Acute Respiratory Distress Syndrome

Dr Samir SahuConsultant Intensivist

BBSR

ARDS

• First described - 1920• Adult Respiratory Distress

Syndrome - Ashbaugh - 1967• Acute Respiratory Distress

Syndrome ATS & European consensus

Conference - 1991

ARDS- INTRODUCTION• Incidence-86.2cases/100,000 p/y

Rubenfeld NEJM 2005

• Incidence of 7.2/100,000/year The ALIEN study, Intensive Care Med 2011

• Cause - variety of insults• Most common cause - SEPSIS• Mortality – 60-70%(late 1980s)

- 30-40% (last 2 decades)

– Mild(27%), Mod(32%), Severe(45%) JAMA 2012

• Higher mortality in Sepsis

Incidence and Outcomes of Acute Lung Injury

Rubenfeld GD, Caldwell E, Peabody E, et alN Engl J Med. 2005;353:1685-1693

• The incidence of ALI was 80 cases per 100,000 person-years, with an associated in hospital mortality rate of 38% & 41% in ARDS.

• The incidence of ALI increased with age, as did mortality.

• Approximately 75% of identified patients met the more severe hypoxemia criteria for ARDS.

ARDS - Diagnosis

• Bilateral infiltrates on CXR• Hypoxaemia - PAO2/FIO2 <200• No elevation of LAP (PAP <18)• One or more underlying disease

process known to cause ARDS

American European Consensus Conference on ARDS - 1994

ARDS Berlin Definition JAMA, 2012

Mild Moderate Severe

Timing Acute onset <1 wk

Hypoxemia PaO2 /FiO2 201-300 with PEEP > 5

PaO2 /FiO2 < 200 with PEEP > 5

PaO2 / FiO2 < 100

with PEEP > 10

Origin of Edema Respiratory failure or fluid overload*

not fully explained by cardiac failure

Radiological Abnormalities

Bilateral opacities**

Bilateral opacities**

Opacities involving at least 3 quadrants

Additional Physiological Derangement

N/A N/A VE CORR >10 L/minorCRS < 40 ml/cm H2O

ARDS Berlin Definition** Not fully explained by effusions, nodules,

masses, or lobar/lung collapse;

* Need objective assessment if no risk factor present

• VE corr = VE X PaCO2/40 (corrected for Body Surface Area)

• VE corr = Corrected minute ventilation; (an indirect assessment of lung dead space)

• CRS = Lung compliance at rest

ARDS - Radiology

CXR - widespread involvement of all lung fields Stage I (1-24h)-latent stageStage II(24-36h)-dense airspace consolidationStage III(>72h)airspace consolidn decreases

ARDS - Radiology

CT: Consolidation & Collapse in dependant

areas - Recruitable - Non recruitable NormalBilateral-92%,Dependant-86%Basilar-68%,Patchy-75% Gatinoni 1986

ARDSHeterogenous

Low compliance

High Pressures

Baby Lung

VILI

ARDS-Lung Injury Score• CXR 0 - 4• Hypoxaemia PAO2/FIO2 >300 - 0

<100 - 4 • PEEP <5mm - 0 >15mm - 4• Compliance >80ml/c - 0 <19ml/c - 4 >2.5 - Severe Lung Injury Murray 1983

ARDS - Clinical suspicion

• A disease known to cause ARDS• Tachypnoea• Hypoxia SpO2• CXR - bilateral infiltratesShift patient to ICU for monitoringEarly intubation (before the pt gets

tired or collapses)

ARDS - VILI• Ventilator Induced Lung Injury (VILI) has become

a major concern in Mechanical Ventilation in ARDS

• Causes - End inspiratory overdistension (volutrauma) - Insufficient alveolar recruitment - Frank derecruitment at end expiration

(atelectrauma) – Ventilator induced release of proinflammatory mediators inducing systemic damage to end organs (Biotrauma)

ARDS - Ventilatory Strategy

To improve outcome & limit VILI - reduce Tidal Volume - keep Pplat below 30-35cmH2O -sufficient PEEP International Consensus Conference

1999.

Ventilatory Strategy

Goals

• TV – 6 ml/Kg ideal body weight

• Pplat - < 30 cm H2O (the mean Pplat of the non beneficial trials was 32)

• pH - 7.30 – 7.45

ARDS Network Low VARDS Network Low VTT Trial Trial

Patients with ALI/ARDS (NAECC definitions) of < 36 hours

Ventilator procedures • Volume-assist-control mode• RCT of 6 vs. 12 ml/kg of predicted body weight PBW Tidal Volume

(PBW/Measured body weight = 0.83)• Plateau pressure 30 vs. 50 cmH2O• Ventilator rate setting 6-35 (breaths/min) to achieve a pH goal

of 7.3 to 7.45 • I/E ratio:1.1 to 1.3• Oxygenation goal: PaO2 55 - 80 mmHg/SpO2 88 - 95%

• Allowable combination of FiO2 and PEEP:

FiO2 0.3 0.4 0.4 0.5 0.5 0.6 0.7 0.7 0.7 0.8 0.9 0.9 0.9 1.0 1.0 1.0 1.0

PEEP 5 5 8 8 10 10 10 12 14 14 14 16 18 18 20 22 24

The trial was stopped early after the fourth interim analysis (n = 861 for efficacy; p = 0.005 for the difference in mortality between groups)

ARDS Network. N Engl J Med. 2000.

ARDSnet Ventilatory Strategy

First Stage• Calculate predicted body weight -

0.91x(height in cm-152.4)+50/45.5• Set Mode - VC/AC• Set initial TV to 8 ml/Kg PBW• Add PEEP of 5-7 cm H2O• Reduce TV by 1 ml/kg every 2 hours until

TV = 6 ml/Kg PBW

ARDSnet Ventilatory Strategy

Second Stage• When TV 6 ml/kg measure inspiratory plateau

pressure with 0.5s pause • Target Pplat < 30 cm H2O• Measure Pplat 4hourly & after every change in

PEEP or TV• If Pplat > 30 reduce TV 1 ml/kg until Pplat < 30

or TV 4ml/kg• Pplat < 25 & TV < 6ml/Kg increase TV

ARDSnet Ventilatory Strategy

Third Stage• Monitor ABG for respiratory acidosis• Target pH = 7.3 – 7.45• If pH 7.15 – 7.30 increase RR until pH > 7.30 or RR >

35/min• If pH < 7.15 increase RR to 35• If pH still < 7.15 increase TV at 1 ml/kg increments till pH

> 7.15 • Do not increase RR if PCO2 < 25• If pH < 7.30 & RR 35/min consider Bicarb inf• pH > 7.45 & patient not triggering decrease RR (> 6/min)

ARDSnet Ventilatory Strategy

• Oxygenation goal: PaO2 55 - 80 mmHg/ SpO2 88 - 95%

• FiO2 <70%

• Allowable combination of FiO2 and PEEP:

FiO2 0.3 0.4 0.4 0.5 0.5 0.6 0.7 0.7 0.7 0.8PEEP 5 5 8 8 10 10 10 12 14 14FiO2 0.9 0.9 0.9 1.0 1.0 1.0 1.0PEEP 14 16 18 18 20 22 24

Low Tidal Volume RCTs

• Amato 1998 6.0-12.0 ml

• ARDS Network 20006.0-12.0 ml

• Brochard 1998 7.1-10.3 ml

• Brower 1999 7.3-10.2 ml

• Stewart 1998 7.2-10.8 ml

• Villar 2006 (5-8)-(9-11) ml

Monitoring

• Stress Index – 0.9-1.1(<0.9 tidal recruitment >1 tidal hyperinflation Ranieri Anaesthiology 2000

• CT – Analysis of pulmonary CT images during mechanical ventilation

Tidal Hyperinflation during low TV in ARDS. Terragni,2007

• The lung-protective strategy might not be protective for all patients with ALI

• Patients with large amounts of collapsed lung might be exposed to VILI despite TV & Pplat limitations

6050403020100

1.1

1.0

.9

.8

.7

.6

.5

.4

.3

.2

.1

0.0

DAYS AFTER ENTRY

BROCHARD & BROWER & STEWART & AMATO

P < 0.0001

n = 341CU

MM

UL

AT

IVE

SU

RV

IVA

L

PPLAT > 33

PPLAT < 23

23 27

27 33

( Adjusted for APACHE & pH & PEEP )

15 20 25 30 35 40 45

0

1

2

3

PLATEAU PRESSURES (cmH2O)

RE

LA

TIV

E

RIS

K O

F D

EA

TH

BROCHARD & BROWER & STEWART & AMATO

Pplat at Low TV Hager 2005

Summary

• Ventilation with lower tidal volume (6 ml/Kg PBW) in unselected cases of ARDS can be very effective for short-term lung recovery.

• Ventilation with higher tidal volume and higher plateau pressure is associated with increased risk of death.

• Lower the Pplat, better the outcome.

Summary

• The belief that an intermediate VT of 8–10 mL/kg in conjunction with a Pplat 32 cm H2O is relatively safe is not supported by credible evidence.

• We still do not know what level of Pplat is safe.

Summary

• Further data are required to assess long-term health-related quality of life, long-term cognitive outcomes and cost.

• The best ventilatory strategy should be ideally adapted to the size of aerated lung.

• Individual titration of ventilation is crucial.

Prognosis

• Hypoxemia is the most relevant prognostic variable

• Median duration of mechanical ventilation in survivors:– Mild – 5 days– Moderate – 7 days– Severe – 9 days

ARDS - Management

• Haemodynamic - Vasopressors• Treat Inciting cause• Prevent & treat coexisting other Organ

Failure• Nutrition• Prevent Thromboembolism & GI bleed• Manage Infections - VAP-30-50%• Steroids - Late stage ARDS

PEEP

• The optimal level of PEEP & best method used to set PEEP have not been definitively established

Steroids in ARDS Meduri. Am J Respir Crit Care Med(165). 983–991, 2002

• 58 patients in the methylprednisolone group and 30 from patients in the placebo group.

• Corticoid treatment at moderate doses was administered late (9+3 d) in the course of ARDS to patients failing to improve.

• A loading dose of 2 mg/kg was followed by 2 mg/kg/day from Day 1 to 14, 1 mg/kg/day from Day 15 to 21, 0.5 mg/kg/day from Day 22 to 28, 0.25 mg/kg/day on Days 29 & 30, and 0.125 mg/kg/day on Days 31 & 32.

Steroids in ARDSARDSnet, N Engl J Med 2006;

• A single dose of 2 mg of methylprednisolone/kg of PBW was followed by a dose of 0.5 mg/Kg PBW every 6 hours for 14 days, a dose of 0.5 mg/kg PBW every 12 hours for 7 days, & then tapering of the dose.

• Conclusions These results do not support the routine use of methylprednisolone for persistent ARDS despite the improvement in cardiopulmonary physiology. In addition, starting methylprednisolone therapy more than two weeks after the onset of ARDS may increase the risk of death.

Methylprednisolone Infusion in Early

Severe ARDS Meduri. CHEST 2007;

• Adult intubated patients receiving mechanical ventilation were eligible if, within 72 h of study entry, they met diagnostic criteria for ARDS by the American-European Consensus definition while receiving PEEP.

Methylprednisolone Infusion in EarlySevere ARDS Meduri. CHEST 2007;

• Methylprednisolone or normal saline solution placebo was mixed in 240 mL of normal saline solution and administered daily as an infusion at 10 mL/h and changed to a single oral dose when enteral intake was restored.

• A loading dose of 1 mg/kg was followed by an infusion of 1 mg/kg/d from day 1 to day 14,

• 0.5 mg/kg/d from day 15 to day 21, • 0.25 mg/kg/d from day 22 to day 25, • 0.125 mg/kg/d from day 26 to day 28.

Methylprednisolone Infusion in Early

Severe ARDS Meduri. CHEST 2007;

• If the patient was extubated between days 1 and 14, the patient was advanced to day 15 of drug therapy and tapered according to schedule.

• Diagnostic fiberoptic bronchoscopy with bilateral BAL was performed prior to study entry, and then every 5 to 7 days

Methylprednisolone Infusion in Early

Severe ARDS Meduri. CHEST 2007;

• If the patient failed to improve LIS between study days 7 and 9, the patient left the treatment arm of the study to receive unblinded methylprednisolone therapy (2 mg/kg/d) for unresolving ARDS following a previously reported protocol

Recruitment in ARDS

• Indications – PO2 < 60 with FiO2 > 60• Maneuver – PC 45 + PEEP 15 for 2 min• Other maneuvers – CPAP 40 for 40 sec,

- Intermittent PEEP for 2 breaths, -1-3 sighs/min (PC inflations at 35-45 cm H2O

• -Decremental PEEP

• In ARDS, the percentage of potentially recruitable lung is extremely variable and is strongly associated with the response to PEEP.

Gattinino et al,NEJM,2006

Recommendations in PracticeRecommendations in Practice

Principle of precaution

Limited VT 6 mL/kg PBW to avoid alveolar distension

End-inspiratory plateau pressure < 30 - 32 cm H2O

Adequate end-expiratory lung volumes utilizing PEEP and higher mean airway pressures to minimize atelectrauma and improve oxygenation

Consider recruitment maneuvers

Avoid oxygen toxicity: FiO2 < 0.7 whenever possible

Monitor hemodynamics, mechanics, and gas exchange

Address deficits of intravascular volume

Prioritize patient comfort and safety

Prone Positioning

• Improves oxygenation & decreases incidence of VAP

• Might be considered for patients with refractory hypoxemia in ARDS

Prone ventilation reduces mortalityin patients with acute respiratory failureand severe hypoxemia: systematic review and meta-analysis Intensive Care Med (2010)

• Prone ventilation reduces mortality in patients with severe hypoxemia.

• Given associated risks, this approach should not be routine in all patients with AHRF, but may be considered for severely hypoxemic patients.

Intensive Care Med (2010)• Prone ventilation reduced mortality in

patients with PaO2/FiO2<100 mmHg; but not in patients with PaO2/FiO2 >100 mmHg.

• Prone ventilation improved oxygenation by 27–39% over the first 3 days of therapy but increased the risks of pressure ulcers, endotracheal tube obstruction, and chest tube dislodgement.

NMBA in ARDSPapazian et al. N Engl J Med Sept 16, 2010

• Cis-atracurium infusion for first 48 hours if P/F < 120.

• The mortality rate was about 41% in the patients randomized to placebo vs about 32% or 31% in the patients randomized to the active intervention.

• The absolute risk reduction was about 10%. A number needed to treat of only 10

NIV• PaO2/FiO2 ratio of 146 or less after one hour

of NIV was an independent risk factor for intubation (odds ratio 2.51) Antonelli et al. Intensive Care Med 2001

• Mean PaO2/FiO2 in the NIV success group was 147 and 112 in the failure group

Rana et al. Crit Care 2006

• NIV should be avoided in patients with shock, severe hypoxemia or acidosis.

NIV• APACHE II score of more than 17 and a respiratory

rate of more than 25/min after 1 h of NIV predicts the need for endotracheal intubation in ALI patients treated with NIV.

Yoshida Y et al.J Anaes, 2008.

• Patients should be closely monitored in an intensive care unit setting and, if there is no improvement in oxygenation (PaO2/FiO2 into the range of 150), pH or vital signs within the first 1 to 2 hours, intubated.

Erik Garpestad and Nicholas S HillCritical Care 2006,

Antonelli M et al, A multiple-center survey on the use in clinical practice of noninvasive ventilation as a first line intervention for acute respiratory distress syndrome.

Crit Care Med 2007

• Antonelli’s study found that patients who ultimately ended-up intubated had PaO2/FiO2 ratio less than 175 mm Hg after 1 hour of NIV.

• The hospital mortality rate of those patients was quite high : something like 50%.

• Most of those patients were intubated within 8 to 12 hours for hypoxemia and dyspnea.

• Should have a shorter cut-off time for NIV in those patients whose oxygenation doesn’t improve very quickly.

ALI/ARDS

• Antonelli’s study of NIV in hypoxemic respiratory failure excluded patients in shock or with 2-organ failure,

• People who did okay with NIV had a low mortality rate, but those who failed NIV had a higher mortality rate.

ALI/ARDS

• Antonelli, the cut-off was after 1 to 2 hours,

• Check blood gases after 1 or 2 hours and the PaO2/FiO2 ratio does not improve to over 175 mm Hg, NIV failure is very likely.

• Experienced centers may be able to treat sicker patients successfully with NIV than those with less experience.

Outcome-NIV in ARDS

• Number – 38 cases• Success – 22 (57.8%)• Failure - 16 (42.2%)• Intubated – 13• Delay in intub. – 3• DNI – 2• Death – 10• Survival after intubation

- 5

• Duration(success) – Median – 3 days

(IQR1-2, IQR3-6)• Duration(failure) –

Median 19.5 hrs (IQR1-9, IQR3-72)• Wean – 2• H1N1 – 4(2death)

High Frequency Oscillatory Ventilation

• May be an effective rescue therapy for severe adult ARDS patients

Mehta et al Chest 2004

H1N1/ARDS

• Patients should be managed with a low VT (target VT, 6 mL/kg), open-lung strategy of ventilation, with PEEP titrated based on FiO2 for goal PPLAT 30 to 35 cm H2O and SpO2 88% to 90% per the ARDS Network protocol.

• PEEP levels higher than usually used may be necessary

H1N1 ARDS

• Given the high failure rate and the duration of ventilatory support often required in patients with H1N1-related respiratory failure, routine use of NIV should be avoided.

H1N1 /ARDS• Alternative modes of ventilation, such as

APRV and HFOV, were used in small numbers of patients with no obvious adverse effects. These modes, if available, may be considered in the setting of persistent hypoxemia (SpO2 88–90%, with high PEEP and FiO2 0.8) or when the goals of lung-protective ventilation cannot be met (PPLAT 30–35; VT 8 mL/kg), particularly in the setting of progressive patient decline.

H1N1 /ARDS

• Rescue therapies such as Recruitment Man., neuromuscular blockade, and prone ventilation can be considered if oxygenation goals cannot be met (SpO2 88–90%, with

high PEEP and FiO2 0.8) with the aforementioned ventilatory strategy, particularly in the setting of progressive patient decline.

Extracorporeal Support

• Considered only in patients with severe hypoxemia & hypercapnia which was unresponsive to optimal management

Inhaled Nitric Oxide

• Cannot be recommended for routine treatment of ARDS but may be useful as rescue therapy in patients with refractory hypoxemia

Conservative Fluid ManagementFACTT Study, NEJM, 2006

• Early goal-directed therapy with intravenous fluids and medications for patients with septic shock improves mortality and acidosis but may not improve the overall length of hospital stay or duration of mechanical ventilation.

• The current study demonstrates that liberal and conservative fluid management strategies yield similar 60-day mortality rates among patients with acute lung injury, although conservative fluid management was associated with improved oxygenation, number of ventilator-free days, and central nervous system function

PA & CV in ARDSFACTT Study, NEJM, 2006

• Conclusions PAC-guided therapy did not improve survival or organ function but was associated with more complications than CVC-guided therapy. These results, when considered with those of previous studies, suggest that the PAC should not be routinely used for the management of acute lung injury.

Red Blood Cell Transfusions and the Risk of Acute Respiratory Distress Syndrome Among the Critically Ill:

A Cohort Study

• pRBC use independently correlates with the development of ARDS in ICU patients at risk for this process. The link between transfusion administration follows a dose-response relationship, suggesting that exposure to any pRBC transfusion volume increases the probability for the onset of this severe complication. We urge clinicians to consider this information as they weigh the risks and benefits of transfusion in individual patients and to acknowledge that the burden of proof is shifting to suggest that transfusion avoidance may be the safer paradigm.

Crit Care.  2007;11(3) 

Prediction of Death and Prolonged

Mechanical Ventilation in Acute Lung Injury

• The presence of persistent shock, renal failure, age, immunosuppression, underlying cause of ALI, severity of illness were previously identified as important nonpulmonary outcome determinants

• Overall nonpulmonary organ failures (creatinine, platelet count, bilirubin, and Glasgow Coma Scale score) did not contribute to the discriminative power of our model

Prediction of Death and Prolonged

Mechanical Ventilation in Acute Lung Injury In the ARDS-net low tidal volume study,• Age, • APACHE II score, • Plateau pressure, • The number of organ failures (using the Brussels Organ

Failure Classification), • Number of hospital days before enrollment, • Arterial-alveolar oxygen gradient

were found to be independent prognostic factors, and were used in the mortality adjustments reported in the recent ARDS-net study

Prediction of Death and Prolonged

Mechanical Ventilation in Acute Lung Injury: Second International Study of Mechanical Ventilation and ARDS-net Investigators

• A majority of patients with ALI are at risk for death or prolonged mechanical ventilation. A model derived from

• age, • oxygenation index, • cardiovascular failure

three days after intubation predicts death or prolonged mechanical ventilation and may inform decisions regarding specific interventions such as tracheostomy, particularly in terms of clinical trial design.

Crit Care.

 2007;11(3) ©2007 

Mortality & CostCanadian Critical Care Trials Group

• 75% of the costs associated with adult respiratory distress syndrome (ARDS) are due to the initial hospitalization. The bulk of the remaining healthcare costs are from hospital readmissions and inpatient rehabilitation

• Overall, two-year mortality was 49%. Forty percent died before discharge during the initial hospitalization. However, of those surviving to discharge, 85% were surviving at two years.

Am J Respir Crit Care Med 2006;174:538-544.

The ALIEN study Intensive Care Med (2011)

• The overall ICU and hospital mortality rates (42.7 and 47.8%, respectively)

• The incidence and mortality of ARDS have not changed in Europe 10 years after the original ARDSnet study.

• Recent systematic review of 53 observational studies by Phua et al. in which they found that the pooled mortality for ARDS from 1994 to 2006 was 44%. Am J Respir Crit Care Med 2009

Lung-Protective Ventilation Yields Improved Survival in Acute Lung Injury

BMJ. March 27, 2012.• Prospective cohort study• tidal volume equal to or less than 6.5 mL/kg of

predicted body weight,• plateau pressure equal to or less than 30 cm of water,• Of the 485 patients included in the study, 311 (64%)

died within 2 years. • For each 1 mL/kg predicted body weight increase in

average tidal volume, there was an associated 18% increase in risk for death during the subsequent 2 years.

• the authors, estimated absolute risk reduction in mortality for a typical patient with 50% adherence to lung-protective ventilation was 4.0% (95% CI, 0.8% - 7.2%; P = .012).

• With full, 100% adherence, risks were reduced even further, by 7.8% (95% CI, 1.6% - 14.0%; P = .011).

Quality of LifeCanadian Critical Care Trials Group

• Survivors of ARDS gradually adapt and return to work by two years.

• 65% were able to return to work, although nearly all of the cohort had significant exercise limitations which did not improve during the two years of follow-up.

• Quality of life was significantly and persistently lower than before initial hospitalization

Am J Respir Crit Care Med 2006;174:538-544.

Functional Disability 5 Years after ARDS, Canadian Critical Care Trials Group

N Engl J Med 2011• The median 6-minute walk distance was 436 m

(76% of predicted distance)• Younger patients had a greater rate of recovery

than older patients, but neither group returned to normal predicted levels of physical function at 5 years.

• A constellation of other physical and psychological problems developed or persisted in patients and family caregivers for up to 5 years.

The EDEN Randomized Trial ARDSnet, JAMA. 2012;

• This large study is relatively definitive in showing that for patients with ALI, a delay in initiating enteral nutritional support for up to 6 days does not result in worse outcomes.

• In fact, it suggests that there may be benefits in terms of gastrointestinal symptoms.

ARDS – Causes-2010• Sepsis - 209(112)*AMI - 2(1)• Malaria - 81(51) *Post-PPI-1(1) • Fat Emb. - 15(3) *Leptosp- 1 • Post-CABG - 3(2) *En/My/Ra-1(1)• Pnuemonia – 9(5) *Trauma -2• Peurp/Ecla. – 2 *Drowning-1(1)• Post-op -5(2) Tetanus – 1(1)• TRALI 3(1) Aspiration-1(1) Mortality 178/338(52.6%)

Withdrawal - 10

ARDS - Conclusion

• ARDS is a Multisystem Disease in most cases

• Management is Essentially Supportive

• Outcome depends on -Underlying Disease -Severity of ARDS -Other Organ Dysfunction