• The number of ventilator-free days (VFDs [ Time Frame: number of days after initiating unassisted breathing to day 28 after randomization, assuming a patient survives for at least 2 consecutive days after initiating unassisted breathing and remains free of assisted breathing. ] [ Designated as safety issue: No ]
• The physiologic severity of clinical lung injury as measured by the 4-point acute lung injury scoring system. [ Time Frame: Day 1-28 ] [ Designated as safety issue: No ]
• Number of ICU-free days [ Time Frame: From randomization to day 28 ] [ Designated as safety issue: No ]
• Number of Organ Failure Free Days [ Time Frame: Randomization to day 28 ] [ Designated as safety issue: No ]
• Percentage of patients alive at day 28 in patients with ALI [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
• Percentage of patients discharged alive from hospital within 60 days [ Time Frame: Day 60 ] [ Designated as safety issue: No ]
• Mortality and VFDs in patients with pre- randomization PaO2/FiO2 less than or equal to 200 [ Time Frame: Day 60 ] [ Designated as safety issue: No ]
• Mortality prior to hospital discharge to day 60 in patients who receive norepinephrine, dobutamine, or vasopressin at any point during the treatment period [ Time Frame: Day 60 ] [ Designated as safety issue: No ]
• number of VFDs to day 28 in patients who receive the following intravenous vasoactive agonists (norepinephrine, dobutamine, and vasopressin) at any point during the treatment period [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
• Mortality prior to hospital discharge to day 60 in patients with shock (defined in 2.3.6 in the HEAL protocol) at the time of randomization [ Time Frame: Day 60 ] [ Designated as safety issue: No ]
• number of VFDs to day 28 in patients with shock (defined in 2.3.6 in the HEAL protocol) at the time of randomization [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
• Mortality prior to hospital discharge to day 60 in patients with severe sepsis (defined in 2.3.8 in the HEAL protocol) at the time of randomization. [ Time Frame: Day 60 ] [ Designated as safety issue: No ]
• number of ventilator-free days to day 28 in patients with severe sepsis (defined in 2.3.8) at the time of randomization. [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
• Changes in quasistatic total respiratory system compliance [ Time Frame: Randomization to day 28 ] [ Designated as safety issue: No ]
• Need for vasoactive medication - dose, duration and total amounts of all vasoactive medications. [ Time Frame: Randomization to day 28 ] [ Designated as safety issue: No ]
• Changes in the plasma levels of interleukin-1b, 6 and 8, and TNF-α. [ Time Frame: 60 days ] [ Designated as safety issue: No ]
• Changes in the airspace (bronchoalveolar lavage: BAL) levels of interleukin-1b, 6 and 8, and TNF-α. Changes in BAL cell count and differential. [ Time Frame: 60 days ] [ Designated as safety issue: No ]

The purpose of this study is to test a treatment that tries to reduce the amount of fluid in the lungs of subjects with acute lung injury to see if this is helpful.

To conduct a randomized, controlled trial of a goal directed therapy designed to improve outcome in patients with acute lung injury (ALI). We are comparing two algorithmic approaches in managing patients with ALI - one, the control arm, attempts to reduce the amount of fluid in the lung in patients with ALI by diuresis based on central venous pressure and urine output, the other the treatment arm attempting to reduce lung water by directing therapy to measured lung water and using more sensitive indicators of preload status than CVP. The protocol uses measured extravascular lung water (EVLW) to direct diuresis and appropriate fluid restriction in a goal directed fashion in order to lower EVLW towards the normal range.

• Drug: Diuresis (furosemide) part I
• Other: Fluid Bolus (crystalloid or albumin)
• Drug: Vasopressors (Norepinephrine, Vasopressin, Phenylephrine, Epinephrine)
• Drug: Dobutamine
• Other: Concentrate all drips and nutrition
• Drug: Diuresis (furosemide) part II
• Procedure: Dialysis

• Active Comparator: The investigators control arm consists of a simplified algorithm for conservative management of fluids in patients with ALI, as to be published by the ARDSnet group, based on the protocol used in the FACTT trial. The protocol calls for strict adherence to ARDSnet ventilation, our weaning protocol and use of only select vasoactive, beta-adrenergic drugs as it is felt that variation in these treatments could seriously confound our results. Albuterol administration will not be permitted in the either arm except for life threatening bronchospasm not responsive to ipratropium. Ipratropium may be administered at the treating physician's discretion for bronchospasm. PiCCO's will be placed in each control patient and data recorded twice daily. The treating physician's will be blinded to this data.
• Experimental:

  When EVLW exceeds 9 ml/kg PBW the algorithmic treatment is begun and continued until EVLW ≤9 ml/kg PBW or extubation whichever comes first as tolerated (see figure 6). Furosemide and volume contraction are initiated when sufficient volumetric preload (GEDI) is available to enact volume contraction as a means to decrease measured EVLW without causing concomitant hypoperfusion. Fluid administration is also guided by changes in EVLW. An increase in EVLW > 2ml/kg PBW as a result of fluid administration curtails any further fluid administration until the next scheduled measurement.

  Our ultimate treatment goal is to maximally lower EVLW towards the normal range - thus improving lung mechanics and gas exchange - without causing concomitant hemodynamic compromise and end-organ injury. By doing so we feel this algorithmic, goal directed, therapeutic approach should improve outcome.

• Matthay MA. Alveolar fluid clearance in patients with ARDS: does it make a difference? Chest. 2002 Dec;122(6 Suppl):340S-343S. Review.
• Mitchell JP, Schuller D, Calandrino FS, Schuster DP. Improved outcome based on fluid management in critically ill patients requiring pulmonary artery catheterization. Am Rev Respir Dis. 1992 May;145(5):990-8.
• Eisenberg PR, Hansbrough JR, Anderson D, Schuster DP. A prospective study of lung water measurements during patient management in an intensive care unit. Am Rev Respir Dis. 1987 Sep;136(3):662-8.
• National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network; Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AF Jr, Hite RD, Harabin AL. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006 Jun 15;354(24):2564-75. Epub 2006 May 21.
• Bendjelid K, Romand JA. Fluid responsiveness in mechanically ventilated patients: a review of indices used in intensive care. Intensive Care Med. 2003 Mar;29(3):352-60. Epub 2003 Jan 21. Review.
• Michard F, Teboul JL. Predicting fluid responsiveness in ICU patients: a critical analysis of the evidence. Chest. 2002 Jun;121(6):2000-8. Review.
• Goedje O, Seebauer T, Peyerl M, Pfeiffer UJ, Reichart B. Hemodynamic monitoring by double-indicator dilution technique in patients after orthotopic heart transplantation. Chest. 2000 Sep;118(3):775-81.
• Bernard GR. Acute respiratory distress syndrome: a historical perspective. Am J Respir Crit Care Med. 2005 Oct 1;172(7):798-806. Epub 2005 Jul 14.
• [No authors listed] Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000 May 4;342(18):1301-8.
• Matthay MA, Zimmerman GA. Acute lung injury and the acute respiratory distress syndrome: four decades of inquiry into pathogenesis and rational management. Am J Respir Cell Mol Biol. 2005 Oct;33(4):319-27. Review. No abstract available.
• Groeneveld AB, Polderman KH. Acute lung injury, overhydration or both? Crit Care. 2005 Apr;9(2):136-7. Epub 2005 Jan 17.
• Ware LB, Matthay MA. Alveolar fluid clearance is impaired in the majority of patients with acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med. 2001 May;163(6):1376-83.
• Sakka SG, Klein M, Reinhart K, Meier-Hellmann A. Prognostic value of extravascular lung water in critically ill patients. Chest. 2002 Dec;122(6):2080-6.
• Sartori C, Matthay MA. Alveolar epithelial fluid transport in acute lung injury: new insights. Eur Respir J. 2002 Nov;20(5):1299-313. Review.
• Sporn P. Keep the lung dry--sense or nonsense? Acta Anaesthesiol Scand Suppl. 1996;109:63-5. No abstract available.
• Martin GS, Eaton S, Mealer M, Moss M. Extravascular lung water in patients with severe sepsis: a prospective cohort study. Crit Care. 2005 Apr;9(2):R74-82. Epub 2005 Jan 11.
• Martin GS, Moss M, Wheeler AP, Mealer M, Morris JA, Bernard GR. A randomized, controlled trial of furosemide with or without albumin in hypoproteinemic patients with acute lung injury. Crit Care Med. 2005 Aug;33(8):1681-7.
• Perkins GD, McAuley DF, Thickett DR, Gao F. The beta-agonist lung injury trial (BALTI): a randomized placebo-controlled clinical trial. Am J Respir Crit Care Med. 2006 Feb 1;173(3):281-7. Epub 2005 Oct 27.
• Elings VB, Lewis FR. A single indicator technique to estimate extravascular lung water. J Surg Res. 1982 Nov;33(5):375-85.
• Mihm FG, Feeley TW, Rosenthal MH, Lewis F. Measurement of extravascular lung water in dogs using the thermal-green dye indicator dilution method. Anesthesiology. 1982 Aug;57(2):116-22.
• Mihm FG, Feeley TW, Jamieson SW. Thermal dye double indicator dilution measurement of lung water in man: comparison with gravimetric measurements. Thorax. 1987 Jan;42(1):72-6.
• Sivak ED, Tita J, Meden G, Ishigami M, Graves J, Kavlich J, Stowe NT, Magnusson MO. Effects of furosemide versus isolated ultrafiltration on extravascular lung water in oleic acid-induced pulmonary edema. Crit Care Med. 1986 Jan;14(1):48-51.
• Wickerts CJ, Blomqvist H, Berg B, Rösblad PG, Hedenstierna G. Furosemide, when used in combination with positive end-expiratory pressure, facilitates the resorption of extravascular lung water in experimental hydrostatic pulmonary oedema. Acta Anaesthesiol Scand. 1991 Nov;35(8):776-83.
• Waugh JB, Op't Holt TB, Gadek JE, Clanton TL. High-dose furosemide alters gas exchange in a model of acute lung injury. J Crit Care. 1996 Sep;11(3):129-37.
• Reising CA, Chendrasekhar A, Wall PL, Paradise NF, Timberlake GA, Moorman DW. Continuous dose furosemide as a therapeutic approach to acute respiratory distress syndrome (ARDS). J Surg Res. 1999 Mar;82(1):56-60.
• Martin GS. Fluid balance and colloid osmotic pressure in acute respiratory failure: emerging clinical evidence. Crit Care. 2000;4 Suppl 2:S21-5. Epub 2000 Oct 13. Review.
• Martin GS, Mangialardi RJ, Wheeler AP, Dupont WD, Morris JA, Bernard GR. Albumin and furosemide therapy in hypoproteinemic patients with acute lung injury. Crit Care Med. 2002 Oct;30(10):2175-82.
• Mojtahedzadeh M, Vazin A, Najafi A, Khalilzadeh A, Abdollahi M. The effect of furosemide infusion on serum epidermal growth factor concentration after acute lung injury. J Infus Nurs. 2005 May-Jun;28(3):188-93.
• Molloy WD, Lee KY, Girling L, Prewitt RM. Treatment of canine permeability pulmonary edema: short-term effects of dobutamine, furosemide, and hydralazine. Circulation. 1985 Dec;72(6):1365-71.
• Ali J, Wood LD. Pulmonary vascular effects of furosemide on gas exchange in pulmonary edema. J Appl Physiol. 1984 Jul;57(1):160-7.
• Ali J, Unruh H, Skoog C, Goldberg HS. The effect of lung edema on pulmonary vasoactivity of furosemide. J Surg Res. 1983 Nov;35(5):383-90.
• Ali J, Chernicki W, Wood LD. Effect of furosemide in canine low-pressure pulmonary edema. J Clin Invest. 1979 Nov;64(5):1494-504.
• Hechtman HB, Weisel RD, Vito L, Ali J, Berger RL. The independence of pulmonary shunting and pulmonary edema. Surgery. 1973 Aug;74(2):300-6. No abstract available.
• Baltopoulos G, Zakynthinos S, Dimopoulos A, Roussos C. Effects of furosemide on pulmonary shunts. Chest. 1989 Sep;96(3):494-8.
• Boussat S, Jacques T, Levy B, Laurent E, Gache A, Capellier G, Neidhardt A. Intravascular volume monitoring and extravascular lung water in septic patients with pulmonary edema. Intensive Care Med. 2002 Jun;28(6):712-8. Epub 2002 May 18.
• Halperin BD, Feeley TW, Mihm FG, Chiles C, Guthaner DF, Blank NE. Evaluation of the portable chest roentgenogram for quantitating extravascular lung water in critically ill adults. Chest. 1985 Nov;88(5):649-52.
• Meade MO, Cook RJ, Guyatt GH, Groll R, Kachura JR, Bedard M, Cook DJ, Slutsky AS, Stewart TE. Interobserver variation in interpreting chest radiographs for the diagnosis of acute respiratory distress syndrome. Am J Respir Crit Care Med. 2000 Jan;161(1):85-90.
• Baudendistel L, Shields JB, Kaminski DL. Comparison of double indicator thermodilution measurements of extravascular lung water (EVLW) with radiographic estimation of lung water in trauma patients. J Trauma. 1982 Dec;22(12):983-8.
• Roch A, Michelet P, Lambert D, Delliaux S, Saby C, Perrin G, Ghez O, Bregeon F, Thomas P, Carpentier JP, Papazian L, Auffray JP. Accuracy of the double indicator method for measurement of extravascular lung water depends on the type of acute lung injury. Crit Care Med. 2004 Mar;32(3):811-7.
• Kirov MY, Kuzkov VV, Kuklin VN, Waerhaug K, Bjertnaes LJ. Extravascular lung water assessed by transpulmonary single thermodilution and postmortem gravimetry in sheep. Crit Care. 2004 Dec;8(6):R451-8. Epub 2004 Oct 19.
• Rossi P, Oldner A, Wanecek M, Leksell LG, Rudehill A, Konrad D, Weitzberg E. Comparison of gravimetric and a double-indicator dilution technique for assessment of extra-vascular lung water in endotoxaemia. Intensive Care Med. 2003 Mar;29(3):460-6. Epub 2003 Feb 8.
• Katzenelson R, Perel A, Berkenstadt H, Preisman S, Kogan S, Sternik L, Segal E. Accuracy of transpulmonary thermodilution versus gravimetric measurement of extravascular lung water. Crit Care Med. 2004 Jul;32(7):1550-4.
• Fernández-Mondéjar E, Rivera-Fernández R, García-Delgado M, Touma A, Machado J, Chavero J. Small increases in extravascular lung water are accurately detected by transpulmonary thermodilution. J Trauma. 2005 Dec;59(6):1420-3; discussion 1424.
• Nuckton TJ, Alonso JA, Kallet RH, Daniel BM, Pittet JF, Eisner MD, Matthay MA. Pulmonary dead-space fraction as a risk factor for death in the acute respiratory distress syndrome. N Engl J Med. 2002 Apr 25;346(17):1281-6.
• Tavernier B, Makhotine O, Lebuffe G, Dupont J, Scherpereel P. Systolic pressure variation as a guide to fluid therapy in patients with sepsis-induced hypotension. Anesthesiology. 1998 Dec;89(6):1313-21.
• Calvin JE, Driedger AA, Sibbald WJ. The hemodynamic effect of rapid fluid infusion in critically ill patients. Surgery. 1981 Jul;90(1):61-76.
• Schneider AJ, Teule GJ, Groeneveld AB, Nauta J, Heidendal GA, Thijs LG. Biventricular performance during volume loading in patients with early septic shock, with emphasis on the right ventricle: a combined hemodynamic and radionuclide study. Am Heart J. 1988 Jul;116(1 Pt 1):103-12.
• Reuse C, Vincent JL, Pinsky MR. Measurements of right ventricular volumes during fluid challenge. Chest. 1990 Dec;98(6):1450-4.
• Wagner JG, Leatherman JW. Right ventricular end-diastolic volume as a predictor of the hemodynamic response to a fluid challenge. Chest. 1998 Apr;113(4):1048-54.
• Magder S, Lagonidis D. Effectiveness of albumin versus normal saline as a test of volume responsiveness in post-cardiac surgery patients. J Crit Care. 1999 Dec;14(4):164-71.
• Tousignant CP, Walsh F, Mazer CD. The use of transesophageal echocardiography for preload assessment in critically ill patients. Anesth Analg. 2000 Feb;90(2):351-5.
• Michard F, Boussat S, Chemla D, Anguel N, Mercat A, Lecarpentier Y, Richard C, Pinsky MR, Teboul JL. Relation between respiratory changes in arterial pulse pressure and fluid responsiveness in septic patients with acute circulatory failure. Am J Respir Crit Care Med. 2000 Jul;162(1):134-8.
• Feissel M, Michard F, Mangin I, Ruyer O, Faller JP, Teboul JL. Respiratory changes in aortic blood velocity as an indicator of fluid responsiveness in ventilated patients with septic shock. Chest. 2001 Mar;119(3):867-73.
• Martin GS, Ely EW, Carroll FE, Bernard GR. Findings on the portable chest radiograph correlate with fluid balance in critically ill patients. Chest. 2002 Dec;122(6):2087-95.
• Ely EW, Smith AC, Chiles C, Aquino SL, Harle TS, Evans GW, Haponik EF. Radiologic determination of intravascular volume status using portable, digital chest radiography: a prospective investigation in 100 patients. Crit Care Med. 2001 Aug;29(8):1502-12.
• Michard F. Underutilized tools for the assessment of intravascular volume status. Chest. 2003 Jul;124(1):414-5; author reply 415-6. No abstract available.
• Connors AF Jr. The role of right heart catheterization in the care of the critically ill: benefits, limitations, and risks. Int J Cardiol. 1983 Nov-Dec;4(4):474-7. No abstract available.
• Diebel LN, Wilson RF, Tagett MG, Kline RA. End-diastolic volume. A better indicator of preload in the critically ill. Arch Surg. 1992 Jul;127(7):817-21; discussion 821-2.
• Tomicic V, Graf J, Echevarría G, Espinoza M, Abarca J, Montes JM, Torres J, Núñez G, Guerrero J, Luppi M, Canals C. [Intrathoracic blood volume versus pulmonary artery occlusion pressure as estimators of cardiac preload in critically ill patients] Rev Med Chil. 2005 Jun;133(6):625-31. Epub 2005 Jul 22. Spanish.
• Szakmany T, Toth I, Kovacs Z, Leiner T, Mikor A, Koszegi T, Molnar Z. Effects of volumetric vs. pressure-guided fluid therapy on postoperative inflammatory response: a prospective, randomized clinical trial. Intensive Care Med. 2005 May;31(5):656-63. Epub 2005 Apr 6.
• Nirmalan M, Willard TM, Edwards DJ, Little RA, Dark PM. Estimation of errors in determining intrathoracic blood volume using the single transpulmonary thermal dilution technique in hypovolemic shock. Anesthesiology. 2005 Oct;103(4):805-12.
• Hofmann D, Klein M, Wegscheider K, Sakka SG. [Extended hemodynamic monitoring using transpulmonary thermodilution Influence of various factors on the accuracy of the estimation of intrathoracic blood volume and extravascular lung water in critically ill patients] Anaesthesist. 2005 Apr;54(4):319-26. German.
• Donati A, Loggi S, Coltrinari R, Pelaia P. Intrathoracic blood volume as index of cardiac output variations. Acta Anaesthesiol Scand. 2004 Mar;48(3):386-7. No abstract available.
• Sakka SG, Meier-Hellmann A. Intrathoracic blood volume in a patient with pulmonary embolism. Eur J Anaesthesiol. 2003 Mar;20(3):256-7. No abstract available.
• Kuz'kov VV, Kirov MIu, Nedashkovskiĭ EV. [Volumetric monitoring based on transpulmonary thermodilution in anesthesiology and intensive care] Anesteziol Reanimatol. 2003 Jul-Aug;(4):67-73. Review. Russian.
• Reuter DA, Felbinger TW, Moerstedt K, Weis F, Schmidt C, Kilger E, Goetz AE. Intrathoracic blood volume index measured by thermodilution for preload monitoring after cardiac surgery. J Cardiothorac Vasc Anesth. 2002 Apr;16(2):191-5.
• Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77.
• Eisner MD, Thompson T, Hudson LD, Luce JM, Hayden D, Schoenfeld D, Matthay MA. Efficacy of low tidal volume ventilation in patients with different clinical risk factors for acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med. 2001 Jul 15;164(2):231-6.
• Doyle RL, Szaflarski N, Modin GW, Wiener-Kronish JP, Matthay MA. Identification of patients with acute lung injury. Predictors of mortality. Am J Respir Crit Care Med. 1995 Dec;152(6 Pt 1):1818-24.
• Frezza EE, Mezghebe H. Indications and complications of arterial catheter use in surgical or medical intensive care units: analysis of 4932 patients. Am Surg. 1998 Feb;64(2):127-31.
• Dorman T, Breslow MJ, Lipsett PA, Rosenberg JM, Balser JR, Almog Y, Rosenfeld BA. Radial artery pressure monitoring underestimates central arterial pressure during vasopressor therapy in critically ill surgical patients. Crit Care Med. 1998 Oct;26(10):1646-9.
• MacIntyre NR. Current issues in mechanical ventilation for respiratory failure. Chest. 2005 Nov;128(5 Suppl 2):561S-567S. Review.
• Steinberg KP, Mitchell DR, Maunder RJ, Milberg JA, Whitcomb ME, Hudson LD. Safety of bronchoalveolar lavage in patients with adult respiratory distress syndrome. Am Rev Respir Dis. 1993 Sep;148(3):556-61.
• Brown DL, Hungness ES, Campbell RS, Luchette FA. Ventilator-associated pneumonia in the surgical intensive care unit. J Trauma. 2001 Dec;51(6):1207-16. Review. No abstract available.
• Rouby JJ, Martin De Lassale E, Poete P, Nicolas MH, Bodin L, Jarlier V, Le Charpentier Y, Grosset J, Viars P. Nosocomial bronchopneumonia in the critically ill. Histologic and bacteriologic aspects. Am Rev Respir Dis. 1992 Oct;146(4):1059-66.
• Chesnutt AN, Matthay MA, Tibayan FA, Clark JG. Early detection of type III procollagen peptide in acute lung injury. Pathogenetic and prognostic significance. Am J Respir Crit Care Med. 1997 Sep;156(3 Pt 1):840-5.

Inclusion Criteria:

Acute onset of:

1. PaO2/FiO2 less than or equal to 300.
2. Bilateral infiltrates consistent with pulmonary edema on the frontal chest radiograph.
3. Requirement for positive pressure ventilation through an endotracheal tube or tracheostomy.
4. No clinical evidence of left atrial hypertension that would explain the pulmonary infiltrates. If measured, pulmonary arterial wedge pressure less than or equal to 18 mmHg

Exclusion Criteria:

1. Age younger than 18 years.
2. Greater than 24 hours since all inclusion criteria first met.
3. Neuromuscular disease that impairs ability to ventilate without assistance, such as C5 or higher spinal cord injury, amyotrophic lateral sclerosis, Guillain-Barré syndrome, myasthenia gravis, or kyphoscoliosis (see Appendix I.A)
4. Pregnancy (negative pregnancy test required for women of child-bearing potential).
5. Severe chronic respiratory disease (see Appendix I.C)
6. Severe Chronic Liver Disease (Child-Pugh 11 - 15, see Appendix I.E)
7. Weight > 160 kg.
8. Burns greater than 70% total body surface area.
9. Malignancy or other irreversible disease or conditions for which 6-month mortality is estimated to be greater than 50 % (see Appendix I.A).
10. Known cardiac or vascular aneurysm
11. Contraindications to femoral arterial puncture - platelets < 30, bilateral femoral arterial grafts, INR > 3.0
12. Not committed to full support.
13. Participation in other experimental medication trial within 30 days.
14. Allergy to intravenous lasix or any components of its carrier.
15. History of severe CHF - NYHA class ≥ III, previously documented EF < 30%
16. Diffuse alveolar hemorrhage
17. Presence of reactive airway disease (active will be defined based on recent frequency and amounts of MDI's use and steroids to control the disease)

• Pulsion Medical Systems
• Oregon Clinical and Translational Research Institute