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Trial registered on ANZCTR


Registration number
ACTRN12614001135606
Ethics application status
Approved
Date submitted
30/09/2014
Date registered
27/10/2014
Date last updated
7/06/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
The impact of general anesthesia applied alone or with epidural anesthesia on stress response caused by laparoscopic cholecystectomy, using hormonal, metabolic and inflammatory markers.
Scientific title
A randomized trial to evaluate the impact of general anesthesia alone or supplemented with epidural anesthesia on surgical stress response during laparoscopic cholecystectomy for uncomplicated symptomatic cholelithiasis, using stress hormones, glucose and C-reactive protein, as potential markers.
Secondary ID [1] 285392 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Surgical stress response to laparoscopic cholecystectomy 293129 0
Cholelithiasis 293323 0
Condition category
Condition code
Anaesthesiology 293396 293396 0 0
Other anaesthesiology
Oral and Gastrointestinal 293397 293397 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Surgery 293592 293592 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients undergoing laparoscopic cholecystectomy will be randomly assigned, to receive either general anesthesia or lumbar epidural anesthesia supplemented by general anesthesia. In general anesthesia group, following preoxygenation and an intravenous induction sequence consisting of propofol (2.5 mg/kg), lidocaine (1-1.5 mg/kg), fentanyl (2 microg/kg) and cis-atracurium (0.2 mg/kg), laryngoscopy and orotracheal intubation will be performed.
In lumbar epidural anesthesia with supplemental general anesthesia group, an epidural catheter will be placed through the intervertebral space between T12 and L1 or L1 and L2 before induction of anesthesia. Then, a bolus dose of ropivacaine 10% (15 +/- 2 ml) will be injected while epidural anesthesia will be considered as adequate when sensory blockade reaches the T4 level. Induction of anesthesia will be identical to the one previously described for general anesthesia group.
In both groups, blood samples for resting plasma concentrations of cortisol, human growth hormone, prolactin, glucose and C-reactive protein determination, will be collected at 9 AM on the day prior to surgery, intraoperatively (just before termination of pneumoperitoneum) and on the first postoperative day.
Furthermore, intraoperative hemodynamic data will be recorded on seven predefined time points: following anesthesia induction, during institution of CO2 pneumoperitoneum, 15 minutes, 30 minutes, 45 minutes and termination of pneumoperitoneum and end of surgical procedure.
Intervention code [1] 290306 0
Prevention
Intervention code [2] 290403 0
Treatment: Drugs
Comparator / control treatment
The control treatment will be the performance of laparoscopic cholecystectomy under general anesthesia, which will be tested against to the combination of general plus epidural anesthesia.
Control group
Active

Outcomes
Primary outcome [1] 293227 0
Surgical stress response.
Blood samples for stress hormones determination, will be kept on ice (4 degrees Celsious), until centrifugation at 1000 g for 15 minutes within 30 minutes of collection and thereafter, the serum will be separated and stored at -30 degrees Celcius until further analyzed with radioanosometric method. PRL and GH will be analyzed by a solid-phase, two-site chemiluminescent immunometric assay with a detection limit of 1.9 to 25 ng/ml and 0.06 to 5 ng/ml, respectively. Solid-phase, competitive chemiluminescent enzyme immunoassay will be used for detection of COR with morning normal values range between 5 to 20 microg/dL. Plasma glucose levels will be determined by a glucose oxydase method, while serum concentration of CRP will be measured by an immunoprecipitation method.
Timepoint [1] 293227 0
Blood samples for resting plasma concentrations of cortisol, human growth hormone, prolactin, glucose and C-reactive protein determination, will be collected at 9 AM on the day prior to surgery (baseline), intraoperatively (just before termination of pneumoperitoneum) and on the first
postoperative day.
Primary outcome [2] 293360 0
Hemodynamic variables such as heart rate and mean arterial blood pressure will also be recorded intraoperatively. Heart rate will be assessed by ECG recording and mean arterial pressure will be recorded by direct arterial pressure monitoring.
Timepoint [2] 293360 0
Intraoperative hemodynamic data including heart rate and mean arterial pressure, will also be recorded on seven predefined time points: following anesthesia induction (time point 1), during institution of CO2 pneumoperitoneum, 15 minutes, 22 minutes, 30 minutes, 45 minutes and termination of pneumoperitoneum (time points 2, 3, 4, 5 and 6) and end of surgical procedure (time point 7).
Secondary outcome [1] 310629 0
Postoperative analgesic efficacy will be graded with a 10 cm Visual Analogue Scale.
Timepoint [1] 310629 0
Visual Analogue Scale will be assessed at rest on postoperative hours 1, 6 and 24.

Eligibility
Key inclusion criteria
Adult patients scheduled to undergo elective laparoscopic cholecystectomy for uncomplicated symptomatic cholelithiasis, will be eligible for inclusion.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria are age < 18 years, ASA physical status > 2, body mass index more than 35 kg/m2, a history of spinal cord surgery, pre-existing coagulation disorders, any medication or organ failure known to interact with stress hormones and sensitivity reactions to amide local anesthetics.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis
A sample size of 22 subjects in each group was estimated for a type 1 error of 0.05 (a= 0.05) and a power of 80%. The power was increased to 90% with eight patients in each group. Ultimately, 31 patients were selected in each group to minimize the impact of potential independent variables on stress-hormones release or to compensate for possible drop-outs. An estimated > 25% difference in stress hormones plasma levels between groups was defined as the primary end-point.
Two-way analysis of variance for repeated measurements with Greenhouse-Geisser correction, was conducted to analyze continuous variables over time. Normality of data was assessed by Kolmogorov–Smirnov test. Student’s t-test or Mann Whitney U test were used for comparison of means between two groups, as appropriate. Subgroup comparisons of categorical variables were assessed by a chi-square or Fisher’s exact test.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 6375 0
Greece
State/province [1] 6375 0

Funding & Sponsors
Funding source category [1] 289997 0
Self funded/Unfunded
Name [1] 289997 0
Georgia Tsaousi
Address [1] 289997 0
Maiandrou 32-GR 56224- Thessaloniki
Country [1] 289997 0
Greece
Primary sponsor type
Individual
Name
Georgia Tsaousi
Address
Aristotle University of Thessaloniki
Maiandrou 32-GR 56224- Thessaloniki
Country
Greece
Secondary sponsor category [1] 288682 0
Individual
Name [1] 288682 0
Irini Sidiropoulou
Address [1] 288682 0
Aristotle University of Thessaloniki
Stilponos Kiriakidi 1-GR 54636-Thessaloniki
Country [1] 288682 0
Greece

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293958 0
Ethics Committe of Ahilopouleio General Hospital
Ethics committee address [1] 293958 0
5th YPE of Thessaly and Sterea Ellada
Ethics committee country [1] 293958 0
Greece
Date submitted for ethics approval [1] 293958 0
10/03/2014
Approval date [1] 293958 0
09/04/2014
Ethics approval number [1] 293958 0
6/02-04-2014/120a

Summary
Brief summary
We aim to investigate the impact of general anesthesia alone or supplemented with epidural anesthesia on the perioperative response to surgical stress. Thus, we will study the comparable changes in hemodynamics, stress hormones (cortisol, human growth hormone and prolactin), glucose levels and C-reactive protein levels in patients undergoing laparoscopic cholecystectomy procedures. We would like to test the hypothesis that general anesthesia supplemented with epidural anesthesia exerts a favourable impact on surgical stress hormone compared to general anesthesia alone.
Trial website
Trial related presentations / publications
Not applicable
Public notes

Contacts
Principal investigator
Name 51642 0
A/Prof Georgia Tsaousi
Address 51642 0
Aristotle University of Thessaloniki
Maiandrou 32-GR56224-Thessaloniki
Country 51642 0
Greece
Phone 51642 0
+30 2310994862
Fax 51642 0
+30 2310994860
Email 51642 0
tsaousig@otenet.gr
Contact person for public queries
Name 51643 0
A/Prof Georgia Tsaousi
Address 51643 0
Aristotle University of Thessaloniki
Maiandrou 32-GR56224-Thessaloniki
Country 51643 0
Greece
Phone 51643 0
+30 2310994862
Fax 51643 0
+30 2310994860
Email 51643 0
tsaousig@otenet.gr
Contact person for scientific queries
Name 51644 0
A/Prof Georgia Tsaousi
Address 51644 0
Aristotle University of Thessaloniki
Maiandrou 32-GR56224-Thessaloniki
Country 51644 0
Greece
Phone 51644 0
+30 2310994862
Fax 51644 0
+30 2310994860
Email 51644 0
tsaousig@otenet.gr

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary