- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01902849
Anesthetic Technique on Immune Response in Colorectal Cancer (T-IL-Co-ReCa)
The Influence of Anesthetic Technique on Interleukin Plasma Level in Colorectal Cancer Surgery - TIVA vs Inhalation Anesthesia
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Introduction
Several factors are contributing to perioperative immunosuppression such as: surgery itself, general anesthesia. In vivo and in vitro studies have shown that anesthesia itself may alter the immune response either by direct effect on immune cells (such as natural killer and T helper) ) or indirectly by the influence of anesthetic substances on pro (IL-1, IL-6, tumor necrosis factor alpha ) and anti-inflammatory ( IL-4, IL-10) cytokines release.
The study aims to evaluate the influence of two general anesthetic techniques inhalation versus total intravenous anesthesia- target controlled infusion (TIVA-TCI) on the immune response in patient with colorectal surgery for neoplastic disease, evaluated by the plasma level of the interleukins IL6, IL10.
Study group:
- patients admitted to the Surgical Clinic of the Regional Institute of Gastroenterology and Hepatology Prof Dr Octavian Fodor, undergoing open surgery for colorectal cancer (right/left colectomy, colorectal resection).
After obtaining written informed consent 70 ASA physical status I-III patients scheduled for colorectal cancer resection are randomly allocated to 2 groups of study by computer randomization:
- group I, TIVA-TCI (n=35 patient) receive total intravenous-target controlled infusion anesthesia with propofol and remifentanil
- group II (ISOFLURANE) (n=35 patients) receive inhalatory anesthesia with isoflurane and remifentanil
Methods:
- Premedication with midazolam 7.5 mg orally 30 min before surgery in all patients.
- On arrival in the operating room a venous cannula is inserted and a blood sample for interleukin measurement is performed. This cannula is designated for fluid administration during anesthesia and for blood sampling for subsequent interleukin measurements. A second cannula is inserted for the administration of anesthetic substances.
In group I (TIVA-TCI):
- anesthesia is induced with a target-controlled infusion (TCI) of propofol with an initial target plasma concentration (Cp) of 4 micrograms/ml (modified Marsh model)( Base Primea™, Fresenius, France), adjusted in steps 0.2 micrograms/ml to maintain the BIS values between 40-55 during surgery.
- propofol infusion stops at the end of surgery before the last 2 stitches.
In group II (ISOFLURANE):
- anesthesia is induced with propofol bolus 1,5-2 mg/kg.
- maintenance of anesthesia is achieved with isoflurane 1-1.5 MAC in order to maintain the BIS value between the values of 40-55.
- isoflurane administration cease before the last 2 stitches.
In both groups:
- remifentanil TCI mode (Minto model) (Base Primea™, Fresenius, France) is used for analgesia, with an initial Cp of remifentanil set at 4 ng/ml at induction, and a Cp between 3-8 ng/mL during maintenance(increments of 0.5 ng/ml) depending on the painful moments of surgery and the patient's analgesic needs assessed by changes in heart rate, blood pressure (more than 20% of the previous value of induction), sweating, tearing.
- remifentanil infusion ceases after suturing the wound.
- muscle relaxation is achieved with atracurium, 0.5-0.6 mg/kg at induction, and further maintained on top up doses as needed. At the end of surgery the residual neuromuscular blockade is reversed with atropine 0.02mg/kg and neostigmine 0.0 5mg/kg.
- the lungs are ventilated with an air/oxygen mixture.
Postoperative analgesia:
- morphine patient controlled analgesia(PCA ) with boluses of 1 mg to 5 min interval to maintain the VAS ˂ 4 on 10-point visual analogue scale (VAS). The first dose of morphine 0.1 mg/kg is administered 40 minutes before completing the surgery.
- in addition to morphine, is given paracetamol intravenous, 1g every 8 hours. The first dose of paracetamol is administered intra-operatively before the end of surgery.
Monitoring:
Intraoperative:
- ASA basic monitoring: continuous monitoring ECG, heart rate (HR), arterial blood pressure (BP), pulse oximetry (SpO2), CO2 concentration in expired gases (Et CO2), concentration of isoflurane in exhaled gases (Et Iso), minimum alveolar concentration (MAC) of isoflurane, and core temperature.
- depth of anesthesia - bispectral index (BIS) (BIS Vista -Aspect Medical System, USA).
Systolic, diastolic blood pressure and HR are recorded every minute at induction time and every 5 minutes after endotracheal intubation, until the end of surgery.
Hypotension (defined as a decrease of mean arterial blood pressure by over 20% of baseline values) is treated with higher rate of infusion solutions and intravenous boluses of ephedrine 5 mg.
Inadequate anesthesia (hypertension, tachycardia, lacrimation, sweating) is treated by adjusting the remifentanil infusion as previously mentioned.
Postoperative:
- opioid analgesic requirement in the first 24 hours
- pain score on the visual analog scale (VAS 0-10)in the first 24 hour
- incidence of postoperative nausea and vomiting episodes requiring the administration of antiemetic drug (metoclopramide 20 mg or ondansetron 4 mg)
Blood sampling to determine interleukins IL6 , IL10 plasma levels are drawn at the following moments:
- T0- before the induction of anesthesia (venous cannula insertion time)
T1- after induction but before starting surgery:
- in group I (TIVA -TCI) when the plasma concentration of propofol is 3-3.5 micrograms/ml
- in group II (ISOFLURANE) when concentration of isoflurane in exhaled air (Et Isoflurane) is between 0.3-0.5%
- T2, T3 - at 2 and 24 hours after surgery
The collected blood samples are centrifuged at 2500 rpm / min for 10 minutes and the resulting plasma is stored at -70 ° C until the interleukins assay is performed.
If intraoperatively is revealed local extension of colorectal cancer (tumor invades adjacent organs) or distant metastasis the patient is excluded from the study.
Data collection is done longitudinally prospective, for each patient the following variable are registered:
- quantitative: - weight, plasmatic or brain concentration of the anesthetics used in TIVA-TCI mode, BIS value, plasmatic concentration of the interleukins on 4 intra- and post-operatory moments, the duration of the surgery and anesthesia, number of episodes of nausea and vomiting, opioid analgesic requirement.
- qualitative: ASA score, sex, post-operatory pain score (VAS) Collected data are introduced in a database using the Excel Office programme.
The statistical analysis will be performed using the SPSS 16.0 software (SPSS Inc Chicago, IL, USA). Quantitative variables will be expressed as mean ± SD, and qualitative variables as absolute and relative frequencies. Given multiple measurements at different time intervals, area under curve (AUC) is calculated for each IL and the results will be compared between groups.A p less 0.05 will be considered significant.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
-
Cluj Napoca, Romania, 400162
- University of Medicine and Pharmacy Iuliu Hatieganu; Regional Institute of Gastroenterology and Hepatology Prof Dr Octavian Fodor
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- patients over 18 years with ASA physical status I-III.
- colorectal cancer patients with no sign of local invasion (adjacent organs) and distant metastasis revealed by imaging studies
- surgery performed by the same surgical team
Exclusion Criteria:
- ASA physical status IV patients
- hepatic and renal impairment
- diabetes or other endocrine disorders
- obesity (BMI 30 kg/m2)
- immune disorders or immunosuppressive therapy
- steroid treatment in the last 6 months
- asthma
Study Plan
How is the study designed?
Design Details
- Observational Models: Case-Control
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Group 1 - TIVA-TCI
|
Blood sampling to determine interleukins IL6 , IL10 plasma levels are drawn at the following moments:
|
Group II- ISOFLURANE
|
Blood sampling to determine interleukins IL6 , IL10 plasma levels are drawn at the following moments:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
measurement of interleukins IL6 and IL 10 plasmatic level
Time Frame: -before anesthesia induction (T0 time)
|
-once the intravenous cannula is inserted
|
-before anesthesia induction (T0 time)
|
measurement of interleukins IL6, IL10 plasmatic level
Time Frame: after anesthesia induction but before surgical incision (T1)
|
|
after anesthesia induction but before surgical incision (T1)
|
measurement of interleukins IL6 and IL10 plasmatic level
Time Frame: 2 hours postoperatively (T2)
|
2 hours postoperatively (T2)
|
|
measurement of interleukins IL6 and IL 10 plasmatic level
Time Frame: 24 hours postoperatively (T3)
|
24 hours postoperatively (T3)
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
total opioid analgesic dose (mg)
Time Frame: for the first 24 hours postoperatively
|
for the first 24 hours postoperatively
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pain score on the visual analog scale (VAS 0-10)
Time Frame: for the first 24 hour postoperatively
|
at 15, 30 minutes post surgery 6, 12, 18, 24 hours postoperatively
|
for the first 24 hour postoperatively
|
incidence of postoperative nausea and vomiting episodes requiring antiemetic medication
Time Frame: for the 24 hours postoperatively
|
for the 24 hours postoperatively
|
|
total opioid dose of remifentanil (mg ) used during surgery
Time Frame: an average 3 hours
|
total dose (mg) of remifentanil administered in TCI mode during surgery
|
an average 3 hours
|
Collaborators and Investigators
Investigators
- Principal Investigator: Simona C Margarit, lecturer, University of Medicine and Pharmacy Iuliu Hatieganu
Publications and helpful links
General Publications
- Ke JJ, Zhan J, Feng XB, Wu Y, Rao Y, Wang YL. A comparison of the effect of total intravenous anaesthesia with propofol and remifentanil and inhalational anaesthesia with isoflurane on the release of pro- and anti-inflammatory cytokines in patients undergoing open cholecystectomy. Anaesth Intensive Care. 2008 Jan;36(1):74-8. doi: 10.1177/0310057X0803600113.
- Margarit SC, Vasian HN, Balla E, Vesa S, Ionescu DC. The influence of total intravenous anaesthesia and isoflurane anaesthesia on plasma interleukin-6 and interleukin-10 concentrations after colorectal surgery for cancer: a randomised controlled trial. Eur J Anaesthesiol. 2014 Dec;31(12):678-84. doi: 10.1097/EJA.0000000000000057.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- TICC
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.
Clinical Trials on Colorectal Neoplasms
-
City of Hope Medical CenterRecruitingColorectal Neoplasms | Colorectal Cancer | Colorectal Adenocarcinoma | Colorectal Cancer Stage II | Colorectal Cancer Stage III | Colorectal Cancer Stage IV | Colorectal Neoplasms Malignant | Colorectal Cancer Stage IUnited States, Japan, Italy, Spain
-
NuCana plcCompletedColorectal Neoplasms | Colorectal Cancer | Colorectal Tumors | Colorectal Carcinoma | Neoplasms, ColorectalUnited States, France, United Kingdom
-
Emory UniversityBristol-Myers Squibb; National Cancer Institute (NCI); National Institutes of...Active, not recruitingColorectal Cancer Metastatic | Colorectal Adenocarcinoma | Stage IV Colorectal Cancer | Stage IVA Colorectal Cancer | Stage IVB Colorectal Cancer | Refractory Colorectal Carcinoma | Metastatic Microsatellite Stable Colorectal Carcinoma | Stage IVC Colorectal CancerUnited States
-
The Queen Elizabeth HospitalNovartis; AmgenCompletedColorectal Cancer | Colorectal Tumors | Colorectal Carcinoma | Neoplasms, ColorectalAustralia
-
Novartis PharmaceuticalsCompletedColorectal Cancer | Colorectal Tumors | Colorectal Carcinoma | Neoplasms, ColorectalUnited States
-
Pawel KalinskiNational Cancer Institute (NCI)CompletedColorectal Neoplasms | Colorectal Cancer | Colorectal Tumors | Colorectal Carcinoma | Neoplasms, ColorectalUnited States
-
Jeremy MeyerUniversity Hospital, Geneva; Hôpital Fribourgeois; Spital Biel, SwitzerlandNot yet recruitingColorectal Neoplasms | Colorectal Cancer | Colorectal Adenoma | Colorectal Adenocarcinoma | Colorectal Polyp | Colorectal Neoplasms Malignant | Colorectal Neoplasms, Benign
-
ProgenaBiomeRecruitingColorectal Neoplasms | Colorectal Cancer | Colorectal Cancer Metastatic | Colorectal Carcinoma | Colorectal Adenocarcinoma | Colorectal SarcomaUnited States
-
Bristol-Myers SquibbNovartisActive, not recruitingColorectal Cancer | Colorectal Neoplasm | Colorectal Tumors | Colorectal CarcinomaItaly, United States, Canada, Spain, Argentina, Australia, Belgium, Chile, Czechia, Germany
-
City of Hope Medical CenterRecruitingColorectal Neoplasms | Colorectal Cancer | Colorectal Disorders | Colorectal Adenocarcinoma | Colorectal Cancer Stage II | Colorectal Cancer Stage III | Colorectal Cancer Stage IV | Colorectal Polyp | Colorectal Neoplasms Malignant | Colorectal Adenomatous Polyp | Colorectal Cancer Stage I | Colorectal Adenoma... and other conditionsUnited States, Italy, China, Spain, Japan
Clinical Trials on blood sampling for IL measurement
-
Hospices Civils de LyonCompletedShort Bowel Syndrome | Hyperoxaluria | HyperoxalemiaFrance
-
Hasanuddin UniversityRecruitingVitamin D DeficiencyIndonesia
-
University Hospital, MontpellierNot yet recruitingIdiopathic Intracranial HypertensionFrance
-
Institut Mutualiste MontsourisInstitut National de la Santé Et de la Recherche Médicale, FranceRecruitingRenal Cell Carcinoma | Cancer | Bladder Cancer | MSI-H CancerFrance
-
University Hospital, CaenTerminatedCritical Illness | Kidney Failure, AcuteFrance
-
Nantes University HospitalCompletedNeonatal Acute Renal Failure in PretermFrance
-
GWT-TUD GmbHNovartisCompletedDiabetic Macular EdemaGermany
-
Institut du Cancer de Montpellier - Val d'AurelleLigue contre le cancer, FranceRecruiting