non ventil
TRANSCRIPT
Dr. AKHILESH.K M.DAssistant Professor
Pulmonary MedicineAIMS,KOCHI
Direct insultCommon
Aspiration pneumonia
Pneumonias
Less common
Inhalation injury
Pulmonary contusions
Fat emboli
Near drowning
Reperfusion injury
Indirect insultCommon
Sepsis
Severe trauma
ShockLess common
Acute pancreatitis
Cardiopulmonary bypass
Transfusion-related
Disseminated
intravascular coagulation
Burns
Drug overdose
Insult (direct or indirect)
Activation of inflammatory cells
& mediators
Damage to alveolar capillary membrane
Increased permeability of alveolar capillary membrane
Influx of protein rich edema fluid and inflammatory cells into air spaces
Dysfunction of surfactant
Causative Factors in ARDS
PRIMARY
INJURY
HOST
RESPONSE
CONSEQUENCES
OF THERAPY
1
• TREATMENT OF CAUSE
• e.g. antibiotics for pneumonia
2
• SUPPORTIVE THERAPY (5P’s)
• Perfusion, Position, Protective lung ventilation, Protocol
weaning, Preventing complications
3
• PHARMACOLOGICAL TREATMENT
• Steroids, vasodilators, surfactant, anti inflammatory
Fluid and hemodynamic management
Prone positioning
ECMO/ECCO2 removal
Pharmacotherapy
ARDS characterised by increased alveolar-capillary permeability
Increased extravascular lung water with secondary consequences◦ Decreased compliance – increased WOB
◦ Increased shunt and worsening gas exchange
◦ Pulmonary hypertension
Strategies to limit pulmonary edema and accelerate its resorption◦ Limited evidence on therapeutic benefit
Compared a liberal Vs conservative fluid management strategy in ALI / ARDS subjects
Simultaneously compared PAC versus CVC based fluid management
Used a complex 2*2 factorial table design Studied the effect on mortality, gas exchange, organ
failure and need for MV
N Eng J Med 2006; 354: 2564-75
Used four basic input varaiables except in
shock or in patients on vasopressors for guiding management instructions
MAP
Urine Output
Effectiveness of circulation
Intravascular pressures(CVP or PAOP)
OUTCOME:
No significant difference in 60 day mortality between conservative (25.5%) and liberal (28.4%) strategy
More ventilator free days in conservative strategy(14.6+-0.5 Vs 12.1 +-0.5)
Decreased ICU stay (13.4+-0.4 Vs 11.2+-0.4)
Did not worsen incidence of shock , number of days in shock, Organ failures, rate of use of dialysis
CVC is better for monitoring as PVC is associated with more complications rate
CVP(mm of
Hg)
PAOP(Optional)
Average Urine Output
< 0.5 ml/kg/hr
Average Urine Output
> 0.5 ml/kg/hr
(MAP should be > 60 mm and subject should not be needing vasopressorsfor last 12 hours)
> 8 > 12 FrusemideReassess in 1 hour
FrusemideReassess in 4 hours
4 - 8 8 - 12 Fluid bolus as fast as possibleReassess in 1 hour
FrusemideReassess in 4 hours
< 4 < 8Fluid bolus as fast as possible
Reassess in 4 hours
No interventionReassess in 4 hours
Chest 2007; 131; 913-920
Start off with 20 mg bolus and 3 mg/hr infusion (or last known effective dose)
Double each subsequent dose until goals achieved(intravascular pressure target or reversal of oliguria)
Maximum dose of 160 mg bolus and 24 mg/hr infusion
Maximum daily dose 620 mg
May add dobutamine if subject has heart failure
Avoid diuretic therapy if patient has renal failure or dialysis dependence
(Oliguria with s.creatinine > 2mg/dl or other urinary indices of ARF)
Improves oxygenation without improving overall outcome
Critical Care 2011, 15:R125
Concept: To give rest to the lung and let them get recovered from the injury by using extracorporeal gas exchange temporarily
No significant difference between
conventional and ECCo2 removal method
Used in severe lung disease which warrant
high flow ECMO with full support of oxygenation and CO2 removal
Reliance on patient’s lung to provide oxygenation at high airway pressure eliminate the possibility of “Lung rest”
Deliver fresh gas(4-8 L/ mt) through a modified ET tube
at a point just above carina.
This additional gas remove CO2 rich gas from trachea
and smaller airways there by reduce anatomic dead
space.
: Tracheal erosions,O2 toxicity ,hemodynamic
instability,barotrauma
TGI improves PCO2 but no significant change in PaO2.No
change in airway pressure and hemodynamic variables
in ventilated patients(Chest 1995; 107:1416-19)
May be tried
Beneficial
UselessLate usage
harmful
Use early, low dose, infusion
Chest 2007; 131: 954–963
N Engl J Med 2006;354:1671-84
JAMA 1998; 280: 159-65
Multiple Early Works
Except for glucocorticoids, no pharmacologic therapy has yet been shown to
decrease the mortality of ARDS independent of treating the
underlying cause
Crit Care Clin 2011; 27; 589–607
Paul E. Marik, G. Umberto Meduri, Patricia R.M.Rocco, Djillali Annane
Early Steroid therapy (≤ 3 d of mechanical ventilation)
appeared more strongly associated with mortality than
late administration. Patients receiving steroids had more
acquired pneumonia and a trend to a longer duration of
ventilation. Ajrccm Vol. 183, No. 9 (2011), pp. 1200-1206.
Inflammation is central to the pathogenesis of ARDS
Persisting inflammation has a role in progressive ARDS
Steroids have effects and multiple sites of the inflammatory pathway
CIRCI occurs in ARDS
Predispose to infections; delayed recognition
Inappropriate glycemic control
Neuromuscular weakness and GI bleed
Suppression of endogenous cortisol; rebound inflammation
Unequivocally beneficial in steroid responsive ARDS etiologies◦ AIP
◦ PCP
Steroids may be beneficial in early ARDS
Small dose infusion of methyl prednisolone
Prolonged tapering
Aggressive surveillance for infection
Trophic feeding (20 Kcal/hr )Vs full enteric feeding(80 kcal/hr) for 6days in 1000 patients of newly diagnosed ARDS without obviousmalnutrition.
Despite the full enteric feeding group receiving many more calories(1300 kcal/day vs 400), there were no differences in important clinical outcomes (ventilator- free days at 28 days, 60 day mortality, or
infections).
Those receiving full enteric feedings had more gastrointestinal intolerance
Draw back: Duration of study was too short for a definitive conclusion for adverse events. Larger studies needed
Conclusion: Trophic feeding equal to full enteral feedingBut SCCM and canadian critical care society advise full enteral feeding whenever
possible
Many of the patients enrolled For trophicfeeding group enrolled in Omega trial.
Found out that Omega 3 fatty acid is not helping ; even harm full , increase mortality
Abandoned mid way.
Statins reduce healthy volunteers’ inflammatory response to
inhaled or injected lipopolysaccharide.
80 mg of simvastatin or placebo to 60 patients with ARDS, for up to 14 days.
There were no differences in mortality (30%), ventilator-free days or ICU/hospital stay.
one-third of the treated group who were left to analyze after 14 days had significantly lower SOFA organ dysfunction scores.
They also had a non-statistically significant improvement in hemodynamics at day 14 (0 of 9 [simvastatin] vs. 3-4 of 10 [placebo]
requiring vasopressors or inotropes, p=0.05-0.09)
Significantly lower IL-8 in BAL fluid. No adverse events were noted. Larger trials are underway to explore this further.(n=60).
Patients with High GM CSF in BAL fluid have more Survival
GM CSF maintains homeostasis in lung, maturation of alveolar macrophage, growth of Alveolar epithelial cell ;the cell got destroyed in ARDS
Did not increase ventilator free days
No Statistically significant difference in 28 day mortality between GM CSF group and placebo group.
Paine R 3d et al. A randomized trial of recombinant human granulocyte-macrophage colony stimulating factor for patients with acute lung injury. Crit Care Med 2012;40:90-97.
Surfactant of possible therapeutic use :
Class Origin Example
1. Natural Amniotic Human amniotic fluid surfactant
2. Modified - Bovine Infasurf, alveofact
Natural BLESS, Survanta
- Procine Curosurf
3. Synthetic Exosurf, ALEC, KL4
Surfactant, Venticute
DOSE
Sufficient dose should reach alveolar environment
TIMING
• As early as possible [<48 hr]
• Little benefit at 3 to 5 days [Fibrosis already set]
SURFACTANT REPLACEMENT Improved lungs function , compliance , oxygenation.
Surfactant in infants with RDS is found to be
effective in improving gas exchange, decrease C- PAP requirement, lessen barotrauma and increased survival
In adults Surfactant therapy trials are having disappointing results.
AJRCCM 2011;183:1055-1061.
Inhaled NO selectively vasodilates pulmonary vessels that
subserve ventilated alveoli , divert blood flow to these alveoli
and away from areas of shunt
Lower PVR,PAP
Does not improve survival , only transient improvement in
oxygenation, costly.
Inhaled prostacyclin – Less costly . May improve oxygenation
as much as inhaled NO
(Chest 1995; 107:1107-15)
Stimulate removal of fluid from flooded alveoli by
stimulating sodium pump and promote transport of Na+
out of alveoli
BALT1 trial(2006): iv Albuterol in ARDS reduced their
plateau pressures by 6 cm H2O
Seemed to substantially reduce their “lung water”
(measured by thermodilution)
Increased rate of Supraventricular arrythmias
BALT2 Trial( 2012):Continuous infusion of iv salbutamol
or placebo for 7 days.Increased mortality in B agonist
group( 34% Vs 23%)
Smith FG et al. Effect of intravenous β-2 agonist treatment on clinical outcomes in acute respiratory distress syndrome (BALTI-2): a multicentre, randomised controlled trial. Lancet 2012;379:21-27.
ARDS Net folks randomized 282 patients with ARDS to
receive either 5 mg of nebulized albuterol or placebo
every 4 hours for 10 days (or until 24 hours after being
extubated).
The trial was stopped early
There was no difference in the number of ventilator-free
days (1′ endpoint), nor in survival to hospital discharge
(2′ endpoint).
Attempts to elevate the intravascular oncotic pressure
Decreases transudation into pulmonary interstitium
Mobilises EVLW into circulation
Can worsen intravascular volumes
Combined with diuretics
37 mechanically ventilated subjects
Serum proteins < 5 g/dl
Albumin(25%) 25 grams Q 8 hourly with continuous infusion of frusemide for 5 days◦ targeted to diuresis, weight loss and
serum proteins
No mortality benefit
Improvement in P/F ratio, diuresis and weight loss, duration of MV
Cost effectiveness questionableCrit Care Med 2002: 30: 2175-2182
Retrospective matched, case control studySubjects with ALI and elevated IAP
Treated with high PEEP, hyperoncotic albumin and frusemide
http://www.annalsofintensivecare.com/content/2/S1/S15
Not an RCTHuge diuretic doses
Huge magnitude of difference - ? Biological plausibility
Control group - ? Standard therapyMultiple interventions - ? synergistic
Basic understanding about thepathogenesis is essential indeveloping newer strategiesfor management of ARDS
Most of The trials in nonventilatory strategies giveconflicting results
practical use of thesemodalities are controversial
Cost effective strategies suitable to resource poor
countries need to be developedto apply them in practical use