Prospective Pharmacogenetic Cohort Study of CYP2D6 Metabolizer Phenotype, Analgesic Failure, and Adverse Effects in Postoperative Patients Receiving Tramadol by Elastomeric Infusion Pump

Prospective Pharmacogenetic Cohort Study of CYP2D6 Metabolizer Phenotype, Analgesic Failure, and Adverse Effects in Postoperative Patients Receiving Tramadol by Elastomeric Infusion Pump

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.

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.

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.