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A complete presentation on ARDS and lung protective ventilation

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  1. 1. ARDS ARDS & Lung Protective Strategy By Dr RAHUL
  2. 2. Ventilator associated lung injury Post-perfusion lung or pump lung Shock lung Adult hyaline membrane disease Adult respiratory insufficiency syndrome A. K. A
  3. 3. History • Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) are common problems in the intensive care unit (ICU) and can complicate a wide spectrum of critical illnesses. • First described by Ashbaugh in 1967, the syndrome was initially termed “adult respiratory distress syndrome” to distinguish it from the respiratory distress syndrome of neonates. However, with the recognition that ALI/ARDS can occur in children, the term acute has replaced adult in the nomenclature in recognition of the typical acute onset that defines the syndrome. • In practice, ALI/ ARDS remains largely underdiagnosed and often expert practitioners disagree on the diagnosis, which perpetuates inappropriate or inadequate treatment
  4. 4. Epidemiology • The wide variety of causes and coexisting disease processes has also made identification of cases difficult, both at the clinical and administrative coding level. • The National Institutes of Health first estimated the incidence at 75 per 100,000 population in 1977. • Some studies suggest a decline in the incidence of ARDS over time. • Regardless of the exact incidence, it is clear that ALI/ARDS is a major public health problem that will be encountered frequently by all physicians who care for critically ill patients.
  5. 5. Definition • In order to better standardize the definition of ARDS for epidemiologic and research purposes, in 1994 a joint American– European Conference proposed criteria for characterizing ARDS according to the severity of gas exchange abnormality. Despite some controversy, these criteria were generally accepted and used to guide research study design and enrolment for nearly two decades. • However, in 2012 a new consensus conference proposed the “Berlin Definition” which eliminates the distinction between “acute lung injury” and ARDS, and rather categorizes ARDS by severity based on the degree of hypoxemia (mild, moderate, severe). The three categories are associated with increasing mortality. In contrast to the previous American-European Conference definition, the Berlin Definition of ARDS was empirically evaluated using patient-level meta- analysis, and is thus better validated as a research and descriptive tool.
  7. 7. Risk Factors ALI/ARDS can occur as a result of either DIRECT or INDIRECT injury to the lungs
  8. 8. Risk factor… • Direct cause appear to account for approx. half of all the cases. • It is not clear whether the distinction between direct and indirect lung injury is clinically useful • Patients with direct lung injury may be more likely to have improved lung mechanics with the application of PEEP. • However, in the largest cohort of patients studied to date, there was no difference in mortality between those with direct (pulmonary) and indirect (extra-pulmonary) causes of lung injury. • Regardless of the underlying cause of ALI/ARDS, most patients with ALI/ARDS appear to have a systemic illness with inflammation and organ dysfunction not confined to the lung
  9. 9. Risk factor… • Sepsis is the MC cause of indirect lung injury, with an overall risk of progression to ALI or ARDS of approximately 30% to 40%. • In addition to sepsis itself being a risk factor for development of ARDS, the site of infection may also influence the risk of lung injury. • Severe trauma with shock and multiple transfusions also can cause indirect lung injury. Although the other causes of indirect lung injury are less common, many, such as blood transfusions, are commonplace events in the ICU setting. • The MC cause of direct lung injury is pneumonia, which may be of bacterial, viral, or fungal origin. • The risk of developing ALI/ ARDS increases substantially in the presence of multiple predisposing disorders. • Secondary factors like chronic lung disease, chronic or acute alcohol abuse, increasing age, transfusion of blood products, lung resection and obesity may also increase the risk. • Emerging evidence has suggested that some at-risk patients may actually be protected from the development of ARDS. Several studies have shown that patients with diabetes are less likely to develop ARDS.
  10. 10. Cause of Lung Injury NHLBI ARDS Clinical Trials Network. N Engl J Med. 2004. Aspiration 15% Transfusion 5% Other 10% Pneumonia 40% Sepsis 22% Trauma 8% Aspiration Transfusion Other Pneumonia Sepsis Trauma
  11. 11. • Complex and remains incompletely understood. • Microscopically, lungs from afflicted individuals in the early stages show diffuse alveolar damage with alveolar flooding by proteinaceous fluid, neutrophil influx into the alveolar space, loss of alveolar epithelial cells, deposition of hyaline membranes on the denuded basement membrane, and formation of micro thrombi. Pathophysiology
  12. 12. Pathophysiology… • Alveolar flooding occurs as a result of injury to the alveolar-capillary barrier and is a major determinant of the hypoxemia and altered lung mechanics that characterize early ALI/ARDS. Flooding is characteristically with a protein-rich edema fluid, owing to the increased permeability of the alveolar capillary barrier, in contrast to the low-protein pulmonary edema that results from hydrostatic causes such as congestive heart failure or acute myocardial infarction. • Migration of neutrophils into the alveolar compartment play an important role in the initial inflammatory response in ARDS. • Surfactant dysfunction • Activation of coagulation cascade and impaired fibrinolysis. • Alteration in balance between endogenous oxidants and anti oxidants.
  13. 13. Ventilator Induced Lung Injury • There are several mechanisms by which mechanical ventilation can injure the lung. • Ventilation at very high volumes and pressures can injure even the normal lung, leading to increased permeability pulmonary edema due to capillary stress failure and sustained elevations of circulating plasma cytokines. • In the injured lung, even tidal volumes that are well tolerated in the normal lung can lead to alveolar over-distension in relatively uninjured areas because the lung available for distribution of the administered tidal volume is greatly reduced and because of uneven distribution of inspired gas. • In addition to alveolar over-distension, cyclic opening and closing of atelectatic alveoli can cause lung injury even in the absence of alveolar over-distension. • The combination of alveolar over-distension with cyclic opening and closing of alveoli is particularly harmful and can initiate a pro-inflammatory cascade. Pathophysiology…
  14. 14. Positive pressure ventilation may injure the lung via several different mechanisms VILI Alveolar distension “VOLUTRAUMA” Repeated closing and opening of collapsed alveolar units “ATELECTRAUMA” Oxygen toxicity Lung inflammation “BIOTRAUMA” Multiple organ dysfunction syndrome Pathophysiology…
  15. 15. Diagnosis • Diagnostic uncertainty in ALI/ARDS is a major barrier to initiation of appropriate therapy and one of the main reasons why clinicians fail to initiate lung-protective ventilation in clinically appropriate patients. • There are no specific clinical or laboratory studies that can reliably identify ARDS. • The standardization of definitions for ALI and ARDS has been helpful from several perspectives. New definitions are easy to apply and facilitate rapid identification and appropriate treatment of patients with ALI/ARDS • Although not strictly part of these definitions, an underlying cause of lung injury should be sought. In the absence of an identifiable underlying cause, particular attention should be given to the possibility of other causes of pulmonary infiltrates and hypoxemia, such as hydrostatic pulmonary edema
  16. 16. Based solely on clinical criteria There is no reference to pathogenesis or underlying cause Presence or absence of multi-organ dysfunction is not specified. Bilateral infiltrates has major prognostic significance and is a Hallmark, radiographic findings are not specific for ALI/ARDS However, it should be noted the nature of ALI/ARDS is such that any definition will have significant shortcomings.
  17. 17. • One more potential limitation of the consensus definition is the need for arterial blood gas sampling to calculate a Pao2/Fio2 ratio. Recent work has shown good correlation between the Spo2/Fio2 ratio (measured by pulse oximetry) and the Pao2/Fio2 ratio, with an Spo2/Fio2 ratio of 235 corresponding to a Pao2/Fio2 ratio of 200, and an Spo2/Fio2 ratio of 315 correlating to a Pao2/Fio2 ratio of 300. These calculations are valid only when the Spo2 is less than 98%, because the oxy-haemoglobin dissociation curve is flat above this level. • Oxygen saturation is a non-invasive, continuously available measurement; use of the Spo2/Fio2 ratio may improve the ability of clinicians to diagnose ARDS. Diagnosis…
  18. 18. Alternate methods of Diagnosis To Increase sensitivity and specificity of clinical definitions for ALI/ARDS. Pulmonary edema fluid to plasma protein ratio, if measured early after endotracheal intubation. Circulating bio-markers. Invasive techniques for diagnosis eg • Broncho-alveolar lavage for culture and cytological examination. • Open lung biopsy
  19. 19. Clinical Course Early ALI/ARDS • Radiographic infiltrates • Hypoxemia and Increased work of breathing • Increased pulmonary vascular resistance  Pulmonary HTN  RV Failure Late Fibro-proliferative ALI/ARDS Resolution of ALI/ARDS.
  20. 20. Radiographic infiltrate • Bilateral • Patchy or diffuse • Fluffy or dense • Pleural effusion • Areas of alveolar filling and consolidation occur predominantly in dependent zones, while non- dependent regions can appear relatively spared. Even areas that appear spared in conventional radiographic images may have substantial inflammation when sampled using bronchoalveolar lavage or using FDG- PET scanning.
  21. 21. Hypoxemia • Relatively refractory to supplemental oxygen. • The increased work of breathing in the acute phase of ALI/ARDS is due to decreased lung compliance as a result of alveolar and interstitial edema combined with increased airflow resistance and increased respiratory drive. • Many patients with ARDS also develop evidence of increased pulmonary vascular resistance leading to pulmonary hypertension and RV failure. The prevalence of pulmonary hypertension in patients presenting to the hospital with ARDS may be as high as 92%, and as many as 10% of patients with ARDS may have right ventricular (RV) failure defined by hemodynamic measurements.
  22. 22. ARDS Fibro- proliferative stage Resolution phase
  23. 23. Late fibro-proliferative stage Radiographically, linear opacities develop, consistent with the evolving fibrosis. Histologically, pulmonary edema and neutrophilic inflammation are less prominent. A severe fibro- proliferative process fills the airspaces with granulation tissue that contains extracellular matrix rich in collagen and fibrin, as well as new blood vessels and proliferating mesenchymal cells. Clinically, the late fibro-proliferative phase of ALI/ARDS is characterized by continued need for mechanical ventilation, often with persistently high levels of PEEP and Fio2. Lung compliance may fall even further, and pulmonary dead space is elevated. If it has not developed in the acute phase, pulmonary hypertension may occur now owing to obliteration of the pulmonary capillary bed, and right ventricular failure may appear
  24. 24. Resolution Phase For complete resolution of ALI/ARDS to occur, a variety of processes must be reversed: Alveolar edema is actively reabsorbed by the vectorial transport of sodium and chloride from the distal airway and alveolar spaces into the lung interstitium. Soluble and insoluble protein must also be cleared from the airspaces. Soluble protein probably diffuses by a paracellular route into the interstitium, where it is cleared by lymphatics. Insoluble protein probably is cleared by macrophage phagocytosis or alveolar epithelial cell endocytosis and transcytosis. The denuded alveolar epithelium in ALI/ARDS must be repaired. The alveolar epithelial type II cell serves as the progenitor cell for repopulating the alveolar epithelium. Resolution of neutrophilic inflammation may be predominantly via neutrophil apoptosis and phagocytosis by macrophages. The resolution of fibrotic changes is also not well understood. However, substantial remodeling is necessary to restore a normal or near-normal alveolar architecture. In patients with advanced fibrosis, this process likely takes place over many months.
  25. 25. treatment • Standard supportive therapy Treat predisposing factors Fluid and haemodynamic management Nutrition • Mechanical Ventilation Lung protective ventilation Non Invasive ventilation • Pharmacological therapies • Rescue therapy
  26. 26. Treatment of predisposing factors • First and foremost, a search for the underlying cause of ALI/ARDS should be undertaken. Appropriate treatment for any precipitating infection such as pneumonia is critical to enhance the chance of survival. • In the immunocompromised host or patients without predisposing risk factors, invasive diagnostic evaluation including bronchoscopy may be warranted to look for evidence of opportunistic infections or alternative specific causes of ARDS. • In a patient with sepsis and ALI/ARDS of unknown source, an intra-abdominal process should be considered. Timely surgical management of intra-abdominal sepsis is associated with better outcomes. • In some patients, the cause of lung injury will not be specifically treatable (such as aspiration of gastric contents) or will not be readily identifiable.
  27. 27. Fluid and haemodynamic management • For decades there was disagreement as to the best fluid-management strategy in patients with ARDS. • Proponents of a liberal fluid strategy reasoned that increased circulating volume would preserve end-organ perfusion and protect patients from the development of non-pulmonary organ failures. • Others supported a conservative fluid strategy in an attempt to reduce circulating volume, thereby reducing the driving force for pulmonary edema formation. There is some clinical evidence to support this approach.
  28. 28. Currently, the recommended strategy is to aim to achieve the lowest intravascular volume that maintains adequate tissue perfusion as measured by urine output, other organ perfusion, and metabolic acid-base status, using CVP monitoring to direct therapy. If organ perfusion cannot be maintained in the setting of adequate intravascular volume, administration of vasopressors and/or inotropes should be used to restore end-organ perfusion. Once shock has resolved, patients should be managed with a conservative fluid strategy, with the goal of driving the CVP below 4 to keep each patient’s fluid balance net zero over their ICU stay.
  29. 29. nutrition • The enteral route is preferred to the parenteral route and is associated with fewer infectious complications. • The ARDS Network is currently conducting a randomized trial of trophic (10 mL/h, well below caloric requirements) versus full-calorie enteral feeds in patients with ALI/ARDS. • Until the results of the ARDS Network study become available, the goals of nutritional support in any critically ill patient include providing adequate nutrients for the patient’s level of metabolism and treating and preventing any deficiencies in micro- or macronutrients. • There is still no compelling evidence to support the use of anything other than standard enteral nutritional support, with avoidance of overfeeding, in patients with ALI/ARDS.
  30. 30. Lung protective ventilation In 2000, the NIH ARDS Network published the findings of their first randomized, controlled, multi-center clinical trial in 861 patients. The trial was designed to compare a lower-tidal-volume ventilatory strategy (6 mL/kg predicted body weight, plateau pressure < 30 cm H2O) with a higher tidal volume (12 mL/kg predicted body weight, plateau pressure <50 cm H2O). In this trial, the in-hospital mortality rate was 40% in the 12 mL/kg group and 31% in the 6 mL/kg—a 22% reduction. Ventilator-free days and organ failure–free days were also significantly improved in the low-tidal-volume group. These findings were truly remarkable, since no prior large randomized clinical trial of any specific therapy for ALI/ARDS has ever demonstrated a mortality benefit.
  31. 31. 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 180160140120100806040200 ProportionofPatients Days after Randomization Lower tidal volumes Survival Discharge Traditional tidal values Survival Discharge ARDS Network. N Engl J Med. 2000. ARDS Network: Improved Survival with Low VT
  32. 32. High vs low peep • PEEP by avoiding repetitive opening and collapse of atelectatic lung units, could be protective against VILI. • High PEEP should make the mechanical ventilation less dangerous than low PEEP. • The recruitment is obtained essentially at end-inspiration, and the lung is kept open by using PEEP to avoid end- expiratory collapse. • PEEP, by preserving inspiratory recruitment and reestablishing end-expiratory lung volume, has been shown to prevent surfactant loss in the airways and avoid surface film collapse. • There has never been a consensus regarding the optimum level of PEEP for a given patient with ARDS.
  33. 33. In ALI and ARDS patients, higher PEEP strategy was associated with: • PaO2/FiO2 higher the first seven days post randomization • Plateau pressure higher the first three days post randomization • VT lower the first three days post randomization • No difference in RR, PaCO2, or pH • No difference in mortality rate • No difference in organ failures or barotrauma • No difference in IL-6, ICAM-1, surfactant protein-D “Lower PEEP” (or lower tidal volume) was sufficient to protect against injury from “Atelectrauma” (ventilation at low end-expiratory volumes)? High vs low peep…
  34. 34. Non Invasive ventilation • NIV has been highly successful in avoidance of intubation in patients with acute exacerbation of COPD. NIV is commonly used in pediatric patients with ALI/ARDS, The role for NIV in adults with ALI/ARDS is still unclear. • In one large multi-center study of 354 of 2770 patients with acute hypoxemic respiratory failure who were not already intubated, NIV failed in 30% of patients but failed in 51% of patients with ARDS. • One group of patients in whom NIV is particularly appealing is those patients who are immunosuppressed for various reasons and are at highest risk for nosocomial infections. Encouraging results have now been reported in a variety of patients with acute respiratory failure and immunosuppression.
  35. 35. Pharmacological therapy • Glucocorticoids therapy, as some believe, might hasten the resolution of late fibro- proliferative ALI/ARDS. Compared to patients treated with placebo, those treated with methylprednisolone had an increase in the number of shock-free days and ventilator-free days by day 28, as well as improvements in oxygenation; but they did not have improved survival and had higher rates of re-intubation, perhaps due to neuromuscular weakness.
  36. 36. Corticosteroid Therapy in ARDS: Better late than never? High-dose corticosteroids in early ARDS • Do not lessen the incidence of ARDS among patients at high risk • Do not reverse lung injury in patients with early ARDS/worse recovery • Have no effect on mortality/even increase mortality rate • Significantly increase the incidence of infectious complications High-dose corticosteroids for Unresolving ARDS of  7 days duration who do not have uncontrolled infection • Patient selection: Lack of clinical improvement rather than use of only the LIS • Aggressive search for and treatment of infectious complications is necessary. • Several questions remain: Timing, dosage, and duration of late steroid therapy in ARDS/Appropriate time window for corticosteroid administration, between early acute injury and established post aggressive fibrosis. Kopp R et al., Intensive Care Med 2002 Brun-Buisson C and Brochard L, JAMA 1998
  37. 37. Effect of Prolonged Methylprednisolone in Unresolving ARDS Rationale: Within seven days of the onset of ARDS, many patients exhibit a new phase of their disease marked by fibrotic lung disease or fibrosing alveolitis with alveolar collagen and fibronectin accumulation. Patient selection: Severe ARDS/  7 days of mechanical ventilation/ No evidence of untreated infection Treatment protocol: Methylprednisolone In patients with un-resolving ARDS, prolonged administration of methylprednisolone was associated with improvement in lung injury and MODS scores and reduced mortality. Meduri GU et al., JAMA 1998
  38. 38. recombinant human activated protein C Site-inactivated recombinant factor VIIa HMG-CoA reductase inhibitors (statins) Peroxisome proliferator–activated receptors modulators. Pharmacological therapy…
  39. 39. Rescue therapy In patients who do not respond to conventional treatment with low-tidal-volume ventilation and remain persistently hypoxemic, there are several unproven rescue therapies that may be tried to improve oxygenation in the acute setting: • Extracorporeal membrane oxygenation (ECMO) • High-frequency oscillatory ventilation (HFVO) • prone positioning • pulmonary vasodilator, such as inhaled nitric oxide (iNO) or inhaled prostacyclin. Although none have shown improved mortality, its use has been associated with improvements in oxygenation.
  40. 40. Ventral Dorsal Dorsal Ventral Mechanism of Prone Positioning
  41. 41. While selecting ventilatory strategy REMEMBER THE CONCEPT Buy Time – Doing Least Harm
  42. 42. Complications Barotrauma occurs when air dissects out of the airways or alveolar space into surrounding tissues, leading to pneumothorax, pneumo-mediastinum, pneumatocele, or subcutaneous emphysema. In 861 patients enrolled in the ARDS Network trial, approximately 10% of patients developed some form of barotrauma regardless of whether they were in the 6 or 12 mL/kg tidal volume arm. Further, PEEP level was the only factor that predicted the development of barotrauma in a multivariate analysis. Barotrauma
  43. 43. Nosocomial pneumonia There is yet no consensus regarding the appropriate way to diagnose nosocomial pneumonia in the mechanically ventilated patient. Clinical criteria commonly used in the diagnosis include fever, elevated white blood cell count, purulent secretions, and pulmonary infiltrates. However, these signs are often present in patients with ALI/ARDS even in the absence of nosocomial pneumonia. Regardless of the methods used for diagnosis, early, appropriate, empirical therapy is the mainstay of treatment for nosocomial pneumonia.
  44. 44. MULTISYSTEM ORGAN DYSFUNCTION Multisystem organ dysfunction is a common complication in ALI/ARDS. Organ dysfunction may result from the underlying cause of ALI/ARDS, such as sepsis, or occur independently. Given the simultaneous occurrence of multiple organ failures, it is often difficult to determine the exact cause of death in ALI/ARDS patients, and survival ultimately depends on the successful support of the failing organs
  45. 45. NEUROMUSCULAR WEAKNESS Patients with ALI/ARDS are at high risk for developing prolonged muscle weakness that persists after resolution of pulmonary infiltrates and can complicate weaning from mechanical ventilation and rehabilitation. This clinical syndrome is commonly called critical illness polyneuropathy. Prolonged muscle weakness is most common in critically ill patients who are treated with glucocorticoids. Neuromuscular blockade has also been implicated, and for this reason, the use of neuromuscular blockade should be reserved for those patients who are unable to be adequately oxygenated or who have problematic dyssynchrony with the mechanical ventilator despite deep sedation.
  46. 46. Outcome and Prognosis • In the ARDS Network study of 861 patients with ALI/ARDS, aggregate mortality to hospital discharge was 31% in the 6 mL/kg tidal volume arm and 40% in the 12 mL/kg tidal volume arm. • The risk of in hospital mortality was highest in patients with sepsis (43%), intermediate in those with pneumonia (36%) or aspiration (37%), and lowest in those with multiple trauma (11%). • The low-tidal-volume strategy was effective at reducing mortality across all causes of ALI/ARDS.
  47. 47. • ALI/ARDS survivors frequently have long-term functional disability, cognitive dysfunction, and psychosocial problems. • Interestingly, pulmonary function frequently returns to normal or near normal in survivors. • In a report of 1-year follow-up in 109 survivors from ARDS, lung volumes and spirometry had returned to normal by 6 months. • However, carbon monoxide diffusing capacity was persistently low at 12 months. • Six-minute walk distances were persistently low at 12 months, largely due to muscle wasting and weakness rather than pulmonary function abnormalities. • Survivors of ALI/ARDS have been reported to have reduced health-related quality of life. • In addition to physical and social difficulties after ARDS, survivors have high rates of depression and anxiety Outcome and Prognosis…
  48. 48. Thank You