Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12609001072202
Ethics application status
Approved
Date submitted
8/12/2009
Date registered
15/12/2009
Date last updated
13/12/2019
Date data sharing statement initially provided
13/12/2019
Date results information initially provided
13/12/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
A study investigating whether the administration of local anaesthetic solution via an interpleural catheter improves pain relief after liver resection surgery
Scientific title
A Randomized Clinical Trial Investigating Continuous Interpleural Analgesia for Attenuation of Postoperative Pain after Hepatic Resection
Secondary ID [1] 1196 0
Nil
Universal Trial Number (UTN)
U1111-1112-8014
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Liver surgery 252372 0
Condition category
Condition code
Anaesthesiology 256553 256553 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
For postoperative analgesia, the intervention group will receive a 20 ml loading dose of 0.5% L-bupivicaine administered via the interpleural catheter, followed by a continuous infusion of 0.125% L-bupivacaine at 10ml/hr for at least 24-postoperative hours.

In addition, the interventional group will receive multimodal analgesia with intravenous morphine delivered via a patient controlled analgesia (PCA) device. The dose of the morphine will be 1mg/ml solution, and the device set with a lockout time of 5 minutes (standard hospital protocol). The PCA will be continued for at least 24 postoperative hours. Additional multimodal analgesia will consist of strict paracetamol (1gram) intravenously/orally every 6 hours for 48 postoperative hours. Additional analgesia for breakthrough pain will consist of tramadol 100mg 6 hourly. If pain is still not controlled, an intravenous ketamine infusion will be commenced at 0.1 mg/kg/hr titrated to 0.2mg/kg/hr (as tolerated). Finally, if further rescue analgesia is required, intercostal nerve blocks with 20ml (0.5% L-bupivacaine) will be performed.
Intervention code [1] 255674 0
Treatment: Drugs
Comparator / control treatment
For postoperative analgesia, the control group will receive multimodal analgesia with intravenous morphine.

The dose of the morphine will be 1mg/ml solution, and the device set with a lockout time of 5 minutes (standard hospital protocol). The PCA will be continued for at least 24 postoperative hours. Additional multimodal analgesia will consist of strict paracetamol (1gram) intravenously/orally every 6 hours for 48 postoperative hours. Additional analgesia for breakthrough pain will consist of tramadol 100mg 6 hourly. If pain is still not controlled, an intravenous ketamine infusion will be commenced at 0.1 mg/kg/hr titrated to 0.2 mg/kg/hr (as tolerated). Finally, if further rescue analgesia is required, intercostal nerve blocks with 20ml (0.5% L-bupivacaine) will be performed.
Control group
Active

Outcomes
Primary outcome [1] 253438 0
The primary end-point measured is pain during movement assessed on a visual analog scale (VAS) using a standardized 0-100 mm line, ranging from 0, or no pain, to 100, or the most severe pain
Timepoint [1] 253438 0
The primary endpoint will be measured every hour for the the first 4 postoperative hours, then every 4 hours until 24 hours.
Secondary outcome [1] 262567 0
Cumulative morphine consumption
Timepoint [1] 262567 0
Cumulative morphine consumption will be measured every hour for the the first 4 postoperative hours, then every 4 hours until 24 hours.
Secondary outcome [2] 262623 0
Requirement for additional rescue analgesia (type, amount and duration)
Timepoint [2] 262623 0
Measured every 4 postoperative hours for 24 hours.
Secondary outcome [3] 262624 0
Complications of opioid analgesia (sedation score, respiratory depression, nausea and pruritis, return of bowel function).
Timepoint [3] 262624 0
Measured every 4 postoperative hours for 48 hours.
Secondary outcome [4] 262625 0
All major adverse postoperative outcomes (pneumonia, myocardial infarction, thromboembolic events etc).
Timepoint [4] 262625 0
Collected for 30 days after surgery.
Secondary outcome [5] 262626 0
Patient satisfaction for pain control on a five-point scale.
Timepoint [5] 262626 0
Measured at 24 and 24 postoperative hours.
Secondary outcome [6] 262627 0
Duration of hospital stay.
Timepoint [6] 262627 0
Collected for the patients duration of admission.

Eligibility
Key inclusion criteria
Adults (age > 18 years) having hepatic resection surgery with reverse L-surgical incision (right subcostal incision with a vertical midline extension)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patient refusal.
Moderate/severe renal impairment: serum creatinine > 200ummol/l.
Chronic opioid use: 1 mg or more intravenous or 3 mg or more oral morphine per hour for a period greater than 1 month may be considered to have high-grade opioid tolerance daily oral opioids.
Known allergy or intolerance to morphine or local anaesthetic solutions.
Abnormal pre-operative coagulopathy: International normalised ratio (INR) > 1.4. Thrombocytopaenia < 75 x 109/l.
Contraindication to interpleural catheter i.e. local skin infection, active pleural disease

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)
Written informed consent is obtained at the preoperative anaesthesia admission clinic 1-2 weeks prior to surgery.

For postoperative analgesia patients are randomised to one of two groups: a control group receiving intravenous morphine delivered via a patient controlled analgesic (PCA) decivce system (PCA group), and an interventional group consisting of intravenous morphine delivered via a PCA system in combination with continuous interpleural analgesia with local anaesthetic solution consisting (L-bupivacaine) – the Interpleural group. Before the study, a random-number table is electronically generated specifying the group to which each patient would be assigned. For each patient, an opaque envelope containing the group assignment is prepared, sealed and sequentially numbered. On the morning of surgery the anaesthetist will open the envelope and randomised the patients into one of the two groups.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Subjects will be randomised according to a random-number table, electronically generated, specifying the group to which each patient would be assigned.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
19/10/2006
Actual
19/10/2006
Date of last participant enrolment
Anticipated
Actual
29/06/2017
Date of last data collection
Anticipated
Actual
29/12/2018
Sample size
Target
200
Accrual to date
Final
213
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 256155 0
Hospital
Name [1] 256155 0
Austin Hospital
Country [1] 256155 0
Australia
Primary sponsor type
Hospital
Name
Austin Hospital
Address
Department of Anaesthesia
Studley Road
Heidelberg, Victoria, 3084
Country
Australia
Secondary sponsor category [1] 251494 0
None
Name [1] 251494 0
Address [1] 251494 0
Country [1] 251494 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258255 0
Austin Hospital Research Ethics Committee
Ethics committee address [1] 258255 0
Research Ethics Committee
Studley Road, Heidelberg 3084
Victoria
Ethics committee country [1] 258255 0
Australia
Date submitted for ethics approval [1] 258255 0
Approval date [1] 258255 0
01/10/2006
Ethics approval number [1] 258255 0
Project Number: 02636

Summary
Brief summary
It is not known from published data how to best provide postoperative pain relief for patients who undergo major liver surgery. Many institutions that specialise in hepatobiliary surgery like Austin Health use intravenous morphine in addition to regional techniques such as an epidural or an interpleural catheter to provide postoperative analgesia. Research however shows that after patients undergo major liver surgery, there are significant disturbances in the clotting system of the body. This may increase the risk of bleeding complications. For this reason many institutions now consider epidural catheters to be unsafe in this setting because of the increased risk of epidural haematoma with the devastating neurological complication of spinal cord compression and paraplegia. At Austin Health, the standard accepted practice in providing postoperative analgesia after liver surgery is intravenous morphine, either alone or in combination with an interpleural catheter. An interpleural catheter is a small tube that is placed between the linings layers of the lungs by the anaesthetist at the end of the operation. A solution of local anaesthetic is infused continuously into the interpleural space, which then numbs the nerves that supply the skin over the surgical wound, reducing postoperative pain. Interpleural catheters have been shown to be effective in the management of pain following thoracic and upper abdominal surgery with minimal risks. However, no study has investigated whether the routine use of interpleural catheters after liver surgery is advantageous over morphine alone. The theoretical advantages of using an interpleural catheter is that it may result in less morphine being used, thereby reducing morphine related complications such as respiratory depression, sedation, nausea, vomiting and itch. However an interpleural catheter may not improve pain at all, therefore its use may be an unnecessary intervention that can be associated with uncommon complications such as infection, local anaesthetic toxicity and rarely a punctured lung. These questions have never been investigated in any scientific way before; therefore this study will help answer these questions and make a valuable contribution to caring for patients undergoing liver surgery.

The purpose of this study is to compare whether the use of an interpleural catheter together with morphine provides better postoperative pain relief than just morphine alone. The provision of postoperative analgesia and the management of the patient in the postoperative period will not be changed or modified in any way as per the current postoperative guidelines and practices for analgesia after liver surgery. Patients undergoing suitable liver surgery will be invited to participate in the study. They will be approached after consenting for surgery in the hepatobiliary or anaesthetic outpatient clinics. All patients will have a general anaesthetic and surgery performed according to the usual practice of their caring clinicians. All patients will receive intravenous morphine together with simple analgesic adjuvants such as paracetamol. This is standard practice at Austin for all patients undergoing liver resection. Consenting patients will then be randomised into 2 groups. One group will receive an interpleural catheter with an infusion of local anaesthetic solution, the other group will not. Both techniques are considered standard practice at many centers that specialise in hepatobiliary surgery, including Austin Health.

The main study aim will be to collect data from the patient’s postoperative records and assess there level of pain and how much morphine each group uses. These are standard parameters and observations routinely recorded in the patients records. We will use standard statistical tests to analyse the differences between the two groups of patients. The primary end-point will be pain on movement during the first 24 postoperative hours. Other end points will be cumulative 24 hour morphine consumption, with sufficient subjects being enrolled to find a 25% difference in morphine use between the two groups. Other end-points to be measured at 6, 12, 24 and 48 hours and will include patient rated scores for pain, nausea and itchiness, nurse-rated sedation score, and cumulative morphine doses. These are standard parameters and observations recorded for all patients. Subjects will be asked to rate their satisfaction with their postoperative analgesia on a qualitative scale at the completion of the trial.

All patients will be managed by the Austin Health acute pain service guidelines, in accordance with standard practices for morphine and interpleural catheter based regimes.
Trial website
Trial related presentations / publications
Publication: Weinberg L, Scurrah N, Parker F, Story D, McNicol L.Interpleural analgesia for attenuation of postoperative pain after hepatic resection. Anaesthesia. 2010 Jul;65(7):721-8. doi: 10.1111/j.1365-2044.2010.06384.x. Epub 2010 Ju
Public notes

Contacts
Principal investigator
Name 30601 0
A/Prof Laurence Weinberg
Address 30601 0
Department of Anaesthesia, Austin Hospital, Studley Road, Heidelberg, 3084, Victoria
Country 30601 0
Australia
Phone 30601 0
+61394965000
Fax 30601 0
+6139496421
Email 30601 0
laurence.weinberg@austin.org.au
Contact person for public queries
Name 13848 0
A/Prof Dr Laurence Weinberg
Address 13848 0
Department of Anaesthesia
Studley Road, Heidelberg, Victoria, 3084
Country 13848 0
Australia
Phone 13848 0
+61 3 94965000
Fax 13848 0
+6139496421
Email 13848 0
Laurence.Weinberg@austin.org.au
Contact person for scientific queries
Name 4776 0
A/Prof Laurence Weinberg
Address 4776 0
Department of Anaesthesia
Studley Road, Heidelberg, Victoria, 3084
Country 4776 0
Australia
Phone 4776 0
+61 3 94965000
Fax 4776 0
+61394966421
Email 4776 0
Laurence.Weinberg@austin.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.