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Corticosteroids in ARDS. 醫七 游智傑. Acute lung injury(ALI). Definition A syndrome of acute and persistent lung inflammation with increased vascular permeability Clinical features 1. Bilateral radiographic infiltrates 2. PaO2/FiO2 201-300mmHg
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Corticosteroids in ARDS 醫七 游智傑
Acute lung injury(ALI) • Definition A syndrome of acute and persistent lung inflammation with increased vascular permeability • Clinical features 1. Bilateral radiographic infiltrates 2. PaO2/FiO2 201-300mmHg 3. No clinical evidence for an elevated left atrial pressure (pulmonary capillary wedge pressure ≦ 18 mmHg)
Acute Respiratory Distress Syndrome • Definition Same as ALI except worse hypoxia Acute in onset • Clinical features 1. Bilateral radiographic infiltrates 2. PaO2/FiO2 less than 200 3. No clinical evidence for an elevated left atrial pressure (pulmonary capillary wedge pressure ≦ 18 mmHg)
Epidemiology • ALI Age-adjusted incidence 86 per 100,000 In-hospital mortality 39% • ARDS Age-adjusted incidence 64 per 100,000 In-hospital mortality 41% Overall mortality 25-58%
Pathophysiology - Baseline • 3 mechanisms keep normal lung from alveolar edema: 1. Intravascular protein 2. Interstitial lymphatics 3. Tight junctions between alveolar epithelial cells
Pathophysiology - Injury • Pro-inflammatory cytokines(ex.TNF, IL-1, IL-6, IL-8) • Neutrophils recruited, activated, release toxic mediators • Damage capillary endothelium and alveolar epithelium • Normal barriers lost
Pathophysiology - Consequence • Impair gas exchange increase physiologic dead space • Decrease lung compliance due to stiffness of poorly or nonaerated lung • Pulmonary hypertension occur in up to 25% ARDS patients acute cor pulmonale is rare
Pathologic stages • Exudative stage diffuse alveolar damage • Proliferative stage resolution of pulmonary edema and proliferation of type II alveolar cells, squamous metaplasia, myofibroblasts infiltration, early collagen deposition • Fibrotic stage obliteration of normal lung architecture, diffuse fibrosis, cyst formation
Treatment • Supportive care sedatives and neuromuscular blockade hemodynamic management nutritional support control of blood glucose treatment of nosocomial pneumonia ventilator prophylaxis against deep venous thrombosis and gastrointestinal bleeding • Novel therapy beta agonist surfactant inhaled vasodilator ECMO anti-inflammatory anti-oxidant
ARDS • Ongoing inflammation, parenchymal-cell proliferation, disordered deposition of collagen • May be responsive to corticosteroid?
Related Studies • 4 trials of high-dose, short-course for early ARDS failed to show survival improvement • Small case series suggest benefit of moderate-dose in persistent ARDS • A 24-patients trial: moderate-dose improve lung function and survival for ARDS 7 or more days
Related studies • High-dose increase the risk of secondary infections? • Hyperglycemia, poor wound healing, psychosis, pancreatitis, prolonged muscle weakness, impaired function status
NHLBI ARDS Clinical Trials Network • 180 patients from 1997 to 2003 • 7 to 28 days after onset of ARDS • PaO2:FIO2 less than 200 • Protocol of methylprednisolone given 1. Single dose of 2mg/kg predicted BW 2. 0.5mg/kg Q6H for 14 days 3. 0.5mg/kg Q12H for 7 days 4. Tapering
Results • No difference in 60-day or 180-day hospital mortality rate, in days in ICU or hospitalization • Steroid group had more ventilator-free days, more improvement in PaO2:FiO2, improved compliance, higher serum glucose level, lower suspected or probable pneumonia
Discussion • Routinely use of steroids in ARDS patient is NOT supported • Increased mortality rate if Initiation 2 or more weeks after onset of ARDS • Improve cardiopulmonary physiology, increase ventilator-free days, ICU-free days, and shock-free days • Not increase infection, but may increase risk of neuromyopathy
4B1 06-1 詹X塗 • 86-year-old man 1. RUL adenocarcinoma, status post VATS RUL lobectomy and LN dissection 2. Pneumonia with septic shock 3. hematuria 4. BPH s/p TURP
SICU course • Increase infiltration of bil. lung • Fail to wean • 3/6 sputum culture: 1. Pseudomonas aeruginosa 3+ 2. Neisseria species 3+ 3. Viridans streptococci 3+ • 3/14 1. O2 desaturation, unstable hemodynamic status 2. FiO2 100%, SaO2 lower than 80%. On VA ECMO
ARDS • 3/4: PaO2/FiO2: 94.7/40%: 236.75 • 3/5: PaO2/FiO2: 75.3/40%: 188.25
Steroid, timing and dosage • Body weight: 74kg • 3/14 Solu-Cortef 50mg stat • 3/15 Solu-Medro 40mg Q8H • 3/23 Solu-Medro 40mg Q12H Protocol of methylprednisolone given 1. Single dose of 2mg/kg predicted BW 2. 0.5mg/kg Q6H for 14 days 3. 0.5mg/kg Q12H for 7 days 4. Tapering
The Final Chapter • 3/29 Hypoglycemia Asystole, recover after bosmin injection • 3/30 Asystole again Family decided to hold ECMO support. Passed away at 10:57am