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ARDS and Lung Protection

Kristina Sullivan, MDAssociate Professor

University of California, San FranciscoDepartment of Anesthesia and Perioperative Care

Division of Critical Care Medicine

Overview

• Definition and causes of ARDS• Low tidal volume strategy • Fluid conservative therapy• Interventions for refractory hypoxemia• Evidence for low tidal volume strategy in the

operating room

Case

52 y.o. man admitted 7 days prior with severe pancreatitis s/f pancreatic debridement. The patient has ARDS and is currently being mechanically ventilated with a low tidal volume strategy. His blood pressure and heart rate are within normal range. He is not currently requiring pressors.

Case

• How is the patient’s ARDS currently being managed in the ICU?

• How can you extend that care in the operating room?

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Acute Respiratory Distress Syndrome

• What is ARDS?– non-cardiogenic pulmonary capillary leak

syndrome

• Criteria– PaO2/FiO2 ratio < 300 (Acute Lung Injury or ALI)

– PaO2/FiO2 ratio < 200 (ARDS) – Bilateral infiltrates on CXR

– no evidence of left atrial hypertension or wedge < 18

Conditions that Predispose to ARDS

• Infection – pneumonia, sepsis• Aspiration – gastric contents, near drowning,

toxic inhalation• Trauma – pulmonary contusion, fat emboli,

burns, multiple fractures• Other - pancreatitis, massive transfusion,

cardiopulmonary bypass, drug reaction, BMT

Pathogenesis of ARDS

• Pathogenesis– Loss of integrity of alveolar capillary membrane

– Alveolar and interstitial edema– Flooding of alveoli with proteinaceous exudate

and inflammatory cells– Development of pulmonary fibrosis

PIP versus PplatPIP versus Pplat

Normal High Raw

Low Compliance

Time (sec)

Paw

(cm

H

2O)

PIP

PIP

PIP

PPlatPPlat

PPlat

Peak pressure = Dynamic + Static Resistance

Plateau pressure = Static Resistance

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NHLBI ARDS Network

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N Engl J Med 2006;354:2564-75

Fluid and Catheter Treatment Trial (FACTT) Comparison of two fluid-management strategies in ALI

N Engl J Med 2006;354:2564-75

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Calfee and Matthay, Chest 2007

Simplified Fluid Conservative Protocol

• Patient must be out of shock for at least 12 hrs• Target CVP < 4 with urine output ≥ 0.5 ml/kg/hr

• Net even fluid balance over first seven days

Case

You go up to see the patient in preparation for surgery and you find that the patient has gone into severe respiratory failure requiring an FiO2 = 90% and a high level of PEEP. The patient is noted to have a respiratory acidosis with a pH = 7.15.

What other therapies might this patient be receiving?

Other Therapies for Severe Acute Lung Injury

– High PEEP– Recruitment maneuvers

– Alternative Ventilator Strategies:• High-frequency oscillatory ventilation

– Inhaled Nitric Oxide– Prone Positioning

– ECMO

– ParalyticsDiaz et al, CCM 2010

Gropper et al, A & A 2010

High versus standard PEEP:Is high PEEP safe?

• ARDSnet ALVEOLI trial, NEJM 2004

• 2 trials on standard vs. high PEEP (JAMA 2008)– Multifaceted Lung Open Ventilation study (LOV)– Positive End-expiratory Pressure Setting in Adults with

ALI (EXPRESS)

• No difference in mortality in any of these three trials

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Recruitment Maneuvers• What is a recruitment maneuver?

– Sustained inspiratory hold (~30-60 seconds) at higher than normal airway pressures

– Sustained pressure = 40-45 cm H20

• What is the goal? – to recruit atelectatic/flooded alveoli – Increase lung capacity

• What are the potential adverse effects?– Hypotension– Barotrauma– Requirement for sedation +/- paralysis

• Not recommended or discouraged based on current evidence

High Frequency Oscillatory Ventilation (HFOV)

• Oscillating piston (180-900 x/minute)– Very small tidal volumes (1-2.5 ml/kg)

• High mean airway pressure– Goal is to recruit atelectatic lung segments and improve

oxygenation

• May require heavy sedation +/- paralysis

• Can lead to hypotension from high intrathoracicpressures

• No confirmed mortality benefit

• Skilled health care team is necessary (MD’s, RT’s, nursing)

Inhaled Nitric Oxide

• Selective pulmonary vasodilator• Delivered only to ventilated alveolar units • Improvement in V/Q matching and

PaO2/FiO2 ratio

Copyright ©2007 BMJ Publishing Group Ltd.

Adhikari, N. K J et al. BMJ 2007;334:779

Effect of nitric oxide on mortality

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Prone positioning

• Better matching of ventilation and perfusion

• Opening of dependent collapsed lung segments

• Improves oxygenation in about 70% of patients

• Now at least four large RCT’s showing no improvement in mortality

• Technically challenging

Extracorporeal Membrane Oxygenation (ECMO)

• Veno-venous circuit that relieves lungs from role in gas exchange

• Oxygenation and removal of CO2• Requires large bore IV access and

anticoagulation

• Severe ARDS: – Lung injury score > 3, hypercapnic acidosis with pH<7.2

• Randomized to usual care or transfer to an ECMO center

• Intervention group had lower rate of composite endpoint of death/severe disability at 6 months (47 vs 63%, p=0.03)– Unclear whether ECMO improved outcomes versus other

aspects of care

Lancet 2009

When is ECMO Considered?

• No firm criteria• CESAR trial criteria:

– Lung injury score > 3 (consolidation, P/F ratio, PEEP, and compliance) or

– Hypercapnic respiratory failure with pH<7.2

• Other criteria:– Respiratory failure judged to be reversible– Early in course of disease– No contraindication to anticoagulation

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Cisatracurium for Early Severe ARDS

• N=340• P:F ratio < 150 on PEEP ≥ 5• Within 48 h of presentation• Cisatracurium for 48 h

– Bolus followed by infusion of 37.5 mg/hr

• HR for death 0.68 (95% CI, 0.48 to 0.98; p=0.04)

• Improvement in 90 day survival and increased time off vent without increasing muscle weakness

Papazian L et al. N Engl J Med 2010;363:1107-1116

Treatment of Severe Respiratory Acidosis

• Increase respiratory rate

• Buffer therapy– THAM (tromethamine) vs. bicarbonate

• Continuous renal replacement therapy

• ECMO

Kallet et al, AJRCCM 2000

Operating room guidelines in patients with normal lung function:

can we prevent ALI/ARDS?

Do ventilator settings in the operating room affect post-operative lung function?

Ventilator associated lung injury in patients without lung injury at the onset of

mechanical ventilation• Retrospective cohort study• 332 patients who received mechanical ventilation

for >48 hours in the ICU• Risk factors independently associated with the

development of ARDS included the size of the tidal volume during the first day, receipt of transfused blood products, a history of restrictive lung disease, and acidemia

• Short patients and women received statistically larger tidal volumes than men

Gajic et al, Crit Care Med 2004

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Ventilator Settings as a risk factor for ARDS in mechanically ventilated patients

• Retrospective study of 3,261 patients who required >48 hours of mechanical ventilation

• 205 out of 3,261 patients developed ARDS• Development of ARDS was independently

associated with a high initial VT setting, high peak airway pressures, and the use of high PEEP

Gajic et al, Intensive Care Med 2005

Does tidal volume in the operating room matter?

Interleukin levels and TNF

• Mixed data on whether conventional tidal volume compared with low tidal volume ventilation in healthy patients undergoing elective surgery results in increased concentration of inflammatory cytokines

• 4 RCT show no difference

-52 patients undergoing esophagectomy-conventional vs. protective ventilation strategy during OLV-protective strategy resulted in

- lower interleukin and TNF levels- higher P/F ratio at 1 hour- decreased duration of mechanical ventilation

Anesthesiology 2006; 105:911-19

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-100 patients ASA I or II s/f elective lobectomy-conventional versus protective strategy during OLV

-Single center randomized controlled trial -149 patients undergoing elective cardiac surgery-Median ventilation time not significantly different-low VT group had a higher proportion free of ventilation at 6 hours

-Fewer patients in low VT group required reintubation

May 2011

Fernandez-Perez et al, Thorax 2009; 64(2): 121-127

-4420 consecutive patients without ALI undergoing highrisk elective surgery

-ALI most common cause of post-operative respiratory failure (83 total patients)

-Intraoperative peak airway pressure but not tidal volume was associated with increased risk

Summary

• Low tidal volume ventilation and fluid conservative treatment are the mainstays of ARDS treatment

• For refractory hypoxemia, patients may receive alternative/rescue therapies such as higher PEEP, recruitment maneuvers, and/or nitric oxide

• If available, ECMO is a reasonable option for refractory hypoxemia or severe respiratory acidosis

• Consider lower tidal volumes at PBW in mechanically ventilated patients in the operating room (especially those undergoing single lung ventilation)