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

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

Detailed Description
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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.

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

Conditions
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Hypernatremia

Intervention / Treatment
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* Procedure: Skin biopsies
* Other: Blood and urine analysis
* Other: Blood collection for RNA-investigation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Septic patients<br>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<br>* 2 3mm skin biopsies will be taken<br>Other: Blood and urine analysis<br>* Measurement of sodium, potassium and kidneyfunction in blood and urine.<br>Other: Blood collection for RNA-investigation<br>* A blood sample that, in case of relevant differences between groups, could be used for RNA-profiling.<br>|
| CABG patients<br>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<br>* 2 3mm skin biopsies will be taken<br>Other: Blood and urine analysis<br>* Measurement of sodium, potassium and kidneyfunction in blood and urine.<br>Other: Blood collection for RNA-investigation<br>* A blood sample that, in case of relevant differences between groups, could be used for RNA-profiling.<br>|
| Patients before hip replacement<br>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<br>* 2 3mm skin biopsies will be taken<br>Other: Blood and urine analysis<br>* Measurement of sodium, potassium and kidneyfunction in blood and urine.<br>Other: Blood collection for RNA-investigation<br>* A blood sample that, in case of relevant differences between groups, could be used for RNA-profiling.<br>|

What is the study measuring?
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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 | Measure Description | 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 |