Acute Respiratory Distress Syndrome(ARDS)

The Extreme

Sue A. Ravenscraft, MDPulmonary, Sleep, and Critical Care

Park Nicollet/Methodist HospitalClinical Professor of Medicine

University of Minnesota Medical School

The Case

ECMO

Management of ARDS• Mechanical Ventilation strategies• Prone Ventilation• Novel/Adjunctive Therapy

Case

19 year old female college student• Lives in the dormitory• Healthy, non-smoker• No recent travel, trauma, exposures• Influenza vaccine current

Emergency Department1 day of dry cough/emesis

T = 99.3, Sat 97% Lungs: left base

• Influenza negative• Azithromycin

Urgent Care (Day 2)Fever with persistent cough,

appetite Physical exam:

Temp: 39.2, RR 32, HR 144, BP 108/82, 93% on RAModerately dehydrated and febrile wbc 5.8

2 L IV SalineIM CeftriaxoneΔ oral Levofloxacin

ED/Admission (Day 3)Continued cough and emesis with

diarrhea, fever and chest pain

Temp 100.8, 169/87, HR 128, RR 18 O2 96 % (3 L/min)

Creat 2.3Given fluids, Ceftriaxone,

azithromycinAdmitted to Medicine floor

Admission CXR

RETTachypneic (rr=60) and O2 sats

40%. Patient complaining of dyspnea, chest pain with coughing and deep inspiration

2130 0000 0434 0445

BP 127/72 126/79 158/87

HR 118 108 137 138

Temp 98.6 99.1 99.7

Resp 48 40 69

O2 94% 93% 60% 79%

RET Temp 99.7, HR 137, BP 158/87, RR 68, O2

60%Alert in severe distress, speaking in 1 word phrasesLungs: coarse BS, breath sounds

• Moved to ICU • Non-invasive

ventilation (BiPAP)

7.38/36/45/20

ICU• Increased work of breathing continues on high flow oxygen • Intubated

A/P:Respiratory failure with ARDS and

bilateral pneumonia• Low tidal volume: VT 380, RR 24, PEEP 10, FiO2 90%• Nebulized Epoprostenol (Flolan™)• Bronchoscopy when stable• Consult Nephrology and ID

Berlin Definition of ARDS 2012(JAMA 2012; 307:2526)

• Symptoms within 1 week of clinical insult, or new or worsening symptoms during week

• Bilateral opacities consistent with pulmonary edema on CXR/CT Opacities not be explained by pleural effusions, lobar collapse, or pulmonary nodules

• No underlying cardiac failure or fluid overload• Measured PaO2/FiO2 on PEEP ≥ 5 cm H20

Mild: > 200 mmHg ≤ 300 mmHgModerate: > 100 mmHg ≤ 200 mmHgSevere: ≤ 100 mmHg

pH: 7.38/36.2/ 45.5/20.8 Oxymizer 15L (delivers between 65-75% FiO2)Pa02/Fi02: 65 mmHg

Incidence: ARDS inpatient 15-19 years of age: 16 per 10,000 persons-years

ARDS: Etiology

Common causes: (> 60 identified)• Sepsis *• Aspiration *• Pneumonia *• Severe trauma• Massive Transfusion• Transfusion related acute lung injury (TRALI)• Lung and hematopoietic stem cell transplant• Drug and alcohol

Risk factors: Genetic determinants, cigarette smoking, cardiopulmonary bypass, pneumonectomy, acute pancreatitis, obesity, and near drowning

ARDS: Definition Disease of the lung parenchyma that leads

to impaired gas exchange. It is associated with pulmonary cytokine release, impaired endothelial barriers, loss of surfactant, fluid accumulation in the alveoli and, later, fibrotic changes.

ICU Day 5Nephrology: likely acute kidney injury in

setting of critical illness with subsequent transition to ATN• Creat 4.5• Oliguric• 5 kg in 24 hours• Multiple labs sent

Infectious Disease: Bilateral pneumonia/pneumonitis in immunocometent host• Serologies, cultures and bronchoscopy non-

diagnostic• Vancomycin, Pipracillin-Tazobactam/Levofloxacin

7.23/40/69/16Sat 93.9

VT 380 ml, FIO2 60%, PEEP 10 PaO2/FiO2: 116 (Moderate ARDS)

• Continues nebulized high-dose Epoprostenol (Flolan)

• Patient drops saturations with movement recovers quickly

• Anuric and started CRRT today

• Prone ventilation deferred due to CRRT

ICU Day 6

7.21/69/66/27 Sats 91.8%RR 24, FIO2 80%, PEEP 12, PC +25PaO2/FiO2: 83 (severe ARDS)

• Sats marginal with permissive hypercapnia.

• Bronchoscopy done with removal of thick secretions

• Proned

ICU Day 8

pH 7.30/50/122/24RR 24, VT 430 ml, FiO2

100%, PEEP 12, PC 33

Marginal improvement after proning; continues to be very difficult to ventilate and oxygenate

CRRT tolerated while prone

ICU Day 9

It Didn’t Work!

ICU Day 10• Worsened overnight• Intolerant of supine position• Sats in 70s with any

movement• Unable to transfer• U of MN contacted

and arranged for transport on ECMO

The Transport:One Chance

The Team:U of MN

Cardiac surgeon, Fellow

2 prefusionists

Transport paramedicsMethodist

ICU nurses, OR nurses, RT, Intensivist, Critical Care Fellow, Nephrologist, Cardiologist, Echo Tech

Catheters Placed

UMN: Day 3

• ECMO continues• Lung transplant

Considered• No improvement

Lung Transplant Consult: (Day 4)

Renal failure a significant contraindicationNeurologic status is not knownDiscussed poor prognosis and the general

survival data of lung transplant with patient’s family. Agreeable with lung transplant as a last option.

Median survival for single-lung recipients is 4.6 years. Median survival for double-lung recipients is 6.6 years

Lung Transplant evaluation

Decision made by transplant surgeon and pulmonologist on service to proceed with emergent listing for bilateral lung transplant

LAS score (Lung allocation score)May 2005

Reducing the number of deaths on lung transplant waiting list

Ensuring the efficient and equitable allocation of lungs to active transplant candidates

Assigns a score ranging from 0 to 100 to all candidates older than age 12. It is a weighted combination of the predicted risk of death during the following year on the waiting list and the predicted likelihood of survival during the first year following transplantation.

 Higher lung allocation scores indicate the patient is more likely to benefit from a lung transplant.

UMN: Day 10

• Bilateral sequential lung transplantation with cardiopulmonary bypass support

• Chest closure (4 days afterwards)

• Tracheostomy (11 days afterwards)

EDDay 0

UCDay 2

AdmissionDay 3

RET

ICUDay 4

Transplantevaluation

UMN

ECMO(Day 10)

Dialysis Prone position

Lung Transplantation (Day 20)

Native Lung

Pathology: Diffuse alveolar damage

Follow-up: Present day

19 year-old, healthy, female with ARDS of unknown etiology despite extensive infectious, rheumatologic, and pulmonary workup. ECMO as bridge to BSLTx

Slow recovery requiring tracheostomy and rehab

Home 3 months after transplant

Kidney function did not return.Successful living related donor kidney transplant 5 months later

Now home and off dialysis

ECMO(Extracorporeal Membrane

Oxygenation)Mechanical devices to

temporarily support the failing heart or lungs• Cardiopulmonary bypass used in

OR for short term support• VA ECMO drains from RA or IJ

through membrane lung returned to femoral or subclavian artery (cardiac)

• VV ECMO drains from IVC through membrane lung returned to IJ (lung)

VV ECMO

VV ECMO

Cannulas are large (31 Fr)• Double lumen available• Flow 4-5 L/min

Minimal lung ventilation• Plateau pressure 20 cmH2O• FIO2 50%

Anticoagulated

ECMO: Does it work?75 matched pairs with H1N1 induced ARDS found

that referral and transfer to an ECMO center was associated with lower hospital mortality (23.7 versus 52.5 percent)

(JAMA. 2011;306(15):1659)

Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial.

(Lancet 2009;374(9698):1351)n=90 each groupECMO group 68 (75%) received ECMO

63% no disability at 6 monthsConventional group

47% no disability at 6 months

Mechanical Ventilation in ARDS

• High ventilating pressures cause ventilator induced lung injury

• Lung Protective Ventilation• Low VT improves mortality

• Meta-analysis 6 trails (n=1297)• 6 ml/kg vs 12 ml/kg• 28 day mortality 27% vs 37%

(Ann Intern Med 2009;157:566)

Mechanical Ventilation: ARDS

Low Tidal Volume VentilationSlowly drop VT to 6 ml/kg IBW and maintain Pplat ≤ 30 cmH2O

(Plateau)

Mechanical Ventilation: ARDS

Low Tidal Volume VentilationPermissive Hypercapnia• PaCO2 increases to keep pH ≥

7.25• PEEP to keep lung open and

minimize cyclic atelectasis (8-16 cmH20)

• Goal to drop FIO2 ≤ 60% before decreasing PEEP and increasing VT

• Consider recruitment maneuvers

ARDS: Prone Positioning

Improves ventilation/perfusion matching

Oxygenation and Proning

ARDS: Prone Positioning

Multicenter randomized trial• Prone > 16 hours/day vs supine

(n=230/group)

Severe ARDS PaO2/FIO2 <150 mmHg• Lung protective ventilation

– VT 6 ml/kg, Pplat < 30 cmH2O, pH > 7.2

– Ventilated < 36 hours• Primary endpoint 28 day

mortalityN Engl J Med. 2013;368(23):2159

N Engl J Med. 2013;368(23):2159

16% (p < 0.001)

38%28 Day mortality

ARDS: Adjunctive/Novel Therapy

Inhaled VasodilatorsSelectively dilate vessels in well ventilated lung zones and improve oxygenation by improved V/Q matching. Also improve pulmonary hypertension

ARDS: Inhaled Vasodilators

Inhaled Prostacyclin (Epoprostenol,Flolan™)• Nebulized in inspiratory line• Vary strength• No sophisticated equipment• Improves oxygenation, not mortality

ARDS: Inhaled Vasodilators

Nitric Oxide• Requires specialized system• Byproduct nitrogen dioxide highly toxic • oxygenation

ARDS: Adjunctive/Novel Therapy

Surfactant• Rationale: prevent atelectasis• No conclusive data in adults• Some positive data infants and

children

Antioxidants (dietary oils)• Rationale: reactive oxygen species

and partial depletion of antioxidant defense appear important in propagation of ARDS

• A few early trial promising• Recent trials negative, more ongoing

ARDS: Adjunctive/Novel Therapy

High Frequency Ventilation• Rationale: benefit of low VT ventilation

known• f > 60 and VT smaller than dead space • Used after 3 days of hypoxemia• Clinical expertise critical• Used in infants

ARDS: Adjunctive/Novel Therapy

Glucocorticoids (steroids)• Ongoing controversy: trials both

positive and neutral• Likely most helpful early and

should not be initiated after 14 days (after fibroproliferative phase of disease)

ARDS: Patient Outcome

Mortality ≅ 25-30%Psychiatric: PTSD, depression,

anxiety 30-60% at one yearPhysical: abnormal exercise

test 66% at 1 and 3 years Pulmonary: most patients 80%

predicted by 6 months

And to think we complained about hand hygiene!

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