Acute Respiratory Distress Syndrome

Introduction

• Syndrome NOT disease
• Acute Respiratory Distress Syndrome
  • First described 1967 (Ashbaugh  et al.)
  • Stated ‘illness closely resembled the infantile respiratory distress syndrome’
• Incidence
  • Variable
  • 1.5 per 100 000 (Rubenfeld) to 79 per 100 000 (Villar)
  • Up to 10 fold higher incidence in US vs. Europe

Definitions

Pathology

CXR in ARDS

• Diffuse bilateral coalescent opacification
• Typically CXR features arise within 12-24 hours secondary to proteinaceous interstitial oedema

Diffuse alveolar damage

• Pathological hallmark of ARDS
• Only seen in 50% of cases
• Hyperaemia, alveolar atelectasis, interstitial and intra-alveolar haemorrhage/oedema, numerous alveolar macrophages and hyaline membranes
• Subsequent alveolar microvascular permeability and surfactant inactivation
• May be ventilator associated
• Associated with higher mortality if found on open lung biopsy

LUNG SAFE TRIAL (Bellani et al.)

• Algorithmic diagnosis using Berlin criteria vs. Clinical
• 34% diagnosed Day 1 and 60% by end of ICU stay
• Secondary endpoints
  • 83% received PEEP <12
  • 35% Vt >8mL/kg without Pplat measurement
• Conclusions
  • ARDS under-recognised and under-treated
• Problems
  • 17% of patients with ‘ARDS’ didn’t have it 24 hours later
  • Measured prevalence from ICU population only (not general population)
  • If no patients in 4 week period, ICU excluded from analysis (falsely high prevalence)
  • Seasonal peak so not true prevalence

Mortality (Ranieri et al.)

Risk factors for ARDS (Rubenfeld et al.)

• Severe sepsis with suspected pulmonary source (46%)
• Severe sepsis with suspected non-pulmonary source (33%)
• Witnessed aspiration (11%)
• Severe trauma (7%)
• Blood transfusion (3%)
• Drug overdose (3%)
• Pancreatitis (3%)
• Other (14%)
  • Pulmonary contusion, severe burns, non-cardiogenic shock, pulmonary vasculitis and drowning

Diagnostic workup (Papazian et al.)

• Blood culture
• Urinary antigen testing
  • Legionella pneumophila type 1
  • S. pneumoniae
• Atypical serology
  • Chlamydia, Mycoplasma, Legionella longbeachie/pneumophila
• Respiratory viral PCR
• Fibreoptic BAL
  • Gram-stain
  • Giemsa-stain
    • Better visualisation of host cell morphology e.g. viral inclusions, improved detection of bacteria, especially intracellular bacteria and detection of some protozoa/fungi
  • Culture and PCR for respiratory viruses, Pneumocystis and Aspergillus 
  • Specific staining for Legionella, Pneumocystis and Toxoplasma gondii
• If no clinical risk factors for ARDS:
  • BAL fluid cytology
  • CT chest
  • Specific immunological examinations
  • Consider malignancy: Adenocarcinoma, lymphangitis
  • Consider open lung biopsy

Treatment

• Treat underlying aetiology + supportive cares
• Supplemental oxygen
• Non-invasive ventilation
• Intubation and ventilation with lung protective strategy
• Recruitment manoeuvres
• Prone
• Pulmonary vasodilators
• Surfactant
• Oscillation
• ECMO

Non-invasive ventilation

• No benefit of CPAP O2 vs. O2 (Delclaux et al.)
• BiPAP may reduce mortality and intubation rates (Ferrer et al.)
  • Tested acute type 1 respiratory failure
  • No benefit in ARDS sub-group but not designed for this
• BiPAP may be useful as first-line intervention in type 1 respiratory failure including mild ARDS (Thille et al.)
  • Probably not helpful and possibly harmful in moderate/severe ARDS

Lung Protective Strategy
(ARDS-Network)

• Traditional: Vt 10-15mL/kg with control of arterial pH and PaCO2 taking precedence over lung protection
• Study aimed to ascertain if lower tidal volumes with permissive hypercapnoea/acidosis would improve clinical outcomes
• 861 patients, 10 ICU’s, intubated and MV with acute P/F ratio <300, bilateral pulmonary infiltrates and no clinical evidence of LA hypertension or PCWP <18
• Traditional tidal volume vs. lung protective strategy
• Outcomes
  • 31% lung protective vs. 39.8% traditional mortality (P=0.005)

• Initial Vt = 8mL/kg PBW
• Reduce Vt by 1mL/kg at <2 hr intervals to 6mL/kg PBW
• Set initial rate to baseline MV (not > 35)
• Adjust Vt and RR to achieve pH and Pplat goals below

• Oxygenation goal
  • PaO2 55-80, minimum PEEP 5
  • Can use FiO/PEEP combinations as below
    (not mandatory)

• Plateau pressure goal <30cm H20
• Check at least q4h and after each change in PEEP or Vt
• If Pplat >30: Decrease Vt by 1mL/kg (min 4mL/kg)
• If Pplat <25 and Vt <6mL/kg increase Vt by 1mL/kg until Pplat >25 or Vt = 6mL/kg
• If Pplat <30 and breath-stacking or dys-synchrony: May increase Vt in 1mL/kg increments to 7-8mL/kg if Pplat remains <30

• pH Goal 7.30-7.45
  • If pH 7.15-7.30: Increase RR up to max 35 until pH >7.30 or PCO2 <25
  • If pH <7.15: Increase RR to 35. If pH remains <7.15, Vt can be increased by 1mL/kg steps. Can exceed Pplat >30 if necessary. Can consider HCO3
  • If pH > 7.45: Decrease RR if possible
• I:E ratio goal
  • Aim duration of inspiration <= duration of expiration (i.e. 1: >1)

Open lung ventilation strategy

• Involves increased PEEP in setting of lung protective tidal volumes
• No universal protocol
• May incorporate recruitment manoeuvres
• Potential benefits to increased PEEP
  • Maximal recruitment of alveoli 
  • Minimises cyclic atelectasis and shear trauma
  • Minimises de-nitrogenation atelectasis and oxygen toxicity (by allowing lower FiO2)
  • Reduces inflammatory mediator release from alveolar collapse

Optimal PEEP

• Balance between regional over-stretch and regional de-recruitment
• May change over time
• Methods
  • Adjust according to FiO2 (as per ARDSnet)
  • Staircase recruitment manoeuvres
  • Higher than the upper or lower inflection point on pressure-volume curve
  • Adjust to maximise static compliance (Tv/Pplat-PEEP)
  • Lowest intra-pulmonary shunt (highest mixed venous O2 saturation in pulmonary artery)

Optimal target PaO2

LOCO2 (Barrot et al.) was a prospective, multi-centre RCT in France with patients randomised to either conservative oxygenation (target PaO2 55-70mmHg) or liberal oxygenation (target PaO2 90-105mmHg)

Total of 205 patients randomised, with no statistical difference in primary outcome of death from any cause at day 28.

There was, however, a statistically significant trend towards higher mortality at 90 days in conservative group vs. liberal group (44.4% vs. 30.4%)

The trial was terminated early after 5 episodes of mesenteric ischaemia in the conservative group occurred.

Evidence for open lung strategy

• ALVEOLI (2004) – No difference in mortality between high and low PEEP with lung protective strategy
• LOVS (2008) – Improved oxygenation and less rescue intervention (i.e. ECMO) but no difference in mortality
• EXPRESS (2008) – More ventilator-free days, more organ-failure free days but no difference in mortality
• Briel (2010) –Meta-analysis of above 3 showed higher PEEP improved mortality among ARDS but not ALI patients

Pressure-volume (compliance) curves 

P-V curves in ARDS

• Appears sigmoidal between FRC and TLC
  • Normally linear and concave down at higher lung volumes between FRC and TLC in healthy subjects
• Lower volume excursion to TLC
• Entire curve shifted down on absolute volume axis

• Static compliance
  • Vt/(Ppeak – PEEP) (i.e. ΔP/ Δ V)
  • Assumes linear relationship when true curve sigmoidal
  • If increase PEEP, improved static compliance may just be movement up pressure-volume curve
• Quasi-static PV curves
  • Multiple methods but essentially measure multiple P-V points with tidal breaths in between along both inspiratory and expiratory limbs to generate curve
  • Reflects balance of chest wall and lung parenchymal forces
  • Lung volume where outward chest expansion balances inward retraction of lung parenchyma = FRC
  • Chest wall contributes to most curvature below FRC; lung contributes most to curvature above FRC

Hysteresis

• Increased compliance on descending limb of P-V curve vs. inspiratory limb
• Minimal with small volume changes but increases as volume excursion increases
• Mainly determined by air-liquid surface interactions within alveoli
• Results from 4 processes:
  • Recruitment/derecruitment
  • Surfactant
  • Stress relaxation of lung i.e. previously collapsed or fully inflated prior to measurements
  • Gas absorption during measurements of P-V curves

Recruitment manoeuvres

• Involves transient elevation in airway pressure applied during mechanical ventilation to ‘recruit’ lung units and increase number of alveoli involved in gas exchange
• Cochrane review (Hodgson et al.)
  • 10 trials (1658 patients) involved. Heterogenous study group and many co-interventions that could lead to bias
  • Reduced ICU mortality (RR 0.83, P=0.02)
  • No difference in 28 day mortality
  • No difference in in-hospital mortality
  • No difference in risk of barotrauma

• Methods
  • 40cmH20 for 40-60 seconds
  • 3 consecutive sighs/min with Pplat of 45cmH20
  • 2 min peak pressure of 50cmH20 and PEEP above upper inflection point
  • RAMP: Low slow increase in insp pressure up to 40cmH20
  • Stepped increase in pressure (e.g. Staircare Recruitment Manoeuvre)

• Disadvantages
  • May require heavy sedation/paralysis
  • Transient benefits at times
  • Haemodynamic instability (reduced preload)
  • Hypercapnoea
  • May worsen VQ matching
  • Overdistension and repeated opening of lung leading to ventilator-induced lung injury (VILI)
  • Risk of pneumothorax

Steroids

• Early high-dose methylprednisolone no benefit on mortality (Bernard et al.)
• Prolonged low-dose methylprednisolone in prolonged ARDS (>7 days) no benefit on mortality (Steinberg et al.)
  • Significantly increased mortality if initiated 2 weeks or more after onset
• Early (before day 14) and prolonged (>7 days) glucocorticoids accelerate resolution and decrease hospital mortality (Meduri et al.)
• Unclear which steroid (hydrocortisone or methylprednisolone) or what level of dosing provides benefit

Neuromuscular blockade
(Papazian et al.)

• Hypothesised to assist open lung ventilation strategy
  
• In moderate-severe ARDS, Cisatracurium infusion vs. placebo significantly improved mortality once adjusted for baseline P/F ratio, plateau pressure and SAP II score

Prone positioning

• Potential benefits (Pelosi/Gattinoni/Pappert/Gillart)
  • Prone positioning optimises both lung recruitment and VQ matching
  • Collapse due to gravity of ventral lung segments in prone is less than that of dorsal segments in supine position, while lung perfusion in prone is more evenly distributed
  • Enhanced postural drainage of secretions

• Meta-analysis (Sud et al.) showed prone positioning >14 hours per day for median 4.7 days improved mortality in subgroup with P/F ratio <140
  • Reduced VAP
  • Risks of pressure ulcers, ET obstruction and dislodgements
• RCT of only P/F ratio <150 (Guerin et al. PROSEVA) showed at least 16 hrs continuous proning per day showed significantly reduced mortality (16% vs. 32%)

Nitric oxide

• Inhaled nitric oxide is selective pulmonary vasodilator with minimal systemic effects
  
• Taylor et al. 
  • No significant effect on mortality in moderate-severe ARDS but induced rapid improvement in oxygen lasting 24 hours

Prostacyclin

• No study performed with primary mortality outcomes
• Shown to improve PaO2 and reduce PAP as well as inhaled NO (Van heerden et al.; Walmrath et al.; Zwissler et al.)
• Cochrane study found insufficient evidence to support or refute its use
• IV prostacyclin
  • Systemic vasodilation leading to reduced systemic arterial pressure
  • Non-selective pulmonary vasodilation with reversal of hypoxic pulmonary vasoconstriction leading to perfused of non-ventilated alveoli

Surfactant

• Paediatric studies have shown improved oxygenation, reduced duration of ventilation and improved survival in:
  • Preterm infants with surfactant deficiency
  • Term infants with pneumonia and meconium aspiration [Auten/Findlay/Khammash/Lotze]
    
• 5 RCT’s of exogenous surfactant use in adult ARDS failed to demonstrate sustained benefit

High-frequency oscillatory ventilation (HFOV)

• Lungs held inflated to maintain oxygenation
• CO2 cleared by small volumes of gas moved in and out of lungs at 3-15Hz
• Theoretically minimises shear forces and opening/closing trauma

• OSCAR trial (Young et al. 2013)
  • No significant difference in mortality at 1 month in moderate-severe ARDS
    
• OSCILLATE (Ferguson et al. 2013)
  • Study terminated early due to markedly higher mortality in HFOV group (47% vs. 35%)

ECMO

• Rationale for use
  • Rescue therapy for severe refractory hypoxaemia, hypercapnoea or both 
    • Typically venovenous ECMO or venoarterial if significant cardiac dysfunction
  • To replace/reduce mechanical ventilation and reduce harmful effects of ventilator-induced lung injury
    • Venovenous ECMO or ECCO2R (studies ongoing)
• H1N1 Pandemic (Davies et al.)
  • 68 patients received ECMO in Aus/NZ
  • 78% survival rate vs. 52-70% in previous studies without ECMO support

• CESAR
  • 2009 UK prospective RCT
  • Severe respiratory failure taken to central site and treated with ECMO vs. conventional ventilation
  • 90 patients in each group from 68 centres
  • Significant improvement in mortality (37% vs. 53%)
  • Issues
    • Not all patients assigned to ECMO received it (some died on the way or improved enough to not need it)
    • Only a few of conventional group received protective ventilation strategy

ECCO2R

• SUPERNOVA and REST studies ongoing
  • Ultraprotective strategy with extracorporeal low-flow CO2 removal
  • Ongoing multicentre pilot study of lower Vt at 4mL/kg facilitated by ECCO2R

Prevention

• Aspirin (Kor et al.)
  • Aspirin vs. placebo in patients at risk of ARDS showed no statistical difference in incidence of ARDS or mortality
    
• Statins (Xiong et al.)
  • Statin vs. placebo meta-analysis of patients at risk of diagosed with ALI/ARDS showing no significant difference in incidence of ARDS or mortality

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Last Updated on December 29, 2021 by Andrew Crofton