain abscess, remove infected line, decompress obstructed urinary/biliary tract).
- Targets: MAP β₯65, normalizing lactate, UOP >0.5 mL/kg/h, mental status improving.
Antibiotic Pearls
- Empiric coverage = source-directed: think pulmonary, urinary, abdominal, skin/soft tissue, line, CNS.
- Default broad: vancomycin + pip-tazo or cefepime. Add anaerobic coverage for intra-abdominal source.
- De-escalate based on cultures within 48β72 h. Daily review of antibiotic necessity.
- Procalcitonin can guide de-escalation β never the decision to start.
Clinical Pearls
- Balanced crystalloids (LR, Plasma-Lyte) β₯ 0.9% NS in critically ill patients (SMART, BaSICS, PLUS).
- "Fluid responsiveness" matters more than blindly giving 30 mL/kg in patients with HF/CKD β consider passive leg raise, IVC variation, dynamic indices.
- Albumin reasonable adjunct in patients receiving large volumes of crystalloid (SAFE, ALBIOS β neutral but safe).
- Mortality drops with each hour antibiotics are not delayed in septic shock β get cultures fast, but do not let them delay therapy.
- Stress-dose steroids: hydrocortisone 200 mg/d IV (50 mg q6 h or continuous) in pressor-dependent septic shock. APROCCHSS adds fludrocortisone 50 Β΅g PO/d.
- VTE prophylaxis, glucose 140β180, lung-protective ventilation (Vt 6 mL/kg IBW, plateau <30) all part of the bundle.
- Re-evaluate antibiotics daily β narrow once organism known; stop if no infection identified after 48β72 h.
Lactate Β· Cultures Β· Abx Β· Fluids Β· Pressors
Norepi first
Key Trials
ARISE / ProCESS / ProMISeNEJM 2014β2015Three large RCTs across 3 continents: protocolized "Early Goal-Directed Therapy" (Rivers) was not superior to usual care β simplified the bundle and dropped CVP/ScvOβ targets.
ADRENALNEJM 2018Hydrocortisone 200 mg/d in septic shock (n=3,800) β no mortality benefit at 90 d, but faster shock resolution and shorter ICU stay.
APROCCHSSNEJM 2018Hydrocortisone + fludrocortisone in septic shock β 90-d mortality 43.0% vs 49.1% (RR 0.88). Established add-on steroids in severe shock.
CLOVERSNEJM 2023Restrictive (early pressors) vs liberal (more fluid) strategy in septic shock β no 90-d mortality difference. Either approach acceptable; tailor to patient.
SMARTNEJM 2018Balanced crystalloids reduced major adverse kidney events vs saline in critically ill (see also Talk 5). Particularly relevant in sepsis.
VICTAS / VITAMINSJAMA 2020 / 2020Vitamin C + thiamine + hydrocortisone "Marik cocktail" β no benefit. Cooled enthusiasm for high-dose vitamin C in sepsis.
Learning Objective: Recognize and grade an AECOPD, deliver the bronchodilatorβsteroidβantibiotic core, and know when to escalate to NIV.
Recognize
- Anthonisen criteria (cardinal symptoms): β dyspnea, β sputum volume, β sputum purulence.
- Triggers: viral (rhinovirus, influenza, RSV, COVID) and bacterial (H. influenzae, S. pneumoniae, M. catarrhalis; Pseudomonas if severe/frequent abx).
- Workup: ABG, CXR, ECG, BNP, troponin, viral panel β always rule out PE, MI, HF, pneumothorax.
Severity (GOLD 2025)
- Mild: SABA only.
- Moderate: SABA + oral steroids Β± antibiotics.
- Severe: requires hospitalization or ED visit; ABG with respiratory acidosis.
- Use the new Rome severity classification: dyspnea (VAS), RR, HR, SpOβ/FiOβ, CRP, ABG.
Treatment Core β "ABCs of COPD"
- Albuterol + ipratropium nebs q1β4 h.
- Steroids: prednisone 40 mg PO Γ 5 days (REDUCE trial β no benefit beyond 5 d).
- Antibiotics if β₯2 cardinal symptoms with purulence, or mechanical ventilation: azithromycin / doxycycline / amox-clav Γ 5 d. Cover Pseudomonas if frequent exacerbations or recent abx.
- Controlled Oβ: target SpOβ 88β92% β avoid hyperoxia (COβ retention).
Escalation
- NIV (BiPAP) for hypercapnic respiratory failure (pH <7.35, PaCOβ >45) β reduces intubation and mortality (Class I).
- Intubate if: failure of NIV, AMS, hemodynamic instability, copious secretions, severe acidosis (pH <7.25).
- Prevent next exacerbation: smoking cessation, vaccines (flu, COVID, pneumococcal, RSV, Tdap), pulm rehab, optimize inhalers (LAMA/LABA Β± ICS).
Clinical Pearls
- Don't be afraid of oxygen β but titrate. Hypoxia kills faster than hypercapnia. AVOID Venturi-based runaway FiOβ in COβ retainers.
- Frequent exacerbator phenotype (β₯2/yr or 1 hospitalization) β escalate to triple therapy (LABA/LAMA/ICS) per GOLD; mortality benefit shown with budesonide-containing triple (ETHOS).
- Consider azithromycin prophylaxis 250 mg daily in select non-smokers with frequent exacerbations despite optimal therapy (Albert NEJM 2011).
- Add eosinophil count: peripheral eos β₯300 favors ICS-responsive phenotype; eos <100 β ICS unlikely to help and may β pneumonia risk.
- Pulmonary rehab within 4 weeks of hospitalization reduces readmission and mortality (Class I).
- Long-term Oβ if PaOβ β€55 or SpOβ β€88% at rest β only intervention besides smoking cessation proven to reduce mortality in COPD.
SABA Β· Steroids Β· Antibiotics Β· BiPAP
SpOβ 88β92%
Key Trials
REDUCEJAMA 20135 days vs 14 days of prednisone 40 mg in AECOPD β non-inferior re-exacerbation; less steroid exposure. Basis for short-course steroids.
Plant et al. (BiPAP)Lancet 2000NIV in hypercapnic AECOPD on the ward β reduced intubation (15% vs 27%) and in-hospital mortality (10% vs 20%). Use early in pH 7.25β7.35.
Anthonisen criteriaAnn Intern Med 1987Original RCT defining cardinal symptoms (dyspnea, sputum volume, purulence) β antibiotics benefit those with β₯2. Still the basis of antibiotic decision today.
IMPACTNEJM 2018Triple therapy (fluticasone/umeclidinium/vilanterol) vs LAMA/LABA β fewer moderate-severe exacerbations; mortality signal favoring triple.
ETHOSNEJM 2020Triple ICS/LAMA/LABA (budesonide-based) vs LAMA/LABA β 49% reduction in all-cause mortality at higher ICS dose. Confirmed mortality benefit of triple therapy.
Albert (Macrolide)NEJM 2011Daily azithromycin 250 mg in COPD patients with prior exacerbation β reduced exacerbation frequency (HR 0.73). Watch for QTc prolongation and hearing loss.
Learning Objective: Resuscitate first, localize the bleed, give the right empiric drug for the suspected etiology, and know endoscopy timing.
Localize
- UGIB (proximal to ligament of Treitz): hematemesis, coffee-ground emesis, melena, BUN/Cr >30. Common: PUD, varices, Mallory-Weiss, esophagitis, malignancy, AVM.
- LGIB: hematochezia (but brisk UGIB can present as hematochezia + shock β always consider NG lavage or EGD first if unstable).
- Common LGIB: diverticulosis, angiodysplasia, ischemic colitis, hemorrhoids, malignancy, post-polypectomy.
Risk Stratify
- Glasgow-Blatchford for UGIB: score 0β1 β outpatient management possible.
- Oakland score for LGIB: β€8 may be safe for discharge.
- Predictors of severe bleed: hemodynamic instability, ongoing bleeding, transfusion need, low Hb, comorbidities, anticoagulation.
Resuscitation & Empiric Therapy
| Step | Action |
|---|
| Access | 2 large-bore (β₯18 g) IVs. Type & cross. CBC, BMP, LFTs, coags, lactate. |
| Fluids | Crystalloid resuscitation. Mass transfusion protocol if unstable. |
| Transfuse RBCs | Restrictive Hb threshold <7 g/dL (target 7β9). <8 in active CV disease. Outperforms liberal in stable UGIB (Villanueva NEJM). |
| Platelets / FFP / PCC | Plt <50 if active bleed. Reverse warfarin with 4F-PCC + vit K. Reverse DOACs (idarucizumab for dabi, andexanet for FXa). |
| Empiric UGIB | PPI bolus + drip (esomeprazole/pantoprazole 80 mg β 8 mg/h). Pre-endoscopy erythromycin 250 mg IV 30β90 min before EGD (clears stomach). |
| If cirrhosis / variceal suspected | Octreotide 50 Β΅g bolus β 50 Β΅g/h Γ 3β5 d. Ceftriaxone 1 g IV Γ 7 d (reduces SBP, mortality). Consider NSBB hold during acute bleed. |
| Endoscopy timing | UGIB: within 24 h. Variceal: within 12 h. Unstable: after resuscitation. LGIB: colonoscopy after prep; CT angio first if ongoing bleeding/unstable. |
Clinical Pearls
- Don't over-resuscitate variceal bleed β aim Hb ~7 to avoid increasing portal pressure.
- Consider early TIPS within 72 h in high-risk variceal bleeders (Child-Pugh B with active bleeding at endoscopy or Child-Pugh C β€13) β reduces rebleeding and mortality.
- Restart anticoagulation as soon as hemostasis is durable β usually ~7 days, balanced against thrombotic risk; resume DOACs over warfarin where possible.
- ASA for secondary CV prevention should be resumed within ~3β5 days after hemostasis (don't permanently stop) β withdrawal triples MACE risk (Sung 2010).
- Stigmata of recent bleeding on EGD (Forrest classification): active bleeding, visible vessel, adherent clot β endoscopic hemostasis (clip/cautery/injection) + IV PPI 72 h.
- LGIB workup if colonoscopy negative in ongoing bleed: tagged RBC scan, CT angio, or push enteroscopy/capsule for small bowel sources.
- Reverse anticoagulation cautiously: 4F-PCC for warfarin, idarucizumab (dabigatran), andexanet alfa (apixaban/rivaroxaban β variable availability). Vitamin K for warfarin always added.
Resuscitate β Localize β Drug β Scope
Hb < 7 transfuse
Key Trials
VillanuevaNEJM 2013Restrictive (Hb <7) vs liberal (Hb <9) transfusion in 921 UGIB patients β restrictive improved 6-week survival (95% vs 91%) and lowered rebleeding. Transformed transfusion thresholds.
TRIGGERLancet 2015Cluster RCT in UK confirming feasibility and safety of restrictive Hb <8 strategy in UGIB β supports restrictive approach broadly.
Lau (Pre-EGD PPI)NEJM 2007High-dose IV PPI before EGD in UGIB β reduced active bleeding stigmata at endoscopy and need for endoscopic therapy. Doesn't reduce rebleeding/mortality.
Early TIPS (GarcΓa-PagΓ‘n)NEJM 2010Pre-emptive TIPS within 72 h in high-risk variceal bleed β 1-year survival 86% vs 61%. Drove early-TIPS recommendation in AASLD/Baveno.
Sort (SBP albumin)NEJM 1999Albumin 1.5 g/kg + 1 g/kg in SBP β reduced renal failure (10% vs 33%) and in-hospital mortality (10% vs 29%). Key to current SBP protocol.
Chavez-Tapia (Antibiotics in cirrhosis GIB)Cochrane 2010Prophylactic antibiotics in cirrhotic patients with GI bleeding β reduced bacterial infection, rebleeding, and mortality. Ceftriaxone 1 g IV Γ 7 d standard.
Learning Objective: Recognize and treat the four classic decompensations β variceal bleed, ascites/SBP, hepatic encephalopathy, and hepatorenal syndrome.
Decompensations
- Variceal hemorrhage
- Ascites & SBP
- Hepatic encephalopathy
- Hepatorenal syndrome (HRS-AKI)
- Each carries dramatically worse prognosis β assess for transplant eligibility (MELD 3.0, Na included).
Ascites & SBP
- Diagnostic paracentesis on every admission and any clinical deterioration.
- SAAG β₯1.1 = portal HTN. Total protein <1 β SBP risk.
- SBP: ascitic PMN β₯250 β ceftriaxone 2 g IV Γ 5 d + albumin 1.5 g/kg day 1, 1 g/kg day 3 (reduces HRS & mortality).
- Diuretics: spironolactone + furosemide (100:40 ratio). Salt restriction <2 g/d. Avoid NSAIDs/ACEi.
Hepatic Encephalopathy
- Triggers: infection, GIB, constipation, dehydration, electrolytes, sedatives, TIPS, AKI.
- Lactulose titrated to 2β3 soft stools/day (1st line).
- Rifaximin 550 mg BID for recurrence prevention (HE-2 trial).
- Check ammonia is not diagnostic β treat clinically. Identify and reverse precipitant.
HRS-AKI
- AKI in cirrhosis with no other cause; bland UA, FENa <1%, no improvement with 48 h albumin challenge (1 g/kg/d).
- Terlipressin + albumin (CONFIRM trial) β first-line in US since 2022.
- Alternatives: norepinephrine + albumin, or midodrine + octreotide + albumin (outside ICU).
- Definitive treatment = liver transplant.
Clinical Pearls
- "Bad meds in cirrhosis": NSAIDs, aminoglycosides, IV contrast (relative), benzos (use sparingly β prefer oxazepam/lorazepam, no active metabolites), high-dose acetaminophen (limit 2 g/d if active drinker β but acetaminophen is preferred analgesic over NSAIDs).
- Vaccinate: Hep A & B, pneumococcal, flu, COVID, RSV, Tdap. All cirrhotics should also receive a one-time PPSV23 + age-appropriate PCV.
- HCC screening: abdominal US Β± AFP every 6 months in all cirrhotics β improves survival when caught early.
- Refer for transplant at MELD 3.0 β₯ 15, refractory ascites, hepatopulmonary syndrome, recurrent SBP, HRS, or recurrent variceal bleeding despite TIPS.
- SBP prophylaxis: norfloxacin/cipro daily for prior SBP; ceftriaxone Γ 7 d during any GIB; consider in low-protein ascites + advanced disease.
- Coagulopathy in cirrhosis is "rebalanced" β INR doesn't reflect bleeding risk; prophylactic FFP not recommended.
Tap every admit
Albumin saves kidneys
Key Trials
Sort (SBP)NEJM 1999Cefotaxime + IV albumin vs cefotaxime alone for SBP β reduced renal failure (10% vs 33%) and in-hospital mortality (10% vs 29%). Albumin (1.5 g/kg D1, 1 g/kg D3) is now standard.
HE-2 (Bass)NEJM 2010Rifaximin 550 mg BID for HE recurrence prevention (n=299) β 58% reduction in HE breakthrough (HR 0.42). Standard secondary prophylaxis with lactulose.
CONFIRMNEJM 2021Terlipressin + albumin vs placebo + albumin in HRS-1 β HRS reversal 29% vs 16%. Led to 2022 FDA approval. Watch for respiratory failure and ischemia.
ANSWERLancet 2018Long-term IV albumin (40 g BIW for 18 months) in decompensated cirrhosis with ascites β reduced 18-month mortality (38%β22%) and complications. Use varies by region.
Moreau (CANONIC, ACLF)Gastroenterology 2013Defined Acute-on-Chronic Liver Failure as a distinct syndrome with high short-term mortality. Drove early ICU triage and transplant evaluation.
Early TIPS (GarcΓa-PagΓ‘n)NEJM 2010See Talk 8 β pre-emptive TIPS in high-risk variceal bleed reduced rebleeding and mortality.
Learning Objective: Decide rate vs rhythm control, choose the right rate-control drug for the comorbidity, and stratify stroke and bleeding risk for anticoagulation.
First Question: Stable?
- Unstable (hypotension, ischemia, decompensated HF, AMS) β synchronized cardioversion (Class I).
- Stable: identify and treat reversible triggers β "PIRATES" (PE, Ischemia, Resp/sepsis, Anemia/Atrial enlargement, Thyroid, Ethanol, Sepsis/Sympathetic).
- Always look for new HF, thyroid disease, OSA, infection, pulmonary disease, electrolytes.
Rate Control (target HR <110 lenient, <80 strict)
- Beta-blockers (metoprolol, esmolol) β first line.
- Non-DHP CCBs (diltiazem, verapamil) β preferred in COPD, asthma; avoid in HFrEF.
- Digoxin β adjunct in HFrEF, hypotensive patients (slow onset).
- Amiodarone β reserve for refractory rate control or critically ill (technically rhythm control).
Rhythm Control
- Favored in: symptomatic, young, HFrEF (CASTLE-AF), first episode, athlete, failed rate control.
- Cardioversion: if AFib <48 h or on therapeutic AC β₯3 wk or TEE rules out clot.
- 2023 guidelines emphasize early rhythm control within 1 year (EAST-AFNET 4) β reduces CV events.
- Catheter ablation Class I for symptomatic paroxysmal AFib refractory to drugs; Class 2a for persistent.
Anticoagulation
- CHAβDSβ-VASc (men β₯2, women β₯3) β anticoagulate. Score 1 (men) or 2 (women) β consider.
- DOACs > warfarin in non-valvular AFib (Class I).
- Warfarin still preferred in moderate-severe mitral stenosis and mechanical valves.
- Use HAS-BLED to identify modifiable bleeding risks β not to withhold AC.
- LAA occlusion (Watchman) for those with high stroke + contraindication to long-term AC.
Clinical Pearls
- 2023 guideline: AFib is now staged (1β4) like cancer/HF β with focus on lifestyle (weight loss to BMI <27, OSA treatment, alcohol <3 drinks/week, aerobic exercise) as primary therapy. LEGACY trial: 10% weight loss β 6Γ more AFib-free survival.
- Don't slow the rate in septic AFib aggressively β fix the underlying problem first; Ξ²-blockers can drop CO.
- Diltiazem drip works fast: 0.25 mg/kg bolus β 5β15 mg/h drip; bridge to PO once controlled.
- WPW + AFib: avoid AV nodal blockers (BB, CCB, digoxin, adenosine) β use procainamide or cardiovert. Wide irregular rhythm = think this.
- "Pill in pocket" approach: flecainide or propafenone PO + AV nodal blocker for select paroxysmal AFib without structural heart disease.
- Reversible AFib: post-op (especially cardiothoracic), thyrotoxicosis-induced, alcohol "holiday heart," sepsis-induced β still anticoagulate based on CHAβDSβ-VASc; high recurrence risk.
Stable? Β· Rate vs Rhythm Β· CHAβDSβ-VASc
Find PIRATES
Key Trials
EAST-AFNET 4NEJM 2020Early rhythm control (within 1 yr of dx) vs usual care in 2,789 patients β 21% reduction in CV death/stroke/HF/ACS hospitalization (HR 0.79). Shifted philosophy toward early rhythm control.
CASTLE-AFNEJM 2018Catheter ablation vs medical therapy in AFib + HFrEF β 38% reduction in death or HF hospitalization (HR 0.62). Class I indication for ablation in this population.
RACE IINEJM 2010Lenient (HR <110) vs strict (HR <80) rate control β non-inferior at 3 years for CV death/morbidity. Drove move to lenient targets in stable patients.
ARISTOTLENEJM 2011Apixaban vs warfarin in non-valvular AFib β fewer strokes (HR 0.79), less major bleeding (HR 0.69), and lower all-cause mortality (HR 0.89). DOACs preferred over warfarin.
RE-LY / ROCKET-AF / ENGAGENEJM 2009β2013Dabigatran, rivaroxaban, edoxaban each non-inferior or superior to warfarin for stroke prevention with similar/less bleeding. Reinforced DOAC class effect.
PROTECT-AF / PREVAILJAMA 2014 / JACC 2014Watchman LAA closure vs warfarin β non-inferior for stroke prevention; option for patients with high stroke risk and contraindication to long-term anticoagulation.
LEGACYJACC 201510% weight loss in obese AFib patients β 6Γ higher AFib-free survival than minimal weight loss. Supports lifestyle as primary therapy in 2023 guideline.
Learning Objective: Predict severity, pick a benzodiazepine strategy, and prevent the lethal complications β DTs, seizures, and Wernicke's.
Timeline
- 6β12 h: minor β tremor, anxiety, insomnia, GI upset, mild autonomic.
- 12β24 h: alcoholic hallucinosis (clear sensorium).
- 24β48 h: withdrawal seizures (generalized tonic-clonic).
- 48β96 h: delirium tremens β confusion, hallucinations, severe autonomic instability. Mortality up to 5%.
Predict Severity β PAWSS
- Prediction of Alcohol Withdrawal Severity Scale, score β₯4 β high risk for severe withdrawal.
- Risk factors: prior DTs/seizures, heavy daily use, prior failed detox, comorbid medical illness, age >65, abnormal labs (BAL on arrival, LFTs).
- Use CIWA-Ar for symptom monitoring (10 items, 0β67). Not for use in delirium/intubated patients.
Treatment Strategy
| Strategy | When to Use | How |
|---|
| Symptom-triggered (preferred) | Mildβmoderate; reliable monitoring | CIWA q1β4 h. Diazepam 10β20 mg or lorazepam 2β4 mg PO/IV when CIWA β₯8β10. |
| Front-loading | Severe withdrawal, prior DTs/seizures | Diazepam 20 mg PO q1β2 h until calm/sedated, then prn. |
| Fixed-schedule | Outpatient or unable to assess CIWA | Diazepam taper over 3β5 d (e.g., 10 mg q6 h Γ 1 d β taper). |
| Refractory DTs | Benzo-resistant after >200 mg diazepam equivalents | Add phenobarbital or propofol in ICU; intubate as needed. Dexmedetomidine for autonomic control (adjunct, not monotherapy). |
Don't Forget β "Banana Bag Plus"
- Thiamine 500 mg IV TID Γ 3 d for suspected Wernicke; then 100 mg/d. Always before glucose.
- Folate 1 mg, multivitamin, replete magnesium, phosphorus, potassium.
- Treat underlying β pancreatitis, hepatitis, infection, head trauma.
- Choice of benzo: lorazepam in liver disease/elderly (no active metabolites); diazepam/chlordiazepoxide for smoother taper otherwise.
Long-Term
- Always offer medications for AUD: naltrexone (1st line, avoid in active opioid use/severe liver dz), acamprosate (preferred in liver dz), disulfiram (selected motivated patients).
- Brief intervention + referral to treatment (SBIRT). Connect to AA/SMART/peer support.
- Address comorbid psychiatric disease β depression, anxiety, PTSD highly prevalent.
Clinical Pearls
- Adequate benzodiazepines save lives in DTs β under-treatment kills more often than over-sedation.
- Phenobarbital is gaining ground β single-dose 10 mg/kg loading or symptom-triggered dosing shortens LOS, reduces ICU need, and reaches both GABA-A and reduces glutamatergic activity. Know your hospital's protocol.
- Don't use antipsychotics alone β they lower seizure threshold and don't address GABA deficit. Adjunct only if hallucinations remain after adequate benzo loading.
- "Wet brain" is preventable: Wernicke triad = ophthalmoplegia, ataxia, encephalopathy β permanent Korsakoff (anterograde amnesia, confabulation) if untreated.
- Outpatient detox is reasonable for low-risk patients: PAWSS <4, no prior DTs/seizures, no severe medical/psych comorbidity, supportive home, can return for daily checks.
- Don't miss alternative diagnoses: sepsis, intracranial bleed (falls common), hypoglycemia, hepatic encephalopathy, hyperthyroidism, sympathomimetic toxicity β all can mimic AWS.
- Address co-occurring tobacco use disorder β high overlap, motivation often comes simultaneously.
PAWSS Β· CIWA
Thiamine before glucose
Key Trials
SaitzJAMA 1994Symptom-triggered (CIWA-driven) vs fixed-schedule chlordiazepoxide in alcohol withdrawal β reduced total benzodiazepine use (100 vs 425 mg) and treatment duration (9 h vs 68 h). Foundational for CIWA-based dosing.
RosensonJ Emerg Med 2013Single IV phenobarbital 10 mg/kg in ED for AWS β reduced ICU admission (8% vs 25%) and rate of complications. Drove protocol changes toward phenobarbital-based pathways.
GoldCrit Care Med 2007Phenobarbital + benzo for severe AWS in ICU β reduced ICU LOS and need for mechanical ventilation vs benzo alone.
COMBINEJAMA 2006Naltrexone + medical management vs placebo in AUD (n=1,383) β naltrexone improved % days abstinent. Established naltrexone as first-line MAT.
Mason (Acamprosate)Cochrane 2010Acamprosate reduced relapse to any drinking (RR 0.86); preferred in liver disease since not hepatically metabolized.
Caine et al. (Wernicke)JNNP 1997Demonstrated under-recognition of Wernicke's; only 16% of confirmed cases had classic triad. Drove low-threshold high-dose IV thiamine.