Propofol and Perioperative Inflammation

Propofol and/or Its Solvent Modify the Course of Inflammatory Response After Surgical Stress: A Randomized, Controlled, Double-blind Study

The inflammatory properties of propofol are still under debate. Apolipoprotein A-I (Apo A-I) is involved in the inflammatory process. This study was designed to determine whether and how propofol or its solvent modulate Apo A-I and the inflammatory response after surgical stress. The investigators study hypothesis was that propofol might modify the Apo A-I blood levels, and thus, modulate the postoperative inflammatory course.

Study Overview

• Status: Completed
• Conditions: Inflammation
• Intervention / Treatment: Drug: propofol; Drug: Saline; Drug: Intralipid 10%

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • Geneva, Switzerland, 1211
    • Service of Anesthesiology; Geneva University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• American Society of Anesthesiologists (ASA) I or II
• scheduled for uni- or bilateral elective laparoscopic totally extraperitoneal hernia repair

Exclusion Criteria:

• Body mass index (BMI) < 18.5 or > 39.9kg/m2
• treatments with steroids (>5mg/d prednisone equivalent, for the last 30 days)
• with opioids/non-steroidal anti-inflammatory drugs (NSAIDs) for chronic pain during the last 30 days
• immunosuppression (AIDS, neutropenia <1000 cells/ml, transplant surgery, chemotherapy)
• known lipid disorder (triglycerides >2.00mmol/l, low-density lipoprotein (LDL)-cholesterol >2.50mmol/l or high-density lipoprotein (HDL)-cholesterol < 1.00mmol/l)
• hypolipemic treatment before admission
• thyroid metabolism disorder (thyroid-stimulating hormone >6.0 mUI/l or <0.4mUI/l)
• renal insufficiency (creatinine >106umol/l)
• liver disorder (bilirubin >20umol/l, thromboplastin time <60%)
• insulin dependant diabetes
• parenteral nutrition or after any lipid-containing medication (propofol, intralipid, etomidate) during the last 30 days
• antihypertensive medication with diltiazem or other calcium channel blockers
• known chronic alcoholism (men: >65-75 ml alcohol/day)
• multidrug abuse (cocaine, heroin, methadone, or other narcotics, sedatives or stimulants)
• mental illness
• known allergy to propofol after randomization:
• change of surgical strategy
• protocol violation
• major bleeding (>0.5l)

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Propofol; Propofol anesthesia	Drug: propofol; Induction with propofol (1.5 to 2mg/kg) and maintenance of anesthesia with propofol 1% (target controlled infusion with concentration levels of 3-5 ug/ml); Other Names: Propofol, Ansiven
Active Comparator: Control; Anesthesia with isoflurane alone	Drug: Saline; Induction of anesthesia with thiopental (3-5mg/kg) and maintenance of anesthesia with isoflurane (end-expired concentration = 0.5%-2.0%); Other Names: NaCl 0.9%
Active Comparator: Solvent; Anesthesia with isoflurane together with the solvent of propofol (intralipid)	Drug: Intralipid 10%; Induction of anesthesia with thiopental (3-5mg/kg) and maintenance of anesthesia with isoflurane (end-expired concentration = 0.5%-2.0%) as well as the solvent of propofol 1% (Intralipid 10%; corresponding to a target-controlled infusion of propofol with concentration levels of 3-5ug/ml); Other Names: Intralipid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Apolipoprotein A-I level	24 hours after surgery

Secondary Outcome Measures

Outcome Measure	Time Frame
Interleukin-6 level	5 hours after surgery
C-reactive protein (CRP) level	24 hours after surgery
Cortisol level	15 min after induction of anesthesia

Collaborators and Investigators

• Sponsor: University Hospital, Geneva
• Investigators: Study Chair: Bara Ricou, Prof., Service of Intensive Care, Geneva University Hospital; Principal Investigator: Oliver Bandschapp, M.D., Service of Intensive Care, Geneva University Hospital

Publications and helpful links

General Publications

• Chenaud C, Merlani PG, Roux-Lombard P, Burger D, Harbarth S, Luyasu S, Graf JD, Dayer JM, Ricou B. Low apolipoprotein A-I level at intensive care unit admission and systemic inflammatory response syndrome exacerbation. Crit Care Med. 2004 Mar;32(3):632-7. doi: 10.1097/01.ccm.0000114820.47460.0a.
• Hyka N, Dayer JM, Modoux C, Kohno T, Edwards CK 3rd, Roux-Lombard P, Burger D. Apolipoprotein A-I inhibits the production of interleukin-1beta and tumor necrosis factor-alpha by blocking contact-mediated activation of monocytes by T lymphocytes. Blood. 2001 Apr 15;97(8):2381-9. doi: 10.1182/blood.v97.8.2381.

Study record dates

Study Major Dates

• Study Start: March 1, 2005
• Primary Completion (Actual): December 1, 2005
• Study Completion (Actual): December 1, 2005

Study Registration Dates

• First Submitted: April 27, 2010
• First Submitted That Met QC Criteria: May 3, 2010
• First Posted (Estimate): May 4, 2010

Study Record Updates

• Last Update Posted (Estimate): May 19, 2010
• Last Update Submitted That Met QC Criteria: May 17, 2010
• Last Verified: April 1, 2010

More Information

Terms related to this study

• Keywords: inflammation; propofol; lipids; perioperative; Apolipoprotein A-I
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Hypnotics and Sedatives; Pharmaceutical Solutions; Parenteral Nutrition Solutions; Fat Emulsions, Intravenous; Propofol; Soybean oil, phospholipid emulsion
• Other Study ID Numbers: APSIC 04-014; CER: 04-189 (Other Identifier: Ethics Comission)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No