Kinetics of Surfactant Proteins, Phosphatidylcholine and Body Water in Intensive Care Unit (ICU)

Not Applicable

Completed

• Conditions: Sepsis Syndrome; ARDS
• Interventions: Drug: Injection of 1-13 Carbon Leucine and deuterated water

• Registration Number: NCT03371680
• Lead Sponsor: University of Padova

Brief Summary

Analysis of kinetics of phosphatidylcholine and specific surfactant proteins, total body water and water turnover in patients with acute respiratory distress syndrome (ARDS) and in intensive care unit (ICU) patients by using non radioactive isotopes as deuterium and Carbon-13.

Detailed Description

Patients with adult respiratory distress syndrome (ARDS) have low concentrations of disaturated-phosphatidylcholine and surfactant protein-B and C in bronchoalveolar lavage fluid and altered fluid metabolism.

Injection of stable isotopes such as 13 Carbon Leucine and deuterated water allows the analysis of disaturated-phosphatidylcholine and surfactant protein-B and C kinetics, total body water and water turnover in patients with ARDS and in human adults with normal lungs (controls).

Study Timeline

• Study Start: 2010-10
• Primary Completion: 2013-12-31
• Study Completion: 2013-12-31
• Study First Submitted: 2017-10-31
• Status Verified: 2017-12
• Study First Submitted QC: 2017-12-12
• Last Update Submitted: 2017-12-12
• Study First Posted: 2017-12-13
• Last Update Posted: 2017-12-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

Inclusion criteria were:

• adult patients older than 18 years
• expected intensive care unit (ICU) length of stay greater than 120 hours from the onset of acute respiratory failure, defined according to the acute respiratory syndrome (ARDS) Berlin criteria or patients admitted for acute neurological failure defined as Glasgow coma scale < 8.
• All patients with ARDS also had sepsis syndrome or septic shock according to the surviving sepsis campaign criteria at the admission to the ICU, while no patients with acute neurological failure was septic.

At the start of the study, patients with ARDS/sepsis fulfilled also the following criteria:

• start of the study within 72 hours from the onset of the respiratory failure;
• stable hemodynamic conditions, defined as no need of fluid boluses for at least 6 hours before the start of the study;
• serum urea and creatinine within the normal ranges.

Patients with acute neurological failure fulfilled the following inclusion criteria:

• normal chest radiograph;
• arterial partial pressure of oxygen / fraction of inspired oxygen (PaO2/FiO2) >300;
• no evidence of sepsis, according to body temperature, C reactive protein, white cell count and differential count within normal ranges;
• intubation and mechanical ventilation started within 72 h before the beginning of the study.

Exclusion Criteria

Exclusion criteria for all study subjects were:

• presence of liver failure or renal failure (transaminases > 3 and creatinine > 2 times the normal values),
• burns > 30% of body surface bone marrow or lung transplantation,
• need of fluid boluses to maintain hemodynamic conditions during the study or extracorporeal circulatory support.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Injection of stable isotopes	Injection of 1-13 Carbon Leucine and deuterated water	Injection of 1-13 Carbon Leucine and deuterated water: all patients received a constant intravenous infusion of 1 g 1-13 Carbon Leucine (Cambridge Isotope Laboratories, Andover, MA) dissolved in saline for 24 h. Deuterated water (Cambridge Isotope Laboratories, Andover, MA) was administered as a 25 ml bolus at the study start and then, every 12 hours over the next 36 hours, as intermittent boluses corresponding to 0.0625% of fluid intake, to maintain steady state of deuterium enrichment in body water

Primary Outcome Measures

Name	Time	Method
Disaturated phosphatidylcholine (DSPC) fractional synthesis rate	48 hours	DSPC deuterium incorporation, change from baseline. The following kinetic parameter will be calculated: fractional synthesis rate (expressed as percentage/day)

Secondary Outcome Measures

Name	Time	Method
Disaturated phosphatidylcholine (DSPC) secretion time	48 hours	DSPC deuterium incorporation, change from baseline. The following kinetic parameter will be calculated: secretion time (expressed in hours).
Volume of Total Body water	10 hours	Measured by the isotope dilution method using deuterium oxide. Total body water will be expressed in liters
Surfactant protein B and Surfactant protein C secretion time	48 hours	Surfactant protein B and Surfactant protein C 1 -13 Carbon leucine incorporation, change from baseline. The following kinetic parameter will be calculated: Secretion time (expressed in hours).
Surfactant protein B and Surfactant protein C half life	48 hours	Surfactant protein B and Surfactant protein C 1 -13 Carbon leucine incorporation, change from baseline. The following kinetic parameter will be calculated: half life (expressed in hours).
Surfactant protein B and Surfactant protein C synthesis rate	48 hours	Surfactant protein B and Surfactant protein C 1 -13 Carbon leucine incorporation, change from baseline. The following kinetic parameter will be calculated: fractional synthetic rate (expressed as percentage/day)