What’s New In Pediatric ARDS Nancy G. Hoover, MD Medical Director, PICU Walter Reed AMC
New and Improved Acute  Respiratory Distress Syndrome Ashbaugh,  Lancet , 1967 Adult  Respiratory Distress Syndrome To dis...
ARDS:  New Definition <ul><li>Criteria </li></ul><ul><ul><li>Acute onset </li></ul></ul><ul><ul><li>Bilateral CXR infiltra...
Clinical Disorders Associated with ARDS <ul><li>Direct Injury </li></ul><ul><li>Common Causes </li></ul><ul><ul><li>Pneumo...
The Problem: Lung Injury Other 4% Hemorrhage 5% Trauma 5% Noninfectious Pneumonia 14% Cardiac Arrest 12% Septic Syndrome 3...
ARDS - Pathogenesis <ul><li>Instigation </li></ul><ul><li>Endothelial injury: increased permeability of alveolar - capilla...
ARDS Pathogenesis <ul><li>Resolution </li></ul><ul><li>Equally important </li></ul><ul><li>Alveolar edema - resolved by ac...
ARDS - Pathophysiology <ul><li>Decreased compliance </li></ul><ul><li>Alveolar edema </li></ul><ul><li>Heterogenous </li><...
 
 
Phases of ARDS <ul><li>Acute - exudative, inflammatory </li></ul><ul><ul><li>(0 - 3 days) </li></ul></ul><ul><li>Subacute ...
Phases of ARDS
ARDS - Outcomes <ul><li>Most studies - mortality 40% to 60% </li></ul><ul><li>Majority of deaths sepsis or MOD rather than...
ARDS - Principles of Therapy <ul><li>Provide adequate gas exchange </li></ul><ul><li>Avoid secondary injury </li></ul>
It would seem ironic that the very existence of humans is fully dependent on a gas that, in excess quantities, is toxic an...
Therapies for ARDS Innovations: iNO PLV Proning Surfactant Anti-Inflammatory Mechanical Ventilation Gentle ventilation: Pe...
The Dangers of Overdistention <ul><li>Repetitive shear stress </li></ul><ul><ul><li>inflammatory response </li></ul></ul><...
<ul><li>  compliance </li></ul><ul><li>  intrapulmonary shunt </li></ul><ul><li>  FiO 2 </li></ul><ul><li>WOB  </li></ul><...
Lung Injury Zones Atelectasis “ Sweet Spot” Overdistention
“Mechanical” Therapies in ARDS <ul><li>Lower tidal volumes but avoidance of atelectasis with higher PEEP </li></ul><ul><li...
Lower Tidal Volumes for ARDS <ul><li>Multi-center trial, 861 adult ARDS </li></ul><ul><li>Randomized: </li></ul><ul><ul><l...
Lower Tidal Volumes for ARDS * * * p < .001 ARDS Network, NEJM, 342: 2000 22% decrease
Ventilator Goals <ul><li>Set the PEEP slightly higher than the lower inflection point </li></ul><ul><li>Lower tidal volume...
Permissive Hypercapnia <ul><li>Defined:  presence of hypercapnia in the setting of a mechanically ventilated patient recei...
Physiologic Effects of Hypercapnia <ul><li>RESP: Net effect is improvement in oxygenation by </li></ul><ul><ul><li>enhanci...
Physiologic Effects of Hypercapnia <ul><li>CV: Net effect is often hemodynamic compromise </li></ul><ul><ul><li>Sympatheti...
Physiologic Effects of Hypercapnia <ul><li>RENAL:  </li></ul><ul><ul><li>Compensatory bicarb reabsorption </li></ul></ul><...
Permissive Hypercapnia Is it worth it? <ul><li>Early adult ARDS trial showed a reduction in expected mortality of 56% to a...
High Frequency Oscillation: A Whole Lotta Shakin’ Goin’ On
It’s not absolute pressure, but  volume  or  pressure  swings that promote lung injury or atelectasis. Reese Clark
<ul><li>Rapid rate </li></ul><ul><li>Low tidal volume </li></ul><ul><li>Maintain open lung </li></ul><ul><li>Minimal volum...
Differences Between CMV and HFOV
HFOV vs. CMV in Pediatric  Respiratory Failure: Results <ul><li>Greater survival without severe lung disease </li></ul><ul...
HFOV vs. CMV in Pediatric Respiratory Failure - Arnold et al,  CCM , 1994 *
<ul><li>Reduces cost, severity of chronic lung disease and decreases airleak in neonatal RDS </li></ul><ul><li>Decreases n...
<ul><li>Severe persistent airleak </li></ul><ul><li>Neonatal:  HMD (*) </li></ul><ul><li>Pneumonia </li></ul><ul><li>Mecon...
Is turning the ARDS patient “prone” helpful?
Prone Positioning in ARDS <ul><li>Theory: let gravity improve matching perfusion to well-ventilated lung </li></ul><ul><li...
 
 
Prone Positioning in Adult ARDS <ul><li>Randomized trial </li></ul><ul><li>Standard therapy vs. standard + prone positioni...
Conflicting Evidence for Proning? <ul><li>Mancebo, Am J of Resp & CCM, 2006 </li></ul><ul><ul><li>136 adults, randomized t...
Pharmacological Therapies in ARDS <ul><li>Surfactant  </li></ul><ul><li>iNO </li></ul><ul><li>Steroids </li></ul><ul><li>P...
Surfactant in ARDS <ul><li>ARDS: </li></ul><ul><ul><li>surfactant deficiency </li></ul></ul><ul><ul><li>surfactant present...
Calf’s Lung Surfactant Extract in Acute Pediatric Respiratory Failure <ul><li>Multicenter trial-uncontrolled, observationa...
Steroids in ARDS <ul><li>Theoretical anti-inflammatory, anti-fibrotic benefit </li></ul><ul><li>Previous randomized studie...
Effects of Prolonged Steroids in Unresolving ARDS <ul><li>Randomized, double-blind, placebo-controlled trial </li></ul><ul...
Steroids in Unresolving ARDS <ul><li>By day 10, steroids improved: </li></ul><ul><ul><li>PaO 2 /FiO 2  ratios </li></ul></...
Steroids in Unresolving ARDS * * p<.01 *
What about after first 28 days? <ul><li>NHLBI ARDS Clinical Trials Network,  NEJM , 2006 </li></ul><ul><li>180 adult patie...
Inhaled Nitric Oxide in Respiratory Failure <ul><li>Neonates </li></ul><ul><ul><li>Beneficial in term neonates with PPHN <...
ECMO and NO in Neonates <ul><li>ECMO improves survival in neonates with PPHN (UK study) </li></ul><ul><li>iNO decreases ne...
Effects of Inhaled Nitric Oxide In Children with AHRF <ul><li>Randomized, controlled, blinded multi-center trial </li></ul...
 
Inhaled NO and HFOV In Pediatric ARDS Dobyns et al.,  J Peds , 2000
Partial Liquid Ventilation <ul><li>Mechanisms of action </li></ul><ul><ul><li>oxygen reservoir </li></ul></ul><ul><ul><li>...
Liquid Ventilation <ul><li>Pediatric trials started in 1996 </li></ul><ul><ul><li>Partial: FRC (15 - 20 cc/kg) </li></ul><...
ARDS- “Mechanical” Therapies Low tidal volumes  Outcome benefit in      large study  Prone positioning Unproven outcome be...
Pharmacologic Approaches to ARDS: Randomized Trials Steroids - acute no benefit - fibrosing alveolitis lowered mortality, ...
“…We must discard the old approach and continue to search for ways to improve mechanical ventilation.  In the meantime, th...
If you think about ECMO,  it is worth a call to consider ECMO
 
Pediatric ECMO <ul><li>Potential candidates </li></ul><ul><li>Neonate - 18 years </li></ul><ul><li>Reversible disease proc...
Impact of ECMO on Survival in Pediatric Respiratory Failure <ul><li>Retrospective, multicenter cohort analysis </li></ul><...
Impact of ECMO on Survival in Pediatric Respiratory Failure % Mortality p<0.05 Green et al,  CCM , 1996 mortality risk qua...
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  • Ashbaugh first described the syndrome of severe respiratory failure similar to infant hyline membrane disease
  • PCWP higher than 18 mmHg are generally considered to be c/w left-heart failure and may be the cause of cargiogenic pulmonary edema.
  • Gattinoni “Concept of Baby Lung”, Intensive Care Medicine, 2005: The &amp;quot; baby lung &amp;quot; concept originated as an offspring of computed tomography examinations which showed in most patients with acute lung injury/acute respiratory distress syndrome that the normally aerated tissue has the dimensions of the lung of a 5- to 6-year-old child (300-500 g aerated tissue). DISCUSSION: The respiratory system compliance is linearly related to the &amp;quot; baby lung &amp;quot; dimensions, suggesting that the acute respiratory distress syndrome lung is not &amp;quot;stiff&amp;quot; but instead small, with nearly normal intrinsic elasticity. Initially we taught that the &amp;quot; baby lung &amp;quot; is a distinct anatomical structure, in the nondependent lung regions. However, the density redistribution in prone position shows that the &amp;quot; baby lung &amp;quot; is a functional and not an anatomical concept. This provides a rational for &amp;quot;gentle lung treatment&amp;quot; and a background to explain concepts such as baro- and volutrauma. CONCLUSIONS: From a physiological perspective the &amp;quot; baby lung &amp;quot; helps to understand ventilator-induced lung injury. In this context, what appears dangerous is not the V(T)/kg ratio but instead the V(T)/&amp;quot; baby lung &amp;quot; ratio. The practical message is straightforward: the smaller the &amp;quot; baby lung ,&amp;quot; the greater is the potential for unsafe mechanical ventilation.
  • Axial CT of an experimental model of ARDS showing the heterogeneous distribution of lung disease. The gravitationally nondependent lung region (ventral) is relatively spared, whereas the dependent lung region (dorsal) exhibits greater involvement
  • Extrapulmonary techniques ECMO IVOX IV gas exchange Total Implantable Artificial Lung
  • 40% vs. 31% mortality Vent-free days in the first 28 days was significantly higher in the low tidal volume group (12 +/- 11 vs. 10 +/-11;p=0.007
  • In Stewart’s study, If peak pressure is &lt;30 and tidal volume is &lt;8 mL/kg, then there was no difference in mortality.
  • Hickling, Intensive Care Med 1990
  • When hypercapnia is produced through the limitation of tidal volumes and inspiratory airway pressures without adequate PEEP, the Qs/Qt ratio increases secondary to progressive derecruitment of alveolar units. Under such conditions, oxygenation will be further impaired by the hypercapnia-induced increase in cardiac output. This increase in cardiac output induces a worsening Qs/Qt ratio as blood flow increases preferentially to the gravitationally dependent, poorly ventilated lung regions and results in additional intrapulmonary shunting The increase in Qs/Qt can frequently be counteracted through the optimization of lung volume by means of recruitment maneuvers and application of suitable levels of PEEP. Hypercapnic acidosis enhances hypoxic pulmonary vasoconstriction, thus improving ventilation-perfusion matching, decreasing Qs/Qt, and increasing the PaO2. Hypercapnic acidosis positively affects oxygen availability to tissues by promoting a right shift in the oxygen–hemoglobin dissociation curve. Net effect is improvement in oxygenation
  • Hypercapnic acidosis has been shown to cause marked sympathetic stimulation with predictable increases in cardiac output due to the augmentation of heart rate and stroke volume secondary to decreased systemic vascular resistance
  • Within hours of the onset of sustained hypercapnic acidemia, the kidneys initiate compensatory net reabsorption of sodium bicarbonate, generally returning blood pH to physiologic levels within 2 days.
  • Effect of prone position on ventilation distribution. In the supine position, the distribution of ventilation is preferentially distributed to the ventral regions. When the patient is prone, the stiffness of the dorsal chest wall favors the distribution of ventilation to the dorsal regions, facilitating reinflation in this area.
  • Post-hoc analysis showed an improvement in 10-day mortality in the prone group but overall ventilator-free days, ICU discharge and length of hospitalization was unchanged
  • In the study by Curely et al, you probably won’t see a benefit because with all of the other therapies, the mortality was so low, it would take a huge number of patients to show a mortality difference.
  • Ards hoover

    1. 1. What’s New In Pediatric ARDS Nancy G. Hoover, MD Medical Director, PICU Walter Reed AMC
    2. 2. New and Improved Acute Respiratory Distress Syndrome Ashbaugh, Lancet , 1967 Adult Respiratory Distress Syndrome To distinguish from neonatal HMD/RDS Acute Respiratory Distress Syndrome American-European Consensus conference, 1994
    3. 3. ARDS: New Definition <ul><li>Criteria </li></ul><ul><ul><li>Acute onset </li></ul></ul><ul><ul><li>Bilateral CXR infiltrates </li></ul></ul><ul><ul><li>PA pressure < 18 mm Hg </li></ul></ul><ul><ul><li>Classification </li></ul></ul><ul><ul><ul><li>Acute lung injury - P a O 2 : F 1 O 2 < 300 </li></ul></ul></ul><ul><ul><ul><li>Acute respiratory distress syndrome - P a O 2 : F 1 O 2 < 200 </li></ul></ul></ul>1994 American-European Consensus Conference
    4. 4. Clinical Disorders Associated with ARDS <ul><li>Direct Injury </li></ul><ul><li>Common Causes </li></ul><ul><ul><li>Pneumonia </li></ul></ul><ul><ul><li>Gastric aspiration </li></ul></ul><ul><li>Less Common Causes </li></ul><ul><ul><li>Pulmonary contusion </li></ul></ul><ul><ul><li>Fat emboli </li></ul></ul><ul><ul><li>Near drowning </li></ul></ul><ul><ul><li>Inhalational injury </li></ul></ul><ul><li>Indirect Injury </li></ul><ul><li>Common Causes </li></ul><ul><ul><li>Sepsis </li></ul></ul><ul><ul><li>Shock after severe trauma </li></ul></ul><ul><li>Less Common Causes </li></ul><ul><ul><li>Cardiopulm. bypass </li></ul></ul><ul><ul><li>Drug overdose </li></ul></ul><ul><ul><li>Acute pancreatitis </li></ul></ul><ul><ul><li>Massive blood transfusions </li></ul></ul>
    5. 5. The Problem: Lung Injury Other 4% Hemorrhage 5% Trauma 5% Noninfectious Pneumonia 14% Cardiac Arrest 12% Septic Syndrome 32% Infectious Pneumonia 28% Davis et al., J Peds 1993;123:35
    6. 6. ARDS - Pathogenesis <ul><li>Instigation </li></ul><ul><li>Endothelial injury: increased permeability of alveolar - capillary barrier </li></ul><ul><li>Epithelial injury : alveolar flood, loss of surfactant, barrier vs. infection </li></ul><ul><li>Proinflammatory mechanisms </li></ul>
    7. 7. ARDS Pathogenesis <ul><li>Resolution </li></ul><ul><li>Equally important </li></ul><ul><li>Alveolar edema - resolved by active sodium transport </li></ul><ul><li>Alveolar type II cells - re-epithelialize </li></ul><ul><li>Neutrophil clearance needed </li></ul>
    8. 8. ARDS - Pathophysiology <ul><li>Decreased compliance </li></ul><ul><li>Alveolar edema </li></ul><ul><li>Heterogenous </li></ul><ul><li>“ Baby Lungs” </li></ul>
    9. 11. Phases of ARDS <ul><li>Acute - exudative, inflammatory </li></ul><ul><ul><li>(0 - 3 days) </li></ul></ul><ul><li>Subacute - proliferative </li></ul><ul><ul><li>(4 - 10 days) </li></ul></ul><ul><li>Chronic - fibrosing alveolitis </li></ul><ul><ul><li>( > 10 days) </li></ul></ul>
    10. 12. Phases of ARDS
    11. 13. ARDS - Outcomes <ul><li>Most studies - mortality 40% to 60% </li></ul><ul><li>Majority of deaths sepsis or MOD rather than primary respiratory </li></ul><ul><li>Outcomes similar for adults and children </li></ul><ul><li>Mortality may be decreasing </li></ul><ul><ul><li>53/68 % 39/36 % </li></ul></ul>
    12. 14. ARDS - Principles of Therapy <ul><li>Provide adequate gas exchange </li></ul><ul><li>Avoid secondary injury </li></ul>
    13. 15. It would seem ironic that the very existence of humans is fully dependent on a gas that, in excess quantities, is toxic and lethal Lynn D. Martin
    14. 16. Therapies for ARDS Innovations: iNO PLV Proning Surfactant Anti-Inflammatory Mechanical Ventilation Gentle ventilation: Permissive hypercapnia Low tidal volume Open-lung HFOV ARDS Extrapulmonary Gas Exchange
    15. 17. The Dangers of Overdistention <ul><li>Repetitive shear stress </li></ul><ul><ul><li>inflammatory response </li></ul></ul><ul><ul><li>air trapping </li></ul></ul><ul><li>Phasic volume swings: volutrauma </li></ul><ul><li>Injury to normal alveoli </li></ul>
    16. 18. <ul><li> compliance </li></ul><ul><li> intrapulmonary shunt </li></ul><ul><li> FiO 2 </li></ul><ul><li>WOB </li></ul><ul><li>inflammatory response </li></ul>The Dangers of Atelectasis
    17. 19. Lung Injury Zones Atelectasis “ Sweet Spot” Overdistention
    18. 20. “Mechanical” Therapies in ARDS <ul><li>Lower tidal volumes but avoidance of atelectasis with higher PEEP </li></ul><ul><li>Permissive hypercapnia </li></ul><ul><li>HFOV </li></ul><ul><li>Prone positioning </li></ul>
    19. 21. Lower Tidal Volumes for ARDS <ul><li>Multi-center trial, 861 adult ARDS </li></ul><ul><li>Randomized: </li></ul><ul><ul><li>Tidal volume 12 cc/kg </li></ul></ul><ul><ul><li>Plateau pressure < 50 cm H2O </li></ul></ul><ul><ul><li>vs. </li></ul></ul><ul><ul><li>Tidal volume 6 cc/kg </li></ul></ul><ul><ul><li>Plateau pressure < 30 cm H2O </li></ul></ul>ARDS Network, NEJM, 342: 2000
    20. 22. Lower Tidal Volumes for ARDS * * * p < .001 ARDS Network, NEJM, 342: 2000 22% decrease
    21. 23. Ventilator Goals <ul><li>Set the PEEP slightly higher than the lower inflection point </li></ul><ul><li>Lower tidal volume (generally < 6 mL/kg) </li></ul><ul><li>Static peak pressure <40 cm H 2 0 </li></ul><ul><li>Wean oxygen to <60% </li></ul>
    22. 24. Permissive Hypercapnia <ul><li>Defined: presence of hypercapnia in the setting of a mechanically ventilated patient receiving limited inspiratory pressures and reduced tidal volumes </li></ul>Hickling, Int Care Med , 1990
    23. 25. Physiologic Effects of Hypercapnia <ul><li>RESP: Net effect is improvement in oxygenation by </li></ul><ul><ul><li>enhancing hypoxic pulmonary vasoconstriction and decreases intrapulmonary shunting </li></ul></ul><ul><ul><li>Right-shift of oxygen-hemoglobin dissociation curve </li></ul></ul>
    24. 26. Physiologic Effects of Hypercapnia <ul><li>CV: Net effect is often hemodynamic compromise </li></ul><ul><ul><li>Sympathetic stimulation with increased C.O. </li></ul></ul><ul><ul><ul><li>Increased HR and SV, decreased SVR </li></ul></ul></ul><ul><ul><li>Intracellular acidosis of cardiomyocyte is reversible when due to hypercarbia compared to metabolic acidosis </li></ul></ul><ul><ul><li>When combined with high PEEP strategy, can lead to severely decreased preload and cardiovascular compromise </li></ul></ul>
    25. 27. Physiologic Effects of Hypercapnia <ul><li>RENAL: </li></ul><ul><ul><li>Compensatory bicarb reabsorption </li></ul></ul><ul><ul><li>Acidosis leads to direct renal vasoconstriction </li></ul></ul><ul><ul><li>Sympathetic-meditated release of norepinephrine (NE) </li></ul></ul><ul><ul><li>Indirectly, hypercapnia causes a decrease in SVR that in turn releases NE, stimulates the renin-angiotensin-aldosterone system, leading to a further decrease in renal blood flow </li></ul></ul>
    26. 28. Permissive Hypercapnia Is it worth it? <ul><li>Early adult ARDS trial showed a reduction in expected mortality of 56% to an actual mortality of 26% </li></ul><ul><li>Included in adult trauma patients protocol for mechanical ventilation </li></ul><ul><li>Several pediatric studies showing benefit when used in conjunction with low TV and high PEEP </li></ul><ul><li>Caution in patients with elevated ICP </li></ul>Hickling, CCM , 1994 Nathens, J Trauma, 2005 Sheridan, J Trauma , 1995 Paulson, J Pediatr , 1996
    27. 29. High Frequency Oscillation: A Whole Lotta Shakin’ Goin’ On
    28. 30. It’s not absolute pressure, but volume or pressure swings that promote lung injury or atelectasis. Reese Clark
    29. 31. <ul><li>Rapid rate </li></ul><ul><li>Low tidal volume </li></ul><ul><li>Maintain open lung </li></ul><ul><li>Minimal volume swings </li></ul>High Frequency Ventilation
    30. 32. Differences Between CMV and HFOV
    31. 33. HFOV vs. CMV in Pediatric Respiratory Failure: Results <ul><li>Greater survival without severe lung disease </li></ul><ul><li>Greater crossover to HFOV and improvement </li></ul><ul><li>Failure to respond to HFOV strong predictor of death </li></ul>Arnold et al, CCM, 1994
    32. 34. HFOV vs. CMV in Pediatric Respiratory Failure - Arnold et al, CCM , 1994 *
    33. 35. <ul><li>Reduces cost, severity of chronic lung disease and decreases airleak in neonatal RDS </li></ul><ul><li>Decreases need for ECMO in eligible neonates </li></ul><ul><li>Improves survival without CLD in pediatric ARDS </li></ul>HFOV: Outcomes of Randomized Controlled Trials
    34. 36. <ul><li>Severe persistent airleak </li></ul><ul><li>Neonatal: HMD (*) </li></ul><ul><li>Pneumonia </li></ul><ul><li>Meconium aspiration </li></ul><ul><li>Lung hypoplasia </li></ul><ul><li>Acute respiratory distress syndrome </li></ul>Indications for HFOV
    35. 37. Is turning the ARDS patient “prone” helpful?
    36. 38. Prone Positioning in ARDS <ul><li>Theory: let gravity improve matching perfusion to well-ventilated lung </li></ul><ul><li>Improvement is immediate </li></ul><ul><li>Decreased shunt: improved PaO 2 but variable (75%) </li></ul><ul><li>Uncertain effect on outcome </li></ul>
    37. 41. Prone Positioning in Adult ARDS <ul><li>Randomized trial </li></ul><ul><li>Standard therapy vs. standard + prone positioning </li></ul><ul><li>Improved oxygenation </li></ul><ul><li>No difference in mortality, time on ventilator </li></ul><ul><li>No difference in complications </li></ul>Gattinoni et al., NEJM, 2001
    38. 42. Conflicting Evidence for Proning? <ul><li>Mancebo, Am J of Resp & CCM, 2006 </li></ul><ul><ul><li>136 adults, randomized to 20 h/day proning within 48h of intubation for severe ARDS </li></ul></ul><ul><ul><li>Same ventilator treatment protocols in both groups </li></ul></ul><ul><ul><li>25 % relative reduction in ICU mortality </li></ul></ul><ul><li>Curley, JAMA, 2005 </li></ul><ul><ul><li>Shorter proning times and multiple protocols for vent mgt with lung-protective stragegy and weaning, sedation, nutrition, etc </li></ul></ul><ul><ul><li>Only 8% mortality and no benefit from prone positioning </li></ul></ul>
    39. 43. Pharmacological Therapies in ARDS <ul><li>Surfactant </li></ul><ul><li>iNO </li></ul><ul><li>Steroids </li></ul><ul><li>Partial Liquid Ventilation </li></ul>
    40. 44. Surfactant in ARDS <ul><li>ARDS: </li></ul><ul><ul><li>surfactant deficiency </li></ul></ul><ul><ul><li>surfactant present is dysfunctional </li></ul></ul><ul><li>Surfactant replacement improves physiologic function </li></ul>
    41. 45. Calf’s Lung Surfactant Extract in Acute Pediatric Respiratory Failure <ul><li>Multicenter trial-uncontrolled, observational </li></ul><ul><li>Calf lung surfactant (Infasurf) - intratracheal </li></ul><ul><li>Immediate improvement and weaning in 24/29 children with ARDS and 14% mortality </li></ul><ul><li>In several other studies, there is no evidence for sustained benefit from Surfactant administration </li></ul>Wilson et al, CCM , 24:1996 Wilson et al, JAMA , 2005
    42. 46. Steroids in ARDS <ul><li>Theoretical anti-inflammatory, anti-fibrotic benefit </li></ul><ul><li>Previous randomized studies </li></ul><ul><li>Acute use (1st 5 days) </li></ul><ul><ul><li>No benefit </li></ul></ul><ul><ul><li>Increased 2  infection </li></ul></ul>
    43. 47. Effects of Prolonged Steroids in Unresolving ARDS <ul><li>Randomized, double-blind, placebo-controlled trial </li></ul><ul><li>Adult ARDS ventilated for > 7 days without improvement </li></ul><ul><li>Randomized: </li></ul><ul><ul><li>Placebo </li></ul></ul><ul><ul><li>Methylprednisolone 2 mg/kg/day x 4 days, tapered over 1 month </li></ul></ul>Meduri et al, JAMA , 1998
    44. 48. Steroids in Unresolving ARDS <ul><li>By day 10, steroids improved: </li></ul><ul><ul><li>PaO 2 /FiO 2 ratios </li></ul></ul><ul><ul><li>Lung injury/MOD scores </li></ul></ul><ul><ul><li>Static lung compliance </li></ul></ul><ul><li>Steroids decreased procollagen metabolites </li></ul><ul><li>24 patients enrolled; study stopped due to survival difference </li></ul>Meduri et al, JAMA , 1998
    45. 49. Steroids in Unresolving ARDS * * p<.01 *
    46. 50. What about after first 28 days? <ul><li>NHLBI ARDS Clinical Trials Network, NEJM , 2006 </li></ul><ul><li>180 adult patients with ARDS >7 days </li></ul><ul><li>No difference in mortality with steroids </li></ul><ul><ul><li>EXCEPT, if the patient was entered into the study after 14 days of ARDS </li></ul></ul><ul><ul><li>THEN, there was an increase in 60 and 180 day mortality </li></ul></ul>
    47. 51. Inhaled Nitric Oxide in Respiratory Failure <ul><li>Neonates </li></ul><ul><ul><li>Beneficial in term neonates with PPHN </li></ul></ul><ul><ul><li>Decreased need for ECMO </li></ul></ul><ul><li>Adults/Pediatrics </li></ul><ul><ul><li>Benefits - lowers PA pressures, improves gas exchange </li></ul></ul><ul><ul><li>Randomized trials: No difference in mortality or days of ventilation </li></ul></ul>
    48. 52. ECMO and NO in Neonates <ul><li>ECMO improves survival in neonates with PPHN (UK study) </li></ul><ul><li>iNO decreases need for ECMO in neonates with PPHN: 64% vs 38% </li></ul>Clark et al, NEJM, 2000
    49. 53. Effects of Inhaled Nitric Oxide In Children with AHRF <ul><li>Randomized, controlled, blinded multi-center trial </li></ul><ul><li>108 children, median age 2.5 years </li></ul><ul><ul><li>Entry: OI > 15 x 2 </li></ul></ul><ul><li>Randomized: Inhaled NO 10 ppm vs. mechanical ventilation alone </li></ul>Dobyns, et al., J. Peds, 1999
    50. 55. Inhaled NO and HFOV In Pediatric ARDS Dobyns et al., J Peds , 2000
    51. 56. Partial Liquid Ventilation <ul><li>Mechanisms of action </li></ul><ul><ul><li>oxygen reservoir </li></ul></ul><ul><ul><li>recruitment of lung volume </li></ul></ul><ul><ul><li>alveolar lavage </li></ul></ul><ul><ul><li>redistribution of blood flow </li></ul></ul><ul><ul><li>anti-inflammatory </li></ul></ul>
    52. 57. Liquid Ventilation <ul><li>Pediatric trials started in 1996 </li></ul><ul><ul><li>Partial: FRC (15 - 20 cc/kg) </li></ul></ul><ul><ul><li>Study halted 1999 due to lack of benefit </li></ul></ul><ul><li>Adult study 2001 </li></ul><ul><ul><li>no effect on outcome </li></ul></ul>
    53. 58. ARDS- “Mechanical” Therapies Low tidal volumes Outcome benefit in large study Prone positioning Unproven outcome benefit Open-lung strategy Outcome benefit in small study HFOV Outcome benefit in small study ECMO Proven in neonates unproven in children
    54. 59. Pharmacologic Approaches to ARDS: Randomized Trials Steroids - acute no benefit - fibrosing alveolitis lowered mortality, small study Surfactant possible benefit in children Inhaled NO no benefit PLV no benefit
    55. 60. “…We must discard the old approach and continue to search for ways to improve mechanical ventilation. In the meantime, there is no substitute for the clinician standing by the ventilator…” Martin J. Tobin, MD
    56. 61. If you think about ECMO, it is worth a call to consider ECMO
    57. 63. Pediatric ECMO <ul><li>Potential candidates </li></ul><ul><li>Neonate - 18 years </li></ul><ul><li>Reversible disease process </li></ul><ul><li>Severe respiratory/cardiac failure </li></ul><ul><li>< 10 days mechanical ventilation </li></ul><ul><li>Acute, life-threatening deterioration </li></ul>
    58. 64. Impact of ECMO on Survival in Pediatric Respiratory Failure <ul><li>Retrospective, multicenter cohort analysis </li></ul><ul><li>331 patients, 32 hospitals </li></ul><ul><li>Use of ECMO associated with survival (p < .001) </li></ul><ul><li>53 diagnosis and risk-matched pairs: </li></ul><ul><ul><li>ECMO decreased mortality (26% vs 47%, p < .01) </li></ul></ul>-Green et al, CCM, 24:1996
    59. 65. Impact of ECMO on Survival in Pediatric Respiratory Failure % Mortality p<0.05 Green et al, CCM , 1996 mortality risk quartile
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