History: quality of sensation, tempo, positional dependence, exac./allev. factors, exertionCardiopulmonary exam, SaO2, CXR, ECG, ABG, U/S- Predictors of CHF: h/o CHF, PND, S3, CXR w/ venous congestion, AF (AMA 2005;294:1944)- Dyspnea w/ nl CXR: CAD, asthma, PE, PHT, early ILD, anemia, acidosis, NM diseaseBased on results of initial evaluation: PFT, chest CT, TTE, cardiopulmonary testingBNP & NT-proBNP 1 ↑ CHF (also ↑ T in AF, RV strain from PE, COPD flare, PHT, ARDS) - BNP <100 pg/mL to r/o CHF (90% Se), > 400 to r/i (NEM 2002;347:161) - NT-proBNP <300 pg/mL to r/o CHF (99% Se); age-related cut points to r/i:>450 pg/mL (<50 y), > 900 (50-75 y), > 1800 (>75 y) (ЕН 2006:27:330)↑ in chronic HF, ∴ need to compare to known "dry BNP." May be falsely low in obesity.
Spirometry: evaluate for obstructive diseaseFlow-volume loops: diagnose and/or localize obstructionBronchodilator: indicated if obstruction at baseline or asthma clinically suspected Methacholine challenge: helps dx asthma if spirometry nl, > 20% ↓ FEV1 → asthmaLung volumes: evaluate for hyperinflation or restrictive disease including NM causesDLCO: evaluates functional surface area for gas exchange; helps differentiate causes of obstructive and restrictive diseases and screens for vascular disease & early ILD
Definition and epidemiology:- Chronic inflam disorder w/ airway hyperresponsiveness + variable airflow obstruction- Affects 5-10% population; ~85% of cases by age 40 yClinical manifestations - Classic triad = wheezing, cough, dyspnea; others include chest tightness, sputum; symptoms typically chronic with episodic exacerbation- Precipitants (triggers)respiratory irritants (smoke, perfume, etc.) & allergens (pets, dust mites, pollen, etc.) infections (URI, bronchitis, sinusitis)drugs (eg, ASA & NSAIDs via leukotrienes, βB via bronchospasm, MSO4, via histamine) emotional stress, cold air, exercise (increase in ventilation dries out airways)Physical examination:- Wheezing and prolonged expiratory phase- Presence of nasal polyps, rhinitis, rash → allergic component- Exacerbation → ↑ RR, ↑ HR, accessory muscle use, diaphoresis, pulsus paradoxusDiagnostic studies - Spirometry: ↓ FEV1, ↓ FEV1/FVC, coved flow-volume loop; lung volumes: ± ↑ RV & TLC ⊕ bronchodilator response (↑ FEV1 ≥12% & ≥200 mL) strongly suggestive of asthma methacholine challenge (↓ FEV1, ≥20%) if PFTs nI: Se > 90%- Allergy suspected → consider checking serum IgE, eos, skin testing/RASTDdx ("all that wheezes is not asthma...")- Hyperventilation & panic attacks- Upper airway obstruction or inh foreign body; laryngeal/vocal cord dysfxn (eg, 2° to GERD)- CHF ("cardiac asthma"; COPD; bronchiectasis; ILD (including sarcoidosis); vasculitis; PE"Asthma plus" syndromes- Atopy = asthma + allergic rhinitis + atopic dermatitis- Aspirin-exacerbated respiratory disease (Samter's syndrome) = asthma + ASA sensitivity + nasal polyps ( Allergy Clin Immunol 2015;135:676)- ABPA = asthma + pulmonary infiltrates + hypersensitivity to Aspergillus (Chest 2009;135:805) Dx: TIgE to Asperg. & total (> 1000), ↑ Asperg. IgG levels, ↑ eos, central bronchiectasis Rx: steroids ± itra-/voriconazole for refractory cases (NEJM 2000;342:756)- Eosinophilic granulomatosis w/ polyangitis (EGPA, previously Churg-Strauss) = asthma + eosinophilia + granulomatous vasculitis
"Reliever" medications (used prn to quickly relieve sx)- Low-dose inhaled corticosteroids (ICS) + long acting inh β2-agonists (LABA): budesonide-formoterol (NEIM 2019;380:2020)- Short-acting inh β2-agonists (SABA): albuterol Rx of choice- Short-acting inh anticholinergics (ipratropium) ↑ β2-agonists delivery → ↑ bronchodilation"Controller" meds (taken daily to keep control) - ICS Rx of choice. Superior to LAMA if sputum w/ ≥2% eos . PO steroids may be needed for severely uncontrolled asthma; avoid if possible b/c of systemic side effects.- LABA (eg, salmeterol, formoterol) safe & ↓ exacerb. when added to ICS - Long-acting inh antimuscarinics (LAMA; eg, tiotropium, umeclidinium): may consider if sx despite ICS+LABA - Leskotriene receptor antagonists (LTRA): some Pts very responsive, esp. ASA-sens and exercise-induced. Warning for serious neuropsychiatric effects, including suicide.- Nedocromil/cromolyn: limited use in adults. Useful in young Pts, exercise-induced bronchospasm; ineffective unless used before trigger or exercise exposure.Immunotherapies - Allergen ImmunoRx ("allergy shots") may help if sig. allerg. component - Anti-IgE (omalizumab) for uncontrolled mod-to-severe allergic asthma (w/ IgE > 30) on ICS ± LABA (AMA 2017; 318:279); ↓ exacerbations in severe asthma - Anti-IL5 (mepolizumab, reslizumab) ↓ exacerb in severe asthma - Anti-IL5Rα (benralizumab) ↓ steroid use, ↓ exac, in sev asthma w/ eos - Anti-ILARα (dupllumab) blocks IL-4 & IL-13; ↓ exacerb in severe asthma, ↓ steroid use, ↑ FEV1- Anti-TSLP (tezepelumab.ekko) ↓ exacerbations in severe asthma; can use in non-allergic/non-eosinophilic asthma Principles of treatment- Education and avoidance of environmental triggers; yearly flu shot- Use quick-relief rescue medication as needed for all Pts- Goal to achieve complete control = daily sx ≤2/wk, ∅ nocturnal sx or limitation of activity reliever med =2/wk, nl peak expiratory low rate or FEV1; partly controlled = 1-2 of the above present in a wk; uncontrolled = ≥3 of the above present in a wk- Step up treatment as needed to gain control, step down as tolerated- Can abort exacerb by quadrupling ICS if deteriorating control (NEJM 2018:378:902)
History: baseline PEF, steroid requirement, ED visits, hospital admissions, prior intubation - Current exacerbation: duration, severity, potential precipitants, meds used - Risk factors for life-threatening: prior intubation, h/o near-fatal asthma, ED visit/hosp for asthma w/in 1 y, current/recent PO steroids, not using ICS, overdependent on SABA, ⍦, h/o noncompliancePhysical exam: VS, pulm, accessory muscle use, pulsus paradoxus, abdominal paradox - Assess for barotrauma: asymmetric breath sounds, tracheal deviation, subcutaneous air → pneumothorax, precordial (Hamman's) crunch → pneumomediastinumDiagnostic studies: peak expiratory flow (know personal best; <80% personal best c/w poor control, <50% c/w severe exacerbation); SaO2; CXR to r/o PNA or PTX; ABG if severe (low PaCO2 initially; n/ or high PaCO2 may signify tiring)
- Oxygen to keep SaO2 ≥ 93-95%- Inhaled SABA (eg, albuterol) by MDI (4 8 puffs) or nebulizer (2.5-5 mg) q20min- Corticosteroids: prednisone 40-60 mg PO if outPt; methy|pred IV if ED or inPt- Ipratropium MDI (46 pufis) or nebullzer (0.5 mg) 20min if severe (Chest 2002:121.1977)- Reassess after 60-90 min of RxMild-mod exacerbation: cont SABA qlhSev exacerbation: SABA & pratropium gih or cont, if refractory, consider Mg ± heliox- Decide disposition within 4 h of presentation and after 1-3 h of Rx- High-dose steroids: methylpred 125 mg IV qoh (NEJM 1999:340:1941)
- Progressive airflow limitation caused by airway and parenchymal inflammation
- Cigarette smoke (centrilobular emphysema, affects 15-20% of smokers)- Recurrent airway infections- (x1-antitrypsin deficiency: early-onset panacinar emphysema or signif basilar disease, 1-3% of COPD cases. Suspect if age <45, lower lungs affected, extrathoracic manifestations (liver disease [not if heterozygote MZ], FMD, pancreatitis). √ serum A1ATlevel (nb, acute phase reactant).- Low FEV1 in early adulthood associated w/ COPD
- Chronic cough, sputum production, dyspnea; later stages → freq exacerb, AM HA, wt loss- Exacerbation triggers: infection, other cardiopulmonary disease, including PE Infxn: overt tracheobronchitis/pneumonia from viruses, S. pneumoniae, H. influenzae, M. catarrhalis or triggered by changes in strain of colonizers - Physical exam: ↑ AP diameter of chest ("barrel chest"), hyperresonance, ↓ diaphragmatic excursion, ↓ breath sounds, ↑expiratory phase, rhonchi, wheezes during exacerbation: tachypnea, accessory muscle use, pulsus paradoxus, cyanosis- Asthma-COPD overlap syndrome (ACOS; NEJM 2015;373:1241): features of both present. For example: reversibility of airway obstruction w/ bronchodilator in COPD; neutrophilic inflammation in asthma (more classic in COPD); eos in COPD.
- CXR: hyperinflation, flat diaphragms, ± interstitial markings & bullae - PFTs: obstruction: ↓↓ FEV1, ↓ FVC, FEV1/FVC <0.7 (no sig ∆ post bronchodilator), expiratory coving of flow-volume loop; hyperinflation: ↑↑ RV, ↑ TLC, ↑ RV/TLC; abnormal gas exchange: ↓ DLCO (in emphysema)- ABG: ↓ PaO2, ± ↑ PaCO2 (in chronic bronchitis, usually only if FEV1 <1.5 L) and ↓ pH- Screen symptomatic Pts w/ spirometry; don't screen if asx; screen for α1-AT deficiency
- Bronchodilators (1st-line): long-acting muscarinic antag (LAMA), β2-agonists (LABA) LAMA (eg, tiotropium): ↓ exacerb, slows ↓ FEV1, ↓ admit, ↓ resp failure; better than ipratropium or LABALABA: ~11% ↓ in exacerbations, no ↑ in CV events (Lancet 2016;387:1817)LAMA + LABA: ↑ FEV1, ↓ sx vs. either alone (Chest 2014;145:981) and superior to LABA + inh steroid - Corticosteroids (inhaled, ICS): ~11% ↓ in exacerbations & slows ↓ FEV1; no ∆ in mortality. Greatest benefit if eos >300 - "Triple Therapy" (LAMA + LABA +ICS) ↓ exac, ↓ hosp, ↑ PNA - Roflumilast (PDE-4 inhib) + bronchodil: ↑ FEV1, ↓ exacerb in Pts with severe COPD, chronic bronchitis, and a hx of exacerbations- Anti-IL5 (eg, mepolizumab, benralizumab): mixed data on ↓ exacerb in Pts w/ eos - Antibiotics: daily azithro ↓ exacerbations, but not routine (AMA 2014:311:2225)- Oxygen: if PaO2, ≤55 mmHg or SaO2 ≤89% (during rest, exercise, or sleep) to prevent cor pulmonale; only Rx proven to ↓ mortality (Annals 1980,93:391; Lancet 1981;:681); no benefit in Pts w/ moderate hypoxemia (SaO2, 89-93%) (NEJM 2016;375:1617) or nocturnal O2 alone (NEJM 2020;383:1129); unknown benefit of isolated exertional O2 (AJRCCM 2020:202:121).- Night NPPV if recent exacerb & PaCO2 >53 ↓ risk of readmit or death (AMA 2017;317:2177)- Prevention: Flu/Pneumovax; smoking cessation → 50% ↓ in lung function decline (AJRCM 2002;166:675) and ↓ long-term mortality (Annals 2005;142:223)- Rehabilitation: ↓ dyspnea and fatigue, ↑ exercise tolerance, ↑ QoL (NEJM 2009:360:1329)Surgery & bronchoscopic interventions- Lung volume reduction surgery: ↑ exercise capacity, ↓ mortality if FEV1 >20%, upper lobe, low exercise capacity (NEJM 2003:348:2059)- Bronchoscopic lung reduction w/ endobronchial valves or coils: ↑ lung fxn but significant complications (PTX, PNA) (NEJM 2015;373:2325; Lancet 2015;386:1066; JAMA 2016;315:175)- Lung transplant: ↑ QoL and ↓ sx (Lancet 1998;351.24), ? survival benefit (Am J Transplant 20099:1640)
-Assess breathlessness, cough, sputum, exercise capacity & energy (tools such as CAT and mMRC may be used as part of assessment)- Ratio of diam PA/aorta >1 associated with ~3x ↑ risk of exacerbations (NEJM 2012:367:913)- FEV1 stages: I = ≥80%; II = 50-79% (~11% 3-y mort.); III = 30-49% (~15% 3-y mort.); IV = <30% (~24% 3-y mort.)
- Systemic factors (eg, ↑ PCWP, ↓ oncotic pressure) → transudative effusion- Local factors (ie, ∆ pleural surface permeability) → exudative effusion
- Congestive heart failure (40%): 80% bilateral, ± cardiomegaly on CXR occasionally exudative (especially after aggressive diuresis or if chronic)- Constrictive pericarditis (knock on exam, calcification or thickening on imaging)- Cirrhosis ("hepatic hydrothorax"): diaphragmatic pores allow passage of ascitic fluid often right-sided (⅔) & massive (even w/o marked ascites)- Nephrotic syndrome: usually small, bilateral, asymptomatic (r/o PE b/c hypercoag)- Other: PE (usually exudate), malignancy (lymphatic obstruction), myxedema, CAPD
Lung parenchymal infection (25%)- Bacterial (parapneumonic): can evolve along spectrum of exudative (but sterile) → fibropurulent (infected fluid) → organization (fibrosis & formation of rigid pleural peel). Common causes: Strep pneumo, Staph aureus, Strep milleri, Klebsiella, Pseudomonas, Haemophilus, Bacteroides, Peptostreptococcus, mixed flora in aspiration pneumonia.- Mycobacterial: >50% lymphs 80% of the time, ADA >40, pleural bx ~70% Se - Fungal, viral (usually small), parasitic (eg, amebiasis, echinococcosis, paragonimiasis)Malignancy (15%): - Primary lung cancer most common, metastases (esp. breast, lymphoma, etc.), mesothelioma (√ serum osteopontin levels; NEJM 2005;353:15)Pulmonary embolism (10%)- Effusions in ~40% of PEs; exudate (75%) >transudate (25%); hemorrhagic-must have high suspicion b/c presentation highly variableCollagen vascular disease:- RA (large), SLE (small), GPA, EGPAAbdominal disease:- Pancreatitis, cholecystitis, esophageal rupture, abdominal abscess Hemothorax (Hcteff/Hctblood >50%): trauma, PE, malignancy, coagulopathy, leaking aortic aneurysm, aortic dissection, pulmonary vascular malformationChylothorax (triglycerides >110): thoracic duct damage due to trauma, malignancy, LAMOther:- Post-CABG: left-sided; initially bloody, clears after several wks- Dresser's syndrome (pericarditis & pleuritis post-Ml), uremia, post-radiation therapy- Asbestos exposure: benign; ⊕ eosinophils- Drug-induced (eg, nitrofurantoin, methysergide, bromocriptine, amiodarone): ⊕ eos- Uremia; post-XRT; sarcoidosis- Meigs' syndrome: benign ovarian tumor → ascites & pleural effusion- Yellow-nail syndrome: yellow nails, lymphedema, pleural effusion, bronchiectasis
Thoracentesis (ideally U/S guided)- Indications: all effusions >1 cm in decubitus viewif suspect due to CHF, can diurese and see if effusions resolve (75% do so in 48 h); asymmetry, fever, chest pain or failure to resolve → thoracentesis parapneumonic effusions should be tapped ASAP (cannot exclude infxn clinically)- Diagnostic studies: √ total protein, LDH, glucose, cell count w/ differential, Gram stain & culture, pH; remaining fluid for additional studies as dictated by clinical scenario- Complications: PT (5-10%), hemothorax (~1%), re-expansion pulm edema (if >1.5 L removed), spleen/liver lac.; post-tap CR not routinely needed (Annals 1996;124:816)↓ PTX w/U/S and experienced supervisor; even with INR~1.9, on DOAC, or on clopi, risk of bleed low w/U/S & experienced operator (Mayo 2019:94:1535)Transudate vs exudate- Light's criteria: exudate = TPeff/TPserum >0.5 or LDHeff/LDHserum >0.6 or LDHeff > ⅔ ULN of LDHserum; 97% Se, 85% Sp; best Se of all methods; however, will misidentify 25% of transudates as exudates; ∴ if clinically suspect transudate but meets criterion for exudate, confirm w/ test w/ higher Sp- Exudative criteria w/ better Sp: choleff >55 mg/dL (95-99% Sp); choleff >45 mg/dL and LDHeff >200 (98% Sp); choleff/cholserum >0.3 (94% Sp); serum-effusion alb gradient ≤1.2 (92% Sp); serum-effusion TP gradient ≤3.1 (91% Sp)- CHF effusions: TP may ↑ with diuresis or chronicity → "pseudoexudate"; alb gradient ≤1.2, choleff >60 mg/dL (Se 54%, Sp 92%) or clin judgment to distinguish (Chest 2002;122:1524)Complicated vs. uncomplicated parapneumonic- Complicated = ⊕ Gram stain or culture or pH <7.2 or glucose <60- Complicated parapneumonic effusions usually require tube thoracostomy for resolution empyema = frank pus, also needs tube thoracostomy (Thorac CV Surg 2017;153:129)Additional pleural fluid studies (NEJM 2002;346:1971)- NTproBNP ≥1500 pg/mL has 91% Se & 93% Sp for CHF (Am | Med 2004;116:417)- WBC & diff.: exudates tend to have ↑ WBC vs. transudates but nonspecificneutrophils → parapneumonic, PE, pancreatitislymphocytes (>50%) → cancer, TB, rheumatologiceos (>10%) → blood, air, drug rxn, asbestos, paragonimiasis, Churg-Strauss, PE- RBC: Hcteff 1-20% → cancer, PE, trauma; Hcteff/Hctblood > 50% → hemothorax- AFB: yield in TB 0-10% w/ stain, 11-50% w/ culture, ~70% w/ pleural bx adenosine deaminase (ADA): seen w/ granulomas, >70 suggests TB, <40 excludes TB- cytology: ideally ≥150 mL and at least 60 mL should be obtained (Chest 2010;137:68)- glucose: <60 mg/dL → malignancy, infection, RA- amylase: seen in pancreatic disease and esophageal rupture (salivary amylase)- rheumatoid factor, CH50, ANA: limited utility in dx collagen vascular disease- triglycerides: >110 → chylothorax, 50-110 → √ lipoprotein analysis for chylomicrons- cholesterol: >60; seen in chronic effusions (eg, CHF, RA, old TB)- creatinine: effusion/serum ratio >1 → urinothorax- fibulin-3: ↑ plasma and/or effusion levels → mesothelioma (NEJM 2012;367:1417)Chest CT; pleural biopsy; VATSUndiagnosed persistent pleural effusions (Clin Chest Med 2006:27:309)- Transudative: most commonly CHF or hepatic hydrothorax. √ s/s CHF or cirrhosis, NT-proBNPeff; consider intraperitoneal injection of technetium-99m sulfur colloid- Exudative (ensure using Sp test listed above): most commonly malig, empyema, TB, PE. √ s/s malig, chest CT (I+), ADA or IFN-γ release assay; consider thoracoscopy.
Treatment- Symptomatic effusion: therapeutic thoracentesis, treat underlying disease process- Parapneumonic effusion (Chest 2000;118:1158)uncomplicated → antibiotics for pneumonia>½ hemithorax or complicated or empyema → tube thoracostomy (otherwise risk of organization and subsequent need for surgical decortication)loculated→ tube thoracostomy or VATS; intrapleural t-PA + DNase ↓ need for surgery- Malignant effusion: serial thoracenteses vs. tube thoracostomy + pleurodesis (success rate ~80-90%) vs. indwelling pleural catheter, which ↓ hosp days but ↑ adverse events (JAMA 2017;318:1903); systemic steroids & pH <7.2 a/w ↑ pleurodesis failure rate- TB effusions: effusion will often resolve spontaneously; however, treat Pt for active TB- Hepatic hydrothoraxRx: ∆ pressure gradient (ie, ↓ ascitic fluid volume, NIPPV)avoid chest tubes; prn thoracenteses, pleurodesis, TIPS or VATS closure of diaphragmatic defects if medical Rx fails; NIPPV for acute short-term managementspontaneous bacterial empyema (SBEM) can occur (even w/o SBP being present), ∴ thoracentesis if suspect infectiontransplant is definitive treatment and workup should begin immediately
- Superficial thrombophlebitis: pain, tenderness, erythema along superficial vein- Deep venous thrombosis (DVT): Proximal = thrombosis of iliac, femoral, or popliteal veins (nb, "superficial" femoral vein part of deep venous system). Distal = calf veins below knee; lower risk of PE/death than proximal (Thromb Haem 2009;102:493).- Pulmonary embolism (PE): thrombosis originating in venous system and embolizing to pulmonary arterial circulation; 1 case/1000 person y; 250,000/y (Archives 2003;163:1711)
- Virchow's triad for thrombogenesis. Stasis: bed rest, inactivity, CHF, CVA w/in 3 mo, air travel >6 h. Injury to endothelium: trauma, surgery, prior DVT, inflam, central catheter. Thrombophilia: genetic disorders (qv), HIT, OCP, HRT, tamoxifen, raloxifene.- Malignancy (12% of "idiopathic" DVT/PE; Circ 2013;128:2614)- History of thrombosis (greater risk of recurrent VTE than genetic thrombophilia)- Obesity, smoking, acute infection, postpartum
- Calf pain, swelling (>3 cm c/w unaffected side), venous distention, erythema, warmth, tenderness, palpable cord, ⊕ Homan's sign (calf pain on dorsiflexion, seen in <5%)- 50% of Pts with sx DVT have asx PE- Popliteal (Baker's) cyst: may lead to DVT due to compression of popliteal vein
- For UE DVT. + 1 point each for venous cath, local pain, & unilateral edema, -1 if alternative dx. ≤1 = unlikely; ≥2 = likely. U/S if likely or if unlikely but abnl D-dimer (Annals 2014;160.451)
- D-dimer: <500 helps r/o;? use 1000 as threshold if low risk (Annals 2013;158:93)- Compression U/S >95% Se & Sp for sx DVT (lower if asx); survey whole leg if ≥ mod prob
- Dyspnea (~50%), pleuritic chest pain (~40%), cough (~23%), hemoptysis (~8%)- ↑ RR (>70%), crackles (51%), ↑ HR (30%), fever, cyanosis, pleural friction rub, loud P2- Massive: syncope, HoTN, PEA; ↑ JVP, R-sided S3, Graham Steell (PR) murmur
- CXR (limited Se & Sp): 12% nl, atelectasis, effusion, ↑ hemidiaphragm, Hampton hump (wedge-shaped density abutting pleura); Westermark sign (avascularity distal to PE)- ECG (limited Se & Sp): sinus tachycardia, AF; signs of RV strain → RAD, P pulmonale, RBBB, SIQIIITIII & TWIV1-V4 (McGinn-White pattern; Chest 1997;111:537)- ABG: hypoxemia, hypocapnia, respiratory alkalosis, ↑ A-a gradient (Chest 1996;109:78) 18% w/ room air PaO2 85-105 mmHg, 6% w/ nl A-a gradient (Chest 1991;100:598)- D-dimer: high Se, poor Sp (~25%); ELISA has >99% NPV ∴ use to r/o PE if "unlikely" pretest prob (AMA 2006.295:172); cut-off 500 if <50 y, 10x age if ≥50y (AMA 2014311:1117)- Echocardiography: useful for risk stratification (RV dysfxn), but not dx (Se <50%)- VIQ scan: high Se (~98%), low Sp (~10%). Sp improves to 97% for high-prob VQ Use if pretest prob of PE high and CT not available or contraindicated. Can also exclude PE if low pretest prob, low-prob VQ, but 4% false (JAMA 1990;263:2753).- CT angiography (CTA; see Radiology inserts; JAMA 2015:314:74): Se~90% & Sp ~95%; PPV & NPV >95% if imaging concordant w/ clinical suspicion, ≤ 80% if discordant (∴ need to consider both); ~1/4 of single & subseg may be false ⊕; CT may also provide other dx- Lower extremity compression U/S shows DVT in ~9%, sparing CTA
- Thrombophilia workup: √ if ⊕ FH; may be helpful but consider timing as thrombus, heparin and warfarin ∆ results. Useful for relatives, if dx APLAS (given requires warfarin), or if not planning lifelong anticoagulation for Pt- Malignancy workup: 12% Pts w/ "idiopathic" DVT/PE will have malignancy; age-appropriate screening adequate; avoid extensive w/u
Clinical: Simplified PE Severity Index (sPESI) risk factors include age >80 y; h/o cancer; h/o cardiopulm. disease; HR 2110; SBP < 100; SaO2 < 90%Imaging: TTE for RV dysfxn; CTA for RV/LV dimension ratio >0.9. Biomarker: Tn & BNP.Classification (EHJ 2020;41:543)- High risk ("massive"): hemodyn unstable w/ arrest, obstructive shock, or persistent HoTN- Intermediate risk ("submassive"): sPESI ≥1"Intermediate-high" if both RV dysfunction & elevated Tn"Intermediate-low" if either or neither RV dysfunction or elevated Tn- Low risk: clinically stable, sPESI = 0, normal RV function, normal Tn
- Superficial venous thrombosis: elevate extremity, warm compresses, compression stockings, NSAIDs for sx. Anticoag if high risk for DVT (eg, ≥5 cm, proximity to deep vein ≤5 cm, other risk factors) for 4 wk as ~10% have VTE w/in 3 mo (Annals 2010;152:218).- LE DVT: proximal → anticoag; distal → anticoag if severe sx, o/w consider serial imaging over 2wk and anticoag if extends (although if bleeding risk low, many would anticoag).- VE DVT: anticoagulate (same guidelines as LE; NEJM 2011;364:861). If catheter-associated, need not remove if catheter functional and ongoing need for catheter.- PE: anticoagulate (unless isolated subsegmental and risk for recurrent VTE low)
Initiate immediately if high or intermed suspicion but dx test results will take ≥4 h- Either (a) initial parenteral → long-term oral or (b) solely DOAC if no interven. planned- LMWH (eg, enoxaparin 1 mg/kg SC bid or dalteparin 200 lU/kg SC qd) Preferred over UFH (especially in cancer) except: renal failure (CrCl <25),? extreme obesity, hemodynamic instability or bleed risk (Cochrane 2004;CD001100)- IV UFH: 80 U/kg bolus → 18 U/kg/h → titrate to PTT 1.5-2.3 × cntl (eg, 60-85 sec); preferred option when contemplating thrombolysis or catheter-based Rx (qv)- IV direct thrombin inhibitors (eg, argatroban, bivalirudin) used in HIT ⊕ Pts- Fondaparinux: 5-10 mg SC qd (NE|M 2003;349:1695); use if HIT ⊕; avoid if renal failure- Direct oral anticoag (DOAC; NEJM 2010;363:2499; 2012;366: 1287; 2013;369:799 & 1406) Preferred b/c as good/better than warfarin in preventing recurrent VTE w/ less bleedingApixaban (10 mg bid x 7d → 5 bid) or rivaroxaban rivaroxaban mg bid for 1st 3 wk → 20 mg/d) can be given as sole anticoagulant w/ initial loading doseEdoxaban or dabigatran can be initiated after ≥5 d of parenteral anticoag- DVT & low-risk PE w/o comorbidities and able to comply with Rx can be treated as outPt- Generally safe to anticoagulate if platelets >50,000 but contraindicated if <20,000
- Typically TPA 100 mg over 2 h or wt-adjusted TNK bolus; risk of ICH ~2-5%, ↑ w/ age- Consider if low bleed risk w/ acute PE + HoTN or cardiopulm deterioration after anticoag- High-risk PE: ↓ death & recurrent PE each by ~50% (JAMA 2014:311:2414; EH) 2015:36:605)- Intermediate-risk PE: ↓ hemodyn decompensation, ↑ ICH & major bleeding, ↓ mortality in short- but not long-term;? consider if y and/or low bleed risk (JAMA 2014:311:2414)- Half-dose lytic (50 mg or 0.5 mg/kg if <50 kg; 10-mg bolus → remainder over 2h) in ~intermed. PE: ↓ pulm HTN & ? PE or death w/ ≈ bleeding vs. heparin alone (AC 2013:111:273)- DVT: consider if (a) acute (<14 d) & extensive (eg, iliofemoral), (b) severe sx swelling or ischemia, and (c) low bleed
- Catheter-directed pharmacomech: low-dose lytic infused (eg, tPA 1 mg/h for 12-24 hr per catheter) + U/S or mech fragmentation of clot. Consider if hemodyn. compromise or high risk & not candidate for systemic lysis or surgical thrombectomy. Preferred to systemic lytic by some centers. Also consider if intermediate-high risk and evidence of early hemodynamic deterioration (Circ 2014;129:479). Lack of data on hard outcomes.- Catheter-based clot extraction (eg, AngioVac or FlowTriever): ↓ PA pressure- Surgical embolectomy: if large, proximal PE + hemodynamic compromise + contraindic. to lysis; consider in experienced ctr if large prox. PE + RV dysfxn- IVC filter: use if anticoag contraindic.; no benefit to adding to anticoag (JAMA 2015;313:1627) Complications: migration, acute DVT, ↑ risk of recurrent DVT & IVC obstruction (5–18%)
- Superficial venous thrombosis: 4 wk- 1st prox DVT or PE 2° reversible/time-limited risk factor or distal DVT: 3-6 mo- 1st unprovoked prox DVT/PE: ≥3 mo, then reassess; benefit to prolonged Rx. Consider clot, bleed risk, Pt preference, and intensity of Rx when crafting strategy- 2nd VTE event or cancer: indefinite (or until cancer cured) (NEJM 2003;348:1425)
- For nonpregnant Pt without severe renal dysfunction or active cancer → DOAC- For severe renal insufficiency or APLAS → warfarin. Start w/ parenteral anticoag unless ? need for lytic, catheter-based Rx or surg; bridge to INR ≥2 × ≥24 h.- Pregnancy or unable to take oral therapy → LMWH or fondaparinux- Cancer → DOAC (but in Pts w/ UGl cancers, more GI bleeding w/ riva) or LMWH
- After ≥6 mo of anticoag, following regimens compared w/ no extended Rx (or ASA):- Full-dose DOAC: 80-90% ↓ recurrent VTE, 2-5x bleeding, but no signif excess in major bleeding (NEIM 2010;363:2499; 2013;368:699 & 709)- ½ dose apixa or riva: ≥75% ↓ recur. VTE, w/o ↑ bleeding (NEJM 2013:368:699 & 2017;376:1211)
- Postthrombotic syndrome (23-60%): pain, edema, venous ulcers- Recurrent VTE: 1%/y (after 1st VTE) to 5%/y (after recurrent VTE)- Chronic thromboembolic PHT after acute PE ~2-3%, consider thromboendarterectomy- Mortality: ~10% for DVT and ~10-15% for PE at 3-6 mo (Circ 2008:117:1711)
- Pneumonia: s/s (fever, cough, purulent sputum, dyspnea) + new infiltrate on chest imaging- Community-acquired pneumonia (CAP): pneumonia acquired outside of hospital setting- Hospital-acquired pneumonia (HAP): pneumonia acquired ≥48 hrs after hospitalization- Ventilator-associated pneumonia (VAP): pneumonia acquired ≥48 hrs after intubation- Lung empyema: accumulation of pus in pleural space- Lung abscess: parenchymal necrosis with confined cavitation- Aspiration pneumonitis: acute lung injury after inhalation of gastric contents without infection, though bacterial infection can occur within 24-72 hrs of injury
- Sputum Gram stain/Cx: reliable if high quality (ie, sputum not saliva; <10 squam cells/lpf). If bacterial PNA should be purulent (>25 PMN/lpf). Yield ↓ > 10 h after ab (CID 201458:1782).- Procalcitonin: ↑ in acute bacterial (not viral) PNA. Consider stopping abx if levels <0.25 ng/ml (<0.5 ng/mL in ICU Pts) or ↓ ≥80% from peak. ↓ abx exposure by 2-3 d (Lancet ID 2016;16:819 & 2018;18:95). Not validated in immunosuppressed hosts. Levels harder to interpret in CKD. False ⊕ in cardiac arrest, shock, burns, surgery- CXR (PA & lateral)- HIV test (if unknown); MRSA nares swab in HAP/VAP (if ⊖96% NPV for MRSA PNA)Consider in severe disease (otherwise not recommended):Legionella urinary Ag (detects L pneumophila L1 serotype, 60-70% of clinical disease)S. pneumoniae urinary Ag (Se 70%, Sp >90%)Blood cultures (before antibiotics!): ⊕ in ~10% of inPts, depending on pathogen- If clinical suspicion for mTB: (induced) sputum AFB stain X3 q≥8h (wl ≥1 early morning). Mycobact. cx (empiric respiratory isolation while pending): MT DNA PCR if smear ⊕- Viral testing (DFA or CR) on nasopharyngeal swab or sputum- Bronchoscopy: immunosupp., critically ill, failure to respond, suspected PCP, inadequate/⊖ sputum cx (send Gram stain/cx, Legionella cx, fungal cx/wet prep, mycobacterial cx/smear, modified AFB stain, galactomannan)Reasons for failure to improve on initial treatment:- Insufficient time: may take ≥72 h to see improvement (fever persists >4 d in ~20%)- Insufficient drug levels for lung penetration (eg, vanco trough <15-20 ug/mL)- Resistant organisms or superinfxn: eg, MRSA, Pseudo.; consider bronchoscopy- Wrong dx: fungal/viral, chemical pneumonitis, PE, CHF, ARDS, DAH, ILD; consider CT- Parapneumonic effusion/empyema/abscess: if CR ⊖, consider bedside US or CT. If effusion >1 cm, drain & send fluid pH, gluc, Gram stain & Cx.- Metastatic infection (eg, endocarditis, septic arthritis)
- qSOFA predicts poor outcomes, prolonged ICU stay, and in-hospital mortality if >2 of 3: RR>22, AMS, SBP<100 (AMA 2016; 315:801)
- Avoid quinolones if suspect TB. When possible, de-escalate ab based on sensitivities.- Steroids: not unless indicated for shock or COPD exacerbation; may ↓ mortality, mech vent, & ARDS in severe CAP (Cochrane 2017;12:CD007720). Avoid in influenza.- Duration: CAP: 5-7 days, can de-escalate IV abx to PO after clinical improvement. HAP/VAP: 7 days. Empyema/abscess: 2-6 wks based on complexity, drainage.
- All persons >65 or age 19-64 w/ CHF, lung disease, cirrhosis, DM, EtOH, smoker, immunosupp. (eg, ESRD, organ transplant, HIV, leukemia, lymphoma, asplenia)- PCV20 vaccine or PCV15 + PPSV23 1 yr later
- Typical pathogens: Short, mild = rhinovirus, other non-SARS-CoV-2 coronavirus.- Longer, more severe or complicated = influenza, parainfluenza, RSV, adenovirus, metapneumovirus, COVID-19 (vide infra). Can be esp. severe in immunosupp.
- Sx: fever, cough, myalgias, SOB, wheezing, sore throat, rhinorrhea, malaise, confusion- Respiratory viral panel on nasal swab or sputum/BAL; rapid flu nasopharyngeal swab preferred to nasal swab (Se 50-70%, Sp >90%); RT-PCR for flu A/B (>95% Se & Sp)
Influenza (A & B):- Neuraminidase inhib. (eg, oseltamivir); must start w/in 48 h of sx for low-risk; for critically ill or immunosupp., start ASAP even if>48 h. PeramivirIVif unable to tolerate PO.Endonuclease inhib. (baloxavir), superior to oseltamivir in ↓ sx & viral load on 1st day of Rx, but resistance emerging; no data in severe influenza (NEJM 2018; 379:913)RSV: - can consider inhaled ribavirin in immunosupp, but very expensive & rarely used
- Inactivated influenza vaccine: rec for all >6 mo of age.- Isolation, droplet precautions for inpatients strongly recommended- Ppx for high-risk contacts of confirmed influenza: oseltamivir × 7 d or baloxavir single dose
- Person-to-person transmission via respiratory particles; as & pre-s transmission can occur- Incubation period: up to 14 days, median time of 4-5 days from exposure to sx onset
- Ranges from asx to severe illness. Of those with sx, 81% mild-to-moderate, 14% severe (hypoxia), 5% critical (ARDS, shock, multiorgan failure) (AMA 2020:323:13)- Common sx: fever, chills, cough, dyspnea, myalgias, HA, N/V, diarrhea, loss of smell/taste- Risk factors for severe illness: age ≥65, CVD, DM, stroke, lung dx, CKD, obesity
- RT-PCRtesting of nasopharynx, lower respiratory tract, or anterior nares- Rapid antigen testing of anterior nares (less Se than PCR)- CXR: typically bilateral opacities (esp peripheral), can be nl early; consider CT if dx?
- Non-hospitalized: mAb, paxlovid and molnupiravir if risk factors for severe disease- Hospitalized wl suppl O2: dexamethasone ± remdesivir (inhibits vRNA polymerase)- Hospitalized w/ mechanical ventilation or ECMO: dexamethasone + anti IL6 (tocilizumab/sarilumab) or anti JAK (baricitinib/tofacitin) if rapidly ↑ O2 requirement but not intubated- Anticoag. due to high rate of thrombosis; Ppx vs. Rx dosing based on severity and risk
- Vaccines against spike protein highly effective. Infxn may occur but severity much lower.- See CDC website for quarantine guidelines
