Investigation on Differences in Skin Sodium Content Between Normal Subjects and ICU-patients (InCa)

Onderzoek Naar Intracutane Natriumopslag Bij Intensive Care patiënten (InCa-studie)

This study investigates the differens in sodium storage in skin between normal subjects, patients after cardiac surgery and septic patients.

Study Overview

• Status: Completed
• Conditions: Hypernatremia
• Intervention / Treatment: Procedure: Skin biopsies; Other: Blood and urine analysis; Other: Blood collection for RNA-investigation

Detailed Description

According to the current paradigm ICU-acquired hypernatremia is mainly an iatrogenic problem, caused by sodium overload or water deficit. In spite of several interventions to reduce sodium intake and optimize fluid balance, critically ill patients still develop hypernatremia. These patients also seem to have an inability to excrete sodium, hence develop a positive sodium balance. In animals sodium storage in the third compartment was found. Our hypothesis is that sodium storage in the third compartment is different in critically ill patients and this difference could play a role in the development of ICU-acquired hypernatremia.

• Study Type: Observational
• Enrollment (Actual): 45

Contacts and Locations

Study Locations

• Netherlands
  • Leeuwarden, Netherlands
    • Medisch Centrum Leeuwarden

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

• 15 patients admitted to the ICU with systemic inflammatory response syndrom in the presence of a(n expected) new infection
• 15 patients admitted to the ICU after coronary artery bypass surgery, matched by gender and age (+/- 10 years) to the septic patients
• 15 patients undergoing a hip replacement for arthrosis, matched by gender and age (+/- 10 years) to the septic patients

Description

Inclusion Criteria:

• 50-80 years (septic patients), 45-85 years (CABG and hip replacement-patients)
• Patients undergoing hip replacement: no relevant medical history (i.e. chronic and/or systemic diseases with a suspected influence on sodium / sodium handling)
• Septic patients: fulfilling the criteria for the systemic inflammatory response syndrome in the presence of a(n expected) new infection

Exclusion Criteria:

• Absence of both upper legs
• Skin disease that makes skin biopsies in healthy skin impossible
• Subjects with in their history formation of exaggerated scar tissue
• Subjects suffering from psoriasis or lichen ruber
• Use of skin corticosteroids on all skin of both upper legs < 2 weeks before inclusion
• Tattoos covering the whole surface of both upper legs
• Use of diuretics in the past month
• Current renal replacement therapy
• Septic patients: not being sedated
• Patients undergoing hip replacement: hip replacement because of an inflammatory disease

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Septic patients; Patients admitted to the ICU that fulfill the criteria for the systemic inflammatory response syndrome in the presence of a(n expected) new infection. 2 3mm skin biopsies will be taken, blood and urine analysis will take place and also blood collection for RNA-investigation.	Procedure: Skin biopsies; 2 3mm skin biopsies will be taken; Other: Blood and urine analysis; Measurement of sodium, potassium and kidneyfunction in blood and urine.; Other: Blood collection for RNA-investigation; A blood sample that, in case of relevant differences between groups, could be used for RNA-profiling.
CABG patients; Patients admitted to the ICU after coronary artery bypass grafting. 2 3mm skin biopsies will be taken, blood and urine analysis will take place and also blood collection for RNA-investigation.	Procedure: Skin biopsies; 2 3mm skin biopsies will be taken; Other: Blood and urine analysis; Measurement of sodium, potassium and kidneyfunction in blood and urine.; Other: Blood collection for RNA-investigation; A blood sample that, in case of relevant differences between groups, could be used for RNA-profiling.
Patients before hip replacement; Patients that will undergo a hip replacement because of arthrosis. 2 3mm skin biopsies will be taken, blood and urine analysis will take place and also blood collection for RNA-investigation.	Procedure: Skin biopsies; 2 3mm skin biopsies will be taken; Other: Blood and urine analysis; Measurement of sodium, potassium and kidneyfunction in blood and urine.; Other: Blood collection for RNA-investigation; A blood sample that, in case of relevant differences between groups, could be used for RNA-profiling.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in sodium concentration in skin biopsy between groups	Skin biopsies will be taken within the described time frame, analysis will take place after all biopsies of all subjects are included	Different for the separate groups: before hip replacement, within 2 hours after CABG and within 12 hours after admission for septic patients

Secondary Outcome Measures

Outcome Measure	Time Frame
Immunohistochemistry: outcomes of proteoglycans	Different for the separate groups: before hip replacement, within 2 hours after CABG and within 12 hours after admission for septic patients
Immunohistochemistry: binding capacity of proteoglycans	Different for the separate groups: before hip replacement, within 2 hours after CABG and within 12 hours after admission for septic patients
Immunohistochemistry: density of lymph capillaries	Different for the separate groups: before hip replacement, within 2 hours after CABG and within 12 hours after admission for septic patients
Immunohistochemistry: presence of macrophage influx	Different for the separate groups: before hip replacement, within 2 hours after CABG and within 12 hours after admission for septic patients
Quantification of different matrix components / proteoglycans: decorine - if enough tissue is available	Different for the separate groups: before hip replacement, within 2 hours after CABG and within 12 hours after admission for septic patients
Quantification of different matrix components / proteoglycans: versican (if enough tissue is available)	Different for the separate groups: before hip replacement, within 2 hours after CABG and within 12 hours after admission for septic patients
Quantification of different matrix components / proteoglycans: biglycan- if enough tissue is available	Different for the separate groups: before hip replacement, within 2 hours after CABG and within 12 hours after admission for septic patients
mRNA profiling of proteoglycans and synthesizing enzymes by way of RNA-isolation - if enough tissue is available	Different for the separate groups: before hip replacement, within 2 hours after CABG and within 12 hours after admission for septic patients

Collaborators and Investigators

• Sponsor: Medical Centre Leeuwarden
• Collaborators: University Medical Center Groningen
• Investigators: Principal Investigator: Christiaan Boerma, MD PhD, Medical Center Leeuwarden; Principal Investigator: Jaap van den Born, PhD, University Medical Center Groningen

Publications and helpful links

General Publications

• Titze J, Lang R, Ilies C, Schwind KH, Kirsch KA, Dietsch P, Luft FC, Hilgers KF. Osmotically inactive skin Na+ storage in rats. Am J Physiol Renal Physiol. 2003 Dec;285(6):F1108-17. doi: 10.1152/ajprenal.00200.2003. Epub 2003 Jul 29.
• Polderman KH, Schreuder WO, Strack van Schijndel RJ, Thijs LG. Hypernatremia in the intensive care unit: an indicator of quality of care? Crit Care Med. 1999 Jun;27(6):1105-8. doi: 10.1097/00003246-199906000-00029.
• Waite MD, Fuhrman SA, Badawi O, Zuckerman IH, Franey CS. Intensive care unit-acquired hypernatremia is an independent predictor of increased mortality and length of stay. J Crit Care. 2013 Aug;28(4):405-12. doi: 10.1016/j.jcrc.2012.11.013. Epub 2013 Jan 29.
• Lee JW. Fluid and electrolyte disturbances in critically ill patients. Electrolyte Blood Press. 2010 Dec;8(2):72-81. doi: 10.5049/EBP.2010.8.2.72. Epub 2010 Dec 31.
• Titze J, Krause H, Hecht H, Dietsch P, Rittweger J, Lang R, Kirsch KA, Hilgers KF. Reduced osmotically inactive Na storage capacity and hypertension in the Dahl model. Am J Physiol Renal Physiol. 2002 Jul;283(1):F134-41. doi: 10.1152/ajprenal.00323.2001.

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2016
• Primary Completion (Actual): September 5, 2017
• Study Completion (Actual): September 5, 2017

Study Registration Dates

• First Submitted: September 13, 2016
• First Submitted That Met QC Criteria: September 20, 2016
• First Posted (Estimate): September 23, 2016

Study Record Updates

• Last Update Posted (Actual): September 8, 2017
• Last Update Submitted That Met QC Criteria: September 5, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Water-Electrolyte Imbalance; Hypernatremia
• Other Study ID Numbers: NL 56729.099.16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Depending on the requests of the magazine involved.