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.

NCT01880190 | Completed

• 1 other identifier: 301
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

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.

Conditions

Postoperative Inflammation

Outcome Measures

Primary Outcomes (1)

• Measurement of inflammatory biomarkers (MMP-9, MMP-13, TIMP-1, IL-6, IL-8 ICAM-1) in abdominal surgery.

  24 hours postoperatively

Study Arms (2)

Ringer's Lactate

ACTIVE COMPARATOR

Crystalloid solution

Other: Ringer's Lactate

HES 130/0.4 and Ringer's Lactate

ACTIVE COMPARATOR

Colloid solution

Other: HES 130/0.4 and Ringer's Lactate

Interventions

Ringer's Lactate OTHER

Ringer's Lactate

HES 130/0.4 and Ringer's Lactate OTHER

HES 130/0.4 and Ringer's Lactate

Eligibility Criteria

• Age: 18 Years - 76 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ASA (American Society of Anesthesiologists) I and ASA II

You may not qualify if:

• 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

Sponsors & Collaborators

• Paraskevi Matsota: lead

Study Sites (1)

2nd Department of Anesthesiology, Attikon University Hospital

Athens, Attica, 12462, Greece

Location

MeSH Terms

Interventions

Ringer's Lactate; Hydroxyethyl Starch Derivatives

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Starch; Dietary Carbohydrates; Carbohydrates; Glucans; Polysaccharides

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Anesthesiology, MD, PhD

Study Record Dates

• First Submitted: June 14, 2013
• First Posted: June 18, 2013
• Study Start: December 1, 2008
• Primary Completion: April 1, 2010
• Last Updated: July 15, 2013

Record last verified: 2013-07

Locations

GR (1)