Lung Ultrasound Guided Protocol for Fluid Management for the Critically Ill Patient: a Randomized Study

Inclusion criteria

• Age 18 or older admitted to the Intensive Care Unit

Exclusion criteria

• Due to LUS measurement limitation: patients with known persistent pleurisy, pulmonary fibrosis or pneumectomy;
• Unwillingness to participate in the study.

Active arm diuretic administration algorithm

• Intravenous diuretics will be used only to decrease the BLS to \< 15;
• A stepped diuretic administration algorithm is provided below;
• Investigators may opt-out of the stepped diuretic administration algorithm if they feel it is in the best interests of the patient care;
• Intravenous diuretics can be decreased or temporarily discontinued if there is a decrease in blood pressure or an increase in creatinine that is felt to be due to a transient episode of intravascular volume depletion. After the patient has stabilized, if BLS ≥ 15, intravenous diuretics should be reinitiated until the patient's BLS is \<15.

Active arm Initial BLS ≥ 15 Diuretic dose Previous Dose Suggested dose Furosemide (/day) Furosemide (/day) Hydrochlorothiazide (/day)

1. ≤ 80 mg 40 mg iv bolus + 5 mg/h 0
2. 81-160 mg 80 mg iv bolus + 10 mg/h 12.5 mg
3. 161-240 mg 80 mg iv bolus + 20 mg/h 25 mg
4. >240 mg 80 mg iv bolus + 30 mg/h 25 mg

At 24 hours Persistent BLS ≥ 15 Negative fluid balance > 1000 ml - reduce current diuretic regimen if desired Negative fluid balance \< 1000 ml - maintain current diuretic regimen Positive fluid balance - advance to next step in table

Dialysis initiation AKI will be diagnosed based on changes in the serum creatinine, urine output, or both (according to the KDIGO recommendations). Creatinine measurements will be performed twice per day. Every patient will have a urinary catheter and urine output will be measured every hour.

Criteria for renal replacement therapy initiation:

Stage 3 AKI (urine output \<0.3 mL/kg/h for ≥24 h and/or >3 fold increase in serum creatinine level compared with baseline or serum creatinine of ≥4 mg/dL with an acute increase of at least 0.5 mg/dL within 48 hours or

If any of the following absolute indications for RRT were present:

• Blood urea nitrogen level higher than 112 mg/dL;
• Serum potassium level higher than 6 mEq/L and/or with electrocardiography abnormalities;
• Urine production lower than 200 mL per 12 hours or anuria (according to the KDIGO recommendations);
• Organ edema in the presence of AKI resistant to diuretic treatment;
• A pH below 7.15 in the context of either pure metabolic acidosis (Paco2 below 35 mm Hg) or mixed acidosis (Paco2 of 50 mm Hg or more without the possibility of increasing alveolar ventilation)
• Acute pulmonary edema due to fluid overload responsible for severe hypoxemia requiring an oxygen flow rate greater than 5 liters per minute to maintain a Spo2 greater than 95% or requiring a Fio2 greater than 50% in patients receiving mechanical ventilation and despite diuretic therapy.