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Acute Respiratory Distress Syndrome
Allan Wardhaugh
Definition Aetiology Pathophysiology and CT work Molecular pathophysiologyConventional ventilation strategies Advanced treatments HFOV Surfactant iNOProne postioningSteroids
Definition (2012)Acute onset of respiratory symptoms (within 7days of trigger illness)CXR or CT chest with bilateral infiltratesnot fully explained by cardiac failure or fluid overload PaO2/FiO2:
200-300 mmHg mild100-200 mmHg moderate<100 mmHg severe
Acute Respiratory Distress SyndromeThe Berlin DefinitionThe ARDS Definition Task Force*JAMA. 2012;307(23):2526-2533. doi:10.1001/jama.2012.5669.
Aetiology Pulmonary
Infective pneumonia Aspiration pneumonia
Extra-pulmonary Trauma Sepsis Burns Other causes of SIRS
CT studies Demonstrate dependent oedema Shows heterogeneity of lung appearances Proportion of recruitable lung small
Gattinoni et al. Am J Respir Crit Care Med 2001; 164:1701-1711¡�
CT scan through the carina 5 d after severe trauma shows diffuse groundglass opacification, right greater than left. There is a nondependent to dependent gradient. Incidentally noted is pneumomediastinum and achest tube draining a pneumothorax
Seven days later, there is partialclearing of both the diffuse ground glass opacification and the gravity-dependent atelectasis. The pneumomediastinum is almost completely resolved.
Five days later, ground glass opacificationhas a more reticular pattern. There is now a pneumatocele in the left midlung and increasing atelectasis adjacent to it.
Fluid distribution
Molecular pathophysiology
Ventilation causes inflammation
Rat lungs (removed from body) ventilated for 2 hours at one of : -
Vt 7ml/kg, PEEP3Vt 15ml/kg, PEEP 10Vt 15ml/kg, PEEP 0Vt 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
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 ClinInvest 1997; 99: 944-952
Ventilation strategies
PEEP Low tidal volume Permissive hypercapnia
Inflation pressures Volume
Optimum PEEP
Inflection point
Pressure
PEEP good, overdistension bad PIP 14 PIP 30 PIP 45
PEEP 0No lung damage
Perivascularoedema
Severe alveoalaroedema,
death by 1 hour
PEEP 10 Perivascular
oedema
Perivascularoedema, but no alveolar oedema -survived
Webb HH, Tierney DF. Am Rev Respir Dis 1974; 110: 556-565
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
Low tidal volume improves outcome?
Tidal volumes 5ml/kg, PIP < 40, permissive hypercapnia
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: 372-377
Yes, low tidal volume improves outcome
Vt 6ml/kg vs 12ml/kg, PIP < 30, Sats 88% -95%. pH 7.3-7.45 Relative improvement in mortality 22%. Number needed to treat 11.4.
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;342:1301-1308¡
Ultra-low tidal volumes - HFOV Vt 1-3ml/kg Minimal pressure swings
HFOV improves outcome in children….
Prospective MCRCT . N=58. HFOV vs CMV (cross-over allowed). 12 dropouts. Patients were > 1month, <35kg, OI> 13. 30 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 diseaseCMV only 30% ″ ″ ″CMV→HFOV 21% ″ ″ ″HFOV→CMV 0% ″ ″ ″
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
…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 meta-analysis. BMJ 2010;340:c2327
…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 2013. DOI: 10.1056/NEJMoa1215554
OSCARYoung D, Lamb S, Shah S et al. High Frequency Oscillation for Acute Respiratory Distress Syndrome. N Engl J Med 2013. DOI: 10.1056/NEJMoa1215716
HFOV - OSCILLATE
HFOV - OSCILLATE
HFOV-OSCILLATE
HFOV-OSCAR
HFOV-OSCAR
HFOV-OSCAR
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 31-32 Trial stopped after interim analysis
Results
Mpred Placebo pICU Mortality 0% 63%
63%
0%
0.02
Hospital mortality 13% 0.03
Extubated by day 10
46% 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): 159 – 65
ARDS network 2006
180 adult patientsARDS > 7daysRandomised placebo or methylprednisilonePrimary endpoint 60 day mortality
Results
Methylpred Placebo60 day mortality
29.2 % (20.8 to 39.4)
28.6% (20.3 to 38.6)
P = 1.0
180 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; 354:1671-1684
NMJ blockade
Papazian L, Forel JM, Gacouin A et al. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010 doi: 10.1056/NEJMoa1005372.
NMJ blockade
iNOOne 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, 2003. Oxford: Update Software.
*Macrae D et al. Inhaled nitric oxide therapy in neonates and children: reaching a European consensus. Intensive Care Medicine 2004; 30:372-380
iNO - mode of ventilation may be important
Dobyns EL, Anas NG, Fortenberry JD, Deshpande J, Cornfield DN, Tasker RC, Liu P, EellsPL, 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: 2425-9.
Surfactant ARDS causes abnormalities in surfactant production and recycling Initial studies showed poor effect aerosolised surfactant used.Pilot study adults
bovine surfactantRCT (non-blinded) 50mg/kg 4 doses; 100mg/kg 4 doses; 100mg/kg 8 doses N = 59 100mg/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):1309-15, 1997
Surfactant - Children RCT, n = 35. 44/40 - 14 yrs, ventilated 12 - 120 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
Prone positioning improves oxygenation….
…but not survival (adults)
Gattinoni L., Tognoni G., Pesenti A., Taccone P., Mascheroni D., Labarta V., MalacridaR., 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; 345:568-573, Aug 23, 2001
Prone positioning - childrenUncontrolled 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.
Curley MA. Thompson JE. Arnold JH. The effects of early and repeated prone positioning in pediatric patients with acute lung injury. Chest. 2000; 118:156-63
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yARDS prognosis (adults)
J. A. Milberg, D. R. Davis, K. P. Steinberg, and L. D. Hudson. Improved survival of patients with acute respiratory distress syndrome (ARDS): 1983-1993 JAMA, Jan 1995; 273: 306 – 309.
ARDS prognosis (adults)ARDS Severity PaO2/FiO2 Mortality
Mild 200 – 300 27%
Moderate 100 – 200 32%
Severe <100 45%
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: 699 – 705
SummaryARDS 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