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ARDS - Management. By H P Shum Sept 2005. ARDS - Definition. Bilateral acute lung infiltration Hypoxemia No clinical evidence of elevated left atrial pressure or PAWP <=18mmHg Differentiated from Acute lung injury by PaO2/FiO2 <300mmHg. ARDS - pathophysiology.

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ards management

ARDS - Management

By H P Shum

Sept 2005

ards definition
ARDS - Definition
  • Bilateral acute lung infiltration
  • Hypoxemia
  • No clinical evidence of elevated left atrial pressure or PAWP <=18mmHg
  • Differentiated from Acute lung injury by PaO2/FiO2 <300mmHg
ards pathophysiology
ARDS - pathophysiology
  • Formation of protein-rich alveolar edema after damage to the integrity of the lung’s alveolar-capillary barrier
  • Can be initiated by physical or chemical injury or by extensive activation of innate inflammatory responses
ards causes
ARDS - Causes
  • Sepsis or SIRS
  • Severe traumatic injury
  • Massive transfusion
  • Near drowning
  • Smoke inhalation
  • Drug overdose (commonly TCA)
ards physiological derangement
ARDS – physiological derangement
  • Ventilation-perfusion mismatch
  • Intrapulmonary shunt
  • Surfactant inactivation leading to atelectasis
  • Decreases lung compliance (stiff lung)
ards ventilator setting
ARDS – ventilator setting
  • Tidal volume
  • PEEP
  • Use of specific ventilation modalities
ards ventilator setting1
ARDS – ventilator setting
  • Low tidal volume
    • Mortality benefit mainly based on two studies

Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome

  • Amato MB et al. N Engl J Med. 1998 Feb 5;338(6):347-54
  • N=53
  • Conventionalventilation
    • Lowest possible PEEP
    • TV 12ml/kg
    • Aim normal PaCO2
  • Protective ventilation
    • PEEP above the lowerinflection point on the static pressure–volume curve
    • TV <6ml/kg
    • driving pressures< 20 cm of water above the PEEP value
    • permissivehypercapnia


Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network

N Engl J Med 2000 May 4;342(18):1301-8

  • N=861
  • Traditional gp
    • TV 12ml/kg
    • plateau pressure <=50mmH2O
  • Low TV gp
    • TV 6ml/kg
    • plateau pressure <=30mmH2O


But …. Not all studies using low TV ventilation give rise to good outcome compare with conventional ventilation methods


Evaluation of a ventilation strategy to prevent barotrauma in patients at high risk for acute respiratory distress syndrome. Pressure- and Volume-Limited Ventilation Strategy Group

Stewart TE et al. N Engl J Med 1998 Feb 5;338(6):355-61

  • N =120
  • Limited ventilation gp
    • TV 8ml/min
    • Plateau pressure <30mmH2O
  • Conventional gp
    • TV 10-15ml/kg
    • Plateau pressure <50mmH2O
  • Important to avoid over-distension of alveoli in the relatively normal parts of lung
    • start at 6-7 ml/kg predicted BW (to maintain plateau pressure <30 cm H2O)
    • allow PCO2 to rise slowly (i.e. giving kidneys time to compensate for respiratory acidosis), aim to keep pH > 7.25 (instead of aiming for a target PCO2, but advisable not to allow Pco2 to rise above 20 kPa)
    • Allow upper limit of RR to 35 bpm
    • Use sedation if needed
positive end expiratory pressure peep
Positive end-expiratory pressure (PEEP)
  • Insufficient PEEP may result in:
  • alveolar derecruitment
  • cyclical atelectasis
  • progressive lung injury
  • refractory hypoxemia

Excessive PEEP, particularly in combination with hypovolemia, can decrease cardiac output and oxygen delivery, and increase the risk of barotrauma

Am J Respir Crit Care Med 2002 Apr 1;165(7):978-82

what peep level is good for ards high vs low
What PEEP level is good for ARDS? High vs low ….
  • Amato study using low TV 6ml/kg with high PEEP (average >16mmH2O) showed improved mortality
  • However …

Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome

Brower RG et al. N Engl J Med 2004 Jul 22;351(4):327-36

  • N=549
  • low PEEP gp
    • 8.3mmH2O
  • High PEEP gp
    • 13mmH2O

peep setting
PEEP setting
  • Optimal PEEP will change from patient to patient, based in different pathophysiology and depending upon the stage and severity of the disease
  • no optimal way to assess "best PEEP"
    • PEEP is added in increments of 2-5 cm until the "best/optimal PEEP" is obtained, choose the level which provides the highest static compliance and the lowest airway plateau pressure
    • PEEP above lower inflection point on static P-V curve
  • PEEP > 20 cmH2O is rarely beneficial and usually results in additional pressure-induced lung injury
  • Level of PEEP used in ARDS still controversial
recruitment maneuvers
Recruitment maneuvers
  • utilizing a CPAP of 35 to 40 cmH20 for 40 seconds
  • can improve oxygenation and alveolar recruitment, but are relatively less effective than a continuous high PEEP level

Intensive Care Med 2000 May;26(5):501-7

Am J Respir Crit Care Med 2002 Jan 15;165(2):165-70

ventilator modes
Ventilator modes
  • fully supported modes of ventilation are favored over partially-supported modes
inverse ratio ventilation irv
Inverse ratio ventilation (IRV)
  • I:E ratio > 1 may be able to improve oxygenation in patients who remain hypoxic despite PEEP
  • But …
    • A lot of negative studies a/v showed that IRV do not had survival benefit

Anesthesiology. 2001 Nov;95(5):1182-8

Anesthesiology. 1998 Jan;88(1):35-42

Am J Respir Crit Care Med 1997 May;155(5):1637-42

    • increases the risk of air trapping, barotrauma, hemodynamic instability
    • require significant sedation and possibly neuromuscular blockade which may increase ICU stay and risk of critical illness neuromyopathy
prone ventilation
Prone ventilation
  • routine use of prone positioning in all patients with ALI / ARDS cannot be currently recommended due to a lack of clinical data support
  • Indications:
    • as an adjunctive therapy to improve oxygenation in established ALI and ARDS
    • considered in patients who require PEEP >12 cmH2O and a FiO2 >0.60
  • should better used early within 36 hours of the onset of ARDS
  • optimum duration unknown

Effect of prone positioning on the survival of patients with acute respiratory failure

Gattinoni Let al. N Engl J Med 2001 Aug 23;345(8):568-73

  • N =304
  • Multicenter RCT
  • tx gp
    • prone >=6h/d 10d
  • control gp
    • supine


Effects of systematic prone positioning in hypoxemic acute respiratory failure: a randomized controlled trial

Guerin Cet al. JAMA 2004 Nov 17;292(19):2379-87

  • N=791
  • propective, unblinded, multicenter RCT
  • prone gp
    • > = 8hr /d
  • control gp
    • supine

airway pressure release ventilation aprv
Airway pressure release ventilation (APRV)
  • lung volume and hence oxygenation is maintained by continuous positive airway pressure
  • CO2 clearance is achieved by the transient release of circuit pressure allowing gas to escape and lung volume to fall
  • CPAP is then re-established to the previous level, allowing the entry of fresh gas into the system

Also resulted in significant improvement in the cardiac index, systemic haemodynamic, O2 delivery, and vasopressor requirement and renal perfusion

Crit Care 2001 Aug;5(4):221-6

Intensive Care Med 2002 Oct;28(10):1426-33


Long-term effects of spontaneous breathing during ventilatory support in patients with acute lung injury

Putensen C et al. Am J Respir Crit Care Med 2001 Jul 1;164(1):43-9

  • determine whether use of APRV with spontaneous breathing better prevents deterioration of cardiopulmonary function
  • N = 30, MV trauma pt at risk of ARDS
  • PCV vs APRV for 72 hr, cross over study

high frequency ventilation
High frequency ventilation
  • proposed as an alternate form of lung protective ventilation that could theoretically prevent overdistension and cyclical atelectasis
  • lung inflated and kept open with very low tidal volumes and low airway pressure, aimed to produce minimal shear injury

However …

Risks of barotrauma and hemodynamic compromise with high frequency ventilation can approximate those of conventional ventilation

Chest 1993 May;103(5):1413-20


High-frequency ventilation versus conventional ventilation for treatment of acute lung injury and acute respiratory distress syndrome

Wunsch H et al. Cochrane Database Syst Rev 2004;(1):CD004085

  • only include RCT =2
  • one recruit children, n =58
  • other recruit adult, n =148

insufficient evidence to support the broad application of HFV to all patient with ALI / ARDS

inhaled vasodilator
Inhaled vasodilator
  • Nitric oxide vs prostacyclin
  • Act locally and short half life
  • Minimal systemic effect
  • Rarely cause hypotension

Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial. Inhaled Nitric Oxide in ARDS Study Group

Dellinger RP et al. Crit Care Med 1998 Jan;26(1):15-23

  • Prospective, multicenter, randomized, double-blind, placebo-controlled study
  • N = 177
  • placebo vs NO at 1.25, 5, 20, 40, or 80 ppm
  • responsive if PaO2 >=20%

PaO2 improved on first 4 hrs of tx

Percentage of pt who alive and off MV at D28


Low-dose inhaled nitric oxide in patients with acute lung injury: a randomized controlled trial

Taylor RW et al. JAMA 2004 Apr 7;291(13):1603-9

  • Multicenter, randomized, placebo-controlled study, triple blinded
  • n = 385
  • placebo vs NO 5ppm to 28d
nitric oxide
nitric oxide
  • produce toxic radicals
  • NO2 and methemoglobin concentrations may increase
  • immunosuppressant properties that theoretically could increase the risk of nosocomial infection
  • cause DNA strand breakage and base alterations that are potentially mutagenic

Prostacyclin (PG I2) improve PaO2 and decrease PAP

  • No study shown improvement of mortality associated with prostacyclin use in ARDS

inhaled vasodilators, if used at all, should be reserved for patients with intractable, life-threatening hypoxemia despite conventional management

function of endogenous surfactant
Function of endogenous surfactant
  • modulate alveolar surface tension
  • prevent atelectasis
  • facilitates mucous clearance
  • scavenges oxygen radicals
  • suppresses inflammation
  • Surfactant dysfx occur in ARDS and in theory exogenous surfactant can offer helps

Treatment of acute respiratory distress syndrome with recombinant surfactant protein C surfactant

Spragg RG et al. Am J Respir Crit Care Med 2003 Jun 1;167(11):1562-6

  • N=40
  • high dose (1ml 4x in 24 hr)
  • low dose (0.5ml 4x in 24 hr)
  • control

Effect of recombinant surfactant protein C-based surfactant on the acute respiratory distress syndrome

Spragg RG et al. N Engl J Med 2004 Aug 26;351(9):884-92

  • multicenter, randomized, double-blind trials
  • N = 448
  • 1ml 4x in 24hr for tx gp

Improvement of PaO2/FiO2 but no survival benefit was detected

partial liquid ventilation
Partial liquid ventilation
  • involves filling the lungs with a fluid (perfluorocarbon, also called Liquivent or Perflubron) which has
    • very low surface tension, similar to surfactant
    • high density, oxygen readily diffuses through it
    • may have some anti-inflammatory properties
  • The lungs are filled with the liquid, the patient is then ventilated with a conventional ventilator using a protective lung ventilation strategy.
  • Liquid will help the transport of oxygen to parts of the lung that are flooded and filled with debris, help remove this debris and open up more alveoli improving lung function. 

All of them are case report, some indicate beneficial outcome in true of improved survival and oxygenation but negative reports present as well

Larger studies are needed to determine what role, if any, PLV will play in the treatment of ARDS


Extracorporeal membrane oxygenation (ECMO)

  • withdrawing arterial or venous blood, passing it through a membrane oxygenator, and returning it to the arterial circulation
  • Very expensive and survival benefit still in doubt
  • JAMA 1979 Nov 16;242(20):2193-6
  • Crit Care Med 1994 Oct;22(10):1659-67
  • clearly have a role in situations when ARDS has been precipitated by a steroid-responsive process, eg eosinophilic pneumonia
  • Other cases, efficacy not clear
  • May be useful in fibroproliferative phase of ARDS, which is characterized by fever, purulent secretions, and new pulmonary infiltrates without evidence of infection

Chest 1991 Oct;100(4):943-52

Chest 1994 May;105(5):1516-27

  • But other even showed increased risk of ARDS and infective complications

Arch Surg 1985 May;120(5):536-40

  • Preliminary results of a large, randomized, controlled trial, performed by the NIH-sponsored ARDSNET presented in ATS May 2004, suggest no mortality advantage when patients with later phase ARDS are treated withsteriod
prostaglandin e1 pge1
Prostaglandin E1 (PGE1)
  • enhance oxygen delivery by increasing cardiac output

Chest 1990 Aug;98(2):405-10

Chest 1990 Mar;97(3):684-92

Crit Care Med 1999 Aug;27(8):1478-85

  • significant survival advantage at 30 days

Ann Surg 1986 Apr;203(4):371-8

  • However, subsequent trials failed to confirm this effect

Chest 1989 Jul;96(1):114-9

Crit Care Med 1999 Aug;27(8):1478-85

neutrophil elastase inhibitor
Neutrophil elastase inhibitor
  • Neutrophil elastase produces tissue injury at sites of inflammation
  • play a role in the endothelial injury and increased vascular permeability associated with acute lung injury
  • Selevelestat (ONO 5046) is a reversible competitive inhibitor of neutrophil elastase, and early animal and human studies suggested this agent improved outcomes following acute lung injury

Crit Care Med 2002 May;30(5 Suppl):S281-7

Eur J Pharmacol 2004 Mar 19;488(1-3):173-80

Transpl Int 2003 May;16(5):341-6

  • However, multicenter RCT of 492 MV pts with ALI treated with selevestat or placebo found no difference between groups in 28-day all cause mortality, ventilator requirement, or respiratory mechanics

Crit Care Med 2004 Aug;32(8):1695-702

key points
Key points
  • Low TV ventilation with appropriate PEEP
  • Oxygenation can be improved with prone ventilation, increased I:E ratio, recruitment maneuvers and APRV
  • Potential benefit of HFV, NO, exogenous surfactant, partial liquid ventilation still need further investigations