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Adult Respiratory Distress Syndrome. Case presentation A 45-year-old man develops ARDS after sustaining multiple broken bones in an automobile accident.

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Presentation on theme: "Adult Respiratory Distress Syndrome. Case presentation A 45-year-old man develops ARDS after sustaining multiple broken bones in an automobile accident."— Presentation transcript:

1 Adult Respiratory Distress Syndrome

2 Case presentation A 45-year-old man develops ARDS after sustaining multiple broken bones in an automobile accident. The man weighs 70 kg. Mechanical ventilation is initiated in the AC mode with the following settings: (PEEP), 10 cm H2O; (FiO2), 70%; respiration rate, 12/min. The most appropriate Tidal volume at this point: A.1000 ml B.420 ml C.500 ml D.560 ml E.700 ml

3 ARDS Definition  The 1994 North American-European Consensus Conference (NAECC) criteria:  Onset - Acute and persistent  Radiographic criteria - Bilateral pulmonary infiltrates consistent with the presence of edema  Oxygenation criteria - Impaired oxygenation regardless of the PEEP concentration, with a Pao2/Fio2 ratio  300 torr (40 kPa) for ALI and  200 torr (27 kPa) for ARDS  Exclusion criteria - Clinical evidence of left atrial hypertension or a pulmonary-artery catheter occlusion pressure of  18 mm Hg. Bernard GR et al., Am J Respir Crit Care Med 1994

4 Stratification System of Acute Lung Injury GOCA Artigas A, et al. Am J Respir Crit Care Med. 1998.

5 Rouby JJ, et al. Eur Respir J. 2003. Rouby JJ, et al. Anesthesiology. 2004. The ARDS Lung

6 Gattinoni L, et al. Am J Respir Crit Care Med. 1998. The ARDS Lung

7 ARDS Mortality Trend 28% 2006

8 Crit Care Med 2009 Vol. 37, No. 5

9 24% Crude 60-day mortality among Acute Respiratory Distress Syndrome (ARDS) Network patients, 1996–2005.

10 Baby Lung Concept In acute lung injury/acute respiratory distress syndrome, the normally aerated tissue has the dimensions of the lung of a 5- to 6- year-old child (300–500 g aerated tissue) What appears dangerous is not the VT/kg ratio but instead the VT/”baby lung” ratio. The practical message is straightforward: the smaller the “baby lung,” the greater is the potential for unsafe mechanical ventilation.

11 ARDS: Baby lungs

12 The amount of normally aerated tissue, measured at end-expiration, was in the order of 200–500 g in severe ARDS, i.e., roughly equivalent to the normally aerated tissue of a healthy boy of 5/6 years.

13

14 Stiff or Small? ARDS lung is not “stiff” at all, but small The elasticity of the residual inflated lung is nearly normal, as indicated by: – The specific tissue compliance: (compliance/normally aerated tissue) “baby lung” was a healthy anatomical structure, located in the nondependent regions of the original lungs

15 Ventilating ARDS with Normal VT Straining of the “baby lung”

16 Supine Prone Supine

17 The densities in the dependent lung regions are in fact due not to an increase in the amount of edema but to a loss of alveolar gases, as the result of the compressive gravitational forces, including the heart weight Sponge Lung Concept

18 Superimposed Pressure Inflated 0 Alveolar Collapse (Reabsorption) 20-60 cmH 2 O Small Airway Collapse 10-20 cmH 2 O Consolidation  ) (from Gattinoni) Lung Units at Risk for Tidal Opening & Closure = Opening pressure Baby lung at end-inspiration Spectrum of Regional Opening Pressures

19 Elastic fibers (spring) Collagen fibers (string). Baby Lung and VILI

20 Transpulmonary Pressure

21

22 Ventilator Induced Lung Injury

23 Recognized Mechanisms of Airspace Injury “Stretch” “Shear” Airway Trauma

24 End-Expiration Tidal Forces (Transpulmonary and Microvascular Pressures) Extreme Stress/Strain Moderate Stress/Strain Mechano signaling via integrins, cytoskeleton, ion channels inflammatory cascade Cellular Infiltration and Inflammation Rupture Signaling Marini / Gattinoni CCM 2004 Pathways to VILI

25 FTFT min max Mead J et al. J. Appl. Physiol. 28(5):596-608 1970 L. Gattinoni, 2003 Stress distribution homogeneous system

26 min max Mead J et al. J. Appl. Physiol. 28(5):596-608 1970 L. Gattinoni, 2003 Stress distribution High Stiffness Zone

27 Copyright ©2008 Canadian Medical Association or its licensors Gattinoni, L. et al. CMAJ 2008;178:1174-1176 Ventilator-induced lung injury is initiated by the application of excessive stress

28 NEJM 2000;342:1334-1349

29

30 ARDS

31 PEEP = 5 mbar Pinsp = 40 mbar Cytokines, complement, prostanoids, leukotrienes, O 2 - Proteases Volutrauma Atelectrauma Biotrauma

32 Barotrauma

33 Biophysical Injury shear overdistention cyclic stretch  intrathoracic pressure  alveolar-capillary permeability  cardiac output  organ perfusion Biochemical Injury (Biotrauma) mmmm cytokines, complement, PGs, LTs, ROS, proteases cytokines, complement, PGs, LTs, ROS, proteases bacteria Epithelium/ interstitium neutrophils Distal Organ Dysfunction MV and MODS: A Possible Link Slutsky, Tremblay Am J Resp Crit Care Med. 1998;157:1721-5 DEATH ? sFasL

34 PRINCIPLES AND GOALS OF MECHANICAL VENTILATION IN ARDS

35 Healthy subject In normal healthy volunteers, the P/V curve explore the mechanical properties of the respiratory system (lung + chest wall) ARDS RV, Residual volume; FRC, Functional residual capacity; TLC, Total lung capacity; UIP, Upper inflection point; LIP, Lower inflection point. The critical opening pressure above which most of the collapsed units open up and may be recruited - CLIN Compliance of the intermediate, linear segment of the P/V curve Maggiore SS, et al. Eur Respir J. 2003. Rouby JJ, et al. Eur Respir J. 2003. Respiratory Pressure/Volume (P/V) Curve

36 Ventilator-induced Lung Injury (VILI) Upper Deflection point Lower Inflection point

37 Principles and Goals of MV in ARDS Appropriate oxygenation (PO 2 = 55-60) Accept hypercapnea and mild acidosis (pH ~ 7.3) Limit distending pressure=limit transpulmonary pressure: Pplateau <28 cm H 2 O Limit tidal volume: 4-6 ml/Kg Best PEEP: 10-16 cm H 2 O

38 Preventing Overdistention and Under-Recruitment Injury “Lung Protective” Ventilation VOLUMEVOLUME VOLUMEVOLUME Pressure Limit Distending Pressure Add PEEP Limit VT Transpulmonary Pressure= Airway Pressure-Pleural Pressure 4-6 mL/kg < 28 cm H 2 O10-16 cm H 2 O

39

40 Pelosi P et al, AJRCCM 2001;164:122-130 CT at end-expiration Lung protective ventilatory strategy

41 P "safe" window zone of overdistension V atelectrauma volutrauma LIP UIP zone of derecruitment and atelectasis DON’T EVEN THINK OF PARKING HERE Lung Protective Ventilator Strategies

42 1998 53 patientsInterventionControl TV <6 ml/Kg PEEP >P Flex TV (10-12 ml/Kg) Lowest PEEP 28 day mortalityInterventionControl 38%71%

43 ARMA Trial 861 patientsInterventionControl TV (4-6 ml/Kg) PEEP 8.5 TV (10-12 ml/Kg) PEEP 8.6 861 patientsInterventionControl P plateau <30 P plateau <50 28 day mortalityInterventionControl 31%40%

44 NIH ARDS Network trial NEJM 2000;342:1301 ARDS net mortality Reducing from 12 to 6 ml/kg VT saved lives

45 NIH ARDS Network trial NEJM 2000;342:1301 Reducing from 12 to 6 ml/kg VT saved lives Low TV High TV P = Mortality31400.007 Days of free MV 12100.007 Days free of organ failure 15120.006

46 Tradeoffs with 6 ml/kg Crs also better in the HIGH Vt group

47 ARDS Network: Improved Survival with Low VT 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 180160140120100806040200 Proportion of Patients Days after Randomization Lower tidal volumes Survival Discharge Traditional tidal values Survival Discharge ARDS Network. N Engl J Med. 2000.

48 1996-9 Randomized Trials of MV in ARDS 1990s

49 10-16 20-26 25-32 29-38

50

51 Tidal hyperinflation during Low TV ventilation in ARDS 30 patients with ARDS Ventilatory strategy (ARMA protocol) – 6 ml/Kg IBW BAL ► cytokine measurements CT scan on mechanical ventilation Hyperinflated Normally aerated Poorly aerated Non-aerated

52 Tidal hyperinflation during low TV ventilation in ARDS Poorly aerated Non-aerated Hyperinflated Normally aerated Less protectedMore protected

53 30 % of patients hyperinflated 30 % of patients hyperinflated Plateau Pressure: Plateau Pressure: – Protected (25.5  0.5) vs. unprotected (28.9  0.9) Higher inflammatory cytokines in unprotected Higher inflammatory cytokines in unprotected Number of ventilator-free days: Number of ventilator-free days: – Protected (7  8) vs. unprotected (1  2) Mortality: Mortality: – Protected (30%) vs. unprotected (40%) Limit plateau pressure to < 28 Despite the use of protective ventilatory strategy (6 ml/Kg) …..

54 Papazian L et al. N Engl J Med 2010;363:1107-1116 Neuromuscular Blockers in Early Acute Respiratory Distress Syndrome 340 patients Cisatracurium besylatePlacebo # of Patients178162 TV6-8 ml/Kg PEEP> 5 90 day mortality31.6%40.7% p= 0.08

55 Papazian L et al. N Engl J Med 2010;363:1107-1116 Neuromuscular Blockers in Early Acute Respiratory Distress Syndrome Hazard Ratio: 0.68 (95% confidence interval [CI], 0.48 to 0.98; P = 0.04)

56 Possible Mechanisms by Which Neuromuscular Blocking Agents Might Lead to improved Survival

57

58 P "safe" window zone of overdistension V atelectrauma volutrauma LIP UIP zone of derecruitment and atelectasis Optimal PEEP

59 The PEEP Effect NEJM 2006;354:1839-1841

60 Higher vs. Lower PEEP Recruitment Overinflated

61 Positive End-Expiratory Pressure Setting in Adults With Acute Lung Injury and Acute Respiratory Distress Syndrome (EXPRESS) ALVEOLI Ventilation Strategy Using Low Tidal Volumes, Recruitment Maneuvers, and High Positive End-Expiratory Pressure for Acute Lung Injury and Acute Respiratory Distress Syndrome “LOVS”

62 1998 53 patientsInterventionControl TV <6 ml/Kg PEEP >P Flex TV (10-12 ml/Kg) Lowest PEEP 28 day mortalityInterventionControl 38%71%

63 50 patients53 Patients InterventionControl TV 5-8 ml/Kg 9-11 ml/Kg PEEP Pflex + 2 cm H 2 O >5 cm H2O ICU Mortality 32%53% P= 0.04 Crit Care Med 2006. 34l 1311

64 385 patients382 Patients InterventionControl TV 6 ml/Kg PEEP Plateau 28-30 16±3 cm H 2 O 5-9 cm H2O ICU Mortality NS Mercat A, Richard JM, Vielle B, et al. (EXPRESS). JAMA. 2008;299:646-655 Positive End-Expiratory Pressure Setting in Adults With Acute Lung Injury and Acute Respiratory Distress Syndrome (EXPRESS)

65 549 patients Low PEEPHigh PEEP TV6 ml/Kg PEEP8.3 ± 3.213.2 ± 3.5 ICU Mortality24.9%27.5% NS N E J Med 2004. 351: 327 ALVEOLI

66 475 patients508 Patients InterventionControl TV 6 ml/Kg PEEP Pplat < 40 PEEP 20 cm H 2 O RM Pplat < 30 Low PEEP ICU Mortality 36.4%40.4% NS Meade et al JAMA. 2008;299(6):637-645. LOVS Ventilation Strategy Using Low Tidal Volumes, Recruitment Maneuvers, and High Positive End-Expiratory Pressure for Acute Lung Injury and Acute Respiratory Distress Syndrome

67 PEEP in ARDS Good Bad

68 JAMA, March 3, 2010—Vol 303, No. 9

69 Time to Unassisted Breathing for Higher and Lower Positive End-Expiratory Pressure (PEEP) Stratified by Presence of Acute Respiratory Distress Syndrome (ARDS) at Baseline

70 Time to Death in Hospital for Higher and Lower Positive End- Expiratory Pressure (PEEP) Stratified by Presence of Acute Respiratory Distress Syndrome (ARDS) at Baseline

71 Optimal PEEP

72 PEEP Table by ARDSNet ARDS Network, 2000: Multicenter, randomized 861 patients Principle for FiO2 and PEEP Adjustment FiO20.30.40.50.60.70.80.91.0 PEEP55-88-101010-141414-1818-24 NEJM 2000; 342: 1301-1308

73 Rotta, J Pediatr (Rio J0 2003:79(Suppl 2):S149 Best PEEP PV Curve

74 Issues with PV Curves Require sedation/paralysis Difficult to identify “inflection points” May require esophageal pressure to separate lung from chest wall effects Pressure volume curves of individual lung units are not known

75 Optimal PEEP by Compliance 15 normovolemic patients requiring MV for ARF PEEP resulting in maximum oxygen transport and the lowest dead space fraction resulted in highest compliance Optimal PEEP varied from 0- to 15 cm H2O Mixed venous PO2 increased from 0 PEEP to the PEEP resulting in maximum oxygen transport, but then decreased at higher PEEP Conclusion: compliance may be used to indicated the PEEP likely to result in optimum cardiopulmonary function Suter, N Eng J Med 1975:292:284

76 Concerns when using lung-protective strategy… Heterogeneous distribution Hypercapnia Auto-PEEP Sedation and paralysis Patient-ventilator dyssynchrony Increased intrathoracic pressure Maintenance of PEEP

77 Permissive Hypercapnia Low Vt (6ml/kg) to prevent over-distention Increase respiratory rate to avoid very high level of hypercapnia If Respiratory rate can’t be increased further then the PaCO2 allowed to rise Accept PH > 7.25 Usually well tolerated May be beneficial (shift oxygen dissociation curve to the right) May use bicarb infusion till the kidney is able to retain bicarb

78 Permissive Hypercapnia – When would you NOT do it? Renal failure High intracranial pressures Cardiovascular problems

79 Conclusion “Lung Protective” Ventilation VOLUMEVOLUME VOLUMEVOLUME Pressure Limit Distending Pressure Add PEEP Limit VT 4-6 mL/kg < 28 cm H 2 O10-16 cm H 2 O

80 Management of refractory hypoxemia PEEP Pee (diuresis) Prone Paralysis Pleural evacuation (pleural effusion drainage) Prostacyclin (or iNO) More PEEP/recruitment maneuvers

81 What next? Prone position Inhaled nitric oxide High-frequency oscillation ECMO

82 Other Ventilator Strategies Lung recruitment maneuvers Prone positioning High-frequency oscillatory ventilation (HFOV) ECMO

83 Recruitment Maneuvers Application of high airway pressure (35- 40cmH2O) for approximately 40 seconds. Most common methodology – 40 cm H2O CPAP – 40 seconds Employed to open atelectatic alveolar units that occur with ARDS and particularly with any disconnection from ventilator If successful, PaO2 will increase by 20% or more. Must use PEEP after procedure to keep recruited alveoli open.

84 Effects of Recruitment Maneuvers to Promote Homogeneity within the Lung Malhotra A. N Engl J Med 2007;357:1113-1120

85 Lung Recruitment To open the collapsed alveoli A sustained inflation of the lungs to higher airway pressure and volumes – Ex.: PCV, Pi = 45 cmH2O, PEEP = 5 cmH2O, RR = 10 /min, I : E = 1:1, for 2 minutes NEJM 2006; 354: 1775-1786

86 ARDSnet protocol Vs open lung protocol ARDSnet protocol – Tv 6 ml/kg – Plateau pressure <30 – Conventional PEEP (titrate for FIO2 <0.6) Experimental protocol – Tv 6 ml/kg – Plateau pressure <40 – Recruitment maneuvers – High PEEP (10-15) JAMA, February 2008

87 ARDSnet protocol Vs open lung protocol

88 Lung Recruitment NEJM 2006; 354: 1775-1786

89 Lung Recruitment NEJM 2006; 354: 1775-1786

90 Potentially recruitable (PEEP 5  15 cmH2O) – Increase in PaO2:FiO2 – Decrease in PaCO2 – Increase in compliance The effect of PEEP correlates with the percentage of potentially recruitalbe lung The percentage of recruitable lung correlates with the overall severity of lung injury Lung Recruitment Sensitivity : 71% Specificity : 59% NEJM 2007; 354: 1775-1786

91 The percentage of potentially recruitable lung: – Extremely variable, – Strongly associated with the response to PEEP Not routinely recommended Lung Recruitment

92 Prone Position

93 Mechanisms to improve oxygenation: – Increase in end- expiratory lung volume – Better ventilation- perfusion matching – More efficient drainage of secretions

94 Improved gas exchange More uniform alveolar ventilation Recruitment of atelectasis in dorsal regions Improved postural drainage Redistribution of perfusion away from edematous, dependent regions Prone Position

95 Prone Positioning

96 Prone Position NEJM 2001;345:568-573

97 Prone Position NEJM 2001;345:568-573

98 Improve oxygenation in about 2/3 of all treated patients No improvement on survival, time on ventilation, or time in ICU Might be useful to treat refractory hypoxemia Optimum timing or duration ? Routine use is not recommended Prone Position

99 High-Frequency Oscillatory Ventilation (HFOV)

100 HFV - the “ultimate” lung protective strategy? Over-distended Protected Under-recruit

101 HFOV Frequency: 180-600 breaths/min (3-10Hz)

102 Effect of HFOV on gas exchange in ARDS patients AJRCCM 2002; 166:801-8

103 Survival difference of ARDS patients treated with HFOV or CMV 30-day: P=0.057 90-day: P=0.078 AJRCCM 2002; 166:801-8

104 HFOV Complications: – Recognition of a pneumothorax – Desiccation of secretions – Sedation and paralysis – Lack of expiratory filter Failed to show a mortality benefit Combination with other interventions ? Chest 2007; 131:1907-1916

105 Acute Lung injury Decreased lung compliance results in high airway pressures Low tidal volume 6-8 ml/kg ideal body weight Maintain IPP  30 cm H 2 O PEEP to improve oxygenation

106 Conclusions The only treatment that shows mortality benefit: – lung-protective ventilation strategy – Low tidal volume (6ml/Kg), high PEEP, adequate Pplat (<30 cmH2O) Modalities to improve oxygenation: – Prone position, steroid, fluid treatment, steroid, HFOV, NO Combining other treatments: – Antibiotics, EGDT…etc

107 The University of Michigan


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