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

Kinetics of Disaturated-phosphatidylcholine and Specific Surfactant Proteins Turnover, Water Turnover and Total Body Water in Acute Respiratory Distress Syndrome (ARDS) in Intensive Care Unit (ICU) Patients and in Control Patients

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.

Study Overview

• Status: Completed
• Conditions: ARDS; Sepsis Syndrome
• Intervention / Treatment: Drug: Injection of 1-13 Carbon Leucine and deuterated water

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 Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Injection of stable isotopes; 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

Drug: 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; Other Names: Isotopes came from Cambridge Isotope Laboratories, MA

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disaturated phosphatidylcholine (DSPC) secretion time	DSPC deuterium incorporation, change from baseline. The following kinetic parameter will be calculated: secretion time (expressed in hours).	48 hours
Surfactant protein B and Surfactant protein C synthesis rate	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)	48 hours
Surfactant protein B and Surfactant protein C secretion time	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).	48 hours
Surfactant protein B and Surfactant protein C half life	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).	48 hours
Volume of Total Body water	Measured by the isotope dilution method using deuterium oxide. Total body water will be expressed in liters	10 hours

Collaborators and Investigators

• Sponsor: University of Padova
• Collaborators: Città della Speranza, Padova

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2010
• Primary Completion (Actual): December 31, 2013
• Study Completion (Actual): December 31, 2013

Study Registration Dates

• First Submitted: October 31, 2017
• First Submitted That Met QC Criteria: December 12, 2017
• First Posted (Actual): December 13, 2017

Study Record Updates

• Last Update Posted (Actual): December 13, 2017
• Last Update Submitted That Met QC Criteria: December 12, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Inflammation; Disease; Shock; Sepsis; Toxemia; Syndrome; Systemic Inflammatory Response Syndrome
• Other Study ID Numbers: 1235P

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No