Acute Respiratory Distress Syndrome. Allan Wardhaugh

Transcription

1 Acute Respiratory Distress Syndrome Allan Wardhaugh

2 Definition Aetiology Pathophysiology and CT work Molecular pathophysiology Conventional ventilation strategies Advanced treatments HFOV Surfactant ino Prone postioning Steroids

3 Definition (2012) Acute onset of respiratory symptoms (within 7days of trigger illness) CXR or CT chest with bilateral infiltrates not fully explained by cardiac failure or fluid overload PaO2/FiO2: mmhg mild mmhg moderate <100 mmhg severe Acute Respiratory Distress SyndromeThe Berlin Definition The ARDS Definition Task Force* JAMA. 2012;307(23): doi: /jama

4 Aetiology Pulmonary Infective pneumonia Aspiration pneumonia Extra-pulmonary Trauma Sepsis Burns Other causes of SIRS

5 CT studies Demonstrate dependent oedema Shows heterogeneity of lung appearances Proportion of recruitable lung small

6 Gattinoni et al. Am J Respir Crit Care Med 2001; 164:

7 CT scan through the carina 5 d after severe trauma shows diffuse ground glass opacification, right greater than left. There is a nondependent to dependent gradient. Incidentally noted is pneumomediastinum and a chest tube draining a pneumothorax Seven days later, there is partial clearing of both the diffuse ground glass opacification and the gravity-dependent atelectasis. The pneumomediastinum is almost completely resolved. Five days later, ground glass opacification has a more reticular pattern. There is now a pneumatocele in the left midlung and increasing atelectasis adjacent to it.

8 Fluid distribution

9

10 Molecular pathophysiology

11 Tremblay L, Valenza F, Ribeiro SP, Li J, Slutsky AS. Injurious ventilatory strategies increase cytokines and c-fos m-rna expression in an isolated rat lung model. J Clin Invest 1997; 99: Ventilation causes inflammation Rat lungs (removed from body) ventilated for 2 hours at one of : - Vt 7ml/kg, PEEP3 Vt 15ml/kg, PEEP 10 Vt 15ml/kg, PEEP 0 Vt 40ml/kg PEEP 0 BAL fluid analysed for TNF α, IL 1β, IL 10. Inflammatory cytokines higher in lungs with no PEEP and highest in high tidal volume

12 Ventilation strategies PEEP Low tidal volume Permissive hypercapnia

13 Inflation pressures Volume Inflection point Optimum PEEP Pressure

14 PEEP good, overdistension bad PIP 14 PIP 30 PIP 45 PEEP 0 No lung damage Perivascular oedema Severe alveoalar oedema, death by 1 hour PEEP 10 Perivascular oedema Perivascular oedema, but no alveolar oedema - survived Webb HH, Tierney DF. Am Rev Respir Dis 1974; 110:

15 Tidal volume vs pressure Rat model ventilated with 5 strategies: - Low Volume, low pressure (controls) Low volume, high pressure (chest and abdomen strapped) High pressure (45cm), High volume (40ml/kg) High pressure with PEEP 10cm, volume 25ml/kg High volume, low pressure (iron lung). Ventilation at high volume, irrespective of pressure produces pulmonary oedema and alveolar cell damage. Pressure on its own does not cause damage

16 Hickling KG, Henderson SJ, Jackson R. Low mortality associated with low volume pressure limited ventilation with permissive hypercapnia in severe adult respiratory distress syndrome. Intensive Care Med 1990; 16: Low tidal volume improves outcome? Tidal volumes 5ml/kg, PIP < 40, permissive hypercapnia

17 Yes, low tidal volume improves outcome Vt 6ml/kg vs 12ml/kg, PIP < 30, Sats 88% - 95%. ph Relative improvement in mortality 22%. Number needed to treat The Acute Respiratory Distress Syndrome 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:

18 Ultra-low tidal volumes - HFOV Vt 1-3ml/kg Minimal pressure swings

19 Arnold JH. Hanson JH. Toro-Figuero LO. Gutierrez J. Berens RJ. Anglin DL. Prospective, randomized comparison of high-frequency oscillatory ventilation and conventional mechanical ventilation in pediatric respiratory failure. Critical Care Medicine. 22(10):1530-9, 1994 HFOV improves outcome in children. Prospective MCRCT. N=58. HFOV vs CMV (cross-over allowed). 12 dropouts. Patients were > 1month, <35kg, OI> day outcomes. FDA have used the results of this trial to allow HFOV in children with OI > 13 for over 6 hours. HFOV only 83% survive without severe lung disease CMV only 30% CMV HFOV 21% HFOV CMV 0%

20 and adults Sud S, Sud M, Friedrich JO et al. High frequency oscillation in patients with acute lung injury and acute respiratorydistress syndrome (ARDS): systematic review and metaanalysis. BMJ 2010;340:c2327

21 or does it? OSCILLATE Ferguson N, Cook DJ, Guyatt GH et al. High-Frequency Oscillation in Early Acute Respiratory Distress Syndrome. N Engl J Med DOI: /NEJMoa OSCAR Young D, Lamb S, Shah S et al. High Frequency Oscillation for Acute Respiratory Distress Syndrome. N Engl J Med DOI: /NEJMoa

22 HFOV - OSCILLATE

23 HFOV - OSCILLATE

24 HFOV-OSCILLATE

25 HFOV-OSCAR

26 HFOV-OSCAR

27 HFOV-OSCAR

28 Steroids improve outcome? Randomised double blinded controlled trial Memphis. N = 24. Patients ventilated >7 days with ARDS Methylpred 2mg/kg load IV, then 2mg/kg/day in 6 hourly doses from day 1-extubation or day 14; 1mg/kg 15-21; 0.5mg/kg 22-28; 0.25mg/kg 29-30; 0.125mg/kg Trial stopped after interim analysis

29 Results Mpred Placebo p ICU Mortality 0% 63% 0.02 Hospital mortality 13% 63% 0.03 Extubated by day 10 46% 0% 0.05 Meduri GU, Headley AS, Golden E, Carson SJ, Umberger RA, Kelso T, Tolley EA. Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: a randomised controlled trial. JAMA 1998; 280(8):

30 ARDS network adult patients ARDS > 7days Randomised placebo or methylprednisilone Primary endpoint 60 day mortality

31 Results Methylpred Placebo 60 day mortality 29.2 % (20.8 to 39.4) 28.6% (20.3 to 38.6) P = day mortality 31.5% (22.8 to 41.7) 31.9% (23.2 to 42.0) P = 1.0 Starting methylprednisolone therapy more than two weeks after the onset of ARDS may increased risk of death The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network Efficacy and Safety of Corticosteroids for Persistent Acute Respiratory Distress Syndrome. N Engl J Med 2006; 354:

32 NMJ blockade Papazian L, Forel JM, Gacouin A et al. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med doi: /NEJMoa

33 NMJ blockade

34 ino One RCT including children Only briefly increases oxygenation but does not improve outcomes*. Cochrane - 5 RCTs, n = 535. No effect on mortality or ventilator free days. One study showed transient improvement in oxygenation in first 72 hours Sokol J, Jacobs SE, Bohn D Inhaled nitric oxide for acute hypoxemic respiratory failure in children and adults (Cochrane Review). In: The Cochrane Library, Issue 2, Oxford: Update Software. *Macrae D et al. Inhaled nitric oxide therapy in neonates and children: reaching a European consensus. Intensive Care Medicine 2004; 30:

35 ino - mode of ventilation may be important Dobyns EL, Anas NG, Fortenberry JD, Deshpande J, Cornfield DN, Tasker RC, Liu P, Eells PL, Griebel J, Kinsella JP, Abman SH. Interactive effects of high-frequency oscillatory ventilation and inhaled nitric oxide in acute hypoxemic respiratory failure in pediatrics. Crit Care Med. 2002;30:

36 Surfactant ARDS causes abnormalities in surfactant production and recycling Initial studies showed poor effect aerosolised surfactant used. Pilot study adults bovine surfactant RCT (non-blinded) 50mg/kg 4 doses; 100mg/kg 4 doses; 100mg/kg 8 doses N = mg/kg 4 doses showed sustaine dimprovement oxygenation 120 hours Mortality 18.8% (surf) vs. 43% (control) p=0.07 Gregory TJ. Steinberg KP. Spragg R. Gadek JE. Hyers TM. Longmore WJ. Moxley MA. Cai GZ. Hite RD. Smith RM. Hudson LD. Crim C. Newton P. Mitchell BR. Gold AJ. Bovine surfactant therapy for patients with acute respiratory distress syndrome. American Journal of Respiratory & Critical Care Medicine. 155(4): , 1997

37 Surfactant - Children RCT, n = /40-14 yrs, ventilated hours 100mg/kg bovine surfactant PaO2: FiO2 improved at 48hours if patients had extra-pulmonary ARDS and initial PaO2: FiO2 >65 Study stopped because of recruitment difficulties Moller JC. Schaible T. Roll C. Schiffmann JH. Bindl L. Schrod L. Reiss I. Kohl M. Demirakca S. Hentschel R. Paul T. Vierzig A. Groneck P. von Seefeld H. Schumacher H. Gortner L. Surfactant ARDS Study Group. Treatment with bovine surfactant in severe acute respiratory distress syndrome in children: a randomized multicenter study. Intensive Care Medicine. 29(3):437-46, 2003

38 Prone positioning improves oxygenation.

39 but not survival (adults) Gattinoni L., Tognoni G., Pesenti A., Taccone P., Mascheroni D., Labarta V., Malacrida R., Di Giulio P., Fumagalli R., Pelosi P., Brazzi L., Latini R., the Prone Supine Study Group. Effect of Prone Positioning on the Survival of Patients with Acute Respiratory Failure. N Engl J Med 2001; 345: , Aug 23, 2001

40 Curley MA. Thompson JE. Arnold JH. The effects of early and repeated prone positioning in pediatric patients with acute lung injury. Chest. 2000; 118: Prone positioning - children Uncontrolled pilot study 25 paediatric patients 2 months - 17years with ALI/ARDS. Early and repeated prone positioning for median 4 days. 21/25 decreased OI by >10% and improved PaO2/ FiO2 ratios 20mmHg No serious adverse events, but 25% had pressure sores from prone positioning.

41 ARDS prognosis (adults) 70 Risk adjusted hospital mortality J. A. Milberg, D. R. Davis, K. P. Steinberg, and L. D. Hudson. Improved survival of patients with acute respiratory distress syndrome (ARDS): JAMA, Jan 1995; 273:

42 ARDS prognosis (adults) ARDS Severity PaO2/FiO2 Mortality Mild % Moderate % Severe <100 45%

43 ARDS prognosis - children Peters MJ, Tasker RC, Kiff KM, Yates R, Hatch DJ. Acute hypoxaemic respiratory failure in children: case mix and the utility of respiratory severity indices. Intensive Care Med 1998; 24:

44 Summary ARDS is a dynamic process Ventilation at low tidal volumes improves outcomes in adults Some evidence that HFOV improves outcomes in children Steroids don t improve mortality in prolonged ARDS in adults Other strategies improve physiological end points but do not improve survival Prognosis has improved in adults Prognosis in children closely related to underlying cause and presence of multi-organ failure