Hemodynamics and Extravascular Lung Water in Acute Lung Injury

Phase 2

Completed

Conditions: Acute Lung Injury

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

Registration Number: NCT00624650

Lead Sponsor: Oregon Health and Science University

Brief Summary: 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.

Detailed Description: The objective of this study is to conduct a randomized, controlled trial of a goal directed therapy designed to improve outcome in patients with acute lung injury (ALI). The investigators 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 33

Inclusion Criteria

Acute onset of:

PaO2/FiO2 less than or equal to 300.
Bilateral infiltrates consistent with pulmonary edema on the frontal chest radiograph.
Requirement for positive pressure ventilation through an endotracheal tube or tracheostomy.
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

Age younger than 18 years old.
Greater than 24 hours since all inclusion criteria first met.
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).
Pregnancy (negative pregnancy test required for women of child-bearing potential).
Severe chronic respiratory disease (see Appendix I.C).
Severe Chronic Liver Disease (Child-Pugh 11 - 15, see Appendix I.E)
Weight > 160 kg.
Burns greater than 70% total body surface area.
Malignancy or other irreversible disease or conditions for which 6-month mortality is estimated to be greater than 50 % (see Appendix I.A).
Known cardiac or vascular aneurysm.
Contraindications to femoral arterial puncture - platelets < 30, bilateral femoral arterial grafts, INR > 3.0.
Not committed to full support.
Participation in other experimental medication trial within 30 days.
Allergy to intravenous lasix or any components of its carrier.
History of severe CHF - NYHA class ≥ III, previously documented EF < 30%.
Diffuse alveolar hemorrhage.
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).

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Modified FACTT (control)	Fluid Bolus (crystalloid or albumin)	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.
Modified FACTT (control)	Diuresis (furosemide) part II	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.
Modified FACTT (control)	Dialysis	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.
Modified FACTT (control)	Diuresis (furosemide) part I	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.
Modified FACTT (control)	Vasopressors (Norepinephrine, Vasopressin, Phenylephrine, Epinephrine)	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.
EVLW	Diuresis (furosemide) part I	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.
EVLW	Fluid Bolus (crystalloid or albumin)	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.
EVLW	Vasopressors (Norepinephrine, Vasopressin, Phenylephrine, Epinephrine)	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.
EVLW	Concentrate all drips and nutrition	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.
EVLW	Diuresis (furosemide) part II	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.
EVLW	Dialysis	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.
Modified FACTT (control)	Dobutamine	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.
EVLW	Dobutamine	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.

Primary Outcome Measures

Name	Time	Method
The Primary Efficacy Variable Will be the Total Reduction in Measured Lung Water	The first seven days of treatment

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (3): Legacy Good Samaritan
🇺🇸
Portland, Oregon, United States
Oregon Health and Science University
🇺🇸
Portland, Oregon, United States
Kaiser Permanente Sunnyside
🇺🇸
Clackamas, Oregon, United States