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NCT Number: NCT04004481

Metabolites of Tramadol in the Postoperative Surgical Patients

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.

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Key information

Conditions

Abdominal Surgery Agnosia Digestive System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Liver Diseases Liver Dysfunction Male Urogenital Diseases Multiorgan Failure Multiple Organ Failure Nervous System Diseases Neurobehavioral Manifestations Neurologic Manifestations Pathologic Processes Pathological Conditions, Signs and Symptoms Perceptual Disorders Renal Failure Renal Insufficiency Respiration Disorders Respiratory Failure Respiratory Insufficiency Respiratory Tract Diseases Shock Signs and Symptoms Urogenital Diseases Urologic Diseases

Age range

18 year–90 year

Sex eligibility

All sexes

Study type

Observational

Primary location

University Hospital Osijek

Osijek, 31000, Croatia

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Postoperative analgesia using tramadol

Drug

Tramadol 100 mg will be given to the patients in the postoperative period.

Other names: Morphine for rescue analgesia

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

Sponsors and collaborators

Lead sponsor

Osijek University Hospital

Other

Collaborators

  • Josip Juraj Strossmayer University of Osijek

Registry information

Official study title

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

Acronym: METRAS

Important dates

Study start
2019
Primary completion
2020
Study completion
2020
First posted
Jul 2, 2019
Registry last updated
Jul 9, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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