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Pulmonary/CC Board Review

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1 Pulmonary/CC Board Review

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3 Thyroid function tests
A 25-year-old woman is evaluated for recurrent episodes of acute dyspnea associated with rapid breathing, tightness in her chest and throat, voice changes, and inspiratory difficulty. When she has these episodes she feels that she “can’t get enough air.” The symptoms typically start and resolve abruptly, and treatment with albuterol provides only minimal relief. On physical examination, her vital signs are normal. Lungs are clear. Spirometry shows an FEV1 of 2.8 L (88% of predicted) and FEV1/FVC ratio of 80%. Which of the following is the most appropriate next diagnostic step? Chest radiography CT scan of the neck Flow volume loops Thyroid function tests Symptoms often begin and end abruptly and do not usually respond to inhaled B agonists VCD the airflow limitation occurs mainly during inspiration Flow volume loops may also be normal when the patient is aymptomatic between episodes

4 Vocal Cord Dysfunction

5 Bronchoscopy with biopsy Inhalation challenge with chlorine
A 35-year-old man is evaluated for episodic wheezing, dyspnea, and cough. Two months ago he had an acute episode of cough, dyspnea, wheezing, and chest tightness within minutes of inhaling high concentrations of ammonia solution after an accidental spill at work. In the emergency department, the chest radiograph was normal, and he received inhaled bronchodilators and a brief course of oral corticosteroids. The patient does not have a history of asthma or allergies and is otherwise healthy and takes no medications. The physical examination is normal. Spirometry shows an FEV1 of 90% of predicted; FEV1/FVC ratio is 82%. Which of the following is the most appropriate next test in this patient’s evaluation? Asthma occuring after an acute, high-level exposure to Chlorine derivative, acids, ammonia, bromie, bleaches, isocyanates, formaldehyde, etc an irritant is called the RADS (reactive airways dysfunction syndrome) Within minutes the patiens develops cough, wheezing, dyspnea, and chest tightness, symtpoms persist for years after exposure Based on history and confirmed with positive methacholine challenge test This is different from occupational asthma Bronchoscopy with biopsy Inhalation challenge with chlorine Methacholine challenge test Spirometry before and after work

6 Asthma- Diagnosis Spiromery shows low FEV1/FVC ratio and reversibility 12% of greater improvement in FEV1 after administration of bronchodilators Next step bronchial challenge test

7 24-Hour esophageal pH monitoring Bronchoscopy CT scan of the chest
A 27-year-old man is evaluated for a 6-month history of cough, which is worse at night and after exposure to cold air. Often his cough is brought on by taking a deep breath or by laughter. He does not have postnasal drip, wheezing, or heartburn. He has a strong family history of allergies. Physical examination, chest radiograph, and spirometry are normal. He receives no benefit from a 3-month trial of gastric acid suppression therapy, intranasal corticosteroids, and an antihistamine-decongestant combination. Which of the following would likely provide the diagnosis of this patient’s chronic cough? Diagnosis is cough-variant asthma Suggested by the presence of airway hyperresponsiveness and confirmed when cough resolves with a trial of albuterol Most common causes of chronic cough: Ashtma, postnasal drip syndrome, and GERD Cold air is a clinical marker of airway hyperresponsiveness confirmed with metacholine challenge test Really good at ruling out asthma 24-Hour esophageal pH monitoring Bronchoscopy CT scan of the chest CT scan of the sinuses Trial of inhaled albuterol

8 Vocal Cord Dysfunction Aspirin-Sensitive Asthma
Exercise-Induced Bronchospasm ABPA GERD and Asthma Cough-Variant Asthma Virus-Induced Asthma Reactive Airways Dysfunction Syndrome Occupational Asthma

9 Inhaled Albuterol as needed
A 28-year-old man is evaluated for a 6-month history of episodic dyspnea, cough, and wheezing. As a child, he had asthma and allergies, but he has been asymptomatic since his early teenage years. His recent symptoms started after an upper respiratory tract infection, and they are often triggered by exercise or exposure to cold air. He is also awakened with asthma symptoms 5 or 6 nights a month. He is otherwise healthy and takes no medications. On physical examination, vital signs are normal. There is scattered wheezing in both lung fields. Chest radiograph is normal. Spirometry shows an FEV1 of 70% of predicted with a 15% improvement after inhaled albuterol. Which of the following is the most appropriate therapy for this patient? 2 or more days a week or 2 or more nights a month defines persistent asthma Inhaled corticosteriods are the cornerstone of therapy for persistent asthma Associated with improved pulmonary function, reduced airway hyperresponsiveness, decreased asthma exacerabtions, and decreased mortality Use lowest dose for symptom control Reevaluate every 3-6 months (adjustments made is the step up or step down approach) Long acting beta agonists provide 13 hours of bronchodilation and good for exercise induced asthma But do not use along… use with corticosteriods because they may mask control and lead to increased asthma related deaths Azithromycin Inhaled Albuterol as needed Inhaled low-dose corticosteroids plus inhaled albuterol as needed Long-acting B-agonist Long-acting B- agonist plus inhaled albuterol as needed

10 Persistent Components of Severity Intermittent Mild Moderate Severe Impairment Symptoms ≤2 days/week > 2 days/week Daily Throughout the day Nighttime awakenings ≤2 ×/month 3-4 ×/month >1 ×/week but not nightly Often 7 ×/week SABA use for symptom control (not prevention of EIB) >2 days/week but not more than 1 ×/d Several times a day Interference with normal activity None Minor limitation Some limitation Extremely limited Lung function Normal FEV1 between exacerbations FEV1 >80% of predicted FEV1/FVC normal FEV1 >80% of predicted FEV1/FVC normal FEV1 >60% but <80% of predicted FEV1/FVC reduced 5% FEV1 <60% of predicted FEV1/FVC reduced >5% Risk Exacerbations (consider frequency and severity)b,c 0-2/year >2/year Recommended step for initiating treatment (see Figure 4 for treatment steps)d Step 1 Step 2 Step 3; consider short courses of systemic corticosteroids Step 4 or 5; consider short courses of systemic corticosteroids

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12 Chronic Obstructive Pulmonary Disease
A 70-year-old woman is evaluated for a 6-month history of fatigue, an unintentional weight loss of 4.4 kg (10 lb), an increase in chronic cough with sputum production, and a decrease in exercise capacity. The patient has a 40-pack-year history of cigarette smoking but stopped smoking 10 years ago when chronic obstructive pulmonary disease was diagnosed. She has no other symptoms and specifically denies abdominal pain, nausea, vomiting, diarrhea, or change in her bowel habits. Her medications are albuterol as needed, an inhaled corticosteroid, and salmeterol. She has been on stable dosages of these drugs for 18 months. Age- and sex-appropriate cancer screening tests done 6 months ago were normal. On physical examination, the temperature is 37.5 °C (99.5 °F), the blood pressure is 128/76 mm Hg, the pulse rate is 94/min and regular, the respiration rate is 16/min, and the BMI is 20. Heart sounds are distant, and breath sounds are diminished bilaterally. There are no abdominal masses or organomegaly and no peripheral edema. Labs: Hg: 15, Alb: 3.0, Cr: 0.8, TSH: 2.0 Spirometry shows an FEV1 of 40% of predicted and an FEV1/FVC ratio of 45%. Chest radiograph shows hyperinflation. Which of the following is the most likely reason for this patient’s weight loss? Severe COPD can cause systemic effects including unintentional weight loss; skeletal muscle dysfunction and increased risk of CV disease, osteoporosis, and depression Breast Cancer Cervical Cancer Colon Cancer Chronic Obstructive Pulmonary Disease

13 At risk of chronic obstructive pulmonary disease (COPD)
A 50-year-old man is evaluated for a 1-year history of cough productive of mucoid sputum. He has not had fever or lost weight during that time. The patient has smoked one pack of cigarettes a day for 20 years. He has no history of allergic disease or gastroesophageal reflux disease. On physical examination, the temperature is 37.0 °C (98.6 °F), the blood pressure is 124/76 mm Hg, the pulse rate is 78/min and regular, and the respiration rate is 15/min; BMI is 25. The lungs are clear, and the chest radiograph is normal. Spirometry shows an FEV1 of 85% of predicted and an FEV1/FVC ratio of 75%; there is no change in results after administration of a bronchodilator. Which of the following is the most likely diagnosis? Smokers with chronic cough, sputum production, and normal lung function are classified as “at risk” for COPD Asthma At risk of chronic obstructive pulmonary disease (COPD) Mild (GOLD stage I) COPD Moderate (GOLD stage II) COPD

14 COPD All in patient with FEV1/FVC < 70% Table 8 At risk ---
Normal Spirometry Chronic Symptoms GOLD 1 Mild FEV1/FVC <70% FEV >80% of predicted GOLD 2 Moderate 50%<FEV1<80% of predicted GOLD 3 Severe FEV1/FVC<70% 30% < FEV1< 50% of predicted GOLD 4 Very Severe FEV1< 30% of predicted

15 An inhaled corticosteroid Ipratropium N-acetylcysteine Oral Prednisone
A 55-year-old man with a 7-year history of severe chronic obstructive pulmonary disease is evaluated after being discharged from the hospital following an acute exacerbation; he has had three exacerbations over the previous 18 months. He is a long-term smoker who stopped smoking 1 year ago. He adheres to therapy with albuterol as needed and inhaled salmeterol and tiotropium and has demonstrated proper inhaler technique. On physical examination, vital signs are normal. Breath sounds are decreased bilaterally; there is no edema or cyanosis. Oxygen saturation after exertion is 92% on ambient air. Spirometry shows an FEV1 of 32% of predicted and an FEV1/FVC ratio of 40%. Chest radiograph done in the hospital 3 weeks ago showed no active disease. Which of the following should be added to this patient’s therapeutic regimen? Inhaled corticosteriods reduced exacerbations by 24% Consider in patient with FEV1 < 50% and those who have exacerbations Benefit is generally greater when an inhaled corticosteriod is combined with long acting B2 agonist An inhaled corticosteroid Ipratropium N-acetylcysteine Oral Prednisone

16 Level of Airflow Obstruction
Recommended Therapy FEV % of predicted (THINK GOLD 1 or 2) Inhaled bronchodilator therapy (short acting anticholinergic or short acting B2 agonist) FEV1< 60% of predicted (THINK GOLD 3) Daily monotherapy with an Inhaled bronchodilator therapy (long acting anticholinergic or long acting B2 agonist) Consider combination inhaled therapy (long acting anticholinergic, long acting B2 agonist, or cortisteroid) FEV1< 50% of predicted (THINK GOLD 3 and 4) Consider adding pulmonary rehabilitation

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18 Cryptogenic organizing pneumonia Idiopathic pulmonary fibrosis
A 64-year-old woman is evaluated for a 6-week history of dyspnea, dry cough, fever, chills, night sweats, and fatigue, which have not responded to treatment with azithromycin and levofloxacin; she has lost 2.2 kg (5 lb) during that time. The patient had a thorough examination 6 months ago while she was asymptomatic that included routine laboratory studies, age- and sex-appropriate cancer screening, and a chest radiograph; all results were normal. The patient has never smoked, has had no known environmental exposures, and has not traveled recently or been exposed to anyone with a similar illness. Her only medications are aspirin and a multivitamin. On physical examination, temperature is 37.8 °C (100.0 °F); other vital signs are normal. Cardiac examination is normal. There are scattered crackles in the mid-lung zones with associated rare expiratory wheezes. There is no digital clubbing. Musculoskeletal and skin examinations are normal. Chest radiograph is shown . Which of the following is the most likely diagnosis? Subacute with migratory opacities Cryptogenic organizing pneumonia Idiopathic pulmonary fibrosis Lyphocyti interstitial pneumonia Nonspecific interstitial pneumonia

19 55 year old F with fever, dyspnea, malaise for 2 weeks…
48-year-old man with cryptogenic organizing pneumonia. Patchy ground-glass opacity, consolidation, and nodule (small arrow, B) mainly with peribronchovascular distribution. Reversed halo signs (central ground-glass opacity and surrounding air-space consolidation of crescentic and ring shapes) (large arrows). Organizing pneumonia, alveolitis, bronchiolitis

20 Cryptogenic Organizing Pneumonia
History: Insidious onset (weeks to 1-2 months), often failed outpatient treatment for viral pneumonitis or bacterial pneumonia Epidemiology: M=F, Age=middle aged HPI: Cough, fever, dyspnea, malaise, and myalgias PE: Rales Imaging: bronchial thickening, some interstitial findings patchy bilateral alveolar infiltrates, MIGRATES Histology: organizing pneumonia, bronchiolitis and chronic alveolitis (open lung bx preferred, often adequate with TBB) Associations: Penicillamines and RA Treatment: Good prognosis, responds to steroids. Slow taper to avoid exacerbations

21 55 year old male presents with 6 months dyspnea, cough…
Usual Interstitial pneumonia CXR: interstitial findings CT: ground glass early, honeycomibing late

22 Idiopathic Pulmonary Fibrosis (IPF)
History: VERY slow onset, at least 6 months Epidemiology: M=F, average age = 55 HPI: dyspnea, poor exercise tolerance, cough, NO FEVER PE: no extrapulmonary manifestations, CLUBBING usually seen, coarse, dry crackles at lung bases Imaging: CT “ground glass” early, “honeycombing “late, CXR interstitial Histology: Usual Interstitial Pneumonia (UIP) Associations: smoking exacerbates, ~ 10% low titers of ANA or RF, no associations with infections, drugs, chemicals Treatment: steroids +/- cyclophosphamide or azathiprine (20-30% improve), Single-lung transplant in late cases Response: A-a gradient response to exercise.

23 45 year old F, h/o IVDA, with dyspnea and cough over last 2-3 months…
Basilar, mid-lung reticular changes, spares the subpleural region, rarely honeycombing, ground glass in mid to lowerlung

24 Nonspecific Interstitial Pneumonitis (NSIP)
History: subacute presentation 2-3 months coughing, dyspnea PE: bibasilar crackles, stimata of CTD Imaging: basilar or mid-lung reticular changes, (spares subpleural region) rarely with honeycombing, pattern of ground-glass opacification in the mid- and lower-lung zones Diagnosis: requires open lung biopsy (difficult to differentiate fro IPF) Histo: lymphoplasmacytic interstitial infiltration in a uniform pattern, accompanied by chronic fibrosis (NSIP) Associations: HIV, CTD, HSP, drug induced lung disease Treatment: steroids +/- cytotoxic meds Prognosis: better that IPF, but still grim when fibrosis on bx

25 38 year old F presents with acute onset shortness of breath…
Honeycombing, cystic lesions throughout the lung, DIFFUSELY, differentiates from langerhans histocytosis Hamartomas Adenoma sebaceum Ash leaf spot

26 Lymphangioleiomyomatosis
Epidemiology: Premenopausal women Pathophys: Immature smooth muscle proliferation in lymph, vasc, and alveolar wall/perbronchial structures cysts and constriction in these structures HPI: often presents with pneumothorax PE: hamartomas, ash leaf spots, adenoma sebaceum Imaging: honeycombing diffusely throughout the lung (in contrast to upper lung in Langerhans) Associations: Pneumothorax, chylous pleural effusions (TG >110 +/- chlomicrons, common with Tuberous Sclerosis or multiple hamartomas (Cowden’s Syndrome) Treatment: Oophorectomy with progestin treatment, lung transplant (may recur)

27 32 year M, smoker, presents with gradual worsening of shortness of breath/cough…
Thin walled cystic lesions, upper lung predominant

28 Pulmonary Langerhans Cell Histocytosis
History: 10% present with pneumothorax, 50% will have PTX sometime during illness Epidemiology: M>F, smokers, majority <40 y/o PFTs: OBSTRUCTIVE Imaging: interstitial changes and small cystic spaces in upper lung fields, honeycomb, Histology: Langerhans cells Associations: smoking Treatment: stop smoking, steroids generally do not help. Occasional spontaneous resolution Hand-Schuller Christian syndrome: lytic bone lesions, diabetes insipidius, exophthalmus Smoking related ILDs: Pulm Langerhans, Resp Bronchiolitis, DSIP

29 60 year old F with h/o asthma presents with 3 months insidious cough, wheezing, night sweats, low grade fevers… ESR: 82 BAL: high percentage eosinophils Bilateraly very peripheral infiltrates, photographic negative of pumonary edema

30 Eosinophilic Pneumonias
Acute, benign eosinophilic pneumonia: Loefflers syndrome, minimal resp symptoms. MIGRATORY infiltrates. Peripheral eosinophilia. Rule out drugs and parasites. Acute eosinophilic pneumonia: acute, febile, hypoxemic resp failure resembling ARDS. Steroids and vent support. Chronic Eosinophilic pneumonia: most common in U.S. Middle aged women. Subacute. CXR bilateral, very peripheral infiltrates, photographic negative of pulm edema, High ESR. Steroids. Relapse common.

31 55 year old f presents with joint pain, Rash & fevers…
Hilar adenopathy

32 Sarcoidosis Stage Radiographic Pattern Normal I Hilar lymphadenopathy with normal parenchyma II Hilar lymphadenopathy with abnormal parenchyma III No lymphadenopathy with abnormal lung parenchyma IV Parenchymal chagnes with fibrosis and architectural distortion Lofgren’s sndrome: Erythema nodosum (good prognosis), polyarthralgias, hilar LAD, and fever Multisystem disease Imaging: bilateral hilar and/or mediastinal adenopathy (disappears as dz progresses), +/- parenchymal infiltrates Histo: noncaseating granuloma BAL: increased lymphs, helper/supressor ratio of > 4:1 (opposite of HSP) Associations: ACE level, hypercalcemia, hypergammaglobulinemia Treatment: 75 % recover without treatment, steroids for severe cases

33 Histology Clinical Diagnosis UIP IPF/ Cryptogenic fibrosing alveolitis CTD associated lung disease Radiation NSIP NSIP (CTD, HIV, Drugs) Organizing Pneumonia Cryptogenic Organizing Pneumonia Respiratory Bronchiolitis Respiratory Bronchiolitis ILD -DSIP Lymphoid Interstitial pneumonia Diffuse Alveolar Damage Acute Interstitial Pneumonia

34 Flexible bronchoscopy Pleural biopsy
A 30-year-old medical resident is evaluated for cough, right-sided chest pain, and fever of 21 days’ duration. He has no significant medical history or family history, and he takes no medications. Hemoglobin is 14 g/dL (140 g/L), and the leukocyte count is 8000/µL (8 × 109/L). Chest radiograph shows a right pleural effusion occupying approximately 50% of the hemithorax without other abnormalities. Thoracentesis yields turbid, yellow fluid, and analysis shows: RBC Count: 500 uL, Nucleated Cell count: 3500 with 20% neutrophils, 60%lymphocytes, 10% macrophages, 4%mesothelial cell, and 6% eosinophils Total Protein: 4.2, LDH: 240, pH: 7.35, Glucose: 68 Serum total protein is 7.0 g/dL and serum lactate dehydrogrenase is 100U/L. Gram stain shows no organism and culture is pending. Which of the following is the most appropriate next step in management? Subacute duration Isolated pleural effusion, age Exudative by protein and LDH The cellular response in the pleural fluid is lymphocytic Can be neutrophilic in the first 2 weeks Cultures are positive in less than 1/3 of cases Chest CT scan Flexible bronchoscopy Pleural biopsy Repeat chest radiograph after a 5-day course of azithromycin

35 Parapneumonic Effusion Post-cardiac injury syndrome Pulmonary embolism
A 70-year-old man is evaluated in the emergency department for a 2-day history of dyspnea with exertion, orthopnea, and paroxysmal nocturnal dyspnea. He has ischemic heart disease with left ventricular dysfunction and had coronary artery bypass graft surgery 6 weeks ago. His medications include aspirin, nitroglycerin, metoprolol, lisinopril, and furosemide. On physical examination, the patient is sitting upright and breathing with difficulty; the temperature is 37 °C (98.6 °F), the blood pressure is 150/85 mm Hg, the pulse rate is 105/min and regular, and the respiration rate is 28/min. Oxygen saturation is 89% on ambient air. There are fine crackles at the lung bases bilaterally, and breath sounds are diminished at the right base. There is a regular tachycardia and an S3 at the apex. There is no jugular venous distention or peripheral edema. Hemoglobin is 12.5 g/dL (125 g/L), and the leukocyte count is 10,500/µL (10.5 × 109/L). Chest radiograph shows cardiomegaly and small bilateral pleural effusions, greater on the right than the left. Thoracentesis is performed, and pleural fluid analysis shows: Nucleated Cell Count: 450/UL with 3% neutrophils, 70% lymphocytes, 10% macrophages, 15% mesothelial cells, and 2% eosinophils Pleural Fluid to serum total protein ratio: 0.54, Plerual fluid to upper limits of normal serum LDH ration: 0.52, Glucose: 80, Total Protein: 3.7, pH: 7.45, Albumin: 1.5, Cholestrol 35, The serum-pleural fluid albumin gradient is Which is the most likely diagnosis? Protein discordant exudate (an exudate by protein criteria only) Pleural fluid to serum total protein of 0.54 ad a LDH to ULN of 0.52 Consistent with patients with heart failure receiving diuretics Serum: pleural fluid albumin gradient greater than 1.2 suggests a transudate in cases where other findings suggest exudate Diuretics cause more efficient clearance of pleural liquid than pleural protein Heart Failure Parapneumonic Effusion Post-cardiac injury syndrome Pulmonary embolism

36 Pleural Fluid Pearls WBC>1000 (exduate), >10,000 (parapneumonic effusion); >100,000 (pus/empyema) Eosinophils>10% (pneumothorax, drug reaction, parasites, fungus, asbestos) Lymphocytes>50% (TB, or cancer) Glucose ~80 (TB); ~60 (cancer or empyema); <30 (RA) Amylase (pancreatic fistula, esophageal rupture, local malignancy) pH<7.0 (loculated effusion/empyema), <7.2 (PLACE CHEST TUBE), < 7.3 (with malignancy, suggests high tumor burder) TG>115= chylous; <50= pseudochylous

37 A 64-year-old woman who resides in a nursing home and has a history of end-stage kidney disease for which she receives hemodialysis presents with fever, copious sputum production, and hypoxemia. Chest radiograph shows a right-sided infiltrate. She is intubated and started on vancomycin, levofloxacin, and piperacillin-tazobactam for treatment of diffuse right-sided pneumonia. On day 3 in the hospital, she has been afebrile for 48 hours, and her secretions are scant and white. On physical examination, the temperature is 36.9 °C (98.5 °F), pulse rate is 88/min, respiration rate is 14/min, and blood pressure is 140/86 mm Hg; oxygen saturation is 96% on FiO There are diffuse right-sided inspiratory crackles. Leukocyte count is 9600/µL (9.6 × 109/L) (20,400/µL [20.4 × 109/L] on admission). Admission sputum culture is now growing methicillin-resistant Staphylococcus aureus; blood cultures are negative. Chest radiograph shows slight improvement in the right-sided infiltrate compared with admission. Which of the following is the most appropriate antibiotic therapy at this time? Complete an 8-day course of all three antibiotics Complete an 8-day course of vancomycin and discontinue the other antibiotics Complete a 14-day course of all three antibiotics Complete a 14-day course of vancomycin and discontinue the other antibiotics Discontinue all antibiotics

38 A 30-year-old woman develops bilateral pulmonary infiltrates and hypoxemia 48 hours after undergoing repair of multiple long-bone fractures. Her initial arterial blood gases are pH 7.48, PCO2 30 mm Hg, and PO2 45 mm Hg on 100% oxygen by nonrebreather mask. The patient is intubated and placed on mechanical ventilation. The temperature is 38.3 °C (101.0 °F), the pulse rate is 100/min, the respiration rate is 28/min, and the blood pressure is 120/60 mm Hg. The patient weighs 60 kg (132.3 lb). Oxygen saturation is 83%. She is sedated, hemodynamically normal, and not using accessory muscles to breathe. There are bilateral inspiratory crackles. The ventilator settings are as follows: volume control mode, respiration rate 26/min, tidal volume 360 mL, positive end-expiratory pressure (PEEP) 5 cm H2O, FiO Arterial blood gases are pH 7.45, PCO2 33 mm Hg, and PO2 50 mm Hg. Which of the following is the most appropriate next step in the management of this patient? Primary cause of hypoxemia is shunt Wont correct with 100% oxygen Increase PEEP improves gas exchanged by recruiting flooded and collapsed alveoli Titrate up PEEP to a plateau pressure of 28-30 Low tidal volume stradegy Paralysis is reserved for patients who have marked dyssynchrony and or are on maximal ventilator support Increase FiO2 to 1.0 Increase PEEP to 10 cm H2O Increase respiration rate to 32/min Increase tidal volume to 700 mL Start vecuronium infusion

39 ALI/ARDS ALI ARDS PaO2/FiO2< 300 Bilateral infiltrates
PCWP <18mg Hg ARDS PaO2/FiO2<200 PCWP < 18 mg Hg

40 ARDS


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