Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001567718
Ethics application status
Approved
Date submitted
9/12/2022
Date registered
19/12/2022
Date last updated
19/12/2022
Date data sharing statement initially provided
19/12/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
Postoperative pain and outcomes using spinal analgesia in hepatobiliary-pancreatic surgery
Scientific title
Postoperative pain and outcomes following multimodal spinal analgesia using intrathecal morphine in hepatobiliary-pancreatic surgery: a multicentre retrospective study
Secondary ID [1] 308588 0
None
Universal Trial Number (UTN)
U1111-1285-9685
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Post-operative pain 328453 0
Analgesia following liver surgery 328455 0
Condition category
Condition code
Surgery 325485 325485 0 0
Surgical techniques
Anaesthesiology 325486 325486 0 0
Pain management
Oral and Gastrointestinal 325487 325487 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cancer 325488 325488 0 0
Liver
Cancer 325489 325489 0 0
Pancreatic

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This is a retrospective analysis of intrathecal analgesia in adult patients who underwent liver and pancreatic resection between January 2010 and June 2021 using a standardized enhanced recovery after surgery protocol. The enhanced recovery after surgery protocol was introduced across all hospitals in January 2010.

We will compare patients who received intrathecal morphine only to those patients who received intrathecal morphine in combination with intrathecal clonidine and bupivacaine.

Patients who underwent surgery at three university teaching hospitals will be included. Austin Hospital, is a university hospital in Melbourne, Australia with a dedicated high volume hepato-pancreatic-biliary and liver transplant centre. Knox Private and Warringal Private Hospitals are teaching hospitals with expertise in major hepato-pancreatic-biliary surgery.

Eligible patients were identified by International Statistical Classification of Diseases (ICD) codes that included the following surgical categories:
i.) excision of lesion of liver
ii.) segmental resection of liver
iii.) lobectomy of liver,
iv.) trisegmental resection of liver
v.) Whipples procedure
vi). Distal pancreatectomy with or without splenectomy
vii). Other pancreatic resection (total or central pancreatectomy)

Patients will be followed-up until hospital discharge from their index admission. As this is a retrospective study, there is no patient involvement.
Intervention code [1] 325032 0
Diagnosis / Prognosis
Comparator / control treatment
A comparison is being made between patients who received intrathecal morphine only and patients who received intrathecal morphine in combination with intrathecal clonidine and bupivacaine.
Control group
Active

Outcomes
Primary outcome [1] 333335 0
The primary outcome is cumulative oral morphine equivalent daily dose in milligrams (oMEDD) on post operative Day 1. This will be collected from the electronic medical records.
Timepoint [1] 333335 0
Oral morphine equivalent daily dose in milligrams amounts on postoperative Day 1 will be collected from the patient's hospital electronic medical record. Oral morphine equivalent will be calculated using the Opioid Dose Equivalence document endorsed by the Faculty of Pain Medicine, Australian and New Zealand College of Anaesthetists
Secondary outcome [1] 416666 0
The secondary outcome is cumulative oral morphine equivalent daily dose in milligrams (oMEDD) on post operative Day 2. This will be collected from the electronic medical records.
Timepoint [1] 416666 0
Oral morphine equivalent daily dose in milligrams on postoperative day 2 amounts will be collected from the patient's hospital electronic medical record. Oral morphine equivalent will be calculated using the Opioid Dose Equivalence document endorsed by the Faculty of Pain Medicine, Australian and New Zealand College of Anaesthetists
Secondary outcome [2] 416667 0
The secondary outcome is cumulative oral morphine equivalent daily dose in milligrams (oMEDD) on post operative Day 3. This will be collected from the electronic medical records.
Timepoint [2] 416667 0
Oral morphine equivalent daily dose in milligrams on postoperative day 3 amounts will be collected from the patient's hospital electronic medical record. Oral morphine equivalent will be calculated using the Opioid Dose Equivalence document endorsed by the Faculty of Pain Medicine, Australian and New Zealand College of
Secondary outcome [3] 416668 0
Postoperative pain scores at rest will be assessed in the post-anaesthetic care unit (PACU). These data will be collected from the electronic medical records. Pain scores are quantified using the Numerical Pain Rating Scale (NRS), which is an 11-point numerical scale that defines a respondent’s severity of perceived pain between no pain designated a score of 0 and the worst possible pain designated a score of 10.
Timepoint [3] 416668 0
This will be measured on postoperative days 0-3,
Secondary outcome [4] 416669 0
Postoperative opioid-related adverse events collected from the electronic medical records. These events include respiratory depression, nausea and vomiting and sedation scores.
Timepoint [4] 416669 0
This will be determined by the period from completion of surgery to hospital discharge
Secondary outcome [5] 416670 0
Complications will be defined as any deviation from the normal postoperative course, guided by the European Perioperative Clinical Outcome definitions. Complications will be recorded by two independent clinicians, and then graded using Clavien-Dindo Classification - a widely used and validated approach to surgical outcome assessment that assigns severity grades to surgical complications. These data will be collected from the electronic medical records.
Timepoint [5] 416670 0
Complications will be determined by the period from completion of surgery to hospital discharge.
Secondary outcome [6] 416671 0
Length of hospital stay (LOS) will be collected from the patient's hospital electronic medical record.
Timepoint [6] 416671 0
LOS will be determined by the period from completion of surgery to discharge
Secondary outcome [7] 416875 0
Operation type, which will include whether the surgery is one of the following:

1.. Major liver surgery
2. Minor liver surgery
3. Whipple’s procedure
4. Other pancreatic resection

This will be collected from the electronic medical records.
Timepoint [7] 416875 0
Duration of surgery.
Secondary outcome [8] 416876 0
Operation length in minutes. This will be collected from the medical records.
Timepoint [8] 416876 0
From skin incision to completion of surgery.
Secondary outcome [9] 416877 0
Intraoperative Equivalent IV Morphine Equivalent (mg), This will be collected from the electronic medical records.
Timepoint [9] 416877 0
From start of anaesthesia to completion of surgery.
Secondary outcome [10] 416966 0
Postoperative pain scores during movement will be assessed in the post-anaesthetic care unit (PACU). These data will be collected from the electronic medical records. Pain scores are quantified using the Numerical Pain Rating Scale (NRS), which is an 11-point numerical scale that defines a respondent’s severity of perceived pain between no pain designated a score of 0 and the worst possible pain designated a score of 10.
Timepoint [10] 416966 0
This will be measured on postoperative days 0-3,

Eligibility
Key inclusion criteria
Inclusion criteria will be
1. Patients who underwent liver surgery will be identified as candidates for this study using International Statistical Classification of Diseases (ICD) codes including but not limited to excision of lesion of liver, lobectomy of liver, segmental resection of liver.

2. Patients undergoing pancreatic surgery will be identified using ICD codes for the following surgical categories: Whipple’s procedure, total pancreatectomy, central pancreatectomy, and distal pancreatectomy with or without splenectomy.

Patients will be included in the study if they were older than 18 years old, underwent major liver or pancreatic surgery as listed previously, and received either intrathecal morphine alone or intrathecal morphine in combination with intrathecal clonidine and bupivacaine.

Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
We will exclude the following patients
1. Patients receiving epidural analgesia
2. Patients undergoing liver or pancreatic surgery secondary to other procedures
3. Patients with a history of chronic pain disorder or chronic opioid use (>60mg oral morphine equivalent daily).

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Retrospective
Statistical methods / analysis
Data analysis will be performed using R v4.2.0 (R Core Team (2022) and associated packages.

The dataset will be analysed for missing data to assess whether this impacted on the significance of the associated statistical analysis. Appropriate statistical adjustment will be applied according to the degree and type of missing data. Continuous variables will be tested for normality by using the graphical method of a quantile-quantile plot.

To investigate the association of patient characteristics and postoperative outcomes between the ‘Intrathecal Morphine Only’ and ‘Multimodal Spinal Analgesia’ group, we will use the Wilcoxon–Mann–Whitney test for continuous variables, and the Fisher’s exact test or Chi-squared test for categorical variables.

All calculated P-values were two sided. A P-value of 0.05 will be considered significant. Boxplots will be used to highlight the difference in the OMEDD (mg) usage, pain scores at rest, and pain scores on movement in the postoperative period the between the ‘Intrathecal Morphine Only’ and ‘Multimodal Spinal Analgesia’ groups.

This will be calculated for Day 0, Day 1, Day 2, and Day 3 in the post-operative period. The Wilcoxon–Mann–Whitney test will be used to compare the statistical significance between ‘‘Multimodal Spinal Analgesia’ groups in their respective time periods.

To investigate the OMEDD (mg) usage in the post-operative period, we will use bootstrapped quantile regression to investigate the associated adjusted difference in OMEDD (mg) usage between the ‘Intrathecal Morphine Only’ and ‘Multimodal Spinal Analgesia’ group. OMEDD (mg) will be used as the dependent variable, and the allocation to either the ‘Intrathecal Morphine Only’ or ‘Multimodal Spinal Analgesia’ group will be used as the independent variable.

Age (years), Body Mass Index (BMI), Hospital Allocation/Location, Operation Type (Major Liver, Minor Liver, Whipple’s, Other Pancreatic), Operation Length (min), and Intraoperative Equivalent IV Morphine Equivalent (mg) will be a priori selected covariates.

We will use quantile regression models to assess the association between a set of input variables and specific percentiles (or quantiles) of the outcome variable and estimates differences in the quantiles of the outcome variable between the ‘Intrathecal Morphine Only’ and ‘Multimodal Spinal Analgesia’ groups.

We will include three quantile regression models: the 25th percentile, the 50th percentile (median), and the 75th percentile.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
23/04/2022
Date of last participant enrolment
Anticipated
Actual
23/04/2022
Date of last data collection
Anticipated
Actual
9/12/2022
Sample size
Target
273
Accrual to date
Final
273
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 23696 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 23697 0
Warringal Private Hospital - Heidelberg
Recruitment hospital [3] 23698 0
Knox Private Hospital - Wantirna
Recruitment postcode(s) [1] 39131 0
3084 - Heidelberg
Recruitment postcode(s) [2] 39132 0
3152 - Wantirna

Funding & Sponsors
Funding source category [1] 312837 0
Hospital
Name [1] 312837 0
Austin Health
Country [1] 312837 0
Australia
Primary sponsor type
Hospital
Name
Austin Health
Address
Department of Anaesthesia, Austin Health, 145 Studley Road, Heidelberg VIC, 3084
Country
Australia
Secondary sponsor category [1] 314479 0
None
Name [1] 314479 0
Address [1] 314479 0
Country [1] 314479 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312115 0
Austin Health Research Ethics Commitee
Ethics committee address [1] 312115 0
Ethics committee country [1] 312115 0
Australia
Date submitted for ethics approval [1] 312115 0
03/02/2022
Approval date [1] 312115 0
22/03/2022
Ethics approval number [1] 312115 0
HREC/2022/Austin/34

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 123530 0
Prof Laurence Weinberg
Address 123530 0
Department of Anaesthesia, Austin Health, 145 Studley Road Heidelberg VIC 3084
Country 123530 0
Australia
Phone 123530 0
+61394963800
Fax 123530 0
+61394966421
Email 123530 0
[email protected]
Contact person for public queries
Name 123531 0
Laurence Weinberg
Address 123531 0
Department of Anaesthesia, Austin Health, 145 Studley Road Heidelberg VIC 3084
Country 123531 0
Australia
Phone 123531 0
+61394965000
Fax 123531 0
+61394966421
Email 123531 0
[email protected]
Contact person for scientific queries
Name 123532 0
Laurence Weinberg
Address 123532 0
Department of Anaesthesia, Austin Health, 145 Studley Road Heidelberg VIC 3084
Country 123532 0
Australia
Phone 123532 0
+61394965000
Fax 123532 0
+61394966421
Email 123532 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Patients have not consented to sharing of their data


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
17815Study protocol  [email protected]
17816Ethical approval  [email protected]



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.