management of acute respiratory distress syndrome of acute respiratory distress syndrome ronald...
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Management of Acute Respiratory Distress Syndrome
Ronald Pearl, MD, PhD Professor and Chair Department of Anesthesiology Stanford University [email protected]
2015 Winter Anesthesia Conference
• No financial disclosures
Disclosures
• At the conclusion of the activity participants should be able to: – Discuss mechanisms of ventilator-associated
lung injury and how appropriate ventilator management of the patient with ARDS can prevent such injury
– Discuss fluid management of the patient with ARDS in the context of issues of systemic perfusion
– Recognize complications associated with the use of high tidal volume, low PEEP ventilation in the operating room and the ICU
Learning Objectives
Intraoperative Ventilation in ARDS • Blum, Anesthesiology 2011; 115:75
U. Michigan database 2005-2009 8.7 ml/kg TV 5 cm PEEP FIO2 0.9 PIP ≈ 30 cm
Acute Respiratory Distress Syndrome
• 23 year old woman involved in MVA – Bilateral chest contusions – Ruptured spleen – 15 units PRBC – Over next 2 days develops diffuse fever,
tachycardia, bilateral infiltrates, hypoxemia on mechanical ventilation with 100% oxygen, increased bilirubin
– What is the management and prognosis?
Acute Respiratory Distress Syndrome
• 23 year old man involved in MVA – Bilateral chest contusions – Ruptured spleen – Massive transfusion in the ED – Over next 2 days develops diffuse fever,
tachycardia, bilateral infiltrates, and hypoxemia
– What is the management and prognosis?
ARDS • Which of the following interventions have
been demonstrated to improve outcome in the patient with ARDS: – Tidal volume of 6 mL/kg – Fluid restriction – Pulmonary artery catheter monitoring – Inhaled nitric oxide – High dose steroids
ARDS
• Ashbaugh, Lancet 1967;12;319 – 12 patients with tachypnea, hypoxemia,
and decreased compliance following trauma, aspiration, or pulmonary infection
– Improved oxygenation with PEEP – 60% mortality – Hyaline membrane formation on autopsy – “Adult respiratory distress syndrome”
American-European Consensus Conference (1994)
• Acute lung injury – a syndrome of inflammation and increased
permeability – cannot be explained by left atrial or
pulmonary capillary hypertension – acute in onset and persistent
Acute Lung Injury and ARDS
Timing Chest X-ray Oxygenation PAWP
ALI Acute Bilateral infiltrates
PaO2/FIO2 < 300 mm Hg <18 mm Hg
ARDS Acute Bilateral infiltrates
PaO2/FIO2 < 200 mm Hg <18 mm Hg
Berlin Definition of ARDS
Timing Within 1 week of clinical insult
Chest imaging
Bilateral opacities not fully explained by effusions, lobar
collapse, or nodules Origin of edema
Not fully explained by cardiac failure or fluid overload
Oxygenation Mild
Moderate Severe
Measured on ≥ 5 cm PEEP PaO2/FIO2 200 - 300 mm Hg PaO2/FIO2 100 - 200 mm Hg
PaO2/FIO2 < 100 mm Hg
JAMA 2012; 307:2526
Incidence of ARDS
• 200,000 patients/year • Probability depends upon number of
risk factors and the specific risk factors • Mortality 40%
Was This Patient At Risk of ARDS?
Causes of ARDS
• Direct lung injury – Pneumonia – Aspiration – Pulmonary contusion – Near-drowning – Fat embolism – Reperfusion injury
• Indirect lung injury – Sepsis – Shock – Multiple transfusions – Acute pancreatitis – Burns – Cardiopulmonary
bypass
Stages of ARDS
• Acute exudative phase – Hypoxemia – Bilateral infiltrates – Pulmonary edema – Neutrophils
Stages of ARDS • Established injury phase
– Severe tachypnea, tachycardia – Refractory hypoxemia – Hypermetabolic state – Diffuse alveolar infiltrates – Protein-rich alveolar edema – Neutrophil and mononuclear cells – Early fibroblast proliferation
• Progresses to recovery, death, or fibrosing alveolitis stage
Stages of ARDS
• Fibrosing alveolitis phase – Bilateral infiltrates – Pulmonary edema – Persistent hypoxemia – Increased dead space – Decreased compliance
Therapy in ARDS
• Supportive care –Infection therapy, nutrition, GI
prophylaxis, DVT prophylaxis • Ventilatory therapy • Adjunctive therapy
Goals Of Mechanical Ventilation • Oxygenation • Alveolar ventilation (CO2 exchange) • Prevent lung injury
Ventilator-Associated Lung Injury
Dreyfuss, AJRCCM 1998; 157:294
45 cm H2O x 5 min 45 cm H2O x 20 min Normal
Ventilator-Associated Lung Injury
Dreyfuss, AJRCCM 1998; 157:294
What Ventilatory Factors Cause Lung Injury?
Ventilator-Associated Lung Injury
• Mechanisms –Volutrauma –Barotrauma –Oxygen toxicity –Atelectrauma –Biotrauma
Matthay, Annu Rev Pathol 2011;6:147.
Lung-Protective Strategy
• ARDS Network, NEJM 2000;342:1301 –Mortality with 12 ml/kg PBW: 40% –Mortality with 6 ml/kg PBW: 30%
Lung-Protective Strategy
How Should We Choose PEEP?
Allowable FIO2/PEEP Combinations
FIO2 PEEP 0.3 5 0.4 5 or 8 0.5 8 or 10 0.6 10 0.7 10, 12, or 14 0.8 14 0.9 14, 16, or 18 1.0 18, 20, 22, or 24
Efficacy of Lung-Protective Ventilation
• Needham D, BMJ 2012; 344:e212 • Survival related to adherence to LPV
– TV ≤ 6.5 ml/kg; Pplat ≤ 30 – 8% absolute risk reduction if both variables
What TV Do We Use?
• 23 year old woman • Height 5’5” • Weight 80 kg
Predicted Body Weight
• Males: 50 + 2.3 (Height inches – 60) – 5’9”: PBW 71 kg; TV 424 ml
• Females: 45.5 + 2.3 (Height inches – 60) – 5’5”: PBW 57 kg; TV 342 ml
• 9
Lellouche, Anesthesiology 2012; 116:985
9.2 11.5
Is Lung Protective Ventilation Relevant to Patients without ARDS?
Two-Hit Hypothesis of ARDS
• Ventilatory impact only in patients already primed for ARDS
• Heterogeneity among patients – Degree of atelectasis – Underlying lung disease – Inflammation
Tidal Volume Without ARDS
• Gajic, Intens Care Med 2005; 31:922 – ICU patients requiring mechanical
ventilation who initially did not have ARDS
– Tidal volume > 700 ml increased risk of ARDS by 2.6-fold
Tidal Volume Without ARDS
• Determann, Crit Care 2010; 14:R1 – 150 critically ill patients without ALI – Randomized to 6 vs. 10 ml/kg PBW
Tidal Volume Without ALI
• Serpa Neto, JAMA 2012; 308: 1651 – Meta-analysis of 20 articles (n = 2,822) – Decreased ALI (RR 0.33; NNT 11) – Decreased mortality (RR 0.64; NNT 23) – Decreased pulmonary infection (RR 0.45) – Decreased hospital LOS (7 vs. 9 days) – Minor increase PaCO2 (3 mm Hg) – Minor decrease pH (0.03) – No difference in oxygenation
OR Applications
• Patients undergoing major surgery may benefit from decreased tidal volumes and moderate levels of PEEP
• Tidal volumes during one lung ventilation should not exceed 6 ml/kg, plus should also use PEEP
Tidal Volume During Pneumonectomy
• Fernandez-Perez, Anesthesiology 2006; 105:14 – Patients undergoing pneumonectomy who
developed postoperative respiratory failure had higher tidal volume (8.3 vs. 6.7 ml/kg PBW)
– Odds ratio of 1.56 for each ml/kg increase in tidal volume
Tidal Volume During Pneumonectomy
• Jeon, Anaesth Intensive Care 2009; 37:14 – Development of ALI/ARDS following
pneumonectomy – OR 3.37 per ml/kg increase in tidal
volume during OLV – OR 2.32 per cm H2O increase in airway
pressure during OLV
Tidal Volume During Lobectomy
• Yang, Chest 2011; 139:530 – 100 patients undergoing lobectomy – Randomized during OLV to: – VCV with TV 10 ml/kg, no PEEP, FIO2 1.0 – PCV with 6 ml/kg, 5 cm PEEP, FIO2 0.5 – Pulmonary dysfunction (PaO2/FIO2 < 300,
infiltrates, or atelectasis) decreased from 22% to 4%
Tidal Volume During Cardiac Surgery
• Sundar, Anesthesiology 2011; 114:1102 – Patients undergoing cardiac surgery
randomized to 6 vs. 10 ml/kg TV after induction of anesthesia until extubation
– Median ventilation time 450 vs. 643 min (P = 0.10)
– Higher proportion extubated at 6 h (37% vs. 20%; P = 0.02)
– Decreased reintubation (1.3 vs. 9.5%; P = 0.03)
Lung Protective Ventilation for Donors
• Mascia, JAMA 2010; 304:2620 – Potential donors (n = 118) randomized to:
• TV 10-12 ml/kg with 3-5 cm PEEP • TV 6-9 ml/kg, 5-8 cm PEEP, and CPAP
during apnea test and airway suction – 46% vs. 5% no longer met donor eligibility
(P/F > 300) at 6 hours (NNT = 3) – 27% vs. 54% transplanted
Effects of PEEP • Improved oxygenation
– Decreased intrapulmonary shunting • Decreased cardiac output
– Decreased venous return – Increased PVR
• Variable effect on VALI – Decreased VALI due to prevention of cyclic
collapse of alveoli – Increased VALI due to end-inspiratory
overdistention of alveoli
How Should We Choose PEEP?
• Patient develops severe ARDS – FiO2 0.80 – PEEP 14
• Will higher PEEP be of benefit?
Alveoli Study
• Brower RG, N Engl J Med 2004;351:327 • Compared combinations of low PEEP/high
FIO2 and high PEEP/low FIO2(n = 550) • PEEP: 9 ± 3.5 vs. 14.6 ± 3.6 • No difference in outcome
Briel, JAMA 2010;303:865
Meta-analysis of 3 trials
Intraoperative PEEP
• Imberger, Cochrane Database Syst Rev 2010; CD007922. – 8 RCTs, 330 patients – Higher PaO2/FIO2 on POD 1 (+23) – Decreased postop atelectasis by CT scan – No significant effect on mortality (relative
risk 0.95, 95% CI 0.14 to 6.39) – Mortality study would require 21,200
patients
Postoperative CPAP
• Ferreyra, Ann Surg 2008; 247:617 – Meta-analysis of 9 RCT of postop CPAP – 34% decrease in postoperative pulmonary
complications
How Do We Optimize Fluid
Management? • FiO2 0.80 • PEEP 14 MAP 68 mm Hg • CVP 8 mm Hg • Urine output 15 ml/h • Warm extremities with good capillary refill • Should we place a PA catheter? • Should we give fluid or dobutamine to
optimize urine output?
Fluid Therapy and ALI
• ARDSnet, NEJM 2006;354:2213 – 1000 patients with ALI – Randomized to CVP vs. PAC – Randomized to fluid restriction vs. liberal
fluid strategy
Fluid Management Decisions
• ARDSnet, NEJM 2006;354:2564 – First priority was management of hypotension – Fluid management then dependent upon two
factors • Adequate urine output (≥ 0.5 ml/kg/h) • Presence of ineffective circulation
–PAC group: CI < 2.5 L/min/m2
–CVP group: Cold, mottled extremities with slow capillary refill (> 2 seconds)
Target CVP Range
Effective circulation with UOP ≥ 0.5 ml/kg/h
Effective circulation with UOP < 0.5 ml/kg/h
Ineffective circulation
Liberal 10-14 14-15 15-18
Conservative <4 8-9 9-13
• Conservative group received more furosemide and less fluid, resulting in a less positive fluid balance but no increase in renal insufficiency
• Average fluid balance prior to enrollment was positive by 2700 ml
Daily Fluid Balance
-500
0
500
1000
1500
2000
2500
3000
1 2 3 4 5 6 7
LiberalConservative
Case Example
• MAP 68 mm Hg • Urine output 15 ml/h • Warm extremities with good capillary refill • CVP 8 mm Hg
Target CVP Range
Effective circulation with UOP ≥ 0.5 ml/kg/h
Effective circulation with UOP < 0.5 ml/kg/h
Ineffective circulation
Conservative <4 8-9 9-13
Adjunctive Therapies in ARDS • Continued severe ARDS
– FiO2 1.0 – PEEP 22 – PaO2 55 – Optimal diuresis
• Are there additional therapies which will improve oxygenation and outcome?
New Therapies in ARDS • Liquid ventilation • Surfactant replacement therapy • Beta-agonists • Immunonutrition • Anti-mediator therapies • Prone position • Steroids • Inhaled nitric oxide • ECMO
Prone Position and ARDS
Gattinoni, N Engl J Med 2001; 345:56
Prone Position and ARDS
Sud, CMAJ 2014; 186: E38
But more pressure ulcers, ETT complications and unintended extubations
Steroids and ARDS
• ARDSnet, N Engl J Med 2005; 354:1671 • RCT, n = 180 at 7-28 days • Methylprednisolone 0.5 mg/kg q 6h x 14
days, then q 12 h x 7 days, then tapered • Increased mortality in patients enrolled
after 14 days
Steroids and ARDS
ARDSnet, N Engl J Med 2005; 354:1671
Inhaled Nitric Oxide
Inhaled Nitric Oxide and Neonatal Respiratory Failure
• Neonatal inhaled nitric oxide study (NINOS) group – New Engl J Med 1997; 338:597 – Randomized to 100% oxygen or to NO – 20 ppm NO followed by 80 ppm NO if
needed
NINOS Results
CONTROL INO Change in PaO2 10 58 Response to gas 25% 66% Death or ECMO 64% 46%
Inhaled NO and ARDS
Control NO (18 ppm) Prostacyclin PaO2/FIO2 152 ± 15 199 ± 23* 114 ± 11* Normal V/Q (%) 55 ± 6 60 ± 5* 44 ± 4* QS/QT (%) 36 ± 5 31 ± 5* 45 ± 4*
Rossaint NEJM 1993; 328:399
Vasodilators and ARDS
PGI2 PGI2
Intravenous PGI2
Inhaled NO and ARDS
• No improvement in oxygenation in 1/3 of patients
• No sustained improvement in oxygenation • Rebound with discontinuation • No improvement in survival in multiple
RCTs
ELSO Registry
• ECMO for respiratory failure – Newborn: 75% survival (n = 24,017) – Pediatrics: 56% survival (n - 4,635) – Adults: 53% survival (n = 2,121)
UK Experience with H1N1
• Noah, JAMA 2011; 306:1659 – Patients referred to 4 ECMO centers in the UK – P/F 55, age 36, 80% on FIO2 1.0, half received
adjunctive treatments (prone position, INO, HFO)
– Lung protective ventilation during ECMO – Mortality of 24% vs. 52% in patients not
referred (RR 0.45, CI 0.26 – 0.79)
CESAR Trial
• Peek, Lancet 2009; 374:135 – Randomized 180 patients to conventional
therapy vs. transfer to central ECMO center – Age 18-65 – Severe but potentially reversible respiratory
failure – Murray LIS ≥ 3 or pH < 7.20 – Mechanical ventilation < 7 days – During ECMO, FIO2 = 0.3, rate 10, PIP ≤ 20,
PEEP 10
CESAR Results • Survival at 6 months without severe
disability increased from 47% to 63% • $31,000 per QALY • But results may have been due to better
treatment at ECMO center (1/4 patients did not receive ECMO)
Defining the Role of ECMO • EOLIA Trial: ECMO to Rescue Lung Injury in
Severe ARDS • French REVA group • 3 entry pathways
– PaO2/ FIO2 < 50 on FIO2 ≥ 0.8 for at least 3 hours – PaO2/ FIO2 < 80 on FIO2 ≥ 0.8 for at least 6 hours – pH < 7.25 for at least 6 hours with respiratory rate
of 35 breaths per minute
EOLIA • Up to 331 patients with early respiratory failure
(MV ≤ 6 days) • Protocolized treatment in both groups
– EXPRESS trial protocol in CMV group – FIO2 < 0.6 and Ppl < 25 in ECMO group
• Veno-venous ECMO with centrifugal pump and heparinized circuit
• Endpoint of mortality at day 60 – 80% power based on 60% mortality with CMV and
absolute mortality reduction of 20% with ECMO • Will complete enrollment this year (2013)
What Is Her Prognosis?
• Likelihood of survival? • Functional recovery?
Prognosis of ARDS
• Initial prognostic variables – Chronic liver disease – Nonpulmonary organ dysfunction – Sepsis – Advanced age – Not related to oxygenation indices or lung
injury score • Failure to improve during the first week is a
major negative prognostic factor
Prognosis of ARDS
– One organ failure for 3 days • 30% mortality
– Two organ failure for 3 days • 60% mortality
– Three or more organ failure for 5 or more days • >90% mortality
Outcome in ARDS
• Continuous improvement in survival over time –34-36% in two major studies from
mid-1990’s
Survival in ARDS
Milberg, JAMA 1995; 273:306
Survival in ARDS
Phua, Am J Respir Crit Care Med 2009; 179:220
Outcome in ARDS
• Relatively normal pulmonary function – FVC, FEV1, TLC, RV, DLCO
• Decreased quality of life (Herridge, NEJM 2003; 348:683 – Less than half return to work within first
year – 6 minute walk, physical measures on SF-
36
Herridge NEJM 2011; 364:1293
ARDS • Which of the following interventions have
been demonstrated to improve outcome in the patient with ARDS: – Tidal volume of 6 mL/kg – Fluid restriction – Pulmonary artery catheter monitoring – Inhaled nitric oxide – High dose steroids
Prevention of Lung Injury in the OR • Tidal volume 6-8 ml/kg • Limit plateau pressures to 20-25 cm • Moderate levels of PEEP
– During induction, anesthesia, and postoperatively • Prevent atelectasis by using PSV during spontaneous
ventilation; reverse atelectasis with recruitment maneuvers
• Avoid 100% oxygen • Volatile anesthetics and propofol may protect during
inflammation and ischemia-reperfusion injury • Limit fluid administration • Avoid blood transfusion
THANK YOU!