Investigation of Inflammatory Parameters in a Perioperative Closed-meshed Standard Progress in CPB Patients

February 16, 2018 updated by: Dr. Martin Bernardi, Medical University of Vienna

Similar to poly-trauma, acute myocardial infarction, or stroke, the speed and appropriateness of therapy administered in the initial hours after severe sepsis develops are likely to influence outcome. However, the crux of matter is the "early diagnosis" lacking of high sensitive and specific test, in contrary to, for instance, the acute coronary syndrome, where the highly sensitive Troponin T is measured and increased values are fix component of the diagnosis and definition of acute myocardial infarction. Cardiac surgery can initiate a systemic inflammatory response syndrome (SIRS) induced by extrinsic and intrinsic factors, which are associated in the pathogenesis of postoperative complications. SIRS is closely related to sepsis, but in contrast sepsis is induced by infection. This strong inflammatory response induces malfunction of the peripheral circulation with increased lactate levels, pronounced fluid accumulation and increased need of vasopressors.

The investigators want to assess the timing dynamic of release of IL-6 apart from established markers like CRP, leukocytes, PCT. Target of this is to estimate the time-scope and -advance of an "IL-6 axis panel" toward the measurement of standard inflammation parameters in inflammatory response to surgical trauma as a pre-figuration of non-infectious SIRS and to search for a eligible "cut-off" of IL-6.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Similarly for early detection of SIRS/Sepsis, interleukin 6 (IL-6) assays have been brought up for discussion and have been studied extensively over last years. IL-6 is pro-and anti-inflammatory cytokine with multimodal functions in physiology and patho- physiology: As a major regulator of hepatic acute phase response, IL-6 induces the expression of C- reactive protein, fibrinogen and serum amyloid-A protein among others. However, along with pro-inflammatory effects IL-6 is described as an anti- inflammatory agent. Especially in systemic inflammatory response syndrome (SIRS) and sepsis the pro-inflammatory impact of IL-6 is of paramount interest: Via trans-signaling using the soluble IL-6 receptor (sIL-6R) pathway adherent junctions of endothelial VE-cadherin are disconnected causing a loss of barrier function. Increased endothelial permeability results in trans-endothelial flow of fluid and interstitial oedema with consecutive impairment of tissue oxygenation and increased blood viscosity.

Recent publications suggest, that regenerative or anti-inflammatory activities of IL-6 are mediated by classic signalling via a membrane bound IL-6 receptor, whereas pro-inflammatory responses of interleukin-6 are rather mediated by trans-signalling using soluble IL-6.

The IL-6, sIL-6R, soluble glycoprotein 130- buffer:

Since all cells in body express glycoprotein (gp) 130, one of the crucial molecules in signal-transduction of IL-6, they all are susceptible to activation by the complex of IL-6 and sIL-6-Receptor. Thus, under steady state conditions there must be a control mechanism, which prevents IL-6/sIL-6R trans-signalling and hence unbounded activation of pro- inflammatory axis conterminously with a kind of "buffer system" for the IL-6 activity. For such a buffer, at least three different molecules have been taken into account: IL-6 itself, the -above mentioned- sIL-6Receptor and the soluble form of gp130 (sgp130).

Under steady-state and non- inflammatory conditions levels of sIL-6R and sgp130 are almost 1000 fold higher than IL-6, meaning IL-6 is once secreted, it will form a complex with sIL-6R and consecutively will be neutralized by association to sgp130. The immunological impact of circulating IL-6 is a function of the serum IL-6, sIL-6R and sgp130 concentration, respectively of the proportion of the proteins to each other.

Kinetic of IL-6 and the impact of procalcitonin:

In the early nineties, the use of procalcitonin (PCT) has been described by Assicot et al. for the diagnosis of, in particular, bacterial sepsis. However, for discrimination of the acute inflammatory pattern of sepsis from other causes of generalized inflammation (e.g., postoperative, other forms of shock) no recommendation has been given for the use PCT to distinguish between severe infection and other acute inflammatory states in the actual guidelines. Nevertheless, conflicting to this reference, a recent high impact meta-analysis concluded that PCT can differentiate effectively between sepsis and systemic inflammatory response syndrome (SIRS) of non- infectious origin with a cut-off of between 1·0 and 2·0 ng/mL.

The drawback of PCT and e.g. C-reactive Protein (CRP) in relation to members of the IL-6 axis is, that these molecules are downstream of the IL-6 axis and therefore the increase caused by endotoxin or for instance by surgical trauma is delayed.

Study Type

Observational

Enrollment (Actual)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Vienna, Austria, 1090
        • Divison of Cardiothoracic Anaesthesia and Intensive Care, Medical University of Vienna

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Prospective observational cohort study in patients with elective cardiac surgery.

Description

Exclusion Criteria:

  • Emergency procedures
  • Heart transplantation
  • Elective left ventricular assist device (LVAD) implantation
  • Pulmonary thrombendarterectomy
  • Declined informed consent
  • Chronic renal failure on renal replacement therapy
  • Body mass index < 18
  • Age < 18 years
  • Pregnant woman
  • Receiving chemotherapy or diagnosed with any disease state (e.g., AIDS)

that has produced leukopenia

  • Receiving anti-leucocyte drugs, immunosuppression or TNF-α Blockers
  • CRP > 2mg.dl-1
  • Patients receiving postoperative extracorporeal membrane oxygenation (ECMO)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Sepsis
Patients, who developed postoperative sepsis
Procedure: Cardiac Surgery
SIRS
Patients, who developed postoperative SIRS
Procedure: Cardiac Surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of IL-6
Time Frame: 10 days
Change of IL-6 over the observation period, peak and nadir comparison
10 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of PCT
Time Frame: 10 days
Change of PCT over the observation period, peak and nadir comparison
10 days
Change of bioelectrical impedance analysis
Time Frame: 10 days
Change of percent Total Body Water, Fat Free Mass over the observation period
10 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University of Vienna

Investigators

  • Principal Investigator: Martin H Bernardi, MD, Medical University of Vienna, Dept. of Cardiothoracic and Vascular Anesthesia and Intensive Care

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 30, 2016

Primary Completion (Actual)

January 26, 2018

Study Completion (Actual)

February 5, 2018

Study Registration Dates

First Submitted

July 6, 2016

First Submitted That Met QC Criteria

November 14, 2016

First Posted (Estimate)

November 15, 2016

Study Record Updates

Last Update Posted (Actual)

February 19, 2018

Last Update Submitted That Met QC Criteria

February 16, 2018

Last Verified

February 1, 2018

More Information

Terms related to this study

Other Study ID Numbers

  • 1518/2016

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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