Pulmonary Edema: Fluids or Diuretics?


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Lecture presented by Dr.Yasser Nassar at Pulmonary Critical care Egypt 2014, the leading medical educational event and exhibition for Intensive Care medicine in Egypt

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Pulmonary Edema: Fluids or Diuretics?

  1. 1. Yasser Nassar, MD, DIU-CI Assistant Professor Critical Care Medicine Cairo University Hospitals
  2. 2. 300 million Alveoli , Surface area 160m2 size of a Tennis Court Interstitial space can accommodate upto 500 ml of Edema Fluid before Alveolar Flooding ( Matthay MA, Physiol Rev 2002)
  3. 3.  Incidence Higher than Past Estimates 150,000 – 200,000 per year in US alone. • Sepsis most common associated cause • Mortality persists at 30-45% • Current Rx is supportive only • There remains a major need for novel therapeutic strategies to treat ARDS.
  4. 4. -- Compliance ++WOB -- Gas Exchange Hypoxia ++ PVR Pulm HTN, RVF Heterogenous VALI, Inflamation
  5. 5. Epithelial Damage ++ HMW Ptns  -- Alv Clearance  -- Gas Exchange  Hypoxia Inflam cell Accum Septic Shock  Pulm Fibrosis  Prolonged MV  MOF
  6. 6. Single Layer of Alveolar Epithelium on Basement Membrane Single Layer of Vascular Endothelium on Basement Membrane So Close that Basement Membranes may FUSE
  7. 7.  Hydrostatic pressure gradient producing a flow of fluid out Vs Oncotic pressure gradient,opposing this transudation.  Jv : flow of fluid through the capillary wall  K :capillary hydraulic filtration coefficient reflecting  endothelial water permeability  Pc : capillary hydrostatic pressure  Pi : interstitial hydrostatic pressure  S : oncotic reflection coefficient,reflecting endothelial protein and oncotics permeability  πc : capillary oncotic pressure  πi : interstitial oncotic pressure
  8. 8.  Two principal mechanisms can work toward an increase in pulmonary water  Increase in Pulmonary Microvascular Pressure  Increase in Alveolocapillary Memb Permeability.  (a fundamental element in the formation of pulmonary edema in ARDS) (Dudek et al , J Appl Physiol 2001,91:1487-1500.)
  9. 9.  Interstitial water is drained by the lymphatic network. Interstitial pressure is always low, with the pressure remaining in favor of transudation of the vascular sector toward the interstitium (i.e. resorption of interstitial edema is not by pulmonary vascular resorption ).
  10. 10.  Interstitial water is drained by the lymphatic network.  Once the Lymphatic network is saturated, fluid accumulates in the loose peri- bronchovascular conjunctive tissue of the hilar zones, the first accumulation site in pulmonary edema and they have very low resistance to fluid flux .  Interstitial drainage will depend on the capacity of lymphatic flow to increase as well as the capacity of the perihilar tubes to drain into the mediastinum and the interstitial edema to evacuate toward the pleura and then the lymphatic system.
  11. 11.  Alveolar water is active transported with an alongside ionic osmotic gradient from apical to basolateral side of Epithelial Cell Type II Interstitial edema drainage circuit.  ARDS damage of epithelial cells and alveolocapillary barrier, alters active transport of ions and fluid by the epithelium leading to diminished Alveolar Clearance 
  12. 12.  Pulmonary lymphatic vessels are classically along the peribronchial vascular sheaths, interlobular septa, and pleural connective tissue. Lymphatic capillaries are lined by a single layer of overlapping endothelial cells, and in contrast to blood vessels,lack a continuous basement membrane and pericyte coverage.They ensure the drainage of excess proteins and fluid in this part of the lung. (Swartz 2001).
  13. 13.  Lymphatic channels are present emerging from interalveolar interstitium,and around small blood vessels constituting the paraalveolar lymphatics.This intralobular lymphatic network may play a key pathophysiological role in a wide variety of alveolar and interstitial lung diseases.  (J Histochem Cytochem 57:643–648,2009)
  14. 14. PAOP < 18 REMOVED ,as high PAOP hydrostatic PE & ARDS may Coexist
  15. 15.  1) PAOP underestimates capillary filtration pressure,especially in ARDS where the pulmonary venous resistance is increased .  2) Critical hydrostatic pressure above which pulmonary edema will develop will be lower than in normal lungs permeability.  e.g. If the capillary hydraulic filtration coefficient is doubled,critical hydrostatic pressure is only 10 mmHg in abnormal memb permeability ARDS.  This constitutes the theoretical justification for limiting pulmonary filtration pressure
  16. 16.  The majority of patients with ARDS have a PAOP that is superior to critical filtration pressure values when the barrier is damaged
  17. 17. 300 million Alveoli , Surface area 160m2 size of a Tennis Court Interstitial space can accommodate upto 500 ml of Edema Fluid before Alveolar Flooding ( Matthay MA, Physiol Rev 2002)
  18. 18. Edema drainage is enhanced if:  Right Atrial Pressure (CVP )  Pleural pressure (Ppl) Decreasing Edema formation if:  PAOP
  19. 19. Decreases Pulmonary Capillary Pressure By: Hypovolemia  Low CVP  Low PAOP
  20. 20. Reduction of PAOP in ARDS patients improves mortality. ( Humphrey et al, Chest 1990, 97:1176-1180) Lung water amount indexed with PBW on day 1 of ARDS was predictive of death.  (Phillips CR et al ,Crit Care Med 2008, 36:69-73.)  Surviving Sepsis Campaign recommends a conservative fluid strategy in patients with ARDS and in the absence of shock.  (Dellinger RP, et al Intensive Care Med 2008, 34:17-60.)
  21. 21.  Edema forms faster and at a lower hydrostatic pressure threshold when one has first damaged the alveolocapillary barrier before progressively increasing the left atrium pressure.  (Guyton Circ Res 1965,16:452-460.)  Modest decrease in pulmonary capillary pressure in ARDS animal models can limit the formation of pulmonary edema  ( Prewitt RM et al. J Clin Invest 1981, 67:409-418.)  Reducing edema may have beneficial effects on respiratory function and eventually outcome
  22. 22.  Goal was to obtain a CVP of 8 mmHg or less in the “conservative-strategy”group or 14  mmHg in the “liberal-strategy”group.  In the patients monitored by pulmonary arterial catheter, the objectives of PAOP were 12 mmHg in the “conservative-strategy”group and 18 mmHg in the “liberal-strategy”group.  The protocol was applied for 7 days after inclusion of the patient but was not applied in cases of hypotension.
  23. 23.  Conservative vs Liberal fluid :  Improved the oxygenation index  Improved Lung Injury Score  Lowered plateau airway pressure  Increased the number of ventilator-free days  (14.6 ± 0.5vs. 12.1 ± 0.5; P = .0002) Increased ICU-free days (13.4 ± 0.4 vs 11.2 ± 0.4;P =.0003) to day 28. Nonsignificant Reduction 2.9% in the 60-day mortality 25.5%vs.28.4%,respectively;p=0.30  Better neurological status -desedated earlier because of  better respiratory status, perhaps less severe cerebral edema.  Fewer transfusions with its potentially deleterious role.
  24. 24.  During early phase of aggressive inflammation when the edema is developing,therapeutic strategy is usually oriented toward systemic hemodynamic resuscitation with volume and vasopressors !! (i.e. contradictory with goals to reduce the pulmonary capillary pressure).  Difficulty of measuring and evaluating pulmonary capillary filtration pressure. Hypovolemia diminishes pulmonary capillary pressure,whereas local vasoconstrictors or myocardial depression can increase it.
  25. 25.  In ARDS complicating septic shock.  Nonperformance of early adapted fluid administration and the Absence of a negative fluid balance during a minimum of the first 2 consecutive days within the 7 days following  the occurrence of septic shock were independent mortality factors in multivariate analysis.  This highlights the importance of a “Biphase”fluid strategy.  (Murphy CV,et al Chest 2009,136:102-109).  Surviving Sepsis Campaign recommends a conservative fluid strategy in patients with ARDS and in the absence of shock.  (Dellinger RP, et al Intensive Care Med 2008, 34:17-60.)
  26. 26. Early Phase (Unstable Hemodynamics): Sepsis, Hypovolemia Fluids or else organ dysfunction and mortality Later phase (Stabilized Hemodynamics)  Zero balance.
  27. 27.  Resorption of alveolar edema does not occur by manipulation of vascular pressures, but rather by stimulation of active water transport from the alveoli toward interstitium.  Despite severe epithelial lesions in ARDS, alveolar clearance is usually pharmacologically stimulable.  cAMP agonists,in particular beta-2 agonists,accelerates the resolution of edema through an increase in the quantity and activity of Na/K pumps in the basal membrane and Na canals in the pneumocyte apical membrane whose effect is to increase the sodium gradient between the alveoli and the interstitium and therefore the absorption of water. 
  28. 28. IV salbutamol 15 μg/kg/h for 7 d in ARDS patients made it possible to diminish the quantity of pulmonary water measured by transpulmonary thermodilution without affecting oxygenation, duration of mechanical ventilation, or outcome. (Perkins GD,a Am J Respir Crit Care Med 2006, 173:281-287).
  29. 29.  Whereas pulmonary edema begins to develop  at a pressure of 24 mmHg when oncotic pressure is normal,it begins at 11 mmHg when it is reduced.(Guyton AC .Circ Res 1965, 16:452-460).  Hypoprotinemia therefore facilitates the development of hydrostatic pulmonary edema.However,the importance of oncotic pressure in the limitation of flux is only conceivable if the barrier is intact.  In case of endothelial lesions (ARDS),an interstitial edema will be all the richer in proteins than the plasma, theoretically limiting the interest of increasing the plasmatic oncotic pressure.
  30. 30. 37 mechanically ventilated pts with ALI and serum protein ≤ 5.0 g/dl 2. Randomized to receive five-day protocolized regimen of 25g albumin every 8 hours with continuous infusion of furosemide vs. dual placebo Furosemide titrated every 8 hours to achieve a daily weight loss ≥ 1 kg/day
  31. 31. Improved fluid balance 5.3 kg more weight loss in treatment group (p =.04) Improved oxygenation PaO2/FiO2 - 171 to 236 (p =.02) Improved hemodynamics MAP increased 80 to 88 mmHg (p = .10) Heart rate decreased 110 to 95 (p = .008) Trend towards improved mortality –not powered Follow-up study showed increased efficacy furosemide with albumin vs. furosemide alone in 40 hypoproteinemic ALI pts
  32. 32.  A discrete improvement in oxygenation when albumin (75 g/d) for 5 days was associated with diuretic treatment compared with diuretic  treatment alone.  (Martin GS, Crit Care Med 2005,33:1681-1687).  At this stage, the very limited clinical data do not make it possible to recommend the administration of albumin with the goal to improve pulmonary function and respiratory morbidity in ARDS patients.
  33. 33.  ARDS is particularly characterized by pulmonary edema caused by an increase in pulmonary capillary permeability. Epithelial damage is more prominent than Endothelial damage.  Conservative fluid strategy aiming for Zero fluid balance in ARDS patients ( without shock or renal failure needing early and adapted vascular filling ) significantly increases the number of days without mechanical ventilation.   Biphasic fuild strategy (Liberal followed by Conservative strategies ) are complementary and should ideally follow each other as hemodynamic state progressively stabilizes.
  34. 34.  Albumin treatment has been suggested to improve oxygenation transiently in ARDS patients, but no sufficient evidence to date justifies its use to mitigate pulmonary edema.  Resorption of alveolar edema occurs through an active mechanism,which can be pharmacologically upregluated.  Beta-2 agonists may be beneficial but further studies are needed to confirm preliminary promising results.
  35. 35.  ARDS not in shock :  . Diuretics  . Fluid restriction  . Albumin+furosemide in selected patients with hypoproteinemia  B2 agonists  Monitoring:  Central pressures,Weight, fluid balance, EVLW  ( Charles Philips MD ,ISICEM 2009)