Clinical Management of ARDS: Concepts and Controversies

Transcription

1 Clinical Management of ARDS: Concepts and Controversies Kristin Miller, MD Assistant Professor Department of Internal Medicine Division of Pulmonary & Critical Care Medicine November 5, 2011

2 Objectives Review the definition of ARDS Discuss etiology, pathophysiology of ARDS Review ARDSnet protocol and Landmark trials: evidence for low tidal volume ventilation Discuss controversial treatment modalites in ARDS

3 Case 42 yo male who presented to the ED with 5 day hx of cough, fevers, myalgias. No pmh, nonsmoker. VS in the ED: BP 159/89 P 128 R 18 T % on 3L, 90% on RA. Labs: wbc 4.3 hemog 14.4 plt 145 na 139 bun/cr 10/1.3 glc 189. Pt was admitted to internal medicine service with diagnosis of CAP.

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5 Case HD #2: Pt required intubation secondary to increased work of breathing and worsening hypoxemia. ABG just prior to intubation (on NRB): 7.16/62/63

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7 Case Bronchoscopy performed, only positive culture was Influenza. He remained on antiviral medications as well as broad spectrum antimicrobials. There was no evidence of cardiac dysfunction. Dx: ARDS due to influenza (H1N1) pneumonia.

8 ARDS: Historical Perspectives First described by David Asbaugh and colleagues in 1967 (The Lancet) Initially termed adult respiratory distress syndrome Description of 12 pts with acute onset of tachypnea, hypoxemia and poor lung compliance not responding to usual and ordinary methods of respiratory therapy Speculated about the role of PEEP and surfactant Asbaugh et al. Acute Respiratory Distress in Adults. The Lancet, Saturday 12 August 1967.

9 ARDS: Historical Perspectives Noted that these pts exhibited similar features compared to the infantile respiratory distess syndrome (hyaline membrane disease) Etiologies discussed: infection (pneumonia), pancreatitis, trauma, shock CXR: patchy, bilateral infiltrates, frequently confused with pulmonary edema 7 of the 12 patients died, autopsy revealed hyaline membranes Peep seemed to help Asbaugh et al. Acute Respiratory Distress in Adults. The Lancet, Saturday 12 August 1967.

10 ARDS: Definition (1994) Acute onset Bilateral pulmonary infiltrates on CXR PA wedge pressure < 18 mmhg or the absence of clinical evidence of left atrial hypertension Acute lung injury considered to be present if PaO2/FiO2 is < 300 ARDS considered to be present if PaO2/FiO2 <200 Bernard et al American-European Consensus Conference Committee.

11 ARDS: Epidemiology Incidence: 200,000 pts annually in the US Affects children and adults Overall mortality: 40% Some studies suggest increased mortality in African American and Hispanic population May manifest as single or multi-organ failure Direct and indirect causes

12 ARDS: Direct and Indirect Injury

13 Clinical Disorders Associated with the Development of the Acute Respiratory Distress Syndrome. Ware LB, Matthay MA. N Engl J Med 2000;342:

14 ARDS: Clinical, Pathological, Radiographic Features Syndrome, can be progressive. Stages: Acute (exudative): rapid onset of respiratory failure in pt with risk factor(s), refractory hypoxemia, radiographic looks like pulmonary edema Progress to fibrosing alveolitis Recovery phase. Ware and Matthay. NEJM :1334

15 Acute (exudative phase) Fibrosing alveolitis Resolution Rapid onset of respiratory failure Persistent hypoxemia, increased alveolar dead space, further decrease in compliance Gradual resolution of hypoxemia, improved lung compliance Identifiable risk factor for ARDS Refractory hypoxemia Pulmonary hypertension due to obliteration of pulmonary capillary bed, may be severe and lead to RV failure Pneumothorax may occur CXR: bilateral patchy airspace opacities CXR: linear opacities (fibrotic pattern) Typically, the radiographic abnormalities resolve completely CT: alveolar consolidation, atelectasis predominantly in dependent lung zones CT: diffuse interstitial opacities, bullae Path: DAD, neutrophils, macrophages, hyaline membranes Protein rich edema in alveolar spaces, capillary, endothelial and epithelial injury Path: fibrosis, acute and chronic inflammatory cells, partial resolution of pulmonary edema Not well characterized

16 Radiographic and Computed Tomographic (CT) Findings in the Acute, or Exudative, Phase (Panels A and C) and the Fibrosing-Alveolitis Phase (Panels B and D) of Acute Lung Injury and the Acute Respiratory Distress Syndrome. Ware LB, Matthay MA. N Engl J Med 2000;342:

17 ARDS: Pathophysiology Exudation of protein-rich fluid from microvasculature into interstitial space and alveoli Disruption of surfactant, reducing lung compliance and promoting atelectasis Persistent inflammation, fibrotic repair Failure of hypoxic vasoconstriction resulting in shunt and severe hypoxemia Slide:Sessler 2011

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19 The Normal Alveolus (Left-Hand Side) and the Injured Alveolus in the Acute Phase of Acute Lung Injury and the Acute Respiratory Distress Syndrome (Right-Hand Side). Ware LB, Matthay MA. N Engl J Med 2000;342:

20 Management of ARDS Treat underlying condition Support oxygenation and ventilation Mechanical ventilation; avoid / minimize barotrauma Use lung protective ventilation Supportive (non-ventilatory) therapy Conservative fluid management Corticosteroids? Rescue for severe hypoxemia paralytics, ino, prone positioning Slide: Sessler 2011

21 Concept: what ventilator settings do we institute in pts with ARDS?

22 Lung Protective Mechanical Ventilation for ARDS Lung injury is heterogeneous, but with functional compartments : Normal lung (B) potential for overdistention Atelectatic, but recruitable lung (C) potential for cyclic recruitment / collapse Densely consolidated Slide: Sessler lung 2011 (A) poorly recruitable Moloney & Griffiths Br J Anaesth 2004; 92:261-70

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24 ARDSNET: Landmark Publications Ventilation with Lower Tidal Volumes as Compared to Traditional Tidal Volumes For Acute Lung Injury and the Acute Respiratory Distress Syndrome Randomized trial of conventional TV (11.8 ml/kg) vs low TV (6.2 ml/kg) ventilation in 861 patients with ALI Exclusion Criteria: >36 hrs since eligible, pregnancy, Increased ICP, sickle cell disease, vasculitis with alveolar hemorrhage, severe chronic liver disease, severe NM disease, HSCT, lung transplant. NEJM 2000; 342:

25 Lower Tidal Volume Ventilation for ALI and ARDS ARDS Network. N Engl J Med 2000; 342:1301 Low TV Conventional *p <.01 Randomized trial of conventional TV (11.8 ml/kg) vs low TV (6.2 ml/kg) ventilation in 861 patients with ALI Mortality Vent-free days Organ failurefree days * * * Barotrauma Percent of cases

26 Probability of Survival and of Being Discharged Home and Breathing without Assistance during the First 180 Days after Randomization in Patients with Acute Lung Injury and the Acute Respiratory Distress Syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med 2000;342:

27 ARDSNet Recommendations for Mechanical Ventilation in ARDS N Engl J Med 2000; 342:1301 Volume - Assist Control Mode Tidal volume (Vt) = 8 ml/kg PBW* Reduce Vt by 1 ml/kg until Vt = 6 ml/kg Set inspiratory flow > pt demand (usually > 80L/min) Adjust RR and Vt to achieve Pplat & ph goals Aim for Pplat < 30 cm H 2 O Aim for ph = by increasing RR (to 35 if necessary) and adding bicarbonate * PBW = predicted body weight: M = [height (inches) - 60], Slide: Sessler, 2011 F = [height (inches) - 60]

28 Utilize Strategies to Improve Lung Protective Ventilation: Protocols Sessler, C. Hypoxemic Respiratory Failure, in ACCP Pulmonary Board Review 2009

29 ARDSNET: Landmark Publications Higher versus Lower Positive End-Expiratory Pressures in Patients with the Acute Respiratory Distress Syndrome 549 pts with ALI/ARDS received MV with either lower or higher peep levels (up to 24 cm water). Traditional low volume TV (6 cc/kg IBW) and plateau pressure <30 used.. NEJM 2004; 351:

30 Higher versus Lower Positive End-Expiratory Pressures in Patients with the Acute Respiratory Distress Syndrome. NEJM 2004; 351:

31 ARDSNET: Landmark Publications Higher versus Lower Positive End- Expiratory Pressures in Patients with the Acute Respiratory Distress Syndrome 549 pts with ALI/ARDS received MV with either lower or higher peep levels (up to 24 cm water). Traditional low volume TV (6 cc/kg IBW) and plateau pressure <30 used. Clinical outcomes (mortality, VFD) were similar but improved oxygenation in pts with higher applied Peep. NEJM 2004; 351:

32 Controversies among Nonventilatory Treatment Strategies: Steroids for Fibroproliferative ARDS? The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. N Engl J Med 2006;354:

33 Nonventilatory Strategies: Steroids for Fibroproliferative ARDS? 180 pts with ARDS of at least 7 days duration, randomly assigned to placebo or Methylprednisolone Primary end point: mortality at 60 days Secondary end point: VFD, organ failure free days, infection, biomarkers of inflammation

34 Nonventilatory Strategies: Steroids for Fibroproliferative ARDS? No decrease in mortality Increase in mortality in pts who received steroids after 14 days after the onset of ARDS Methylprednisolone increased the number of Ventilator Free Days and shock free days during the first 28 days as well as improvement in oxygenation, compliance No increase risk of infection, but increase in NM weakness in steroid group

35 Corticosteroids in ARDS: Discussion Use of low dose, longer duration corticosteroids is associated with more rapid recovery and may be associated with reduced mortality risk Consistent in randomized & non-randomized studies But, small studies, methodological quality issues No increase in adverse events If use corticosteroids in ARDS Avoid starting after day 14 Methylprednisolone 2 g/kg/d, taper over 4 weeks Infection surveillance, avoid NMBA Sessler & Gay. Respir Care 2010; 55:175-83

36 Nonventilatory Strategies: Fluid Management-the Factt Trial The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. N Engl J Med 2006;354:

37 Relationship between pulmonary hydrostatic pressure and lung edema formation under normal conditions and increased permeability. Calfee C S, Matthay M A Chest 2007;131: by American College of Chest Physicians

38 Fluid Management Strategies in ALI: Outcomes RCT comparing conservative and liberal strategies for fluid management using explicit protocols applied for 7 days in 1000 patients with ALI Parameter Conservative Liberal P value Mortality 25.5% 28.4% 0.30 Ventilator-free d ICU-free d Electrolyte abnl RRT 10% 14%.06 Slide:Sessler: 2011al. N Engl J Med 2006; 354:

39 Overview of the Protocol for Conservative and Liberal Fluid Management in the Group Assigned to a Pulmonary-Artery Catheter (PAC) and the Group Assigned to a Central Venous Catheter (CVC). The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. N Engl J Med 2006;354:

40 Slide: Sessler 2011

41 Rescue Therapy for Lifethreatening Hypoxemia in ARDS Ventilatory Higher PEEP Recruitment maneuvers Higher mean airway pressure Longer Tinsp APRV HFOV Non-ventilatory Neuromuscular blockade Prone positioning Inhaled pulmonary vasodilator (ino) ECMO Esan et al. Chest 2010;137:1203 Raoof et al. Chest 2010;137:1437

42 Prone Positioning in ARDS Improves oxygenation in 70% pts Proposed mechanisms increased end-expiratory lung volume improved ventilation-perfusion matching regional changes in ventilation Requires personnel (4-5) and planning to safely turn patient Potential for complications: unintended tube/line removal Slide: Sessler 2011

43 Mean (±SE) Ratios of the Partial Pressure of Arterial Oxygen (PaO 2 ) to the Fraction of Inspired Oxygen (FiO 2 ) Immediately before Prone Positioning (Circles), after One Hour (Squares), at the End of the Period of Pronation (Triangles), and on the Morning of the Following Day (Diamonds) during the 10-Day Study Period. Gattinoni L et al. N Engl J Med 2001;345:

44 Inhaled Nitric Oxide Endogenous vasodilator Inhalation of 2-40 ppm produces selective dilation of pulmonary vessels RVEF and RVEDV Rapidly inactivated by combining with hemoglobin and by oxidation

45 Routine use of inhaled NO is not supported Oxygenation benefit for up to 4 days (5-20ppm) No methemoglobin or hno 2 unless 40ppm Improves oxygenation but not mortality Costly What is the Role for Nitric Oxide in ARDS? Potential role for inhaled NO as rescue therapy for severe refractory hypoxemia Demonstrate clinically significant benefit to continue

46 ACURASYS French multicenter RCT comparing cisatracurium (CIS) or placebo x 48h in severe ARDS (PaO2:FiO2 < 150 mmhg) CIS group deeply sedated (Ramsay 6), paralyzed CIS group Lower 90d mortality rate (31.6% vs 40.7%, p = 0.08) Lower 28d mortality (23.7% vs 33.3%, p = 0.05) More ventilator-free days (10.6 vs 8.5, p = 0.04) Fewer pneumothoraces (4% vs 11.7%, p = 0.01) No difference in rate of ICU-acquired paresis Papazian et al. N Engl J Med 2010; 363:

47 Probability of Survival through Day 90, According to Study Group. Papazian L et al. N Engl J Med 2010;363:

48 ARDS: Summary Recognize ARDS in the appropriate setting using clinical/radiographic data Use lung protective approach 6 ml/kg IBW in eligible pts Aim for plateau pressure <30 cmh2o; allow permissive hypercapnea if needed Use PEEP Implementation of protocols---calculate IBW, multidiscliplinary effort

49 ARDS: Summary Conservative fluid management: KEEP THE LUNGS DRY Consider low-dose, long duration methylpred if < 14d ARDS (controversial) Consider higher PEEP, ino, prone positioning, and use of paralytics in severe ARDS with refractory hypoxemia

50 Acknowledgements: Curtis Sessler, MD