Acute Postoperative Pain, Pharmacogenetic Variation, Tramadol Adverse Effect
Conditions
Keywords
CYP2D6, Tramadol, Pharmacogenetics, Analgesic Failure, Adverse Drug Reaction, Postoperative Pain
Brief summary
This prospective pharmacogenetic cohort will enroll postoperative patients receiving a standardized tramadol-containing elastomeric analgesia pump. CYP2D6 genotype will be measured but will not determine treatment during the 72-hour study window. Participants with non-normal metabolizer phenotypes will be compared with normal metabolizers for analgesic treatment failure and adverse effects. Pain, rescue medication, pump discontinuation, sedation, respiratory status, nausea/vomiting, and other adverse events will be assessed at prespecified times.
Detailed description
All participants will receive the same institutional tramadol pump regimen as routine postoperative care. A preoperative or immediate postoperative sample will undergo CYP2D6 genotyping, including copy-number assessment under the validated laboratory method. Pain and adverse effects will be recorded repeatedly through 72 hours while clinical care remains unrestricted. The primary analysis compares any non-normal phenotype with normal metabolizers, as proposed by the investigator. Because reduced- and increased-function phenotypes may affect different outcomes, separate poor/intermediate and rapid/ultrarapid analyses are prespecified. Models will account for CYP2D6 inhibitors, organ function, surgical procedure, anesthesia, and concomitant analgesia.
Interventions
DRUGStandardized Tramadol Elastomeric Analgesia Pump
All participants receive the same institutionally approved tramadol-based pump formulation, basal rate, duration, and allowed co-analgesics as routine care. Exact concentration, total dose, infusion rate, rescue regimen, and stopping criteria must be inserted in the final protocol. Linked arm/group(s): Non-Normal CYP2D6 Phenotype, Normal CYP2D6 Metabolizer.
GENETICCYP2D6 Genotyping and Metabolizer Phenotype Assignment
A validated clinical assay will detect prespecified CYP2D6 alleles and copy-number variation. Genotypes will be translated to activity score and metabolizer phenotype using a locked laboratory algorithm. Results will remain unavailable to the care team during the 72-hour observational window unless the ethics-approved safety plan requires disclosure. Linked arm/group(s): Non-Normal CYP2D6 Phenotype, Normal CYP2D6 Metabolizer.
Sponsors
Research Inc
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Elective surgery followed by the institution's standardized tramadol-containing elastomeric analgesia pump. * Ability to report pain on a 0-to-10 numeric rating scale. * Provision of a blood or buccal sample for CYP2D6 genotyping before or immediately after surgery. * Written informed consent for genetic testing, storage of genotype data, and clinical follow-up.
Exclusion criteria
* Known tramadol allergy or contraindication. * Chronic opioid therapy, opioid use disorder, or opioid tolerance requiring an individualized regimen. * Severe renal or hepatic dysfunction outside the standardized pump eligibility criteria. * Concomitant medication or condition that requires deviation from the standard pump before the first outcome assessment. * Pregnancy or breastfeeding. * Inability to provide reliable pain scores or complete 72-hour monitoring.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Analgesic Treatment Failure | 1 week | Proportion of participants with at least one prespecified failure criterion: pain score 4 or higher at two consecutive scheduled assessments despite protocol-allowed adjustment, rescue opioid above the locked threshold, premature pump discontinuation for inadequate analgesia, or replacement by another analgesic technique. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Tramadol-Related Adverse Effects | 1 week | Proportion with treated nausea/vomiting, excessive sedation, respiratory depression, dizziness, pruritus, confusion, hallucinations, or another event adjudicated as probably or definitely related to tramadol. |
| Phenotype-Specific Composite Outcome | 1 week | Separate estimates for poor/intermediate, normal, and rapid/ultrarapid metabolizers for analgesic failure and adverse-effect outcomes; these analyses address the expected opposite directions of reduced and increased CYP2D6 activity. |
Countries
Colombia
Contacts
CONTACTEdison Osorio, MD, Plastic surgeon
PRINCIPAL_INVESTIGATOREdison Osorio, MD, plastic surgery
Outcome results
None listed