Clinical trial NCT04004481: Metabolites of Tramadol in the Postoperative Surgical Patients
Official title: Metabolites of Tramadol in the Postoperative Surgical Patients Admitted in the ICU
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Abdominal Surgery
Respiratory Failure
Renal Failure
Liver Dysfunction
Multiorgan Failure
Keywords: Tramadol
CYP2D6 polymorphism
analgesia
intensive care
organ failure
Lead sponsor: Osijek University Hospital
Sponsor class: OTHER
Collaborators: name: Josip Juraj Strossmayer University of Osijek
First posted: 2019-07-02
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Serum Concentration of Tramadol and Tramadol Metabolites With Respect to Metabolic Phenotype
timeFrame: 1, 2, and 4 hours after first dose and immediately before 2nd, 3rd, and 5th dose, up to 24 hours
Secondary outcomes:
measure: Analgesic Effect of Tramadol Measured by Numeric Rating Scale (NRS)
timeFrame: Before each dose of tramadol and 30 minutes after tramadol dose, up to 24 hours
measure: Analgesic Effect of Tramadol Measured by Critical Care Pain Observation Tool (CPOT)
timeFrame: Pain was assessed before and 30 minutes after each tramadol dose, up to 24 hours.
measure: Number of Participants With Nausea and Vomiting After Tramadol
timeFrame: Nausea and vomiting was assessed during first 30 minutes after tramadol administration
measure: Number of Patients With Respiratory Depression After Tramadol
timeFrame: Respiratory depression was observed up to 30 minutes after tramadol administration
measure: Length of ICU Stay
timeFrame: Up to 6 months
Other outcomes:
Locations:
city: Osijek
country: Croatia
facility: University Hospital Osijek
Study officials:
affiliation: Osijek University Hospital
name: Nenad Neskovic, MD
role: PRINCIPAL_INVESTIGATOR
References:
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