Acute Respiratory Distress Syndrome

ByDr. Istikhar Ali Sajjad

PGR Pulmonology

Review the causes and differentials for ARDS Briefly discuss the pathophysiology Discuss the clinical manifestations of ARDS Understand evidence based treatment

options

Objectives

ARDS is also referred with variety of terms like • Stiff Lung• Shock lung• Wet lung• Post traumatic lung• Adult respiratory distress syndrome• Adult hyaline membrane disease• Capillary leak syndrome & • Congestive atelectasis.

Acute Respiratory Distress Syndrome

June 20, 2012, Vol 307, No. 23

et al. JAMA 2012; 307:2530

-European Society of Intensive Care Medicine with endorsement from American Thoracic Society and Society of Critical Care Medicine-Devised three mutually exclusive severity categories: Mild, Moderate and Severe-Took into account: timing, chest imaging, origin of edema, oxygenation

et al. JAMA 2012; 307:2530

Bernard et al. AJRCCM 1994; 149:818Rice et al. Chest 2007: 132: 410

Epidemiology Annual incidence: 60/100,000 20% ICU patients meet criteria for ARDS

Morbidity / Mortality 26-44%, most (80%) deaths attributed to non-

pulmonary organ failure or sepsis Risk Factors

Advanced age, pre-existing organ dysfunction or chronic medical illness

Patient with ARDS from direct lung injury has higher incidence of death than those from non-pulmonary injury

Statistics

Levy BD, & Choi AM, Harrison’s Principles of Internal Medicine, 2012

Direct Lung Injury Common causes

Aspiration of gastric contents or other substances.

Viral/bacterial pneumonia Less Common causes

Chest traumaEmbolism: fat, air, amniotic fluid Inhalation of toxic substancesNear-drowningO2 toxicityRadiation pneumonitis

ETIOLOGY & RISK FACTORS

Indirect Lung Injury Common causes

Sepsis Severe traumatic injury

Less common causes Acute pancreatitis Anaphylaxis Prolonged Cardiopulmonary bypass surgery Disseminated intravascular coagulation Multiple blood transfusions Narcotic drug overdose (e.g., heroin) Nonpulmonary systemic diseases Severe head injury Shock Massive blood transfusion.

ETIOLOGY & RISK FACTORS

Early signs/symptoms Restlessness Dyspnea Low blood pressure Confusion Extreme tiredness Change in patient’s behavior

Mood swing Disorientation Change in LOC

If pneumonia is causing ARDS then client may have Cough Fever

CLINICAL MANIFESTATIONS

Late signs & symptoms Severe difficulty in breathing i.e., labored,

rapid breathing. Shortness of breath. Tachycardia Cyanosis (blue skin, lips and nails) Think frothy sputum Metabolic acidosis Abnormal breath sounds, like crackles PaCo2 with respiratory alkalosis. PaO2

CLINICAL MANIFESTATIONS CONTD…………

History of above symptoms On physical examination

Auscultation reveals abnormal breath sounds The first tests done are :

Arterial blood gas analysis Bood tests Chest x-ray Sputum cultures and analysis

Other tests are : Chest CT Scan Echocardiogram

DIAGNOSITC EVALUATION

Common complications are; Nosocomial pneumonia: Barotrauma Renal failure

Other complications are : O2 toxicity, stress ulcers, Tracheal ulceration, Blood clots leading to deep vein thrombosis & pulmonary embolism.

COMPLICATIONS

Left ventricular failure/volume overload Mitral stenosis Pulmonary veno-occlusive disease Lymphangitic spread of malignancy Interstitial and/or airway disease

Hypersensitivity pneumonia Acute eosinophilic pneumonia Acute interstitial pneumonitis

Differentials

Pathophysiology

1. Direct or indirect injury to the alveolus causes alveolar macrophages to release pro-inflammatory cytokines

Ware et al. NEJM 2000; 342:1334

Pathophysiology

2. Cytokines attract neutrophils into the alveolus and interstitum, where they damage the alveolar-capillary membrane (ACM).

Ware et al. NEJM 2000; 342:1334

Pathophysiology

3. ACM integrity is lost, interstitial and alveolus fills with proteinaceous fluid, surfactant can no longer support alveolus

Ware et al. NEJM 2000; 342:1334

Physical/ chemical injuryActivation Innate

Inflammatory Cascade

Leakage Protein Rich Oedema FluidInflammatory Cellular

Infiltrates

Diffusion AbnormalitiesV/Q Mismatch

Hypoxia

Respiratory Failure

Physical/ chemical injuryActivation Innate

Inflammatory Cascade

Cellular InfiltrateAtelectasis

Oedema Fluid

Reduced Thoracic Compliance + Vasoconstriction

Hypoxia

Respiratory Failure

Physical/ chemical injuryActivation Innate

Inflammatory Cascade

Small Vessel Thrombosis

Increased Dead Space

Hypoxia

Respiratory Failure

Exudative Phase Neutrophilic Infiltrate Alveolar Haemorrhage Proteinaceous Pulmonary Oedema Cytokines (TNF, IL1,8)

↑ Inflammation ↑ Oxidative Stress and Protease Activity ↓ Surfactant Activity Atelectasis

Histologically

Elastase- induced capillary and alveolar damage

↑ Alveolar flooding ↓ Fluid clearance Capillary thrombosis

↓ Anticoagulant proteins ↑ Procoagulant proteins (Tissue Factor) ↑ Anti- fibrinolytic Protein (Plasminogen Activator

Inhibitor)

Histologically

Fibroproliferative Phase Variable time period Fibrosis Chronic Inflammation Neovascularisation

Resolution3

Improvement of hypoxaemia Improved dead space and lung compliance Resolution radiographic abnormalities Can take up to 1 year Residual restrictive or obstructive picture

Post Acute Phase

Chronic Respiratory Disease Muscle Fatigue Muscle Wasting Weakness

Long Term

Treat the underlying cause Low tidal volume ventilation Use PEEP Conservative fluid management Positioning Reduce potential complications

Evidence based management of ARDS

Hypothesis:In patients with ALI, ventilation with smaller tidal volumes (6 mL/kg)

will result in better clinical outcomes than traditional tidal volumes (12 mL/kg) ventilation.

ARDS Network N Engl J Med 2000; 342:1301

• When compared to larger tidal volumes, Vt of 6ml/kg of ideal body weight:• Decreased mortality• Increased number of ventilator free days• Decreased extrapulmonary organ failure

• Mortality is decreased in the low tidal volume group despite these patients having:• Worse oxygenation• Increased pCO2 (permissive hypercapnia)• Lower pH

ARDSnet. NEJM 2000; 342: 1301

Low Tidal Volume Ventilation

Low Tidal Volume Ventilation

ARDS affects the lung in a heterogeneous fashion• Normal alveoli• Injured alveoli can

potentially participate in gas exchange, susceptible to damage from opening and closing

• Damaged alveoli filled with fluid, do not participate in gas exchange

Protective measure to avoid over distention of normal alveoli

Uses low (normal) tidal volumes Minimizes airway pressures Uses Positive end-expiratory pressure (PEEP)

Low Tidal Volume Ventilation

Hypothesis:In patients with ALI ventilated with 6 mL/kg, higher levels of

PEEP will result in better clinical outcomes than lower levels of PEEP.

N Engl J Med 2004; 351:327

Higher levels of PEEP/FiO2 does not improve outcomes may negatively impact outcomes:

Causing increased airway pressure Increase dead space Decreased venous return Barotrauma

PEEP

• Positive End Expiratory Pressure• Every ARDS patient needs it• Goal is to maximize alveolar recruitment and

prevent cycles of recruitment/derecruitment

PEEP

Meade, M et al, JAMA. 2008; 299(6):637-645

-983 patients, randomized into control group with ALI protocol, low Vt and PEEP vs. Open lung group with low Vt, higher PEEP and recruitment maneuvers-No statistically significant difference in mortality outcomes

Mercatt, M, et al. JAMA. 2008; 299(6):646-655.

-Multicenter randomized trial, 767 patients. Set a PEEP aimed to increase alveolar recruitment while limiting hyperinflation-Randomly assigned two groups: moderate PEEP (5-9cm H2O) vs. level of PEEP to reach a plateau pressure of 28-30cm H2O-Found that it didn’t significantly reduce mortality; however, it did improve lung function and decreased days on vent and organ failure duration

As FiO2 increases, PEEP should also increase

PEEP

ARDSnet. NEJM 2004; 351, 327

Plateau pressure is most predictive of lung injury Goal plateau pressure < 30, the lower the better

• Decreases alveolar over-distention and reduces risk of lung strain

Adjust tidal volume to ensure plateau pressure at goal

It may be permissible to have plateau pressure > 30 in some cases• Obesity• Pregnancy• Ascites

Airway Pressures in ARDS

Terragni et al. Am J Resp Crit Care Med. 2007; 175(2):160

Assess cause of high Plateau Pressures Always represents some pathology:

Stiff, non-compliant lung: ARDS, heart failure Pneumothorax Auto-peeping Mucus Plug Right main stem intubation Compartment syndrome Chest wall fat / Obesity

Permissible Plateau Pressures

Airway Pressures

Peak Inspiratory Pressure

Plateau Pressure

PEEP

Airway Pressures

Time

N Engl J Med 2006; 354: 2213

Fluid and Catheter Treatment Trial--No need for routine PAC use is ALI patients--Support use of conservative strategy fluid management in patients with ALI

Using the data from a PAC compared to that from a CVC in an explicit protocol: Did not alter survival. Did not improve organ function. Did not change outcomes for patients entering

in shock compared to those without shock. PAC use resulted in more non-fatal

complications, mostly arrhythmias.

Results

N Engl J Med 2006; 354: 2213

N Engl J Med. 2006;354:2564

~Hypothesis: Diuresis or fluid restriction may improve lung function but could jeopardize extrapulmonary organ perfusion

~Conclusion: Conservative fluid management improved lung function and shortened mechanical ventilation times and ICU days without increasing nonpulmonary organ failures

Fluid Management• Increased lung water is the

underlying cause of many of the clinical abnormalities in ARDS (decreased compliance, poor gas exchange, atelectasis)

• After resolution of shock, effort should be made to attempt diuresis

• CVP used as guide, goal <4• Shortens time on vent and ICU

length of stay (13 days vs 11 days)

ARDSnet. NEJM 2006; 354: 2564

Hypothesis: Early application of prone positioning would improve survival in patients with severe ARDS.

Conclusion: Early application of prolonged prone positioning significantly decreased 28 day and 90 mortality in patients with severe ARDS.

Guerin et al. NEJM. 2013; 368:2159

Prone positioning Redistribution of blood & ventilation to least

affected areas of lung Secretion clearance Shifts mediastinum anteriorly – assists

recruitment of atelectatic areas ? reduce lung injury Reduced lung compression by abdominal

contents

Positioning

Supine Ventilation

± 40% lung volume under lung, especially patients with large hearts

Prone Ventilation

PATIENT LYING PRONE ON VOLLMAN PRONE POSITIONER

49

Daily CPAP breathing trial FiO2 <.40 and PEEP <8 Patient has acceptable spontaneous breathing efforts No vasopressor requirements, use judgement

Pressure support weaning PEEP 5, PS at 5cm H2O if RR <25 If not tolerated, ↑RR, ↓Vt – return to A/C

Unassisted breathing T-piece, trach collar Assess for 30minutes-2 hours

Weaning

Tolerating Breathing Trial? SpO2 ≥90 Spontaneous Vt ≥4ml/kg PBW RR ≤35 pH ≥7.3 Pass Spontaneous Awakening Trial (SAT) No Respiratory Distress ( 2 or more)

HR > 120% baseline Accessory muscle use Abdominal Paradox Diaphoresis Marked Dyspnea

If tolerated, consider extubation

Weaning

1) Calculate patient’s predicted body weight:• Men (kg) = 50 + 2.3(height in inches – 60)• Females (kg) = 45.5 + 2.3(height in inches – 60)

2) Set Vt = predicted body weight x 6cc3) Set initial rate to approximate baseline

minute ventilation (RR x Vt)4) Set FiO2 and PEEP to obtain SaO2 goal of

>=88%5) Diurese after resolution of shock 6) Refer to ARDSnet guidelines

Putting it all together

Troubleshooting Common Problems

Mechanical Trouble (tubing, ventilator, ptx, plugging)

Neuromuscular blockade Recruitment maneuvers – positioning, “good lung

down” optimizes V/Q mismatch Increase PEEP Inhaled epoprostenol sodium (Flolan)

When inhaled, the vasodilator reaches the normal lung, is concentrated in normal lung segments and recruits blood flow to functional alveoli where it is oxygenated.  This decreases shunting and hypoxemia

High frequency ventilation

Refractory Hypoxia

Papazian, L, et al. NEJM 2010; 363: 1107-1116.

-Neuromuscular blocking agents may increase oxygenation and decrease ventilator associated lung injury in severe ARDS patients-Multicenter double blind trial with 340 patients; received 48hrs of cisatracurium (Nimbex) or placebo-Found that early administration of NBA improved 90 day survival and increased time off vent without increase in muscle weakness

Treat underlying infection DVT prophylaxis / stress ulcer prevention Hand washing Use full barriers with chlorhexadine Sedation / analgesia Feeding protocol Avoid contrast nephropathy Pressure ulcer prevention, turning Q2h Avoid steroid use

Supportive Therapies

~No benefit of corticosteroids on survival

~When initiated 2 weeks after onset of ARDS, associated with significant increase in mortality rate compared to placebo group

N Engl J Med. 2006; 354:1671

Recovery dependent on health prior to onset Within 6 months, will have reached max recovery At 1 year post-extubation, >1/3 have normal

spirometry• Significant burden of emotional and depressive

symptoms with increased depression in ARDS survivors Survivor clinic catches symptoms early by screening

patients New treatment modalities, lung protective

ventilation

Conclusion

Levy BD, & Choi AM, Harrison’s Principles of Internal Medicine, 2012