Hemodynamics and Extravascular Lung Water in Acute Lung Injury
Condition: Acute Lung Injury
MeSH terms: Lung Injury; Acute Lung Injury; Wounds and Injuries
Intervention: Diuresis (furosemide) part I; Fluid Bolus (crystalloid or albumin); Fluid Bolus (crystalloid or albumin); Vasopressors (Norepinephrine, Vasopressin, Phenylephrine, Epinephrine); Vasopressors (Norepinephrine, Vasopressin, Phenylephrine, Epinephrine); Dobutamine; Dobutamine; Concentrate all drips and nutrition; Diuresis (furosemide) part II; Dialysis
Intervention description: Goal: Overall I/O net negative 50ml/hour
Initiation:
Continuous IV furosemide at 3mg/hour or last known protocol specified dose
Titrate up or down by 3mg/hour increments every hour as needed to establish diuresis goal
Do not exceed 30mg/hour
Furosemide Bolus:
If unable to establish adequate diuresis at maximum dose may attempt furosemide bolusing as follows
By intravenous bolus give 30, then 60, then 80, and 120 mg - one bolus dose every hour until urine output results in 1 ml/kg PBW/hr net negative fluid balance per hour
Bolusing trials may be done at will but total furosemide dose may not exceed 800mg/24hour period; 15 ml/kg PBW crystalloid (round to nearest 250 ml) or 25 grams albumin as rapidly as possible. Used for patients with a measured CVP<8 or measured PaOP <12mmHg in addition to concurrent urine output of <0.5 ml/kg/hr; 10 ml/kg PBW crystalloid (round to nearest 70ml) or 25 grams albumin as rapidly as possible.
Perform thermodilution immediately before and after and 60 minutes after each bolus. If EVLW increases > 2ml/kg PBW within 60 minutes after a bolus do not give any further boluses until next regularly scheduled measurement. This therapy is available for patients with a map < 60 or who are on vasopressors that also have a measured GEDI less than goal; (may use any alone or in combination)
Norepinephrine - 0.05mcg/kg/min - increase for effect not to exceed (NTE) 1mcg/kg/min.
Vasopressin - 0.04 international units/hour
Phenylephrine - 7mcg/min - may increase to for effect not to exceed 500mcg/min.
Epinephrine - 1 mcg/min - may increase for effect not to exceed 20mcg/min.
Weaning: When MAP ≥ 60 mm/Hg on stable dose of vasopressor begin reduction of vasopressor by greater than or equal to 25% stabilizing dose at intervals ≤ 4 hours to maintain MAP ≥ 60 mm/Hg.; (may use alone or in combination)
Norepinephrine - 0.05mcg/kg/min - increase for effect not to exceed (NTE) 1mcg/kg/min.
Vasopressin - 0.04 international units/hour
Phenylephrine - 7mcg/min - may increase to for effect not to exceed 500mcg/min.
Epinephrine - 1 mcg/min - may increase for effect not to exceed 20mcg/min.
Weaning: When MAP ≥ 60 mm/Hg on stable dose of vasopressor begin reduction of vasopressor by greater than or equal to 25% stabilizing dose at intervals ≤ 4 hours to maintain MAP ≥ 60 mm/Hg.
In the experimental arm vasopressors are a treatment option in patients with a Mean Arterial Pressure of < 60; Begin at 5mcg/kg/min and increase by 3 mcg/kg/min increments at 15 minute intervals until C.I. ≥ 2.5 or maximum dose of 20mcg/kg/min has been reached.
Begin weaning 4 hours after low CI is reversed. Wean by ≥ 25% of the stabilizing dose at intervals of ≤ 4 hours to maintain hemodynamic algorithm goals.
If patient is on dobutamine as a result of an earlier cell assignment, dobutamine should be ignored for the purpose of subsequent assignment, but should be continued to be weaned per protocol.
Used in patients with a measured cardiac index < 2.5; Begin at 5mcg/kg/min and increase by 3 mcg/kg/min increments at 15 minute intervals until C.I. ≥ 2.5 or maximum dose of 20mcg/kg/min has been reached.
Begin weaning 4 hours after low CI is reversed. Wean by ≥ 25% of the stabilizing dose at intervals of ≤ 4 hours to maintain hemodynamic algorithm goals.
If patient is on dobutamine as a result of an earlier cell assignment, dobutamine should be ignored for the purpose of subsequent assignment, but should be continued to be weaned per protocol.; Concentrate all drips and nutrition in order to minimize fluid volume as much as possible. Intravenous fluid to be run at keep vein open rate.
EVLW arm: Patients with a MAP > 60 and off vasopressors for >12 hours, as well as patients with a measured cardiac index >2.5 that also have a measured GEDI > goal.; Withhold furosemide if:
Significant hypokalemia (K+ <= 2.5 meq/L), or hypernatremia (Na+ >= 155 meq/L) occurs within last 12 hours may then be restarted if the prevailing condition no longer exists
Dialysis dependence
Oliguria (less than 0.5ml/kg/hour) with either creatinine > 3, or clinical suspicion of rapidly evolving ARF
More than 800mg has been given in less then 24 hours
Creatinine increases > 1.5 mg/dl in any 24 hour period; Need for CVVHD or intermittent hemodialysis to be determined by treating clinicians.
CVC arm: If fluid management to be accomplished with dialysis then fluid balance goals to be determined per clinicians.
EVLW arm: Fluid balance as per algorithm
When using intermittent HD it is recommended that no more than 2 liters net negative fluid is removed per dialysis session. Total fluid removal per run to be estimated by the clinicians to attain CVP or GEDI goals per algorithm.
Intervention MeSH terms: Phenylephrine; Dobutamine; Furosemide; Vasopressins; Arginine Vasopressin; Epinephrine; Racepinephrine; Oxymetazoline; Norepinephrine; Vasoconstrictor Agents; Epinephryl borate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Acute Lung Injury; Extravascular Lung Water; Acute Respiratory Distress Syndrome

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.
    

Eligibility criteria:

        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 old.

          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).