Acute Respiratory Distress Syndrome (ARDS):Evidence Based Management

Transcription

1 Acute Respiratory Distress Syndrome (ARDS):Evidence Based Management John C. Klick, M.D., F.C.C.P. Assistant Professor Department of Anesthesiology and Perioperative Medicine University Hospitals Case Medical Center Case Western Reserve University School of Medicine Cleveland, OH

2 Acute Lung Injury (ALI)! Acute lung injury and acute respiratory distress syndrome are gradations of the same lung process! American-European Consensus Conference Conference (1994) established 4 diagnostic criteria:! Acute onset! Bilateral patchy airspace disease! PCWP<18 or no evidence of increased LVEDP! PaO2/FiO2<300=ALI! PaO2/FiO2<200=ARDS Bernard GR et al., AJRCCM 94

3 ALI/ARDS! ARDS is a syndrome, not a distinct disease entity! There are multiple potential causes! ARDS is NEVER an xray diagnosis!

4 Etiologies for ALI/ARDS! Direct Injury ( Intrapulmonary ARDS )!Aspiration!Pneumonia!Near drowning!inhalation injury!traumatic lung contusion Attabai & Matthay, Thorax. 2000

5 Etiologies for ALI/ARDS! Indirect Injury ( Extrapulmonary ARDS )! Sepsis! Severe acute pancreatitis! Shock! DIC! Trauma/multiple fractures! Hypertransfusion (TRALI)! Burns! Head injury! Cardiopulmonary bypass! Drug overdose Attabai & Matthay, Thorax

6 Causes of ARDS

7 Causes of ARDS Other 10% Multiple transfusions 5% Pneumonia 40% Trauma 8% Aspiration 15% Sepsis 22%

8 Causes of ARDS Other 10% Multiple transfusions 5% Pneumonia 40% Trauma 8% Aspiration 15% Sepsis 22% High PEEP/Low PEEP, ARDS-Net, 04

9 Incidence! Approximately 5-75 cases/100,000/year! Impact! All ages-no longer the Adult Respiratory Distress Syndrome! Previously healthy individuals! Prolonged ICU course! Decrease in subsequent quality of life

10 ARDS Outcomes! Factors associated with higher mortality rates:! Age! Sepsis! Number of failing organs! Degree of lung compliance, pulmonary hypertension

11 ARDS Outcomes McHugh, et al., AJRCCM 94! Lung function will improve over time! Degree of long term recovery of lung function decreases with worsening severity! Most deaths actually due to multi-organ failure, NOT pulmonary complications

12 ARDS Outcomes McHugh, et al., AJRCCM 94! Lung function will improve over time! Degree of long term recovery of lung function decreases with worsening severity! Most deaths actually due to multi-organ failure, NOT pulmonary complications

13 ARDS Outcomes! Typical mortality rates are about 30% at 28days and 45% at 6 months! Quality of life of ARDS survivors is significantly compromised (Angus et al., AJRCCM 01)! Survivors can suffer cognitive and affective impairment (Hopkins et al., AJRCCM 98)! Muscle weakness is very common! Only 50% of survivors return to work (Herrige et al., NEJM 03)

14 Pathophysiology of ALI/ARDS! Increased intrapulmonary shunt (refractory to increasing FiO2)! Decreased static compliance (Vt/Pplat- PEEP)<50cc/cmH2O! Development of secondary pulmonary hypertension with disease progression

15 ARDS Lungs! Increased lung density secondary to alveolar edema and inflammationpredominates in cephalic portions of lung! Lung collapse in dependent lung areas! High pressure exerted by abdominal contents and enlarged heart! Pleural fluid accumulation! Weight of edematous lung

16 ARDS Lungs! External forces applied to lower lobes at end inspiration and end expiration in a supine mechanically ventilated patient with PEEP! Large blue arrows=forces from tidal ventilation! Small blue arrows=forces from PEEP! Green arrows=forces exerted by abdominal contents and heart Ruby JJ et al., Anesthesiology, 2004

17 Anatomy Courtesy of W. Zapol, MD

18 Anatomy Early Late Diffuse Alveolar Damage- DAD Ware & Matthay, NEJM 00

19 Anatomy Early Late Diffuse Alveolar Damage- DAD Ware & Matthay, NEJM 00

20 Anatomy Early Late Diffuse Alveolar Damage- DAD Ware & Matthay, NEJM 00

21 Acute Respiratory Distress Syndrome (ARDS) EARLY LATE MGH, October 2001

22 Acute Respiratory Distress Syndrome (ARDS) EARLY LATE MGH, October 2001

23 Acute Respiratory Distress Syndrome (ARDS) EARLY LATE MGH, October 2001

24 ANATOMY! Diffuse Alveolar Damage (DAD)! Endothelial Injury! Increased Capillary Permeability! Edema! Hemorrhage! Hyaline membranes! Activation of Cells and Mediators! Leukocyte activation and adhesion! Release of inflammatory cytokines and cytotoxic enzymes! Platelet Activation! Hypercoaguability! Pathological changes in pulmonary vascular tone

25 Diffuse Alveolar Damage! Type II Alveolar Cell Injury! Decreased removal of alveolar edema! Reduced surfactant production! Compromised regeneration and repair of Type I alveolar cells! Can contribute to systemic SIRS and shock! Net result is disorganized repair and fibrosis

26 DAD Early Phase Ware & Matthay, NEJM 00

27 DAD Early Phase Ware & Matthay, NEJM 00

28 DAD Late Phase Ware & Matthay, NEJM 00

29 DAD Late Phase Ware & Matthay, NEJM 00

30 Vascular Changes! Pulmonary Hypertension! Contributes to even further increases in pulmonary edema! Increased RV workload! Failure to normalize PAP associated with increased mortality Zapol & Snider, NEJM 77 Nuckton et al., NEJM 02

31 ARDS Network! Clinical network established in 1994 by the National Heart, Lung, and Blood Institute, and the National Institutes of Health! Goal is to hasten development of effective therapies for ARDS by initiating multicenter clinical trials! Testing will include any promising agents, devices, or management strategies

32 Ventilator Induced Lung Injury (VILI)

33 Ventilator Induced Lung Injury (VILI)

34 Ventilator Induced Lung Injury (VILI)! Lung injury secondary to:! Overdistension/shear-physical injury! Mechanotransduction-biotrauma! Repetitive opening/closing! Shear at open/collapsed lung interface Volutrauma Atalectrauma! Systemic Inflammation from systemic release of cytokines, endotoxin, bacteria, proteases

35 VILI Slutsky &Tremblay, AJRCCM, 98

36 VILI Slutsky &Tremblay, AJRCCM, 98

37 VILI! High permeability type pulmonary edema! End-inspiratory lung volume>>pip (Volutrauma)! Alteration of alveolar-capillray barrier permeability! Surfactant inactivation! Mechanical distortion and disruption of endothelial cells! Regional activation of Inflammatory Cells! Increased transmural vascular pressures Rouby, JJ et al., Anesthesiology, 2004 Ricard, JD et al., Eur. Respir. J., 2003

38 VILI! Mechanical overinflation/distortion of lung structures! Emphysema-like lesions, bronchiectasis, lung cysts! Factors determining degree of overinflation:! Tidal volume! Peak airway pressure! Duration of mechanical ventilation! Time exposed to FiO2>60% Rouby, JJ et al., Anesthesiology, 2004

39 VILI! Lung Inflammation and Biotrauma! Lung overinflation leads to regional and systemic inflammation that can generate or amplify multi-system organ failure! Probable culprits:! Repetitive opening and closing of atalectatic lung segments! Surfactant alterations! Bacterial translocation! Loss of alveolar-capillary barrier function! Overinflation of healthy lung regions Rouby, JJ. et al., Anesthesiology, 2004 Dreyfuss, D. et al, AJRCCM, 2003

40 Traditional Approach to Mechanical Ventilation in ARDS! Maintain normal acid-base balancemaintain normal range PCO2! Normal range tidal volumes of 10-12cc/kg

41 New Approach to Mechanical Ventilation in ARDS! Lung protection is paramount! Low tidal volumes! Use of adequate PEEP! Permissive Hypercapnea! Limit Plateau Pressures

42 ARDSnet 2000! Landmark article in NEJM truly revolutionized approach to mechanical ventilation of the ARDS patient! Trial used lower tidal volumes of 6cc/kg predicted body weight! Trial maintained plateau pressures<30 cm H2O! Demonstrated improved MORTALITY of almost 10% ARDS Network, NEJM, 2000

43 Open Lung Concept! Use of higher levels of PEEP to maintain open alveoli and thus prevent atalectrauma! Recruitment maneuvers! Based on examination of pressure/volume curves and determining lower inflection point to set PEEP! ARDSnet ALVEOLI trial cancelled for futility Amato et al., NEJM, 1998 Amato et al., AJRCCM, 1995

44 Open Lung Concept

45 Open Lung Concept Papadakos & Lachman, Mt. Sinai Journal Of Medicine, 2002

46 Optimizing PEEP! Use of the Lower Inflection Point (LIP) on the Pressure/Volume Curve: indicates closing pressure for alveoli and point of optimal PEEP Kacmarek, Current Opinion in Critical Care, 2001

47 Permissive Hypercapnia! Tolerating high PCO2 for the sake of maintaining lung protective ventilatory settings! Experimental data to support therapeutic effect of hypercapnic acidosis! Attenuation of lung and systemic organ injury! Downregulation of inflammatory mediators! Reduced lung neutrophil infiltration! Attenuation of NFK-B at genomic level! Even extreme degrees of hypercapnia are usually well tolerated! May actually improve V/Q matching via vasodilating effect on pulmonary arterioles Chonghaile et. Al., Current Opinion in Critical Care, 2005

48 Permissive Hypercapnia! Hypercapnic acidosis, rather than acidosis itself seems to be lung protective! Severe hypercarbia can decrease SVR, but also increase CO! At present, data is insufficient to support deliberate induction of hypercarbic acidosis-it should only be used in context of lung protective ventilation O Croinin et al., Critical Care, 2005

49 Use of Buffers! No real data to support what degree of acidosis is acceptable when using permissive hypercapnia.! No role for bicarbonate-it worsens intracellular acidosis and raises PCO2! Tris-hydroxymethyl aminomethane (THAM) is an effective intravenous buffer that decreases intracellular acidosis and is not converted to CO2! THAM is dependent on renal excretion and should be used with caution in renal insufficiency Kallet et al., AJRCCM, 2000

50 RECRUITMENT MANEUVERS! The ARDS lung is recruited throughout lung inflation! High surface tension of collapsed lung segments may require very high alveolar pressure to expand and recruit these areas! These pressures may lead to short-term overdistension of already inflated alveoli! Recruiting collapsed alveoli increases PaO2 Kacmarek, Current Opinion in Critical Care, 2001

51 Recruitment Maneuvers! Preventing derecruitment decreases lung injury induced by repetitive opening and closing of alveoli! Collapsed alveoli are more prone to infection and surfactant inactivation! Recruitment maneuvers require sustained high pressure application! RMs allow better global recruitment than just an increase in PEEP Kacmarek,Current Opinion in Critical Care, 2001

52 Recruitment Maneuvers! Maintenance of lung recruitment requires increased levels of PEEP to prevent collapse of recruited alveoli! Most effective maneuver seems to be maintenance of high PIP from 30 seconds to several minutes, followed by an increase in PEEP! Hemodynamic collapse from limiting venous return is a real concern! The stiffness of the ARDS lung will often prevent pressure transmission to the vasculature and limit hemodynamic compromise Kacmarek, Current Opinion in Critical Care, 2001

53 Prone Ventilation Supine Prone

54 Prone Ventilation Supine Prone

55 Prone Ventilation Supine Prone

56 Prone Ventilation! Prone position results in improved oxygenation! Reduces pulmonary shunt from poor V/Q matching! Allows reexpansion of formerly dependent consolidated lung! Reduces cardiac compression of dependent lung zones! Larger dorsal lung surface area, so lower volume of dependent atalectasis when prone Blanch et al., Current Opinion in Critical Care, 1999

57 Prone Ventilation! Often enables significant reduction in FiO2 and may allow reduction of PEEP! RMs often much more effective in prone position! More likely to be effective early in the course of disease process! Practically, moving a patient to prone position is associated with significant risk Blanch et al., Current Opinion in Critical Care 1999

58 Prone Ventilation! Potential Risks of Proning: unplanned extubation, ETT malposition, loss of vascular access, increaed difficulty performing CPR, peripheral nerve injury, damage to eyes Blanch, et al., Current Opinion in Critical Care, 1999

59 Prone Ventilation! Implementation of prone position in the ARDS patient Blanch et al., Current Opinion in Critical Care, 2001

60 Fluid Management and Hemodynamic!!! Monitoring FACTT Trial-Fluid and Catheter Treatment Trial!! conducted by the ARDS Network Compared ARDS patient outcomes in patients who received Hemodynamic monitoring via Pulmonary Artery Catheter (PAC) versus Central Venous Line (CVL) Results showed no improvement in outcome in PAC group Over CVL group but a higher incidence of catheter related Complications ARDS Network, 2006

61 FACTT Trial! Study results show no difference in mortality between liberal versus conservative fluid therapy! Conservative fluid arm did show an increase in both ventilator-free and ICU-free days! Protocol s use of the PAC is a potential confounding variable! In clinical practice, many ARDS patients are also in severe septic shock, necessitating fluid resuscitation ARDS Network, 2006

62 Corticosteroids! Previous reports suggested a possible role for steroids in the late fibroproliferative phase of ARDS! ARDS Network performed randomized controlled trial to evaluate! Results do not support routine use of corticosteroids for persistent ARDS! Starting methylprednisolone more than 2 weeks after onset of ARDS may increase risk of death ARDS Network, 2006

63 Inhaled Nitric Oxide! Inhaled NO is a selective pulmonary arterial vasodilator! Decreases PVR! Redistributes pulmonary blood flow toward ventilated alveoli in ARDS patients! Net effect is better V/Q matching and improved oxygenation Griffiths & Evans, NEJM, 2005

64 ino! Not shown to improve long term mortality! Use is relegated to a short-term salvage maneuver to improve oxygenation when unable to improve via standard means! Buys a window of time to manipulate other variables to improve long-term oxygenation! Extremely expensive Griffiths & Evans, NEJM, 2005

65 ino Griffiths & Evans, NEJM, 2005

66 ino Griffiths & Evans, NEJM, 2005

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68 55

69 56

70 Alternative Ventilatory Strategies! No conclusive evidence to support advantage of these modes over ARDSnet protocol! Theoretical advantages based on knowledge of pulmonary pathophysiology and institutional experience! Multicenter randomized controlled trials have yet to be done

71 Pressure Controlled Inverse Ratio Ventilation (PCIRV)! Normal expiratory time in a vented patient is longer than inspiratory time! PCIRV dramatically increases inspiratory time and shortens expiratory time, inverting I:E! Goal is to improve gas exchange while limiting peak airway pressures! Theory is that PCIRV will allow sustained elevation of mean airway pressure but limit peak airway pressure-net result should be to limit transalveolar pressure and barotrauma but maintain more uniform recruitment Marcy & Marini, Chest, 1991

72 PCIRV! Can induce a significant degree of auto-peep which can be compensated for by applied PEEP! Patients require high levels of sedation to tolerate! Patients may even require paralysis to prevent any additional triggering which could cause dangerous increase in auto-peep Marcy & Marini, Chest, 1991

73 Airway Pressure Release Ventilation (APRV)! Induces high level of CPAP and then transiently releases pressure to a lower CPAP level! Inverses I:E! Minimizes peak airway pressure while increasing mean airway pressure! Permits spontaneous ventilation at each level of CPAP Cane, et al., Chest, 1991

74 APRV! Spontaneous ventilation minimizes basal atalectasis! Minimizes need for sedation and eliminates need for paralysis! Spontaneous ventilation should minimize hemodynamic compromise by maximizing right heart venous return Putensen& Wrigge, Critical Care, 2004

75 High Frequency Oscillatory Ventilation (HFOV)! Rapid delivery of small tidal volumes (RR bpm)! Application of high mean airway pressures! Prevents cyclical derecruitment of lung! Small TVs limit alveolar overdistension! 2 RCTs encouraging but showed no mortality benefit in adults Chan, et al., Chest, 2007

76 HFOV! HFOV waveforms vs. Conventional PCV Chan, et al., Chest, 2007

77 HFOV! Mechanisms of gas exchange in HFOV-Convection and diffusion Chan et al., Chest, 2007

78 Partial and Total Liquid Ventilation! Theory: Fill the lung with fluid in which O2 and CO2 are highly soluble (perfluorocarbons)! Requires 3X less pressure to expand a liquid filled lung vs. an air filled lung! Should improve oxygenation and facilitate lung protective ventilation Kaisers et al., British Journal of Anaesthesia, 2003

79 Liquid Ventilation! No data to support improved mortality! Most experience is in neonates Kaisers et al., British Journal of Anaesthesia, 2003

80 Liquid Ventilation

81 Extracorporeal Membrane Oxygenation (ECMO)

82 ECMO! Early trials in adults showed no improvement in mortality, but definite impact in neonates with acute respiratory failure! Mostly reserved as a last ditch salvage technique in ARDS! Allows lung protective ventilation with extracorporeal oxygenation and CO2 removal Mielk & Quintel, Current Opinion in Critical Care, 2005

83 Findings 766 patients were screened; 180 were enrolled and randomly allocated to consideration for treatment by ECMO (n=90 patients) or to receive conventional management (n=90). 68 (75%) patients actually received ECMO; 63% (57/90) of patients allocated to consideration for treatment by ECMO survived to 6 months without disability compared with 47% (41/87) of those allocated to conventional management (relative risk 0!69; 95% CI 0!05 0!97, p=0!03). Referral to consideration for treatment by ECMO treatment led to a gain of 0!03 quality-adjusted life-years (QALYs) at 6-month follow-up. A lifetime model predicted the cost per QALY of ECMO to be 19"252 (95% CI "200) at a discount rate of 3!5%. The Lancet, Volume 374, Issue 9698, Pages , 17 October 2009

84 ECMO! Basic components include vascular cannulas, tubing, a driving pump, and a gas exchange unit! Uses Fr heparin bonded percutaneous cannulas! Requires systemic anticoagulation! Pumpless ECMO now available-uses AV cannula and patient s own arterial BP to drive the circuit flow Mielck & Quintel, Current Opinion in Critical Care, 2005

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87 ECMO! Veno-venous access cannulas for ECMO

88 ECMO

89 ECMO! Risks and Complications include bleeding, infection, hemolysis, circuit thrombosis, and plasma leakage! Possibility of inducing a SIRS response from blood contact with foreign surface and destruction of blood components Ruettimann et al, Canadian Journal of Anesthesia, 2006

90 Pumpless ECMO System

91 Novalung extracorporeal pumpless lung assist device

92 Novalung extracorporeal pumpless lung assist device

93 79