Metabolites of Tramadol in the Postoperative Surgical Patients (METRAS)

June 16, 2021 updated by: Osijek University Hospital

Metabolites of Tramadol in the Postoperative Surgical Patients Admitted in the ICU

Tramadol is opioid analgesic widely used to treat moderate to severe pain. It is metabolized by cytochrome CYP2D6 into two major metabolites: pharmacologically active metabolite O-desmethyltramadol (M1) and inactive N-desmethyltramadol (M2), respectively. Tramadol kinetics in a population of patients undergoing major abdominal surgical procedures, and in patients with a greater or lesser degree of organic failure, is still not well researched. The investigators will measure plasma concentrations of tramadol and its metabolites after usual tramadol doses in ICU patients after major abdominal surgery. Also analgesic affect and side effect of tramadol will be recorded.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The blood samples for the CYP2D6 gene polymorphism analysis will be taken from all patients included in the study. The patients will be categorized as slow (PM), normal (NM) or ultra-fast metabolizers (UM) of tramadol using analysis of the CYP2D6 phenotype. Standard laboratory findings including red blood cells, urea, creatinine, and cholinesterase will be done before surgery.

The patients will receive 500 mg of tramadol intravenously divided into 5 doses during the first 24 postoperative hours in the ICU. The plasma concentrations of tramadol, O-desmethyltramadol and N-desmethyltramadol will be measured 1, 2 and 4 hours after the first dose, and immediately before the 2nd, 3rd and 5th dose. There will therefore be 6 measurements of tramadol and its metabolites.

The analgesic effect of tramadol will be measured in awake patients with Numeric Rating Scale - NRS (0 - without pain, 10 - strong pain) 30 minutes before and 30 minutes after tramadol administration. The NRS value of 3 or less will be considered as adequate analgesia. In case of inadequate analgesia rescue analgesic (morphine) will be used according to the local protocol.

In unconscious patients the analgesic effect of tramadol will be tested by Critical Care Pain Observation Tool (CPOT). The CPOT value of less than 2 will be considered as adequate analgesia. In case of inadequate analgesia rescue analgesic (morphine) will be used according to the local protocol. During the first 24 hours side effect of tramadol, such as nausea, vomiting and new respiratory depression will be recorded.

Study Type

Observational

Enrollment (Actual)

50

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Croatia
      • Osijek, Croatia, 31000
        • University Hospital Osijek

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 90 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The patients undergoing major open abdominal cancer surgery in Osijek University Hospital who are admitted in the ICU after surgery, age between 18 and 90 years, BMI >18 and <35, who signed the informed consent will be included in the study.

Description

Inclusion Criteria:

  • patients after major abdominal surgery will be observed.
  • surgical interventions requiring a laparotomy and involving resection of the organs of the digestive system
  • postoperative ICU admission.

Exclusion Criteria:

  • allergic reaction to tramadol
  • patients under 18 years old
  • patient over 90 years old
  • BMI <18 and >35
  • laparoscopic surgery
  • chronic therapy with tramadol, cimetidine, paroxetine, pimozide, metoclopramide, amiodarone, olanzapine, chlorpromazine, fluphenazine, haloperidol, thioridazine, risperidone and clozapine

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Adult patients undergoing major open abdominal surgery
Observational study. In the patients undergoing major open abdominal surgery for cancer tramadol will be used for postoperative analgesia. In the postoperative period parent compound and metabolites of tramadol will be measured. Postoperative analgesia and adverse effects will be registered and compared between CYP2D6 phenotypes observed.
Drug: Postoperative analgesia using tramadol
Tramadol 100 mg will be given to the patients in the postoperative period.
Other Names:
  • Morphine for rescue analgesia

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum Concentration of Tramadol and Tramadol Metabolites With Respect to Metabolic Phenotype
Time Frame: 1, 2, and 4 hours after first dose and immediately before 2nd, 3rd, and 5th dose, up to 24 hours
The plasma concentrations of tramadol, O-desmethyltramadol (ODT) and N-desmethyltramadol (NDT) will be measured 1, 2 and 4 hours after the first dose of 100 mg tramadol i.v., and immediately before the 2nd, 3rd and 5th dose. There will therefore be 6 measurements of tramadol and its metabolites.
1, 2, and 4 hours after first dose and immediately before 2nd, 3rd, and 5th dose, up to 24 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Analgesic Effect of Tramadol Measured by Numeric Rating Scale (NRS)
Time Frame: Before each dose of tramadol and 30 minutes after tramadol dose, up to 24 hours
The analgesic effect of tramadol will be measured in awake patients with Numeric Rating Scale (NRS, 0 - without pain, 10 - the worst pain) 30 minutes before and 30 minutes after tramadol administration. The NRS value of 3 or less will be considered as adequate analgesia. In case of inadequate analgesia morphine will be used according to the local protocol.
Before each dose of tramadol and 30 minutes after tramadol dose, up to 24 hours
Analgesic Effect of Tramadol Measured by Critical Care Pain Observation Tool (CPOT)
Time Frame: Pain was assessed before and 30 minutes after each tramadol dose, up to 24 hours.
In unconsciousness patents, the analgesic effect of tramadol will be tested by Critical Care Pain Observation Tool (CPOT). Highest score on a scale is 8 (worst pain) and lowest is 0 (no pain). The CPOT value of less than 2 will be considered as adequate analgesia.
Pain was assessed before and 30 minutes after each tramadol dose, up to 24 hours.
Number of Participants With Nausea and Vomiting After Tramadol
Time Frame: Nausea and vomiting was assessed during first 30 minutes after tramadol administration
Nausea and/or vomiting during treatment with tramadol in ICU will be recorded.
Nausea and vomiting was assessed during first 30 minutes after tramadol administration
Number of Patients With Respiratory Depression After Tramadol
Time Frame: Respiratory depression was observed up to 30 minutes after tramadol administration
Respiratory depression after tramadol is considered to be any drop in saturation below 90% or drop in respiratory rate below 10/min.
Respiratory depression was observed up to 30 minutes after tramadol administration
Length of ICU Stay
Time Frame: Up to 6 months
Length of stay in ICU will be recorded and correlated with standard laboratory values and tramadol and metabolites concentration.
Up to 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Osijek University Hospital

Collaborators

Josip Juraj Strossmayer University of Osijek

Investigators

  • Principal Investigator: Nenad Neskovic, MD, Osijek University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

January 25, 2019

Primary Completion (ACTUAL)

February 28, 2020

Study Completion (ACTUAL)

March 13, 2020

Study Registration Dates

First Submitted

June 25, 2019

First Submitted That Met QC Criteria

June 29, 2019

First Posted (ACTUAL)

July 2, 2019

Study Record Updates

Last Update Posted (ACTUAL)

July 9, 2021

Last Update Submitted That Met QC Criteria

June 16, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OsijekUH

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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