Acute Respiratory Distress syndrome

Sophy sony, BMCON

DEFINIION
 ARDS is a severe lung disease caused by a
variety of direct and indirect issues.  It is characterized by inflammation of the lung parenchyma leading to impaired gas exchange with concomitant systemic release of inflammatory mediators causing inflammation, inflammation, hypoxemia and frequently resulting in multiple organ failure. failure.  This is often fatal, usually requiring mechanical ventilation and admission to an intensive care unit. A less severe form is called unit. acute lung injury (ALI). ALI).

Aiso known as.

 Noncardiogenic pulmonary edema;
IncreasedIncreased-permeability pulmonary edema; Stiff lung; Shock lung; ARDS; Acute lung injur

Historical Background
 Since WWI physicians have recognized a syndrome of
respiratory distress, diffuse lung infiltrates and respiratory failure in pt with various medical conditions including from battle trauma to severe sepsis, pancreatitis, massive transfusions etc

 In 1967, Ashbaugh et al become the first to describe the

syndrome which they referred to as adult respiratory distress syndrome in 12 such patients (1)

Historical Background
 in 1971, Ashbaugh and Petty further defined the
syndrome in a form that summarized the clinical features well (but lacked specific criteria to identify pts systematically) (2)

- severe dyspnea - cyanosis refractory to O2 - decreased pulm compliance - diffuse alveolar infiltrates on CXR - atelectasis, vascular congestion, hemorrhage, pulm edema and hyaline membranes at autopsy

Historical Background
 in 1988, a more expanded definition was proposed that
quantified the physiologic respiratory impairment through the use of 4-point lung injury scoring system (3) 4- level of PEEP - P/F RATIO - static lung compliance - degree of infiltration on CXR - *also included nonpulm organ dysfunction  This definition still had its shortcomings in that it specific criteria to r/o cardiogenic pulm edema and is not predictive of outcomes

Historical Background
 1994 American - European Consensus Conference
Committee (AECC) came up with definition that became widely accepted syndrome from adult respiratory distress - Acute onset - bilateral infiltrates on CXR - PCWP =< 18 mmHg - P/F ratio =< 200 ( ALI if P/F ratio =< 300 )

 also changed the name to acute respiratory distress  defined it as a spectrum of ALI

Epidemiology
 the problem has always been how to identify the cases  attempts at extrapolating incidences based on the various
definitions offered above have resulted in various numbers (1.5-8.3 (1.575/100,000) Scandinavia (reported incidence of 17.6/100,000 for ALI and 13.5/100,000 for ARDS (4) Washington 4/1999-7/2000) reported much higher numbers for age4/1999ageadjusted incidence (5) - ALI - 86.2/100,000 person-yrs (reaching 306 in ages 75-84) person75- estimated annually cases base on these stats 190,600 - mortality 74, 500/yr

 the first study using the 1994 AECC definition was done in

 More recently the ARDSNet study (done in King County,

Morbidity and Mortality

 prior to ARDSNet study - mortality rate for ARDS    
has been estimated at 40-70% 40ARDSNet found a much lower overall mortality rate 30-40% (6) 30notable that MR increases with age: 24 % ages 1515-19 and 60 % in > 85 yrs 2/2 co-morbid conditions coMortality is attributable to sepsis or multiorgan dysfunction

Morbidity and Mortality

 Morbidity
- prolonged hospital course- nosocomial courseinfections especially VAP - wt loss - muscle weakness - functional impairment in months following

Causes
DIRECT LUNG INJURY(primary lung injury)
COMMON  PNA  Aspiration LESS COMMON  Pulm contusion  Fat emboli  Near-drowning Near Inhalation injury  Reperfusion pulmonary edema after CPbypass

INDIRECT LUNG INJURY(secondry) INJURY(secondry)

COMMON  Sepsis  Severe trauma with shock and multiple transfusions LESS COMMON  Cardiopulm bypass  Acute pancreatitis  Transfusions  Drug overdose  Anaphylaxis  DIC  Nonpulmonary sys.diseases  Severe head injury

Pathophysiology
 Diffuse alveolar damage  Lung capillary damage  Inflammation/pulm edema*  Resulting severe hypoxemia and
decreased lung compliance

Pathophysiology ARDS

Injury to the alv .cap.memb release of imflm. mediators imflm. Damaged type2 alv cell

 Surfactant production alv. Cap.mem. alv. vascular  permiability narrowing &  Alv.compliance & recoil obsrtn  BROCHOCOSTRICTION  Atelectasis outward migration  of bld.cells& fld bld.cells&  hyaline mem. formation mem. from capillaries     
impairment in gas exchange ARDS pul.oedema

lung compliance

Pul.HTN

Pathophysiology
Occurs in stages 1. Exudative ( Acute Phase) 2. Proliferative 3. Fibrotic 4. Recovery

Exudative phase (Acute Phase)(1Phase)(17days)

 Alveolar-capillary barrier is formed by Alveolarmicrovascular endothelium and alveolar epithelium  Under normal conditions epithelial barrier is much less permeable than endothelium  Epithelium is made up of type I and II cells  Type I cells are injured easily and Type II cells are more resistant

Exudative Phase
 In ALI/ARDS damage to either one
occurs,adherence of neutrophils to vas.endothelium--vas.endothelium--resulting in increased permeability of the barrier. Ie. Ie. Capilary permiability. Engorgement of perivascular permiability. & peribronchial interstitial space interstitial edema, fluid crosses the alv. Epithelium alv. Influx of proteinproteinrich edema fluid into the alveolar space intra pulmonary shunt as blood passing through them can not be O2nated. WOB, dyspnoea. dyspnoea.  Injury of Type I cells results loss of epithelial integrity and fluid extravasation (edema)  Injury of Type II cells then impairs the removal of the edema fluid

Exudative Phase
 Dysfunction of Type II cells
production and turnover of surfactant to alveolar collapse  Widespred atelectasis lung complance, complance, compromised gas exchange, hypoxemia

 If severe injury to epithelium occurs

disorganized/insufficient epithelial repair occurs ie, ie, hyaline membrane begins to line the alveoli resulting in fibrosis and atelectasis. atelectasis.  In addition to inflammatory process, there is evidence that the coagulation system is also involved pul.microvascular occlusion PA bld flow to ventilated portions dead space, PulHTN

Exudative Phase

Proliferative Phase
 After acute phase, some pt will have     
uncomplicated course and rapid resolution. Still may have dyspnoea,tachypnoea, & hypoxemia. dyspnoea,tachypnoea, Histologically first sigs of resolution are -initiation of lung repair -organization of alveolar exudate -a shift from neutro to lympho predominant pul. pul. Infiltrate. -Proliferation of type-2 pneumocyte along alv. typealv. Basement memb. & syn. of new pul.surfactant memb. and differentiate into ty-1 pneumocytes. ty- pneumocytes.

Proliferative/repertivePhase(7Proliferative/repertivePhase(7-21days)

 With intervention (mechanical ventilation) there    

is clearance of alveolar fluid Soluble proteins are removed by diffusion between alveolar epithelial cells Influx of neutro., mono.,lympho., & fibroblasts neutro., mono.,lympho., proliferation as a part of the inflm. Response. inflm. Insoluble proteins are removed by endocytosis and transcytosis through epithelial cells and phagocytosis through macrophages Injured has immune regenerrative capacity after a/c lung injury.

Proliferative Phase

Proliferative Phase
 Type II cells begin to differentiate into Type I
cells and reepithelialize denuded alveolar epithelium. Further epithelialization leads to increased alveolar clearance  This phase is complete when the diseased lung is characterised by -dense firouse tissue pul.VR & PHTN lung compliance(Bcos interstitial fibrosis) compliance(Bcos Hypoxemia(due to thick alv.mem diffusion limitation & shunting. *if repe. Phase persists repe. widespread firosis,if arrested.leasion firosis,if arrested.leasion resolves.

Fibrotic Phase (chronic/late)

 Intense inflammation leads to obliteration of the     
normal lung architecture Occurs about 2-3 wks after the initial injury. 2Alveolar space is filled with mesenchymal cells and their products Reepithelialization and new blood vessel formation occurs in disorganized manner Fibroblasts also proliferate, collagen is deposited resulting in thickening of interstitium Fibrosing alveolitis and cyst formation

Fbrotic phase

 Diffuse scaring & fibrosis

lung compliance + marked reduction in surface area bcos of int.fibrosis hypoxemia  PHTN from pul.vas. desruction & fibrosis pul. pul. dead space . risk of pneumonia, morbidity

Consequences
 Impaired gas exhange leading to severe
hypoxemia - 2/2 ventilation-perfusion mismatch, ventilationincrease in physiologic deadspace  Decreased lung compliance due to the stiffness of poorly or nonaerated lung  Pulm HTN 25% of pts, due to hypoxic vasoconstriction, Vascular compression by positive airway compression, airway collapse and lung parenchymal destruction

Clinical Features
 Pts are critically ill  develop rapidly worsening tachypnea, dyspnea, tachypnea, dyspnea,
hypoxia requiring high conc of O2  Occurs within hours to days ( usually12-48 usually12hours) of inciting event  Early clinical features reflects precipitants of ARDS  Physical exam shows cyanosis, tachycardia, tachypnea and diffuse rales and other signs of inciting event

Clinical Features
     
Initial presentation often insidious . Initially may not experience res.sympts. res.sympts. Or only cough,dyspnoea, tacypnoea, & restlessnes cough,dyspnoea, tacypnoea, Chest aus.may be N or reveal fine scatterd crackles

 ABG- mild hypoxemia, & res.alkalosis caused by ABGhyperventilation.

 Resp. alk. From hypoxemia&juxtra cap.receptors(+) alk. cap.receptors(+)  Cxr-N or evidance of minimal scattered interstistial Cxrinfiltrates( on x-ray only after 30% in fld x-

c/f contd contd

 As ARDS progressesworsening of sympts
bse of fld accmln & lung compliance - WOB, tachypnea, I.C & suprasternal retraction tachypnea, - PFT- lung compliance & lung vol. esp FRC PFT- Tachycardia, diaphoresis, change in sensorium with alt.mentation, alt.mentation, cyanosis , pallor - O/A- scattered to diffuse crackles,rhonchi O/A- Cxr- diffuse extensive B/L intestitial & alv infiltration, pl.effusion Cxr- PAWP-does not PAWPas the cause is non cardiac - Hallmark of ARDS hypoxemia, PaO2 / FiO2 <200 despite fio2 wth mask, canula or ETT - ABG initially N or paCO2 despite s.dyspnea& hypoxemia. s.dyspnea& - Hypercapnea signifies hypoventilation is occuring & no longer able to maintain ventilation & later Xray- WHITEOUT/ XrayWHITELUNG due to widespred consolidation & infiltration

complications
               
INFECION Cath.rel.inf HAP Sepsis RESPIRA TORY O2 toxicity Pul.barotruma Pul.emboli Pul. Pul. Fibrosis VAP GI Paralytic ileus Pneumoperitonium Stress ulcer & Hage Hyper metabolic state RENAL - ARF CARDIAC -dysrrthmias - CO HEMATOLOGIC anemia DIC thrombocytopenia ET intubation related laryngeal ulceration tracheal malacia, stenosis, ulceration malacia, stenosis, CNS / PSYCHOLOGIC Delirium, sleep deprivation post traumatic stress disorder

Work Up
 ARDS is a clinical diagnosis  No specific lab abnormality beyond
disturbance in gas exchange is evident  Radiologic findings may be consistent but not diagnostic  w/u therefore is useful in identifying inciting event or excluding other causes of lung injury

Diagnostic findings in ARDS

REFRACTORY HYPOXEMIA PAO2<50 mmHg On FiO2> 40% with PEEP >5cm H2O Pao2 / Fio2 ratio < 2oo CHEST Xray New B/L and alv.infiltrates PAWP </= 18 mmhg and no evidence of HF PREDISPOSING CONDITIONS identification of predisposing condtions for ARDS within 48 hrs of clinical manifestations

CXR findings
diffuse, fluffy alveolar infiltrates with prominent air bronchograms

CT findings

Treatment
 No specific therapy for ARDS exists  Mainstay of treatment is supportive care  Treat underlying/inciting conditions

Collaborative therapy
    
RESPIRATORY THERAPY O2 administration PEEP Alternative modes of MV PSV, pressure release ventilation, pressurercontol ventilation, inverse ratio ventilation, high frequency ventilation, Permissive hypercapnoea,extra corporial CO2 removal, ECMO  NO causes selective vasodilation in the pul.vas.system and a powrful bronchodilator PAH without SBP  Positioning stategies( Kinetic therapy) stategies( - Prone positioning - Lateral rotation therapy

Collaborative therapy
 SUPPORTIVE THERAPY
identification & Tt of cause MAINTENANCE OF CO & TISSSUE PERFUSION HD monitoring Ionotpic / vasopressors -dopamine -dobutamine -norepinephrine Diuretics IV fluids Sedation / analgesia Neuromuscular blockade Maintain Hb< > 9-10gm% + Sa. O2 >/= 90% Hb< 9-

 

    

Treatment Fluids
 ARDSNet study comparing a conservative and a     
liberal fluid stategies (9) Rationale behind this study is decreasing pulm edema by restricting fluids Randomized, using explicit protocols applied for 7 days in 1000 pts in ALI Randomization was into fluid liberal vs fluid conservative Primary end point was death at 60 days Secondary end points included vent-free days, ventorgan failure free days

Treatment Fluids
 Study did not show any significant difference in 60 day
mortality  However pts treated with fluid conservative strategy had an improved oxygenation index and lung injury score  In addition, there was an increased in vent-free days ventwithout increase in nonpulm organ failures  Also noted in this study is that in fluid conservative group the fluid balance was more even than negative which may indicate the observed benefit may be underestimated

Treatment - Ventilation
Goals of ventilation in ARDS are to:  Maintain oxygenation by keeping O2 sats at 85-90% 85 Avoiding oxygen toxicity and complication of mechanical ventilation decreasing FiO2 to less than 65% within the 1st 24-48 hours 24-

Treatment - Ventilation
 Known TV in normal persons at rest is 667ml/kg  But historically TV of 12-15ml/kg was 12recommended in ALI/ARDS  It was also recognized this strategy of high TV causes Vent-associated lung injury as Ventearly as 1970s  Then came the land mark ARDSNet study which compared traditional TV to lower TV

Treatment Ventilation ARDSNet ( low vs traditional TV)

 861 pts with ALI/ARDS at 10 centers  Patients randomized to tidal volumes of 12
mL /kg or 6 ml/kg (volume control, assist control)  In group receiving lower TV, plateau pressure cannot exceed 30 cm H2O  22% reduction in mortality in patients receiving smaller tidal volume  Number-needed to treat: 12 patients Number-

ARDSNet
    
PaCO2 Respiratory rate PaO2/F /FIO2 Plateau pressure PEEP 6ml/kg 43 12 30 7 160 68 26 7 9.2 3.6 12m/kg 36 9 17 7 177 81 34 9 8.6 4.2

ARDSNet low vs traditional TV protocol

 * Calculated predicted body weight(pbw)
male: 50+2.3[height(inches)-60] 50+2.3[height(inches)female: 45.5+2.3[height(inches)-60] 45.5+2.3[height(inches)Mode: Volume assist-control assistChange rate to adjust minute ventilation (not>35/min) PH goal 7.30-7.45 7.30Plateau press<30cmh20 PaO2 goal: 55-80mmhg or SpO2 88-95% 5588FiO2/PEEP combination to achieve oxygenation goal.

Treatment - Ventilation What about PEEP?

 Another ARDS net study compared higher
vs lower PEEP in ARDS  This study was conducted because of the observation that low tidal volume pt required high PEEP and this may have contributed improved survival  In the same token, there has always been a concern that high levels of PEEP may contribute to vent-associated lung injury vent-

Treatment - Ventilation What about PEEP?

pts  Low Tidal volume strategy - calculated predicted body weight (pbw) male: 50+2.3[height(inches)-60] 50+2.3[height(inches)female: 45.5+2.3[height(inches)-60] 45.5+2.3[height(inches)Mode: Volume assist-control assistChange rate to adjust minute ventilation(not>35/min) PH goal 7.30-7.45 7.30Plateau press<30cmh20 PaO2 goal: 55-80mmhg or SpO2 88-95% 5588FiO2/PEEP combination to achieve oxygenation goal

 Another multicentered, randomized study involved 549

Treatment - Ventilation What about PEEP?

 Result of the study showed no benefit from
higher levels of PEEP in either mortality or secondary outcomes ( vent- free days, icuventicufree stays or organ failure)  No significant increase in lung injury was noted either  So PEEP really does not matter!

How to select vent settings

 PEEP/FiO relationship to maintain
2

adequate PaO2/SpO2  PaO2 goal: 55-80mmHg or SpO2 88-95% 5588use FiO2/PEEP combination to achieve oxygenation goal

How to select vent settings

other ventilation strategies

 Recruitment maneuvers  Prone  Inhaled nitric oxide  High frequency oscillation

Treatment
 Treatment strategy is one of low volume and high frequency
ventilation (ARDSNet protocol) - Low Vt (6ml/kg) to prevent over-distention over- increase respiratory rate to avoid very high level of hypercapnia - PaCO2 allowed to rise, usually well tolerated - May be beneficial - low CVPs Search for and treat the underlying cause; surgery if needed Ensure adequate nutrition and place on GI/DVT prophylaxis Prevent and treat nosocomial infx Consider short course of high dose steroids in pts w/ severe dz that is not resolving.

   

ARDSnet and Long-term outcome Long120pts randomized to low Vt or high Vt a) 25%mortality w/ low tidal volume b) 45% mortality w/ high tidal volume 20% had restricitve defect and 20% had obstructive defect 1 yr after recovery About 80% had DLCO reduction 1 yr after recovery Standardized tested showed health-related quality of life lower than healthnormal No difference in long-term outcomes between tidal volume group long-

References
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References
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The NHLBI ARDS Clinical Trials Network. Comparison of two fluid-management fluidstrategies inacute lung injury. N Engl J Med. Jun 15 2006;354(24):2564-75 Med. 2006;354(24):2564The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distres syndrome. N Engl J Med. May 4 2000;342(18):1301-8 Med. 2000;342(18):1301Brower RG, Lanken PN, MacIntyre N, Matthay MA, Morris A, Ancukiewicz M. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory enddistress syndrome. N Engl J Med. Jul 22 2004;351(4):327-36 Med. 2004;351(4):327Esteban A, Alia I, Gordo F. Prospective randomized trial comparing pressure-controlled pressureventilation and volume-controlled ventilation in ARDS. For the Spanish Lung Failure volumeCollaborative Group. Chest. Jun 2000;117(6):1690-6 Chest. 2000;117(6):1690Griffiths MJ, Evans TW. Inhaled nitric oxide therapy in adults. N Engl J Med. Dec Med. 22 2005;353(25):2683-95. 2005;353(25):2683-

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