SDRA de origine pulmonara

Radu T. Stoica, ATI

Institutul de Pneumoftiziologie

Marius Nasta, Bucuresti

Definitie

Sindromul de Detresa Respiratorie Acuta (SDRA) sau ARDSDescris in 1967 (12 pacienti)

Cianoza refractara la oxigen

Complianta pulmonara scazuta

RX: Infiltrate pulmonare

(Ashbaugh DG et al, Lancet 1967; 2: 319)

Definitia moderna (1994)

Debut acut

RX: infiltrate bilaterale

Wedge < 18 mmHG sau absenta semnelor de ICStg

PaO2/FiO2 < 200 ( daca > 200, ALI)

Fara prognostic previzibil in 48-72 ore)

(Bernard GR et al, Report of the American-European consensus conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994; 149: 818)

Etiologie-Incidenta

85% of predisposing conditions:Sepsis, pneumonia, trauma, aspiration

50% secondary to sepsis

Incidenta: 60/100.000 (NIH report 1972) exagerata

(Bernard GR, et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med. 1994;149(pt 1):818-624.)

Numeroase boli acute ale parenchimului pulmonar confundate cu SDRA sau ARDS (hemoragia difuza alveolara, pneumonia cu eozinofile, pneumonia acuta interstitiala, sa.)

Etiology of ARDS Chicken or the egg ?

Etiologie ARDS de origine pulmonara

PneumoniaAspiratia pulmonaraInhalatia toxica (ex. fum, alte volatile)Arsuri directeTraumatisme (contuzia pulmonara)Post-rezectie pulmonara (postpneumonectomy ARDS)ExploziiVolutrauma (!!!Ventilatia mecanica!!!)Alte cauze rare (Sarcoidoza Sabbagh et. al, Torax 2002)EPA de altitudine, EPA ex-vacuo, Conc. Crescuta de oxigen, sa.

Fiziopatologie

ARDS prin injurie pulmonara directa, de cauza pulmonara sau ARDS primar (ex pneumonia, aspiratia, arsurile)ARDS prin injurie pulmonara indirecta, de cauza extrapulmonara sau ARDS secundar (ex. sepsis, pancreatita)

Fiziopatologie

Injurie directa/indirecta

Raspuns inflamator

Celular Humoral

PMN, MM, Limfocite Complement, Tulb. coagulare

Sist. Kinin

Mediatori

Cytokine, oxidanti, proteaze, NO, neuropepetide

Factori de crestere, mediatori lipidici, etc.

(Gattinoni L et al, Acute Respiratory Distress Syndrome in Clinical Critical care medicine Mosby, , 2006, cap 25:237

Edem pulmonar necardiogen

Fiziopatologie

Faza exudativa, initiala 24-72 oreFaza fibroproliferativa pana la max 14 zileUneori faza de fibroza

Diagnostic Hipoxemia

Schimburile gazoase, ABG

Alcaloza respiratorie + Hipoxemie relativ rezistenta la oxigenoterapieSe agraveaza pe masura ce creste acumularea de fluid intraalveolarPerturbarea grava a V/QDetermina necesitatea suportului ventilatorPaO2/FiO2 la debut, ca o expresie a schimburilor gazoase, se coreleaza cu prognosticul Bone et al.1989

Diagnostic Hipoxemia

Cantitatea de apa extravasculara din plamani poate fi masurata:

Tehnica: Thermal Indocyanine Green

Extrem de rar practicata in clinica

Limita superioara a normalului:500 ccMedia in ARDS : 1500 cc

6 - 8 ori normalul !

(4 litri de fluid)

Diagnostic radiologic

Rx : infiltratele pulmonare difuze sugereau o afectare omogena Apar la 4-24 ore dupa primele semne radiologice

Diagnostic radiologic

Imaginea CT a schimbat complet modelul, leziunile nu sunt difuze ci heterogene. Baby lung cu 3 zone pulmonare:

- Normal aerat , non-dependent (baby lung) corespondent al unui plaman de copil de 5-6 ani

- Aproape normal in zona subiacenta, complianta mai scazuta

- Plaman anormal, zona de colaps alveolar, complianta pierduta, consolidata in portiunea decliva

Diagnostic radiologic

Diagnostic Hemodinamica

Nu exista un profil hemodinamic specific ARDS

Caracteristici in ARDS:

Edem pulmonar

Debit cardiac crescut

PAOP normala sau scazuta

Stare hiperdinamica

Diagnostic Hemodinamica

In starile critice exista numerosi factori depresivi ai functiei cardiace care interfera cu mecanismele fiziopatologice din ARDS

Monitorizarea cardiaca invaziva joaca un rol important in managementul ARDS

In faza initiala pentru a exclude EPA Optimizarea administraii fluidelor cu scopul de a obtine un debit cardiac maxim

Diferente ARDS pulmonar si extra-pulmonar

Leziunea initiala: alveolara in ARDSp, interstitiala in ARDSexp (pot co-exista!)Imaginea CT: predomonent consolidare in ARDSp, predominent sticla mata in ARDS exp Elastanta pulmonara crescuta in ARDSp, toracica in ARDSexpPEEP si prone position ar trebui sa fie mai eficiente in ARDSexp

(Pelosi P, Caironi P,Gattinoni L, Semin Respir Crit Care Med 22(3):259-268, 2001 )

Clinica ARDS de origine pulmonara
ARDS in cadrul gripei A H1N1

ARDS PN cu Ps Aeruginosa

ARDS: PN cu Ps. Aeruginosa

ARDS dupa inhalare fum

ARDS dupa rezectiile pulmonare

Tratament: Strategii ne-ventilatorii

Tratament

Strategia ne-ventilatorie: nespecifica

Tratamentul medical sau chirurgical al factorilor predispozanti si al co-morbiditatilor

Tratament suportiv:

Sustinere a vietii

Buy time pentru vindecare

Prevenirea complicatiilor indeosebi VALI

Suportul ventilator: placa turnanta a managementului ARDS

Strategiile ne-ventilatorii

Strategii de reducere a martalitatii (management in sepsisul sever): early goal-directed therapy, Antibioterapia precoce si adecvata, controlul strict al glicemiei, steroizi in doze de stress la cei cu insuficienta relativa corticosuprarenaliana si activated protein C (xigris)

Stress Dose Corticosteroids in Sepsis

Studiu dublu-orb, placebo controlat din Franta: 300 pacienti randomizati sa primeasca o doza de steroizi (stress dose) de hydrocortisone 50 mg q6h si fludrocortisone (50 mcg daily) or placebo for 7 daysPacientii au facut initial un test de stimulare cu cortrosyn pentru a determina relativa insuficienta corticosuprarenaliana.

Annane, JAMA 2002;288:862

Tratamentul cu doze scazute de steroizi in Socul Septic: Study Design

Time 0

Onset of shock

Randomization

Within 8 Hours

Hydrocortisone IV 50mg

every 6 hours x 7 days

+

Fludrocortisone 50mcg NG

daily x 7 days

Placebo

X 7 days

Cortrosyn stimulation

Primary Outcome:

28-day survival

Annane D, et. al. JAMA 2002;288(7):862.

This slide illustrates the study design of the combination or hydrocortisone and fludrocortisone on mortality in septic shock study.

In original study design, randomization had to occur within 3 hours of the onset of shock. Later this was amended to allow for randomization within 8 hours after the onset of shock.

A short corticotropin stimulation test was performed in all patients by intravenously injecting 250-mcg IV bolus of tetracosactrin; blood samples were taken immediately before the test (time 0) and 30 (T30) and 60 (T60) minutes after the test. Then the patients were randomized to steroids or placebo. Samples were measured at a central laboratory.

Cortisol response was defined as the difference between the highest of the concentrations taken after the test and those taken before the test. Relative adrenal insufficiency (ie., nonresponders) was defined by a response of 9 mcg/dL or less.( p. 864.)

Three-level prognostic classifications are defined (p. 865):

Good: cortisol concentrations before corticotropin test < 34 mcg/dL and response to corticotropin test > 9 mcg/dLIntermediate: cortisol concentrations before corticotropin test < 34 mcg/dL and response to corticotropin test < 9 mcg/dL, or cortisol concentrations before corticotropin test > 34 mcg/dL and response to corticotropin test > 9 mcg/dLPoor: cortisol concentrations before corticotropin test > 34 mcg/dL and response to corticotropin test < 9 mcg/dL

Treatment had to be initiated in the 8 hours following the onset of shock and given for 7 days.

Mortaliatatea la 28 de zile (Non-responders vs. Responders)

Pacientii cu Insuf Relativa suprarenalal (ACTH Test Non-responders) (77%)

Pacientii fara Insuf Relativa suprarenala (ACTH Test Responders) (23%)

p = 0.04

p = 0.96

N=114

N=36

N=34

N=115

28-day Mortality

Annane D, et. al. JAMA 2002;288(7):862.

Low-dose Steroids

Placebo

ACTH Test Responders contained a total N of 70, this is 23% of the total study population (N=299). Responder placebo patients = 34 ( 18 deaths at 28 days, 53% mortality) and intervention patients = 36 ( 22 deaths at 28 days, 61% mortality).ACTH Test Non-responders contained a total N of 229 which is 77% of the total study population (N=299). Non-responder placebo patients = 115 (73 deaths at 28 days, 63% mortality), intervention patients = 114 (60 deaths at 28 days, 53% mortality)Placebo = 149 patients Intervention = 150 patientsP value for entire study population = 0.09Notes information from p. 868.

Alte strategii: Administrarea fluidelor

Atunci cand presiunea in capilarul pulmonar e redusa (PCWP) edemul pulmonar se produce doar daca permeabilitatea vasculara e crescuta Cateva studii (cazuri putine) sugereaza ca balanta negativa a lichidelor in primele zile de ARDS s-ar asocia cu un prognostic mai bun

Simplified Algorithm for Conservative Management of Fluids in Patients With ALI

MAP 60 mm Hg and Not Receiving

Vasopressors for 12 h

Calfee CS, Matthay MA: Nonventilatory treatmens for acute lung injury and ARDS, 2007, CHEST 131: 913

CVPmmHg(Recommended)PAOP mmHg(optional)Average urine out.: < 0,5mL/Kg/hAv. urine out.: > 0,5mL/Kg/h> 8> 12FurosemideReassess in 1hFurosemideReassess in 4h4-88-12Fluid bolus, fastReassess in 1hFurosemideReassess in 4h

Strategii terapeutice care necesita in continuare studii

Balanta negativa a lichidelorTerapia de substitutie cu surfactant Corticoterapia in ARDS tardiv Imunonutritia

Tratament medical

Surfactant exogenCorticosteroiziAntioxidantiVasodilatatoareOxid NitricAntiendotoxinKetoconazoleInhibitori EicosanoidVasoconstrictoarPentoxifilineAntibiotice?Corticosteroizi?

Strategiile ventilatorii

Ventilatia mecanica

Modurile clasice de VM, controlate, assist/control si asistate. VMNI?Particularitatile VM in ARDS legate de zonele pulmonare afectate in mod diferit:

Zona de plaman normal aerat (baby lung)

Zone recrutabile de plaman (zone colabate care pot fi deschise cu presiune adecvata)

Zone de plaman consolidate (alveole cu edem, pline de lichid, zone pneumonice, etc)

Ventilatia mecanica

Zona normala

Zona recrutabila

Zona consolidata

Ventilatia mecanica

Principiile de ventilatie

Open the lung and keep it open!!!

PCV initial ar reduce complicatiile (Esteban A et al, Prospective randomized trial comparing pressure-controlled ventilation and volume-controlled ventilation in ARDS, Chest 2000, 117:1690-1696)

Inflatie si recrutare alveolara

Presiune pozitiva pentru deschiderea cailor aeriene mici (10-20 cm H2O) si pentru colapsul alveolar (>30cmH2O)

Mentinerea deschisa a alveolelor: PEEP

Ventilatia mecanica

Strategii protective:

VT reduse (6ml/kg corp) Hipercapnie permisiva

Mod ventilator: assist/control

Presiune platou 7,30

FiO2< 0,5-0,6

(The ARDS Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome) N Engl J Med,2000; 342:1301-1308)

Pozitia prona

(RT Stoica, Managing support ventilation in extrapulmonary ARDS: old and new strategies, in

INTRA-ABDOMINAL SEPSIS UNRESOLVED ISSUES, Ed. C. Vasilescu, HG Berger, 2006, Editura Acadamiei Romane

Ventilatia protectiva in ventilatia pe un singur plaman

Strategia Protectiva ventilatorie in cursul OLV scade raspunsul inflamator, imbunatateste functia pulmonara si determina extubare precoce

Michelet P et al. Protective ventilation influences systemic inflammation after esophagectomy: a randomized controlled study. Anesthesiology 2006; 105:911-919.

32 pacienti cu resectii pulmonare: nivelul markerilor inflamatori in BAL a fost mai mare dupa OLV cu 10ml/Kg vs. 5 ml/kg

Schilling T et al. The pulmonary immune effects of mechanical ventilation in patients undergoing thoracic surgery. Anesth Analg 2005; 101:957-965

Manevrele de recrutare alveolare : la inceputul anesteziei sau cand se porneste OLV!

ARDS: Direct vs Indirect

Suportul ventilator este obligatorDiferente:

Tratament etiologic (ex. Pneumonia)

Aspectul CT

Mecanica respiratorie: diferenta in elastanta, edem vs. consolidare)

Strategie ventilatorie (recrutarea alveolara mai eficienta in ARDS indirect)

(Pelosi P et al., Semin Respir Crit Care Med 22(3):259-268, 2001

(Gattinoni et al., Acute respiratory distress syndrome caused by pulmonary and extrapulmonary disease. Different syndrome?, Am J Respir Crit Care,(1998,158:3-11)

(HFJV?)

Outcome and Prognosis

Severity of politrauma lesionsARDS. Failure of ARDS to improve after 4-6 days is associated with a high incidence of deathVentricular arrhythmias suggest myocardial injury Many patients require tracheostomy atelectasis, thromboembolism, infection, and air embolism Mortality rate remains high, 30-50%, frequently caused by sistemic complications (sepsis and MSOF)

Noutati?

Implicarea factorilor genetici: varianta de polimorfism a genei pentru Surfactant Protein-B asociata cu predispozitia doar la femei catre ARDS prin injurie directa (Gong MN et al, Chest 2004;125:203)Daca gradul de afectare al epiteliului alveolar este mai redus: vindecare mai rapida (ex ARDS in intox. cu heroina) (Gluecker T, RadioGraphics 1999;19:1507)Rolul imagisticii va creste considerabil in diagnostic, evaluare si monitorizare terapeutica (inclusiv PET, impedanta magnetica pentru ventilatia regionala)

(Richard JC et al, Electrical impedance tomography compared to positron emission tomography

for the measurement of regional lung ventilation: an experimental study, Critical Care 2009, 13:R82)

Antagonisti specifici ai unor mediatori ai inflamatiei (PAF, Il-8) (Zerch KJ, et al., Ann Thorac Surg; 1995, 59;328)

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