Hemodynamics and Extravascular Lung Water in Acute Lung Injury: A Prospective Randomized Controlled Multicentered Trial of Goal Directed Treatment of EVLW Versus Standard Management for the Treatment of Acute Lung Injury

Goal: Overall I/O net negative 50ml/hour Initiation: 1. Continuous IV furosemide at 3mg/hour or last known protocol specified dose 2. Titrate up or down by 3mg/hour increments every hour as needed to establish diuresis goal 3. Do not exceed 30mg/hour Furosemide Bolus: 1. If unable to establish adequate diuresis at maximum dose may attempt furosemide bolusing as follows 2. 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 3. 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) 1. Norepinephrine - 0.05mcg/kg/min - increase for effect not to exceed (NTE) 1mcg/kg/min. 2. Vasopressin - 0.04 international units/hour 3. Phenylephrine - 7mcg/min - may increase to for effect not to exceed 500mcg/min. 4. 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) 1. Norepinephrine - 0.05mcg/kg/min - increase for effect not to exceed (NTE) 1mcg/kg/min. 2. Vasopressin - 0.04 international units/hour 3. Phenylephrine - 7mcg/min - may increase to for effect not to exceed 500mcg/min. 4. 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

1. 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. 2. 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. 3. 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

1. 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. 2. 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. 3. 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: 1. 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 2. Dialysis dependence 3. Oliguria (less than 0.5ml/kg/hour) with either creatinine \> 3, or clinical suspicion of rapidly evolving ARF 4. More than 800mg has been given in less then 24 hours 5. Creatinine increases \> 1.5 mg/dl in any 24 hour period

1. Need for CVVHD or intermittent hemodialysis to be determined by treating clinicians. 2. CVC arm: If fluid management to be accomplished with dialysis then fluid balance goals to be determined per clinicians. 3. EVLW arm: Fluid balance as per algorithm 4. 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.