| Criteria | Include | Exclude |
|---|---|---|
| Population | All patient groups undergoing a surgical procedure | Patients not undergoing surgical procedures. Non-human studies |
| Concept | Studies using a total opioid burden metric as a primary or secondary outcome (Such as oral morphine equivalence (OME), milligram morphine equivalence (MME) or opioid equivalence) | Outcomes not including opioid totals |
| Context | Patients undergoing surgical procedures | Palliative care studies or Pharmacology studies |
| Other | Any studies comparing a control against and intervention or two interventions. | Studies with no difference between intervention groups |
Supplementary material D — Literature Rapid Review Of Total Opioid Burden Metric Methodology And Reporting Within Preoperative Care Research: Protocol
Registration: The rapid review protocol is pre-registered on the Open Science Framework
D.1 Introduction
D.1.1 Rationale
There are a wide range of different opioid used across the range of medical specialities and patient groups, each with their own potency to provide analgesia. Opioid conversion values have offered the ability to convert a specific opioid into the equivalent units of a reference opioid, usually morphine, to produce doses in oral morphine equivalent milligrams (OME mg) or milligram morphine equivalent (MME).
A number of conversion value tables have been published in an attempt to provide a best estimate of the conversion values between opioids. Within clinical practice, these cited value sets are a good surrogate for the true conversion value when used in opioid rotation5. Despite this, application of the value sets remains variable in both clinical and research practice.
It is unclear how well the methodology is described and reported within research.
D.1.2 Objectives
Primary research question: - Describe the methodologies of reporting of TOB metrics used in the perioperative literature.
Secondary research question(s)
What proportion of study report the opioid proportions between comparative groups
What proportion go study report the conversion values used to calculate the TOB metrics.
To extract and calculate the outcomes de-novo for studies that publish the required minimum data of mean opioid doses within groups.
D.1.3 Methods
The eligibility criteria is set using the PCCO framework as described in Table D.1. Only papers published in 2025 will be considered to ensure the methodology reviewed is representative of current practice.
D.1.4 Search strategy
Databases searched will include PUBMED, SCOPUS and Web of Science though their respective web portals using the respective search string. No gray literature will be included as the review aims to capture the practice of current and published research methodologies.
NotePUBMED search term
((((((“opioid equivalent” OR “oral morphine equivalence” OR “oral morphine equivalent” OR “oral morphine equivalents” OR “OME” OR “morphine milligram equivalents” OR “morphine milligram equivalence” OR “MME” OR “morphine equivalent daily dose” OR “MEDD”) AND (“perioperative” OR “peri-operative” OR “postoperative” OR “post-operative” OR “surgical” OR “surgery” OR “post-surgical” OR “postsurgical”))) AND (“2025/01/01”[Date - Publication] : “2025/12/31”[Date - Publication]))) AND (“clinical trial”[Filter] OR “clinical trial” OR “controlled clinical trial” OR “randomized controlled trial” OR “interventional” OR “intervention study” OR “clinical trials as topic”[MeSH Terms] OR “cohort studies”[MeSH Terms] OR “cohort” OR “prospective” OR “retrospective” OR “case-control” OR “comparative study” OR “evaluation study”))
NoteSCOPUS search term
TITLE-ABS-KEY ( “opioid equivalent” OR “oral morphine equivalence” OR “oral morphine equivalent” OR “oral morphine equivalents” OR “OME” OR “morphine milligram equivalents” OR “morphine milligram equivalence” OR “MME” OR “morphine equivalent daily dose” OR “MEDD” ) AND TITLE-ABS-KEY ( “perioperative” OR “peri-operative” OR “postoperative” OR “post-operative” OR “surgical” OR “surgery” OR “post-surgical” OR “postsurgical” ) AND TITLE-ABS-KEY ( “clinical trial” OR “controlled clinical trial” OR “randomized controlled trial” OR “interventional” OR “intervention study” OR “cohort” OR “prospective” OR “retrospective” OR “case-control” OR “comparative study” OR “evaluation study” ) AND PUBYEAR = 2025
NoteWeb of Science search term
TS=(“opioid equivalent” OR “oral morphine equivalence” OR “oral morphine equivalent” OR “oral morphine equivalents” OR “OME” OR “morphine milligram equivalents” OR “morphine milligram equivalence” OR “MME” OR “morphine equivalent daily dose” OR “MEDD”) AND TS=(“perioperative” OR “peri-operative” OR “postoperative” OR “post-operative” OR “surgical” OR “surgery” OR “post-surgical” OR “postsurgical”) AND TS=(“clinical trial” OR “controlled clinical trial” OR “randomized controlled trial” OR “interventional” OR “intervention study” OR “cohort” OR “prospective” OR “retrospective” OR “case-control” OR “comparative study” OR “evaluation study”) AND PY=(2025)
D.1.5 Study records and screening
D.1.5.1 Data management
Extracts from each search term will be uploaded to the Covidence review platform. Duplicate items will be removed. At each stage, records will be extracted and stored for backup.
D.1.5.2 Selection process
Screening of title and abstract will happen within the Covidence platform screening section. It will be performed by one reviewer with a subset review of 20% being reviewed by a second author to reduce bias and verify quality. Any discrepancies will reviewed and resolved though a moderation discussion.
D.1.5.3 Data collection process
Data collection will occur in two phases
Full text screening and primary data extraction - Manuscripts that pass screening will have a full text review. If at this stage it is not eligible it will be removed, if it is eligible it will have data extracted. Primary data collection will then occur by a single reviewer with a subset review of 20% being reviewed by a second author to reduce bias and verify quality
Secondary data extraction - A second stage data extraction will be performed for papers that cite/describe either a conversion value or report the opioid doses within control and intervention groups. This will provide further details, for that papers that do report their methodology. This will then occur by a single reviewer with a subset review of 20% being reviewed by a second author to reduce bias and verify quality.
D.1.6 Data items
Standard metadata including author, title, data of publication, journal of publication, doi and abstract (where possible) will be extracted at the search stage.
Primary data extraction: Review specific data will be extracted from all papers that pass screening using the proforma as detailed in Table D.2.
| Variable | Options | Description |
|---|---|---|
| Study type | Randomised controlled trial, Cohort study, Case controlled study, Other | What is the methodology of the study? If the study is not comparing an intervention between two groups, return to screening and mark as not eligable. |
| Intervention type | Surgical, Anaesthetic, Analgesia, Other | What type of intervention is given. For trials comparing surgical technique, approach, methods or surgical tools select surgical. For trials comparing anaesthesia technique, blocks, interoperative medications select anaesthesia. For trials comparing analgeisa including analgesia protocols, postoperative analgesic medications, etc select analgeisa Otherwise, select other and describe the intervention in the free text box. |
| Conversion set | Described, Cited, Not described | In the manuscript, is the conversion set used to generate the TOB metric described. If it is cited, copy the citation into the free text box below. If values are given, state the values in the free text box. This should usually be included in the methods section but may be included in other places of the manuscript such as tables or footnotes. |
| Opioid proportions | Reported, Not reported | Assess the results section, Is it possible to establish the proportion, mean or total doses of each opioid between intervention groups. If authors explicilty state only one type of opioid used in the TOB metric select ‘Reported’. |
Secondary data extraction: The data will be collected using an excel spreadsheet with the following data item names and descriptors (Table D.3).
| Sheet | Data item | Description |
|---|---|---|
| conversion_values | cite_ref_number | [autoassigned] incremented id number for this spreadsheet |
| conversion_values | cite_ref_text | [autoassigned] The copied citatation from the source referance list |
| conversion_values | zotero_cite_key | [autoassigned] The zotero citation key of the retrived article where appliable |
| conversion_values | year | Year of publication |
| conversion_values | sources | If described, what sources or ciations does the article give of the conversion values |
| conversion_values | format | What is the methods of generating the conversion values? [Suggested options: metanalysis, systamatic review, local guideline, RCT protocol, other] |
| conversion_values | provides_value_set | Does the article provide explicit conversion sets? [Selection: yes or no] |
| conversion_values | aim | If explicluty stated, what is the purpose of the conversion sets? [Selection: Clinical care or Research] |
| conversion_values | referance | If expliclity stated, what is the referance drug given [Suggestion: Oral morphine, IV moprhine, morphine, other] |
| conversion_values | morphine_oral | Conversion value stated (add further opioids as required) |
| conversion_values | morphine_iv | Conversion value stated (add further opioids as required) |
| conversion_values | morphine_sc | Conversion value stated (add further opioids as required) |
| conversion_values | morphine_epidural | Conversion value stated (add further opioids as required) |
| conversion_values | morphine_intrathecal | Conversion value stated (add further opioids as required) |
| conversion_values | oxycodone_oral | Conversion value stated (add further opioids as required) |
| conversion_values | methadone_oral | Conversion value stated (add further opioids as required) |
| conversion_values | fentanyl_iv | Conversion value stated (add further opioids as required) |
| conversion_values | fentanyl_sc | Conversion value stated (add further opioids as required) |
| conversion_values | remifentanil_iv | Conversion value stated (add further opioids as required) |
| conversion_values | sufentanil_iv | Conversion value stated (add further opioids as required) |
| conversion_values | fentanyl_transdermal | Conversion value stated (add further opioids as required) |
| conversion_values | codeine_oral | Conversion value stated (add further opioids as required) |
| conversion_values | hydrocodone | Conversion value stated (add further opioids as required) |
| conversion_values | hydromorphone | Conversion value stated (add further opioids as required) |
| conversion_values | oxymorphone | Conversion value stated (add further opioids as required) |
| conversion_values | tapentadol | Conversion value stated (add further opioids as required) |
| conversion_values | tramadol | Conversion value stated (add further opioids as required) |
| study_summary | covidence_ref | [autoassigned] The referance number of the manuscript from covidence |
| study_summary | authors | [autoassigned] The referance name of the manuscript from covidence [eg Baran 2025] |
| study_summary | control_group | Text description of the treatment in the control group [EG Erector spinae plane block (ESPB)] |
| study_summary | control group size | Number of patients within the control group |
| study_summary | intervention_group | Text description of the treatment in the control group [eg ESPB plus Serratus anetrior plane block] |
| study_summary | NA | Number of patients within the intervention group |
| study_summary | population | Text description of the eligiable partipants [eg Patients aged 18–75 years scheduled for their first minimally invasive cardiac surgery with ASA score I-III] |
| study_summary | note | Any notes with regards to the data collection [eg median values provided] |
| study_summary | reported_control_group_mean | Reported numerical value of the control group mean |
| study_summary | reported_intervnetion_group_mean | Reported numerical value of the intervention group mean |
| study_summary | reported_p_val | reported p value of the test of significant difference between the group means where applicable |
| study_doses | covidence_ref | [autoassigned] The referance number of the manuscript from covidence |
| study_doses | authors | [autoassigned] The referance name of the manuscript from covidence [eg Baran 2025] |
| study_doses | opioid | name of the opioid |
| study_doses | control_mean_dose | If reported, the mean dose of the opioid in the control group |
| study_doses | control_sd | If reported, the standard deviation of the dose of the opioid in the control group |
| study_doses | control_median_dose | If reported, the median dose of the opioid in the control group |
| study_doses | control_q1 | If reported, the first quartile of the dose of the opioid in the control group |
| study_doses | control_q3 | If reported, the third quartile of the dose of the opioid in the control group |
| study_doses | intervention_mean_dose | If reported, the mean dose of the opioid in the intervention group |
| study_doses | intervention_sd | If reported, the standard deviation of the dose of the opioid in the intervention group |
| study_doses | intervention_median_dose | If reported, the median dose of the opioid in the intervention group |
| study_doses | intervention_q1 | If reported, the first quartile of the dose of the opioid in the intervention group |
| study_doses | intervention_q3 | If reported, the third quartile of the dose of the opioid in the intervention group |
| study_doses | conversion_value_stated | The conversion value used to calcualte the TOB meteric if stated within the manuscript |
| study_doses | Note | Any free text notes about any assumptions made within the paper or the data collection |
D.2 Outcomes
Primary outcomes:
- To report the proportion of manuscripts that use a total opioid burden metrics in perioperative research that report the conversion values used and the opioid doses within groups.
Secondary outcomes:
To report the range and variability of the opioid conversion values used within the perioperative literature
To report the variability in the reported outcomes and de-novo calculates outcome for studies that report the opioid doses within groups
D.3 Data synthesis
Data will be analysed quantitative. For papers that are eligible and have primary data extraction, the counts and proportions will be presented.
No qualitative analysis will be performed.
D.3.1 Subgroup analysis
For papers that provide a conversion value or the papers cited, the conversion values for each opioid will be be presented with the range, mean and median.
For papers that provide opioid proportions, the reported outcome will be presented alongside the de-novo point estimate and the range estimate utilising the range presented previously.
D.4 Meta-bias
No planned assessment of meta-biases
D.5 Confidence in cumulative evidence
This is a rapid review of the methodology reporting, it aims to look at all published studys regardless of methodologies or study design therefore the body of evidence will not be assessed for strength.