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.
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.
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.
Adults undergoing elective surgery who receive a standardized tramadol-containing elastomeric analgesia pump and consent to CYP2D6 genotyping.
Cohort
Prospective
Standardized Tramadol Elastomeric Analgesia Pump
DrugAll 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.
CYP2D6 Genotyping and Metabolizer Phenotype Assignment
GeneticA 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.
Incidence of Analgesic Treatment Failure
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.
Incidence of Tramadol-Related Adverse Effects
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
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.
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