Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000484347
Ethics application status
Approved
Date submitted
12/02/2017
Date registered
3/04/2017
Date last updated
3/04/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Influence of central venous pressure reducing manouvres on the postoperative outcome in patients undergoing major liver surgery
Scientific title
The influence of two different central venous pressure (CVP) reducing regimes used in patients undergoing liver resection using low CVP anesthesia principle on their clinical outcome, hemodynamic stability and global oxygen balance.
Secondary ID [1] 290511 0
None
Universal Trial Number (UTN)
U1111-1189-6855
Trial acronym
HOLIRES (Hemodynamic Optimization in LIver REsection Surgery)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
perioperative outcomes 300912 0
liver resection 300913 0
low central venous pressure anesthesia 302026 0
hemodynamic stability 302027 0
Condition category
Condition code
Anaesthesiology 300727 300727 0 0
Other anaesthesiology
Oral and Gastrointestinal 301774 301774 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Comparison of two strategies of reaching low central venous pressure (Low-CVP; below 5 mmHg) during liver resection surgery.
One strategy is using absolute fluid restriction (Arm 1 - intervention), the other one relative volume redistribution caused by systemic vasodilation (Arm 2 - control). Treatments in both groups will be administered by treating anaesthesiologist (member of the study team) according to the randomization during the preoperative (from morning till surgery) and intraoperative period. Treatments in both arms will be graded into predefined steps.
In the Arm 1 absolute restriction of circulating volume will be provided by reduction of preoperative fluids (neither intravenous nor oral intake 6 hours prior surgery) coupled with minimal (1ml/kg/hour, Ringerfundin solution - B´Braun) intraoperative intravenous supplementation. If needed, given the CVP value assessed by the treating anaesthesiologist, diuretics will be further administered (Furosemide 10mg intravenous per step, maximum 3 doses allowed i.e. up to three steps) to reach the low-CVP target. Participants will receive only the minimal number of steps required to reach the 5mmHg CVP target.
Intervention code [1] 296365 0
Treatment: Other
Intervention code [2] 297358 0
Treatment: Drugs
Comparator / control treatment
In the Arm 2 standard preoperative intravenous fluid replacement for fasting (6 hours prior surgery, 100ml/hour Plasmalyte solution - Baxter) will be provided coupled with restrictive fluid loading in the pre-resection period (2ml/kg/hour, Ringerfundin solution- B´Braun). Relative fluid redistribution using volatile anesthetics (inhaled sevoflurane in O2 + N2O mixture; 1.6 and 2 times minimal alveolar concentrations as steps 1 and 2) and continuous infusion of vasodilators (isosorbid dinitrate 0.1% 5ml/hour intravenous – step 3) will be used to decrease the central venous pressure till the end of liver resection phase. Participants will receive only the minimal number of steps required to reach the 5mmHg CVP target.
Control group
Active

Outcomes
Primary outcome [1] 300136 0
Ease of reaching low central venous pressure (CVP lower 5 mmHg) measured as number of predefined protocol steps needed
Timepoint [1] 300136 0
intraoperatively, prospectively - number of predefined steps of intervention needed to reach the target
Primary outcome [2] 300137 0
Composite postoperative outcome (rate of postoperative complications and/or death). Postoperative complications will be assessed by clinical, radiological or laboratory examination; screened events: death of any origin, complications - infectious (pneumonia, abdominal, urinary, catheter related blood stream infections), respiratory (respiratory failure, fluidothorax, atelectasis), cardiovascular or thrombotic (myocardial infarction, deep vein thrombosis, pulmonary embolization, stroke, postoperative bleeding), acute kidney injury and gastrointestinal (biliary leakage, hepatic dysfunction, ileus).
Timepoint [2] 300137 0
30 days,assessed by daily observation by member of the study group unaware of patients group allocation
Primary outcome [3] 300138 0
Hospital length of stay
Timepoint [3] 300138 0
till discharge, assessed by daily observation by member of the study group unaware of patients group allocation
Secondary outcome [1] 329173 0
Intraoperative blood loss
Timepoint [1] 329173 0
Intraoperatively, prospectivelly collcted by the treating anesthesiologist
Secondary outcome [2] 329174 0
Composite secondary outcome concerning oxygen debt markers (serum lactate levels and mixed venous oxygen saturation)
Timepoint [2] 329174 0
In the end of operation and 4, 8, 24 hours postoperatively
Secondary outcome [3] 331931 0
Intraoperative hemodynamic stabíility
Timepoint [3] 331931 0
Assessed prospectivelly during the operation in 3 minutes intervals using advanced hemodynamic monitoring (Vigileo/FloTrac). Time spent in hypodynamic state (Cardiac index below 2 l/min/m2) will be collected.

Eligibility
Key inclusion criteria
patients scheduled for hepatic resection of more than 2 liver segments, general anesthesia, regullar heart rhythm, signed informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
body weight less than 50 kg or more than 150 kg, irregular heart rythm, severe cardiovascular disease (chronic heart failure, valvular abnormality, cardiomyopathy etc.), severe liver dysfunction (Child Pugh score B or C)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization be performed by random drafting of sealed envelopes containing group allocation (Intervention vs. Control; 1:1 ratio)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
As the treating anesthesiologist will provide the intervention he cannot be blinded to the group allocation. All other members and hospital staff will be unaware of the group allocation (partial blinding).
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Study is designed as a hypothesis and sample size generating for further research. It is limited by study time, no calulation of minimal number of participants has been made.
The analysis will be performed using the MedCalc software (Frank Schoonjans, MedCalc Software, Broekstraat 52, 9030, Mariekerke, Belgium). The Kolmogorov –Smirnov test will be used for normality assessment. Difference in normaly distributed data will be assessed using paired or unpaired student´s t test and Mann Whitney test will be used for abnormally distributed data. For time-dependent variables, repeated measures ANOVA test or Friedman test will be performed. Categorical variables will be tested using the Chi-square test.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
11/01/2012
Date of last participant enrolment
Anticipated
Actual
4/02/2015
Date of last data collection
Anticipated
Actual
4/03/2015
Sample size
Target
30
Accrual to date
Final
34
Recruitment outside Australia
Country [1] 8383 0
Czech Republic
State/province [1] 8383 0

Funding & Sponsors
Funding source category [1] 294925 0
University
Name [1] 294925 0
Charles University Research Fund (project number P36)
Country [1] 294925 0
Czech Republic
Primary sponsor type
University
Name
Dpt. of Anesthesia and Intensive Care of The Faculty of Medicine Plzen - Charles University Prague)
Address
The University hospital and The Faculty of Medicine in Plzen
Charles University Prague
alej Svobody 80
Plzen
304 06
Country
Czech Republic
Secondary sponsor category [1] 294433 0
None
Name [1] 294433 0
Address [1] 294433 0
Country [1] 294433 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296301 0
Local ethics committee of the Charles University hospital in Plzen
Ethics committee address [1] 296301 0
Charles University hospital in Plzen
E. Benese 13
Plzen
305 99
Ethics committee country [1] 296301 0
Czech Republic
Date submitted for ethics approval [1] 296301 0
04/08/2010
Approval date [1] 296301 0
12/08/2010
Ethics approval number [1] 296301 0

Summary
Brief summary
The aim of the study is to compare the effectivity of two methods of lowering central venous pressure (CVP) on the ease to reach the predefined target of CVP lower than 5 mmHg. Patients´ postoperative outcome assessed via composite morbidity (complications rate) and mortality till 30 days and hospital length of stay as well as intraoperative safety outcomes (hemodynamic stability, markers of global oxygen debt, blood loss,) will be assessed, allowing to define simple, standardized and safe approach of low-CVP anesthesia.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 70370 0
A/Prof Jan Benes, M.D. Ph.D.
Address 70370 0
Dpt. of Anesthesiology and Intensive Care Medicine
Faculty of Medicine and Hospital in Plzen, Charles University
alej Svobody 80
Plzen, 32300
Country 70370 0
Czech Republic
Phone 70370 0
+420377104381
Fax 70370 0
+420377104359
Email 70370 0
benesj@fnplzen.cz
Contact person for public queries
Name 70371 0
Dr Jan Zatloukal
Address 70371 0
Dpt. of Anesthesiology and Intensive Care Medicine
Faculty of Medicine and Hospital in Plzen, Charles University
alej Svobody 80
Plzen, 32300
Country 70371 0
Czech Republic
Phone 70371 0
+420377104381
Fax 70371 0
+420377104359
Email 70371 0
zatloukalj@fnplzen.cz
Contact person for scientific queries
Name 70372 0
Dr Jan Zatloukal
Address 70372 0
Dpt. of Anesthesiology and Intensive Care Medicine
Faculty of Medicine and Hospital in Plzen, Charles University
alej Svobody 80
Plzen, 32300
Country 70372 0
Czech Republic
Phone 70372 0
+420377104381
Fax 70372 0
+420377104359
Email 70372 0
zatloukalj@fnplzen.cz

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