Lung Ultrasound-Guided Fluid Deresuscitation in ICU Patients

Objective:

The aim of this study is to assess the effect of LUS-guided deresuscitation on duration of invasive ventilation in ICU patients.

Hypothesis:

LUS-guided fluid deresuscitation is superior to routine fluid deresuscitation (not using LUS) with regard to duration of invasive ventilation.

Study design:

The CONFIDENCE study is an investigator-initiated, national, multicenter, randomized clinical trial in critically ill invasively ventilated patients admitted to the ICUs of participating hospitals.

Study population:

Adult patients admitted to ICUs in multiple countries

Sample size calculation:

The sample size is computed on the basis of the hypothesis that LUS guided deresuscitation is associated with a reduction of two days of ventilation. Assuming a mean (±SD) number of VFD-28 of 13±11 days, the ivenstigators estimate that a sample of 1000 patients (500 per group) is needed to have 80% power, at a two-tailed significance level of 0.05, to detect a mean between-group difference of 2 VFD-28, and allowing an anticipated dropout rate of 5%.

Methods:

Patients in participating intensive care units (ICU) are screened for eligibility. Inclusion and randomization will occur within 24 hours after meeting the inclusion criteria. If possible, informed consent from the legal representative will be obtained before randomization but no longer than 48 hours after meeting the inclusion criteria.

Patients are eligible if they are admitted to one of the participating ICUs, are invasively ventilated for less than 24 hours at randomization and expected to be under invasive ventilation for longer than 24 hours after randomization.

Randomization will be performed using Castor Electronic Data Capture (EDC). A dedicated, password protected, encrypted website. Randomization sequence is generated by a dedicated computer randomization software program. Due to the nature of the intervention, blinding of the caregivers is not possible.

Patients will be randomly assigned in a 1:1 ratio to lung guided fluid deresuscitation or routine fluid deresuscitation. Randomization will be stratified per center.

Lung ultrasound guided deresuscitation: with lung ultrasound (LUS)-guided fluid deresuscitation, LUS examinations are performed at least onze a day in hemodynamically stable patients, defined as a mean arterial pressure (MAP) ≥ 65 mmHg (with vasopressor dose decreasing and norepinephrine ≤ 0.2 μg/kg/min), and no new clear signs of hypoperfusion such as mottled skin and capillary refill time \> 3 seconds and/or new oliguria (urine output \< 0.3-0.5ml/kg/hour for the previous 6 hours). Target MAP can be changed in conditions in which 65 mmHg is not sufficient (i.e. history of chronic hypertension). In these cases the target MAP is at the discretion of the treating physician. 12-region LUS is performed, by a trained healthcare provider, and each region is scanned for the presence of B-lines and pleural effusions and scored using the lung ultrasound score. After extubation, lung ultrasound is continued once a day until day 28 or until discharge (whatever comes first) to monitor reappearance of pulmonary fluid overload or pleural effusion. In case of reappearance (or increase) of pulmonary fluid overload or pleural effusion, fluid withdrawal is started again according to the treatment protocol.

Routine deresuscitation: in routine fluid deresuscitation, in which fluid withdrawal is started and continued at the discretion of the treating physician, factors guiding fluid deresuscitation are chosen by the treating physician and may include the following: physical examination, laboratory values (e.g. BNP), chest x-ray, PiCCO or pulmonary artery catheters. LUS examinations are not performed to guide fluid deresuscitation in this group.

In both groups patients are extubated if standard extubation criteria are fulfilled, i.e., normal body temperature, patient awake and responsive/cooperative, adequate cough reflex, adequate oxygenation and ventilation, and hemodynamically stable.

Monitoring:

Monitoring of patients safety and reviewing of safety issues is performed by a designated independent Data Safety and Monitoring Board (DSMB).The DSMB watches over the ethics of conducting the study in accordance with the Declaration of Helsinki.

• Duration of ventilation [Time frame: 28 days]
• ICU length of stay [Time frame: 28 days]
• Hospital length of stay [Time frame: 28 days]
• 28 day mortality [Time frame: 28 days]
• 90 day mortality [Time frame: 90 days]
• Incidences of reintubations [Time frame: 28 days]
• Cumulative fluid balances after randomization [Time frame: 7 days]
• Cumulative fluid balances after start of lung ultrasound examination [Time frame: 7 days]
• Incidence of acute kidney injury [Time frame: 28 days]