ACUTE RESPIRATORY DISTRESS SYNDROME pptx

Acute respiratory distress syndrome, its diagnosis and management

1. ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS) Pathophysiology and Management MODERATOR –DR. Medha Mohta PRESENTER –DR. Surbhi Tyagi

2. ARDS History Definition Aetiology Pathophysiology Clinical presentation and radiographic findings Management Ventilation strategy Other supportive treatment

3. First defined by Ashbaugh and colleagues in 1967 A syndrome of acute respiratory failure with hypoxia and loss of compliance after a variety of clinical insults patients did not respond to usual methods of respiratory therapy and positive end-expiratory pressure (PEEP) was most helpful in combating atelectasis and hypoxemia The clinical and pathological features closely resembled those seen in infants with respiratory distress and hence these patients were described as having acute respiratory distress in adults DEFINITION

4. MURRAY & MATHAY LUNG INJURY SCORE,1988 Chest radiology findings Score No alveolar consolidation One quadrant 1 Two quadrant 2 Three quadrant 3 Four quadrant 4 Oxygenation status (Hypoxemia Score) PaO2 / FiO2 Score > 300 mmHg 0 225-299 mmHg 1 175-224 mmHg 2 100-174 mmHg 3 < 100 mmHg 4

5. Pulmonary compliance Compliance (ml/cmH2O) Score > 80 0 60-79 1 40-59 2 20-39 3 < 19 4 PEEP settings PEEP (cmH2O) Score < 5 0 6-8 1 9-11 2 12-14 3 > 15 4

6. Acute lung injuries are assessed by dividing sum of above points by 4, if: 0 points No pulmonary injury 1-2.5 points Mild to moderate > 2.5 points Severe (ARDS)

7. AMERICAN EUROPEAN CONSENSUS CONFERENCE 1994 According to this definition, ARDS must be characterised by : Acute onset Severe hypoxaemia (PaO2/Fio2 ≤ 200) Bilateral infiltrates on chest x-ray No clinical e/o left atrial HTN or pulmonary artery wedge pressure ≤18 mmHg New term included – Acute lung injury(ALI) with less severe degree of hypoxaemia (Pao2/Fio2 ≤ 300)

8. Limitations of Consensus Conference definition No definition of acute time frame Confusing ALI/ ARDS term Inconsistency of PaO2/Fio2 ration due to effect of PEEP/ Fio2 PAWP <18 may not always be discriminative Poor interobserver reliability of chest radiograph interpretation, PAWP and clinical assessments of LAH

9. THE BERLIN DEFINITION, 2012 Timing within 1 week of a known clinical insult or new or worsening respiratory symptoms Chest imaging (chest x-ray or CT scan) Bilateral opacities – not fully explained by effusions, lobar/lung collapse or nodules Origin of edema Respiratory failure not fully explained by cardiac failure or fluid overload Need objective assessment e.g., Echocardiography to exclude hydrostatic edema if no risk factor present Oxygenation PaO2/FiO2* Mild Moderate Severe Severity 200 < PaO2/FiO2 ≤300 *With PEEP or CPAP ≥ 5cmH 2 O 100 < PaO2/FiO2 ≤200 PaO2/FiO2  ≤100

10. RISK FACTORS Direct Lung Injury/ Primary or pulmonary ARDS Indirect Lung Injury/ Secondary or nonpulmonary ARDS Pneumonia Sepsis – most common cause Gastric Aspiration Prolonged systemic hypotension and shock Pulmonary embolism Massive transfusions (TRALI) Toxic inhalation (phosgene, cocaine, smoke, high O2 concentration ) Severe trauma Reperfusion injury (post lung transplantation or pulmonary embolectomy) Gynecologic causes(abruptio placentae, amniotic embolism , eclampsia) Lung contusion Acute pancreatitis Near drowning Burn injury Post-cardiopulmonary bypass Fulminant hepatic failure Sickle cell crisis

11. PATHOPHYSIOLOGY In normal healthy lungs, there is a small amount of fluid that leaks into the interstitium The lymphatic system removes this fluid and returns it into the circulation keeping the alveoli dry Activation of inflammatory mediators and cellular components release of pro-inflammatory cytokines: TNF, IL-1, IL-6 and IL-8 resulting in damage to capillary endothelial and alveolar epithelial cells allows proteins to escape from the vascular space oncotic gradient that favours resorption of fluid is lost and fluid pours into the interstitium, overwhelming the lymphatic system

12. Increased permeability of alveolar capillary membrane Influx of protein rich edema fluid and inflammatory cells into air spaces Impaired gas exchange and decreased compliance Dysfunction of surfactant

13. PATHOPHYSIOLOGY… Alveolar macrophages release pro-inflammatory cytokines (TNF- ɑ , IL-6, IL-8) Attract neutrophils to the lungs Release reactive oxygen species and proteolytic enzymes Damage of alveolar epithelium and endothelium Proteinaceous edema fluid filling alveolar space

14. STAGES OF ARDS

15. HISTOPATHOLOGY Exudative phase (1 st week) Diffuse damage to alveoli and blood vessels Influx of proteinaceous fluid and inflammatory cells - alveolar and interstitial edema Capillary congestion Destruction of type I and type II pneumocytes Early hyaline membrane formation Cellular debris and condensed plasma proteins Short, fully reversible

16. HISTOPATHOLOGY… Proliferative Phase (2 nd to 4 th week) Increased type II pneumocytes Fibroblasts proliferation in alveolar basement membrane and intra-alveolar spaces Organization of hyaline membranes The terms "stiff lung" and "shock lung" frequently used to characterize this stage.

17. HISTOPATHOLOGY… Fibrosis Phase (>3 to 4 weeks) Inflammation resolves Fibrosis of hyaline membranes and alveolar septum Intra-alveolar and interstitial fibrosis Complete normalization of lung compliance and oxygenation 6 to 12 months after the illness Irreversible pulmonary fibrosis in 5-10% patients, depending on severity and duration

18. ARDS exudative and fibrotic phases Exudative (acute) phase Fibrotic phase

19. CLINICAL FINDINGS IN ARDS Phase 1 Acute Injury Normal physical examination and chest X- Ray Tachycardia, Tachypnea, Respiratory alkalosis Phase 2 Latent Period Lasts approximately 6-48 hrs. after injury Patient appears clinically stable Hyperventilation and hypocapnia persists Mild increase in work of breathing Widening of alveolar-arterial oxygen gradient Minor abnormalities on physical examination and chest x-ray

20. Phase 3 Acute Respiratory Failure Marked tachypnea and dyspnea Coarse crepitations Decreased Lung Compliance Diffuse infiltrates on chest x-ray Phase 4 Severe Abnormalities Severe Hypoxemia unresponsive to therapy Metabolic and respiratory acidosis Look for signs of congestive heart failure or intravascular volume overload to distinguish ARDS from cardiogenic pulmonary edema

21. Cardiogenic/ Hydrostatic Prior h/o cardiac disease Third heart sound Cardiomegaly Infiltrates: Central distribution Widening of vascular pedicle PCWP >18 mmHg Positive fluid balance BAL: Transudative Low protein and noninflammatory Non-cardiogenic/ Non-hydrostatic Absence of heart disease No third heart sound Normal sized heart Peripheral distribution Normal width of vascular pedicle PCWP ≤18 Negative fluid balance BAL: Exudative High protein and inflammatory, marked cellular influx CARDIOGENIC VS NON-CARDIOGENIC PULMONARY EDEMA

22. CARDIOGENIC VS NON-CARDIOGENIC PULMONARY EDEMA Cardiomegaly, Bilateral perihilar and basilar alveolar Infiltrates, bilateral pleural effusion Normal cardiac size, Diffuse peripheral patchy Infiltrates homogenously distributed throughout

23. MANAGEMENT OF ARDS Identify and manage underlying cause of ARDS Maintain oxygenation Mechanical ventilation Adjuncts to ventilation Restrictive fluid management Permissive hypercapnia Prone positioning Recruitment maneuvers

24. MANAGEMENT OF ARDS….. Salvage intervention for patients with severe hypoxemia with ARDS Inverse ratio ventilation (IRV) Airway pressure release ventilation (APRV) Tracheal gas insufflation ECMO HFOV Pharmacological interventions Neuromuscular blockers Inhaled vasodilators (NO, prostacyclins) Systemic corticosteroids Miscellaneous

25. Enhance patient-ventilator synchrony and patient comfort by use of sedation, amnesia, opioid analgesia, and pharmacological paralysis, if necessary Wean from mechanical ventilation when patient can breathe without assisted ventilation Support or treat other organ system dysfunction or failure General critical care Analgesia, antibiotics, sedation, Nutritional support, Optimization of hemodynamics Prophylaxis against deep vein thrombosis (DVT) Gastrointestinal (GI) bleeding prophylaxis MANAGEMENT OF ARDS…..

26. Ventilator induced lung injury(VILI) ARDS is a heterogenous process in which some alveoli will never inflate, some will open and close cyclically while others will be continuously distended and damaged Significant reduction in amount of normally aerated lung tissue - “Baby Lung” Tidal hyperinflation of the ‘baby lung’ and cyclic atelectasis of already injured lung units – VILI (Ventilator induced lung injury) In VILI Volutrauma – strain due to overdistension of compliant alveoli Barotrauma – stress due to high inspiratory pressures ( Pplat ) Atelectrauma – shear stress due to cyclic opening and closing of alveoli Biotrauma – release of inflammatory mediators from lung

27. Ventilator induced lung injury(VILI)….

28. VENTILATORY STRATEGY IN ARDS PATIENTS Protective ventilation strategies should aim at preventing stress/strain at the end of inspiration and expiration Open lung approach Lung protective ventilatory approach Alternative and rescue ventilation strategies Inverse-ratio ventilation Airway pressure release ventilation High frequency ventilation Extracorporeal support

29. OPEN LUNG APPROACH Static Pressure Volume curve of lung Used to select an optimum PEEP level and V T On the inspiratory limb: Lower Inflection Point ( P flex ) – most recruitable alveoli opened, below which alveolar closure is hypothesized to occur Upper Inflection Point (UIP) – beyond which overdistention of alveolar units occurs, PEEP set 2 cmH 2 O above P flex

30. OPEN LUNG APPROACH Maintaining inflation & deflation between 2 inflection points during entire respiratory cycle is called Open Lung Ventilation Ventilatory setting where PEEP > P flex & Tidal volume is reduced so that P plat < UIP is basis for lung protective strategies Advantages - avoids repetitive opening & closing of alveoli (ATELECTRAUMA)

31. OPEN LUNG APPROACH Volume Pressure Zone of Overdistention Safe window Zone of Derecruitment and atelectasis Goal is to avoid injury zones and operate in the safe window

32. LUNG PROTECTIVE VENTILATION ARDS NETWORK STUDY 2000 Low tidal volume ventilation to prevent tidal hyperinflation and application of PEEP to improve hypoxemia and limit cyclic atelectasis

33. ARDSnet protocol 2000 Calculate predicted body weight (PBW) Male: 50+2.3[height(inches)-60] Female: 45.5+2.3[height(inches)-60] Mode: Volume assist-control or pressure control ventilation TV = 6ml/kg (adjusted acc. plateau press) Change rate to adjust minute ventilation (not >35/min) pH goal 7.30-7.45 Plateau pressure <30cm H20 PaO2 goal: 55-80mmhg or SpO2 88-95%

34. FiO2/PEEP combination to achieve oxygenation goal PaO2 goal: 55-80mmHg or SpO2 88-95% use FiO2/PEEP combination to achieve oxygenation goal How to titrate PEEP Incremental Method : Point of best compliance at increasing levels of PEEP Keep ↑ PEEP till change in P Plat is less than or equal to the change in PEEP. Decremental method : Start at high PEEP (24-20 cms of H2O)→ Keep ↓ ing PEEP while checking compliance → PEEP at which compliance starts ↓ ing → PEEP just above FiO2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 PEEP 5 5-8 8-10 10 10-14 14 14-18 18-24

35. HIGH PEEP VS. LOW PEEP 3 RCT: Alveoli 2004, Lovs 2008, ExPress 2008 Increased hospital mortality in patients with lower PEEP The LUNG SAFE study, 2016: potentially modifiable factors contributing to outcome from ARDS Higher PEEP Lower peak pressure Lower plateau pressure Lower driving pressure Lower respiratory rate Associated with improved survival from ARDS

36. RECRUITMENT MANEUVERS A sustained increase in pressure in the lungs with the goal of opening maximum collapsed lung units thereby improving oxygenation and volume distribution Once the lungs are recruited, they are kept open by maintaining an adequate PEEP above the LIP PIP kept lower than UIP Applied PEEP: uninterrupted, greater than any superimposed gravitational pressures from lungs and heart

37. RECRUITMENT MANEUVERS Most commonly used methods are sustained inflation/ traditional and incremental PEEP/ staircase/ stepwise recruitment maneuver Sustained inflation/ Traditional: CPAP mode, using pressures of 35−50 cmH2O for 20−40 s while ensuring that the pressure support is set to zero to avoid additional pressure increases

38. RECRUITMENT MANEUVERS Staircase or incremental PEEP: Stepwise increase in PEEP every 2−3 min while maintaining constant driving pressure (plateau pressure − PEEP), followed by stepwise decrease in PEEP to the optimal PEEP level which is determined by compliance and oxygenation Recruitment occurs across entire range of lung volume from residual volume to total lung capacity.

39. Steps before Recruitment maneuvers Hemodynamic stabilization Fluid resuscitation Check for pneumothorax/ pneumomediastinum SaO 2 / PaO 2 ETCO 2 / PaCO 2 Compliance Adequate sedation/ NM-blockade Hazards: Significant ↑ in thoracic pressures for an extended period Decrease in venous return, cardiac output and BP

40. PERMISSIVE HYPERCAPNIA Hickling and colleagues 1990 “Degree of hypercapnia permitted in patients subjected to lower tidal volumes” Strategy to minimize VILI Low tidal volume & low peak airway pressures Advantages Increased surfactant secretion (animal models) – improved V/Q match, oxygenation (improved compliance) Increased cardiac output and oxygen delivery (sympathoadrenal effects predominate over cardio depressant effects) Increased cerebral blood flow and tissue oxygenation

41. PERMISSIVE HYPERCAPNIA Disadvantages: Pulmonary hypertension Decrease myocardial contractility Decreased renal blood flow Elevated intracranial pressure Release of endogenous catecholamine No ‘safe’ permitted levels of arterial carbon dioxide or lower limit of pH for metabolic acidosis defined Induced hypercapnia could be controlled by treating metabolic acidosis with sodium bicarbonate when pH level is below 7.2 Extracorporeal removal of carbon dioxide (ECCO2 R)

42. PERMISSIVE HYPERCAPNIA Contraindications: raised ICP acute CVA myocardial ischemia pulmonary hypertension uncorrected severe metabolic acidosis sickle cell anemia pregnancy

43. PRONE POSITION VENTILATION The prone ventilation of patients with ARDS first described in the 1970s Large RCT by Gattinoni and colleagues in 2001 PROSEVA trial, 2013: Proning improved mortality in severe ARDS by 16.8% (p < 0.001) >16 hours/day in patients with severe ARDS (PF<150) Suggested mechanisms include Better ventilation – perfusion matching from alteration in regional blood flow Increase in functional residual capacity Alteration in respiratory mechanics and the creation of more uniform lung expansion Change in regional diaphragm motion Recruitment of collapsed alveoli Better clearance of secretions

44. PROBLEMS OF PRONE POSITION Facial edema Airway obstruction Difficulties with enteral feeding Vascular and nerve compression Loss of venous accesses and probes Loss of chest drain and catheters Accidental extubation Apical atelectasis Increased need for sedation Pressure sores

45. CONTRAINDICATIONS OF PRONE POSITION VENTILATION Unstable spine Head injury with raised ICP Unstable Cardiac rhythm Severe abdominal and soft tissue infection

46. FLUID MANAGEMENT FACTT trial, 2006 - conservative strategy of fluid management is associated with improved lung function and shortened duration of mechanical ventilation and intensive care without increasing non pulmonary-organ failures Patients with ARDS should receive intravenous fluids only sufficient to achieve an adequate cardiac output, tissue oxygen delivery, and organ function, as assessed by urine output, acid-base status, and arterial pressure.

47. INVERSE RATIO VENTILATION I:E ratio > 1 Improvement in oxygenation by – increases mean airway pressure, auto PEEP, decreased dead space ventilation, improved V/Q mismatch, reduced intrapulmonary shunting. Disadvantages – barotrauma, sedation/muscle paralysis required

48. HIGH FREQUENCY VENTILATION Mechanical ventilatory support using higher than normal breathing frequencies Special ventilators required Types – HIGH FREQUENCY JET VENTILATION (HFJV): A nozzle/injector creates high velocity ‘jet’ of gas directed into the lung HIGH FREQUENCY OSCILLATORY VENTILATION (HFOV): Characterized by rapid oscillations of a diaphragm where very low tidal volumes (1-2mL/ Kg) are delivered at high frequencies (3-15 Hz) Trials including  OSCILLATE 2013, and  OSCAR 2014: failed to show any significant difference in outcomes between HFOV and conventional ventilation In fact,  OSCILLATE , 2013 showed increased mortality (47 vs 35%, p=0.005) in the HFOV group vs. the control group

49. ECMO (Extracorporeal membrane oxygenation) Extracorporeal life support modality used to temporarily support patients with respiratory and/or cardiac failure that are refractory to conventional treatment Venovenous ECMO (VV-ECMO) : patients with respiratory failure with preserved cardiac function Venoarterial ECMO (VA-ECMO) : patients with cardiac failure with or without respiratory failure

50. ECMO (Extracorporeal membrane oxygenation)…. The  CESAR Trial , 2009 : demonstrated improved outcomes (63 vs 47% survival to 6 months without disability) Contraindications: Terminal illness with life expectancy < 6 months Uncontrolled metastatic cancer, acute intracranial hemorrhage or infarction Or any contraindication to systemic anticoagulation

51. AIRWAY PRESSURE RELEASE VENTILATION(APRV) Uses a continuous positive airway pressure with an intermittent release phase CPAP (P high) is applied for prolonged time (T high) to maintain adequate lung volume and alveolar recruitment with a time cycled release phase to lower set pressure ( P low) for a short period of time (T low) Allows patient to breathe spontaneously Potential benefits : ↑ V/Q match ↓ diaphragmatic atrophy during critical illness ↑ cardiac output and oxygen delivery ↑ splanchnic perfusion ↑ renal and hepatic function Fewer days on mechanical ventilation Fewer days in ICU

52. TRACHEAL GAS INSUFFLATION Normal ventilatory cycle - bronchi and trachea filled with alveolar gas at end expiration In the next inspiration, CO2 laden gas forced back into alveoli. TGI - stream of fresh gas (at 4-8L/min) insufflated through a small catheter/channels in the wall of endotracheal tube into the lower trachea CO2 laden gas flushed out of the trachea before next inspiration Disadvantages Dessication of secretions Inadequate humidification Airway mucosal injury Accumulation of secretions in the TGI catheter Creation of auto PEEP from expiratory flow and resistance of the ventilator-exhalation tubes and valve

53. PHARMACOLOGICAL INTERVENTIONS INHALED VASODILATORS: NITRIC OXIDE NO is a selective pulmonary vasodilator NO acts selectively on well ventilated alveoli and redirecting blood flow from poorly ventilated lung units, hence Improves ventilation-perfusion mismatch NO – immunomodulator C/I – absolute methemoglobinemia, relative bleeding diathesis, intracranial bleed, severe LVF PROSTACYCLINS: Inhaled Epoprostenol In refractory hypoxemia and pre-existing pulmonary vasoconstriction potent vasodilator, improve VQ mismatch

54. PHARMACOLOGICAL INTERVENTIONS… Neuromuscular Blockers (NMB): ACURASYS, 2010: decreased mortality in cisatracurium group (30.8%) vs control group (44.6%) better patient-ventilator synchrony Decrease pro-inflammatory response Indication: selective patients with severe ARDS with refractory hypoxemia, patient-ventilator desynchrony and high risk of barotrauma Surfactant therapy: Surfactant dysfunction exist in ARDS, surfactant decreases alveolar surface tension and alveolar edema Anticytokine effect – inhibition of IL-1, IL-6, TNF

55. Pharmacological Interventions Systemic Corticosteroids High dose corticosteroids- promote collagen breakdown and inhibit fibrosis Moderate to severe ARDS Methylprednisolone at dose of 1mg/kg/day( upto 7 days since onset) Early administration within 14 days Weaned slowly over 6−14 days and not stopped rapidly Reduce duration of mechanical ventilation and overall mortality Routine use – not advocated esp. in acute phase Adverse events: Hyperglycaemia

56. Miscellaneous Intravenous salbutamol Keratinocyte growth factor Granulocyte-macrophage colony stimulating factor Ketoconazole – inhibit Tx synthesis Activated protein C Intravenous interferon b-1a

57. MECHANICAL VENTILATION Lung protective ventilation: It is strongly recommended to use lung protective ventilation; tidal volume of 4−8 mL/Kg of predicted body weight and plateau pleasure of < 30 cmH2O in all ARDS patients. PEEP: PEEP is recommended in all patients with ARDS, and high PEEP may be considered on a case-by-case basis (conditional recommendation) in patients with moderate to severe ARDS.

58. Recruitment Maneuvers: Mixed evidence and routine use of recruitment maneuvers not supported may be considered in selective patients with severe ARDS and persistent hypoxemia. Modes of Ventilation: standard modes of ventilation (VC or PC) are recommended in patients with ARDS. There is no evidence that alternative modes of ventilation such as pressure controlled inverse ratio or airway pressure release ventilation provide additional benefit. HFOV is not recommended in the management of patients with moderate to severe ARDS.

59. PHARMACOLOGICAL INTERVENTIONS Neuromuscular Blockers (NMB) Use of NMBs in patients with moderate to severe ARDS should be individualized based on practitioner’s experience, facility protocols, and equipment/staff availability Systemic Corticosteroids Early administration of corticosteroids within 14 days of onset of moderate to severe ARDS can reduce the duration of mechanical ventilation and overall mortality provided no contraindications.

60. Inhaled Vasodilators No survival benefits seen Not recommended for routine use but may be used as bridge while waiting for other therapies such as ECMO. Miscellaneous No proven benefit

61. NON-PHARMACOLOGICAL INTERVENTIONS Prone Positioning prone positioning for more than 12 hr/day is strongly recommended in ventilated patients with severe ARDS Extracorporeal Membrane Oxygenation (ECMO) use of ECMO should be considered in a selected number of patients with severe ARDS on lung protective ventilation with Murray Score >3 or pH < 7.2 due to uncompensated hypercapnia. Additional factors such as age, comorbidities, etiology of ARDS and availability of ECMO also need to be taken into consideration

62. COMPLICATIONS ASSOCIATED WITH ARDS Pulmonary: barotrauma ,volutrauma, pulmonary embolism, pulmonary fibrosis, ventilator-associated pneumonia (VAP), Oxygen toxicity Gastrointestinal: hemorrhage (ulcer), dysmotility, pneumoperitoneum, bacterial translocation Cardiac: Arrhythmias, myocardial dysfunction Renal: acute renal failure (ARF), fluid retention Mechanical: vascular injury, tracheal injury/stenosis (result of intubation and/or irritation by endotracheal tube) Nutritional: malnutrition, anemia, electrolyte deficiency Hematologic: DIC, thrombocytopenia, anemia Infection: sepsis, nosocomial pneumonia

63. REFERENCES Egans Respiratory Care, 12 th ed. Pilbeam’s mechanical ventilation, 6 th ed. Paul L. Marino 4 th ed. The American Journal Of The Medical Sciences Volume 362 Number 1 July 2021 Harrison’s Principle of Internal Medicine, 19th ed.

64. THANK YOU