A Comparative Study of Volume Replacement With HES 130/0.4 Versus Ringer's Lactate (RL) Regarding Their Effects on Inflammatory Biomarkers (Cytokines and Matrix Metalloproteinases) Responses to Major Abdominal Surgery.

Sponsor

Paraskevi Matsota (Other)

Overall Status

Completed

CT.gov ID

NCT01880190

Collaborator

(none)

Enrollment

Location

Arms

Study Details

Study Description

Brief Summary

Various stimuli such as trauma, infection and major surgery may alter the physiologic immune balance and initiate systemic inflammatory processes. This pathophysiological event is characterized by the release of potent inflammatory mediators into the circulation.

Among these, pro- and anti-inflammatory cytokines such as interleukin-6 (IL-6), IL-8 or IL-10, ICAM-1 play a dominant role as local or systemic regulators in the acute inflammatory response. Recent studies have also investigated the role of matrix metalloproteinases (MMPs) in the inflammatory response. The MMPs constitute a family of enzymes that are structurally related neutral proteinases. MMPs can degrade essentially all extracellular matrix (ECM) components and play an important role in wound healing and remodeling of the ECM. The Tissutal Inhibitor MetalloProteine (TIMPs) are important regulator of MMPs activity.

The inflammatory response coming of surgery mainly affects surgical patients' outcome. Many factors may attributed to this response, such as the kind of operation, the extent of surgical trauma, the patient's medical history and therapy, as well as the type of anesthesia used. Apart from that, the kind of fluids administered for volume replacement was revealed to alter the inflammatory processes. Several studies have addressed on this issue mainly involved abdominal surgery and provided compelling evidence that perioperative fluid optimization produces benefits for the patient, with regard to inflammatory biomarkers such as cytokines, matrix metalloproteinases, intercellular adhesion molecule-1(ICAM-1). They support that the different volume replacement strategies, using only crystalloids or combination of crystalloids with colloids (HES 130/0,4), may have important impact on immune response. However, the relevant studies investigated different inflammatory biomarkers, and usually involved either metalloproteinases, and their inhibitors (TIMPs) or cytokines.

In our study we investigated the hypothesis that intra- and postoperative volume replacement with HES attenuates inflammatory response to elective abdominal surgery compared to RL fluid therapy. For this purpose both metalloproteinases, MMP-9, MMP-13, their inhibitor, TIMP-1, cytokines, IL-6, IL-8 and the intercellular adhesion molecule-1, ICAM-1 were investigated postoperatively. Their changes during the first 24 postoperative hours consisted our primary outcomes.

Condition or Disease	Intervention/Treatment	Phase
Postoperative Inflammation	Other: Ringer's Lactate Other: HES 130/0.4 and Ringer's Lactate	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

47 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Outcomes Assessor)

Official Title:

Volume Replacement With HES 130/0.4 Attenuates Inflammatory Response to Major Abdominal Surgery Compared to Ringer's Lactate (RL); the Effect on Cytokines and Matrix Metalloproteinases

Study Start Date :

Dec 1, 2008

Actual Primary Completion Date :

Apr 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Ringer's Lactate Crystalloid solution	Other: Ringer's Lactate
Active Comparator: HES 130/0.4 and Ringer's Lactate Colloid solution	Other: HES 130/0.4 and Ringer's Lactate

Arm

Intervention/Treatment

Active Comparator: Ringer's Lactate

Crystalloid solution

Other: Ringer's Lactate

Active Comparator: HES 130/0.4 and Ringer's Lactate

Colloid solution

Other: HES 130/0.4 and Ringer's Lactate

Outcome Measures

Primary Outcome Measures

Measurement of inflammatory biomarkers (MMP-9, MMP-13, TIMP-1, IL-6, IL-8 ICAM-1) in abdominal surgery. [24 hours postoperatively]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 76 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

ASA (American Society of Anesthesiologists) I and ASA II

Exclusion Criteria:

cardiac insufficiency ( > New York Heart Association (NYHA) class II)
renal insufficiency (serum creatinine > 200μm/L)
severe pulmonary disease (chronic obstructive lung disease, PaO2 < 70 mmHg when FiO2= 0.21)
liver disfunction (AST > 40 U/L, ALT > 40 U/L)
diabetes mellitus
autoimmune disease
pre-existing signs of bacterial (WBC > 10000, body temperature > 38.0 C)or viral infection (HBV, HCV, HIV, CMV)
pre-existing signs of active inflammation (CRP > 4)
malignant neoplasia
morbid obesity
patients in extreme muscular activity (athletes)
patients with chronic use of corticosteroids or β- blockers or non-steroid anti-inflammatory substances
known allergic reactions to colloids solutions

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	2nd Department of Anesthesiology, Attikon University Hospital	Athens	Attiki	Greece	12462

Sponsors and Collaborators

Paraskevi Matsota

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Paraskevi Matsota, Assistant Professor of Anesthesiology, MD, PhD, Attikon Hospital

ClinicalTrials.gov Identifier:

NCT01880190

Other Study ID Numbers:

First Posted:

Jun 18, 2013

Last Update Posted:

Jul 15, 2013

Last Verified:

Jul 1, 2013

Additional relevant MeSH terms:

Inflammation

Study Results

No Results Posted as of Jul 15, 2013