Download Free Medical Acute Respiratory Distress Syndrome PowerPoint Presentation

Acute Respiratory Distress Syndrome PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : Check out this medical PowerPoint presentation titled "Acute Respiratory Distress Syndrome" by David Sweet.

This medical PowerPoint presentation talks about Acute Respiratory Distress Syndrome (ARDS), a severe lung condition that can develop rapidly, typically in response to an underlying injury or illness such as pneumonia, sepsis, or trauma. ARDS is characterized by inflammation in the lungs, which causes the tiny air sacs (alveoli) in the lungs to fill with fluid, making it difficult for the lungs to properly oxygenate the blood.

Symptoms of ARDS include shortness of breath, rapid breathing, low oxygen levels, chest pain, and a cough that produces a frothy or bloody sputum. ARDS can be a life-threatening condition, and treatment often involves supportive measures such as mechanical ventilation, oxygen therapy, and medications to reduce inflammation.

The severity and duration of ARDS can vary, and recovery can take weeks to months. Some people may experience long-term lung damage or other complications as a result of ARDS. Prevention of ARDS is key, and it is important to promptly treat underlying conditions that may increase the risk of developing ARDS, such as pneumonia or sepsis.

Tags : Acute Respiratory Distress Syndrome, ARDS, severe lung condition, inflammation in the lungs, critical care medicine, critical care medicine PowerPoint presentation

Published on : Mar 28, 2023 | Views : 938 | Downloads : 3

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

Acute Respiratory Distress Syndrome David Sweet
Slide 2-

CASE GF, is a 57 yo male who presents to SPH with a one week history of feeling unwell. His wife states that he was having intermittent fevers, general feelings of malaise and dry cough. Over the last 24 hours he has become progressively unwell with more severe cough and mild confusion. At 8 AM when he refused to get off the couch and his lips looked blue; GFs wife called the ambulance. When probed wife states has had decrease oral intake and occasional diarrhea over the last 48hrs.
Slide 3-

Case PMHx: EtOH Prev pancreatitis in 2004 HTN BPH Raynauds syndrome Prev episode of stable VT with negative angio and EP studies for inducible VT 4 months previous. He had a UTI 1 months ago.
Slide 4-

Case Social: Lives in apt complex with his wife and his pet parrot. Has two children not living at home. Currently doing home renovations. Meds: norvasc, amiodarone, thiazide. avodart Allergies: nil
Slide 5-

Case Upon arrival to the Emergency room he was in obvious respiratory distress with RR=40 and Sats 85% on double flow non-rebreather. He was intubated by the emergency physician using etomidate and succinylcholine. His blood pressure dropped post intubation requiring phenylephrine and has now received 2 L of NS. As you are standing in the Emergency Dept, you are consulted immediately as there is a septic patient coming though the doors (88 yo DNR that is hypotensive and you hear the EP ask for dopamine…….sigh).
Slide 6-

Case The EP tells you that he has ordered blood work and a ABG. You go to the patients bedside. He is just being placed on the ventilator by the RT. He is stated as “stable” by the bedside nurse, Sats 96 on Fio2=1.00, 110/54, 130, temp 36.2, and is dyssynchronous with the Vent. You have a excellent resident who immediately takes over bedside management. Orders another L of NS, ensures BC have been drawn and asks for moxifloxacin to be given. Orders a CXR, sedates the patient. Places an arterial line, IJ central line and continues resuscitating him.
Slide 7-

Case His physical exam reveals crackles in his bases bilaterally. His skin is mottled and cold with no rash. Neuro (no meningeal signs prev to intubation), CV, abd, genital, ext exam in non-contributory. Initial CXR shows bilateral basilar infiltrate. ECG= NS tachy.
Slide 8-

ppt slide no 8 content not found
Slide 9-

Case Hb 150, Hct 0.55 WCC 18.2, Neut 12.3 Plat 79 Film – few schistocyes, toxic granulation. INR 1.4, PTT 42, Fib 2.78 Na 134, K 4.4, Cl 107, HCO3 13, Urea 18.8, creat 178 CK 508, Trop <0.1 LDH 540 Albumin 20, Lactate 8.1
Slide 10-

Case ABG pre intubation sent by RT: pH=7.22, CO2=27, PaO2=98, HCO3=13, Base excess= neg 16. New ABG returns as you are looking at the computer (post intubation): ABG= pH=7.11, PaCO2=38, PaO2=105, HCO3=12, Base excess=neg 17. FiO2=1.00
Slide 11-

Case Questions: 1) What is the differential diagnosis? Are there any clues in the story to the etiology? What is the most likely diagnosis? 2) Based on the laboratory/ABG results what concurrent issues are present in this disorder? What is the likely precipitants in this case? 3) Any further investigations? 4) What treatments would you recommend now? Do you agree with the abx choice? 5) What initial ventilator settings would you have this patient on?
Slide 12-

Case The resident feels this is a pneumonia and comments that it likely meets criteria for ARDS. A medical student then speaks up and asks “what is ARDS”? 6. What is the Definition of ARDS? 7. What is the Epidemiology of ARDS?. 8. What is the Pathophysiology/Clinical Stages and likely causes of ARDS.?
Slide 13-

ARDS During 1960s, with widespread use of PPV a distinct form of bilateral lung disease noted. Coined “Shock Lung” in trauma patients in Viet Nam surgical hospitals. Then referred as Adult Respiratory Distress Syndrome. Currently described as Acute Respiratory Distress Syndrome. Bernard, GR. Acute Respiratory Distress Syndrome: A Historical Perspective. Am J Respir Crit Care Med 2005; 172:798
Slide 14-

What defines ARDS?
Slide 15-

Definitions For more than 20 yrs there was lack of a uniformed description of ARDS. 1994 American-European Consensus Conference on ARDS issued the following definitions for: 1)ALI= Acute lung injury 2)ARDS= Acute Respiratory Distress Syndrome Bernard, G, Artigas, A, Carlet, J, et al. The American-European consensus conference on ARDS: Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994; 149:818.
Slide 16-

Definitions ALI: Bilateral radiographic inflitrates PaO2/FiO2 between 201 and 300 regardless of level of PEEP No clinical evidence for elevated left atrial pressure. If measured, the pulmonary capillary wedge pressure is 18 mmHg or less
Slide 17-

Definitions ARDS: Bilateral radiographic inflitrates PaO2/FiO2 less than 200 regardless of level of PEEP No clinical evidence for elevated left atrial pressure. If measured, the pulmonary capillary wedge pressure is 18 mmHg or less
Slide 18-

Definitions By definition is ACUTE. Typically will develop over 4-48 hrs and will persist for days to weeks. Some equate with the pathophysiologic entity of increased capillary permeability. This is discouraged as there are other pathophysiologic mechanisms in ARDS.
Slide 19-

Definitions Early pathologic features of ARDS are generally described as diffuse alveolar damage (DAD). There is minimal alveolar septal thickening, hyperplasia of pneumocytes, and eosinophilic hyaline membranes present. Beskow, CO, Drachenberg, CB, Bourquin, PM, et al. Diffuse alveolar damage. Morphologic features in bronchoalveolar lavage fluid. Acta Cytol 2000; 44:640.
Slide 20-

Epidemiology
Slide 21-

Epidemiology ALI= - Age-adjusted incidence of 86 per 100,000 person-years Mortality of 39% ARDS= - Age-adjusted incidence of 64 per 100,00 person-years Mortality of 41% **190,600 cases of ALI in US each year, which associated with 74,500 deaths. Rubenfeld, GD, Caldwell, E, Peabody, E, et al. Incidence and outcomes of acute lung injury. N Engl J Med 2005; 353:1685.
Slide 22-

Epidemiology Intensive Care Units: 10-15% of admitted patients meet criteria for ARDS 20% of mechanically ventilated patients meet criteria for ARDS Mortality rate varies on the basis of underlying cause, most dying of MOF rather than resp. insufficiency. Large trials suggest overall mortality of ARDS ranges from 25-58%. Frutos-Vivar, F, Nin, N, Esteban, A. Epidemiology of acute lung injury and acute respiratory distress syndrome. Curr Opin Crit Care 2004; 10:1 Maccallum, NS, Evans, TW. Epidemiology of acute lung injury. Curr Opin Crit Care 2005; 11:43.
Slide 23-

Pathophysiology
Slide 24-

Pathophysiology In healthy lung, a tight regulation on movement of fluid to maintain dry alveoli and a small amount of interstitial fluid. In lung injury this regulation is lost. There is excess fluid in both interstitium and alveoli. Results in impaired gas exchange, dec compliance, and increased pulmonary arterial pressures.
Slide 25-

Pathophysiology Normal pulmonary capillary endothelium is selectively permeable; serum protein remains intravascular, fluid crosses the membranes under control of: Hydrostatic forces Osmotic forces George, RB, Chesson, AL, Rennard, SI. Functional anatomy of the respiratory system. In: George, RB, Light, RW, Matthay, MA, et al (Eds), 3rd ed, Chest Medicine. Essentials of Pulmonary and Critical Care Medicine, Williams & Wilkins, Baltimore, 1995, p. 3
Slide 26-

Pathophysiology The Starling equation describes the forces that direct fluid movement. Simplified version of the equation is: Q=K * [(Pmv – Ppmv) – rc (mv – pmv)] Q= net transvascular flow K= permeability Pmv= hydrostatic pressure in lumen Ppmv= hydrostatic pressure in perimicrovascular space Rc= reflection coefficient of capillary barrier Mv= oncotic pressure of circ Pmv= oncotic pressure of perimicrovasc comp
Slide 27-

Pathophysiology The balance of equation usually allows small amounts of fluid into interstitium but 3 mech prevent alveolar edema. Retained intravascular protein Interstitial lymphatics can return large quantities of fluid to circulation Tight junctions between alveolar epithelial cells
Slide 28-

Pathophysiology Clinical ARDS is result of inflammatory injury to alveoli producing DAD. Lungs are very vulnerable to injury b/c they receive the entire CO and as pro-inflammatory mediators (TNF, IL-1, IL-6, IL-8) released into blood stream the lungs feel their full effect. Additionally, neutrophils are recruited to the lungs, become activated and release reactive oxygen species and proteases which damage endothelium and alveoli.
Slide 29-

Pathophysiology As a result, the normal barriers to alveolar edema are lost. Protein escapes vascular space, oncotic gradient lost. Fluid pours into interstitium and overwhelms the lymphatics. Air spaces fill with bloody, proteinaceous edema fluid and debris from degenerating cells. Functional surfactant is lost, resulting in alveolar collapse. Ware, LB, Matthay, MA. Alveolar fluid clearance is impaired in the majority of patients with acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med 2001; 163:1376.
Slide 30-

Pathophysiology Consequences: Impaired gas exchange= V/Q mismatching and shunting. Dec lung compliance= Low compliance is due to stiffness of poorly or nonaerated lung more so than changes in PV characteristics of residual fxning lung units. (Baby lung) Pulmonary HTN= present in up to 25% of Px with ARDs. Multifactorial. RV dysfunction associated with inc risk of death! Monchi, M, Bellenfant, F, Cariou, A, et al. Early predictive factors of survival in the acute respiratory distress syndrome. A multivariate analysis. Am J Respir Crit Care Med 1998; 158:1076
Slide 31-

Clinical Stages
Slide 32-

Clinical Stages ARDs progresses through three relatively discrete pathologic stages. 1) Exudative stage: DAD, in 1st week progresses to 2) Proliferative stage: characterized by resolution of pulmonary edema and proliferation of type II alveolar cells, squamous metaplasia, interstitial infiltration by myofibroblasts, and early deposition of collagen. 3) Fibrotic stage: obliteration of normal lung architecture, diffuse fibrosis, and cyst formation. Tomashefski, JFJ. Pulmonary pathology of the adult respiratory distress syndrome. Clin Chest Med 1990; 11:593
Slide 33-

ppt slide no 33 content not found
Slide 34-

Clinical Stages Initial Course (exudative phase): Usually symptoms predominated by cause of ARDs (eg abd pain from pancreatitis, fever and shock from sepsis) Pulmonary dysfunction develops within 24-48 hrs of inciting event. Worsening tachypnea, dyspnea, hypoxemia and diffuse crackles on exam.
Slide 35-

Clinical Stages Labs non-specific. May show inc WBC, DIC and lactic acidosis. ABG= acute resp alkalosis, inc DAaO2, severe hypoxemia CXR= Bilateral patchy infiltrates, does not need to be widespread or severe opacification. CT= generally demonstrates patchy abn with inc density in dependent lung zones.
Slide 36-

ppt slide no 36 content not found
Slide 37-

ppt slide no 37 content not found
Slide 38-

Clinical Stages Proliferative stage: Oxygenation tends to improve somewhat over first few days as edema resolves, most patients remain ventilator-dependent due to: Continued hypoxemia High minute vent requirements (Classically the Dead Space may begin to increase at this stage and ventilation may become more of an issue) Poor compliance Gattinoni, L, Bombino, M, Pelosi, P, et al. Lung structure and function in different stages of severe adult respiratory distress syndrome. JAMA 1994; 271:1772
Slide 39-

Clinical Stages CXR= Densities become less dense as edema resolves, interstitial infiltrates remain. May start to develop interstitial emphysema and lung cysts. At this point may become dominated by complications such as barotrauma, nosocomial infection or dev of MODS. (discussed later)
Slide 40-

ppt slide no 40 content not found
Slide 41-

Clinical Stages Fibrotic Stage: Will see progressive increasing airway pressures, progressive pulmonary HTN and a honeycomb appearance on CXR
Slide 42-

ppt slide no 42 content not found
Slide 43-

Etiology
Slide 44-

Causes and predisposing conditions Traditionally conceptualized as a pattern of injury that does not differ significantly depending upon cause. Now called in question with revolution of CT scan. Additionally studies have found more severe reductions in lung compliance and less responsiveness to PEEP in ARDS from a pulmonary process than those with extrapulmonary precipitant. Gattinoni, L, Pelosi, P, Suter, P, et al. Acute respiratory distress syndrome caused by pulmonary and extrapulmonary disease: Different syndromes. Am J Respir Crit Care Med 1998; 158:3. Tugrul, S, Akinci, O, Ozcan, PE, et al. Effects of sustained inflation and postinflation positive end-expiratory pressure in acute respiratory distress syndrome: focusing on pulmonary and extrapulmonary forms. Crit Care Med 2003; 31:738.
Slide 45-

Abbreviated list of conditions associated with ARDS Sepsis Aspiration Infectious pneumonia Severe trauma Surface burns Multiple blood transfusions Leukoagglutin reactions Pancreatitis Drug overdose Near drowning Smoke inhalation Following bone marrow transplantation Drug reaction Venous air embolism Amniotic fluid embolism Neurogenic pulmonary edema Acute eosinophilic pneumonia* Bronchiolitis obliterans organizing pneumonia (BOOP)* Miliary tuberculosis* Cardiopulmonary bypass Pulmonary contusion Multiple fractures Following upper airway obstruction
Slide 46-

Causes and predisposing conditions Sepsis: most common cause Risk of developing ARDS with sepsis may be especially high in patients with alcoholism. One prospective study analyzed the incidence of ARDS in 220 Px with septic shock. 70% in chronic alcohol abusers 31% in non-alchohol abusers ? Proposed mechanism= dec levels of glutathione in epithelial lining, predispose to oxidative injury. Doyle, RL, Szaflarski, N, Modin, GW, et al. Identification of patients with acute lung injury. Predictors of mortality. Am J Respir Crit Care Med 1995; 152:1818. Moss, M, Bucher, B, Moore, FA, et al. The role of chronic alcohol abuse in the development of acute respiratory distress syndrome in adults. JAMA 1996; 2
Slide 47-

Causes and predisposing conditions Trauma: Several mechanism can lead to ARDS Bilateral lung contusions Fat embolism: 12-24 hrs after injury, less common now as fractures are immobilized prior to transfer. Sepsis Massive tissue injury ALI and ARDS contribute to length of critical illness, these disorders don not appear to inc risk of death. In comparison to other causes of ARDS, trauma-related is associated with better prognosis. Rubenfeld, GD, Caldwell, E, Peabody, E, et al. Incidence and outcomes of acute lung injury. N Engl J Med 2005; 353:1685.
Slide 48-

Causes and predisposing conditions Transfusion related More than 15 pRBCs is an important risk factor even without trauma. Transfusion of smaller volumes of pRBCs may also increase risk of developing ARDS and inc mortality in Px with established ARDS. TRALI: even one unit of plasma-containing blood can result in TRALI. FFP, plts, pRBCs all implicated. Symptoms become apparent within 6 hours. Gong, MN, Thompson, BT, Williams, P, et al. Clinical predictors of and mortality in acute respiratory distress syndrome: potential role of red cell transfusion. Crit Care Med 2005; 33:1191. Khan, H, Belsher, J, Yilmaz, M, et al. Fresh-frozen plasma and platelet transfusions are associated with development of acute lung injury in critically ill medical patients. Chest 2007; 131:1308.
Slide 49-

Causes and predisposing conditions Toxicological causes?: ASA Opioids Phenothiazines TCAs Also idosyncratic rxn to protamine, nitrofuantoin, chemotherapeutics, contrast material
Slide 50-

Case The resident also states that the chest X-ray looks very similar to previous cases of pulmonary edema that she has seen. She asks you if there are any diagnostic tests and evidence that can help you determine if this is ARDS vs cardiogenic pulmonary edema? (Aside from clinical exam)
Slide 51-

Cardiogenic pulmonary edema vs ARDS
Slide 52-

Diagnosis During first several days ARDS will resemble acute cardiogenic pulmonary edema in both a clinical and radiographic sense. Distinction usually made from clinical circumstances associated with onset but occasionally additional diagnostic tests may help. 1) BNP 2) Echo 3) PAC
Slide 53-

Diagnosis BNP: May be helpful in distinguishing ARDS from hemodynamic pulmonary edema. A level below 100 pg/ml indicates heart failure unlikely. A higher level is not helpful. On study looking at 24 px with Severe Sepsis or Septic Shock and 51 px with acute heart failure found that values not significantly different. Rubenfeld, GD, Caldwell, E, Granton, J, et al. Interobserver variability in applying a radiographic definition for ARDS. Chest 1999; 116:1347. Rudiger, A, Gasser, S, Fischler, M, et al. Comparable increase of B-type natriuretic peptide and amino-terminal pro-B-type natriuretic peptide levels in patients with severe sepsis, septic shock, and acute heart failure. Crit Care Med 2006; 34:2140.
Slide 54-

Diagnosis Echocardiography: Most commonly used test to distinguish questionable cardiogenic component of ARDS. Can detect LV dysfunction, severe aortic or mitral valve abnormalities, estimation of diastolic dysfuction and volume overload. Interpretation may be difficult in the presence of over/under resuscitation, renal failure, sepsis induced myocardial dysfunction, PPV.
Slide 55-

Diagnosis Pulmonary artery catheterization (PAC): Classically clinicians would look for a wedge > 18 mmHg. Need to be interpreted with caution in the face of patients on high levels of PPV and PEEP. Also, it is estimated that as many as 20% of px with ARDS have concomitant LV dysfxn. Ware, LB, Matthay, MA. Clinical practice. Acute pulmonary edema. N Engl J Med 2005; 353:2788. Montgomery, A, Stager, M, Carico, C, et al. Causes of mortality in patients with the adult respiratory distress syndrome. Am Rev Respir Dis 1985; 132:485.
Slide 56-

Diagnosis Therefore, the dx cannot be made easily when the wedge pressure is elevated. More useful to follow the wedge pressure with treatment and how infiltrates and hypoxemia change with treatment. If the infiltrates and hypoxemia do not improve appreciable within 24-48 hrs after normalization of wedge pressure more likely ARDS has occurred as well.
Slide 57-

Diagnosis Additionally, PAC has never been shown to confer benefit in ARDS. Recent multi-center trail (FACTT) found no improvement in survival or organ function, but more complications in PAC group vs CVC monitoring. Wheeler, AP, Bernard, GR, Thompson, BT, et al. Pulmonary-artery versus central venous catheter to guide treatment of acute lung injury. N Engl J Med 2006; 354:2213.
Slide 58-

ppt slide no 58 content not found
Slide 59-

Case The patient is moved to the ICU. The patient receives EGDT and you modify the antibiotic choices. Over the next 24 hrs the patient receives 9L of crystalloid and colloid. Currently on 20 ug/min of Levophed, ScvO2 has always been greater than 70% and dobutamine was never used nor was transfusion. A Stat ECHO on arrival reveals a mildly reduced EF (40%) but no wall motion abn and RV is mildly dilated and PA systolic is 45. Arrival CXR to the ICU shows worsening bilateral infiltrates and you make the decision to do early bronchoscopy/BAL. 10. Your resident asks how bronchoscopy is going to help you management?
Slide 60-

ppt slide no 60 content not found
Slide 61-

Bronchoscopy in ARDs Useful tool if cannot determine etiology from history. Able to visualize airways and perform bronchoalveolar lavage. Occult aspiration= see acute inflammation localized to dependent regions and see food material. DAH= finding of frothy blood in airways and increasing bloody returns with recurrent lavage. Find hemosiderin-laden macrophages on microscopy.
Slide 62-

Bronchoscopy in ARDs Gram stain= Can identify organisms and cellular components. Culture and staining= look for aerobic bacteria, mycobacteria, legionella pneumophila, pneumocystis, viruses. Cytologic preps examined for eosinophils, viral inclusion bodies and cancer. Others= eg) foamy macrophages seen with BOOP and amiodarone toxicity.
Slide 63-

Case During bronchoscopy you find moderate amounts of secretions and no bloody returns. Initial gram stain only shows neutrophils, negative for foamy macrophages. hemosiderin-laden macrophages and few esinophils.
Slide 64-

Case 11. Your fantastic senior fellow then states there are several clinical syndromes that present with inflammatory prodrome and acute respiratory failure. They have specific treatments and prognosis, therefore should be considered.
Slide 65-

Case 1) Diffuse alveolar hemorrage syndromes (DAH) 2) Acute interstitial pneumonia (Hammer-Rich) 3) Idiopathic acute eosinophilic pneumonia 4) Cryptogenic organizing pneumonia Briefly describe each of these entities with respect to symptoms, diagnosis and treatment!
Slide 66-

DAH
Slide 67-

DAH Is included in the differential of hypoxia with bilateral infiltrates. Hemopysis will be absent in 33% of cases. Is defined by injury to alveolar-capillary basement membrane and bleeding into alveolar spaces. Collard, HR, Schwarz, MI. Diffuse alveolar hemorrhage. Clin Chest Med 2004; 25:583
Slide 68-

DAH A variety of diseases are associated with the development of diffuse alveolar hemorrhage syndrome. All fit within one of three histological patterns Pulmonary capillaritis Bland pulmonary hemorrhage Diffuse alveolar damage
Slide 69-

DAH Pulmonary Capillaritis Systemic vasculitides: Wegener's granulomatosis Microscopic polyangiitis Henoch-Schoenlein purpura Collagen vascular diseases: Systemic lupus erythematosus Polymyositis Rheumatoid arthritis Scleroderma
Slide 70-

DAH Bland pulmonary hemorrhage - Goodpasture's syndrome - Systemic lupus erythematosus - Post bone marrow transplant - Severe coagulopathies - Mitral stenosis - Penicillamine, nitrofurantoin, amiodarone
Slide 71-

DAH Diffuse alveolar damage ARDS and its causes
Slide 72-

DAH Clinical presentation: Onset is often abrupt or of short duration (<7 days) Cough, fever and dyspnea and may present in extremis requiring PPV. May have constellation of new alveolar infiltrates, falling hgb and hemorragic fluid on sequential bronchoalveolar lavage
Slide 73-

DAH
Slide 74-

DAH CXR: Diffuse, bilateral, patchy, basal consolidation on chest radiograph (sparing the apex) Resembles pulmonary edema but normal heart size can be clue. CT: alveolar densities with sparing of peripheral lung fields
Slide 75-

ppt slide no 75 content not found
Slide 76-

DAH A number of diseases that cause DAH are also associated with pulmonary-renal syndrome. Usually cause a focal segmental necrotizing glomerulonephritis. Will see elevated creatinine and abn urinalysis (red blood cells, white blood cells, red and white cell casts.)
Slide 77-

DAH As previously mentioned in DAH will see progressive hemorrhagic return with BAL. Will also see hemosiderin-laden macrophages, which may be demonstrated by prussian blud staining. Additionally, specific diagnosis/etiology can be made from specific auto-antibodies or lung/kidney/skin biopsy.
Slide 78-

DAH Many of the possible diagnosis are treated with either corticosteroids, immunosuppressive therapy or plasmapheresis. Therefore must think of these diagnosis in the setting of ARDS. Failure to treat in the settting of acute hypoxic respiratory failure may significantly worsen prognosis. Schwarz, MI, Mortenson, RL, Colby, TV, et al. Pulmonary capillaritis. The association with progressive irreversible airflow limitation and hyperinflation. Am Rev Respir Dis 1993; 148:507
Slide 79-

Acute Interstitial Pneumonia Hamman-Rich Syndrome
Slide 80-

Acute Interstitial Pneumonia Rare and fulminate form of lung injury described by Hamman and Rich in 1935. Occurs in previously healthy individuals without a history of lung disease who present within days to weeks following onset of symptoms. Similar in presentation to ARDS, and likely is a subset of idiopathic ARDS. Hamman, L, Rich, AR. Fulminating diffuse interstitial fibrosis of the lungs. Trans Am Clin Climatol Assoc 1935; 51:154 Hamman, L, Rich, AR. Acute diffuse interstitial fibrosis of the lungs. Bull Johns Hopkins Hosp 1944; 74:177
Slide 81-

Acute Interstitial Pneumonia Exact mechanism of damage to pulmonary endothelium unknow. Likely neutrophil-mediated. Results in damage of alveolar walls, inc alveolar capillary permeability, interstitial edema, intralveolar haline membranes. As with ARDS after initial insult also have a fibroblast proliferation phase
Slide 82-

Acute Interstitial Pneumonia Most patients over age of 40. Usually begins with a prodromal illness lasting 7-14 days prior to presentation. Fever, cough and shortness of breath. Labs nonspecific. Primack, SL, Hartman, TE, Ikezoe, J, et al. Acute interstitial pneumonia: Radiographic and CT findings in nine patients. Radiology 1993; 188:817
Slide 83-

Acute Interstitial Pneumonia CXR= diffuse, bilateral air-space opacification. CT= A combination of ground-glass attenuation, airspace consolidation, traction bronchiectasis, and architectural distortion The extent of ground-glass attenuation and traction bronchiectasis increases with disease duration.
Slide 84-

ppt slide no 84 content not found
Slide 85-

ppt slide no 85 content not found
Slide 86-

Acute Interstitial Pneumonia Diagnosis is based upon two findings: Presence of a clinical syndrome of idiopathic ARDS. Pathologic confirmation. Thus a open or thoracoscopic lung biopsy is required to confirm the diagnosis.
Slide 87-

Acute Interstitial Pneumonia AIP should be distiguished from two other forms of idiopathic interstitial pneumonia: Usual interstitial pneumonia (UIP) Desquamative interstitial pneumonia (DIP) These both have a more subacute/chronic presentations and therefore are not included in differential of a acute ARDS picture. Vourlekis, JS, Brown, KK, Cool, CD, et al. Acute interstitial pneumonitis. Case series and review of the literature. Medicine (Baltimore) 2000
Slide 88-

UIP
Slide 89-

DIP
Slide 90-

Acute Interstitial Pneumonia Treatment: Mainly supportive care. Mech vent is often required. Currently unclear if steroid therapy is effective. Mortality is high (>60%), and majority die within 6 months of presentation. If survive usual do so with complete recovery of lung function. Vourlekis, JS, Brown, KK, Cool, CD, et al. Acute interstitial pneumonitis. Case series and review of the literature. Medicine (Baltimore) 2000; 79:369
Slide 91-

Idiopathic Acute Eosinophilic Pneumonia (AEP)
Slide 92-

Idiopathic Acute Eosinophilic Pneumonia First described as a cause of respiratory failure in 1989. Etiology: Unknown, some feel is an acute hypersensitivity reaction to unidentified inhaled antigen in otherwise healthy people. Several reports people have been involved in unusual outdoor activities just prior to illness. Temporal relationship noticed to recent onset of cigarette smoking. Philit, F, Etienne-Mastroianni, B, Parrot, A, et al. Idiopathic acute eosinophilic pneumonia: a study of 22 patients. Am J Respir Crit Care Med 2002; 166:1235 Miki, K, Miki, M, Nakamura, Y, et al. Early-phase neutrophilia in cigarette smoke-induced acute eosinophilic pneumonia. Intern Med 2003; 42:839
Slide 93-

Idiopathic Acute Eosinophilic Pneumonia Ages of 20 and 40. Begins with acute febrile illness of less than 3 weeks duration; most less than 7 days. Malaise, myalgias, night sweats, nonproductive cough and dyspnea are present in almost every patient. O/E= fever (often high) and tachypnea, bilateral basilar crackles.
Slide 94-

Idiopathic Acute Eosinophilic Pneumonia Labs: generally elevated WBCs with neutrophilic leukocytosis. With progression of disease the eosinophil fraction becomes markedly elevated. CXR= bilateral diffuse mixed alveolar and reticular opacities are seen. Bilateral effusions are often present (if tap will have marked eosinophilia with high pH.) CT= bilateral, random, and patchy group-glass or reticular opacities. In height of disease will have peripheral ground-glass opacities along the bronchovascular bundles. Hayakawa, H, Sato, A, Toyoshima, M, et al. A clinical study of idiopathic eosinophilic pneumonia. Chest 1994; 105:1462 Ogawa, H, Fujimura, M, Matsuda, T, et al. Transient wheeze. Eosinophilic bronchobronchiolitis in acute eosinophilic pneumonia. Chest 1993; 104:493
Slide 95-

Idiopathic Acute Eosinophilic Pneumonia
Slide 96-

ppt slide no 96 content not found
Slide 97-

ppt slide no 97 content not found
Slide 98-

Idiopathic Acute Eosinophilic Pneumonia BAL is useful in making the diagnosis. Often show a very high (>25%) and total number of eosinophils. The proportions of BAL lymphocytes and neutrophils are also frequently increased. Rarely will need to do open lung biopsy. Philit, F, Etienne-Mastroianni, B, Parrot, A, et al. Idiopathic acute eosinophilic pneumonia: a study of 22 patients. Am J Respir Crit Care Med 2002; 166:1235
Slide 99-

Idiopathic Acute Eosinophilic Pneumonia Treatment: Spontaneous improvement has been reported. Uniformly respond to IV and oral corticosteroid therapy. Response is often dramatic, occurring within 12 to 48 hours, and there is no relapse following withdrawl of the steroids.
Slide 100-

Cryptogenic Organizing Pneumonia Idiopathic BOOP
Slide 101-

Cryptogenic Organizing Pneumonia Distinct clinical entity with features of pneumonia. Due to proliferation of granulation tissue within small airways (proliferative bronchiolitis) and alveolar ducts, chronic inflammation in surrounding alveoli. Pathogenesis remains unknown. Abnormal vascuar endothelial growth factor and matrix metalloproeinase regulation. Choi, KH, Lee, HB, Jeong, MY, et al. The role of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in cryptogenic organizing pneumonia. Chest 2002; 121:1478
Slide 102-

Cryptogenic Organizing Pneumonia
Slide 103-

Cryptogenic Organizing Pneumonia Presents in the 40s and 50s May have had symptoms for up to month or more before presentation. Mimics CAP. Heralded by flu-like illness (fever, malaise, fatigue, and cough). Also may have weight loss. Labs= Inc WBC, Inc ESR, Inc CRP.
Slide 104-

Cryptogenic Organizing Pneumonia CXR= bilateral, diffuse alveolar opacities with normal lung volumes. May be peripherally located. The infiltrates may also be migratory and recurrent. CT= patchy air-space consolidation, ground-glass opacities, small nodular opacities, and bronchial wall thickening and dilation. More often in the periphery and lower lung zones. Davison, AG, Heard, BE, McAllister, WAC, Turner-Warwick, MEH. Cryptogenic organizing pneumonitis. Q J Med 1983; 52:382 Ujita, M, Renzoni, EA, Veeraraghavan, S, et al. Organizing pneumonia: perilobular pattern at thin-section CT. Radiology 2004; 232:757
Slide 105-

ppt slide no 105 content not found
Slide 106-

ppt slide no 106 content not found
Slide 107-

ppt slide no 107 content not found
Slide 108-

Cryptogenic Organizing Pneumonia Diagnosis: BAL is very helpful: Classically a “mixed cellular pattern” Similar to hypersensitivity pneumonitis. Proportion of macrophages is lower, lymphocytes, neutrophils and eosinophils are higher. Foamy macrophages Occasionally, mast cells and plasma cells King, TE Jr, Mortenson, RL. Cryptogenic organizing pneumonia. The North American experience. Chest 1992; 102:8S
Slide 109-

Cryptogenic Organizing Pneumonia An open biopsy or thoracoscopic lung biopsy is suggested to confirm diagnosis. Need generous amount of lung tissue. Important to provide pathologist with adequate clinical information to guide search for specific lesions and to rule out other possible causes that have similar pathologic picture. Miyagawa, Y, Nagata, N, Shigematsu, N. Clinicopathological study of migratory lung infiltrates. Thorax 1991; 46:233
Slide 110-

Cryptogenic Organizing Pneumonia Treatment: Supportive Corticosteroid pulse then taper. Some who cant tolerate steroids or deteriorate are treated with cyclophophamide. Prognosis= 2/3 recover in weeks to months. 1/3 will have persistant disease. May relapse.
Slide 111-

Case The patient then slowly deteriorates from an oxygenation point of view and after a brief period of a FiO2 of 0.60 is now requiring 0.80. The CXR has now blossomed into severe bilateral infiltrates. A CT scan was performed and shows a diffuse bilateral groundglass appearance with consolidation in the dorsal aspects of the lung.
Slide 112-

ppt slide no 112 content not found
Slide 113-

Case The urin output has picked up and the creatinine is dropping. You are currently on a volume control ventilation (6cc/kg, rate=28, plat are 28, PEEP=7 nil autoPEEP). ABG: pH=7.35, PaCo2=35, PaO2=75 HCO3=20. 12) She questions if the amount of fluid she has given the patient and if this is detrimental? Is there any evidence to how we should manage the fluid balance in Px with ARDS?
Slide 114-

Fluid management in ARDS
Slide 115-

Fluid management in ARDS Pulmonary edema in ARDS is directly related to increased vascular permeability but the quantity depends on hydrostatic pressure. Mitchell, JP, Schuller, D, Calandrino, FS, et al. Improved outcome based on fluid management in critically ill patients requiring pulmonary artery catheterization. Am Rev Respir Dis 1992; 145:990
Slide 116-

Fluid management in ARDS Thus, even in px who are not overloaded a conservative strategy approach may be beneficial.
Slide 117-

Fluid management in ARDS RCT, n=1000 Conservative group=CVP <4 mmHg, PAOP< 8 mmHg. (Unable to obtain in study) Liberal group= CVP 10-14, PAOP 14-18. Fluid balance= -136 cc vs 6992 cc
Slide 118-

Fluid management in ARDS Vent free days= 15 vs 12 (p=0.001) ICU free days= 13 vs 11 (p=0.001) 60 day mortality 25.5% vs 28.4% (p=0.30)
Slide 119-

Fluid management in ARDS Important to know Needed to be out of shock for 12 hrs before diuretics given. Requiring dialysis was contraindication to the study Average time to study entry was 43 hours. Study found no difference between prevalence of shock or need for renal replacement therapy once randomized.
Slide 120-

Fluid management in ARDS Can we incorporate this into our practice? Likely we should attempt a conservative strategy of fluid management in select px with ARDS or ALI. Attempt goals of CVP <4 and PAOP < 8 (may be difficult to obtain.) Must be balanced with EGDT and early phases of sepsis when fluid replacement is crucial.
Slide 121-

ppt slide no 121 content not found
Slide 122-

Fluid management in ARDS Simplified algorithm for conservative fluid management.
Slide 123-

Case 13. The fellow asks the resident if there is anything else we can do with conventional ventilation or the PEEP. 14. What are the primary mechanisms of Ventilator induced lung injury (VILI)? 15. What is the concept of “Baby Lung”? 16. Do you have a strategy to determining the “Best PEEP”? 17. Is there any evidence for higher PEEP and Open Lung ventilation (not including oscillators)
Slide 124-

Mechanical Ventilation Mechanical Ventilation is the corner stone of supportive therapy ARDS management. Primary issue in ARDS is that it is a heterogeneous disease process within the lungs. Much of the lungs is so consolidated it cannot be recruited to participate in gas exchange. Therefore, the effective lung being ventilated is much smaller than usual. This is the concept of “baby lung”. Fan, E, Needham, DM, Stewart, TE. Ventilatory management of acute lung injury and acute respiratory distress syndrome. JAMA 2005; 294:2889
Slide 125-

Mechanical Ventilation Additionally, different areas of lung have different “time constants” What are time constants? Different physiologic properties pertaining to their compliance, inflation and deflation times relative to each other. Therefore, at a set driving pressure and PEEP, some areas will never inflate while others will open and close cyclically and still others will be continuously distended and damaged.
Slide 126-

Mechanical Ventilation Last 15 years there has been a growing appreciation of ventilator-related morbidity and Ventilator Induced Lung Injury (VILI). Clinicians strive to determine the optimal modes of ventilation to reduce VILI and improve survival.
Slide 127-

Mechanical Ventilation Primary mechanisms of VILI are felt to be barotrauma and biotrauma. Barotrauma= High airway/alveolar pressure results in air migrating into extrapulmonary compartments (discuss later). Biotrauma= Both tidal hyperinflation and cyclic atelectasis. Terragni, PP, Rosboch, G, Tealdi, A, et al. Tidal Hyperinflation during Low Tidal Volume Ventilation in Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med 2007; 175
Slide 128-

Mechanical Ventilation What is tidal hyperinflation and cyclic atelectasis? Tidal hyperinflation= over-inflation of aerated lung units. Cyclic atelectasis= areas of diseased lung appear to collapse and open cyclically with each breath. This places stress and damages adjacent lung that remains open.
Slide 129-

Mechanical Ventilation Key protective modalities/ideologies are Low tidal volume ventilation (ARDSnet ARMA study) and the idea of the “baby lung”. Use of PEEP and open lung ventilation to improve hypoxemia and limit cyclic atelectasis. Fan, E, Needham, DM, Stewart, TE. Ventilatory management of acute lung injury and acute respiratory distress syndrome. JAMA 2005; 294:2889
Slide 130-

Mechanical Ventilation Clinical value of low tidal volume ventilation “clearly” demonstrated in ARDSnet study. ARMA (originally called KARMA….know why?)
Slide 131-

Mechanical Ventilation RCT of 861 patients. 6 cc/kg IBW and Plat <30cm H2O 12 cc/kg IBC and Plat <50cm H2O Stopped early at interim analysis b/c of significant lower mortality (31 vs 40 % p=0.007).
Slide 132-

ppt slide no 132 content not found
Slide 133-

Mechanical Ventilation Issues: 1) Was study control group tidal volume inappropriate high? (studies showed no true standard of care!) 2) Practice Misalignment?
Slide 134-

Mechanical Ventilation Issues: 3) People fear that low tidal volume will result in more discomfort, therefore inc sedation? Secondary analysis of one ARDSnet center showed neither inc dose nor duration of sedation. 4) Hypercapnia does occur when attempting to use low tidal volume ventilation! Is this safe? Multiple studies have shown that modest, permissive hypercapnia is safe! Kahn JM et al. Low tidal volume ventilation does not increase sedation use ni patients with acute lung injury. Crit Care Med 2005; 33:766-771 Laffey JG et al. Permissive hypercapnia role in protective lung ventilation strategies. Intensive Care Med 2004; 30247-356.
Slide 135-

PEEP and Open Lung Ventilation
Slide 136-

PEEP and Open Lung Ventilation Rational behind PEEP= Preventing subsequent recollapse of difficult to recruit lung units. Several benefits: Improve V/Q matching. Alveoli will not have to repeatedly construct surfactant monolayer, and this improves compliance. Prevent cyclic atalectasis. Overall goal is to improve oxygenation and reduce the levels of required FiO2 to less toxic levels. Plotz FB, Slutsky AS, van Vught AJ, Heijnen CJ. Ventilator-induced lung injury and multiple system organ failure: a critical review of facts and hypotheses. Intensive Care Med. 2004;30:1865-1872
Slide 137-

PEEP and Open Lung Ventilation
Slide 138-

PEEP and Open Lung Ventilation 3 basic approaches to setting appropriate level of PEEP. Visual- variety of radiologic, nuc med, CT tech to determine amount of recruitable and over distended lung…..currently not readily available. Mechanical- using pressure-volume relationships….not easy to capture regional variations within lung. Tech challenging.
Slide 139-

PEEP and Open Lung Ventilation 3) Gas-exchange approaches- use FiO2, PaO2 or calculated shunt fraction to target and adjust PEEP. Many of the PEEP studies (such as ALVEOLI by ARDSnet) use predetermined algorithms based on this idea.
Slide 140-

PEEP and Open Lung Ventilation
Slide 141-

PEEP and Open Lung Ventilation ALVEOLI (ARDSnet group) N=549 RCT of aggressive PEEP (12-24 cm H2O) vs conservative PEEP (5-24 cm H2O) approach guided by gas exchange. All low tidal volume
Slide 142-

PEEP and Open Lung Ventilation Successfully achieved different levels of PEEP High PEEP Low PEEP Day 1 14.7 8.9 Day 3 12.9 8.5 Day 7 12.9 8.4
Slide 143-

PEEP and Open Lung Ventilation Aggressive strategy improved gas exchange, atalectasis and compliance, the plateau pressue was higher but the mortality was unchanged. P = 0.48
Slide 144-

If hi PEEP reduced atelectasis more, why didn’t outcomes improve? Maybe it really did Sig imbalances in age and P/F favored low PEEP, adjustments showed “trends” for hi PEEP Might “recruitable” subgroups benefit? But maybe it didn’t Benefits of more recruitment countered by overdistention elsewhere In setting of low VT and recruitment of “easy” alveoli, further recruitment of “tough” alveoli adds little benefit (prevent cyclic injury, allow fixed)
Slide 145-

PEEP and Open Lung Ventilation In 2007, two additional, large RCTs studying aggressive vs conservative PEEP were completed and preliminary analysis reported. Canadian/Australian/Saudi Arabian Lung Open Ventilation Study (LOVS) French ExPress study. Meade MO, Cook DJ, Arabi Y, et al. A multinational randomized controlled trial of a lung open ventilation strategy in ALI/ARDS -- preliminary results. Am J Respir Crit Care Med. 2007;A507 Mercat A, Richard JC, Brochard L, et al. Comparison of two strategies for setting PEEP in ALI/ARDS (ExPress study). Am J Respir Crit Care Med. 2007;A507
Slide 146-

PEEP and Open Lung Ventilation In both the new trials: Higher vent-free days and better compliance in the aggressive PEEP group. No mortality benefit. Non significant subgroup benefit in sickest patients. ??? What will meta-analysis show?
Slide 147-

PEEP and Open Lung Ventilation So……how should we manage our PEEP? Thoughts? Use enough PEEP to reduce FiO2 to 0.6 or less while still keeping your plat <30 (after maximizing your MAP). If unable to do this…..think about tech (ie HFOV.) There is association between higher PEEP and barotrauma.
Slide 148-

PEEP and Open Lung Ventilation What about recruitment maneuvers in the ALVEOLI study? First 80 patients in the High PEEP group were randomized to recruitment maneuvers vs sham maneuvers. Resulted in only small and transient increases in PaO2….therefore was discontinued.
Slide 149-

Case The patient continues to deteriorate and is now on inverse ratio PC ventilation (2:1) with a PEEP of 18. The PaO2 is 68 on FiO2 of 0.80. Hemodynamically they have actually improved and are requiring only 10 of levophed. They are currently deeply sedated on propofol and fentenyl and you gain no benefit from paralysis. There is adequate urin output and the creatine and lactate have returned to normal. Your BAL cultures comes back negative viral, bacterial and fungal.
Slide 150-

Case 18.Your resident asks if there is anything else we can do in this situation and if there are any other treatments? (Your fellow comments on the fact we don’t have a diagnosis!) 19. What is the role of lung biopsy in ARDS I Love Meduri!!!!!!!!
Slide 151-

Lung biopsy in ARDS
Slide 152-

Lung Biopsy In general, reserved for carefully selected patients with ARDs of unclear etiology. Suspected Dx of CA, DAH, cryptogenic organizing pneumonitis, undiagnosis underlying lung disease such as sarcoidosis, acute interstitial pneumonia (Hamman-Rich Syndrome). Patel, SR, Karmpaliotis, D, Ayas, NT, et al. The role of open-lung biopsy in ARDS. Chest 2004; 125:197 Papazian, L, Thomas, P, Bregeon, F, et al. Open-lung biopsy in patients with acute respiratory distress syndrome. Anesthesiology 1998; 88:935
Slide 153-

Lung Biopsy Considered reasonably safe  Retrospective review of 57 px with ARDS mean PaO2/FiO2 ratio of 145 mmHg that received open lung biopsy. Major complication rate=7% (death, hemothorax, new dialysis), no deaths from procedure. Overall complication rate=39% (most air leaks) Results of biopsy resulted in additional tx in 60% and withdrawl of unnecessary tx in 37%. Patel, SR, Karmpaliotis, D, Ayas, NT, et al. The role of open-lung biopsy in ARDS. Chest 2004; 125:197.
Slide 154-

Case 20. Your Fellow is also a believer of Meduri and asks if we should start steroids? How do you interpret the literature? what is the best evidence currently? 21. Your fellow then sheepishly brings up nitric and pronation. What is the current evidence for these therapeutic maneuvers? 22. What are the potential harms with proning and NO. 23. Is there currently any role for the use oscillation? What is the current evidence for oscillation?
Slide 155-

Corticosteroids in ARDS
Slide 156-

Corticosteroids in ARDS Studied extensively in ARDS. There are clear roles in situations when ARDS has been precipitated by a steroid-responsive process (AEP). Uncertain how they should be used in other cases of ARDS. Davis, WB, Wilson, HE,Wall, RL. Eosinophilic alveolitis in acute respiratory failure. A clinical marker for a non-infectious etiology. Chest 1986; 90:7
Slide 157-

Corticosteroids in ARDS Empirically used for ARDS in 70s and early 80s. Used less after several studies found that they had no benefit and may cause harm. In the last several years we have seen many new studies re-looking at steroids in ARDS. Weigelt, JA, Norcross, JF, Borman, KR, et al. Early steroid therapy for respiratory failure. Arch Surg 1985; 120:536 Luce, JM, Montgomery, AB, Marks, JD, et al. Ineffectiveness of high-dose methylprednisolone in preventing parenchymal lung injury and improving mortality in patients with septic shock. Am Rev Respir Dis 1988; 138:62 Bernard, GR, Luce, JM, Sprung, CL, et al. High-dose corticosteroids in patients with the adult respiratory distress syndrome. N Engl J Med 1987; 317:1565
Slide 158-

Corticosteroids in ARDS
Slide 159-

Corticosteroids in ARDS Recent studies have looked more at the use of steroids in late ARDS. Best and largest study to date is the ARDSnet groups study. Steinberg, KP, Hudson, LD, Goodman, RB, et al. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med 2006; 354:1671
Slide 160-

Corticosteroids in ARDS Double Blind RCT 180 px with persistent ARDS to receive either methylprednisolone or placebo for 21 days. Persistent ARDS= ongoing disease 7 to 28 days after onset. No diff in 60 day mortality (29.2% vs 28.6%) or 180 day mortality (31.5% vs 31.9%)
Slide 161-

Corticosteroids in ARDS Px randomized 7-13 days, steroid caused a nonstatistically significant reduction in 60 day mortality (27% vs 36%) and 180 day mortality (27% vs 39%). Px randomized more than 14 days after onset; inc 60 day mortality (35% vs 8%) and 180 day mortality (44% vs 12%) Steroids inc ventilator free days, shock free days, oxygenation, lung compliance, and blood pressure but also inc neuromuscular weakness. Px in steroid group had a significant inc in reintubation (9% vs 28% p=0.006) as the steroids were stopped post extubation….did they not find mortality benefit because of this? Based on this trial corticosteroids cannot be recommended in early or late ARDS.
Slide 162-

Corticosteroids in ARDS Recently Meduri revisited steroid use in Early ARDS. Double blind RCT. N= 91 in 2:1 ratio. Early ARDS (<72 hrs). Compared to previous studies, this study gave steroids in lower doses and for longer duration.
Slide 163-

Corticosteroids in ARDS Reduced mech vent, length of ICU stay, ICU mortality (21% vs 43%)….too good to be true? Needs repetition and confirmation before can be advised!
Slide 164-

NO
Slide 165-

NO Conceptually NO is a local vasodilator. Several well done studies have looked at NO. One Multicenter RCT assigned 385 px with moderate/severe ARDS to placebo vs NO at 5 ppm. Induced short-term improvement and oxygenation; however, no improvement in duration of mech vent, 28 day mortality, or one year survival. Taylor, RW, Zimmerman, JL, Dellinger, RP, et al. Low-dose inhaled nitric oxide in patients with acute lung injury. A randomized controlled trial. JAMA 2004; 291:1603
Slide 166-

NO Another multicenter double blind RCT N=177 Used increasing concentrations of inhaled NO or placebo. Improved oxygenation modestly but was not sustained. No difference in 28 day mortality (not powered for this). Dellinger, RP, Zimmerman, JL, Taylor, RW, et al. Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: Results of a randomized phase II trial. Inhaled Nitric Oxide in ARDS Study Group. Crit Care Med 1998; 26:15
Slide 167-

NO In addition, meta-analysis of 10 RCTs (1237 px) Comparing inhaled NO vs placebo or conventional Tx. NO did not improve mortality, duration of MV, or ventilator free days. It did increase P/F ratio on first day of tx, but there was no effect on mean pulmonary arterial pressure. Adhikari, NK, Burns, KE, Friedrich, JO, et al. Effect of nitric oxide on oxygenation and mortality in acute lung injury: systematic review and meta-analysis. BMJ 2007; 334:779
Slide 168-

NO Need to keep in mind that there are some potential harms. May produce toxic radicals (unknown if worse than high FiO2). Methemoglobin and NO2 may inc when high does of NO are given, and these should both be watched. Inhaled NO have immunosuppressant properties then could in theory in risk of infection. NO can cuase DNA strand breaks and base alteration. Eichacker, PQ. Inhaled nitric oxide in adult respiratory distress syndrome: Do we know the risks versus benefits? [editorial]. Crit Care Med 1997; 25:563 Adhikari, NK, Burns, KE, Friedrich, JO, et al. Effect of nitric oxide on oxygenation and mortality in acute lung injury: systematic review and meta-analysis. BMJ 2007; 334:779 Greene, JH, Klinger, JR. The efficacy of inhaled nitric oxide in the treatment of acute respiratory distress syndrome. An evidence-based medicine approach. Crit Care Clin 1998; 14:387 Weinberger, B, Laskin, DL, Heck, DE, Laskin, JD. The toxicology of inhaled nitric oxide. Toxicol Sci 2001; 59:5
Slide 169-

NO Current recommendation? What do you think? Can be used as a temporizing measure in the face of profound hypoxia? Can be used as a bridge while attempting recruitment?
Slide 170-

Prone Ventilation
Slide 171-

Prone Ventilation Mechanisms of action: More homogeneous Ppl gradient in ventrodorsal and cephalocaudal planes. Increased FRC and V/Q matching. Improved bronchial drainage. Improved aerosol delivery. Abdomen is unsupported. Pelosi, P, Brazzi, L, Gattinoni, L. Prone position in acute respiratory distress syndrome. Eur Respir J 2002; 20:1017
Slide 172-

Prone Ventilation Efficacy: Two primary outcomes that have been studied are oxygenation and mortality. Oxygenation: Originally reported to improve in case series in the 70s. Prospective studies have now shown that prone position will increase oxygenation in 60-80% of Px. Some will maintain improved oxygenation even after return to supine. Piehl, MA, Brown, RS. Use of extreme position changes in acute respiratory failure. Crit Care Med 1976; 4:13 Papazian, L, Gainnier, M, Marin, V, et al. Comparison of prone positioning and high-frequency oscillatory ventilation in patients with acute respiratory distress syndrome. Crit Care Med 2005; 33:2162 Chatte, G, Sab, JM, Dubois, JM, et al. Prone position in mechanically ventilated patients with severe acute respiratory failure. Am J Respir Crit Care Med 1997; 155:473 Fridrich, P, Krafft, P, Hochleuthner, H, Mauritz, W. The effects of long-term prone positioning in patients with trauma-induced adult respiratory distress syndrome. Anesth Analg 1996; 83:1206
Slide 173-

Prone Ventilation Additionally, patients whose oxygenation improves during trial of prone positioning tend to improve each time prone positioning repeated. Chatte, G, Sab, JM, Dubois, JM, et al. Prone position in mechanically ventilated patients with severe acute respiratory failure. Am J Respir Crit Care Med 1997; 155:473 Fridrich, P, Krafft, P, Hochleuthner, H, Mauritz, W. The effects of long-term prone positioning in patients with trauma-induced adult respiratory distress syndrome. Anesth Analg 1996; 83:1206
Slide 174-

Prone Ventilation Mortality: Published studies have not shown a survival advantage!! RCT, N=304 with ALI/ARDS randomized to supine vent or six hours prone daily for 10 days. Improved PaO2/FiO2 but not 10-day, ICU, 6 months mortality. Risk of complications similar. Post-hoc suggest dec 10 day mort in sickest Px with PaO2/FiO2 < 88 (23.1% vs 47.2%) ?? Relatively short duration of proning, used low levels of PEEP and Vt of >10cc/kg Gattinoni, L, Tognoni, G, Pesenti, A, et al. Effect of prone positioning on the survival of patients with acute respiratory failure. N Engl J Med 2001; 345:568
Slide 175-

Prone Ventilation Another RCT, N=791 with ALI randomized to supine vs prone for 8 hr/day (most got only 4 days worth) Inc PaO2/FiO2 for first 28 days (p<0.001), but no change 28 day (32.4% vs 31.5%), 90 day mortality (43.4% vs 42.2%) or duration of Mech Vent. Statistically significant inc in complications. Selective intubation (p=0.01) ETT obstruction (p=0.002) Pressure sores (p=0.005) Guerin, C, Gaillard, S, Lemasson, S, et al. Effects of systematic prone positioning in hypoxemic acute respiratory failure: a randomized controlled trial. JAMA 2004; 292:2379
Slide 176-

Prone Ventilation More recent well designed trial by Mancebo. Multicenter RCT, N=136 with ARDS. Randomized to supine vs “high dose” prone vent. Both groups had standardized ventilation and weaning strategy. Px proned were that way for average of 17 hrs a day for mean of 10 days. Improved mortality (43% vs 58% p=0.12) Multivariate analysis found that supine position was independent predictor of mortality! Mancebo, J, Fernandez, R, Blanch, L, et al. A multicenter trial of prolonged prone ventilation in severe acute respiratory distress syndrome. Am J Respir Crit Care Med 2006; 173:1233
Slide 177-

Prone Ventilation Predicting Benefit based on physiology: Px with early diffuse lung injury with edematous lungs and dependent collapse respond best to prone position. Px with anterior predominance of infiltrates or injury with marked consolidation or fibrosis do not! Therefore, Px with an extrapulmonary cause of ARDS and diffuse disease are more likely to benefit! Additionally, Px with inc IAP and poor chest wall compliance may benefit. Lim, CM, Kim, EK, Lee, JS, et al. Comparison of the response to the prone position between pulmonary and extrapulmonary acute respiratory distress syndrome. Intensive Care Med 2001; 27:477 Mure, M, Glenny, RW, Domino, KB, Hlastala, MP. Pulmonary gas exchange improves in the prone position with abdominal distension. Am J Respir Crit Care Med 1998; 157:1785
Slide 178-

Prone Ventilation Contraindications: Spinal instability Hemodynamic and cardiac rhythm disturbances Multiple trauma Pregnancy Raised intracranial pressure Abdominal surgery Curley, MA. Prone positioning of patients with acute respiratory distress syndrome: a systematic review. Am J Crit Care 1999; 8:397
Slide 179-

Prone Ventilation Complications: Nerve compression Crush injury Venous stasis Airway security Pressure sores Dislodging vascular catheters Retinal damage
Slide 180-

Prone Ventilation Conclusions: Improve oxygenation but not mortality. May benefit the sickest ARDS Px if used early and for prolonged periods (? Px with diffuse, non-pulmonary ARDS). Think about in people with high abd pressures and non-compliant chest walls. May attempt if goals of lung-protective vent are not being met, if there is persistent acidosis or tissue hypoxia despite standard ventilation. Another study showed improved oxygenation with HFOV post proning!!
Slide 181-

High-frequency Ventilation
Slide 182-

High-frequency Ventilation Proposed as alternate form of lung protective ventilation. Theoretically could prevent overdistention and cyclic atelectasis. Combines very high respiratory rates with tidal volumes that are smaller than the anatomic dead space. Multiple mechanisms of gas transport. Wunsch, H, Mapstone, J. High-frequency ventilation versus conventional ventilation for treatment of acute lung injury and acute respiratory distress syndrome. Cochrane Database Syst Rev 2004; :CD004085
Slide 183-

High-frequency Ventilation
Slide 184-

High-frequency Ventilation 4 basic types: High-frequency positive pressure ventilation. High-frequency jet ventilation (HFJV) High-frequency oscillatory ventilation (HFOV) High-frequency percussive ventilation (FFPV) ** We only use HFOV and is what will be discussed!
Slide 185-

High-frequency Ventilation Vt is employed using a oscillatory pump. Set the MAP (which is higher than conventional ventillarion) by adjusting flow rate and expiratory back pressure. The ventilator then oscillates around this MAP and avoids low end-expiratory pressures and high peak pressures.
Slide 186-

High-frequency Ventilation Optimize oxygenation by manipulating MAP and FiO2. Optimize ventilation by adjusting amplitude (Vt), frequency, or introduction of a cuff leak. Primarily studied in children and neonates. Several non-randomized trials showed improvements in oxygenation but not mortality. Derdak, S, Mehta, S, Stewart, TE, et al. High-frequency oscillatory ventilation for acute respiratory distress syndrome in adults: a randomized, controlled trial. Am J Respir Crit Care Med 2002; 166:801
Slide 187-

High-frequency Ventilation Multicenter RCT, N=148, HFOV vs PCV (6-10cc/kg) MAP was higher in HFOV group compared to PCV (expected) HFOV group showed earlier improvements in PaO2/FiO2 (<16 hours, p=0.0008). This did not last longer than 24 hours. 30 day mortality rate was lower in HFOV but no stat. sig. (37% vs 52%, p=0.10) Control group had higher tidal volumes than recommended (8 +/- 2 ml/kg) Derdak, S, Mehta, S, Stewart, TE, et al. High-frequency oscillatory ventilation for acute respiratory distress syndrome in adults: a randomized, controlled trial. Am J Respir Crit Care Med 2002; 166:801
Slide 188-

High-frequency Ventilation Another RCT, N=61 with ARDS, HFOV vs conventional. Improvement in oxygenation but not in mortality. But trial was small and had poor recruitment, early termination, and unequal oxygenation index in groups after randomization. Both of these trials enrolled Px before the benefits of low tidal volume ventilation were know! Bollen, CW, van Well, TJ, Sherry, T, et al. High frequency oscillatory ventilation compared with conventional mechanical ventilation in adult respiratory distress syndrome: a randomized controlled trial (ISRCTN24242669). Crit Care, 2005, 9:430
Slide 189-

High-frequency Ventilation Risks of barotrauma and hemodynamic compromise with high frequency are comparable to conventional ventilation. We are currently waiting for the results of the OSCILLATE trial! Demory, D, Michelet, P, Arnal, JM, et al. High-frequency oscillatory ventilation following prone positioning prevents a further impairment in oxygenation. Crit Care Med 2007; 35:106 Gluck, E, Heard, S, Patel, C, et al. Use of ultrahigh frequency ventilation in patients with ARDS: A preliminary report. Chest 1993; 103:1413
Slide 190-

Other contraversial treatments ECMO= CAESAR study (?positive) to be presented at SCCM Partial liquid ventilation= Negative, not recommended Current multicenter phase II trial looking at APC in ALI (expected to finish 2008) GM-CSF Aerosolized B-agonist therapy in ALI/ARDS. ECCO2R (Novalung)
Slide 191-

Other contraversial treatments Also know about: IRV APRV Currently found to have short-term physiologic benefits but b/c lack of RCT not recommended for routine use at this time.
Slide 192-

Complications of ARDS
Slide 193-

Complications Primary complications: Barotrauma Nosocomial infection MOF DVT Untoward effects from sedation and paralysis
Slide 194-

Barotrauma When air escapes the alvolar space and migrates into the extrapulmonary compartments. Includes pneumothorax, interstitial emphysema, SC emphysema, pneumomediastinum, pneumoperitoneum and air embolism. In one study specifically looking at barotrauma in 100 ARDS Px: 13% of ARDS Px. Directly contributed to death in less than 2%. Schnapp, LM, Chin, DP, Szaflarski, N, et al. Frequency and importance of barotrauma in 100 patients with acute lung injury. Crit Care Med 1995; 23:272
Slide 195-

Barotrauma In another study of 84 Px with ARDS mortality rates were: 66% in Px with pneumothorax. 46% in Px without pneumothorax. In different study looking at 725 Px with ARDS there was no significant difference in mortality among Px with and without barotrauma. Gattinoni, L, Bombino, M, Pelosi, P, et al. Lung structure and function in different stages of severe adult respiratory distress syndrome. JAMA 1994; 271:1772 Weg, JG, Anzueto, A, Balk, RA, et al. The relation of pneumothorax and other air leaks to mortality in the acute respiratory distress syndrome. N Engl J Med 1998; 338:341
Slide 196-

Barotrauma Currently unclear if results from high airway pressures or is simply a marker of severe lung injury. Retrospective analysis of ARDSnet trial found that peak, mean, plateau and driving pressures do not seem to correlate with risk of pneumothorax. They did find that higher levels of PEEP associated with increased risk of barotrauma. Eisner, MD, Thompson, BT, Schoenfeld, D, et al. Airway pressures and early barotrauma in patients with acute lung injury and acute respiratory distress syndrome. Am J Respir Crit Care Med 2002; 165:978
Slide 197-

Outcome
Slide 198-

Outcome Survival has improved for Px with ARDS, with mortality decreasing from 67% in 1990 to 30% in 2006. Likely related to improved supportive care and ventilatory strategies. One study suggests that the improved mortality is limited to Px with ARDS and no sepsis (eg Trauma related ARDS) Wheeler, AP, Bernard, GR, Thompson, BT, et al. Pulmonary-artery versus central venous catheter to guide treatment of acute lung injury. N Engl J Med 2006; 354:2213 Wiedemann, HP, Wheeler, AP, Bernard, GR, et al. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med 2006; 354:2564 Stapleton, RD, Wang, BM, Hudson, LD, et al. Causes and timing of death in patients with ARDS. Chest 2005; 128:525
Slide 199-

Outcomes Survivors may have abnormalities in pulmonary function and exercise endurance, which can persist for years (no changes with low tidal volume vent). In addition, impaired neurocognitive function and quality of life have been reported two years after acute illness. Neff, TA, Stocker, R, Frey, HR, et al. Long-term assessment of lung function in survivors of severe ARDS. Chest 2003; 123:845 Orme, J Jr, Romney, JS, Hopkins, RO, et al. Pulmonary function and health-related quality of life in survivors of acute respiratory distress syndrome. Am J Respir Crit Care Med 2003; 167:690 Hopkins, RO, Weaver, LK, Collingridge, D, et al. Two-Year Cognitive, Emotional, and Quality-of-Life Outcomes in Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med 2005; 171:340
Slide 200-

Outcomes Factors that are correlated with abnormal lung fxn one year after recovery: Duration of PPV Lowest static thoracic compliance Mean PA pressure Requiring FiO2 >0.6 for more than 24 hrs.
Slide 201-

Outcomes Factors correlating with better functional outcome at one year: Absence of steroid treatment Absence of illness acquired during ICU stay Rapid resolution of lung injury Herridge, MS, Cheung, AM, Tansey, CM, et al. One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med 2003; 348:683 Elliott, CG, Rasmusson, BY, Crapo, RO, et al. Prediction of pulmonary function abnormalities after adult respiratory distress syndrome (ARDS). Am Rev Respir Dis 1987; 135:634 Ghio, AJ, Elliott, CG, Crapo, RO, et al. Impairment after adult respiratory distress syndrome. An evaluation based on American Thoracic Society recommendations. Am Rev Respir Dis 1989; 139:1158
Slide 202-

Conclusions
Slide 203-

Conclusions ARDS common entity in the ICU. Think about other diagnosis that can present like ARDS. DAD AIP IAEP ICP
Slide 204-

Conclusion Use bronchoscopy/BAL early. Think about lung biopsy if diagnosis uncertain. Low tidal volume, optimize PEEP for now. NO as a bridge? Proning in specific cases. Say no to drugs! (steroids) Watch for OSCILLATE/ CEASAR